Assessing national vector control micro-planning in Zambia using the 2021 malaria indicator survey.

BACKGROUND: In 2020, the Zambia National Malaria Elimination Centre targeted the distribution of long-lasting insecticidal nets (LLINs) and indoor-residual spraying (IRS) campaigns based on sub-district micro-planning, where specified geographical areas at the health facility catchment level were assigned to receive either LLINs or IRS. Using data from the 2021 Malaria Indicator Survey (MIS), the objectives of this analysis were to (1) assess how well the micro-planning was followed in distributing LLINs and IRS, (2) investigate factors that contributed to whether households received what was planned, and (3) investigate how overall coverage observed in the 2021 MIS compared to the 2018 MIS conducted prior to micro-planning. METHODS: Households' receipt of ≥ 1 LLIN, and/or IRS within the past 12 months in the 2021 MIS, was compared against the micro-planning area under which the households fell. GPS points for 3,550 households were overlayed onto digitized micro-planning maps in order to determine what micro-plan the households fell under, and thus whether they received their planned intervention. Mixed-effects regression models were conducted to investigate what factors affected whether these households: (1) received their planned intervention, and (2) received any intervention. Finally, coverage indicators between the 2021 and 2018 MIS were compared. RESULTS: Overall, 60.0% (95%CI 55.4, 64.4) of households under a micro-plan received their assigned intervention, with significantly higher coverage of the planned intervention in LLIN-assigned areas (75.7% [95%CI 69.5, 80.9]) compared to IRS-assigned areas (49.4% [95%CI: 44.4, 54.4]). Regression analysis indicated that households falling under the IRS micro-plan had significantly reduced odds of receiving their planned intervention (OR: 0.34 [95%CI 0.24, 0.48]), and significantly reduced odds of receiving any intervention (OR: 0.51 [95%CI 0.37, 0.72] ), compared to households under the LLIN micro-plan. Comparison between the 2021 and 2018 MIS indicated a 27% reduction in LLIN coverage nationally in 2021, while IRS coverage was similar. Additionally, between 2018 and 2021, there was a 13% increase in households that received neither intervention. CONCLUSIONS: This analysis shows that although the micro-planning strategy adopted in 2020 worked much better for LLIN-assigned areas compared to IRS-assigned areas, there was reduced overall vector control coverage in 2021 compared to 2018 before micro-planning.

Master statistical analysis plan: attractive targeted sugar bait phase III trials in Kenya, Mali, and Zambia.

This manuscript is a master statistical analysis plan for each of three-cluster randomized controlled trials to evaluate the efficacy of attractive targeted sugar baits (ATSB) described in an already published protocol. The master SAP contains an overarching plan for all three trials, which can be adapted to trial-specific circumstances. The primary objective of the trials is to evaluate the efficacy of ATSB in the presence of universal vector control coverage with insecticide-treated nets (ITN) or indoor residual spraying (IRS) after two transmission seasons on clinical malaria incidence as compared with universal vector control coverage with ITN or IRS alone. The primary outcome measure is the incidence rate of clinical malaria, assessed in cohorts aged 12 months to less than 15 years (≥ 5 years to 15 years in Mali) during monthly follow-up visits. The primary unadjusted analysis will be conducted on the intention-to-treat analysis population without adjustment for any anticipated confounding variables. The primary outcome will be analyzed using a multi-level model constructed on a generalized linear model framework with a Poisson likelihood and a log link function. Random intercepts will be included for each study cluster and a fixed effect for study-arm. The analyst will be blinded to study arm assignment. Several secondary outcomes will be analyzed, as well as a pooled analysis (individual patient data meta-analysis) across the three trial sites. Additionally, a standard meta-analysis is expected to be conducted using combined data from all sites.

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.

Spatial Clustering and Risk Factors for Malaria Infections and Marker of Recent Exposure to Plasmodium falciparum from a Household Survey in Artibonite, Haiti.

Targeting malaria interventions in elimination settings where transmission is heterogeneous is essential to ensure the efficient use of resources. Identifying the most important risk factors among persons experiencing a range of exposure can facilitate such targeting. A cross-sectional household survey was conducted in Artibonite, Haiti, to identify and characterize spatial clustering of malaria infections. Household members (N = 21,813) from 6,962 households were surveyed and tested for malaria. An infection was defined as testing positive for Plasmodium falciparum by either a conventional or novel highly sensitive rapid diagnostic test. Seropositivity to the early transcribed membrane protein 5 antigen 1 represented recent exposure to P. falciparum. Clusters were identified using SaTScan. Associations among individual, household, and environmental risk factors for malaria, recent exposure, and living in spatial clusters of these outcomes were evaluated. Malaria infection was detected in 161 individuals (median age: 15 years). Weighted malaria prevalence was low (0.56%; 95% CI: 0.45-0.70%). Serological evidence of recent exposure was detected in 1,134 individuals. Bed net use, household wealth, and elevation were protective, whereas being febrile, over age 5 years, and living in either households with rudimentary wall material or farther from the road increased the odds of malaria. Two predominant overlapping spatial clusters of infection and recent exposure were identified. Individual, household, and environmental risk factors are associated with the odds of individual risk and recent exposure in Artibonite; spatial clusters are primarily associated with household-level risk factors. Findings from serology testing can further strengthen the targeting of interventions.

Acceptability, Feasibility, Drug Safety, and Effectiveness of a Pilot Mass Drug Administration with a Single Round of Sulfadoxine-Pyrimethamine Plus Primaquine and Indoor Residual Spraying in Communities with Malaria Transmission in Haiti, 2018.

For a malaria elimination strategy, Haiti's National Malaria Control Program piloted a mass drug administration (MDA) with indoor residual spraying (IRS) in 12 high-transmission areas across five communes after implementing community case management and strengthened surveillance. The MDA distributed sulfadoxine-pyrimethamine and single low-dose primaquine to eligible residents during house visits. The IRS campaign applied pirimiphos-methyl insecticide on walls of eligible houses. Pre- and post-campaign cross-sectional surveys were conducted to assess acceptability, feasibility, drug safety, and effectiveness of the combined interventions. Stated acceptability for MDA before the campaign was 99.2%; MDA coverage estimated at 10 weeks post-campaign was 89.6%. Similarly, stated acceptability of IRS at baseline was 99.9%; however, household IRS coverage was 48.9% because of the high number of ineligible houses. Effectiveness measured by Plasmodium falciparum prevalence at baseline and 10 weeks post-campaign were similar: 1.31% versus 1.43%, respectively. Prevalence of serological markers were similar at 10 weeks post-campaign compared with baseline, and increased at 6 months. No severe adverse events associated with the MDA were identified in the pilot; there were severe adverse events in a separate, subsequent campaign. Both MDA and IRS are acceptable and feasible interventions in Haiti. Although a significant impact of a single round of MDA/IRS on malaria transmission was not found using a standard pre- and post-intervention comparison, it is possible there was blunting of the peak transmission. Seasonal malaria transmission patterns, suboptimal IRS coverage, and low baseline parasitemia may have limited the effectiveness or the ability to measure effectiveness.

Effectiveness of community case management of malaria on severe malaria and inpatient malaria deaths in Zambia: a dose-response study using routine health information system data.

BACKGROUND: Community case management of malaria (CCM) has been expanded in many settings, but there are limited data describing the impact of these services in routine implementation settings or at large scale. Zambia has intensively expanded CCM since 2013, whereby trained volunteer community health workers (CHW) use rapid diagnostic tests and artemether-lumefantrine to diagnose and treat uncomplicated malaria. METHODS: This retrospective, observational study explored associations between changing malaria service point (health facility or CHW) density per 1000 people and severe malaria admissions or malaria inpatient deaths by district and month in a dose-response approach, using existing routine and programmatic data. Negative binomial generalized linear mixed-effect models were used to assess the impact of increasing one additional malaria service point per 1000 population, and of achieving Zambia's interim target of 1 service point per 750 population. Access to insecticide-treated nets, indoor-residual spraying, and rainfall anomaly were included in models to reduce potential confounding. RESULTS: The study captured 310,855 malaria admissions and 7158 inpatient malaria deaths over 83 districts (seven provinces) from January 2015 to May 2020. Total CHWs increased from 43 to 4503 during the study period, while health facilities increased from 1263 to 1765. After accounting for covariates, an increase of one malaria service point per 1000 was associated with a 19% reduction in severe malaria admissions among children under five (incidence rate ratio [IRR] 0.81, 95% confidence interval [CI] 0.75-0.87, p < 0.001) and 23% reduction in malaria deaths among under-fives (IRR 0.77, 95% CI 0.66-0.91). After categorizing the exposure of population per malaria service point, there was evidence for an effect on malaria admissions and inpatient malaria deaths among children under five only when reaching the target of one malaria service point per 750 population. CONCLUSIONS: CCM is an effective strategy for preventing severe malaria and deaths in areas such as Zambia where malaria diagnosis and treatment access remains challenging. These results support the continued investment in CCM scale-up in similar settings, to improve access to malaria diagnosis and treatment.

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.

Evaluating the Impact of Programmatic Mass Drug Administration for Malaria in Zambia Using Routine Incidence Data.

BACKGROUND: In 2016, the Zambian National Malaria Elimination Centre started programmatic mass drug administration (pMDA) campaigns with dihydroartemisinin-piperaquine as a malaria elimination tool in Southern Province. Two rounds were administered, 2 months apart (coverage 70% and 57%, respectively). We evaluated the impact of 1 year of pMDA on malaria incidence using routine data. METHODS: We conducted an interrupted time series with comparison group analysis on monthly incidence data collected at the health facility catchment area (HFCA) level, with a negative binomial model using generalized estimating equations. Programmatic mass drug administration was conducted in HFCAs with greater than 50 cases/1000 people per year. Ten HFCAs with incidence rates marginally above this threshold (pMDA group) were compared with 20 HFCAs marginally below (comparison group). RESULTS: The pMDA HFCAs saw a 46% greater decrease in incidence at the time of intervention than the comparison areas (incidence rate ratio = 0.536; confidence interval = 0.337-0.852); however, incidence increased toward the end of the season. No HFCAs saw a transmission interruption. CONCLUSIONS: Programmatic mass drug administration, implemented during 1 year with imperfect coverage in low transmission areas with suboptimal vector control coverage, significantly reduced incidence. However, elimination will require additional tools. Routine data are important resources for programmatic impact evaluations and should be considered for future analyses.

The Immediate Effects of a Combined Mass Drug Administration and Indoor Residual Spraying Campaign to Accelerate Progress Toward Malaria Elimination in Grande-Anse, Haiti.

BACKGROUND: Haiti is planning targeted interventions to accelerate progress toward malaria elimination. In the most affected department (Grande-Anse), a combined mass drug administration (MDA) and indoor residual spraying (IRS) campaign was launched in October 2018. This study assessed the intervention's effectiveness in reducing Plasmodium falciparum prevalence. METHODS: An ecological quasi-experimental study was designed, using a pretest and posttest with a nonrandomized control group. Surveys were conducted in November 2017 in a panel of easy access groups (25 schools and 16 clinics) and were repeated 2-6 weeks after the campaign, in November 2018. Single-dose sulfadoxine-pyrimethamine and primaquine was used for MDA, and pirimiphos-methyl as insecticide for IRS. RESULTS: A total of 10 006 participants were recruited. Fifty-two percent of the population in the intervention area reported having received MDA. Prevalence diminished between 2017 and 2018 in both areas, but the reduction was significantly larger in the intervention area (ratio of adjusted risk ratios, 0.32 [95% confidence interval, .104-.998]). CONCLUSIONS: Despite a moderate coverage, the campaign was effective in reducing P. falciparum prevalence immediately after 1 round. Targeted MDA plus IRS is useful in preelimination settings to rapidly decrease the parasite reservoir, an encouraging step to accelerate progress toward malaria elimination.

Rapid Screening for Non-falciparum Malaria in Elimination Settings Using Multiplex Antigen and Antibody Detection: Post Hoc Identification of Plasmodium malariae in an Infant in Haiti.

Haiti is targeting malaria elimination by 2025. The Grand'Anse department in southwestern Haiti experiences one-third to half of all nationally reported Plasmodium falciparum cases. Although there are historical reports of Plasmodium vivax and Plasmodium malariae, today, non-falciparum infections would remain undetected because of extensive use of falciparum-specific histidine-rich protein 2 (HRP2) rapid diagnostic tests (RDT) at health facilities. A recent case-control study was conducted in Grand'Anse to identify risk factors for P. falciparum infection using HRP2-based RDTs (n = 1,107). Post hoc multiplex Plasmodium antigenemia and antibody (IgG) detection by multiplex bead assay revealed one blood sample positive for pan-Plasmodium aldolase, negative for P. falciparum HRP2, and positive for IgG antibodies to P. malariae. Based on this finding, we selected 52 samples with possible P. malariae infection using IgG and antigenemia data and confirmed infection status by species-specific PCR. We confirmed one P. malariae infection in a 6-month-old infant without travel history. Congenital P. malariae could not be excluded. However, our finding-in combination with historical reports of P. malariae-warrants further investigation into the presence and possible extent of non-falciparum malaria in Haiti. Furthermore, we showed the use of multiplex Plasmodium antigen and IgG detection in selecting samples of interest for subsequent PCR analysis, thereby reducing costs as opposed to testing all available samples by PCR. This is of specific use in low-transmission or eliminating settings where infections are rare.

Retrospective evaluation of the effectiveness of indoor residual spray with pirimiphos-methyl (Actellic) on malaria transmission in Zambia.

BACKGROUND: Widespread insecticide resistance to pyrethroids could thwart progress towards elimination. Recently, the World Health Organization has encouraged the use of non-pyrethroid insecticides to reduce the spread of insecticide resistance. An electronic tool for implementing and tracking coverage of IRS campaigns has recently been tested (mSpray), using satellite imagery to improve the accuracy and efficiency of the enumeration process. The purpose of this paper is to retrospectively analyse cross-sectional observational data to provide evidence of the epidemiological effectiveness of having introduced Actellic 300CS and the mSpray platform into IRS programmes across Zambia. METHODS: Health facility catchment areas in 40 high burden districts in 5 selected provinces were initially targeted for spraying. The mSpray platform was used in 7 districts in Luapula Province. An observational study design was used to assess the relationship between IRS exposure and confirmed malaria case incidence. A random effects Poisson model was used to quantify the effect of IRS (with and without use of the mSpray platform) on confirmed malaria case incidence over the period 2013-2017; analysis was restricted to the 4 provinces where IRS was conducted in each year 2014-2016. RESULTS: IRS was conducted in 283 health facility catchment areas from 2014 to 2016; 198 health facilities from the same provinces, that received no IRS during this period, served as a comparison. IRS appears to be associated with reduced confirmed malaria incidence; the incidence rate ratio (IRR) was lower in areas with IRS but without mSpray, compared to areas with no IRS (IRR = 0.91, 95% CI 0.84-0.98). Receiving IRS with mSpray significantly lowered confirmed case incidence (IRR = 0.75, 95% CI 0.66-0.86) compared to no IRS. IRS with mSpray resulted in lower incidence compared to IRS without mSpray (IRR = 0.83, 95% CI 0.72-0.95). CONCLUSIONS: IRS using Actellic-CS appears to substantially reduce malaria incidence in Zambia. The use of the mSpray tool appears to improve the effectiveness of the IRS programme, possibly through improved population level coverage. The results of this study lend credence to the anecdotal evidence of the effectiveness of 3GIRS using Actellic, and the importance of exploring new platforms for improving effective population coverage of areas targeted for spraying.

Data on selected antimalarial drug resistance markers in Zambia.

This article describes data on selected resistance markers for antimalarial drugs used in Zambia. Antimalarial drug resistance has hindered the progress in the control and elimination of malaria. Blood samples were collected during a cross-sectional household survey, conducted during the peak malaria transmission, April to May of 2017. Dried blood spots were collected during the survey and transported to a laboratory for analysis. The analysed included polymerase chain reaction (PCR) followed by high resolution melt (HRM) for mutations associated with Sulfadoxine-pyrimethamine resistance in the Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and P. falciparum dihydropteroate synthase (Pfdhps) genes. Mutations associated with artemether-lumefantrine resistance in falciparum multi-drug resistance gene 1 (Pfmdr1) were also assessed using PCR and HRM analysis, whereas the P. falciparum Kelch 13 (PfK13) gene was assessed using nested PCR followed by amplicon sequencing.

Management of uncomplicated malaria among children under five years at public and private sector facilities in Mali.

BACKGROUND: Prompt and effective malaria diagnosis and treatment is a cornerstone of malaria control. Case management guidelines recommend confirmatory testing of suspected malaria cases, then prescription of specific drugs for uncomplicated malaria and for severe malaria. This study aims to describe case management practices for children aged 1-59 months seeking treatment with current or recent fever from public and private, rural and urban health providers in Mali. METHODS: Data were collected at sites in Sikasso Region and Bamako. Health workers recorded key information from the consultation including malaria diagnostic testing and result, their final diagnosis, and all drugs prescribed. Children with signs of severe diseases were ineligible. Consultations were not independently observed. Appropriate case management was defined as both 1) tested for malaria using rapid diagnostic test or microscopy, and 2) receiving artemisinin combination therapy (ACT) and no other antimalarials if test-positive, or receiving no antimalarials if test-negative. RESULTS: Of 1602 participating children, 23.7% were appropriately managed, ranging from 5.3% at public rural facilities to 48.4% at community health worker sites. The most common reason for 'inappropriate' management was lack of malaria diagnostic testing (50.4% of children). Among children with confirmed malaria, 50.8% received a non-ACT antimalarial (commonly artesunate injection or artemether), either alone or in combination with ACT. Of 215 test-negative children, 44.2% received an antimalarial drug, most commonly ACT. Prescription of multiple drugs was common: 21.7% of all children received more than one type of antimalarial, while 51.9% received an antibiotic and antimalarial. Inappropriate case management increased in children with increasing axillary temperatures and those seeking care over weekends. CONCLUSIONS: Multiple limitations in management of febrile children under five were identified, including inconsistent use of confirmatory testing and apparent use of severe malaria drugs for uncomplicated malaria. While we cannot confirm the reasons for these shortcomings, there is a need to address the high use of non-ACT antimalarials in this context; to minimize potential for drug resistance, reduce unnecessary expense, and preserve life-saving treatment for severe malaria cases. These findings highlight the challenge of managing febrile illness in young children in a high transmission setting.

Surveillance of molecular markers for antimalarial resistance in Zambia: Polymorphism of Pfkelch 13, Pfmdr1 and Pfdhfr/Pfdhps genes.

Antimalarial resistance is an inevitable feature of control efforts and a key threat to achieving malaria elimination. Plasmodium falciparum, the deadliest of several species causing human malaria, has developed resistance to essentially all antimalarials. This study sought to investigate the prevalence of molecular markers associated with resistance to sulfadoxine-pyrimethamine (SP) and artemether-lumefantrine (AL) in Southern and Western provinces in Zambia. SP is used primarily for intermittent preventive treatment during pregnancy, while AL is the first-line antimalarial for uncomplicated malaria in Zambia. Blood samples were collected from household members of all ages in a cross-sectional survey conducted during peak malaria transmission, April to May of 2017, and amplified by polymerase chain reaction (PCR). Amplicons were then analysed by high-resolution melt following PCR to identify mutations associated with SP resistance in the P. falciparum dihydrofolate reductase (Pfdhfr) and P. falciparum dihydropteroate synthase (Pfdhps) genes and lumefantrine resistance in the P. falciparum multi-drug resistance 1 (Pfmdr1) gene. Finally, artemether resistance was assessed in the P. falciparum Kelch 13 (PfK13) gene using nested PCR followed by amplicon sequencing. The results showed a high frequency of genotypic-resistant Pfdhps A437G (93.2%) and Pfdhfr C59R (86.7%), N51I (80.9%), and S108N (80.8%) of which a high proportion (82.4%) were quadruple mutants (Pfdhfr N51I, C59R, S108N +Pfdhps A437G). Pfmrd1 N86Y, Y186F, and D1246Y - NFD mutant haplotypes were observed in 41.9% of isolates. The high prevalence of quadruple dhps/dhfr mutants indicates strong antifolate drug pressure from SP or other drugs (e.g., co-trimoxazole). Three samples contained PfK13 mutations, two synonymous (T478 and V666) and one non-synonymous (A578S), none of which have been associated with delayed clearance. This suggests that artemisinin remains efficacious in Zambia, however, the moderately high prevalence of approximately 40% Pfmdr1 NFD mutations calls for close monitoring of AL.

Estimating malaria chemoprevention and vector control coverage using program and campaign data: A scoping review of current practices and opportunities.

BACKGROUND: Accurate estimation of intervention coverage is a vital component of malaria program monitoring and evaluation, both for process evaluation (how well program targets are achieved), and impact evaluation (whether intervention coverage had an impact on malaria burden). There is growing interest in maximizing the utility of program data to generate interim estimates of intervention coverage in the periods between large-scale cross-sectional surveys (the gold standard). As such, this study aimed to identify relevant concepts and themes that may guide future optimization of intervention coverage estimation using routinely collected data, or data collected during and following intervention campaigns, with a particular focus on strategies to define the denominator. METHODS: We conducted a scoping review of current practices to estimate malaria intervention coverage for insecticide-treated nets (ITNs); indoor residual spray (IRS); intermittent preventive treatment in pregnancy (IPTp); mass drug administration (MDA); and seasonal malaria chemoprevention (SMC) interventions; case management was excluded. Multiple databases were searched for relevant articles published from January 1, 2015 to June 1, 2018. Additionally, we identified and included other guidance relevant to estimating population denominators, with a focus on innovative techniques. RESULTS: While program data have the potential to provide intervention coverage data, there are still substantial challenges in selecting appropriate denominators. The review identified a lack of consistency in how coverage was defined and reported for each intervention type, with denominator estimation methods not clearly or consistently reported, and denominator estimates rarely triangulated with other data sources to present the feasible range of denominator values and consequently the range of likely coverage estimates. CONCLUSIONS: Though household survey-based estimates of intervention coverage remain the gold standard, efforts should be made to further standardize practices for generating interim measurements of intervention coverage from program data, and for estimating and reporting population denominators. This includes fully describing any projections or adjustments made to existing census or population data, exploring opportunities to validate available data by comparing with other sources, and explaining how the denominator has been restricted (or not) to reflect exclusion criteria.

Assessment of the Acceptability of Testing and Treatment during a Mass Drug Administration Trial for Malaria in Zambia Using Mixed Methods.

From 2014 to 2016, a community-randomized controlled trial in Southern Province, Zambia, compared mass drug administration (MDA) and focal MDA (fMDA) with the standard of care. Acceptability of the intervention was assessed quantitatively using closed-ended and Likert scale-based questions posed during three household surveys conducted from April to May in 2014, 2015, and 2016 in 40 health catchments that implemented MDA and fMDA and 20 catchments that served as trial controls. In 2014 and 2015, 47 households per catchment were selected, targeting 1,880 households in MDA and fMDA trial arms; in 2016, 55 households per catchment were selected for a target of 2,200 households in MDA and fMDA trial arms. Concurrently, 27 focus group discussions and 23 in-depth interviews with 248 participants were conducted on reasons for testing and treatment refusal, reasons for nonadherence, and community perception of the MDA campaign. Results demonstrated that the MDA campaign was highly accepted with more than 99% of respondents stating that they would take treatment if positive for malaria. High acceptability at baseline could be associated with test-and-treat campaigns recently conducted in the study area. There was a large increase in the acceptability of prophylactic treatment if negative for malaria from the baseline to follow-up survey for adults and children, from 62% to 96% for each. This likely resulted from an intensive community-wide sensitization program that occurred before the first treatment round at each household during community health worker visits.

Pyrethroid and Carbamate Resistance in Anopheles funestus Giles along Lake Kariba in Southern Zambia.

Whereas data on insecticide resistance and its underlying mechanisms exist for parts of Zambia, data remain limited in the southern part of the country. This study investigated the status of insecticide resistance, metabolic mechanisms, and parasite infection in Anopheles funestus along Lake Kariba in southern Zambia. Indoor-resting mosquitoes were collected from 20 randomly selected houses within clusters where a mass drug administration trial was conducted and raised to F1 progeny. Non-blood-fed 2- to 5-day-old female An. funestus were exposed to WHO insecticide-impregnated papers with 0.05% deltamethrin, 0.1% bendiocarb, 0.25% pirimiphos-methyl, or 4% dichloro-diphenyl-trichloroethane (DDT). In separate assays, An. funestus were pre-exposed to piperonyl butoxide (PBO) to determine the presence of monooxygenases. Wild-caught An. funestus that had laid eggs for susceptibility assays were screened for circumsporozoite protein of Plasmodium falciparum by ELISA, and sibling species were identified by polymerase chain reaction. Anopheles funestus showed resistance to deltamethrin and bendiocarb but remained susceptible to pirimiphos-methyl and DDT. The pre-exposure of An. funestus to PBO restored full susceptibility to deltamethrin but not to bendiocarb. The overall sporozoite infection rate in An. funestus populations was 5.8%. Detection of pyrethroid and carbamate resistance in An. funestus calls for increased insecticide resistance monitoring to guide planning and selection of effective insecticide resistance management strategies. To prevent the development of resistance and reduce the underlying vectorial capacity of mosquitoes in areas targeted for malaria elimination, an effective integrated vector management strategy is needed.

A Longitudinal Cohort to Monitor Malaria Infection Incidence during Mass Drug Administration in Southern Province, Zambia.

Rigorous evidence of effectiveness is needed to determine where and when to apply mass drug administration (MDA) or focal MDA (fMDA) as part of a malaria elimination strategy. The Zambia National Malaria Elimination Centre recently completed a community-randomized controlled trial in Southern Province to evaluate MDA and fMDA for transmission reduction. To assess the role of MDA and fMDA on infection incidence, we enrolled a longitudinal cohort for an 18-month period of data collection including monthly malaria parasite infection detection based on polymerase chain reaction and compared time to first infection and cumulative infection incidence outcomes across study arms using Cox proportional hazards and negative binomial models. A total of 2,026 individuals from 733 households were enrolled and completed sufficient follow-up for inclusion in analysis. Infection incidence declined dramatically across all study arms during the period of study, and MDA was associated with reduced risk of first infection (hazards ratio: 0.36; 95% CI: 0.16-0.80) and cumulative infection incidence during the first rainy season (first 5 months of follow-up) (incidence rate ratio: 0.34; 95% CI: 0.12-0.95). No significant effect was found for fMDA or for either arm over the full study period. Polymerase chain reaction infection status at baseline was strongly associated with follow-up infection. The short-term effects of MDA suggest it may be an impactful accelerator of transmission reduction in areas with high coverage of case management and vector control and should be considered as part of a malaria elimination strategy.

Cost-Effectiveness of Focal Mass Drug Administration and Mass Drug Administration with Dihydroartemisinin-Piperaquine for Malaria Prevention in Southern Province, Zambia: Results of a Community-Randomized Controlled Trial.

Community-wide administration of antimalarial drugs in therapeutic doses is a potential tool to prevent malaria infection and reduce the malaria parasite reservoir. To measure the effectiveness and cost of using the antimalarial drug combination dihydroartemisinin-piperaquine (DHAp) through different community-wide distribution strategies, Zambia's National Malaria Control Centre conducted a three-armed community-randomized controlled trial. The trial arms were as follows: 1) standard of care (SoC) malaria interventions, 2) SoC plus focal mass drug administration (fMDA), and 3) SoC plus MDA. Mass drug administration consisted of offering all eligible individuals DHAP, irrespective of a rapid diagnostic test (RDT) result. Focal mass drug administration consisted of offering DHAP to all eligible individuals who resided in a household where anyone tested positive by RDT. Results indicate that the costs of fMDA and MDA per person targeted and reached are similar (US$9.01 versus US$8.49 per person, respectively, P = 0.87), but that MDA was superior in all cost-effectiveness measures, including cost per infection averted, cost per case averted, cost per death averted, and cost per disability-adjusted life year averted. Subsequent costing of the MDA intervention in a non-trial, operational setting yielded significantly lower costs per person reached (US$2.90). Mass drug administration with DHAp also met the WHO thresholds for "cost-effective interventions" in the Zambian setting in 90% of simulations conducted using a probabilistic sensitivity analysis based on trial costs, whereas fMDA met these criteria in approximately 50% of simulations. A sensitivity analysis using costs from operational deployment and trial effectiveness yielded improved cost-effectiveness estimates. Mass drug administration may be a cost-effective intervention in the Zambian context and can help reduce the parasite reservoir substantially. Mass drug administration was more cost-effective in relatively higher transmission settings. In all scenarios examined, the cost-effectiveness of MDA was superior to that of fMDA.