case study on tuberculosis

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• v.9(9); 2017 Sep

Verification of Diagnosis in Tuberculosis: A Case Report and Discussion

Amanda m dave.

1 School of Medicine, Creighton University Medical Center

Abed Adelrahman

2 Internal Medicine, Creighton University Medical Center

Vishisht Mehta

Stephen cavalieri.

3 Pathology, Creighton University Medical Center

Renuga Vivekanadan

4 Infectious Disease, Creighton University Medical Center

Tuberculosis (TB), caused by strains of Mycobacterium tuberculosis complex (M. tuberculosis), is a pulmonary infection that is spread by airborne droplet transmission. The development and spread of drug-resistant strains of M. tuberculosisgreatly jeopardize TB control efforts. We report the case of a previously healthy 43-year-old male, visiting from China, who presented to the emergency department complaining of hemoptysis of 10 days' duration. Cultures were positive for acid fast bacteria and negative for fungi. M. tuberculosis infection was confirmed by a deoxyribonucleic acid (DNA) probe. The patient was initially started on first-line therapy of isoniazid, rifampin, pyrazinamide, and ethambutol, with pyridoxine. His country of origin, China, increased suspicion for drug-resistant tuberculosis. Two weeks later, susceptibility testing of the M. tuberculosis isolate showed resistance to isoniazid, pyrazinamide, and ethambutol. Therapy was subsequently changed to amikacin, linezolid, moxifloxacin, and rifampin. The isolate was subsequently sent to the Center for Disease Control (CDC) for evaluation. Repeat testing showed that the isolate was susceptible to rifampin, pyrazinamide, and ethambutol. The patient was then restarted on his initial anti-TB regimen and was able to return to China.

The main goals for the treatment of TB are to treat the individual patient and to minimize transmission. Clues that point to the possibility of multiple drug resistant tuberculosis (MDR-TB) include contact with a patient with MDR-TB, origin from an endemic region, or failure of therapy with documented supervision. Collaboration with experts was imperative in ensuring appropriate patient care.

Introduction

Tuberculosis (TB) is caused by strains of Mycobacterium tuberculosis (M. Tuberculosis). TB is a primarily pulmonary infection spread by airborne droplet transmission. The development and spread of drug-resistant strains of M. tuberculosis greatly jeopardize TB control efforts. In the US, 91 cases of MDR-TB were reported in 2014. It is estimated that preventing a single case of MDR-TB would save the US healthcare system more than $250,000 [ 1 ]. As such, appropriate testing is imperative in the diagnosis and management of TB.

Case presentation

We report the case of a 43-year-old male, visiting from China, who presented to the emergency department complaining of hemoptysis of 10 days’ duration. This was associated with mild right-sided pleuritic chest pain and night sweats. The patient denied any shortness of breath, fever, or weight loss. The patient did not report any history of sick contacts. The patient was admitted from the emergency department to the floor. On admission, the patient had a normal physical examination and no significant laboratory abnormalities. Informed consent was obtained. A chest computed tomography scan showed a cavitary lesion with an air-crescent sign in the apical segment of his right lower lobe, suggestive of fungal infection. 

Acid fast bacillus and fungal cultures were performed on three consecutive early morning sputum specimens after admission; all were positive for acid fast bacteria but were negative for fungi. M. tuberculosis infection was confirmed by the DNA probe method. The patient was discharged on first-line therapy with isoniazid, rifampin, pyrazinamide, and ethambutol with pyridoxine. The patient’s country of origin, China, created concern for MDR-TB; as a result, further evaluation of the isolates was performed.

A molecular test for the rpoB gene coding for rifampin resistance was negative. Two weeks later, susceptibility testing of the isolate showed resistance to isoniazid, pyrazinamide, and ethambutol. Therapy was subsequently changed to amikacin, linezolid, moxifloxacin, and rifampin. After discussion with the Center for Disease Control (CDC), the isolate was sent to the CDC for evaluation of resistance genes. Over the following two weeks, the patient’s symptoms were stable. Results from the CDC were negative for resistance genes. Repeat susceptibility testing showed that the strain was susceptible to isoniazid, pyrazinamide, and ethambutol. With these results in hand, the patient was restarted on his original anti-TB regimen. The patient was then able to return to China. It is our suspicion that the initial susceptibility test was contaminated with oral flora or a respiratory tract organism that was resistant to isoniazid, pyrazinamide, and ethambutol.

The main goals of the treatment of TB are to treat the individual patient and to minimize transmission [ 1 ]. In non-human immunodeficiency virus (HIV) patients, first-line treatment of active pulmonary TB includes isoniazid, rifampin, pyrazinamide, and ethambutol with pyridoxine for eight weeks followed by isoniazid and rifampin for 16 weeks. TB can be successfully treated if the appropriate antibiotics are administered for the correct length of time [ 2 ]. Multiple drug resistant tuberculosis (MDR-TB) is significantly more difficult and expensive to treat than drug susceptible TB [ 3 ]. Therefore, the timely detection and confirmation of MDR-TB are crucial. MDR-TB is resistant to at least isoniazid and rifampin. Extremely drug resistant TB (XDR-TB) is also resistant to quinolones and at least one of the injectable drugs (e.g., amikacin, kanamycin, or capreomycin). TB is endemic in China, with 1.4 million cases and 130,000 deaths annually [ 4 - 5 ]. When treating TB patients from high-resistance areas, it is important to consider both MDR-TB and XDR-TB during evaluation and management [ 4 ].

Intrinsic resistance to one anti-tuberculosis drug is present from one in 106 to one in 108 organisms. About one in 1014 organisms has intrinsic resistance to two anti-TB drugs. As a result, anti-TB treatment, irrespective of the resistance on testing, involves multiple anti-TB drugs. Clear and accurate resistance testing is the key to selecting the correct treatment and to keeping resistance to a minimum [ 6 ]. Clues in the history that may point to the possibility of MDR-TB include a previous history of TB, a short course of treatment, inadequate treatment, and unsupervised therapy. Additional factors include patient contact with a patient with MDR-TB, origin from an endemic region, or failure of therapy with documented supervision. Furthermore, special attention should be paid to TB patients who are immunocompromised, especially in cases of HIV co-infection.

It is important to verify laboratory results if they are questionable. The molecular tests offered by the Center for Disease Control were instrumental in this regard and served to aid in the diagnosis, treatment, and control of TB in this case. 

The incorrect selection of drugs and/or the insufficient duration of therapy frequently leads to MDR-TB. As a result, the treatment of MDR-TB should be done by an expert. Directly observed therapy has also been a key component of keeping resistance rates low; cities that have instituted such programs have seen resistance rates drop [ 1 ].

New modalities to identify MDR-TB include line-probe assays, GeneXpert MTB/RIF, and MTBDRplus. Line-probe assays can be used to determine resistance to fluoroquinolones, injectable drugs, and ethambutol. It is used to ‘rule in’ resistance for fluoroquinolones and injectable agents. However, negative tests are not very reliable. GeneXpert MTB/RIF is an automated nucleic acid amplification assay. It detects M. Tuberculosis DNA and the rpoB gene, which demonstrates rifampin resistance [ 7 - 8 ]. It produces results in under two hours, does not require skilled technicians to perform it, nor does it need stringent biosafety conditions. It can also estimate the disease burden via an inverse correlation with the number of reaction cycles required to obtain a positive result. GeneXpert MTB/RIF is endorsed by the World Health Organization (WHO) for the rapid detection of MDR-TB; it can also be applied to smear negative TB. MTBDRplus is an assay that detects mutations responsible for rifampin and isoniazid resistance (rpoB gene - rifampin; katG and inhA gene - isoniazid) [ 8 - 9 ]. The turnaround time is one to two days. However, the assay does provide results in the presence of contamination and in smear negative cases.

While new tests continue to emerge, the smear, the slide, and the microscope are still the backbone of M. Tuberculosis detection. This is especially true in countries with limited resources. Using sputum or other tissue samples, cultures are obtained and evaluated for drug sensitivity [ 3 ]. Testing is ideally done in a reference laboratory; this requires skilled technicians to carry out an evaluation. Significant pitfalls to this modality include time needed to culture and the inability to detect resistance.

Conclusions

Tuberculosis is a primarily pulmonary infection that is endemic to China and has significant potential for morbidity and mortality. For patients from endemic regions, it is important to consider tuberculosis in the differential; this is particularly important if the patient reports contact with infected individuals or presents with symptoms of hemoptysis, night sweats, or weight loss.

If laboratory evaluations are questionable or suspicious, it is imperative to verify the results. Alternatively, repeat testing can be pursued. Furthermore, in some circumstances, it may prove necessary to collaborate with experts to ensure appropriate patient care. The molecular tests offered by the CDC were instrumental in this regard; repeat susceptibility testing and molecular tests for resistance genes were vital in making a proper diagnosis. Once a diagnosis has been confirmed, appropriate management and precautions, if necessary, can be initiated.

The authors have declared that no competing interests exist.

Human Ethics

Consent was obtained or waived by all participants in this study

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34:  Tuberculosis

David Cluck

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Patient presentation.

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Chief Complaint

“I have a cough that won’t go away.”

History of Present Illness

A 63-year-old male presents to the emergency department with complaints of cough/shortness of breath which he attributes to a “nagging cold.” He states he fears this may be something worse after experiencing hemoptysis for the past 3 days. He also admits to waking up in the middle of the night “drenched in sweat” for the past few weeks. When asked, the patient denies ever having a positive PPD and was last screened “several years ago.” His chart indicates he was in the emergency department last week with similar symptoms and was diagnosed with community-acquired pneumonia and discharged with azithromycin.

Past Medical History

Hypertension, dyslipidemia, COPD, atrial fibrillation, generalized anxiety disorder

Surgical History

Appendectomy at age 18

Family History

Father passed away from a myocardial infarction 4 years ago; mother had type 2 DM and passed away from a ruptured abdominal aortic aneurysm

Social History

Retired geologist recently moved from India to live with his son who is currently in medical school in upstate New York. Smoked ½ ppd × 40 years and drinks 6 to 8 beers per day, recently admits to drinking ½ pint of vodka “every few days” since the passing of his wife 6 months ago.

Sulfa (hives); penicillin (nausea/vomiting); shellfish (itching)

Home Medications

Albuterol metered-dose-inhaler 2 puffs q4h PRN shortness of breath

Aspirin 81 mg PO daily

Atorvastatin 40 mg PO daily

Budesonide/formoterol 160 mcg/4.5 mcg 2 inhalations BID

Clonazepam 0.5 mg PO three times daily PRN anxiety

Lisinopril 20 mg PO daily

Metoprolol succinate 100 mg PO daily

Tiotropium 2 inhalations once daily

Venlafaxine 150 mg PO daily

Warfarin 7.5 mg PO daily

Physical Examination

Vital signs.

Temp 100.8°F, P 96, RR 24 breaths per minute, BP 150/84 mm Hg, pO 2 92%, Ht 5′10″, Wt 56.4 kg

Slightly disheveled male in mild-to-moderate distress

Normocephalic, atraumatic, PERRLA, EOMI, pale/dry mucous membranes and conjunctiva, poor dentition

Bronchial breath sounds in RUL

Cardiovascular

NSR, no m/r/g

Soft, non-distended, non-tender, (+) bowel sounds

Genitourinary

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• Case report
• Open access
• Published: 19 November 2022

A case report of persistent drug-sensitive pulmonary tuberculosis after treatment completion

• Sergo A. Vashakidze 1 , 2 ,
• Abivarma Chandrakumaran 3 ,
• Merab Japaridze 1 ,
• Giorgi Gogishvili 1 ,
• Jeffrey M. Collins 4 ,
• Manana Rekhviashvili 1 &
• Russell R. Kempker 4  

BMC Infectious Diseases volume  22 , Article number:  864 ( 2022 ) Cite this article

5364 Accesses

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Mycobacterium tuberculosis (Mtb) has been found to persist within cavities in patients who have completed their anti-tuberculosis therapy. The clinical implications of Mtb persistence after therapy include recurrence of disease and destructive changes within the lungs. Data on residual changes in patients who completed anti-tuberculosis therapy are scarce. This case highlights the radiological and pathological changes that persist after anti-tuberculosis therapy completion and the importance of achieving sterilization of cavities in order to prevent these changes.

Case presentation

This is a case report of a 33 year old female with drug-sensitive pulmonary tuberculosis who despite successfully completing standard 6-month treatment had persistent changes in her lungs on radiological imaging. The patient underwent multiple adjunctive surgeries to resect cavitary lesions, which were culture positive for Mtb. After surgical treatment, the patient’s chest radiographies improved, symptoms subsided, and she was given a definition of cure.

Conclusions

Medical therapy alone, in the presence of severe cavitary lung lesions may not be able to achieve sterilizing cure in all cases. Cavities can not only cause reactivation but also drive inflammatory changes and subsequent lung damage leading to airflow obstruction, bronchiectasis, and fibrosis. Surgical removal of these foci of bacilli can be an effective adjunctive treatment necessary for a sterilizing cure and improved long term lung health.

Peer Review reports

Mycobacterium tuberculosis treatment has been evolving over the years, especially with the introduction of newer drugs and shorter regimens [ 1 , 2 ]. Apart from the cavitary nature of tuberculous disease, patients who have been treated with current regimens often are given the designation of cure without achieving proper sterilization. Patients who complete the tuberculous regimen are given the definition of cure after they achieve sputum negativity but many of these patients harbor bacilli within cavities that continue to exert their effects on the respiratory system [ 3 ]. The residual changes that occur in patients who have completed medical therapy have been poorly attended to in the literature. Patients that underwent surgical and medical sterilization have been reported to have better pulmonary health in the long term, especially after the removal of cavities [ 4 ].

Here, we report a patient who underwent a complete regimen of medical therapy for pulmonary tuberculosis and later had to have surgical resection of her cavities, which grew tuberculous bacilli even after achieving sputum negativity.

A 33-year-old female from the country of Georgia presented to a tuberculosis dispensary on July 10, 2020, with a temperature of 38° C and symptoms of malaise, productive cough, and night sweats. The patient had no known medical problems. She reported smoking ~ 10 cigarettes daily and denied alcohol or illicit drug use. She had 3 children and her husband was a prisoner being treated for pulmonary tuberculosis. Upon physical examination there were decreased breath sounds in the upper lobes of the lungs with dullness to percussion. The patient had a body mass index (BMI) of 16.3 kg/m 2 . A complete blood count revealed a moderate leukocytosis of 10.2 × 10 9 /L and an erythrocyte sedimentation rate (ESR) of 42 mm/h. Biochemical blood parameters were normal. Sputum testing found a negative acid-fast bacilli (AFB) microscopy, positive Xpert MTB/RIF test (no RIF resistance), and positive culture for Mycobacterium tuberculosis (Mtb). Additionally, drug susceptibility testing (DST) revealed sensitivity to rifampin, isoniazid, and ethambutol. Chest radiography revealed multiple small foci in the upper lobes of both lungs and a cavity in the right lung (Fig.  1 A). The patient was initiated on daily outpatient treatment with three pills of a fixed dosed combination pill containing isoniazid 75 mg, rifampin 150 mg, ethambutol 275 mg and pyrazinamide 400 mg. Treatment was given through directly observed therapy (DOT). She converted her sputum cultures to negative at 2 months and continued rifampin and isoniazid to finish 6 months of treatment. An end of treatment chest x-ray revealed fibrosis and honeycombing in the right upper lung, and fibrosis and dense focal shadows in the 1st and 2nd intercostal spaces of the left lung (Fig.  1 B). The complete treatment timeline is summarized in Fig.  2 .

A (left): Baseline chest X-ray showing a cavity in the right lung and multiple foci in the upper lobes of both lungs. B (right): End of initial treatment chest X-ray, showing fibrosis, local honeycombing and dense focal shadows in both lungs

Patient treatment timeline ( HRZE isoniazid, rifampin, pyrazinamide, ethambutol; HR isoniazid & rifampin; DOTS directly observed therapy, short-course; CT computed tomography; AFB acid fast bacilli)

A follow up chest computed tomography (CT) scan demonstrated a cavity in the right upper lobe measuring 12 × 10 mm in size with a thick and heterogeneous wall and nodules and bronchiectasis in the left lung (Fig.  3 A–D). Based on CT findings and in accordance with National tuberculosis guidelines, the patient was offered surgical resection of the affected portion of the lung. It should be noted that the patient reported no symptoms, complaints, or functional disability before the surgery. Preoperative workup including pulmonary function testing, an echocardiogram, bronchoscopy, and blood chemistries were normal. The patient consented to surgery and underwent a surgical resection of the S1 and S2 segments of the right lung 2 weeks later. Intraoperatively, moderate adhesions were visualized in the S1 and S2 area with a palpable dense formation ~ 3.0 cm in diameter, in addition to a dense nodule. Gross pathology of the resected lesion showed a thick-walled fibrous cavity filled with caseous necrosis (Fig.  4 A) corresponding to the right preoperative CT lesion seen on Fig.  3 A, C.

CT scan (January 11, 2021) showing, A a cavity in the upper lobe of the right lung with heterogeneous thick walls. B S1 and S2 segments of the left lung shows a 23 × 18 mm oval shaped calcified inclusions; C , D areas with calcified, compacted nodules 13 × 20 mm in size with additional traction bronchiectasis

A Gross pathological image of a resected cavity with caseous material from first surgery (S1 & S2 segment of right lung). B The gross pathology from the second surgery showed the presence of a blocked cavity measuring up to 2 cm in diameter filled with caseous material in the S1, S2 and C Tuberculoma in S6 segment

Microbiological analysis on the resected tissue revealed acid-fast bacilli on microscopy, and positive Xpert MTB/RIF and culture results. Mtb grew from the caseous center, inner and outer walls of the cavity and a resected foci located ~ 3 cm from the cavity. DST revealed sensitivity to isoniazid, rifampin, and ethambutol.

Pathological examination of the resected lesion showed findings consistent with fibrocavernous tuberculosis. No postoperative complications were experienced, and the patient reinitiated first-line therapy via DOT on the 2nd postoperative day and was discharged on postoperative day 11.

A follow up CT scan performed after 3 months showed postoperative changes in the right upper lobe, and an unchanged left lung (Fig.  5 A–C). Based on the persistent conglomerate of tuberculomas and multiple small tuberculous foci, growth of Mtb from the previous surgical specimen, and the patient’s social situation (mother of three young children) a second surgery to optimize the chance of cure was recommended. The patient reported no symptoms, complaints, or functional disability before the surgery. Preoperative sputum testing found negative AFB smear microscopy and culture. The patient underwent the second operation on May 18, 2021, in which the S1, S2 and part of the S6 segment of the left lung were resected. Intraoperatively, moderate adhesions seen along with a dense palpable ~ 3 cm mass in the S1 and S2 region and a dense focus in S6.

A – C Follow-up CT scan after first adjunctive surgery showing postoperative changes of the right lung and radiological changes in the left lung, that were unchanged compared to the initial CT. D Final CT scan showing normal postoperative changes with no cavities as previously seen

Microbiological examinations performed on resected tissue revealed positive AFB smear microscopy and Xpert MTB/RIF results and a negative AFB culture. The pathological examination of the surgical samples indicated a variety of destructive changes in addition to ongoing inflammation. The gross specimen of S1 and S2 segments of the left lung showed fibrocavernous tuberculosis shown in Fig.  4 B, which corresponds to the left lung lesion seen on the first preoperative CT in Figs.  3 B and 5 A in the second preoperative CT; the gross specimen of the S6 segment showed progressive tuberculoma seen in Fig.  4 C, which corresponds to the left lung lesion seen on the first preoperative CT in Figs.  3 D and 5 C in the second preoperative CT.

There were no postoperative complications, and tuberculosis (TB) treatment was reinitiated. The patient successfully completed treatment with normalization of clinical and laboratory parameters and a clinical outcome of cure in September 2021, ~ 14 months after beginning treatment. The patient had reported near complete resolution of her symptoms, having a much better ability to perform her daily activities. The patient appreciated the effects surgery had on her recovery and was happy to have gone through that treatment route. A post treatment CT scan demonstrated postoperative changes in the upper segments of both lungs (Fig.  5 D). Results from post treatment lung function testing were all within normal range.

Discussion and conclusions

We present this case to highlight the heterogeneous nature of pulmonary tuberculosis and need for an individualized treatment approach, especially for patients with cavitary disease. Over the last decade, novel diagnostics, drugs, and treatment regimens have revolutionized TB management including a recent landmark clinical trial demonstrating an effective 4-month regimen for drug-susceptible TB [ 1 ]. The move towards shorter regimens is critical to improve treatment completion rates and help meet TB elimination goals. However, during a transition to shorter treatment durations it is imperative that clinicians remain aware of complex and severe pulmonary TB cases that may require longer durations of treatment and adjunctive therapies such as surgery. Supporting evidence comes from a recent landmark study finding persistent inflammation on imaging associated with finding Mtb mRNA in sputum after successful treatment and a meta-analysis demonstrating a hard-to-treat TB phenotype not cured with the standard 6 months of treatment [ 2 , 5 ]. However, regarding recommendations for prolonging treatment beyond 6 months for drug-susceptible pulmonary tuberculosis, ATS/CDC/IDSA recommends (expert opinion) extended treatment for persons with cavitary disease and a positive 2 month culture (our patient would not have met this criteria); World Health Organization (WHO) does not recommend extended treatment for any persons with drug-susceptible TB [ 6 , 7 ]. Accumulating evidence demonstrates surgical resection may be an effective adjunctive treatment in cases with cavitary disease [ 8 , 9 , 10 , 11 , 12 ]. Ultimately, a precision medicine approach towards TB will be able to identify patients who would benefit from short course therapy and those who would benefit from longer therapy and adjunctive treatment including surgery [ 13 ].

Mtb has a unique ability and propensity to induce cavities in humans with various studies showing cavitary lesions in ~ 30 to 85% of patients with pulmonary tuberculosis [ 14 ]. Lung cavities are more common in certain groups including patients with diabetes mellitus and undernutrition such as our patient who had a baseline BMI of 16.3 kg/m 2 [ 15 , 16 ]. Their presence indicates more advanced and severe pulmonary disease as evidenced by their association with worse clinical outcomes. Cavitary disease has been associated with higher rates of treatment failure, disease relapse, acquired drug resistance, and long term-term pulmonary morbidity [ 2 , 17 , 18 , 19 ]. The impact of cavitary disease may be more pronounced in drug-resistant disease as shown in an observational study from our group which found a five times higher rate of acquired drug resistance and eight times higher rate of treatment failure among patients multidrug- or extensively drug-resistant cavitary disease compared to those without [ 20 ].

Mtb cavities are characterized by a fibrotic surface with variable vascularization, a lymphocytic cuff at the periphery followed by a cellular layer consisting of primarily macrophages and a necrotic center with foamy apoptotic macrophages and high concentrations of bacteria. Historically, each portion of the TB cavity has been conceptualized as concentric layers of a spherical structure due to its appearance on histologic cross-sections. However, recent studies using more detailed imaging techniques have shown most TB cavities exhibit complex structures with diverse, branching morphologies [ 21 ]. A dysregulated host immune response to Mtb is thought to contribute to the development of lung cavities, which may explain why cavitary lesions are seen less frequently among immunosuppressed patients including people living with Human Immunodeficiency Virus (HIV) [ 14 ]. The center of the TB cavity (caseum) is characterized by accumulation of pro-inflammatory lipid signaling molecules (eicosanoids) and reactive oxygen species, which result in ongoing tissue destruction, but do little to control Mtb replication [ 22 ]. Conversely, the cellular rim and lymphocytic cuff are characterized by a lower abundance of pro-inflammatory lipids and increases in immunosuppressive signals including elevated expression of TGF-beta and indoleamine-2,3-dioxygenase-1 [ 22 ]. The anti-inflammatory milieu within these TB cavity microenvironments impairs effector T cell responses, further limiting control of bacterial replication [ 23 , 24 , 25 ].

The combination of impaired cell-mediated immune responses with accumulation of inflammatory mediators at the rim of the caseum leads to ongoing tissue destruction with the potential for long-term pulmonary sequelae. Many with cavitary tuberculosis suffer chronic obstructive pulmonary disease after successful treatment and the risk may be greater in those with multidrug-resistant disease [ 3 , 4 ]. This has led to research into adjunctive treatment with immune modulator therapies with a goal of mitigating the over-exuberant inflammatory response at the interior edge of the cavity to limit tissue damage. In a recent randomized clinical trial, patients with radiographically severe pulmonary tuberculosis treated with adjunctive everolimus or CC-11050 (phosphodiesterase inhibitor with anti-inflammatory properties) achieved better long-term pulmonary outcomes versus those who received placebo [ 26 ]. Such results suggest the inflammatory response can be modified with appropriate host-directed therapies to improve pulmonary outcomes, particularly in those with cavitary tuberculosis.

Tuberculosis cavities not only hinder an effective immune response, but also prevent anti-tuberculosis drugs from achieving sterilizing concentrations throughout the lesion and especially in necrotic regions. The necrotic center of cavitary lesions is associated with extremely high rates of bacilli (up to 10 9 per milliliter), many of which enter a dormant state with reduced metabolic activity. Bacilli in this dormant state may be less responsive to the host immune response and exhibit phenotypic resistance to some anti-tuberculosis drugs thereby preventing sterilization and increasing chances of relapse [ 14 , 27 , 28 ]. The fact that the specimens from our patient’s second surgery were Xpert and AFB positive, but culture negative may indicate the presence of either dead bacilli or metabolically altered(dormant) bacilli that may be alive, but not culturable by standard techniques. Further, genomic sequencing studies have also found distinct strains of Mtb within different areas of the cavity that have varying drug-susceptibilities demonstrating cavities as a potential incubator for drug resistance [ 27 , 29 ].

Emerging literature has started to elucidate the varying abilities of drugs to penetrate into cavitary lesions and the importance of adequate target site concentrations. One notable study found that decreasing tissue concentrations within resected cavitary TB lesions were associated with increasing drug phenotypic MIC values [ 30 ]. Innovative studies using MALDI mass spectrometry imaging have further demonstrated varied spatiotemporal penetration of anti-TB drugs in human TB cavities [ 31 ]. This study found rifampin accumulated within caseum, moxifloxacin preferentially at the cellular rim, and pyrazinamide throughout the lesion, demonstrating the need to consider drug penetration when designing drug regimens in patients with cavitary TB. Computational modeling studies have further demonstrated the importance of complete lesion drug coverage to ensure relapse-free cure [ 32 ]. Furthermore, clinical trials are now incorporating these principles into study design by (1) using radiological characteristics to determine treatment length and (2) incorporating tissue penetration into drug selection and regimen design [ 33 , 34 ]. Beyond tissue penetration, varying drug levels and rapid INH acetylation status can also lead to suboptimal pharmacokinetics and poor clinical outcomes [ 35 , 36 ]. As highlighted in a recent expert document, clinical standards to optimize and individualize dosing need to be developed to improve outcomes [ 37 ].

Available literature points to a benefit of adjunctive surgical resection particularly among patients with drug resistant tuberculosis. A meta-analysis of 24 comparative studies found surgical intervention was associated with favorable treatment outcomes among patients with drug-resistant TB (odds ratio 2.24, 95% CI 1.68–2.97) [ 38 ]. Additionally, an individual patient data meta-analysis found that partial lung resection (adjusted OR 3.9, 95% CI 1.5–5.9) but not pneumectomy was associated with treatment success [ 39 ]. In two observational studies, we have also found that adjunctive surgical resection was associated with high and improved outcomes compared to patients with cavitary disease not undergoing surgery and was associated with less reentry into TB care. It should be noted that all studies of surgical resection for pulmonary TB were observational studies, which may be subject to selection bias, and no clinical trials (very difficult to implement in practice) were conducted to provide more conclusive evidence. Based on available evidence, the WHO has provided guidance to consider surgery among certain hard to treat cases of both drug-susceptible and resistant cavitary disease [ 40 ]. Criteria for surgical intervention included (1) failure of medical therapy (persistent sputum culture positive for M. tuberculosis ), (2) a high likelihood of treatment failure or disease relapse, (3) complications from the disease, (4) localized cavitary lesion, and (5) sufficient pulmonary function to tolerate surgery. For our patient, the severity of disease, lack of improvement of radiological imaging despite appropriate treatment, and high risk of relapse were the main indicators for surgery. Contraindications for surgery included a forced expiratory volume (FEV1) < 1000 mL, severe malnutrition, or patients at high risk for perioperative cardiovascular complications. With strict adherence to indications and contraindications for surgery, an acceptable level of postoperative complications are noted (5–17%) [ 4 , 38 ]. Our results also demonstrate the safety of adjunctive surgery, as our post-operative complication rate (8%) was low with the majority being minor complications [ 41 ].

As our case highlights, patients with persistent cavitary disease at the end of treatment require close clinical follow up and a tailored, individualized plan to determine the best approach for disease elimination and cure. In certain cases, including those with persistent cavitary disease and end of treatment, and where available, surgical resection is an effective adjunctive treatment option that can reduce disease burden and aid anti-tuberculosis agents in providing a sterilizing cure. As we enter an era of welcomed new shorter treatment options for tuberculosis it is imperative for clinicians to be able to identify and recognize complicated TB cases that require prolonged treatment and potentially adjunctive surgery.

Availability of data and materials

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Abbreviations

Acid fast bacilli

American Thoracic Society

Body mass index

Center for Disease Control

Computed tomography

Directly observed therapy

Drug sensitive tuberculosis

Erythrocyte sedimentation rate

Human Immunodeficiency Virus

Infectious Diseases Society of America

Mycobacterium tuberculosis

• Tuberculosis

World Health Organization

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Acknowledgements

The authors thank the physicians, nurses, and staff at the NCTLD in Tbilisi, Georgia, who provided care for the patient described in this report. Additionally, the authors are thankful for the patient with pulmonary tuberculosis who was willing to have their course of illness presented and help contribute meaningful data that may help future patients with the same illness.

This study did not receive any specific funding.

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Thoracic Surgery Department, National Center for Tuberculosis and Lung Diseases, 50 Maruashvili, 0101, Tbilisi, Georgia

Sergo A. Vashakidze, Merab Japaridze, Giorgi Gogishvili & Manana Rekhviashvili

The University of Georgia, Tbilisi, Georgia

Sergo A. Vashakidze

Tbilisi State Medical University, Tbilisi, Georgia

Abivarma Chandrakumaran

Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

Jeffrey M. Collins & Russell R. Kempker

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SAV: Conceptualization; Data collection and interpretation; Scientific Writing including initial draft preparation and manuscript revision and editing. AC: Data interpretation; Table and Figure preparation; Literature review; Scientific Writing including initial draft preparation and manuscript revision and editing. MJ: Data collection; Scientific Writing including manuscript review and editing. GG: Data collection; Scientific Writing including manuscript review and editing. JMC: Data interpretation; Scientific Writing including manuscript review and editing. MR: Data interpretation; Scientific Writing including manuscript review and editing. RRK: Conceptualization; Literature review; Scientific Writing including manuscript review and editing. All authors read and approved the final manuscript.

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Vashakidze, S.A., Chandrakumaran, A., Japaridze, M. et al. A case report of persistent drug-sensitive pulmonary tuberculosis after treatment completion. BMC Infect Dis 22 , 864 (2022). https://doi.org/10.1186/s12879-022-07836-y

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Living with tuberculosis: a qualitative study of patients’ experiences with disease and treatment

• Juliet Addo 1 ,
• Dave Pearce 2 ,
• Marilyn Metcalf 3 ,
• Courtney Lundquist 1 ,
• Gillian Thomas 4 ,
• David Barros-Aguirre 5 ,
• Gavin C. K. W. Koh 6 &
• Mike Strange 1  

BMC Public Health volume  22 , Article number:  1717 ( 2022 ) Cite this article

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Although tuberculosis (TB) is a curable disease, treatment is complex and prolonged, requiring considerable commitment from patients. This study aimed to understand the common perspectives of TB patients across Brazil, Russia, India, China, and South Africa throughout their disease journey, including the emotional, psychological, and practical challenges that patients and their families face.

This qualitative market research study was conducted between July 2020 and February 2021. Eight TB patients from each country ( n  = 40) completed health questionnaires, video/telephone interviews, and diaries regarding their experiences of TB. Additionally, 52 household members were interviewed. Patients at different stages of their TB treatment journey, from a range of socioeconomic groups, with or without TB risk factors were sought. Anonymized data underwent triangulation and thematic analysis by iterative coding of statements.

The sample included 23 men and 17 women aged 13–60 years old, with risk factors for TB reported by 23/40 patients. Although patients were from different countries and cultural backgrounds, experiencing diverse health system contexts, five themes emerged as common across the sample. 1) Economic hardship from loss of income and medical/travel expenses. 2) Widespread stigma, delaying presentation and deeply affecting patients’ emotional wellbeing. 3) TB and HIV co-infection was particularly challenging, but increased TB awareness and accelerated diagnosis. 4) Disruption to family life strained relationships and increased patients’ feelings of isolation and loneliness. 5) The COVID-19 pandemic made it easier for TB patients to keep their condition private, but disrupted access to services.

Conclusions

Despite disparate cultural, socio-economic, and systemic contexts across countries, TB patients experience common challenges. A robust examination of the needs of individual patients and their families is required to improve the patient experience, encourage adherence, and promote cure, given the limitations of current treatment.

Peer Review reports

Tuberculosis (TB) is a communicable infectious disease affecting around one quarter of the world’s population [ 1 ]. The ‘BRICS’ countries of Brazil​, Russia, India, China, and South Africa account for 47% of the total number of TB cases annually [ 1 , 2 , 3 ].

Caused by the bacillus Mycobacterium tuberculosis , around 5–10% of those infected will develop active disease. In 2019, 10 million new active cases and 1.4 million deaths were reported [ 1 ]. In 2020, the coronavirus disease 2019 (COVID-19) pandemic severely impacted the reporting of new cases and impeded diagnosis and treatment [ 3 ]. Treatment for multidrug-resistant TB (MDR-TB) also declined by 15% (from 177,100 in 2019 to 150,359 in 2020), with only about a third of patients who needed this treatment obtaining access [ 3 ].

Ambitious targets to end the TB epidemic by 2035 were established in 2015 by the WHO’s End TB Strategy [ 4 ], aligned with the United Nations Sustainable Development Goals [ 5 ]. In 2018, a United Nations General Assembly High-Level Meeting on Tuberculosis resulted in a Political Declaration on Tuberculosis, committing to end TB globally by 2030 [ 6 ]. Achieving these goals requires more equitable deployment of existing measures, and the development of new tools for TB prevention, diagnosis and treatment [ 7 ]. Progress towards ending TB also demands that interventions are aligned to patients’ experiences and address the challenges that they face [ 8 , 9 ].

TB typically involves the lungs (pulmonary TB) and is acquired via inhalation of droplet nuclei in the air following exposure usually over several hours. Close contact and the infectiousness of the source patient are key risk factors for the infection of tuberculin-negative persons [ 10 ]. Current treatment of drug-susceptible TB requires combination therapy consisting of an intensive phase of 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol, followed by a continuation phase of 4 months of isoniazid and rifampin [ 11 ]. Directly observed therapy (DOT) is recommended to ensure adherence to the complex regimen and to deter the emergence and spread of MDR-TB. Treatment is successful in around 85% of patients following 6 months’ therapy [ 1 ]. Also, individuals can become non-infectious within two weeks of treatment initiation, restraining disease transmission [ 1 ]. Thus, prompt initiation of therapy is important for both the patient and their close contacts. However, the management of TB is complicated by the increasing prevalence of MDR-TB, which requires prolonged and complex therapy, and is more likely to be associated with poor outcomes [ 12 ]. Even after successful treatment, patients may have ongoing lung disease and a decreased life expectancy [ 13 , 14 , 15 ].

The drugs used to treat tuberculosis are well understood clinically, and susceptibility testing will indicate which treatment regimen is appropriate [ 11 , 12 ]. However, treatment effectiveness depends on patient adherence to a demanding and lengthy treatment regimen with associated side effects. In this context, a patient-focused approach which considers the individual’s specific circumstances is needed to ensure sufficient adherence and good outcomes from therapy. Interest in this field has been building steadily and is most suited to a qualitative investigational approach which allows deep exploration of motivations, reactions, goals, aspirations, and circumstances. However, studies more often consider the challenges faced by healthcare workers caring for TB patients [ 16 ], or the implementation of new management tools [ 17 , 18 ].

Previous studies have examined how patients manage their illness and the impact that TB has on their daily lives, their families, and the wider community [ 19 , 20 ], as well as the stigma associated with poverty and HIV and the effects of discrimination [ 21 ]. However, defining studies on the experiences of TB patients and their families are not available for all the BRICS countries, and comparison between studies with different methodologies and objectives is problematic. It is, therefore, unclear to what extent the experiences of TB patients are shared across countries.

We report the findings of a qualitative evaluation of TB patients’ experiences across the five BRICS countries. The study aimed to identify commonalities across the different country contexts, by examining the perspectives of TB patients throughout their full disease journey, including the emotional, psychosocial and practical challenges that patients and their families face. A greater understanding of these factors could inform care more focused on patients’ needs, with the aim of improving outcomes and directing the development of new tools to end TB.

Study design

This qualitative market research study was designed collaboratively by GSK and Adelphi Research and conducted between July 2020 and February 2021 across the five BRICS countries (Brazil, Russia, India, China, and South Africa). The study was non-interventional and without clinical endpoints. The aim was to achieve a better understanding of the TB market across the BRICS countries by identifying common challenges faced by TB patients and their families in their daily lives throughout their treatment journey.

The study conformed to ethical principles laid down in the Declaration of Helsinki, all national data protection laws and industry guidelines. Participants’ data was protected by compliance with General Data Protection Regulation [ 22 ]. All participating patients and household members provided written voluntary informed consent, and parents provided written consent for children under the age of consent. Consent was also provided for anonymized publication of the findings. For consent forms see supplementary materials, Additional file 1.

To investigate the experiences, meanings, and perspectives of TB patients, qualitative methodology was employed to identify themes within and across countries from in-depth interviews and self-recorded videos, supported by a self-completed health questionnaire.

Participants with experiences relevant to the study objectives were actively recruited from BRICS countries because they account for more TB cases than any other country in their respective WHO regions, and because of the different additional challenges confronting these countries such as the burden of TB-HIV co-infection in South Africa, the diversity of private sector care in India, and the burden of MDR-TB in India, China and Russia [ 1 , 2 , 23 ]. Remote data collection both preserved the privacy of participants and ensured the safety of moderators given the infectious nature of TB and the timing of the study during the COVID-19 pandemic.

Recruitment

Participants were recruited through independent healthcare fieldwork agencies in the different countries via referral from healthcare professionals and social or community workers, as well as using market research databases, posters and adverts in TB clinics, patient groups, and word of mouth referrals. Participants had the opportunity to discuss the study with recruiters before completing a screening guide to confirm patient eligibility (Additional file 2). Recruited participants received an honorarium at fair market value for their participation.

Recruitment continued until TB patients from 40 households, that is 8 per country, plus 1–5 members of their households had been sampled. The minimum target sample size was 80 participants. Previous studies have indicated that for this type of qualitative research as few as 6 interviews per setting are required to identify major themes [ 24 , 25 ], with saturation occurring within 12 interviews [ 26 ].

Participants

Eligible participants had a confirmed diagnosis of TB and were receiving treatment or had completed treatment within the previous 12 months. Close family and other household members were included where appropriate for support and additional information, except for China where the social stigma prevented discussion with individuals other than the patient. Participants were recruited from a range of socio-economic backgrounds, assessed based on income, education levels, and living standard. At least three participants from each country were to be female. The study sought to include a range of specific patient types, for example, persons living with HIV (PLWH), those with diabetes, smokers, those with a history of excessive alcohol consumption, and those with MDR-TB/relapsed TB. At least two patients per country were to be living in households which included a child diagnosed with TB or receiving preventive treatment. No participant was excluded because of lack of access to technology as the necessary equipment was loaned to participants where needed.

Data collection

The interview moderators, fluent in the local languages, were taken through a training process in each setting, detailing study objectives, inclusion criteria, and study methodology, followed by subsequent monitoring of the process and active feedback to ensure quality control. Data quality was assured by consistent and thorough briefing of the field workers, including regular follow up to ensure study procedures were followed. The discussion guide and videoing instructions were carefully designed to contain clear respondent instructions at each question.

Patients first completed a 5-min health questionnaire based on their physical health over the previous four weeks. Interviews with TB patients and household members were conducted remotely by a trained moderator in the form of either a 60-min video-streamed interview or a 60-min telephone interview. The questionnaire and interview guides are provided in the supplementary materials (Additional file 3). Participants also completed a 45-min follow up video task to create four short videos on a mobile phone in their own time to capture their personal experience, such as their living environment, changes in their living arrangements as a result of TB, the biggest challenges since the diagnosis, perception of the changes in their life from others around them, and their hopes and expectations for the future.

The interviews were transcribed verbatim from the original languages, that is: Brazil, Portuguese; Russia, Russian; India, Hindi and English; China, Mandarin; South Africa, English, Sesotho, isiZulu, Tswana, or Afrikaans with switching between languages as necessary. Following translation into English, the information was analysed manually using a thematic and comparative analysis approach to identify key themes both within countries and across all participants’ responses [ 27 , 28 ]. Analysts had no access to patient medical records and all patient identifying information was anonymized.

Interviews were coded thematically by three analysts, aiming to reach consensus through regular team meetings where the emerging findings were discussed. Additionally, non-verbal communication (including visual evidence of living conditions) present in the videos from the streamed interviews and the video tasks were shared with the full team at regular intervals and discussed/analysed using the thematic framework developed from the transcripts. Triangulation across the different data sources was done using cross-checking to assess convergence, complementarity and divergence at the individual participant level, between patients and their families, and at the country level between informants from the same country. The analysis was therefore grouped initially by country and then analysed for cross-cutting themes across all respondents. Quality control was achieved by continuous review by two senior analysts, one of whom was not involved in the initial analysis, plus a final check through all the analyses.

The sample consisted of 40 TB patients (8 from each country) plus 52 household members. Each patient was assigned an identifier to illustrate their country and number. Of the TB patients, 23 were men and 17 women, ranging between 13 and 60 years old. Fourteen were receiving first-line treatment, 10 second-line treatment, 2 patients had received multiple treatment lines, 11 had completed treatment, and 3 patients (all from Russia) were on a treatment break (Table 1 , Fig.  1 ). Risk factors for TB were reported in 23/40 patients, with some patients having multiple risk factors (Table 1 , Fig.  1 ). Most patients were of medium socio-economic status for their country (26/40), and no patients with high socio-economic status were recruited (Table 1 ). Except for India and South Africa, it was not possible to recruit at least two households with a child diagnosed with TB or receiving preventive treatment (Table 1 ).

Summary of patient characteristics. Note that patients may have had more than one risk factor/co-morbidity

Patient health status

The self-reported health questionnaire indicated that most respondents (25/40) found that the physical impact of TB limited their activity. A higher proportion of patients who were currently receiving treatment (69.6% [16/23]) reported a physical impact of TB compared with those that had completed treatment (57.1% [8/14]) or who were on a treatment break (33.3% [1/3]). Most patients whose physical activity was impacted by TB reported that this affected them all or most of the time (88.0% [22/25]) (Fig.  2 A). Most patients (38/40) reported that their daily living was impacted in at least two ways (Fig.  2 B). Seven patients, five of whom were receiving treatment and two who had completed first-line treatment, stated that they were impacted by all six areas assessed (Fig.  2 B). Looking at specific impacts, the most reported were that TB stopped patients doing things that they liked to do (35/40), and economic hardship (28/40) (Fig.  2 C). Overall, it was clear that TB had significantly impaired the health status of patients and had a negative impact on daily living.

Results of a self-reported health questionnaire. A The effect of TB on limiting daily activity due to patients’ physical health; B ) the impact of TB on daily living; and C ) the number of impacts on daily living experienced by patients

Patient journey

Pre-diagnosis.

The most common initial symptoms reported by patients were a long-lasting cough increasing in severity over time, fever, weight loss, and tiredness. Some patients experienced more severe symptoms such as haemoptysis, and pleural effusion. However, symptoms were often non-specific, and unless they were aware of a source of infection or had known risk factors (e.g. HIV), most patients did not consider TB as a potential cause. Notably, patients in South Africa were more likely to suspect TB because of a higher awareness in the community and the link with HIV. In India, recent typhoid infection was suspected as the cause of symptoms in some cases.

Patients tended to hope that the symptoms would resolve on their own using over-the-counter products and traditional medicine. Patients with addiction to alcohol did not always perceive the severity of their symptoms and were less willing to engage with healthcare providers. However, avoidance of healthcare providers was common across all settings, because of concerns for the associated costs.

“The symptoms were there for the last 2 ½ months but I did not know. He was coughing a lot, so I asked him to go to the doctor. He did not listen to me. He feared talking to the doctor.” Relative of TB patient, India (IN19). “One day, I started to have fever in the afternoon. After work, I went to receive infusion in a small local clinic. I remember my body temperature was 39.5 to 39.6 degrees Celsius. The doctor said my condition was very serious, so he prescribed 5 bottles of infusion to me, and I received all of them. But my fever persisted after such a lengthy infusion.” China (CN09).

The pathway for TB cases depended on symptom severity at presentation but navigating the healthcare system was tortuous for some patients. Patients first sought help using a familiar and accessible route (Fig.  3 ).

The TB patient pathway. *There were no deaths during the study

Across all countries, the TB diagnosis came as a shock to most patients – their initial thought was ‘Will I die?’. PLWH were less surprised as they were aware of the association with TB. Some patients in South Africa believed they had been vaccinated against TB as children and were therefore protected. Many patients questioned how they had caught TB and worried about the negative misconceptions associated with the disease, particularly in Russia and Brazil. Patients feared that they would be ostracized and shunned by their families and communities. Young people with TB feared for their future, for example their careers, education, and prospects of marriage. Further concerns expressed by patients included the potential disruption to their life, job security and providing for their dependents, especially in India. Overall, there was uncertainty among patients as to whether they could cope; some expressed the fear of unintentional disclosure of their TB diagnosis to others. Notably, across all countries, families were often fearful of the potential costs, with a lack of clarity regarding which elements of treatment would be covered by insurance (where available) or were refundable from the public health system.

“[I thought] it is some kind of prison disease, which occurs more and more often in people who have served a sentence somewhere. That is, more disadvantaged groups of the population. I always thought about it in this way until I met it myself.” Russia (RU10).

Following diagnosis, healthcare providers were quick to reassure patients that TB is treatable but that it will take time and that they must try not to infect others. In South Africa some patients reported being warned of drug resistance. However, beyond this, TB-focused education was limited, and patients often conducted their own research via the Internet and word of mouth, though patient-friendly resources were described as inadequate in some settings.

“[The nurse] said if you don’t take your meds, they send you to [a TB hospital] and then you will receive extreme treatment. They inject you with needles and stuff. That is if you don’t use this meds at home, they will send you there and stay for six months.” South Africa (SA05).

Treatment side effects, pill burden, lifestyle restrictions and the long-term commitment required were very challenging for patients (Fig.  4 ). Patients generally did not know the names of their medications, but described having to take many pills of different types several times a day. Patients reported intolerable side effects, including nausea and vomiting, and patients with MDR-TB faced painful daily injections. In Russia, and to a lesser extent in China, patients were admitted to hospital to increase adherence. In Russia, patients recounted being admitted to sanatoriums for the treatment of TB.

“I take many anti-TB pills every day, covering 4–5 classes, about 20 tablets in total. Sometimes, it’s difficult for me to take medication, as I was quite reluctant to take it initially, but I had no choice, but to take it as a treatment.” China (CN11).

Factors identified by patients as affecting adherence to TB therapy

Monitoring and adherence

Across countries and socioeconomic bands, patients perceived minimal therapy monitoring by healthcare providers, with little evidence of DOT. It is possible that this was because of interruption to normal healthcare services because of the COVID-19 pandemic (see below). Most patients visited healthcare settings frequently to pick up their medications. Less frequently, their weight was measured during clinic visits, sputum tests were conducted, and some patients were informed when they were no longer infectious and could return to work/education. Family played a key role in monitoring during treatment, encouraging patients to continue with their treatment, sharing regular reminders, and helping to pick up medication from health centres. Motivation to comply was prompted by the desire to get back to normal family life and work, the fear of death, potential drug resistance, and hospitalization. Although patients would briefly lapse without serious consequences, they were usually encouraged to continue treatment by family and healthcare providers.

“Sometimes [redacted] forgets to take the medication, and I argue with him because if one of us forgets the treatment and the other one doesn’t then it won’t work, if we don’t take it together, it won’t work.” Brazil (BR04).

Once treatment was initiated, health improvements were quickly apparent to most patients, with resolution of fever and abatement in cough. Although this increased patients’ optimism and secured a return to some of their previous activities, it could also lead patients to believe that they had recovered, undermining adherence to therapy. Adherence was also jeopardized where there were high barriers to accessing treatment, a poor understanding of drug resistance, and when patients were alcohol dependent (Fig.  4 ). Patients who did adhere to treatment were often well supported by family and well informed of the consequences of non-adherence. Conversely, those who did not adhere to treatment were often unaware of the consequences.

“By December I was already feeling like I’m already cured, I nearly decided not to continue with the treatment.” South Africa (SA01). “Actually, they didn’t tell me about the details then. It was very important to emphasize it to me, but the physician didn’t do it. If he did, it would draw my attention and it won’t lead to drug resistance, as I often missed the dose I was supposed to take.” China (CN06). “I live in a little town which is quite far from the city. I can either go by bus which takes at least an hour and a half, or I can get to the nearest bullet train, but there aren’t many trains available and they are expensive.” China (CN08).

Completion of treatment

Eleven patients had completed treatment, 4 from South Africa, 4 from India, 2 from Brazil, and 1 from China. All had recovered, 10 following first-line treatment and 1 following second-line treatment (India). Some respondents said that their time in isolation was a time of reflection where their lives had been ‘put on pause’ making them ‘appreciate the little things in life’ they had really missed. A few patients said that their experience with TB has driven them to want to increase awareness, and remove stigma around the disease e.g., patients in Brazil and China set up informal support networks with fellow patients, particularly where patients met during hospital stays. Most patients expressed relief that they were cured, and that treatment was over, and were generally hopeful for their future.

"My TB is cured, and I want to start again with my studies. I was preparing for a railway job but I had to give that up because of TB. Now I will start my studies again and apply for a government job." India (IN04). "Thanks to this [TB] I got rid of bad habits, I do not drink alcohol now and smoke less… And I found a job, and I earn some money at the moment, during the first period my brother supported me fully, thanks to him, and my mother helped what she could.” Russia (RU05). "After these three months since I have recovered, this is what it has brought me, the willingness to fight, to battle, also to take even more care of my health, not just mine but also of people around me, and take this story, my testament, my lived experience with TB… So it’s a goal in my life, to spread information among all those who are close to me." Relative of TB patient (BR01).

Access to services

Before TB was diagnosed, in some cases patients consulted healthcare providers in the private sector, for example, the local family doctor, traditional medicine providers, or pharmacies. Following diagnosis, more affluent patients claimed on insurance or paid for private sector treatment due to poor perceptions of the public sector, and some sought support in the private sector for a ‘second opinion’ or for problems which they felt were not being addressed in the public sector. However, the majority of patients (36/40) obtained their TB care through the public sector; three patients used the private sector with one accessing both public and private sector healthcare. Treatment was provided for free through the national programs, with relatively good access in most settings, though travel distance and wait times were a barrier to access. There were reports of drug stock outs and out of pocket expenses for additional diagnostic tests or prescriptions, including having to pay for MDR-TB treatment in some settings (China). A minority of patients reported being turned away from the public sector for not having the correct paperwork or not being able to book an appointment. The public sector had a poor reputation for long queues and poor service and most patients aspired to be able to afford private treatment where services were described as being better.

“In public [sector healthcare] those nurses don’t care, I remember when I accompanied him, I was told I was not allowed to get inside, so he went in on his own. You go in pick up whatever you need and get out because those people don’t have time for anything.” Relative of TB patient, South Africa (SA01). “In the Government hospital, the doctors do not listen to us. They come when they wish and give medicines. As it is, the doctors do not listen to poor people. I had to buy some medicines from outside.” Relative of TB patient, India (IN17). “Obtaining the medication – because the drugs can only be obtained in the hospital, you can’t buy them in retail pharmacies. If I run out of my medication, I wouldn’t be able to buy it from the retail pharmacy, I would have to go the hospital, which is inconvenient.” China (CN08).

The use of sanatoriums in Russia was unique. Following diagnosis, patients were sent to a dedicated facility or a TB unit within a hospital where they remained for at least 3–4 months, though confinement could last for up to a year. They were only allowed to leave with permission, for example, at weekends or holidays. Although patients generally accepted that it was for the ‘greater good’ it was frightening at first because some other patients on the ward had very severe disease. However, some patients expressed surprise that other patients were ‘normal’, because they believed the disease to be often associated with homelessness and prisons.

“They told me I had a resistant form of TB and that the treatment is very, very long lasting. At first, they said I would have to be hospitalized three to four months and that then I would be able to go home but when I got to the hospital, the ‘girls’ told me that three to four months is optimistic… In short, eight months. Eight in the hospital and a year after the hospital. That was a shock.” Russia (RU12). “In my room there were all young women and all were so great. All of them were socially adapted: an accountant, a paediatrician student. So, let’s say it was good company.” Russia (RU01).

Thematic analysis

Five major themes were identified as common across all the countries studied (Fig.  5 ).

Thematic areas identified as common across five countries describing the challenges faced by TB patients

Economic hardship

Loss of earnings has the greatest economic impact for TB patients. Most patients stopped work because they felt too unwell to continue or were embarrassed by the symptoms, such as the persistent cough and severe weight loss. Some patients also felt the need to stay away from work to limit transmission to others or were ‘asked to leave’ by their employers as they were not covered by contracts. Many had no entitlement to sick pay. In some cases, patients were concerned that their financial situation could get worse as their diagnosis may mean prospective employers may be reluctant to take them on.

“The main problem is money. There is no problem greater than financial problems.” India (IN01). “I had to keep away from work because there was a lot of dust involved.” Brazil (BR15). “I cannot officially get a job, and I cannot unofficially either. But, what? Am I going to work as a loader? I cannot. This has seriously affected my finances… And who would hire if information comes out that there was TB? You will not get a job. I received a disability [payment].” Russia (RU05).

Even in regions where TB treatment was publicly funded, associated costs such as tests, hospitalization, prescriptions, travel, special food/supplements to manage weight loss, and medications to manage adverse effects were often borne by patients. The financial impact of TB meant that most patients had to rely on family or sometimes charities for support or take out loans. Time off for appointments still impacted earnings even after patients had returned to work.

“I also buy medications at my own expense [for gastric side effects] i.e. for TB, everything is free of charge due to the medical insurance policy, everything is fine, but if there is something secondary or something else not related to the diagnosis, then that is at your own expense.” Russia (RU07). “We are not educated people. I just wanted my child to recover. We are poor people; we could not work during lockdown. We had to borrow money from many people and requested help from doctors too. I thought my child would recover, but he did not. We were very stressed out.” Relative of TB patient, India (IN21). “To avoid delaying treatment, the doctor told me to take these four drugs upon diagnosis, and urged me to buy them elsewhere, as they were unavailable in the hospital. My wife found they were unavailable in many pharmacies either. Finally, she found them in several pharmacies, from where we bought them in early stage.” China (CN09).

Stigma associated with TB

Across all countries stigma was associated with TB, though it manifested in different ways. In China, TB was often kept a secret, even from family, whereas in South Africa, there was greater openness. In Brazil, though patients were open with family, there was reluctance to acknowledge their diagnosis with their community as TB is associated with wider social issues such as poverty, incarceration and ‘immoral lifestyles’. In India, TB patients felt discriminated against for other reasons, such as poverty, as well as TB. Stigma in Russia was related to the personal circumstances of the patient.

Young patients faced bullying at school/college and being dropped by friendship groups. Adults were ostracized by friends and relatives afraid of contracting TB, and relationships with friends and family suffered, leading to loneliness and depression. Respondents described instances when they were not invited to family events even after they had completed treatment and were cured. In some cases, TB appeared to ‘run in families’ meaning the stigma was intergenerational. Importantly, a family with TB was often considered a ‘low status’ family and this was compounded by the financial difficulties that accompany TB.

“A lot of my friends kept away from me because of this, because that’s what people know, that it’s contagious, but they don’t understand that the person on the other side is suffering as well, and we don’t only suffer a little bit, at least myself, it’s a very painful process, very painful, very complicated.” Relative of TB patient, Brazil (BR01). “The community was no longer as close to us because we are staying with a person that has TB – people at the queue at shops would turn around and come back when we have left.” Relative of TB patient, South Africa (SA14). “When a person has TB he becomes very annoyed as he has to go through a lot of things, plus there also comes a phase were people start avoiding you, they feel that if we come in contact with this person even we might acquire it.” India (IN01). “A person who has TB is not somebody who is well-regarded.” Brazil (BR04).

HIV co-infection played a major role in the TB experience, particularly in South Africa. Awareness of TB was higher among PLWH given their greater risk and regular contact with healthcare services. Also, the path to diagnosis was shorter given their engagement with HIV services with rapid referral reflecting the associated co-infection risks. In many cases, the HIV and TB clinics were co-located improving patient access. However, PLWH were highly aware of the stigma that TB carries with fear around the community reaction during the early stages of their journey.

"Now I’m scared I’m HIV positive, I have TB and now there’s Corona [COVID-19], what’s going to happen when I have all three of them?" South Africa (SA18). “So people were really scared, I think they are now more afraid of TB than HIV. I told my neighbour that I was diagnosed with TB and luckily she doesn’t talk much but still I was aware of their behaviour when they came by to do my laundry they would wait outside to hand it over to them and when they are done they would leave it by the door." South Africa (SA10).

Disruption to family life

A diagnosis of TB affects everyone in the household and the wider family. Cleaning and disinfecting routines have to be established and maintained, and there was a general awareness that separate cutlery must be used, living spaces needed good ventilation, and clothes and bedding should be washed more frequently. Sleeping arrangements to isolate TB patients were particularly problematic in India and South Africa where large families live together, and parental co-sleeping with children was no longer possible where this was practiced. In some cases, children were looked after in the homes of extended family members, away from parents with TB. Married patients feared abandonment or divorce and respondents felt ‘lucky’ that their partners had stayed with them despite their TB status. The reduced family contact, demands of treatment and financial hardship often strained family relationships.

“Life at home isn’t the same because I had to begin separating my cutlery and a glass – my clothes had to be washed separately, we have to clean down the house and open the windows to let the air circulate.” Brazil (BR15). “I’m worried I may infect my parents. So I’ve had to reduce my interactions with them, the time spent with them, the number of occasions I’m with them. And as they get older, they become confused and they don’t understand why I stay away.” China (CN08). “Our house always used to be full at weekends, friends would come around to watch films, sometimes we would make lunch, get pizza and sit and watch films, and then suddenly the house was empty.” Relative of TB patient, Brazil (BR01).

Mixed effects of COVID-19

Some TB patients observed that the COVID-19 pandemic normalized the idea of infection prevention, with mask wearing becoming common. Also, TB patients were able to hide their diagnosis more easily with social distancing measures. There was also less fear that they could infect the wider community. However, access to healthcare and medication was compromised with restrictions to movement and hospitals not accepting admissions for other conditions. Patients were fearful of ‘catching’ COVID-19 given their impaired respiratory health and existing co-morbidities, such as HIV and diabetes. Some respondents who were coming to the end of their isolation and anticipating greater freedoms and a return to a more normal life then faced COVID-19 restrictions.

“During the pandemic I was unable to go to the hospital for my regular follow-ups and prescription renewal, and so because of that my condition worsened, and I eventually ended up infecting my family.” CN08.

Assuming that efficacious treatment is provided, TB is curable. However, outcomes are often sub-optimal. This study aimed to explore common themes in the experiences of TB patients and their families in the five BRICS countries from diagnosis to completion of treatment. Using consistent methodology, economic hardship, stigma, TB-HIV co-infection, disruption to family life, and the mixed effects of COVID-19 were identified as themes encompassing the challenges facing TB patients across the five BRICS countries (Fig.  5 ). These factors, therefore, appear to be independent of the country setting. Further research should investigate the degree to which these factors and are potentially mutable by targeting systemic changes in healthcare and social provision and providing attention to patients’ individual needs.

Economic hardship was reported across all countries. TB is associated with economic vulnerability but can also drive families into poverty through loss of income, the costs of transportation and food supplements, and associated medical expenses [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. Programs providing social protection to TB patients have been linked to improved outcomes and the increased uptake of preventive therapy but must be easily accessible [ 29 , 37 , 38 ]. Improvement of TB services can also reduce the number of families facing financial hardship [ 39 ]. Even though most healthcare systems in our study provided TB drugs free of charge, to be effective, treatment should encompass the wider economic impacts that patients experience. Despite various approaches, patients from all of the countries surveyed found themselves struggling financially and a more holistic approach to patient support is needed.

Stigma attached to TB is culturally distinct, but stems from a lack of awareness of TB and the persistence of stereotypes [ 40 , 41 ]. For example, in Russia, an association with prisons and poverty has persisted, despite TB affecting all sectors of society [ 42 ]. Stigma was most acutely felt in China, and a recent study described psychological distress in nearly two-thirds of TB patients, associated with a high experienced stigma [ 43 ]. In our study, some patients did not even disclose their diagnosis to close family. In newly diagnosed Chinese TB patients, non-disclosure of their TB status magnified patient-perceived stigma and was associated with depression – a risk factor for non-adherence [ 44 , 45 ]. Social support and doctor–patient communication appeared key factors for reducing TB-related stigma in China [ 46 ]. Also, educational approaches to raise awareness of TB diagnosis and treatment among the public are needed, particularly focused on those with low educational levels and more rural communities [ 40 , 47 , 48 ].

The association between TB and HIV is well documented. However, the impact on patients is less well understood. In this study, PLWH were more aware of TB and were more likely to seek care early and be diagnosed quickly. This is in contrast to a study in Thailand where PLWH had low TB awareness and attributed their early symptoms to AIDS, resulting in delayed TB diagnosis [ 49 ]. This emphasizes the importance of raising TB awareness in PLWH. In South Africa, TB and HIV services are often co-located and integrated [ 50 ]. However, a detailed analysis in South Africa of the challenges faced by PLWH who had MDR-TB highlighted similar issues to those described here for all TB patients, such as fear, stigma, dissociation from family and social networks, poor provider support, drug adverse events, and financial insecurity [ 51 ]. Also, patients tended to prioritize adherence to anti-retroviral therapy versus TB therapy because it was less challenging in terms of pill burden and adverse effects [ 52 ]. Until less demanding treatment regimens are available, targeted support to address the challenges of adherence in patients co-infected with TB-HIV is necessary.

The respondents in this study described a severely disrupted home life following a TB diagnosis. Patients were isolated and often infirm, and the economic and care responsibilities for family members were considerable. Families also suffered socially, being isolated or shunned by friends and the wider family. In many cases, it was family members who ensured adherence to medication, and social and family support for patients has been previously shown as a key factor in therapy adherence [ 41 , 53 , 54 ]. Despite this, the impact of the TB diagnosis on the family and how family members can best be supported has been rarely investigated [ 47 ], and we identify this as an important area for further research.

The COVID-19 epidemic has disrupted healthcare access globally [ 55 ]. In our study, TB patients reported drug shortages and restrictions to services during the period. TB patients also expressed concern regarding the consequences of contracting COVID-19. Similarly, a recent study in Brazil reported that TB patients were fearful of attending medical appointments [ 56 ]. TB patients do appear to be at greater risk of death or poor outcome with COVID-19 [ 57 ], and should therefore socially isolate or ‘shield’ [ 58 ]. TB patients did feel less stigmatized as social distancing and infection control measures were deployed for COVID-19. However, the interruption of treatment, with the risk of therapy failure, selection of MDR-TB, and increased transmissibility is a major threat to TB patients and their close contacts [ 59 ].

This study has several limitations. Although participants were identified through a variety of channels and a range of socioeconomic groups were sampled, this was not a randomized sample and we acknowledge that both marginalized and privileged groups may not engage in this kind of research. Also, there were no data on whether susceptibility testing was conducted following the TB diagnosis, so the appropriateness of therapy could not be assessed. Neither did we examine the differences between patients’ experiences of drug-susceptible versus MDR-TB; patients were not consistently aware of the difference and most patients were receiving or had recently completed first-line therapy. The patient pathway was not integrated into the thematic analysis but analysed separately in terms of the systemic challenges that patients face. This was because the complexity of the pathway did not map onto the themes in a meaningful way. For example, patients experienced economic hardship, stigma, and disruption to family life at most stages in the patient pathway, whereas TB-HIV co-infection had an important effect on the speed of diagnosis. Thus, patient pathway was examined systematically and separately to the thematic analysis which focused on the emotional, socio-economic and practical impacts of TB on patients’ daily lives. The analysis methods sought to remain impartial with repeated reviews by multiple analysts to reach consensus. However, the analysts were all based in the UK and we recognize that the cultural subtleties of some of the patients’ experiences may not have been fully appreciated.

In our study, TB patients’ perceptions and needs were expressed in their own words, from within their home environment, in confidence, to interviewers who were not involved in their healthcare. Most had struggled to adjust to their diagnosis, had poor access to information, lacked support from healthcare workers, were under significant financial pressure, and were highly conscious of stigma and the burden TB placed on their families.

Our findings highlight that much work still needs to be done before the goal of ending TB can be achieved. Structural changes require simplification of the TB patient pathway, reliable access to services, and the alleviation of financial pressures. Health education for patients, their families, healthcare providers and the public to increase awareness of TB symptoms and diagnosis, to encourage adherence, and to reduce stigma around the disease is needed. Importantly, TB patients do better with strong family and social networks to sustain them, and a greater understanding of how these can be better supported at the level of the individual patient throughout the TB treatment journey requires further investigation.

Despite the different cultural, political, and healthcare settings across the BRICS countries, TB patients faced very similar challenges. This commonality would not necessarily have been expected. It suggests that these factors are not only a product of the healthcare provision in the countries or the social, economic, and cultural pressures that patients face, but reflect an overarching insufficiency in the treatment of TB. The efficient delivery of comprehensive individualized care and support would certainly mitigate the negative impacts of TB on patients. However, these issues will likely not be fully resolved until treatment options are available that rapidly cure TB and prevent onward transmission.

Availability of data and materials

All relevant data are included in this publication. Recorded interviews will not be made available in order to maintain patient confidentiality. However, anonymised transcripts are available on reasonable request to the authors for ten years following study completion. For data requests please contact the corresponding author at [email protected].

Abbreviations

Coronavirus disease of 2019 (severe acute respiratory syndrome coronavirus 2)

Human immunodeficiency virus

Multidrug-resistant tuberculosis

People living with HIV

• Tuberculosis

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Acknowledgements

Naomi Richardson of Magenta Communications Ltd. in collaboration with Juliet Addo developed the first draft of this article from a research report, provided editorial and graphic services and was funded by GSK. Elizabeth Kehler, Francesca Trewartha and Thea Westwater Smith of Adelphi were co-authors of the original report and co-analysts. Carly Davies, Vera Gielen and Myriam Drysdale from GSK reviewed and provided comments on the screening and interview guides.

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J.A. made substantial contributions to the conception and design of the work, interpretation of the data and drafting of the manuscript. C.L., M.M., M.S., D.B-A., G.C.K.W.K. and D.P. made substantial contributions to the conception and design of the work and interpretation of the data and critically revised the manuscript for intellectual content. G.T. made significant contributions to the design of the work, the acquisition of data, analysis and interpretation of data for the work and critically revised the manuscript for intellectual content. All authors read and approved the final manuscript.

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The research was conducted in accordance with the Helsinki Declaration, and all national data protection laws. In compliance with European Union and UK legislation, General Data Protection Regulation guidelines were followed to ensure full patient data confidentiality [ 22 ]. Informed consent was obtained electronically from all individual participants included in the study or their parents/guardians if under the age of consent. Consent was also provided for anonymized consolidated publication of the findings. Participants’ rights and privacy were protected at all times throughout the study. Participants were granted the right to withdraw from the study at any time during the study conduct and to withhold information as they saw fit. All information/data that could identify respondents to third parties was kept strictly confidential; all respondents remained anonymous by using nicknames for the study.

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Addo, J., Pearce, D., Metcalf, M. et al. Living with tuberculosis: a qualitative study of patients’ experiences with disease and treatment. BMC Public Health 22 , 1717 (2022). https://doi.org/10.1186/s12889-022-14115-7

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Case study of a patient with tuberculosis

15 Case study of a patient with tuberculosis Maria Mercer Chapter aims • To provide you with a case study of a patient who has been diagnosed with pulmonary tuberculosis (TB) together with the rationale for care • To encourage you to research and deepen your knowledge of TB Introduction This chapter provides you with an example of the nursing care that a patient with pulmonary TB might require. The case study has been written by a TB nurse specialist and provides you with a patient profile to enable you to understand the context of the patient. The case study aims to guide you through the assessment, nursing action and evaluation of a patient with pulmonary TB together with the rationale for care. Activity In Chapter 1 you were asked to revise the normal anatomy and physiology of the respiratory system (see Montague et al 2005 ) and a brief definition of TB was given. Before reading the case study below, find out how pulmonary TB would affect the respiratory system and what symptoms a patient with TB might present with. The following article may help you: William VG (2006). Tuberculosis: clinical features, diagnosis and management. Nursing Standard 20(22):49–53. Online. Available at: http://nursingstandard.rcnpublishing.co.uk/archive/article-tuberculosis-clinical-features-diagnosis-and-management (accessed July 2011). Patient profile Mr Patel is a 21-year-old gentleman who lives in a shared flat with friends and studies English at a local college. He is a new arrival to the UK having arrived from Bangladesh in October 2009. There are six adults, including Mr Patel, who share a two-bedroom flat. They share three adults to a room. He was referred to accident and emergency (A&E) via his GP with a 2-month history of a productive cough (no episodes of haemoptysis), associated fevers, drenching night sweats, loss of appetite and a 5-kg weight loss. In the last 7 days his symptoms have worsened and warranted the admission via A&E. Assessment on admission Mr Patel has a pyrexia of 38.5°C, he is cachectic and has pleuritic chest pain. His respiratory rate is slightly raised at 18 per minute and he has a tachycardia of 114 beats per minute. Blood pressure is normal. Inflammatory markers – erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) – are raised at 72 mm/h and 65.4 mg/L. A chest X-ray has been reported as abnormal: ‘Patchy shadowing seen in left upper lobe? Pulmonary TB.’ Activity See Appendix 4 in Holland et al ( 2008 ) for possible questions to consider during the assessment stage of care planning. Mr Patel’s problems Based on your assessment of Mr Patel, the following problems should form the basis of your care plan: • Mr Patel has a potential diagnosis of pulmonary TB which can be an infectious disease and public health risk. • Mr Patel feels stigmatised because of respiratory isolation measures and the potential diagnosis of TB. • Mr Patel has a temperature, raised inflammatory markers, a slightly elevated respiratory rate and a tachycardia. • Mr Patel is nutritionally compromised because of a 5-kg weight loss due to anorexia. • Mr Patel has pleuritic chest pain associated with coughing and expectoration of sputum. Mr Patel’s nursing care plans 1. Problem: Mr Patel has an infection. Pulmonary TB is felt to be the primary diagnosis. Goal: To limit transmission of TB to other patients and staff and ensure prompt treatment is commenced. Nursing action Rationale Mr Patel to be isolated in a side room with bathroom facilities with respiratory isolation measures in place immediately The door to the side room must be shut at all times Appropriate face masks (FFP2 or FFP3, depending on risk assessment – refer to infection control/TB policy) should be worn when entering Mr Patel’s room and he should wear the appropriate face mask if he needs to leave the side room for investigations Gloves and aprons do not need to be worn unless handling bodily secretions Liaise with bed managers and infection control team to expedite bed availability as necessary To reduce the risk of TB transmission to other patients and staff Collect three consecutive sputum specimens for acid-fast bacilli (AFB) Send one sputum specimen urgently on day of admission To ascertain diagnosis and ensure the appropriate treatment is commenced promptly Ensure Mr Patel is aware that sputum specimens need to be collected consecutively. Label 3 sputum pots clearly and leave in side room. Instruct Mr Patel to inform the nurse caring for him when the sputum for each day is ready so it can be collected and sent to the Laboratory as soon as possible. To ascertain diagnosis and ensure the appropriate treatment is commenced promptly. Contact the TB nurses to perform a Mantoux test if prescribed by the medical staff. To facilitate prompt diagnosis and obtain specialist nursing advice and support Ensure effective communication with Mr Patel explaining why the above measures are necessary and providing reassurance and support To alleviate fear and anxiety Evaluation:

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Case Report: Pulmonary tuberculosis and raised transaminases without pre-existing liver disease- Do we need to modify the antitubercular therapy?

Sanjeev Gautam Roles: Data Curation, Writing – Original Draft Preparation Keshav Raj Sigdel Roles: Conceptualization, Supervision, Writing – Review & Editing Sudeep Adhikari Roles: Writing – Original Draft Preparation, Writing – Review & Editing Buddha Basnyat Roles: Conceptualization, Supervision, Writing – Review & Editing Buddhi Paudyal Roles: Supervision, Writing – Review & Editing Jiwan Poudel Roles: Writing – Review & Editing Ujjwol Risal Roles: Writing – Review & Editing

This article is included in the Oxford University Clinical Research Unit (OUCRU) gateway.

tuberculosis, transaminitis, standard ATT, liver friendly regimen

Revised Amendments from Version 1

The changes have been made in the revised manuscript as suggested by the reviewers. The concerns of reviewers regarding limited workup of the patient for liver disease has been addressed in the manuscript. This is a single case report and further studies are required to make a firm recommendation for management of pulmonary tuberculosis with transaminitis without pre-existing liver disease. We have acknowledged the fact in the revised manuscript.

See the authors' detailed response to the review by Vivek Neelakantan See the authors' detailed response to the review by Neesha Rockwood See the authors' detailed response to the review by Prajowl Shrestha and Ashesh Dhungana

Tuberculosis is the biggest infectious disease killer in the world 1 , and is endemic in Nepal with the national prevalence at 416 cases per 100000 population 2 . Pulmonary tuberculosis is the most common form. In Nepal, tuberculosis prevalence is more in productive age group (25–64 years) and men. Poverty, malnutrition, overcrowding, immunocompromised state like HIV infection, alcohol, smoking, air pollution, diabetes and other comorbidities are important risk factors for acquiring the disease 3 . Though under-reported, involvement of liver with tuberculosis is encountered often in clinical practice in endemic areas like Nepal.Liver can be involved; a) diffusely as a part of disseminated miliary tuberculosis or as primary miliary tuberculosis of liver, or b) focal involvement as hepatic tuberculoma or abscess, as was classified by Reed in 1990 4 . The biochemical pattern of liver function abnormality in these forms of extrapulmonary tuberculosis is cholestatic (predominantly raised alkaline phosphatase and gamma-glutamyltranspeptidase) rather than hepatocellular (predominantly raised transaminases) 5 , 6 . The hepatocellular pattern of liver injury is seen in cases with pre-existing liver disease including hepatotoxic drug use, which are unrelated to tuberculosis 7 , 8 .

As per national protocol of Nepal, any patient with tuberculosis receives combination antitubercular therapy (ATT) including four drugs; Isoniazid (H), Rifampicin (R), Pyrazinamide (Z) and Ethambutol (E) for initial 2 months popularly known as HRZE. This is followed by 4 months of two drugs; HR. Treatment is given under Directly Observed Treatment Short- Course (DOTS) to improve the patient compliance which could otherwise be compromised owing to lower socioeconomic status of patients, longer duration of treatment and side effects 9 . Patients with extrapulmonary hepatic tuberculosis are treated with full dose of standard ATT 5 , 6 . But three out of the four drugs (H, R and Z) are hepatotoxic 7 . So the patients having pre-existing liver disease usually require liver-friendly modified regimens to protect the liver but they may be suboptimal for eradicating underlying tuberculosis 8 . The protocol of Nepal does not warrant baseline investigations except chest X-ray and sputum smear microscopy to be done routinely before prescribing ATT in programmatic setting 9 . However in hospital setting like our case, baseline blood investigations including liver function tests are usually done before starting treatment even in absence of features suggesting liver injury and therapy modified accordingly.

Here we present a case of pulmonary tuberculosis with predominant transaminitis but there was no feature of pre-existing liver disease nor a history of hepatotoxic drug use. The liver injury was attributed to the pulmonary tuberculosis itself, and treated with standard first line ATT which led to resolution of liver function abnormalities.

Case presentation

A 33 year old Newar housewife from Kathmandu, Nepal, with no known comorbidity, presented to Patan Hospital Emergency Department in November, 2019 with a history of cough with occasional sputum production over the previous 20 days and low grade fever for 10 days. There was no history of chest pain, difficulty breathing, headache, vomiting, altered mentation, abdominal pain, yellowish discoloration of eyes, burning urine, hair loss, photosensitivity, joint pain, or rash but she had decreased appetite and weight loss. There was no past history of tuberculosis or jaundice. She did not consume alcohol or any drugs including acetaminophen, aflatoxin or herbal products. Her father-in-law had been diagnosed with pulmonary tuberculosis five years earlier, but there was no family history of liver disease.

Initial examination showed temperature of 101 o F with pulse of 110 beats/minute and respiratory rate of 26 breaths/minute. There was diffuse fine crepitation on the left side on auscultation of the chest. There was no lymphadenopathy, icterus, peripheral edema or wheezes. Neck veins were not distended. Liver and spleen were not palpable, and abdomen examination was normal.

Laboratory parameters with normal ranges in parenthesis are as follow:

Complete blood count before transfusion: white cell count 7.8 (4–10) × 10 9 /L; neutrophils 80%; lymphocytes 16%; monocytes 4%; red blood cells 3.6 (4.2–5.4) × 10 12 /L; haemoglobin 10.6 (12–15) g/dL; platelets 410 (150–400) × 10 9 /L.

Biochemistry: random blood sugar 126 (65–110) mg/dL; urea 39 (17–45) mg/dL; creatinine 1.1 (0.8–1.3) mg/dL; sodium 138 (135–145) mmol/L and potassium 4 (3.5–5) mmol/L.

Chest X-ray ( Figure 1 ) showed thick walled cavitating lesions in the left upper lobe and patchy infiltrates in left middle and lower zones. There were hyperinflated lung fields with blunting of left costophrenic angle. Sputum smear examination showed 3+ acid fast bacilli. Sputum Gene Xpert was positive for Rifampicin sensitive tubercle bacilli. A diagnosis of pulmonary tuberculosis was made, and planned for starting ATT.

Figure 1. Chest X-ray showing thick walled cavitating lesions in the left upper lobe and patchy infiltrates in left middle and lower zones.

Liver function test was performed as baseline workup before starting treatment which showed the following results (with normal ranges in parenthesis): bilirubin total 1.1 (0.1–1.2) mg/dL and direct 0.5 (0–0.4) mg/dL; alanine transaminase 308 (5–30) units/L; aspartate transaminase 605 (5–30) units/L; alkaline phosphatase 149 (50–100) IU/L; gamma-glutamyltranspeptidase66 (9–48) units/L. The raised transaminases led us to perform further workup for liver disease. There was no clinical evidence of chronic liver disease or portal hypertension. Liver synthetic functions were as following;albumin 3.5 (3.5–5) g/dL; total protein 6.5 (6–8.3) g/dL; prothrombin time 14 (11–13.5) s. Serologies for HIV, HBsAg, Hepatitis C virus (HCV), Hepatitis A virus (HAV) and Hepatitis E virus (HEV) were nonreactive. Testing for other hepatotropic viruses was not done because of unavailability of the tests. Neurological examinations and the slit lamp examination of eye were normal. Ultrasound of the abdomen showed a normal sized liver with smooth outline and echotexture. However fibroscan, upper gastrointestinal endoscopy, abdominal CT scan and liver biopsy were not done due to financial constraints of the patient.

She was admitted to the respiratory isolation unit. At first there was some hesitation in starting the full treatment for her pulmonary tuberculosis because of her liver function tests. But taking into consideration her presentation and laboratory findings, we opted for the full treatment rather than a modified TB regimen. We started standard four drugs ATT based on her weight as per national TB guidelines which included three tablets of HRZE given once daily with each tablet containing 75 mg isoniazid (H), 150 mg rifampicin (R), 400 mg pyrazinamide (Z) and 275 mg ethambutol (E). This led to improvement in her clinical status. She was closely observed for possible worsening of her liver disease due to the hepatotoxic antitubercular drugs. Providentially, at 1 week after starting treatment, she was afebrile and continuing to improve and her liver function test showed a total bilirubin of 0.7 mg/dl, aspartate transaminase of 40 IU/L and alanine transaminase of 62 IU/L.

She was discharged with advice to follow up in 1 month. At 1 month follow up she had no symptoms and therefore no further tests were done. At 2 months, she was still asymptomatic and her sputum smear was negative for acid fast bacilli. Her liver function test showed a total bilirubin of 0.6 mg/dl, aspartate transaminase of 30 IU/L and alanine transaminase of 35 IU/L. She was switched to3 tablets of HR to be taken for 4 months.

Our patient with pulmonary tuberculosis had predominantly raised transaminases (hepatocellular pattern)during the initial presentation, with only modest elevation in alkaline phosphatase and gamma glutamyltranspeptidase. The workup for liver disease could not be performed completely because of resource limitation. Looking for clinical evidences by history and examination, and performing liver function tests, abdominal ultrasound and serology for common hepatotropic viruses are usually considered sufficient in our limited setup. We perform further tests only if the initial workup hints towards another etiology. There were no clinical features of chronic liver disease or portal hypertension. She had no risk factors for liver disease such as family history, alcohol, drugs, toxins, features suggesting autoimmune or metabolic liver diseases. Her viral hepatitis serologies were negative. Ultrasound also showed normal liver architecture and size.Though incomplete, the initial workup led us to believe that she had no pre-existing liver injury.

Patients with extrapulmonary hepatic tuberculosis as classified by Reed (diffuse or focal)usually present withnonspecific symptoms like abdominal pain, jaundice, fever, night sweats, fatigue, weight loss and hepatomegaly. They havecholestatic pattern of liver function abnormality with normal transaminases, increased protein- albumin gap owing to raised serum globulin. Hepatic imaging with ultrasound or CT scan reveal abnormalities in 76 and 88% cases respectively. Liver biopsy and demonstration of caseating granuloma and mycobacterial culture remain gold standard for diagnosing hepatic tuberculosis 4 – 6 . Following points in our patient precluded making the diagnosis of hepatic tuberculosis; a) absence of abdominal symptoms and hepatomegaly; b) predominantly raised transaminases (hepatocellular pattern) and normal protein- albumin gap; and c) normal ultrasound finding (though CT and biopsy were not done).

There is another classification schema, given by Levine in 1990 which has incorporated additional entity under hepatic tuberculosis which is ‘pulmonary tuberculosis withliver involvement’ 10 . In the absence of obvious pre-existing liver disease or drug and the presence of active cavitary tuberculosis in lungs, we attributed the transaminitisin our patient to the pulmonary tuberculosis itself. In our anecdotal experience, we have found many such patients though we do not have any formal data to back this up. They are often managed with modified liver-friendly antitubercular regimens for fear of increasing the hepatotoxicity and causing acute liver failure with the use of standard regimen. Few case reports are available in literature reporting the use of the modified regimens 11 , 12 . We believe such cases are underreported, and firm guidelines have not been established to guide clinicians in these cases. Given this, many clinicians in low-middle income countries, including Nepal, who have been treating tuberculosis patients tend to be skeptical in using full doses of first line ATT in such patients and tend to use a modified regimen. However, this practice may potentially lead to under-treatment and therefore increase fatality 13 . The use of modified regimen may also increase the risk of developing drug-resistant tuberculosis because of exclusion of more potent drugs 14 . Though there was some hesitation at first in our case, we soon started treatment with the standard ATT in our patient with close monitoring. This we believe led to the resolution of liver injury, evidenced by the normalization of transaminases.

However, acknowledging that the patient may develop drug induced liver injury (DILI) with the hepatotoxic antitubercular drugs, we should monitorsuch patients closely in an inpatient basis to look forclinical deterioration or any feature suggesting liver failureand liver function test repeated regularly. Though there is no firm recommendation for when to repeat the tests, patient should not be discharged till there is significant improvement in the transaminases level. The close monitoring is important in those with higher risks for developing DILI associated with ATT such as elderly, females, alcohol consumers, the malnourished and those with genetic susceptibility like slow acetylators 7 . Such monitoring is even more important in our setup because there are possibilities of missing occult hepatic diseases owing tolimited workup.Our patient had improving transaminases evidenced till 2 months follow up.

Though limited by incomplete investigations, we concluded pulmonary tuberculosis as the cause for transaminitis in our patient, and the normalization of transaminases after starting the standard dose of ATT further supports this conclusion. We believe pulmonary TB presenting with transaminitis is a common problem and that treatment may often be compromised because of decreased dosing of ATT.We further aim to perform case series study to explore the magnitude of problem and reach specific conclusions.

When treating a tuberculosis patient with transaminitis, it is important to look for any possibility of pre-existing liver disease or drug use. If none is found, then the use of standard ATT from the beginning with close inpatient monitoring of the patient may be essential for optimal management of tuberculosis, and this may help resolve any liver injury caused by the tuberculosis. This is a single case report, so further case series or cohort studies would be helpful to reach some conclusion and provide concrete recommendations.

Written informed consent for publication of their clinical details and clinical images was obtained from the patient.

Data availability

Underlying data.

All data underlying the results are available as part of the article and no additional source data are required.

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• 14.   Kumar N, Kedarisetty CK, Kumar S, et al. : Antitubercular therapy in patients with cirrhosis: challenges and options. World J Gastroenterol. 2014; 20 (19): 5760–72. PubMed Abstract | Publisher Full Text | Free Full Text

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Open peer review.

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Tuberculosis, Interventional Pulmonology, ILD

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Reviewer Expertise: History of Tuberculosis, Global Health, South and Southeast Asia, Medical Humanities

Is the background of the case’s history and progression described in sufficient detail?

Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes?

Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment?

Is the case presented with sufficient detail to be useful for other practitioners?

Reviewer Expertise: Management of HIV/tuberculosis; PK/PD for tuberculosis

• Author Response 16 Oct 2020 Sudeep Adhikari , Internal Medicine, Patan Academy of Health Sciences, Lalitpur, Nepal 16 Oct 2020 Author Response We would like to whole-heartedly thank you for spending so much time and effort to improve our manuscript. Here below is the point by point response. The title needs to convey that ... Continue reading We would like to whole-heartedly thank you for spending so much time and effort to improve our manuscript. Here below is the point by point response. The title needs to convey that this is new onset transaminitis attributed to tuberculosis prior to commencement of anti tubercular therapy  Response: Title has been modified. Thank you Background Please outline the baseline work up for TB in programmatic setting in Nepal. Do all patients have baseline LFTs done? Response: Programmatic setting does not require any baseline workup except sputum smear and in chest Xray. But in hospital setting, we perform baseline blood investigations like blood counts, renal function, electrolytes and liver function tests before starting treatment, so that treatment can be modified accordingly. Changes have been made in the background section.    Case presentation  Has this patient had normal LFTs recorded prior to current TB presentation?  Response: No prior LFT testing was done by the patient Mention drug history incl. paracetamol, aflatoxin exposure, family history of liver disease. Text has been modified to state the fact. Thank you  The liver screen is incomplete - e.g. autoimmune and inherited liver disease, paracetamol levels, ferritin, occult hep B. Also liver fibrosis assessment.   Baseline GGT and clotting needs to be given.  Please give a table of ALT, AST, GGT, Alk phos, Albumin and clotting during first 2 weeks of treatment (and any further tests during 6 months of treatment) Of note, there is no clear evidence of disseminated miliary TB on CXR. Abdominal or liver CT was not done. Hence, no comment can be made regarding  liver/splenic micronodular abscesses. It appears no mycobacterial blood cultures were taken to assess for bacteraemia. Nor was a liver biopsy done. All relevant negatives and limitations should be mentioned. Response: The liver disease screen is incomplete as the reviewer pointed out. However, because of resource limitation and financial constraints, it is not usually possible to perform full liver disease screening in Nepal. So we usually opt for limited screen, and rely more on history, physical examination and initial limited investigations. Then we perform further tests only if the initial workup hints towards another etiology. Text has been modified to include investigations and other limitations.  When was she discharged?  Response: She was discharged after 1 week after becoming afebrile and improvement in transaminases. Considering she was never symptomatic from the point of view of GI/hepatobiliary system, was there no further blood work to monitor LFTs since discharge?  Response: LFT was repeated first at 1 week before discharge, then at 2 months follow up after discharge. Discussion:  Briefly explain classifications of liver TB e.g. Reed, Alvarez, Levine. The authors do not clearly say what clinical, biochemical, radiological and histopathological presentation would be seen with disseminated TB involving liver. This case does not clearly illustrate steps to confirm a transaminitis secondary disseminated miliary TB. Response: Text has been modified to include further discussion. Thank you  The implications of this case report would have greater impact and relevance for practitioners in the context of a case series or retrospective cohort and the authors should consider doing this. Response: Yes we hope further case reports and case series would be published in future, and we look forward to do case series and we have included this notion in the ms. Thank you.  Further discussion is needed of considerations such as potentiated toxicity with pharmacogenomic factors e.g. slow acetylators, the need for individualized monitoring e.g. therapeutic drug monitoring.  Response: Further discussion has been added. Unfortunately such therapeutic drug monitoring is not widely available in Nepal. How long should these patients have monitoring of their LFTs? Is there are risk of paradoxical reactions? Unlike Drug induced liver injury, there is no specific monitoring protocols for patients described in our case. The monitoring should be done till the deranged tests normalize and patient becomes clinically well. We have not encountered paradoxical reactions so far. We would like to whole-heartedly thank you for spending so much time and effort to improve our manuscript. Here below is the point by point response. The title needs to convey that this is new onset transaminitis attributed to tuberculosis prior to commencement of anti tubercular therapy  Response: Title has been modified. Thank you Background Please outline the baseline work up for TB in programmatic setting in Nepal. Do all patients have baseline LFTs done? Response: Programmatic setting does not require any baseline workup except sputum smear and in chest Xray. But in hospital setting, we perform baseline blood investigations like blood counts, renal function, electrolytes and liver function tests before starting treatment, so that treatment can be modified accordingly. Changes have been made in the background section.    Case presentation  Has this patient had normal LFTs recorded prior to current TB presentation?  Response: No prior LFT testing was done by the patient Mention drug history incl. paracetamol, aflatoxin exposure, family history of liver disease. Text has been modified to state the fact. Thank you  The liver screen is incomplete - e.g. autoimmune and inherited liver disease, paracetamol levels, ferritin, occult hep B. Also liver fibrosis assessment.   Baseline GGT and clotting needs to be given.  Please give a table of ALT, AST, GGT, Alk phos, Albumin and clotting during first 2 weeks of treatment (and any further tests during 6 months of treatment) Of note, there is no clear evidence of disseminated miliary TB on CXR. Abdominal or liver CT was not done. Hence, no comment can be made regarding  liver/splenic micronodular abscesses. It appears no mycobacterial blood cultures were taken to assess for bacteraemia. Nor was a liver biopsy done. All relevant negatives and limitations should be mentioned. Response: The liver disease screen is incomplete as the reviewer pointed out. However, because of resource limitation and financial constraints, it is not usually possible to perform full liver disease screening in Nepal. So we usually opt for limited screen, and rely more on history, physical examination and initial limited investigations. Then we perform further tests only if the initial workup hints towards another etiology. Text has been modified to include investigations and other limitations.  When was she discharged?  Response: She was discharged after 1 week after becoming afebrile and improvement in transaminases. Considering she was never symptomatic from the point of view of GI/hepatobiliary system, was there no further blood work to monitor LFTs since discharge?  Response: LFT was repeated first at 1 week before discharge, then at 2 months follow up after discharge. Discussion:  Briefly explain classifications of liver TB e.g. Reed, Alvarez, Levine. The authors do not clearly say what clinical, biochemical, radiological and histopathological presentation would be seen with disseminated TB involving liver. This case does not clearly illustrate steps to confirm a transaminitis secondary disseminated miliary TB. Response: Text has been modified to include further discussion. Thank you  The implications of this case report would have greater impact and relevance for practitioners in the context of a case series or retrospective cohort and the authors should consider doing this. Response: Yes we hope further case reports and case series would be published in future, and we look forward to do case series and we have included this notion in the ms. Thank you.  Further discussion is needed of considerations such as potentiated toxicity with pharmacogenomic factors e.g. slow acetylators, the need for individualized monitoring e.g. therapeutic drug monitoring.  Response: Further discussion has been added. Unfortunately such therapeutic drug monitoring is not widely available in Nepal. How long should these patients have monitoring of their LFTs? Is there are risk of paradoxical reactions? Unlike Drug induced liver injury, there is no specific monitoring protocols for patients described in our case. The monitoring should be done till the deranged tests normalize and patient becomes clinically well. We have not encountered paradoxical reactions so far. Competing Interests: none Close Report a concern Reply -->
• The authors describe a patient with pulmonary tuberculosis and raised liver enzymes (Transaminases). They do mention that the patient did not have any preexisting liver disease or drug use, but do not mention how they systematically ruled out other causes of tansaminitis (other non A-E viral hepatitis like GBV, Hep G, EBV,TT virus and other tropical infections).
• “In this report, we gave full dose standard antitubercular drugs, and the liver injury resolved evidenced by normalization of transaminases”. The authors should make their message more clear to “presence of transamnitis with no obvious common underlying etiology may not warrant a modification of standard antitubercular regimen”
• Evaluation of patient: Diagnostic work-up is incomplete and should also include evaluation for degree of hepatocellular injury. Prothrombin time is not mentioned, GGT levels not mentioned, Serum globulin levels not mentioned (hepatic TB has inverted albumin to globulin ration), imaging was limited (only USG performed, CT not done), liver biopsy not performed. More investigations should have been performed to rule out underlying chronic liver diseases: Fibroscan, upper GI endoscopy for Portal HTN)  
• Figure 1: The quality of the image is suboptimal. The entire bony cage is not visible. Right costophrenic angle is not visible. Finding of hyperinflated lung fields and blunting of left CP angle are not described. Did the patient have underlying obstructive airway disease? If so did she also have pulmonary hypertension?. Could hepatic congestion due to RHF explain the raised liver enzymes?  
• Follow up: The patient improved significantly at 1 month follow up. It would be desirable to have a complete follow up of the patient with evaluation of liver enzymes at least once during treatment as patient initially also did not have any liver specific symptoms.
• The authors argue that the patient did not have underlying liver disease or liver involvement due to tuberculosis as there was no features of Granuloma and cholestatic pattern of liver enzyme elevation. To ascribe the transamnitis to be caused by TB would be an arbitrary statement especially in the absence of liver biopsy.  
• The authors mention that they have found many patients of pulmonary TB to have predominant transamnitis and without any preexisting liver disease in their experience. Such statement is not backed by any formal data.  
• The authors conclude that pulmonary TB was the cause of transamnitis in their patient, not hepatic TB or underlying liver disease. In the absence of complete workup, such strong conclusions should not be made.
• Author Response 16 Oct 2020 Sudeep Adhikari , Internal Medicine, Patan Academy of Health Sciences, Lalitpur, Nepal 16 Oct 2020 Author Response We would like to whole-heartedly thank you for spending so much time and effort to improve our manuscript. Here below is the point by point response. Title: The title ... Continue reading We would like to whole-heartedly thank you for spending so much time and effort to improve our manuscript. Here below is the point by point response. Title: The title is unclear as to whether the transaminitis in the index patient is caused by tuberculosis (as proposed by the authors in the subsequent report) or a consequence of other coexisting condition. The title needs to be rephrased as to impart a message that the authors want to convey Response: Title has been modified to make our message clearer. Thank you Abstract: The authors describe a patient with pulmonary tuberculosis and raised liver enzymes (Transaminases). They do mention that the patient did not have any preexisting liver disease or drug use, but do not mention how they systematically ruled out other causes of tansaminitis (other non A-E viral hepatitis like GBV, Hep G, EBV,TT virus and other tropical infections). ○ References: DOI: 10.5812/hepatmon.188651; Alter HJ, Bradley DW. Non-A, non-B hepatitis unrelated to the hepatitis C virus (non ABC) Semin Liver Dis 1995; 15:110-1202; Current Opinion in Infectious Diseases: October 2002 - Volume 15 - Issue 5 - p 529-5343. Testing of other viruses were not done due to unavailability.Since raised transaminases resolved after starting ATT we assumed tuberculosis was most likely explanation. “In this report, we gave full dose standard antitubercular drugs, and the liver injury resolved evidenced by normalization of transaminases”. The authors should make their message more clear to “presence of transaminitis with no obvious common underlying etiology may not warrant a modification of standard antitubercular regimen” Response: Text has been modified to make our message clearer. Thank you Case report Evaluation of patient: Diagnostic work-up is incomplete and should also include evaluation for degree of hepatocellular injury. Prothrombin time is not mentioned, GGT levels not mentioned, Serum globulin levels not mentioned (hepatic TB has inverted albumin to globulin ration), imaging was limited (only USG performed, CT not done), liver biopsy not performed. More investigations should have been performed to rule out underlying chronic liver diseases: Fibroscan, upper GI endoscopy for Portal HTN) Response: The liver disease screen is incomplete as the reviewers pointed out. However, because of resource limitation and financial constraints, it is not usually possible to perform full liver disease screening in Nepal. So we usually opt for limited screen, and rely more on history, physical examination and initial limited investigations. Then we perform further tests only if the initial workup hints towards another etiology. Text has been modified to include further lab reports. The limitations have been acknowledged. Figure 1: The quality of the image is suboptimal. The entire bony cage is not visible. Right costophrenic angle is not visible. Finding of hyperinflated lung fields and blunting of left CP angle are not described. Did the patient have underlying obstructive airway disease? If so did she also have pulmonary hypertension?. Could hepatic congestion due to RHF explain the raised liver enzymes? Response: There was no history of underlying lung disease. Although echocardiography was not done hepatic congestion due to RHF is unlikely as there was no suggestive history and examination findings and patient responded without any diuretics or fluid restrictions. Follow up: The patient improved significantly at 1 month follow up. It would be desirable to have a complete follow up of the patient with evaluation of liver enzymes at least once during treatment as patient initially also did not have any liver specific symptoms. Response: Text has been modified to include follow up reports. LFT was repeated first at 1 week before discharge, then at 2 months follow up after discharge. Discussion: The authors argue that the patient did not have underlying liver disease or liver involvement due to tuberculosis as there was no features of Granuloma and cholestatic pattern of liver enzyme elevation. To ascribe the transaminitis to be caused by TB would be an arbitrary statement especially in the absence of liver biopsy. Response: Imaging and further investigations were limited, so hepatic tuberculosis could not be ruled out with certainty especially without biopsy of liver. However this would not make much difference. Because even if the diagnosis of hepatic tuberculosis had been considered in our patient, the management would be the same, i.e. with standard ATT as we did in our patient. The point we wanted to make here is that modification in treatment may not be required in the absence of pre-existing liver disease. Text has been modified to include the limitations. Thank you The authors mention that they have found many patients of pulmonary TB to have predominant transaminitis and without any preexisting liver disease in their experience. Such statement is not backed by any formal data. Response: We need more data but unfortunately not much is being published from low middle income countries even for endemic diseases like tuberculosis. There is no formal data to back up our claim, and this has been acknowledged as limitation. The authors conclude that pulmonary TB was the cause of transaminitis in their patient, not hepatic TB or underlying liver disease. In the absence of complete workup, such strong conclusions should not be made. Response: Due to rapid resolution of raised transaminases after starting ATT, preexisting liver disease would be unlikely cause. Although hepatic tb is a possibility, it was our opinion that standard dose ATT can be safely started in the patient and further imaging would not be cost effective in terms of treatment. We agree with the reviewer that the strong conclusions are not justified due to incomplete workup and this section has been toned down and modified to highlight the limitations. Thank you Conclusion The authors recommend use of full dose standard ATT for patients with transaminitis and no underlying liver disease. This recommendation should not be made based on a single case report. Response: We agree. Text have been modified to include our limitations. Thank you.  Opinion: The case report describes a common scenario especially in low income countries while treating patients with tuberculosis. The availability of resources limit the diagnostic workup of such patients in our settings. I opine that this case report is suitable for indexing with modifications. Response: Thank you We would like to whole-heartedly thank you for spending so much time and effort to improve our manuscript. Here below is the point by point response. Title: The title is unclear as to whether the transaminitis in the index patient is caused by tuberculosis (as proposed by the authors in the subsequent report) or a consequence of other coexisting condition. The title needs to be rephrased as to impart a message that the authors want to convey Response: Title has been modified to make our message clearer. Thank you Abstract: The authors describe a patient with pulmonary tuberculosis and raised liver enzymes (Transaminases). They do mention that the patient did not have any preexisting liver disease or drug use, but do not mention how they systematically ruled out other causes of tansaminitis (other non A-E viral hepatitis like GBV, Hep G, EBV,TT virus and other tropical infections). ○ References: DOI: 10.5812/hepatmon.188651; Alter HJ, Bradley DW. Non-A, non-B hepatitis unrelated to the hepatitis C virus (non ABC) Semin Liver Dis 1995; 15:110-1202; Current Opinion in Infectious Diseases: October 2002 - Volume 15 - Issue 5 - p 529-5343. Testing of other viruses were not done due to unavailability.Since raised transaminases resolved after starting ATT we assumed tuberculosis was most likely explanation. “In this report, we gave full dose standard antitubercular drugs, and the liver injury resolved evidenced by normalization of transaminases”. The authors should make their message more clear to “presence of transaminitis with no obvious common underlying etiology may not warrant a modification of standard antitubercular regimen” Response: Text has been modified to make our message clearer. Thank you Case report Evaluation of patient: Diagnostic work-up is incomplete and should also include evaluation for degree of hepatocellular injury. Prothrombin time is not mentioned, GGT levels not mentioned, Serum globulin levels not mentioned (hepatic TB has inverted albumin to globulin ration), imaging was limited (only USG performed, CT not done), liver biopsy not performed. More investigations should have been performed to rule out underlying chronic liver diseases: Fibroscan, upper GI endoscopy for Portal HTN) Response: The liver disease screen is incomplete as the reviewers pointed out. However, because of resource limitation and financial constraints, it is not usually possible to perform full liver disease screening in Nepal. So we usually opt for limited screen, and rely more on history, physical examination and initial limited investigations. Then we perform further tests only if the initial workup hints towards another etiology. Text has been modified to include further lab reports. The limitations have been acknowledged. Figure 1: The quality of the image is suboptimal. The entire bony cage is not visible. Right costophrenic angle is not visible. Finding of hyperinflated lung fields and blunting of left CP angle are not described. Did the patient have underlying obstructive airway disease? If so did she also have pulmonary hypertension?. Could hepatic congestion due to RHF explain the raised liver enzymes? Response: There was no history of underlying lung disease. Although echocardiography was not done hepatic congestion due to RHF is unlikely as there was no suggestive history and examination findings and patient responded without any diuretics or fluid restrictions. Follow up: The patient improved significantly at 1 month follow up. It would be desirable to have a complete follow up of the patient with evaluation of liver enzymes at least once during treatment as patient initially also did not have any liver specific symptoms. Response: Text has been modified to include follow up reports. LFT was repeated first at 1 week before discharge, then at 2 months follow up after discharge. Discussion: The authors argue that the patient did not have underlying liver disease or liver involvement due to tuberculosis as there was no features of Granuloma and cholestatic pattern of liver enzyme elevation. To ascribe the transaminitis to be caused by TB would be an arbitrary statement especially in the absence of liver biopsy. Response: Imaging and further investigations were limited, so hepatic tuberculosis could not be ruled out with certainty especially without biopsy of liver. However this would not make much difference. Because even if the diagnosis of hepatic tuberculosis had been considered in our patient, the management would be the same, i.e. with standard ATT as we did in our patient. The point we wanted to make here is that modification in treatment may not be required in the absence of pre-existing liver disease. Text has been modified to include the limitations. Thank you The authors mention that they have found many patients of pulmonary TB to have predominant transaminitis and without any preexisting liver disease in their experience. Such statement is not backed by any formal data. Response: We need more data but unfortunately not much is being published from low middle income countries even for endemic diseases like tuberculosis. There is no formal data to back up our claim, and this has been acknowledged as limitation. The authors conclude that pulmonary TB was the cause of transaminitis in their patient, not hepatic TB or underlying liver disease. In the absence of complete workup, such strong conclusions should not be made. Response: Due to rapid resolution of raised transaminases after starting ATT, preexisting liver disease would be unlikely cause. Although hepatic tb is a possibility, it was our opinion that standard dose ATT can be safely started in the patient and further imaging would not be cost effective in terms of treatment. We agree with the reviewer that the strong conclusions are not justified due to incomplete workup and this section has been toned down and modified to highlight the limitations. Thank you Conclusion The authors recommend use of full dose standard ATT for patients with transaminitis and no underlying liver disease. This recommendation should not be made based on a single case report. Response: We agree. Text have been modified to include our limitations. Thank you.  Opinion: The case report describes a common scenario especially in low income countries while treating patients with tuberculosis. The availability of resources limit the diagnostic workup of such patients in our settings. I opine that this case report is suitable for indexing with modifications. Response: Thank you Competing Interests: none Close Report a concern Reply -->
• Author Response 16 Oct 2020 Sudeep Adhikari , Internal Medicine, Patan Academy of Health Sciences, Lalitpur, Nepal 16 Oct 2020 Author Response We would like to whole-heartedly thank you for spending so much time and effort to improve our manuscript. Here below is the point by point response.  Title:  ... Continue reading We would like to whole-heartedly thank you for spending so much time and effort to improve our manuscript. Here below is the point by point response.  Title:  Drug-resistant TB is a hot topic in medicine today. Research on TB treatment-associated transaminitis would further the existing scholarly understanding on drug-resistant TB. A close keyword search on PubMed revealed only 17 hit on TB AND transaminitis. For this reason, the  case report is potentially publishable but suffers from several drawbacks in its current draft that must be remedied before the contribution is re-refereed.  But the title itself is unclear. “With” is repeated twice. It is not clear to a medical historian what transaminitis is. A better framing of the title is urgently needed. A cogent argument can be organised around the title. What is four-drugs therapy? It is clear to medical practitioners but not clear to the larger scholarly community. Avoid jargons in the title. 1)    What is transaminitis? Why not provide a brief explanation at the start so that the general reader can follow the rest of the article. 2)    The two levels of transaminitis: (a) pre-existing liver disease leads to transaminitis. (b) Hepatoxicity of anti-TB drugs. This needs to be made explicit in the very beginning. The authors have not been explicit about the two levels of transaminitis and that is where the problem begins. “While encountering such patients, it is important to differentiate if the patient had pre-existing liver disease or if the present infection with tuberculosis has impacted on the liver, as the approach to management differs given the hepatotoxicity associated with first line drugs.” Rewrite this sentence. Make more explicit. Response: Title and text have been modified to make our message clearer. Thank you Summary and Abstract:  The writers present a case of pulmonary TB with transaminitis without pre-existing liver damage. The therapeutic regimen of the authors included anti-TB drugs and liver injury resolved evidenced by normalization of transaminase. The abstract merits rewriting for clarity. Response: Abstract has been modified to make our message clearer Background:  Needs to sketch out the larger socio-economic picture of TB patients in Nepal. Medicine for whom?  Response: Background has been modified to make it clear. The socioeconomic picture of TB patients in Nepal has been highlighted. In Nepal, tuberculosis prevalence is more in productive age group (25-64 years) and men. Poverty, malnutrition, overcrowding, immunocompromised state like HIV infection, alcohol, smoking, air pollution, diabetes and other comorbidities are important risk factors for acquiring the disease. All patients diagnosed with TB receive treatment as per the national protocol which has been mentioned in the text. Case Presentation:   How do you define compliance with TB treatment? How socio-economic factors militate against the successful completion of treatment?  Response: To improve the treatment compliance, treatment of TB is done under DOTS program all over Nepal, which stands for ‘Directly Observed Treatment Short Course’. Otherwise the compliance would be compromised owing to the lower socioeconomic status of patients, longer duration of therapy and side effects of drugs.  Specific quote from the report: “In our anecdotal experience, we have found many patients with pulmonary tuberculosis, similarly to subject of this case report, present with predominant transaminitis and without pre-existing liver disease or drugs-use. They are often managed with modified liver-friendly antitubercular regimens for fear of increasing the hepatotoxicity and causing acute liver failure with the use of standard regimen. Few case reports are available in literature reporting the use of the modified regimens. We believe such cases are underreported, and firm guidelines have not been established to guide clinicians in these cases. Given this, many clinicians in low-middle income countries, including Nepal, who have been treating tuberculosis patients tend to be skeptical in using full doses of first line ATT in such patients and tend to use a modified regimen. However, this practice may potentially lead to undertreatment and therefore increase fatality9. Though there was some hesitation at first in our case, we soon started treatment with the standard ATT in our patient with close monitoring. This we believe led to the resolution of liver injury, evidenced by the normalization of transaminases.” What is your sample size? Unclear. What guidelines can be established with the aid of the study?" Make explicit and elaborate Response: Our opinion is that there are cases of pulmonary tb with some hepatic involvement, which are sometimes being managed with modified regimen when it can be safely managed with standard regimen. Unfortunately very few published research is available from low middle income countries. Text has been edited to include limitation of evidence. This is a case report only and further research is needed. Conclusion:   The report lacks an inevitable conclusion.  The conclusion needs to point to the “so what” question? So, what are the implications of this study? What protocols could be devised? How does this case history further medical practitioners’ as well as policymakers’ understanding of drug-resistant TB? Response: Being a case report and paucity of previous research, we have toned down our previous strong conclusions, also as suggested above by another reviewer. We hope that further reports will be published. The use of modified drug regimen excluding more potent drugs, instead of standard regimen may promote drug resistance, and how far such practices are prevalent can be another area of further study. Other points:  Please make sure that the manuscript is thoroughly copyedited for legibility of prose, clarity of argument, and grammar.  The social context of TB in Nepal merits attention (alcoholism is a contributing factor). You need to compare transaminitis with case studies from other countries. Carefully refer to the PLoS Response: Text has been revised to correct errors. Social context of TB in Nepal has been mentioned in the text. Thank you Murphy, Richard A., Vincent C. Marconi, Rajesh T. Gandhi, Daniel R. Kuritzkes, and Henry Sunpath. "Coadministration of lopinavir/ritonavir and rifampicin in HIV and tuberculosis co-infected adults in South Africa." PLoS One 7, no. 9 (2012): e447931. Sarda, Pawan, S. K. Sharma, Alladi Mohan, Govind Makharia, Arvind Jayaswal, R. M. Pandey, and Sarman Singh. "Role of acute viral hepatitis as a confounding factor in antituberculosis treatment induced hepatotoxicity." Indian Journal of Medical Research 129, no. 1 (2009): 642. How does your case differ from the 2 references mentioned above? Response: As compared to first article our patient did not have HIV. As compared to second article, our patient did not have antituberculous drug induced hepatotoxicity but liver injury likely due to tuberculosis itself. Thank you We would like to whole-heartedly thank you for spending so much time and effort to improve our manuscript. Here below is the point by point response.  Title:  Drug-resistant TB is a hot topic in medicine today. Research on TB treatment-associated transaminitis would further the existing scholarly understanding on drug-resistant TB. A close keyword search on PubMed revealed only 17 hit on TB AND transaminitis. For this reason, the  case report is potentially publishable but suffers from several drawbacks in its current draft that must be remedied before the contribution is re-refereed.  But the title itself is unclear. “With” is repeated twice. It is not clear to a medical historian what transaminitis is. A better framing of the title is urgently needed. A cogent argument can be organised around the title. What is four-drugs therapy? It is clear to medical practitioners but not clear to the larger scholarly community. Avoid jargons in the title. 1)    What is transaminitis? Why not provide a brief explanation at the start so that the general reader can follow the rest of the article. 2)    The two levels of transaminitis: (a) pre-existing liver disease leads to transaminitis. (b) Hepatoxicity of anti-TB drugs. This needs to be made explicit in the very beginning. The authors have not been explicit about the two levels of transaminitis and that is where the problem begins. “While encountering such patients, it is important to differentiate if the patient had pre-existing liver disease or if the present infection with tuberculosis has impacted on the liver, as the approach to management differs given the hepatotoxicity associated with first line drugs.” Rewrite this sentence. Make more explicit. Response: Title and text have been modified to make our message clearer. Thank you Summary and Abstract:  The writers present a case of pulmonary TB with transaminitis without pre-existing liver damage. The therapeutic regimen of the authors included anti-TB drugs and liver injury resolved evidenced by normalization of transaminase. The abstract merits rewriting for clarity. Response: Abstract has been modified to make our message clearer Background:  Needs to sketch out the larger socio-economic picture of TB patients in Nepal. Medicine for whom?  Response: Background has been modified to make it clear. The socioeconomic picture of TB patients in Nepal has been highlighted. In Nepal, tuberculosis prevalence is more in productive age group (25-64 years) and men. Poverty, malnutrition, overcrowding, immunocompromised state like HIV infection, alcohol, smoking, air pollution, diabetes and other comorbidities are important risk factors for acquiring the disease. All patients diagnosed with TB receive treatment as per the national protocol which has been mentioned in the text. Case Presentation:   How do you define compliance with TB treatment? How socio-economic factors militate against the successful completion of treatment?  Response: To improve the treatment compliance, treatment of TB is done under DOTS program all over Nepal, which stands for ‘Directly Observed Treatment Short Course’. Otherwise the compliance would be compromised owing to the lower socioeconomic status of patients, longer duration of therapy and side effects of drugs.  Specific quote from the report: “In our anecdotal experience, we have found many patients with pulmonary tuberculosis, similarly to subject of this case report, present with predominant transaminitis and without pre-existing liver disease or drugs-use. They are often managed with modified liver-friendly antitubercular regimens for fear of increasing the hepatotoxicity and causing acute liver failure with the use of standard regimen. Few case reports are available in literature reporting the use of the modified regimens. We believe such cases are underreported, and firm guidelines have not been established to guide clinicians in these cases. Given this, many clinicians in low-middle income countries, including Nepal, who have been treating tuberculosis patients tend to be skeptical in using full doses of first line ATT in such patients and tend to use a modified regimen. However, this practice may potentially lead to undertreatment and therefore increase fatality9. Though there was some hesitation at first in our case, we soon started treatment with the standard ATT in our patient with close monitoring. This we believe led to the resolution of liver injury, evidenced by the normalization of transaminases.” What is your sample size? Unclear. What guidelines can be established with the aid of the study?" Make explicit and elaborate Response: Our opinion is that there are cases of pulmonary tb with some hepatic involvement, which are sometimes being managed with modified regimen when it can be safely managed with standard regimen. Unfortunately very few published research is available from low middle income countries. Text has been edited to include limitation of evidence. This is a case report only and further research is needed. Conclusion:   The report lacks an inevitable conclusion.  The conclusion needs to point to the “so what” question? So, what are the implications of this study? What protocols could be devised? How does this case history further medical practitioners’ as well as policymakers’ understanding of drug-resistant TB? Response: Being a case report and paucity of previous research, we have toned down our previous strong conclusions, also as suggested above by another reviewer. We hope that further reports will be published. The use of modified drug regimen excluding more potent drugs, instead of standard regimen may promote drug resistance, and how far such practices are prevalent can be another area of further study. Other points:  Please make sure that the manuscript is thoroughly copyedited for legibility of prose, clarity of argument, and grammar.  The social context of TB in Nepal merits attention (alcoholism is a contributing factor). You need to compare transaminitis with case studies from other countries. Carefully refer to the PLoS Response: Text has been revised to correct errors. Social context of TB in Nepal has been mentioned in the text. Thank you Murphy, Richard A., Vincent C. Marconi, Rajesh T. Gandhi, Daniel R. Kuritzkes, and Henry Sunpath. "Coadministration of lopinavir/ritonavir and rifampicin in HIV and tuberculosis co-infected adults in South Africa." PLoS One 7, no. 9 (2012): e447931. Sarda, Pawan, S. K. Sharma, Alladi Mohan, Govind Makharia, Arvind Jayaswal, R. M. Pandey, and Sarman Singh. "Role of acute viral hepatitis as a confounding factor in antituberculosis treatment induced hepatotoxicity." Indian Journal of Medical Research 129, no. 1 (2009): 642. How does your case differ from the 2 references mentioned above? Response: As compared to first article our patient did not have HIV. As compared to second article, our patient did not have antituberculous drug induced hepatotoxicity but liver injury likely due to tuberculosis itself. Thank you Competing Interests: none Close Report a concern Reply -->

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• Vivek Neelakantan , Independent Medical Historian, Mumbai, India
• Prajowl Shrestha , Bir Hospital, Kathmandu, Nepal Ashesh Dhungana , Bir Hospital, Kathmandu, Nepal
• Neesha Rockwood , University of Cape Town, London, UK; University of Cape Town, Cape Town, South Africa; University of Colombo, Colombu, Sri Lanka

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Racial, ethnic disparities persist in U.S. tuberculosis cases

April 8, 2024—Racial and ethnic disparities in tuberculosis (TB) incidence persist among the U.S.-born population, according to a new study led by researchers at Harvard T.H. Chan School of Public Health.

The study was published April 2 in Annals of Internal Medicine. The authors included Yunfei Li and Mathilda Regan , postdoctoral research fellows; Nicolas Menzies , associate professor; and Nicole Swartwood , senior research analyst, all in the Department of Global Health and Population .

More than 70% of TB cases in the U.S. occur among people born outside the country, and between 2000 and 2019, cases among people born in the country decreased by more than 45%. Nonetheless, each year thousands of cases of the highly infectious disease continue to occur within the U.S.-born population—the demographics of which few studies have investigated.

To fill this gap, the researchers looked at the racial and ethnic breakdown of nearly 32,000 TB cases reported within the U.S.-born population between 2011 and 2021. TB incidence was in some cases 14 times higher among those who identified as American Indian/Alaska Native, Asian, Black, or Hispanic compared with those who identified as white, the study found. Disparities were particularly marked among women belonging to racial/ethnic minority groups, who experienced TB incidence rates more than four times higher than white women.

Eliminating such disparities, the researchers calculated, could reduce the U.S.’s TB incidence by more than 60% among the U.S.-born population.

“Given the substantial excess burden of TB among racial/ethnic minority populations, addressing these disparities in TB incidence is necessary for achieving health equity goals,” the authors wrote, calling accessible TB prevention tools, diagnostics, and treatment “essential.”

Read a HealthDay article about the study: Persistent Disparities Seen by Race/Ethnicity in Incidence of TB

Photo: National Institute of Allergy and Infectious Diseases (NIAID)

• Open access
• Published: 10 April 2024

War related disruption of clinical tuberculosis services in Tigray, Ethiopia during the recent regional conflict: a mixed sequential method study

• Kibrom Gebreselasie Gebrehiwot 1 ,
• Gebremedhin Berhe Gebregergis 2 ,
• Measho Gebreslasie Gebregziabher 2 ,
• Teklay Gebrecherkos 1 ,
• Wegen Beyene Tesfamariam 1 ,
• Hailay Gebretnsae 3 ,
• Gebregziabher Berihu 2 ,
• Letebrhan Weldemhret 3 ,
• Goyitom Gebremedhn 3 ,
• Tsegay Wellay 2 ,
• Hadish Bekuretsion 3 ,
• Aregay Gebremedhin 4 ,
• Tesfay Gebregzabher Gebrehiwet 2 &
• Gebretsadik Berhe 2  

Conflict and Health volume  18 , Article number:  29 ( 2024 ) Cite this article

Metrics details

More than 70% of the health facilities in Tigray, northern Ethiopia, have been totally or partially destroyed by the recent war in the region. Diagnosis and management of tuberculosis were among many health services that suffered. In this study we assess the status of tuberculosis care in health facilities of Tigray during the recent war and compare it with the immediate pre-war state.

Using sequential mixed method, we analyzed and compared the availability of diagnostic services in 69 health facilities and the utilization of tuberculosis care in 50 of them immediately before the war (September-October 2020) and during the war (November-July 2021). TB focal persons in each selected health facility were interviewed to evaluate the status of diagnostic services. Patient service utilization was assessed using health facility registrations. We also compared the average monthly case detection rate of multidrug resistant tuberculosis in the region before and during the war. We computed summary statistics and performed comparisons using t-tests. Finally, existing challenges related to tuberculosis care in the region were explored via in-depth interviews. Two investigators openly coded and analyzed the qualitative data independently via thematic analysis.

Among the 69 health facilities randomly selected, the registers of 19 facilities were destroyed by the war; data from the remaining 50 facilities were included in the TB service utilization analysis. In the first month of the war (November 2021) the number of tuberculosis patients visiting health facilities fell 34%. Subsequently the visitation rate improved steadily, but not to pre-war rates. This reduction was significant in northwest, central and eastern zones. Tuberculosis care in rural areas was hit hardest. Prior to the war 60% of tuberculosis patients were served in rural clinics; this number dropped to an average of 17% during the war. Health facilities were systematically looted. Of the 69 institutions assessed, over 69% of the microscopes in health centers, 87.5% of the microscopes in primary hospitals, and 68% of the microscopes in general hospitals were stolen or damaged. Two GeneXpert nucleic acid amplification machines were also taken from general hospitals. Regarding drug resistant TB, the average number of multidrug resistant tuberculosis (MDR TB) cases detected per month was reduced by 41% during the war with p-value < 0.001. In-depth interviews with eight health care workers indicated that the main factors affecting tuberculosis care in the area were lack of security, health facility destruction, theft of essential equipment, and drug supply disruption.

Conclusion and recommendation

Many tuberculosis patients failed to visit health facilities during the war. There was substantial physical damage to health care facilities and systematic looting of diagnostic equipment. Restoring basic public services and revitalizing clinical care for tuberculosis need urgent consideration.

Introduction

The recent war in Tigray, Ethiopia, devastated the health care system, leaving 85% of the health centers and 70% of the hospitals partially or completely non-functional. They were looted and destroyed by combatants, as reported by Médecins Sans Frontières [ 1 ]. Some medical personnel were put to death while others fled or were forcibly relocated. Of 312 ambulances in Tigray, 274 were stolen or destroyed [ 1 , 2 ]. In addition, the war caused massive civilian displacement, starvation, overcrowding, and the shutdown of basic public services (telecommunication, banking, and transportation). Nearly three million civilians were displaced internally or fled to Sudan [ 3 ]. When active fighting decreased, the government imposed a siege. The war created fertile ground for the spread of TB and emergence of drug resistance. Under such conditions, TB-related morbidity usually doubles or triples [ 4 ].

In 2020, just before the conflict, there were about 6,697 tuberculosis (TB) patients (including 89 with multidrug-resistant TB), 43,000 people living with HIV/AIDS (PLWHA) patients, and 24,253 diabetes patients on follow-up [ 5 ].

We assessed the availability and utilization of TB clinical services in Tigray during the recent war (between November 2020 and July 2021) and compared it with the pre-war state. Furthermore, we assessed the challenges of providing TB clinical services in the region, including the damage to laboratory services. This will hopefully be an input as the region struggles to recover.

Tigray is one of twelve regional states in Ethiopia. It is situated in the northernmost part of the nation, bordering Eritrea to the north, Sudan to the west, the Amhara region to the south, and the Afar region to the east. As of 2022, the region’s population was estimated at 5.7 million ( https://www.citypopulation.de/en/ethiopia/admin/ET01__tigray/ ). Before the war, Tigray had two referral hospitals, 14 general hospitals, 24 primary hospitals, 231 health centers, and 741 health posts in its 7 zones (Refer to Fig.  1 ) [ 8 ]. TB diagnostic and treatment services were provided free of charge in all public health facilities.

During the study period Western Tigray was in the hands of foreign forces, with reports of ongoing ethnicity-based massacres of civilians. Access to the area was also denied to United Nations investigators and journalists. It was therefore excluded and the study conducted in the remaining six zones.

Map of Ethiopia showing the location of Tigray and its different zones

Study design and population

We used an explanatory sequential mixed method. First, we collected TB patient data (both susceptible and multidrug resistant forms) from health facility registries and we interviewed TB focal persons to assess laboratory-related damage. Next, we carried out in-depth interviews with TB case team coordinators, TB focal persons, laboratory staff, and medical directors to gather qualitative data regarding the difficulties faced in the diagnosis, management and treatment of TB.

Sample size determination and sampling procedures

Out of 229 health facilities in six zones, we randomly selected and visited 69 facilities (six general hospitals, twelve primary hospitals, and 51 health centers). Damage assessment related to laboratory diagnostics was possible in all 69 health facilities. However, we were unable to obtain the registers of 19 health institutions, as they were destroyed during the war; thus, TB service utilization data were collected from the 50 health facilities only. Eight in-depth interviews were conducted and saturation of information was used to indicate when to terminate recruitment and interview. The study participants were selected based on their position, professional relevance, and work experience. The participants were from a health center, a referral hospital, a reference laboratory, a district health office, and regional health bureau.

Data collection procedure and quality assurance

We developed a data abstraction format for the quantitative data collection. This contained the name and location of the health facility (urban or rural), total number of TB patients seen per month (September-July), the number of new MDR TB patients registered in any given month during the study period, and whether the patients received treatment. We used a different data collection tool to determine the amount of diagnostic equipment (microscopes, acid fast stain reagents, microscope slides, and GeneXpert machines) at each medical facility prior to and during the conflict. This data was used to evaluate the damage sustained by individual laboratories.

Health professionals experienced in data collection were recruited for data collection and the study team supervised the process. Four experienced investigators conducted the IDI in private settings with minimum noise. The demographics of respondents, the state of TB-related services in the respondent’s medical facility before and after the war in terms of diagnostics, the sufficiency of supplies, the effectiveness of the health delivery system, the case detection rate, and treatment outcomes were the primary topics covered in the interviews.

One day of training was given to the data collectors and supervisors. A pretest of the instruments was conducted in three health facilities outside of the study setting. Comments forwarded by the discussants and supervisors were incorporated.

Data analysis

Descriptive statistics were developed using percentages and means with standard deviations. We used a t-test to compare the patient visit data before and during the war. We performed stratified analysis by setting (urban vs. rural) and by zone.

With regard to the qualitative data, each audio-taped interview was reviewed multiple times, transcribed verbatim, and imported into Atlas.ti version 7.5 for coding and analysis. The transcribed and translated versions were read and reread. Filed notes and investigators’ memos were linked to the software. Two investigators openly coded and analyzed the data independently. The investigators held debriefing sessions throughout the data collection and analysis period. Thematic analysis was used; codes were developed based on the original terms used by participants, and then descriptions were subsequently developed followed by identification of the most frequently observed categories and development of themes.

Ethical clearance

Ethical clearance was obtained from Mekelle University College of Health Sciences Institutional Review Board (Ref.No. MU-IRB 2025/2022). Support letters were obtained from Tigray Health Bureau. In addition, permission was obtained from the head of each health facility before data collection. Verbal informed consent was obtained from each interview participant. Transcripts and voice recordings were kept on a password-protected computer and accessed only by the study team.

Quantitative section

Of the 69 institutions included in the study, we were able to analyze patient TB service consumption from 50 of them; as noted above, the registers of 19 health facilities were destroyed during the conflict, including nine from the Northwest zone, six from Central, two from Southeastern, and two from Southern zones 1 .

Pre-war (September-October), an average of 259 TB patients were seen each month in 50 health facilities. After the outbreak of war (November) this dropped to 169, a 34.5% reduction. Over time patients slowly resumed visiting, but the numbers remained lower than pre-war visit rate (Fig.  2 ).

Number of TB patients visiting study health facilities in Tigray before and during the war. The vertical line indicates the start of the war (November 4, 2020)

Reductions were statistically significant in the central, northwestern, and eastern zones (Table  2 ) and were higher in the central (72%) and northwestern (79%) zones (Fig.  3 ). Prior to the war 60% of tuberculosis patients were served in rural clinics; this number dropped to an average of 17% during the war (Fig.  4 ).

Map comparing tuberculosis patient visits shortly before (September and October average) and at the beginning of the conflict (November) in different zones of Tigray

TB patient visits in rural and urban health facilities before and during the war in Tigray

Multidrug-resistant TB patient care

In comparison to the pre-war period, the monthly average number of MDR TB patients decreased by 41% during the war. This decrease was statistically significant with p-value < 0.001 (Fig.  5 ).

New MDR TB cases reported by health facilities before and during the war in Tigray

TB diagnostic service in health facilities

The data indicated clearly that microscopes and other equipment were systematically looted. Fifty-three (69.7%), 35 (87.5%), and 15 (68%) microscopes were taken from or damaged in health centers, primary hospitals, and general hospitals, respectively, as depicted in Table  3 . Acid fast bacilli (AFB) staining chemicals were unavailable in 82%, 25% and 33% of the health centers, primary hospitals, and general hospitals, respectively. In addition, 2 GeneXpert PCR machines were stolen in the study area.

Qualitative section

Socio-demographic status of participants.

The interview participants were aged 27—60 years. Their level of education ranged from diploma to MSc/specialist physician. We interviewed a regional TB case team coordinator, a district (woreda) communicable diseases expert, an internist from a tertiary hospital, two TB focal persons from a health center and a primary hospital, a laboratory official from Tigray Health Research Institute, a laboratory technician from a primary hospital, and a medical director.

Pre-war TB diagnosis and treatment services in Tigray

Before the war, clinical care of tuberculosis was available in all public health facilities free of charge. The private sector diagnosed 28–35% of new cases in Tigray, but once diagnosed, 80% of them were referred to public health facilities for treatment and follow-up. The Ethiopian pharmaceuticals supply agency (EPSA), a government body, supplied all TB medications and reagents every two months through its two hubs in Tigray. Prior to the war there were no major obstacles with supply.

AFB microscopy was available in all health centers and hospitals. The 14 GeneXpert machines in the region were located in the 14 general hospitals, two referral hospitals and in THRI (the Tigray Health Research Institute). ” “ Culture was available only in THRI. Before the war, THRI received about 1000 samples annually for culture and drug susceptibility tests . Tuberculosis focal person in Tigray Health Research Institute.

Prior to the war Tigray enjoyed a well integrated three-tier health care system. More than 1200 health extension workers played a key role in tuberculosis case detection in the community. They identified and referred presumptive TB patients to their catchment health centers. Some 80% of Tigray’s population lives in rural areas. Health extension workers received TB patients for directly observed therapy, DOTS treatment and follow-up close to their homes.

The health extension program was first started in Tigray 20 years ago with a main focus on maternal health and infectious disease prevention and later tuberculosis was added to the package. Tuberculosis case team coordinator from the regional health bureau.

The post office facilitated the transport of samples for GeneXpert and mycobacterial culture. Over time the case detection rate, treatment success rate and cure rate showed good improvement. All health facilities regularly reported all tuberculosis data (diagnosis, treatment and outcome) quarterly to the region’s health bureau using DHIS2.

TB diagnosis and treatment services in Tigray during the war

When Tigray was occupied by the allied forces (mainly Ethiopian National Defense Forces and Eritrean troops), a region-wide curfew was imposed. For two months, all basic public services including telecommunication, electricity, banking and transportation were stopped. Even ambulances were not allowed to work. Many health facilities were used as military stations, ruined deliberately and looted. Many health care workers, fearing for their lives, fled.

They used our hospital as a camp and took our microscopes. ” “We were running for our lives, but we were visiting the hospital occasionally. Five of the 10 patients came to the hospital after some stabilization, and I told them to go to Mekelle [the city least affected by the war and 72kms far]. A nurse from a primary hospital.

The largest hospital in Tigray, Ayder Comprehensive Specialized Hospital, located in the state capital Mekelle, was not directly attacked. But the surge of internally displaced people and lack of resources severely hampered patient care.

Our TB clinic served many patients asking for anti-TB medication but without any documents or referral. They came from the rural areas. An internist from Ayder Hospital.

About two months after the start of the war, active war became localized to some specific areas in Tigray and many public services (telecommunication, banking and transportation) began providing limited services. After eight months of occupation, the Tigray Defense Force expelled Ethiopian National Defense Force and Eritrean troops from Tigray. The federal government responded by blocking all telecommunication, electricity, banking and transportation and imposing a complete blockade, including food and fuel. It also suspended civil servant salaries and severely restricted the supply of anti-TB and other medications.

We walked on foot to and from the health facilities because there was no transportation as a result of fuel shortage. But at least we enjoyed peace and there was no one who would kill us. A nurse from a primary hospital. Only moral values kept us working without any payment for 14 months. An internist from Ayder Hospital.

Steps towards recovery

At the time of writing, most part of Tigray is free of active conflict after 2 years of all rounded siege, though the western Tigray, some part of southern Tigray and many areas bordering Eritrea remain tenuous. Telecommunications, banking, and other public services are functioning.

Tracing patients who were lost to follow-up is a challenge. Laboratory testing is essential to check for development of drug resistance (multidrug or extensively drug resistant). For patients with MDR TB, there are no second-line medications.

We can’t talk about TB control without having even a microscope. Patients who came back after stopping medications will require either GeneXpert test or drug susceptibility tests to make sure the disease hasn’t progressed to the next stage of resistance, but we don’t have them. Currently, GeneXpert is functional only in Mekelle. A health bureau TB coordinator.

Other interviewees were less pessimistic. An official at the THRI laboratory said they had organized mass screening in IDP centers for tuberculosis and other diseases, and they have found some TB patients lost to follow up, including MDR TB patients. These patients have been linked to facilities in Mekelle. They also hope to distribute 6000 anti-TB kits, some microscopes and reagents in collaboration with EPSA.

In this study, we assessed the status of clinical care related to TB services and its utilization by patients in health facilities in Tigray during the war period and compared it with the short and immediate pre-war period. The damage sustained by laboratories was assessed and challenges to the regional TB prevention and control program evaluated.

At the start of the conflict the number of TB patients using TB related medical services decreased by 34% in Tigray, by 79% in the northwest. This reduction persisted throughout the duration of the study, though it got progressively milder. A 38% increase in patient flow to Mekelle and Southeastern zones only partially compensated the 254% reduction in the other four zones. Mekelle and Southeastern zones are located in the center of Tigray and the war was most active in the peripheral part of the region. The large decrease in the detection of multidrug resistant forms of tuberculosis is very worrisome.

The primary causes of the decreased service utilization were the intentional destruction of medical facilities, the blockade of essential pharmaceuticals, the targeting of civilians and security fears, the migration of patients (both internal and abroad), and the cessation of critical public services. These results align with other studies and reports from Tigray [ 1 , 6 , 7 , 8 , 9 ]. Health institutions in the study area have lost more than 75% of their TB laboratory diagnostic capacity with 103 of 138 microscopes having been stolen or damaged. The global objective of delivering patient-centered tuberculosis care is undermined by patients having to travel from their communities to metropolitan health institutions in order to receive medical care [ 10 ].

When TB patients cannot access appropriate care their options are limited: they can move to less affected areas, look for alternative medicine from traditional healers and religious sites, or die at home. Ethiopians frequently travel to holy water sites in search of remedies [ 11 , 12 ]. These all could result in the disease spreading widely, leading to higher mortality and the emergence of drug resistance. Currently the nation has a relatively low MDR TB prevalence, just 1.1% of newly diagnosed cases and 7.5% of those who have received treatment [ 13 , 14 , 15 ].

Patients who migrate in large numbers to safer areas run the risk of spreading the disease during travel and when they seek shelter in internally displaced person shelters. IDP centres are too often characterized by hunger and overcrowding. Moreover, medical facilities in less impacted areas are unlikely to be able to deal effectively with a sudden surge in demand. Once in refugee camps, the stigma associated with TB is high. This can reduce patients’ health-seeking behaviour and compliance with medications [ 16 ]. These patients not only continue to transmit the disease but are also at high risk of death (up to 2/3rd of them) or severe disability [ 17 ]. In addition, a substantial proportion of MDR TB patients with primary drug resistance and associated mortality could be anticipated in the region as has been shown in previous armed conflicts [ 18 ].

Continuation of the TB program in countries with complex emergency situations is possible, as reported in different studies [ 16 ]. However, this requires a strong commitment from governmental and nongovernmental actors. During the Tigray war, no government or non-governmental agency was able to sustain the tuberculosis program in the region, despite repeated pleas from the region’s healthcare workers.

The health system in Tigray has sustained enormous damage: interruption of childhood vaccines (including vaccines against TB), migration of health care workers, destruction of health facilities, looting of medical equipment, stock-out of essential supplies, and dismantled referral and reporting system. Restoration of this system requires much work and investment. Healthcare providers who do not receive their wages for months are forced to migrate. This requires an urgent solution [ 19 ].

This study has several limitations. The clinical TB service utilization part of the study covered only the first part of the war (eight months) and excluded areas worst affected (western Tigray and villages bordering Eritrea) for security reasons. The comparative pre-war period, the two months immediately before the war, may not be representative as the looming war could have affected TB care even before the war. Any or all of these factors can lead to underestimation of the impact of the war. In addition, data from 27% of the study health facilities were unavailable due to the damage to the health facilities or TB registries and the number of TB cases in the study might have been underestimated (both before and during the war). Regarding the interviews, the process might have been influenced by the researchers’ background, experience, prior assumptions, and values. This may have shaped the conversation and affect the participants’ replies.

We propose undertaking a more comprehensive study assessing the prevalence of the disease in the population and the magnitude of lost to follow-up patients.

The war has resulted in enormous disruption of TB care and requires urgent restoration. The result will be higher mortality, higher disease prevalence, and possibly different patterns of disease, including higher rates of drug resistant TB. Bringing the region back to the pre-war level of TB diagnosis, treatment, and monitoring will take many years and considerable investment.

Data availability

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Acknowledgements

We want to acknowledge the staff of school of public health (Mekelle University), Tigray regional health bureau and Tigray health research institute for assisting in the data collection. We particularly thank Belaynesh Debesay from Tigray regional health bureau for collecting the MDR TB data. We also extend our thanks to Dr. Marc Clark for his thorough revision of the manuscript

The authors did not receive any funding for this work.

Author information

Authors and affiliations.

School of Medicine, College of Health Science, Mekelle University, PO Box: 1871, Mekelle, Ethiopia

Kibrom Gebreselasie Gebrehiwot, Teklay Gebrecherkos & Wegen Beyene Tesfamariam

School of Public Health, College of Health Science, Mekelle University, Mekelle, Ethiopia

Gebremedhin Berhe Gebregergis, Measho Gebreslasie Gebregziabher, Gebregziabher Berihu, Tsegay Wellay, Tesfay Gebregzabher Gebrehiwet & Gebretsadik Berhe

Tigray Health Research Institute, Mekelle, Tigray, Ethiopia

Hailay Gebretnsae, Letebrhan Weldemhret, Goyitom Gebremedhn & Hadish Bekuretsion

Tigray Regional Health Bureau, Mekelle, Tigray, Ethiopia

Aregay Gebremedhin

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KG and TGG contributed to the conception of the study, study design, data analysis, and manuscript writing. TGG, GBG, HG, HB, LW, GG, AG, GB, TW, TG, MG, WBT, and GB contributed to the research design, data collection, and analysis. All authors read and approved the final manuscript.

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Correspondence to Kibrom Gebreselasie Gebrehiwot .

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Ethical clearance was obtained from Mekelle University, College of Health Sciences Institutional Review Board (Ref.No. MU-IRB 2025/2022). Support letters were obtained from Tigray Health Bureau. In addition, permission was obtained from the head of each health facility before data collection. Verbal informed consent was obtained from each in-depth interview participant.

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Gebrehiwot, K.G., Gebregergis, G.B., Gebregziabher, M.G. et al. War related disruption of clinical tuberculosis services in Tigray, Ethiopia during the recent regional conflict: a mixed sequential method study. Confl Health 18 , 29 (2024). https://doi.org/10.1186/s13031-024-00583-8

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Received : 11 May 2023

Accepted : 14 March 2024

Published : 10 April 2024

DOI : https://doi.org/10.1186/s13031-024-00583-8

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Health | Girl, 5, at migrant shelter recovering from…

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Health | Girl, 5, at migrant shelter recovering from tuberculosis, her father says, as city officials confirm ‘small number’ of cases

The worried father stood watch throughout the night Monday as his 5-year-old suffered through a strong fever. He put rags on her forehead, forced her to drink sips of water and tried to calm her down.

The Venezuelan man said he had pleaded for help from staff that night at the city-run migrant shelter on Ogden Avenue where they are staying, but he was told he’d have to pay for the ambulance himself.

“Because I don’t have a work permit or any money, I didn’t have any way to pay for it,” said the man who didn’t want to share his name out of fear of being kicked out of the shelter for talking to reporters.

On Tuesday afternoon, he said his daughter tested positive for tuberculosis, apparently one out of a “small number” of confirmed tuberculosis cases in migrants at city-run shelters. The Chicago Department of Public Health declined to answer questions on the exact number of migrants with active cases of tuberculosis and which shelters were affected. 

The father told the Tribune that hours after the girl’s fever was at its peak, health care officials sent the man’s daughter to the hospital. She stayed there for days, he said, and then was given medication and released back to the West Loop shelter.

“My daughter should not be in a shelter right now,” he said. “The hospital told me she needs to have a high level of medical care — an area where there is a low risk of infection.”

According to Jacob Martin, a spokesperson for CDPH, there have been tuberculosis cases detected in shelters since migrants first were bused to the city in 2022, but almost all are latent cases. In shelters, migrants who have active cases of tuberculosis are assigned a nurse case manager who conducts a contact tracing investigation. The city has yet to confirm any cases in Chicago which resulted from exposure to new arrivals, Martin said.

Martin emphasized that there is no tuberculosis outbreak, and no cause for public concern. It’s still unclear how many active cases have been detected in shelters in recent days. 

“It is absolutely not an outbreak,” Martin said. “In order for us to characterize something as an outbreak, we need to have evidence of person-to-person transmission, which we do not have.”

It’s the latest infectious disease confirmed to reach shelters after a measles outbreak last month leading to questions about the health and safety of the nearly 9,700 migrants who live in close quarters in 21 shelters run by the city and state.

Since March 7, there have been 56 cases of measles in Chicago, including 33 children under the age of 4, according to the CDPH. 

Tuberculosis is a serious bacterial infection that usually attacks the lungs, but can spread to other parts of the body. It’s rare, but 100 to 150 cases are detected in Chicago each year. The disease usually requires several hours of prolonged contact for airborne transmission and is treatable with antibiotics. 

Latent tuberculosis is when a person is infected but remains asymptomatic and non-contagious, according to the CDPH.​​ In around 5% of those cases, the bacteria will reactivate, causing symptoms later in life. 

Martin said it was “important to note that an estimated 10% to 20% of residents of Central and South America have latent TB infection, which is asymptomatic and not transmissible to others, but does result in a positive TB test.”

More than 38,500 migrants have arrived in Chicago since Texas Gov. Greg Abbott began busing new arrivals from the southern border in August 2022. 

Given how many people are exposed to tuberculosis in certain developing countries, it’s not surprising or concerning to see cases in shelters, according to Emily Landon, an infectious disease doctor at the University of Chicago Medicine and the hospital’s executive medical director of infection prevention and control.

“I’m surprised by how few cases that we’ve seen, actually,” Landon said. “(Tuberculosis) doesn’t pose a huge risk to the public, certainly not as much as measles does.”

The disease is usually diagnosed with a blood test and chest X-ray, and a patient is considered noncontagious after two weeks of taking an antibiotic. 

“The vast majority of cases that we do see are people who contracted it years and years ago, and it reactivates in their body and they get sick, but it’s not because they got it from somebody else,” Martin said.

Though it’s considered less infectious than measles, there’s still a chance for primary cases to develop in crowded shelters, according to Bessey Geevarghese, a pediatric infectious disease specialist at Northwestern Medicine Central DuPage Hospital.

“The risk is definitely highest with close encounters,” Geevarghese said. “So, you know, especially in the shelters, where there’s a lot of people and people may already have latent tuberculosis, they’re slightly at higher risk.”

At a shelter in Pilsen Thursday afternoon, few migrants had heard of tuberculosis cases. But some had grown alarmed after watching the news and finding out of another contagious disease spreading in the heavily populated spaces, they said.

“We don’t want the same thing that happened with measles to happen again,” said Alejandra Hernandez, a mother of three young children. “They (the city) should let us know as soon as possible for us to find ways to protect our children.”

Hernandez said that her children were all vaccinated against tuberculosis but that nonetheless she is worried about how or if the infectious bacterial disease could affect other migrant children.

What also makes tuberculosis difficult to navigate is its longer incubation period, which can make contact tracing difficult, experts said. People can be infected but not have any symptoms for up to a month. 

“I’m hoping that the health department is doing a really good contact tracing to make sure that they identify anybody that’s exposed, and make sure that they’re screening those people sooner than later,” Geevarghese said.

When migrants first arrive in Chicago at landing zones, they’re screened for acute medical issues, including symptoms of tuberculosis, according to Martin. Those who exhibit symptoms are sent to local hospitals and receive further evaluation. 

New arrivals are also screened for vaccine eligibility, including measles, the flu and COVID-19. While there is a tuberculosis vaccine, it’s mainly used in countries where the disease is more common. It also doesn’t guarantee immunity. 

Still, Landon said she felt confident in the city’s ability to detect and prevent active tuberculosis cases. 

“There’s a lot of concerns with shelters, but I don’t think everybody getting TB is one of them,” Landon said. “That’s probably not high on my list of things that are concerning.”

Meanwhile, the father of the 5-year-old said his daughter is recovering. She was given medicine to take for the next four months, he said.

But he remains worried. He said almost all of the children at the shelter have a cough or a cold. All three of his children are sick, and he wishes the shelter staff provided more care.

On Thursday, a friend gave him $10 so he could buy soup for his daughter.

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US tuberculosis cases were at the highest level in a decade in 2023

This 2006 electron microscope image provided by the Centers for Disease Control and Prevention shows Mycobacterium tuberculosis bacteria, which causes the disease tuberculosis. The number of U.S. tuberculosis cases in 2023 was the highest in a decade, according to a report released by the CDC on Thursday, March 28, 2024. (Janice Carr/CDC via AP)

This 1966 microscope photo provided by the U.S. Centers for Disease Control and Prevention shows Mycobacterium tuberculosis bacilli, the organism responsible for causing the disease tuberculosis. The number of U.S. tuberculosis cases in 2023 were the highest in a decade, according to a report released by the CDC on Thursday, March 28, 2024. (Elizabeth S. Mingioli/CDC via AP)

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NEW YORK (AP) — The number of U.S. tuberculosis cases in 2023 were the highest in a decade, according to a new government report.

Forty states reported an increase in TB , and rates were up among all age groups, the Centers for Disease Control and Prevention said Thursday. More than 9,600 cases were reported, a 16% increase from 2022 and the highest since 2013.

Cases declined sharply at the beginning of the COVID-19 pandemic, but have been rising since.

Most U.S. TB cases are diagnosed in people born in other countries. Experts say the 2023 number is in part a combination of a surge in TB cases internationally — the World Health Organization said TB was behind only COVID-19 in infectious fatal diseases worldwide in 2022. And there are also increases in migration and post-pandemic international travel.

But other factors are also at play, including other illnesses that weaken the immune system and allow latent TB infections to emerge.

CDC officials expected TB numbers would rise, but the 2023 count “was a little more than was expected,” said Dr. Philip LoBue, director of the agency’s Division of Tuberculosis Elimination.

Despite the jump, the number and rate of new TB cases each year remains smaller than it was in the past, and the U.S. has a lower rate of new TB cases than most countries.

Tuberculosis is caused by bacteria that usually attack the lungs, and is spread through the air when an infectious person coughs or sneezes. If not treated properly, it can be fatal. In the late 1800s, TB killed one out of every seven people living in the United States and Europe. But the development of antibiotics and public health efforts succeeded in treating infections and tracking down those they infected, leading to cases falling for decades.

The new CDC statistics are not a count of how many people were newly infected in 2023, but rather of how many people developed a cough or other symptoms and were diagnosed.

An estimated 85% of the people counted in 2023 were infected at least a year or two earlier and had what’s called latent TB, when the bacteria enters the body and hibernates in the lungs or other parts of the body. Experts estimate as many as 13 million Americans have latent TB and are not contagious.

When the immune system is weakened — by certain medications or other illnesses like diabetes and HIV — the TB wakes up, so to speak. Nicole Skaggs said she was infected in 2020, but didn’t develop symptoms until 2022 — after she got sick from COVID-19.

“Anything that can take out or lower your immune system can put you at risk,” said Skaggs, 41, a property manager in Bothell, Washington.

CDC officials called the idea that COVID-19 has played a role in increased reactivation of TB “an important question.” Scientists are still learning what causes latent TB to reactivate and “I would consider it an unknown at this point,” LoBue said.

“It’s too early to tell” what will happen to TB trends in the next few years, he also said.

There are TB vaccines being developed, and public health workers that were focused on COVID are now back to trying new approaches to preventing TB. New York City, which saw cases jump 28% last year, is hiring TB case managers and community health workers and increasingly using video monitoring of patients taking medications to keep treatment rates high, said Dr. Ashwin Vasan, the city’s health commissioner.

On the other hand, federal TB funding for state and local health department efforts has been flat, and one of the key antibiotics used against TB has been in short supply in recent years. Plus, drug-resistant TB infections have popped up in a fraction of cases.

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.