Attractive targeted sugar bait phase III trials in Kenya, Mali, and Zambia.

BACKGROUND: Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) target night-time indoor biting mosquitoes and effectively reduce malaria transmission in rural settings across Africa, but additional vector control tools are needed to interrupt transmission. Attractive targeted sugar baits (ATSBs) attract and kill mosquitoes, including those biting outdoors. Deployment of ATSBs incorporating the insecticide dinotefuran was associated with major reductions in mosquito density and longevity in Mali. The impact of this promising intervention on malaria transmission and morbidity now needs to be determined in a range of transmission settings. METHODS/DESIGN: We will conduct three similar stand-alone, open-label, two-arm, cluster-randomized, controlled trials (cRCTs) in Mali, Kenya, and Zambia to determine the impact of ATSB + universal vector control versus universal vector control alone on clinical malaria. The trials will use a "fried-egg" design, with primary outcomes measured in the core area of each cluster to reduce spill-over effects. All household structures in the ATSB clusters will receive two ATSBs, but the impact will be measured in the core of clusters. Restricted randomization will be used. The primary outcome is clinical malaria incidence among children aged 5-14 years in Mali and 1-14 years in Kenya and Zambia. A key secondary outcome is malaria parasite prevalence across all ages. The trials will include 76 clusters (38 per arm) in Mali and 70 (35 per arm) in each of Kenya and Zambia. The trials are powered to detect a 30% reduction in clinical malaria, requiring a total of 3850 person-years of follow-up in Mali, 1260 person-years in Kenya, and 1610 person-years in Zambia. These sample sizes will be ascertained using two seasonal 8-month cohorts in Mali and two 6-month seasonal cohorts in Zambia. In Kenya, which has year-round transmission, four 6-month cohorts will be used (total 24 months of follow-up). The design allows for one interim analysis in Mali and Zambia and two in Kenya. DISCUSSION: Strengths of the design include the use of multiple study sites with different transmission patterns and a range of vectors to improve external validity, a large number of clusters within each trial site, restricted randomization, between-cluster separation to minimize contamination between study arms, and an adaptive trial design. Noted threats to internal validity include open-label design, risk of contamination between study arms, risk of imbalance of covariates across study arms, variation in durability of ATSB stations, and potential disruption resulting from the COVID-19 pandemic. TRIAL REGISTRATION: Zambia: ClinicalTrials.gov NCT04800055 . Registered on March 15, 2021 Mali: ClinicalTrials.gov NCT04149119 . Registered on November 4, 2019 Kenya: ClinicalTrials.gov NCT05219565 . Registered on February 2, 2022.

Determinants of malaria infections among children in refugee settlements in Uganda during 2018-2019.

BACKGROUND: While 5% of 247 million global malaria cases are reported in Uganda, it is also a top refugee hosting country in Africa, with over 1.36 million refugees. Despite malaria being an emerging challenge for humanitarian response in refugee settlements, little is known about its risk factors. This study aimed to investigate the risk factors for malaria infections among children under 5 years of age in refugee settlements in Uganda. METHODS: We utilized data from Uganda's Malaria Indicator Survey which was conducted between December 2018 and February 2019 at the peak of malaria season. In this national survey, household level information was obtained using standardized questionnaires and a total of 7787 children under 5 years of age were tested for malaria using mainly the rapid diagnostic test. We focused on 675 malaria tested children under five in refugee settlements located in Yumbe, Arua, Adjumani, Moyo, Lamwo, Kiryadongo, Kyegegwa, Kamwenge and Isingiro districts. The extracted variables included prevalence of malaria, demographic, social-economic and environmental information. Multivariable logistic regression was used to identify and define the malaria associated risk factors. RESULTS: Overall, malaria prevalence in all refugee settlements across the nine hosting districts was 36.6%. Malaria infections were higher in refugee settlements located in Isingiro (98.7%), Kyegegwa (58.6%) and Arua (57.4%) districts. Several risk factors were significantly associated with acquisition of malaria including fetching water from open water sources [adjusted odds ratio (aOR) = 1.22, 95% CI: 0.08-0.59, P = 0.002], boreholes (aOR = 2.11, 95% CI: 0.91-4.89, P = 0.018) and water tanks (aOR = 4.47, 95% CI: 1.67-11.9, P = 0.002). Other factors included pit-latrines (aOR = 1.48, 95% CI: 1.03-2.13, P = 0.033), open defecation (aOR = 3.29, 95% CI: 1.54-7.05, P = 0.002), lack of insecticide treated bed nets (aOR = 1.15, 95% CI: 0.43-3.13, P = 0.003) and knowledge on the causes of malaria (aOR = 1.09, 95% CI: 0.79-1.51, P = 0.005). CONCLUSIONS: The persistence of the malaria infections were mainly due to open water sources, poor hygiene, and lack of preventive measures that enhanced mosquito survival and infection. Malaria elimination in refugee settlements requires an integrated control approach that combines environmental management with other complementary measures like insecticide treated bed nets, indoor residual spraying and awareness.

LLIN Evaluation in Uganda Project (LLINEUP2)-Factors associated with coverage and use of long­lasting insecticidal nets following the 2020-21 national mass distribution campaign: a cross-sectional survey of 12 districts.

BACKGROUND: In 2020-2021, long-lasting insecticidal nets (LLINs) were distributed nationwide in Uganda during the COVID-19 pandemic. A cross-sectional survey was conducted in 12 districts to evaluate the impact of the campaign 1-5 months after LLIN distribution. METHODS: During April-May 2021, households were randomly selected from target areas (1-7 villages) surrounding 12 government-run health facilities established as Malaria Reference Centres; at least 50 households were enrolled per cluster. Outcomes included household ownership of LLINs distributed through the universal coverage campaign (UCC) (at least one UCC LLIN), adequate coverage of UCC LLINs (at least one UCC LLIN per 2 residents), and use of LLINs (resident slept under a LLIN the previous night). Multivariate logistic regression models were used to identify household- and individual-level factors associated with outcomes, controlling for clustering around health facilities. RESULTS: In total, 634 households, with 3342 residents and 1631 bed-nets, were included. Most households (93.4%) owned at least 1 UCC LLIN, but only 56.8% were adequately covered by UCC LLINs. In an adjusted analysis, the factor most strongly associated with adequate coverage by UCC LLINs was fewer household residents (1-4 vs 7-14; adjusted odds ratio [aOR] 12.96, 95% CI 4.76-35.26, p < 0.001; 5-6 vs 7-14 residents; aOR 2.99, 95% CI 1.21-7.42, p = 0.018). Of the 3166 residents of households that owned at least one UCC LLIN, only 1684 (53.2%) lived in adequately covered households; 89.9% of these used an LLIN the previous night, compared to 1034 (69.8%) of 1482 residents living in inadequately covered households. In an adjusted analysis, restricted to residents of inadequately covered households, LLIN use was higher in children under-five than those aged 5-15 years (aOR 3.04, 95% CI 2.08-4.46, p < 0.001), and higher in household heads than distantly-related residents (aOR 3.94, 95% CI 2.38-6.51, p < 0.001). CONCLUSIONS: Uganda's 2021-21 campaign was successful, despite the COVID-19 pandemic. In future campaigns, strategies should be adopted to ensure high LLIN coverage, particularly for larger households. A better understanding of the drivers of LLIN use within households is needed to guide future interventions, educational messages, and behaviour change communication strategies; school-aged children and distantly-related residents appear vulnerable and could be targeted.

Implementation of a malaria prevention education intervention in Southern Ethiopia: a qualitative evaluation.

BACKGROUND: Though school-aged children (SAC) are at high risk of malaria, they are the ones that benefit the least from malaria prevention measures. A cluster randomized controlled trial was conducted to evaluate the effect of malaria prevention education (MPE) on insecticide-treated bed net (ITN) utilization and prompt diagnosis, reported incidence and treatment (PDAT) of malaria. Qualitative evaluation of the implementation of such interventions is vital to explain its effectiveness and will serve as guidance for future interventions. Therefore, this study aimed to evaluate the implementation of the MPE in southern Ethiopia.  METHODS: The trial was registered in Pan African Clinical Trials Registry (PACTR202001837195738) on 21/01/2020. A descriptive qualitative study using semi-structured interview with participants of the MPE was conducted in January 2020 and January 2021. The collected data were transcribed verbatim and analyzed thematically. The analysis of the data was supported by NVivo. RESULTS: The four themes identified after evaluation of MPE training were the setup of the training, challenges for the success of the training, anticipated challenges for practice as per the protocol and experienced immediate influences of the training. Participants appreciated the training: content covered, way of delivery and the mix of the participants. The context specific facilitators to bed net use were the collateral benefits of ITN and perceived at high risk of malaria while its barriers were quality and quantity of the bed nets, bed net associated discomforts, malaria health literacy and housing condition. Severeness of malaria symptoms and malaria health literacy were reported as both barriers and facilitators of the PDAT of malaria. The identified facilitators of PDAT of malaria were health professionals' attitude and exposure to MPE while its barriers were poverty, use of traditional medicine, health facility problems and Coronavirus Disease 2019 (COVID-19) pandemic. CONCLUSION: Low attendance of parents in the training was the major challenge for the success of MPE. National malaria program should ensure the access to malaria prevention measures; and future studies using increased frequency of the intervention embedded with monitoring adherence to the intervention protocol shall be conducted to improve the gains from existing malaria interventions.

Digitalized long-lasting insecticidal nets mass distribution campaign in the context of Covid-19 pandemic in Kongo Central, Democratic Republic of Congo: challenges and lessons learned.

BACKGROUND: The Democratic Republic of the Congo (DRC) organized a first mass distribution campaign of long-lasting insecticidal nets (LLINs) with digitalized data management with coordinated support from the Ministry of Health (MOH) and Santé Pour Tous En Milieu Rural-an 'Association sans but lucratif' (SANRU Asbl), in the context of the Covid-19 pandemic in Kongo Central province. This article describes the planning and implementation process of this campaign as well as the challenges and lessons learned. METHODS: The planning and implementation process was performed in line with the standard guidance issued by the National Malaria Control Programme (NMCP) following the start of Covid-19. The changes and adaptations put in place as well as the challenges encountered are described. RESULTS: A total of 5,629,211 people were registered (7.7% above projection) in 1,065,537 households (6.2% below projection) giving an average of 5.3 people per household. Of a total of 3,062,850 LLINs ordered, 2,886,096 were distributed to households (94%). Out of 11,070 villages and 3,947 teams planned, 91.7% of villages were reached and 93% of teams were established. CONCLUSION: The revision of standards of campaign implementation during Covid-19, as well as effective coordination supported by real-time decision-making through digital data management, have been factors in the success of this campaign. Maintaining this momentum is essential to ensure the continuity of malaria prevention services for the population.

A practical approach for geographic prioritization and targeting of insecticide-treated net distribution campaigns during public health emergencies and in resource-limited settings.

BACKGROUND: The use of data in targeting malaria control efforts is essential for optimal use of resources. This work provides a practical mechanism for prioritizing geographic areas for insecticide-treated net (ITN) distribution campaigns in settings with limited resources. METHODS: A GIS-based weighted approach was adopted to categorize and rank administrative units based on data that can be applied in various country contexts where Plasmodium falciparum transmission is reported. Malaria intervention and risk factors were used to rank local government areas (LGAs) in Nigeria for prioritization during mass ITN distribution campaigns. Each factor was assigned a unique weight that was obtained through application of the analytic hierarchy process (AHP). The weight was then multiplied by a value based on natural groupings inherent in the data, or the presence or absence of a given intervention. Risk scores for each factor were then summated to generate a composite unique risk score for each LGA. This risk score was translated into a prioritization map which ranks each LGA from low to high priority in terms of timing of ITN distributions. RESULTS: A case study using data from Nigeria showed that a major component that influenced the prioritization scheme was ITN access. Sensitivity analysis results indicate that changes to the methodology used to quantify ITN access did not modify outputs substantially. Some 120 LGAs were categorized as 'extremely high' or 'high' priority when a spatially interpolated ITN access layer was used. When prioritization scores were calculated using DHS-reported state level ITN access, 108 (90.0%) of the 120 LGAs were also categorized as being extremely high or high priority. The geospatial heterogeneity found among input risk factors suggests that a range of variables and covariates should be considered when using data to inform ITN distributions. CONCLUSION: The authors provide a tool for prioritizing regions in terms of timing of ITN distributions. It serves as a base upon which a wider range of vector control interventions could be targeted. Its value added can be found in its potential for application in multiple country contexts, expediated timeframe for producing outputs, and its use of systematically collected malaria indicators in informing prioritization.

[Organization of a free mass distribution campaign of long-lasting insecticidal mosquito nets in the context of COVID-19 in Niger]. / Organisation d´une campagne de masse et gratuite de distribution des moustiquaires imprégnées d´insecticides à longue durée d´action dans le contexte de la COVID-19 au Niger.

Long-lasting insecticidal mosquito nets (LLIMNs) are needed for malaria vector control. However, their distribution is not yet optimal in sub-Saharan regions. According to projections, COVID-19 pandemic will further delay the distribution of LLIMNs. In Niger, a distribution campaign of LLIMNs with a multi-sectoral approach (state-partner-civil society) was organized in compliance with barrier measures for preventing transmission of COVID-19. A door-to-door strategy was chosen to implement this campaign, in order to avoid entry into confined spaces and to engage community. A total of 13,994,681 people received LLIMNs (reflecting a success rate of 101%) in six targeted regions. A collective effort is needed to sustain the fight against malaria in the COVID-19 era.

Insecticide-treated net distribution in Western Kenya: impacts related to COVID-19 and health worker strikes.

We examined the impact of coronavirus disease (COVID) mitigation, supply and distribution interruptions on the delivery of long-lasting insecticide-treated nets (LLINs) in Western Kenya. The median monthly distribution of LLINs declined during COVID mitigation strategies (March-July 2020) and during the health worker strikes (December 2020-February 2021). Recovery periods followed initial declines, indicative of a 'catching up' on missed routine distribution. Mass community campaigns were delayed by 10 months. These observations offer encouragement for routine net distribution resilience, but complete interruptions of planned mass distributions require alternate strategies during pandemics.

Study design and operational framework for a community-based Malaria Elimination Demonstration Project (MEDP) in 1233 villages of district Mandla, Madhya Pradesh.

BACKGROUND: In the past decade substantial reduction in malaria morbidity and mortality has been observed through well-implemented case management and vector control strategies. India has also achieved a significant reduction in malaria burden in 2018 and has committed to eliminate malaria by 2030. The Mandla Malaria Elimination Demonstration Project (MEDP) was started in 2017 in 1233 villages of District Mandla to demonstrate malaria elimination in a tribal district with hard-to-reach areas was possible using active and passive surveillance, case management, vector control, and targeted information, education and communication campaigns. An operational plan was developed to strengthen the existing surveillance and malaria elimination systems, through fortnightly active case detection to ensure that all cases including those that are introduced into the communities are rapidly identified and treated promptly. The plan also focused on the reduction of human-mosquito contact through the use of Long-Lasting Insecticial Nets (LLINs) and Indoor Residual Spray (IRS). The operational plan was modified in view of the present COVID-19 pandemic by creating systems of assistance for the local administration for COVID-related work while ensuring the operational integrity of malaria elimination efforts. RESULTS: The use of MEDP study design and operational plan, with its built-in management control systems, has yielded significant (91%) reduction of indigenous cases of malaria during the period from June 2017 to May 2020. The malaria positivity rate was 0.33% in 2017-18, 0.13% in 2018-19, and 0.06% in 2019-20. Mass screening revealed 0.18% malaria positivity in September-October 2018, followed by 0.06% in June 2019, and 0.03% in December 2019, and these were mostly asymptomatic cases in the community. The project has been able to sustain the gains of the past three years during the ongoing COVID-19 pandemic. CONCLUSION: This paper provides the study design and the operational plan for malaria elimination in a high-burden district of Central India, which presented difficulties of hard to reach areas, forest malaria, and complex epidemiology of urban and rural malaria. The lessons learned could be used for malaria elimination efforts in rest of the country and other parts of South Asia with comparable demography and epidemiology.

Indirect effects of the COVID-19 pandemic on malaria intervention coverage, morbidity, and mortality in Africa: a geospatial modelling analysis.

BACKGROUND: Substantial progress has been made in reducing the burden of malaria in Africa since 2000, but those gains could be jeopardised if the COVID-19 pandemic affects the availability of key malaria control interventions. The aim of this study was to evaluate plausible effects on malaria incidence and mortality under different levels of disruption to malaria control. METHODS: Using an established set of spatiotemporal Bayesian geostatistical models, we generated geospatial estimates across malaria-endemic African countries of the clinical case incidence and mortality of malaria, incorporating an updated database of parasite rate surveys, insecticide-treated net (ITN) coverage, and effective treatment rates. We established a baseline estimate for the anticipated malaria burden in Africa in the absence of COVID-19-related disruptions, and repeated the analysis for nine hypothetical scenarios in which effective treatment with an antimalarial drug and distribution of ITNs (both through routine channels and mass campaigns) were reduced to varying extents. FINDINGS: We estimated 215·2 (95% uncertainty interval 143·7-311·6) million cases and 386·4 (307·8-497·8) thousand deaths across malaria-endemic African countries in 2020 in our baseline scenario of undisrupted intervention coverage. With greater reductions in access to effective antimalarial drug treatment, our model predicted increasing numbers of cases and deaths: 224·1 (148·7-326·8) million cases and 487·9 (385·3-634·6) thousand deaths with a 25% reduction in antimalarial drug coverage; 233·1 (153·7-342·5) million cases and 597·4 (468·0-784·4) thousand deaths with a 50% reduction; and 242·3 (158·7-358·8) million cases and 715·2 (556·4-947·9) thousand deaths with a 75% reduction. Halting planned 2020 ITN mass distribution campaigns and reducing routine ITN distributions by 25%-75% also increased malaria burden to a total of 230·5 (151·6-343·3) million cases and 411·7 (322·8-545·5) thousand deaths with a 25% reduction; 232·8 (152·3-345·9) million cases and 415·5 (324·3-549·4) thousand deaths with a 50% reduction; and 234·0 (152·9-348·4) million cases and 417·6 (325·5-553·1) thousand deaths with a 75% reduction. When ITN coverage and antimalarial drug coverage were synchronously reduced, malaria burden increased to 240·5 (156·5-358·2) million cases and 520·9 (404·1-691·9) thousand deaths with a 25% reduction; 251·0 (162·2-377·0) million cases and 640·2 (492·0-856·7) thousand deaths with a 50% reduction; and 261·6 (167·7-396·8) million cases and 768·6 (586·1-1038·7) thousand deaths with a 75% reduction. INTERPRETATION: Under pessimistic scenarios, COVID-19-related disruption to malaria control in Africa could almost double malaria mortality in 2020, and potentially lead to even greater increases in subsequent years. To avoid a reversal of two decades of progress against malaria, averting this public health disaster must remain an integrated priority alongside the response to COVID-19. FUNDING: Bill and Melinda Gates Foundation; Channel 7 Telethon Trust, Western Australia.

Digitalized mass distribution campaign of insecticide-treated nets (ITNs) in the particular context of Covid-19 pandemic in Benin: challenges and lessons learned.

BACKGROUND: In 2020, Benin has implemented a digitalized mass distribution campaign of insecticide-treated nets (ITNs) in the particular context of COVID-19 pandemic. This paper describes the implementation process as well as the challenges and lessons learned from this campaign. METHODS: A descriptive design was used for reporting the planning and implementation process of ITNs campaign. Moreover, the changes and adaptations related to COVID-19 pandemic are described. RESULTS: A total of 3,175,773 households were registered corresponding to a total of 14,423,998 persons (13.55% more from projection). Moreover, 94.16% (13,581,637 people) of enumerated population were protected. A total of 7,652,166 ITNs were distributed countrywide. CONCLUSIONS: High political commitment, engagement and support add to the financial and technical supports from partners were the essential factors that make 2020 ITNs mass campaign success in Benin despite the particular context of COVID-19 pandemic. It is essential to maintain the prevention activities for malaria and this could substantially reduce the overall impact of the COVID-19 pandemic for the populations at malaria risk.