Assessment of sociodemographic factors associated with time to self-reported COVID-19 infection among a large multi-center prospective cohort population in the southeastern United States.

OBJECTIVE: We aimed to investigate sociodemographic factors associated with self-reported COVID-19 infection. METHODS: The study population was a prospective multicenter cohort of adult volunteers recruited from healthcare systems located in the mid-Atlantic and southern United States. Between April 2020 and October 2021, participants completed daily online questionnaires about symptoms, exposures, and risk behaviors related to COVID-19, including self-reports of positive SARS CoV-2 detection tests and COVID-19 vaccination. Analysis of time from study enrollment to self-reported COVID-19 infection used a time-varying mixed effects Cox-proportional hazards framework. RESULTS: Overall, 1,603 of 27,214 study participants (5.9%) reported a positive COVID-19 test during the study period. The adjusted hazard ratio demonstrated lower risk for women, those with a graduate level degree, and smokers. A higher risk was observed for healthcare workers, those aged 18-34, those in rural areas, those from households where a member attends school or interacts with the public, and those who visited a health provider in the last year. CONCLUSIONS: We identified subgroups within healthcare network populations defined by age, occupational exposure, and rural location reporting higher than average rates of COVID-19 infection for our surveillance population. These subgroups should be monitored closely in future epidemics of respiratory viral diseases.

Evaluating trends in damage to attractive targeted sugar baits (ATSBs) deployed during the second year of a two-year Phase III trial in Western Zambia.

BACKGROUND: Attractive Targeted Sugar Baits (ATSBs) are a proposed new vector control tool for malaria that contain sugar and an ingestion toxicant, and are designed to attract and kill sugar-feeding mosquitoes. During a two-arm cluster randomized Phase III trial conducted in Zambia to test the efficacy of ATSB stations on malaria incidence, ATSB stations deployed on eligible household structures within intervention clusters were routinely monitored to ensure their good physical condition and high coverage. This study investigates trends in prevalence and rate of damage to ATSB stations during year 2 of the two-year trial. METHODS: The analysis was conducted using monitoring data collected in year 2, which included types of damage observed, location, and date of removal and/or replacement of ATSB stations. The study evaluated temporal trends in the prevalence of overall damage and different damage types among 68,299 ATSB stations deployed. A profile of all ATSB stations installed on each structure was constructed, and spatial analyses conducted on overall damage and different damage types observed on 18,890 structures. Mixed effects regression analyses were conducted to investigate drivers of damage to ATSB stations on these structures. RESULTS: Prevalence of overall damage and different damage types was temporally and spatially heterogeneous. Among damaged ATSB stations observed during monitoring, tears and mold had the highest prevalences on average, with tears maintaining above 50.0% prevalence through most of the monitoring period, while mold prevalence increased steadily during the first few months, peaking in February. Overall, 45.6% of structures had at least one damaged ATSB station, however this varied spatially across the trial site. Both structure characteristics and environmental factors significantly impacted the odds and rate of damage to ATSB stations on structures, including: ATSB stations' level of protection from rainfall and sunshine; roof and wall material of the structure; night-time temperature; rainfall; enhanced vegetation index, and land cover. CONCLUSION: Damage to ATSB stations in this setting was common and was temporally and spatially heterogeneous. This has implications on operational feasibility, sustainability, and cost of future deployment. Further research is required to understand the mechanisms of damage, and to minimize prevalence and rate of damage to ATSB stations.

Community acceptance of a novel malaria intervention, Attractive Targeted Sugar Baits, in the Zambia phase III trial.

BACKGROUND: Community acceptance is an important criterion to assess in community trials, particularly for new tools that require high coverage and use by a target population. Installed on exterior walls of household structures, the attractive targeted sugar bait (ATSB) is a new vector control tool designed to attract and kill mosquitoes. ATSBs were evaluated in Western Zambia during a two-year cluster randomized controlled trial to assess the efficacy of ATSBs in reducing malaria transmission. Community acceptance of ATSBs was critical for successful trial implementation. METHODS: A community engagement strategy outlined activities and key messages to promote acceptance. Annual cross-sectional surveys, conducted during the peak transmission period, assessed households for presence of ATSBs as well as perceived benefits, concerns, and willingness to use ATSBs. Sixteen focus group discussions and 16 in-depth interviews, conducted at the end of each ATSB station deployment period, obtained a range of perceptions and household experiences with ATSB stations, as well as ITN use in the context of ATSB deployment. RESULTS: Methods used during the study to promote acceptance and continued use of ATSBs were effective in achieving greater than 90% coverage, a high (greater than 70%) level of perceived benefits, and fewer than 10% of households reporting safety concerns. Common facilitators of acceptance included the desire for protection against malaria and reduction of mosquitoes, trust in health initiatives, and understanding of the product. Common barriers to acceptance included misconceptions of product impact on mosquitoes, continued cases of malaria, association with satanism, and damage to household structures. DISCUSSION: Future use of the ATSB intervention will likely require activities that foster community acceptance before, during, and after the intervention is introduced. Additional research may be needed to understand the impact of different levels of community engagement on ATSB station coverage, ATSB station perception, and ITN use. CONCLUSION: There was high acceptance of ATSB stations during the trial in Western Zambia. Continuous and intense community engagement efforts contributed to sustained ATSB coverage and trust in the product. Acceptance of ATSBs during programmatic delivery requires further research.

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).

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.

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.

Residual bioefficacy of attractive targeted sugar bait stations targeting malaria vectors during seasonal deployment in Western Province of Zambia.

BACKGROUND: The primary vector control interventions in Zambia are long-lasting insecticidal nets and indoor residual spraying. Challenges with these interventions include insecticide resistance and the outdoor biting and resting behaviours of many Anopheles mosquitoes. Therefore, new vector control tools targeting additional mosquito behaviours are needed to interrupt transmission. Attractive targeted sugar bait (ATSB) stations, which exploit the sugar feeding behaviours of mosquitoes, may help in this role. This study evaluated the residual laboratory bioefficacy of Westham prototype ATSB® Sarabi v.1.2.1 Bait Station (Westham Ltd., Hod-Hasharon, Israel) in killing malaria vectors in Western Province, Zambia, during the first year of a large cluster randomized phase-III trial (Clinical Trials.gov Identifier: NCT04800055). METHODS: This was a repeat cross-sectional study conducted within three districts, Nkeyema, Kaoma, and Luampa, in Western Province, Zambia. The study was conducted in 12 intervention clusters among the 70 trial clusters (35 interventions, 35 controls) between December 2021 and June 2022. Twelve undamaged bait stations installed on the outer walls of households were collected monthly (one per cluster per month) for bioassays utilizing adult female and male Anopheles gambiae sensu stricto (Kisumu strain) mosquitoes from a laboratory colony. RESULTS: A total of 84 field-deployed ATSB stations were collected, and 71 ultimately met the study inclusion criteria for remaining in good condition. Field-deployed stations that remained in good condition (intact, non-depleted of bait, and free of dirt as well as mold) retained high levels of bioefficacy (mean induced mortality of 95.3% in males, 71.3% in females, 83.9% combined total) over seven months in the field but did induce lower mortality rates than non-deployed ATSB stations (mean induced mortality of 96.4% in males, 87.0% in females, 91.4% combined total). There was relatively little variation in corrected mortality rates between monthly rounds for those ATSB stations that had been deployed to the field. CONCLUSION: While field-deployed ATSB stations induced lower mortality rates than non-deployed ATSB stations, these stations nonetheless retained relatively high and stable levels of bioefficacy across the 7-month malaria transmission season. While overall mean mosquito mortality rates exceeded 80%, mean mortality rates for females were 24 percentage points lower than among males and these differences merit attention and further evaluation in future studies. The duration of deployment was not associated with lower bioefficacy. Westham prototype ATSB stations can still retain bioefficacy even after deployment in the field for 7 months, provided they do not meet predetermined criteria for replacement.

Using a mobile nanopore sequencing lab for end-to-end genomic surveillance of Plasmodium falciparum: A feasibility study.

Genomic epidemiology holds promise for malaria control and elimination efforts, for example by informing on Plasmodium falciparum genetic diversity and prevalence of mutations conferring anti-malarial drug resistance. Limited sequencing infrastructure in many malaria-endemic areas prevents the rapid generation of genomic data. To address these issues, we developed and validated assays for P. falciparum nanopore sequencing in endemic sites using a mobile laboratory, targeting key antimalarial drug resistance markers and microhaplotypes. Using two multiplexed PCR reactions, we amplified six highly polymorphic microhaplotypes and ten drug resistance markers. We developed a bioinformatics workflow that allows genotyping of polyclonal malaria infections, including minority clones. We validated the panels on mock dried blood spot (DBS) and rapid diagnostic test (RDT) samples and archived DBS, demonstrating even, high read coverage across amplicons (range: 580x to 3,212x median coverage), high haplotype calling accuracy, and the ability to explore within-sample diversity of polyclonal infections. We field-tested the feasibility of rapid genotyping in Zanzibar in close collaboration with the local malaria elimination program using DBS and routinely collected RDTs as sample inputs. Our assay identified haplotypes known to confer resistance to known antimalarials in the dhfr, dhps and mdr1 genes, but no evidence of artemisinin partial resistance. Most infections (60%) were polyclonal, with high microhaplotype diversity (median HE = 0.94). In conclusion, our assays generated actionable data within a few days, and we identified current challenges for implementing nanopore sequencing in endemic countries to accelerate malaria control and elimination.

Outreach Training and Supportive Supervision for Quality Malaria Service Delivery: A Qualitative Evaluation in 11 Sub-Saharan African Countries.

Quality improvement of malaria services aims to ensure that more patients receive accurate diagnosis, appropriate treatment, and referral. The Outreach Training and Supportive Supervision Plus (OTSS+) approach seeks to improve health facility readiness and provider competency through onsite supportive supervision, troubleshooting, and on-the-job training. As part of a multicomponent evaluation, qualitative research was conducted to understand the value of the OTSS+ approach for malaria quality improvement. Semistructured key informant interviews, focus group discussions, and structured health facility-based interviews were used to gather stakeholder perspectives at subnational, national, and global levels. Data were collected globally and in 11 countries implementing OTSS+; in-depth data collection was done in four: Cameroon, Ghana, Niger, and Zambia. Study sites and participants were selected purposively. Verbatim transcripts were analyzed thematically, following the Framework approach. A total of 262 participants were included in the analysis; 98 (37.4%) were supervisees, 99 (37.8%) were supervisors, and 65 (24.8%) were other stakeholders. The OTSS+ approach was perceived to improve provider knowledge and skills in malaria service delivery and to improve data and supply management indirectly. Improvements were attributed to a combination of factors. Participants valued the relevance, adaptation, and digitization of supervision checklists; the quality and amount of contact with problem-solving supervisors; and the joint identification of problems and solutions, and development of action plans. Opportunities for improvement were digitized checklist refinement, assurance of a sufficient pool of supervisors, prioritization of health facilities, action plan dissemination and follow-up, and data review and use. The OTSS+ approach was perceived to be a useful quality improvement approach for malaria services.

Seasonal Malaria Chemoprevention Therapy in Children Up To 9 Years of Age: Protocol for a Cluster-Randomized Trial Study.

BACKGROUND: Seasonal malaria chemoprevention (SMC) is recommended by the World Health Organization for the sub-Sahel region in sub-Saharan Africa for preventing malaria in children 3 months old to younger than 5 years. Since 2016, the Malian National Malaria Control Program has deployed SMC countrywide during its high malaria transmission season at a rate of 4 monthly cycles annually. The standard SMC regimen includes sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ). Resistance against SP is suspected to be rising across West Africa; therefore, assessing the effectiveness of an alternative antimalarial drug for SMC is needed to provide a second-line regimen when it is ultimately needed. It is not well understood whether SMC effectively prevents malaria in children aged 5 years or older. OBJECTIVE: The primary goal of the study is to compare 2 SMC regimens (SP-AQ and dihydroartemisinin-piperaquine [DHA-PQ]) in preventing uncomplicated Plasmodium falciparum malaria in children 3 months to 9 years old. Secondly, we will assess the possible use of DHA-PQ as an alternative SMC drug in areas where resistance to SP or AQ may increase following intensive use. METHODS: The study design is a 3-arm cluster-randomized design comparing the SP-AQ and DHA-PQ arms in 2 age groups (younger than 5 years and 5-9 years) and a control group for children aged 5-9 years. Standard SMC (SP-AQ) for children younger than 5 years was provided to the control arm, while SMC with SP-AQ was delivered to children aged 3 months to 9 years (arm 2), and SMC with DHA-PQ will be implemented in study arm 3 for children up to 9 years of age. The study was performed in Mali's Koulikoro District, a rural area in southwest Mali with historically high malaria transmission rates. The study's primary outcome is P falciparum incidence for 2 SMC regimens in children up to 9 years of age. Should DHA-PQ provide an acceptable alternative to SP-AQ, a plausible second-line prevention option would be available in the event of SP resistance or drug supply shortages. A significant byproduct of this effort included bolstering district health information systems for rapid identification of severe malaria cases. RESULTS: The study began on July 1, 2019. Through November 2022, a total of 4556 children 3 months old to younger than 5 years were enrolled. Data collection ended in spring 2023, and the findings are expected to be published later in early 2024. CONCLUSIONS: Routine evaluation of antimalarial drugs is needed to establish appropriate SMC age targets. The study goals here may impact public health policy and provide alternative therapies in the event of drug shortages or resistance. TRIAL REGISTRATION: ClinicalTrials.gov NCT04149106, https://clinicaltrials.gov/ct2/show/NCT04149106. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51660.

Can Outreach Training and Supportive Supervision Improve Competency in Malaria Service Delivery? An Evaluation in Cameroon, Ghana, Niger, and Zambia.

Outreach Training and Supportive Supervision (OTSS) of malaria services at health facilities has been adopted by numerous malaria-endemic countries. The OTSS model is characterized by a hands-on method to enhance national guidelines and supervision tools, train supervisors, and perform supervision visits. An independent evaluation was conducted to evaluate the effectiveness of OTSS on health worker competence in the clinical management of malaria, parasitological diagnosis, and prevention of malaria in pregnancy. From 2018 to 2021, health facilities in Cameroon, Ghana, Niger, and Zambia received OTSS visits during which health workers were observed directly during patient consultations, and supervisors completed standardized checklists to assess their performance. Mixed-effects logistic regression models were developed to assess the impact of increasing OTSS visit number on a set of eight program-generated outcome indicators, including overall competency and requesting a confirmatory malaria test appropriately. Seven of eight outcome indicators showed evidence of beneficial effects of increased OTSS visits. Odds of health workers reaching competency thresholds for the malaria-in-pregnancy checklist increased by more than four times for each additional OTSS visit (odds ratio [OR], 4.62; 95% CI, 3.62-5.88). Each additional OTSS visit was associated with almost four times the odds of the health worker foregoing antimalarial prescriptions for patients who tested negative for malaria (OR, 3.80; 95% CI, 2.35-6.16). This evaluation provides evidence that successive OTSS visits result in meaningful improvements in indicators linked to quality case management of patients attending facilities for malaria diagnosis and treatment, as well as quality malaria prevention services received by women attending antenatal services.

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.

Risk of imported malaria infections in Zanzibar: a cross-sectional study.

BACKGROUND: Zanzibar has made substantial progress in malaria control with vector control, improved diagnosis, and artemisinin-based combination therapy. Parasite prevalence in the population has remained around 1% but imported infections from mainland Tanzania contribute to sustained local transmission. Understanding travel patterns between mainland Tanzania and Zanzibar, and the risk of malaria infection, may help to control malaria importation to Zanzibar. METHODS: A rolling cross-sectional survey linked to routine reactive case detection of malaria was carried out in Zanzibar between May 2017 and October 2018. Households of patients diagnosed with malaria at health facilities were surveyed and household members were tested for malaria using rapid diagnostic tests and a sub-sample by quantitative PCR (qPCR). Interviews elicited a detailed travel history of all household members who had travelled within the past two months, including trips within and outside of Zanzibar. We estimated the association of malaria infection with travel destinations in pre-defined malaria endemicity categories, trip duration, and other co-variates using logistic regression. RESULTS: Of 17,891 survey participants, 1177 (7%) reported a recent trip, of which 769 (65%) visited mainland Tanzania. Among travellers to mainland Tanzania with travel destination details and a qPCR result available, 241/378 (64%) reported traveling to districts with a 'high' malaria endemicity and for 12% the highest endemicity category was 'moderate'. Travelers to the mainland were more likely to be infected with malaria parasites (29%, 108/378) than those traveling within Zanzibar (8%, 16/206) or to other countries (6%, 2/17). Among travellers to mainland Tanzania, those visiting highly endemic districts had a higher odds of being qPCR-positive than those who travelled only to districts where malaria-endemicity was classified as low or very low (adjusted odd ratio = 7.0, 95% confidence interval: 1.9-25.5). Among travellers to the mainland, 110/378 (29%) never or only sometimes used a mosquito net during their travel. CONCLUSIONS: Strategies to reduce malaria importation to Zanzibar may benefit from identifying population groups traveling to highly endemic areas in mainland Tanzania. Targeted interventions to prevent and clear infections in these groups may be more feasible than attempting to screen and treat all travellers upon arrival in Zanzibar.

Multiplexed ddPCR-amplicon sequencing reveals isolated Plasmodium falciparum populations amenable to local elimination in Zanzibar, Tanzania.

Zanzibar has made significant progress toward malaria elimination, but recent stagnation requires novel approaches. We developed a highly multiplexed droplet digital PCR (ddPCR)-based amplicon sequencing method targeting 35 microhaplotypes and drug-resistance loci, and successfully sequenced 290 samples from five districts covering both main islands. Here, we elucidate fine-scale Plasmodium falciparum population structure and infer relatedness and connectivity of infections using an identity-by-descent (IBD) approach. Despite high genetic diversity, we observe pronounced fine-scale spatial and temporal parasite genetic structure. Clusters of near-clonal infections on Pemba indicate persistent local transmission with limited parasite importation, presenting an opportunity for local elimination efforts. Furthermore, we observe an admixed parasite population on Unguja and detect a substantial fraction (2.9%) of significantly related infection pairs between Zanzibar and the mainland, suggesting recent importation. Our study provides a high-resolution view of parasite genetic structure across the Zanzibar archipelago and provides actionable insights for prioritizing malaria elimination efforts.

Modelling the impact of interventions on imported, introduced and indigenous malaria infections in Zanzibar, Tanzania.

Malaria cases can be classified as imported, introduced or indigenous cases. The World Health Organization's definition of malaria elimination requires an area to demonstrate that no new indigenous cases have occurred in the last three years. Here, we present a stochastic metapopulation model of malaria transmission that distinguishes between imported, introduced and indigenous cases, and can be used to test the impact of new interventions in a setting with low transmission and ongoing case importation. We use human movement and malaria prevalence data from Zanzibar, Tanzania, to parameterise the model. We test increasing the coverage of interventions such as reactive case detection; implementing new interventions including reactive drug administration and treatment of infected travellers; and consider the potential impact of a reduction in transmission on Zanzibar and mainland Tanzania. We find that the majority of new cases on both major islands of Zanzibar are indigenous cases, despite high case importation rates. Combinations of interventions that increase the number of infections treated through reactive case detection or reactive drug administration can lead to substantial decreases in malaria incidence, but for elimination within the next 40 years, transmission reduction in both Zanzibar and mainland Tanzania is necessary.

Feeding rates of malaria vectors from a prototype attractive sugar bait station in Western Province, Zambia: results of an entomological validation study.

BACKGROUND: Attractive targeted sugar bait (ATSB) stations are a promising new approach to malaria vector control that could compliment current tools by exploiting the natural sugar feeding behaviors of mosquitoes. Recent proof of concept work with a prototype ATSB® Sarabi Bait Station (Westham Co., Hod-Hasharon, Israel) has demonstrated high feeding rates and significant reductions in vector density, human biting rate, and overall entomological inoculation rate for Anopheles gambiae sensu lato (s.l.) in the tropical savannah of western Mali. The study reported here was conducted in the more temperate, rainier region of Western Province, Zambia and was designed to confirm the primary vector species in region and to estimate corresponding rates of feeding from prototype attractive sugar bait (ASB) Sarabi Bait Stations. METHODS: The product evaluated was the Sarabi v1.1.1 ASB station, which did not include insecticide but did include 0.8% uranine as a dye allowing for the detection, using UV fluorescence light microscopy, of mosquitoes that have acquired a sugar meal from the ASB. A two-phase, crossover study design was conducted in 10 village-based clusters in Western Province, Zambia. One study arm initially received 2 ASB stations per eligible structure while the other initially received 3. Primary mosquito sampling occurred via indoor and outdoor CDC Miniature UV Light Trap collection from March 01 through April 09, 2021 (Phase 1) and from April 19 to May 28, 2021 (Phase 2). RESULTS: The dominant vector in the study area is Anopheles funestus s.l., which was the most abundant species group collected (31% of all Anophelines; 45,038/144,5550), had the highest sporozoite rate (3.16%; 66 positives out of 2,090 tested), and accounted for 94.3% (66/70) of all sporozoite positive specimens. Of those An. funestus specimens further identified to species, 97.2% (2,090/2,150) were An. funestus sensu stricto (s.s.). Anopheles gambiae s.l. (96.8% of which were Anopheles arabiensis) is a likely secondary vector and Anopheles squamosus may play a minor role in transmission. Overall, 21.6% (9,218/42,587) of An. funestus specimens and 10.4% (201/1,940) of An. gambiae specimens collected were positive for uranine, translating into an estimated daily feeding rate of 8.9% [7.7-9.9%] for An. funestus (inter-cluster range of 5.5% to 12.7%) and 3.9% [3.3-4.7%] for An. gambiae (inter-cluster range of 1.0-5.2%). Feeding rates were no different among mosquitoes collected indoors or outdoors, or among mosquitoes from clusters with 2 or 3 ASBs per eligible structure. Similarly, there were no correlations observed between feeding rates and the average number of ASB stations per hectare or with weekly rainfall amounts. CONCLUSIONS: Anopheles funestus and An. gambiae vector populations in Western Province, Zambia readily fed from the prototype Sarabi v1.1.1 ASB sugar bait station. Observed feeding rates are in line with those thought to be required for ATSB stations to achieve reductions in malaria transmission when used in combination with conventional control methods (IRS or LLIN). These results supported the decision to implement a large-scale, epidemiological cluster randomized controlled trial of ATSB in Zambia, deploying 2 ATSB stations per eligible structure.

Livelihood activities, human mobility, and risk of malaria infection in elimination settings: a case-control study.

BACKGROUND: Livelihood activities and human movements participate in the epidemiology of vector-borne diseases and influence malaria risk in elimination settings. In Saudi Arabia, where malaria transmission intensity varies geographically, it is vital to understand the components driving transmission within specific areas. In addition, shared social, behavioural, and occupational characteristics within communities may provoke the risk of malaria infection. This study aims to understand the relationship between human mobility, livelihood activities, and the risk of malaria infection in the border region of Jazan to facilitate further strategic malaria interventions. In addition, the study will complement and reinforce the existing efforts to eliminate malaria on the Saudi and Yemen border by providing a deeper understanding of human movement and livelihood activities. METHODS: An unmatched case-control study was conducted. A total of 261 participants were recruited for the study, including 81 cases of confirmed malaria through rapid diagnostic tests (RDTs) and microscopy and 180 controls in the Baish Governorate in Jazan Provinces, Saudi Arabia. Individuals who received malaria tests were interviewed regarding their livelihood activities and recent movement (travel history). A questionnaire was administered, and the data was captured electronically. STATA software version 16 was used to analyse the data. Bivariate and multivariate analyses were conducted to determine if engaging in agricultural activities such as farming and animal husbandry, recent travel history outside of the home village within the last 30 days and participating in spiritual gatherings were related to malaria infection status. RESULTS: A logistical regression model was used to investigate components associated with malaria infection. After adjusting several confounding factors, individuals who reported travelling away from their home village in the last 30 days OR 11.5 (95% CI 4.43-29.9), and those who attended a seasonal night spiritual gathering OR 3.04 (95% CI 1.10-8.42), involved in animal husbandry OR 2.52 (95% CI 1.10-5.82), and identified as male OR 4.57 (95% CI 1.43-14.7), were more likely to test positive for malaria infection. CONCLUSION: Human movement and livelihood activities, especially at nighttime, should be considered malaria risk factors in malaria elimination settings, mainly when the targeted area is limited to a confined borderland area.

An insight to better understanding cross border malaria in Saudi Arabia.

BACKGROUND: Border malaria is a major obstacle for the malaria elimination in Saudi Arabia. Today, the southern border of Saudi Arabia is a region where malaria cases are resurging, and malaria control is dwindling mainly due to the humanitarian crisis and the conflict in Yemen. This study analyses the current border malaria epidemiology along the southern border of Saudi Arabia from 2015 to 2018. METHODS: All reported cases maintained by the malaria elimination centres in Aledabi and Baish, Jazan Province, Saudi Arabia, from 2015 to 2018 were analysed to examine the epidemiological changes over time. Pearson's Chi-Square test of differences was utilized to assess differences between the characteristics of imported and local causes and between border cases. A logistic regression model was used to predict imported status was related to living along side of the border area. RESULTS: A total of 3210 malaria cases were reported in Baish and Aledabi malaria centres between 2015 and 2018, of which 170 were classified as local cases and 3040 were classified as imported cases. Reported malaria cases were mainly among males, within the imported cases 61.5% (1868/3039) were residents of the border areas. CONCLUSIONS: Given the complexity of cross-border malaria, creating a malaria buffer zone that covers a certain margin from both sides of the border would allow for a joint force, cross-border malaria elimination programme. To initiate a malaria elimination activity and cases reported as belonging to this zone, rather than being pushed from one country to the other, would allow malaria elimination staff to work collaboratively with local borderland residents and other stakeholders to come up with innovative solutions to combat malaria and reach malaria-free borders.

Aedes aegypti and Aedes albopictus (Diptera: Culicidae) Oviposition Activity and the Associated Socio-environmental Factors in the New Orleans Area.

The transmission of Aedes-borne viruses is on the rise globally. Their mosquito vectors, Aedes aegypti (Linnaeus, Diptera: Culicidae) and Ae. albopictus (Skuse, Diptera: Culicidae), are focally abundant in the Southern United States. Mosquito surveillance is an important component of a mosquito control program. However, there is a lack of long-term surveillance data and an incomplete understanding of the factors influencing vector populations in the Southern United States. Our surveillance program monitored Ae. aegypti and Ae. albopictus oviposition intensity in the New Orleans area using ovicups in a total of 75 sites from 2009 to 2016. We found both Aedes spp. throughout the study period and sites. The average number of Ae. aegypti and Ae. albopictus hatched from collected eggs per site per week was 34.1 (SD = 57.7) and 29.0 (SD = 46.5), respectively. Based on current literature, we formed multiple hypotheses on how environmental variables influence Aedes oviposition intensity, and constructed Generalized Linear Mixed Effect models with a negative binomial distribution and an autocorrelation structure to test these hypotheses. We found significant associations between housing unit density and Ae. aegypti and Ae. albopictus oviposition intensity, and between median household income and Ae. albopictus oviposition intensity. Temperature, relative humidity, and accumulated rainfall had either a lagged or an immediate significant association with oviposition. This study provides the first long-term record of Aedes spp. distribution in the New Orleans area, and sheds light on factors associated with their oviposition activity. This information is vital for the control of potential Aedes-borne virus transmission in this area.

Estimating population ITN access at council level in Tanzania.

BACKGROUND: Since 2013, the National Malaria Control Programme in mainland Tanzania and the Zanzibar Malaria Elimination Programme have implemented mass insecticide-treated net (ITN) distribution campaigns, routine ITN distribution to pregnant women and infants, and continuous distribution through primary schools (mainland) and community leaders (Zanzibar) to further malaria control efforts. Mass campaigns are triggered when ITN access falls below 40%. In this context, there is a need to monitor ITN access annually to assess whether it is below threshold and inform quantification of ITNs for the following year. Annual estimates of access are needed at the council level to inform programmatic decision-making. METHODS: An age-structured stock and flow model was used to predict annual net crops from council-level distribution data in Tanzania from 2012 to 2020 parameterized with a Tanzania-specific net median lifespan of 2.15 years. Annual nets-per-capita (NPC) was calculated by dividing each annual net crop by mid-year council projected population. A previously fit nonparametric conditional quantile function for the proportion of the population with access to an ITN (ITN access) as a function of NPC was used to predict ITN access at the council level based on the predicted NPC value. These estimates were compared to regional-level ITN access from large household surveys. RESULTS: For regions with the same ITN strategy for all councils, predicted council-level ITN access was consistent with regional-level survey data for 79% of councils. Regions where ITN strategy varied by council had regional estimates of ITN access that diverged from the council-specific estimates. Predicted ITN access reached 60% only when "nets issued as a percentage of the council population" (NPP) exceeded 15%, and approached 80% ITN access when NPP was at or above 20%. CONCLUSION: Modelling ITN access with country-specific net decay rates, council-level population, and ITN distribution data is a promising approach to monitor ITN coverage sub-regionally and between household surveys in Tanzania and beyond.