A neglected disease

David Shaproski

Introduction

In the Americas, the bite of a certain large blood-sucking insect has historically been described as a “kiss of death” owing to the transmission of potentially fatal parasites. Charles Darwin, while on a survey in Argentina, described such an attack:

It is most disgusting to feel soft wingless insects, about an inch long, crawling over one’s body. Before sucking they are quite thin, but afterwards they become round and bloated with blood…

Chagas disease, also known as American trypanosomiasis, has affected human health since antiquity but wasn’t formally described until 1909. The disease is caused by Trypanosoma cruzi, a parasite transmitted mainly by bugs of the subfamily Triatominae. The disease is endemic in Latin America, where it represents the most important parasitic infection and causes much suffering. Due to migration, imported infections in non-endemic countries are on the rise.

Burden of disease

Chagas disease is present in eighteen countries on the American continents, ranging from the southern United States to southern Argentina. As with many neglected diseases, the true misery caused by Chagas disease is in morbidity rather than in mortality. Latin America suffers under a burden of 670 000 DALYs (disability-adjusted life years) lost while the costs of the disease drain an estimated US$ 8 billion from the regional economy. Only HIV, diarrheal diseases and tuberculosis cause more harm. Even beyond endemic areas, countries with an influx of Latin American immigrants have witnessed greater spread of T. cruzi. In the United States alone at least 300 000 people are infected, representing a tangible threat to the safety of donated blood.

In the 1980s, 100 million people in Latin America were at risk of infection, while 17.4 million people were already infected. In 2005, the prevalence decreased to 7.7 million, while the number of those at risk increased slightly. Although the disease is badly underreported, mortality is estimated to have dropped from 50 000 in 1990 to between 13 000 and 25 000 in 2006.

This drop in infections can be attributed to several vector control campaigns. Brazil launched a T. infestans eradication initiative in 1983 that attained 75% of its objectives. However, the campaign became subordinate to a control programme for yellow fever, leading to a subsequent rise in Chagas disease. The Southern Cone Initiative, started in 1991 by several Latin American countries, refocused efforts on Chagas through vector elimination. Spraying of homes costs only US$4 per year, though this may still be too costly for many poor endemic areas. Nonetheless, the campaign was successful, and Chile and Uruguay were declared transmission-free by 1999.

Transmission

The epidemiology of Chagas disease is complicated by multiple transmission mechanisms, although spreading of parasites occurs primarily via Triatoma infestans, the kissing bug Darwin described. Many mammals, including livestock, act as reservoirs while poorly constructed homes serve as perfect breading grounds for bugs.

Apart from T. infestans, additional non-vectorial modes of transmission exist which have become important for transmission in cities and non-endemic countries. Blood transfusion is the most common, causing about 15% of new infections. Vertical transmission from mother to child occurs in 5% of newborns, while oral transmission via contaminated food takes place more rarely.

Clinical Presentation

Chagas disease is characterized by a mostly asymptomatic acute phase followed by a long chronic phase. Acute symptoms are generally seen in children. At the inoculation site, a chagoma (skin lesion) or Romaña’s sign (unilateral periorbital oedema) becomes visible. Nonspecific symptoms include headache, paleness, muscle pain, shortness of breath, oedema and lymph node enlargement. Even without treatment, symptoms generally resolve spontaneously in 90% of patients. More serious symptoms, including heart failure and meningoencephalitis, cause death in 5% of infected children under two.

In the chronic phase, approximately two thirds of those infected are asymptomatic with normal ECG findings while testing positive for T. cruzi antibodies. However, these patients are vulnerable to sudden death due to heart problems. The remaining one third will develop a chronic form of Chagas disease ten to thirty years after infection. This chronic form causes life-threatening heart and digestive system disorders. In the digestive system, the parasite causes enlargement and obstruction of the colon and oesophagus, leading to difficult swallowing and consequent malnutrition, while bowel obstruction can lead to constipation and abdominal pain. Cardiac problems include progressive myocarditis, which leads to cardiac arrhythmias and other abnormalities found with an ECG. Heart failure, mostly due to right side decompensation, is a serious manifestation of later stages. Pulmonary embolism and stroke are also common complications.

Diagnosis

In the acute stage, diagnosis occurs by traditional microscopic detection of trypomastigotes in the patient’s blood. During the chronic phase, diagnosis is more difficult and must be confirmed by serological methods such as ELISA. While PCR is a promising method for diagnosis, it requires expensive laboratory facilities which are often only available in the larger hospitals.

Treatment

The antitrypanosomal drugs benznidazole and nifurtimox are the only medicines available to treat Chagas disease, although their effectiveness is mainly limited to children in the acute and early chronic stages. Many infected individuals who are asymptomatic in the acute phase therefore miss this opportunity for a possible cure. Effective treatment with these antiparasitic drugs takes one or two months, and is accompanied by significant side effects; therefore patient non-compliance is high. Clearly, new drugs which are consistently effective in both the acute and chronic phases are urgently needed.

Some researchers focus on the use of existing antifungal triazoles to treat Chagas disease, in order to reduce the risk and time associated with developing completely new drugs. However, pharmaceutical companies conduct little, if any, research devoted to Chagas disease, owing to the lack of a viable commercial market. Therefore most new research projects, including those exploring potential vaccines, unfortunately remain in the preclinical phases of development.

Case study

An otherwise healthy 26-year old French woman was hospitalized after a two-month family visit to French Guiana. Her complaints were fever, headache, photophobia, sporadic chest pain, shortness of breath and joint pain. Physical examination showed typical Romaña sign under her left eye. The ECG revealed anterior ST-segment depression, while direct microscopic examination of the Romaña’s sign revealed T. cruzi. Blood smears and cultures were negative. The patient recovered after receiving benznidazole daily for seven weeks, although treatment was suspended when peripheral neuropathy developed. Serum antibodies were detected four months later.

About the author

David Shaproski is a fifth year medical student at Leiden University. He conducted biomedical research concerning the diagnostics of schistosomiasis, another neglected disease.

Further reading

- Clayton J. Chagas disease: pushing through the pipeline. Nature. 2010. Rassi A Jr et al. Chagas disease. Lancet. 2010.