Chagas disease

Chagas disease.

Topics covered: 

  • Essentials
  • Introduction and aetiology
  • Epidemiology
  • Pathogenesis and pathology
  • Clinical features
  • Laboratory diagnosis
  • Treatment
  • Prevention and control
  • Unanswered questions and future research
  • Trypanosoma rangeli
  • Further reading

Essentials

Trypanosoma cruzi, the protozoan parasite which causes Chagas disease, is a zoonosis with many mammal host and vector species. It is transmitted to humans by contamination of mucous membranes or abraded skin with infected faeces of bloodsucking triatomine bugs, also by blood transfusion, organ transplantation, transplacentally, and orally by food contaminated with infective forms. It multiplies intracellularly (pseudocysts) as amastigotes in mammalian cells, particularly heart and smooth muscle, from which flagellated trypomastigotes emerge to reinvade cells or circulate in blood. Around 10 million people are infected in Latin America; imported cases and congenital cases may occur elsewhere.

Clinical features

There are classically three phases. (1) Acute—may be asymptomatic, or with manifestations including fever, myalgia, headache, vomiting, diarrhoea, anorexia, facial or generalized oedema, rash, generalized lymphadenopathy, and hepatosplenomegaly; there may be a lesion at the portal of entry; fatal in less than 10%. (2) Meningoencephalitic—rare in adults, excepting those who are immunocompromised (most typically with HIV/AIDS); also seen in congenital cases. (3) Chronic—occurs in up to 30% of those recovering from the acute phase; most often with cardiac involvement (typically cardiomyopathy leading to congestive cardiac failure, with risk of arrhythmia and ECG abnormalities due to focal inflammatory lesions of the conducting system), also megaoesophagus and megacolon. Infection is opportunistic, relapsing in the immunocompromised.

Diagnosis

(1) Acute phase—parasitaemia is scanty, but circulating trypomastigotes may be detectable in the acute phase by microscopy of blood, enhanced by concentration methods. (2) Chronic phase—multiple blood cultures or feeding and subsequent dissection of laboratory-reared triatomines (xenodiagnosis) may reveal infection. (3) Serological testing—can demonstrate evidence of infection, but needs to be standardized with reference sera and by external quality control.

Treatment

(1) Acute phase—proven cases should be treated promptly with nifurtimox or benznidazole, but there is no guarantee that a full course of treatment will eliminate the infection. (2) Chronic phase—the value of drug treatment for adults is still debated; supportive care may include the following (a) for heart disease—conventional drug treatment for cardiac failure and arrhythmias; cardiac pacemaker; (b) for megaoesophagus—dilatation; segmentary removal of stomach muscle; replacement of the distal oesophagus; (c) megacolon—resection and anastomosis with the rectal stump.

Prevention

Proven methods of controlling domestic triatomine bugs include insecticide spraying (with pyrethroids), health education, community support, and house improvement. Serological surveillance of children detects residual endemic foci or congenital transmission and is vital for monitoring the success of control programmes. The Southern Cone programme against Triatoma infestans is considered a model for international cooperation in disease control. There is no vaccine.

Introduction and aetiology

In 1907, in the space of a few months, the Brazilian scientist Carlos Chagas discovered the disease that bears his name and described the entire lifecycle of the causative organism. Chagas first found the protozoan agent Trypanosoma cruzi in the gut of the large blood-sucking insect vector, the triatomine bug (order Hemiptera, family Reduviidae, subfamily Triatominae). Later he returned to bug-infested houses and detected T. cruzi in the blood of sick children.

adult female triatome bug

Above: Adult female triatomine bug (Panstrongylus megistus)

T. cruzi is a kinetoplastid protozoan. In addition to the nucleus, it has a second, microscopically visible DNA-containing organelle, the kinetoplast. The main lifecycle stages (trypomastigote, amastigote, epimastigote) are distinguished by the position of the kinetoplast relative to the nucleus and by the presence or absence of a free flagellum.

Vector-borne transmission of T. cruzi is by contamination of the mammal host with infected faeces of triatomine bugs, not by their bite. During or shortly after feeding, bugs release blackish liquid faeces and urine on to the skin of the host. Infective forms (metacyclic trypomastigotes) penetrate mucous membranes or abraded skin. Inside the mammal, T. cruzi is primarily an intracellular parasite. Trypomastigotes enter nonphagocytic or phagocytic cells, in which they transform to ovoid or round aflagellate amastigotes that multiply inside the cell by binary fission to produce a pseudocyst 

Pseudocyst of Trypanosoma cruzi

Above: Pseudocyst of Trypanosoma cruzi

After 5 days or more, the pseudocyst ruptures to release numerous new trypomastigotes, which reinvade cells or circulate in the blood. Multiplication may occur at the site of infection, but pseudocysts subsequently predominate in muscle, especially heart and smooth muscle. In the blood, trypomastigotes are small, often C-shaped, with a large terminal kinetoplast.

Trypanosoma cruzi C-shaped trypomastigote in blood

Above: Trypanosoma cruzi C-shaped trypomastigote in blood

In fulminating or experimental infections, slender highly motile trypomastigotes may also sometimes be seen. Trypomastigotes do not multiply in the blood. Triatomine bugs become infected by taking a blood meal from an infected mammal; birds and reptiles are not susceptible to infection. Infection in the bug is confined to the alimentary tract, where T. cruzi multiplies by binary fission as epimastigotes (kinetoplast adjacent to the nucleus).

Trypanosoma cruzi C-shaped trypomastigote in blood

Above: Trypanosoma cruzi C-shaped trypomastigote in blood

Metacyclic trypomastigotes are produced in the hindgut and rectum of the bug. All stages of the T. cruzi lifecycle can be cultured in vitro. T. cruzi can also be transmitted by blood transfusion and organ transplantation, across the placenta, via breast milk (rarely), and orally through food contaminated by triatomine faeces and the raw meat of infected mammals. Sexual transmission has not been documented. 

Cycles of chagas disease

Epidemiology

T. cruzi is confined to the Americas, although closely related organisms of the same subgenus (Schizotrypanum) are cosmopolitan in bats. The vast majority of the 140 triatomine bug species are also restricted to the Americas. Their natural habitats are the refuges of mammals, birds, and reptiles, in trees, in burrows, and among rocks. All mammals are thought to be susceptible to T. cruzi, which has been reported from at least 150 mammal species. The opossum (Didelphis spp.) is the most common sylvatic host. A few triatomine species thrive as domestic colonies. More than 10 000 bugs have been found in a single house. Before the recent Southern Cone initiative to control Triatoma infestans, the species was widespread in rural housing of the Southern Cone countries of South America (Argentina, Bolivia, Brazil, Chile, Paraguay, Uruguay, and southern Peru). Rhodnius prolixus is the common vector in northern South America and also occurs in Central America, with Triatoma dimidiata as secondary vector in the same regions. Panstrongylus megistus (picture above) infests central and eastern Brazil, and Triatoma brasiliensis north-eastern Brazil. Animals that share human dwellings, such as guinea pigs (cuy), dogs, cats, rats, and mice are domestic reservoirs of T. cruzi infection. Chickens, although not susceptible to T. cruzi, encourage bug infestation and can sustain large colonies.

Serological surveys suggest that about 10 million people may now be infected with T. cruzi in South and Central America, a figure which is reduced from up to 20 million around four decades ago. In some communities, seropositivity rates may still exceed 50%. As expected from the precarious contaminative route of transmission, prevalence rises with age. Based on prevalence, before recent control initiatives, it was estimated that up to 300 000 new infections might occur in Latin America each year; this is now reduced to around 60 000/year. Only approximately 1000 cases are known from the Amazon basin, about half of these due to oral transmission by drinking fruit juices (e.g. from berries of açaí or bacaba palms or cane sugar garapa) in which infected bugs have been accidentally ground up. Oral outbreaks may also occur elsewhere: one among schoolchildren in Caracas, Venezuela, due to guava juice, involved 103 cases. There are relatively few Amazonian cases because the local forest vectors do not colonize houses. For the same reason, autochthonous infection is very rare in the United States of America.

Not surprisingly, sporadic T. cruzi infections may be found among migrants from Latin America to the United States of America and elsewhere. This gives rise to occasional cases of transmission by blood or organ donors and to rare congenital cases. Fear of blood transfusion transmission suggests a need to screen some blood donors outside traditional endemic areas. In 2007, the World Health Organization (WHO) launched a ‘Global Network for Chagas Elimination’ to raise global awareness and coordinate prevention of transmission.

chagas disease distribution map

Above: Chagas disease distribution map

Initial acute infections are frequently asymptomatic or overlooked. It is thought that less than 10% of acute infections in children are fatal. Morbidity due to Chagas disease arises primarily from the chronic infection. Once acquired, infection is usually carried for life. Around 30% of those infected will subsequently display ECG abnormalities and chagasic cardiomyopathy, and a proportion of those have associated megaoesophagus or megacolon.

There are marked regional differences in the epidemiology of Chagas disease. Megasyndromes are common in central and eastern Brazil but seldom described in northern South America and Central America. Research in molecular genetics has shown that T. cruzi is not a Single entity, but a species with at least six genetic lineages. Until Recently these were divided into TCI and TCIIa–e, but they have now, more logically, been re-designated as six distinct groups TCI, TCII, TCIII, TCIV, TCV, and TCVI, with differences between ecologies, hosts, vectors, geographical, and disease distributions. The common opossum Didelphis is the most ubiquitous host of TCI, whereas TCIII is associated with the armadillo Dasypus. North of the Amazon the principal agent of Chagas disease is TCI, which causes severe and fatal cardiomyopathy. In contrast, in the Southern Cone countries, where megaoesophagus and megacolon are common, Chagas disease is predominantly caused by TCII, TCV, and TCVI. It has been proved that T. cruzi has an extant capacity for genetic exchange, and TCV and TCVI are natural TCII /TCIII hybrids, which are particularly prevalent in humans in Paraguay, Chile, Bolivia, and adjacent regions.

Pathogenesis and pathology

At the portal of entry, local multiplication of T. cruzi may lead to unilateral conjunctivitis or to a skin lesion (below).

Romaña’s sign in acute Chagas disease

Above: Romaña’s sign in acute Chagas disease

Unruptured pseudocysts in muscle apparently generate no inflammatory response. Pseudocyst rupture is followed by infiltration of lymphocytes, monocytes, and/or polymorphonuclear cells. Antigens released from pseudocysts may spread and be adsorbed on to adjacent uninfected cells. Such uninfected cells may be attacked by the immune response of the host and be destroyed. In this way, expanded focal lesions may be produced. Postmortem histology of human hearts and experimental studies in dogs has demonstrated a clear association between ECG abnormalities and focal lesions in the conducting system of the heart. Much damage may occur in the acute phase of infection, particularly if pseudocysts are numerous. Postmortem histology has demonstrated that neuron loss is a feature of chagasic cardiopathy and of megasyndromes that is exacerbated by further disease or age-related loss. Thus, a threshold may be reached, often many years after the acute infection, at which organ function is perturbed. Further ECG abnormalities, aperistalsis, and organ enlargement may ensue. This ‘neurogenic’ pathogenesis has been linked to sudden death.

It is proposed that pathological exposure of normal host-sequestered antigens, or sharing of antigens between T. cruzi and its host, may precipitate autoimmune pathogenesis. Some chronic chagasic cardiomyopathy is said to display a renewed intense inflammatory response and a progressive diffuse myocarditis, and a slow decline in cardiac function.

The contribution of the lifelong infection to the pathogenesis of chronic Chagas disease is somewhat controversial, although published studies suggest that elimination of residual infection may improve long-term prognosis. After the initial acute phase, trypomastigotes are detectable in the blood only by sensitive indirect methods. Similarly, pseudocysts in the tissues are infrequent, but are detectable immunologically and by amplification of T. cruzi DNA.

T. cruzi infection is controlled primarily by a cell-mediated immune response, especially the Th1 arm of the immune response. Patients immunocompromised by AIDS have impaired Th1 responses. Thus HIV-positive patients chronically infected with T. cruzi may suffer reactivated acute Chagas disease, with microscopically patent parasitaemia and poor prognosis. 

At the level of gross pathology, substantial megacardia may be seen. Thinning of the myocardium may be present, with focal aneurysms visible upon transillumination, especially at the apex of the left ventricle and thrombus in the right atrial appendage.

Gross pathology of chronic Chagas cardiomyopathy (four-chamber frontal view)

Above: Gross pathology of chronic Chagas cardiomyopathy (four-chamber frontal view)

Apical aneurysm is considered to be a pathognomonic sign of chronic chagasic cardiomyopathy.

Above: Thrombus in right atrial appendage

Megaoesophagus and megacolon may show enormous dilatation and thinning of the wall. Chagasic megaoesophagus is more frequent than chagasic megacolon, but both may occur in the same patient and are often accompanied by chagasic heart disease. Chagasic megaoesophagus may be a prelude to carcinoma.

Chagas' megaesophagus in 2 different Brazilian patients showing dysrhythmic contractions, disturbance of tone and moderate dilatation of the esophagus

Above: Chagas' megaesophagus in 2 different Brazilian patients showing dysrhythmic contractions, disturbance of tone and moderate dilatation of the esophagus.

Megacolon in chronic Chagas' disease

Above: Megacolon in chronic Chagas' disease

Occasionally megasyndromes may arise in infants, following congenital infection.

Clinical features

Classically, there are three clinical phases of Chagas disease. In the acute phase, symptoms include fever, myalgia, headache, hepatosplenomegaly, generalized lymphadenopathy, facial or generalized oedema, rash, vomiting, diarrhoea, and anorexia. If T. cruzi has been inoculated through the conjunctiva, Romaña’s sign may be present: unilateral conjunctivitis, chemosis, and periophthalmic oedema. If the portal of entry is the skin, an indurated oedematous cutaneous lesion (chagoma) may be seen. Regional lymphadenopathy may be present. Multiple chagomas may occasionally occur in acute-phase infections in infants. ECG abnormalities may include sinus tachycardia, increased PR interval, T-wave changes, and low QRS voltage. The incubation period may be as short as 2 weeks or as long as several months if infection is due to transfusion of contaminated blood. General lymphadenopathy and splenomegaly are frequent in blood transfusion-acquired infections. 

Congenital acute infection may cause fever, oedema, metastatic chagomas, neurological signs such as convulsions, tremors, and weak reflexes, and apnoea. Hepatosplenomegaly is frequent. The ECG is usually normal but low-voltage complexes, reduced T-wave height, and longer atrioventricular (AV) conduction time may be present.

Meningoencephalitis is rare in adults, more frequent in infants, and common in immunocompromised patients. It carries a poor prognosis.

The clinical picture of AIDS-associated chagasic meningoencephalitis may be similar to toxoplasmosis. Haemorrhagic necrotic encephalitis is described in the nests of trypanosomes in microglia. Congenital infection may resemble toxoplasmosis, cytomegalovirus infection, or syphilis, with an increased likelihood of abortion and premature birth. Congenital infection is well known in Bolivia but less frequently reported from Venezuela and Brazil.

Symptomatic or asymptomatic acute infection may be followed by a symptom-free indeterminate phase of unpredictable length, which may be life long. Chronic-phase symptoms may emerge in up to 30% of patients recovering from the acute phase.

Cardiac symptoms include arrhythmias, palpitations, chest pain, oedema, dizziness, syncope, and dyspnoea. The cardiac enlargement may be massive with chronic congestive cardiac failure, apical aneurysm, and thrombus in the right atrial appendage. The cardiac conducting system is involved, especially the sinus node, bundle of His and AV node, in which there is mononuclear and mast-cell infiltration, inflammation, and fibrosis. Characteristic ECG abnormalities are right bundle branch block (RBBB) and left anterior hemiblock (LAH). AV conduction abnormalities, including AV block, may be present. Arrhythmias may include sinus bradycardia, sinoatrial block, ventricular tachycardia, primary T-wave changes, and abnormal Q-waves. The severity of heart disease is graded by the degree of disturbance. Sudden death is attributable, not to ruptured aneurysm, but to arrhythmias often precipitated by exercise (e.g. on the football field). Radiography may reveal megacardia. Signs of oesophageal involvement include loss of peristalsis, regurgitation, and dysphagia. Parotid enlargement may be associated.

In megacolon, there may be failure of defaecation, constipation, and faecaloma. Progressive dilatation of either organ can be graded clinically according to severity and may be detectable by radiography. Megaduodenum and megaureter are also described. The lymph nodes between the pulmonary trunk and the aorta are frequently enlarged.

Chest radiograph showing gross cardiac enlargement in chronic Chagas disease.

Above: Chest radiograph showing gross cardiac enlargement in chronic Chagas disease.

The differential diagnosis includes other types of heart disease and causes of ECG abnormalities. RBBB and LAH are indicative, but a history of exposure to T. cruzi infection and laboratory diagnostic evidence must be considered (see below).

Laboratory diagnosis

A history of exposure to triatomine bugs, to potentially contaminated transfused blood, or a prolonged stay in endemic regions must be considered.

Motile trypomastigotes might be seen in unstained, wet blood preparations examined by microscopy. Nevertheless, parasitaemia is often scanty or undetectable by this method. The sensitivity of parasitological diagnosis may be enhanced by microscopy of samples prepared with concentration methods, such as the centrifugation pellet from separated serum (Strout’s method), the haematocrit buffy coat layer, Giemsa-stained thick films, or the centrifugation sediment after lysis of red blood cells with 0.87% ammonium chloride. All these tests may be negative if parasitaemia is low. Potentially infected blood must be handled with care, especially during haematocrit centrifugation, as a single trypomastigote can cause infection. Multiple blood cultures may also be performed, with a sensitive blood agar-based medium and physiological saline overlay. Even more sensitive than blood culture is xenodiagnosis, in which hungry fourth or fifth instar bugs from a clean triatomine colony, raised from bug eggs and fed only on birds, are allowed to feed on the patient. Bugs are applied in a plastic pot contained discretely in a black bag, which is tied beneath the patient’s forearm. The bugs are dissected 20 to 25 days later. The hindgut and rectum are drawn out into a drop of sterile physiological saline, mixed with a blunt instrument (microspatula), and observed microscopically for motile epimastigotes and trypomastigotes. Dissection should be performed behind a small, Perspex safety screen or in a microbiological safety cabinet. R. prolixus is the most avid feeder for xenodiagnosis but may cause delayed hypersensitivity reactions in sensitized patients. Anaphylaxis is rare but two cases are known. The local vector should be used as the susceptibility of triatomine species varies with the strain of T. cruzi.

After the acute-phase infection, all the above methods of parasitological diagnosis will fail except xenodiagnosis and, possibly, multiple blood cultures. Up to 50% of patients in chronic phase may yield a positive xenodiagnosis, providing at least 10 triatomine bugs are used. Although polymerase chain reaction amplification of T. cruzi DNA is sensitive and specific, it is not yet available as a routine diagnostic test. Serum antibody is produced within a few days of T. cruzi infection and persists for life in untreated patients. There is an early IgM response, but it is not sustained at the high levels seen in African trypanosomiasis. Persistent IgG may be detected by the enzyme-linked immunosorbent assay, the indirect fluorescent-antibody test, or the indirect haemagglutination test. Complement fixation, developed in 1913, is effective but now seldom used. Crossreactions may occur with visceral and mucocutaneous leishmaniasis, with treponematoses, and possibly with other hyperimmune responses or autoimmune diseases. Recombinant antigens have been used to improve species specificity and some are commercially available; rapid tests have also been introduced. The majority of diagnostic kits are prepared from T. cruzi II preparations but are presumed to be equally applicable to other lineages. Serological assays must be standardized with negative and positive control sera and by reference to experienced external reference centres to check reproducibility. Quality of commercial tests should not be presumed without reference to authoritative comparative studies. Transplacentally acquired IgG may persist for up to 9 months in infants born of seropositive mothers. However, IgM-specific seropositivity in such infants is an indicator of congenital infection. Note that IgM may decline rapidly in filter paper blood spots if they are used as the source of serum. Serology may be performed post mortem using pericardial fluid.

Treatment

Proven acute cases must be treated promptly in an effort to minimize tissue damage and neuron loss. The synthetic oral nitrofuran, nifurtimox (Lampit) was the first successful drug for the treatment of Chagas disease.

Lampit aka nifurtimox

Bayer has recently safeguarded supply by restarting production in El Salvador. Nifurtimox is given in three divided daily doses at 8 to 10 mg/kg for 90 days, up to double doses for infected children. Adverse effects, which may lead to interruption of treatment, can include anorexia, loss of weight, psychological disturbances, excitability, nausea, and vomiting. Benznidazole is an oral nitroimidazole.

Radanil (Benznidazol)

The adult dosage is 5 to 7 mg/kg in two divided doses for 60 days; for children, 10 mg/kg also in two divided doses for 60 days. Adverse effects may also demand interruption of treatment. These include rashes, fever, nausea, peripheral polyneuritis, leukopenia, and, rarely, agranulocytosis. Double or even higher doses have been used for immunocompromised patients, especially if meningoencephalitis is present. There is no guarantee that a full course of treatment will eliminate the infection. Although the value of drug treatment for chronic infections is still debated, it is favoured for children under 12 years or by some for those under 15 years, because children tolerate treatment better than adults. Favourable access to these drugs may be obtained via WHO.

Chemotherapy is an important part of supportive treatment. In acute-phase heart failure, sodium intake is restricted and diuretics and digitalis may be indicated. Meningoencephalitis may require anticonvulsants, sedatives, and intravenous mannitol. Heart failure due to Chagas disease may require vasodilatation (angiotensin-converting enzyme inhibitors) and maintenance of normal serum potassium levels; digitalis is a last resort because it may aggravate arrhythmias. A pacemaker may be fitted to improve bradycardia not responding to atropine, or for atrial fibrillation with a slow ventricular response that is not responsive to vagolytic drugs, or for complete AV block. Amiodarone has been suggested as the most useful drug to treat arrhythmias but it may still be aggravating. For ventricular extrasystoles lidocaine, mexiletine, propafenone, flecainide, and β-adrenoreceptor antagonists may be effective. Lidocaine may be used intravenously in emergencies. It is essential to consult detailed WHO expert reports and physicians with substantial experience in the management of chagasic heart disease.

Surgery is a vital part of case management for Chagas disease. Resection of ventricular aneurysms has been suggested. Specialized surgery has been developed in Brazil for the treatment of megaoesophagus and megacolon. Early megaoesophagus may respond to balloon dilatation. The Heller–Vasconcelos operation, in which a portion of muscle at the junction of the oesophagus and stomach is removed, may alleviate megaoesophagus. Severe megaoesophagus requires replacement of the distal oesophagus, e.g. with a portion of jejenum. The modified Duhamel–Haddad operation has been considered the most successful surgery for correction of a megacolon: after resection, the colon is lowered through the retrorectal stump as a perineal colostomy. Subsequent suturing, under peridural anaesthesia, gives a wide junction between the colon and the rectal stump.

Prognosis, even in treated patients who show serological reversion, is unpredictable as the sequelae of damage due to the acute phase of Chagas disease cannot be foreseen.

Prevention and control 

There is no vaccine against Chagas disease and no immunotherapy.

Chagas disease flourishes where there is poverty and poor housing conditions. There are proven methods of controlling domestic triatomine bugs. These depend on insecticide spraying, health education, community support, and house improvement. Synthetic pyrethroids are the insecticides of choice and several commercial sources are available. Vector control programmes consist of preparatory, attack, and vigilance phases. In the preparatory phase, the distribution of all dwellings must be mapped, the presence of infested houses assessed, and the attack and vigilance phases costed and planned. The attack phase involves spraying all houses and peridomestic buildings, irrespective of whether bugs have been found. During the vigilance phase, the community plays an essential role in reporting residual bug infestations, which elicit a rapid respraying response for the affected sites. Serology is vital for monitoring the success of control programmes. Children born after control programmes begin should be serologically negative beyond 9 months of age (to exclude transplacental transfer of IgG) except for infrequent cases of congenital transmission.

Blood donors in or from endemic areas should be screened serologically. If conditions demand the use of seropositive blood, it can be decontaminated with crystal violet (250 mg/litre) and storage at 4°C for at least 24 h. Potentially infected organ donors or recipients should be screened serologically. Seropositive immunosuppressed recipients are likely to suffer reactivated acute-phase infection. Prophylactic chemotherapy with benznidazole may be effective.

The Southern Cone programme launched a massive effort to eliminate T. infestans from Argentina, Bolivia, Brazil, Chile, Paraguay, Uruguay, and southern Peru.

The Southern Cone programme

Domestic infestation in Brazil has been reduced by 85%. Uruguay and Chile are essentially free of vector-borne and blood-transfusion transmission. Substantial progress has also been made in the other participating countries. Similar international collaborations have been initiated in Central America and the Andean Pact countries. Reinvasion of sylvatic bugs into domestic habitats may complicate vector control in some regions. One example is T. brasiliensis in north-eastern Brazil, which reinvades houses from adjacent rock piles. A second example is R. prolixus, which, in some regions of Venezuela and Colombia, has the capacity to reinvade houses from adjacent infested palm trees, as demonstrated by comparative population genetics. A surveillance programme and rapid responses to new domestic triatomine populations has been planned to protect the Amazon against domiciliation of vectors.

Unanswered questions and future research

T. cruzi is of immense research interest. It is not entirely clear how the organism evades the host immune response. Furthermore, the pathogenesis of Chagas disease is not fully understood. Molecular methods have radically changed our understanding of the epidemiology of T. cruzi infection. Molecular features unique to trypanosomatids (trypanosomes and leishmanias) make T. cruzi an attractive model for molecular biologists.

Mario Grijalva, Ph.D., professor of biomedical sciences and director of the Tropical Disease Institute and Maria Rodionova, OMS II.

Above: Mario Grijalva, Ph.D., professor of biomedical sciences and director of the Tropical Disease Institute and Maria Rodionova, OMS II.
 
The Tropical Disease Institute (TDI) received additional funding from two sources that will expand its Chagas disease research and blood safety monitoring efforts.
The Ministry of Health of Ecuador approved nearly $107,000, a 46 percent increase from 2012, to fund a renewal of the External Performance Evaluation of Blood Screening in Ecuador for 2013. The project ensures blood screening is performed correctly by strict daily monitoring of every screening test performed, inter-laboratory proficiency evaluations and technician training and certification.
 
“Our program has played a major role in the transformation of the blood bank system in Ecuador,” said Mario Grijalva, Ph.D., professor of biomedical sciences and director of TDI. Dr. Grijalva manages the project through the TDI’s Center for Infectious Disease Research at the Pontifical Catholic University of Ecuador in Quito
 
Further research is required to produce a nontoxic, low-cost oral drug, which would eliminate the reservoir of infection in humans, and to clarify further the population genetics and epidemiological significance of diverse strains. The origins and evolution of the organism and its vectors are also of considerable academic interest.

Trypanosoma rangeli  

The second human trypanosomiasis in the New World is due to T. rangeli infection. T. rangeli is also transmitted by triatomine bugs, in particular the genus Rhodnius. In Rhodnius species, however, T. rangeli traverses the wall of the alimentary tract, infects the haemocoel, and reaches the salivary glands, in which the metacyclic infective trypomastigotes are produced. T. rangeli is thus transmitted by the bite of the triatomine bug and not by contamination with bug faeces. Although enzootic T. rangeli infection is widespread in Latin America, transmission to humans is virtually confined to areas in which R. prolixus is the domestic vector of T. cruzi. Coinfections of T. cruzi and T. rangeli may occur. The organism appears to be nonpathogenic in humans. T. rangeli can be pathogenic to Rhodnius species The importance of T. rangeli lies in the fact that it may confuse xenodiagnosis to detect T. cruzi. With care and experience, T. rangeli can be distinguished from T. cruzi either by its long slender epimastigotes (up to 80 μm in length) and its smaller kinetoplast or by its presence in the haemolymph or salivary glands of some xenodiagnosis bugs. The lifecycle in the mammalian host is uncertain, but T. rangeli is thought to divide in the peripheral blood. Trypomastigotes are rarely seen in human blood: they are much larger than T. cruzi, with a small subterminal kinetoplast. Antibodies to T. cruzi certainly crossreact strongly with T. rangeli. Based on experimental work in mice,T. rangeli infections are thought to induce very low crossreactive antibody titres to T. cruzi. As with T. cruzi, there is subspecies genetic heterogeneity, with at least two and up to four distinct T. rangeli lineages, thought to be linked to two species groups within the triatomine genus Rhodnius. 

Further reading

Top

Castro JA, de Mecca M M, Bartel LC (2006). Toxic side effects of drugs used to treat Chagas disease (American trypanosomiasis). Hum Exp Toxicol, 25, 471–9. [The potential side effects of treatment.]

Gaunt MW, et al. (2003). Mechanism of genetic exchange in American trypanosomes. Nature, 421, 936–39. [The first experimental proof that T. cruzi has an extant capacity for genetic exchange.] 

Maudlin I, Holmes P, Miles MA (eds) (2004). The Trypanosomiases. CABI Publishing, Wallingford, UK. [A detailed review of diverse aspects of both the South American and the African trypanosomiases.]

Miles MA (2004). The discovery of Chagas disease: progress and prejudice. Infect Dis Clin North Am, 18, 247–60. [An account of historical and political aspects of the unusual discovery of Chagas disease.]

Miles MA, Feliciangeli MD, Arias AR (2003). American trypanosomiasis (Chagas disease) and the role of molecular epidemiology in guiding control strategies. Br Med J, 326, 1444–8. [A synthesis of the application of molecular epidemiology to elucidate transmission of T. cruzi and guide interventions.]

Raia AA (1983). Manifestações digestivas da moléstia de Chagas. Sarvier, São Paulo, Brazil. [For the surgeon, fascinating accounts of the development of lifesaving procedures, especially correction of megaoesophagus and megacolon (in Portuguese).]

Riera C, et al. (2006). Congenital transmission of Trypanosoma cruzi in Europe (Spain): a case report. Am J Trop Med Hyg, 75, 1078–81. [A case history of congenital transmission in Europe.]

Schmuniz GA (2007). Epidemiology of Chagas disease in non endemic countries: the role of international migration. Mem Inst Oswaldo Cruz, 30 (Suppl. 1), 75–85. [Forewarning on the occurrence of Chagas disease outside traditional endemic regions.]

World Health Organization (2002). Control of Chagas disease, Technical Report Series 905. WHO, Geneva. [Not strictly on control, but one of the best clinical reviews of Chagas disease in the English language.]

Miles MA, et al. (2009). The molecular epidemiology and phylogeography of Trypanosoma cruzi and parallel research on Leishmania: looking back and to the future. Parasitology, 136, 1509–28.