Abstract In the United States, there is a largely hidden burden of diseases caused by a group of chronic and debilitating parasitic, bacterial, and congenital infections known as the neglected infections of poverty. Like their neglected tropical disease counterparts in developing countries, the neglected infections of poverty in the US disproportionately affect impoverished and under-represented minority populations. The major neglected infections include the helminth infections, toxocariasis, strongyloidiasis, ascariasis, and cysticercosis; the intestinal protozoan infection trichomoniasis; some zoonotic bacterial infections, including leptospirosis; the vector-borne infections Chagas disease, leishmaniasis, trench fever, and dengue fever; and the congenital infections cytomegalovirus (CMV), toxoplasmosis, and syphilis. These diseases occur predominantly in people of color living in the Mississippi Delta and elsewhere in the American South, in disadvantaged urban areas, and in the US–Mexico borderlands, as well as in certain immigrant populations and disadvantaged white populations living in Appalachia. Preliminary disease burden estimates of the neglected infections of poverty indicate that tens of thousands, or in some cases, hundreds of thousands of poor Americans harbor these chronic infections, which represent some of the greatest health disparities in the United States. Specific policy recommendations include active surveillance (including newborn screening) to ascertain accurate population-based estimates of disease burden; epidemiological studies to determine the extent of autochthonous transmission of Chagas disease and other infections; mass or targeted treatments; vector control; and research and development for new control tools including improved diagnostics and accelerated development of a vaccine to prevent congenital CMV infection and congenital toxoplasmosis.

Citation: Hotez PJ (2008) Neglected Infections of Poverty in the United States of America. PLoS Negl Trop Dis 2(6): e256. https://doi.org/10.1371/journal.pntd.0000256 Editor: Simon Brooker, London School of Hygiene & Tropical Medicine, United Kingdom Published: June 25, 2008 Copyright: © 2008 Peter J. Hotez. 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 author received no specific funding for this study. Competing interests: PJH is Executive Director of the Global Network for Neglected Tropical Disease Control (GNNTDC), the Director of the Human Hookworm Vaccine Initiative (HHVI), and President of the Sabin Vaccine Institute. He is an inventor on an international patent for a hookworm vaccine. The author recused himself from all editorial decisions regarding this paper.

Introduction In the United States of America, the mortality rate resulting from infectious diseases has declined precipitously over the course of the twentieth century [1], and major scourges such as typhoid fever and malaria are no longer serious public health threats [2]. However, among the poorest populations living in the US there remains highly prevalent a group of serious parasitic and bacterial diseases such as Chagas disease, cysticercosis, and toxocariasis [3], which, like the neglected tropical diseases (NTDs), are characterized by their high prevalence, chronic and disabling features, and disproportionate effect on the poor [3],[4]. These infections occur outside of tropical regions of Africa, Asia, and Latin America, and I refer to them as neglected infections of poverty, because they not well known to the US public-health community, and they promote poverty because of their impact on child development, pregnancy outcomes, and worker productivity [5]. In this review I highlight the largely underappreciated burden of the neglected infections of poverty in the US and make policy recommendations for addressing such health disparities.

Policy Recommendations Based on my estimates of prevalence (Table 2) and other health and socioeconomic impacts, the most important neglected helminth infections of poverty in the US are the helminth diseases toxocariasis (inner cities and the American South), ascariasis (Appalachia and the American South), strongyloidiasis (Appalachia), and cysticercosis (US–Mexico borderlands). Among the important vector-borne neglected infections are dengue and Chagas disease in the US–Mexico borderlands and in post-Katrina Louisiana. Congenital infections such as congenital CMV and congenital syphilis stand out as health disparities in inner cities and the American South. Trench fever and leptospirosis are important among the homeless and other disadvantaged urban populations. Among the common features of these neglected infections are (1) their highly disproportionate health impact on people of color and people living in poverty; (2) their chronic, largely insidious, and disabling features; and (3) their ability to promote poverty because of their impact on child development, pregnancy outcome, and productive capacity. It is important to note that, while some of these neglected infections occur exclusively among recent immigrant populations, most do not. Instead, poverty is the single most important determinant. Control of these neglected infections needs to be prioritized by policy makers and public-health experts because it is both a highly cost-effective mechanism for lifting disadvantaged populations out of poverty and consistent with our shared American values of equity and equality [150]. The World Health Organization also recognizes that control of neglected diseases represents a fundamental human right [151]. An important obstacle to the control or elimination of the neglected infections of poverty in the US is the absence of reliable population-based estimates of prevalence and disease burden data about these conditions [3],[19]. These neglected infections are underdiagnosed and most are not reportable to the CDC. The estimates I provide here are preliminary and based on very few active surveillance studies, including some obtained by analyses of sera collected from National Health and Examination Surveys. For some of the neglected infections of poverty, seropositivity may be equated with active infection [89],[90],[95],[109],[113], whereas for others it may reflect both current and past infections [53],[74]. For infections such as Chagas disease estimates reported here vary widely. We also lack a system for the national collection of fecal samples for intestinal parasitic infections. Expanded measures are urgently needed to implement active surveillance and obtain population-based estimates of the neglected infections (Table 3). An added measure would be to expand newborn screening for toxoplasmosis [3],[152], and possibly congenital Chagas disease. Screening for congenital toxoplamosis would also likely benefit persons of all socioeconomic circumstances [61]. Such efforts would create opportunities to determine the extent and true disease burden of these neglected infections. PPT PowerPoint slide

PowerPoint slide PNG larger image

larger image TIFF original image Download: Table 3. Priority Needs for Enhanced Surveillance, Treatment, and Prevention Efforts for the High Priority Neglected Infections of Poverty. https://doi.org/10.1371/journal.pntd.0000256.t003 There is also an urgent need to better define the transmission dynamics of some of the neglected diseases (Table 3). For Chagas disease, and to some extent, dengue and leishmaniasis, the full extent of authochthonous transmission in Louisiana and the US–Mexico borderlands is poorly understood. A full appreciation of Chagas disease transmission mechanisms would include molecular genotyping of the parasite to determine whether different strains or demes are endemic, and a complete characterization of the different vectors and animal reservoir hosts. Similarly, the extent of autochthonous cysticercosis transmission in the US is largely unstudied, as it is for many of the bacterial zoonoses including urban foci of leptospirosis and trench fever. For toxocariasis, the contribution of feral versus domesticated animal reservoirs to transmission is also not well understood. Following enhanced surveillance and improved understanding of transmission dynamics, there are several opportunities to treat or prevent neglected infections of poverty in the US using existing drugs or other control tools (Table 3). Through either population-based drug administration or case identification and treatment, the soil-transmitted helminths could be controlled by administration of albendazole and ivermectin [22], while expanded use of praziquantel would treat schistosomiasis among selected immigrant populations [90] and prevent transmission of T. solium eggs and possibly reduce the incidence of cysticercosis [153]. Metronidazole and tinidazole are available for the treatment of trichomoniasis and giardiasis [154],[155], and nitazoxanide is available for cryptosporidiosis and giardiasis [144],[156]. Pyrimethamine plus sulfadiazine is used for the treatment of toxoplasmosis, and the optimal length of treatment and its impact on child development and neurological sequelae need to be determined [61]. Antibiotics are available for the treatment of leptospirosis and other bacterial zoonoses [157]. An important role also exists for veterinary public health interventions to prevent zoonotic transmission to humans, possibly including the mass treatment of Toxocara-infected dogs, Toxoplasma-infected cats, and other measures [158]. The control of almost all of the neglected infections of poverty would also benefit from improvements in environmental sanitation, piped clean water, and improvements in housing in some of the poorest endemic areas. For Chagas disease, dengue, and leishmaniasis, consideration of expanded vector control approaches is warranted [55],[159]. Development of new control and prevention tools is needed (Table 3). Currently, the serologic-based diagnostic tests for most of the parasitic infections rely on extracts or crude preparations of parasite antigens and would benefit from the development of improved and widely available diagnostic kits that utilize standardized and purified recombinant antigens. For Chagas disease there is a particularly urgent need for rapid diagnostic tests and polymerase chain reaction-based assays for detection of acute and congenital infections. Furthermore, no drugs adequately and reliably treat Chagas disease [160], dengue [161], or congenital CMV infection [162]. Although vaccines for dengue [163] and CMV infection [164] are under development, progress has been slow because of inadequate resources and commercial incentives [5]. A pediatric dengue vaccine initiative was recently established through support by the Gates Foundation [163]. For CMV infection, both a live attenuated vaccine and a recombinant vaccine have been developed [164], but clinical testing in pregnant women to determine the impact of these vaccines on vertical transmission has been severely lagging because of inadequate support—a tragedy, given that more than 10,000 congenital CMV infections occur among infants of color annually [64]. In 2006, the annual budget of the National Institute of Allergy and Infectious Diseases (NIAID) was $4.4 billion, with approximately $1.6 billion of this amount spent on biodefense [165]. Of the selected disease-specific areas targeted for funding by the NIAID in their published annual report, none specifically mentions a neglected infection of poverty [165]. A consequence of this lack of targeted funding for neglected diseases is that the development of critically needed new tools for these conditions has lagged behind those for biodefense. The Global Forum on Health Research has coined the term “the 10/90 gap” to describe how only 10% of resources are devoted to 90% of the global burden of disease, i.e., that represented by disease disproportionately occurring in developing countries [166]. The absence of development of new tools for neglected infections of poverty, such as those outlined above, highlights a unique American 10/90 gap for poor people and people of color in the US.

Acknowledgments I wish to thank Drs. Mark Eberhard and Peter Schantz from the US Centers for Disease Control and Prevention for their helpful discussions and insights.