EDITORIAL
Whac-a-mole: future trends in Chagas transmission and the importance of a global perspective on disease control ‘...large numbers of infected individuals mean that the risk for congenital transmission remains a real concern.’
Patricia Dorn†, Pierre Buekens & Elaine Hanford †Author
for correspondence Loyola University New Orleans, Department of Biological Sciences, New Orleans, LA 70118, USA Tel.: +1 504 865 2288; Fax: +1 504 865 2920;
[email protected]
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‘Whac!’ Like the mallet in the arcade game, the Southern Cone Initiative landed flat on the head of the mole, Chagas disease, in Brazil, to the extent that by June, 2006, Brazil was declared free of transmission of this parasitic disease by the predominant insect vector, Triatoma infestans [1]. In 1990, when this initiative was launched, 16–18 million people throughout Latin America were infected with the Chagas parasite, Trypanosoma cruzi, causing approximately 50,000 deaths annually. Most die from heart failure owing to chronic cardiomyopathy, although megasyndrome (enlarged colon and/or esophagus) is also observed in South America. Chagas is “the most serious of the parasitic diseases in Latin America” [2]. Through the Southern Cone Initiative, Chagas disease was effectively ‘whac’d’ by intergovernmental partnerships supervised by the Pan American Health Organization (PAHO), and transmission halted in Uruguay (1997), Chile (1999), and in most areas of Argentina, Paraguay and Bolivia, by eliminating the insect vectors and blood transfusion transmission. Called the silent killer, Chagas disease usually demonstrates mild symptoms during the initial weeks following infection (swelling at the site of infection, fever, malaise and lymphadenopathy), so diagnosis at this stage is rare. Most patients progress to the ‘silent’, sometimes decades-long asymptomatic period before 20–40% of infected people advance to fatal heart disease and/or megasyndrome. Around 80% of transmission occurs via insect vectors; parasites in the feces typically gain access through the bite wound or mucous membranes. Transmission by blood products and solid-organ transplantation, congenitally and even by contaminated food or drink also occurs. Different strains of T. cruzi may be responsible for different pathologies and preliminary evidence from animal models suggests that strains may differ in their transmissibility from mother to offspring [Hall C, Pers. Comm.].
10.2217/17460913.2.4.365 © 2007 Future Medicine Ltd ISSN 1746-0913
The Southern Cone Initiative ‘whac’ on Chagas disease was a model of interinstitutional cooperation. PAHO was effective in setting priorities, coordinating the response, avoiding duplication and certifying results. Success was also aided by the nearly exclusive domestic nature of the main vector, T. infestans. Fumigation of houses resulted in elimination of the bug from many endemic areas. Add to that mandatory blood screening, and the transmission of the disease is almost eliminated, except from mother to offspring. The results have been impressive. Chagas infection in Southern Cone countries is down by 94%, so overall the T. cruzi infection level in Latin America has dropped from 16–18 million in 1990 down to approximately 9 million [1]. ‘...globalization of infectious disease means that Chagas has been diagnosed in nonendemic countries, as far afield as Japan, Canada, Germany, Romania, Spain and the USA.’
The successes of the Southern Cone Initiative spawned initiatives in other regions such as Central America and the Andes (both launched in 1997); the Amazon (2005); and Mexico may join the Central American effort. Considerable strides have been made with domestic vectors (e.g., Rhodnius prolixus in Central America) and blood screening for T. cruzi is mandatory in nearly all Latin American countries. However, resource limitations mean that coverage and reporting are incomplete in some countries [3] and major challenges for Chagas control remain due to the peridomestic and sylvan foci of vectors that recolonize treated houses. But wait! Just like the arcade game, the Chagas disease ‘mole’ pops up where it was previously unrecognized. Chagas is usually associated with substandard housing and the rural poor. However, it is increasingly being found in major cities such as: Merida, Mexico; Tegucigalpa, Honduras; Caracas, Venezuela; and Guayaquil, Ecuador as people migrate from rural to urban areas, and as awareness of the disease increases. Even in countries that have enjoyed elimination Future Microbiol. (2007) 2(4), 365–367
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of vectoral and transfusional transmission, the large numbers of infected individuals mean that the risk for congenital transmission remains a real concern. In some countries, congenital transmission has surpassed vector-transmitted acute cases tenfold [4]. The globalization of infectious disease means that Chagas has been diagnosed in nonendemic countries, as far afield as Japan, Canada, Germany, Romania, Spain [5] and the USA, owing to the immigration of people from endemic areas. The migration of infected Latin Americans poses two challenges: the misdiagnosis or nondiagnosis of Chagasic heart disease and the possibility of transmission of Chagas disease through blood or blood products, organ transplants and congenitally. Most infected individuals are probably undiagnosed or misdiagnosed as having idiopathic cardiac disease. Estimates in the 1990s suggested the potential number of infected Latin American immigrants in the USA to be 370,000. Recognizing a rapidly growing Latin American immigrant population that includes both documented and undocumented individuals, that number could be as high as 1 million [6]. If conservatively 20% of these progress to cardiac disease, 200,000 cases of Chagasic heart disease would result. ‘...most infected individuals are probably undiagnosed or misdiagnosed as having idiopathic cardiac disease.’
Seven cases of transfusion-associated transmission have been documented in the last 20 years in the USA and Canada, all in immunosuppressed individuals [7]. Since Chagas is not on the radar screen for most physicians, it is very likely that transfusion cases in immunocompetent individuals are missed. Simply deferring blood donors with risk factors is ineffective as blood donors may be unaware of their infection, fail to disclose risk for T. cruzi infection, and individuals previously identified as infected have made repeat donations. With the recent substantial influx of Hispanic immigrants into the USA, seroprevalence rates have increased. In Los Angeles county, rates increased from one in 9850 donations in 1996, to one in 7200 donations in 1997 and one in 5400 donations in 1998 [8]. A new ELISA blood-donor screening test (Ortho-Clinical Diagnostics) was tested in August 2006–January 2007 on 148,969 blood donations. One in 4655 were positive on the ELISA and confirmed by Future Microbiol. (2007)
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radioimmunoprecipitation assay (RIPA) [7]. In December 2006, the US FDA approved this ELISA for blood donation screening, and widescale screening has just begun in the USA. As of July 6, 2007, 458 donations were repeat reactive by ELISA and 124 donations have been confirmed positive by RIPA in the USA [101]. ‘...developing effective prevention and healthcare policies will be dependent upon a better understanding of T. cruzi strains...’
The risk of an infected mother passing the parasite on to her offspring is not well known but is estimated to be between 1–7% [9]. Newborns may die from the disease but most will progress to chronic Chagas much later in life. If identified early enough, the infected newborns can be treated and cured [10]. Multi-generational transmission of Chagas disease has been reported, suggesting a very long-term risk of mother-tooffspring transmission even in the absence of vector-borne transmission. It has been estimated that the number of congenitally infected newborns could be approximately 2000 per year in Mexico and approximately 200 a year in the USA [11]. Despite the presence of T. cruzi in more than 18 species of mammals and the relatively high rates of infection in indigenous triatomine bugs across the southern states, only rarely has Chagas disease transmission to humans been reported in the USA. Six autochthonous cases of Chagas disease have been diagnosed: three infants in Texas, one infant in Tennessee, a 56-year-old woman in California, and in 2006, a 74-year-old woman in Louisiana [12]. These low rates have been attributed to potentially lower virulence of North American T. cruzi strains, lack of suitable insect habitats in houses and lower levels of domestication, reduced vector competency such as delayed defecation following feeding, and perhaps most importantly, a low index of suspicion. Increasing global temperatures will likely extend the range of the vector and parasite into more northern regions. As yet unknown is the interaction among introduced triatomine species and indigenous species, and especially the introduction of new, and potentially more virulent strains of T. cruzi. Developing effective prevention and healthcare policies will be dependent upon a better understanding of T. cruzi strains, vector and host species, their interactions, range and rates of infection, as well as the related ecological factors future science group
Chagas transmission and the importance of a global perspective on disease control – EDITORIAL
of Chagas disease transmission. As an emerging disease, the potential of a large human reservoir, including the possibility of multi-generational congenital transmission, must be considered. The Chagas ‘mole’ popping up in nonendemic countries should not come as a surprise. It is just one of many recent examples of the cross-border transit of infectious diseases, compounded by the low priority accorded to immigrant health in wealthy countries. The PAHO arm of the WHO was effective in the cross-border Southern Cone Initiative. Surveillance is improving. The revised International Health Regulations (2005) are in force as of June 15, 2007. This legally binding agreement will provide notification of healthcare emergencies to WHO member states, however, only for emerging and re-emerging diseases with epidemic potential. Surveillance Bibliography 1.
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Schofield CJ, Jannin J, Salvatella R: The future of Chagas disease control. Trends Parasitol. 22(12), 583–588 (2006). Dias JC, Silveira AC, Schofield CJ: The impact of Chagas disease control in Latin America: a review. Mem. Inst. Oswaldo Cruz. 97(5), 603–612 (2002). Schmunis GA, Cruz JR: Safety of the blood supply in Latin America. Clin. Microbiol. Rev. 18(1), 12–29 (2005). Gürtler RE, Segura EL, Cohen JE: Congenital transmission of Trypanosoma cruzi infection in Argentina. Emerg. Infect. Dis. 9(1), 29–32 (2003). Riera C, Guarro A, Kassab HE et al.: Congenital transmission of Trypanosoma cruzi in Europe (Spain): a case report. Am. J. Trop. Med. Hyg. 75(6), 1078–1081 (2006). Hanford EJ, Zhan FB, Lu Y, Giordano A: Chagas disease in Texas: recognizing the significance and implications of evidence in the literature. Soc. Sci. Med. 65(1), 60–79 (2007) Stramer S, Dodd RY, Leiby DA et al.: Blood donor screening for Chagas disease – United States, 2006–2007. MMWR Morb. Mortal. Wkly Rep. 56(7), 141–143 (2007).
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for nonepidemic diseases needs to improve, including anticipation of diseases coming in with refugee and immigrant populations. Healthcare workers need broader training so that they can identify previously nonendemic diseases. Developed countries need to allocate resources to fight infectious diseases in developing countries, not just based on humanitarian motivation but on the real benefits accrued [13]. We don’t know when, and we don’t know where, but what we do know is that the T. cruzi ‘mole’ will pop up and when it and other diseases do, we need to be prepared to strike. Financial disclosure The authors have no relevant financial interests including employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties related to this manuscript.
Leiby DA, Herron RM, Read EJ, Lenes BA, Stumpf RJ: Trypanosoma cruzi in Los Angeles and Miami blood donors: impact of evolving donor demographics on seroprevalence and implications for transfusion transmission. Transfusion 42(5), 549–555 (2002). WHO: Control of Chagas disease (Second Report). In: WHO Technical Report Series 905. WHO (Ed.) World Health Organization, Geneva, Switzerland (2002). Carlier Y, Torrico F: Congenital infection with Trypanosoma cruzi: from mechanisms of transmission to strategies for diagnosis and control. Rev. Soc. Bras. Med. Trop. 36, 767–771 (2003). Buekens P, Almendares O, Carlier Y et al.: Mother-to-child transmission of Chagas’ disease in North America: why don’t we do more? Maternal Child Health J. (2007) DOI: 10.1007/s10995-007-0246-8 (In Press). Dorn P, Perniciaro L, Yabsley M et al.: Autochthonous transmission of Trypanosoma cruzi, Louisiana. Emerg. Infect. Dis. 13, 605–607 (2007). Smith R, Woodward D, Acharya A, Beaglehole R, Drager N: Communicable disease control: a ‘Global Public Good’ perspective. Health Policy Plan. 19(5), 271–278 (2004).
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Website 101. AABB: AABB Chagas’ Biovigilance Network.
www.aabb.org/Content/Programs_and_Servi ces/Data_Center/Chagas/
Affiliations • Patricia Dorn, PhD, Associate Professor Loyola University New Orleans, Department of Biological Sciences, New Orleans, LA 70118, USA Tel.: +1 504 865 2288; Fax: +1 504 865 2920;
[email protected] • Pierre Buekens, MD, PhD, Professor and Dean Tulane University Health Sciences Center, Dean’s Office, New Orleans, LA 70112, USA Tel.: +1 504 988 5397; Fax: +1 504 988 5718;
[email protected] • Elaine Hanford, PG, Professor of Environmental Science Collin College – Preston Ridge, Frisco, TX 75035, USA Tel.: +1 972 377 1589; Fax: +1 972 377 1586;
[email protected]
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