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.

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.

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.

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.

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.

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.

Estimation of bed net coverage indicators in Tanzania using mobile phone surveys: a comparison of sampling approaches.

BACKGROUND: Threats to maintaining high population access with effective bed nets persist due to errors in quantification, bed net wear and tear, and inefficiencies in distribution activities. Monitoring bed net coverage is therefore critical, but usually occurs every 2-3 years through expensive, large-scale household surveys. Mobile phone-based survey methodologies are emerging as an alternative to household surveys and can provide rapid estimates of coverage, however, little research on varied sampling approaches has been conducted in sub-Saharan Africa. METHODS: A nationally and regionally representative cross-sectional mobile phone survey was conducted in early 2021 in Tanzania with focus on bed net ownership and access. Half the target sample was contacted through a random digit dial methodology (n = 3500) and the remaining half was reached through a voluntary opt-in respondent pool (n = 3500). Both sampling approaches used an interactive voice response survey. Standard RBM-MERG bed net indicators and AAPOR call metrics were calculated. In addition, the results of the two sampling approaches were compared. RESULTS: Population access (i.e., the percent of the population that could sleep under a bed net, assuming one bed net per two people) varied from a regionally adjusted low of 48.1% (Katavi) to a high of 65.5% (Dodoma). The adjusted percent of households that had a least one bed net ranged from 54.8% (Pemba) to 75.5% (Dodoma); the adjusted percent of households with at least one bed net per 2 de facto household population ranged from 35.9% (Manyara) to 55.7% (Dodoma). The estimates produced by both sampling approaches were generally similar, differing by only a few percentage points. An analysis of differences between estimates generated from the two sampling approaches showed minimal bias when considering variation across the indicator for households with at least one bed net per two de facto household population. CONCLUSION: The results generated by this survey show that overall bed net access in the country appears to be lower than target thresholds. The results suggest that bed net distribution is needed in large sections of the country to ensure that coverage levels remain high enough to sustain protection against malaria for the population.

Breakthrough SARS-CoV-2 Infections after Vaccination in North Carolina.

We characterize the overall incidence and risk factors for breakthrough infection among fully vaccinated participants in the North Carolina COVID-19 Community Research Partnership cohort. Among 15,808 eligible participants, 638 reported a positive SARS-CoV-2 test after vaccination. Factors associated with a lower risk of breakthrough in the time-to-event analysis included older age, prior SARS-CovV-2 infection, higher rates of face mask use, and receipt of a booster vaccination. Higher rates of breakthrough were reported by participants vaccinated with BNT162b2 or Ad26.COV2.S compared to mRNA-1273, in suburban or rural counties compared to urban counties, and during circulation of the Delta and Omicron variants.

The impact of reactive case detection on malaria transmission in Zanzibar in the presence of human mobility.

Malaria persists at low levels on Zanzibar despite the use of vector control and case management. We use a metapopulation model to investigate the role of human mobility in malaria persistence on Zanzibar, and the impact of reactive case detection. The model was parameterized using survey data on malaria prevalence, reactive case detection, and travel history. We find that in the absence of imported cases from mainland Tanzania, malaria would likely cease to persist on Zanzibar. We also investigate potential intervention scenarios that may lead to elimination, especially through changes to reactive case detection. While we find that some additional cases are removed by reactive case detection, a large proportion of cases are missed due to many infections having a low parasite density that go undetected by rapid diagnostic tests, a low rate of those infected with malaria seeking treatment, and a low rate of follow up at the household level of malaria cases detected at health facilities. While improvements in reactive case detection would lead to a reduction in malaria prevalence, none of the intervention scenarios tested here were sufficient to reach elimination. Imported cases need to be treated to have a substantial impact on prevalence.

Annual distributions of insecticide-treated nets to schoolchildren and other key populations to maintain higher ITN access than with mass campaigns: a modelling study for mainland Tanzania.

BACKGROUND: Since 2013, the National Malaria Control Programme in mainland Tanzania has deployed annual distributions of insecticide-treated nets (ITNs) through primary schools to maintain ITN access and use. This School Net Programme (SNP) is slated to be used throughout mainland Tanzania by 2023. This modelling study projects ITN access under different ITN distribution strategies and quantification approaches. METHODS: A stock and flow model with a Tanzania-specific ITN decay rate was used to calculate annual net crops for four different ITN distribution strategies, varying quantification approaches within each strategy. Annual nets-per-capita (NPC) was derived from net crop and a standardized population projection. Nonparametric conditional quartile functions for the proportion of the population with access to an ITN (ITN access) as a function of NPC were used to predict ITN access and its variability. The number of ITNs required under the varying quantification approaches for the period 2022-2030 was calculated. RESULTS: Annual SNP quantified using a "population times 15%" approach maintained ITN access between 80 and 90%, when combined with reproductive and child health (RCH) ITN distribution, requiring 133.2 million ITNs. The same strategy quantified with "population times 22%" maintained ITN access at or above 90%, requiring 175.5 million ITNs. Under 5-year mass campaigns with RCH distribution for pregnant women and infants, ITN access reached 90% post-campaign and fell to 27-35% in the 4th year post-campaign, requiring 120.5 million ITNs over 8 years. 3-yearly mass campaigns with RCH reached 100% ITN access post-campaign and fell to 70% in the 3rd year post-campaign, requiring 154.4 million ITNs. CONCLUSION: Given an ITN retention time in Tanzania of 2.15 years, the model predicts that mass campaigns conducted every 3 years in mainland Tanzania will not maintain ITN access at target levels of 80%, even with strong RCH channels. Mainland Tanzania can however expect to maintain ITN access at 80% or above by quantifying SNP using "population × 15%", in addition to RCH ITN delivery. This strategy requires 14% fewer ITNs than a 3-year campaign strategy while providing more consistent ITN coverage. Meeting the targets of 80% ITN use would require maintaining 90% ITN access, achievable using a "population times 22%" quantification approach for SNP.

Self-Reported SARS-CoV-2 Vaccination Is Consistent with Electronic Health Record Data among the COVID-19 Community Research Partnership.

Introduction: Observational studies of SARS-CoV-2 vaccine effectiveness depend on accurate ascertainment of vaccination receipt, date, and product type. Self-reported vaccine data may be more readily available to and less expensive for researchers than assessing medical records. Methods: We surveyed adult participants in the COVID-19 Community Research Partnership who had an authenticated Electronic Health Record (EHR) (N = 41,484) concerning receipt of SARS-CoV-2 vaccination using a daily survey beginning in December 2020 and a supplemental survey in September-October 2021. We compared self-reported information to that available in the EHR for the following data points: vaccine brand, date of first dose, and number of doses using rates of agreement and Bland-Altman plots for visual assessment. Self-reported data was available immediately following vaccination (in the daily survey) and at a delayed interval (in a secondary supplemental survey). Results: For the date of first vaccine dose, self-reported "immediate" recall was within ±7 days of the date reported in the "delayed" survey for 87.9% of participants. Among the 19.6% of participants with evidence of vaccination in their EHR, 95% self-reported vaccination in one of the two surveys. Self-reported dates were within ±7 days of documented EHR vaccination for 97.6% of the "immediate" surveys and 92.0% of the "delayed" surveys. Self-reported vaccine product details matched those in the EHR for over 98% of participants for both "immediate" and "delayed" surveys. Conclusions: Self-reported dates and product details for COVID-19 vaccination can be a good surrogate when medical records are unavailable in large observational studies. A secondary confirmation of dates for a subset of participants with EHR data will provide internal validity.

Incremental cost and cost-effectiveness of the addition of indoor residual spraying with pirimiphos-methyl in sub-Saharan Africa versus standard malaria control: results of data collection and analysis in the Next Generation Indoor Residual Sprays (NgenIRS) project, an economic-evaluation.

BACKGROUND: Malaria is a major cause of morbidity and mortality globally, especially in sub-Saharan Africa. Widespread resistance to pyrethroids threatens the gains achieved by vector control. To counter resistance to pyrethroids, third-generation indoor residual spraying (3GIRS) products have been developed. This study details the results of a multi-country cost and cost-effectiveness analysis of indoor residual spraying (IRS) programmes using Actellic®300CS, a 3GIRS product with pirimiphos-methyl, in sub-Saharan Africa in 2017 added to standard malaria control interventions including insecticide-treated bed nets versus standard malaria control interventions alone. METHODS: An economic evaluation of 3GIRS using Actellic®300CS in a broad range of sub-Saharan African settings was conducted using a variety of primary data collection and evidence synthesis methods. Four IRS programmes in Ghana, Mali, Uganda, and Zambia were included in the effectiveness analysis. Cost data come from six IRS programmes: one in each of the four countries where effect was measured plus Mozambique and a separate programme conducted by AngloGold Ashanti Malaria Control in Ghana. Financial and economic costs were quantified and valued. The main indicator for the cost was cost per person targeted. Country-specific case incidence rate ratios (IRRs), estimated by comparing IRS study districts to adjacent non-IRS study districts or facilities, were used to calculate cases averted in each study area. A deterministic analysis and sensitivity analysis were conducted in each of the four countries for which effectiveness evaluations were available. Probabilistic sensitivity analysis was used to generate plausibility bounds around the incremental cost-effectiveness ratio estimates for adding IRS to other standard interventions in each study setting as well as jointly utilizing data on effect and cost across all settings. RESULTS: Overall, IRRs from each country indicated that adding IRS with Actellic®300CS to the local standard intervention package was protective compared to the standard intervention package alone (IRR 0.67, [95% CI 0.50-0.91]). Results indicate that Actellic®300CS is expected to be a cost-effective (> 60% probability of being cost-effective in all settings) or highly cost-effective intervention across a range of transmission settings in sub-Saharan Africa. DISCUSSION: Variations in the incremental costs and cost-effectiveness likely result from several sources including: variation in the sprayed wall surfaces and house size relative to household population, the underlying malaria burden in the communities sprayed, the effectiveness of 3GIRS in different settings, and insecticide price. Programmes should be aware that current recommendations to rotate can mean variation and uncertainty in budgets; programmes should consider this in their insecticide-resistance management strategies. CONCLUSIONS: The optimal combination of 3GIRS delivery with other malaria control interventions will be highly context specific. 3GIRS using Actellic®300CS is expected to deliver acceptable value for money in a broad range of sub-Saharan African malaria transmission settings.