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Eliminating Chagas Disease: Challenges and a Roadmap S Pl Millions of People in Central and South America Are Affected by Chagas Disease

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Eliminating Chagas Disease: Challenges and a Roadmap S Pl Millions of People in Central and South America Are Affected by Chagas Disease ANALYSIS Eliminating Chagas disease: challenges and a roadmap PL S Millions of people in Central and South America are affected by Chagas disease. Richard Reithinger and colleagues explain VOLKER STEGER/ VOLKER Triatomine bug: the vector for T Cruzi the difficulties of elimination and suggest a strategy In 2007, the World Health Organization host cells but are only transiently in the blood- ease is also hampered by several operational announced a renewed strategy to eliminate stream and thus difficult to detect, with symp- and policy challenges and knowledge gaps.15 Chagas disease in the Americas by 2010.1 The toms not evident for years or even decades. For example, increasing insecticide resistance intention was “to answer key questions about Eventually, however, up to 40% of infected of bugs and the recolonisation of households the treatment and control of Chagas disease, people develop chronic Chagas disease. This by bugs after insecticide treatment are reduc- and to coordinate global efforts towards the chronic stage of the disease is characterised by ing the impact of vector control; no consensus prevention of transmission through a new Glo- cardiac or gastrointestinal complications, which exists on whether benznidazole and nifurtimox bal Network for Chagas Elimination.”1 The if left untreated are severely debilitating and is the best treatment for adult chronic infection announcement was welcome because it put the often fatal. Indeed, Chagas disease is the most (the most prevalent presentation) and the drugs spotlight on Chagas disease, which has been common cause of cardiomyopathy in South and have been in short supply16 17; there is no agreed overshadowed by other priorities, such as HIV Central America and the leading cause of car- standard for diagnosis, with laboratories using a and malaria, in recent years. However, two diovascular death in disease endemic areas.6 In combination of serological tests that may give years later, WHO has yet to produce a clear people who have suppressed immune systems inconclusive or false negative results18; and strategy for elimination and we are unaware of (because of HIV infection or chemotherapy, for there is no vaccine to prevent Chagas disease. any new operational activities to eliminate the example), Chagas disease can reactivate with Whether the intention of WHO is to stop disease. Too many challenges remain. abundant parasites found in the blood and the development of Chagas disease in popula- tissues commonly leading to severe meningo- tions at risk or halt vector borne transmission Scale of the problem encephalitis, which is fatal if untreated. of T cruzi to humans is not clear. Too many Chagas disease is both a disease of poverty and, T cruzi is found in triatomine bugs, wildlife, challenges persist to expect successful elimina- like other neglected tropical diseases, poverty domestic animals, and humans throughout tion of Chagas disease by 2010. Resurgence promoting.2 An estimated 10-20 million people much of rural and peri-urban areas of North, of vector borne transmission after apparent live with the condition and it is responsible for a Central, and South America (figure). Although elimination, as witnessed in Argentina during burden of 670 000 disability adjusted life years,3 autochthonous vector borne human cases are the 1990s, shows that without proper planning making it the most important parasitic disease scarce in the United States,7 8 and non-exist- or emphasis on consolidation and sustainabil- in the Americas. ent in Canada and Europe, T cruzi has been ity, successes may be short lived. T cruzi trans- The disease is caused by the protozoan para- detected in triatomine bugs, dogs, and wildlife mission still persists in many regions of Latin site Trypanosoma cruzi,4 which is transmitted in the US7 9 and is increasingly detected in the America (two large outbreaks of orally trans- through the faeces of blood feeding triatomine US, Canada, and Europe among immigrants or mitted T cruzi were reported in Venezuela in bugs; trypomastigotes in the faeces contaminate tourists from Latin America.10-12 After the detec- the past 15 months) and has entered peri-urban the wound or enter through mucosal surfaces.5 tion of a number of cases in blood donors,13 the areas in some places, such as Arequipa, Peru.19 It can also be transmitted by blood transfusions, US FDA approved a screening assay for blood A realistic, sustainable strategy to interrupt the organ donations, through the placenta, or by donors in 2007. human transmission of T cruzi should be devel- eating contaminated food. Most people do not Large regional control programmes have oped and a strategy to treat and manage the know that they have become infected with T reduced the incidence of Chagas disease in millions of currently infected individuals needs cruzi because the acute symptoms tend to be the southern tier of South America and some to be established. unspecific or benign (fever, swollen lymph other regions in the last decade.14 Vector borne The first step is to get a good understanding glands, inflammation at the biting site or a transmission has been reduced or even halted, of the extent of the disease. WHO stated “cur- swollen eye, and, rarely, severe myocarditis mainly through residual spraying of domestic rent estimates suggest that less than 8 million or meningoencephalitis). In mammals, T cruzi and peridomestic household structures with people remain infected,”1 but with no recent must invade host cells in order to replicate. It insecticide, and blood donations are routinely nationwide surveys of T cruzi infection (except ultimately destroys these cells, stimulating tissue screened for T cruzi. Uruguay, Chile, and Brazil in Brazil and Chile), the estimate is suspect. No inflammation and releasing infective extracel- are currently declared free of T cruzi transmis- up to date data on the burden and distribu- lular trypanomastigote forms, which propagate sion by the main vector Triatoma infestans. tion of Chagas disease exist for Mexico, Peru, the infection through the body. Colombia, Costa Rica, and much of the Ama- After the acute phase, which lasts a few weeks Challenges of elimination zonian region. Indeed, as recently as 2005 only or months, the infection is generally well con- Eradication of Chagas disease is impossible 361 cases of the disease were reported by the trolled by the host immune response. Nonethe- because of the zoonotic characteristics of the Mexican Ministry of Health,20 yet focal studies less, parasites continue to cycle in and out of T cruzi transmission cycle.4 Control of the dis- in rural areas showed seroprevalence of up to 1044 BMJ | 2 MAY 2009 | VOLUME 338 ANALYSIS 30% and up to 82.5% of patients with congestive only makes it impossible to determine the ability of safe, effective, and affordable drugs. heart failure testing seropositive for T cruzi.21 true impact of Chagas disease but also makes Currently available drugs (nifurtimox and the development of new diagnostics extremely benznidazole)27 are generally accepted to be Road map challenging. effective in treating acute and early chronic Given these challenges and gaps,15 how should A WHO consultative meeting last year high- infections in children younger than 15 years we develop a comprehensive strategy for elimi- lighted the need for substantial investment in but their efficacy and availability is not uniform nating Chagas disease? Below we outline what the development of new and better diagnos- through all endemic regions. Treatment efficacy we believe should be the main components. tics, using the increased understanding of the in longer term chronic infections, however, genetic makeup and diversity of T cruzi and remains controversial,16 17 as are the criteria Better monitoring and estimation of true new technologies for improved, rapid, and (conventional serology and direct methods to burden of disease cost effective diagnostics.23 A uniform set of evaluate parasitaemia) currently used to assess Cost constraints mean that a disease specific diagnostic standards obtained from the entire drug efficacy. This, coupled with the common regional surveillance system is probably not geographic range of T cruzi and incorporating occurrence of side effects, leads many doctors feasible. Instead there should be advocacy to confirmed but problematic samples (positive to view the risk:benefit ratio of such treatments integrate Chagas disease into a country’s health on some current tests but negative on others) as unfavourable. Despite important advances in monitoring information system or other disease must be established. Though for many years preclinical studies,27 no new drugs have entered surveillance programmes (malaria, dengue, or WHO and the Pan American Health Organi- clinical trials in more than a decade. In the tuberculosis). Additionally, representative sur- sation have supported external validation of meantime a strategy to manage these patients veys (similar to the malaria indicator surveys samples in selected reference laboratories, it is is urgently required and should be part of any developed under Roll Back Malaria’s monitor- unclear how many local laboratories use that elimination efforts. ing and evaluation reference group)22 should service. A first step in reaching this goal may be carried out regularly to estimate domestic be the recent decision to develop and provide Increased spraying coverage and monitoring of infestation, the incidence of Chagas disease, a panel of reference samples to laboratories
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