thesis statement about malaria

• UNC Chapel Hill

MALARIA RESEARCH

• 1 Within Host Diversity of Malaria Infections
• 2 Spatial Epidemiology of Malaria
• 3 Diagnosis Resistant Malaria
• 4.1 Molecular Epidemiology of Drug Resistance
• 4.2 Chloroquine Resistance in Plasmodium vivax
• 4.3 Impacts of ACT Partner Drugs on Population Structure
• 5 Population Genetics of Plasmodium vivax
• 6 Malaria Vaccine Antigen Diversity
• 7 Transmission of Malaria
• 8 Malaria Relapse

Within Host Diversity of Malaria Infections

A major focus of IDEEL@Carolina’s research has been studying the diversity of malaria parasites both within populations as well as within people. Early on, our work focused on studying drug resistance and outcomes of clinical trials and the impact that with-in host diversity might have on interpreting studies. We were the first investigators to report on the presence of low level variants containing drug resistance in polyclonal malaria infections. These “minority variant” parasite strains in these infections have the potential to act as a reservoir of rug resistance in a population. This could limit the re-introduction of drugs to areas where sensitive parasites have repopulated after withdrawal of an antimalarial therapy. These minority variants also have the potential to lead to misclassification of results from clinical trials . We showed that WHO recommended genotyping methods can miss variants within an infection potentially leading to misclassification of trial results and impacting drug efficacy estimates.

After these initial advances, Dr. Juliano began to leverage second generation sequencing technologies to understand with-in host diversity of malaria infections. He was the first person to publish using these techniques , showing a much higher with-in host diversity of infections than previously thought. Since that time, he and other IDEEL@Carolina investigators have continued to use these methods for not only describing with-in host diversity, but to try to understand basic biology processes that occur within the host, such as strain selection by antimalarials or relapse patterns in Plasmodium vivax .

Key to this work has been the collaboration with Dr. Jeffrey Bailey at UMass (see Collaborators). Dr. Bailey’s group has been critical in developing the bioinformatic tools necessary for conducting these studies. His group has launched a free analysis tool, called SeekDeep , for analysis of deep sequencing data from polyclonal infection. This tool is not only applicable to malaria, but can be used to analyze microbiome data or other systems in which more than one strain infects the same host.

The advances in bioinformatics has allowed us to now use these tools to track the relative frequency of parasite strains with-in individuals over time. Using these tools, IDEEL@Carolina investigators have found parasite strains that clear more slowly in Africa to artemisinin combination therapies. The clearance half-lives are similar to those of artemisinin resistant parasites currently found in SE Asia. We are currently following up these initial results with a clinical study with our collaborators in Tanzania and Kenya.

Spatial Epidemiology of Malaria

As has been historically seen in India and Sri Lanka, when malaria control efforts are reduced, malaria resurges. However, it is unclear how malaria is being reintroduced to areas where control has waned. This reintroduction could occur due to immigration of infected people or mosquitoes. We do not know how quickly this occurs, what geographic factors are most important, nor the relative contributions of infected mosquitoes and people.

Ecologists use landscape genetics to measure geographic factors which promote as well as prevent dispersal of infectious diseases, as measured by genetic intermingling. For example, grey wolf populations are less genetically related the farther apart they are and if there are bodies of water intervening. Landscape genetics is just starting to be used to measure rate of disease spread, using the rate of gene flow as a proxy. While the rates of gene flow in malaria have never been measured, determinants of genetic distance (Fst/[1-Fst]) have been studied for P. falciparum isolates from different islands on the Comoros archipelago. Genetic distance tended to increase with increasing Euclidian distance, and to decrease as the numbers of travelers between islands increased. Our group has been keenly interested in studying how malaria moves through the environment across landscape, as knowledge of the factors involved are critical for helping with malaria eradication and elimination. As an example, we have used gene flow to study the i mportation of malaria to Guatemala from the Congo as part of UN Peacekeeping efforts .

Recently, in collaboration with our colleagues at the University of Massachussetts and Imperial College, we constructed maps of P. falciparum genotypes using molecular inversion probes.   We found little structure among neutral markers (not under selection) but marked geographic structure for drug-resistant parasites.

Diagnosis Resistant Malaria

We recently completed the first national population-based study of P. falciparum parasites with deletions of the pfhrp2 gene, which produces the antigen (HRP2) detected by commonly deployed malaria rapid diagnostic tests (RDTs). RDTs currently account for 70% of malaria diagnoses in Africa and represent a major investment by multilateral donors. Because the vast majority of rapid diagnostic tests deployed in Africa are HRP2-based, pfhrp2 -deleted parasites can escape detection.

Dr. Parr and Dr. Meshnick led a multi-disciplinary effort to describe the prevalence and evolution of these mutant parasites in the Democratic Republic of Congo (DRC), resulting in the discovery of two clusters of pfhrp2 -deleted parasites. Initial population genetic analyses indicate that mutant parasites from these clusters are genetically distinct from wild-type parasites. Additional studies are underway to characterize their evolution using novel next-generation sequencing approaches and to understand their clinical impact. Through collaboration with the WHO and other partners, we are working to develop strategies for surveillance and improved policies for malaria control programs.

Malaria Drug Resistance

Molecular epidemiology of drug resistance.

The emergence of drug resistance to antimalarial has been a major impediment to global control of malaria. Resistance emerges rapidly to every antimalarial that has been used globally. Molecular epidemiology studies can help with understanding how resistance emerges and spreads.

Molecular markers of resistance have now been described for many antimalarials and have been useful for helping to monitor resistance. IDEEL@Carolina investigators have been involved with studies of these molecular markers in multiple countries around the globe. Recent work has included studying how resistance to sulfadoxine-pyramethamine (SP) developed and segregated between Eastern and Western Africa in the DRC , the global distribution of SP resistance mutations and their implications for SP use in IPTp as part of the Malaria in Pregnancy Consortium , and the emergence of mefloquine resistance in SE Asia . They have also been involved in developing new ways to monitor these molecular markers. They were the first group to use a pooling approach to assay for drug resistance mutations using next generation sequencing . Using these techniques, they were the first group to publish on K13 mutations , the gene associated with artemisinin resistance in SE Asia, in a large scale survey of African malaria infections (>1,000 individuals).

Chloroquine Resistance in Plasmodium vivax

Dr. Juliano has been working in a collaboration led by Thomas Wellems at the NIH to discover the genetic mechanisms behind chloroquine resistance in Plasmodium vivax . Chloroquine resistance has been spreading slowly since the 1980’s, starting in Indonessia and Papau and spreading globally. The molecular mechanism of resistance in P. vivax is different than that in Plasmodium falciparum , as coding mutations in the ortholog ( pvcrt ) of the gene associated with resistance in falciparum ( pfcrt) are not associated with resistance. Using a genetic cross generated in a chimpanzee, this team has been searching for genetic loci associated with resistance. Dr. Juliano’s lab has been responsible for the genome sequencing in this project and have help to identify a critical loci associated with resistance to chloroquine in the cross progeny.

The work on the NIH cross has led to a potential molecular marker of chloroquine resistance for P. vivax . Drs. Juliano and Lin are currently working with AFRIMS in Thailand and the Eijkman Institute of Molecular Biology in Indonesia to study these polymorphisms in natural parasite populations and to evaluate their relationship to chloroquine failure using well characterized clinical samples.

Impacts of ACT Partner Drugs on Population Structure

and Juliano have been using whole genome sequencing to study the potential impacts of artemisinin combination therapy (ACT) partner drug resistance on the population structure of Plasmodium falciparum in Cambodia. Their work suggests that partner drug resistance is promoting clonal expansion of artemisinin resistant parasites in the region. These findings have implications for understanding the evolution of partner drug resistance in the face of artemisinin resistance, and have implications for the use of triple ACTs in the region.

Population Genetics of Plasmodium vivax

Drs. Lin and Juliano have been studying the population structure, demographic history and genomic signatures of selection on the P. vivax populations in Cambodia using whole genome sequencing. Their work suggests that modification of transcription regulation might underly vivax malaria’s resilience to control measures in the region. The work highlights the needs for a better understanding of transcriptional regulation in malaria in order to better inform elimination and control efforts.

Malaria Vaccine Antigen Diversity

Although tremendous gains have been made against malaria, global control and elimination are unlikely to occur without the development of an effective vaccine. Many of the candidate vaccine antigens for malaria are highly polymorphic in natural parsite populations, leading to concerns about strain specific immunity decreasing vaccine efficacy. IDEEL@Carolina investigators have been involved in characterizing vaccine antigen diversity for many antigen using our deep sequencing approaches including: 1) pfs 25 and pfs 48/45 in P. falciparum , 2) circumsporozoite protein (the antigen in RTS,S) in P. falciparum and P. vivax , 3) apical membrane antigen 1 in P. falciparum and 4) merozoite surface protein 1 in P. vivax .

These types of studies can help elucidate critical aspects of how the antigen interacts with the human immune systems . Currently, we have a large effort going into understanding the diversity of var2csa from P. falciparum in a project led by Dr. Meshnick. This antigen is the ligand responsible for malaria binding to the placenta. An effective vaccine targeting this antigen could prevent placental malaria, a leading preventable cause of low birth weight infants in Africa. This work is being done in conjunction with the Institute Pasteur.

Transmission of Malaria

Efforts to eliminate malaria altogether hinge on the ability to prevent transmission. Dr. Lin is working with investigators at AFRIMS to assess the effect of transmission-blocking drugs and other interventions on human to mosquito transmission of malaria in SE Asia. Since much malaria is asymptomatic and microscopic, we are interested in learning the contribution of the asymptomatic reservoir to ongoing transmission and which field deployable diagnostics are most suited to elimination efforts. We are also studying the genetics of the parasite in the mosquito stages to learn how mosquito-borne transmission affects the spread of drug resistance.

Malaria Relapse

Plasmodium vivax is the second most prevalent malaria species in the world and causes much morbidity through its ability to reactivate from the liver and cause relapse. Interestingly, relapses of vivax malaria commonly occur after treatment of falciparum malaria . Safe and effective treatments are lacking, further complicated by the difficulty of distinguishing re-infections from relapse. IDEEL investigators have teamed with investigators in Thailand, Cambodia, and Indonesia to characterize genotypic signatures of relapse and are applying next generation sequencing techniques to samples from patients with multiple relapses as well as soldiers returning to non-endemic regions with known relapse. The long term goal of this work is to identify genetic determinants of relapse that can guide the development of new therapies.

• Open access
• Published: 12 September 2023

Knowledge, attitude and practices of malaria preventive measures among mothers with children under five years in a rural setting of Ghana

• Prince Adum 1 ,
• Veronica Adwoa Agyare 2 , 5 ,
• Joseph Owusu-Marfo 3 &
• Yaa Nyarko Agyeman 4  

Malaria Journal volume  22 , Article number:  268 ( 2023 ) Cite this article

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Malaria remains a major public health concern around the world, particularly in resource-constrained countries. Malaria still accounts for 40% of all Out-Patient Department (OPD) cases in Ghana, with children under the age of five being the most vulnerable group. The study assessed the knowledge, attitudes, and practices of malaria preventive measures among mothers with children under 5 years old in a rural setting in Ghana.

A cross-sectional study design with a quantitative approach was used in this study. The study was facility based and involved the use of interviewer administered questionnaires to collect data from 281 mothers with children under the age of five. Simple random sampling method was used to select the respondents. The data collected was analysed using the statistical package for the social sciences (SPSS) version 22 and results presented in tables.

There were 281 mothers, with 59.4% having children at the age of a year. The findings revealed that the majority of participants have a high level of knowledge about malaria’s causes, signs, and symptoms. Again, the majority of participants demonstrated a positive attitude toward malaria prevention, such as seeking treatment at a hospital within 24 h of suspecting their children had malaria and demonstrating good knowledge of malaria prevention practices. Despite this, 35.5% of respondents were not actively engaged in malaria prevention practices in a day prior to the interview. Respondents’ occupation, level of education, and religion had a statistically significant association with mothers’ attitude towards prevention (p-values < 0.05 and 0.01).

The study’s findings clearly demonstrate that the majority of mothers were knowledgeable about the causes, signs and symptoms, and preventive measures of malaria in children under the age of five. There was also statistically significant association between mothers’ demographic information, including level of education, occupation, religion, and their attitude towards malaria prevention. A keen interest should be directed toward the consistent application of low-cost preventive measures.

Despite significant efforts over the century to eradicate or manage malaria, it continues to be a serious public health problem throughout the world, affecting more pregnant women and children due to their vulnerability [ 1 ]. Malaria has been regarded as a long-standing global health problem because of the high morbidity and death rates among pregnant women and children [ 2 ]. In addition to that, malaria is viewed as a life-threatening condition caused by parasites that are transferred to people by the bites of infected female Anopheles mosquitoes [ 3 ]. Malaria is one of the most deadliest infectious disease, with an estimated 229 million cases and 409,000 deaths worldwide in 2019 [ 4 ]. According to Limoukou et al. [ 4 ], children under the age of five accounted for 67% (274,000) of all malaria fatalities worldwide. The African Region of the World Health Organization (WHO) bears a disproportionately large share of the global malaria burden, accounting for 94% of malaria cases and fatalities in 2019 [ 5 ]. In addition, malaria was responsible for more than 18% of under-five deaths in sub-Saharan Africa in 2019 [ 6 ].

Malaria is noted to be more geographically distributed in regions with warm climates and high levels of mosquito activity [ 7 ]. Therefore, extensive public health promotion initiatives are required in Africa to achieve long-term malaria control by focusing on contemporary and proven malaria prevention and management strategies, as well as the need to investigate the importance of malaria transmission with an emphasis on knowledge, attitude, and practices (KAP) [ 8 ]. Malaria’s poor outcomes were attributed to ineffective treatment and inadequate maternal knowledge of preventive measures, examples; poor logistics systems leading to undersupply of drugs and diagnostics, health workers issues, lack of self efficacy of women to provide the treatment as required, socio-cultural determinants of health, side effects management, partial drug resistance [ 9 ].

Ghana has not been left out, as it continues to battle malaria cases in children under-fives. According to Anaba et al. [ 10 ], Ghana recorded 2.3 million cases of malaria in out-patient department (OPD) in the first quarter of 2017. This figure represents a 1.5% increase over the number of cases reported in the first quarter of 2016 [ 10 ]. A nationwide survey in Ghana found that the average parasite prevalence among children aged 6 to 59 months was 28%. [ 11 ]. Malaria is also responsible for 40% of all out-patient visits in Ghana, with children under the age of five and pregnant women being the most vulnerable groups [ 12 ]. Over the last 2 years, significant efforts have been made to strengthen malaria prevention, as it remains the leading cause of death in Ghana, primarily among children under the age of five [ 13 ]. This demonstrates that the government’s efforts to strengthen malaria prevention are still insufficient to reduce the death rate. According to the evidence, strategies for controlling malaria in an endemic country include health education, changing attitudes and practices [ 14 ]. KAP studies are also important for developing epidemiological and behavioural baselines in malaria surveillance programmes, because misconceptions about malaria, for example, can lead to self-medication and incorrect use of insecticide-treated nets. As a result, assessing the population’s KAP in relation to malaria prevention is critical [ 15 ]. Despite some success in lowering malaria morbidity and mortality rates, some rural districts, such as Kintampo North, continue to have a high prevalence of malaria cases when compared to urban areas. According to Kwofie et al. [ 16 ], the rural and urban areas have 28% and 4% of the population, respectively. Adequate malaria knowledge among mothers has a strong correlation with lower morbidity and mortality among children under the age of five [ 17 ]. The investigation of local communities’ malaria KAP in Ghana is critical for the design and implementation of effective malaria control programmes [ 18 ]. Malaria cases increased marginally (1659, 1737, 1983) from 2016 to 2018, then decreased (1392) in 2019, with a further decrease to (1023) in 2020, according to Kintampo North Municipal Hospital annual reviews. Though there has been some progress, the numbers remain in the thousands and have not decreased significantly. The decrease in 2020 could be attributed to underreporting to hospitals as a result of the covid-19 pandemic. Several malaria studies have been conducted in Kintampo North Municipality, according to the literature reviewed [ 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Of all these studies conducted in Ghana, only the study by Anim [ 25 ] examined factors associated with reported severe malaria among children under 5 years old at the Kintampo Municipal Hospital. However, it did not specifically focus on prevention strategies. It has therefore become very clear that, to curtail the increasing cases of malaria in the municipality, much attention is required on the prevention of the malaria infection. The study aimed at assessing the KAP of malaria preventive measures among mothers with children under 5 years using a cross sectional study design. Only Anim [ 25 ] looked at the factors associated with reported severe malaria among children under 5 years old in the Kintampo Municipal Hospital, and even then, it was not focused on prevention. As a result, it is clear that, in order to reduce the rising number of malaria cases in the municipality, much emphasis must be placed on malaria infection prevention. A cross-sectional study design was used to assess the KAP of malaria preventive measures among mothers with children under 5 years old.

Study setting

The research was carried out at Kintampo North Municipal Hospital. Kintampo North Municipality, with Kintampo as its capital, was established in 1988 by legislative instrument 1480 as part of the Government’s decentralization programme. Kintampo North Municipality is one of 11 districts that comprise the newly formed Bono East Region. The total land area occupied is approximately 5108 km 2 (1192 sqmi). The total population is 109,448 people, with 4337 pregnant women and 21,889 children under the age of five. The municipality is strategically located in the centre of Ghana, serving as a transit point between the country’s northern and southern sectors. It is located between latitudes 80 45’ N and 70 45’ N, and longitudes 10 20’ W and 20 1’ E. The West African Frontier Force established the Kintampo Municipal Hospital as a clinic in 1940, and it was later upgraded to a district hospital. The Kintampo Health Research Centre and the College of Health and Wellbeing share the hospital’s boundaries and are located in the township’s heart. The research facility is the only referral facility in Kintampo North Municipality at the moment. The hospital has 160 beds, 3 medical officers, 10 physician assistants, and 200 nurses. The hospital provides medical, surgical, radiological, and laboratory services. The OPD and the Paediatric ward served as research recruitment points. The Paediatric ward can accommodate 30 patients.

Study design and sample size

A cross-sectional study design was employed with a quantitative approach. The study engaged mothers with children under 5 years old within the Kintampo north Municipal in the Bono East Region of Ghana. In all, a total of 281 mothers were selected for the study. Taro Yamane method of calculating sample size was used to determine the number of respondents needed for this study [ 26 ]:

n = N/(1 + N(e) 2 )

where n signifies the sample size, N signifies the population understudy, e signifies the margin of error (0.05), n = 1,000/ (1 + 1,000(0.05) 2 ), n = 1,000/3.6, n = 277.77, n = 278.

An assumed non-response rate of 1% was calculated on the sample size of 278. Thus, the final sample size of 281 of mothers with children under 5 years were recruited for this study.

Sampling technique

The study employed a facility-based sampling method, specifically targeting participants within the chosen healthcare facility. Within this facility, a combination of sampling techniques was used to ensure a diverse representation of mothers with children under the age of five. These techniques included selecting mothers who visited the emergency department, outpatient department (OPD), mothers of children admitted to the paediatric ward, and those who were able to communicate verbally. To minimize any potential bias in participant selection, a table of random numbers was utilized. However, it’s important to note that the choice of the study facility itself was intentional, as it served as the primary treatment centre catering to children under the age of five in the surrounding area. All mothers who met the inclusion criteria and were willing to participate were considered eligible for the study. It is worth mentioning that informed consent, obtained through signing or thumbprinting an informed consent form, was a prerequisite for participation. Mothers who did not provide such consent were excluded from the study. Participation was completely voluntary for all the respondents in the study facility.

Data collection instruments and procedure

The primary data collection instrument in this study was a structured questionnaire based on questions from similar published articles [ 4 , 15 , 27 ]. This study’s questionnaire included an introduction section with consent to participate, as well as four sections: Section A was the socio-demographic data, which included mothers’ age, marital status, number of children under the age of five, religion, educational level, and occupation. Section B dealt with mothers’ malaria knowledge, Section C with mothers’ malaria prevention practices, and Section D with mothers’ attitudes toward malaria prevention. Data was collected over a four-week period, from July 12th, 2021 to August 11th, 2021. The questionnaire was created in an electronic form on a computer using the Google Forms web application to minimize contact with study participants in order to control the spread of COVID-19 infection as well as the quality of data collected. The research assistants were trained on how to use Google forms to administer the questionnaire to the respondents one at a time. The link to the Google form was shared with those who could read and understand. However, for those who were unable to read or write, research assistants assisted them in answering electronic questionnaires by reading to them and selecting the appropriate response of the participants. The electronic questionnaire was read to the participants and translated in their preferred local language(s).

The following procedures were taken to ensure uniformity in the translation of the electronic questionnaire for participants who desired it to be read to them. First, qualified bilingual individuals were chosen who were fluent in both the questionnaire language and the participants’ preferred local language. These people were educated on the study procedure, questionnaire content, and the necessity of consistency in translation. These trained professionals read the questions aloud to the participants in their preferred local language throughout the administration of the questionnaire. All participants were treated with care to guarantee proper translation and consistency in tone, emphasis, and clarity. Any concerns or explanations requested by participants were consistently answered, in accordance with pre-established guidelines supplied to trained individuals. Several procedures were adopted to avoid bias in order to examine the potential discrepancies in replies between self-administered questionnaires and research assistant interviews. Interview procedures were thoroughly taught to research assistants, including the significance of neutrality, non-directiveness, and avoiding leading questions. They were told not to give further explanations or emphasize specific sections of the questions unless specifically requested by the participant. Furthermore, the interviewing skills of research assistants were regularly monitored and supervised to guarantee conformity to the specified guidelines. Any deviations or biases discovered throughout the monitoring phase were addressed immediately by retraining and reinforcing interview procedures. Although steps were made to reduce bias, it is vital to recognize that the presence of research assistants may have introduced some level of bias, such as accidental influence or urging. Attempts were made, however, to minimize these possible biases and maintain consistency in data collection across both self-administered questionnaires and research assistant interviews by giving explicit rules and regular supervision.

Pre-testing

The questionnaire was pre-tested on 20 randomly chosen mothers with children under 5 years old at the Sunkwa Clinic (a private rural clinic located in the Kintampo Municipality), and their feedback was used to update the questionnaire before the actual data collection began on the 11th of July, 2021. This was also to make the research assistants conversant with the electronic questionnaire.

Data processing and analysis

The data collected with the Google forms were exported to excel, validated, cleaned before importing into the IBM statistical package for the social sciences (SPSS) version 22 for data analysis. The data were analysed based on the study objectives and the main study variables. Descriptive statistics (frequencies and their percentages) and were computed and summarized in simple tables for categorical variables. Partial correlation of demographic variables and mothers’ attitude towards malaria prevention was also tested. All the results were summarised and presented in tables. Class intervals were also computed for percentages based on the study’s confidence interval of 95%.

Most of the mothers were between the ages of 30 to 34 years old (35.2%), married (76.9%) and had one child under the age of five (59.4%). The median age among the mothers was 30–34 years group. Majority of the respondents were Christians (50.5%), while most of them had tertiary level of education (28.5%). The least category of mother’s education level was primary education representing 14.2%. The majority of the respondents were self-employed (35.6) with civil servants forming the least (9.6%) (Table  1 ).

Most of the mothers interviewed had heard about malaria before (99.6%) (95% Cl: 98.9, 100). The dichotomous variable, with only two possible answers, was used for the question about whether physical contact can transmit malaria. In this case, 9.3% of them answered Yes (95% Cl: 5.7, 13.5), while 90.7% (Table  2 ).

Table  3 presents the main causes of malaria, including too much sun, a dirty environment, witchcraft, and mosquitoes. In all, 49.5% of the participants indicated mosquitoes as a factor for causing malaria. Meanwhile, mosquitoes were implicated in 97.5% of the multiple factors that cause malaria. The results in Table  4 listed the signs and symptoms of malaria as weakness, fever, and loss of appetite. Also, the study listed ‘all of the above (all)’ and ‘none of the above’ as possible answers. Majority (52.7%) of the respondents selected ‘all’ (weakness, fever and loss of appetite) as the signs and symptoms of malaria.

The results in Table  5 show mothers’ attitudes towards malaria prevention, including whether it is possible to recover from malaria without treatment, whether anyone can become infected with malaria, whether they seek health care when their children exhibit signs and symptoms of malaria, how quickly mothers seek treatment when their children are sick, and where they seek that treatment. With the possibility of recovering from malaria without treatment, the options were Yes or No. Most of the respondents (81.1%) responded No. It was discovered that 254 out of a total of 281 participants (90.4%) seek treatment at a hospital. It was also revealed that 5.3% use drugs at home and 4.3% use herbal preparations. When asked if anyone could contract malaria, 93.2% said yes. When it comes to how quickly respondents seek treatment, 46.3% seek treatment within 12 h, 42.7% within 24 h, 7.8% within 48 h, and 1.4% within 72 h. Most of the mothers know that malaria is a life-threatening disease (96.1%), seek medical attention when their children show signs and symptoms of malaria (98.2%) and dangerous not to complete malaria treatment (89.7%).

Table  6 depicts the association between the demographic information of the respondents, such as; (age, marital status, number of children under 5 years, religion, level of education and occupation) and the attitude of the mothers towards malaria prevention. Respondents’ occupation had a statistically significant association with mothers’ attitude towards malaria prevention (p-values < 0.05 and 0.01). Also, mothers’ marital status had a statistically significant association with mothers’ attitude towards malaria prevention such as; Malaria being a life-threatening disease (p-value < 0.05), promptness of seeking malaria treatment (p-value < 0.01), where to seek treatment (p-value < 0.01) and the danger not completing malaria treatment (p-value < 0.01). Other demographic information, such as religion, educational level and mothers’ number of children under 5 years of age had statistically significant association with mothers’ attitude towards malaria prevention.

The socio-demographic characteristics of the study is relevant in the prevention of malaria. Individuals’ educational attainment and their age emerged as particularly important factors for understanding the etiology of malaria. With education, the results revealed that all individuals with at least primary level of education correctly attributed the cause of malaria to a mosquito. This was in line with a study conducted in Douala, Cameroon [ 28 ], which found that the level of education was associated with the correct knowledge on the causative agent of malaria. It is, therefore, not surprising of the findings as governmental interventions to increase access to education in Ghana could have an additional effect of improving the overall health outcomes of the under-five population regarding malaria prevention in future. The relevance of age was also a factor, with the majority of respondents being between the ages of 20 and 35. It should be noted, however, that age alone does not determine an individual’s awareness or capacity in safeguarding their children from malaria. Education, access to information, and awareness campaigns may have a greater impact on knowledge levels about malaria prevention and child protection [ 15 ].

The current study revealed that majority of the participants knew that mosquitoes were the main causes of malaria among children despite the fact that they also added some other causes such as too much sun, witch craft, dirty environment, busy area. This is consistent with a study conducted by Asuamah et al. [ 29 ], in Northern Ghana where majority of the students knew about the cause of malaria. Also, a study among pregnant women in Kassena-Nankana East showed that overwhelming majority of study participants knew that mosquitoes causes malaria [ 30 ]. Similarly, the study by Talipouo et al. [ 1 ] in the city of Yaoundé noted that a majority of the women believed malaria was caused by mosquito bite. According to the WHO Global report [ 5 ], Ghana is among the 15 countries globally with the highest burden of malaria. Ghana is among the many countries that have adopted malaria prevention campaigns to reduce the incidence of malaria in the continent especially among pregnant women and children under 5 years. These campaigns adopted by the Movement of Ghana (MOG) could explain the higher appreciation of the cause of malaria. Similarly, there are deliberate attempts by the Ministry of Health through its agencies with the support of Non-Governmental Organizations, such as WHO or UNICEF, to increase knowledge on malaria prevention. These attempts in Ghana could be the reason for higher study participants knowing the actual cause of malaria. Due to the support received by most African countries on malaria prevention, it is difficult to get contrary views on the cause of malaria [ 31 , 32 ]. The high level of knowledge realized in this current study about signs and symptoms of malaria, agrees with a study conducted in South African on the knowledge, attitude and practices on malaria transmission at the Mamfene and KwaZulu—Natal Province where majority of the participants were able to identify three or four signs or symptoms of malaria [ 33 ]. This trend was also observed in Cameroun, where almost all the participants (90%) recognized the signs and symptoms of malaria [ 15 ]. This could be due to the fact that they are higher proportions of participants being educated and mature in age. This current study also had (99.6%) of participants who had heard about malaria. This finding corroborated with some studies in Ghana [ 34 , 35 , 36 ] where majority of the respondents have heard about malaria. Majority of the participants in this current study also attributed their source of malaria information to radio and television. These findings are similar to those of Asumah et al. [ 30 ] where the media was the major source of information on malaria issues. In the Kintampo Municipality in the Bono East of Ghana, the public health unit visits the radio stations twice every week to educate the population on disease conditions and their preventions. It could be that with the radio talk shows, these women are comfortable in their homes and listen attentively. Also, they can call into the programme to seek clarity. This could explain why majority of the current study participants obtained information on malaria via the media (Radio and TV). However, it should be noted that individual preferences and circumstances may influence the level of engagement. Factors such as the timing of the radio messages, including potential conflicts with meal preparation or water fetching time, could affect the listenership and attentiveness of women. This study revealed that majority of mothers have good attitude towards malaria prevention by seeking healthcare within 24 h when child experiences signs and symptoms of malaria in spite of some few misconceptions. This is in contradiction with another study conducted in Ghana at Asutsuare, a rural irrigated farming community in the Greater Accra Region which revealed that only 3% immediately visit a health facility for treatment whenever they suspected they had malaria [ 18 ]. The overwhelming majority indicated they only visit a healthcare facility for treatment if they felt the suspected malaria illness was severe or other treatment options had failed. The difference in the above studies could be due to the fact that this study only used mothers and was also conducted in the hospital whereas [ 9 ] study was conducted among a whole community which have different people from different ethnic groups and that could also have influenced the late reporting. Similar studies conducted in different countries in Africa [ 9 , 37 , 38 ] also affirms to the findings of this study on the conclusion that, despite some respondents delay in seeking health care for their children under 5 years, majority seek health care within 12 to 24 h when they suspected malaria infection. This is a good sign to improve child under five mortalities. Respondents’ occupation had a statistically significant association with mothers’ attitude towards malaria prevention. Also, mothers’ marital status had a statistically significant association with mothers’ attitude towards malaria prevention such as; Malaria being life-threatening disease, promptness of seeking malaria treatment, where to seek treatment and the danger not completing malaria treatment. Other demographic information such as; religion, educational level and mothers with number of children under 5 years of age had statistically significant association with mothers’ attitude towards malaria prevention. These studies have shown that education about attitude towards seeking healthcare at the right time should be intensified to save all children under 5 years.

Shockingly, 18.9% of the mothers in this study believe they could recover from malaria without taking any treatment. Malaria ought to be treated at all cost to avoid the cascading complication, such as anaemia [ 39 ]. The sickness pose by malaria can also make the mother weak hence her inability to breastfeed on demand. This suggest that for mother to think they could actually recover from malaria without taking medications; they tend to risk the safety of their babies [ 40 ]. Therefore, if the right drugs are used, people who have malaria can be cured and all the malaria parasites can be cleared from their body. However, the disease can continue if it is not treated or if it is treated with the wrong drug. The motivation for this is not known as far as the researcher is concern. The study, therefore, recommends more in-depth research to unravel the thinking that goes into this choice by the mothers.

In relation to above, the study further established that majority of the participants felts its dangerous not to complete the malaria treatment. Malaria parasite-based diagnosis is uncommon in the private health sector, particularly in the informal private retail sector dominated by patent and proprietary drug suppliers (PPMVs). There is availability of malaria test kits in every pharmacy. Just like any other laboratory test, they are false positives and false negative. Some do not even test to know their status [ 41 ]. As a result, malaria drugs are sold and used without parasitological proof. This overuse of artemisinin-based combinations may result in malaria parasite resistance, negating the need to investigate the true cause of fever and, more crucially, glossing over life-threatening infections that might be deadly. Overall, the objective of delivering effective malaria case management, improving parasitological testing availability, and meeting national and global targets may be jeopardized. Overdiagnosis and overtreatment of malaria have been observed in Nigeria [ 42 ], Tanzania [ 43 ] and Ghana [ 42 ]. Malaria treatment should not be prescribed unless malaria is confirmed. This will help in limiting resistance of malaria infection towards the anti-malarial drugs. The knowledge about malaria prevention and the successful implementation of malaria control efforts will depend on understanding by all people involved [ 44 ].

From this study, it could be deduced that even though mothers seeking treatment from Kintampo Municipal Hospital have a high knowledge on malaria preventive practices, it is poorly reflected in their practice. The study conducted in a city of Yaoundé among urban dwellers on malaria prevention practice was not significantly different as the study affirmed the assertion that even though the urban dwellers have good knowledge on malaria prevention measures, few people apply the preventive measures [ 1 ].

The study findings indicate that the participants employed various strategies to protect themselves against malaria, including the use of insecticide-treated bed nets (ITNs), mosquito coils, mosquito sprays, and good nutrition. Insecticide-treated bed nets (ITNs) have been proven effective in reducing malaria illness, severe disease, and mortality, particularly among children under 5 years old [ 30 , 45 , 46 ]. As a result, pregnant women are encouraged to use ITNs for sleeping. Indoor Residual Spraying (IRS) and ITNs are recommended as highly effective preventive measures, reducing mosquito-human contact through insecticidal effects and physical barriers, respectively. According to a report by the WHO, ITN coverage increased in Africa from 29% to 2010 to approximately half of the population at risk of malaria between 2015 and 2017 [ 47 ].

Despite these interventions, malaria still incurs substantial costs, with approximately $12 million spent annually on diagnosis and treatment, causing an estimated economic loss of 1.3% in highly endemic countries [ 48 ]. The use of mosquito coils, although popular in malaria-endemic regions, is not recommended as a preventive measure against mosquitoes [ 49 ]. Mosquito coils contain insecticides that slowly vaporize when lit, aiming to provide protection against mosquitoes. However, the smoke emitted by mosquito coils can contribute to indoor air pollution and potentially lead to acute respiratory infections (ARIs) and other illnesses [ 50 ]. While mosquito coils are widely used in developing nations due to their affordability and accessibility, they can emit harmful emissions such as carbon monoxide, particulate matter, polycyclic aromatic hydrocarbons (PAHs), aldehydes, ketones, and various volatile organic chemicals (VOCs) [ 49 , 51 ]. These emissions result from incomplete combustion, intentionally designed to delay the release of the pesticide. Exposure to these pollutants may have adverse health effects, with particulate matter linked to ARIs and VOCs and PAHs associated with cancer [ 51 , 52 ]. To summarize, the study findings emphasize the importance of ITNs as an effective preventive measure against malaria, while cautioning against the use of mosquito coils due to potential health risks associated with indoor air pollution.

The findings of this study also corroborated with a health facility base study in Ethiopia to establish the prevalence of malaria and KAP towards malaria among febrile patients at Chagni health centre, which concluded that participants have high knowledge on the causes of malaria, good attitude towards malaria and good preventive practices [ 53 ]. Aside all that, there were some misconceptions about the knowledge, attitude and practices. Similarities in study findings could be due to the fact that both studies were conducted in a hospital setting with adult population. The study has some limitations; it is admitted that because KAP ratings are based on self-reported actions, this study is susceptible to recall and courtesy bias. These claimed actions may not necessarily correspond to actual practices, emphasizing the importance of additional observational studies to corroborate the reported behaviors. Furthermore, when interpreting the data, the well-known KAP-GAP, which refers to the gap between knowledge, attitudes, and behaviours, should be considered. Furthermore, the study acknowledges the role of the larger health system and social-cultural-economic variables on adherence, which can alter reported behaviours. These aspects should be considered when interpreting the findings and extrapolating them to other scenarios.

The findings of the study pointed out that, majority of the mothers were knowledgeable about the causes, signs and symptoms and preventive measures of malaria in children under 5 years old. However, few misconceptions still exit on the part of some mothers. It was seen that; formal education does have influence on mother’s knowledge on malaria. There was statistically significant association between mothers’ demographic information such as level of education, occupation, religion, and their attitude towards malaria prevention. The study found that ITN, mosquito coils, and mosquito spray were the most effective malaria-prevention methods used by mothers of children under the age of five. Even though, mothers have good knowledge on the preventive methods of malaria, a lot of mothers are still adamant in using the protective methods. Mothers go to hospital earlier to seek treatment when they suspect their children are having malaria and that is a positive sign in the ongoing prevention of mortalities related to malaria in children under 5 years. Interventions should intensify sensitization targeted on the use of known preventive measures. Monitoring strategies to visit homes to encourage mothers on the use of preventive methods.

Implication of the study

The study’s findings can assist improve public health strategies and programmes focused at reducing malaria prevalence and boosting preventative practices among mothers in rural areas. Policymakers and healthcare professionals can establish focused initiatives to address knowledge, attitudes, and practices gaps and promote effective malaria prevention measures by identifying gaps in information, attitudes, and practices. The study emphasizes the relevance of education in improving malaria preventive knowledge. The findings can be used to influence the development of educational campaigns aimed at boosting awareness about the causes, symptoms, and preventive measures of malaria among rural mothers. This can lead to more informed decision-making and more aggressive malaria prevention strategies. The study emphasizes the need of mothers seeking medical attention as soon as their infants show signs and symptoms of malaria. The findings can help politicians and healthcare practitioners emphasize the necessity of obtaining treatment as soon as possible and enhance rural access to healthcare facilities. This could include initiatives like expanding the availability of healthcare facilities, assuring treatment affordability, and raising knowledge about the consequences of postponing treatment. The research identifies shortcomings in the actual application of preventive measures among rural women. The findings of this study can help to improve the adoption and consistent use of preventative measures such as insecticide-treated bed nets (ITNs), adequate sanitation practices, and environmental management to reduce mosquito breeding places. The study can help lower the burden of malaria in rural regions and enhance the overall health outcomes of children under the age of five by addressing these gaps. The study gives unique insights into the malaria prevention knowledge, attitudes, and practices of women in a rural context. These findings can be used to guide future study on related themes, allowing researchers to investigate additional factors that influence preventive measures, assess the effectiveness of interventions, or investigate specific obstacles experienced in rural locations. This can contribute to a more comprehensive understanding of malaria prevention and support evidence-based public health decision-making. In summary, the findings of this study have the potential to inform public health interventions, improve educational campaigns, improve access to healthcare, strengthen preventive practices, and guide future research efforts in malaria prevention among mothers with children under the age of five in rural Ghana.

Availability of data and materials

Data can be obtained from the corresponding author on reasonable request.

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Prince Adum

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Veronica Adwoa Agyare

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Joseph Owusu-Marfo

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Authors, PA, VAA and JOM conceived and designed the study, JOM performed the data analysis. PA, VAA, JOM, and YNA interpreted the analysis for intellectual content. PA wrote the draft manuscript. VAA, JOM, and YNA edited the manuscript. All authors revised the manuscript, read and approved the final manuscript.

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The study was approved by the Ethics Review Committee of the Ghana Health Service (GHS) with reference number GHS-ERC: 057/04/21 before data collection. Participants were given consent forms to read before being interviewed and those who could not read had them translated into a Ghanaian language of their choice so they could understand and decide whether or not to participate. Those who agreed to take part of the study gave their consent by signing or thumbprinting based on their ability to write. Husbands acted as surrogates and consented on behalf of their wives who were under the age of 18 years after explaining the study’s rationale, benefits, and potential hazards to them. Anonymity was achieved for them through the use of codes. Also, data will be stored with their codes which will prevent anyone from tracing the information to them. The electronic version of the questionnaire of each interview in the personal computer of the researcher was labelled with the participants codes and stored in an identifiable folder and security code provided. This was to make them inaccessible to any other person except the researcher and supervisor.

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Adum, P., Agyare, V.A., Owusu-Marfo, J. et al. Knowledge, attitude and practices of malaria preventive measures among mothers with children under five years in a rural setting of Ghana. Malar J 22 , 268 (2023). https://doi.org/10.1186/s12936-023-04702-3

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Two new malaria vaccines are being rolled out across Africa: how they work and what they promise

Principal Medical Scientist and Head of Laboratory for Antimalarial Resistance Monitoring and Malaria Operational Research, National Institute for Communicable Diseases

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Jaishree Raman receives funding from the Global Fund, the Gates Foundation, the South Africa Research Trust, the South African Medical Research Council, the National Research Foundation, and the National Institute for Communicable Diseases. She is affiliated with the Wits Research Institute for Malaria, University of Witwatersrand, and the Institute for Sustainable Malaria Control, the University of Pretoria.

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Malaria incidents are on the rise. There were 249 million cases of this parasitic disease in 2022, five million more than in 2021. Africa suffers more than any other region from malaria, with 94% of cases and 95% of deaths worldwide.

This year two revolutionary malaria vaccines are being rolled out across the continent. Nadine Dreyer asks Jaishree Raman if 2024 will be the year the continent takes a significant leap towards beating the disease.

The RTS,S malaria vaccine

The RTS,S vaccine was the first to target a parasite. It was developed by the Walter Reed Army Research Institute after 30 years of intense research and approved by the World Health Organization in 2021.

What is special about it?

The long-awaited vaccine was described as a breakthrough for science, child health and malaria control. It is being aimed at children under the age of 5, who make up about 80% of all malaria deaths in Africa.

A multi-country trial involving Ghana, Malawi and Kenya confirmed the safety of the vaccine, with limited side effects, a high level of acceptability among the affected communities, and the feasibility of a four-dose vaccine regime within a rural African healthcare setting.

Among children aged 5 and 17 months who received 4 doses of RTS,S, the vaccine prevented about 30% of them from developing severe malaria.

Although a 30% prevention rate might seem low, a recent study published in The Lancet Infectious Diseases in August 2023 showed that giving young children RTS,S alongside other antimalarial prevention treatments before the rainy season reduced malaria by nearly two-thirds .

How far along is the rollout?

Since 2019 more than 2 million children in Ghana, Kenya and Malawi have been vaccinated with the RTS,S malaria vaccine.

The world’s first routine vaccine programme using the RTS,S started in Cameroon in January 2024. The country is offering the vaccine free of charge to all infants up to the age of six months. This has been described as a transformative chapter in Africa’s public health history .

About 18 million doses of the vaccine were allocated to 12 African countries. They are Benin, Burkina Faso, Burundi, Cameroon, the Democratic Republic of Congo, Ghana, Kenya, Liberia, Malawi, Niger, Sierra Leone and Uganda.

What are the holdups?

Since the WHO approved and prequalified the vaccine, demand has been unprecedented. The manufacturer, GlaxoSmithKline, is unable to produce enough doses.

The vaccine and AS01 adjuvant , a chemical compound used to boost immune responses, have complex synthesis processes. This is what’s limiting the projected vaccine production for the next two years to 18 million doses.

This is significantly lower than the estimated 60 million doses already pre-ordered by numerous countries were malaria is endemic.

R21/Matrix M

After decades of vaccine research, a second malaria vaccine was approved just two years after the RTS,S vaccine. The R21/Matrix is a second-generation RTS,S vaccine. It was developed by Oxford University’s Jenner Institute and approved by the WHO in October 2023.

What’s special about it?

The R21 vaccine is a significant improvement on the RTS,S vaccine, with 75% efficacy over a year.

The production process is much less complicated, which means it can be manufactured in vast amounts. The world’s largest vaccine manufacturer, the Serum Institute of India, has already established production capacity for 100 million doses per annum . This is great news for 40 million children born every year in malaria areas in Africa.

The R21/Matrix M vaccine is very cost-effective, projected to retail at $2-$4 a dose, comparable in price to other childhood vaccines used in Africa.

How advanced is the rollout of the R21 vaccine?

Data from a clinical trial in 2020 involving 450 children aged between 5 and 36 months from Burkina Faso confirmed vaccine safety and protection against severe disease, with an efficacy of 77% after 12 months.

These very encouraging findings prompted several malaria-endemic African countries, including Ghana and Nigeria , to approve use of the R21/Matrix M vaccine well before the World Health Organization.

Oxford University took the proactive step of signing a manufacturing agreement with the Serum Institute of India even though WHO approval and prequalification had not been granted.

This forward-thinking approach has ensured that the first batches of the R21 vaccine will be available in the second half of this year.

The Serum Institute has committed to producing twice as many doses in 2025, alleviating some of the demand for the RTS,S vaccine, and ensuring vulnerable young African children in high burden areas receive protection against malaria.

Without WHO approval and prequalification, several international organisations, including Unicef and Gavi, the Vaccine Alliance, were unable to fund the procurement or production of the vaccine.

The WHO finally approved and prequalified R21/Matrix M for use in the last quarter of 2023.

This vaccine is due to be rolled out in several African countries from May 2024.

No silver bullet

While the fight against malaria has been significantly bolstered by the availability of these vaccines, they are not the silver bullets that are going to get us to an Africa free of malaria.

They are, nonetheless, a welcome addition to the malaria elimination toolbox and ideally should be used together with other control strategies like long-lasting insecticide-treated bed nets, rapid diagnosis, and treatment with an effective antimalarial.

This will be the year that many vulnerable young African children will have access to not one, but two malaria vaccines.

• Serum Institute of India
• Health challenges Africa

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Plasmodium falciparum malaria in pregnancy and fetal, newborn, and maternal outcomes among a cohort of pregnant women in coastal Kenya, 2006 - 2009

Add to collection, downloadable content.

• March 22, 2019
• Affiliation: Gillings School of Global Public Health, Department of Epidemiology
• Plasmodium falciparum malaria in pregnancy causes adverse pregnancy outcomes, most notably reduced birth weight and maternal anemia. Preventive treatment that is safe during pregnancy has been shown to effectively reduce rates of malaria in pregnancy, yet in malaria-endemic regions rates of adverse pregnancy outcomes remain high. We sought to explore the association of malaria in pregnancy and other risk factors with poor outcomes, among a cohort of pregnant women who received the recommended preventative treatment for malaria at antenatal care. The prevalence of malaria at the first antenatal care visit was 11%, and malaria infection was associated with lower measures of fetal growth, as measured by ultrasound. Among live, term births, the mean birth weight was not significantly different for malaria-positive vs. malaria-negative women. However, among women with under-nutrition, as measured by low body-mass-index, malaria exposure was associated with significantly decreased birth weight (mean difference -370 grams, 95% CI -728, -12 g). The rates of maternal anemia (hemoglobin <11.0 g/dL) and moderate/severe anemia (hemoglobin < 9.0 g/dL) at antenatal care were 70% and 27%, respectively. Moderate/severe maternal anemia at first antenatal care was associated with malaria as diagnosed by microscopy (aRR 2.06, 95% CI 1.24, 3.44) as was high-intensity hookworm infection in multivariate regression (aRR 2.37, 95% CI 1.44, 3.91). Our findings suggest the importance of good preventative treatment for malaria in pregnancy to minimize the impact of exposure to malaria on fetal and newborn growth. However, under-nutrition has an important role and research and programs to improve maternal nutritional health may be important to important to further improving birth outcomes in low-resource settings. Furthermore, given the high prevalence of anemia seen in our study, also associated with under-nutrition, as well as hookworm, and malaria, further research is needed to optimize interventions around pregnancy to improve maternal and newborn health in malaria-endemic regions.
• Epidemiology
• https://doi.org/10.17615/1jfw-vm95
• Dissertation
• In Copyright
• Meshnick, Steven R.
• Doctor of Philosophy
• University of North Carolina at Chapel Hill

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Malaria: Obstacles and Opportunities (1991)

Chapter: 1. conclusions and recommendations, conclusions and recommendations, defining the problem.

The outlook for malaria control is grim. The disease, caused by mosquito-borne parasites, is present in 102 countries and is responsible for over 100 million clinical cases and 1 to 2 million deaths each year. Over the past two decades, efforts to control malaria have met with less and less success. In many regions where malaria transmission had been almost eliminated, the disease has made a comeback, sometimes surpassing earlier recorded levels. The dream of completely eliminating malaria from many parts of the world, pursued with vigor during the 1950s and 1960s, has gradually faded. Few believe today that a global eradication of malaria will be possible in the foreseeable future.

Worldwide, the number of cases of malaria caused by Plasmodium falciparum , the most dangerous species of the parasite, is on the rise. Drug-resistant strains of P. falciparum are spreading rapidly, and there have been recent reports of drug resistance in people infected with P. vivax , a less virulent form of the parasite. Furthermore, mosquitoes are becoming increasingly resistant to insecticides, and in many cases, have adapted so as to avoid insecticide-treated surfaces altogether.

In large part because of the spread of drug and insecticide resistance, there are fewer tools available today to control malaria than there were 20 years ago. In many countries, the few remaining methods are often ap-

plied inappropriately. The situation in many African nations is particularly dismal, exacerbated by a crumbling health infrastructure that has made the implementation of any disease control program difficult.

Malaria cases among tourists, business travelers, military personnel, and migrant workers in malarious areas have been increasing steadily in the last several years, posing new concerns that the disease will be introduced to currently nonmalarious areas. Recent epidemics have claimed tens of thousands of lives in Africa, and there is an increasing realization that malaria is a major impediment to socioeconomic development in many countries. Unless practical, cost-effective strategies can be developed and successfully implemented, malaria will continue to exact a heavy toll on human life and health around the world.

Although often considered a single disease, malaria is more accurately viewed as many diseases, each shaped by subtle interactions of biologic, ecologic, social, and economic factors. The species of parasite, the behavior of the mosquito host, the individual's immune status, the climate, human activities, and access to health services all play important roles in determining the intensity of disease transmission, who will become infected, who will get sick, and who will die.

Gem miners along the Thailand-Cambodia border, American tourists on a wildlife safari in East Africa, villagers living on the central highlands in Madagascar, residents of San Diego County, California, a young pregnant woman in Malawi, Swiss citizens living near Geneva International Airport, children in Africa south of the Sahara, and a U.S. State Department secretary in Tanzania seem to have little in common, yet they are all at risk of contracting malaria. Because of the disease's variable presentations, each will be affected differently, as illustrated below.

For the hundreds of thousands of Thai seasonal agricultural workers who travel deep into the forest along the Thailand-Cambodia border to mine for gems, malaria is the cost of doing business. These young men are exposed to aggressive forest mosquitoes, and within two to three weeks after arriving, almost every miner will get malaria. Many gem miners seek medications to prevent and self-treat mild cases of the disease. But because malaria in this part of the world is resistant to most antimalarial drugs, the few effective drugs are reserved for the treatment of confirmed cases of malaria. To complicate matters, there are no health services in the forest to treat patients, and the health clinics in Thailand are overburdened by the high demand for treating those with severe malaria, most of whom are returning gem miners. A similar scenario involving over 400,000 people exists among gold miners in Rondonia, Brazil.

Each year, over seven million U.S. citizens visit parts of the world

where malaria is present. Many, at the recommendation of their travel agent or physician, take antimalarial medications as a preventive measure, but a significant number do not. Tourists and other travelers who have never been exposed to malaria, and therefore have never developed protective immunity, are at great risk for contracting severe disease. Ironically, it is not the infection itself that poses the biggest danger, but the chance that treatment will be delayed because of misdiagnosis upon the individual's return to the United States. Most U.S. doctors have never seen a patient with malaria, are often confused by the wide array of symptoms, and are largely unaware that malaria in a nonimmune person can be a medical emergency, sometimes rapidly fatal.

Prior to 1950, malaria was the major cause of death in the central highlands of the African island nation of Madagascar. In the late 1950s, an aggressive program of indoor insecticide spraying rid the area of malaria-carrying mosquitoes, and malaria virtually disappeared. By the 1970s, confident of a victory in the battle against malaria, Madagascar began to phase out its spraying program; in some areas spraying was halted altogether. In the early 1980s, the vector mosquitoes reinvaded the central highlands, and in 1986 a series of devastating epidemics began. The older members of the population had long since lost the partial immunity they once had, and the younger island residents had no immunity at all. During the worst of the epidemics, tens of thousands of people died in one three-month period. The tragedy of this story is that it could have been prevented. A cheap antimalarial drug, chloroquine, could have been a powerful weapon in Madagascar, where drug resistance was not a significant concern. Because of problems in international and domestic drug supply and delivery, however, many people did not receive treatment and many died. In the last 18 months, surveillance has improved, spraying against the mosquito has resumed, and more effective drug distribution networks have been established. Malaria-related mortality has declined sharply as a result.

Malaria, once endemic in the southern United States, occurs relatively infrequently. Indeed, there have been only 23 outbreaks of malaria since 1950, and the majority of these occurred in California. But for each of the past three years, the San Diego County Department of Health Services has had to conduct an epidemiologic investigation into local transmission of malaria. An outbreak in the late summer of 1988 involved 30 persons, the largest such outbreak in the United States since 1952. In the summer of 1989, three residents of San Diego County—a migrant worker and two permanent residents—were diagnosed with malaria; in 1990, a teenager living in a suburb of San Diego County fell ill with malaria. All of the cases were treated successfully, but these incidents raise questions about the possibility of new and larger outbreaks in the future. Malaria

transmission in San Diego County (and in much of California) is attributed to the presence of individuals from malaria-endemic regions who lack access to medical care, the poor shelter and sanitation facilities of migrant workers, and the ubiquitous presence of Anopheles mosquitoes in California.

A 24-year-old pregnant Yao woman from the Mangochi District in Malawi visited the village health clinic monthly to receive prenatal care. While waiting to be seen by the health provider, she and other women present listened to health education talks which were often about the dangers of malaria during pregnancy, and the need to install screens around the house to keep the mosquitoes away, to sleep under a bednet, and to take a chloroquine tablet once a week. Toward the end of her second trimester of pregnancy, the woman returned home from her prenatal visit with her eight tablets of chloroquine wrapped in a small packet of brown paper. She promptly gave the medicine to her husband to save for the next time he or one of their children fell ill. The next week she developed a very high malarial fever and went into labor prematurely. The six-month-old fetus was born dead.

Over a two-week period in the summer of 1989, five Swiss citizens living within a mile of Geneva International Airport presented at several hospitals with acute fever and chills. All had malaria. Four of the five had no history of travel to a malarious region; none had a history of intravenous drug use or blood transfusion. Apart from their symptoms, the only thing linking the five was their proximity to the airport. A subsequent epidemiologic investigation suggested that the malaria miniepidemic was caused by the bite of stowaway mosquitoes en route from a malaria-endemic country. The warm weather, lack of systematic spraying of aircraft, and the close proximity of residential areas to the airport facilitated the transmission of the disease.

Malaria is a part of everyday life in Africa south of the Sahara. Its impact on children is particularly severe. Mothers who bring unconscious children to the hospital often report that the children were playing that morning, convulsed suddenly, and have been unconscious ever since. These children are suffering from the most frequently fatal complication of the disease, cerebral malaria. Other children succumb more slowly to malaria, becoming progressively more anemic with each subsequent infection. By the time they reach the hospital, they are too weak to sit and are literally gasping for breath. Many children are brought to hospitals as a last resort, after treatment given for “fever” at the local health center has proved ineffective. Overall, children with malaria account for a third of all hospital admissions. A third of all children hospitalized for malaria die. In most parts of Africa, there are no effective or affordable options to prevent the

disease, so children are at high risk until they have been infected enough times to develop a partial immunity.

A 52-year-old American woman, the secretary to the U.S. ambassador in Tanzania, had been taking a weekly dose of chloroquine to prevent malaria since her arrival in the country the year before. She arrived at work one morning complaining of exhaustion, a throbbing headache, and fever. A blood sample was taken and microscopically examined for malaria parasites. She was found to be infected with P. falciparum , and was treated immediately with high doses of chloroquine. That night, she developed severe diarrhea, and by morning she was found to be disoriented and irrational. She was diagnosed as having cerebral malaria, and intravenous quinine treatment was started. Her condition gradually deteriorated—she became semicomatose and anemic, and approximately 20 percent of her red blood cells were found to be infected with malaria parasites. After continued treatment for several days, no parasites were detected in her blood. Despite receiving optimal care, other malaria-related complications developed and she died just nine days after the illness began. The cause of death: chloroquine-resistant P. falciparum .

These brief scenarios give a sense of the diverse ways that malaria can affect people. So fundamental is this diversity with respect to impact, manifestation, and epidemiology that malaria experts themselves are not unanimous on how best to approach the disease. Malariologists recognize that malaria is essentially a local phenomenon that varies greatly from region to region and even from village to village in the same district. Consequently, a single global technology for malaria control is of little use for specific conditions, yet the task of tailoring strategies to each situation is daunting. More important, many malarious countries do not have the resources, either human or financial, to carry out even the most meager efforts to control malaria.

These scenarios also illustrate the dual nature of malaria as it affects U.S. policy. In one sense, it is a foreign aid issue; a devastating disease is currently raging out of control in vast, heavily populated areas of the world. In another sense, malaria is of domestic public health concern. The decay of global malaria control and the invasion of the parasite into previously disease-free areas, coupled with the increasing frequency of visits to such areas by American citizens, intensify the dangers of malaria for the U.S. population. Tourists, business travelers, Peace Corps volunteers, State Department employees, and military personnel are increasingly at risk, and our ability to protect and cure them is in jeopardy. What is desperately needed is a better application of existing malaria control tools and new methods of containing the disease.

In most malarious regions of the world, there is inadequate access to malaria treatment. Appropriate health facilities may not exist; those that do exist may be inaccessible to affected populations, may not be supplied with effective drugs, or may be staffed inappropriately. In many countries, the expansion of primary health care services has not proceeded according to expectations, particularly in the poorest (and most malarious) nations of the tropical world.

In some countries, antimalarial interventions are applied in broad swaths, without regard to underlying differences in the epidemiology of the disease. In other countries, there are no organized interventions at all. The malaria problem in many regions is compounded by migration, civil unrest, poorly planned exploitation of natural resources, and their frequent correlate, poverty.

During the past 15 years, much research has focused on developing vaccines for malaria. Malaria vaccines are thought to be possible in part because people who are naturally exposed to the malaria parasite acquire a partial immunity to the disease over time. In addition, immunization of animals and humans by the bites of irradiated mosquitoes infected with the malaria parasite can protect against malaria infection. Much progress has been made, but current data suggest that effective vaccines are not likely to be available for some time.

Compounding the difficulty of developing more effective malaria prevention, treatment, and control strategies is a worldwide decline in the pool of scientists and health professionals capable of conducting field research and organizing and managing malaria control programs at the country level. With the change in approach from malaria eradication to malaria control, many malaria programs “lost face,” admitting failure and losing the priority interest of their respective ministries of health. As external funding agencies lost interest in programs, they reduced their technical and financial support. As a consequence, there were fewer training opportunities, decreased contacts with international experts, and diminished prospects for improving the situation. Today, many young scientists and public health specialists, in both the developed and developing countries, prefer to seek higher-profile activities with better defined opportunities for career advancement.

It is against this backdrop of a worsening worldwide malaria situation that the Institute of Medicine was asked to convene a multidisciplinary committee to assess the current status of malaria research and control and to make recommen-

dations to the U.S. government on promising and feasible strategies to address the problem. During the 18-month study, the committee reviewed the state of the science in the major areas of malariology, identified gaps in knowledge within each of the major disciplines, and developed recommendations for future action in malaria research and control.

Organization

Chapter 2 summarizes key aspects of the individual state-of-the-science chapters, and is intended to serve as a basic introduction to the medical and scientific aspects of malaria, including its clinical signs, diagnosis, treatment, and control. Chapter 3 provides a historical overview of malaria, from roughly 3000 B.C. to the present, with special emphasis on efforts in this century to eradicate and control the disease. The state-of-the-science reviews, which start in Chapter 4 , begin with a scenario titled “Where We Want To Be in the Year 2010.” Each scenario describes where the discipline would like to be in 20 years and how, given an ideal world, the discipline would have contributed to malaria control efforts. The middle section of each chapter contains a critical review of the current status of knowledge in the particular field. The final section lays out specific directions for future research based on a clear identification of the major gaps in scientific understanding for that discipline. The committee urges those agencies that fund malaria research to consult the end of each state-of-the-science chapter for suggestions on specific research opportunities in malaria.

Sponsorship

This study was sponsored by the U.S. Agency for International Development, the U.S. Army Medical Research and Development Command, and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

CONCLUSIONS AND RECOMMENDATIONS

A major finding of the committee is the need to increase donor and public awareness of the growing risk presented by the resurgence of malaria. Overall, funding levels are not adequate to meet the problem. The committee believes that funding in the past focused too sharply on specific technologies and particular control strategies (e.g., indiscriminate use of insecticide spraying). Future support must be balanced among the needs outlined in this report. The issue for prioritization is not whether to select specific technologies or control strategies, but to raise the priority for solv-

ing the problem of malaria. This is best done by encouraging balanced research and control strategies and developing a mechanism for periodically adjusting support for promising approaches.

This report highlights those areas which the committee believes deserve the highest priority for research or which should be considered when U.S. support is provided to malaria control programs. These observations and suggestions for future action, presented below in four sections discussing policy, research, control, and training, represent the views of a multidisciplinary group of professionals from diverse backgrounds and with a variety of perspectives on the problem.

The U.S. government is the largest single source of funds for malaria research and control activities in the world. This investment is justified by the magnitude of the malaria problem, from both a foreign aid and a public health perspective. The increasing severity of the threat of malaria to residents of endemic regions, travelers, and military personnel, and our diminishing ability to counter it, should be addressed by a more comprehensive and better integrated approach to malaria research and control. However, overall U.S. support for malaria research and control has declined over the past five years. The committee believes that the amount of funding currently directed to malaria research and control activities is inadequate to address the problem.

Over the past 10 years, the majority of U.S. funds available for malaria research have been devoted to studies on immunity and vaccine development. Although the promise of vaccines remains to be realized, the committee believes that the potential benefits are enormous. At the same time, the relative paucity of funds available for research has prevented or slowed progress in other areas. Our incomplete knowledge about the basic biology of malaria parasites, how they interact with their mosquito and human hosts, and how human biology and behavior affect malaria transmission and control remains a serious impediment to the development and implementation of malaria control strategies. The committee believes that this situation must be addressed without reducing commitment to current research initiatives. The committee further believes that such research will pay long-term dividends in the better application of existing tools and the development of new drugs, vaccines, and methods for vector control.

The committee recommends that increased funds be made available so that U.S. research on malaria can be broadened according to the priorities addressed in this report, including laboratory and field research on the biology of malaria parasites, their mosquito vectors, and their interaction with humans.

The committee believes that the maximum return on investment of funds devoted to malaria research and control can be achieved only by rigorous review of project proposals. The committee further believes that the highest-quality review is essential to ensure that funding agencies spend their money wisely. The committee believes that all U.S.-supported malaria field activities, both research and control, should be of the highest scientific quality and relevance to the goals of malaria control.

The committee recommends decisions on funding of malaria research be based on scientific merit as determined by rigorous peer review, consistent with the guidelines of the National Institutes of Health or the United Nations Development Program/World Bank/ World Health Organization Special Programme for Research and Training in Tropical Diseases, and that all U.S.-supported malaria field projects be subject to similar rigorous review to ensure that projects are epidemiologically and scientifically sound.

Commitment and Sustainability

For malaria control, short-term interventions can be expected to produce only short-term results. The committee believes that short-term interventions are justified only for emergency situations. Longer-term interventions should be undertaken only when there is a national commitment to support sustained malaria surveillance and control.

The committee recommends that malaria control programs receive sustained international and local support, oriented toward the development of human resources, the improvement of management skills, the provision of supplies, and the integration of an operational research capability in support of an epidemiologically sound approach to malaria control.

Surveillance

During the major effort to eradicate malaria from many parts of the world that began in the late 1950s and ended in 1969, it was important to establish mechanisms to detect all malaria infections. As a result, systems were established in many countries to collect blood samples for later microscopic examination for the presence of parasites. Each year, the results from more than 140 million slides are reported to the World Health Organization, of which roughly 3 to 5 percent are positive for malaria. This approach seeks to answer the question posed 30 years ago: How many people are infected with the malaria parasite? It does not answer today's questions: Who is sick? Where? Why? The committee concludes that the mass collection of blood slides requires considerable resources, poses seri-

ous biosafety hazards, deflects attention from the treatment of ill individuals, and has little practical relevance for malaria control efforts today.

Instead of the mass collection of slides, the committee believes that the most effective surveillance networks are those that concurrently measure disease in human populations, antimalarial drug use, patterns of drug resistance, and the intensity of malaria transmission by vector populations. The committee believes that malaria surveillance practices have not received adequate recognition as an epidemiologic tool for designing, implementing, and evaluating malaria control programs.

The committee recommends that countries be given support to orient malaria surveillance away from the mass collection and screening of blood slides toward the collection and analysis of epidemiologically relevant information that can be used to monitor the current situation on an ongoing basis, to identify high-risk groups, and to detect potential epidemics early in their course.

Inter-Sectoral Cooperation

The committee believes that insufficient attention has been paid to the impact that activities in non-health-related sectors, such as construction, industry, irrigation, and agriculture, have on malaria transmission. Conversely, there are few assessments of the impact of malaria control projects on other public health initiatives, the environment, and the socioeconomic status of affected populations. Malaria transmission frequently occurs in areas where private and multinational businesses and corporations (e.g., hotel chains, mining operations, and industrial plants) have strong economic interests. Unfortunately and irresponsibly, some local and multinational businesses contribute few if any resources to malaria control in areas in which they operate.

The committee recommends greater cooperation and consultation between health and nonhealth sectors in the planning and implementation of major development projects and malaria activities. It also recommends that all proposed malaria control programs be analyzed for their potential impact on other public health programs, the environment, and social and economic welfare, and that local and multinational businesses be recruited by malaria control organizations to contribute substantially to local malaria control efforts.

New Tools for Malaria Control

The committee believes that, as a policy directive, it is important to support research activities to develop new tools for malaria control. The

greatest momentum for the development of new tools exists in vaccine and drug development, and the committee believes it essential that this momentum be maintained. The committee recognizes that commendable progress has been made in defining the characteristics of antigens and delivery systems needed for effective vaccines, but that the candidates so far tested fall short of the goal. Much has been learned which supports the hope that useful vaccines can be developed. To diminish activity in vaccine development at this stage would deal a severe blow to one of our best chances for a technological breakthrough in malaria control.

The committee recommends that vaccine development continue to be a priority of U.S.-funded malaria research.

Only a handful of drugs are available to prevent or treat malaria, and the spread of drug-resistant strains of the malaria parasite threatens to reduce further the limited pool of effective drugs. The committee recognizes that there is little economic incentive for U.S. pharmaceutical companies to undertake antimalarial drug discovery activities. The committee is concerned that U.S. government support of these activities, based almost entirely at the Walter Reed Army Institute of Research (WRAIR), has decreased and is threatened with further funding cuts. The committee concludes that the WRAIR program in antimalarial drug discovery, which is the largest and most successful in the world, is crucial to international efforts to develop new drugs for malaria. The benefits of this program in terms of worldwide prevention and treatment of malaria have been incalculable.

The committee strongly recommends that drug discovery and development activities at WRAIR receive increased and sustained support.

The next recommendation on policy directions reflects the committee 's concern about the lack of involvement in malaria research by the private sector. The committee believes that the production of candidate malaria vaccines and antimalarial drugs for clinical trials has been hampered by a lack of industry involvement. Greater cooperation and a clarification of the contractual relationships between the public and private sectors would greatly enhance the development of drugs and vaccines.

The committee recommends that mechanisms be established to promote the involvement of pharmaceutical and biotechnology firms in the development of malaria vaccines, antimalarial drugs, and new tools for vector control.

Coordination and Integration

The committee is concerned that there is inadequate joint planning and coordination among U.S.-based agencies that support malaria research and

control activities. Four government agencies and many nongovernmental organizations in the United States are actively involved in malaria-related activities. There are also numerous overseas organizations, governmental and nongovernmental, that actively support such activities worldwide.

The complexity and variability of malaria, the actual and potential scientific advances in several areas of malariology, and most important the worsening worldwide situation argue strongly for an ongoing mechanism to assess and influence current and future U.S. efforts in malaria research and control.

The committee strongly recommends the establishment of a national advisory body on malaria.

In addition to fulfilling a much needed coordinating function among U.S.-based agencies and between the U.S. and international efforts, the national advisory body could monitor the status of U.S. involvement in malaria research and control, assess the relevant application of knowledge, identify areas requiring further research, make recommendations to the major funding agencies, and provide a resource for legislators and others interested in scientific policy related to malaria. The national advisory body could convene specific task-oriented scientific working groups to review research and control activities and to make recommendations, when appropriate, for changes in priorities and new initiatives.

The committee believes that the national advisory body should be part of, and appointed by, a neutral and nationally respected scientific body and that it should actively encourage the participation of governmental and nongovernmental organizations, industry, and university scientists in advising on the direction of U.S. involvement in malaria research and control.

The increasing magnitude of the malaria problem during the past decade and the unpredictability of changes in human, parasite, and vector determinants of transmission and disease point strongly to the need for such a national advisory body, which can be responsive to rapidly changing problems, and advances in scientific research, relating to global efforts to control malaria.

Malaria Research Priorities

Malaria control is in crisis in many areas of the world. People are contracting and dying of severe malaria in unprecedented numbers. To address these problems, the committee strongly encourages a balanced research agenda. Two basic areas of research require high priority. Research that will lead to improved delivery of existing interventions for malaria, and the development of new tools for the control of malaria.

Research in Support of Available Control Measures

Risk Factors for Severe Malaria People who develop severe and complicated malaria lack adequate immunity, and many die from the disease. Groups at greatest risk include young children and pregnant women in malaria endemic regions; nonimmune migrants, laborers, and visitors to endemic regions; and residents of regions where malaria has been recently reintroduced. For reasons that are largely unknown, not all individuals within these groups appear to be at equal risk for severe disease. The committee believes that the determinants of severe disease, including risk factors associated with a population, the individual (biologic, immunologic, socioeconomic, and behavioral), the parasite, or exposure to mosquitoes, are likely to vary considerably in different areas.

The committee recommends that epidemiologic studies on the risk factors for severe and complicated malaria be supported.

Pathogenesis of Severe and Complicated Malaria Even with optimal care, 20 to 30 percent of children and adults with the most severe form of malaria—primarily cerebral malaria—die. The committee believes that a better understanding of the disease process will lead to improvements in preventing and treating severe forms of malaria. The committee further believes that determining the indications for treatment of severe malarial anemia is of special urgency given the risk of transmitting the AIDS virus through blood transfusions, the only currently available treatment for malarial anemia. Physicians need to know when it is appropriate to transfuse malaria patients.

The committee recommends greater support for research on the pathogenesis of severe and complicated malaria, on the mechanisms of malarial anemia, and on the development of specific criteria for blood transfusions in malaria.

Social Science Research The impact of drugs to control disease or programs to reduce human-mosquito contact is mediated by local practices and beliefs about malaria and its treatment. Most people in malaria-endemic countries seek initial treatment for malaria outside of the formal health sector. Programs that attempt to influence this behavior must understand that current practices satisfy, at some level, local concerns regarding such matters as access to and effectiveness of therapy, and cost. These concerns may lead to practices at odds with current medical practice. Further, many malaria control programs have not considered the social, cultural, and behavioral dimensions of malaria, thereby limiting the effectiveness of measures undertaken. The committee recognizes that control programs often fail to incorporate household or community concerns and resources

into program design. In most countries, little is known about how the demand for and utilization of health services is influenced by such things as user fees, location of health clinics, and the existence and quality of referral services. The committee concludes that modern social science techniques have not been effectively applied to the design, implementation, and evaluation of malaria control programs.

The committee recommends that research be conducted on local perceptions of malaria as an illness, health-seeking behaviors (including the demand for health care services), and behaviors that affect malaria transmission, and that the results of this research be included in community-based malaria control interventions that promote the involvement of communities and their organizations in control efforts.

Innovative Approaches to Malaria Control Malaria control programs will require new ideas and approaches, and new malaria control strategies need to be developed and tested. There is also a need for consistent support of innovative combinations of control technologies and for the transfer of new technologies from the laboratory to the clinic and field for expeditious evaluation. Successful technology transfer requires the exchange of scientific research, but more importantly, must be prefaced by an improved understanding of the optimal means to deliver the technology to the people in need (see Chapter 11 ).

The committee recommends that donor agencies provide support for research on new or improved control strategies and into how new tools and technologies can be better implemented and integrated into on-going control efforts.

Development of New Tools

Antimalarial Immunity and Vaccine Development Many people are able to mount an effective immune response that can significantly mitigate symptoms of malaria and prevent death. The committee believes that the development of effective malaria vaccines is feasible, and that the potential benefits of such vaccines are enormous. Several different types of malaria vaccines need to be developed: vaccines to prevent infection (of particular use for tourists and other nonimmune visitors to endemic countries), prevent the progression of infection to disease (for partially immune residents living in endemic areas and for nonimmune visitors), and interrupt transmission of parasites by vector populations (to reduce the risk of new infections in humans). The committee believes that each of these directions should be pursued.

The committee recommends sustained support for research to identify mechanisms and targets of protective immunity and to exploit the

use of novel scientific technologies to construct vaccines that induce immunity against all relevant stages of the parasite life cycle.

Drug Discovery and Development Few drugs are available to prevent or treat malaria, and the spread of drug-resistant strains of malaria parasites is steadily reducing the limited pool of effective chemotherapeutic agents. The committee believes that an inadequate understanding of parasite biochemistry and biology impedes the process of drug discovery and slows studies on the mechanisms of drug resistance.

The committee recommends increased emphasis on screening compounds to identify new classes of potential antimalarial drugs, identifying and characterizing vulnerable targets within the parasite, understanding the mechanisms of drug resistance, and identifying and developing agents that can restore the therapeutic efficacy of currently available drugs.

Vector Control Malaria is transmitted to humans by the bites of infective mosquitoes. The objective of vector control is to reduce the contact between humans and infected mosquitoes. The committee believes that developments are needed in the areas of personal protection, environmental management, pesticide use and application, and biologic control, as well as in the largely unexplored areas of immunologic and genetic approaches for decreasing parasite transmission by vectors.

The committee recommends increased support for research on vector control that focuses on the development and field testing of methods for interrupting parasite transmission by vectors.

Malaria Control

Malaria is a complex disease that, even under the most optimistic scenario, will continue to be a major health threat for decades. The extent to which malaria affects human health depends on a large number of epidemiologic and ecologic factors. Depending on the particular combination of these and other variables, malaria may have different effects on neighboring villages and people living in a single village. All malaria control programs need to be designed with a view toward effectiveness and sustainability, taking into account the local perceptions, the availability of human and financial resources, and the multiple needs of the communities at risk. If community support for health sector initiatives is to be guaranteed, the public needs to know much more about malaria, its risks for epidemics and severe disease, and difficulties in control.

Unfortunately, there is no “magic bullet” solution to the deteriorating worldwide malaria situation, and no single malaria control strategy will be applicable in all regions or epidemiologic situations. Given the limited available financial and human resources and a dwindling pool of effective

antimalarial tools, the committee suggests that donor agencies support four priority areas for malaria control in endemic countries.

The committee believes that the first and most basic priority in malaria control is to prevent infected individuals from becoming severely ill and dying. Reducing the incidence of severe morbidity and malaria-related mortality requires a two-pronged approach. First, diagnostic, treatment, and referral capabilities, including the provision of microscopes, training of technicians and other health providers, and drug supply, must be enhanced. Second, the committee believes that many malaria-related deaths could be averted if individuals and caretakers of young children knew when and how to seek appropriate treatment and if drug vendors, pharmacists, physicians, nurses, and other health care providers were provided with up-to-date and locally appropriate treatment and referral guidelines. The development and implementation of an efficient information system that provides rapid feedback to the originating clinic and area is key to monitoring the situation and preventing epidemics.

The committee believes that the second priority should be to promote personal protection measures (e.g., bednets, screens, and mosquito coils) to reduce or eliminate human-mosquito contact and thus to reduce the risk of infection for individuals living in endemic areas. At the present time, insecticide-treated bednets appear to be the most promising personal protection method.

In many environments, in addition to the treatment of individuals and use of personal protection measures, community-wide vector control is feasible. In such situations, the committee believes that the third priority should be low-cost vector control measures designed to reduce the prevalence of infective mosquitoes in the environment, thus reducing the transmission of malaria to populations. These measures include source reduction (e.g., draining or filling in small bodies of water where mosquito larvae develop) or the application of low-cost larval control measures. In certain environments, the use of insecticide-impregnated bednets by all or most members of a community may also reduce malaria transmission, but this approach to community-based malaria control remains experimental.

The committee believes that the fourth priority for malaria control should be higher cost vector control measures such as large-scale source reduction or widespread spraying of residual insecticides. In certain epidemiologic situations, the use of insecticides for adult mosquito control is appropriate and represents the method of choice for decreasing malaria transmission and preventing epidemics (see Chapter 7 and Chapter 10 ).

The committee recommends that support of malaria control programs include resources to improve local capacities to conduct prompt diagnosis, including both training and equipment, and to ensure the availability of antimalarial drugs.

The committee recommends that resources be allocated to develop and disseminate malaria treatment guidelines for physicians, drug vendors, pharmacists, village health workers, and other health care personnel in endemic and non-endemic countries. The guidelines should be based, where appropriate, on the results of local operational research and should include information on the management of severe and complicated disease. The guidelines should be consistent and compatible among international agencies involved in the control of malaria.

The committee recommends that support for malaria control initiatives include funds to develop and implement locally relevant communication programs that provide information about how to prevent and treat malaria appropriately (including when and how to seek treatment) and that foster a dialogue about prevention and control.

Organization of Malaria Control

One of the major criticisms of malaria control programs during the past 10 to 15 years has been that funds have been spent inappropriately without an integrated plan and without formal evaluation of the efficacy of control measures instituted. In many instances, this has led to diminished efforts to control malaria.

The committee strongly encourages renewed commitment by donor agencies to support national control programs in malaria-endemic countries.

The committee recommends that U.S. donor agencies develop, with the advice of the national advisory body, a core of expertise (either in-house or through an external advisory group) to plan assistance to malaria control activities in endemic countries.

The committee believes that the development, implementation, and evaluation of such programs must follow a rigorous set of guidelines. These guidelines should include the following steps:

Identification of the problem

Determine the extent and variety of malaria. The paradigm approach described in Chapter 10 should facilitate this step.

Analyze current efforts to solve malaria problems.

Identify and characterize available in-country resources and capabilities.

Development of a plan

Design and prioritize interventions based on the epidemiologic situation and the available resources.

Design a training program for decision makers, managers, and technical staff to support and sustain the interventions.

Define specific indicators of the success or failure of the interventions at specific time points.

Develop a specific plan for reporting on the outcomes of interventions.

Develop a process for adjusting the program in response to successes and/or failures of interventions.

Review of the comprehensive plan by a donor agency review board

Modification of the plan based on comments of the review board

Implementation of the program

Yearly report and analysis of outcome variables

To guide the implementation of the activities outlined above, the committee has provided specific advice on several components, including an approach to evaluating malaria problems and designing control strategies (the paradigm approach), program management, monitoring and evaluation, and operational research.

Paradigm Approach

Given the complex and variable nature of malaria, the committee believes that the epidemiologic paradigms (see Chapter 10 ), developed in conjunction with this study, may form the basis of a logical and reasoned approach for defining the malaria problems and improving the design and management of malaria control programs.

The committee recommends that the paradigm approach be field tested to determine its use in helping policymakers and malaria program managers design and implement epidemiologically appropriate and cost-effective control initiatives.

The committee recognizes that various factors, including the local ecology, the dynamics of mosquito transmission of malaria parasites, genetically determined resistance to malaria infection, and patterns of drug use, affect patterns of malaria endemicity in human populations and need to be considered when malaria control strategies are developed. In most endemic countries, efforts to understand malaria transmission through field studies of vector populations are either nonexistent or so limited in scope that they have minimal impact on subsequent malaria control efforts. The committee recognizes that current approaches to malaria control are clearly inadequate. The committee believes, however, that malaria control strategies are sometimes applied inappropriately, with little regard to the underlying differences in the epidemiology of the disease.

The committee recommends that support for malaria control programs include funds to permit a reassessment and optimization of antimalarial tools based on relevant analyses of local epidemiologic, parasitologic, entomologic, socioeconomic, and behavioral determinants of malaria and the costs of malaria control.

Poor management has contributed to the failure of many malaria control programs. Among the reasons are a chronic shortage of trained managers who can think innovatively about health care delivery and who can plan, implement, supervise, and evaluate malaria control programs. Lack of incentives, the absence of career advancement options, and designation of responsibility without authority often hinder the effectiveness of the small cadre of professional managers that does exist. The committee recognizes that management technology is a valuable resource that has yet to be effectively introduced into the planning, implementation, and evaluation of most malaria control programs.

The committee recommends that funding agencies utilize management experts to develop a comprehensive series of recommendations and guidelines as to how basic management skills and technology can be introduced into the planning, implementation, and evaluation of malaria control programs.

The committee recommends that U.S. funding of each malaria control program include support for a senior manager who has responsibility for planning and coordinating malaria control activities. Where such an individual does not exist, a priority of the control effort should be to identify and support a qualified candidate. The manager should be supported actively by a multidisciplinary core group with expertise in epidemiology, entomology, the social sciences, clinical medicine, environmental issues, and vector control operations.

Monitoring and Evaluation

Monitoring and evaluation are essential components of any control program. For malaria control, it is not acceptable to continue pursuing a specific control strategy without clear evidence that it is effective and reaching established objectives.

The committee recommends that support for malaria control programs include funds to evaluate the impact of control efforts on the magnitude of the problem and that each program be modified as necessary on the basis of periodic assessments of its costs and effectiveness.

Problem Solving (Operational Research) and Evaluation

At the outset of any malaria prevention or control initiative and during the course of implementation, gaps in knowledge will be identified and problems will arise. These matters should be addressed through clearly defined, short-term, focused studies. Perhaps the most difficult aspects of operational research are to identify the relevant problem, formulate the appropriate question, and design a study to answer that question.

The committee recommends that a problem-solving (operational research) component be built into all existing and future U.S.-funded malaria control initiatives and that support be given to enhance the capacity to perform such research. This effort will include consistent support in the design of focused projects that can provide applicable results, analysis of data, and dissemination of conclusions.

The committee concludes that there is a need for additional scientists actively involved in malaria-related research in the United States and abroad. To meet this need, both short- and long-term training at the doctoral and postdoctoral levels must be provided. This training will be of little value unless there is adequate long-term research funding to support the career development of professionals in the field of malaria.

The committee recommends support for research training in malaria.

Whereas the curricula for advanced degree training in basic science research and epidemiology are fairly well defined, two areas require attention, especially in the developing world: social sciences and health management and training.

The committee recommends that support be given for the development of advanced-degree curricula in the social sciences, and in health management and training, for use in universities in developing and developed countries.

The availability of well-trained managers, decision makers, and technical staff is critical to the implementation of any malaria prevention and control program. The development of such key personnel requires a long term combination of formal training, focused short courses, and a gradual progression of expertise.

The committee recommends support for training in management, epidemiology, entomology, social sciences, and vector control. Such training for malaria control may be accomplished through U.S.-funded grant programs for long-term cooperative relationships

between institutions in developed and developing countries; through the encouragement of both formal and informal linkages among malaria-endemic countries; through the use of existing training courses; and through the development of specific training courses.

The committee recommends further that malaria endemic countries be supported in the development of personnel programs that provide long-term career tracks for managers, decision makers, and technical staff, and that offer professional fulfillment, security, and competitive financial compensation.

Malaria is making a dramatic comeback in the world. The disease is the foremost health challenge in Africa south of the Sahara, and people traveling to malarious areas are at increased risk of malaria-related sickness and death.

This book examines the prospects for bringing malaria under control, with specific recommendations for U.S. policy, directions for research and program funding, and appropriate roles for federal and international agencies and the medical and public health communities.

The volume reports on the current status of malaria research, prevention, and control efforts worldwide. The authors present study results and commentary on the:

• Nature, clinical manifestations, diagnosis, and epidemiology of malaria.
• Biology of the malaria parasite and its vector.
• Prospects for developing malaria vaccines and improved treatments.
• Economic, social, and behavioral factors in malaria control.

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An Essay on Malaria and Its Consequences

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