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Case Study: Euro Disney Failure – Failed Americanism?

Many of Businesses in America make detailed assumptions about the potential of expand their business to other countries and structural models of organizing which can be easily failed to consider the cultural differences. One of the examples of the outcome to intercultural business is Disney Corporation’s European venture. Due to lack of cultural information of France as well as Europe, further on their inability to forecast problems, Disney acquired a huge debt. False assumptions led to a great loss of time, money and even reputation for corporation itself. Instead of analyzing and learning from its potential visitors, Disney chose to make assumptions about the preference of Europeans, which turned out that most of those assumptions were wrong.

Euro Disney Disaster

Until 1992, the Walt Disney Company had experienced nothing but success in the theme park business. Its first park, Disneyland, opened in Anaheim, California, in 1955. Its theme song, “It’s a Small World After All,” promoted an idealized vision of America spiced with reassuring glimpses of exotic cultures all calculated to promote heartwarming feelings about living together as one happy family. There were dark tunnels and bumpy rides to scare the children a little but none of the terrors of the real world . . . The Disney characters that everyone knew from the cartoons and comic books were on hand to shepherd the guests and to direct them to the Mickey Mouse watches and Little Mermaid records. The Anaheim park was an instant success.

In the 1970s, the triumph was repeated in Florida, and in 1983, Disney proved the Japanese also have an affinity for Mickey Mouse with the successful opening of Tokyo Disneyland. Having wooed the Japanese, Disney executives in 1986 turned their attention to France and, more specifically, to Paris, the self-proclaimed capital of European high culture and style. “Why did they pick France?” many asked. When word first got out that Disney wanted to build another international theme park, officials from more than 200 locations all over the world descended on Disney with pleas and cash inducements to work the Disney magic in their hometowns. But Paris was chosen because of demographics and subsidies. About 17 million Europeans live less than a two-hour drive from Paris. Another 310 million can fly there in the same time or less. Also, the French government was so eager to attract Disney that it offered the company more than $1 billion in various incentives, all in the expectation that the project would create 30,000 French jobs. From the beginning, cultural gaffes by Disney set the tone for the project. By late 1986, Disney was deep in negotiations with the French government. To the exasperation of the Disney team, headed by Joe Shapiro, the talks were taking far longer than expected. Jean-Rene Bernard, the chief French negotiator, said he was astonished when Mr. Shapiro, his patience depleted, ran to the door of the room and, in a very un-Gallic gesture, began kicking it repeatedly, shouting, “Get me something to break!” There was also snipping from Parisian intellectuals who attacked the transplantation of Disney’s dream world as an assault on French culture; “a cultural Chernobyl,” one prominent intellectual called it. The minister of culture announced he would boycott the opening, proclaiming it to be an unwelcome symbol of American cliches and a consumer society.

Euro Disney Failure - Euro Disney Disaster Case Study

Unperturbed, Disney pushed ahead with the planned summer 1992 opening of the $5 billion park. Shortly after Euro-Disneyland opened, French farmers drove their tractors to the entrance and blocked it. This globally televised act of protest was aimed not at Disney but at the US government, which had been demanding that French agricultural subsidies be cut. Still, it focused world attention upon the loveless marriage of Disney and Paris. Then there were the operational errors. Disney’s policy of serving no alcohol in the park, since reversed caused astonishment in a country where a glass of wine for lunch is a given. Disney thought that Monday would be a light day for visitors and Friday a heavy one and allocated staff accordingly, but the reality was the reverse. Another unpleasant surprise was the hotel breakfast debacle. “We were told that Europeans ‘don’t take breakfast,’ so we downsized the restaurants,” recalled one Disney executive. “And guess what? Everybody showed up for breakfast. We were trying to serve 2,500 breakfasts in a 350-seat restaurant at some of the hotels. The lines were horrendous. Moreover, they didn’t want the typical French breakfast of croissants and coffee, which was our assumption. They wanted bacon and eggs.” Lunch turned out to be another problem. “Everybody wanted lunch at 12:30. The crowds were huge. Our smiling cast members had to calm down surly patrons and engage in some ‘behavior modification’ to teach them that they could eat lunch at 11:00 AM or 2:00 PM.” There were major staffing problems too. Disney tried to use the same teamwork model with its staff that had worked so well in America and Japan, but it ran into trouble in France. In the first nine weeks of Euro-Disneyland’s operation, roughly 1,000 employees, 10 percent of the total, left. One former employee was a 22-year old medical student from a nearby town who signed up for a weekend job. After two days of “brainwashing,” as he called Disney’s training, he left following a dispute with his supervisor over the timing of his lunch hour. Another former employee noted, “I don’t think that they realize what Europeans are like . . . that we ask questions and don’t think all the same way.”

One of the biggest problems, however, was that Europeans didn’t stay at the park as long as Disney expected. While Disney succeeded in getting close to 9 million visitors a year through the park gates, in line with its plans, most stayed only a day or two. Few stayed the four to five days that Disney had hoped for. It seems that most Europeans regard theme parks as places for day excursions. A theme park is just not seen as a destination for an extended vacation. This was a big shock for Disney. The company had invested billions in building luxury hotels next to the park-hotels that the day-trippers didn’t need and that stood half empty most of the time. To make matters worse, the French didn’t show up in the expected numbers. In 1994, only 40 percent of the park’s visitors were French. One puzzled executive noted that many visitors were Americans living in Europe or, stranger still, Japanese on a European vacation! As a result, by the end of 1994 Euro-Disneyland had cumulative losses of $2 billion.

At this point, Euro-Disney changed its strategy. First, the company changed the name to Disneyland Paris in an attempt to strengthen the park’s identity. Second, food and fashion offerings changed. To quote one manager, “We opened with restaurants providing French-style food service, but we found that customers wanted self service like in the US parks. Similarly, products in the boutiques were initially toned down for the French market, but since then the range has changed to give it a more definite Disney image.” Third, the prices for day tickets and hotel rooms were cut by one-third. The result was an attendance of 11.7 million in 1996, up from a low of 8.8 million in 1994.

Read More: The Not So Wonderful World of Euro Disney

The Three Mistakes

In determining the target market did not take into account cultural differences Euro Disney’s choice of location focus on the aspects of financial and population, then Euro Disney theme park located in the populous central Europe. Disney executives did not see that Mickey Mouse and intellectuals in the region of the left bank of the Seine in Paris can not live in harmony and France is serious about their intellectual. In retrospect, Paris is not the best place to establish such a theme park, so the establishment of the Disney parks is a declaration of war to intellectuals of French. Disney’s manager stated publicly some of the criticism is “the nonsense of a small number of business” would not help them a favor. This may can be well operated according to American culture, while the French pay more attention to their own cultural elite and regard this refute as attack of national quality.

Having not adequately take into account the habits of the French when arrange the service kinds Disney do not provide breakfast because they think that the Europeans do not eat breakfast. In addition, the Disney company does not provide alcoholic beverages within the park, but the French habits are different, they are used to drinking a cup while taking lunch, which aroused the anger of the French. Disney executives did not estimate that the European are not interested in vacation in theme park so much, in the attitude of Disney Company the European will be happy about spending a few days in a theme park like the American and Japanese, but middle-class in Europe just want to “get away from everything around” and go to the coast or the mountains, and Euro Disney is the lack of such appeal.

No combination of French culture to the local staff management Disney has taken global standard model as same as the Japanese business, they transplanted the American culture to France directly then doing this result with a serious clash of cultures. The Disney Company use many measures that departed with the local culture, for example, in the Euro Disney, the France worker are requested to comply with the strict appearance code as the other theme parks in United States and Japan do, the workers are asked to break their ancient cultural aversions to smiling and being consistently polite to the park guest even must mirror the multi-country makeup of its guest. In addition, the Disney Company brought their U.S. Pop culture to France and fought hard for a greater “local cultural context”. The French people think that this is an attack on their native culture, so they adopted an unfriendly attitude toward to the arrival of the Disney, including the protest come from the intellectual and the local residence and farmers.

The Three Lessons

Multinational companies should target market accurately even in the same country or regional market, the traditional culture makes different control power to different people. Multinational companies should be fully based on detailed market research to find the weak links in the market and make a breakthrough, use the “point to an area” model to expand. For example, McDonald’s opened in the Chinese market, its target is no longer work for the busy working-class, but the children. The golden arches mark, the joy atmosphere of the shop, the furnished toys, full of playful ads, as well as various promotional activities specifically carry out for children, these have a tremendous appeal to the target customers. McDonald think that adult eating habits difficult to change, only those children whose taste not yet formed are the potential customers of Western fast food culture, the McDonald received Broad market recognition and have huge market potential.

Multinational enterprises should pay full attention to the importance of the influence of cultural differences on marketing face to the new multiple culture environment, the multinational enterprise should take an objective acknowledge about the cultural differences of the consumer demand and behavior and respect it, abandoning the prejudice and discrimination of culture completely. Moreover, multinational enterprises should be good at finding out and using the base point of communication and collaboration of different cultures and regard this base point as the important consideration factor when plan to enter the target country market. After all, the fundamental criterion for a successful business enterprise is whether it can integrate into the local social and cultural environment. The multinational enterprises should improve the sensitivity and adaptability to the different culture environment.

Multinational enterprises should make full use of the competitive advantages of cultural differences and promote international marketing. The objective of international cultural differences can also be the basic demand points of different competitive strategy . In the international market, launching culture marketing activities and highlighting the exotic culture and cultural differences in the target market can open the market quickly. Companies should strive to build cross-cultural “two-way” communication channels, it is necessary to adapt to the host’s cultural environment and values and carry out the business strategy of localization to make it can be widely accepted by the host country local government, local partners, consumers and other relevant stakeholders. Effective cross-cultural communication on the one hand contribute to cultural integration, but also can create a harmonious internal and external human environment for corporate management.

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Euro Disney or Euro Disaster?

By: Goir Sheikholeslami, Leslie Grayson, Kunihiko Amano, Thomas Falk, Virginia Kleinclaus

Length: 11 page(s)
Publication Date: Oct 31, 1994
Discipline: General Management
Product #: UV0020-PDF-ENG

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Concerns the troubles that Euro Disney experienced from the start. Euro Disney claimed that the major cause of its poor financial performance was the European recession and the strong French franc. The timing of the park's opening could not have been more inopportune. If the recession had been the only cause of Euro Disney's problems, the financial restructuring would only need to carry the park forward to better economic times. Only when Europeans began spending freely again would investors learn the answers to some uncomfortable questions: Was the whole idea of Euro Disney misconceived? Were there other fundamental cultural problems that could inhibit the park's success? Would Euro Disney fail to recover even though other European companies did? And, if so, why was the Disney theme park concept successful in Japan and not in France?

Learning Objectives

To decide what factors played a role in the poor performance of Euro Disney.

Oct 31, 1994 (Revised: Sep 1, 1995)

Discipline:

General Management

Geographies:

Industries:

Amusement and theme parks

Darden School of Business

UV0020-PDF-ENG

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Euro Disney: The First 100 Days

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Mickey goes to france: a case study of the euro disneyland negotiations.

Lauren A. Newell , Ohio Northern University Follow

Document Type

Recommended citation.

Lauren A. Newell, Mickey Goes to France: A Case Study of the Euro Disneyland Negotiations, 15 Cardozo J. Conflict Resol. 193 (2013).

Euro Disneyland (since renamed Disneyland Resort Paris) in Marne-la-Vallée, France was declared a success even before it was built, and yet it narrowly escaped a humiliating bankruptcy after opening. This article applies intercultural negotiation theory to examine how The Walt Disney Company proved fallible in its negotiations with the French government and citizens in the course of constructing and operating Euro Disneyland.

Through a case study of the negotiations, this article reveals why the reality proved so different from the expectations. It concludes with advice for how The Walt Disney Company — and, by implication, any multinational firm — should approach international deal-making in the future to avoid repeating past mistakes.

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Publication date: 20 January 2017

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This case concerns the troubles that Euro Disney experienced from the start. Euro Disney claimed that the major cause of its poor financial performance was the European recession and the strong French franc. The timing of the park's opening could not have been more inopportune. If the recession had been the only cause of Euro Disney's problems, the financial restructuring would only need to carry the park forward to better economic times. Only when Europeans began spending freely again would investors learn the answers to some uncomfortable questions: Was the whole idea of Euro Disney misconceived? Were there other fundamental cultural problems that could inhibit the park's success? Would Euro Disney fail to recover even though other European companies did? And, if so, why was the Disney theme-park concept successful in Japan and not in France?

Capital structure
International case
Diversity case
International
Cross-cultural behavior

Grayson, L.E. and Sheikholeslami, G. (2017), "Euro Disney or Euro Disaster?", . https://doi.org/10.1108/case.darden.2016.000110

University of Virginia Darden School Foundation

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Case Study Disney in France for Cross Culture Management

Until 1992, the Walt Disney Company had experienced nothing but success in the theme park business. Its first park, Disneyland, opened in Anaheim, California, in 1955. Its theme song, It’s a Small World After All, promoted an idealized vision of America spiced with reassuring glimpses of exotic cultures all calculated to promote heartwarming feelings about living together as one happy family. There were dark tunnels and bumpy rides to scare the children a little but none of the terrors of the real world. The Disney characters that everyone knew from the cartoons and comic books were on hand to shepherd the guests and to direct them to the Mickey Mouse watches and Little Mermaid records. The Anaheim park was an instant success.

From the beginning, cultural gaffes by Disney set the tone for the project. By late 1986, Disney was deep in negotiations with the French government. To the exasperation of the Disney team, headed by Joe Shapiro, the talks were taking far longer than expected. Jean-Rene Bernard, the chief French negotiator, said he was astonished when Mr. Shapiro, his patience depleted, ran to the door of the room and, in a very un-Gallic gesture, began kicking it repeatedly, shouting, “Get me something to break!”

There was also snipping from Parisian intellectuals who attacked the transplantation of Disney’s dream world as an assault on French culture; “a cultural Chernobyl,” one prominent intellectual called it. The minister of culture announced he would boycott the opening, proclaiming it to be an unwelcome symbol of American clichés and a consumer society. Unperturbed, Disney pushed ahead with the planned summer 1992 opening of the $5 billion park. Shortly after Euro-Disneyland opened, French farmers drove their tractors to the entrance and blocked it. This globally televised act of protest was aimed not at Disney but at the US government, which had been demanding that French agricultural subsidies be cut. Still, it focused world attention upon the loveless marriage of Disney and Paris.

Then there were the operational errors. Disney’s policy of serving no alcohol in the park, since reversed caused astonishment in a country where a glass of wine for lunch is a given. Disney thought that Monday would be a light day for visitors and Friday a heavy one and allocated staff accordingly, but the reality was the reverse. Another unpleasant surprise was the hotel breakfast debacle. “We were told that Europeans ‘don’t take breakfast,’ so we downsized the restaurants,” recalled one Disney executive. “And guess what? Everybody showed up for breakfast. We were trying to serve 2,500 breakfasts in a 350-seat restaurant at some of the hotels. The lines were horrendous. Moreover, they didn’t want the typical French breakfast of croissants and coffee, which was our assumption. They wanted bacon and eggs.” Lunch turned out to be another problem. “Everybody wanted lunch at 12:30. The crowds were huge. Our smiling cast members had to calm down surly patrons and engage in some ‘behavior modification’ to teach them that they could eat lunch at 11:00 AM or 2:00 PM.”

There were major staffing problems too. Disney tried to use the same teamwork model with its staff that had worked so well in America and Japan, but it ran into trouble in France. In the first nine weeks of Euro-Disneyland’s operation, roughly 1,000 employees, 10 percent of the total, left. One former employee was a 22-year-old medical student from a nearby town who signed up for a weekend job. After two days of “brainwashing,” as he called Disney’s training, he left following a dispute with his supervisor over the timing of his lunch hour. Another former employee noted, “I don’t think that they realize what Europeans are like… that we ask questions and don’t think all the same way.”

At this point, Euro-Disney changed its strategy. First, the company changed the name to Disneyland Paris in an attempt to strengthen the park’s identity. Second, food and fashion offerings changed. To quote one manager, “We opened with restaurants providing Frenchstyle food service, but we found that customers wanted self-service like in the US parks. Similarly, products in the boutiques were initially toned down for the French market, but since then the range has changed to give it a more definite Disney image.” Third, the prices for day tickets and hotel rooms were cut by one-third. The result was an attendance of 11.7 million in 1996, up from a low of 8.8 million in 1994.

Many mistakes have been made in the realization of the Euro Disney entertainment park in France. They literally transplanted US culture in France without taking into consideration the cultural clash that this might have caused. US imposed their culture over the French one, and this was seen as an attack to French traditions and customs, resulting in protests from local residence and farmers.

First of all, there was a general misunderstanding of the French culture both under the lifestyle and legal aspects. The top management made wrong assumptions, which led them to take wrong management decisions. In fact, French habits and traditions were not taken in to account. For example, breakfast at the park was not served; instead in the French culture breakfast is one of the most important “moments” of the day. Moreover, alcoholic drinks were not allowed in the park: contrary French always have a glass of wine during their main meals. In addition, also the dress code requirements did not meet the French standards in work environments. And the fact that they were supposed to be always smiling and kind did not reflect the French attitude and the staff was not comfortable with these policies. Furthermore, the top management positions were al given to American, which made the situation even worse because they were incapable to fix the mistakes made from the very start. Instead, if they had hired French people to manage the park, they would have been able to assess these cultural differences in a more efficient way, avoiding such a cultural clash.

Second, it was given for granted that French entertainment culture was as the US one. Thus, staff and resources were allocated in the wrong way, because the peek days were not the same as the US Disney Land. This led to a lack of staff in crowded days and a surplus of staff in empty days affecting efficiency and profitability of the park negatively. Moreover, they assumes French would have gone to the park with their private transportation, thus they built many car parks which were most of the time empty, instead the parking were not big enough for buses, which was the more used transport used to get to the park.

Third, recession signs were not taken into consideration and too high expectations were placed in the profitability of this new Euro Disney. Thus, too high revenue expectations were set and the park did not even manage to sell the tickets available also due to the quite high price imposed. Moreover, the wrong allocation of staff and resources made the situation even worse and the park’s expenses almost were more than its revenues.

From this case study, many lessons can be learned. First of all, never give for granted that if one project is successful according to the parameters of one society and culture, this does not mean that if we export it else where this success will remain unchanged. Cultural factors are crucial for the success of any business and to disregard and to “attack” others traditions and customs can be destructive. Before opening a business already well established in another country, the company has to do a very deep and targeted market research in order to better understand both the culture and how that same business can adapt to the different kind of need clients in the country might have. Moreover, the success of an organization depends on how united the organization is especially the executive, and it is essential to resolve workplace issues, make employees happy with policies and have excellent communication tools. In conclusion, a company should make use of cultural differences to have a competitive advantage over other entertainment parks and make it unique, not only a copy of the already existing ones.

References:

http://www.depa.univ-paris8.fr/IMG/pdf/Disney_Case_Study.pdf

https://geert-hofstede.com/national-culture.html

https://en.wikipedia.org/wiki/Hofstede%27s_cultural_dimensions_theory

https://www2.gwu.edu/~umpleby/recent_papers/2003_cross_cultural_differences_managin_international_projects_anbari_khilkhanova_romanova_umpleby.htm

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Bibliographic information

Why Euro Disney Is A 22-Year Money-Losing Failure

Even Mickey Mouse is not exempt from France's financial troubles .

Walt Disney announced on Monday a €1 billion ($1.25 billion) bailout plan to rescue its subsidiary Disneyland Paris, the Financial Times reported .

The French theme park is still Europe's top tourist destination, but it has been hit by the financial crisis more than other competitors. To make a profit, the park needs about 15 million visitors a year: there were 14.1 in the past 12 months. Losses are expected in the order of €110 million to € 120 million ($138 million to $ 150 million).

The park is burdened by its debt, which is calculated at about €1.75 billion ($2.20 billion) and roughly 15 times its gross average earnings. Speaking with the FT, Mark Stead, the company's financial director, said: “Our Achilles' heel has always been our debt ratio, which compared to our rivals is off the charts.”

Euro Disney Case Study

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Mechanical engineering

Several catastrophic building collapses 1 , 2 , 3 , 4 , 5 occur because of the propagation of local-initial failures 6 , 7 . Current design methods attempt to completely prevent collapse after initial failures by improving connectivity between building components. These measures ensure that the loads supported by the failed components are redistributed to the rest of the structural system 8 , 9 . However, increased connectivity can contribute to collapsing elements pulling down parts of a building that would otherwise be unaffected 10 . This risk is particularly important when large initial failures occur, as tends to be the case in the most disastrous collapses 6 . Here we present an original design approach to arrest collapse propagation after major initial failures. When a collapse initiates, the approach ensures that specific elements fail before the failure of the most critical components for global stability. The structural system thus separates into different parts and isolates collapse when its propagation would otherwise be inevitable. The effectiveness of the approach is proved through unique experimental tests on a purposely built full-scale building. We also demonstrate that large initial failures would lead to total collapse of the test building if increased connectivity was implemented as recommended by present guidelines. Our proposed approach enables incorporating a last line of defence for more resilient buildings.

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Disasters recorded from 2000 to 2019 are estimated to have caused economic losses of US$2.97 trillion and claimed approximately 1.23 million lives 11 . Most of these losses can be attributed to building collapses 12 , which are often characterized by the propagation of local-initial failures 13 that can arise because of extreme or abnormal events such as earthquakes 13 , 14 , 15 , 16 , floods 17 , 18 , 19 , 20 , storms 21 , 22 , landslides 23 , 24 , explosions 25 , vehicle impacts 26 and even construction or design errors 6 , 26 . As the world faces increasing trends in the frequency and intensity of extreme events 27 , 28 , it is arguably now more important than ever to design robust structures that are insensitive to initial damage 13 , 29 , irrespective of the underlying threat causing it.

Most robustness design approaches used at present 8 , 9 , 30 , 31 aim to completely prevent collapse initiation after a local failure by providing extensive connectivity within a structural system. Although these measures can ensure that the load supported by a failed component is redistributed to the rest of the structure, they are neither viable nor sustainable when considering larger initial failures 13 , 25 , 32 . In these situations, the implementation of these approaches can even result in collapsing parts of the building pulling down the rest of the structure 10 . The fact that several major collapses have occurred because of large initial failures 6 raises serious concerns about the inadequacy of the current robustness measures.

Traditionally, research in this area has focused on preventing collapse initiation after initial failures rather than on preventing collapse propagation. This trend dates back to the first impactful studies in the field of structural robustness, which were performed after a lack of connectivity enabled the progressive collapse of part of the Ronan Point tower in 1968 (ref. 33 ). Although completely preventing any collapse is certainly preferable to limiting the extent of a collapse, the occurrence of unforeseeable incidents is inevitable 34 and major building collapses keep occurring 1 , 2 , 3 .

Here we present an original approach for designing buildings to isolate the collapse triggered by a large initial failure. The approach, which is based on controlling the hierarchy of failures in a structural system, is inspired by how lizards shed their tails to escape predators 35 . The proposed hierarchy-based collapse isolation design ensures sufficient connectivity for operational conditions and after local-initial failures for which collapse initiation can be completely prevented through load redistribution. These local-initial failures can even be greater than those considered by building codes. Simultaneously, the structural system is also designed to separate into different parts and isolate a collapse when its propagation would otherwise be inevitable. As in the case of lizard tail autotomy 35 , this is achieved by promoting controlled fracture along predefined segment borders to limit failure propagation. In this work, hierarchy-based collapse isolation is applied to framed building structures. Developing this approach required a precise characterization of the collapse propagation mechanisms that need to be controlled. This was achieved using computational simulations that were validated through a specifically designed partial collapse test of a full-scale building. The obtained results demonstrate the viability of incorporating hierarchy-based collapse isolation in building design.

Hierarchy-based collapse isolation

Hierarchy-based collapse isolation design makes an important distinction between two types of initial failures. The first, referred to as small initial failures, includes all failures for which it is feasible to completely prevent the initiation of collapse by redistributing loads to the remaining structural system. The second type of initial failure, referred to as large initial failures, includes more severe failures that inevitably trigger at least a partial collapse.

The proposed design approach aims to (1) arrest unimpeded collapse propagation caused by large initial failures and (2) ensure the ability of a building to develop alternative load paths (ALPs) to prevent collapse initiation after small initial failures. This is achieved by prioritizing a specific hierarchy of failures among the components on the boundary of a moving collapse front.

Buildings are complex three-dimensional structural systems consisting of different components with very specific functions for transferring loads to the ground. Among these, vertical load-bearing components such as columns are the most important for ensuring global structural stability and integrity. Therefore, hierarchy-based collapse isolation design prevents the successive failure of columns, which would otherwise lead to catastrophic collapse. Although the exact magnitude of dynamic forces transmitted to columns during a collapse process is difficult to predict, these forces are eventually limited by the connections between columns and floor systems. In the proposed approach, partial-strength connections are designed to limit the magnitude of transmitted forces to values that are lower than the capacity of columns to resist unbalanced forces (see section ‘ Building design ’). This requirement guarantees a specific hierarchy of failures during collapse, whereby connection failures always occur before column failures. As a result, the collapse following a large initial failure is always restricted to components immediately adjacent to those directly involved in the initial failure. However, it is still necessary to ensure a lower bound on connection strengths to activate ALPs after small initial failures. Therefore, cost-effective implementation of hierarchy-based collapse isolation design requires finding an optimal balance between reducing the strength of connections and increasing the capacity of columns.

To test and verify the application of our proposed approach, we designed a real 15 m × 12 m precast reinforced concrete building with two 2.6-m-high floors. This basic geometry represents a building size that can be built and tested at full-scale while still being representative of current practices in the construction sector. The structural type was selected because of the increasing use of prefabricated construction for erecting high-occupancy buildings such as hospitals and malls because of several advantages in terms of quality, efficiency and sustainability 36 .

The collapse behaviour of possible design options (Extended Data Fig. 1 ) subjected to both small and large initial failures was investigated using high-fidelity collapse simulations (Fig. 1 ) based on the applied element method (AEM; see section ‘ Modelling strategy ’). The ability of these simulations to accurately represent collapse phenomena for the type of building being studied was later validated by comparing its predictions to the structural response observed during a purposely designed collapse test of a full-scale building (Extended Data Fig. 2 and Supplementary Video 7 ).

a , Partial-strength beam–column connection optimized for hierarchy-based collapse isolation. b , Partial collapse of a building designed for hierarchy-based collapse isolation (design H) after the loss of a corner column and two penultimate-edge columns. c , Total collapse of conventional building design (design C) after the same large initial failure scenario.

Following the preliminary design of a structure to resist loads suitable for office buildings, two building design options considering different robustness criteria were further investigated (see section ‘ Building design ’). The first option, design H (hierarchy-based), uses optimized partial-strength connections and enhanced columns (Fig. 1a ) to fulfil the requirements of hierarchy-based collapse isolation design. The second option, design C (conventional), is strictly based on code requirements and provides a benchmark comparison for evaluating the effectiveness of the proposed approach. It uses full-strength connections to improve robustness as recommended in current guidelines 37 and building codes 8 , 9 .

Simulations predicted that both design H and design C could develop stable ALPs that are able to completely prevent the initiation of collapse after small initial failure scenarios that are more severe than those considered in building codes 8 , 9 (Extended Data Fig. 3 ).

When subjected to a larger initial failure, simulations predict that design H can isolate the collapse to only the region directly affected by the initial failure (Fig. 1b ). By contrast, design C, with increased connectivity, causes collapsing elements to pull down the rest of the structure, leading to total collapse (Fig. 1c ). These two distinct outcomes demonstrate that the prevention of unimpeded collapse propagation can only be ensured when hierarchy-based collapse isolation is implemented (Extended Data Fig. 4 and Supplementary Video 1 ).

Testing a full-scale precast building

To confirm the expected performance improvement that can be achieved with the hierarchy-based collapse isolation design, a full-scale building specimen corresponding to design H was purposely built and subjected to two phases of testing as part of this work (Fig. 2a and Supplementary Information Sections 1 and 2 ). The precast structure was constructed with continuous columns cast together with corbels (Supplementary Video 4 ). The columns were cast with prepared dowel bars and sleeves for placing continuous top beam reinforcement bars through columns (Fig. 2b,c ). The bars used for these two types of reinforcing element (Fig. 1a ) were specifically selected to produce partial-strength connections. These connections are strong enough for the development of ALPs after small initial failures but weak enough to enable hierarchy-based collapse isolation after large initial failures.

a , Full-scale precast concrete structure and columns removed in different testing phases. The label used for each column is shown. The location of beams connecting the different columns is indicated by the dotted lines above the second-floor level. The expected collapse area in the second phase of testing is indicated. b , Typical first-floor connection before placement of beams during construction. c , Typical second-floor connection after placement of precast beams during construction. Both b and c show columns with two straight precast beams on either side (C2, C3, C6, C7, C10 and C11). d , Device used for quasi-static removal of two columns in the first phase of testing. e , Three-hinged mechanism used for dynamic removal of corner column in the second phase of testing.

After investigating different column-removal scenarios from different regions of the test building (see section ‘ Experiment and monitoring design ’, Extended Data Fig. 5 and Supplementary Video 2 ), two phases of testing were defined to capture relevant collapse-related phenomena and validate the effectiveness of hierarchy-based collapse isolation. Separating the test into two phases allowed two different aspects to be analysed: (1) the prevention of collapse initiation after small initial failures and (2) the isolation of collapse after large initial failures.

Phase 1 involved the quasi-static removal of two penultimate-edge columns using specifically designed removable supports (Fig. 2d and Extended Data Fig. 6 ). This testing phase corresponds to a small initial failure scenario for which design H was able to develop ALPs to prevent collapse initiation. Phase 2 reproduced a large initial failure through the dynamic removal of the corner column found between the two previously removed columns using a three-hinged collapsible column (Fig. 2e ).

During both testing phases, a distributed load (11.8 kN m −2 ) corresponding to almost twice the magnitude specified in Eurocodes 38 for accidental design situations (6 kN m −2 ) was imposed on bays expected to collapse in phase 2 (Fig. 2a and Supplementary Video 5 ). Predictive simulations indicated that the failure mode and overall collapse would be almost identical when comparing this partial loading configuration with that in which the entire building is loaded (Supplementary Video 3 ). However, the partial loading configuration turns out to be more demanding for the part of the structure expected to remain upright as evidenced by the greater drifts it produces during collapse (see section ‘ Experiment and monitoring design ’ and Extended Data Fig. 7 ). The structural response during all phases of testing was extensively monitored with an array of different sensors (see section ‘ Experiment and monitoring design ’ and Supplementary Information Section 3 ) that provided the information used as a basis for the analyses presented in the following sections.

Preventing collapse initiation

Collapse initiation was completely prevented after the removal of two penultimate-edge columns in phase 1 of testing (Fig. 3a ), demonstrating that design H complies with the robustness requirements included in current building standards 8 , 9 , 39 . As this initial failure scenario is more severe than those considered by standardized design methods 8 , 9 , 30 , it represents an extreme case for which ALPs are still effective. As such, the outcome of phase 1 demonstrates that implementing hierarchy-based collapse isolation design does not impair the ability of this structure to prevent collapse initiation.

a , Test building during phase 1 of testing after removal of columns C8 and C11. The beam depth ( h ) used to compute the ratio plotted in b is shown and the location of the strain measurement plotted in c is indicated. b , Evolution of beam deflection expressed as a ratio of beam depth at the location of removed column C11. The chord rotation of the beams bridging over this removed column is also indicated using a secondary vertical axis. c , Strain increase in continuity reinforcement in the second-floor beam between C12 and C11.

Source Data

Analysis of the structural response during phase 1 (Supplementary Information Section 4 ) shows that collapse was prevented because of the redistribution of loads through the beams (Fig. 3b,c ), columns (Extended Data Fig. 8 ) and slabs (Supplementary Report 4 ) adjacent to the removed columns. The beams bridging over the removed columns sustained loads through flexural action, as evidenced by the magnitude of the vertical displacement recorded at the removal locations (Fig. 3b ). These values were far too small to allow the development of catenary forces, which only begin to appear when displacements exceed the depth of the beam 40 .

The flexural response of the structure after the loss of two penultimate-edge columns was only able to develop because of the specific reinforcement detailing introduced in the design. This was verified by the increase in tensile strains recorded in the continuous beam reinforcement close to the removed column (Fig. 3c ) and in ties placed between the precast hollow-core planks in the floor system close to column C7 (Supplementary Information Section 4 ). The latter also proves that the slabs contributed notably to load redistribution after column removal.

In general, the structure experienced only small movements and suffered very little permanent damage during phase 1 (Supplementary Information Section 4 ), despite the high imposed loads used for testing. The only reinforcement bars showing some signs of yielding were the continuous reinforcement bars of beams close to the removed columns (Fig. 3c ).

Arresting collapse propagation

Following the removal of two penultimate-edge columns in phase 1, the sudden removal of the C12 corner column in phase 2 triggered a collapse that was arrested along the border delineated by columns C3, C7, C6 and C10 (Fig. 4a–d and Supplementary Video 6 ). Thus, the viability of hierarchy-based collapse isolation design is confirmed.

a , Collapse sequence during phase 2 of testing. b , Partial collapse of full-scale test building (design H) after the removal of three columns. The segment border in which collapse propagation was arrested is indicated. The axes shown at column C9 correspond to those used in f to indicate the changing direction of the resultant drift measured at this location. c , Failure of beam–column connections at collapse border. d , Debonding of reinforcement in the floor at collapse border. e , Change in average axial strains measured in column C7. A negative change represents an increase in compressive strains. f , Magnitude of resultant drift measured at C9. g , Change in direction of resultant drift measured at C9. The initial drift after phase 1 of testing and the residual drift after the upright part of the building stabilized are also shown in the plot.

During the initial stages following the removal of C12, the collapsing bays next to this column pulled up the columns on the opposite corner of the building (columns C1, C3 and C6). During this process, column C7 behaves like a pivot point, experiencing a significant increase in compressive forces (Fig. 4e and Supplementary Information Section 5 ). This phenomenon was enabled by the connectivity between collapsing parts and the rest of the structure. If allowed to continue, this could have led to successive column failures and unimpeded collapse propagation. However, during the test, the rupture of continuous reinforcement bars (Fig. 4c ) occurred as the connections failed and halted the transmission of forces to columns. These connection failures occurred before any column failures, as intended by the hierarchy-based collapse isolation design of the structural system. Specifically, this type of connection failure occurred at the junctions with the two columns (C7 and C10) immediately adjacent to the failure origin (around C8, C11 and C12), effectively segmenting the structure along the border shown in Fig. 4b . Segmentation along this border was completed by the total separation of the floor system, which was enabled by the debonding of slab reinforcements at the segment border (Fig. 4d and Supplementary Video 8 ).

Observing the building drift measured at the top of column C9 (Fig. 4f ) enabled us to better understand the nature of forces acting on the building further away from the collapsing region. The initial motion shows the direction of pulling forces generated by the collapsing elements (Fig. 4g ). This drift peaks very shortly after the point in time when separation of the collapsing parts occurs (Fig. 4f ). After this peak, the upright part of the structure recoiled backwards and experienced an attenuated oscillatory motion before finding a new stable equilibrium (Fig. 4g ). The magnitude of the measured peak drift is comparable to the drift limits considered in seismic regions when designing against earthquakes with a 2,500-year return period 41 (Supplementary Information Section 5 ). This indicates that the upright part of the structure was subjected to strong dynamic horizontal forces as it was effectively tugged by the collapsing elements falling to the ground. The building would have failed because of these unbalanced forces had hierarchy-based collapse isolation design not been implemented.

The upright building segment suffered permanent damages as evidenced by the residual drift recorded at the top of column C9 (Fig. 4g ). This is further corroborated by the fact that several reinforcement bars in this part of the structure yielded, particularly in areas close to the segment border (Supplementary Report 5 ). Despite the observed level of damage, safe evacuation and rescue of people from this building segment would still be possible after an extreme event, saving lives that would have been lost had a more conventional robustness design (design C) been used instead.

Discussion and future outlook

Our results demonstrate that the extensive connectivity adopted in conventional robustness design can lead to catastrophic collapse after large initial failures. To address this risk, we have developed and tested a collapse isolation design approach based on controlling the hierarchy of failures occurring during the collapse. Specifically, it is ensured that connection failures occur before column failures, mitigating the risk of collapse propagation throughout the rest of the structural system. The proposed approach has been validated through the partial collapse test of a full-scale precast building, showing that propagating collapses can be arrested at low cost without impairing the ability of the structure to completely prevent collapse initiation after small initial failures.

The reported findings show a last line of defence against major building collapses due to extreme events. This paves the way for the proposed solution to be developed, tested and implemented in different building types with different building elements. This discovery opens opportunities for robustness design that will lead to a new generation of solutions for avoiding catastrophic building collapses.

Building design

Our hierarchy-based collapse isolation approach ensures buildings have sufficient connectivity for operational conditions and small initial failures, yet separate into different parts and isolate a collapse after large initial failures. We chose a precast construction as our main structural system for our case study. A notable particularity of precast systems compared with cast-in-place buildings is that the required construction details can be implemented more precisely. We designed and systematically investigated two precast building designs: designs H and C.

Design H is our building design in which the hierarchy-based collapse isolation approach is applied. Design H was achieved after several preliminary iterations by evaluating various connections and construction details commonly adopted in precast structures. The final design comprises precast columns with corbels connected to a floor system (partially precast beams and hollow-core slabs) through partial-strength beam–column connections (Extended Data Fig. 1 and Supplementary Information Section 1 ). This partial-strength connection was achieved by (1) connecting the bottom part of the beam (precast) to optimally designed dowel bars anchored to the column corbels and (2) passing continuous top beam bars through the columns. With this partial-strength connection, we have more direct control over the magnitude of forces being transferred from the floor system to the columns, which is a key aspect for achieving hierarchy-based collapse isolation. The hierarchy of failures was initially implemented through the beam–column connections (local level) and later verified at the system (global) level.

At the local level, three main components are designed according to the hierarchy-based concept: (1) top continuity bars of the beams; (2) dowel bars connecting beams to corbels; and (3) columns.

Top continuity bars of beams: To allow the structural system to redistribute the loads after small initial failures, top reinforcement bars in all beams were specifically designed to fulfil structural robustness requirements (Extended Data Fig. 3 ). Particularly, we adopted the prescriptive tying rules (referred to as Tie Forces) of UFC 4-023-03 (ref. 9 ) to perform the design of the ties. The required tie strength F i in both the longitudinal and transverse directions for the internal beams is expressed as

For the peripheral beams, the required tie strength F P is expressed as

where w F = floor load (in kN m −2 ); D = dead load (in kN m −2 ); L = live load (in kN m −2 ); L 1 = greater of the distances between the centres of the columns, frames or walls supporting any two adjacent floor spaces in the direction under consideration (in m); L P = 1.0 m; and W C = 1.2 times dead load of cladding (neglected in this design).

These required tie strengths are fulfilled with three bars (20 mm diameter) for the peripheral beams and three bars (25 mm diameter) for the internal beams. These required reinforcement dimensions were implemented through the top bars of the beam and installed continuously (lap-spliced, internally, and anchored with couplers at the ends) throughout the building (Extended Data Fig. 1 ).

Dowel bars connecting the beam and corbel of the column: The design of the dowel bars is one of the key aspects in achieving partial-strength connections that fail at a specific threshold to enable segmentation. These dowel bars would control the magnitude of the internal forces between the floor system and column while allowing for some degree of rotational movement. The dowels were designed to resist possible failure modes using expressions proposed in the fib guidelines 37 . Several possible failure modes were checked: splitting of concrete around the dowel bars, shear failure of the dowel bars and forming a plastic hinge in the dowel. The shear capacity of a dowel bar loaded in pure shear can be determined according to the Von Mises yield criterion:

where f yd is the design yield strength of the dowel bar and A s is the cross-sectional area of the dowel bar. In case of concrete splitting failure, the highly concentrated reaction transferred from the dowel bar shall be designed to be safely spread to the surrounding concrete. The strut and tie method is recommended to perform such a design 42 . If shear failure and splitting of concrete do not occur prematurely, the dowel bar will normally yield in bending, indicated by the formation of a plastic hinge. This failure mode is associated with a significant tensile strain at the plastic hinge location of the dowel bar and the crushing of concrete around the compression part of the dowel. The shear resistance achieved at this state for dowel (ribbed) bars across a joint of a certain width (that is, the neoprene bearing) can be expressed as

where α 0 is a coefficient that considers the bearing strength of concrete and can be taken as 1.0 for design purposes, α e is a coefficient that considers the eccentricity, e is the load eccentricity and shall be computed as the half of the joint width (half of the neoprene bearing thickness), Φ and A s are the diameter and the cross-sectional area of the dowel bar, respectively, f cd,max is the design concrete compressive strength at the stronger side, σ sn is the local axial stress of the dowel bar at the interface location, ${f}_{{\rm{yd}},{\rm{red}}}={f}_{{\rm{yd}}}-{\sigma }_{{\rm{sn}}}$ is the design yield strength available for dowel action, f yd is the yield strength of the dowel bar and μ is the coefficient of friction between the concrete and neoprene bearing. By performing the checks on these three possible failure modes, we selected the final (optimum) design with a two dowel bars (20 mm diameter) configuration.

Columns: The proposed hierarchy-based approach requires columns to have adequate capacity to resist the internal forces transmitted by the floor system during a collapse. By fulfilling this strength hierarchy, we can ensure and control that failure happens at the connections first before the columns fail, thus preventing collapse propagation. The columns were initially designed according to the general procedure prescribed by building standards. Then, the resulting capacity was verified using the modified compression field theory (MCFT) 43 to ensure that it was higher than the maximum expected forces transmitted by the connection to the floor system. MCFT was derived to consistently fulfil three main aspects: equilibrium of forces, compatibility and rational stress–strain relationships of cracked concrete expressed as average stresses and strains. The principal compressive stress in the concrete f c 2 is expressed not only as a function of the principal compressive strain ε 2 but also of the co-existing principal tensile strain ε 1 , known as the compression softening effect:

where f c 2max is the peak concrete compressive strength considering the perpendicular tensile strain, ${f}_{c}^{{\prime} }$ is the uniaxial compressive strength, and ${\varepsilon }_{{c}^{{\prime} }}$ is the peak uniaxial concrete compressive strain and can be taken as −0.002. In tension, concrete is assumed to behave linearly until the tensile strength is achieved, followed by a specific decaying function 43 . Regarding aggregate interlock, the shear stress that can be transmitted across cracks v ci is expressed as a function of the crack width w , and the required compressive stress on the crack f ci (ref. 44 ):

where a refers to the maximum aggregate size in mm and the stresses are expressed in MPa. The MCFT analytical model was implemented to solve the sectional and full-member response of beams and columns subjected to axial, bending and shear in Response 2000 software (open access) 45 , 46 . In Response 2000, we input key information, including the geometries of the columns, reinforcement configuration and the material definition for the concrete and the reinforcing bars. Based on this information, we computed the M – V (moment and shear interaction envelope) and M – N (moment and axial interaction envelope) diagrams that represent the capacity of the columns. The results shown in Extended Data Fig. 4 about the verification of the demand and capacity envelopes were obtained using the analytical procedure described here.

At the global level, the initially collapsing regions of the building generate a significant magnitude of dynamic unbalanced forces. The rest of the building system must collectively resist these unbalanced forces to achieve a new equilibrium state. Depending on the design of the structure, this phenomenon can lead to two possible scenarios: (1) major collapse due to failure propagation or (2) partial collapse only of the initially affected regions. The complex interaction between the three-dimensional structural system and its components must be accounted for to evaluate the structural response during collapse accurately. Advanced computational simulations, described in the ‘ Modelling strategy ’ section, were adopted to analyse the global building to verify that major collapse can be prevented. The final design obtained from the local-level analysis (top continuity bars, dowel bars and columns) was used as an input for performing the global computational simulations. Certain large initial failures deemed suitable for evaluating the performance of this building were simulated. In case failure propagation occurs, the original hierarchy-based design must be further adapted. An iterative process is typically required involving several simulations with various building designs to achieve an optimum result that balances the cost and desired collapse performance. The final iteration of design H, which fulfils both the local and global hierarchy checks, is provided in Extended Data Fig. 1 .

Design C is a conventional building design that complies with current robustness standards but does not explicitly fulfil our hierarchy-based approach. The same continuity bars used in design H were used in design C. We adopted a full-strength connection as recommended by the fib guideline 37 . The guideline promotes full connectivity to enhance the development of alternative load paths for preventing collapse initiation. In design C, we used a two dowel bars (32 mm diameter) configuration to ensure full connectivity when the beams are working at their maximum flexural capacity. Another main difference was that the columns in design C were designed according to codes and current practice (optimal solution) without explicitly checking that hierarchy-based collapse isolation criteria are fulfilled. The final design of the columns and connections adopted in design C is provided in Extended Data Fig. 1 .

Modelling strategy

We used the AEM implemented in the Extreme Loading for Structures software to perform all the computational simulations presented in this study 47 (Extended Data Figs. 2 – 5 and 7 and Supplementary Videos 1 , 2 , 3 and 7 ). We chose the AEM for its ability to represent all phases of a structural collapse efficiently and accurately, including element separation (fracture), contact and collision 47 . The method discretizes a continuum into small, finite-size elements (rigid bodies) connected using multiple normal and shear springs distributed across each element face. Each element has six degrees of freedom, three translational and three rotational, at its centre, whereas the behaviour of the springs represents all material constitutive models, contact and collision response. Despite the simplifying assumptions in its formulation 48 , its ability to accurately account for large displacements 49 , cyclic loading 50 , as well as the effects of element separation, contact and collision 51 has been demonstrated through many comparisons with experimental and theoretical results 47 .

Geometric and physical representations

We modelled each of the main structural components of the building separately, including the columns, beams, corbels and hollow-core slabs. We adopted a consistent mesh size with an average (representative) size of 150 mm. Adopting this mesh configuration resulted in a total number of 98,611 elements. We defined a specialized interface with no tensile or shear strength between the precast and cast-in-situ parts to allow for localized deformations that occur at these locations. The behaviour of the interface was mainly governed by a friction coefficient of 0.6, which was defined according to concrete design guidelines 52 , 53 , 54 . The normal stiffness of these interfaces corresponded to the stiffness of the concrete cast-in-situ topping. The elastomeric bearing pads supporting the precast beams on top of the corbels were also modelled with a similar interface having a coefficient of friction of 0.5 (ref. 55 ).

Element type and constitutive models

We adopted an eight-node hexahedron (cube) element with the so-called matrix-springs connecting adjacent cubes to model the concrete parts. We adopted the compression model in refs. 56 , 57 to simulate the behaviour of concrete under compression. Three specific parameters are required to define the response envelope: the initial elastic modulus, the fracture parameter and the compressive plastic strain. For the behaviour in tension, the spring stiffness is assumed to be linear (with the initial elastic modulus) until reaching the cracking point. The shear behaviour is considered to remain linear up to the cracking of the concrete. The interaction between normal compressive and shear stress follows the Mohr–Coulomb failure criterion. After reaching the peak, the shear stress is assumed to drop to a certain residual value affected by the aggregate interlock and friction at the cracked surface. By contrast, under tension, both normal and shear stresses drop to zero after the cracking point. The steel reinforcement bars were simulated as a discrete spring element with three force components: the normal spring takes the principal/normal forces parallel to the rebar, and two other springs represent the reinforcement bar in shear (dowelling). Three distinct stages are considered: elastic, yield plateau and strain hardening. A perfect bond behaviour between the concrete and the reinforcement bars was adopted. We assigned the material properties based on the results of the laboratory tests performed on reinforcement bars and concrete cylinders (Supplementary Information Section 2 ).

Boundary conditions and loading protocol

We assumed that all the ground floor columns are fully restrained in all six degrees of freedom at the base location. This assumption is reasonable, as we expected that the footing would provide sufficient rigidity to constrain any significant deformations. We assigned the reflecting domain boundaries to allow a realistic representation of the collapsing elements (debris) that might fall and rebound after hitting the ground. The ground level was assumed to be at the same elevation at which the column bases are restrained. We applied the additional imposed uniform distributed load as an extra volume of mass assigned to the slabs. To perform the column removal, we used the element removal feature that allows some specific designated elements to be immediately removed at the beginning of the loading stage. This represents a dynamic (sudden) removal, as we expected from the actual test.

Extended Data Tables 1 and 2 summarize all key parameters and assumptions adopted in the modelling process. To validate these assumptions for simulating the precast building designs described previously, it was ensured that the full-scale test performed as part of this work captured all relevant phenomena influencing collapse (large displacements, fracture, contact and collision).

Experiment and monitoring design

We used computational simulations of design H subjected to different initial failure scenarios to define a suitable testing sequence and protocol. The geometry, reinforcement configurations, connection system and construction details of the purpose-built specimen representing design H are provided in Supplementary Information Section 1 and Supplementary Video 4 .

Initial failure scenarios

Initial failure scenarios occurring in edge and corner regions of the building were prioritized for this study because they are usually exposed to a wider range of external threats 58 , 59 , 60 , 61 . After performing a systematic sensitivity study, we identified three critical scenarios (Extended Data Fig. 5 and Supplementary Video 2 ):

Scenario 1: a scenario involving a two-column failure—a corner column and the adjacent edge column. We determined that the required gravity loads to induce collapse equal 11.5 kN m −2 and that partial collapse would occur locally.

Scenario 2: a scenario involving a three-column failure—two corner columns and the edge column in between the two corner columns. We determined that the required gravity loads to induce collapse equal 8.5 kN m −2 and that segmentation (partially collapsing two bays) would take place only across one principal axis of the building.

Scenario 3: a scenario involving a three-column failure: one corner column and two edge columns on both sides of the corner column. We determined that the required gravity loads to induce collapse equal 7.0 kN m −2 and that segmentation (partially collapsing three bays) would take place across both principal axes of the building.

Scenario 3 was ultimately chosen after considering three main aspects: (1) it requires the lowest gravity loads to trigger partial collapse; (2) the failure mode involves activating segmentation mechanisms in two principal axes of the building (more realistic collapse pattern); and (3) the ratio of the area of the intact part and the collapsed part was predicted to be 50:50, leading to the largest collapse area among the three scenarios.

Testing phases

To allow us to investigate the behaviour of the building specimen under small and large initial failures in only one building specimen, we decided to perform two separate testing phases. Phase 1 involved the quasi-static (gradual) removal of two edge columns (C8 and C11), whereas phase 2 involved the sudden removal of the corner column (C12) found between the columns removed in phase 1. A uniformly distributed load of 11.8 kN m −2 was applied only on the bays directly adjacent to these three columns without loading the remaining bays (Supplementary Video 5 ). This was achieved by placing more than 8,000 sandbags in the designated bays on the two floors (the first- and second-floor slabs). We performed additional computational simulations to compare this partial loading configuration and loading of the entire building. The simulations indicated that both would have resulted in almost identical final collapse states (Extended Data Fig. 7 and Supplementary Video 3 ). However, the partial loading configuration introduced a higher magnitude of unbalanced moment to surrounding columns, which induces more demanding bending and shear in columns. Simulations confirmed that the lateral drift of the remaining part of the building would be higher when only three bays are loaded, indicating that its stability would be tested to a greater extent with this loading configuration (Extended Data Fig. 7 ).

Specially designed elements to trigger initial failures

We designed special devices to perform the column removal (Extended Data Fig. 6 ). For phase 1, we constructed two hanging concrete columns (C8 and C11) supported only on a vertical hydraulic jack. The pressure in the jack could be gradually released from a safe distance to remove the vertical reaction supporting the column. In phase 2, a three-steel-hinged column was used as the corner column. The middle part of the column represents a central hinge that was able to rotate if unlocked. During the second testing phase, we unlocked the hinge by pulling the column from outside the building using a forklift to induce a slight destabilization. This resulted in a sudden removal of the corner column C12 and the initiation of the collapse.

Monitoring plan

To monitor the structural behaviour, we heavily instrumented the building specimen with multiple sensors. A total of 57 embedded strain gauges, 17 displacement transducers and 5 accelerometers were placed at key locations in different parts of the structure (Extended Data Fig. 8 and Supplementary Information Section 3 ) during all phases of testing. The data from these sensors (Supplementary Information Sections 4 and 5 ) were complemented by the pictures and videos of the structural response captured by five high-resolution cameras and two drones (Supplementary Videos 6 and 8 ).

Data availability

All experimental data recorded during testing of the full-scale building are available from Zenodo ( https://doi.org/10.5281/zenodo.10698030 ) 62 . Source data are provided with this paper.

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Acknowledgements

This article is part of a project (Endure) that has received funding from the European Research Council (ERC) under the Horizon 2020 research and innovation programme of the European Union (grant agreement no. 101000396). We acknowledge the assistance of the following colleagues from the ICITECH-UPV institute in preparing and executing the full-scale building tests: J. J. Moragues, P. Calderón, D. Tasquer, G. Caredda, D. Cetina, M. L. Gerbaudo, L. Marín, M. Oliver and G. Sempértegui. We are also grateful to the Levantina, Ingeniería y Construcción S.L. (LIC) company for providing human resources and access to their facilities for testing. Finally, we thank A. Elfouly and Applied Science International for their support in performing simulations.

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Contributions

N.M. prepared the main text, performed the computational simulations and validated the test results. A.S. analysed the experimental data, performed data curation and prepared the Methods section. M.B. contributed to the design of the building specimen, the design of the test and data curation. J.M.A. contributed to the design of the research methodology, supervised the research and was responsible for funding acquisition. N.M., A.S. and M.B. contributed to the execution of the experimental test and to preparing figures, extended data and supplementary information. All authors interpreted the test and simulation results and edited the paper.

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Correspondence to Jose M. Adam .

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Extended data figures and tables

Extended data fig. 1 summary of building designs..

General building layout, connection details, and reinforcement configurations of Design H (“Hierarchy-based”) and Design C (“Conventional”).

Extended Data Fig. 2 Comparison of measured experimental data and simulation predictions.

a, Location of shown comparisons. All data shown in panels b to d refer to the change in structural response following the sudden removal of column C12 (after having removed columns C8 and C11 in a previous phase). b, Change in axial load in lower part of column C7. c, Change in axial load in lower part of column C9. d , Change in drift measured in both directions parallel to each building side.

Extended Data Fig. 3 Computational simulations of Design H and Design C subjected to small initial failures.

Principal strains and relative vertical displacement at the location of column C11 after removal of columns C8 and C11 from Design H ( a ) and Design C ( b ).

Extended Data Fig. 4 Demand and capacity envelopes of internal forces in Designs H and C subjected to large initial failures.

Evolution of axial loads, bending moments, and shear forces in column C7 compared to lower and upper bounds of its capacity after the removal of columns C8, C11, and C12 from Design H ( a ) and Design C ( b ).

Extended Data Fig. 5 Initial failure scenarios considered for testing.

Simulation of three different initial failure scenarios that were considered for testing. Scenario 3 was selected for the experimental test.

Extended Data Fig. 6 Specially designed removable supports to perform column removals.

Removable supports designed for quasi-static column removals in phase 1 and sudden column removal in phase 2.

Extended Data Fig. 7 Comparison of simulations of fully loaded and partially loaded building specimen.

a, Loaded bays, deformed shape, and principal normal strains following the sudden removal of column C12 (after having removed columns C8 and C11 in a previous phase). b, Horizontal displacement in the east-west and north-south directions at the top of columns C1 and C9 (2nd floor).

Extended Data Fig. 8 Measured redistribution of column axial forces during phase 1.

Maximum change in axial load of columns during phase 1 of testing based on recorded strain measurements.

Supplementary information

Supplementary information.

This file contains a supplementary test report that covers as-built building design, material properties, monitoring plan, structural response in phase 1 of testing and structural response in phase 2 of testing.

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Supplementary video 1.

Structural response of designs H and C.

Supplementary Video 2

Initial failure scenarios.

Supplementary Video 3

Comparison of partial and full loading.

Supplementary Video 4

Construction of the building.

Supplementary Video 5

An aerial view of the building before the test.

Supplementary Video 6

Multiple perspectives of the partial collapse of the building specimen in testing phase 2.

Supplementary Video 7

Experimental and simulation comparison of the partial collapse in testing phase 2.

Supplementary Video 8

Post-collapse inspection drone video.

Source data

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Makoond, N., Setiawan, A., Buitrago, M. et al. Arresting failure propagation in buildings through collapse isolation. Nature 629 , 592–596 (2024). https://doi.org/10.1038/s41586-024-07268-5

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Case Report
Open access
Published: 27 May 2024

A complex case study: coexistence of multi-drug-resistant pulmonary tuberculosis, HBV-related liver failure, and disseminated cryptococcal infection in an AIDS patient

Wei Fu 1 , 2 na1 ,
Zi Wei Deng 3 na1 ,
Pei Wang 1 ,
Zhen Wang Zhu 1 ,
Zhi Bing Xie 1 ,
Yong Zhong Li 1 &
Hong Ying Yu 1

BMC Infectious Diseases volume 24 , Article number: 533 ( 2024 ) Cite this article

Metrics details

Hepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various opportunistic infections, which can occur concurrently. The treatment process is further complicated by the potential occurrence of immune reconstitution inflammatory syndrome (IRIS), which presents significant challenges and contributes to elevated mortality rates.

Case presentation

The 50-year-old male with a history of chronic hepatitis B and untreated human immunodeficiency virus (HIV) infection presented to the hospital with a mild cough and expectoration, revealing multi-drug resistant pulmonary tuberculosis (MDR-PTB), which was confirmed by XpertMTB/RIF PCR testing and tuberculosis culture of bronchoalveolar lavage fluid (BALF). The patient was treated with a regimen consisting of linezolid, moxifloxacin, cycloserine, pyrazinamide, and ethambutol for tuberculosis, as well as a combination of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) for HBV and HIV viral suppression. After three months of treatment, the patient discontinued all medications, leading to hepatitis B virus reactivation and subsequent liver failure. During the subsequent treatment for AIDS, HBV, and drug-resistant tuberculosis, the patient developed disseminated cryptococcal disease. The patient’s condition worsened during treatment with liposomal amphotericin B and fluconazole, which was ultimately attributed to IRIS. Fortunately, the patient achieved successful recovery after appropriate management.

Enhancing medical compliance is crucial for AIDS patients, particularly those co-infected with HBV, to prevent HBV reactivation and subsequent liver failure. Furthermore, conducting a comprehensive assessment of potential infections in patients before resuming antiviral therapy is essential to prevent the occurrence of IRIS. Early intervention plays a pivotal role in improving survival rates.

Peer Review reports

HIV infection remains a significant global public health concern, with a cumulative death toll of 40 million individuals [ 1 ]. In 2021 alone, there were 650,000 deaths worldwide attributed to AIDS-related causes. As of the end of 2021, approximately 38 million individuals were living with HIV, and there were 1.5 million new HIV infections reported annually on a global scale [ 2 ]. Co-infection with HBV and HIV is prevalent due to their similar transmission routes, affecting around 8% of HIV-infected individuals worldwide who also have chronic HBV infection [ 3 ]. Compared to those with HBV infection alone, individuals co-infected with HIV/HBV exhibit higher HBV DNA levels and a greater risk of reactivation [ 4 ]. Opportunistic infections, such as Pneumocystis jirovecii pneumonia, Toxoplasma encephalitis, cytomegalovirus retinitis, cryptococcal meningitis (CM), tuberculosis, disseminated Mycobacterium avium complex disease, pneumococcal pneumonia, Kaposi’s sarcoma, and central nervous system lymphoma, are commonly observed due to HIV-induced immunodeficiency [ 5 ]. Tuberculosis not only contributes to the overall mortality rate in HIV-infected individuals but also leads to a rise in the number of drug-resistant tuberculosis cases and transmission of drug-resistant strains. Disseminated cryptococcal infection is a severe opportunistic infection in AIDS patients [ 6 ], and compared to other opportunistic infections, there is a higher incidence of IRIS in patients with cryptococcal infection following antiviral and antifungal therapy [ 7 ]. This article presents a rare case of an HIV/HBV co-infected patient who presented with MDR-PTB and discontinued all medications during the initial treatment for HIV, HBV, and tuberculosis. During the subsequent re-anti-HBV/HIV treatment, the patient experienced two episodes of IRIS associated with cryptococcal infection. One episode was classified as “unmasking” IRIS, where previously subclinical cryptococcal infection became apparent with immune improvement. The other episode was categorized as “paradoxical” IRIS, characterized by the worsening of pre-existing cryptococcal infection despite immune restoration [ 8 ]. Fortunately, both episodes were effectively treated.

A 50-year-old male patient, who is self-employed, presented to our hospital in January 2022 with a chief complaint of a persistent cough for the past 2 months, without significant shortness of breath, palpitations, or fever. His medical history revealed a previous hepatitis B infection, which resulted in hepatic failure 10 years ago. Additionally, he was diagnosed with HIV infection. However, he ceased taking antiviral treatment with the medications provided free of charge by the Chinese government for a period of three years. During this hospital visit, his CD4 + T-cell count was found to be 26/μL (normal range: 500–1612/μL), HIV-1 RNA was 1.1 × 10 5 copies/ml, and HBV-DNA was negative. Chest computed tomography (CT) scan revealed nodular and patchy lung lesions (Fig. 1 ). The BALF shows positive acid-fast staining. Further assessment of the BALF using XpertMTB/RIF PCR revealed resistance to rifampicin, and the tuberculosis drug susceptibility test of the BALF (liquid culture, medium MGIT 960) indicated resistance to rifampicin, isoniazid, and streptomycin. Considering the World Health Organization (WHO) guidelines for drug-resistant tuberculosis, the patient’s drug susceptibility results, and the co-infection of HIV and HBV, an individualized treatment plan was tailored for him. The treatment plan included BIC/TAF/FTC (50 mg/25 mg/200 mg per day) for HBV and HIV antiviral therapy, as well as linezolid (0.6 g/day), cycloserine (0.5 g/day), moxifloxacin (0.4 g/day), pyrazinamide (1.5 g/day), and ethambutol (0.75 g/day) for anti-tuberculosis treatment, along with supportive care.

The patient’s pulmonary CT scan shows patchy and nodular lesions accompanied by a small amount of pleural effusion, later confirmed to be MDR-PTB

Unfortunately, after 3 months of follow-up, the patient discontinued all medications due to inaccessibility of the drugs. He returned to our hospital (Nov 12, 2022, day 0) after discontinuing medication for six months, with a complaint of poor appetite for the past 10 days. Elevated liver enzymes were observed, with an alanine aminotransferase level of 295 IU/L (normal range: 0–40 IU/L) and a total bilirubin(TBIL) level of 1.8 mg/dL (normal range: 0–1 mg/dL). His HBV viral load increased to 5.5 × 10 9 copies/ml. Considering the liver impairment, elevated HBV-DNA and the incomplete anti-tuberculosis treatment regimen (Fig. 2 A), we discontinued pyrazinamide and initiated treatment with linezolid, cycloserine, levofloxacin, and ethambutol for anti-tuberculosis therapy, along with BIC/TAF/FTC for HIV and HBV antiviral treatment. Additionally, enhanced liver protection and supportive management were provided, involving hepatoprotective effects of medications such as glutathione, magnesium isoglycyrrhizinate, and bicyclol. However, the patient’s TBIL levels continued to rise progressively, reaching 4.4 mg/dL on day 10 (Fig. 3 B). Suspecting drug-related factors, we discontinued all anti-tuberculosis medications while maintaining BIC/TAF/FTC for antiviral therapy, the patient’s TBIL levels continued to rise persistently. We ruled out other viral hepatitis and found no significant evidence of obstructive lesions on magnetic resonance cholangiopancreatography. Starting from the day 19, due to the patient’s elevated TBIL levels of 12.5 mg/dL, a decrease in prothrombin activity (PTA) to 52% (Fig. 3 D), and the emergence of evident symptoms such as abdominal distension and poor appetite, we initiated aggressive treatment methods. Unfortunately, on day 38, his hemoglobin level dropped to 65 g/L (normal range: 120–170 g/L, Fig. 3 A), and his platelet count decreased to 23 × 10 9 /L (normal range: 125–300 × 10 9 /L, Fig. 3 C). Based on a score of 7 on the Naranjo Scale, it was highly suspected that “Linezolid” was the cause of these hematological abnormalities. Therefore, we had to discontinue Linezolid for the anti-tuberculosis treatment. Subsequently, on day 50, the patient developed recurrent fever, a follow-up chest CT scan revealed enlarged nodules in the lungs (Fig. 2 B). The patient also reported mild dizziness and a worsening cough. On day 61, the previous blood culture results reported the growth of Cryptococcus. A lumbar puncture was performed on the same day, and the cerebrospinal fluid (CSF) opening pressure was measured at 130 mmH 2 O. India ink staining of the CSF showed typical encapsulated yeast cells suggestive of Cryptococcus. Other CSF results indicated mild leukocytosis and mildly elevated protein levels, while chloride and glucose levels were within normal limits. Subsequently, the patient received a fungal treatment regimen consisting of liposomal amphotericin B (3 mg/kg·d −1 ) in combination with fluconazole(600 mg/d). After 5 days of antifungal therapy, the patient’s fever symptoms were well controlled. Despite experiencing bone marrow suppression, including thrombocytopenia and worsening anemia, during this period, proactive symptom management, such as the use of erythropoietin, granulocyte colony-stimulating factor, and thrombopoietin, along with high-calorie dietary management, even reducing the dosage of liposomal amphotericin B to 2 mg/kg/day for 10 days at the peak of severity, successfully controlled the bone marrow suppression. However, within the following week, the patient experienced fever again, accompanied by a worsened cough, increased sputum production, and dyspnea. Nevertheless, the bilirubin levels did not show a significant increase. On day 78 the patient’s lung CT revealed patchy infiltrates and an increased amount of pleural effusion (Fig. 2 C). The CD4 + T-cell count was 89/μL (normal range: 500–700/μL), indicating a significant improvement in immune function compared to the previous stage, and C-reactive protein was significantly elevated, reflecting the inflammatory state, other inflammatory markers such as IL-6 and γ-IFN were also significantly elevated. On day 84, Considering the possibility of IRIS, the patient began taking methylprednisolone 30 mg once a day as part of an effort to control his excessive inflammation. Following the administration of methylprednisolone, the man experienced an immediate improvement in his fever. Additionally, symptoms such as cough, sputum production, dyspnea, and poor appetite gradually subsided over time. A follow-up lung CT showed significant improvement, indicating a positive response to the treatment. After 28 days of treatment with liposomal amphotericin B in combination with fluconazole, liposomal amphotericin B was discontinued, and the patient continued with fluconazole to consolidate the antifungal therapy for Cryptococcus. Considering the patient’s ongoing immunodeficiency, the dosage of methylprednisolone was gradually reduced by 4 mg every week. After improvement in liver function, the patient’s anti-tuberculosis treatment regimen was adjusted to include bedaquiline, contezolid, cycloserine, moxifloxacin, and ethambutol. The patient’s condition was well controlled, and a follow-up lung CT on day 117 indicated a significant improvement in lung lesions (Fig. 2 D).

Upon second hospitalization admission ( A ), nodular lesions were already present in the lungs, and their size gradually increased after the initiation of ART ( B , C ). Notably, the lung lesions became more pronounced following the commencement of anti-cryptococcal therapy, coinciding with the occurrence of pleural effusion ( C ). However, with the continuation of antifungal treatment and the addition of glucocorticoids, there was a significant absorption and reduction of both the pleural effusion and pulmonary nodules ( D )

During the patient's second hospitalization, as the anti-tuberculosis treatment progressed and liver failure developed, the patient’s HGB levels gradually decreased ( A ), while TBIL levels increased ( B ). Additionally, there was a gradual decrease in PLT count ( C ) and a reduction in prothrombin activity (PTA) ( D ), indicating impaired clotting function. Moreover, myelosuppression was observed during the anti-cryptococcal treatment ( C )

People living with HIV/AIDS are susceptible to various opportunistic infections, which pose the greatest threat to their survival [ 5 ]. Pulmonary tuberculosis and disseminated cryptococcosis remain opportunistic infections with high mortality rates among AIDS patients [ 9 , 10 ]. These infections occurring on the basis of liver failure not only increase diagnostic difficulty but also present challenges in treatment. Furthermore, as the patient’s immune function and liver function recover, the occurrence of IRIS seems inevitable.

HIV and HBV co-infected patients are at a higher risk of HBV reactivation following the discontinuation of antiviral drugs

In this case, the patient presented with both HIV and HBV infections. Although the HBV DNA test was negative upon admission. However, due to the patient’s self-discontinuation of antiretroviral therapy (ART), HBV virologic and immunologic reactivation occurred six months later, leading to a rapid increase in viral load and subsequent hepatic failure. Charles Hannoun et al. also reported similar cases in 2001, where two HIV-infected patients with positive HBsAg experienced HBV reactivation and a rapid increase in HBV DNA levels after discontinuing antiretroviral and antiviral therapy, ultimately resulting in severe liver failure [ 11 ]. The European AIDS Clinical Society (EACS) also emphasize that abrupt discontinuation of antiviral therapy in patients co-infected with HBV and HIV can trigger HBV reactivation, which, although rare, can potentially result in liver failure [ 12 ].

Diagnosing disseminated Cryptococcus becomes more challenging in AIDS patients with liver failure, and the selection of antifungal medications is significantly restricted

In HIV-infected individuals, cryptococcal disease typically manifests as subacute meningitis or meningoencephalitis, often accompanied by fever, headache, and neck stiffness. The onset of symptoms usually occurs approximately two weeks after infection, with typical signs and symptoms including meningeal signs such as neck stiffness and photophobia. Some patients may also experience encephalopathy symptoms like somnolence, mental changes, personality changes, and memory loss, which are often associated with increased intracranial pressure (ICP) [ 13 ]. The presentation of cryptococcal disease in this patient was atypical, as there were no prominent symptoms such as high fever or rigors, nor were there any signs of increased ICP such as somnolence, headache, or vomiting. The presence of pre-existing pulmonary tuberculosis further complicated the early diagnosis, potentially leading to the clinical oversight of recognizing the presence of cryptococcus. In addition to the diagnostic challenges, treating a patient with underlying liver disease, multidrug-resistant tuberculosis, and concurrent cryptococcal infection poses significant challenges. It requires considering both the hepatotoxicity of antifungal agents and potential drug interactions. EACS and global guideline for the diagnosis and management of cryptococcosis suggest that liposomal amphotericin B (3 mg/kg·d −1 ) in combination with flucytosine (100 mg/kg·d −1 ) or fluconazole (800 mg/d) is the preferred induction therapy for CM for 14 days [ 12 , 14 ]. Flucytosine has hepatotoxicity and myelosuppressive effects, and it is contraindicated in patients with severe liver dysfunction. The antiviral drug bictegravir is a substrate for hepatic metabolism by CYP3A and UGT1A1 enzymes [ 15 ], while fluconazole inhibits hepatic enzymes CYP3A4 and CYP2C9 [ 16 ]. Due to the patient's liver failure and bone marrow suppression, we reduced the dosage of liposomal amphotericin B and fluconazole during the induction period. Considering the hepatotoxicity of fluconazole and its interaction with bictegravir, we decreased the dosage of fluconazole to 600 mg/d, while extending the duration of induction therapy to 28 days.

During re-antiviral treatment, maintaining vigilance for the development of IRIS remains crucial

IRIS refers to a series of inflammatory diseases that occur in HIV-infected individuals after initiating ART. It is associated with the paradoxical worsening of pre-existing infections, which may have been previously diagnosed and treated or may have been subclinical but become apparent due to the host regaining the ability to mount an inflammatory response. Currently, there is no universally accepted definition of IRIS. However, the following conditions are generally considered necessary for diagnosing IRIS: worsening of a diagnosed or previously unrecognized pre-existing infection with immune improvement (referred to as “paradoxical” IRIS) or the unmasking of a previously subclinical infection (referred to as “unmasking” IRIS) [ 8 ]. It is estimated that 10% to 30% of HIV-infected individuals with CM will develop IRIS after initiating or restarting effective ART [ 7 , 17 ]. In the guidelines of the WHO and EACS, it is recommended to delay the initiation of antiviral treatment for patients with CM for a minimum of 4 weeks to reduce the incidence of IRIS. Since we accurately identified the presence of multidrug-resistant pulmonary tuberculosis in the patient during the early stage, we promptly initiated antiretroviral and anti-hepatitis B virus treatment during the second hospitalization. However, subsequent treatment revealed that the patient experienced at least two episodes of IRIS. The first episode was classified as “unmasking” IRIS, as supported by the enlargement of pulmonary nodules observed on the chest CT scan following the initiation of ART (Fig. 2 A). Considering the morphological changes of the nodules on the chest CT before antifungal therapy, the subsequent emergence of disseminated cryptococcal infection, and the subsequent reduction in the size of the lung nodules after antifungal treatment, although there is no definitive microbiological evidence, we believe that the initial enlargement of the lung nodules was caused by cryptococcal pneumonia. As ART treatment progressed, the patient experienced disseminated cryptococcosis involving the blood and central nervous system, representing the first episode. Following the initiation of antifungal therapy for cryptococcosis, the patient encountered a second episode characterized by fever and worsening pulmonary lesions. Given the upward trend in CD4 + T-cell count, we attributed this to the second episode of IRIS, the “paradoxical” type. The patient exhibited a prompt response to low-dose corticosteroids, further supporting our hypothesis. Additionally, the occurrence of cryptococcal IRIS in the lungs, rather than the central nervous system, is relatively uncommon among HIV patients [ 17 ].

Conclusions

From the initial case of AIDS combined with chronic hepatitis B, through the diagnosis and treatment of multidrug-resistant tuberculosis, the development of liver failure and disseminated cryptococcosis, and ultimately the concurrent occurrence of IRIS, the entire process was tortuous but ultimately resulted in a good outcome (Fig. 4 ). Treatment challenges arose due to drug interactions, myelosuppression, and the need to manage both infectious and inflammatory conditions. Despite these hurdles, a tailored treatment regimen involving antifungal and antiretroviral therapies, along with corticosteroids, led to significant clinical improvement. While CM is relatively common among immunocompromised individuals, especially those with acquired immunodeficiency syndrome (AIDS) [ 13 ], reports of disseminated cryptococcal infection on the background of AIDS complicated with liver failure are extremely rare, with a very high mortality rate.

A brief timeline of the patient's medical condition progression and evolution

Through managing this patient, we have also gained valuable insights. (1) Swift and accurate diagnosis, along with timely and effective treatment, can improve prognosis, reduce mortality, and lower disability rates. Whether it's the discovery and early intervention of liver failure, the identification and treatment of disseminated cryptococcosis, or the detection and management of IRIS, all these interventions are crucially timely. They are essential for the successful treatment of such complex and critically ill patients.

(2) Patients who exhibit significant drug reactions, reducing the dosage of relevant medications and prolonging the treatment duration can improve treatment success rates with fewer side effects. In this case, the dosages of liposomal amphotericin B and fluconazole are lower than the recommended dosages by the World Health Organization and EACS guidelines. Fortunately, after 28 days of induction therapy, repeat CSF cultures showed negative results for Cryptococcus, and the improvement of related symptoms also indicates that the patient has achieved satisfactory treatment outcomes. (3) When cryptococcal infection in the bloodstream or lungs is detected, prompt lumbar puncture should be performed to screen for central nervous system cryptococcal infection. Despite the absence of neurological symptoms, the presence of Cryptococcus neoformans in the cerebrospinal fluid detected through lumbar puncture suggests the possibility of subclinical or latent CM, especially in late-stage HIV-infected patients.

We also encountered several challenges and identified certain issues that deserve attention. Limitations: (1) The withdrawal of antiviral drugs is a critical factor in the occurrence and progression of subsequent diseases in patients. Improved medical education is needed to raise awareness and prevent catastrophic consequences. (2) Prior to re-initiating antiviral therapy, a thorough evaluation of possible infections in the patient is necessary. Caution should be exercised, particularly in the case of diseases prone to IRIS, such as cryptococcal infection. (3) There is limited evidence on the use of reduced fluconazole dosage (600 mg daily) during antifungal therapy, and the potential interactions between daily fluconazole (600 mg) and the antiviral drug bictegravir and other tuberculosis medications have not been extensively studied. (4) Further observation is needed to assess the impact of early-stage limitations in the selection of anti-tuberculosis drugs on the treatment outcome of tuberculosis in this patient, considering the presence of liver failure.

In conclusion, managing opportunistic infections in HIV patients remains a complex and challenging task, particularly when multiple opportunistic infections are compounded by underlying liver failure. Further research efforts are needed in this area.

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All data generated or analyzed during this study are included in this published article.

Abbreviations

Hepatitis B virus

Acquired immunodeficiency virus disease

Immune reconstitution inflammatory syndrome

Human immunodeficiency virus

Multi-drug resistant pulmonary tuberculosis

Bronchoalveolar lavage fluid

Bictegravir/tenofovir alafenamide/emtricitabine

Cryptococcal meningitis

World Health Organization

Computed tomography

Total bilirubin

Cerebrospinal fluid

European AIDS Clinical Society

Intracranial pressure

Antiretroviral therapy

Prothrombin activity

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Acknowledgements

We express our sincere gratitude for the unwavering trust bestowed upon our medical team by the patient throughout the entire treatment process.

This work was supported by the Scientific Research Project of Hunan Public Health Alliance with the approval No. ky2022-002.

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Wei Fu and Zi Wei Deng contributed equally to this work.

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Center for Infectious Diseases, Hunan University of Medicine General Hospital, Huaihua, Hunan, China

Wei Fu, Pei Wang, Zhen Wang Zhu, Ye Pu, Zhi Bing Xie, Yong Zhong Li & Hong Ying Yu

Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical University, XinXiang, Henan, China

Department of Clinical Pharmacy, Hunan University of Medicine General Hospital, Huaihua, Hunan, China

Zi Wei Deng

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Contributions

WF and ZWD integrated the data and wrote the manuscript, YHY contributed the revision of the manuscript, PW and YP provided necessary assistance and provided key suggestions, ZWZ, YZL and ZBX contributed data acquisition and interpretation for etiological diagnosis. All authors reviewed and approved the final manuscript.

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Correspondence to Hong Ying Yu .

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The study was approved by the Ethics Committee of the Hunan University of Medicine General Hospital (HYZY-EC-202306-C1), and with the informed consent of the patient.

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Fu, W., Deng, Z.W., Wang, P. et al. A complex case study: coexistence of multi-drug-resistant pulmonary tuberculosis, HBV-related liver failure, and disseminated cryptococcal infection in an AIDS patient. BMC Infect Dis 24 , 533 (2024). https://doi.org/10.1186/s12879-024-09431-9

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