Despite their promise, the NTD vertical and integrated control efforts are still fragile owing to their one- dimensional reliance on a single chemical agent or drug combination to achieve their intended goals (Hotez, 2004b). Therefore unanticipated drug resistance or other product failures could reverse their success. An example is the near eradication of malaria in India in the early 1960s, which was undermined by the rising costs of DDT to control mosquito populations, outright DDT resistance, and chloroquine anti-malarial drug resistance (Harrison, 1978). As a result, malaria returned to previous levels. Had ongoing R&D continued to generate new control tools, malaria could possibly have been eliminated in India. Similarly, vertical and integrated control efforts directed against hookworm are not likely to be effective in reducing transmission because of the variable efficacy of benzimidazole anthel-minthic agents (e.g., albendazole or mebendazole), the high rates of post-treatment hookworm re-infection that occurs in areas of high transmission, and the diminishing efficacy of benzimidazoles with frequent and periodic use (Hotez et al., 2005). These lessons raise the stakes for the activities of the PPPs and IDCs. Unless new control tools are developed the promise for eliminating the NTDs may not be realized.
Successful elimination will therefore require further R&D investment. In 2003, the NIH Director established a Roadmap for the development of new therapies (www.nih.gov/roadmap). Although primarily intended for disease in the industrialized world, this also affords an opportunity to target the NTDs (Hotez, 2004b). In addition, the Bill and Melinda Gates Foundation has made significant investments in the development of new generation vaccines for NTDs including leishmaniasis and hookworm, and new drugs for African sleeping sickness, leishmaniasis, Chagas disease (www.gatesfoundation.org) (Hotez, 2001; Hotez et al., 2005). These new tools could become urgently needed in the face of emerging drug resistance. We might be facing once-in-a-lifetime opportunities to forever eliminate humankind's most ancient scourges. Never has the time been so propitious for ending centuries of neglect.
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