Chagas, leishmaniasis and schistosomiasis: when to think

A fifty-two-year-old man, born in a South American country and living for fifteen years in a large European city, sees the clinician for fatigue on exertion and palpitations. He has already been through two visits, received guidance about anxiety and work stress, and came back because the symptoms continue. The electrocardiogram shows a right bundle branch block. No one asked where he grew up or what kind of house he lived in during childhood. The scene is fictional and was written for teaching. This text uses that picture as a setting for clinical reasoning: why diseases such as Chagas disease, leishmaniasis and schistosomiasis are forgotten outside the areas where they are common, when to think of them, and what stigma and lack of access add to the problem.

NEXO is a daily medical diagnosis game: one clinical case a day, up to six progressive clues, and ICD-10 proximity feedback across five levels.

The text avoids being a protocol. The diagnosis and treatment of these diseases follow national and international guidelines and depend on tests that not every service has. The interest here is reasoning: how the patient's life history changes the list of hypotheses, why a low probability in the local population is not the same as a low probability in the patient in front of you, and how the consultation can be a gateway to access. If you play the case of the day on NEXO, you will recognize the move: the clue about the patient's origin can take the guess to another chapter.

Key points

• Neglected tropical diseases follow people when they migrate, and appear in clinics in countries where they are not transmitted.
• The low frequency of these diseases in the local population means they are forgotten, even in patients from endemic areas.
• Chagas disease can cause heart disease years after infection, and the electrocardiogram offers important clues.
• Leishmaniasis has a cutaneous form and a visceral form, and schistosomiasis can lead to liver fibrosis with portal hypertension.
• Stigma and access barriers are part of the picture, and clinical reasoning includes thinking about how the patient reaches care.

Why neglected diseases are a setting for reasoning

The World Health Organization groups these diseases under the name neglected tropical diseases and keeps a roadmap for the period from 2021 to 2030. Weiss describes that the stigma linked to them imposes a hidden burden, which does not appear in epidemiological data (Weiss, 2008).

These diseases challenge clinical reasoning in two ways. In the endemic area, they compete with many other causes for the same symptoms. Outside it, they simply do not enter the list of hypotheses. The physician who has never seen a patient with Chagas disease tends not to think of it, even when the history points in that direction.

Diseases that migrate with people

Pérez-Molina and Molina describe Chagas disease as originating in the Americas and spread beyond its original limits by migration (Pérez-Molina and Molina, 2018). Burza and colleagues report that conflicts and forced displacement in endemic areas of cutaneous leishmaniasis led to an increase in cases in those areas and in clinics around the world (Burza and colleagues, 2018).

A consultation that starts earlier

Many of these patients have already been through other services before reaching the consultation where the diagnosis is made. Each earlier visit left a record, a provisional diagnosis and, sometimes, an explanation accepted without all the clues being checked. Reading those records carefully, and asking the patient what has already been said to them, helps to notice when the earlier explanation left loose ends. The reasoning does not need to start from zero, but it also does not need to inherit the conclusions of those who came before.

What the scene teaches

In the opening scene, the patient went through two visits without anyone asking about his origin. The most common explanation, anxiety, was accepted without the remaining clues being explained. The post about signs, symptoms and history shows how the patient's life history is part of the clinical history.

The low local base rate

The post on pretest probability in diagnosis explains why the frequency of a disease in the reference population weighs on the interpretation of clues. The central point here is choosing the right reference population. For a patient born in an endemic area, the relevant frequency is that of the place of origin, not that of the city where they live today.

The size of the problem outside endemic areas

Requena-Méndez and colleagues gathered studies on Chagas disease in Latin American migrants living in Europe and found a pooled prevalence of 4.2 per 100, reaching 18.1 per 100 among people from Bolivia (Requena-Méndez and colleagues, 2015). Nunes and colleagues, in a scientific statement from the American Heart Association, estimate that Chagas disease affects at least 300 thousand residents of the United States (Nunes and colleagues, 2018).

How many are diagnosed

Basile and colleagues compared the number of people with Chagas disease diagnosed in European countries, 4290, with the expected estimate, between 68 thousand and 122 thousand. The underdiagnosis rate was between 94 and 96 per 100 (Basile and colleagues, 2011). The authors also estimated between 20 and 183 congenital infections per year in these countries.

The question that is missing

Most of the time, the diagnosis is not missed for lack of testing, but for lack of a guess. Asking where the person was born, where they grew up, what the childhood home was like, whether they had contact with fresh water in rural areas and whether the mother came from an endemic region takes a few minutes. The post on pretest probability shows how these answers change the value of tests before they are even ordered.

Chagas disease: when to think of it

Rassi and colleagues estimate that Chagas disease affects about 8 million people in Latin America, and that 30 to 40 per 100 of them have or will develop heart disease, digestive megasyndromes or both (Rassi and colleagues, 2010). The authors point out that the disease is becoming an emerging health problem in non-endemic areas because of population movements, and that detection and treatment of people still without symptoms are little used.

A disease of years

The acute phase usually goes unnoticed, and complications appear much later. Pérez-Molina and Molina describe that, after the acute phase, the chronic disease can manifest with cardiomyopathy, arrhythmias, megaviscera and, more rarely, polyneuropathy and stroke (Pérez-Molina and Molina, 2018). The authors also note that the affected population is older and more complex, with immunosuppressed patients and patients with cancer.

Treatment exists

Rassi and colleagues describe treatment with benznidazole, or nifurtimox, as reasonably safe and effective, with a recommendation for an ever larger group of patients (Rassi and colleagues, 2010). For reasoning, this changes the weight of the guess: when treatment is available, failing to diagnose has a real consequence.

The chagasic heart and the electrocardiogram

Nunes and colleagues describe Chagas disease as an important cause of heart failure, stroke, arrhythmia and sudden death, and argue that professionals and health systems outside Latin America should be prepared to recognize it (Nunes and colleagues, 2018).

What the electrocardiogram shows

Rojas and colleagues gathered 49 population studies and found electrocardiogram abnormalities in 40.1 per 100 people with Chagas disease, against 24.1 per 100 in people without the disease (Rojas and colleagues, 2018). Among the abnormalities associated with the disease were complete right bundle branch block, left anterior superior fascicular block, first-degree atrioventricular block and atrial fibrillation.

The table of the three diseases

The table below summarizes, in a didactic way, exposure clues and forms of presentation of the three diseases mentioned in this text. It simplifies a complex field and should be read together with the sources.

Disease	Exposure clue	Forms that concern
Chagas disease	Birth or childhood in an endemic area of the Americas, mother from these areas	Cardiomyopathy, arrhythmias, megaviscera
Leishmaniasis	Residence or travel to endemic areas, displacement due to conflict	Cutaneous form and visceral form
Schistosomiasis	Contact with fresh water in endemic areas	Katayama syndrome, periportal fibrosis with portal hypertension

The ECG as a clue, not as proof

The right bundle branch block from the opening scene, on its own, has many possible causes. Combined with the patient's origin and with symptoms that are not otherwise explained, it takes on another weight. The post on differential diagnosis with clues shows how a poorly specific clue can be decisive when it adds up with the others.

Leishmaniasis: cutaneous and visceral

Burza and colleagues describe leishmaniasis as a disease linked to poverty, with two main clinical forms, visceral and cutaneous, and estimate 0.7 to 1 million new cases per year in nearly 100 endemic countries (Burza and colleagues, 2018). The authors describe the visceral form as fatal and report that, in East Africa, the number of patients remains high.

Two diseases with the same name

The cutaneous form and the visceral form call for different reasoning. In the cutaneous form, the main clue is in the skin, and the differential includes other causes of chronic lesions. In the visceral form, the picture is systemic, and the disease enters the differential of prolonged fever with general compromise. What unites them is the question about exposure: where the person lived, where they traveled and whether they passed through areas of conflict or displacement.

A topic of international priority

Burza and colleagues recall that the World Health Organization includes leishmaniasis among the neglected tropical diseases for which the development of new treatments is a priority, and that major evidence gaps remain (Burza and colleagues, 2018). For clinical reasoning, this means that management depends heavily on the region and the service, and that referral to reference centers is part of the decision.

Asking about the route

In people who moved through several regions before arriving in the current country, the question about exposure is not limited to the country of origin. The whole route counts: where the person stayed, for how long, in what housing conditions and with what access to water and sanitation. These answers can be hard to give, and the professional needs time and care to obtain them. In many services, the support of professional interpreters makes this conversation possible and more accurate.

The lesion that does not heal

A skin lesion that does not heal, in a patient from an endemic area, deserves one more question. The post on heuristics in clinical reasoning shows how the most familiar diagnosis tends to take the place of less known hypotheses.

Schistosomiasis: from fresh water to the liver

Colley and colleagues estimate that at least 230 million people worldwide are infected by Schistosoma species (Colley and colleagues, 2014). Adult worms live for years in human blood vessels, and eggs trapped in tissues cause inflammation. The consequences range from anemia and impaired growth to periportal fibrosis with portal hypertension and inflammation and scarring in the urogenital tract.

Katayama syndrome

Ross and colleagues describe Katayama syndrome as an early manifestation of schistosomiasis, which appears 14 to 84 days after exposure in people without prior immunity (Ross and colleagues, 2007). The picture usually includes night fever, cough, muscle pain, headache and abdominal pain. Nearly all patients have eosinophilia and a history of contact with fresh water in that interval. Because of the delay between exposure and symptoms and the poorly specific picture, it is the form of the disease most likely to be misdiagnosed in non-endemic countries.

The chronic form

At the other extreme, chronic schistosomiasis can present years later, with an enlarged liver and spleen and signs of portal hypertension (Colley et al., 2014). In a patient who never drank excessively and has no viral hepatitis, asking about contact with fresh water in childhood can provide the missing clue. The post about diagnostic uncertainty discusses how to keep investigating when the usual explanation is not confirmed.

Stigma and access

Weiss describes that the stigma associated with neglected tropical diseases has important social consequences, with differences between men and women, and that this burden is not captured by the usual epidemiological measures (Weiss, 2008). Basile et al. point out that migrants without regularized legal status face difficulties accessing the health system, which contributes to the underdiagnosis of Chagas disease in Europe (Basile et al., 2011).

What stigma changes in the consultation

A patient who fears being judged may withhold information, delay seeking care or drop out of follow-up. Clinical reasoning depends on a complete history, and the history depends on trust. Asking about origin and living conditions respectfully, explaining why the question matters, helps obtain the information without driving the patient away.

The consultation as a gateway

For many migrants, a consultation for another reason is the only opportunity to screen for these diseases. Rassi et al. recall that detection and treatment of people still without symptoms are little used (Rassi et al., 2010). Thinking about screening when the history indicates exposure, and not only when symptoms appear, makes an ordinary consultation an opportunity for diagnosis.

Time and patience in follow-up

Diagnosing a neglected disease usually requires more than one consultation: ordering specific tests, waiting for results that sometimes come from reference laboratories and referring to specialized services. Each step is a chance for the patient to be lost along the way. Agreeing on the next step clearly, checking whether the person can get to the indicated service and recording in the chart what remains to be done help keep the reasoning alive to the end.

Family and congenital transmission

When a woman has Chagas disease, the question extends to her children. The estimate of congenital infections in Europe made by Basile et al. shows that the problem crosses generations, including in children born outside endemic areas (Basile et al., 2011). Reasoning about one patient can thus open care to the whole family.

The bias of the disease that does not exist here

Croskerry described how cognitive errors lead to diagnostic errors and proposed strategies to reduce them (Croskerry, 2003). Graber et al. showed that cognitive factors, such as premature closure, are present in a good part of diagnostic errors in internal medicine (Graber et al., 2005). With neglected diseases, one bias stands out: treating local rarity as rarity in the patient.

The comfort of the common diagnosis

Anxiety, stress and fatigue are frequent explanations and often correct. The problem arises when they are accepted before the other clues are checked. In the opening scene, a bundle branch block on the electrocardiogram and the patient's origin were left unexplained. Reasoning that asks what the chosen hypothesis leaves out tends to find these mismatches in time.

Rare here, common there

The phrase "that does not exist here" mixes two things: local transmission and the presence of the disease. Chagas disease may not be transmitted by insects in the European city of the scene, but the patient brought the infection from somewhere else. The reasoning needs to separate the two questions.

Pause before closing

Before accepting a generic explanation for persistent symptoms, a brief pause helps: did I ask where the patient came from? Are the remaining clues explained? The post about diagnostic pause shows how a short moment of checking protects against premature closure.

Questions that protect

Some questions help keep the focus:

1. Where was the patient born and where did they spend childhood?
2. Did they have contact with fresh water in rural areas of endemic regions?
3. Did the mother come from an endemic area for Chagas disease?
4. Do the electrocardiogram or the tests bring any clue still unexplained?
5. Are there access barriers that can delay follow-up?

How NEXO helps train this reasoning

In NEXO, the case of the day is fictional, with a real clinical presentation and up to six progressive clues. You propose a diagnosis by looking for the code in ICD-10 and receive feedback on proximity at five levels, which shows whether the guess landed on the exact code, the same category, the same group, the same chapter or a different chapter. This format connects with the theme of this text: a clue about the patient's origin can move the guess from the chapter of cardiovascular diseases to that of infectious and parasitic diseases.

To use the case of the day as training, try three habits. Before each guess, ask which reference population is the right one for that patient. When a common explanation seems sufficient, ask which clues it leaves unexplained. After the result, note which question about the history would have anticipated the diagnosis.

Three exercises with cases

Change the reference population. Reread a case imagining that the patient was born on another continent and see how the differential changes.

Explain every clue. List the clues in the case and mark which ones your guess explains and which ones it leaves out.

Think about who else. Faced with an infectious diagnosis, ask who else in the family may have had the same exposure.

The post about case-based learning in clinical practice shows how cases help fix patterns that rarely appear in daily practice.

The limits on using the game are described on the NEXO economy page. If you research the teaching of clinical reasoning, the page for researchers explains how to get in touch. Professionals who write or review cases find information under curation and creators, and institutions can learn about the proposal on the partnerships page.

Frequently asked questions

What are neglected tropical diseases?

They are diseases linked to poverty and to tropical regions, which receive little attention and little investment. The World Health Organization maintains an international roadmap to tackle them.

Why do these diseases appear outside endemic areas?

Because people migrate and carry the infection with them. Chagas disease, for example, can manifest years later, in someone who already lives in another country.

When should you think of Chagas disease?

When the patient was born or lived in an endemic area of the Americas, or is the child of a mother from those regions, and presents cardiac symptoms, electrocardiogram changes or digestive symptoms without another explanation. Screening also applies to those with this history who do not yet have symptoms.

What is the difference between cutaneous and visceral leishmaniasis?

The cutaneous form affects the skin, and the visceral form is systemic and severe. Both share the same initial question: where the person lived or traveled.

What is Katayama syndrome?

It is an early manifestation of schistosomiasis, which appears weeks after contact with contaminated fresh water, with fever, cough, muscle pain and eosinophilia.

Why does stigma matter in clinical reasoning?

Because a patient who fears being judged may withhold information or delay seeking care. A respectful approach helps obtain the full history.

Final checklist

• I asked where the patient was born, grew up and lived.
• I chose the right reference population to estimate the probability.
• I considered Chagas disease in the presence of cardiac symptoms or ECG changes in someone with exposure.
• I asked about skin lesions that do not heal and about contact with fresh water.
• I thought about screening and the family, and not only about today's symptom.
• I approached the history respectfully and considered access barriers.

Want to practice reasoning with progressive clues? Play the case of the day.

References

1. Basile L, Jansa JM, Carlier Y, et al. Chagas disease in European countries: the challenge of a surveillance system. Euro Surveill. 2011. PMID 21944556.
2. Burza S, Croft SL, Boelaert M. Leishmaniasis. Lancet. 2018. PMID 30126638.
3. Colley DG, Bustinduy AL, Secor WE, King CH. Human schistosomiasis. Lancet. 2014. PMID 24698483.
4. Croskerry P. The importance of cognitive errors in diagnosis and strategies to minimize them. Acad Med. 2003. PMID 12915363.
5. Graber ML, Franklin N, Gordon R. Diagnostic error in internal medicine. Arch Intern Med. 2005. PMID 16009864.
6. Nunes MCP, Beaton A, Acquatella H, et al. Chagas cardiomyopathy: an update of current clinical knowledge and management: a scientific statement from the American Heart Association. Circulation. 2018. PMID 30354432.
7. Pérez-Molina JA, Molina I. Chagas disease. Lancet. 2018. PMID 28673423.
8. Rassi A Jr, Rassi A, Marin-Neto JA. Chagas disease. Lancet. 2010. PMID 20399979.
9. Requena-Méndez A, Aldasoro E, de Lazzari E, et al. Prevalence of Chagas disease in Latin-American migrants living in Europe: a systematic review and meta-analysis. PLoS Negl Trop Dis. 2015. PMID 25680190.
10. Rojas LZ, Glisic M, Pletsch-Borba L, et al. Electrocardiographic abnormalities in Chagas disease in the general population: a systematic review and meta-analysis. PLoS Negl Trop Dis. 2018. PMID 29897909.
11. Ross AG, Vickers D, Olds GR, et al. Katayama syndrome. Lancet Infect Dis. 2007. PMID 17317603.
12. Weiss MG. Stigma and the social burden of neglected tropical diseases. PLoS Negl Trop Dis. 2008. PMID 18478049.
13. World Health Organization. Ending the neglect to attain the Sustainable Development Goals: a road map for neglected tropical diseases 2021 to 2030. 2020. Publication page.