Chagas' Disease

Although it has been more than a century since its discovery and full cycle description, Chagas disease is still a threat to more than 20 million people in the Americas [1, 2]. In past decades, it has become a threat also to non-endemic countries in the Americas, Western Pacific and European regions [1], mainly as a result of increased people mobility. Nowadays, it is estimated that more than 100 million people are exposed to the risk of Chagas disease.

The evolution of the disease can be roughly divided in two parts: an acute and a chronic phase. During the acute phase, high parasitemia triggers human immune response which ultimately results in immunological control of parasite replication. Treatment during this early phase has a high chance of success. After the immunological control of the infection, the disease goes into an asymptomatic clinical form that can last several years. The chronic phase is usually manifested after more than 15 years of the infection, and is typically characterized by enlargement of the heart, liver, colon or esophagus [1].
Traditional diagnostic methods are laborious and time-consuming. Besides, these methods show poor sensitivities in case of low-level parasitemias [2]. During the acute phase, diagnosis is primarily achieved by xenodiagnosis, hemoculture, or blood smear. After the onset of the immune response, the current method of choice for diagnosing Chagas disease is the screening for anti-T. cruzi antibodies [3-5]. However, this method is prone for false positives due to cross-reactivity to other antigens. Also, this method is useless in several instances, such as in immune compromised patients or newborns testing from serological-positive mothers. Nowadays, about 25 tests are commercially available worldwide, while only 2 tests are FDA approved. All of them are antibody based.
    Since the 1990’s, the possibility of detecting the parasite’s DNA in blood samples through the application of the polymerase chain reaction (PCR) has opened new possibilities. Although PCR procedures have shown variable levels of sensitivity and specificity, it has proven to be very useful when serological methods cannot be used [2, 6]. An international collaborative evaluation is currently underway aiming the technical improvement and development of an international standard operational procedure for T. cruzi PCR [2, 7]. This method uses a large sample volume (10 ml) and purification of DNA from lysed samples through membrane-based spin columns. Both these features are not suitable for an integrated and portable point-of-care device.

References

  1. WHO, T.D.P., First WHO report on neglected tropical diseases 2010: Working to overcome the global impact of neglected tropical diseases. 2010.
  2. Schijman, A.G., et al., International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients. PLoS Negl Trop Dis, 2011. 5(1): p. e931.
  3. Almeida, E., et al., Use of recombinant antigens for the diagnosis of Chagas disease and blood bank screening. Mem Inst Oswaldo Cruz, 1990. 85(4): p. 513-7.
  4. Gomes, Y.M., et al., Serodiagnosis of chronic Chagas infection by using EIE-Recombinant-Chagas-Biomanguinhos kit. Mem Inst Oswaldo Cruz, 2001. 96(4): p. 497-501.
  5. Krieger, M.A., et al., Use of recombinant antigens for the accurate immunodiagnosis of Chagas' disease. Am J Trop Med Hyg, 1992. 46(4): p. 427-34.
  6. Duffy, T., et al., Accurate real-time PCR strategy for monitoring bloodstream parasitic loads in chagas disease patients. PLoS Negl Trop Dis, 2009. 3(4): p. e419.
  7. Salud, O.P.d.l., Taller internacional de estandarización y validación analítica de la PCR en     tiempo real para cuantificar ADN de Trypanosoma cruzi en sangre periférica de indivíduos con     enfermedad de Chagas. 2011.