Citation: Hotez PJ, Dumonteil E, Woc-Colburn L, Serpa JA, Bezek S, Edwards MS, et al. (2012) Chagas Disease: “The New HIV/AIDS of the Americas”. PLoS Negl Trop Dis 6(5): e1498. https://doi.org/10.1371/journal.pntd.0001498
Published: May 29, 2012
Copyright: © 2012 Hotez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors received no funding for this work.
Competing interests: Drs. Hotez and Bottazzi are principal investigators on a vaccine in development against Chagas disease.
Endemic Chagas disease has emerged as an important health disparity in the Americas. As a result, we face a situation in both Latin America and the US that bears a resemblance to the early years of the HIV/AIDS pandemic.
Neglected tropical diseases (NTDs) are among the most common conditions afflicting the estimated 99 million people who live on less than US$2 per day in the Latin American and Caribbean (LAC) region . Almost all of the “bottom 100 million” living in the Americas suffer from at least one NTD , and according to some estimates, the NTDs cause a burden of disease in the LAC region that closely approximates or even exceeds that resulting from HIV/AIDS . Chagas disease (American trypanosomiasis) is a vector-borne disease and a leading cause of the deaths and disability-adjusted life years (DALYs) lost that result from NTDs in the LAC region . With approximately 10 million people living with Chagas disease, this condition is one of the most common NTDs affecting the bottom 100 million in the region, a prevalence exceeded only by hookworm and other soil-transmitted helminth infections , . Moreover, among the NTDs in the Americas, Chagas disease ranks near the top in terms of annual deaths and DALYs lost , .
While most of the world's cases of Chagas disease occur in the LAC region, there is increasing recognition that many people with Trypanosoma cruzi infection also live in the US and Europe . In practical terms, the “globalization” of Chagas translates to up to 1 million cases in the US alone, with an especially high burden of disease in Texas and along the Gulf coast , , although other estimates suggest that there are approximately 300,000 cases in the US , in addition to thousands of cases documented in Canada, Europe, Australia, and Japan . Among those living with Chagas disease around the world today, 20%–30% (roughly 2–3 million people) are either currently suffering from Chagasic cardiomyopathy or will develop this clinical sequela . Chagasic cardiomyopathy is a highly debilitating condition characterized by cardiac arrhythmias, heart failure, and risk of sudden death from ventricular fibrillation or tachycardia or thromboembolic events . Another estimate suggests that up to 5.4 million people living today will develop Chagasic cardiomyopathy , . Damage to the gastrointestinal tract can also produce debilitating megaesophagus and megacolon .
There are a number of striking similarities between people living with Chagas disease and people living with HIV/AIDS, particularly for those with HIV/AIDS who contracted the disease in the first two decades of the HIV/AIDS epidemic. Both diseases are health disparities, disproportionately affecting people living in poverty , . Both are chronic conditions requiring prolonged treatment courses: a lifetime of antiretroviral therapy for HIV/AIDS patients, and one to three months of therapy for those with Chagas disease . Treatment for HIV/AIDS is lifesaving, although it seldom if ever results in cure, while for Chagas disease, the treatment has proven efficacy only for the acute stages of the infection or in children up to 12 years of age during the early chronic phase of the infection . For both diseases the treatment is expensive—in the case of Chagas disease, the expected cost of treatment per patient year is $1,028, with lifetime costs averaging $11,619 per patient . Exacerbating costs, Chagas disease itself is a serious opportunistic infection of people living with HIV/AIDS, and is associated with meningoencephalitis, cerebral lesions, and high mortality . As with patients in the first two decades of the HIV/AIDS epidemic, most patients with Chagas disease do not have access to health care facilities. A recent analysis indicates that many patients do not have access to the essential medicines for Chagas disease, in particular, the first line of therapy, the drug benznidazole . According to Médecins Sans Frontières (MSF, Doctors Without Borders), many highly endemic countries, including Paraguay and Bolivia, face acute shortages of benznidazole, forcing thousands of newly diagnosed patients to postpone treatment . Both diseases are also highly stigmatizing, a feature that for Chagas disease further complicates access to benznidazole and other essential medicines, as well as access to serodiagnosis and medical counseling. For some individuals with T. cruzi living in the US, immigration status presents an additional challenge to seeking care and prevention services. Just as stigma due to sexual orientation has been a barrier to HIV care and prevention, especially in the beginning of the epidemic, immigration status may function as a deterrent to Chagas disease care and prevention.
Based on the assertions outlined above—the chronic morbidities and high mortalities, the prolonged and expensive treatment courses, the lack of therapeutic options, and barriers to access to essential medicines—a patient living with Chagas disease faces formidable challenges that resemble those faced by someone living with HIV/AIDS, especially the challenges that occurred in the early years of the HIV/AIDS epidemic. Shown in Table 1 is a quantitative comparison between people living with Chagas disease , , , ,  and those living with HIV/AIDS in the LAC region and the Americas –. Briefly, the roughly 10 million people living with Chagas disease (including 2–5 million individuals with Chagasic cardiomyopathy) is comparable in number to the 1.6 million people living with HIV/AIDS in the LAC region and the 1–2 million living with HIV/AIDS in North America (including Mexico). However, based on current estimates, both the number of annual DALYs lost and the attributed deaths are about five times higher for HIV/AIDS. The morbidity and mortality estimates for both Chagas disease and HIV/AIDS are undergoing revision by the University of Washington Institute of Health Metrics and Evaluation.
There are additional parallels. Chagas disease has emerged as an important blood transfusion–related risk throughout the Americas just as HIV/AIDS did in the early 1980s, prior to the implementation of widespread blood screening and testing –. Moreover, mother-to-child transmission leading to congenital Chagas disease and other adverse neonatal outcomes is increasingly recognized – (Table 2). Both congenital Chagas disease and HIV/AIDS have a recognized clinical syndrome , , with adverse birth outcomes as well as deleterious maternal effects in pregnancy , , . During pregnancy, the rate of vertical transmission of T. cruzi infection is approximately 5% (although some investigators believe the rate could be as high as 10%), whereas it is 15%–40% for untreated HIV/AIDS  and 1%–2% for mothers who receive antiretroviral therapy . The Pan American Health Organization estimates that there are over 14,000 cases of congenital Chagas disease in Latin America , with 2,000 newborns infected annually in North America alone , compared to 36,000 pediatric HIV/AIDS cases in Latin America .
It is only appropriate to point out that there are important differences between Chagas disease and HIV/AIDS. Whereas HIV/AIDS is almost always a fatal condition in the absence of antiviral therapy, up to 70%–80% of people with Chagas disease do not progress to cardiomyopathy. Moreover, Chagas disease is a true NTD and there is a paucity of anti-protozoan drugs available for this condition, whereas HIV/AIDS can no longer be considered neglected in this sense as there is an armamentarium of antiretroviral drugs currently available (although for both conditions, patients in developing countries suffer from lack of access to essential medicines). As another contrast between the two diseases, there is also evidence for oral transmission of Chagas through food contamination in the Amazon basin .
Over the last three decades of the global HIV/AIDS pandemic, an aggressive and committed activist community has achieved success in promoting widespread access to antiretroviral drugs in developed and developing countries. As a result, at present millions of people living with HIV/AIDS receive antiretroviral therapy, and pediatric HIV/AIDS has been nearly eliminated as a public health problem in the US . Patient advocacy and global efforts to promote access to benznidazole and other therapies for Chagas disease, on the other hand, are at a much earlier stage. In the last decade, MSF has launched efforts to screen more than 80,000 people in Bolivia, Colombia, Guatemala, Honduras, Nicaragua, and Paraguay, having diagnosed and treated more than 6,000 and 4,000 individuals, respectively . Other non-governmental organizations have also been engaged in Chagas disease treatments. Of great concern is a looming shortage of benznidazole, as well as the over-reliance on a single drug manufacturer, and inadequate international efforts to organize global production and distribution of the drug in Latin America . Nifurtimox, another drug commonly used in the treatment of Chagas disease, should also be made available for the LAC region.
In parallel with global advocacy efforts, expansion of operational research activities is crucial to optimize the efficacy of existing control and elimination efforts, including the testing of more field-adapted tools . There are also requirements to expand vector control activities and health education in the communities affected by Chagas disease, in addition to providing training for local health care providers in endemic areas . The importance of a research and development agenda to develop new and improved Chagas disease drugs cannot be overlooked. As noted above, both antitrypanosomal drugs used for the treatment of Chagas disease, benznidazole and nifurtimox, require prolonged and expensive treatment courses; moreover, the efficacy of either drug for the treatment of late chronic infection and Chagasic cardiomyopathy still remains uncertain and unproven , . Toxicities and the frequency of side effects of both medicines frequently require patients to interrupt or halt treatments, and both drugs are contraindicated in pregnancy –. In response to this crisis, the product development partnership (PDP) Drugs for Neglected Diseases initiative (DNDi) is accelerating the development of new Chagas disease drugs in the non-profit sector, in parallel with a small group of academic laboratories that are pursuing several drug targets , . Finally, just as the International AIDS Vaccine Initiative (IAVI) PDP is developing several experimental HIV/AIDS vaccines, the Sabin Vaccine Institute PDP is accelerating the development of a new therapeutic Chagas disease vaccine in collaboration with several key universities and public sector biotechnology and manufacturing institutions in Mexico . In further support of this research, a recent analysis by Lee and his colleagues confirms the potential cost effectiveness of Chagas disease vaccines .
Stark similarities exist between today's global Chagas disease epidemic and the first two decades of the HIV/AIDS epidemic. This translates into a humanitarian catastrophe for the poorest people in the Americas and elsewhere. This perceptible health disparity demands urgent attention by global health policy makers to prioritize Chagas disease and develop a comprehensive strategy for control and elimination efforts, blood screening and point-of-care testing, maternal and child interventions, health education, and parallel research and development. Successfully addressing the vast burden of Chagas disease will require overcoming the current lack of available drugs, together with expanding vector control strategies and developing new and innovative control tools. To this end, eliminating Chagas disease will require a commitment from international health agencies, governments of the disease-endemic countries, PDPs, and patient advocacy groups.
- 1. Hotez PJ, Dumonteil E, Heffernan MJ, Bottazzi ME (2012) Innovation for “the bottom 100 million”: eliminating neglected tropical diseases in the Americas through mass drug administration and new vaccines for hookworm and Chagas disease. Adv Exp Med Biol. PJ HotezE. DumonteilMJ HeffernanME Bottazzi2012Innovation for “the bottom 100 million”: eliminating neglected tropical diseases in the Americas through mass drug administration and new vaccines for hookworm and Chagas disease.Adv Exp Med BiolIn press. In press.
- 2. Hotez PJ, Bottazzi ME, Franco-Paredes C, Ault S, Periago MR (2008) The neglected tropical diseases of Latin America and the Caribbean: a review of disease burden and distribution and a roadmap for control and elimination. PLoS Negl Trop Dis 2: e300.PJ HotezME BottazziC. Franco-ParedesS. AultMR Periago2008The neglected tropical diseases of Latin America and the Caribbean: a review of disease burden and distribution and a roadmap for control and elimination.PLoS Negl Trop Dis2e300
- 3. Gascon J, Bern C, Pinazo MJ (2010) Chagas disease in Spain, the United States, and other non-endemic countries. Acta Trop 115: 22–27.J. GasconC. BernMJ Pinazo2010Chagas disease in Spain, the United States, and other non-endemic countries.Acta Trop1152227
- 4. Hotez PJ (2008) Neglected infections of poverty in the United States of America. PLoS Negl Trop Dis 2: e256.PJ Hotez2008Neglected infections of poverty in the United States of America.PLoS Negl Trop Dis2e256
- 5. Bern C, Kjos S, Yabsley MJ, Montgomery SP (2011) Trypanosoma cruzi and Chagas' disease in the United States. Clin Microbiol Rev 24: 655–681.C. BernS. KjosMJ YabsleySP Montgomery2011Trypanosoma cruzi and Chagas' disease in the United States.Clin Microbiol Rev24655681
- 6. Bern C, Montgomery SP (2009) An estimate of the burden of Chagas disease in the United States. Clin Infect Dis 49: e52–e54.C. BernSP Montgomery2009An estimate of the burden of Chagas disease in the United States.Clin Infect Dis49e52e54
- 7. Rassi A Jr, Rassi A, Marin-Neto JA (2010) Chagas disease. Lancet 375: 1388–1402.A. Rassi JrA. RassiJA Marin-Neto2010Chagas disease.Lancet37513881402
- 8. Pan American Health Organization-World Health Organization (2007) Health in the Americas 2007; Regional, scientific, and technical publication 622. Washington (DC): Pan American Health Organization. Pan American Health Organization-World Health Organization2007Health in the Americas 2007; Regional, scientific, and technical publication 622Washington (DC)Pan American Health Organization
- 9. Marin-Neto JA, Cunha-Neto E, Maciel BC, Simoes MV (2007) Pathogenesis of chronic Chagas heart disease. Circulation 115: 1109–1123.JA Marin-NetoE. Cunha-NetoBC MacielMV Simoes2007Pathogenesis of chronic Chagas heart disease.Circulation11511091123
- 10. De Andrade AL, Zicker F, de Oliveira RM, Almeida Silva S, Luguetti A, et al. (1996) Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. Lancet 348: 1407–1413.AL De AndradeF. ZickerRM de OliveiraS. Almeida SilvaA. Luguetti1996Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection.Lancet34814071413
- 11. Castillo-Riqueime M, Guhl F, Turriago B, Pinto N, Rosas F, et al. (2008) The costs of preventing and treating Chagas disease in Colombia. PLoS Negl Trop Dis 2: e336.M. Castillo-RiqueimeF. GuhlB. TurriagoN. PintoF. Rosas2008The costs of preventing and treating Chagas disease in Colombia.PLoS Negl Trop Dis2e336
- 12. Medécins Sans Frontières (MSF) (2011) The shortage of benznidazole leaves thousands of Chagas patients without treatment. Medécins Sans Frontières (MSF)2011The shortage of benznidazole leaves thousands of Chagas patients without treatment.Briefing Document, October 2011. Briefing Document, October 2011.
- 13. World Health Organization (2004) Annex table 3. Burden of disease in DALYs by cause, sex and mortality stratum in WHO regions, estimates for 2002. World Health Organization2004Annex table 3. Burden of disease in DALYs by cause, sex and mortality stratum in WHO regions, estimates for 2002.In: The world health report 2004. Available: http://www.who.int/whr/2004/annex/topic/en/annex_3_en.pdf. Accessed 2 October 2011.
- 14. World Health Organization (2004) Annex table 2. Deaths by cause, sex and mortality stratum in WHO regions, estimates for 2002. World Health Organization2004Annex table 2. Deaths by cause, sex and mortality stratum in WHO regions, estimates for 2002.In: The world health report 2004. Available: http://www.who.int/whr/2004/annex/topic/en/annex_2_en.pdf. Accessed 2 October 2011.
- 15. UNAIDS. UNAIDS.Fact sheet: Central and South America. Available: http://www.unaids.org/documents/20101123_FS_csa_em_en.pdf. Accessed 2 October 2011. Fact sheet: Central and South America. Available: http://www.unaids.org/documents/20101123_FS_csa_em_en.pdf. Accessed 2 October 2011.
- 16. UNAIDS. UNAIDS.Fact sheet: Caribbean. Available: http://www.unaids.org/documents/20101123_FS_carib_em_en.pdf. Accessed 2 October 2011. Fact sheet: Caribbean. Available: http://www.unaids.org/documents/20101123_FS_carib_em_en.pdf. Accessed 2 October 2011.
- 17. UNAIDS. UNAIDS.Fact sheet: North America and Western Europe. Available: http://www.unaids.org/documents/20101123_FS_nawe_em_en.pdf. Accessed 2 October 2011. Fact sheet: North America and Western Europe. Available: http://www.unaids.org/documents/20101123_FS_nawe_em_en.pdf. Accessed 2 October 2011.
- 18. Young C, Losikoff P, Chawla A, Glasser L, Forman E (2007) Transfusion-acquired Trypanosoma cruzi infection. Transfusion 47: 540–544.C. YoungP. LosikoffA. ChawlaL. GlasserE. Forman2007Transfusion-acquired Trypanosoma cruzi infection.Transfusion47540544
- 19. Perkins HA, Busch MP (2010) Transfusion-associated infections: 50 years of relentless challenges and remarkable progress. Transfusion 50: 2080–2099.HA PerkinsMP Busch2010Transfusion-associated infections: 50 years of relentless challenges and remarkable progress.Transfusion5020802099
- 20. Jackson Y, Getaz L, Wolff H, Holst M, Mauris A, Tardin A, et al. (2010) Prevalence, clinical staging and risk for blood-borne transmission of Chagas disease among Latin American migrants in Geneva, Switzerland. PLoS Negl Trop Dis 4: e592.Y. JacksonL. GetazH. WolffM. HolstA. MaurisA. Tardin2010Prevalence, clinical staging and risk for blood-borne transmission of Chagas disease among Latin American migrants in Geneva, Switzerland.PLoS Negl Trop Dis4e592
- 21. Theiler RN, Rasmussen SA, Treadwell TA, Jamieson DJ (2008) Emerging and zoonotic infections in women. Infect Dis Clin North Am 22: 755–772; vii–viii.RN TheilerSA RasmussenTA TreadwellDJ Jamieson2008Emerging and zoonotic infections in women.Infect Dis Clin North Am22755772; vii–viii
- 22. Siriano L da R, Luguetti AO, Avelar JB, Marra NL, de Castro AM (2011) Chagas disease: increased parasitemia during pregnancy detected by hemoculture. Am J Trop Med Hyg 84: 569–574.R. Siriano L daAO LuguettiJB AvelarNL MarraAM de Castro2011Chagas disease: increased parasitemia during pregnancy detected by hemoculture.Am J Trop Med Hyg84569574
- 23. Perez-Lopez FR, Chedraui P (2010) Chagas disease in pregnancy: a non-endemic problem in a globalized world. Arch Gynecol Obstet 282: 595–599.FR Perez-LopezP. Chedraui2010Chagas disease in pregnancy: a non-endemic problem in a globalized world.Arch Gynecol Obstet282595599
- 24. Buekens P, Almendares O, Carlier Y, Dumonteil E, Eberhard M (2008) Mother-to-child transmission of Chagas disease in North America: why don't we do more? Matern Child Health J 12: 283–286.P. BuekensO. AlmendaresY. CarlierE. DumonteilM. Eberhard2008Mother-to-child transmission of Chagas disease in North America: why don't we do more?Matern Child Health J12283286
- 25. Camacho-Gonzalez AF, Ross AC, Chakraborty R (2010) The clinical care of the HIV-1-infected infants. Clin Perinatol 37: 873–885.AF Camacho-GonzalezAC RossR. Chakraborty2010The clinical care of the HIV-1-infected infants.Clin Perinatol37873885
- 26. Ryder RW, Temmerman M (1991) The effect of HIV-1 infection during pregnancy and the perinatal period on maternal and child health in Africa. AIDS 5: Suppl1S75–S85.RW RyderM. Temmerman1991The effect of HIV-1 infection during pregnancy and the perinatal period on maternal and child health in Africa.AIDS5Suppl1S75S85
- 27. Newell ML (2001) Prevention of mother-to-child transmission of HIV: challenges for the current decade. Bull World Health Organ 79: 1138–1144.ML Newell2001Prevention of mother-to-child transmission of HIV: challenges for the current decade.Bull World Health Organ7911381144
- 28. Siegfried N, van der Merwe L, Brocklehurst P, Sint TT (2011) Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database Syst Rev (7): CD003510.N. SiegfriedL. van der MerweP. BrocklehurstTT Sint2011Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection.Cochrane Database Syst Rev7CD003510
- 29. Pan American Health Organization, World Health Organization (2006) Pan American Health Organization, World Health Organization2006Estimación cuantitativa de la enfermedad de Chagas en las Américas (OPS/HDM/CD/425-06). Estimación cuantitativa de la enfermedad de Chagas en las Américas (OPS/HDM/CD/425-06).
- 30. Beltrao Hde B, Cerroni Mde P, Freitas DR, Pinto AY, Valente Vda C, et al. (2009) Investigation of two outbreaks of suspected oral transmission of acute Chagas disease in the Amazon region, Para State, Brazil, in 2007. Trop Doct 39: 231–232.B. Beltrao HdeP. Cerroni MdeDR FreitasAY PintoC. Valente Vda2009Investigation of two outbreaks of suspected oral transmission of acute Chagas disease in the Amazon region, Para State, Brazil, in 2007.Trop Doct39231232
- 31. Fowler MG, Gable AR, Lampe MA, Etima M, Owor M (2010) Perinatal HIV and its prevention: progress toward an HIV-free generation. Clin Perinatol 37: 699–719.MG FowlerAR GableMA LampeM. EtimaM. Owor2010Perinatal HIV and its prevention: progress toward an HIV-free generation.Clin Perinatol37699719
- 32. Perez-Molina JA, Perez-Ayala A, Moreno S, Fernandez-Gonzalez MC, Zamora J, et al. (2009) Use of benznidazole to treat chronic Chagas' disease: a systematic review with a meta-analysis. J Antimicrob Chemo 64: 1139–1147.JA Perez-MolinaA. Perez-AyalaS. MorenoMC Fernandez-GonzalezJ. Zamora2009Use of benznidazole to treat chronic Chagas' disease: a systematic review with a meta-analysis.J Antimicrob Chemo6411391147
- 33. Marin-Neto JA, Rassi A Jr, Morillo CA, Avezum A, Connolly SJ, et al. (2008) Rationale and design of a randomized placebo-controlled trial assessing the effects of etiologic treatment in Chagas cardiomyopathy: the BENznidazole Evaluation For Interrupting Trypanosomiasis (BENEFIT). Am Heart J 156: 37–43.JA Marin-NetoA. Rassi JrCA MorilloA. AvezumSJ Connolly2008Rationale and design of a randomized placebo-controlled trial assessing the effects of etiologic treatment in Chagas cardiomyopathy: the BENznidazole Evaluation For Interrupting Trypanosomiasis (BENEFIT).Am Heart J1563743
- 34. Sarli Issa V, Alcides Bocchi E (2010) Antitrypanosomal agents: treatment or threat? Lancet 376: 768–769.V. Sarli IssaE. Alcides Bocchi2010Antitrypanosomal agents: treatment or threat?Lancet376768769
- 35. Pinazo M-J, Munoz J, Posada E, Lopez-Chejade P, Gallego M (2010) Tolerance of benznidazole in treatment of Chagas' disease in adults. Antmicrob Agents Chemotherap 54: 4896–4899.M-J PinazoJ. MunozE. PosadaP. Lopez-ChejadeM. Gallego2010Tolerance of benznidazole in treatment of Chagas' disease in adults.Antmicrob Agents Chemotherap5448964899
- 36. Viotti R, Vigliano C, Lococo B, Alvarez MG, Petti M, et al. (2009) Side effects of benznidazole as treatment in chronic Chagas disease: fears and realities. Expert Rev Anti-infective Therap 7: 157–163.R. ViottiC. ViglianoB. LococoMG AlvarezM. Petti2009Side effects of benznidazole as treatment in chronic Chagas disease: fears and realities.Expert Rev Anti-infective Therap7157163
- 37. Apt W (2010) Current and developing therapeutic agents in the treatment of Chagas disease. Drug Design, Develop Ther 4: 243–253.W. Apt2010Current and developing therapeutic agents in the treatment of Chagas disease.Drug Design, Develop Ther4243253
- 38. Buckner FS, Navabi N (2010) Advances in Chagas disease drug development: 2009–2010. Curr Op Infect Dis 23: 609–616.FS BucknerN. Navabi2010Advances in Chagas disease drug development: 2009–2010.Curr Op Infect Dis23609616
- 39. Lee BY, Bacon KM, Connor DL, Willig AM, Bailey RR (2010) The potential economic value of a Trypanosoma cruzi (Chagas disease) vaccine in Latin America. PLoS Negl Trop Dis 4: e916.BY LeeKM BaconDL ConnorAM WilligRR Bailey2010The potential economic value of a Trypanosoma cruzi (Chagas disease) vaccine in Latin America.PLoS Negl Trop Dis4e916
- 40. Centers for Disease Control and Prevention (2011) HIV Surveillance–United States, 1981–2008. MMWR Morb Mortal Wkly Rep 60(21): 689–693.Centers for Disease Control and Prevention2011HIV Surveillance–United States, 1981–2008.MMWR Morb Mortal Wkly Rep6021689693Available: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6021a2.htm. Accessed 21 October 2011. Available: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6021a2.htm. Accessed 21 October 2011.