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Collateral Benefits of Preventive Chemotherapy — Expanding the War on Neglected Tropical Diseases Peter J

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Collateral Benefits of Preventive Chemotherapy — Expanding the War on Neglected Tropical Diseases Peter J View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by LSTM Online Archive The NEW ENGLAND JOURNAL of MEDICINE Perspective Collateral Benefits of Preventive Chemotherapy — Expanding the War on Neglected Tropical Diseases Peter J. Hotez, M.D., Ph.D., Alan Fenwick, Ph.D., and David H. Molyneux, D.Sc.​​ Collateral Benefits of Preventive Chemotherapy he collateral and extended effects of preven- nearly 15 years after mass drug tive chemotherapy, many of which were un- administration for NTDs was first proposed, the existence of such Tanticipated, have reduced disease burdens collateral benefits can be verified and saved lives on a scale that appears to have ex- (see table). In an Australian aboriginal ceeded the intended impact on in the disease burden and disabil- community, a single dose of iver- seven neglected tropical diseases ity-adjusted life years (DALYs, or mectin (200 μg per kilogram of (NTDs) — the three major soil- lost years of healthy life) — as body weight) delivered in two transmitted helminth infections much as a 46% decrease in DALYs community mass drug adminis- (ascariasis, trichuriasis, and hook- — attributable to the seven NTDs, trations 12 months apart not only worm infection), schistosomiasis, allowing some countries to achieve prevented ascariasis, trichuriasis, lymphatic filariasis, onchocercia- their elimination targets for tra- and hookworm infections, but also sis, and trachoma. choma, lymphatic filariasis, and significantly reduced the preva- The concept of integrated pro- onchocerciasis. Moreover, it has lence of strongyloidiasis. A simi- grams of mass drug administra- led to cost savings for the world’s lar effect on strongyloidiasis was tion (also referred to as preventive poorest people, by reducing cata- achieved in Cambodia with a sin- chemotherapy) was first proposed strophic health expenditures.1 gle mass ivermectin administra- in the early 2000s, and such in- Scientists and public health ex- tion. Ivermectin also reduces the terventions now reach more than perts realized at the outset of prevalence of loiasis (human Loa 1 billion people per year in low- this program that the primary loa infection) in places where both and middle-income countries of drugs used for preventive chemo- onchocerciasis and loiasis are en- Africa, Asia, and Latin America.1 therapy, including albendazole demic. A recently published clin- Implementation of the World or mebendazole, ivermectin, pra- ical trial suggests that ivermectin Health Organization (WHO) pre- ziquantel, and azithromycin, might could help reduce the prevalence ventive chemotherapy strategy has affect conditions beyond their of mansonelliasis in the Amazon, resulted in substantial reductions originally intended targets. Now, although it’s less clear whether n engl j med nejm.org 1 The New England Journal of Medicine Downloaded from nejm.org at LIVERPOOL SCHOOL OF TROPICAL MEDICINE on May 9, 2019. For personal use only. No other uses without permission. Copyright © 2019 Massachusetts Medical Society. All rights reserved. PERSPECTIVE Collateral Benefits of Preventive Chemotherapy Extended Targets of Medications Used for Preventive Chemotherapy against NTDs. ate doses for control of lymphatic filariasis and onchocerciasis might Drug Original Targets Extended Targets also reduce malaria transmission Albendazole or Ascariasis Oesophagostomiasis has yet to be investigated. mebendazole Trichuriasis Strongyloidiasis In 2009, in a trachoma-endemic Hookworm infection area of Ethiopia, mass azithro- Ivermectin Lymphatic filariasis Scabies mycin administration was found Onchocerciasis Strongyloidiasis Loiasis to be associated with dramatic Mansonelliasis reductions in overall child mor- Malaria transmission tality. The findings were consid- Praziquantel Schistosomiasis Foodborne trematodiases ered astonishing, given that tra- Taeniasis choma is not a fatal childhood Azithromycin Trachoma Yaws infection, and it was hard to Child mortality understand how a single dose of azithromycin would affect the outcome of serious bacterial co- this effect could be replicated in the addition of scabies to the infections such as pneumonia or Africa. In addition, mass admin- WHO list of NTDs and high- diarrheal disease. But in a large, istration of albendazole appears lighting mass drug administra- randomized follow-up study in to have reduced the prevalence of tion as an appropriate intervention Malawi, Niger, and Tanzania, the oesophagostomiasis (Oesophagosto- strategy.2 Similarly, mass admin- MORDOR (Macrolides Oraux pour mum bifurcum infection) in humans, istration of azithromycin designed Réduire les Décès avec un Oeil sur even to the point of elimination for trachoma elimination has la Résistance) group confirmed in northern Ghana and Togo. shown enormous promise for the that overall child mortality was Mass administration of single- treatment and elimination of lower among preschool children dose praziquantel for schistoso- yaws.3 A major study from Papua who received azithromycin.5 The miasis also appears to be effective New Guinea in 2015 found that public health effect occurs pri- for the treatment of opisthorchi- mass azithromycin administration marily in the first 3 months af- asis (in Southeast Asia) and hu- substantially reduced the preva- ter the distribution of the drug, man tapeworm infections. lence of yaws,3 as did a single which suggests that azithromycin Furthermore, preventive chemo- round of such treatment in Ghana. could have substantial benefits if therapy is showing substantial More recent studies have administered to populations more collateral benefits for two neglect- shown that plasma containing frequently than once, or even ed skin diseases — scabies and ivermectin has the capacity to re- twice, per year. A follow-up yaws.2,3 Although the Global Bur- duce transmission of Plasmodium MORDOR II study is planned for den of Disease Study does not vivax malaria, thanks to the drug’s Burkina Faso to test these, and provide estimates for yaws, it has effects on the viability of both other, ideas. revealed that scabies (and its as- anopheles mosquito vectors and Since the original drug pack- sociated secondary bacterial infec- the malaria parasites themselves. aging for the preventive chemo- tions, especially impetigo) has one In Kenya, among adults treated therapy strategy was proposed, of the largest public health effects with both high-dose ivermectin some exciting possibilities have among the NTDs. Beginning in and dihydroartemisinin–pipera- been identified for drug substitu- 2012, large-scale studies, includ- quine, blood containing ivermec- tions or additions. Among these ing randomized clinical trials, tin was shown to reduce survival possibilities are new anthelmintic conducted in the South Pacific of Anopheles gambiae mosquitoes agents, such as tribendimidine (for and Africa showed the benefits that fed on it, which suggests that foodborne trematodiases and soil- of mass administration of iver- this approach could also help in transmitted helminth infections); mectin for scabies.2 The Interna- controlling P. falciparum malaria.4 the addition of either tribendimi- tional Alliance for the Control of These results, though exciting, are dine or oxantel pamoate to alben- Scabies has been leading global still preliminary, and the ques- dazole, to increase the efficacy efforts to raise awareness about tion of whether mass administra- of treatment for trichuriasis and scabies and impetigo, promoting tion of ivermectin in the appropri- hookworm; and moxidectin (re- 2 n engl j med nejm.org The New England Journal of Medicine Downloaded from nejm.org at LIVERPOOL SCHOOL OF TROPICAL MEDICINE on May 9, 2019. For personal use only. No other uses without permission. Copyright © 2019 Massachusetts Medical Society. All rights reserved. PERSPECTIVE Collateral Benefits of Preventive Chemotherapy cently approved by the Food and chemotherapy programs for the that reaches more than a billion Drug Administration) in place of possible emergence of drug- of the world’s most vulnerable ivermectin in some settings. A fur- resistant respiratory and gastro- people each year. ther proposed addition is nitazox- intestinal bacterial pathogens, Disclosure forms provided by the authors anide to target the intestinal and anthelmintic drug resistance are available at NEJM.org. protozoa giardia and cryptosporid- may also emerge. A further con- From the National School of Tropical Medi- ium. Finally, recent studies have sideration is the integration of cine, Baylor College of Medicine and Texas indicated that chemoprophylaxis preventive chemotherapy for NTDs Children’s Hospital, Houston (P.J.H.); and the Department of Infectious Disease Epi- with single-dose rifampin in with approaches to preventing demiology, Imperial College London (A.F.), household contacts of people malaria and HIV/AIDS.1 For exam- and Liverpool School of Tropical Medicine, with leprosy may reduce leprosy ple, the findings regarding iver- Liverpool (D.H.M.) — both in the United Kingdom. transmission and prevalence in mectin’s effect on malaria may some settings. These medications inspire greater interaction between This article was published on May 8, 2019, require additional clinical testing NTD- and malaria-prevention pro- at NEJM.org. and regulatory approvals or oper- grams, and there is also renewed 1. Hotez PJ, Fenwick A, Ray SE, Hay SI, ational research before they can interest in treating female genital Molyneux DH. “Rapid impact” 10 years after: be fully incorporated
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