Chagas disease

Chagas disease
Photomicrograph of Giemsa-stained Trypanosoma cruzi crithidia (CDC)
ICD-10	B57
ICD-9	086
DiseasesDB	13415
MedlinePlus	001372
MeSH	D014355

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Diagnosis

History and Symptoms | Physical Examination | Staging | Laboratory tests | Electrocardiogram | X Rays | CT | MRI Echocardiography or Ultrasound | Other images | Alternative diagnostics

Treatment

Medical therapy | Surgical options | Primary prevention | Secondary prevention | Financial costs | Future therapies

Laboratory diagnosis

Diagnosis of chronic Chagas disease is made after consideration of the patient's clinical findings, as well as by the likelihood of being infected, such as having lived in an endemic country. Diagnosis is generally made by testing with at least two different serologic tests.

Demonstration of the causal agent is the diagnostic procedure in acute Chagas' disease. It almost always yields positive results, and can be achieved by:

Trypanosoma cruzi in blood smears, Giemsa stain.

Trypanosoma cruzi in blood smears, Giemsa stain.

• Microscopic examination: a) of fresh anticoagulated blood, or its buffy coat, for motile parasites; and b) of thin and thick blood smears stained with Giemsa, for visualization of parasites; it can be confused with the 50% longer Trypanosoma rangeli, which has not shown any pathogenicity in humans yet.
• Isolation of the agent by: a) inoculation into mice; b) culture in specialized media (e.g., NNN, LIT); and c) xenodiagnosis, where uninfected Reduviidae bugs are fed on the patient's blood, and their gut contents examined for parasites 4 weeks later.
• Various Immunodiagnostic tests; (also trying to distinguish strains (zymodemes) of T.cruzi with divergent pathogenicities).
  • Complement fixation
  • indirect hemagglutination
  • IFA, Indirect fluorescent assay
  • RIA, Radio-immunoassay
  • ELISA, Enzyme-Linked Immunosorbent Assay
• Diagnosis based on Molecular Biology techniques.
  • PCR, Polymerase chain reaction, most promising

Antibody Detection:

Positive IFA result

Infections with Trypanosoma cruzi are common in Mexico, Central America, and South America. Many immigrants from areas where Chagas disease is endemic currently reside in the United States and are potential sources for parasite transmission via contaminated blood. During the acute phase of illness, blood film examination generally reveals the presence of trypomastigotes. During the chronic phase of infection, parasitemia is low; immunodiagnosis is a useful technique for determining whether the patient is infected.

The indirect fluorescent antibody (IFA) test is available at CDC. IFA antigen slides are prepared from a suspension of epimastigotes. Although IFA is very sensitive, cross-reactivity can occur with sera from patients with leishmaniasis, a protozoan disease that occurs in some of the same geographical areas as T. cruzi. Various serologic methods are commercially available in the U.S. and other countries for laboratory diagnosis of Chagas disease. The sensitivity and specificity of these tests are highly variable.

Prognosis

An index for classification of patients who have Chagas' disease was published in the August 24, 2006 edition of the New England Journal of Medicine. Based on over 500 patients, this index includes clinical aspects, X-ray findings, EKG, echocardiography and Holter.

Chagas' risk factors

Risk factor	points
NYHA class III or IV	5
Cardiomegaly	5
Wall motion abnormalities	3
non-sustained ventricular tachycardia	3
low voltage on ECG	2
male sex	2

Total points	Risk of death in 10 years
0–6	10%
7–11	40%
12–20	85%

Treatment

There are two approaches to therapy, both of which can be life saving:

• antiparasitic treatment, to kill the parasite; and
• symptomatic treatment, to manage the symptoms and signs of infection.

Medication for Chagas' disease is usually only effective when given during the acute stage of infection. The drugs of choice are azole or nitroderivatives such as benznidazole or nifurtimox (under an Investigational New Drug protocol from the CDC Drug Service), but resistance to these drugs has already been reported. Furthermore, these agents are very toxic and have many adverse effects, and cannot be taken without medical supervision. The antifungal agent Amphotericin B has been proposed as a second-line drug, but cost and this drug's relatively high toxicity have limited its use. Moreover, 10-year study of chronic administration of drugs in Brazil has revealed that current chemotherapy does not totally remove parasitemia. Thus, the decision about whether to use antiparasitic therapy should be individualized in consultation with an expert.

In the chronic stage, treatment involves managing the clinical manifestations of the disease, e.g., drugs and heart pacemaker for chronic heart failure and heart arryhthmias; surgery for megaintestine, etc., but the disease per se is not curable in this phase. Chronic heart disease caused by Chagas' disease is now a common reason for heart transplantation surgery. Until recently, however, Chagas' disease was considered a contraindication for the procedure, since the heart damage could recur as the parasite was expected to seize the opportunity provided by the immunosuppression that follows surgery. The research that changed the indication of the transplant procedure for Chagas' disease patients was conducted by Dr. Adib Jatene's group at the Heart Institute of the University of São Paulo, in São Paulo, Brazil. The research noted that survival rates in Chagas' patients can be significantly improved by using lower dosages of the immunosuppressant drug cyclosporin. Recently, direct stem cell therapy of the heart muscle using bone marrow cell transplantation has been shown to dramatically reduce risks of heart failure in Chagas patients. Patients have also been shown to benefit from the strict prevention of reinfection, though the reason for this is not yet clearly understood.

Some examples for the struggle for advances:

• Use of oxidosqualene cyclase inhibitors and cysteine protease inhibitors has been found to cure experimental infections in animals.
• Dermaseptins from frog species Phyllomedusa oreades and P. distincta. Anti-Trypanosoma cruzi activity without cytotoxicity to mammalian cells.
• Design of inhibitors to enzymes involved in trypanothione metabolism, which is unique to the kinetoplastid group of parasites.
• The sesquiterpene lactone dehydroleucodine (DhL) affects the growth of cultured epimastigotes of Trypanosoma cruzi
• The genome of Trypanosoma cruzi has been sequenced. Proteins that are produced by the disease but not by humans have been identified as possible drug targets to defeat the disease.

Prevention

Vector insect Triatoma infestans (Kissing Bug)

A reasonably effective vaccine was developed in Ribeirão Preto in the 1970s, using cellular and subcellular fractions of the parasite, but it was found economically unfeasible. More recently, the potential of DNA vaccines for immunotherapy of acute and chronic Chagas' disease is being tested by several research groups.

Prevention is centered on fighting the vector (Triatoma) by using sprays and paints containing insecticides (synthetic pyrethroids), and improving housing and sanitary conditions in the rural area. For urban dwellers, spending vacations and camping out in the wilderness or sleeping at hostels or mud houses in endemic areas can be dangerous, a mosquito net is recommended. If the traveller intends to travel to the area of prevalence, he/she should get information on endemic rural areas for Chagas' disease in traveller advisories, such as the CDC.

In most countries where Chagas' disease is endemic, testing of blood donors is already mandatory, since this can be an important route of transmission. The United States FDA has recently licensed a test for antibodies against T. cruzi for use on blood donors but has not yet mandated its use. The AABB recommends that past recipients of blood components from donors found to be infected be notified and themselves tested. In the past, donated blood was mixed with 0,25 g/L of gentian violet successfully to kill the parasites. Early detection and treatment of new cases, including mother-to-baby cases, will also help reduce the burden of disease.

With all these measures, some landmarks were achieved in the fight against Chagas' disease in Latin America: a reduction by 72% of the incidence of human infection in children and young adults in the countries of the Initiative of the Southern Cone, and at least two countries (Uruguay, in 1997, and Chile, in 1999), were certified free of vectorial and transfusional transmission. In Brazil, with the largest population at risk, 10 out of the 12 endemic states were also certified free.

Some stepstones of vector control:

• A yeast trap has been tested for monitoring infestations of certain species of the bugs:"Performance of yeast-baited traps with Triatoma sordida, Triatoma brasiliensis, Triatoma pseudomaculata, and Panstrongylus megistus in laboratory assays."
• Promising results were gained with the treatment of vector habitats with the fungus Beauveria bassiana, (which is also in discussion for malaria- prevention):"Activity of oil-formulated Beauveria bassiana against Triatoma sordida in peridomestic areas in Central Brazil."
• Targeting the symbionts of Triatominae through paratransgenesis.

See also

• Tropical disease
• Drugs for Neglected Diseases Initiative
• Distinguish from: Chaga mushroom

References

• CDC, Division of Parasitic Diseases. Chagas Disease Fact Sheet. (23 September 2004). Accessed 24 September 2006.
• Dumonteil E, Escobedo-Ortegon J, Reyes-Rodriguez N, Arjona-Torres A, Ramirez-Sierra M (2004). "Immunotherapy of Trypanosoma cruzi infection with DNA vaccines in mice". Infect Immun. 72 (1): 46–53. PMID 14688079.CS1 maint: Multiple names: authors list (link)
• CDC, Division of Parasitic Diseases.Chagas Disease(23 October 2007). Accessed 16 August 2007.
• CDC, Division of Parasitic Diseases.Chagas Disease Epidemiology.(23 October 2007). Accessed 16 August 2007.
• CDC, Division of Parasitic Diseases. Treatment(23 October 2007). Accessed 16 August 2007.

Further reading

• Coutinho M (1999). "Ninety years of Chagas disease: a success story at the periphery". Soc Stud Sci. 29 (4): 519–49. PMID 11623933.
• Dias J, Silveira A, Schofield C (2002). "The impact of Chagas disease control in Latin America: a review". Mem Inst Oswaldo Cruz. 97 (5): 603–12. PMID 12219120.CS1 maint: Multiple names: authors list (link)
• Kropf S, Azevedo N, Ferreira L (2003). "Biomedical research and public health in Brazil: the case of Chagas' disease (1909–50)". Soc Hist Med. 16 (1): 111–29. PMID 14598820.CS1 maint: Multiple names: authors list (link)
• "International Symposium to commemorate the 90th anniversary of the discovery of Chagas disease (Rio de Janeiro, April 11–16, 1999)". Memorias do Instituto Oswaldo Cruz. 94 (Suppl. I). 1999.
• Moncayo A. "Progress towards interruption of transmission of Chagas disease". Mem Inst Oswaldo Cruz. 94 Suppl 1: 401–4. PMID 10677765.
• Prata A. "Evolution of the clinical and epidemiological knowledge about Chagas disease 90 years after its discovery". Mem Inst Oswaldo Cruz. 94 Suppl 1: 81–8. PMID 10677694.
• Franco-Paredes C (2007). "Chagas disease: an impediment in achieving the Millennium Development Goals in Latin America". BMC International Health and Human Rights. 7: 7. PMID 17725836.
• Kevin M. Tyler & Michael A. Miles (ed.). World Class Parasites. Volume 7: American Trypanosomiasis. Kluwer Academic Publishers. ISBN 1-4020-7323-2. Amazon review

External links

• VCU Virtual Parasite Project
• All About Chagas Disease, Chagas' disease Information & Prevention, Identification, also in Spanish.
• Chagaspace, also in Spanish.
• ChagMex: Database on-line. UNAM-Instituto de Biología.
• Chagas Disease. PanAmerican Health Organization.
• Disease Information. American Trypanosomiasis or Chagas' Disease. Travel Medicine Program. Health Canada.
• Links to Chagas' Disease pictures (Hardin MD/Univ of Iowa)
• Link to "The Kiss of Death". An anthropological view of Chagas' disease (Joseph Bastien/Univ of Texas at Arlington).

Recent news and events

• Chagas' disease parasite found in desert blood samples
• Chagas Control in the Southern Cone Countries: History of an International Initiative, 1991/2001, PAHO. (Full text e-book)
• Genome Sequencing Project
• Parasites' genetic code 'cracked' From BBC
• Catholic Relief Services. Housing Improvement and Chagas' Disease Prevention Project
• 2006: Nature.com / Scott M. Landfear: Flagella are whip-like structures that power the movement of certain cells. Analysis of a single-cell parasite, the African trypanosome, reveals that flagella are also essential for viability in this organism. (restricted commercial access now)
• Science Magazine Search Results: Chagas

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