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.

Improving the Quality and Use of Malaria Surveillance Data: Results from Evaluating an Integrated Malaria Information Storage System at the Health Facility Level in Selected Districts in Mozambique.

Mozambique addressed critical malaria surveillance system challenges by rolling out an integrated malaria information storage system (iMISS) at the district level in February 2021. The iMISS integrates malaria data from existing systems across thematic program areas to improve data availability and use. In seven districts, the platform was extended to health facilities (HFs), allowing HFs to access iMISS and use tablets to submit monthly malaria reports to a central database, eliminating the need for paper-based reporting to districts. A structured evaluation of the iMISS rollout to HFs was carried out in February-July 2021. The four evaluation areas were data quality (reporting rate, timeliness, and fidelity) of monthly malaria reports electronically submitted to the iMISS, adoption of the iMISS for data-informed decision-making, system maintenance, and acceptability of the iMISS among target users. All 94 HFs in the seven targeted districts were assessed. Over the 6-month period, 86.1% of reported cases on the iMISS were consistent with cases recorded in paper-based reports, allowing for up to 10% discrepancy. In addition, 69.0% of expected monthly district meetings were held, and information from iMISS was discussed during 58.6% of these meetings. Maintenance issues, mostly related to tablet access and internet connectivity, were experienced by 74.5% of HFs; 33.7% of issues were resolved within 1 month. The iMISS and electronic submission of malaria reports were well accepted by HF- and district-level users. Continued political commitment and timely execution of issue management workflows are crucial to ensure trust in the new platform and facilitate higher levels of data use.

Multiple Anopheles species complicate downstream analysis and decision-making in a malaria pre-elimination area in southern Mozambique.

BACKGROUND: Different anopheline species (even within a species group/complex) can differ in their feeding and resting behaviours, which impact both malaria transmission patterns as well as the efficacy of vector control interventions. While morphological identification of sampled specimens is an important first step towards understanding species diversity and abundance, misidentification can result in the implementation of less effective vector control measures, and consequently smaller reductions in the number of local malaria cases. Focusing on southern Mozambique, a malaria pre-elimination area where malaria remains persistent, the aims of this preliminary study were to use molecular identification (CO1 and ITS2 barcoding) to (1) validate the results from the morphological identification (with a particular focus on Anopheles pharoensis and Anopheles squamosus), and (2) have a closer look at the Anopheles coustani group (which includes Anopheles tenebrosus and Anopheles ziemanni). METHODS: Female anopheline mosquitoes (n = 81) were identified morphologically and subsequently sequenced at the ribosomal DNA internal transcribed spacer region 2 (ITS2) and/or cytochrome oxidase subunit 1 (CO1) loci towards species determination. RESULTS: Out of the 62 specimens that were identified morphologically to species, 4 (6.5%) were misidentified. Regarding the An. coustani group, morphological identification showed that several members are present in southern Mozambique, including An. coustani sensu lato (s.l.), An. ziemanni and An. tenebrosus. However, based on both ITS2 and CO1 sequences, the exact species remains unknown for the latter two members until voucher sequences are available for comparison. CONCLUSION: The reason(s) for morphological misidentification of anopheline mosquitoes need to be mitigated. This is usually related to both the capacity (i.e. training) of the microscopist to identify anopheline species, and the information provided in the dichotomous identification key. As the An. coustani complex contributes to (residual) malaria transmission in sub-Saharan Africa, it may play a role in the observed persistent malaria in southern Mozambique. A better baseline characterizing of the local anophelines species diversity and behaviours will allow us to improve entomological surveillance strategies, better understand the impact of vector control on each local vector species, and identify new approaches to target those vector species.

Improving the Quality and Use of Malaria Surveillance Data: Results from Evaluating an Integrated Malaria Information Storage System at the Health Facility Level in Selected Districts in Mozambique

Mozambique addressed critical malaria surveillance system challenges by rolling out an integrated malaria information storage system (iMISS) at the district level in February 2021. The iMISS integrates malaria data from existing systems across thematic program areas to improve data availability and use. In seven districts, the platform was extended to health facilities (HFs), allowing HFs to access iMISS and use tablets to submit monthly malaria reports to a central database, eliminating the need for paper-based reporting to districts. A structured evaluation of the iMISS rollout to HFs was carried out in February-July 2021. The four evaluation areas were data quality (reporting rate, timeliness, and fidelity) of monthly malaria reports electronically submitted to the iMISS, adoption of the iMISS for data-informed decision-making, system maintenance, and acceptability of the iMISS among target users. All 94 HFs in the seven targeted districts were assessed. Over the 6-month period, 86.1% of reported cases on the iMISS were consistent with cases recorded in paper-based reports, allowing for up to 10% discrepancy. In addition, 69.0% of expected monthly district meetings were held, and information from iMISS was discussed during 58.6% of these meetings. Maintenance issues, mostly related to tablet access and internet connectivity, were experienced by 74.5% of HFs; 33.7% of issues were resolved within 1 month. The iMISS and electronic submission of malaria reports were well accepted by HF- and district-level users. Continued political commitment and timely execution of issue management workflows are crucial to ensure trust in the new platform and facilitate higher levels of data use.

In vivo efficacy and safety of artemether-lumefantrine and amodiaquine-artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018

Artemisinin-based combination therapy (ACT) has been the recommended first-line treatment for uncomplicated malaria in Mozambique since 2006, with artemether-lumefantrine (AL) and amodiaquine-artesunate (AS-AQ) as the first choice. To assess efficacy of currently used ACT, an in vivo therapeutic efficacy study was conducted. Methods: The study was conducted in four sentinel sites: Montepuez, Moatize, Mopeia and Massinga. Patients between 6 and 59 months old with uncomplicated Plasmodium falciparum malaria (2000-200,000 parasites/µl) were enrolled between February and September of 2018, assigned to either an AL or AS-AQ treatment arm, and monitored for 28 days. A Bayesian algorithm was applied to differentiate recrudescence from new infection using genotyping data of seven neutral microsatellites. Uncorrected and PCR-corrected efficacy results at day 28 were calculated. Results: Totals of 368 and 273 patients were enrolled in the AL and AS-AQ arms, respectively. Of these, 9.5% (35/368) and 5.1% (14/273) were lost to follow-up in the AL and AS-AQ arms, respectively. There were 48 and 3 recurrent malaria infections (late clinical and late parasitological failures) in the AL and AS-AQ arms, respectively. The day 28 uncorrected efficacy was 85.6% (95% confidence interval (CI) 81.3-89.2%) for AL and 98.8% (95% CI 96.7-99.8%) for AS-AQ, whereas day 28 PCR-corrected efficacy was 97.9% (95% CI 95.6-99.2%) for AL and 99.6% (95% CI 97.9-100%) for AS-AQ. Molecular testing confirmed that 87.4% (42/48) and 33.3% (1/3) of participants with a recurrent malaria infection in the AL and AS-AQ arms were new infections; an expected finding in a high malaria transmission area. Adverse events were documented in less than 2% of participants for both drugs. Conclusion: Both AL and AS-AQ have therapeutic efficacies well above the 90% WHO recommended threshold and remain well-tolerated in Mozambique. Routine monitoring of therapeutic efficacy should continue to ensure the treatments remain efficacious. Trial registration Clinicaltrials.gov

Reduced exposure to malaria vectors following indoor residual spraying of pirimiphos-methyl in a high-burden district of rural Mozambique with high ownership of long-lasting insecticidal nets: entomological surveillance results from a cluster-randomized trial

Background: The need to develop new products and novel approaches for malaria vector control is recognized as a global health priority. One approach to meeting this need has been the development of new products for indoor residual spraying (IRS) with novel active ingredients for public health. While initial results showing the impact of several of these next-generation IRS products have been encouraging, questions remain about how to best deploy them for maximum impact. To help address these questions, a 2-year cluster-randomized controlled trial to measure the impact of IRS with a microencapsulated formulation of pirimiphos-methyl (PM) in an area with high ownership of long-lasting insecticidal nets (LLINs) was conducted in a high-transmission district of central Mozambique with pyrethroid resistant vectors. Presented here are the results of the vector surveillance component of the trial. Methods: The 2 year, two-armed trial was conducted in Mopeia District, Zambezia Province, Mozambique. In ten sentinel villages, five that received IRS with PM in October-November 2016 and again in October-November 2017 and five that received no IRS, indoor light trap collections and paired indoor-outdoor human landing collections catches (HLCs) were conducted monthly from September 2016 through October 2018. A universal coverage campaign in June 2017, just prior to the second spray round, distributed 131,540 standard alpha-cypermethrin LLINs across all study villages and increased overall net usage rates in children under 5 years old to over 90%. Results: The primary malaria vector during the trial was Anopheles funestus sensu lato (s.l.), and standard World Health Organization (WHO) tube tests with this population indicated variable but increasing resistance to pyrethroids (including alpha-cypermethrin, from > 85% mortality in 2017 to 7% mortality in 2018) and uniform susceptibility to PM (100% mortality in both years). Over the entire duration of the study, IRS reduced An. funestus s.l. densities by 48% (CI95 33-59%; p < 0.001) in indoor light traps and by 74% (CI95 38-90%; p = 0.010) during indoor and outdoor HLC, though in each study year reductions in vector density were consistently greatest in those months immediately following the IRS campaigns and waned over time. Overall there was no strong preference for An. funestus to feed indoors or outdoors, and these biting behaviours did not differ significantly across study arms: observed indoor-outdoor biting ratios were 1.10 (CI95 1.00-1.21) in no-IRS villages and 0.88 (CI95 0.67-1.15) in IRS villages. The impact of IRS was consistent in reducing HLC exposures both indoors (75% reduction: CI95 47-88%; p = 0. < 0.001) and outdoors (68% reduction: CI95 22-87%; p = 0.012). While substantially fewer Anopheles gambiae s.l. were collected during the study, trends show a similar impact of IRS on this key vector group as well, with a 33% (CI95 7-53%; p = 0.019) reduction in mosquitoes collected in light traps and a non-statistically significant 39% reduction (p = 0.249) in HLC landing rates. Conclusion: IRS with PM used in addition to pyrethroid-only LLINs substantially reduced human exposures to malaria vectors during both years of the cluster-randomized controlled trial in Mopeia-a high-burden district where the primary vector, An. funestus s.l., was equally likely to feed indoors or outdoors and demonstrated increasing resistance to pyrethroids. Findings suggest that IRS with PM can provide effective vector control, including in some settings where pyrethroid-only ITNs are widely used. Trial registration clinicaltrials.gov , NCT02910934. Registered 22 September 2016, https://www.clinicaltrials.gov/ct2/show/NCT02910934.

Cost and cost-effectiveness of indoor residual spraying with pirimiphos-methyl in a high malaria transmission district of Mozambique with high access to standard insecticide-treated nets

Background: As malaria cases increase in some of the highest burden countries, more strategic deployment of new and proven interventions must be evaluated to meet global malaria reduction goals. Methods: The cost and cost-effectiveness of indoor residual spraying (IRS) with pirimiphos-methyl (Actellic®300 CS) were assessed in a high transmission district (Mopeia) with high access to pyrethroid insecticide-treated nets (ITNs), compared to ITNs alone. The major mosquito vectors in the area were susceptible to primiphos-methyl, but resistant to pyrethoids. A decision analysis approach was followed to conduct deterministic and probabilistic sensitivity analyses in a theoretical cohort of 10,000 children under five years of age (U5) and 10,000 individuals of all ages, separately. Model parameters and distributions were based on prospectively collected cost and epidemiological data from a cluster-randomized control trial and a literature review. The primary analysis used health facility-malaria incidence, while community cohort incidence and cross-sectional prevalence rates were used in sensitivity analyses. Lifetime costs, malaria cases, deaths and disability-adjusted life-years (DALYs) were calculated to determine the incremental costs per DALY averted through IRS. Results: The average IRS cost per person protected was US$8.26 and 51% of the cost was insecticide. IRS averted 46,609 (95% CI 46,570-46,646) uncomplicated and 242 (95% CI 241-243) severe lifetime cases in a theoretical children U5 cohort, yielding an incremental cost-effectiveness ratio (ICER) of US$400 (95% CI 399-402) per DALY averted. In the all-age cohort, the ICER was higher: US$1,860 (95% CI 1,852-1,868) per DALY averted. Deterministic and probabilistic results were consistent. When adding the community protective effect of IRS, the cost per person protected decreased (US$7.06) and IRS was highly cost-effective in children U5 (ICER = US$312) and cost-effective in individuals of all ages (ICER = US$1,431), compared to ITNs alone. Conclusion: This study provides robust evidence that IRS with pirimiphos-methyl can be cost-effective in high transmission regions with high pyrethroid ITN coverage where the major vector is susceptible to pirimiphos-methyl but resistant to pyrethroids. The finding that insecticide cost is the main driver of IRS costs highlights the need to reduce the insecticide price without jeopardizing effectiveness. Trial registration: ClinicalTrials.gov identifier NCT02910934 (Registered 22 September 2016). https://clinicaltrials.gov/ct2/show/NCT02910934?term=NCT02910934&draw=2&rank=1.

Assessment of the Feasibility, Acceptability, and Impact of Implementing Seasonal Malaria Chemoprevention in Nampula Province, Mozambique: Protocol for a Hybrid Effectiveness-Implementation Study

Background Malaria is a significant cause of morbidity and mortality in children aged under 5 years in Mozambique. The World Health Organization recommends seasonal malaria chemoprevention (SMC), the administration of four monthly courses of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ), to children aged 3-59 months during rainy season. However, as resistance to SP is widespread in East and Southern Africa, SMC has so far only been implemented across the Sahel in West Africa. Objective This protocol describes the first phase of a pilot project that aims to assess the protective effect of SP and AQ when used for SMC and investigate the levels of molecular markers of resistance of Plasmodium falciparum to antimalarial medicines in the study districts. In addition, it is important to understand whether SMC is a feasible and acceptable intervention in the context of Nampula Province, Mozambique. Methods This study will adopt a hybrid effectiveness-implementation design to conduct a mixed methods evaluation with six objectives: a molecular marker study, a nonrandomized controlled trial, an analysis of reported malaria morbidity indicators, a documentation exercise of the contextual SMC adaptation, an acceptability and feasibility assessment, and a coverage and quality assessment. Results Ethical approval for this study was granted by the Mozambican Ministry of Health National Bioethics Committee on September 15, 2020. Data collection began in October 2020, and data analysis is expected to be completed by August 2021. Conclusions This research will make a unique contribution to our understanding of whether the combination of SP and AQ, when used for SMC, can confer a protective effect against malaria in children aged 3-59 months in a region where malaria transmission is seasonal and SP resistance is expected to be high. If the project is successful, subsequent phases are expected to provide a more comprehensive assessment of the effectiveness and sustainability of SMCs.

Prospective surveillance study to detect antimalarial drug resistance, gene deletions of diagnostic relevance and genetic diversity of Plasmodium falciparum in Mozambique: protocol

Introduction: Genomic data constitute a valuable adjunct to routine surveillance that can guide programmatic decisions to reduce the burden of infectious diseases. However, genomic capacities remain low in Africa. This study aims to operationalise a functional malaria molecular surveillance system in Mozambique for guiding malaria control and elimination. Methods and analyses: This prospective surveillance study seeks to generate Plasmodium falciparum genetic data to (1) monitor molecular markers of drug resistance and deletions in rapid diagnostic test targets; (2) characterise transmission sources in low transmission settings and (3) quantify transmission levels and the effectiveness of antimalarial interventions. The study will take place across 19 districts in nine provinces (Maputo city, Maputo, Gaza, Inhambane, Niassa, Manica, Nampula, Zambézia and Sofala) which span a range of transmission strata, geographies and malaria intervention types. Dried blood spot samples and rapid diagnostic tests will be collected across the study districts in 2022 and 2023 through a combination of dense (all malaria clinical cases) and targeted (a selection of malaria clinical cases) sampling. Pregnant women attending their first antenatal care visit will also be included to assess their value for molecular surveillance. We will use a multiplex amplicon-based next-generation sequencing approach targeting informative single nucleotide polymorphisms, gene deletions and microhaplotypes. Genetic data will be incorporated into epidemiological and transmission models to identify the most informative relationship between genetic features, sources of malaria transmission and programmatic effectiveness of new malaria interventions. Strategic genomic information will be ultimately integrated into the national malaria information and surveillance system to improve the use of the genetic information for programmatic decision-making. Ethics and dissemination: The protocol was reviewed and approved by the institutional (CISM) and national ethics committees of Mozambique (Comité Nacional de Bioética para Saúde) and Spain (Hospital Clinic of Barcelona). Project results will be presented to all stakeholders and published in open-access journals.

Challenges for malaria surveillance during the COVID-19 emergency response in Nampula, Mozambique, January - May 2020

Since the announcement of the coronavirus disease (COVID-19) pandemic in January 30th 2020, 68 countries reported to the World Health Organization that they were experiencing disruptions in malaria diagnosis and treatment. This situation had the potential to lead to delays in diagnosis and treatment, which could result in an increase in severe cases and deaths. This analysis was based on findings from a field visit, carried out between June 30th and July 1st, 2020, to a warehouse, to two health facilities, and a meeting with a community health worker, and an descriptive epidemiologic data analysis of health information system (HIS) to evaluate trends of the number of people tested for malaria and number of malaria cases reported, by comparing data from 2018, 2019 and 2020 for the period between January and May. The two health facilities and the warehouse had about two months of stock of antimalarial drugs, and patients with malaria symptoms were being tested for malaria at the COVID-19 screening site. The HIS data showed that the number of reported malaria cases decreased by 3.0% (177.646/172.246) in April, and 7.0% (173.188/161.812) in May, when comparing 2019 and 2020 data. People tested for malaria in community increased by 39.0% (190.370/264.730), between 2019 and 2020. The COVID-19 may have had a negative impact on the diagnosis and treatment of malaria in health facility (HF). The decrease in people tested for malaria in the health facilities may have overwhelmed the activities of the community.

In vivo efficacy and safety of artemetherlumefantrine and amodiaquine­artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018

Background: Artemisinin-based combination therapy (ACT) has been the recommended first-line treatment for uncomplicated malaria in Mozambique since 2006, with artemether­lumefantrine (AL) and amodiaquine­artesunate (AS­AQ) as the first choice. To assess efficacy of currently used ACT, an in vivo therapeutic efficacy study was conducted. Methods: The study was conducted in four sentinel sites: Montepuez, Moatize, Mopeia and Massinga. Patients between 6 and 59 months old with uncomplicated Plasmodium falciparum malaria (2000­200,000 parasites/µl) were enrolled between February and September of 2018, assigned to either an AL or AS­AQ treatment arm, and monitored for 28 days. A Bayesian algorithm was applied to differentiate recrudescence from new infection using genotyping data of seven neutral microsatellites. Uncorrected and PCR-corrected efficacy results at day 28 were calculated. Results: Totals of 368 and 273 patients were enrolled in the AL and AS­AQ arms, respectively. Of these, 9.5% (35/368) and 5.1% (14/273) were lost to follow-up in the AL and AS­AQ arms, respectively. There were 48 and 3 recurrent malaria infections (late clinical and late parasitological failures) in the AL and AS­AQ arms, respectively. The day 28 uncorrected efficacy was 85.6% (95% confidence interval (CI) 81.3­89.2%) for AL and 98.8% (95% CI 96.7­99.8%) for AS­AQ, whereas day 28 PCR-corrected efficacy was 97.9% (95% CI 95.6­99.2%) for AL and 99.6% (95% CI 97.9­100%) for AS­AQ. Molecular testing confirmed that 87.4% (42/48) and 33.3% (1/3) of participants with a recurrent malaria infection in the AL and AS­AQ arms were new infections; an expected finding in a high malaria transmission area. Adverse events were documented in less than 2% of participants for both drugs. Conclusion: Both AL and AS­AQ have therapeutic efficacies well above the 90% WHO recommended threshold and remain well-tolerated in Mozambique. Routine monitoring of therapeutic efficacy should continue to ensure the treatments remain efficacious.

Community acceptability to antimalarial mass drug administrations in Magude district, Southern Mozambique: A mixed methods study

Background This study aimed to capture the acceptability prior to, during and after the implementation of the first year of MDA rounds conducted under the Magude project, a malaria elimination project in southern Mozambique. Methods This was amixed-methods study, consisting of focus group discussions (FGDs) prior to the implementation of MDA rounds (September 2015), non-participant observations (NPOs) conducted during the MDA rounds (November 2015 ­beginning of February 2016), and semi-structured interviews (SSIs) after the second round (end of February 2016). Community leaders, women in reproductive age, general members of the community, traditional healers and health professionals were recruited to capture the opinions of all representing key membersofthecommunity. A generic outline of nodes and codes was designed to analyze FGDsandSSIseparately. Qualitative and quantitative NPO information was analyzed following a content analysis approach. Findings 222participants took part in the FGDs (n = 154), and SSIs (n = 68); and 318 household visits during the MDAunderwent NPOs.Thecommunityengagement campaign emerged throughout the study stages as a crucial factor for the acceptability of MDAs. Acceptability wasalso fostered by the community's general will to cooperate in any government-led activity that would reduce malaria burden, the appropriate behavior and knowledge of field workers, or the fact that the intervention was available free of charge to all. Absenteeism of heads of households was identified as the main barrier for the success of the campaign. The most commonly reported factors that negatively affected acceptability were the fear of adverse events, rumors of deaths, being unable to drink alcohol while taking DHAp, or the fear to take DHAp while in anti-retroviral treatment. Pregnancy testing and malaria testing were generally well accepted by the community. Conclusion Magude's community generally accepted the first and second antimalarial MDA rounds, and the procedures associated to the intervention. Future implementation of antimalarial MDAs in southern Mozambique should focus on locally adapted strategies that engage the community to minimize absenteeism and refusals to the intervention.

A multiphase program for malaria elimination in southern Mozambique (the Magude project): A before-after study

Background: Malaria eradication remains the long-term vision of the World Health Organization (WHO). However, whether malaria elimination is feasible in areas of stable transmission in sub-Saharan Africa with currently available tools remains a subject of debate. This study aimed to evaluate a multiphased malaria elimination project to interrupt Plasmodium falciparum malaria transmission in a rural district of southern Mozambique. Methods and findings: A before-after study was conducted between 2015 and 2018 in the district of Magude, with 48,448 residents living in 10,965 households. Building on an enhanced surveillance system, two rounds of mass drug administrations (MDAs) per year over two years (phase I, August 2015-2017), followed by one year of reactive focal mass drug administrations (rfMDAs) (phase II, September 2017-June 2018) were deployed with annual indoor residual spraying (IRS), programmatically distributed long-lasting insecticidal nets (LLINs), and standard case management. The four MDA rounds covered 58%-72% of the population, and annual IRS reported coverage was >70%. Yearly parasite surveys and routine surveillance data were used to monitor the primary outcomes of the study-malaria prevalence and incidence-at baseline and annually since the onset of the project. Parasite prevalence by rapid diagnostic test (RDT) declined from 9.1% (95% confidence interval [CI] 7.0-11.8) in May 2015 to 2.6% (95% CI 2.0-3.4), representing a 71.3% (95% CI 71.1-71.4, p < 0.001) reduction after phase I, and to 1.4% (95% CI 0.9-2.2) after phase II. This represented an 84.7% (95% CI 81.4-87.4, p < 0.001) overall reduction in all-age prevalence. Case incidence fell from 195 to 75 cases per 1,000 during phase I (61.5% reduction) and to 67 per 1,000 during phase II (65.6% overall reduction). Interrupted time series (ITS) analysis was used to estimate the level and trend change in malaria cases associated with the set of project interventions and the number of cases averted. Phase I interventions were associated with a significant immediate reduction in cases of 69.1% (95% CI 57.5-77.6, p < 0.001). Phase II interventions were not associated with a level or trend change. An estimated 76.7% of expected cases were averted throughout the project (38,369 cases averted of 50,005 expected). One malaria-associated inpatient death was observed during the study period. There were 277 mild adverse events (AEs) recorded through the passive pharmacovigilance system during the four MDA rounds. One serious adverse event (SAE) that resulted in death was potentially related to the drug. The study was limited by the incomplete coverage of interventions, the quality of the routine and cross-sectional data collected, and the restricted accuracy of ITS analysis with a short...

Moving towards malaria elimination in southern Mozambique: Cost and cost-effectiveness of mass drug administration combined with intensified malaria control

As new combinations of interventions aiming at interrupting malaria transmission are under evaluation, understanding the associated economic costs and benefits is critical for decision-making. This study assessed the economic cost and cost-effectiveness of the Magude project, a malaria elimination initiative implemented in a district in southern Mozambique (i.e. Magude) between August 2015­June 2018. This project piloted a combination of two mass drug administration (MDA) rounds per year for two consecutive years, annual rounds of universal indoor residual spraying (IRS) and a strengthened surveillance and response system on the back of universal long-lasting insecticide treated net (LLIN) coverage and routine case management implemented by the National Malaria Control Program (NMCP). Although local transmission was not interrupted, the project achieved large reductions in the burden of malaria in the target district.

Setting the scene and generating evidence for malaria elimination in Southern Mozambique

Mozambique has historically been one of the countries with the highest malaria burden in the world. Starting in the 1960s, malaria control efforts were intensified in the southern region of the country, especially in Maputo city and Maputo province, to aid regional initiatives aimed to eliminate malaria in South Africa and eSwatini. Despite significant reductions in malaria prevalence, elimination was never achieved. Following the World Health Organization's renewed vision of a malaria­free­world, and considering the achievements from the past, the Mozambican National Malaria Control Programme (NMCP) embarked on the development and implementation of a strategic plan to accelerate from malaria control to malaria elimination in southern Mozambique. An initial partnership, supported by the Bill and Melinda Gates Foundation and the La Caixa Foundation, led to the creation of the Mozambican Alliance Towards the Elimination of Malaria (MALTEM) and the Malaria Technical and Advisory Committee (MTAC) to promote national ownership and partner coordination to work towards the goal of malaria elimination in local and cross­border initiatives. Surveillance systems to generate epidemiological and entomological intelligence to inform the malaria control strategies were strengthened, and an impact and feasibility assessment of various interventions aimed to interrupt malaria transmission were conducted in Magude district (Maputo Province) through the "Magude Project". The primary aim of this project was to generate evidence to inform malaria elimination strategies for southern Mozambique. The goal of malaria elimination in areas of low transmission intensity is now included in the national malaria strategic plan for 2017­22 and the NMCP and its partners have started to work towards this goal while evidence continues to be generated to move the national elimination agenda forward.

Malaria case management commodity supply and use by community health workers in Mozambique, 2017

Community health workers (CHWs) provide preventive care and integrated community case management (iCCM) to people with low healthcare access worldwide. CHW programmes have helped reduce mortality in myriad countries, but little data on malaria supply chain management has been shared. This project evaluated the current composition, use, and delivery of malaria iCCM kit commodities in Mozambique­rapid diagnostic tests (RDTs) and artemether­lumefantrine (AL) treatments­to better tailor existing resources to the needs of CHWs in diverse practice settings. Methods: Health facilities in Maputo (low malaria burden), Inhambane (moderate), and Nampula (high) Provinces were selected using probability proportionate to the number of CHWs at each facility. All CHWs and their supervisors at selected facilities were interviewed using a structured questionnaire to document experiences with kit commodities. Data were analysed to assess CHW commodity stock levels by province and season. Results: In total, 216 CHWs and 56 supervisors were interviewed at 56 health facilities. CHWs reported receiving an average of 6.7 kits in the last year, although they are intended to receive kits monthly. One-tenth of CHWs reported receiving kits with missing RDTs, and 28% reported lacking some AL treatments. Commodity use was highest in the rainy season. Stockouts were reported by CHWs in all provinces, more commonly in the rainy season. Facility-level stockouts of RDTs or some AL formulation in the past year were reported by 66% of supervisors. Use of CHW kit materials by health facilities was reported by 43% of supervisors; this was most common at facilities experiencing stockouts. Conclusions: Variations in geographic and seasonal malaria commodity needs should be considered in CHW kit distribution planning in Mozambique. Improvements in provision of complete, monthly CHW kits are needed in parallel with improvements in the broader commodity system strengthening. The fndings of this evaluation can help other CHW programmes determine best practices for management of iCCM supply chains. Keywords: Malaria, Mozambique, Community health workers, Supply chain, Integrated community case management

Combination of indoor residual spraying with long-lasting insecticide-treated nets for malaria control in Zambezia, Mozambique: a cluster randomised trial and cost-effectiveness study protocol

Background Most of the reduction in malaria prevalence seen in Africa since 2000 has been attributed to vector control interventions. Yet increases in the distribution and intensity of insecticide resistance and higher costs of newer insecticides pose a challenge to sustaining these gains. Thus, endemic countries face challenging decisions regarding the choice of vector control interventions. Methods A cluster randomised trial is being carried out in Mopeia District in the Zambezia Province of Mozambique, where malaria prevalence in children under 5 is high (68% in 2015), despite continuous and campaign distribution of long-lasting insecticide-treated nets (LLINs). Study arm 1 will continue to use the standard, LLIN-based National Malaria Control Programme vector control strategy (LLINs only), while study arm 2 will receive indoor residual spraying (IRS) once a year for 2 years with a microencapsulated formulation of pirimiphos-methyl (Actellic 300 CS), in addition to the standard LLIN strategy (LLINs+IRS). Prior to the 2016 IRS implementation (the first of two IRS campaigns in this study), 146 clusters were defined and stratified per number of households. Clusters were then randomised 1:1 into the two study arms. The public health impact and cost-effectiveness of IRS intervention will be evaluated over 2 years using multiple methods: (1) monthly active malaria case detection in a cohort of 1548 total children aged 6­59 months; (2) enhanced passive surveillance at health facilities and with community health workers; (3) annual cross-sectional surveys; and (4) entomological surveillance. Prospective microcosting of the intervention and provider and societal costs will be conducted. Insecticide resistance status pattern and changes in local nopheline populations will be included as important supportive outcomes. Discussion By evaluating the public health impact and cost-effectiveness of IRS with a non-pyrethroid insecticide in a high-transmission setting with high LLIN ownership, it is expected that this study will provide programmatic and policy-relevant data to guide national and global vector control strategies.

In-vivo efficacy of chloroquine to clear asymptomatic infections in mozambican adults: a randomized, placebo-controlled Trial with Implications for Elimination Strategies

Recent reports regarding the re-emergence of parasite sensitivity to chloroquine call for a new consideration of this drug as an interesting complementary tool in malaria elimination efforts, given its good safety profile and long half-life. A randomized (2:1), single-blind, placebo-controlled trial was conducted in Manhiça, Mozambique, to assess the in-vivo efficacy of chloroquine to clear plasmodium falciparum (Pf) asymptomatic infections. Primary study endpoint was the rate of adequate and parasitological response (ACPR) to therapy on day 28 (PCR-corrected). Day 0 isolates were analyzed to assess the presence of the PfCRT-76T CQ resistance marker. A total of 52 and 27 male adults were included in the CQ and Placebo group respectively. PCR-corrected ACPR was significantly higher in the CQ arm 89.4% (95%CI 80-98%) compared to the placebo (p < 0.001). CQ cleared 49/50 infections within the first 72 h while placebo cleared 12/26 (LRT p < 0.001). The PfCRT-76T mutation was present only in one out of 108 (0.9%) samples at baseline, well below the 84% prevalence found in 1999 in the same area. This study presents preliminary evidence of a return of chloroquine sensitivity in Mozambican Pf isolates, and calls for its further evaluation in community-based malaria elimination efforts, in combination with other effective anti-malarials.

Normas de tratamento da malária em moçambique, 3ª edição / Malaria treatment standards in mozambique

A malária é uma das principais causas de morbilidade e de mortalidade em Moçambique, particularmente em crianças menores. É a causa mais comum de procura de cuidados médicos, nas consultas externas e de internamento, nas unidades sanitárias do país. A mulher grávida constitui o principal grupo de risco em adultos. A malária é também um problema socioeconómico, uma vez que interfere negativamente no desenvolvimento do País, mantendo o ciclo doença/pobreza devido ao elevado absentismo escolar e laboral bem como a perda de mão-de-obra laboral. O manejo de casos de Malária, consiste no diagnóstico atempado por microscopia ou teste de diagnóstico rápido, suportados por um controlo de qualidade e de um tratamento imediato e correcto com medicamentos eficazes. A presente edição das Normas de Tratamento da Malária contém a actualização das recomendações da OMS baseadas nas novas evidências particularmente relacionadas com o diagnóstico, doses e indicações de tratamento nas crianças e grávidas. Têm como finalidade garantir o uso racional dos medicamentos e são dirigidas a todos profissionais envolvidos no diagnóstico e tratamento da Malária em todas as unidades sanitárias e comunidade (agentes Polivalentes elementares). Servirá ainda aos estudantes dos cursos de Medicina, Técnicos e Agentes de Medicina curativa e enfermeiros Sendo a malária uma doença endémica e de grande impacto em Moçambique, todos os profissionais devem assumir uma postura de responsabilidade, implementando e fazendo cumprir rigorosamente estas normas para benefício da comunidade e da saúde pública no nosso País, de modo a maximizar o benefício dos medicamentos e evitar o surgimento de resistência aos antimaláricos.