Mass drug administration of ivermectin in south-eastern Senegal reduces the survivorship of wild-caught, blood fed malaria vectors

Abstract

Background: In south-eastern Senegal, malaria and onchocerciasis are co-endemic. Onchocerciasis in this region has been controlled by once or twice yearly mass drug administration (MDA) with ivermectin (IVM) for over fifteen years. Since laboratory-raised Anopheles gambiae s.s. are susceptible to ivermectin at concentrations found in human blood post-ingestion of IVM, it is plausible that a similar effect could be quantified in the field, and that IVM might have benefits as a malaria control tool.

Methods: In 2008 and 2009, wild-caught blood fed An. gambiae s.l. mosquitoes were collected from huts of three pairs of Senegalese villages before and after IVM MDAs. Mosquitoes were held in an insectary to assess their survival rate, subsequently identified to species, and their blood meals were identified. Differences in mosquito survival were statistically analysed using a Glimmix model. Lastly, changes in the daily probability of mosquito survivorship surrounding IVM MDAs were calculated, and these data were inserted into a previously developed, mosquito age-structured model of malaria transmission.

Results: Anopheles gambiae s.s. (P < 0.0001) and Anopheles arabiensis (P = 0.0191) from the treated villages had significantly reduced survival compared to those from control villages. Furthermore, An gambiae s.s. caught 1-6 days after MDA in treated villages had significantly reduced survival compared to control village collections (P = 0.0003), as well as those caught pre-MDA (P < 0.0001) and >7 days post-MDA (P < 0.0001). The daily probability of mosquito survival dropped >10% for the six days following MDA. The mosquito age-structured model of malaria transmission demonstrated that a single IVM MDA would reduce malaria transmission (Ro) below baseline for at least eleven days, and that repeated IVM MDAs would result in a sustained reduction in malaria Ro.

Conclusions: Ivermectin MDA significantly reduced the survivorship of An. gambiae s.s. for six days past the date of the MDA, which is sufficient to temporarily reduce malaria transmission. Repeated IVM MDAs could be a novel and integrative malaria control tool in areas with seasonal transmission, and which would have simultaneous impacts on neglected tropical diseases in the same villages.

Figure 1

Percent survivorship of aspirated An. gambiae s.s. grouped by treatment and phase. Percent survivorship of all aspirated An. gambiae s.s. (N = 1265) held five days post-capture from all three replicates. Standard error bars represent the percent survivorship variation of all mosquitoes from each village grouped within each treatment and phase.

Figure 2

Glimmix model estimated percent survivorship of An. gambiae s.s. grouped by treatment and phase. Glimmix model estimated percent survivorship of all An. gambiae s.s. (N = 1265) held five days post-capture from all three replicates. * Treatment by phase was significant (F-value = 18.27, P < 0.0001). Treatment at phase 2 significantly differed from control at phase 2 (t-value = 4.01, P = 0.0003), treatment at phase 1 (t-value = 8.31, P < 0.0001), and treatment at phase 3 (t-value = -4.61, P < 0.0001).

Figure 3

Percent survivorship of aspirated An. arabiensis grouped by treatment and phase. Percent survivorship of all aspirated An. arabiensis (N = 153) held five days post-capture from Nathia and Damboucoye. Standard error bars represent the percent survivorship variation of all mosquitoes from each village grouped within each treatment and phase.

Figure 4

Glimmix model estimated percent survivorship of An. arabiensis grouped by treatment and phase. Glimmix model estimated percent survivorship of all An. arabiensis (N = 153) held five days post-capture from Nathia and Damboucoye. *Treatment was significant (F-value = 7.01, P = 0.0191).

Figure 5

Percent composition of blood meal sources of aspirated An. gambiae s.l. The percent blood meal sources of a subset of An. gambiae s.s. (n = 139) and An. arabiensis (n = 32) aspirated from all five villages in 2008 and 2009.

Figure 6

Predicted relationship between MDA and changes in malaria R₀. Relative malaria R₀ values < 1.0 indicate reduction in transmission potential, values > 1.0 indicate increase in transmission potential, while 1.0 (green line in 6A) indicates no change. A) Ideal situation of 100% coverage with MDA, administered every 7 (black), 14 (blue) or 30 (red) days. B) Average relative R₀ for a range of MDA coverage levels (10% to 100%) and treatment regimes (every 7 to 30 days).