Studies on the development and survival of anopheles gambiae sensu stricto at various temperatures and relative humidities

Anopheles gambiae sensu stricto is the most efficient malaria vector in Africa. Recent advances in mapping the distribution of this vector have exploited the relationship between climatic factors and vector parameters such as growth, survival and reproduction. This work was designed to investigate the effect of temperature and humidity on the development and survival of the vector and to test the use of recently developed tools in describing its distribution. The development rate and survival of the aquatic stages of the vector were investigated at 16 constant temperatures. Adults were produced between 16 -34ºC with a peak development rate at 28ºC and peak number of adults at 22 -26ºC. Larvae survived for less than 7 days at 10º, 12º, 38 º, and 40ºC but for more than 5 weeks, at 14-18ºC without any development of adults. Laboratory models accurately predicted development times at natural breeding sites in The Gambia suggesting the applicability of the models to field situations. The survival and mortality rates of adult An. gambiae s.s. were monitored at combinations of temperatures from 0-45ºC at 5 intervals and 40%, 60%, 80% and 100% relative humidity. Survival was highest at 15-25ºC and 60-100% relative humidity. The temperature - larva development relation was used to produce a distribution map across Africa while climatic data from sites at which chromosomal forms of the insect have been found were used to map the distribution of the forms across West Africa. Climate is an important determinant of insect distribution and the use of climate and vector parameters in describing or predicting vector and disease distribution will provide a cheaper and less labour intensive tool than traditional methods

Consistently high estimates for the proportion of human exposure to malaria vector populations occurring indoors in rural Africa.

BACKGROUND: Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) are highly effective tools for controlling malaria transmission in Africa because the most important vectors, from the Anopheles gambiae complex and the A. funestus group, usually prefer biting humans indoors at night. METHODS: Matched surveys of mosquito and human behaviour from six rural sites in Burkina Faso, Tanzania, Zambia, and Kenya, with ITN use ranging from 0.2% to 82.5%, were used to calculate the proportion of human exposure to An. gambiae sensu lato and An. funestus s.l. that occurs indoors (πi), as an indicator of the upper limit of personal protection that indoor vector control measures can provide. This quantity was also estimated through use of a simplified binary analysis (π(i)(B)) so that the proportions of mosquitoes caught indoors (Pi), and between the first and last hours at which most people are indoors (Pfl) could also be calculated as underlying indicators of feeding by mosquitoes indoors or at night, respectively. RESULTS: The vast majority of human exposure to Anopheles bites occurred indoors (π(i)(B)= 0.79-1.00). Neither An. gambiae s.l. nor An. funestus s.l. strongly preferred feeding indoors (P(i) = 0.40-0.63 and 0.22-0.69, respectively), but they overwhelmingly preferred feeding at times when most humans were indoors (P(fl) = 0.78-1.00 and 0.86-1.00, respectively). CONCLUSIONS: These quantitative summaries of behavioural interactions between humans and mosquitoes constitute a remarkably consistent benchmark with which future observations of vector behaviour can be compared. Longitudinal monitoring of these quantities is vital to evaluate the effectiveness of ITNs and IRS and the need for complementary measures that target vectors outdoors

Ovipositional periodicity of caged Anopheles gambiae individuals

© 2008 Fritz et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Consistently high estimates for the proportion of human exposure to malaria vector populations occurring indoors in rural Africa

Background Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) are highly effective tools for controlling malaria transmission in Africa because the most important vectors, from the Anopheles gambiae complex and the A. funestus group, usually prefer biting humans indoors at night. Methods Matched surveys of mosquito and human behaviour from six rural sites in Burkina Faso, Tanzania, Zambia, and Kenya, with ITN use ranging from 0.2% to 82.5%, were used to calculate the proportion of human exposure to An. gambiae sensu lato and An. funestus s.l. that occurs indoors (πi), as an indicator of the upper limit of personal protection that indoor vector control measures can provide. This quantity was also estimated through use of a simplified binary analysis (πiB) so that the proportions of mosquitoes caught indoors (Pi), and between the first and last hours at which most people are indoors (Pfl) could also be calculated as underlying indicators of feeding by mosquitoes indoors or at night, respectively. Results The vast majority of human exposure to Anopheles bites occurred indoors (πiB = 0.79-1.00). Neither An. gambiae s.l. nor An. funestus s.l. strongly preferred feeding indoors (Pi = 0.40-0.63 and 0.22-0.69, respectively), but they overwhelmingly preferred feeding at times when most humans were indoors (Pfl = 0.78-1.00 and 0.86-1.00, respectively). Conclusions These quantitative summaries of behavioural interactions between humans and mosquitoes constitute a remarkably consistent benchmark with which future observations of vector behaviour can be compared. Longitudinal monitoring of these quantities is vital to evaluate the effectiveness of ITNs and IRS and the need for complementary measures that target vectors outdoor

Presence of the knockdown resistance mutation, Vgsc-1014F in Anopheles gambiae and An. arabiensis in western Kenya

INTRODUCTION: The voltage gated sodium channel mutation Vgsc-1014S (kdr-east) was first reported in Kenya in 2000 and has since been observed to occur at high frequencies in the local Anopheles gambiae s.s. POPULATION: The mutation Vgsc-1014F has never been reported from An. gambiae Complex complex mosquitoes in Kenya. FINDINGS: Molecularly confirmed An. gambiae s.s. (hereafter An. gambiae) and An. arabiensis collected from 4 different parts of western Kenya were genotyped for kdr from 2011 to 2013. Vgsc-1014F was observed to have emerged, apparently, simultaneously in both An. gambiae and An. arabiensis in 2012. A portion of the samples were submitted for sequencing in order to confirm the Vgsc-1014F genotyping results. The resulting sequence data were deposited in GenBank (Accession numbers: KR867642-KR867651, KT758295-KT758303). A single Vgsc-1014F haplotype was observed suggesting, a common origin in both species. CONCLUSION: This is the first report of Vgsc-1014F in Kenya. Based on our samples, the mutation is present in low frequencies in both An. gambiae and An. arabiensis. It is important that we start monitoring relative frequencies of the two kdr genes so that we can determine their relative importance in an area of high insecticide treated net ownership

Efficacy and Safety of High-Dose Ivermectin for Reducing Malaria Transmission (IVERMAL): Protocol for a Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Trial in Western Kenya

Background: Innovative approaches are needed to complement existing tools for malaria elimination. Ivermectin is a broad spectrum antiparasitic endectocide clinically used for onchocerciasis and lymphatic filariasis control at single doses of 150‐200 mcg/kg. It also shortens the lifespan of mosquitoes that feed on individuals recently treated with ivermectin. However, the effect after a 150‐200 mcg/kg oral dose is short‐lived (6‐11 days). Modelling suggests higher doses, that prolong the mosquitocidal effects, are needed to make a significant contribution to malaria elimination. Ivermectin has a wide therapeutic index and previous studies have shown doses up to 2,000 mcg/kg, i.e. 10x the US Food and Drug Administration approved dose, are well tolerated and safe; the highest dose used for onchocerciasis is single‐dose 800 mcg/kg. Objective: To determine the safety, tolerability, and efficacy of ivermectin 0, 300, 600 mcg/kg/day for 3 days, when provided with a standard 3‐day course of the antimalarial dihydroartemisinin‐piperaquine, on mosquito survival. Methods: This is a double‐blind, randomised, placebo‐controlled, parallel‐group, 3‐arm, dose‐finding trial in adults with uncomplicated malaria. Monte Carlo simulations based on pharmacokinetic modelling were performed to determine the optimum dosing regimens to be tested. Modelling showed that a 3‐day regimen of 600 mcg/kg/day achieves similar median (5‐95 percentiles) Cmax concentrations of ivermectin to single‐dose of 800 mcg/kg, while increasing the median time above the LC50 (16 ng/mL) from 1.9 days (1.0‐5.7) to 6.8 (3.8‐13.4) days. The 300 mcg/kg/day dose was chosen at 50% of the higher dose to allow evaluation of the dose response. Mosquito survival will be assessed daily up to 28 days in laboratory‐reared Anopheles gambiae s.s. populations fed on patients’ blood taken at days 0, 2 (Cmax), 7 (primary outcome), 10, 14, 21, and 28 after the start of treatment. Safety outcomes include QT‐prolongation and mydriasis. The trial will be conducted in 6 health facilities in western Kenya and requires a sample size of 141 participants (47 per arm). Sub‐studies include: (1) rich pharmacokinetics and (2) direct skin vs membrane feeding assays. Results: Recruitment started July 20th, 2015. Data collection was completed on July 2nd, 2016. Unblinding and analysis will commence once the database has been completed, cleaned and locked. Discussion: High‐dose ivermectin, if found to be safe and well tolerated, might offer a promising new tool for malaria elimination. Trial registration: ClinicalTrials.gov: NCT02511353 (July 15, 2015)

Anopheles gambiae: historical population decline associated with regional distribution of insecticide-treated bed nets in western Nyanza Province, Kenya

<p>Abstract</p> <p>Background</p> <p>High coverage of insecticide-treated bed nets in Asembo and low coverage in Seme, two adjacent communities in western Nyanza Province, Kenya; followed by expanded coverage of bed nets in Seme, as the Kenya national malaria programme rolled out; provided a natural experiment for quantification of changes in relative abundance of two primary malaria vectors in this holoendemic region. Both belong to the <it>Anopheles gambiae sensu lato (s.l.) </it>species complex, namely <it>A. gambiae sensu stricto (s.s.) </it>and <it>Anopheles arabiensis</it>. Historically, the former species was proportionately dominant in indoor resting collections of females.</p> <p>Methods</p> <p>Data of the relative abundance of adult <it>A. gambiae s.s. </it>and <it>A. arabiensis </it>sampled from inside houses were obtained from the literature from 1970 to 2002 for sites west of Kisumu, Kenya, to the region of Asembo ca. 50 km from the city. A sampling transect was established from Asembo (where bed net use was high due to presence of a managed bed net distribution programme) eastward to Seme, where no bed net programme was in place. Adults of <it>A. gambiae s.l. </it>were sampled from inside houses along the transect from 2003 to 2009, as were larvae from nearby aquatic habitats, providing data over a nearly 40 year period of the relative abundance of the two species. Relative proportions of <it>A. gambiae s.s. </it>and <it>A. arabiensis </it>were determined for each stage by identifying species by the polymerase chain reaction method. Household bed net ownership was measured with surveys during mosquito collections. Data of blood host choice, parity rate, and infection rate for <it>Plasmodium falciparum </it>in <it>A. gambiae s.s. </it>and <it>A. arabiensis </it>were obtained for a sample from Asembo and Seme from 2005.</p> <p>Results</p> <p><it>Anopheles gambiae s.s. </it>adult females from indoor collections predominated from 1970 to 1998 (ca. 85%). Beginning in 1999, <it>A. gambiae </it>s.s decreased proportionately relative to <it>A. arabiensis</it>, then precipitously declined to rarity coincident with increased bed net ownership as national bed net distribution programmes commenced in 2004 and 2006. By 2009, <it>A. gambiae s.s. </it>comprised proportionately ca. 1% of indoor collections and <it>A. arabiensis </it>99%. In Seme compared to Asembo in 2003, proportionately more larvae were <it>A. gambiae s.s.</it>, larval density was higher, and more larval habitats were occupied. As bed net use rose in Seme, the proportion of <it>A. gambiae </it>larvae declined as well. These trends continued to 2009. Parity and malaria infection rates were lower in both species in Asembo (high bed net use) compared to Seme (low bed net use), but host choice did not vary within species in both communities (predominantly cattle for <it>A. arabiensis</it>, humans for <it>A. gambiae s.s.</it>).</p> <p>Conclusions</p> <p>A marked decline of the <it>A. gambiae s.s. </it>population occurred as household ownership of bed nets rose in a region of western Kenya over a 10 year period. The increased bed net coverage likely caused a mass effect on the composition of the <it>A. gambiae s.l. </it>species complex, resulting in the observed proportionate increase in <it>A. arabiensis </it>compared to its closely related sibling species, <it>A. gambiae s.s. </it>These observations are important in evaluating the process of regional malaria elimination, which requires sustained vector control as a primary intervention.</p

Infant and child mortality in relation to malaria transmission in KEMRI/CDC HDSS, Western Kenya: validation of verbal autopsy

Malaria transmission reduction is a goal of many malaria control programmes. Little is known of how much mortality can be reduced by specific reductions in transmission. Verbal autopsy (VA) is widely used for estimating malaria specific mortality rates, but does not reliably distinguish malaria from other febrile illnesses. Overall malaria attributable mortality includes both direct and indirect deaths. It is unclear what proportion of the deaths averted by reducing malaria transmission are classified as malaria in VA.; Both all-cause, and cause-specific mortality reported by VA for children under 5 years of age, were assembled from the KEMRI/CDC health and demographic surveillance system in Siaya county, rural Western Kenya for the years 2002-2004. These were linked to household-specific estimates of the Plasmodium falciparum entomological inoculation rate (EIR) based on high resolution spatio-temporal geostatistical modelling of entomological data. All-cause and malaria specific mortality (by VA), were analysed in relation to EIR, insecticide-treated net use (ITN), socioeconomic status (SES) and parameters describing space-time correlation. Time at risk for each child was analysed using Bayesian geostatistical Cox proportional hazard models, with time-dependent covariates. The outputs were used to estimate the diagnostic performance of VA in measuring mortality that can be attributed to malaria exposure.; The overall under-five mortality rate was 80 per 1000 person-years during the study period. Eighty-one percent of the total deaths were assigned causes of death by VA, with malaria assigned as the main cause of death except in the neonatal period. Although no trend was observed in malaria-specific mortality assessed by VA, ITN use was associated with reduced all-cause mortality in infants (hazard ratio 0.15, 95% CI 0.02, 0.63) and the EIR was strongly associated with both all-cause and malaria-specific mortality. 48.2% of the deaths could be attributed to malaria by analysing the exposure-response relationship, though only 20.5% of VAs assigned malaria as the cause and the sensitivity of VAs was estimated to be only 26%. Although VAs assigned some deaths to malaria even in areas where there was estimated to be no exposure, the specificity of the VAs was estimated to be 85%.; Interventions that reduce P. falciparum transmission intensity will not only significantly reduce malaria-diagnosed mortality, but also mortality assigned to other causes in under-5 year old children in endemic areas. In this setting, the VA tool based on clinician review substantially underestimates the number of deaths that could be averted by reducing malaria exposure in childhood, but has a reasonably high specificity. This suggests that malaria transmission-reducing interventions such as ITNs can potentially reduce overall child mortality by as much as twice the total direct malaria burden estimated from VAs