Before the MDA with ivermectin, the density of the indoor and outdoor populations of Anopheles mosquitoes was lower by more than five times in the intervention communities than in the control communities. This difference was statistically significant between the indoor populations. In contrast, there was no statistically significant difference in the density of Culex between the two study areas. A similar observation was reported in a longitudinal study carried out in north-eastern Tanzania, where a decline in the density of Anopheles was observed while the abundance of Culex mosquitoes remained unaffected [13,14]. Derua et al.  attributed this observation in Tanzania to the use of ivermectin for the control of onchocerciasis and LF in the area for more than 10 years. In our study, the intervention communities had received ivermectin MDA for at least five years while there has been no MDA in the control communities within the same period. Although we did not conduct a longitudinal investigation, the baseline densities observed in our study suggest that the lower density of Anopheles in the intervention communities may also be attributable to the long-term use of ivermectin for onchocerciasis and LF control in the communities.
A reduction in the daily survival rate is recognised as a primary effect of ivermectin MDA on malaria vectors in insectary-based studies . In our field-based evaluation, this translated to a reduction in the abundance of malaria vectors after MDA. In the intervention communities, the indoor density of Anopheles mosquitoes reduced 2-3 days after ivermectin MDA, and a rebound had become noticeable after two weeks. These changes in the malaria vector abundance followed a consistently similar pattern in the two intervention communities. In contrast, the abundance of Culex sp. increased significantly in the intervention communities 2-3 days after ivermectin MDA. Studies have shown that unlike the Anopheles sp., the other mosquito vectors are not readily susceptible to the concentrations of ivermectin found in human blood after MDA with the currently recommended dosage of the drug [17,15]. This indicates that factors other than the MDA likely account for the observed reduction in the indoor density of Culex sp. in one of the intervention communities.
The short-lived reduction in the indoor density of Anopheles sp. in the two intervention communities is similar to observations from previous studies on the life span or survival rate of Anopheles mosquitoes captured from villages treated with ivermectin. In a study carried out in Senegal, Liberia and Burkina Faso, reduction in the daily survival rate of An. gambiae was only observable within the first week after MDA . Also, a clinical trial in Burkina Faso showed that mortality increased for up to 7 days in An. gambiae which were fed with blood from individuals treated with a single dose of ivermectin . It is generally believed that the recommended dose of ivermectin for onchocerciasis and LF control programmes will not have long-lasting lethal effects on malaria vectors [18,17].
On the other hand, disruption in the age structure of Anopheles mosquitoes can last up to three weeks after ivermectin MDA [19,16]. In our study, the proportion of parous (older) female Anopheles of the indoor population also remained significantly reduced by more than 20% in the intervention communities two weeks after ivermectin MDA. This significant shift to a younger population of female Anopheles sp. has important implication for malaria transmission because the older or parous female mosquitoes are commonly the infectious vectors . It has been indicated that the impact on the mosquito population age structure may be the main mechanism by which ivermectin MDA affects malaria transmission . Ivermectin-treated blood meal kills most of the infectious mosquitoes leaving behind a population predominated by young nulliparous mosquitoes, which require some time to become infectious .
Importantly, the reduction in the indoor density of Anopheles mosquitoes by 29.07% in the intervention communities 2-3 days after MDA was statistically significant. However, our models suggest that ivermectin MDA did not show a clear effect on the indoor density of the Anopheles mosquitoes. Using the relative exposure to ivermectin during the three sampling intervals, the model indicated that ivermectin exposure alone showed no significant effect on the indoor density of Anopheles sp. but showed a significant effect when other factors are considered. On the other hand, ivermectin exposure showed a clear effect on the parity rate of the indoor Anopheles mosquitoes in the intervention communities in our generalized linear models. Hence, although ivermectin MDA may not have a long-lasting impact on the density of Anopheles sp., it reduced the proportion of parous older mosquitoes which are critical for the transmission of malaria in the localities.
Our finding suggests that ivermectin MDA will have more profound effects of on the density and parity rate of the Anopheles populations at higher MDA coverage. In Amini, where the coverage of ivermectin MDA was significantly higher, the density and parity rate of the indoor Anopheles population reduced by 63% and 57% respectively 2-3 days after MDA. These reductions in the density and parity rate were higher and statistically significant compared to Kugba-Ajagbe where the MDA coverage was lower. Therefore, higher MDA coverage in the intervention communities has the potential to enhance the mosquitocidal effects of ivermectin than the current observations. However, it is interesting that although ivermectin MDA coverage was lower in Kugba-Ajagbe, the age structure (parity rate) of indoor Anopheles mosquitoes was disrupted for a longer period of time compared to Amini where the coverage was higher. Also, the indoor density of Anopheles in Kugba-Ajagbe did not rebound fully two weeks after MDA unlike in Amini. A study in Burkina Faso suggests that ivermectin accumulates in adipose tissues in female individuals as a slow-release mechanism and accounts for higher plasma concentrations as well as lethal effects that are stronger and more prolonged in the Anopheles mosquitoes that feed on female individuals . In our study, more female individuals constituted the persons treated with ivermectin in Kugba-Ajagbe than Amini. Hence, this may also account for the more prolonged disruption of the density and age structure of the indoor Anopheles population in Kugba-Ajagbe despite the lower MDA coverage.
Ivermectin did not show an effect on the outdoor populations of malaria vectors in our study. Unlike the indoor Anopheles populations, the outdoor density of Anopheles mosquitoes in the intervention communities increased 2-3 days after ivermectin MDA. Although the parity rate of the outdoor Anopheles population decreased progressively after MDA, our models showed no effects of ivermectin MDA on both the density and parity rate of outdoor Anopheles populations. More so, variations in the density and parity rate of the outdoor Anopheles populations in the two intervention communities did not show corresponding patterns as observed for the indoor populations.