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Preventive Anthelmintic Chemotherapy — Expanding the Armamentarium Lorenzo Savioli, M.D

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Preventive Anthelmintic Chemotherapy — Expanding the Armamentarium Lorenzo Savioli, M.D editorials Preventive Anthelmintic Chemotherapy — Expanding the Armamentarium Lorenzo Savioli, M.D. In 2012, more than 260 million tablets of alben- ventive chemotherapy. The combination therapy dazole (at a dose of 400 mg) and mebendazole was associated with an overall higher cure rate (at a dose of 500 mg) were distributed to school- and egg-reduction rate, as compared with the age children as preventive chemotherapy against anthelmintic agents administered alone. soil-transmitted helminthiases; altogether, more In the study area of Pemba Island, human than 700 million people received such treat- densities are high and sanitation levels are low: ment.1,2 Preventive chemotherapy means large- less than 40% of households have a latrine.6 scale preventive treatment against human hel- During the past 25 years, preventive chemother- minthiasis and trachoma with the use of safe, apy has been implemented regularly through single-dose, quality-assured medicines.1 Regular schools and communities or during large-scale treatment of at-risk populations is used as a pub- distribution of various combinations of albenda- lic health tool to prevent illness and, for certain zole, mebendazole, ivermectin, and praziquan- infections, to reduce transmission.1,3 The strat- tel, to control schistosomiasis and soil-trans- egy relies on large-scale donations of medicines mitted helminthiases and to eliminate lymphatic every year by the pharmaceutical industry, dis- filariasis. The cure and egg-reduction rates as- tributed through the World Health Organization sociated with albendazole or mebendazole as (WHO) or other partners. Its purpose with re- measured by the authors, albeit remarkably low, gard to soil-transmitted helminths is not to cure comply with the reference values7,8 and previous infected persons but to decrease the intensity of results from the same island.9 Furthermore, the infection and reduce associated illness with the finding of very high levels of prevalence and in- use of subsequent rounds of single-dose treat- tensity of infection are indicative of intense ment implemented at regular intervals. In fact, a transmission of soil-transmitted helminths, de- single administration of anthelmintic agents is spite previous treatment efforts. This calls for a rarely associated with a 100% cure rate, espe- comprehensive strategy of disease control that cially when affected persons have large numbers cannot rely on preventive chemotherapy alone of worms, but it is consistently associated with but that demands the provision of safe drinking significant egg-reduction rates — the proxy in- water, basic sanitation, health promotion, and dicator for intensity of infection and therefore education, as recommended by the 2013 World illness. Health Assembly resolution on neglected tropi- The development of drug resistance through cal diseases.3 selective pressure is an inherent risk in the A key message is that other anthelmintic large-scale use of existing anthelmintic agents. combinations beyond the one reported by Speich Such risk — even if anthelmintic resistance is et al. should be tested and assessed in large not yet a public health problem in helminthiasis population-based studies. For example, pyrantel in humans — will inevitably increase with the plus oxantel pamoate had been assessed previ- expansion of disease-control activities. The ously, with overall results that were similar to WHO therefore recommends that egg-reduction those observed here with albendazole plus ox- rates in sentinel sites be regularly assessed to antel pamoate.10 However, the pyrantel–oxantel monitor the efficacy of anthelmintic agents in pamoate combination is not readily available on large-scale interventions with preventive chemo- the international market. In addition, at the therapy.4 same research study site, the combination of In this issue of the Journal, Speich et al.5 re- mebendazole plus levamisole has proven more port the results of a randomized trial designed effective than any single anthelmintic agent to compare the combination of albendazole plus against hookworm infection.11 Levamisole — oxantel pamoate with albendazole, oxantel pa- another forgotten anthelmintic agent — is still moate, and mebendazole monotherapies as pre- included in the WHO Model List of Essential n engl j med 370;7 nejm.org february 13, 2014 665 The New England Journal of Medicine Downloaded from nejm.org by NICOLETTA TORTOLONE on February 12, 2014. For personal use only. No other uses without permission. Copyright © 2014 Massachusetts Medical Society. All rights reserved. The new england journal of medicine Medicines and could be effectively used in com- Disclosure forms provided by the author are available with the bination with benzimidazoles. These combina- full text of this article at NEJM.org. tions have the possible advantage of associating From the Department of Control of Neglected Tropical Diseas- benzimidazoles with medicines belonging to es, World Health Organization, Geneva. other anthelmintic families, providing the poten- tial to counter selective drug pressure and delay 1. Preventive chemotherapy in human helminthiasis: coordi- nated use of anthelminthic drugs in control interventions: the onset of resistance. a manual for health professionals and programme managers. It is essential that such combinations are Geneva: World Health Organization, 2006. also assessed for their safety and made available 2. PCT databank. Geneva: World Health Organization, 2013 (http://www.who.int/neglected_diseases/preventive_chemotherapy/ to expand preventive chemotherapy not only for databank/en/index.html). soil-transmitted helminthiases but also for infec- 3. Neglected tropical diseases: World Health Assembly Resolu- tions caused by other nematodes, trematodes, tion WHA66.12. Geneva: World Health Organization, 2013 (http:// www.who.int/neglected_diseases/mediacentre/WHA_66.12_Eng and cestodes. Preventive chemotherapy should .pdf). eventually extend to alternative or combined uses 4. Assessing the efficacy of anthelminthic drug against schis- of medicines with different target sites on the tosomiasis and soil-transmitted helminthiases. Geneva: World Health Organization, 2013 (http://apps.who.int/iris/bitstream/ parasites. For soil-transmitted helminthiases, 10665/79019/1/9789241564557_eng.pdf). this process should entail broadening target 5. Speich B, Ame SM, Ali SM, et al. Oxantel pamoate–alben- sites beyond the β-tubulin, the microtubule pro- dazole for Trichuris trichiura infection. N Engl J Med 2014;370: 610-20. tein against which the action of the benzimid- 6. 2012 Population and housing census. Dar es Salaam, Zanzi- azoles is directed, in order to increase efficacy bar: The United Republic of Tanzania, March 2013 (http://www and delay the development of resistance. .nbs.go.tz/sensa/PDF/Census%20General%20Report%20-%2029% 20March%202013_Combined_Final%20for%20Printing.pdf). Collaboration among WHO and neglected 7. Geerts S, Coles GC, Gryseels B. Anthelminthic resistance in tropical disease constituents with the pharma- human helminths: learning from the problems with worm con- ceutical industry has addressed problems of ac- trol in livestock. Parasitol Today 1997;13:149-51. 8. Albonico M. Treatment of soil-transmitted helminth infec- cess to medicines against neglected tropical dis- tion: prescribing information for disease control. In: Crompton eases. Quality-assured diethylcarbamazine — an DWT, Montresor A, Nesheim MC, Savioli L, eds. Controlling antifilarial agent that had been scarcely available disease due to helminth infections. Geneva: World Health Orga- nization, 2003:109-26. on the market — is again accessible through the 9. Albonico M, Smith PG, Hall A, Chwaya HM, Alawi KS, Savi- WHO, thanks to an innovative approach by a oli L. A randomized controlled trial comparing mebendazole nonproprietary company donating the medicines and albendazole against Ascaris, Trichuris and hookworm in- fections. Trans R Soc Trop Med Hyg 1994;88:585-9. and ensuring their high quality by means of a 10. Albonico M, Bickle Q, Haji HJ, et al. Evaluation of the effi- prequalification process.12 The availability of oth- cacy of pyrantel-oxantel for the treatment of soil-transmitted er medicines that have been considered obsolete nematode infections. Trans R Soc Trop Med Hyg 2002;96:685-90. 11. Albonico M, Bickle Q, Ramsam M, Montressor A, Savioli L, should be addressed with the same pragmatic Taylor M. Efficacy of mebendazole and levamisole alone or in and constructive mindset. Research and devel- combination for the treatment of soil-transmitted nematode in- opment of new anthelmintic agents are urgently fections following repeated targeted mebendazole treatment in Zanzibar. Bull World Health Organ 2003;81:343-52. needed, such as that occurring with the anti- 12. WHO prequalifies first medicine for treatment of a neglect- wolbachia consortium13 and the reformulation ed tropical disease. Press release of the World Health Organiza- of flubendazole14 as macrofilaricides for oncho- tion, August 20, 2013 (http://apps.who.int/prequal/info_press/ documents/PQ_1st_NTD_medicine.pdf). cerciasis and lymphatic filariasis. The work ini- 13. Taylor MJ, Hoerauf A, Townson S, Slatko BE, Ward SA. Anti- tiated by Speich et al., Albonico et al.,9-11 and Wolbachia drug discovery and development: safe macrofilaricides other researchers should be encouraged and ex- for onchocerciasis and lymphatic filariasis. Parasitology 2013 July 18 (Epub ahead of print). panded to include all helminthic infections that 14.
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