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Journal articleNgufor C, Fongnikin A, Fagbohoun J, et al., 2023,
Evaluating the attrition, fabric integrity and insecticidal durability of two dual active ingredient nets (Interceptor ® G2 and Royal® Guard): methodology for a prospective study embedded in a cluster randomized controlled trial in Benin
, Malaria Journal, Vol: 22, ISSN: 1475-2875BackgroundFollowing the World Health Organization (WHO) endorsement of dual active ingredient (AI) nets, an increased uptake of pyrethroid-chlorfenapyr and pyrethroid-pyriproxyfen nets is expected. Studies evaluating their physical and insecticidal durability are essential for making programmatic and procurement decisions. This paper describes the methodology for a prospective study to evaluate the attrition, fabric integrity, insecticidal durability of Interceptor® G2 (alpha-cypermethrin-chlorfenapyr) and Royal Guard® (alpha-cypermethrin-pyriproxyfen), compared to Interceptor® (alpha-cypermethrin), embedded in a 3-arm cluster randomized controlled trial (cRCT) in the Zou Department of Benin.MethodsTen clusters randomly selected from each arm of the cRCT will be used for the study. A total of 750 ITNs per type will be followed in 5 study clusters per arm to assess ITN attrition and fabric integrity at 6-, 12-, 24- and 36-months post distribution, using standard WHO procedures. A second cohort of 1800 nets per type will be withdrawn every 6 months from all 10 clusters per arm and assessed for chemical content and biological activity in laboratory bioassays at each time point. Alpha-cypermethrin bioefficacy in Interceptor® and Royal Guard® will be monitored in WHO cone bioassays and tunnel tests using the susceptible Anopheles gambiae Kisumu strain. The bioefficacy of the non-pyrethroid insecticides (chlorfenapyr in Interceptor® G2 and pyriproxyfen in Royal Guard®) will be monitored using the pyrethroid-resistant Anopheles coluzzii Akron strain. Chlorfenapyr activity will be assessed in tunnel tests while pyriproxyfen activity will be assessed in cone bioassays in terms of the reduction in fertility of blood-fed survivors observed by dissecting mosquito ovaries. Nets withdrawn at 12, 24 and 36 months will be tested in experimental hut trials within the cRCT study area against wild free-flying pyrethroid resistant An. gambiae sensu lato to i
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Journal articleWinskill P, Dhabangi A, Kwambai TK, et al., 2023,
Estimating the burden of severe malarial anaemia and access to hospital care in East Africa.
, Nat Commun, Vol: 14Severe malarial anaemia can be fatal if not promptly treated. Hospital studies may under-represent the true burden because cases often occur in settings with poor access to healthcare. We estimate the relationship of community prevalence of malaria infection and severe malarial anaemia with the incidence of severe malarial anaemia cases in hospital, using survey data from 21 countries and hospital data from Kenya, Tanzania and Uganda. The estimated percentage of severe malarial anaemia cases that were hospitalised is low and consistent for Kenya (21% (95% CrI: 7%, 47%)), Tanzania (18% (95% CrI: 5%, 52%)) and Uganda (23% (95% CrI: 9%, 48%)). The majority of severe malarial anaemia cases remain in the community, with the consequent public health burden being contingent upon the severity of these cases. Alongside health system strengthening, research to better understand the spectrum of disease associated with severe malarial anaemia cases in the community is a priority.
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Journal articleHuang W, Rodrigues J, Bilgo E, et al., 2023,
Delftia tsuruhatensis TC1 symbiont suppresses malaria transmission by anopheline mosquitoes
, Science, Vol: 381, Pages: 533-540, ISSN: 1095-9203Malaria control demands the development of a wide range of complementary strategies. We describe the properties of a naturally occurring, non–genetically modified symbiotic bacterium, Delftia tsuruhatensis TC1, which was isolated from mosquitoes incapable of sustaining the development of Plasmodium falciparum parasites. D. tsuruhatensis TC1 inhibits early stages of Plasmodium development and subsequent transmission by the Anopheles mosquito through secretion of a small-molecule inhibitor. We have identified this inhibitor to be the hydrophobic molecule harmane. We also found that, on mosquito contact, harmane penetrates the cuticle, inhibiting Plasmodium development. D. tsuruhatensis TC1 stably populates the mosquito gut, does not impose a fitness cost on the mosquito, and inhibits Plasmodium development for the mosquito’s life. Contained field studies in Burkina Faso and modeling showed that D. tsuruhatensis TC1 has the potential to complement mosquito-targeted malaria transmission control.
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Journal articleChallenger JD, van Beek SW, Heine RT, et al., 2023,
Modelling the impact of a highly potent Plasmodium falciparum transmission-blocking monoclonal antibody in areas of seasonal malaria transmission
, Journal of Infectious Diseases, Vol: 228, Pages: 212-223, ISSN: 0022-1899Transmission-blocking interventions can play an important role in combatting malaria worldwide. Recently, a highly potent Plasmodium falciparum transmission-blocking monoclonal antibody (TB31F) was demonstrated to be safe and efficacious in malaria-naive volunteers. Here we predict the potential public health impact of large-scale implementation of TB31F alongside existing interventions. We developed a pharmaco-epidemiological model, tailored to two settings of differing transmission intensity with already established insecticide-treated nets and seasonal malaria chemoprevention interventions. Community-wide annual administration (at 80% coverage) of TB31F over a three-year period was predicted to reduce clinical incidence by 54% (381 cases averted per 1000 people per year) in a high-transmission seasonal setting, and 74% (157 cases averted per 1000 people per year) in a low-transmission seasonal setting. Targeting school-aged children gave the largest reduction in terms of cases averted per dose. An annual administration of transmission- blocking monoclonal TB31F may be an effective intervention against malaria in seasonal malaria settings.
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Journal articleSheppard R, Watson OJ, Pieciak R, et al., 2023,
Using mortuary and burial data to place COVID-19 in Lusaka, Zambia within a global context
, Nature Communications, Vol: 14, Pages: 1-15, ISSN: 2041-1723Reported COVID-19 cases and associated mortality remain low in many sub-Saharan countries relative to global averages, but true impact is difficult to estimate given limitations around surveillance and mortality registration. In Lusaka, Zambia, burial registration and SARS-CoV-2prevalence data during 2020 allow estimation of excess mortality and transmission. Relative to pre-pandemic patterns, we estimate age-dependent mortality increases, totalling 3,212 excess deaths (95% CrI: 2,104-4,591), representing an 18.5% (95% CrI: 13.0-25.2%) increase relative to pre-pandemic levels. Using a dynamical model-based inferential framework, we find that these mortalitypatterns and SARS-CoV-2 prevalence data are in agreement with established COVID-19 severity estimates. Our results support hypotheses that COVID-19 impact in Lusaka during 2020 was consistent with COVID-19 epidemics elsewhere, without requiring exceptional explanations for low reported figures. For more equitable decision-making during future pandemics, barriers to ascertaining attributable mortality in low-income settings must be addressed and factored into discourse around reported impact differences.
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Journal articleKont MD, Lambert B, Sanou A, et al., 2023,
Characterising the intensity of insecticide resistance: A novel framework for analysis of intensity bioassay data
, Current Research in Parasitology & Vector-Borne Diseases, Pages: 100125-100125, ISSN: 2667-114X -
Journal articlePaschalidis A, Watson O, Aydemir O, et al., 2023,
<i>coiaf</i>: Directly estimating complexity of infection with allele frequencies
, PLOS COMPUTATIONAL BIOLOGY, Vol: 19, ISSN: 1553-734X- Cite
- Citations: 4
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Journal articleTopazian HM, Schmit N, Gerard-Ursin I, et al., 2023,
Modelling the relative cost-effectiveness of the RTS,S/AS01 malaria vaccine compared to investment in vector control or chemoprophylaxis
, VACCINE, Vol: 41, Pages: 3215-3223, ISSN: 0264-410X- Cite
- Citations: 7
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Journal articleChallenger J, Nash RK, Ngufor C, et al., 2023,
Assessing the variability in experimental hut trials evaluating insecticide-treated nets against malaria vectors
, Current Research in Parasitology & Vector-Borne Diseases, Vol: 3, Pages: 1-11, ISSN: 2667-114XExperimental hut trials (EHTs) are used to evaluate indoor vector control interventions against malaria vectors in a controlled setting. The level of variability present in the assay will influence whether a given study is well powered to answer the research question being considered. We utilised disaggregated data from 15 previous EHTs to gain insight into the behaviour typically observed. Using simulations from generalised linear mixed models to obtain power estimates for EHTs, we show how factors such as the number of mosquitoes entering the huts each night and the magnitude of included random effects can influence study power. A wide variation in behaviour is observed in both the mean number of mosquitoes collected per hut per night (ranging from 1.6 to 32.5) and overdispersion in mosquito mortality. This variability in mortality is substantially greater than would be expected by chance and should be included in all statistical analyses to prevent false precision of results. We utilise both superiority and non-inferiority trials to illustrate our methodology, using mosquito mortality as the outcome of interest. The framework allows the measurement error of the assay to be reliably assessed and enables the identification of outlier results which could warrant further investigation. EHTs are increasingly playing an important role in the evaluation and regulation of indoor vector control interventions so it is important to ensure that these studies are adequately powered.
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Journal articleWhittaker C, Hamlet A, Sherrard-Smith E, et al., 2023,
Seasonal dynamics of Anopheles stephensi and its implications for mosquito detection and emergent malaria control in the Horn of Africa
, Proceedings of the National Academy of Sciences of USA, Vol: 120, Pages: 1-9, ISSN: 0027-8424Invasion of the malaria vector Anopheles stephensi across the Horn of Africa threatens control efforts across the continent, particularly in urban settings where the vector is able to proliferate. Malaria transmission is primarily determined by the abundance of dominant vectors, which often varies seasonally with rainfall. However, it remains unclear how An. stephensi abundance changes throughout the year, despite this being a crucial input to surveillance and control activities. We collate longitudinal catch data from across its endemic range to better understand the vector's seasonal dynamics and explore the implications of this seasonality for malaria surveillance and control across the Horn of Africa. Our analyses reveal pronounced variation in seasonal dynamics, the timing and nature of which are poorly predicted by rainfall patterns. Instead, they are associated with temperature and patterns of land use; frequently differing between rural and urban settings. Our results show that timing entomological surveys to coincide with rainy periods is unlikely to improve the likelihood of detecting An. stephensi. Integrating these results into a malaria transmission model, we show that timing indoor residual spraying campaigns to coincide with peak rainfall offers little improvement in reducing disease burden compared to starting in a random month. Our results suggest that unlike other malaria vectors in Africa, rainfall may be a poor guide to predicting the timing of peaks in An. stephensi-driven malaria transmission. This highlights the urgent need for longitudinal entomological monitoring of the vector in its new environments given recent invasion and potential spread across the continent.
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Journal articleBen A, Watson OJ, Onyango I, et al., 2023,
Malaria Transmission Dynamics in a High-Transmission Setting of Western Kenya and the Inadequate Treatment Response to Artemether-Lumefantrine in an Asymptomatic Population
, CLINICAL INFECTIOUS DISEASES, Vol: 76, Pages: 704-712, ISSN: 1058-4838- Author Web Link
- Cite
- Citations: 1
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Journal articleUnwin H, Sherrard-Smith E, Churcher T, et al., 2023,
Quantifying the direct and indirect protection provided by insecticide treated bed nets against malaria
, Nature Communications, Vol: 14, Pages: 1-12, ISSN: 2041-1723Long lasting insecticidal nets (LLINs) provide both direct and indirect protection against malaria. As pyrethroid resistance evolves in mosquito vectors, it will be useful to understand how the specific benefits LLINs afford individuals and communities may be affected. Here we use modelling to show that there is no minimum LLIN usage needed for users and non-users to benefit from community protection. Modelling results also indicate that pyrethroid resistance in local mosquitoes will likely diminish the direct and indirect benefits from insecticides, leaving the barrier effects intact, but LLINs are still expected to provide enhanced benefit over untreated nets even at high levels of pyrethroid resistance.
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Journal articleOkell LC, Kwambai TK, Dhabangi A, et al., 2023,
Projected health impact of post-discharge malaria chemoprevention among children with severe malarial anaemia in Africa
, Nature Communications, Vol: 14, Pages: 1-10, ISSN: 2041-1723Children recovering from severe malarial anaemia (SMA) remain at high risk of readmission and death after discharge from hospital. However, a recent trial found that post-discharge malaria chemoprevention (PDMC) with dihydroartemisinin-piperaquine reduces this risk. We developed a mathematical model describing the daily incidence of uncomplicated and severe malaria requiring readmission among 0–5-year old children after hospitalised SMA. We fitted the model to a multicentre clinical PDMC trial using Bayesian methods and modelled the potential impact of PDMC across malaria-endemic African countries. In the 20 highest-burden countries, we estimate that only 2–5 children need to be given PDMC to prevent one hospitalised malaria episode, and less than 100 to prevent one death. If all hospitalised SMA cases access PDMC in moderate-to-high transmission areas, 38,600 (range 16,900–88,400) malaria-associated readmissions could be prevented annually, depending on access to hospital care. We estimate that recurrent SMA post-discharge constitutes 19% of all SMA episodes in moderate-to-high transmission settings.
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Journal articleCorbel V, Kont MD, Ahumada ML, et al., 2023,
A new WHO bottle bioassay method to assess the susceptibility of mosquito vectors to public health insecticides: results from a WHO-coordinated multi-centre study
, Parasites and Vectors, Vol: 16, ISSN: 1756-3305BACKGROUND: The continued spread of insecticide resistance in mosquito vectors of malaria and arboviral diseases may lead to operational failure of insecticide-based interventions if resistance is not monitored and managed efficiently. This study aimed to develop and validate a new WHO glass bottle bioassay method as an alternative to the WHO standard insecticide tube test to monitor mosquito susceptibility to new public health insecticides with particular modes of action, physical properties or both. METHODS: A multi-centre study involving 21 laboratories worldwide generated data on the susceptibility of seven mosquito species (Aedes aegypti, Aedes albopictus, Anopheles gambiae sensu stricto [An. gambiae s.s.], Anopheles funestus, Anopheles stephensi, Anopheles minimus and Anopheles albimanus) to seven public health insecticides in five classes, including pyrethroids (metofluthrin, prallethrin and transfluthrin), neonicotinoids (clothianidin), pyrroles (chlorfenapyr), juvenile hormone mimics (pyriproxyfen) and butenolides (flupyradifurone), in glass bottle assays. The data were analysed using a Bayesian binomial model to determine the concentration-response curves for each insecticide-species combination and to assess the within-bioassay variability in the susceptibility endpoints, namely the concentration that kills 50% and 99% of the test population (LC50 and LC99, respectively) and the concentration that inhibits oviposition of the test population by 50% and 99% (OI50 and OI99), to measure mortality and the sterilizing effect, respectively. RESULTS: Overall, about 200,000 mosquitoes were tested with the new bottle bioassay, and LC50/LC99 or OI50/OI99 values were determined for all insecticides. Variation was seen between laboratories in estimates for some mosquito species-insecticide combinations, while other test results were consistent. The variation was generally greater with transfluthrin and flupyradifurone than with the other compounds tested, especially a
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Journal articleThompson HA, Hogan AB, Walker PGT, et al., 2022,
Seasonal use case for the RTS,S/AS01 malaria vaccine: a mathematical modelling study
, The Lancet Global Health, Vol: 10, Pages: e1782-e1792, ISSN: 2214-109XBACKGROUND: A 2021 clinical trial of seasonal RTS,S/AS01E (RTS,S) vaccination showed that vaccination was non-inferior to seasonal malaria chemoprevention (SMC) in preventing clinical malaria. The combination of these two interventions provided significant additional protection against clinical and severe malaria outcomes. Projections of the effect of this novel approach to RTS,S vaccination in seasonal transmission settings for extended timeframes and across a range of epidemiological settings are needed to inform policy recommendations. METHODS: We used a mathematical, individual-based model of malaria transmission that was fitted to data on the relationship between entomological inoculation rate and parasite prevalence, clinical disease, severe disease, and deaths from multiple sites across Africa. The model was validated with results from a phase 3b trial assessing the effect of SV-RTS,S in Mali and Burkina Faso. We developed three intervention efficacy models with varying degrees and durations of protection for our population-level modelling analysis to assess the potential effect of an RTS,S vaccination schedule based on age (doses were delivered to children aged 6 months, 7·5 months, and 9 months for the first three doses, and at 27 months of age for the fourth dose) or season (children aged 5-17 months at the time of first vaccination received the first three doses in the 3 months preceding the transmission season, with any subsequent doses up to five doses delivered annually) in seasonal transmission settings both in the absence and presence of SMC with sulfadoxine-pyrimethamine plus amodiaquine. This is modelled as a full therapeutic course delivered every month for four or five months of the peak in transmission season. Estimates of cases and deaths averted in a population of 100 000 children aged 0-5 years were calculated over a 15-year time period for a range of levels of malaria transmission intensity (Plasmodium falciparum parasite prevalence i
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