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Randomized Controlled Trial
. 2020 Jun 8;14(6):e0008298.
doi: 10.1371/journal.pntd.0008298. eCollection 2020 Jun.

Safety and efficacy of co-administered diethylcarbamazine, albendazole and ivermectin during mass drug administration for lymphatic filariasis in Haiti: Results from a two-armed, open-label, cluster-randomized, community study

Affiliations
Randomized Controlled Trial

Safety and efficacy of co-administered diethylcarbamazine, albendazole and ivermectin during mass drug administration for lymphatic filariasis in Haiti: Results from a two-armed, open-label, cluster-randomized, community study

Christine L Dubray et al. PLoS Negl Trop Dis. .

Abstract

In Haiti, 22 communes still require mass drug administration (MDA) to eliminate lymphatic filariasis (LF) as a public health problem. Several clinical trials have shown that a single oral dose of ivermectin (IVM), diethylcarbamazine (DEC) and albendazole (ALB) (IDA) is more effective than DEC plus ALB (DA) for clearing Wuchereria bancrofti microfilariae (Mf). We performed a cluster-randomized community study to compare the safety and efficacy of IDA and DA in an LF-endemic area in northern Haiti. Ten localities were randomized to receive either DA or IDA. Participants were monitored for adverse events (AE), parasite antigenemia, and microfilaremia. Antigen-positive participants were retested one year after MDA to assess treatment efficacy. Fewer participants (11.0%, 321/2917) experienced at least one AE after IDA compared to DA (17.3%, 491/2844, P<0.001). Most AEs were mild, and the three most common AEs reported were headaches, dizziness and abdominal pain. Serious AEs developed in three participants who received DA. Baseline prevalence for filarial antigenemia was 8.0% (239/3004) in IDA localities and 11.5% (344/2994) in DA localities (<0.001). Of those with positive antigenemia, 17.6% (42/239) in IDA localities and 20.9% (72/344, P = 0.25) in DA localities were microfilaremic. One year after treatment, 84% percent of persons with positive filarial antigen tests at baseline could be retested. Clearance rates for filarial antigenemia were 20.5% (41/200) after IDA versus 25.4% (74/289) after DA (P = 0.3). However, 94.4% (34/36) of IDA recipients and 75.9% (44/58) of DA recipients with baseline microfilaremia were Mf negative at the time of retest (P = 0.02). Thus, MDA with IDA was at least as well tolerated and significantly more effective for clearing Mf compared to the standard DA regimen in this study. Effective MDA coverage with IDA could accelerate the elimination of LF as a public health problem in the 22 communes that still require MDA in Haiti.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Localities randomly assigned to treatment regimen (DA or IDA) and position of houses included in the 2016 census.
DA, diethylcarbamazine plus albendazole; IDA, ivermectin plus diethylcarbamazine and albendazole.
Fig 2
Fig 2
Study diagram for participants included in the safety (solid line) and efficacy study (dash line). DA, diethylcarbamazine plus albendazole; IDA, ivermectin plus diethylcarbamazine and albendazole; CFA, circulating filarial antigenemia; Mf, microfilariae. Cluster randomization was used for treatment allocation for each locality.
Fig 3
Fig 3
Proportion of participants CFA positive (A) and Mf positive (B) by age-group and sex before receiving treatment (baseline). CFA, circulating filarial antigenemia; Mf, microfilariae.
Fig 4
Fig 4
Males (A) and females (B) included in the census who enrolled in the study by age-group.
Fig 5
Fig 5. Forest plot showing adjusted odds ratios for factors associated with adverse events following treatment for lymphatic filariasis.
Fig 6
Fig 6. Frequencies of the most commonly observed adverse events (AEs) by type of treatment.
Frequencies are expressed as percentages of participants who were assessed for AEs after treatment.
Fig 7
Fig 7. FTS score distribution at baseline and one year after treatment by type of treatment.
FTS, Filariasis Test Strip.
Fig 8
Fig 8. Microfilaremia reduction 12 months after treatment by type of treatment.
DA, diethylcarbamazine plus albendazole; IDA, ivermectin plus diethylcarbamazine and albendazole; Mf, microfilariae.

References

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