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Journal articleMori AT, Mallange G, Kuehl M-J, et al., 2024,
Cost of treating severe malaria in children in Africa: a systematic literature review
, MALARIA JOURNAL, Vol: 23- Cite
- Citations: 2
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Journal articleSovi A, Adoha CJ, Yovogan B, et al., 2024,
The effect of next-generation, dual-active-ingredient, long-lasting insecticidal net deployment on insecticide resistance in malaria vectors in Benin: results of a 3-year, three-arm, cluster-randomised, controlled trial
, The Lancet Planetary Health, Vol: 8, Pages: e894-e905, ISSN: 2542-5196BackgroundInsecticide resistance among malaria vector species now occurs in 84 malaria-endemic countries and territories worldwide. Novel vector-control interventions, including long-lasting insecticidal nets (LLINs) that incorporate new active ingredients with distinct modes of action, are urgently needed to delay the evolution and spread of resistance and to alleviate reversals in malaria-control gains. We aimed to assess the longitudinal effect of two dual-active-ingredient LLINs on insecticide resistance during a cluster-randomised, controlled trial in Benin.MethodsThis 3-year, three-arm, cluster-randomised, controlled trial was conducted between Oct 17, 2019, and Oct 24, 2022, in three districts in southern Benin, to compare the effects of LLINs containing chlorfenapyr–pyrethroid or pyriproxyfen–pyrethroid with LLINs containing pyrethroid only. In 19 292 mosquitoes (Anopheles gambiae sensu lato) collected over 36 months—3 months of baseline followed by 3 years post-intervention—we measured longitudinal phenotypic insecticide resistance profiles using bioassays and genotypic resistance profiles using quantitative, real-time, reverse transcriptase PCR of metabolic resistance genes in two clusters per trial group. The trial was registered with ClinicalTrials.gov, NCT03931473.FindingsIn all three trial groups, a significant effect of LLINs on insecticide resistance selection was evident, with the median lethal dose (LD50) of α-cypermethrin approximately halving between baseline and 12 months post-LLIN distribution (pyrethroid-only LLIN cluster 21: LD50 78·78 μg/ml [95% CI 65·75–94·48] vs 35·93 [29·41–43.86] and cluster 31: 79·26 [65·40–96·44] vs 38·71 [30·88–48·53]; chlorfenapyr–pyrethroid LLIN cluster 43: 104·30 [82·97–133·58] vs 43·99 [35·30–54·86]; and pyriproxyfen–
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Journal articleYoung NW, Gashema P, Giesbrecht D, et al., 2025,
High Frequency of Artemisinin Partial Resistance Mutations in the Great Lakes Region Revealed Through Rapid Pooled Deep Sequencing
, JOURNAL OF INFECTIOUS DISEASES, ISSN: 0022-1899 -
Journal articleBiggs J, Challenger J, Hellewell J, et al., 2024,
A systematic review of sample size estimation accuracy on power in malaria cluster randomised trials measuring epidemiological outcomes
, BMC Medical Research Methodology, Vol: 24, ISSN: 1471-2288IntroductionCluster randomised trials (CRTs) are the gold standard for measuring the community-wide impacts of malaria control tools. CRTs rely on well-defined sample size estimations to detect statistically significant effects of trialled interventions, however these are often predicted poorly by triallists. Here, we review the accuracy of predicted parameters used in sample size calculations for malaria CRTs with epidemiological outcomes.MethodsWe searched for published malaria CRTs using four online databases in March 2022. Eligible trials included those with malaria-specific epidemiological outcomes which randomised at least six geographical clusters to study arms. Predicted and observed sample size parameters were extracted by reviewers for each trial. Pair-wise Spearman’s correlation coefficients (rs) were calculated to assess the correlation between predicted and observed control-arm outcome measures and effect sizes (relative percentage reductions) between arms. Among trials which retrospectively calculated an estimate of heterogeneity in cluster outcomes, we recalculated study power according to observed trial estimates.ResultsOf the 1889 records identified and screened, 108 articles were eligible and comprised of 71 malaria CRTs. Among 91.5% (65/71) of trials that included sample size calculations, most estimated cluster heterogeneity using the coefficient of variation (k) (80%, 52/65) which were often predicted without using prior data (67.7%, 44/65). Predicted control-arm prevalence moderately correlated with observed control-arm prevalence (rs: 0.44, [95%CI: 0.12,0.68], p-value < 0.05], with 61.2% (19/31) of prevalence estimates overestimated. Among the minority of trials that retrospectively calculated cluster heterogeneity (20%, 13/65), empirical values contrasted with those used in sample size estimations and often compromised study power. Observed effect sizes were often smaller than had been predicted at the sample size stage
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Journal articleMartin JL, Messenger LA, Rowland M, et al., 2024,
Bio-efficacy of field aged novel class of long-lasting insecticidal nets, against pyrethroid-resistant malaria vectors in Tanzania: a series of experimental hut trials
, PLOS Global Public Health, Vol: 4, ISSN: 2767-3375New classes of long-lasting insecticidal nets (LLINs), have been recommended by the World Health Organization (WHO) to control malaria vectors resistant to pyrethroid insecticides. This study was nested in a large-scale cluster-randomized controlled trial conducted (cRCT) in Tanzania. A series of experimental hut trials (EHTs) aimed to evaluate the bio-efficacy of trial LLINs on mosquito indicators most pertinent to malaria transmission over 3 years of use in the community in order to better understand the outcomes of the cRCT. The following field-collected LLINs were assessed: 1) Olyset Plus (combining piperonyl butoxide synergist and permethrin), 2) Interceptor G2 (chlorfenapyr and alpha-cypermethrin), 3) Royal Guard (pyriproxyfen and alpha-cypermethrin), 4) Interceptor (alpha-cypermethrin only) conducted in parallel with 5) a new Interceptor, and 6) an untreated net. Thirty nets of each type were withdrawn from the community at 12, 24, and 36 months after distribution and used for the EHTs. Pre-specified outcomes were 72-hour mortality for Interceptor G2, 24-hour mortality for Olyset Plus, and fertility based on egg development stage for Royal Guard. Overall, Interceptor G2 LLINs induced higher 72-hour mortality compared to standard LLINs of the same age up to12 months (44% vs 21%, OR: 3.5, 95% CI: 1.9–6.6, p-value < 0.001), and 24-hour mortality was only significantly higher in Olyset Plus when new (OR: 13.6, 95%CI: 4.4–41.3, p-value < 0.001) compared to standard LLINs but not at 12 months (17% vs 13%; OR: 2.1, 95% CI: 1.0–4.3; p-value = 0.112). A small, non-significant effect of pyriproxyfen on Anopheles fertility was observed for Royal Guard up to 12 months (75% vs 98%, OR: 1.1, 95% CI: 0.0–24.9, p-value = 0.951). There was no evidence of a difference in the main outcomes for any of the new classes of LLINs at 24 and 36 months compared to standard LLINs. Interceptor G2 LLINs showed superior bio-efficacy compared to standard LLINs
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Journal articleMartinez-Vega R, Mbacham WF, Ali I, et al., 2024,
Parasite clearance and protection from <i>Plasmodium falciparum</i> infection (PCPI): a three-arm, parallel, double-blinded, placebo-controlled, randomised trial of presumptive sulfadoxine-pyrimethamine versus sulfadoxine-pyrimethamine plus amodiaquine versus artesunate monotherapy among asymptomatic children 3-5 years of age in Cameroon
, BMC INFECTIOUS DISEASES, Vol: 24 -
Journal articleSovegnon PM, Akoton R, Stopard IJ, et al., 2024,
Efficacy of Interceptor G2, Royal Guard and PermaNet 3.0 against pyrethroid-resistant Anopheles gambiae s.l. from Za-Kpota, southern Benin: an experimental hut trial
, Parasites and Vectors, Vol: 17, ISSN: 1756-3305BackgroundThe widespread use of insecticide-treated nets (ITNs) has significantly contributed to the reduction in malaria cases and deaths observed across Africa. Unfortunately, this control strategy is threatened by the rapid spread of pyrethroid resistance in malaria vectors. Dual-active-ingredient insecticidal nets are now available to mitigate the impact of pyrethroid resistance. To facilitate evidence-based decisions regarding product selection in specific use settings, data are needed on the efficacy of these different nets against local mosquito populations.MethodsTwo experimental hut trials were performed in Za-Kpota, southern Benin in 2021 to evaluate the performance of Interceptor G2 (BASF), Royal Guard (Disease Control Technologies) and PermaNet 3.0 (Vestergaard Frandsen), all dual-active-ingredient bednets, in comparison to untreated or standard pyrethroid-treated bednets, against free-flying wild Anopheles gambiae mosquitoes. The performance of some of these next-generation nets was compared to the same type of nets that have been in use for up to 2 years. Mosquitoes collected in the huts were followed up after exposure to assess the sublethal effects of treatments on certain life-history traits.ResultsThe predominant species in the study site was Anopheles gambiae sensu stricto (An. gambiae s.s.). Both Anopheles coluzzii and An. gambiae s.s. were resistant to pyrethroids (deltamethrin susceptibility was restored by piperonyl butoxide pre-exposure). In the experimental hut trials, the highest blood-feeding inhibition (5.56%) was recorded for the Royal Guard net, relative to the standard PermaNet 2.0 net (44.44% inhibition). The highest 72-h mortality rate (90.11%) was recorded for the Interceptor G2 net compared to the PermaNet 2.0 net (56.04%). After exposure, the risk of death of An. gambiae sensu lato (An. gambiae s.l.) was 6.5-fold higher with the Interceptor G2 net and 4.4-fold higher with the PermaNet 3.0 net compared to the respective untreated n
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Journal articleOkiring J, Gonahasa S, Maiteki-Sebuguzi C, et al., 2024,
LLIN Evaluation in Uganda Project (LLINEUP): modelling the impact of COVID-19-related disruptions on delivery of long-lasting insecticidal nets on malaria indicators in Uganda
, Malaria Journal, Vol: 23, ISSN: 1475-2875BACKGROUND: Disruptions in malaria control due to COVID-19 mitigation measures were predicted to increase malaria morbidity and mortality in Africa substantially. In Uganda, long-lasting insecticidal nets (LLINs) are distributed nationwide every 3-4 years, but the 2020-2021 campaign was altered because of COVID-19 restrictions so that the timing of delivery of new nets was different from the original plans made by the National Malaria Control Programme. METHODS: A transmission dynamics modelling exercise was conducted to explore how the altered delivery of LLINs in 2020-2021 impacted malaria burden in Uganda. Data were available on the planned LLIN distribution schedule for 2020-2021, and the actual delivery. The transmission model was used to simulate 100 health sub-districts, and parameterized to match understanding of local mosquito bionomics, net use estimates, and seasonal patterns based on data collected in 2017-2019 during a cluster-randomized trial (LLINEUP). Two scenarios were compared; simulated LLIN distributions matching the actual delivery schedule, and a comparable scenario simulating LLIN distributions as originally planned. Model parameters were otherwise matched between simulations. RESULTS: Approximately 70% of the study population received LLINs later than scheduled in 2020-2021, although some areas received LLINs earlier than planned. The model indicates that malaria incidence in 2020 was substantially higher in areas that received LLINs late. In some areas, early distribution of LLINs appeared less effective than the original distribution schedule, possibly due to attrition of LLINs prior to transmission peaks, and waning LLIN efficacy after distribution. On average, the model simulations predicted broadly similar overall mean malaria incidence in 2021 and 2022. After accounting for differences in cluster population size and LLIN distribution dates, no substantial increase in malaria burden was detected. CONCLUSIONS: The model results sugge
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Journal articleMousa A, Cuomo-Dannenburg G, Thompson HA, et al., 2024,
Measuring protective efficacy and quantifying the impact of drug resistance: A novel malaria chemoprevention trial design and methodology
, PLOS MEDICINE, Vol: 21, ISSN: 1549-1277 -
Journal articleSuh E, Stopard IJ, Ben L, et al., 2024,
Estimating the effects of temperature on transmission of the human malaria parasite, Plasmodium falciparum
, Nature Communications, Vol: 15, ISSN: 2041-1723Despite concern that climate change could increase the human risk to malaria in certain areas, the temperature dependency of malaria transmission is poorly characterized. Here, we use a mechanistic model fitted to experimental data to describe how Plasmodium falciparum infection of the African malaria vector, Anopheles gambiae, is modulated by temperature, including its influences on parasite establishment, conversion efficiency through parasite developmental stages, parasite development rate, and overall vector competence. We use these data, together with estimates of the survival of infected blood-fed mosquitoes, to explore the theoretical influence of temperature on transmission in four locations in Kenya, considering recent conditions and future climate change. Results provide insights into factors limiting transmission in cooler environments and indicate that increases in malaria transmission due to climate warming in areas like the Kenyan Highlands, might be less than previously predicted.
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Journal articleDjègbè NDC, Da DF, Somé BM, et al., 2024,
Anopheles aquatic development kinetic and adults' longevity through different seasons in laboratory and semi-field conditions in Burkina Faso
, Parasites and Vectors, Vol: 17, ISSN: 1756-3305BackgroundAnopheles mosquitoes are ectothermic and involved in numerous pathogen transmissions. Their life history traits are influenced by several environmental factors such as temperature, relative humidity and photoperiodicity. Despite extensive investigations of these environmental conditions on vector population ecology, their impact on the different life stages of Anopheles at different seasons in the year remains poorly explored. This study reports the potential impact of these abiotic factors on the immature and adult stages of Anopheles gambiae sensu lato during different seasons.MethodsEnvironmental conditions were simulated in the laboratory using incubators to mimic the environmental conditions of two important periods of the year in Burkina Faso: the peak of rainy season (August) and the onset of dry season (December). Eggs from wild An. coluzzii and An. gambiae s.l. were reared separately under each environmental condition. For Anopheles coluzzii or An. gambiae s.l., eggs were equally divided into two groups assigned to the two experimental conditions. Four replicates were carried out for this experiment. Then, egg hatching rate, pupation rate, larval development time, larva-to-pupae development time, adult emergence dynamics and longevity of Anopheles were evaluated. Also, pupae-to-adult development time from wild L3 and L4 Anopheles larvae was estimated under semi-field conditions in December.ResultsA better egg hatching rate was recorded overall with conditions mimicking the onset of the dry season compared to the peak of the rainy season. Larval development time and longevity of An. gambiae s.l. female were significantly longer at the onset of the dry season compared than at the peak of the rainy season. Adult emergence was spread over 48 and 96 h at the peak of the rainy season and onset of dry season conditions respectively. This 96h duration in the controlled conditions of December was also observed in the semi-field conditions in December.Concl
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Journal articleConnelly SV, Brazeau NF, Msellem M, et al., 2024,
Strong isolation by distance and evidence of population microstructure reflect ongoing Plasmodium falciparum transmission in Zanzibar.
, medRxivThe Zanzibar archipelago of Tanzania has become a low-transmission area for Plasmodium falciparum. Despite being considered an area of pre-elimination for years, achieving elimination has been difficult, likely due to a combination of imported infections from mainland Tanzania, and continued local transmission. To shed light on these sources of transmission, we applied highly multiplexed genotyping utilizing molecular inversion probes to characterize the genetic relatedness of 282 P. falciparum isolates collected across Zanzibar and in Bagamoyo District on the coastal mainland from 2016-2018. Overall, parasite populations on the coastal mainland and Zanzibar archipelago remain highly related. However, parasite isolates from Zanzibar exhibit population microstructure due to rapid decay of parasite relatedness over very short distances. This, along with highly related pairs within shehias, suggests ongoing low level local transmission. We also identified highly related parasites across shehias that reflect human mobility on the main island of Unguja and identified a cluster of highly related parasites, suggestive of an outbreak, in the Micheweni district on Pemba island. Parasites in asymptomatic infections demonstrated higher complexity of infection than those in symptomatic infections, but have similar core genomes. Our data support importation as a main source of genetic diversity and contribution to the parasite population on Zanzibar, but they also show local outbreak clusters where targeted interventions are essential to block local transmission. These results highlight the need for preventive measures against imported malaria and enhanced control measures in areas that remain receptive for malaria reemergence due to susceptible hosts and competent vectors.
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Journal articleCox H, Roeder F, Okell L, et al., 2024,
The private market for antimicrobials: an exploration of two selected mining and frontier areas of Guyana
, Pan American Journal of Public Health, Vol: 48, ISSN: 0030-0632Objective. To identify challenges that may raise pathogens’ resistance to antimicrobial drugs by exploring theprivate market for antimicrobials in two selected mining and frontier areas of Guyana.Methods. The private sector supply was mapped by approaching all authorized pharmacies and informaloutlets, e.g., street vendors and grocery stores, around the two selected towns. Interviews were conductedwith a) sellers on the availability of drugs, expiration dates, prices, and main producers; and b) customers onpurchased drugs, diagnoses, and prescriptions received before purchasing drugs, and intention to completethe treatment. The information collected was described, and the determinants of the self-reported intention ofcustomers to complete the whole treatment were identified.Results. From the perspective of the supply of antimicrobials, essential medicines faced low and insecureavailability, and prescriptions frequently deviated from diagnoses. From the perspective of the demand forantimicrobials, one-third of purchased antibiotics had a high potential for antimicrobial resistance as per theWorld Health Organization AWaRe classification. A high price reduced the self-reported intention to completethe treatment among those who had a prescription, while buying the medication in a licensed pharmacyincreased such intention.Conclusions. In Guyana, there persists a need to establish and revise policies addressing both supply anddemand, such as restricting the sale of antimicrobials to licensed pharmacies and upon prescription, improving prescription practices while reducing the financial burden to patients, guaranteeing access to first-linetreatment drugs, and instructing patients on appropriate use of antimicrobials. Revising such policies is anessential step to contain antimicrobial resistance in the analyzed areas and across Guyana.
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Journal articleMoradi Marjaneh M, Challenger J, salas A, et al., 2023,
Analysis of blood and nasal epithelial transcriptomes to identify mechanisms associated with control of SARS-CoV-2 viral load in the upper respiratory tract
, Journal of Infection, Vol: 87, Pages: 538-550, ISSN: 0163-4453Objectives:The amount of SARS-CoV-2 detected in the upper respiratory tract (URT viral load) is a key driver of transmission of infection. Current evidence suggests that mechanisms constraining URT viral load are different from those controlling lower respiratory tract viral load and disease severity. Understanding such mechanisms may help to develop treatments and vaccine strategies to reduce transmission. Combining mathematical modelling of URT viral load dynamics with transcriptome analyses we aimed to identify mechanisms controlling URT viral load.Methods:COVID-19 patients were recruited in Spain during the first wave of the pandemic. RNA sequencing of peripheral blood and targeted NanoString nCounter transcriptome analysis of nasal epithelium were performed and gene expression analysed in relation to paired URT viral load samples collected within 15 days of symptom onset. Proportions of major immune cells in blood were estimated from transcriptional data using computational differential estimation. Weighted correlation network analysis (adjusted for cell proportions) and fixed transcriptional repertoire analysis were used to identify associations with URT viral load, quantified as standard deviations (z-scores) from an expected trajectory over time.ResultsEighty-two subjects (50% female, median age 54 years (range 3–73)) with COVID-19 were recruited. Paired URT viral load samples were available for 16 blood transcriptome samples, and 17 respiratory epithelial transcriptome samples. Natural Killer (NK) cells were the only blood cell type significantly correlated with URT viral load z-scores (r = −0.62, P = 0.010). Twenty-four blood gene expression modules were significantly correlated with URT viral load z-score, the most significant being a module of genes connected around IFNA14 (Interferon Alpha-14) expression (r = −0.60, P = 1e-10). In fixed repertoire analysis, prostanoid-related gene expression was significantly associated with higher vir
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Journal articleMayor A, Ishengoma DS, Proctor JL, et al., 2023,
Sampling for malaria molecular surveillance
, TRENDS IN PARASITOLOGY, Vol: 39, Pages: 954-968, ISSN: 1471-4922
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