BACKGROUND: Artemether-lumefantrine (AL) is the first line anti-malarial drug for the treatment of uncomplicated malaria in Tanzania. The World Health Organization (WHO) recommends regular efficacy monitoring of anti-malarial drugs to inform case management policy decisions. This study assessed the safety and efficacy of AL for treating uncomplicated P. falciparum malaria in Tanzania in 2022. METHODS: Children 6 months to 10 years with uncomplicated P. falciparum malaria were recruited from four sentinel sites and treated with the standard 6 dose, 3-day regimen for AL. Clinical and parasitological responses were monitored for 28 days using the WHO standard protocol. Genotyping based on msp1, msp2 and glurp was used to distinguish recrudescence from reinfection. SANGER sequencing was used to detect K13 mutations. RESULTS: 352 participants, 88 per site, were enrolled. Four withdrew and 55 experienced parasite recurrence. The PCR corrected Kaplan-Meier efficacies were, 89.9% in Pwani, 95.0% in Kigoma, 94.4% in Tanga, and 98.9% in Morogoro. No K13 mutations were found. CONCLUSIONS: Artemether-lumefantrine remains highly efficacious in three regions of Tanzania but the PCR-corrected efficacy in Pwani fell below the WHO-defined 90% threshold at which policy change is recommended. Implementing strategies to diversify ACTs to ensure effective case management in Tanzania is critical.

BACKGROUND: Therapeutic efficacy studies (TESs) and detection of molecular markers of drug resistance are recommended by the World Health Organization (WHO) to monitor the efficacy of artemisinin-based combination therapy (ACT). This study assessed the trends of molecular markers of artemisinin resistance and/or reduced susceptibility to lumefantrine using samples collected in TES conducted in Mainland Tanzania from 2016 to 2021. METHODS: A total of 2,015 samples were collected during TES of artemether-lumefantrine at eight sentinel sites (in Kigoma, Mbeya, Morogoro, Mtwara, Mwanza, Pwani, Tabora, and Tanga regions) between 2016 and 2021. Photo-induced electron transfer polymerase chain reaction (PET-PCR) was used to confirm presence of malaria parasites before capillary sequencing, which targeted two genes: Plasmodium falciparum kelch 13 propeller domain (k13) and P. falciparum multidrug resistance 1 (pfmdr1). RESULTS: Sequencing success was ≥ 87.8%, and 1,724/1,769 (97.5%) k13 wild-type samples were detected. Thirty-seven (2.1%) samples had synonymous mutations and only eight (0.4%) had non-synonymous mutations in the k13 gene; seven of these were not validated by the WHO as molecular markers of resistance. One sample from Morogoro in 2020 had a k13 R622I mutation, which is a validated marker of artemisinin partial resistance. For pfmdr1, all except two samples carried N86 (wild-type), while mutations at Y184F increased from 33.9% in 2016 to about 60.5% in 2021, and only four samples (0.2%) had D1246Y mutations. pfmdr1 haplotypes were reported in 1,711 samples, with 985 (57.6%) NYD, 720 (42.1%) NFD, and six (0.4%) carrying minor haplotypes (three with NYY, 0.2%; YFD in two, 0.1%; and NFY in one sample, 0.1%). Between 2016 and 2021, NYD decreased from 66.1% to 45.2%, while NFD increased from 38.5% to 54.7%. CONCLUSION: This is the first report of the R622I (k13 validated mutation) in Tanzania. N86 and D1246 were nearly fixed, while increases in Y184F mutations and NFD haplotype were observed between 2016 and 2021. Despite the reports of artemisinin partial resistance in Rwanda and Uganda, this study did not report any other validated mutations in these study sites in Tanzania apart from R622I suggesting that intensified surveillance is urgently needed to monitor trends of drug resistance markers and their impact on the performance of ACT.

Malaria in pregnancy (MiP) is associated with maternal anemia, spontaneous abortion, and infant and maternal death. In Tanzania, MiP service data are collected through routine Malaria Services and Data Quality Improvement (MSDQI) supportive supervision rounds at antenatal care (ANC) facilities. Using structured assessment tools, the U.S. President's Malaria Initiative Impact Malaria Project reviewed two annual rounds of MSDQI data (492 facilities in 2021 and 522 facilities in 2022), including ANC records and client satisfaction interviews. We assessed coverage of key MiP care components, used logistic regression to analyze uptake of the recommended three or more doses of intermittent preventive treatment in pregnancy (IPTp3+), and assessed client satisfaction. Coverage of most MiP care components exceeded 80%; however, only 38% of women received all components. Odds of receiving IPTp3+ were much lower among late ANC initiators than among those who initiated ANC during their first trimester (odds ratio [OR], 0.46; 95% CI, 0.38-0.57). Uptake of IPTp3+ increased almost exponentially by number of ANC visits. Women with seven visits were 30 times more likely than those with three visits to receive IPTp3+ (OR, 30.71; 95% CI, 11.33-83.22). Just 54% of clients had anemia screening and only 46% received IPTp3+. Client satisfaction with services and provider communication was high (98% and 97%, respectively); only 8% of client visits exceeded 3 hours. Increased ANC visits could boost IPTp3+ coverage. Routine MSDQI supportive supervision data are useful to assess quality of care, identify service delivery gaps, and guide policies to improve quality of MiP services.

Testing and treating asymptomatic populations have the potential to reduce the population's parasite reservoir and reduce malaria transmission. Zanzibar's malaria case notification (MCN) platform collects detailed sociodemographic and epidemiological data from all confirmed malaria cases to inform programmatic decision-making. We describe the design and operationalization process of the platform and other malaria surveillance resources that are enabling Zanzibar's progress toward malaria elimination.The MCN platform consists of an interactive short message service (SMS) system for case notification, a software application for Android mobile devices, a visual question set and workflow manager, a back-end database server, and a web browser-based application for data analytics, configuration, and management. Malaria case data were collected from August 2012 to December 2021 and reported via SMS from all public and private health facilities to a central database and then to district malaria surveillance officers' mobile devices. Data included patient names, shehia (administrative area), and date of diagnosis, enabling officers to track patients, ideally within 24 hours of reporting. Patients' household members were tested for malaria using conventional rapid diagnostic tests (RDTs). Treatment using artemisinin-based combination therapy was provided for persons testing positive.Between 2012 and 2021, a total of 48,899 index malaria cases were confirmed at health facilities, 22,152 (45.3%) within 24 hours of reporting; 41,886 (85.7%) cases were fully investigated and followed up to the household level. A total of 111,811 additional household members were tested with RDTs, of whom 10,602 (9.5%) were malaria positive.The MCN platform reports malaria case data in near real time, enabling prompt follow-up of index cases and prompt testing and treatment of members in index case households. Along with routine testing and treatment and other preventive interventions, the MCN platform is foundational to the programmatic efforts in further reducing malaria and ultimately eliminating autochthonous malaria transmission in Zanzibar.

In 2018, Zanzibar developed a national malaria strategic plan IV (2018-2023) to guide elimination of malaria by 2023. We assessed progress in the implementation of malaria activities as part of the end-term review of the strategic plan. The review was done between August and October 2022 following the WHO guideline to assess progress made towards malaria elimination, effectiveness of the health systems in delivering malaria case management; and malaria financing. A desk review examined available malaria data, annual work plans and implementation reports for evidence of implemented malaria activities. This was complemented by field visits to selected health facilities and communities by external experts, and interviews with health management teams and inhabitants to authenticate desk review findings. A steady increase in the annual parasite incidence (API) was observed in Zanzibar, from 2.7 (2017) to 3.6 (2021) cases per 1,000 population with marked heterogeneity between areas. However, about 68% of the detected malaria cases were imported into Zanzibar. Malaria case follow-up and investigation increased from <70% in 2017 to 94% and 96% respectively, in 2021. The review noted a 3.7-fold increase of the health allocation in the country's budget, from 31.7 million USD (2017/18) to 117.3 million USD (2022/23) but malaria allocation remained low (<1%). The varying transmission levels in the islands suggest a need for strategic re-orientation of the elimination attempts from a national-wide to a sub-national agenda. We recommend increasing malaria allocation from the health budget to ensure sustainability of malaria elimination interventions.

Testing and treating asymptomatic populations has the potential to reduce the population's parasite reservoir and reduce malaria transmission. Zanzibar's electronic malaria case notification (MCN) platform collects detailed socio-demographic and epidemiological data from all confirmed malaria cases to inform programmatic decision-making. This Field Action Report describes the design and operationalization process of the platform, as well as other malaria surveillance resources that are enabling Zanzibar to progress toward malaria elimination. The MCN platform consists of an interactive short message service (SMS) system for case notification, a software application for Android mobile devices, a visual question set and workflow manager, a back-end database server, and a web browser-based application for data analytics, configuration, and management. Malaria case data were collected from August 2012 to December 2021 and reported via SMS from all public and private health facilities to a central database, and then to District Malaria Surveillance Officers' mobile devices. Data included patient names, shehia and date of diagnosis, which enabled the officers to track patients, ideally within 24 hours of reporting. Patients' household members were tested for malaria using conventional rapid diagnostic tests (RDTs). Treatment using artemisinin-based combination therapy was provided for persons testing positive. Between 2012 and 2021, a total of 48,899 index malaria cases were confirmed at health facilities, 22,152 (45.3%) of whom within 24 hours of reporting; 41,886 (85.7%) cases were fully investigated and followed up to household level. A total of 111,811 additional household members were tested with RDTs, of whom 10,602 (9.5%) were malaria positive. The MCN platform reports malaria case data in near real-time, enabling prompt testing and treatment of members in index case households. Along with routine testing and treatment and other preventive interventions, combined with comprehensive reactive-case detection efforts, the continued use of the MCN platform is likely to reduce malaria transmission and malaria morbidity even further, thereby enhancing malaria elimination in Zanzibar. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.

Background: Despite the continued high coverage of malaria interventions, malaria elimination in Zanzibar remains elusive, with the annual number of cases increasing gradually over the last 3 years. The aims of the analyses presented here were to (i) assess the spatio-temporal dynamics of malaria in Zanzibar between 2015 and 2020, and (ii) identify malaria hotspots that would allow Zanzibar to develop an epidemiological stratification for more effective and granular intervention targeting, thereby allowing for more effective programmatic resource allocations. Method(s): Data routinely collected by Zanzibar's Malaria Case Notification (MCN) system were analyzed. The system collects detailed socio-demographic and epidemiological data from all malaria cases who are passively detected and reported at the islands' 313 public and private health facilities (defined as primary index cases), as well as through case follow-up and reactive case detection (defined as secondary cases). Using these data, spatio-temporal analyses were performed to identify the spatial heterogeneity of case reporting at shehia (ward) level during transmission seasons and its correlation with 2015-2020 rainfall. Result(s): From January 1, 2015, to April 30, 2020, 22,686 index cases were notified by health facilities and reported through the MCN system. Number of cases reported showed declining trends from 2015 to 2017, followed by an increase from 2018 to 2020. More than 40% of cases had a travel history outside Zanzibar in the month prior to testing positive for malaria. The proportion of followed-up index cases was approximately 70% for all years. Change point analysis identified 10 distinct periods of malaria transmission across the study period, and the seasonality of reported index cases was significantly correlated to the amount of precipitation that occurred during the previous rainy season. Out of Zanzibar's 388 shehias, 79 (20.3%) were identified as malaria hotspots in any given year between 2015 and 2020; these hotspots reported 52% of all index cases during the study period. Of the 79 shehias identified as hotspots, 12 (3% of all shehias) were hotspots in more than four years, i.e., considered temporally stable, reporting 14.5% of all index cases. Conclusion(s): Our findings confirm that the scale-up of malaria interventions has greatly reduced malaria transmission in Zanzibar since 2006, with mean annual shehia incidence being 3.8 cases per 1,000 over the 2015-2020 study period. Spatio-temporal analyses identified hotspots, some of which were stable across multiple years. From a programmatic perspective, malaria efforts should progress from an approach that is based on universal coverage of interventions to an approach that is more tailored and nuanced, with resources prioritized and allocated to a select number of hotspot shehias. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Efforts to achieve malaria elimination need to consider both falciparum and nonfalciparum infections. The prevalence and geographic distribution of four Plasmodium species were determined by real-time PCR using dried blood spots collected during the 2017 School Malaria Parasitological Survey of eight regions of Tanzania. Among 3,456 schoolchildren, 22% had P. falciparum, 24% P. ovale spp., 4% P. malariae, and 0.3% P. vivax. Ninety-one percent of P. ovale infections had very low parasite densities, based on amplification at later cycle thresholds. Sixty-four percent of P. ovale infections were single-species, and 35% of these were detected in low malaria endemicity regions. P. malariae infections were predominantly co-infections with P. falciparum (73%). P. vivax was largely detected in northern and eastern regions. Overall, 43% of children with P. falciparum were co-infected with at least one nonfalciparum species. A large, previously under-appreciated burden of P. ovale spp. infection exists among Tanzanian schoolchildren. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

Achieving malaria elimination requires considering both Plasmodium falciparum and non-P. falciparum infections. We determined prevalence and geographic distribution of 4 Plasmodium spp. by performing PCR on dried blood spots collected within 8 regions of Tanzania during 2017. Among 3,456 schoolchildren, 22% had P. falciparum, 24% had P. ovale spp., 4% had P. malariae, and 0.3% had P. vivax infections. Most (91%) schoolchildren with P. ovale infections had low parasite densities; 64% of P. ovale infections were single-species infections, and 35% of those were detected in low malaria endemic regions. P. malariae infections were predominantly (73%) co-infections with P. falciparum. P. vivax was detected mostly in northern and eastern regions. Co-infections with >1 non-P. falciparum species occurred in 43% of P. falciparum infections. A high prevalence of P. ovale infections exists among schoolchildren in Tanzania, underscoring the need for detection and treatment strategies that target non-P. falciparum species.

BACKGROUND: Insecticide resistance is a serious threat to the continued effectiveness of insecticide-based malaria vector control measures, such as long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS). This paper describes trends and dynamics of insecticide resistance and its underlying mechanisms from annual resistance monitoring surveys on Anopheles gambiae sensu lato (s.l.) populations conducted across mainland Tanzania from 2004 to 2020. METHODS: The World Health Organization (WHO) standard protocols were used to assess susceptibility of the wild female An. gambiae s.l. mosquitoes to insecticides, with mosquitoes exposed to diagnostic concentrations of permethrin, deltamethrin, lambdacyhalothrin, bendiocarb, and pirimiphos-methyl. WHO test papers at 5× and 10× the diagnostic concentrations were used to assess the intensity of resistance to pyrethroids; synergist tests using piperonyl butoxide (PBO) were carried out in sites where mosquitoes were found to be resistant to pyrethroids. To estimate insecticide resistance trends from 2004 to 2020, percentage mortalities from each site and time point were aggregated and regression analysis of mortality versus the Julian dates of bioassays was performed. RESULTS: Percentage of sites with pyrethroid resistance increased from 0% in 2004 to more than 80% in the 2020, suggesting resistance has been spreading geographically. Results indicate a strong negative association (p = 0.0001) between pyrethroids susceptibility status and survey year. The regression model shows that by 2020 over 40% of An. gambiae mosquitoes survived exposure to pyrethroids at their respective diagnostic doses. A decreasing trend of An. gambiae susceptibility to bendiocarb was observed over time, but this was not statistically significant (p = 0.8413). Anopheles gambiae exhibited high level of susceptibility to the pirimiphos-methyl in sampled sites. CONCLUSIONS: Anopheles gambiae Tanzania's major malaria vector, is now resistant to pyrethroids across the country with resistance increasing in prevalence and intensity and has been spreading geographically. This calls for urgent action for efficient malaria vector control tools to sustain the gains obtained in malaria control. Strengthening insecticide resistance monitoring is important for its management through evidence generation for effective malaria vector control decision.

BACKGROUND: Despite high coverage of malaria interventions, malaria elimination in Zanzibar remains elusive, with the annual number of cases increasing gradually over the last 3 years. OBJECTIVE: The aims of the study were to (1) assess the spatiotemporal dynamics of malaria in Zanzibar between 2015 and 2020 and (2) identify malaria hotspots that would allow Zanzibar to develop an epidemiological stratification for more effective and granular intervention targeting. METHODS: In this study, we analysed data routinely collected by Zanzibar's Malaria Case Notification (MCN) system. The system collects sociodemographic and epidemiological data from all malaria cases. Cases are passively detected at health facilities (ie, primary index cases) and through case follow-up and reactive case detection (ie, secondary cases). Analyses were performed to identify the spatial heterogeneity of case reporting at shehia (ward) level during transmission seasons. RESULTS: From 1 January 2015 to 30 April 2020, the MCN system reported 22 686 index cases. Number of cases reported showed a declining trends from 2015 to 2016, followed by an increase from 2017 to 2020. More than 40% of cases had a travel history outside Zanzibar in the month prior to testing positive for malaria. The proportion of followed up index cases was approximately 70% for all years. Out of 387 shehias, 79 (20.4%) were identified as malaria hotspots in any given year; these hotspots reported 52% of all index cases during the study period. Of the 79 hotspot shehias, 12 were hotspots in more than 4 years, that is, considered temporally stable, reporting 14.5% of all index cases. CONCLUSIONS: Our findings confirm that the scale-up of malaria interventions has greatly reduced malaria transmission in Zanzibar since 2006. Analyses identified hotspots, some of which were stable across multiple years. Malaria efforts should progress from a universal intervention coverage approach to an approach that is more tailored to a select number of hotspot shehias.

BACKGROUND: Tanzania has made remarkable progress in reducing malaria burden and aims to transition from malaria control to sub-national elimination. In 2013, electronic weekly and monthly reporting platforms using the District Health Information System 2 (DHIS2) were introduced. Weekly reporting was implemented through the mobile phone-based Integrated Disease Surveillance and Response (eIDSR) platform and progressively scaled-up from 67 to 7471 (100%) public and private health facilities between 2013 and 2020. This study describes the roll-out and large-scale implementation of eIDSR and compares the consistency between weekly eIDSR and monthly DHIS2 malaria indicator data reporting, including an assessment of its usefulness for malaria outbreak detection and case-based surveillance (CBS) in low transmission areas. METHODS: The indicators included in the analysis were number of patients tested for malaria, number of confirmed malaria cases, and clinical cases (treated presumptively for malaria). The analysis described the time trends of reporting, testing, test positivity, and malaria cases between 2013 and 2021. For both weekly eIDSR and monthly DHIS2 data, comparisons of annual reporting completeness, malaria cases and annualized incidence were performed for 2020 and 2021; additionally, comparisons were stratified by malaria epidemiological strata (parasite prevalence: very low < 1%, low 1 ≤ 5%, moderate 5 ≤ 30%, and high > 30%). RESULTS: Weekly eIDSR reporting completeness steadily improved over time, with completeness being 90.2% in 2020 and 93.9% in 2021; conversely, monthly DHIS2 reporting completeness was 98.9% and 98.7% in 2020 and 2021, respectively. Weekly eIDSR reporting completeness and timeliness were highest in the very low epidemiological stratum. Annualized malaria incidence as reported by weekly eIDSR was 17.5% and 12.4% lower than reported by monthly DHIS2 in 2020 and 2021; for both 2020 and 2021, annualized incidence was similar across weekly and monthly data in the very low stratum. CONCLUSION: The concurrence of annualized weekly eIDSR and monthly DHIS2 reporting completeness, malaria cases and incidence in very low strata suggests that eIDSR could be useful tool for early outbreak detection, and the eIDSR platform could reliably be expanded by adding more indicators and modules for CBS in the very low epidemiological stratum.

BACKGROUND: Transmission of malaria in sub-Saharan Africa has become increasingly stratified following decades of malaria control interventions. The extent to which environmental and land cover risk factors for malaria may differ across distinct strata of transmission intensity is not well known and could provide actionable targets to maximize the success of malaria control efforts. METHODS: This study used cross-sectional malaria survey data from a nationally representative cohort of school-aged children in Tanzania, and satellite-derived measures for environmental features and land cover. Hierarchical logistic regression models were applied to evaluate associations between land cover and malaria prevalence within three distinct strata of transmission intensity: low and unstable, moderate and seasonal, and high and perennial. RESULTS: In areas with low malaria transmission, each 10-percentage point increase in cropland cover was associated with an increase in malaria prevalence odds of 2.44 (95% UI: 1.27, 5.11). However, at moderate and higher levels of transmission intensity, no association between cropland cover and malaria prevalence was detected. Small associations were observed between greater grassland cover and greater malaria prevalence in high intensity settings (prevalence odds ratio (POR): 1.10, 95% UI: 1.00, 1.21), and between greater forest cover and reduced malaria prevalence in low transmission areas (POR: 0.74, 95% UI: 0.51, 1.03), however the uncertainty intervals of both estimates included the null. CONCLUSIONS: The intensity of malaria transmission appears to modify relationships between land cover and malaria prevalence among school-aged children in Tanzania. In particular, greater cropland cover was positively associated with increased malaria prevalence in areas with low transmission intensity and presents an actionable target for environmental vector control interventions to complement current malaria control activities. As areas are nearing malaria elimination, it is important to re-evaluate environmental risk factors and employ appropriate interventions to effectively address low-level malaria transmission.

BACKGROUND: Over the past two decades, Zanzibar substantially reduced malaria burden. As malaria decreases, sustainable improvements in control interventions may increasingly depend on accurate knowledge of malaria risk factors to further target interventions. This study aimed to investigate the risk factors associated with malaria infection in Zanzibar. METHODS: Surveillance data from Zanzibar's Malaria Case Notification system from August 2012 and December 2019 were analyzed. This system collects data on malaria cases passively detected and reported by all health facilities (index cases), and household-based reactive case detection (RCD) activities linked to those primary cases. All members of households of the index cases were screened for malaria using a malaria rapid diagnostic test (RDT). Individuals with a positive RDT were treated with artemisinin-based combination therapy. Univariate and multivariate logistic regression analyses were done to investigate the association between RDT positivity among the household members and explanatory factors with adjustment for seasonality and clustering at Shehia level. RESULTS: A total of 30,647 cases were reported of whom household RCD was completed for 21,443 (63%) index case households and 85,318 household members tested for malaria. The findings show that younger age (p-value for trend [Ptrend] < 0.001), history of fever in the last 2 weeks (odds ratio [OR] = 35.7; 95% CI 32.3-39.5), travel outside Zanzibar in the last 30 days (OR = 2.5; 95% CI 2.3-2.8) and living in Unguja (OR = 1.2; 95% CI 1.0-1.5) were independently associated with increased odds of RDT positivity. In contrast, male gender (OR=0.8; 95% CI 0.7-0.9), sleeping under an LLIN the previous night (OR = 0.9; 95% CI 0.7-0.9), having higher household net access (Ptrend < 0.001), and living in a household that received IRS in the last 12 months (OR = 0.8; 95% CI 0.7-0.9) were independently associated with reduced odds of RDT positivity. A significant effect modification of combining IRS and LLIN was also noted (OR = 0.7; 95% CI 0.6-0.8). CONCLUSIONS: The findings suggest that vector control remains an important malaria prevention intervention: they underscore the need to maintain universal access to LLINs, the persistent promotion of LLIN use, and application of IRS. Additionally, enhanced behavioural change and preventive strategies targeting children aged 5-14 years and travellers are needed.