Contextual Factors to Improve Implementation of Malaria Chemoprevention in Children: A Systematic Review.

Malaria remains a leading cause of childhood morbidity and mortality in sub-Saharan Africa, particularly among children under 5 years of age. To help address this challenge, the WHO recommends chemoprevention for certain populations. For children and infants, the WHO recommends seasonal malaria chemoprevention (SMC), perennial malaria chemoprevention (PMC; formerly intermittent preventive treatment in infants [IPTi]), and, more recently, intermittent preventive treatment in school children (IPTsc). This review describes the contextual factors, including feasibility, acceptability, health equity, financial considerations, and values and preferences, that impact implementation of these strategies. A systematic search was conducted on July 5, 2022, and repeated April 13, 2023, to identify relevant literature. Two reviewers independently screened titles for eligibility, extracted data from eligible articles, and identified and summarized themes. Of 6,295 unique titles identified, 65 were included. The most frequently evaluated strategy was SMC (n = 40), followed by IPTi (n = 18) and then IPTsc (n = 6). Overall, these strategies were highly acceptable, although with IPTsc, there were community concerns with providing drugs to girls of reproductive age and the use of nonmedical staff for drug distribution. For SMC, door-to-door delivery resulted in higher coverage, improved caregiver acceptance, and reduced cost. Lower adherence was noted when caregivers were charged with giving doses 2 and 3 unsupervised. For SMC and IPTi, travel distances and inclement weather limited accessibility. Sensitization and caregiver education efforts, retention of high-quality drug distributors, and improved transportation were key to improving coverage. Additional research is needed to understand the role of community values and preferences in chemoprevention implementation.

Interpersonal communication, cultural norms, and community perceptions associated with care-seeking for fever among children under age five in Magoé district, Mozambique.

BACKGROUND: Malaria is endemic throughout Mozambique, contributing significantly to the country's burden of disease. Prompt and effective treatment for fevers in children can limit the mortality and morbidity impacts of the disease but many children in the country are not taken for formal care when ill. Using an ideational model of behaviour, this study assesses the magnitude of the relationships for potential drivers of care-seeking, including interpersonal communication, malaria messaging, and knowledge and attitudes about malaria, with actual care-seeking behaviours for under-five children with fever in Magoé district, Mozambique. METHODS: Data on the care-seeking behaviours for fever come from a 2019 household malaria survey in Magoé district. Households were randomly selected for interview from among those with at least one child under age five and one net for every two household members. From 1621 mother-child dyads, the analytical sample consists of 300 children under age five with a fever in the 2 weeks prior to the survey. Multilevel random effects logistic regression models are estimated to test for associations between care-seeking behaviours and hypothesized behavioural determinants, including interpersonal communication (IPC), malaria messaging, ideational factors (e.g., norms, attitudes, beliefs, risk perceptions), and community characteristics. RESULTS: Overall, 18.5% of children under age five (N = 300) were reported to have fever in the previous 2 weeks and, of these, 68.5% were taken to a formal sector health care provider. Multivariate models highlight significant roles for interpersonal communication; care-seeking was highest among mothers who spoke only with friends/community members about malaria (94.0%, p < 0.001), followed by those who spoke only with their husband (78.6%, p = 0.015), relative to 63.3% who spoke with no one. Care-seeking decisions made by a child's grandmother were associated with a 25.0% point (p = 0.001) greater likelihood of seeking care relative to decisions made by the mother alone. Exposure to any malaria messaging was also positively associated with care-seeking (90.5% versus 62.7%, p < 0.001). In contrast, among all individual- and community-level ideational factors, only perceptions of self-efficacy to seek care were related to care-seeking behaviours. CONCLUSIONS: These results suggest that social and behaviour change interventions that focus on encouraging families and community members to talk about malaria and the need to promptly seek treatment for fevers in children may be particularly effective at increasing this behaviour in this and similar settings. Such messaging and IPC should consider grandmothers as a target audience, as they appear to be perceived as highly influential in care-seeking decision-making in this community.

Mask use in public places in Maputo City, Mozambique: Cross-sectional survey.

INTRODUCTION: The use of face masks is one of the preventive measures that Mozambique adopted in order to limit the spread of COVID-19. A study carried out from May 25 to June 6, 2020 found that although many wore masks, incorrect use was observed in 27.5% of the population observed. This data collection aimed to measure the degree of mask use compliance during a more protracted, higher second wave of transmission. METHODOLOGY: A cross-sectional study was conducted in the City of Maputo from 19 to 28 October 2020 through direct observation of mask use of all individuals present in markets, supermarkets and bus terminals. The data were collected using mobile phones with the Open Data Kit Collect (ODK) data collection program. Sociodemographic characteristics, mask use, and type of mask used were documented. Factors associated with incorrect mask use were evaluated considering sex, age, observation period and location. RESULTS: A total of 49,404 individuals were observed, of whom 24,977(50.6%) were male, 46,484 (94.1%) were adults and 17,549 (35.5%) were observed in the markets. An observed 41,786 (84.6%) wore a mask, of whom 33,851 (81.0%) used it correctly. Not covering the mouth and nose was common; observed in 4,649 (58.5%) of those using incorrectly. Of different types of masks, fabric masks were most often used incorrectly 7,225 (21.4%). The factors associated with incorrect mask use were female gender (OR = 1.2 [1.1-1.3], p <0.001), observation in peri-urban versus urban areas (OR = 1.9 [1.8-2.1], p <0.001) and observation during the afternoon (OR = 1.5 [1.5-1.6], p <0. 001). CONCLUSION: A high proportion of observed individuals wore a mask in the context of prevention of COVID-19, however some non-use and incorrect use persists. Intensified public awareness of the correct use of the mask is recommended, especially in peri-urban areas and at the end of the day.

Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique.

Mozambique is one of the four African countries which account for over half of all malaria deaths worldwide, yet little is known about the parasite genetic structure in that country. We performed P. falciparum amplicon and whole genome sequencing on 2251 malaria-infected blood samples collected in 2015 and 2018 in seven provinces of Mozambique to genotype antimalarial resistance markers and interrogate parasite population structure using genome-wide microhaplotyes. Here we show that the only resistance-associated markers observed at frequencies above 5% were pfmdr1-184F (59%), pfdhfr-51I/59 R/108 N (99%) and pfdhps-437G/540E (89%). The frequency of pfdhfr/pfdhps quintuple mutants associated with sulfadoxine-pyrimethamine resistance increased from 80% in 2015 to 89% in 2018 (p < 0.001), with a lower expected heterozygosity and higher relatedness of microhaplotypes surrounding pfdhps mutants than wild-type parasites suggestive of recent selection. pfdhfr/pfdhps quintuple mutants also increased from 72% in the north to 95% in the south (2018; p < 0.001). This resistance gradient was accompanied by a concentration of mutations at pfdhps-436 (17%) in the north, a south-to-north increase in the genetic complexity of P. falciparum infections (p = 0.001) and a microhaplotype signature of regional differentiation. The parasite population structure identified here offers insights to guide antimalarial interventions and epidemiological surveys.

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.

Ideational factors and their association with insecticide treated net use in Magoe District, Mozambique.

BACKGROUND: Insecticide treated bed nets (ITN) are considered a core malaria vector control tool by the WHO and are the main contributor to the large decline in malaria burden in sub-Saharan Africa over the past 20 years, but they are less effective if they are not broadly and regularly used. ITN use may depend on factors including temperature, relative humidity, mosquito density, seasonality, as well as ideational or psychosocial factors including perceptions of nets and perceptions of net use behaviours. METHODS: A cross-sectional household survey was conducted as part of a planned randomized controlled trial in Magoe District, Mozambique. Interviewers captured data on general malaria and ITN perceptions including ideational factors related to perceived ITN response efficacy, self-efficacy to use an ITN, and community norms around ITN using a standardized questionnaire. Only households with sufficient ITNs present for all children to sleep under (at least one ITN for every two children under the age of five years) were eligible for inclusion in the study. Additional questions were added about seasonality and frequency of ITN use. RESULTS: One-thousand six hundred sixteen mother-child dyads were interviewed. Responses indicated gaps in use of existing nets and net use was largely independent of ideational factors related to ITNs. Self-reported ITN use varied little by season nor meaningfully when different methods were used to solicit responses on net use behaviour. Mothers' perceived response efficacy of ITNS was negatively associated with net use (high perceived response efficacy reduced the log-odds of net use by 0.27 (95% CI - 0.04 to - 0.51), implying that stronger beliefs in the effectiveness of ITNs might result in reduced net use among their children. CONCLUSIONS: In this context, ITN use among children was not clearly related to mothers' ideational factors measured in the study. Scales used in solicitation of ideation around ITN use and beliefs need careful design and testing across a broader range of populations in order to identify ideational factors related to ITN use among those with access.

Inferring the epidemiological benefit of indoor vector control interventions against malaria from mosquito data.

The cause of malaria transmission has been known for over a century but it is still unclear whether entomological measures are sufficiently reliable to inform policy decisions in human health. Decision-making on the effectiveness of new insecticide-treated nets (ITNs) and the indoor residual spraying of insecticide (IRS) have been based on epidemiological data, typically collected in cluster-randomised control trials. The number of these trials that can be conducted is limited. Here we use a systematic review to highlight that efficacy estimates of the same intervention may vary substantially between trials. Analyses indicate that mosquito data collected in experimental hut trials can be used to parameterize mechanistic models for Plasmodium falciparum malaria and reliably predict the epidemiological efficacy of quick-acting, neuro-acting ITNs and IRS. Results suggest that for certain types of ITNs and IRS using this framework instead of clinical endpoints could support policy and expedite the widespread use of novel technologies.

Missed Plasmodium ovale Infections Among Symptomatic Persons in Angola, Mozambique, and Ethiopia.

The majority of symptomatic malaria in sub-Saharan Africa is caused by Plasmodium falciparum. Infection with Plasmodium ovale is often not recorded and not considered clinically relevant. Here, we describe 8 cases of P ovale infection from 3 African countries-all of which were misdiagnosed at the presenting health facility.

Adaptation to a Multiplex Bead Assay and Seroprevalence to Rift Valley Fever N Protein: Nampula Province, Mozambique, 2013-2014.

Rift Valley fever virus (RVFV) is endemic in sub-Saharan Africa (SSA), with outbreaks reported in the Arabian Peninsula and throughout SSA. The natural reservoir for RVFV are ruminants, with livestock populations exceeding 50% exposure rates in some areas of SSA. Transmission to humans can occur through exposure to infected livestock products or multiple species of mosquito vectors. In 2013 and 2014, cross-sectional surveys occurred in two districts of Nacala-a-Velha and Mecubúri in northern Mozambique, and participants provided blood samples for later serological assays. IgG against the N protein of RVFV was detected through multiplex bead assay (MBA). Of the 2,278 persons enrolled between the two surveys and study sites, 181 (7.9%, 95% confidence interval (CI): 6.9%-9.1%) were found to be IgG seropositive with increasing seroprevalence with older age and significantly higher seroprevalence in Nacala-a-Velha (10.5%, 8.8%-12.5%) versus Mecubúri (5.7%, 4.5%-7.1%). Seroprevalence estimates were not significantly different between the 2013 and 2014 surveys. Significant spatial clustering of IgG positive persons were consistent among surveys and within the two districts, pointing toward the consistency of serology data for making population-level assumptions regarding RVFV seroprevalence. A subset of persons (n = 539) provided samples for both the 2013 and 2014 surveys, and a low percentage (0.81%) of these were found to seroconvert between these two surveys. Including the RVFV N protein in an MBA antigen panel could assist elucidate RVFV exposure in SSA. IMPORTANCE Due to sporadic transmission, human contact with Rift Valley Fever Virus (RVFV) is difficult to ascertain at a population level. Detection of antibodies against RVFV antigens assist in estimating exposure as antibodies remain in the host long after the virus has been cleared. In this study, we show that antibodies against RVFV N protein can be detected from dried blood spot (DBS) samples being assayed by multiplex bead assay. DBS from two districts in northern Mozambique were tested for IgG against the N protein, and 7.9% of all enrolled persons were seropositive. Older persons, males, and persons residing closer to the coast had higher RVFV N protein seroprevalence. Spatial clustering of IgG positive persons was noted in both districts. These results show low exposure rates to RVFV in these two northern districts in Mozambique, and the ability to perform serology for the RVFV N protein from dried blood samples.

Factors associated with malaria care seeking among children under 5 years of age in Mozambique: a secondary analysis of the 2018 Malaria Indicator Survey.

BACKGROUND: Mozambique is ranked fourth in a list of the 29 countries that accounted for 95% of all malaria cases globally in 2019. The aim of this study was to identify factors associated with care seeking for fever, to determine the association between knowledge about malaria and care seeking and to describe the main reasons for not seeking care among children under five years of age in Mozambique. METHODS: This is a quantitative, observational study based on a secondary data analysis of the 2018 Malaria Indicator Survey. This weighted analysis was based on data reported by surveyed mothers or caregivers of children aged 0-59 months who had fever in the two weeks prior to the survey. RESULTS: Care was reportedly sought for 69.1% [95% CI 63.5-74.2] of children aged 0-59 months old with fever. Care-seeking was significantly higher among younger children, < 6 months old (AOR = 2.47 [95% CI 1.14-5.31]), 6-11 months old (AOR = 1.75 [95% CI 1.01-3.04]) and 12-23 months old (AOR = 1.85 [95% CI 1.19-2.89]), as compared with older children (48-59 months old). In adjusted analysis, mothers from the middle (AOR = 1.66 [95% CI 0.18-3.37]) and richest (AOR = 3.46 [95% CI 1.26-9.49]) wealth quintiles were more likely to report having sought care for their febrile children than mothers from the poorest wealth quintile. Additionally, mothers with secondary or higher education level were more likely to seek care (AOR = 2.16 [95% CI 1.19-3.93]) than mothers with no education. There was no association between maternal malaria knowledge or reported exposure to malaria messages and care-seeking behaviours. The main reasons reported for not seeking care included distance to health facility (46.3% of respondents), the perception that the fever was not severe (22.4%) and the perception that treatment was not available at the health facility (15%). CONCLUSION: Health facility access and socioeconomic barriers continue to be important constraints to malaria service utilization in Mozambique.

Factors associated with knowledge about malaria prevention among women of reproductive age, Tete Province, Mozambique, 2019-2020.

BACKGROUND: Mozambique is a malaria endemic country with an estimated prevalence of malaria in children 6-59 months old that is twice as high in rural areas (46.0%) as in urban areas (18.0%). However, only 46.0% of women aged 15-49 years had complete knowledge about malaria in 2018. This study aimed to identify the factors associated with malaria knowledge among women of reproductive age in a high malaria burden district. METHODS: Data from a cross-sectional study, using a population-based malaria research study in Mágoe District, 2019, were analysed. This analysis included women aged 15-49 years. A multivariate logistic regression model was developed to determine factors associated with complete knowledge of malaria that calculated adjusted odds ratio (aOR) and 95% confidence interval (CI) at a p < 0.05 significance level. Complete malaria knowledge was defined as when a woman correctly identified: fever as a malaria symptom, mosquito bites as the means of malaria transmission, mosquito nets as a tool for malaria prevention, malaria as curable, and were able to name an anti-malarial. RESULTS: A total of 1899 women were included in this analysis. There was complete malaria knowledge among 49% of the respondents. Seventy one percent mentioned fever as one of malaria symptoms, 92% mentioned mosquito bite as the cause of malaria infection, 94% identified that mosquito nets prevent malaria, 92% agreed that malaria has cure, and 76% were able to name at least one anti-malarial medicine. In the multivariate analysis, the following characteristics were associated with significantly higher odds of having complete malaria knowledge: having a secondary school or above education level (adjusted Odds Ratio, aOR = 2.5 CI [1.3-4.6] p = 0.005), being from the middle socioeconomic status group (aOR = 1.5 CI [1.1-2.1] p = 0.005), being from older age group of 35-39 (aOR = 1.9; CI [1.1-3.1] p < 0.001), having 1-2 children (aOR = 1.8; CI [1.2-2.6] p = 0.003), and having interviews completed in Portuguese or Cinyungwe (aOR = 2.3; CI [1.3-4.1] p = 0.004 and aOR = 2.1; CI [1.5-2.8] p < 0.001, respectively). CONCLUSION: Most women in this study had some malaria knowledge, but gaps in complete knowledge remained. In order to broaden knowledge, educational messages about malaria prevention should be more effectively targeted to reach younger, less-educated women and in non-dominant languages.

In vivo efficacy and safety of artemether-lumefantrine and amodiaquine-artesunate 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 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: NCT04370977.

Molecular surveillance for polymorphisms associated with artemisinin-based combination therapy resistance in Plasmodium falciparum isolates collected in Mozambique, 2018.

BACKGROUND: Due to the threat of emerging anti-malarial resistance, the World Health Organization recommends incorporating surveillance for molecular markers of anti-malarial resistance into routine therapeutic efficacy studies (TESs). In 2018, a TES of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) was conducted in Mozambique, and the prevalence of polymorphisms in the pfk13, pfcrt, and pfmdr1 genes associated with drug resistance was investigated. METHODS: Children aged 6-59 months were enrolled in four study sites. Blood was collected and dried on filter paper from participants who developed fever within 28 days of initial malaria treatment. All samples were first screened for Plasmodium falciparum using a multiplex real-time PCR assay, and polymorphisms in the pfk13, pfcrt, and pfmdr1 genes were investigated by Sanger sequencing. RESULTS: No pfk13 mutations, associated with artemisinin partial resistance, were observed. The only pfcrt haplotype observed was the wild type CVMNK (codons 72-76), associated with chloroquine sensitivity. Polymorphisms in pfmdr1 were only observed at codon 184, with the mutant 184F in 43/109 (39.4%) of the samples, wild type Y184 in 42/109 (38.5%), and mixed 184F/Y in 24/109 (22.0%). All samples possessed N86 and D1246 at these two codons. CONCLUSION: In 2018, no markers of artemisinin resistance were documented. Molecular surveillance should continue to monitor the prevalence of these markers to inform decisions on malaria treatment in Mozambique.

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

Malaria prevention knowledge, attitudes, and practices in Zambezia Province, Mozambique.

BACKGROUND: In Mozambique, socio-economic and cultural factors influence the wide adoption of disease preventive measures that are relevant for malaria control strategies to promote early recognition of disease, prompt seeking of medical care, sleeping under insecticide-treated nets (ITNs), and taking intermittent preventive treatment for pregnant women. However, there is a critical information gap regarding previous and ongoing malaria social and behavioural change (SBC) interventions. The aim of this study is to assess the knowledge, attitudes, practices of beneficiaries of SBC interventions. METHODS: A descriptive cross-sectional survey was undertaken in 2018 in two rural districts of Zambezia Province, Mozambique. A structured questionnaire was administered to 773 randomly selected households. Respondents were the adult heads of the households. Descriptive statistics were done. RESULTS: The main results show that 96.4% of respondents recalled hearing about malaria in the previous 6 months, 90.0% had knowledge of malaria prevention, and 70.0% of preventive measures. Of the 97.7% respondents that had received ITNs through a mass ITN distribution campaign, 81.7% had slept under an ITN the night before the survey. In terms of source of health information, 70.5% mentioned the role of community volunteers in dissemination of malaria prevention messages, 76.1% of respondents considered worship places (churches and mosques) to be the main places where they heard key malaria prevention messages, and 79.1% asserted that community dialogue sessions helped them better understand how to prevent malaria. CONCLUSIONS: Results show that volunteers/activists/teachers played an important role in dissemination of key malaria prevention messages, which brought the following successes: community actors are recognized and people have knowledge of malaria transmission, signs and symptoms, preventive measures, and where to get treatment. There is, however, room for improvement on SBC messaging regarding some malaria symptoms (anaemia and convulsions) and operational research is needed to ascertain the drivers of malaria prevalence and inform the SBC approach.

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.

Incremental impact on malaria incidence following indoor residual spraying in a highly endemic area with high standard ITN access in Mozambique: results from a cluster-randomized study.

BACKGROUND: Attaining the goal of reducing the global malaria burden is threatened by recent setbacks in maintaining the effectiveness of vector control interventions partly due to the emergence of pyrethroid resistant vectors. One potential strategy to address these setbacks could be combining indoor residual spraying (IRS) with non-pyrethroids and standard insecticide-treated nets (ITNs). This study aimed to provide evidence on the incremental epidemiological benefit of using third-generation IRS product in a highly endemic area with high ITN ownership. METHODS: A cluster-randomized, open-label, parallel-arms, superiority trial was conducted in the Mopeia district in Zambezia, Mozambique from 2016 to 2018. The district had received mass distribution of alphacypermethrin ITNs two years before the trial and again mid-way. 86 clusters were defined, stratified and randomized to receive or not receive IRS with pirimiphos-methyl (Actellic®300 CS). Efficacy of adding IRS was assessed through malaria incidence in a cohort of children under five followed prospectively for two years, enhanced passive surveillance at health facilities and by community health workers, and yearly cross-sectional surveys at the peak of the transmission season. FINDINGS: A total of 1536 children were enrolled in the cohort. Children in the IRS arm experienced 4,801 cases (incidence rate of 3,532 per 10,000 children-month at risk) versus 5,758 cases in the no-IRS arm (incidence rate of 4,297 per 10,000 children-month at risk), resulting in a crude risk reduction of 18% and an incidence risk ratio of 0.82 (95% CI 0.79-0.86, p-value < 0.001). Facility and community passive surveillance showed a malaria incidence of 278 per 10,000 person-month in the IRS group (43,974 cases over 22 months) versus 358 (95% CI 355-360) per 10,000 person-month at risk in the no-IRS group (58,030 cases over 22 months), resulting in an incidence rate ratio of 0.65 (95% CI 0.60-0.71, p < 0.001). In the 2018 survey, prevalence in children under five in the IRS arm was significantly lower than in the no-IRS arm (OR 0.54, 95% CI, 0.31-0.92, p = 0.0241). CONCLUSION: In a highly endemic area with high ITN access and emerging pyrethroid resistance, adding IRS with pirimiphos-methyl resulted in significant additional protection for children under five years of age. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02910934, registered 22 September 2016, https://clinicaltrials.gov/ct2/show/NCT02910934?term=NCT02910934&draw=2&rank=1 .

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.

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.

Malaria prevention knowledge, attitudes, and practices in Zambezia Province, Mozambique

Background: In Mozambique, socio-economic and cultural factors influence the wide adoption of disease preventive measures that are relevant for malaria control strategies to promote early recognition of disease, prompt seeking of medical care, sleeping under insecticide-treated nets (ITNs), and taking intermittent preventive treatment for pregnant women. However, there is a critical information gap regarding previous and ongoing malaria social and behavioural change (SBC) interventions. The aim of this study is to assess the knowledge, attitudes, practices of beneficiaries of SBC interventions. Methods: A descriptive cross-sectional survey was undertaken in 2018 in two rural districts of Zambezia Province, Mozambique. A structured questionnaire was administered to 773 randomly selected households. Respondents were the adult heads of the households. Descriptive statistics were done. Results: The main results show that 96.4% of respondents recalled hearing about malaria in the previous 6 months, 90.0% had knowledge of malaria prevention, and 70.0% of preventive measures. Of the 97.7% respondents that had received ITNs through a mass ITN distribution campaign, 81.7% had slept under an ITN the night before the survey. In terms of source of health information, 70.5% mentioned the role of community volunteers in dissemination of malaria prevention messages, 76.1% of respondents considered worship places (churches and mosques) to be the main places where they heard key malaria prevention messages, and 79.1% asserted that community dialogue sessions helped them better understand how to prevent malaria. Conclusions: Results show that volunteers/activists/teachers played an important role in dissemination of key malaria prevention messages, which brought the following successes: community actors are recognized and people have knowledge of malaria transmission, signs and symptoms, preventive measures, and where to get treatment. There is, however, room for improvement on SBC messaging regarding some malaria symptoms (anaemia and convulsions) and operational research is needed to ascertain the drivers of malaria prevalence and inform the SBC approach.