Reducing Malaria Incidence Research Articles

Repeat Ivermectin Mass Drug Administrations for Malaria Control II: Protocol for a Double-blind, Cluster-Randomized, Placebo-Controlled Trial for the Integrated Control of Malaria

The gains made against malaria have stagnated since 2015, threatened further by increasing resistance to insecticides and antimalarials. Improvement in malaria control necessitates a multipronged strategy, which includes the development of novel tools. One such tool is mass drug administration (MDA) with endectocides, primarily ivermectin, which has shown promise in reducing malaria transmission through lethal and sublethal impacts on the mosquito vector. The primary objective of the study is to assess the impact of repeated ivermectin MDA on malaria incidence in children aged ≤10 years. Repeat Ivermectin MDA for Malaria Control II is a double-blind, placebo-controlled, cluster-randomized, and parallel-group trial conducted in a setting with intense seasonal malaria transmission in Southwest Burkina Faso. The study included 14 discrete villages: 7 (50%) randomized to receive standard measures (seasonal malaria chemoprevention [SMC] and bed net use for children aged 3 to 59 months) and placebo, and 7 (50%) randomized to receive standard measures and monthly ivermectin MDA at 300 μg/kg for 3 consecutive days, provided under supervision to all eligible village inhabitants, over 2 successive rainy seasons. Nonpregnant individuals >90 cm in height were eligible for ivermectin MDA, and cotreatment with ivermectin and SMC was not permitted. The primary outcome is malaria incidence in children aged ≤10 years, as assessed by active case surveillance. The secondary safety outcome of repeated ivermectin MDA was assessed through active and passive adverse event monitoring. The trial intervention was conducted from July to November in 2019 and 2020, with additional sampling of humans and mosquitoes occurring through February 2022 to assess postintervention changes in transmission patterns. Additional human and entomological assessments were performed over the 2 years in a subset of households from 6 cross-sectional villages. A subset of individuals underwent additional sampling in 2020 to characterize ivermectin pharmacokinetics and pharmacodynamics. Analysis and unblinding will commence once the database has been completed, cleaned, and locked. Our trial represents the first study to directly assess the impact of a novel approach for malaria control, ivermectin MDA as a mosquitocidal agent, layered into existing standard-of-care interventions. The study was designed to leverage the current SMC deployment infrastructure and will provide evidence regarding the additional benefit of ivermectin MDA in reducing malaria incidence in children. ClinicalTrials.gov NCT03967054; https://clinicaltrials.gov/ct2/show/NCT03967054 and Pan African Clinical Trials Registry PACT201907479787308; https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=8219. DERR1-10.2196/41197.

The relative effect of climate variability on malaria incidence after scale-up of interventions in western Kenya: A time-series analysis of monthly incidence data from 2008 to 2019

BackgroundDespite considerable progress made over the past 20 years in reducing the global burden of malaria, the disease remains a major public health problem and there is concern that climate change might expand suitable areas for transmission. This study investigated the relative effect of climate variability on malaria incidence after scale-up of interventions in western Kenya. MethodsBayesian negative binomial models were fitted to monthly malaria incidence data, extracted from records of patients with febrile illnesses visiting the Lwak Mission Hospital between 2008 and 2019. Data pertaining to bed net use and socio-economic status (SES) were obtained from household surveys. Climatic proxy variables obtained from remote sensing were included as covariates in the models. Bayesian variable selection was used to determine the elapsing time between climate suitability and malaria incidence. ResultsMalaria incidence increased by 50% from 2008 to 2010, then declined by 73% until 2015. There was a resurgence of cases after 2016, despite high bed net use. Increase in daytime land surface temperature was associated with a decline in malaria incidence (incidence rate ratio [IRR] = 0.70, 95% Bayesian credible interval [BCI]: 0.59–0.82), while rainfall was associated with increased incidence (IRR = 1.27, 95% BCI: 1.10–1.44). Bed net use was associated with a decline in malaria incidence in children aged 6–59 months (IRR = 0.78, 95% BCI: 0.70–0.87) but not in older age groups, whereas SES was not associated with malaria incidence in this population. ConclusionsVariability in climatic factors showed a stronger effect on malaria incidence than bed net use. Bed net use was, however, associated with a reduction in malaria incidence, especially among children aged 6–59 months after adjusting for climate effects. To sustain the downward trend in malaria incidence, this study recommends continued distribution and use of bed nets and consideration of climate-based malaria early warning systems when planning for future control interventions.

Spatio-temporal trends of malaria incidence from 2011 to 2017 and environmental predictors of malaria transmission in Myanmar

BackgroundMyanmar bears the heaviest malaria burden in the Greater Mekong Subregion (GMS). This study assessed the spatio-temporal dynamics and environmental predictors of Plasmodium falciparum and Plasmodium vivax malaria in Myanmar.MethodsMonthly reports of malaria cases at primary health centers during 2011–2017 were analyzed to describe malaria distribution across Myanmar at the township and state/region levels by spatial autocorrelation (Moran index) and spatio-temporal clustering. Negative binomial generalized additive models identified environmental predictors for falciparum and vivax malaria, respectively.ResultsFrom 2011 to 2017, there was an apparent reduction in malaria incidence in Myanmar. Malaria incidence peaked in June each year. There were significant spatial autocorrelation and clustering with extreme spatial heterogeneity in malaria cases and test positivity across the nation (P < 0.05). Areas with higher malaria incidence were concentrated along international borders. Primary clusters of P. falciparum persisted in western townships, while clusters of P. vivax shifted geographically over the study period. The primary cluster was detected from January 2011 to December 2013 and covered two states (Sagaing and Kachin). Annual malaria incidence was highest in townships with a mean elevation of 500‒600 m and a high variance in elevation (states with both high and low elevation). There was an apparent linear relationship between the mean normalized difference vegetative index and annual P. falciparum incidence (P < 0.05).ConclusionThe decreasing trends reflect the significant achievement of malaria control efforts in Myanmar. Prioritizing the allocation of resources to high-risk areas identified in this study can achieve effective disease control.Graphical

Effect of a fifth round of seasonal malaria chemoprevention in children aged 5–14 years in Dangassa, an area of long transmission in Mali

Despite a significant reduction in the burden of malaria in children under five years-old, the efficient implementation of seasonal malaria chemoprevention (SMC) at large scale remains a major concern in areas with long malaria transmission. Low coverage rate in the unattainable areas during the rainy season, a shift in the risk of malaria to older children and the rebound in malaria incidence after stopping drug administration are mainly reported in these areas. These gaps represent a major challenge in the efficient implementation of SMC measures. An open randomized study was conducted to assess the effect of a fifth additional round to current regime of SMC in older children living in Dangassa, a rural malaria endemic area. Poisson regression Model was used to estimate the reduction in malaria incidence in the intervention group compared to the control group including age groups (5–9 and 10–14 years) and the use of long-lasting insecticidal nets (LLINs; Yes or No) with a threshold at 5%. Overall, a downward trend in participation rate was observed from August (94.3%) to November (87.2%). In November (round 4), the risk of malaria incidence was similar in both groups (IRR = 0.66, 95%CI [0.35–1.22]). In December (round 5), a decrease of 51% in malaria incidence was observed in intervention group compared to control group adjusted for age groups and the use of LLINs (IRR = 0.49, 95%CI [0.26–0.94]), of which 17% of reduction is attributable to the 5th round in the intervention group. An additional fifth round of SMC resulted in a significant reduction of malaria incidence in the intervention group. The number of SMC rounds could be adapted to the local condition of malaria transmission.

Collateral Effects of Insecticide-Treated Nets on Human and Environmental Safety in an Epidemiological Model for Malaria with Human Risk Perception.

Malaria remains a major health problem in many parts of the world, including Sub-Saharan Africa. Insecticide-treated nets, in combination with other control measures, have been effective in reducing malaria incidence over the past two decades. Nevertheless, there are concerns about improper handling and misuse of nets, producing possible health effects from intoxication and collateral environmental damage. The latter is caused, for instance, from artisanal fishing. We formulate a model of impulsive differential equations to describe the interplay between malaria dynamics, human intoxication, and ecosystem damage; affected by human awareness to these risks and levels of net usage. Our results show that an increase in mosquito net coverage reduces malaria prevalence and increases human intoxications. In addition, a high net coverage significantly reduces the risk perception to disease, naturally increases the awareness for intoxications from net handling, and scarcely increases the risk perception to collateral damage from net fishing. According to our model, campaigns aiming at reducing disease prevalence or intoxications are much more successful than those creating awareness to ecosystem damage. Furthermore, we can observe from our results that introducing closed fishing periods reduces environmental damage more significantly than strategies directed towards increasing the risk perception for net fishing.

A systematic review and meta-analysis of the prevalence of caregiver acceptance of malaria vaccine for under-five children in low-income and middle-income countries (LMICs).

Malaria is the second leading cause of death in children after diarrheal disease, with low- and middle-income countries (LMICs) accounting for over 9 in 10 incidence and deaths. Widespread acceptance and uptake of the RTS,S vaccine, recently approved by the world health organization (WHO), is projected to significantly reduce malaria incidence and deaths. Therefore, we conducted this systematic review and meta-analysis with the aim to determine the malaria vaccine acceptance rate and the factors associated with acceptance. We searched six databases including Google Scholar, PubMed, Cochrane, African Index Medicus, The Regional Office for Africa Library, and WHO Institutional Repository for Information Sharing (IRIS) to identify studies evaluating the malaria vaccine acceptance rate. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Studies were included if they were original articles published in the English language in peer-reviewed journals and assessed the prevalence of willingness to accept a free malaria vaccine, and not qualitative. The risk of publication bias was checked using both Beggar's funnel plot and Egger's test, while the I2 statistic was used to assess the heterogeneity of the included studies. Study quality was determined using the Newcastle-Ottawa scale. A meta-analysis was performed using a random effects model to evaluate the pooled prevalence of malaria vaccine acceptance. The protocol for this article was registered prospectively on the International Prospective Register for Systematic Reviews (PROSPERO), with ID number CRD42022334282). Our analysis included 11 studies with a total sample size of 14, 666 participants. The aggregate malaria vaccine acceptance rate was 95.3% (95% CI:93.0%-97.2%). Among the general population, the acceptance rate was 96.3% (95% CI:92.0%-99.0%) and among mothers, it was 94.4% (95% CI:90.8%-97.2%). By country, Nigeria had the highest acceptance rate (97.6%, 95% CI:96.0%-98.8%), followed by Ghana (94.6%, 95% CI:93.8%-95.3%) and Tanzania (92.5%, 95% CI:84.4%-97.8%). Sociodemographic determinants of vaccine acceptance included place of residence, tribe, age, sex, occupation, and religion. Reasons for low acceptance included safety concerns, efficacy profile, vaccine's requirement for multiple injections, and poor level of awareness. Future efforts should be focused on identifying factors that may improve the actual uptake of the RTS,S vaccine in malaria-endemic communities.

Human behaviour directs household-level exposure to malaria vectors in Bandarban, Bangladesh

BackgroundBangladesh has reduced malaria incidence and mortality by over 75% between 2010 and 2020. Widespread long-lasting insecticidal net (LLIN) distribution and use is one of the measures responsible for this success. Recalcitrant malaria hotspots within the Chittagong Hill Tracts districts suggest important drivers of malaria risk may remain uncharacterized.MethodsTowards understanding how household-level human behaviour impacts exposure to mosquitoes, parallel human landing catches and human behavioural observations were conducted in four households for 6 months (May–October) over the rainy season in the Bandarban District. Analysis quantifies spatiotemporal human behaviour-adjusted exposure to Anopheles with and without LLINs.ResultsThis small-scale operational study demonstrates that human spatial and temporal presence along with LLIN use drives exposure to Anopheles. Though the four households had both outdoor and indoor exposure, especially in the evening (1800–2000 h) and early morning (0400–0500 h), data points to household-based heterogeneity in malaria exposure even with similar LLIN access.ConclusionIncorporating human behaviour into exposure estimates can be used to understand the efficacy and limitations of local vector control strategies and identify gaps in protection, as well as where present intervention strategies may be optimized.

Hydroxyurea treatment is associated with lower malaria incidence in children with sickle cell anemia in sub-Saharan Africa

AbstractRealizing Effectiveness Across Continents with Hydroxyurea (REACH, NCT01966731) provides hydroxyurea at maximum tolerated dose (MTD) for children with sickle cell anemia (SCA) in sub-Saharan Africa. Beyond reducing SCA-related clinical events, documented treatment benefits include ∼50% reduction in malaria incidence. To identify associations and propose mechanisms by which hydroxyurea could be associated with lower malaria rates, infections were recorded across all clinical sites (Angola, Democratic Republic of Congo, Kenya, and Uganda). Hazard ratios (HR) with 95% confidence intervals (CIs) for baseline demographics, and time-varying laboratory and clinical parameters were estimated in a modified Cox gap-time model for repeated events. Over 3387 patient-years of hydroxyurea treatment, 717 clinical malaria episodes occurred in 336 of 606 study participants; over half were confirmed by blood smear and/or rapid diagnostic testing with 97.8% Plasmodium falciparum. In univariate analysis limited to 4 confirmed infections per child, malaria risk was significantly associated with absolute neutrophil count (ANC), splenomegaly, hemoglobin, and achieving MTD; age, malaria season, MTD dose, fetal hemoglobin, α-thalassemia, and glucose-6-phosphate dehydrogenase deficiency had no effect. In multivariable regression of confirmed infections, ANC was significant (HR, 1.37 per doubled value; 95% CI, 1.10-1.70; P = .0052), and ANC values <3.0 × 109/L were associated with lower malaria incidence. Compared with nonpalpable spleen, 1- to 4-cm splenomegaly also was associated with higher malaria risk (HR, 2.01; 95% CI, 1.41-2.85; P = .0001). Hydroxyurea at MTD is associated with lower malaria incidence in SCA through incompletely defined mechanisms, but treatment-associated mild myelosuppression with ANC <3.0 × 109/L is salutary. Splenomegaly is an unexplained risk factor for malaria infections among children with SCA in Africa.

Susceptibility of primary, secondary and suspected vectors to Plasmodium vivax and Plasmodium falciparum infection in Ethiopia

BackgroundInsecticide-based vector control interventions in combination with case management with artemisinin-based combination therapy has reduced malaria incidence and prevalence worldwide. Current control methods focus on the primary malaria vectors, Anopheles gambiae sensu lato (s.l.) and the An. funestus group; however, the impact of secondary and suspected vectors has been either sidelined or received limited attention. Defining the susceptibility of secondary, suspected vector species to different parasites in time and space is essential for efficient malaria control and elimination programs. The aim of this study was to assess the susceptibility of An. gambiae s.l., An. coustani complex and An. pharoensis to Plasmodium vivax and P. falciparum infection in Ethiopia.MethodsLarvae of Anopheles spp. were collected from different aquatic habitats and reared to adults under laboratory conditions, with the temperature and humidity maintained at 27 ± 1 °C and 75 ± 5%, respectively. Adult female mosquitoes were identified to species as An. gambiae s.l., An. coustani complex and An. pharoensis. Females of these three Anopheles spp. were allowed to feed in parallel feeding assays on infected blood containing the same gametocytes isolated from P. falciparum and P. vivax gametocyte-positive patients by indirect membrane feeding assays. All blood-fed mosquitoes were held under laboratory conditions. After 7 days, all surviving mosquitoes were dissected to detect mid-gut oocyst and enumerated under a microscope.ResultsOf 5915 female Anopheles mosquitoes exposed to gametocyte-infected blood, 2106 (35.6%)s fed successfully in the 32 independent infection experiments. There was a significant variation in feeding rates among An. gambiae s.l., An. pharoensis and An. coustani complex (G-test = 48.43, P = 3.049e-11). All three exposed mosquito species were receptive to P. vivax and P. falciparum infection development. The percentage of infected mosquitoes following feeding on an infected blood meal was significantly different among species (G-test = 6.49, P = 0.03886). The median infection intensity (II) for An. coustani complex, An. gambiae s.l. and An. pharoensis was 1.16, 2.00 and 1.25, respectively. Although the proportion of infected mosquitoes significantly differed in terms of II, infection rate (IR) and mean oocyst density among the species, mean oocyst density and IR were highly correlated with gametocyte density in all tests (P < 0.001).ConclusionPrimary, secondary and suspected vectors were experimentally susceptible to both P. vivax and P. falciparum infection. An effective malaria elimination program might include surveillance and control tools which target secondary and suspected vectors that might play an outdoor transmission role, possibly resulting in reduced focal malaria transmission.Graphical Comparison of the three species’ mean infection rates with standard deviation

Occurrence of asymptomatic malaria infection and living conditions in the lowlands of Ethiopia: a community-based cross-sectional study

BackgroundA significant decline in malaria burden was documented in previously high burden African countries. Even though the global decline in malaria burden is significant, about 95% of it was typically found in 29 African countries and the decline was affected by COVID-19 in 2020. The considerable reduction in malaria incidence was noted due to effective prevention and treatment efforts, and rapid changes in living conditions. The relationship between the occurrence of asymptomatic malaria infection and household living conditions is well unstudied. This study aimed to determine the association between household living conditions and the occurrence of asymptomatic malaria in the lowlands of Ethiopia.MethodsA community-based cross-sectional study was conducted from January to March 2021 in twelve villages of Gambella, Southern Nation Nationalities and People Region and Afar in Ethiopia. A total of 1366 households were randomly selected, interviewed, and tested for malaria by rapid diagnostic test and blood film microscopic examination. Multiple logistic regression model was used to determine the independent association between living conditions and asymptomatic malaria infection.ResultsThe prevalence of asymptomatic malaria infection among individuals living in dwellings built with traditional floor/wall/roof ranges from 8.1% to 8.4% while it ranges from 2.0% to 4.6% among those living in modern floor/wall/roof houses. Dwellings built with traditional wall materials (P = 0.050), spending nights with cattle in the same house (P < 0.001), and availability of kitchen in the main house with no partition (P = 0.004) were significantly associated with asymptomatic malaria infection.ConclusionsAsymptomatic malaria infection was 4.3 times higher among occupants residing in dwellings built with traditional wall materials; 5.6 times higher among households spending nights with cattle in the same house, and 2.3 times higher among households with kitchen in the main house with no partition. Therefore, policies and strategies on malaria elimination need to address or target improvements of the above listed living conditions for the community. A multi sectoral action is required to use these social determinants as a vector control strategic addition; and malaria elimination programs are expected to coordinate the implementation.

Malaria in Sub-Saharan Africa: Current Situation and Future Strategies

Malaria is a life-treating disease caused by parasites, which can be transmitted by mosquitoes. Some population groups, such as newborn babies, children under five, and people in pregnancy, are vulnerable to malaria and may likely develop severe diseases. Nearly half of the population around the world was at risk of developing malaria in 2020, even though many countries have successfully eliminated malaria already. Thus, there is an urgent need to eradicate malaria around the world. Although malaria incidence has decreased significantly due to the worldwide implementation of various interventions, sub-Saharan Africa (SSA) holds a significant portion of the cases and deaths. Thus, it is critical to reduce malaria incidence in SSA in order to reduce the global malaria burden. This article summarizes the policies implemented from past to present in SSA the challenges that the region currently encounters, and future strategies the region should develop based on the success of past practices of other countries.

A Retrospective Review on Severe Malaria in Colombia, 2007-2020.

Background: Knowledge of severe malaria (SM) or complicated malaria is insufficient in all its components. The least known type is the one associated with Plasmodium vivax, compared to that caused by P. falciparum. The aim of this study was to provide a general overview of epidemiological information about the burden of SM, obtained from the National Public Health Surveillance System (SIVIGILA) for the period 2007–2020 in Colombia. Methods: A descriptive, retrospective, and cross-sectional study of secondary information was performed via SIVIGILA. Results: There were 9881 SM cases among 1,060,950 total malaria cases in Colombia in 2007–2020: 9.31 SM cases per 1000 malaria cases. During this period, there were 7145 SM cases due to the following species: Plasmodium vivax, 57.6%; P. falciparum, 38.6%; severe mixed malaria, 3.2%; and P. malariae, 0.6%. The most compromised organ systems are the hematological system (54.9%), the liver (9.1%), the kidneys (4.2%), the lungs (1.9%) and the brain (1.6%). Conclusions: There has been a reduction in malaria incidence in Colombia in the last 10–15 years, but there has also been a strong increase in SM incidence. We suggest emphasizing the prevention of the onset of severe malaria, with the early and accurate diagnosis of plasmodial infection.

Assessing Thailand’s 1-3-7 surveillance strategy in accelerating malaria elimination

BackgroundThailand’s strong malaria elimination programme relies on effective implementation of its 1-3-7 surveillance strategy, which was endorsed and implemented nationwide in 2016. For each confirmed malaria patient, the Ministry of Public Health’s Division of Vector Borne Diseases (DVBD) ensures completion of case notification within 1 day, case investigation within 3 days, and foci investigation within 7 days. To date, there has not been a comprehensive assessment of the performance and achievements of the 1-3-7 surveillance strategy although such results could help Thailand’s future malaria elimination strategic planning.MethodsThis study examined adherence to the 1-3-7 protocols, tracked progress against set targets, and examined geographic variations in implementation of the 1-3-7 strategy in the programme’s initial 5 years. An auto-regressive integrated moving average (ARIMA) time series analysis with seasonal decomposition assessed the plausible implementation effect of the 1-3-7 strategy on malaria incidence in the programme’s initial 5 years. The quantitative analysis included all confirmed malaria cases from public health and non-governmental community facilities from October 2014 to September 2021 (fiscal year [FY] 2015 to FY 2021) (n = 77,405). The spatial analysis included active foci with known geocoordinates that reported more than five cases from FY 2018 to FY 2021.ResultsFrom FY 2017 to FY 2021, on-time case notification improved from 24.4% to 89.3%, case investigations from 58.0% to 96.5%, and foci investigations from 37.9% to 87.2%. Adherence to timeliness protocols did not show statistically significant variation by area risk classification. However, adherence to 1-3-7 protocols showed a marked spatial heterogeneity among active foci, and the ARIMA model showed a statistically significant acceleration in the reduction of malaria incidence. The 1-3-7 strategy national indicators and targets in Thailand have shown progressive success, and most targets were achieved for FY 2021.ConclusionThe results of Thailand’s 1-3-7 surveillance strategy are associated with a decreased incidence in the period following the adoption of the strategy although there is notable geographic variation. The DVBD will continue to implement and adapt the 1-3-7 strategy to accelerate progress toward malaria elimination. This assessment may be useful for domestic strategic planning and to other countries considering more intensive case and foci investigation and response strategies.

The fight against malaria: Diminishing gains and growing challenges.

Since the year 2000, historic reductions in malaria incidence and mortality have been driven by the widespread distribution of bed nets, drugs, and insecticides for the prevention and treatment of malaria. Scale-up of these tools has been enabled by an increase in malaria financing compounded by price reductions, yet these trends are unlikely to continue at the same rate. Rapid population growth in high-endemic areas requires procurement of more of these tools just to maintain current coverage, even as prices are likely to increase as resistance to drugs and insecticides forces shifts to newer products. Further progress toward the long-term goal of malaria eradication requires a combination of greater funding, more cost-effective resource allocation, and fundamental changes to the global malaria control strategy.

Cost and cost effectiveness of reactive case detection (RACD), reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) to reduce malaria in the low endemic setting of Namibia: an analysis alongside a 2×2 factorial design cluster randomised controlled trial

ObjectivesTo estimate the cost and cost effectiveness of reactive case detection (RACD), reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) to reduce malaria in a low...

Evaluation of the protective efficacy of a spatial repellent to reduce malaria incidence in children in Mali compared to placebo: study protocol for a cluster-randomized double-blinded control trial (the AEGIS program)

BackgroundSpatial repellents have been widely used for the prevention of mosquito bites but their efficacy in reducing mosquito-borne diseases has never been evaluated in Africa. Additionally, spatial repellents have the potential of being critical tools in the prevention of mosquito-borne diseases in contexts where typical vectors control efforts such as insecticide-treated nets (ITNs) and indoor residual spray (IRS) are inaccessible or underutilized such as among displaced populations or in emergency relief settings. To address this knowledge gap, Kolondieba District, Sikasso Region, Mali was selected as a site to estimate the impact of the Mosquito Shield™, a spatial repellent that incorporates transfluthrin on a plastic sheet, on malaria-related outcomes. Over the past decade, the Region of Sikasso, Health districts of Kadiolo, Yorosso, and Kolondieba have remained among the most afflicted, characterized by an annual parasite incidence of more than 116 cases per 1000 population [1] and a Plasmodium falciparum prevalence rate of 29.7% [2].MethodsCluster-randomized, placebo-controlled, double-blinded clinical trial, whereby children ≥ 6 months to < 10 years old will be enrolled and followed to determine the time to malaria infection with monthly blood samples for microscopic diagnosis. A total of 1920 subjects (HHs) will be enrolled in 60 clusters (30 spatial repellent, 30 placebo). Malaria incidence will be estimated and compared to demonstrate and quantify the protective efficacy (PE) of a spatial repellent, in reducing malaria infection. Monthly mosquito collections using CDC light traps will be conducted to determine if there are entomological correlates of spatial repellent efficacy that may be useful for the evaluation of new spatial repellents. Quarterly human landing catches (HLC) will assess the behavioral effects of the intervention.DiscussionFindings will serve as an efficacy trial of spatial repellent products for sub-Saharan Africa. Findings will be submitted to the World Health Organization Vector Control Advisory Group (WHO VCAG) for assessment of whether spatial repellents have “public health value.” Entomological outcomes will also be measured as proxies of malaria transmission to help develop guidelines for the evaluation of future spatial repellent products.Trial registrationClinicalTrials.govNCT04795648. Registered on March 12, 2021.

Evaluation of the protective efficacy of a spatial repellent to reduce malaria incidence in children in western Kenya compared to placebo: study protocol for a cluster-randomized double-blinded control trial (the AEGIS program)

BackgroundSpatial repellents are widely used for prevention of mosquito bites and evidence is building on their public health value, but their efficacy against malaria incidence has never been evaluated in Africa. To address this knowledge gap, a trial to evaluate the efficacy of Mosquito Shield™, a spatial repellent incorporating transfluthrin, was developed for implementation in Busia County, western Kenya where long-lasting insecticidal net coverage is high and baseline malaria transmission is moderate to high year-round.MethodsThis trial is designed as a cluster-randomized, placebo-controlled, double-blinded clinical trial. Sixty clusters will be randomly assigned in a 1:1 ratio to receive spatial repellent or placebo. A total of 6120 children aged ≥6 months to 10 years of age will be randomly selected from the study clusters, enrolled into an active cohort (baseline, cohort 1, and cohort 2), and sampled monthly to determine time to first infection by smear microscopy. Each cohort following the implementation of the intervention will be split into two groups, one to estimate direct effect of the spatial repellent and the other to estimate degree of diversion of mosquitoes and malaria transmission to unprotected persons. Malaria incidence in each cohort will be estimated and compared (primary indicator) to determine benefit of using a spatial repellent in a high, year-round malaria transmission setting. Mosquitoes will be collected monthly using CDC light traps to determine if there are entomological correlates of spatial repellent efficacy that may be useful for the evaluation of new spatial repellents. Quarterly human landing catches will assess behavioral effects of the intervention.DiscussionFindings will serve as the first cluster-randomized controlled trial powered to detect spatial repellent efficacy to reduce malaria in sub-Saharan Africa where transmission rates are high, insecticide-treated nets are widely deployed, and mosquitoes are resistant to insecticides. Results will be submitted to the World Health Organization Vector Control Advisory Group for assessment of public health value towards an endorsement to recommend inclusion of spatial repellents in malaria control programs.Trial registrationClinicalTrials.govNCT04766879. Registered February 23, 2021.

Model-informed target product profiles of long-acting-injectables for use as seasonal malaria prevention.

Seasonal malaria chemoprevention (SMC) has proven highly efficacious in reducing malaria incidence. However, the continued success of SMC is threatened by the spread of resistance against one of its main preventive ingredients, Sulfadoxine-Pyrimethamine (SP), operational challenges in delivery, and incomplete adherence to the regimens. Via a simulation study with an individual-based model of malaria dynamics, we provide quantitative evidence to assess long-acting injectables (LAIs) as potential alternatives to SMC. We explored the predicted impact of a range of novel preventive LAIs as a seasonal prevention tool in children aged three months to five years old during late-stage clinical trials and at implementation. LAIs were co-administered with a blood-stage clearing drug once at the beginning of the transmission season. We found the establishment of non-inferiority of LAIs to standard 3 or 4 rounds of SMC with SP-amodiaquine was challenging in clinical trial stages due to high intervention deployment coverage. However, our analysis of implementation settings where the achievable SMC coverage was much lower, show LAIs with fewer visits per season are potential suitable replacements to SMC. Suitability as a replacement with higher impact is possible if the duration of protection of LAIs covered the duration of the transmission season. Furthermore, optimising LAIs coverage and protective efficacy half-life via simulation analysis in settings with an SMC coverage of 60% revealed important trade-offs between protective efficacy decay and deployment coverage. Our analysis additionally highlights that for seasonal deployment for LAIs, it will be necessary to investigate the protective efficacy decay as early as possible during clinical development to ensure a well-informed candidate selection process.

Indoor residual spraying for preventing malaria in communities using insecticide-treated nets.

Indoor residual spraying for preventing malaria in communities using insecticide-treated nets.

One Health approach to improve the malaria elimination programme in Henan Province.

One Health is a collaborative, multi-sectoral, trans-disciplinary approach with the goal of achieving optimal health outcomes by recognizing the interconnection between people, animals, plants, and the environment and determining how this relates to the control of infectious diseases such as malaria, schistosomiasis and so on. Malarias caused by Plasmodium that commonly infects female Anopheles mosquitoes, which feed on human blood and act as a disease vector. It has been a worldwide important public health problem from ancient times. Also, malaria is one of the infectious diseases with the longest epidemic time and the most serious harm in the history of Henan Province, China. During the past decades, the multi-sectoral, cross-regional, and multi-disciplinary One Health approach contributed to a significant reduction in malaria incidence, resulting in initiation of the Henan Malaria Elimination Action Plan. Herein, we reviewed the history of the fight against malaria in Henan Province. A full picture of malaria epidemics, prevention, and control strategies were showed, with the objective that it will help stakeholders, and policy-makers to take informed decisions on public health issues and intervention designs on malaria control towards elimination in the similar areas.