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Journal articleNash RK, Lambert B, NGuessan R, et al., 2021,
Systematic review of the entomological impact of insecticide-treated nets evaluated using experimental hut trials in Africa, Current Research in Parasitology & Vector-Borne Diseases, Vol: 1, Pages: 1-13, ISSN: 2667-114X
Resistance of anopheline mosquitoes to pyrethroid insecticides is spreading rapidly across sub-Saharan Africa, diminishing the efficacy of insecticide-treated nets (ITNs) – the primary tool for preventing malaria. The entomological efficacy of indoor vector control interventions can be measured in experimental hut trials (EHTs), where hut structures resemble local housing, but allow the collection of mosquitoes that entered, exited, blood-fed and/or died. There is a need to understand how the spread of resistance changes ITN efficacy and to elucidate factors influencing EHT results, including differences in experimental hut design, to support the development of novel vector control tools. A comprehensive database of EHTs was compiled following a systematic review to identify all known trials investigating ITNs or indoor residual spraying across sub-Saharan Africa. This analysis focuses on EHTs investigating ITNs and uses Bayesian statistical models to characterise the complex interaction between ITNs and mosquitoes, the between-study variability, and the impact of pyrethroid resistance. As resistance rises, the entomological efficacy of ITNs declines. They induce less mortality and are less likely to deter mosquitoes from entering huts. Despite this, ITNs continue to offer considerable personal protection by reducing mosquito feeding until resistance reaches high levels. There are clear associations between the different entomological impacts of ITNs, though there is still substantial variability between studies, some of which can be accounted for by hut design. The relationship between EHT outcomes and the level of resistance (as measured by discriminating dose bioassays) is highly uncertain. The meta-analyses show that EHTs are an important reproducible assay for capturing the complex entomological efficacy of ITNs on blood-feeding mosquitoes. The impact of pyrethroid resistance on these measures appears broadly consistent across a wide geographical area onc
Journal articleOkell L, Whittaker C, Ghani A, et al., 2021,
Global patterns of submicroscopic Plasmodium falciparum malaria infection: insights from a systematic review and meta-analysis of population surveys, The Lancet Microbe, Vol: 2, Pages: e366-e374, ISSN: 2666-5247
Background: Adoption of molecular techniques to detect Plasmodium falciparum infection has revealed many previously undetected (by microscopy) yet transmissible low-density infections. The proportion of these infections is typically highest in low transmission settings, but drivers of submicroscopic infection remain unclear. Here, we update a previously conducted systematic review of asexual P. falciparum prevalence by microscopy and polymerase chain reaction (PCR) in the same population. We conduct a meta-analysis to explore potential drivers of submicroscopic infection and identify the locations where submicroscopic infections are most common. Methods: PubMed and Web of Science databases were searched up to 11th October 2020 for cross-sectional studies reporting data on asexual P.falciparum prevalence by both microscopy and PCR. Surveys of pregnant women, where participants had been chosen based on symptoms/treatment or that did not involve a population from a defined location were excluded. Both the number of individuals tested and positive by microscopy and PCR for P. falciparum infection were extracted from each reference. Bayesian regression modelling was used to explore determinants of the size of the submicroscopic reservoir including geography, seasonality, age, methodology and current/historical patterns of transmission.Findings: A total of 166 references containing 551 cross-sectional survey microscopy/PCR prevalence pairs were included. Our results highlight that submicroscopic infections predominate in low transmission settings across all settings, but also reveal marked geographical variation, with the proportion of infections that are submicroscopic being highest in South American surveys and lowest in West African studies. Whilst current transmission levels partly explain these results, we find that historical transmission intensity also represents a crucial determinant of the size of the submicroscopic reservoir, as does the demographic structure of
Journal articleBrazeau NF, Mitchell CL, Morgan AP, et al., 2021,
Journal articleMorris AL, Ghani A, Ferguson N, 2021,
Fine-scale estimation of key life-history parameters of malaria vectors: implications for next-generation vector control technologies, Parasites and Vectors, Vol: 14, Pages: 1-12, ISSN: 1756-3305
BackgroundMosquito control has the potential to significantly reduce malaria burden on a region, but to influence public health policy must also show cost-effectiveness. Gaps in our knowledge of mosquito population dynamics mean that mathematical modelling of vector control interventions have typically made simplifying assumptions about key aspects of mosquito ecology. Often, these assumptions can distort the predicted efficacy of vector control, particularly next-generation tools such as gene drive, which are highly sensitive to local mosquito dynamics.MethodsWe developed a discrete-time stochastic mathematical model of mosquito population dynamics to explore the fine-scale behaviour of egg-laying and larval density dependence on parameter estimation. The model was fitted to longitudinal mosquito population count data using particle Markov chain Monte Carlo methods.ResultsBy modelling fine-scale behaviour of egg-laying under varying density dependence scenarios we refine our life history parameter estimates, and in particular we see how model assumptions affect population growth rate (Rm), a crucial determinate of vector control efficacy.ConclusionsSubsequent application of these new parameter estimates to gene drive models show how the understanding and implementation of fine-scale processes, when deriving parameter estimates, may have a profound influence on successful vector control. The consequences of this may be of crucial interest when devising future public health policy.
Journal articleHogan AB, Winskill P, Watson OJ, et al., 2021,
Within-country age-based prioritisation, global allocation, and public health impact of a vaccine against SARS-CoV-2: a mathematical modelling analysis, Vaccine, Vol: 39, Pages: 2995-3006, ISSN: 0264-410X
The worldwide endeavour to develop safe and effective COVID-19 vaccines has been extraordinary, and vaccination is now underway in many countries. However, the doses available in 2021 are likely to be limited. We extended a mathematical model of SARS-CoV-2 transmission across different country settings to evaluate the public health impact of potential vaccines using WHO-developed target product profiles. We identified optimal vaccine allocation strategies within- and between-countries to maximise averted deaths under constraints on dose supply. We found that the health impact of SARS-CoV-2 vaccination depends on the cumulative population-level infection incidence when vaccination begins, the duration of natural immunity, the trajectory of the epidemic prior to vaccination, and the level of healthcare available to effectively treat those with disease. Within a country we find that for a limited supply (doses for <20% of the population) the optimal strategy is to target the elderly. However, with a larger supply, if vaccination can occur while other interventions are maintained, the optimal strategy switches to targeting key transmitters to indirectly protect the vulnerable. As supply increases, vaccines that reduce or block infection have a greater impact than those that prevent disease alone due to the indirect protection provided to high-risk groups. Given a 2 billion global dose supply in 2021, we find that a strategy in which doses are allocated to countries proportional to population size is close to optimal in averting deaths and aligns with the ethical principles agreed in pandemic preparedness planning.
Journal articleDa DF, McCabe R, Somé BM, et al., 2021,
Detection of Plasmodium falciparum in laboratory-reared and naturally infected wild mosquitoes using near-infrared spectroscopy., Scientific Reports, Vol: 11, Pages: 10289-10289, ISSN: 2045-2322
There is an urgent need for high throughput, affordable methods of detecting pathogens inside insect vectors to facilitate surveillance. Near-infrared spectroscopy (NIRS) has shown promise to detect arbovirus and malaria in the laboratory but has not been evaluated in field conditions. Here we investigate the ability of NIRS to identify Plasmodium falciparum in Anopheles coluzzii mosquitoes. NIRS models trained on laboratory-reared mosquitoes infected with wild malaria parasites can detect the parasite in comparable mosquitoes with moderate accuracy though fails to detect oocysts or sporozoites in naturally infected field caught mosquitoes. Models trained on field mosquitoes were unable to predict the infection status of other field mosquitoes. Restricting analyses to mosquitoes of uninfectious and highly-infectious status did improve predictions suggesting sensitivity and specificity may be better in mosquitoes with higher numbers of parasites. Detection of infection appears restricted to homogenous groups of mosquitoes diminishing NIRS utility for detecting malaria within mosquitoes.
Journal articleAkala HM, Watson OJ, Mitei KK, et al., 2021,
Journal articleFraser KJ, Mwandigha L, Traore SF, et al., 2021,
Estimating the potential impact of Attractive Targeted Sugar Baits (ATSBs) as a new vector control tool for Plasmodium falciparum malaria, Malaria Journal, Vol: 20, ISSN: 1475-2875
BackgroundAttractive targeted sugar baits (ATSBs) are a promising new tool for malaria control as they can target outdoor-feeding mosquito populations, in contrast to current vector control tools which predominantly target indoor-feeding mosquitoes.MethodsIt was sought to estimate the potential impact of these new tools on Plasmodium falciparum malaria prevalence in African settings by combining data from a recent entomological field trial of ATSBs undertaken in Mali with mathematical models of malaria transmission. The key parameter determining impact on the mosquito population is the excess mortality due to ATSBs, which is estimated from the observed reduction in mosquito catch numbers. A mathematical model capturing the life cycle of P. falciparum malaria in mosquitoes and humans and incorporating the excess mortality was used to estimate the potential epidemiological effect of ATSBs.ResultsThe entomological study showed a significant reduction of ~ 57% (95% CI 33–72%) in mosquito catch numbers, and a larger reduction of ~ 89% (95% CI 75–100%) in the entomological inoculation rate due to the fact that, in the presence of ATSBs, most mosquitoes do not live long enough to transmit malaria. The excess mortality due to ATSBs was estimated to be lower (mean 0.09 per mosquito per day, seasonal range 0.07–0.11 per day) than the bait feeding rate obtained from one-day staining tests (mean 0.34 per mosquito per day, seasonal range 0.28–0.38 per day).ConclusionsFrom epidemiological modelling, it was predicted that ATSBs could result in large reductions (> 30% annually) in prevalence and clinical incidence of malaria, even in regions with an existing high malaria burden. These results suggest that this new tool could provide a promising addition to existing vector control tools and result in significant reductions in malaria burden across a range of malaria-endemic settings.
Journal articleChallenger J, Olivera Mesa D, Da DF, et al., 2021,
Transmission-blocking vaccines that interrupt malaria transmission from humans to mosquitoes are being tested in early clinical trials. The activity of such a vaccine is commonly evaluated using membrane-feeding assays. Understanding the field efficacy of such a vaccine requires knowledge of how heavily infected wild, naturally blood-fed mosquitoes are, as this indicates how difficult it will be to block transmission. Here we use data on naturally infected mosquitoes collected in Burkina Faso to translate the laboratory-estimated activity into an estimated activity in the field. A transmission dynamics model is then utilised to predict a transmission-blocking vaccine’s public health impact alongside existing interventions. The model suggests that school-aged children are an attractive population to target for vaccination. Benefits of vaccination are distributed across the population, averting the greatest number of cases in younger children. Utilising a transmission-blocking vaccine alongside existing interventions could have a substantial impact against malaria.
Journal articleDiawara H, Walker P, Cairns M, et al., 2021,
Cost-effectiveness of district-wide seasonal malaria chemoprevention when implemented through routine malaria control programme in Kita, Mali using fixed point distribution, Malaria Journal, Vol: 20, Pages: 1-14, ISSN: 1475-2875
Background: Seasonal malaria chemoprevention (SMC) is a strategy for malaria control recommended by the World Health Organization (WHO) since 2012 for Sahelian countries. The Mali National Malaria Control Programme adopted a plan for pilot implementation and nationwide scale-up by 2016. Given that SMC is a relatively new approach, there is an urgent need to assess the costs and cost effectiveness of SMC when implemented through the routine health system to inform decisions on resource allocation.Methods: Cost data were collected from pilot implementation of SMC in Kita district, which targeted 77,497 children aged 3–59 months. Starting in August 2014, SMC was delivered by fixed point distribution in villages with the first dose observed each month. Treatment consisted of sulfadoxine-pyrimethamine and amodiaquine once a month for four consecutive months, or rounds. Economic and financial costs were collected from the provider perspective using an ingredients approach. Effectiveness estimates were based upon a published mathematical transmission model calibrated to local epidemiology, rainfall patterns and scale-up of interventions. Incremental cost effectiveness ratios were calculated for the cost per malaria episode averted, cost per disability adjusted life years (DALYs) averted, and cost per death averted.Results: The total economic cost of the intervention in the district of Kita was US $357,494. Drug costs and personnel costs accounted for 34% and 31%, respectively. Incentives (payment other than salary for efforts beyond routine activities) accounted for 25% of total implementation costs. Average financial and economic unit costs per child per round were US $0.73 and US $0.86, respectively; total annual financial and economic costs per child receiving SMC were US $2.92 and US $3.43, respectively. Accounting for coverage, the economic cost per child fully adherent (receiving all four rounds) was US $6.38 and US $4.69, if weighted highly adherent, (receivin
Journal articleWinskill P, Mousa A, Oresanya O, et al., 2021,
Does integrated community case management (iCCM) target health inequities and treatment delays? Evidence from an analysis of Demographic and Health Surveys data from 21 countries in the period 2010 to 2018, Journal of Global Health, Vol: 11, Pages: 1-10, ISSN: 2047-2978
BackgroundIntegrated community case management (iCCM) is a programme that can, via community health workers (CHWs), increase access to timely and essential treatments for children. As well as improving treatment coverage, iCCM has an additional equity-focus with the aim of targetingunderserved populations. To assess the success of iCCM programmes it is important that we understand the contribution they are making to equitable health coverage.MethodsWe analysed demographic and health survey data from 21 countries over 9 years to assess evidence and evaluate iCCM programmes. We summarise the contribution CHWs are making relative to other healthcare provider groups and what treatment combinations CHWs are commonly prescribing. We assessed the ability of CHWs to target treatment delays and health inequities by evaluating time to treatment following fever onset and relationships between CHWs and wealth, rurality and remoteness.ResultsThere was good evidence that CHWs are being successfully targeted to improve inequities in healthcare coverage. There is a larger contribution of CHWs in areas with higher poverty, rurality and remoteness. In six surveys CHWs were associated with significantly shorter average timebetween fever onset and advice or treatment seeking, whilst in one they were associated with significantly longer times. In areas with active CHW programmes, the contribution of CHWs relative to other healthcare provider groups varied between 11% to 45% of treatment visits. The distribution of types of treatment provided by CHWs was also very variable between countries.ConclusionsThe success of an iCCM programme depends not only on increasing treatment coverage but addressing inequities in access to timely healthcare. Whilst much work is still needed to attain universal healthcare targets, and despite incomplete data, there is evidence that iCCM is successfully addressing treatment delays and targeting underserved populations.
Journal articleStopard IJ, Churcher TS, Lambert B, 2021,
During sporogony, malaria-causing parasites infect a mosquito, reproduce and migrate to the mosquito salivary glands where they can be transmitted the next time blood feeding occurs. The time required for sporogony, known as the extrinsic incubation period (EIP), is an important determinant of malaria transmission intensity. The EIP is typically estimated as the time for a given percentile, x, of infected mosquitoes to develop salivary gland sporozoites (the infectious parasite life stage), which is denoted by EIPx. Many mechanisms, however, affect the observed sporozoite prevalence including the human-to-mosquito transmission probability and possibly differences in mosquito mortality according to infection status. To account for these various mechanisms, we present a mechanistic mathematical model, which explicitly models key processes at the parasite, mosquito and observational scales. Fitting this model to experimental data, we find greater variation in the EIP than previously thought: we estimated the range between EIP10 and EIP90 (at 27°C) as 4.5 days compared to 0.9 days using existing statistical methods. This pattern holds over the range of study temperatures included in the dataset. Increasing temperature from 21°C to 34°C decreased the EIP50 from 16.1 to 8.8 days. Our work highlights the importance of mechanistic modelling of sporogony to (1) improve estimates of malaria transmission under different environmental conditions or disease control programs and (2) evaluate novel interventions that target the mosquito life stages of the parasite.
Journal articleHellewell J, Sherrard-Smith E, Ogoma S, et al., 2021,
Assessing the impact of low-technology emanators alongside long-lasting insecticidal nets to control malaria, Philosophical Transactions of the Royal Society B: Biological Sciences, Vol: 376, Pages: 1-9, ISSN: 0962-8436
Malaria control in sub-Saharan Africa relies on the widespread use of long-lasting insecticidal nets (LLINs) or the indoor residual spraying of insecticide. Disease transmission may be maintained even when these indoor interventions are universally used as some mosquitoes will bite in the early morning and evening when people are outside. As countries seek to eliminate malaria, they can target outdoor biting using new vector control tools such as spatial repellent emanators, which emit airborne insecticide to form a protective area around the user. Field data are used to incorporate a low-technology emanator into a mathematical model of malaria transmission to predict its public health impact across a range of scenarios. Targeting outdoor biting by repeatedly distributing emanators alongside LLINs increases the chance of elimination, but the additional benefit depends on the level of anthropophagy in the local mosquito population, emanator effectiveness and the pre-intervention proportion of mosquitoes biting outdoors. High proportions of pyrethroid-resistant mosquitoes diminish LLIN impact because of reduced mosquito mortality. When mosquitoes are highly anthropophagic, this reduced mortality leads to more outdoor biting and a reduced additional benefit of emanators, even if emanators are assumed to retain their effectiveness in the presence of pyrethroid resistance. Different target product profiles are examined, which show the extra epidemiological benefits of spatial repellents that induce mosquito mortality.
Journal articleGuglielmo F, Sanou A, Churcher TS, et al., 2021,
Quantifying individual variability in exposure risk to mosquito bites in the Cascades region, Burkina Faso, Malaria Journal, Vol: 20, Pages: 1-14, ISSN: 1475-2875
BackgroundThe Cascades region, Burkina Faso, has a high malaria burden despite reported high insecticide-treated mosquito net (ITN) use. Human and vector activities outside the hours when indoor interventions offer direct protection from infectious bites potentially increase exposure risk to bites from malaria-transmitting Anopheles mosquitoes. This work investigated the degree of variation in human behaviour both between individuals and through time (season) to quantify how it impacts exposure to malaria vectors.MethodsPatterns in human overnight activity (18:00–06:00) to quantify time spent using an ITN across 7 successive nights in two rural communities, Niakore (N = 24 participants) and Toma (71 participants), were observed in the dry and rainy seasons, between 2017 and 2018. Hourly human landing Anopheles mosquito catches were conducted in Niakore specifically, and Cascades region generally, between 2016 and 2017. Data were statistically combined to estimate seasonal variation in time spent outdoors and Anopheles bites received per person per night (bpppn).ResultsSubstantial variability in exposure to outdoor Anopheles bites was detected within and between communities across seasons. In October, when Anopheles densities are highest, an individual’s risk of Anopheles bites ranged from 2.2 to 52.2 bites per person per night (bpppn) within the same week with variable risk dependent on hours spent indoors. Comparably higher outdoor human activity was observed in April and July but, due to lower Anopheles densities estimated, bpppn were 0.2–4.7 and 0.5–32.0, respectively. Males and people aged over 21 years were predicted to receive more bites in both sentinel villages.ConclusionThis work presents one of the first clear descriptions of the degree of heterogeneity in time spent outdoors between people and across the year. Appreciation of sociodemographic, cultural and entomological activities will help refine approaches to vector
Journal articleGuglielmo F, Sanou A, Churcher TS, et al., 2020,
<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background</jats:bold>The Cascades Region, Burkina Faso, has high malaria burden despite reported high insecticide treated bed net (ITN) use. Human and vector activities outside the hours when indoor interventions offer direct protection from infectious bites potentially increase exposure risk to bites from malaria-transmitting <jats:italic>Anopheles </jats:italic>mosquitoes. We investigate the degree of variation in human behaviour both between individuals and through time (season) to quantify how it impacts exposure to malaria vectors.<jats:bold>Methods</jats:bold>Patterns in human overnight activity (18:00-06:00) to quantify time spent using an ITN across 7 successive nights in two rural communities, Niakore (N = 24 participants) and Toma (71 participants), were observed in the dry and rainy seasons, between 2017-2018. Hourly human landing <jats:italic>Anopheles </jats:italic>mosquito catches were conducted in Niakore specifically, and Cascades Region generally, between 2016-2017. Data were statistically combined to estimate seasonal variation in time spent outdoors and <jats:italic>Anopheles </jats:italic>bites received per person per night (bpppn).<jats:bold>Results</jats:bold>Substantial variability in exposure to outdoor <jats:italic>Anopheles</jats:italic> bites was detected within and between communities and across seasons. In October, when <jats:italic>Anopheles </jats:italic>densities are highest, an individual’s risk of <jats:italic>Anopheles</jats:italic> bites ranged from 2.2 to 52.2 bpppn within the same week with variable risk dependent on hours spent indoors. Comparably higher outdoor human activity was observed in April and July but, due to lower <jats:italic>Anopheles </jats:italic>densities estimated bpppn were 0.2 – 4.7 bpppn, and 0.5 &nda
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