Research Article: Triple Co-Administration of Ivermectin, Albendazole and Praziquantel in Zanzibar: A Safety Study

Date Published: January 23, 2008

Publisher: Public Library of Science

Author(s): Khalfan A. Mohammed, Hamad J. Haji, Albis-Francesco Gabrielli, Likezo Mubila, Gautam Biswas, Lester Chitsulo, Mark H. Bradley, Dirk Engels, Lorenzo Savioli, David H. Molyneux, Juerg Utzinger

Abstract: BackgroundPublic health interventions based on distribution of anthelminthic drugs against lymphatic filariasis (LF), onchocerciasis, soil-transmitted helminthiasis (STH) and schistosomiasis have been implemented separately to date. A better use of available resources might be facilitated by a more coordinated approach to control such infections, including the possibility of co-administering the three recommended anthelminthic drugs through a single, large-scale intervention.Methodology/Principal FindingsIvermectin, albendazole and praziquantel were co-administered to 5,055 children and adults living in areas endemic for LF, STH and schistosomiasis in Zanzibar, United Republic of Tanzania, during a pilot intervention aimed at elucidating and quantifying possible side-effects. Subsequently, these drugs were co-administered to about 700,000 individuals during a countrywide intervention targeting a large part of the total population of Zanzibar. Passive and active surveillance measures carried out during both interventions showed that side-effects attributable to the three drugs given at the same time were mild and self-limiting events.Conclusions/SignificanceOur data suggest that co-administration of ivermectin, albendazole and praziquantel is safe in areas where lymphatic filariasis, soil-transmitted helminthiasis and schistosomiasis are co-endemic and where several rounds of treatment with one or two drugs have been implemented in the past. Passive surveillance measures, however, should be continued and detection, management and reporting of possible side-effects should be considered a key component of any health intervention administering drugs.

Partial Text: Lymphatic filariasis (LF), soil-transmitted helminthiasis (STH) and schistosomiasis are diseases of considerable public health importance in tropical and sub-tropical countries. Globally, 1.2 billion people live in areas endemic for LF [1] and nearly one-fourth of them may already have infection [2]. LF is a leading cause of long-term disability [3]. Schistosomiasis occurs in over 70 countries in the tropics and sub-tropics; 779 million are estimated to be at risk of infection and 207 million to be infected [4]–[6]. 2 billion are estimated to be infected with STH, namely the roundworm (Ascaris lumbricoides), the whipworm (Trichuris trichiura), and the hookworms (Ancylostoma duodenale and Necator americanus), worldwide and several million suffer from the chronic debilitating morbidity [7]–[10].

Overall, only 266 individuals, equivalent to 1.4% of the interviewees who swallowed the drugs reported any side-effects, none of which was judged to be significant enough to justify a visit to the nearest health centre. All the side-effects were mild, the most frequent being fatigue (n = 102), abdominal pain (n = 67), dizziness (n = 57), fever (n = 27) and vomiting (n = 13). These side-effects were accepted and managed by those who reported them. They were transient and all counted for less than 24 hours. No difference in nature and frequency of side-effects was documented during the country-wide intervention between areas where ivermectin and albendazole only were distributed and areas where praziquantel was also added to the package.

The results of the pilot intervention in Kinyasini and Mtambile were considered representative of the worst possible epidemiological scenarios in Zanzibar and as such were deemed sufficient to justify the implementation of the first nationwide intervention, in which ivermectin and albendazole currently recommended for elimination of LF and praziquantel for control of schistosomiasis were administered at the same time. The first national scale triple therapy carried out in Africa or indeed globally.



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