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Am J Trop Med Hyg. Jul 1, 2011; 85(1): 3–5.
PMCID: PMC3122335

Ivermectin Mass Drug Administration to Humans Disrupts Malaria Parasite Transmission in Senegalese Villages


Ivermectin mass drug administration (MDA) to humans is used to control onchocerciasis and lymphatic filariasis. Recent field studies have shown an added killing effect of ivermectin MDA against malaria vectors. We report that ivermectin MDA reduced the proportion of Plasmodium falciparum infectious Anopheles gambiae sensu stricto (s.s.) in treated villages in southeastern Senegal. Ivermectin MDA is a different delivery method and has a different mode of action from current malaria control agents. It could be a powerful and synergistic new tool to reduce malaria transmission in regions with epidemic or seasonal malaria transmission, and the prevalence and intensity of neglected tropical diseases.

Every year, malaria afflicts an estimated 500 million people worldwide and kills more than one million people, most of whom are children in sub-Saharan Africa.1,2 Malaria parasite transmission control efforts, especially those intending to scale up to elimination programs, are in urgent need of new integrative tools to achieve their goals.3 Indoor residual spraying and insecticide-treated nets, though highly effective, primarily affect indoor resting and biting Anopheles mosquitoes, and their efficacies are threatened by resistance to currently used insecticides.4 Here, we show that mass drug administration (MDA) of ivermectin to humans in Senegalese villages significantly reduced the proportion of Plasmodium falciparum infectious Anopheles gambiae sensu stricto (s.s.) relative to those caught from nearby control villages for up to 2 weeks post administration. Ivermectin MDA has a different mode of action from currently used malaria parasite transmission control agents, and a unique delivery method that will target malaria vectors regardless of whether they are exophagic, exophilic, or crepuscular blood feeders. Furthermore, ivermectin MDA integrates well with existing malaria control technologies and synergizes with neglected tropical disease (NTD) control efforts.

Ivermectin MDA to humans has been developed as a safe and effective control strategy for NTDs such as onchocerciasis5 and lymphatic filariasis,6 and it can transiently affect the prevalence and intensity of certain soil transmitted helminths.713 Laboratory studies have showed that An. gambiae s.s. mosquitoes can be killed by ivermectin concentrations present in human blood after a standard oral dose.14,15 Results from our field study showed that wild, bloodfed An. gambiae s.s. had significantly reduced survivorship for up to 6 days after ivermectin MDA, and reduced adult Anopheles survivorship from the MDA was predicted in a model to shift the mosquito population age structure so that the basic reproductive number of malaria (R0) was temporarily suppressed.16

Mosquitoes were sampled from five villages in the Sudano-Guinean phytogeographic zone of Senegal in 2008 and 2009. The villages of Boundoucondi, Nathia, Ibel, Damboucoye, and Ndebou are located along a 12 km stretch of road that extends westward from Kédougou, Senegal (Figure 1). Various villages in this region are treated annually by MDA of ivermectin (Mectizan, Merck and Co. Inc., Rahway, NJ) as directed by the African Program for Onchocerciasis Control and the Senegalese Ministry of Health. During this experiment, three villages were treated by ivermectin MDA: Ibel (August 2008), Ndebou (August 2009), and Damboucoye (October 2009). Three pair-matched villages served as untreated controls, Ndebou (August 2008), Boundoucondi (August 2009), and Nathia (October 2009). Permission to collect mosquitoes surrounding these MDAs was given by the Senegalese Ministry of Health and the populations of each village, and the study was reviewed by the Institutional Review Board at Colorado State University. A topographical map (Figure 1) of the villages was created with ArcGIS version 9.3 (ESRI Inc., Redlands, CA).

Figure 1.
Field site map. Topographical map of the five villages where the experiment was conducted in 2008 and 2009.

Indoor resting mosquitoes were aspirated from the insides of peoples' huts for a concurrent study that assessed the effects of ivermectin on Anopheles survivorship and mosquitoes were processed as previously described.16 Anopheles gambiae s.s. that survived 5 days post capture were used for this analysis as they represented the largest group for adequate statistical analysis between treatment and control collections (73.03%, 934/1,279). Individual thoraxes were tested by Taqman polymerase chain reaction for Plasmodium spp. sporozoite detection,17 which used laboratory-confirmed P. falciparum sporozoite-infected An. gambiae s.s. as postitive controls for calibration.

Using accepted rates of adult blood feeding frequency,18,19 we conservatively estimated that it would take 3 days for all potentially infectious An. gambiae present in the area at the time of MDA to imbibe a blood meal from treated people. Therefore, mosquitoes collected from 14 days before ivermectin MDA to 3 days post treatment were placed in the “before” group, whereas mosquitoes collected from 3 days post treatment to 12 days post treatment were placed in the “after” group. However, post-hoc analyses revealed that significant differences were retained between the “before”' and “after” sporozoite rates even if mosquitoes caught 1, 2, and 3 days post ivermectin MDA were placed in the “after” group.

For individual replicates, infection rates were analyzed by logistic regression with effects for village (treated, untreated), period (before, after), and village by period interactions. A combined analysis for all three replicates included effects for village, period, and replicate, village by period, and village by replicate. In both analyses, the village by period interaction tests whether the change in infection rate over period differs between treated and untreated villages. For estimation of means, the village by replicate interaction was removed from the model because the second replicate control village had zero infection rates. Computations were performed with SAS Proc GENMOD.20

Direct measurements presented here show that Plasmodium transmission is indeed significantly disrupted after ivermectin MDA and the effect is sustained for at least 2 weeks. Figure 2 shows a 79% reduction in the mean proportion of P. falciparum sporozoite-infectious An. gambiae s.s. collected 2 weeks following ivermectin MDA in villages from three replicates, whereas there was a 246% increase in the mean proportion of sporozoite-infectious An. gambiae s.s. collected in pair-matched control villages at the same time (treatment by period, degrees of freedom [df] = 1, χ2 = 12.18, P = 0.0005, N = 934).

Figure 2.
The proportion of Plasmodium falciparum infectious Anopheles gambiae s.s. before and after ivermectin MDAs. The mean percent of P. falciparum sporozoite-infectious An. gambiae s.s. were estimated from three replicate collections of mosquitoes in treated ...

This study was conducted on a small spatial scale. All villages are located along a ~12 km stretch of road (Figure 1) where humans, and possibly vectors, moved between treated and control villages, yet there was still a demonstrable effect restricted to treatment villages highlighting that localized Plasmodium transmission control that can be achieved in a single village by MDA. The primary activity of ivermectin is to agonize invertebrate glutamate-gated chloride channels, causing flaccid muscle paralysis and death of the nematodes and insects.21 Insecticides and spatial repellents currently used against malaria vectors do not target these channels,4 and so cross-resistance is less likely. Ivermectin has not been shown to have antimicrobial effects,22 however, our field data do not exclude the possibility that sublethal ivermectin concentrations inhibited the development of Plasmodium in mosquitoes. If such an effect can occur, it may have contributed to the reduction in sporozoite rates and should be tested further.

This study shows that a single ivermectin MDA can significantly reduce the proportion of sporozoite-infectious malaria vectors for at least 2 weeks; further studies are needed to determine the duration of control. If given more frequently, in spaced intervals defined by the duration of control, ivermectin MDAs may be effective for reducing malaria parasite transmission during epidemics or delineated malaria transmission seasons that occur throughout large regions of Africa and other continents. Because many of these regions are co-endemic for ivermectin-susceptible NTDs, more frequent ivermectin MDAs would likely result in enhanced NTD and malaria control.


We thank Doudou Sene, Mactar Mansaly, Rigobert Keita, and Filly Keita for their field support; Meg Gray and Ines Marques da Silva for their laboratory support; the people of Ndebou, Boundoucondi, Damboucoye, Nathia, and Ibel, for allowing us to work in their villages; and the MR-4 repository and Alvaro Molina-Cruz for positive control samples.


Financial support: This work was supported by the NIH grant R21 AI079528, Grand Challenges Explorations grant 51995 from the Bill and Melinda Gates Foundation, and CRC grant 1686174 from Colorado State University.

Authors' addresses: Kevin C. Kobylinski, Massamba Sylla, and Brian D. Foy, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, E-mails: moc.oohay@nivekiksnilybok, ude.etatsoloc@allys.abmassam, and ude.etatsoloc@yof.nairb. Phillip L. Chapman, Department of Statistics, Fort Collins, CO, E-mail: ude.etatsoloc.tats@nampahcp. Moussa D. Sarr, Ministère de la Santé et de la Prévention Médicale, Dakar, Senegal, E-mail: rf.oohay@rrasneidm.

Reprint requests: Brian D. Foy Department of Microbiology, Immunology and Pathology, 1692 Campus delivery, Fort Collins, CO 80523-1692, E-mail: ude.etatsoloc@yof.nairb.


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