Strategies to combat T. cruzi transmission risk through blood transfusion
Two main strategies to prevent T. cruzi transmission through blood transfusion can be mentioned. The first one consists in eliminating T. cruzi in blood units by adding a chemical product with trypanocidal activity. The second one, adopted nearly universally, is based on the selection of donors based on questionnaires and/or serological screening.
Gentian violet, already added to sterilize blood before transfusion in early attempts49 is still being used to eliminate T. cruzi in the chemoprophylaxis of Chagas disease infection via blood transfusion when prior laboratory control is not possible or under emergency circumstances in endemic areas. The addition of gentian violet blackens blood samples, scaring patients and sometimes leading to their refusal of blood transfusion.50 Also, some degree of genotoxicity has been described for this product.51 Given these defects, some studies are currently looking for antiparasitic drugs to sterilize blood samples infected by T. cruzi.51~53
In most endemic countries, blood screening for anti-T. cruzi antibodies was adopted in blood banks to identify the potential blood samples that were carriers of the parasite. At the beginning, there was uncertainty regarding which T. cruzi serological tests were the most effective (i.e., the most sensitive). Different antigens were tested in different multicentric assays as well as in research laboratories.54-59 Today, only commercial kits are used, but there is no gold standard. Most blood banks use one serologic test for screening and then they add other tests for confirmatory serodiagnosis (e.g., in Mexico).60 The current recommendation to use two simultaneous serological tests for serodiagnosis is still in effect to confirm any suspected case of infection at the blood bank. A recent review of available commercial ELISA tests revealed substantial heterogeneity in sensitivity, specificity, or both among the tests, and the overestimation of these indices.61 Consequently, unresolved serologies due to discrepancies between tests sometimes force blood banks to discard blood from possibly uninfected people. Moreover, some cases of negative serology, as previously described in Bolivia, can exist,62 but their frequency remains unknown.
Since the late 1980s, many studies have attempted to detect parasite DNA in the blood of infected patients using molecular methods.63-67 However, their usefulness remains to be clarified and there is not consensus on their routine use.61,68 It is worth noting that their sensitivity is limited to the presence of the parasite in the processed sample, and that some strains of T. cruzi give very low parasitemia, which may be under these methods’ threshold of detection.67,69
In nonendemic countries, it is assumed that prevention efficacy depends on the selection of donors and the use of questionnaires.70-74 The serologic screening is then applied to the donors at risk. Spain (2005) and the United States (2007) were the first countries to implement blood screening for at-risk donors (i.e., people originating from an endemic area, donors with mothers originating from these areas and individuals who had lived in or traveled to endemic areas). In the United States, blood bank regulation is organized by the CDC (Centers for Disease Control).75 Most European countries have also adopted similar safety policies to avoid T. cruzi transmission by transfusion, but the situation varies from one country to another12 (e.g., questionnaire established by the Etablissement francais du sang [EFS] in France, https://www. dondusang.net/rewrite/article/4276/ou-donner/conseils-pratiques/infos-pre-don/infos- pre-don.htm?idRubrique= 1402).
It is important to note that the serological kits used to diagnose T. cruzi infection in Latin America cannot systematically be used in nonendemic countries because of a possibly different cut-off between the pool of normal uninfected sera from endemic and nonendemic countries.76,77 As mentioned above, unresolved cases stemming from discrepancies between tests sometimes force blood banks to discard blood from possibly uninfected people. Research is therefore oriented toward the development of 100% reliable tests and alternative detection of the parasite through biomarkers.78,79
Blood donor counseling is now well developed in most countries because it is considered a key in the blood transfusion system. Historically, guidelines were first developed in response to HIV’s specific challenges, but now guidelines have been extended to the different health problems that can be acquired by transfusion, including Chagas disease.80
