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.

INTRODUCTION: Antenatal care (ANC) interventions improve maternal and neonatal outcomes. However, access to ANC may be inequitable due to sociocultural, monetary and time factors. Examining drivers of ANC disparities may identify those amenable to policy change. METHODS: We conducted an ANC services equity analysis in selected public facilities in Geita, Tanzania, where most services are free to the end-user, and Atlantique, Benin, where every visit incurs user fees. Data on total ANC contacts, quality of care (QoC) indicators and wait times were collected from representative household surveys in the catchment of 40 clinics per country and were analysed by education and wealth. We used indices of inequality, concentration indices and Oaxaca-Blinder decompositions to determine the distribution, direction and magnitude of inequalities and their contributing factors. We assessed out-of-pocket expenses and the benefit incidence of government funding. RESULTS: ANC clients in both countries received less than the recommended minimum ANC contacts: 3.41 (95% CI 3.36 to 3.41) in Atlantique and 3.33 (95% CI 3.27 to 3.39) in Geita. Wealthier individuals had more ANC contacts than poorer ones at every education level in both countries; the wealthiest and most educated had two visits more than the poorest, least educated. In Atlantique, ANC attendees receive similar QoC regardless of socioeconomic status. In Geita, there are wide disparities in QoC received by education or wealth. In Atlantique, out-of-pocket expenses for the lowest wealth quintile are 2.7% of annual income compared with 0.8% for the highest, with user fees being the primary expense. In Geita, the values are 3.1% and 0.5%, respectively; transportation is the main expense. CONCLUSIONS: Inequalities in total ANC visits favouring wealthier, more educated individuals were apparent in both countries. In Atlantique, reduction of user-fees could improve ANC access. In Geita, training and equipping healthcare staff could improve QoC. Community health services could mitigate access barriers.

BACKGROUND: Artemisinin-based combination therapy (ACT) has been a major contributor to the substantial reductions in global malaria morbidity and mortality over the last decade. In Tanzania, artemether-lumefantrine (AL) was introduced as the first-line treatment for uncomplicated Plasmodium falciparum malaria in 2006. The World Health Organization (WHO) recommends regular assessment and monitoring of the efficacy of the first-line treatment, specifically considering that artemisinin resistance has been confirmed in the Greater Mekong sub-region. This study's main aim was to assess the efficacy and safety of AL for treating uncomplicated P. falciparum malaria in Tanzania. METHODS: This was a single-arm prospective antimalarial drug efficacy trial conducted in four of the eight National Malaria Control Programme (NMCP) sentinel sites in 2019. The trial was carried out in outpatient health facilities in Karume-Mwanza region, Ipinda-Mbeya region, Simbo-Tabora region, and Nagaga-Mtwara region. Children aged six months to 10 years with microscopy confirmed uncomplicated P. falciparum malaria who met the inclusion criteria were recruited based on the WHO protocol. The children received AL (a 6-dose regimen of AL twice daily for three days). Clinical and parasitological parameters were monitored during follow-up over 28 days to evaluate drug efficacy. RESULTS: A total of 628 children were screened for uncomplicated malaria, and 349 (55.6%) were enrolled between May and September 2019. Of the enrolled children, 343 (98.3%) completed the 28-day follow-up or attained the treatment outcomes. There were no early treatment failures; recurrent infections during follow-up were common at two sites (Karume 29.5%; Simbo 18.2%). PCR-corrected adequate clinical and parasitological response (ACPR) by survival analysis to AL on day 28 of follow-up varied from 97.7% at Karume to 100% at Ipinda and Nagaga sites. The commonly reported adverse events were cough, skin pallor, and abdominal pain. The drug was well tolerated, and no serious adverse event was reported. CONCLUSION: This study showed that AL had adequate efficacy and safety for the treatment of uncomplicated falciparum malaria in Tanzania in 2019. The high recurrent infections were mainly due to new infections, highlighting the potential role of introducing alternative artemisinin-based combinations that offer improved post-treatment prophylaxis, such as artesunate-amodiaquine (ASAQ).

BACKGROUND: The use of artemisinin-based combination therapy (ACT) is recommended by the World Health Organization for the treatment of uncomplicated falciparum malaria. Artemether-lumefantrine (AL) is the most widely adopted first-line ACT for uncomplicated malaria in sub-Saharan Africa (SSA), including mainland Tanzania, where it was introduced in December 2006. The WHO recommends regular assessment to monitor the efficacy of the first-line treatment specifically considering that artemisinin partial resistance was reported in Greater Mekong sub-region and has been confirmed in East Africa (Rwanda and Uganda). The main aim of this study was to assess the efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in mainland Tanzania. METHODS: A single-arm prospective anti-malarial drug efficacy trial was conducted in Kibaha, Mlimba, Mkuzi, and Ujiji (in Pwani, Morogoro, Tanga, and Kigoma regions, respectively) in 2018. The sample size of 88 patients per site was determined based on WHO 2009 standard protocol. Participants were febrile patients (documented axillary temperature ≥ 37.5 °C and/or history of fever during the past 24 h) aged 6 months to 10 years. Patients received a 6-dose AL regimen by weight twice a day for 3 days. Clinical and parasitological parameters were monitored during 28 days of follow-up to evaluate the drug efficacy and safety. RESULTS: A total of 653 children were screened for uncomplicated malaria and 349 (53.7%) were enrolled between April and August 2018. Of the enrolled children, 345 (98.9%) completed the 28 days of follow-up or attained the treatment outcomes. There were no early treatment failures, but recurrent infections were higher in Mkuzi (35.2%) and Ujiji (23%). By Kaplan-Meier analysis of polymerase chain reaction (PCR) uncorrected adequate clinical and parasitological response (ACPR) ranged from 63.4% in Mkuzi to 85.9% in Mlimba, while PCR-corrected ACPR on day 28 varied from 97.6% in Ujiji to 100% in Mlimba. The drug was well tolerated; the commonly reported adverse events were cough, runny nose, and abdominal pain. No serious adverse event was reported. CONCLUSION: This study showed that AL had adequate efficacy and safety for the treatment of uncomplicated falciparum malaria. The high number of recurrent infections were mainly due to new infections, indicating the necessity of utilizing alternative artemisinin-based combinations, such as artesunate amodiaquine, which provide a significantly longer post-treatment prophylactic effect.

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.

Tanzania is undergoing an epidemiological transition for malaria transmission with some areas of the country having <10% (hypoendemic) and other areas 10% - 50% malaria prevalence (mesoendemic). It is not known whether there is a difference in the quality of malaria case management based on endemicity in Tanzania mainland. We examined the influence of endemicity on the quality of malaria case management at health facilities. We conducted a cross-sectional analysis of 1713 health facilities in Tanzania mainland, using data collected by the National Malaria Control Program through an assessment tool to evaluate quality of malaria case management. The data was gathered from September 2017 to December 2018. Using standard quality factors, mean scores from facilities in the different endemicity regions were compared by a Student's t-test. Simple and multiple linear regression analyses were performed to determine the association between facility performance (score) and endemicity (mesoendemic vs. hypoendemic). Facilities in mesoendemic regions scored higher than those in hypoendemic regions on the overall quality of services [difference in mean scores ([Formula: see text]) = 2.52; (95% Confidence Interval (CI) 1.12, 3.91)], site readiness [[Formula: see text] = 2.97; (95% CI 1.30, 4.61)], availability of malaria reference materials [[Formula: see text] = 4.91; (95% CI 2.05, 7.76)], availability of Health Management Information System tools [[Formula: see text] = 5.86; (95% CI 3.80, 7.92)] and patient satisfaction [[Formula: see text] = 6.61; (95% CI 3.75, 9.48)]. Predictors associated with lower facility scores included; being located in a hypoendemic region [β: -2.49; (95% CI -3.83, -1.15)] and urban area [β: -3.84; (95% CI -5.60, -2.08)]. These findings highlight the differences in quality of malaria case management based on endemicity, but there is still a need to target improvement efforts in underperforming facilities, regardless of endemicity.

OBJECTIVES: Estimates of malaria burden and intervention uptake in Africa are primarily based on household surveys. However, their expense and infrequency limit their utility. We investigated whether data collected during antenatal care (ANC) can provide relevant information for decision-makers. METHODS: Malaria test positivity rates and questionnaire data from ANC attendees at 39 health facilities were compared to questionnaire data and positivity rates among children from two cross-sectional surveys in the facilities' corresponding catchment areas. RESULTS: Trends in parasitemia among ANC attendees were predictive of trends in parasitemia among children at the council level (mean absolute error 6.0%). Primigravid ANC attendees had the lowest rates of net ownership (modeled odds ratio, OR, 0.28, 95% confidence interval, CI, 0.19 - 0.40) and use (OR 0.58, 95% CI 0.42 - 0.79). ANC attendees reported higher levels of care seeking (OR 1.78, 95% CI 1.48 - 2.14), malaria testing (OR 4.16, 95% CI 3.44 - 5.04), and treatment for children with fever (OR 7.66, 95% CI 4.89 - 11.98) compared to women surveyed in households, raising concerns about social desirability bias disproportionately impacting ANC surveys. CONCLUSION: ANC surveillance is an effective strategy for tracking trends in malaria burden. More work is required to elucidate the value in administering questionnaires to ANC attendees.

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.

Over the past 15 years, Zanzibar has made great strides towards malaria elimination; yet progress has stalled. Parasite genetic data of Plasmodium falciparum may inform strategies for malaria elimination by helping to identify contributory factors to parasite persistence. Here we elucidate fine-scale parasite population structure and infer relatedness and connectivity of infections using an identity-by-descent (IBD) approach. We sequenced 518 P. falciparum samples from 5 districts covering both main islands using a novel, highly multiplexed droplet digital PCR (ddPCR)-based amplicon deep sequencing method targeting 35 microhaplotypes and drug-resistance loci. Despite high genetic diversity, we observe strong fine-scale spatial and temporal structure of local parasite populations, including isolated populations on Pemba Island and genetically admixed populations on Unguja Island, providing evidence of ongoing local transmission. We observe a high proportion of highly related parasites in individuals living closer together, including between clinical index cases and the mostly asymptomatic cases surrounding them, consistent with isolation-by-distance. We identify a substantial fraction (2.9%) of related parasite pairs between Zanzibar, and mainland Tanzania and Kenya, consistent with recent importation. We identify haplotypes known to confer resistance to known antimalarials in all districts, including multidrug-resistant parasites, but most parasites remain sensitive to current first-line treatments. Our study provides a high-resolution view of parasite genetic structure across the Zanzibar archipelago and reveals actionable patterns, including isolated parasite populations, which may be prioritized for malaria elimination. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

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.

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.

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.

Tuberculosis (TB) is the leading preventable cause of death among persons living with the human immunodeficiency virus (PLHIV) worldwide. The current US guidelines for the prevention of opportunistic infections in HIV-infected adults and adolescents recommend testing for latent tuberculous infection (LTBI) at the time of HIV diagnosis, regardless of other TB risk factors, and annually thereafter in PLHIV with initial negative LTBI testing results who are at continued high risk of exposure to Mycobacterium tuberculosis.1 Evaluation of PLHIV for TB disease and infection reduces morbidity and mortality, and prevents future TB transmission.2,3 However, we published a study in this Journal that evaluated a nationally representative sample of 2772 PLHIV in care in the United States during 2010–2012, and found that more than 30% of PLHIV diagnosed with HIV infection in the previous 5 years had no documentation of ever being tested for LTBI.4 | | While testing for LTBI among PLHIV in the Netherlands is not routine, the study by van Bentum et al. observed positive LTBI test results among 4.8% of their study population, highlighting the critical importance of screening PLHIV.5

BACKGROUND: Electronic directly observed therapy (eDOT) has been proposed as an alternative to traditional in-person DOT (ipDOT) for monitoring TB treatment adherence. Information about the comparative performance and implementation of eDOT is limited.METHODS: The frequency of challenges during DOT, challenge type, and effect on medication observation were documented by DOT method during a crossover, noninferiority randomized controlled trial. A logistic mixed-effects model that adjusted for the study design was used to estimate the percentage of successfully observed doses when challenges occurred.RESULTS: A total of 20,097 medication doses were scheduled for observation with either eDOT (15,405/20,097; 76.7%) or ipDOT (4,692/20,097; 23.3%) for 213 study participants. In total, one or more challenges occurred during 17.3% (2,672/15,405) of eDOT sessions and 15.6% (730/4,692) of ipDOT sessions. Among 4,374 documented challenges, 27.3% (n = 1,192) were characterized as technical, 65.9% (n = 2,881) were patient-related, and 6.9% (n = 301) were program-related. Estimated from the logistic model (n = 6,782 doses, 173 participants), the adjusted percentage of doses successfully observed during problematic sessions was 21.7% (95% CI 11.2-37.8) for eDOT and 4.2% (95% CI 1.1-14.7) for ipDOT.CONCLUSION: Compared to ipDOT, challenges were encountered in a slightly higher percentage of eDOT sessions but were more often resolved to enable successful dose observation during problematic sessions.

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: Measurement of malaria prevalence is conventionally estimated through infrequent cross-sectional household surveys that do not provide continuous information regarding malaria parasitaemia. Recent studies have suggested that malaria parasitaemia prevalence among women attending antenatal care (ANC) correlates with prevalence among children under 5 years old and that pregnant women could be a sentinel population for tracking malaria prevalence. In mainland Tanzania, 97% of women are tested for malaria parasitaemia during first ANC visits. However, acceptability among pregnant women and healthcare providers of collecting malaria risk factor data during ANC visits is limited. METHODS: A tablet-based questionnaire including 15 questions on insecticide-treated net ownership and use and care-seeking for febrile children was introduced at 40 healthcare facilities in Geita Region, Tanzania. Facilities were randomly selected from among those with 15-120 first ANC visits per month. To assess perspectives regarding introduction of the questionnaire, 21 semi-structured interviews were held with providers and facility in-charges at 12 facilities. Thirty pregnant and recently delivered women participated in focus group discussions at seven facilities to assess the acceptability of spending additional time answering questions about malaria risk. RESULTS: All pregnant women reported that introduction of ANC surveillance and spending 10 more minutes with providers answering questions about their health would be neutral or beneficial. They perceived being asked about their health as standard of care. Providers and in-charges reported that introduction of ANC surveillance was within their scope of practice. Nine of 21 indicated it could potentially benefit women's health. Six providers expressed concern about staffing shortages and need for reimbursement for extra time and noted that data management occurs after hours. CONCLUSIONS: Pregnant women and providers generally perceived ANC surveillance for malaria as acceptable and positive. Pregnant and recently delivered women saw this as a reasonable and even helpful intervention. To be seen as a part of standard practice, efforts are needed to ensure providers perceive a benefit for ANC clients and that staffing concerns are addressed. In addition, staff should receive feedback related to data submissions regarding malaria prevalence and risk factors among women at their facility, with actions to take.

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.

BACKGROUND: Tanzania started implementing single screening and treatment (SST) for all pregnant women attending their first antenatal care (ANC) visits in 2014, using malaria rapid diagnostic tests (RDTs) and treating those who test positive according to the national guidelines. However, there is a paucity of data to show the acceptability of SST to both pregnant women and health care workers (HCWs), taking into consideration the shortage of workers and the added burden of this policy to the health system. This study assessed the perceptions and opinions of health service users and providers to determine the acceptability of SST policy. METHODS: Pregnant women and HCWs in eight health facilities in two districts of Lindi region (Kilwa and Lindi) were interviewed using semi-structured questionnaires with open and close-ended questions. Both qualitative and quantitative data were collected, including demographic characteristics, women's experience, their perception on SST and challenges they face when receiving services for malaria offered at ANC. Experience of HCWs regarding the implementation of SST as part of routine services and the challenges encountered when providing ANC services for malaria in pregnancy (MIP) were also assessed. RESULTS: Of the 143 pregnant women interviewed, 97% viewed testing favourably and would wish to be tested for malaria again, while 95% were satisfied with services and reasons for testing during the first ANC visit. Nearly all (99%) would recommend their fellow pregnant women to be tested for malaria and all women recommended that the Ministry of Health should continue the SST strategy. This was despite the fact that 76% of the women experienced pain and 16% had anxiety as a result of finger prick. Sixteen HCWs (mostly nurses) were interviewed; they also viewed SST implementation favourably and reported feeling empowered to use RDTs for malaria screening. The main challenge identified by HCWs was that nurses are not allowed to prescribe anti-malarials to women who test positive and need to refer them to the outpatient department for treatment. CONCLUSION: SST was considered an acceptable approach to control MIP by HCWs and pregnant women, and they recommended the continuation of the policy. In addition, consideration should be given to implementing a task-shifting policy to allow nurses to dispense anti-malarials to pregnant women.

BACKGROUND: Multiple case definitions are used to identify hospitalized patients with community-acquired acute respiratory infections (ARI). We evaluated several commonly used hospitalized ARI case definitions to identify influenza cases. METHODS: The study included all patients from a population-based surveillance site in Damanhour, Egypt hospitalized for a broad set of criteria consistent with community acquired ARIs. Naso- and oropharyngeal (NP/OP) swabs were tested for influenza using RT-PCR. Sensitivity, specificity and PPV for influenza identification was compared between the 2014 WHO Severe Acute Respiratory Infection (SARI) definition (fever ≥38°C and cough with onset within 10 days), the 2011 WHO SARI definition (fever ≥38°C and cough with onset within 7 days), the 2006 PAHO SARI definition, the International Emerging Infections Program (IEIP) pneumonia case definition, and the International Management of Childhood Illness (IMCI) case definitions for moderate and severe pneumonia. RESULTS: From June 2009-December 2012, 5768 NP/OP swabs were obtained from 6113 hospitalized ARI patients; 799 (13.9%) were influenza positive. The 2014 WHO SARI case definition captured the greatest number of ARI patients, influenza positive patients and ARI deaths compared to the other case definitions examined. Sensitivity for influenza detection was highest for the 2014 WHO SARI definition with 88.6%, compared to the 2011 WHO SARI (78.2%) the 2006 PAHO SARI (15.8%) the IEIP pneumonia (61.0%) and the IMCI moderate and severe pneumonia (33.8% and 38.9%) case definitions (IMCI applies to <5 only). CONCLUSIONS: Our results support use of the 2014 WHO SARI definition for identifying influenza positive hospitalized SARI cases as it captures the highest proportion of ARI deaths and influenza positive cases. Routine use of this case definition for hospital-based surveillance will provide a solid, globally comparable foundation on which to build needed response efforts for novel pandemic viruses.

BACKGROUND: In areas of high transmission, malaria in pregnancy (MiP) primarily causes asymptomatic infections; these infections nonetheless increase the risk of adverse maternal and fetal outcomes. In 2014, Tanzania initiated a single screening and treatment (SST) strategy for all pregnant women at their first antenatal care (ANC) visit using malaria rapid diagnostic tests (RDT) for surveillance purposes. However, there is paucity of data on the effectiveness of SST in the prevention of MiP. The objective of this study was to estimate the number of asymptomatic infections among pregnant women detected by SST, which would have been missed in the absence of the policy. METHODS: Data from pregnant women attending their first ANC visits between October 2017 and June 2018, including gestational age, history of fever, and RDT results, were abstracted from ANC registers in eight health centres in two randomly selected districts, Kilwa and Lindi, in Lindi Region. The proportion of symptomatic (with history of fever in the past 48 h) and asymptomatic pregnant women with positive RDTs were calculated and stratified by trimester (first, second and third). The study areas were categorized as low transmission with prevalence < 10% or moderate/high with ≥ 10%. RESULTS: Over the study period, 1,845 women attended their first ANC visits; 22.1% were in the first trimester (< 12 weeks gestation age). Overall 15.0% of the women had positive RDTs, and there was a trend towards higher malaria prevalence in the first (15.9%) and second (15.2%) trimesters, compared to the third (7.1%), although the differences were not statistically significant (p = 0.07). In total, 6.9% of women reported fever within the past 48 h and, of these, 96.1% were RDT positive. For every 100 pregnant women in the moderate/high and low transmission areas, SST identified 60 and 26 pregnant women, respectively, with asymptomatic infections that would have otherwise been missed. Among the 15.9% of women detected in the first trimester, 50.7% were asymptomatic. CONCLUSION: In areas of moderate/high transmission, many infected women were asymptomatic, and would have been missed in the absence of SST. The benefits on maternal and fetal birth outcomes of identifying these infections depend heavily on the protection afforded by treatment, which is likely to be greatest for women presenting in the first trimester when intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) is contraindicated, and in areas with high SP resistance, such as most parts of Tanzania. An evaluation of the impact and cost-effectiveness of SST across different transmission strata is warranted.

BACKGROUND: Reactive case detection (RCD) is a commonly used strategy for malaria surveillance and response in elimination settings. Many approaches to RCD assume detectable infections are clustered within and around homes of passively detected cases (index households), which has been evaluated in a number of settings with disparate results. METHODS: Household questionnaires and diagnostic testing were conducted following RCD investigations in Zanzibar, Tanzania, including the index household and up to 9 additional neighboring households. RESULTS: Of 12,487 participants tested by malaria rapid diagnostic test (RDT), 3.2% of those residing in index households and 0.4% of those residing in non-index households tested positive (OR = 8.4; 95%CI: 5.7, 12.5). Of 6,281 participants tested by quantitative polymerase chain reaction (qPCR), 8.4% of those residing in index households and 1.3% of those residing in non-index households tested positive (OR = 7.1; 95%CI: 6.1, 10.9). Within households of index cases defined as imported, odds of qPCR-positivity amongst members reporting recent travel were 1.4 times higher than among those without travel history (95%CI: 0.2, 4.4). Amongst non-index households, odds of qPCR-detectable infection were no different between households located within 50 m of the index household as compared with those located farther away (OR = 0.8, 95%CI: 0.5, 1.4). Sensitivity of RDT to detect qPCR-detectable infections was 34% (95%CI: 26.4, 42.3). CONCLUSIONS: Malaria prevalence in index households in Zanzibar is much higher than in non-index households, in which prevalence is very low. Travelers represent a high-risk population. Low sensitivity of RDTs due to a high prevalence of low-density infections results in an RCD system missing a large proportion of the parasite reservoir.

BACKGROUND: Recent malaria control efforts in mainland Tanzania have led to progressive changes in the prevalence of malaria infection in children, from 18.1% (2008) to 7.3% (2017). As the landscape of malaria transmission changes, a sub-national stratification becomes crucial for optimized cost-effective implementation of interventions. This paper describes the processes, data and outputs of the approach used to produce a simplified, pragmatic malaria risk stratification of 184 councils in mainland Tanzania. METHODS: Assemblies of annual parasite incidence and fever test positivity rate for the period 2016-2017 as well as confirmed malaria incidence and malaria positivity in pregnant women for the period 2015-2017 were obtained from routine district health information software. In addition, parasite prevalence in school children (PfPR5to16) were obtained from the two latest biennial council representative school malaria parasitaemia surveys, 2014-2015 and 2017. The PfPR5to16 served as a guide to set appropriate cut-offs for the other indicators. For each indicator, the maximum value from the past 3 years was used to allocate councils to one of four risk groups: very low (< 1%PfPR5to16), low (1- < 5%PfPR5to16), moderate (5- < 30%PfPR5to16) and high (>/= 30%PfPR5to16). Scores were assigned to each risk group per indicator per council and the total score was used to determine the overall risk strata of all councils. RESULTS: Out of 184 councils, 28 were in the very low stratum (12% of the population), 34 in the low stratum (28% of population), 49 in the moderate stratum (23% of population) and 73 in the high stratum (37% of population). Geographically, most of the councils in the low and very low strata were situated in the central corridor running from the north-east to south-west parts of the country, whilst the areas in the moderate to high strata were situated in the north-west and south-east regions. CONCLUSION: A stratification approach based on multiple routine and survey malaria information was developed. This pragmatic approach can be rapidly reproduced without the use of sophisticated statistical methods, hence, lies within the scope of national malaria programmes across Africa.

BACKGROUND: More timely estimates of malaria prevalence are needed to inform optimal control strategies and measure progress. Since 2014, Tanzania has implemented nationwide malaria screening for all pregnant women within the antenatal care system. We aimed to compare malaria test results during antenatal care to two population-based prevalence surveys in Tanzanian children aged 6-59 months to examine their potential in measuring malaria trends and progress towards elimination. METHODS: Malaria test results from pregnant women screened at their first antenatal care visits at health-care facilities (private and public) in all 184 districts of Tanzania between Jan 1, 2014, and Dec 31, 2017, were collected from the Health Management Information Systems and District Health Information System 2. We excluded facilities with no recorded antenatal care attendees during the time period. We standardised results to account for testing uptake and weighted them by the timing of two population-based surveys of childhood malaria prevalence done in 2015-16 (Demographic and Health Survey) and 2017 (Malaria Indicator Survey). We assessed regional-level correlation using Spearman's coefficient and assessed the consistency of monthly district-level prevalence ranking using Kendall's correlation coefficient. FINDINGS: Correlation between malaria prevalence at antenatal care and among children younger than 5 years was high (r>/=0.83 for both surveys), although declines in prevalence at antenatal care were generally smaller than among children. Consistent heterogeneity (p<0.05) in antenatal care prevalence at the district level was evident in all but one region (Kilimanjaro). Data from antenatal care showed declining prevalence in three regions (Arusha, Kilimanjaro, and Manyara) where surveys estimated zero prevalence. INTERPRETATION: Routine antenatal care-based screening can be used to assess heterogeneity in transmission at finer resolution than population-based surveys, and provides sample sizes powered to detect changes, notably in areas of low transmission where surveys lack power. Declines in prevalence at antenatal care might lag behind those among children, highlighting the value of monitoring burden and continuing prevention efforts among pregnant women as transmission declines. The pregnancy-specific benefits and cost-effectiveness of antenatal care-based screening remain to be assessed. FUNDING: None.