Assessing availability, prices, and market share of quality-assured malaria ACT and RDT in the private retail sector in Nigeria and Uganda.

BACKGROUND: An estimated 50% of suspected malaria cases in sub-Saharan Africa first seek care in the private sector, especially in private medicine retail outlets. Quality of care in these outlets is generally unknown but considered poor with many patients not receiving a confirmatory diagnosis or the recommended first-line artemisinin-based combination therapy (ACT). In 2010, a subsidy pilot scheme, the Affordable Medicines Facility malaria, was introduced to crowd out the use of monotherapies in favour of WHO-pre-qualified artemisinin-based combinations (WHO-PQ-ACTs) in the private health sector. The scheme improved the availability, market share, and cost of WHO-PQ-ACTs in countries like Nigeria and Uganda, but in 2018, the subsidies were halted in Nigeria and significantly reduced in Uganda. This paper presents findings from six retail audit surveys conducted from 2014 to 2021 in Nigeria and Uganda to assess whether the impact of subsidies on the price, availability, and market share of artemisinin-based combinations has been sustained after the subsidies were reduced or discontinued. METHODS: Six independent retail audits were conducted in private medicine retail outlets, including pharmacies, drug shops, and clinics in Nigeria (2016, 2018, 2021), and Uganda (2014, 2019, 2020) to assess the availability, price, and market share of anti-malarials, including WHO-PQ-ACTs and non-WHO-PQ-ACTs, and malaria rapid diagnostic tests (RDTs). RESULTS: Between 2016 and 2021, there was a 57% decrease in WHO-PQ-ACT availability in Nigeria and a 9% decrease in Uganda. During the same period, non-WHO-PQ-ACT availability increased in Nigeria by 41% and by 34% in Uganda. The price of WHO-PQ-ACTs increased by 42% in Nigeria to $0.68 and increased in Uganda by 24% to $0.95. The price of non-WHO-PQ-ACTs decreased in Nigeria by 26% to $1.08 and decreased in Uganda by 64% to $1.23. There was a 76% decrease in the market share of WHO-PQ-ACTs in Nigeria and a 17% decrease in Uganda. Malaria RDT availability remained low throughout. CONCLUSION: With the reduction or termination of subsidies for WHO-PQ-ACTs in Uganda and Nigeria, retail prices have increased, and retail prices of non-WHO-PQ-ACTs decreased, likely contributing to a shift of higher availability and increased use of non-WHO-PQ-ACTs.

A qualitative look at bed net access and use in Burkina Faso, Mozambique, Nigeria, and Rwanda following piloted distributions of dual-active ingredient insecticide-treated nets.

BACKGROUND: Universal coverage with insecticide-treated nets (ITNs) is important for malaria control and elimination. The emergence and intensification of insecticide resistance threatens progress made through the deployment of these interventions and has required the development of newer, more expensive ITN types. Understanding malaria prevention behaviour, including barriers and facilitators to net access and use, can support effective decision-making for the promotion and distribution of ITNs. METHODS: In-depth interviews and focus group discussions were conducted in 3 to 4 villages per district, in 13 districts across Burkina Faso, Mozambique, Nigeria and Rwanda from 2019 to 2022. Interviews were conducted in the local language, translated and transcribed in English, French or Portuguese. Transcripts were coded and analysed using Nvivo and ATLAS.ti. RESULTS: ITNs were obtained from mass distribution campaigns, antenatal care and immunization visits, and purchased on the private market in some locations. While there were divergent perspectives in whether the number of distributed nets were adequate, participants consistently expressed concerns of bias, discrimination, and a lack of transparency with the distribution process. ITNs were frequently used alongside other malaria prevention methods. The primary motivation for use was malaria prevention. While some participants reported using nets nightly throughout the year, other participants reported seasonal use, both due to the perceived higher density of mosquitoes and discomfort of sleeping under a net in the increased heat. Other barriers to consistent net use included activities that take place away from the home, sleeping patterns and arrangements, and sensitivity to the insecticides on the nets. CONCLUSIONS: ITNs remain an important malaria control intervention. To ensure adequate and increased net access, distribution campaigns should consider family structures, available sleeping spaces, and other bed sharing preferences when identifying the number of nets needed for distribution. In addition, campaigns should allow for multiple options for net distribution points and timing to accommodate households remote to health services. Continuous distribution channels and complimentary distribution through the private sector could help fill gaps in coverage. Solutions are needed for outdoor malaria transmission, including alternative designs for ITNs, and improving access to complementary personal protective measures.

Perennial malaria chemoprevention with and without malaria vaccination to reduce malaria burden in young children: a modelling analysis.

BACKGROUND: A recent WHO recommendation for perennial malaria chemoprevention (PMC) encourages countries to adapt dose timing and number to local conditions. However, knowledge gaps on the epidemiological impact of PMC and possible combination with the malaria vaccine RTS,S hinder informed policy decisions in countries where malaria burden in young children remains high. METHODS: The EMOD malaria model was used to predict the impact of PMC with and without RTS,S on clinical and severe malaria cases in children under the age of two years (U2). PMC and RTS,S effect sizes were fit to trial data. PMC was simulated with three to seven doses (PMC-3-7) before the age of eighteen months and RTS,S with three doses, shown to be effective at nine months. Simulations were run for transmission intensities of one to 128 infectious bites per person per year, corresponding to incidences of < 1 to 5500 cases per 1000 population U2. Intervention coverage was either set to 80% or based on 2018 household survey data for Southern Nigeria as a sample use case. The protective efficacy (PE) for clinical and severe cases in children U2 was calculated in comparison to no PMC and no RTS,S. RESULTS: The projected impact of PMC or RTS,S was greater at moderate to high transmission than at low or very high transmission. Across the simulated transmission levels, PE estimates of PMC-3 at 80% coverage ranged from 5.7 to 8.8% for clinical, and from 6.1 to 13.6% for severe malaria (PE of RTS,S 10-32% and 24.6-27.5% for clinical and severe malaria, respectively. In children U2, PMC with seven doses nearly averted as many cases as RTS,S, while the combination of both was more impactful than either intervention alone. When operational coverage, as seen in Southern Nigeria, increased to a hypothetical target of 80%, cases were reduced beyond the relative increase in coverage. CONCLUSIONS: PMC can substantially reduce clinical and severe cases in the first two years of life in areas with high malaria burden and perennial transmission. A better understanding of the malaria risk profile by age in early childhood and on feasible coverage by age, is needed for selecting an appropriate PMC schedule in a given setting.

Application of mathematical modelling to inform national malaria intervention planning in Nigeria.

BACKGROUND: For their 2021-2025 National Malaria Strategic Plan (NMSP), Nigeria's National Malaria Elimination Programme (NMEP), in partnership with the World Health Organization (WHO), developed a targeted approach to intervention deployment at the local government area (LGA) level as part of the High Burden to High Impact response. Mathematical models of malaria transmission were used to predict the impact of proposed intervention strategies on malaria burden. METHODS: An agent-based model of Plasmodium falciparum transmission was used to simulate malaria morbidity and mortality in Nigeria's 774 LGAs under four possible intervention strategies from 2020 to 2030. The scenarios represented the previously implemented plan (business-as-usual), the NMSP at an 80% or higher coverage level and two prioritized plans according to the resources available to Nigeria. LGAs were clustered into 22 epidemiological archetypes using monthly rainfall, temperature suitability index, vector abundance, pre-2010 parasite prevalence, and pre-2010 vector control coverage. Routine incidence data were used to parameterize seasonality in each archetype. Each LGA's baseline malaria transmission intensity was calibrated to parasite prevalence in children under the age of five years measured in the 2010 Malaria Indicator Survey (MIS). Intervention coverage in the 2010-2019 period was obtained from the Demographic and Health Survey, MIS, the NMEP, and post-campaign surveys. RESULTS: Pursuing a business-as-usual strategy was projected to result in a 5% and 9% increase in malaria incidence in 2025 and 2030 compared with 2020, while deaths were projected to remain unchanged by 2030. The greatest intervention impact was associated with the NMSP scenario with 80% or greater coverage of standard interventions coupled with intermittent preventive treatment in infants and extension of seasonal malaria chemoprevention (SMC) to 404 LGAs, compared to 80 LGAs in 2019. The budget-prioritized scenario with SMC expansion to 310 LGAs, high bed net coverage with new formulations, and increase in effective case management rate at the same pace as historical levels was adopted as an adequate alternative for the resources available. CONCLUSIONS: Dynamical models can be applied for relative assessment of the impact of intervention scenarios but improved subnational data collection systems are required to allow increased confidence in predictions at sub-national level.

Facilitators and barriers to seasonal malaria chemoprevention (SMC) uptake in Nigeria: a qualitative approach.

BACKGROUND: SMC was adopted in Nigeria in 2014 and by 2021 was being implemented in 18 states, over four months between June and October by 143000 community drug distributors (CDDs) to a target population of 23million children. Further expansion of SMC is planned, extending to 21 states with four or five monthly cycles. In view of this massive scale-up, the National Malaria Elimination Programme undertook qualitative research in five states shortly after the 2021 campaign to understand community attitudes to SMC so that these perspectives inform future planning of SMC delivery in Nigeria. METHODS: In 20 wards representing urban and rural areas with low and high SMC coverage in five states, focus group discussions were held with caregivers, and in-depth interviews conducted with community leaders and community drug distributors. Interviews were also held with local government area and State malaria focal persons and at national level with the NMEP coordinator, and representatives of partners working on SMC in Nigeria. Interviews were recorded and transcribed, those in local languages translated into English, and transcripts analysed using NVivo software. RESULTS: In total, 84 focus groups and 106 interviews were completed. Malaria was seen as a major health concern, SMC was widely accepted as a key preventive measure, and community drug distributors (CDDs) were generally trusted. Caregivers preferred SMC delivered door-to-door to the fixed-point approach, because it allowed them to continue daily tasks, and allowed time for the CDD to answer questions. Barriers to SMC uptake included perceived side-effects of SMC drugs, a lack of understanding of the purpose of SMC, mistrust and suspicions that medicines provided free may be unsafe or ineffective, and local shortages of drugs. CONCLUSIONS: Recommendations from this study were shared with all community drug distributors and others involved in SMC campaigns during cascade training in 2022, including the need to strengthen communication about the safety and effectiveness of SMC, recruiting distributors from the local community, greater involvement of state and national level pharmacovigilance coordinators, and stricter adherence to the planned medicine allocations to avoid local shortages. The findings reinforce the importance of retaining door-to-door delivery of SMC.

Using antenatal care as a platform for malaria surveillance data collection: study protocol.

BACKGROUND: While many malaria-endemic countries have health management information systems that can measure and report malaria trends in a timely manner, these routine systems have limitations. Periodic community cross-sectional household surveys are used to estimate malaria prevalence and intervention coverage but lack geographic granularity and are resource intensive. Incorporating malaria testing for all women at their first antenatal care (ANC) visit (i.e., ANC1) could provide a more timely and granular source of data for monitoring trends in malaria burden and intervention coverage. This article describes a protocol designed to assess if ANC-based surveillance could be a pragmatic tool to monitor malaria. METHODS: This is an observational, cross-sectional study conducted in Benin, Burkina Faso, Mozambique, Nigeria, Tanzania, and Zambia. Pregnant women attending ANC1 in selected health facilities will be tested for malaria infection by rapid diagnostic test and administered a brief questionnaire to capture key indicators of malaria control intervention coverage and care-seeking behaviour. In each location, contemporaneous cross-sectional household surveys will be leveraged to assess correlations between estimates obtained using each method, and the use of ANC data as a tool to track trends in malaria burden and intervention coverage will be validated. RESULTS: This study will assess malaria prevalence at ANC1 aggregated at health facility and district levels, and by gravidity relative to current pregnancy (i.e., gravida 1, gravida 2, and gravida 3 +). ANC1 malaria prevalence will be presented as monthly trends. Additionally, correlation between ANC1 and household survey-derived estimates of malaria prevalence, bed net ownership and use, and care-seeking will be assessed. CONCLUSION: ANC1-based surveillance has the potential to provide a cost-effective, localized measure of malaria prevalence that is representative of the general population and useful for tracking monthly changes in parasite prevalence, as well as providing population-representative estimates of intervention coverage and care-seeking behavior. This study will evaluate the representativeness of these measures and collect information on operational feasibility, usefulness for programmatic decision-making, and potential for scale-up of malaria ANC1 surveillance.

Malaria Frontline Project: strategic approaches to improve malaria control program leveraging experiences from Kano and Zamfara States, Nigeria, 2016-2019.

BACKGROUND: The Malaria Frontline Project (MFP) supported the National Malaria Elimination Program for effective program implementation in the high malaria-burden states of Kano and Zamfara adapting the National Stop Transmission of Polio (NSTOP) program elimination strategies. PROJECT IMPLEMENTATION: The MFP was implemented in 34 LGAs in the two states (20 out of 44 in Kano and all 14 in Zamfara). MFP developed training materials and job aids tailored to expected service delivery for primary and district health facilities and strengthened supportive supervision. Pre- and post-implementation assessments of intervention impacts were conducted in both states. RESULTS: A total of 158 (Kano:83; Zamfara:75) and 180 (Kano:100; Zamfara:80) healthcare workers (HCWs), were interviewed for pre-and post-implementation assessments, respectively. The proportions of HCWs with correct knowledge on diagnostic criteria were Kano: 97.5% to 92.0% and Zamfara: 94.7% to 98.8%; and knowledge of recommended first line treatment of uncomplicated malaria were Kano: 68.7% to 76.0% and Zamfara: 69.3% to 65.0%. The proportion of HCWs who adhered to national guidelines for malaria diagnosis and treatment increased in both states (Kano: 36.1% to 73.0%; Zamfara: 39.2% to 67.5%) and HCW knowledge to confirm malaria diagnosis slightly decreased in Kano State but increased in Zamfara State (Kano: 97.5% to 92.0%; Zamfara: 94.8% to 98.8%). HCWs knowledge of correct IPTp drug increased in both states (Kano: 81.9% to 94.0%; Zamfara: 85.3% to 97.5%). CONCLUSION: MFP was successfully implemented using tailored training materials, job aids, supportive supervision, and data use. The project strategy can likely be adapted to improve the effectiveness of malaria program implementation in other Nigerian states, and other malaria endemic countries.

Design and methods for a quasi-experimental pilot study to evaluate the impact of dual active ingredient insecticide-treated nets on malaria burden in five regions in sub-Saharan Africa.

BACKGROUND: Vector control tools have contributed significantly to a reduction in malaria burden since 2000, primarily through insecticidal-treated bed nets (ITNs) and indoor residual spraying. In the face of increasing insecticide resistance in key malaria vector species, global progress in malaria control has stalled. Innovative tools, such as dual active ingredient (dual-AI) ITNs that are effective at killing insecticide-resistant mosquitoes have recently been introduced. However, large-scale uptake has been slow for several reasons, including higher costs and limited evidence on their incremental effectiveness and cost-effectiveness. The present report describes the design of several observational studies aimed to determine the effectiveness and cost-effectiveness of dual-AI ITNs, compared to standard pyrethroid-only ITNs, at reducing malaria transmission across a variety of transmission settings. METHODS: Observational pilot studies are ongoing in Burkina Faso, Mozambique, Nigeria, and Rwanda, leveraging dual-AI ITN rollouts nested within the 2019 and 2020 mass distribution campaigns in each country. Enhanced surveillance occurring in select study districts include annual cross-sectional surveys during peak transmission seasons, monthly entomological surveillance, passive case detection using routine health facility surveillance systems, and studies on human behaviour and ITN use patterns. Data will compare changes in malaria transmission and disease burden in districts receiving dual-AI ITNs to similar districts receiving standard pyrethroid-only ITNs over three years. The costs of net distribution will be calculated using the provider perspective including financial and economic costs, and a cost-effectiveness analysis will assess incremental cost-effectiveness ratios for Interceptor® G2, Royal Guard®, and piperonyl butoxide ITNs in comparison to standard pyrethroid-only ITNs, based on incidence rate ratios calculated from routine data. CONCLUSIONS: Evidence of the effectiveness and cost-effectiveness of the dual-AI ITNs from these pilot studies will complement evidence from two contemporary cluster randomized control trials, one in Benin and one in Tanzania, to provide key information to malaria control programmes, policymakers, and donors to help guide decision-making and planning for local malaria control and elimination strategies. Understanding the breadth of contexts where these dual-AI ITNs are most effective and collecting robust information on factors influencing comparative effectiveness could improve uptake and availability and help maximize their impact.

Assessment of health service delivery parameters in Kano and Zamfara States, Nigeria.

BACKGROUND: In 2013, the Nigeria Federal Ministry of Health established a Master Health Facility List (MHFL) as recommended by WHO. Since then, some health facilities (HFs) have ceased functioning and new facilities were established. We updated the MHFL and assessed service delivery parameters in the Malaria Frontline Project implementing areas in Kano and Zamfara States. METHODS: We assessed all HFs in each of the 34 project local government areas (LGAs) between July and September 2017. Project staff administered a semi-structured questionnaire developed for this assessment to heads of HFs about the type of facility, category and number of staff working at the facility and to record geo-coordinates of facility. RESULTS: In the Kano State project area, 726 HFs were identified and geo-located: 31 were new facilities, 608 (84%), 116 (16%) and two (0.3%) were Primary Health Care (PHC), secondary and tertiary facilities respectively. Using the national definition, there were 710 (98%) functional facilities and 644 (91%) of these reported to the national health information platform, District Health Information System, version 2 (DHIS2). The Zamfara project area had 739 HFs: eight were new, 715 (97%), 22 (3.0%) and two (0.2%) PHCs, secondary and tertiary facilities respectively. There were 695 (94%) functional facilities with 656 (94%) of these reporting to DHIS2. Using national criteria for primary health care designation, only 95 (9%) of all PHCs in the two States met the minimum human resource requirements. CONCLUSION: Most HFs were functional and reported to DHIS2. A comprehensive MHFL having all the important parameters that should be established and updated regularly by authorities to make it more useful for health services administration and management. Most functional facilities are understaffed.

Caregiver exposure to malaria social and behaviour change messages can improve bed net use among children in an endemic country: secondary analysis of the 2015 Nigeria Malaria Indicator Survey.

BACKGROUND: To reduce the malaria burden in Nigeria, the National Malaria Strategic Plan (NMSP) 2014‒2020 calls for the scale-up of prevention and treatment interventions, including social and behaviour change (SBC). SBC interventions can increase awareness and improve the demand for and uptake of malaria interventions. However, there is limited evidence supporting the implementation of SBC interventions to improve key malaria behaviours, such as insecticide-treated bed net (ITN) use, among children in Nigeria. METHODS: Using data from 2015 Nigeria Malaria Indicator Survey, this study used multiple logistic regression to assess the relationship between caregiver exposure to malaria messages and ITN use among children under five. RESULTS: Caregiver exposure to ITN-related messages was significantly associated with ITN use among children under five (odds ratio [OR] = 1.63, p < 0.001). CONCLUSIONS: The results suggest that caregiver exposure to topic-specific SBC messages improves the use of ITNs among children. Given these results, Nigeria should strive to scale up SBC interventions to help increase ITN use among children in line with the objectives of the NMSP. Further evidence is needed to determine which SBC interventions are the most effective and scalable in Nigeria.

A subnational profiling analysis reveals regional differences as the main predictor of ITN ownership and use in Nigeria.

BACKGROUND: To reduce the malaria burden in Nigeria, the country is scaling up prevention and treatment interventions, especially household ownership and use of insecticide-treated nets (ITNs). Nevertheless, large gaps remain to achieve the goals of the National Malaria Strategic Plan 2014-2020 of universal access to ITNs and their increased use. To inform the targeting of intervention strategies and to maximize impact, the authors conducted a sub-national profiling of household ITN ownership and use in the general population to identify key predictors of ITN ownership and use, and the sub-groups that are at higher risk of low ITN coverage and use. METHODS: The authors conducted a secondary analysis of data from the 2015 Nigeria Malaria Indicator Survey. Using the Chi square automatic interaction detector (CHAID) and multiple logistic regression analysis, the authors examined the key predictors of ITN ownership and use in the general population throughout Nigeria. RESULTS: The CHAID models identified region of the country as the best predictor of household ownership of at least one ITN and its use in the general population, with higher ownership and use observed in the northern regions. The odds of a household owning an ITN were five times greater in the North West region compared with the North Central region (odds ratio [OR] = 5.47, 95% confidence interval [CI] 4.46-6.72, p < 0.001). The odds of ITN use were two times greater for those living in the North West region compared with the North Central region (OR = 2.04, 95% CI 1.73-2.41, p < 0.001). Other significant predictors were household size, head of household education level, household wealth quintile, and place of residence. The CHAID gain index results identified households in the South West, North Central and South Central regions with low ITN ownership, and the general population in the South South, South East and North Central regions with low ITN use. CONCLUSIONS: This study reveals regional differences in ITN ownership and use in Nigeria. Therefore, the findings from this analysis provide evidence that could inform the NMEP to better target future campaign and routine distribution of ITNs, to achieve universal access and increased use by 2020 in Nigeria.

The role of the Deki Reader™ in malaria diagnosis, treatment and reporting: findings from an Africare pilot project in Nigeria.

BACKGROUND: The Deki Reader is a diagnostic device used with rapid diagnostic tests (RDTs) and linked to an online database for real-time uploads of patient information and results. This is in contrast to visual interpretation of malaria RDTs recorded on the District Health Information System (DHIS). This paper compares records for use of the Deki Reader with DHIS records of visual interpretation of RDTs. RESULTS: A total of 4063 patient encounters/tests were recorded on the Deki Reader database between June 1st and December 31st, 2016. These tests were for 2629 persons who presented with fever and had RDT done. In comparison, data from DHIS 2.0 for same period recorded 7201 persons presenting with fever. 2421 out of the 2629 persons (92.1%), received RDT using Deki Reader compared to 6535 out of 7201 persons (90.4%) recorded on DHIS (p = 0.04). From DHIS records, malaria positivity rate was 51.6% (3375 out of 6535 persons) compared to Deki Reader records of 23.6% (572 out of 2421 persons). The difference between these two rates was significant (p < 0.001). The odds ratio (95% CI) for the association between use of Deki Reader and having a positive malaria result was 0.29 (0.26-0.32). DHIS showed that 4008 persons received Artemisinin-based combination therapy (ACT) while 3989 persons tested positive with RDT or microscopy, compared to 691 out of 705 persons (98.0%) using Deki Reader. Finally, Deki Reader identified 618 processing and manufacturers errors with an error rate of 15.3%. CONCLUSION: The Deki Reader is likely a useful tool for malaria diagnosis, treatment, and real-time data management. It potentially improves diagnostic quality, reduces wastage in ACT administration and improves data quality.

Setting a Nigeria national malaria operational research agenda: the process.

BACKGROUND: Employing malaria operational research (MOR) findings in planning national malaria control programmes is gaining increased attention. The malaria control foci are diverse, resources are limited; therefore, agreeing on priority areas is critical. Hitherto, the process of prioritising MOR questions in Nigeria has been limited to few stakeholders. In support of the National Malaria Elimination Programme's (NMEP) effort at setting a MOR agenda, the Nigeria Field Epidemiology and Laboratory Training Programme (NFELTP) in collaboration with NMEP conducted preliminary exploratory study to identify key malaria research gaps and needs, and provide data to inform setting a robust national MOR agenda. The process of generating data is presented in this paper. METHODS: A twelve-member task-team comprising NFELTP, university researchers and NMEP officers was commissioned. Following an inaugural meeting the task-team developed a framework of activities and held five planning meetings, conducted five-week online and self-administered paper-based surveys, key informant interview (KII), two-day desk review workshop, seven-day qualitative data analysis, ten-day result and five-day report writing workshops. Paired group members conducted the interviews across six geopolitical zones of Nigeria. Abridged study report was used for a two-day MOR setting agenda stakeholders' workshop. RESULTS: A structured framework, study protocol and data collection instruments were developed and submitted for ethical approval. The instruments included survey questionnaire for detailed information on researchers and other stakeholders' experience with MOR, the gaps and needs in thematic MOR areas; KII and Delphi guides. After an initial scoping review, primary data were collected from purposively selected survey participants using mixed methods: - online survey (n = 100), self-administered paper-based survey (n = 85), KII (n = 40), desk review workshop (n = 22) and Delphi interviews (n = 8). Comprehensive lists of research gaps/bottlenecks and needs were generated for each thematic area in malaria control. These were used at a two-day national MOR setting stakeholder workshop (n = 54) to guide the development of national MOR agenda document. CONCLUSIONS: A systematic approach involving broad stakeholder engagement provided data and evidence-based information for development of a robust national MOR agenda. The processes involved are recommended for use in malaria endemic settings.

A cluster-randomized trial of client and provider directed financial interventions to align incentives with appropriate case management in private medicine retailers: Results of the TESTsmART trial in Lagos, Nigeria.

Malaria remains a major health priority in Nigeria. Among children with fever who seek care, less than a quarter gets tested for malaria, leading to inappropriate use of the recommended treatment for malaria; Artemisinin-based Combination Therapy (ACT). Here we test an innovative strategy to target ACT subsidies to clients seeking care in Nigeria's private retail health sector who have a confirmed malaria diagnosis. We supported point-of-care malaria testing (mRDTs) in 48 Private Medicine Retailers (PMRs) in the city of Lagos, Nigeria and randomized them to two study arms; a control arm offering subsidized mRDT testing for USD $0.66, and an intervention arm where, in addition to access to subsidized testing as in the control arm, clients who received a positive mRDT at the PMR were eligible for a free (fully subsidized) first-line ACT and PMRs received USD $0.2 for every mRDT performed. Our primary outcome was the proportion of ACTs dispensed to individuals with a positive diagnostic test. Secondary outcomes included proportion of clients who were tested at the PMR and adherence to diagnostic test results. Overall, 23% of clients chose to test at the PMR. Test results seemed to inform treatment decisions and resulted in enhanced targeting of ACTs to confirmed malaria cases with only 26% of test-negative clients purchasing an ACT compared to 58% of untested clients. However, the intervention did not offer further improvements, compared to the control arm, in testing rates or dispensing of ACTs to test-positive clients. We found that ACT subsidies were not passed on to clients testing positive in the intervention arm. We conclude that mRDTs could reduce ACT overconsumption in Nigeria's private retail health sector, but PMR-oriented incentive structures are difficult to implement and may need to be complemented with interventions targeting clients of PMRs to increase test uptake and adherence. Trials registration: Clinical Trials Registration Number: NCT04428307. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816435/ Correction: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476591/.

Malaria parasite density and detailed qualitative microscopy enhances large-scale profiling of infection endemicity in Nigeria.

With global progress towards malaria reduction stalling, further analysis of epidemiology is required, particularly in countries with the highest burden. National surveys have mostly analysed infection prevalence, while large-scale data on parasite density and different developmental forms rarely available. In Nigeria, the country with the largest burden globally, blood slide microscopy of children up to 5 years of age was conducted in the 2018 National Demographic and Health Survey, and parasite prevalence previously reported. In the current study, malaria parasite density measurements are reported and analysed for 7783 of the children sampled across the 36 states within the six geopolitical zones of the country. Asexual and sexual stages, and infections with different malaria parasite species are analysed. Across all states of Nigeria, there was a positive correlation between mean asexual parasite density within infected individuals and prevalence of infection in the community (Spearman's rho = 0.39, P = 0.02). Asexual parasite densities were highest in the northern geopolitical zones (geometric means > 2000 µL-1), extending the evidence of exceptionally high infection burden in many areas. Sexual parasite prevalence in each state was highly correlated with asexual parasite prevalence (Spearman's rho = 0.70, P < 0.001), although sexual parasite densities were low (geometric means < 100 µL-1 in all zones). Infants had lower parasite densities than children above 1 year of age, but there were no differences between male and female children. Most infections were of P. falciparum, which had higher asexual densities but lower sexual parasite densities than P. malariae or P. ovale mono-infections. However, mixed species infections had the highest asexual parasite densities. It is recommended that future large surveys in high burden countries measure parasite densities as well as developmental stages and species, to improve the quality of malaria epidemiology and tracking of future changes.

Non-falciparum malaria infection and IgG seroprevalence among children under 15 years in Nigeria, 2018.

Plasmodium falciparum (Pf) is the dominant malaria parasite in Nigeria though P. vivax (Pv), P. ovale (Po), and P. malariae (Pm) are also endemic. Blood samples (n = 31,234) were collected from children aged 0-14 years during a 2018 nationwide HIV survey and assayed for Plasmodium antigenemia, Plasmodium DNA, and IgG against Plasmodium MSP1-19 antigens. Of all children, 6.6% were estimated to have Pm infection and 1.4% Po infection with no Pv infections detected. The highest household wealth quintile was strongly protective against infection with Pm (aOR: 0.11, 95% CI: 0.05-0.22) or Po (aOR= 0.01, 0.00-0.10). Overall Pm seroprevalence was 34.2% (95% CI: 33.3-35.2) with lower estimates for Po (12.1%, 11.6-12.5) and Pv (6.3%, 6.0-6.7). Pm seropositivity was detected throughout the country with several local government areas showing >50% seroprevalence. Serological and DNA indicators show widespread exposure of Nigerian children to Pm with lower rates to Po and Pv.

Improving health information system for malaria program management: Malaria Frontline Project lessons learned from Kano and Zamfara States, Nigeria, 2016-2019.

The U.S. Centers for Disease Control and Prevention in collaboration with the National Malaria Elimination Program and the African Field Epidemiology Network established the Malaria Frontline Project to provide innovative approaches to improve the malaria program implementation in Kano and Zamfara States, Nigeria. Innovative approaches such as malaria bulletin, malaria monitoring wall chart, conduct of ward level data validation meetings and malaria dashboard have helped improve the use of data for decision making at all levels. Innovative approaches deployed during the project implementation facilitated data analysis and a better understanding of malaria program performance and data utilization for decision making at all levels. These innovative approaches may improve malaria control program performance in Nigeria and other resource limited countries.

Dynamics of IgG antibody response against Plasmodium antigens among Nigerian infants and young children.

Background: Plasmodium falciparum malaria is a leading cause of child mortality in Nigeria. Neonates are born with maternal antibodies from placental transfer which may protect against malaria infection in the first months of life. The IgG dynamics of the transition from passively transferred antimalarial antibodies to actively acquired IgG from natural exposure have not been well elucidated. Methods: Blood samples collected during a 2018 Nigeria nationwide HIV/AIDS household survey were available for 9,443 children under 5 years of age, with a subset of infants under 2 months of age having maternal samples available (n=41). Samples were assayed for the P. falciparum HRP2 antigen and anti-malarial IgG antibodies. LOESS regression examined the dynamics in IgG response in the first 5 years of life. Correlation with maternal IgG levels was assessed for mother/child pairs. Results: Consistent decreases were observed in median IgG levels against all Plasmodium spp. antigen targets for the first months of life. At a population level, P. falciparum apical membrane antigen-1 (AMA1) and merozoite surface protein-1 19kD (PfMSP1) IgG decreased during the first 12 months of life before reaching a nadir, whereas IgGs to other targets only declined for the first 4 months of life. Seropositivity showed a similar decline with the lowest seropositivity against AMA1 and PfMSP1 at 10-12 months, though remaining above 50% during the first 2 years of life in higher transmission areas. No protective association was observed between IgG positivity and P. falciparum infection in infants. Maternal antibody levels showed a strong positive correlation with infant antibody levels for all P. falciparum antigens from birth to 2 months of age, but this correlation was lost by 6 months of age. Discussion: Maternally transferred anti-malarial IgG antibodies rapidly decline during the first 6 months of life, with variations among specific antigens and malaria transmission intensity. From 3-23 months of age, there was a wide range in IgG levels for the blood-stage antigens indicating high individual variation in antibody production as children are infected with malaria. Non-falciparum species-specific antigens showed similar patterns in waning immunity and correlation with paired mother's IgG levels compared to P. falciparum antigens.

Plasmodium falciparum infection prevalence among children aged 6-59 months from independent DHS and HIV surveys: Nigeria, 2018.

Prevalence estimates are critical for malaria programming efforts but generating these from non-malaria surveys is not standard practice. Malaria prevalence estimates for 6-59-month-old Nigerian children were compared between two national household surveys performed simultaneously in 2018: a Demographic and Health Survey (DHS) and the Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS). DHS tested via microscopy (n = 8298) and HRP2-based rapid diagnostic test (RDT, n = 11,351), and NAIIS collected dried blood spots (DBS) which were later tested for histidine-rich protein 2 (HRP2) antigen (n = 8029). National Plasmodium falciparum prevalence was 22.6% (95% CI 21.2- 24.1%) via microscopy and 36.2% (34.6- 37.8%) via RDT according to DHS, and HRP2 antigenemia was 38.3% (36.7-39.9%) by NAIIS DBS. Between the two surveys, significant rank-order correlation occurred for state-level malaria prevalence for RDT (Rho = 0.80, p < 0.001) and microscopy (Rho = 0.75, p < 0.001) versus HRP2. RDT versus HRP2 positivity showed 24 states (64.9%) with overlapping 95% confidence intervals from the two independent surveys. P. falciparum prevalence estimates among 6-59-month-olds in Nigeria were highly concordant from two simultaneous, independently conducted household surveys, regardless of malaria test utilized. This provides evidence for the value of post-hoc laboratory HRP2 detection to leverage non-malaria surveys with similar sampling designs to obtain accurate P. falciparum estimates.

Process and Methodological Considerations for Observational Analyses of Vector Control Interventions in Sub-Saharan Africa Using Routine Malaria Data.

Progress in malaria control has stalled in recent years. With growing resistance to existing malaria vector control insecticides and the introduction of new vector control products, national malaria control programs (NMCPs) increasingly need to make data-driven, subnational decisions to inform vector control deployment. As NMCPs are increasingly conducting subnational stratification of malaria control interventions, including malaria vector control, country-specific frameworks and platforms are increasingly needed to guide data use for vector control deployment. Integration of routine health systems data, entomological data, and vector control program data in observational longitudinal analyses offers an opportunity for NMCPs and research institutions to conduct evaluations of existing and novel vector control interventions. Drawing on the experience of implementing 22 vector control evaluations across 14 countries in sub-Saharan Africa, as well as published and gray literature on vector control impact evaluations using routine health information system data, this article provides practical guidance on the design of these evaluations, makes recommendations for key variables and data sources, and proposes methods to address challenges in data quality. Key recommendations include appropriate parameterization of impact and coverage indicators, incorporating explanatory covariates and contextual factors from multiple sources (including rapid diagnostic testing stockouts; insecticide susceptibility; vector density measures; vector control coverage, use, and durability; climate and other malaria and non-malaria health programs), and assessing data quality before the evaluation through either on-the-ground or remote data quality assessments. These recommendations may increase the frequency, rigor, and utilization of routine data sources to inform national program decision-making for vector control.