Early morning anopheline mosquito biting, a potential driver of malaria transmission in Busia County, western Kenya.

BACKGROUND: Insecticide-treated nets (ITNs) contributed significantly to the decline in malaria since 2000. Their protective efficacy depends not only on access, use, and net integrity, but also location of people within the home environment and mosquito biting profiles. Anopheline mosquito biting and human location data were integrated to identify potential gaps in protection and better understand malaria transmission dynamics in Busia County, western Kenya. METHODS: Direct observation of human activities and human landing catches (HLC) were performed hourly between 1700 to 0700 h. Household members were recorded as home or away; and, if at home, as indoors/outdoors, awake/asleep, and under a net or not. Aggregated data was analysed by weighting hourly anopheline biting activity with human location. Standard indicators of human-vector interaction were calculated using a Microsoft Excel template. RESULTS: There was no significant difference between indoor and outdoor biting for Anopheles gambiae sensu lato (s.l.) (RR = 0.82; 95% CI 0.65-1.03); significantly fewer Anopheles funestus were captured outdoors than indoors (RR = 0.41; 95% CI 0.25-0.66). Biting peaked before dawn and extended into early morning hours when people began to awake and perform routine activities, between 0400-0700 h for An. gambiae and 0300-0700 h for An. funestus. The study population away from home peaked at 1700-1800 h (58%), gradually decreased and remained constant at 10% throughout the night, before rising again to 40% by 0600-0700 h. When accounting for resident location, nearly all bites within the peri-domestic space (defined as inside household structures and surrounding outdoor spaces) occurred indoors for unprotected people (98%). Using an ITN while sleeping was estimated to prevent 79% and 82% of bites for An. gambiae and An. funestus, respectively. For an ITN user, most remaining exposure to bites occurred indoors in the hours before bed and early morning. CONCLUSION: While use of an ITN was estimated to prevent most vector bites in this context, results suggest gaps in protection, particularly in the early hours of the morning when biting peaks and many people are awake and active. Assessment of additional human exposure points, including outside of the peri-domestic setting, are needed to guide supplementary interventions for transmission reduction.

Screening eaves of houses reduces indoor mosquito density in rural, western Kenya.

BACKGROUND: Despite the scale-up of insecticide-treated nets and indoor residual spraying, the bulk of malaria transmission in western Kenya still occurs indoors, late at night. House improvement is a potential long-term solution to further reduce malaria transmission in the region. METHODS: The impact of eave screening on mosquito densities was evaluated in two rural villages in western Kenya. One-hundred-and-twenty pairs of structurally similar, neighbouring houses were used in the study. In each pair, one house was randomly selected to receive eave screening at the beginning of the study while the other remained unscreened until the end of the sampling period. Mosquito sampling was performed monthly by motorized aspiration method for 4 months. The collected mosquitoes were analysed for species identification. RESULTS: Compared to unscreened houses, significantly fewer female Anopheles funestus (RR = 0.40, 95% CI 0.29-0.55), Anopheles gambiae Complex (RR = 0.46, 95% CI 0.34-0.62) and Culex species (RR = 0.53, 95% CI 0.45-0.61) were collected in screened houses. No significant differences in the densities of the mosquitoes were detected in outdoor collections. Significantly fewer Anopheles funestus were collected indoors from houses with painted walls (RR = 0.05, 95% CI 0.01-0.38) while cooking in the house was associated with significantly lower numbers of Anopheles gambiae Complex indoors (RR = 0.60, 95% CI 0.45-0.79). Nearly all house owners (99.6%) wanted their houses permanently screened, including 97.7% that indicated a willingness to use their own resources. However, 99.2% required training on house screening. The cost of screening a single house was estimated at KES6,162.38 (US$61.62). CONCLUSION: Simple house modification by eave screening has the potential to reduce the indoor occurrence of both Anopheles and Culex mosquito species. Community acceptance was very high although education and mobilization may be needed for community uptake of house modification for vector control. Intersectoral collaboration and favourable government policies on housing are important links towards the adoption of house improvements for malaria control.

Human Direct Skin Feeding Versus Membrane Feeding to Assess the Mosquitocidal Efficacy of High-Dose Ivermectin (IVERMAL Trial).

BACKGROUND: Ivermectin is being considered for mass drug administration for malaria, due to its ability to kill mosquitoes feeding on recently treated individuals. In a recent trial, 3-day courses of 300 and 600 mcg/kg/day were shown to kill Anopheles mosquitoes for at least 28 days post-treatment when fed patients' venous blood using membrane feeding assays. Direct skin feeding on humans may lead to higher mosquito mortality, as ivermectin capillary concentrations are higher. We compared mosquito mortality following direct skin and membrane feeding. METHODS: We conducted a mosquito feeding study, nested within a randomized, double-blind, placebo-controlled trial of 141 adults with uncomplicated malaria in Kenya, comparing 3 days of ivermectin 300 mcg/kg/day, ivermectin 600 mcg/kg/day, or placebo, all co-administered with 3 days of dihydroartemisinin-piperaquine. On post-treatment day 7, direct skin and membrane feeding assays were conducted using laboratory-reared Anopheles gambiae sensu stricto. Mosquito survival was assessed daily for 28 days post-feeding. RESULTS: Between July 20, 2015, and May 7, 2016, 69 of 141 patients participated in both direct skin and membrane feeding (placebo, n = 23; 300 mcg/kg/day, n = 24; 600 mcg/kg/day, n = 22). The 14-day post-feeding mortality for mosquitoes fed 7 days post-treatment on blood from pooled patients in both ivermectin arms was similar with direct skin feeding (mosquitoes observed, n = 2941) versus membrane feeding (mosquitoes observed, n = 7380): cumulative mortality (risk ratio 0.99, 95% confidence interval [CI] 0.95-1.03, P = .69) and survival time (hazard ratio 0.96, 95% CI 0.91-1.02, P = .19). Results were consistent by sex, by body mass index, and across the range of ivermectin capillary concentrations studied (0.72-73.9 ng/mL). CONCLUSIONS: Direct skin feeding and membrane feeding on day 7 resulted in similar mosquitocidal effects of ivermectin across a wide range of drug concentrations, suggesting that the mosquitocidal effects seen with membrane feeding accurately reflect those of natural biting. Membrane feeding, which is more patient friendly and ethically acceptable, can likely reliably be used to assess ivermectin's mosquitocidal efficacy. CLINICAL TRIALS REGISTRATION: NCT02511353.

Differences in malaria vector biting behavior and changing vulnerability to malaria transmission in contrasting ecosystems of western Kenya.

BACKGROUND: Designing, implementing, and upscaling of effective malaria vector control strategies necessitates an understanding of when and where transmission occurs. This study assessed the biting patterns of potentially infectious malaria vectors at various hours, locations, and associated human behaviors in different ecological settings in western Kenya. METHODS: Hourly indoor and outdoor catches of human-biting mosquitoes were sampled from 19:00 to 07:00 for four consecutive nights in four houses per village. The human behavior study was conducted via questionnaire surveys and observations. Species within the Anopheles gambiae complex and Anopheles funestus group were distinguished by polymerase chain reaction (PCR) and the presence of Plasmodium falciparum circumsporozoite proteins (CSP) determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Altogether, 2037 adult female anophelines were collected comprising the An. funestus group (76.7%), An. gambiae sensu lato (22.8%), and Anopheles coustani (0.5%). PCR results revealed that Anopheles arabiensis constituted 80.5% and 79% of the An. gambiae s.l. samples analyzed from the lowland sites (Ahero and Kisian, respectively). Anopheles gambiae sensu stricto (hereafter An. gambiae) (98.1%) was the dominant species in the highland site (Kimaeti). All the An. funestus s.l. analyzed belonged to An. funestus s.s. (hereafter An. funestus). Indoor biting densities of An. gambiae s.l. and An. funestus exceeded the outdoor biting densities in all sites. The peak biting occurred in early morning between 04:30 and 06:30 in the lowlands for An. funestus both indoors and outdoors. In the highlands, the peak biting of An. gambiae occurred between 01:00 and 02:00 indoors. Over 50% of the study population stayed outdoors from 18:00 to 22:00 and woke up at 05:00, coinciding with the times when the highest numbers of vectors were collected. The sporozoite rate was higher in vectors collected outdoors, with An. funestus being the main malaria vector in the lowlands and An. gambiae in the highlands. CONCLUSION: This study shows heterogeneity of anopheline distribution, high outdoor malaria transmission, and early morning peak biting activity of An. funestus when humans are not protected by bednets in the lowland sites. Additional vector control efforts targeting the behaviors of these vectors, such as the use of non-pyrethroids for indoor residual spraying and spatial repellents outdoors, are needed.

Impact of indoor residual spraying with pirimiphos-methyl (Actellic 300CS) on entomological indicators of transmission and malaria case burden in Migori County, western Kenya.

Indoor residual spraying (IRS) of insecticides is a major vector control strategy for malaria prevention. We evaluated the impact of a single round of IRS with the organophosphate, pirimiphos-methyl (Actellic 300CS), on entomological and parasitological parameters of malaria in Migori County, western Kenya in 2017, in an area where primary vectors are resistant to pyrethroids but susceptible to the IRS compound. Entomological monitoring was conducted by indoor CDC light trap, pyrethrum spray catches (PSC) and human landing collection (HLC) before and after IRS. The residual effect of the insecticide was assessed monthly by exposing susceptible An. gambiae s.s. Kisumu strain to sprayed surfaces in cone assays and measuring mortality at 24 hours. Malaria case burden data were extracted from laboratory records of four health facilities within the sprayed area and two adjacent unsprayed areas. IRS was associated with reductions in An. funestus numbers in the intervention areas compared to non-intervention areas by 88% with light traps (risk ratio [RR] 0.12, 95% CI 0.07-0.21, p < 0.001) and 93% with PSC collections (RR = 0.07, 0.03-0.17, p < 0.001). The corresponding reductions in the numbers of An. arabiensis collected by PSC were 69% in the intervention compared to the non-intervention areas (RR = 0.31, 0.14-0.68, p = 0.006), but there was no significant difference with light traps (RR = 0.45, 0.21-0.96, p = 0.05). Before IRS, An. funestus accounted for over 80% of Anopheles mosquitoes collected by light trap and PSC in all sites. After IRS, An. arabiensis accounted for 86% of Anopheles collected by PSC and 66% by CDC light trap in the sprayed sites while the proportion in non-intervention sites remained unchanged. No sporozoite infections were detected in intervention areas after IRS and biting rates by An. funestus were reduced to near zero. Anopheles funestus and An. arabiensis were fully susceptible to pirimiphos-methyl and resistant to pyrethroids. The residual effect of Actellic 300CS lasted ten months on mud and concrete walls. Malaria case counts among febrile patients within IRS areas was lower post- compared to pre-IRS by 44%, 65% and 47% in Rongo, Uriri and Nyatike health facilities respectively. A single application of IRS with Actellic 300CS in Migori County provided ten months protection and resulted in the near elimination of the primary malaria vector An. funestus and a corresponding reduction of malaria case count among out-patients. The impact was less on An. arabiensis, most likely due to their exophilic nature.

COVID-19 in sub-Saharan Africa: impacts on vulnerable populations and sustaining home-grown solutions.

This commentary draws on sub-Saharan African health researchers' accounts of their countries' responses to control the spread of COVID-19, including social and health impacts, home-grown solutions, and gaps in knowledge. Limited human and material resources for infection control and lack of understanding or appreciation by the government of the realities of vulnerable populations have contributed to failed interventions to curb transmission, and further deepened inequalities. Some governments have adapted or limited lockdowns due to the negative impacts on livelihoods and taken specific measures to minimize the impact on the most vulnerable citizens. However, these measures may not reach the majority of the poor. Yet, African countries' responses to COVID-19 have also included a range of innovations, including diversification of local businesses to produce personal protective equipment, disinfectants, test kits, etc., which may expand domestic manufacturing capabilities and deepen self-reliance. African and high-income governments, donors, non-governmental organizations, and businesses should work to strengthen existing health system capacity and back African-led business. Social scientific understandings of public perceptions, their interactions with COVID-19 control measures, and studies on promising clinical interventions are needed. However, a decolonizing response to COVID-19 must include explicit and meaningful commitments to sharing the power-the authority and resources-to study and endorse solutions.