Combining Residual Insecticide Spraying Campaigns with Targeted Detection and Specific Chemotherapy for Trypanosoma cruzi Infection in Children

With 10–15 million of people infected with Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae) and many more exposed to risk of infection, the burden of Chagas disease in Latin America amounts to as much as 2.7 times the combined burden of malaria, schistosomiasis, leishmaniasis, and leprosy in 2002 [1]. Following a short, mostly subclinical acute phase and a very long asymptomatic phase with very low parasitemia, 25%–40% of infected humans develop chronic disease with cardiac, digestive, or neurologic manifestations that leads to a reduced life span [2]. Human transmission of T. cruzi is mediated by nearly a dozen blood-sucking species of triatomine bugs that infest resourcelimited, rural houses and their outbuildings, but it may also occur by blood transfusions and from infected mothers to their children. A series of intergovernmental control initiatives led by the Pan American Health Organization were launched in Latin America during the 1990s with the objectives of eliminating transmission of T. cruzi by blood transfusion and by domestic populations of triatomine bugs by the year 2010 [2,3]. Control actions reduced the geographic range and infestation prevalence of major triatomine vectors and led to the interruption of transmission in Uruguay, Chile, and Brazil, and to significant improvements in Central America and elsewhere [2,3]. However, active vector-borne transmission persists in vast areas of Argentina [3,4], El Salvador, and Colombia, among others; and several countries (Mexico, Peru, Colombia, and Costa Rica) have no national programs for the control of Chagas disease vectors [5]. The growing decentralization of vector control operations to the provincial and municipal levels since the early 1980s added the still-unmet challenge of coordinating efforts among districts differing in infestation, control status, resources, and priorities, and between national, provincial, and municipal public health levels [6]. Large-scale screening of blood donors in Latin America began in the 1980s following the emergence of AIDS, and currently is in place in nearly all countries, though at differing coverage rates. These programs brought about a significant reduction in the prevalence of T. cruzi infection among blood donors in most of the region [7]. Although most advances in the safety of the blood supply since 1993 originated from increased screening coverage for infectious diseases and better quality assurance, it has been estimated that tainted blood may have caused T. cruzi infections in 12 of 17 Latin American countries over the period 2001 to 2002 [7]. With the sustained wave of immigration from Latin America to US, Canada, and Western Europe, transplantand transfusionrelated cases of Chagas disease jointly with congenital cases have been reported more frequently in the target destinations. Chagas disease control programs traditionally have focused on interrupting vectorand blood-borne transmission of T. cruzi rather than on active case detection and specific treatment of infected people. One reason for this is that the only available drugs for specific treatment of T. cruzi infection, nifurtimox (since 1967) and benznidazole (since 1972), were traditionally considered effective only during the acute phase of infection or shortly after it. This notion persisted until two randomized clinical trials, conducted with support from the World Health Organization’s Special Programme for Research and Training in Tropical Diseases (TDR) and national agencies during the 1990s, demonstrated that most infections treated with benznidazole during the early chronic phase (i.e., in seropositive children aged #12 y with unknown duration of infection) could be cured [8–11]. In the meantime, experimental studies changed the view that Chagas disease is primarily an autoimmune response toward one that the disease is a problem of parasite persistence [12]. In addition, the progress in vector control status achieved during the last decades has paved the way to conceiving the specific treatment of T. cruzi-infected children residing in traditionally endemic rural settings (e.g., Argentina, Bolivia). More recently, specific treatment has been extended to seropositive children aged #15 y in some countries, and is being offered more frequently to adults with longterm chronic infections because it might moderate disease progression [13]. Because individuals in the chronic stage display a long-lasting serological response to T. cruzi infection after specific treatment, in some cases demonstration of cure by means of conventional serological methods may take more than 10 y [9]. The efficacy of anti-trypanosomal drugs apparently decreases with the duration of infection, whereas their adverse effects increase with age and occasionally may be serious if treatment is not discontinued and proper care given [14,15]. As the new study by Levy et al. [16] published in PLoS Neglected Tropical Diseases stresses, ‘‘. without timely diagnosis, children infected [with T. cruzi] prior to implementation of vector control often miss the window of opportunity for effective chemotherapy. ’’ Another important reason for the observed low rates of specific treatment of children seropositive for T. cruzi is that health services and Chagas disease control programs in Latin America lack or do not allocate sufficient resources for comprehensive serological screening and supervised treatment in the most affected endemic areas. There, health services usually are understaffed and