Deployment of attractive targeted sugar baits in western Zambia: installation, monitoring, removal, and disposal procedures during a Phase III cluster randomized controlled trial.

BACKGROUND: Attractive Targeted Sugar Baits (ATSBs) offer a complementary vector control strategy to interventions targeting blood feeding or larval control by attacking the sugar feeding behaviour of adult mosquitoes using an attract-and-kill approach. Western Zambia was the first location to receive and deploy ATSB Sarabi version 1.2 stations in a Phase III cluster randomized controlled trial. This paper describes ATSB station installation, monitoring, removal, and disposal, quantifies ATSB station coverage, and reports major reasons for ATSB station replacement. METHODS: ATSB stations were deployed during two annual transmission seasons, through scheduled installation and removal campaigns. During deployment, monitoring was conducted per protocol to maintain high coverage of the ATSB stations in good condition. Routine monitoring visits during the trial captured details on ATSB station damage necessitating replacement following pre-defined replacement criteria. Annual cross-sectional household surveys measured ATSB station coverage during peak malaria transmission. RESULTS: A total of 67,945 ATSB stations were installed in Year 1 (41,695 initially installed+ 26,250 installed during monitoring) and 69,494 ATSB stations were installed in Year 2 (41,982 initially installed+ 27,512 installed during monitoring) across 35 intervention clusters to maintain high coverage of two ATSB stations in good condition per eligible household structure. The primary reasons for ATSB station replacement due to damage were holes/tears and presence of mold. Cross-sectional household surveys documented high coverage of ATSB stations across Year 1 and Year 2 with 93.1% of eligible structures having ≥ 2 ATSB stations in any condition. DISCUSSION: ATSB station deployment and monitoring efforts were conducted in the context of a controlled cRCT to assess potential product efficacy. Damage to ATSB stations during deployment required replacement of a subset of stations. High coverage of eligible structures was maintained over the two-year study despite replacement requirements. Additional research is needed to better understand the impact of damage on ATSB station effectiveness under programmatic conditions, including thresholds of threats to physical integrity and biological deterioration on product efficacy. CONCLUSIONS: Optimizing ATSB stations to address causes of damage and conducting implementation research to inform optimal delivery and cost-effective deployment will be important to facilitate scale-up of ATSB interventions.

Entomological effects of attractive targeted sugar bait station deployment in Western Zambia: vector surveillance findings from a two-arm cluster randomized phase III trial.

BACKGROUND: Attractive targeted sugar bait (ATSB) stations are a novel tool with potential to complement current approaches to malaria vector control. To assess the public health value of ATSB station deployment in areas of high coverage with standard vector control, a two-arm cluster-randomized controlled trial (cRCT) of Sarabi ATSB® stations (Westham Ltd., Hod-Hasharon, Israel) was conducted in Western Province, Zambia, a high-burden location were Anopheles funestus is the dominant vector. The trial included 70 clusters and was designed to measure the effect of ATSBs on case incidence and infection prevalence over two 7-month deployments. Reported here are results of the vector surveillance component of the study, conducted in a subset of 20 clusters and designed to provide entomological context to guide overall interpretation of trial findings. METHODS: Each month, 200 paired indoor-outdoor human landing catch (HLC) and 200 paired light trap (LT) collections were conducted to monitor An. funestus parity, abundance, biting rates, sporozoite prevalence, and entomological inoculation rates (EIR). RESULTS: During the study 20,337 female An. funestus were collected, 11,229 from control and 9,108 from intervention clusters. A subset of 3,131 HLC specimens were assessed for parity: The mean non-parous proportion was 23.0% (95% CI 18.2-28.7%, total n = 1477) in the control and 21.2% (95% CI 18.8-23.9%, total n = 1654) in the intervention arm, an OR = 1.05 (95% CI 0.82-1.34; p = 0.688). A non-significant reduction in LT abundance (RR = 0.65 [95% CI 0.30-1.40, p = 0.267]) was associated with ATSB deployment. HLC rates were highly variable, but model results indicate a similar non-significant trend with a RR = 0.68 (95%CI 0.22-2.00; p = 0.479). There were no effects on sporozoite prevalence or EIR. CONCLUSIONS: Anopheles funestus parity did not differ across study arms, but ATSB deployment was associated with a non-significant 35% reduction in vector LT density, results that are consistent with the epidemiological impact reported elsewhere. Additional research is needed to better understand how to maximize the potential impact of ATSB approaches in Zambia and other contexts. TRIAL REGISTRATION NUMBER: This trial was registered with Clinicaltrials.gov (NCT04800055, 16 March 2021).

Characteristics of the Western Province, Zambia, trial site for evaluation of attractive targeted sugar baits for malaria vector control.

BACKGROUND: The attractive targeted sugar bait (ATSB) is a novel malaria vector control tool designed to attract and kill mosquitoes using a sugar-based bait, laced with oral toxicant. Western Province, Zambia, was one of three countries selected for a series of phase III cluster randomized controlled trials of the Westham ATSB Sarabi version 1.2. The trial sites in Kenya, Mali, and Zambia were selected to represent a range of different ecologies and malaria transmission settings across sub-Saharan Africa. This case study describes the key characteristics of the ATSB Zambia trial site to allow for interpretation of the results relative to the Kenya and Mali sites. METHODS: This study site characterization incorporates data from the trial baseline epidemiological and mosquito sugar feeding surveys conducted in 2021, as well as relevant literature on the study area. RESULTS: CHARACTERIZATION OF THE TRIAL SITE: The trial site in Zambia was comprised of 70 trial-designed clusters in Kaoma, Nkeyema, and Luampa districts. Population settlements in the trial site were dispersed across a large geographic area with sparsely populated villages. The overall population density in the 70 study clusters was 65.7 people per square kilometre with a total site population of 122,023 people living in a geographic area that covered 1858 square kilometres. However, the study clusters were distributed over a total area of approximately 11,728 square kilometres. The region was tropical with intense and seasonal malaria transmission. An abundance of trees and other plants in the trial site were potential sources of sugar meals for malaria vectors. Fourteen Anopheles species were endemic in the site and Anopheles funestus was the dominant vector, likely accounting for around 95% of all Plasmodium falciparum malaria infections. Despite high coverage of indoor residual spraying and insecticide-treated nets, the baseline malaria prevalence during the peak malaria transmission season was 50% among people ages six months and older. CONCLUSION: Malaria transmission remains high in Western Province, Zambia, despite coverage with vector control tools. New strategies are needed to address the drivers of malaria transmission in this region and other malaria-endemic areas in sub-Saharan Africa.

A novel, robust peptidyl-lys metalloendopeptidase from Trametes coccinea recombinantly expressed in Komagataella phaffii.

A novel peptidyl-lys metalloendopeptidase (Tc-LysN) from Tramates coccinea was recombinantly expressed in Komagataella phaffii using the native pro-protein sequence. The peptidase was secreted into the culture broth as zymogen (~38 kDa) and mature enzyme (~19.8 kDa) simultaneously. The mature Tc-LysN was purified to homogeneity with a single step anion-exchange chromatography at pH 7.2. N-terminal sequencing using TMTpro Zero and mass spectrometry of the mature Tc-LysN indicated that the pro-peptide was cleaved between the amino acid positions 184 and 185 at the Kex2 cleavage site present in the native pro-protein sequence. The pH optimum of Tc-LysN was determined to be 5.0 while it maintained ≥60% activity between pH values 4.5-7.5 and ≥30% activity between pH values 8.5-10.0, indicating its broad applicability. The temperature maximum of Tc-LysN was determined to be 60 °C. After 18 h of incubation at 80 °C, Tc-LysN still retained ~20% activity. Organic solvents such as methanol and acetonitrile, at concentrations as high as 40% (v/v), were found to enhance Tc-LysN's activity up to ~100% and ~50%, respectively. Tc-LysN's thermostability, ability to withstand up to 8 M urea, tolerance to high concentrations of organic solvents, and an acidic pH optimum make it a viable candidate to be employed in proteomics workflows in which alkaline conditions might pose a challenge. The nano-LC-MS/MS analysis revealed bovine serum albumin (BSA)'s sequence coverage of 84% using Tc-LysN which was comparable to the sequence coverage of 90% by trypsin peptides. KEY POINTS: •A novel LysN from Trametes coccinea (Tc-LysN) was expressed in Komagataella phaffii and purified to homogeneity •Tc-LysN is thermostable, applicable over a broad pH range, and tolerates high concentrations of denaturants •Tc-LysN was successfully applied for protein digestion and mass spectrometry fingerprinting.

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.

Factors Associated With Human IgG Antibody Response to Anopheles albimanus Salivary Gland Extract, Artibonite Department, Haiti, 2017.

Serological data can provide estimates of human exposure to both malaria vector and parasite based on antibody responses. A multiplex bead-based assay was developed to simultaneously detect IgG to Anopheles albimanus salivary gland extract (SGE) and 23 Plasmodium falciparum antigens among 4185 participants enrolled in Artibonite department, Haiti in 2017. Logistic regression adjusted for participant- and site-level covariates and found children under 5 years and 6-15 years old had 3.7- and 5.4-fold increase in odds, respectively, of high anti-SGE IgG compared to participants >15 years. Seropositivity to P. falciparum CSP, Rh2_2030, and SEA-1 antigens was significantly associated with high IgG response against SGE, and participant enrolment at elevations under 200 m was associated with higher anti-SGE IgG levels. The ability to approximate population exposure to malaria vectors through SGE serology data is very dependent by age categories, and SGE antigens can be easily integrated into a multiplex serological assay.

Purification and characterization of a fungal aspartic peptidase from Trichoderma reesei and its application for food and animal feed protein hydrolyses.

BACKGROUND: Various neutral and alkaline peptidases are commercially available for use in protein hydrolysis under neutral to alkaline conditions. However, the hydrolysis of proteins under acidic conditions by applying fungal aspartic peptidases (FAPs) has not been investigated in depth so far. The aim of this study, thus, was to purify a FAP from the commercial enzyme preparation, ROHALASE® BXL, determine its biochemical characteristics, and investigate its application for the hydrolysis of food and animal feed proteins under acidic conditions. RESULTS: A Trichoderma reesei derived FAP, with an apparent molecular mass of 45.8 kDa (sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SDS-PAGE) was purified 13.8-fold with a yield of 37% from ROHALASE® BXL. The FAP was identified as an aspartate protease (UniProt ID: G0R8T0) by inhibition and nano-LC-ESI-MS/MS studies. The FAP showed the highest activity at 50°C and pH 4.0. Monovalent cations, organic solvents, and reducing agents were tolerated well by the FAP. The FAP underwent an apparent competitive product inhibition by soy protein hydrolysate and whey protein hydrolysate with apparent Ki -values of 1.75 and 30.2 mg*mL-1 , respectively. The FAP showed promising results in food (soy protein isolate and whey protein isolate) and animal feed protein hydrolyses. For the latter, an increase in the soluble protein content of 109% was noted after 30 min. CONCLUSION: Our results demonstrate the applicability of fungal aspartic endopeptidases in the food and animal feed industry. Efficient protein hydrolysis of industrially relevant substrates such as acidic whey or animal feed proteins could be conducted by applying fungal aspartic peptidases. © 2022 Society of Chemical Industry.

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.