Peter J. Hotez

Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm

The three main soil-transmitted helminth infections, ascariasis, trichuriasis, and hookworm, are common clinical disorders in man. The gastrointestinal tract of a child living in poverty in a less developed country is likely to be parasitised with at least one, and in many cases all three soil-transmitted helminths, with resultant impairments in physical, intellectual, and cognitive development. The benzimidazole anthelmintics, mebendazole and albendazole, are commonly used to remove these infections. The use of these drugs is not limited to treatment of symptomatic soil-transmitted helminth infections, but also for large-scale prevention of morbidity in children living in endemic areas. As a result of data showing improvements in child health and education after deworming, and the burden of disease attributed to soil-transmitted helminths, the worldwide community is awakening to the importance of these infections. Concerns about the sustainability of periodic deworming with benzimidazole anthelmintics and the emergence of resistance have prompted efforts to develop and test new control tools.

Helminth infections: the great neglected tropical diseases

Helminths are parasitic worms. They are the most common infectious agents of humans in developing countries and produce a global burden of disease that exceeds better-known conditions, including malaria and tuberculosis. As we discuss here, new insights into fundamental helminth biology are accumulating through newly completed genome projects and the nascent application of transgenesis and RNA interference technologies. At the same time, our understanding of the dynamics of the transmission of helminths and the mechanisms of the Th2-type immune responses that are induced by infection with these parasitic worms has increased markedly. Ultimately, these advances in molecular and medical helminth biology should one day translate into a new and robust pipeline of drugs, diagnostics, and vaccines for targeting parasitic worms that infect humans.

Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV/AIDS, tuberculosis, and malaria

Hotez et al. argue that achieving success in the global fight against HIV/AIDS, tuberculosis, and malaria may well require a concurrent attack on the neglected tropical diseases.

Neglected tropical diseases in sub-saharan Africa: review of their prevalence, distribution, and disease burden.

The neglected tropical diseases (NTDs) are the most common conditions affecting the poorest 500 million people living in sub-Saharan Africa (SSA), and together produce a burden of disease that may be equivalent to up to one-half of SSAs malaria disease burden and more than double that caused by tuberculosis. Approximately 85% of the NTD disease burden results from helminth infections. Hookworm infection occurs in almost half of SSAs poorest people, including 40–50 million school-aged children and 7 million pregnant women in whom it is a leading cause of anemia. Schistosomiasis is the second most prevalent NTD after hookworm (192 million cases), accounting for 93% of the worlds number of cases and possibly associated with increased horizontal transmission of HIV/AIDS. Lymphatic filariasis (46–51 million cases) and onchocerciasis (37 million cases) are also widespread in SSA, each disease representing a significant cause of disability and reduction in the regions agricultural productivity. There is a dearth of information on Africas non-helminth NTDs. The protozoan infections, human African trypanosomiasis and visceral leishmaniasis, affect almost 100,000 people, primarily in areas of conflict in SSA where they cause high mortality, and where trachoma is the most prevalent bacterial NTD (30 million cases). However, there are little or no data on some very important protozoan infections, e.g., amebiasis and toxoplasmosis; bacterial infections, e.g., typhoid fever and non-typhoidal salmonellosis, the tick-borne bacterial zoonoses, and non-tuberculosis mycobaterial infections; and arboviral infections. Thus, the overall burden of Africas NTDs may be severely underestimated. A full assessment is an important step for disease control priorities, particularly in Nigeria and the Democratic Republic of Congo, where the greatest number of NTDs may occur.

Rescuing the bottom billion through control of neglected tropical diseases

Here we outline low-cost opportunities to control the neglected tropical diseases through preventive chemotherapy, and propose fi nancial innovations to provide poor individuals with essential drugs.13 parasitic (helminthic and protozoan) and bacterial tropical infections, and dengue are the highest-burden neglected tropical diseases; another 20 include fungal, viral, and ectoparasitic infections (panel 2).

The Neglected Tropical Diseases of Latin America and the Caribbean: A Review of Disease Burden and Distribution and a Roadmap for Control and Elimination

The neglected tropical diseases (NTDs) represent some of the most common infections of the poorest people living in the Latin American and Caribbean region (LAC). Because they primarily afflict the disenfranchised poor as well as selected indigenous populations and people of African descent, the NTDs in LAC are largely forgotten diseases even though their collective disease burden may exceed better known conditions such as of HIV/AIDS, tuberculosis, or malaria. Based on their prevalence and healthy life years lost from disability, hookworm infection, other soil-transmitted helminth infections, and Chagas disease are the most important NTDs in LAC, followed by dengue, schistosomiasis, leishmaniasis, trachoma, leprosy, and lymphatic filariasis. On the other hand, for some important NTDs, such as leptospirosis and cysticercosis, complete disease burden estimates are not available. The NTDs in LAC geographically concentrate in 11 different sub-regions, each with a distinctive human and environmental ecology. In the coming years, schistosomiasis could be eliminated in the Caribbean and transmission of lymphatic filariasis and onchocerciasis could be eliminated in Latin America. However, the highest disease burden NTDs, such as Chagas disease, soil-transmitted helminth infections, and hookworm and schistosomiasis co-infections, may first require scale-up of existing resources or the development of new control tools in order to achieve control or elimination. Ultimately, the roadmap for the control and elimination of the more widespread NTDs will require an inter-sectoral approach that bridges public health, social services, and environmental interventions.

The Global Burden of Disease Study 2010: Interpretation and Implications for the Neglected Tropical Diseases

The publication of the Global Burden of Disease Study 2010 (GBD 2010) and the accompanying collection of Lancet articles in December 2012 provided the most comprehensive attempt to quantify the burden of almost 300 diseases, injuries, and risk factors, including neglected tropical diseases (NTDs) [1]–[3]. The disability-adjusted life year (DALY), the metric used in the GBD 2010, is a tool which may be used to assess and compare the relative impact of a number of diseases locally and globally [4]–[6]. Table 1 lists the major NTDs as defined by the World Health Organization (WHO) [7] and their estimated DALYs [1]. With a few exceptions, most of the NTDs currently listed by the WHO [7] or those on the expanded list from PLOS Neglected Tropical Diseases [8] are disablers rather than killers, so the DALY estimates represent one of the few metrics available that could fully embrace the chronic effects of these infections. Table 1 Estimated DALYs (in millions) of the NTDs from the Global Burden of Disease Study 2010. Disease DALYs from GBD 2010 (numbers in parentheses indicate 95% confidence intervals) [1] NTDs 26.06 (20.30–35.12) Intestinal nematode infections 5.19 (2.98–8.81) Hookworm disease 3.23 (1.70–5.73) Ascariasis 1.32 (0.71–2.35) Trichuriasis 0.64 (0.35–1.06) Leishmaniasis 3.32 (2.18–4.90) Schistosomiasis 3.31 (1.70–6.26) Lymphatic filariasis 2.78 (1.8–4.00) Food-borne trematodiases 1.88 (0.70–4.84) Rabies 1.46 ((0.85–2.66) Dengue 0.83 (0.34–1.41) African trypanosomiasis 0.56 (0.08–1.77) Chagas disease 0.55 (0.27–1.05) Cysticercosis 0.50 (0.38–0.66) Onchocerciasis 0.49 (0.36–0.66) Trachoma 0.33 (0.24–0.44) Echinococcosis 0.14 (0.07–0.29) Yellow fever <0.001 Other NTDs * 4.72 (3.53–6.35) Open in a separate window * Relapsing fevers, typhus fever, spotted fever, Q fever, other rickettsioses, other mosquito-borne viral fevers, unspecified arthropod-borne viral fever, arenaviral haemorrhagic fever, toxoplasmosis, unspecified protozoal disease, taeniasis, diphyllobothriasis and sparganosis, other cestode infections, dracunculiasis, trichinellosis, strongyloidiasis, enterobiasis, and other helminthiases. Even DALYs, however, do not tell the complete story of the harmful effects from NTDs. Some of the specific and potential shortcomings of GBD 2010 have been highlighted elsewhere [9]. Furthermore, DALYs measure only direct health loss and, for example, do not consider the economic impact of the NTDs that results from detrimental effects on school attendance and child development, agriculture (especially from zoonotic NTDs), and overall economic productivity [10], [11]. Nor do DALYs account for direct costs of treatment, surveillance, and prevention measures. Yet, economic impact has emerged as an essential feature of the NTDs, which may trap people in a cycle of poverty and disease [10]–[12]. Additional aspects not considered by the DALY metrics are the important elements of social stigma for many of the NTDs and the spillover effects to family and community members [13], [14], loss of tourism [15], and health system overload (e.g., during dengue outbreaks). Ultimately NTD control and elimination efforts could produce social and economic benefits not necessarily reflected in the DALY metrics, especially among the most affected poor communities [11].

Rapid-impact interventions: how a policy of integrated control for Africa's neglected tropical diseases could benefit the poor.

Controlling seven tropical infections in Africa would cost just 40 cents per person per year, and would permanently benefit hundreds of millions of people.

Human hookworm infection in the 21st century.

The scientific study of human hookworm infection began at the dawn of the twentieth century. In recent years, there have been dramatic improvements in our understanding of many aspects of this globally widespread parasite. This chapter reviews recent advances in our understanding in the biology, immunology, epidemiology, public health significance and control of hookworm, and to look forward to the study of this important parasite in the 21st century. Advances in molecular biology has lead to the identification of a variety of new molecules from hookworms, which have importance either in the molecular pathogenesis of hookworm infection or in the host-parasite relationship; some are also promising vaccine targets. At present, relatively little is known about the immune responses to hookworm infection, although it has recently been speculated that hookworm and other helminths may modulate specific immune responses to other pathogens and vaccines. Our epidemiological understanding of hookworm has improved through the development of mathematical models of transmission dynamics, which coupled with decades of field research across multiple epidemiological settings, have shown that certain population characteristics can now be recognised as common to the epidemiology, population biology and control of hookworm and other helminth species. Recent recognition of the subtle, but significant, impact of hookworm on health and education, together with the simplicity, safety, low cost and efficacy of chemotherapy has spurred international efforts to control the morbidity due to infection. Large-scale treatment programmes are currently underway, ideally supported by health education and integrated with the provision of improved water and sanitation. There are also on-going efforts to develop novel anthelmintic drugs and anti-hookworm vaccines.

Global economic burden of Chagas disease: a computational simulation model

BACKGROUND As Chagas disease continues to expand beyond tropical and subtropical zones, a growing need exists to better understand its resulting economic burden to help guide stakeholders such as policy makers, funders, and product developers. We developed a Markov simulation model to estimate the global and regional health and economic burden of Chagas disease from the societal perspective. METHODS Our Markov model structure had a 1 year cycle length and consisted of five states: acute disease, indeterminate disease, cardiomyopathy with or without congestive heart failure, megaviscera, and death. Major model parameter inputs, including the annual probabilities of transitioning from one state to another, and present case estimates for Chagas disease came from various sources, including WHO and other epidemiological and disease-surveillance-based reports. We calculated annual and lifetime health-care costs and disability-adjusted life-years (DALYs) for individuals, countries, and regions. We used a discount rate of 3% to adjust all costs and DALYs to present-day values. FINDINGS On average, an infected individual incurs US