Kinetoplastids are a group of flagellated protozoans that include the species Trypanosoma and Leishmania, which are human pathogens with devastating health and economic effects. The sequencing of the genomes of some of these species has highlighted their genetic relatedness and underlined differences in the diseases that they cause. As we discuss in this Review, steady progress using a combination of molecular, genetic, immunologic, and clinical approaches has substantially increased understanding of these pathogens and important aspects of the diseases that they cause. Consequently, the paths for developing additional measures to control these "neglected diseases" are becoming increasingly clear, and we believe that the opportunities for developing the drugs, diagnostics, vaccines, and other tools necessary to expand the armamentarium to combat these diseases have never been better.

Chagas disease remains a serious obstacle to health and economic development in Latin America, especially for the rural poor. We report the long-term effects of interventions in rural villages in northern Argentina during 1984 -2006. Two community-wide campaigns of residual insecticide spraying immediately and strongly reduced domestic infestation and infection with Trypanosoma cruzi in Triatoma infestans bugs and dogs and more gradually reduced the seroprevalence of children <15 years of age. Because no effective surveillance and control actions followed the first campaign in 1985, transmission resurged in 2-3 years. Renewed interventions in 1992 followed by sustained, supervised, community-based vector control largely suppressed the reestablishment of domestic bug colonies and finally led to the interruption of local human T. cruzi transmission. Human incidence of infection was nearly an order of magnitude higher in peripheral rural areas under pulsed, unsupervised, community-based interventions, where human transmission became apparent in 2000. The sustained, supervised, community-based strategy nearly interrupted domestic transmission to dogs but did not eliminate T. infestans despite the absence of pyrethroid-insecticide resistance. T. infestans persisted in part because of the lack of major changes in housing construction and quality. Sustained community participation grew out of establishing a trusted relationship with the affected communities and the local schools. The process included health promotion and community mobilization, motivation, and supervision in close cooperation with locally nominated leaders. community participation ͉ deltamethrin ͉ pyrethroids ͉ Triatoma infestans ͉ Trypanosoma cruzi

SUMMARYThe reservoir capacity of domestic cats and dogs for Trypanosoma cruzi infection and the hostfeeding patterns of domestic Triatoma infestans were assessed longitudinally in 2 infested rural villages in north-western Argentina. A total of 86 dogs and 38 cats was repeatedly examined for T. cruzi infection by serology and/or xenodiagnosis. The composite prevalence of infection in dogs (60%), but not in cats, increased significantly with age and with the domiciliary density of infected T. infestans. Dogs and cats had similarly high forces of infection, prevalence of infectious hosts (41-42%), and infectiousness to bugs at a wide range of infected bug densities. The infectiousness to bugs of seropositive dogs declined significantly with increasing dog age and was highly aggregated. Individual dog infectiousness to bugs was significantly autocorrelated over time. Domestic T. infestans fed on dogs showed higher infection prevalence (49%) than those fed on cats (39%), humans (38%) or chickens (29%) among 1085 bugs examined. The basic reproduction number of T. cruzi in dogs was at least 8·2. Both cats and dogs are epidemiologically important sources of infection for bugs and householders, dogs nearly 3 times more than cats.

American trypanosomiasis, or Chagas disease, caused by the protozoan parasite Trypanosoma cruzi and transmitted by blood-feeding triatomine bugs, is a chronic, frequently fatal infection that is common in Latin America. Neither adequate drugs nor a vaccine is available. A mathematical model calibrated to detailed household data from three villages in northwest Argentina shows that householders could greatly reduce the risk of human infection by excluding domestic animals, especially infected dogs, from bedrooms; removing potential refuges for bugs from walls and ceilings; and using domestically applied insecticides. Low-cost, locally practicable environmental management combined with intermittent use of insecticides can sustainably control transmission of T. cruzi to humans in rural Argentina and probably elsewhere. Chagas disease, or American trypanosomiasis, is endemic in Central and South America. An estimated 16 to 18 million persons are infected with Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae), the causative agent of Chagas disease, and 100 million people (roughly one-quarter of the population) are at risk of infection (1). Despite decreasing rates of prevalence and incidence of T. cruzi infection (2, 3), Chagas disease remains a serious obstacle to health and economic development in Latin America, especially for the rural poor. The repertoire of control measures is limited. Two drugs are curative in the acute and early chronic phase of infection but have adverse effects and may not always eliminate T. cruzi. No vaccines are available to prevent infection. Transmission may be interrupted by residual spraying to kill blood-feeding triatomine bugs (the vector of T. cruzi), screening blood donors, and treating infected infants born to infected mothers. A more controversial strategy for interrupting transmission is to divert bugs from humans by the use of animals that are not susceptible to T. cruzi (4). This strategy, called zooprophylaxis, is controversial for other vector-borne diseases (5) as well and may remain so for T. cruzi because it cannot be tested experimentally. Ethical considerations bar a randomized prospective field study in which the human prevalence of T. cruzi infection is compared between households that do, and those that do not, keep domestic animals in bedroom areas in the presence of domestic triatomine infestations.

The authors discuss the key challenges that undermine the control of Chagas disease and that must be urgently addressed to ensure long-term, sustainable control.

BackgroundTransmission of Trypanosoma cruzi by Triatoma infestans remains a major public health problem in the Gran Chaco ecoregion, where understanding of the determinants of house infestation is limited. We conducted a cross-sectional study to model factors affecting bug presence and abundance at sites within house compounds in a well-defined rural area in the humid Argentine Chaco.Methodology/Principal Findings Triatoma infestans bugs were found in 45.9% of 327 inhabited house compounds but only in 7.4% of the 2,584 sites inspected systematically on these compounds, even though the last insecticide spraying campaign was conducted 12 years before. Infested sites were significantly aggregated at distances of 0.8–2.5 km. The most frequently infested ecotopes were domiciles, kitchens, storerooms, chicken coops and nests; corrals were rarely infested. Domiciles with mud walls and roofs of thatch or corrugated tarred cardboard were more often infested (32.2%) than domiciles with brick-and-cement walls and corrugated metal-sheet roofs (15.1%). A multi-model inference approach using Akaike's information criterion was applied to assess the relative importance of each variable by running all possible (17,406) models resulting from all combinations of variables. Availability of refuges for bugs, construction with tarred cardboard, and host abundance (humans, dogs, cats, and poultry) per site were positively associated with infestation and abundance, whereas reported insecticide use showed a negative association. Ethnic background (Creole or Toba) adjusted for other factors showed little or no association.Conclusions/SignificancePromotion and effective implementation of housing improvement (including key peridomestic structures) combined with appropriate insecticide use and host management practices are needed to eliminate infestations. Fewer refuges are likely to result in fewer residual foci after insecticide spraying, and will facilitate community-based vector surveillance. A more integrated perspective that considers simultaneously social, economic and biological processes at local and regional scales is needed to attain effective, sustainable vector and disease control.

The spatio-temporal reinfestation patterns by Triatoma infestans following a blanket insecticide spraying in the rural community of Amama in northwestern Argentina were analyzed using a geographic information system, satellite imagery, and spatial statistics. Domestic and peridomestic reinfestation by triatomine bugs was monitored from 1993 to 1997. Triatoma infestans was detected at least once in 75% of 2,110 sites evaluated. The prevalence of sites positive at least once for T. infestans during the study period increased sharply from 1993-1995 (0.6-2.9%) to November 1997 (32%). The initial source of T. infestans was a pig corral in southern Amama one year post-spraying. Subsequent infestations were clustered around this initial focus at a distance of approximately 400 meters starting in 1995. In 1996, clustering was maximized in sites within the same or in neighboring compounds at distances of 25-175 meters. An effective control program on the community level will be based on the spraying of actual epicenters and sites within 450 meters of these epicenters to prevent the propagation of T. infestans.

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