Citation: Andrus J, Bottazzi ME, Chow J, Goraleski KA, Fisher-Hoch SP, Lambuth JK, et al. (2013) Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas. PLoS Negl Trop Dis 7(6): e2021. doi:10.1371/journal.pntd.0002021
Published: June 27, 2013
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Funding: No specific funding was received for this work. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Competing interests: I have read the journal's policy and have the following conflicts. Drs. Hotez and Bottazzi are principal investigators involved in the development of vaccines for Chagas disease and leishmaniasis.
Peter J. Hotez, MD, PhD, is Co-Editor-in-Chief of PLOS Neglected Tropical Diseases. He is President of the Sabin Vaccine Institute, Professor and Head of the Section of Pediatric Tropical Medicine in the Department of Pediatrics at Texas Children’s Hospital and Baylor College of Medicine, and Dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, Texas, United States of America.
Neglected tropical diseases (NTDs) have been recently identified as significant public health problems in Texas and elsewhere in the American South. A one-day forum on the landscape of research and development and the hidden burden of NTDs in Texas explored the next steps to coordinate advocacy, public health, and research into a cogent health policy framework for the American NTDs. It also highlighted how U.S.-funded global health research can serve to combat these health disparities in the United States, in addition to benefiting communities abroad.
While neglected tropical diseases (NTDs) are usually thought of as a group of chronic parasitic and related infections affecting those living on US$1–2 per day in the poorest developing countries , , there is increasing awareness that the NTDs also strike pockets of impoverished people who live in wealthy countries, including the United States, Canada, many European nations, and Australia –. The NTDs found among the poor in wealthy countries often differ from those found predominantly in low- and middle-income countries (LIMCs), but they nonetheless exhibit many of the same features, including their chronicity and adverse impact on child development, pregnancy outcome, and worker productivity –, . Moreover, the NTDs in the U.S. disproportionately affect people of color and indigenous populations, much as they also do in the Latin American and Caribbean region , . In this sense, the NTDs are important contributors to American health disparities.
Today, an estimated 46 million Americans live below the poverty line (defined as US$22,314 for a family of four in the U.S.), including approximately 20 million existing in so-called “extreme poverty” (50% or less than the poverty line) , . Some of the largest numbers of people who live below the U.S. poverty line live in Texas –. Roughly one in five Texans (approximately 4–5 million people) currently lives below the poverty line, with South Texas counties exhibiting some of the highest rates of poverty in the U.S. –. In June of 2012, the nonprofit education and advocacy organization Research!America, together with the American Society of Tropical Medicine and Hygiene (ASTMH) and several institutions of the Texas Medical Center including the Sabin Vaccine Institute, Texas Children's Hospital Center for Vaccine Development, and the National School of Tropical Medicine at Baylor College of Medicine, sponsored a one-day forum that explored global health research, social determinants of health, and advocacy to highlight the impact of NTDs in Texas and elsewhere on the Gulf Coast and in the American South. The forum proposed several key steps needed to generate advocacy strategies for the development of evidence-based policies to address these diseases both regionally and nationally.
Overview of the NTDs in Texas and the American South
The major NTDs in Texas and other areas of the American South are listed in Box 1. Among their common features is the observation that most of these conditions cause chronic disabilities, which disproportionately affect people living in extreme poverty , , –. Another key feature is that NTDs are important examples of health disparities mostly affecting people of color, particularly African American and Hispanic minorities, largely because of the poverty link , , –.
Neglected Parasitic Infections
Among the parasitic infections, Chagas disease (American trypanosomiasis caused by Trypanosoma cruzi infection) received renewed attention in 2012 based on recently published estimates of large numbers of people infected in the Western Hemisphere, including the high prevalence rates among pregnant women and subsequent maternal-to-child transmission , . Of note, the first reported case of mother-to-child transmission in the U.S. was announced on July 6, 2012 by the Centers for Disease Control and Prevention (CDC) . The CDC estimates that 300,000 cases of Chagas disease are found in the U.S. , whereas other investigators have suggested that almost as many cases occur in Texas alone . Several kissing bug vector species are widespread in Texas and capable of transmitting T. cruzi; a significant percentage of these vectors are polymerase-chain-reaction (PCR) positive for T. cruzi , . In South Texas, a high percentage of dogs, which are natural hosts, are also infected with T. cruzi , and a risk map for humans acquiring Chagas disease in Texas has been developed . However, the extent to which T. cruzi transmission to humans actually occurs in the state is unknown . There is an urgent need to increase surveillance for human T. cruzi infection in the region, possibly through seroprevalence studies, as well as for studies that attempt to document the extent of autochthonous transmission and mother-to-child transmission. In this sense, we are still at the “tip of the iceberg” in terms of our understanding of the epidemiology of Chagas disease in Texas and elsewhere in the American South. An alternative metaphor is that we have only seen the “ears of the armadillo” (similar to the ears of the hippopotamus metaphor sometimes used for malaria in Africa), referring to the nine-banded armadillo (Dasypus novemcinctus), which is native to Texas (Figure 1).
http://en.wikipedia.org/wiki/File:Nine-banded_Armadillo.jpg, accessed August 16, 2012.
Information is also scant for several other key NTDs in Texas. As with Chagas disease, these NTDs appear to be widespread in different areas of the state, but supporting surveillance and transmission studies are either sporadic or missing. Cutaneous leishmaniasis (CL) is another vector-borne parasitic protozoan infection, caused by Leishmania spp. and transmitted by sand flies of the genus Lutzomyia. Human cases of autochthonous CL caused by Leishmania mexicana infection have been recognized in Texas, primarily in the south-central region, since 1903 . In 2008, nine cases were reported in northern Texas, not far from the Dallas-Fort Worth area . There are several important animal reservoirs of Leishmania spp. in the Americas. In Latin America, rodents serve as an important animal reservoir for L. mexicana, and the Southern Plains woodrat has been implicated in Texas  and elsewhere in the southern U.S. Widespread infection of foxhounds in the U.S. with visceralizing L. infantum is also of concern, but the true extent of veterinary and human transmission in Texas and the rest of the U.S. is largely unknown . A recent modeling study suggests that the range of reservoirs and sand fly vectors for CL is likely to expand deeper into the U.S., possibly in association with climate change , and thus, a northward expansion of CL infection in humans is conceivable.
Among the helminthic infections, neurocysticercosis (NCC) is now a major cause of epilepsy in Texas . Most of the recent cases of NCC are believed to have been imported through immigration from Latin America , but autochthonous transmission still remains a possibility. Toxocariasis (Toxocara canis and Toxocara cati infection) is widespread in the American South, particularly among African American and Hispanic minority populations . A covert form of this NTD has been linked to asthma and developmental delays , but the prevalence of toxocariasis in Texas and its potential contribution to chronic sequelae in the state have not been accurately determined.
Neglected Viral and Bacterial Infections
West Nile virus (WNV) infection, a mosquito-transmitted arbovirus infection, emerged in Houston, Texas in 2002 , where it occurs more commonly among people living in proximity to bayous lined with vegetation and other bodies of stagnant or slow-moving water . Texas experienced a historic peak in WNV cases in 2012 affecting several areas of the state . Like other vector-borne NTDs, WNV infection has been linked to poverty and its associated conditions , , . A study in Houston in 2004 found that 7% of homeless people were positive for WNV infection, and that seroprevalence rose to 17% for those who did not seek shelter at night . Risk factors for severe disease from WNV infection include hypertension, diabetes, and alcohol and substance abuse –, which are all chronic morbidities that often go untreated in marginalized populations. In Texas and elsewhere, WNV infection was recently identified as an emerging etiologic agent of chronic renal disease and kidney failure .
Dengue emerged in South Texas in 1980, with additional outbreaks recognized in 1999 and 2005, and where conditions related to poverty also represent major risk factors for infection , . Studies to determine the prevalence of dengue virus infection among residents of city-pairs on the U.S.-Mexico border have shown much higher rates of acute and past infection in Texas than would have been anticipated based on how infrequently the disease is recognized and reported –. In 2004 and 2005, recently contracted dengue virus infections were found among an estimated 2–4% of the residents of Brownsville, Texas, compared to 7–32% of residents of Matamoros, Mexico, with part of the difference having been ascribed to socioeconomic factors , . The under-recognition of an ongoing dengue outbreak in the U.S. was recently highlighted in Key West, Florida ,  and emphasizes the need for better surveillance and education of clinicians about NTDs in the U.S. Severe dengue has occurred in the continental U.S. and is always a concern where frequent dengue virus infections occur. Preliminary studies indicate that dengue may have already emerged in Houston (unpublished data). International air travel increases the risk for importation of dengue virus and possible outbreaks , an especially salient factor given Houston's role as a major international air travel hub and the presence of the mosquito vector.
Among the major bacterial infections, murine typhus (Rickettsia typhi infection, transmitted by cat fleas) is emerging in South Texas . An important evolving scenario lies at the interface of infectious diseases and the pandemic of chronic disease. Substantial evidence documents type 2 diabetes as the most important major risk factor for tuberculosis (TB) along the Texas border with Mexico , , increasing the risk of active TB three-fold. Similar observations have now been made in TB high burden countries across the globe . Altered gene expression in the host and altered immune responses to several other pathogens in diabetes have been identified –. Studies conducted in South Texas were instrumental in uncovering the relationship between TB and diabetes such that additional studies in Texas might help in determining if similar relationships exist for other neglected diseases. The interaction between TB and type 2 diabetes illustrates how a neglected disease may interface with a chronic noncommunicable disease (CNCD). Some data suggest that the NTDs themselves manifest much like the CNCDs with respect to their chronic morbidities , and may certainly account for a hidden burden of CNCD-related morbidity .
Advancing Public Health in the Region
So far we have only seen the ears of the armadillo with respect to the full extent of the NTD problem in Texas. Tragically, minimal surveillance data exist for all of the NTDs highlighted above . This situation is particularly alarming given that the NTDs disproportionately affect vulnerable populations, especially children, pregnant women, people living in poverty, people of color, and indigenous populations –. To that end, there is an urgent need to identify the critical public health gaps and address the specific needs in Texas and the adjacent regions. Paradoxically, within the U.S. biomedical community there has been a diminished emphasis on population-based investigations to determine disease burden and epidemiology in favor of laboratory and clinical investigations, which are thought to be more amenable to receiving support from the U.S. National Institutes of Health and other funding agencies.
Several types of studies must be undertaken . For many of the major NTDs, there is the need to establish robust estimates of their burden in the U.S. through population-based prevalence and/or incidence studies in Texas and other vulnerable areas, coupled with epidemiologic studies to determine modes of disease transmission. For instance, while we believe Chagas disease is widespread in South Texas, we have only a modest evidence base to support this premise, and we know even less about the percentage of human cases transmitted within the state from indigenous vectors and animal reservoirs . Such information is needed to better understand the dynamics of disease transmission and the potential risk of acquiring this disease. For other NTDs, such as dengue, toxocariasis, and WNV, the factors responsible for urban transmission need to be better delineated. Given that many of these diseases are vector-borne, studies about the prevalence and competence of the relevant hosts and reservoirs are also needed. Collection of this data, which will require work in northern Mexico, may be hindered because of the ongoing unrest in the region. There is a need for better mapping and to conduct geographic information system/remote sensing–based research to produce next generation risk maps for acquiring the NTDs. We need to better understand the exact role of poverty in NTD transmission. Why exactly is poverty a major risk factor for most of the NTDs in the U.S.? Inadequate housing with lack of indoor screens and air-conditioning, as well as external degradation linked with absent sanitation, garbage pick-up, or (in the case of WNV virus) neglected swimming pools  may provide part of the answer, but it would be extremely useful to understand the scientific basis for the link between poverty and disease . Some of these factors might be addressed, at least partially, through more outreach by the scientific community to the local citizenry and community-based organizations. For many of the NTDs, case management and treatment algorithms are still at a rudimentary stage. However, once estimates of disease burden are established and populations are identified in the NTD-endemic regions of the U.S., there might be greater interest in conducting treatment and management studies in controlled clinical settings.
Currently, few if any prevention strategies for NTDs are in place in Texas or surrounding states. One exception is an aggressive mosquito-control initiative in Houston and surrounding areas of Harris County to reduce the Culex mosquito population as a means to lower WNV transmission . For all the NTDs, prevention strategies should be defined, the effectiveness of these prevention strategies determined through outcome studies, and their economic and public health value modeled, as has been done for many global health prevention strategies to fight HIV/AIDS, malaria, and other diseases.
It is unclear whether public funds will be available anytime soon to support such public health and prevention studies or to foster community involvement to address the NTD problem in the U.S. There is a dearth of available funding for partnerships with federal (e.g., the CDC), state, and local health agencies for this purpose. One proposal mentioned at the forum is to consider supporting partnering opportunities between major research universities in Texas (e.g., Baylor College of Medicine, University of Texas, Texas A&M University, Texas Tech University, University of Houston, and Rice University) and local universities near the Mexican border (e.g., University of Texas-Pan American) to build local capacity for epidemiologic research. This approach is similar to a U.S. National Institutes of Health Fogarty International Center–sponsored “twinning” initiative in Africa known as MEPI (Medical Education Partnership Initiative) . Possibly, such an approach could become an initiative of The Academy of Medicine, Engineering, and Science of Texas (TAMEST).
Simultaneously, there is a substantial need for workforce development and capacity building within the state to enhance laboratory and diagnostic testing for the NTDs. Many of the current diagnostic assays for conditions such as Chagas disease, cysticercosis, toxocariasis, and the arboviral infections, among others, are not widely or easily available, especially in the impoverished areas of South Texas where the needs are the greatest. In some cases, especially for the neglected viral infections, special containment facilities may be required. Capacity building is needed to train public health officials for the unique needs of surveillance and control of NTDs, including the use of appropriate technology for these conditions. Such efforts include the need to train entomologists or vector biologists in the identification and control of the suspected vector. Physicians, nurse practitioners, and other health care providers must be trained to recognize, manage, and treat these diseases. The new National School of Tropical Medicine in Houston is potentially positioned to work in close partnership with state and local health agencies in this regard , . The existing network of University of Texas public health schools and other public health institutions such as the Pan American Health Organization (PAHO) could also enhance training and other collaborations. Previously, PAHO, together with a network of public health laboratories, was highly effective in coordinating efforts to eliminate polio, measles, rubella, and other infections in the Latin American and Caribbean region .
Advancing Research and Development (R&D) for New Control Tools
In tandem with expanded public health measures, there is a pressing need to develop better control tools for the NTDs, including new drugs, vaccines, diagnostics, insecticides, and mathematical and computational models. For example, for Chagas disease, there is an urgent need for new biomarkers to follow disease progression . The toxicities and other problems inherent in the only two existing medicines currently used to treat Chagas disease (benznidazole and nifurtimox) have been highlighted, prompting a search for alternative drugs and new vaccines , –. We also need new tools to assess vector exposure and transmission of Chagas disease and leishmaniasis. A vaccine for leishmaniasis (including a transmission blocking vaccine from dogs) has also been proposed  and shown to be cost-effective for VL . For NCC, there is a need for more sensitive diagnostic tests and biomarkers, especially for patients with single brain lesions, which have a high false-negative rate . For WNV infection, there is a need to better delineate the role of the virus as a cause of renal disease and to evaluate possible antiviral therapeutic interventions and possibly a vaccine , . For dengue, several prototype vaccines are under development by a number of pharmaceutical companies, as well as new antiviral drugs . Of interest is the development of a new humanized mouse model for dengue, which may accelerate such product development . For all of the vector-borne NTDs, at-risk populations would benefit from improved vector and reservoir control strategies and integrated management. Mosquito control methods could benefit prevention efforts for multiple NTDs in Texas, including dengue, WNV, and Saint Louis encephalitis. We recognize the complexities of implementing vector and reservoir control measures and their integrated management; however, each of these control tools can be modeled to determine when they may be cost-effective or highly cost-effective. Some may even prove to be cost-saving (economically dominant), when an intervention actually saves money (in addition to having health benefits) compared to the status quo. Many of these products may not be financially remunerative and would need to be developed in the nonprofit sector, possibly through similar models as those used by product development partnerships . Finally, and as pointed out above, the finding of syndemic tuberculosis and type 2 diabetes in Texas should also prompt the search for additional links between NTDs and CNCDs. Such research could play an important role in improving health interventions for these conditions.
Strategies for Advocacy: The Way Forward
Given the overall dearth of information currently available on the NTDs in Texas and the rest of the U.S., it is challenging to formulate useful policy guidelines that are fully evidence-based. Yet, without a coordinated plan of advocacy and education on these conditions, public health–directed research and development efforts will not increase, leaving us in the same situation of insufficient data needed to make informed policy decisions, and insufficient interventions to address known threats. It is also true that formulating a successful advocacy strategy faces an uphill battle. NTDs have already fallen through the cracks between the two large international public health movements inaugurated in this first part of the twenty-first century: twelve years of global health outreach beginning in 2000 with the launch of the Millennium Development Goals and the more recent CNCD advocacy effort launched at the United Nations last year. Domestically, while there has been increased attention to health disparities in the U.S. during the landmark health care reform measures over the past two years, the American NTDs, an important contributor to this disparity, have been barely mentioned. To that point, the first summit on NTDs in the U.S. held in Washington, D.C. more than two years ago  helped to stimulate the introduction of the “Neglected infections of impoverished Americans act of 2011” (H.R. 528) as a means to encourage U.S. health officials to collect essential information on some of the major diseases highlighted above , . However, it is unclear whether this effort will be implemented.
There are several possible reasons why the NTDs in the U.S. have not risen higher on the domestic or global health policy agenda, including the fact that these diseases often have complicated names, ecologies, and modes of transmission. It is also likely that NTDs face the same funding obstacles as other diseases that disproportionately affect people of color and those living in extreme poverty. During the Texas forum, it was noted that if these conditions were affecting people living in wealthy suburbs, they might have already gained substantial media attention or even possibly become the subject of congressional hearings. Instead, the U.S. NTDs remain “forgotten diseases of forgotten people” . In this sense, the American NTDs put to the test the nation's commitment to a core principle of public health: an issue of equitable benefits and justice for all populations. But beyond the moral implications, because these diseases respect no border or neighborhood boundaries, even skeptics should understand that tackling diseases of poverty now will confer the pragmatic benefit of dramatically reducing the risk of spread.
Simply put, there is an urgent need to bolster the evidence base for defining the scope and impact of the NTDs in Texas and surrounding states. In Latin America, careful disease burden assessments and cost-effectiveness studies of vaccination and other intervention strategies helped to introduce new vaccines against key diseases . Many of these activities are coordinated through PAHO's ProVac Initiative . Ideally, funds would be made available to launch a similar initiative for NTDs in the U.S., but instead we are faced with a “chicken and egg” situation. We don't have the necessary funding, political will, or infrastructure to support data collection for surveillance, transmission, and disease burden studies, much less the investment needed to produce new interventions. Given these realities, the need for a comprehensive advocacy strategy that factors in these innovative strategies is essential if we are to make a real difference in the lives of “forgotten people” in Texas and elsewhere. However, without more public health evidence and examples of the benefits of new tools, effective advocacy strategies are extremely difficult to formulate.
Despite the hurdles, we must persevere. Research!America, ASTMH, and some of the key Texas universities and institutions can take meaningful first steps by embarking on media outreach, together with science-policy discussions in Washington, D.C., and by engaging the Texas delegation of the U.S. Congress and key congressional caucuses (e.g., the Black and Hispanic Caucuses and the Malaria-NTD Caucus). It is important that we take every opportunity to obtain the data required to make informed decisions and engage in targeted advocacy. Where appropriate, the CDC and other research-oriented institutions or organizations should present their latest epidemiologic and disease burden data offering an informed perspective on both the domestic and international front. With a coordinated effort of multiple stakeholders both within and outside of U.S. government, we can overcome ignorance and apathy and combat NTDs as a compelling and urgent health disparities issue, an emblematic public health imperative, and an insidious global health threat.
We would like to thank Susan Montgomery (Parasitic Diseases Division, Centers for Disease Control and Prevention, Atlanta, Georgia) for her advice and participation in the forum. The list of authors includes the participants in the forum, with the exception of Susan Montgomery, who served as a panelist in the forum, but did not contribute to the paper.
- 1. Hotez PJ, Molyneux DH, Fenwick A, Kumaresan J, Sachs SE, et al. (2007) Control of neglected tropical diseases. N Engl J Med 357: 1018–1027.
- 2. World Health Organization (2010) Working to overcome the global impact of neglected tropical diseases: first WHO report on neglected tropical diseases. Geneva: WHO Press. 172 p.
- 3. Hotez PJ (2009) Neglected diseases amid wealth in the United States and Europe. Health Aff (Millwood) 28: 1720–1725.
- 4. Hotez PJ, Fenwick A, Savioli L, Molyneux DH (2009) Rescuing the bottom billion through control of neglected tropical diseases. Lancet 373: 1570–1575.
- 5. Hotez PJ (2008) Neglected infections of poverty in the United States of America. PLoS Negl Trop Dis 2: e256 doi:10.1371/journal.pntd.0000256.
- 6. Hotez P, Stillwaggon E, McDonald M, Todman L, DiGrazia L (2010) National summit on neglected infections of poverty in the United States. Emerg Infect Dis 16: e1.
- 7. Hotez PJ, Gurwith M (2011) Europe's neglected infections of poverty. Int J Infect Dis 15: e611–619.
- 8. Hotez PJ (2010) Neglected infections of poverty among the indigenous peoples of the arctic. PLoS Negl Trop Dis 4: e606 doi:10.1371/journal.pntd.0000606.
- 9. Kline K, McCarthy JS, Pearson M, Loukas A, Hotez PJ (2013) Neglected tropical diseases of Oceania: review of their prevalence, distribution, and opportunities for control. PLoS Negl Trop Dis 7: e1755 doi:10.1371/journal.pntd.0001755.
- 10. Fisher-Hoch SP, Vatcheva KP, Laing ST, Hossain MM, Rahbar MH, et al. (2012) Missed opportunities for diagnosis and treatment of diabetes, hypertension, and hypercholesterolemia in a Mexican American population, Cameron County Hispanic Cohort, 2003–2008. Prev Chronic Dis 9: 110298.
- 11. Hotez PJ, Bottazzi ME, Franco-Paredes C, Ault SK, 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 doi:10.1371/journal.pntd.0000300.
- 12. Denavas-Walt C, Proctor BD, Smith JC, U.S. Census Bureau (2011) Income, poverty, and health insurance coverage in the United States: 2010. Available: http://www.census.gov/prod/2011pubs/p60-239.pdf. Accessed 25 August 2012.
- 13. Hotez PJ (2012) Fighting neglected tropical diseases in Texas and America. BMJ 13: e6112.
- 14. Barry MA, Bezek S, Serpa JA, Hotez PJ, Woc-Colburn L (2012) Neglected infections of poverty in Texas and the rest of the United States: management and treatment options. Clin Pharmacol Therap 92: 170–181.
- 15. Hotez PJ, Bottazzi ME, Dumonteil E, Valenzuela JG, Kamhawi S, et al. (2012) Texas and Mexico: sharing a legacy of poverty and neglected tropical disease. PLoS Negl Trop Dis 6: e1497 doi:10.1371/journal.pntd.0001497.
- 16. Hotez PJ, Dumonteil E, Woc-Colburn L, Serpa JA, Bezek S, et al. (2012) Chagas disease: “the new HIV/AIDS of the Americas”. PLoS Negl Trop Dis 6: e1498 doi:10.1371/journal.pntd.0001498.
- 17. Barona-Vilar C, Gimenez-Marti MJ, Fraile T, Gonzalez-Steibauer C, Parada C, et al. (2012) Prevalence of Trypanosoma cruzi infection in pregnant Latin American women and congenital transmission rate in a non-endemic area: the experience of the Valencian Health Programme (Spain). Epidemiol Infect 140: 1896–1903.
- 18. Centers for Disease Control and Prevention (2010) Congenital transmission of Chagas disease – Virginia, 2010. MMWR Morb Mortal Wkly Rep 61: 477–479.
- 19. Bern C, Kjos S, Yabsley MJ, Montgomery SP (2012) Trypanosoma cruzi and Chagas' disease in the United States. Clin Microbiol Rev 24: 655–681.
- 20. Hanford EJ, Zhan FB, Lu Y, Giordano A (2007) Chagas disease in Texas: recognizing the significance and implications of evidence in the literature. Soc Sci Med 65: 60–79.
- 21. Sarkar S, Strutz SE, Frank DM, Rivaldi C, Sissel B, et al. (2010) Chagas disease risk in Texas. PLoS Negl Trop Dis 4: e836 doi:10.1371/journal.pntd.0000836.
- 22. Kjos SA, Snowden KF, Craig TM, Lewis B, Ronald N, et al. (2008) Distribution and characterization of canine Chagas disease in Texas. Vet Parasitol 152: 249–256.
- 23. McHugh CP, Melby PC, Lafon SG (1996) Leishmaniasis in Texas: epidemiology and clinical aspects of human cases. Am J Trop Med Hyg 55: 547–555.
- 24. Wright NA, Davis LE, Aftergut KS, et al. (2008) Cutaneous leishmaniasis in Texas: a northern spread of endemic areas. J Am Acad Dermatol 58: 650–652.
- 25. Petersen CA (2009) Leishmaniasis, an emerging disease found in companion animals in the United States. Top Companion Anim Med 24: 182–188.
- 26. González C, Wang O, Strutz SE, González-Salazar C, Sánchez-Cordero V, et al. (2010) Climate change and risk of leishmaniasis in North America: predictions from ecological niche models of vector and reservoir species. PloS Negl Trop Dis 4: e585 doi:10.1371/journal.pntd.0000585.
- 27. Serpa JA, Graviss EA, Kass JS, White AC Jr (2011) Neurocysticercosis in Houston, Texas: an update. Medicine (Baltimore) 90: 81–86.
- 28. Won KY, Kruszon-Moran D, Schantz PM, Jones JL (2008) National seroprevalence and risk factors for zoonotic Toxocara spp. infection. Am J Trop Med Hyg 79: 552–557.
- 29. Hotez PJ, Wilkins PP (2009) Toxocariasis: America's most common neglected infection of poverty and a helminthiasis of global importance? PLoS Negl Trop Dis 3: e400 doi:10.1371/journal.pntd.0000400.
- 30. Lillibridge KM, Parsons R, Randle Y, Travassos Da Rosa APA, Guzman H, et al. (2004) The 2002 introduction of West Nile virus into Harris County, Texas, and area historically endemic for St. Louis Encephalitis. Am J Trop Med Hyg 70: 676–681.
- 31. Nolan MS, Zangeneh A, Khuwaja SA, Martinez D, Rossmann SN, et al. (2012) Proximity of residence to bodies of water and risk for West Nile virus infection: a case-control study in Houston, Texas. J Biomed Biotechnol doi: http://www.hindawi.com/journals/jbb/2012/159578/. Accessed 28 August 2012">10.1155/2012/159578. Available: http://www.hindawi.com/journals/jbb/2012/159578/. Accessed 28 August 2012.
- 32. Petersen L (2012) CDC telebriefing on West Nile update. Available: http://www.cdc.gov/media/releases/2012/t0905_west_nile_update.html. Accessed 16 November 2012.
- 33. Harrigan RJ, Thomassen HA, Buermann W, Cummings RF, Kahn ME, et al. (2010) Economic conditions predict prevalence of West Nile virus. PLoS ONE 5: e15437 doi:10.1371/journal.pone.0015437.
- 34. Meyer T, Bull L, Holmes K, Pascua R, Travassos Da Rosa A, et al. (2007) West Nile virus infection among the homeless, Houston, Texas. Emerg Infect Dis 13: 1500–1503.
- 35. Nash D, Mostashari F, Fine A, Miller J, O'Leary D (2001) The outbreak of West Nile virus infection in the New York City area in 1999. N Engl J Med 344: 1807–1814.
- 36. Murray KO, Baraniuk S, Resnick M, Arafat R, Kilborn C, et al. (2006) Risk factors for developing encephalitis from West Nile virus infection. Epidemiol Infect 134: 1325–1332.
- 37. Bode AV, Sejvar JJ, Pape WJ, Campbell GL, Marfin AA (2006) West Nile virus disease: a descriptive study of 228 patients hospitalized in a 4-county region of Colorado in 2003. Clin Infect Dis 42: 1234–1240.
- 38. Jean CM, Honarmand S, Louie JK, Glaser CA (2007) Risk factors for West Nile virus neuroinvasive disease, California. Emerg Infect Dis 13: 1918–1920.
- 39. Murray KO, Koers E, Baraniuk S, Herrington E, Carter H (2009) Risk factors for encephalitis from West Nile virus: a matched case-control study using hospitalized controls. Zoonoses Public Health 56: 370–375.
- 40. Nolan MS, Podoll AS, Hause AM, Akers KM, Finkel KW, et al. (2012) Prevalence of chronic kidney disease and progression of disease over time among patients enrolled in the Houston West Nile virus cohort. PLoS ONE 7: e40374 doi:10.1371/journal.pone.0040374.
- 41. Brunkard JM, Robles Lopez JL, Ramirez J, Cifuentes E, Rothenberg SJ, et al. (2007) Dengue fever seroprevalence and risk factors, Texas-Mexico border. Emerg Infect Dis 13: 1477–83.
- 42. Reiter P, Lathrop S, Bunning M, Biggerstaff B, Singer D, et al. (2003) Texas lifestyle limits transmission of dengue virus. Emerg Infect Dis 9: 86–89.
- 43. Ramos MM, Mohammed H, Zielinski-Gutierrez E, Hayden MH, Lopez JLR, et al. (2008) Epidemic dengue and dengue hemorrhagic fever at the Texas–Mexico Border: results of a household-based seroepidemiologic survey. Am J Trop Med Hyg 78: 364–369.
- 44. Radke EG, Gregory CJ, Kintziger KW, Sauber-Schatz EK, Hunsperger EA, et al. (2012) Dengue outbreak in Key West, Florida, USA, 2009. Emerg Infect Dis 18: 135–137.
- 45. Bouri N, Sell TK, Franco C, Adalja AA, Henderson DA, et al. (2012) Return of epidemic dengue in the United States: implications for the public health practitioner. Public Health Rep 127: 259–266.
- 46. Gardner LM, Fajardo D, Waller ST, Wang O, Sarkar S (2012) A predictive spatial model to quantify the risk of air-travel-associated dengue importation into the United States and Europe. J Trop Med 2012: 1–11.
- 47. Purcell K, Fergie J, Richman K, Rocha L (2007) Murine typhus in children in South Texas. Emerg Infect Dis 13: 926–927.
- 48. Restrepo BI, Fisher-Hoch SP, Crespo JG, Whitney E, Perez A, et al. (2007) Type 2 diabetes and tuberculosis in a dynamic bi-national border population. Epidemiol Infect 135: 483–491.
- 49. Qu HQ, Rentfro AR, Lu Y, Nair S, Hanis CL, et al. (2012) Host susceptibility to tuberculosis: insights from a longitudinal study of gene expression in diabetes. Int J Tuberc Lung Dis 16: 370–372.
- 50. Harries AD, Lin Y, Satyanarayana S, Lönnroth K, Li L, et al. (2011) The looming epidemic of diabetes-associated tuberculosis: learning lessons from HIV-associated tuberculosis. Int J Tuberc Lung Dis 15: 1436–1444.
- 51. Matthews CE, Martinez P, Bagaria U, Hossain MM, Nahm M, et al. (2012) Impaired antibody response may underlie the increased susceptibility of diabetes patients to pneumococcal infections. Infect Immu 19: 1360–1369.
- 52. Mirza S, Hossain M, Mathews C, Martinez P, Pino P, et al. (2012) Type 2-diabetes is associated with elevated levels of TNF-alpha, IL-6 and adiponectin and low levels of leptin in a population of Mexican Americans: a cross-sectional study. Cytokine 57: 136–142.
- 53. Qu HQ, Rentfro AR, Lu Y, Nair S, Hanis CL, et al. (2012) Host susceptibility to tuberculosis: insights from a longitudinal study of gene expression in diabetes. Int J Tuberc Lung Dis 16: 370–372.
- 54. Restrepo BI, Fisher-Hoch SP, Pino PA, Salinas A, Rahbar MH, et al. (2008) Tuberculosis in poorly controlled type 2 diabetes: altered cytokine expression in peripheral white blood cells. Clin Infect Dis 47: 634–641.
- 55. Hotez PJ, Daar AS (2008) The CNCDs and the NTDs: blurring the lines dividing noncommunicable and communicable chronic diseases. PLoS Negl Trop Dis 2: e312 doi:10.1371/journal.pntd.0000312.
- 56. Moolani Y, Bukhman G, Hotez PJ (2012) Neglected tropical diseases as hidden causes of cardiovascular disease. PLoS Negl Trop Dis 6: e1499 doi:10.1371/journal.pntd.0001499.
- 57. Fredregill CL, Mott GC, Dennett JA, Flatt KL, Bueno R Jr (2011) Thermal fog efficacy tests against mosquitoes in storm drains in Harris County, Texas 2008–09. J Am Mosq Control Assoc 27: 61–68.
- 58. National Institutes of Health. Medical Education Partnership Initiative (MEPI ). Available: http://www.fic.nih.gov/Programs/Pages/medical-education-africa.aspx. Accessed 7 July 2012.
- 59. Hotez P (2010) A national school of tropical medicine and neglected infections of poverty for North America. PLoS Negl Trop Dis 4: e735 doi:10.1371/journal.pntd.0000735.
- 60. Andrus JK, Quadros CA, Castillo Solórzano C, Roses Periago M, Henderson DA (2011) Measles and rubella eradication in the Americas. Vaccine 29: D91–D96.
- 61. Wen JJ, Zago MP, Nunez S, Gupta S, Nunez Burgos F, et al. (2012) Serum proteomic signature of human chagasic patients for the identification of novel protein biomarkers of disease. Mol Cell Proteomics 11: 435–452.
- 62. Vazquez-Chagoyan JC, Gupta S, Garg NJ (2011) Vaccine development against Trypanosoma cruzi and Chagas disease. Adv Parasitol 75: 121–146.
- 63. Lee BY, Bacon KM, Wateska AR, Bottazzi ME, Dumonteil E, et al. (2012) Modeling the economic value of a Chagas' disease therapeutic vaccine. Hum Vaccin Immunother 8: 1–9.
- 64. Dumonteil E, Bottazzi ME, Zhan B, Heffernan MJ, Jones K, et al. (2012) Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects. Expert Rev Vaccines 11: 1043–1055.
- 65. Saldarriaga OA, Travi BL, Park W, Perez LE, Melby PC (2006) Immunogenicity of a multicomponent DNA vaccine against vsiceral leishmaniasis in dogs. Vaccine 24: 1928–1940.
- 66. Lee BY, Bacon KM, Shah M, Kitchen SB, Connor DL, et al. (2012) The economic value of a visceral leishmaniasis vaccine in Bihar State, India. Am J Trop Med Hyg 86: 417–425.
- 67. Murray KO, Walker G, Gould E (2011) The virology, epidemiology, and clinical impact of West Nile virus: a decade of advancements in research since its introduction into the Western Hemisphere. Epidemiol Infect 139: 807–817.
- 68. Schleich K, Numberger C, Sobranski A, Efferth T (2011) Vaccination and antiviral treatment of neglected diseases caused by flavivirus infections. Curr Med Chem 18: 604–614.
- 69. Cox J, Mota J, Sukupolvi-Petty S, Diamond MS, Rico-Hesse R (2012) Mosquito bite delivery of dengue virus enhances immunogenicity and pathogenesis in humanized mice. J Virol 2012 86: 7637–7649.
- 70. Hotez PJ (2011) New antipoverty drugs, vaccines, and diagnostics: a research agenda for the US President's Global Health Initiative (GHI). PLoS Negl Trop Dis 5: e1133 doi:10.1371/journal.pntd.0001133.
- 71. ASTMH Blog. Neglected Infections of Impoverished Americans Act approved by House Committee. Available: http://www.astmh.org/source/blog/post.cfm/house-passes-neglected-infections-of-impoverished-americans-act. Accessed 7 July 2012.
- 72. Hotez PJ (2008) Forgotten people, forgotten diseases: the neglected tropical diseases and their impact on global health and development. Washington: ASM Press. 218 p.
- 73. Andrus JK, Jauregui B, De Oliveira LH, Ruiz Matus C (2011) Challenges to building capacity for evidence-based new vaccine policy in developing countries. Health Aff (Millwood) 30: 1104–1112.