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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., (© 2024. The Author(s).)

Background: Tanzania is currently implementing therapeutic efficacy studies (TES) in areas of varying malaria transmission intensities as per the World Health Organization (WHO) recommendations. In TES, distinguishing reinfection from recrudescence is critical for the determination of anti-malarial efficacy. Recently, the WHO recommended genotyping polymorphic coding genes, merozoite surface proteins 1 and 2 (msp1 and msp2), and replacing the glutamate-rich protein (glurp) gene with one of the highly polymorphic microsatellites in Plasmodium falciparum to adjust the efficacy of antimalarials in TES. This study assessed the polymorphisms of six neutral microsatellite markers and their potential use in TES, which is routinely performed in Tanzania., Methods: Plasmodium falciparum samples were obtained from four TES sentinel sites, Kibaha (Pwani), Mkuzi (Tanga), Mlimba (Morogoro) and Ujiji (Kigoma), between April and September 2016. Parasite genomic DNA was extracted from dried blood spots on filter papers using commercial kits. Genotyping was done using six microsatellites (Poly-α, PfPK2, TA1, C3M69, C2M34 and M2490) by capillary method, and the data were analysed to determine the extent of their polymorphisms and genetic diversity at the four sites., Results: Overall, 83 (88.3%) of the 94 samples were successfully genotyped (with positive results for ≥ 50.0% of the markers), and > 50.0% of the samples (range = 47.6-59.1%) were polyclonal, with a mean multiplicity of infection (MOI) ranging from 1.68 to 1.88 among the four sites. There was high genetic diversity but limited variability among the four sites based on mean allelic richness (R S  = 7.48, range = 7.27-8.03, for an adjusted minimum sample size of 18 per site) and mean expected heterozygosity (H e  = 0.83, range = 0.80-0.85). Cluster analysis of haplotypes using STRUCTURE, principal component analysis, and pairwise genetic differentiation (F ST ) did not reveal population structure or clustering of parasites according to geographic origin. Of the six markers, Poly-α was the most polymorphic, followed by C2M34, TA1 and C3M69, while M2490 was the least polymorphic., Conclusion: Microsatellite genotyping revealed high polyclonality and genetic diversity but no significant population structure. Poly-α, C2M34, TA1 and C3M69 were the most polymorphic markers, and Poly-α alone or with any of the other three markers could be adopted for use in TES in Tanzania., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Background: Despite significant decline in the past two decades, malaria is still a major public health concern in Tanzania; with over 93% of the population still at risk. Community knowledge, attitudes and practices (KAP), and beliefs are key in enhancing uptake and utilization of malaria control interventions, but there is a lack of information on their contribution to effective control of the disease. This study was undertaken to determine KAP and beliefs of community members and service providers on malaria, and how they might be associated with increased risk and persistence of the disease burden in North-western and Southern regions of Tanzania., Methods: This was an exploratory study that used qualitative methods including 16 in-depth interviews (IDI) and 32 focus group discussions (FGDs) to collect data from health service providers and community members, respectively. The study was conducted from September to October 2017 and covered 16 villages within eight districts from four regions of mainland Tanzania (Geita, Kigoma, Mtwara and Ruvuma) with persistently high malaria transmission for more than two decades., Results: Most of the participants had good knowledge of malaria and how it is transmitted but some FGD participants did not know the actual cause of malaria, and thought that it is caused by bathing and drinking un-boiled water, or consuming contaminated food that has malaria parasites without warming it. Reported barriers to malaria prevention and control (by FGD and IDI participants) included shortage of qualified health workers, inefficient health financing, low care-seeking behaviour, consulting traditional healers, use of local herbs to treat malaria, poverty, increased breeding sites by socio-economic activities and misconceptions related to the use of bed nets and indoor residual spraying (IRS). Among the misconceptions, some participants believed that bed nets provided for free by the government came with bedbugs while others reported that free bed nets caused impotence among men., Conclusion: Despite good knowledge of malaria, several risk factors, such as socio-economic and behavioural issues, and misconceptions related to the use of bed nets and IRS were reported. Other key factors included unavailability or limited access to health services, poor health financing and economic activities that potentially contributed to persistence of malaria burden in these regions. Relevant policies and targeted malaria interventions, focusing on understanding socio-cultural factors, should be implemented to reduce and finally eliminate the disease in the study regions and others with persistent transmission., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Malaria rapid diagnostic tests (RDTs) based on the detection of the Plasmodium falciparum histidine-rich protein 2 (HRP2) antigen are widely used for detection of active infection with this parasite and are the only practical malaria diagnostic test in some endemic settings. External validation of RDT results from field surveys can confirm appropriate RDT performance., Methods: A community-based cross-sectional survey was conducted between July and November 2017 enrolling participants of all ages in households from 15 villages in four border regions of Tanzania: Geita, Kigoma, Mtwara and Ruvuma. All participants had an RDT performed in the field and provided a blood sample for later laboratory multiplex antigen detection of HRP2. In assessing the continuous HRP2 levels in participant blood versus RDT result, dose-response logistic regression provided quantitative estimates for HRP2 limit of detection (LOD)., Results: From the 15 study villages, 6941 persons were enrolled that had a RDT at time of enrollment and provided a DBS for later laboratory antigen detection. RDT positive prevalence for the HRP2 band by village ranged from 20.0 to 43.6%, but the magnitude of this prevalence did not have an effect on the estimated LOD of RDTs utilized in different villages. Overall, HRP2 single-target tests had a lower LOD at the 95% probability of positive RDT (4.3 ng/mL; 95% CI 3.4-5.4) when compared to pLDH/HRP2 dual target tests (5.4 ng/mL; 4.5-6.3), though this difference was not significant. With the exception of one village, all other 14 villages (93.3%) showed RDT LOD estimates at 90% probability of positive RDT between 0.5 and 12.0 ng/mL., Conclusions: Both HRP2-only and pLDH/HRP2 combo RDTs utilized in a 2017 Tanzania cross-sectional survey of border regions generally performed well, and reliably detected HRP2 antigen in the low ng/mL range. Though single target tests had lower levels of HRP2 detection, both tests were within similar ranges among the 15 villages. Comparison of quantitative HRP2 detection limits among study sites can help interpret RDT testing results when generating population prevalence estimates for malaria infection., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: To accelerate progress against malaria in high burden countries, a strategic reorientation of resources at the sub-national level is needed. This paper describes how mathematical modelling was used in mainland Tanzania to support the strategic revision that followed the mid-term review of the 2015-2020 national malaria strategic plan (NMSP) and the epidemiological risk stratification at the council level in 2018., Methods: Intervention mixes, selected by the National Malaria Control Programme, were simulated for each malaria risk strata per council. Intervention mixes included combinations of insecticide-treated bed nets (ITN), indoor residual spraying, larval source management, and intermittent preventive therapies for school children (IPTsc). Effective case management was either based on estimates from the malaria indicator survey in 2016 or set to a hypothetical target of 85%. A previously calibrated mathematical model in OpenMalaria was used to compare intervention impact predictions for prevalence and incidence between 2016 and 2020, or 2022., Results: For each malaria risk stratum four to ten intervention mixes were explored. In the low-risk and urban strata, the scenario without a ITN mass campaign in 2019, predicted high increase in prevalence by 2020 and 2022, while in the very-low strata the target prevalence of less than 1% was maintained at low pre-intervention transmission intensity and high case management. In the moderate and high strata, IPTsc in addition to existing vector control was predicted to reduce the incidence by an additional 15% and prevalence by 22%. In the high-risk strata, all interventions together reached a maximum reduction of 76%, with around 70% of that reduction attributable to high case management and ITNs. Overall, the simulated revised NMSP was predicted to achieve a slightly lower prevalence in 2020 compared to the 2015-2020 NMSP (5.3% vs 6.3%)., Conclusion: Modelling supported the choice of intervention per malaria risk strata by providing impact comparisons of various alternative intervention mixes to address specific questions relevant to the country. The use of a council-calibrated model, that reproduces local malaria trends, represents a useful tool for compiling available evidence into a single analytical platform, that complement other evidence, to aid national programmes with decision-making processes., (© 2022. The Author(s).)

Universal coverage with effective vector control remains the mainstay of malaria vector control in sub-Saharan Africa. Tanzania has utilized a number of mechanisms for the maintenance of long-lasting insecticidal net (LLIN) coverage over time. Schools have been identified as one potential channel for continuous distribution of LLIN. This research aims to evaluate an annual school-based LLIN distribution programme in Tanzania that began in 2013, called the School Net Programme (SNP). Following each of the first four rounds of SNP distribution, a household survey was conducted in intervention and comparison districts in Southern and Lake zones of Tanzania (N = 5083 households). Measures of ownership, access and use were compared between intervention and comparison districts. Determinants of reach were assessed in intervention districts. Population access to an LLIN increased from 63.1% (95% CI: 58.8, 67.5) to 76.5% (95% CI: 72.9, 80.0) in the intervention districts between the first and last surveys. Access also rose in the comparison districts from 51.4% (95% CI: 46.9, 55.9) to 79.8% (95% CI: 77.3, 82.0) following mass distribution and implementation of school-based distribution during the study period. LLIN use increased in intervention districts from 44.9% (95% CI: 40.5, 49.3) to 65.6% (95% CI: 59.4, 71.8) and from 57.2% (95% CI: 49.7, 64.7) to 77.4% (95% CI: 69.3, 85.5) specifically amongst primary school-aged children. Households reached by the SNP were wealthier households with children enrolled in school. The SNP in Tanzania was able to maintain population level LLIN ownership, use and access in the absence of mass distribution. The SNP successfully reached households that housed school-aged children. Alternative delivery strategies may need to be considered to reach households without children enrolled in schools that experienced fewer benefits from the programme., (© The Author(s) 2021. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: As insecticide-treated nets (ITNs) wear out and are disposed, some household members are prioritized to use remaining ITNs. This study assessed how nets are allocated within households to individuals of different age categories as ITNs are lost or damaged and as new ITNs are obtained. The study also explored how ITN allocation affects ITN durability., Methods: A cross-sectional household survey and ITN durability study was conducted among 2,875 households across Tanzania to determine the proportion of nets that remain protective (serviceable) 22 months after net distribution aiming for universal coverage. Allocation of study nets within houses, and re-allocation of ITNs when new universal replacement campaign (URC) nets arrived in study households in Musoma District, was also assessed., Results: Some 57.0% (95% CI 53.9-60.1%) of households had sufficient ITNs for every household member, while 84.4% (95% CI 82.4-86.4%) of the population had access to an ITN within their household (assuming 1 net covers every 2 members). In households with sufficient nets, 77.5% of members slept under ITNs. In households without sufficient nets, pregnant women (54.6%), children < 5 years (45.8%) and adults (42.1%) were prioritized, with fewer school-age children 5-14 years (35.9%), youths 15-24 years (28.1%) and seniors > 65 years (32.6%) sleeping under ITNs. Crowding ([Formula: see text] 3 people sleeping under nets) was twice as common among people residing in houses without sufficient nets for all age groups, apart from children < 5. Nets were less likely to be serviceable if: [Formula: see text] 3 people slept under them (OR 0.50 (95% CI 0.40-0.63)), or if nets were used by school-age children (OR 0.72 (95% CI 0.56-0.93)), or if the net product was Olyset®. One month after the URC, only 23.6% (95% CI 16.7-30.6%) of the population had access to a URC ITN in Musoma district. Householders in Musoma district continued the use of old ITNs even with the arrival of new URC nets., Conclusion: Users determined the useful life of ITNs and prioritized pregnant women and children < 5 to serviceable ITNs. When household net access declines, users adjust by crowding under remaining nets, which further reduces ITN lifespan. School-age children that commonly harbour gametocytes that mediate malaria transmission are compelled to sleep under unserviceable nets, crowd under nets or remain uncovered. However, they were accommodated by the arrival of new nets. More frequent ITN delivery through the school net programme in combination with mass distribution campaigns is essential to maximize ITN effectiveness.

High-throughput Plasmodium genomic data is increasingly useful in assessing prevalence of clinically important mutations and malaria transmission patterns. Understanding parasite diversity is important for identification of specific human or parasite populations that can be targeted by control programmes, and to monitor the spread of mutations associated with drug resistance. An up-to-date understanding of regional parasite population dynamics is also critical to monitor the impact of control efforts. However, this data is largely absent from high-burden nations in Africa, and to date, no such analysis has been conducted for malaria parasites in Tanzania countrywide. To this end, over 1,000 P. falciparum clinical isolates were collected in 2017 from 13 sites in seven administrative regions across Tanzania, and parasites were genotyped at 1,800 variable positions genome-wide using molecular inversion probes. Population structure was detectable among Tanzanian P. falciparum parasites, approximately separating parasites from the northern and southern districts and identifying genetically admixed populations in the north. Isolates from nearby districts were more likely to be genetically related compared to parasites sampled from more distant districts. Known drug resistance mutations were seen at increased frequency in northern districts (including two infections carrying pfk13-R561H), and additional variants with undetermined significance for antimalarial resistance also varied by geography. Malaria Indicator Survey (2017) data corresponded with genetic findings, including average region-level complexity-of-infection and malaria prevalence estimates. The parasite populations identified here provide important information on extant spatial patterns of genetic diversity of Tanzanian parasites, to which future surveys of genetic relatedness can be compared., (© 2020 John Wiley & Sons Ltd.)

Background: Histidine-rich protein 2 (HRP2)-based malaria rapid diagnostic tests (RDTs) are effective and widely used for the detection of wild-type Plasmodium falciparum infections. Although recent studies have reported false negative HRP2 RDT results due to pfhrp2 and pfhrp3 gene deletions in different countries, there is a paucity of data on the deletions of these genes in Tanzania., Methods: A community-based cross-sectional survey was conducted between July and November 2017 in four regions: Geita, Kigoma, Mtwara and Ruvuma. All participants had microscopy and RDT performed in the field and provided a blood sample for laboratory multiplex antigen detection (for Plasmodium lactate dehydrogenase, aldolase, and P. falciparum HRP2). Samples showing RDT false negativity or aberrant relationship of HRP2 to pan-Plasmodium antigens were genotyped to detect the presence/absence of pfhrp2/3 genes., Results: Of all samples screened by the multiplex antigen assay (n = 7543), 2417 (32.0%) were positive for any Plasmodium antigens while 5126 (68.0%) were negative for all antigens. The vast majority of the antigen positive samples contained HRP2 (2411, 99.8%), but 6 (0.2%) had only pLDH and/or aldolase without HRP2. Overall, 13 samples had an atypical relationship between a pan-Plasmodium antigen and HRP2, but were positive by PCR. An additional 16 samples with negative HRP2 RDT results but P. falciparum positive by microscopy were also chosen for pfhrp2/3 genotyping. The summation of false negative RDT results and laboratory antigen results provided 35 total samples with confirmed P. falciparum DNA for pfhrp2/3 genotyping. Of the 35 samples, 4 (11.4%) failed to consistently amplify positive control genes; pfmsp1 and pfmsp2 and were excluded from the analysis. The pfhrp2 and pfhrp3 genes were successfully amplified in the remaining 31 (88.6%) samples, confirming an absence of deletions in these genes., Conclusions: This study provides evidence that P. falciparum parasites in the study area have no deletions of both pfhrp2 and pfhrp3 genes. Although single gene deletions could have been missed by the multiplex antigen assay, the findings support the continued use of HRP2-based RDTs in Tanzania for routine malaria diagnosis. There is a need for the surveillance to monitor the status of pfhrp2 and/or pfhrp3 deletions in the future.

Most malaria-endemic countries have struggled in the past decade to establish effective national-scale continuous distribution mechanisms for long-lasting insecticidal nets (LLINs). Since the implementation of the Tanzania National Voucher Scheme in 2004 and mass-distribution campaigns in 2009-2011 and 2015-2016, Tanzania has been committed to finding new and innovative ways of achieving and maintaining universal bed net coverage. Planning for the School Net Programme (SNP) began in 2011 and in 2013, the country piloted a SNP in three regions. Nets were distributed annually to children attending schools in selected primary and secondary grades. Intra-family re-distribution was assumed, and hence the family as a whole, rather than just the children themselves, were the targeted beneficiaries. The programme has since expanded to 14 regions and has seen six rounds of annual distribution. In its fifth year, 3 million nets were distributed at a cost of USD 3.64 per net and USD 0.60 per person-year of protection (including the net). ITN access and use were maintained at a high level (~ 50-75%) over the first 4 years of distribution within selected evaluation areas, even in the absence of a mass distribution event. Net distribution through primary schools has proven to be a feasible and effective strategy for maintaining consistently high coverage in Tanzania.

Background: Insecticide-treated nets (ITNs) are one of the most cost-effective measures for preventing malaria. The World Health Organization recommends both large-scale mass distribution campaigns and continuous distributions (CD) as part of a multifaceted strategy to achieve and sustain universal access to ITNs. A combination of these strategies has been effective for scaling up ITN access. For policy makers to make informed decisions on how to efficiently implement CD or combined strategies, information on the costs and cost-effectiveness of these delivery systems is necessary, but relatively few published studies of the cost continuous distribution systems exist., Methods: To address the gap in continuous distribution cost data, four types of delivery systems-CD through antenatal care services (ANC) and the expanded programme on immunization (EPI) (Ghana, Mali, and mainland Tanzania), CD through schools (Ghana and mainland Tanzania), and a combined community/health facility-based distribution (Zanzibar, Tanzania), as well as mass distributions (Mali)-were costed. Data on costs were collected retrospectively from financial and operational records, stakeholder interviews, and resource use surveys., Results: Overall, from a full provider perspective, mass distributions and continuous systems delivered ITNs at overlapping economic costs per net distributed (mass distributions: 4.37-4.61 USD, CD channels: 3.56-9.90 USD), with two of the school-based systems and the mass distributions at the lower end of this range. From the perspective of international donors, the costs of the CD systems were, for the most part, less costly than the mass distributions (mass distributions: 4.34-4.55 USD, Ghana and Tanzania 2017 school-based: 3.30-3.69 USD, health facility-based: 3.90-4.55 USD, combined community/health facility 4.55 USD). The 2015 school-based distribution (7.30 USD) and 2016 health facility-based distribution (6.52 USD) programmes in Tanzania were an exception. Mass distributions were more heavily financed by donors, while CD relied more extensively on domestic resource contributions., Conclusions: These results suggest that CD strategies can continue to deliver nets at a comparable cost to mass distributions, especially from the perspective of the donor.

Background: More than ever, it is crucial to make the best use of existing country data, and analytical tools for developing malaria control strategies as the heterogeneity in malaria risk within countries is increasing, and the available malaria control tools are expanding while large funding gaps exist. Global and local policymakers, as well as funders, increasingly recognize the value of mathematical modelling as a strategic tool to support decision making. This case study article describes the long-term use of modelling in close collaboration with the National Malaria Control Programme (NMCP) in Tanzania, the challenges encountered and lessons learned., Case Description: In Tanzania, a recent rebound in prevalence led to the revision of the national malaria strategic plan with interventions targeted to the malaria risk at the sub-regional level. As part of the revision, a mathematical malaria modelling framework for setting specific predictions was developed and used between 2016 and 2019 to (1) reproduce setting specific historical malaria trends, and (2) to simulate in silico the impact of future interventions. Throughout the project, multiple stakeholder workshops were attended and the use of mathematical modelling interactively discussed., Evaluation: In Tanzania, the model application created an interdisciplinary and multisectoral dialogue platform between modellers, NMCP and partners and contributed to the revision of the national malaria strategic plan by simulating strategies suggested by the NMCP. The uptake of the modelling outputs and sustained interest by the NMCP were critically associated with following factors: (1) effective sensitization to the NMCP, (2) regular and intense communication, (3) invitation for the modellers to participate in the strategic plan process, and (4) model application tailored to the local context., Conclusion: Empirical data analysis and its use for strategic thinking remain the cornerstone for evidence-based decision-making. Mathematical impact modelling can support the process both by unifying all stakeholders in one strategic process and by adding new key evidence required for optimized decision-making. However, without a long-standing partnership, it will be much more challenging to sensibilize programmes to the usefulness and sustained use of modelling and local resources within the programme or collaborating research institutions need to be mobilized.

Introduction: The decision-making process for malaria control and elimination strategies has become more challenging. Interventions need to be targeted at council level to allow for changing malaria epidemiology and an increase in the number of possible interventions. Models of malaria dynamics can support this process by simulating potential impacts of multiple interventions in different settings and determining appropriate packages of interventions for meeting specific expected targets., Methods: The OpenMalaria model of malaria dynamics was calibrated for all 184 councils in mainland Tanzania using data from malaria indicator surveys, school parasitaemia surveys, entomological surveillance, and vector control deployment data. The simulations were run for different transmission intensities per region and five interventions, currently or potentially included in the National Malaria Strategic Plan, individually and in combination. The simulated prevalences were fitted to council specific prevalences derived from geostatistical models to obtain council specific predictions of the prevalence and number of cases between 2017 and 2020. The predictions were used to evaluate in silico the feasibility of the national target of reaching a prevalence of below 1% by 2020, and to suggest alternative intervention stratifications for the country., Results: The historical prevalence trend was fitted for each council with an agreement of 87% in 2016 (95%CI: 0.84-0.90) and an agreement of 90% for the historical trend (2003-2016) (95%CI: 0.87-0.93) The current national malaria strategy was expected to reduce the malaria prevalence between 2016 and 2020 on average by 23.8% (95% CI: 19.7%-27.9%) if current case management levels were maintained, and by 52.1% (95% CI: 48.8%-55.3%) if the case management were improved. Insecticide treated nets and case management were the most cost-effective interventions, expected to reduce the prevalence by 25.0% (95% CI: 19.7%-30.2) and to avert 37 million cases between 2017 and 2020. Mass drug administration was included in most councils in the stratification selected for meeting the national target at minimal costs, expected to reduce the prevalence by 77.5% (95%CI: 70.5%-84.5%) and to avert 102 million cases, with almost twice higher costs than those of the current national strategy. In summary, the model suggested that current interventions are not sufficient to reach the national aim of a prevalence of less than 1% by 2020 and a revised strategic plan needs to consider additional, more effective interventions, especially in high transmission areas and that the targets need to be revisited., Conclusion: The methodology reported here is based on intensive interactions with the NMCP and provides a helpful tool for assessing the feasibility of country specific targets and for determining which intervention stratifications at sub-national level will have most impact. This country-led application could support strategic planning of malaria control in many other malaria endemic countries., Competing Interests: The authors have declared that no competing interests exist.

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., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: With increasing spatial heterogeneity of malaria transmission and a shift of the disease burden towards older children and adults, pregnant women attending antenatal care (ANC) have been proposed as a pragmatic sentinel population for malaria surveillance. However, the representativeness of routine ANC malaria test-positivity and its relationship with prevalence in other population subgroups are yet to be investigated., Methods: Monthly ANC malaria test-positivity data from all Tanzanian health facilities for January 2014 to May 2016 was compared to prevalence data from the School Malaria Parasitaemia Survey 2015, the Malaria Indicator Survey (MIS) 2015/16, the Malaria Atlas Project 2015, and a Bayesian model fitted to MIS data. Linear regression was used to describe the difference between malaria test-positivity in pregnant women and respective comparison groups as a function of ANC test-positivity and potential covariates., Results: The relationship between ANC test-positivity and survey prevalence in children follows spatially and biologically meaningful patterns. However, the uncertainty of the relationship was substantial, particularly in areas with high or perennial transmission. In comparison, modelled data estimated higher prevalence in children at low transmission intensities and lower prevalence at higher transmission intensities., Conclusions: Pregnant women attending ANC are a pragmatic sentinel population to assess heterogeneity and trends in malaria prevalence in Tanzania. Yet, since ANC malaria test-positivity cannot be used to directly predict the prevalence in other population subgroups, complementary community-level measurements remain highly relevant.

Background: The Tanzanian National Malaria Control Programme (NMCP) and its partners have been implementing regular therapeutic efficacy studies (TES) to monitor the performance of different drugs used or with potential use in Tanzania. However, most of the recent TES focused on artemether-lumefantrine, which is the first-line anti-malarial for the treatment of uncomplicated falciparum malaria. Data on the performance of other artemisinin-based combinations is urgently needed to support timely review and changes of treatment guidelines in case of drug resistance to the current regimen. This study was conducted at two NMCP sentinel sites (Kibaha, Pwani and Ujiji, Kigoma) to assess the efficacy and safety of artesunate-amodiaquine (ASAQ) and dihydroartemisinin-piperaquine (DP), which are the current alternative artemisinin-based combinations in Tanzania., Methods: This was a single-arm prospective evaluation of the clinical and parasitological responses of ASAQ and DP for directly observed treatment of uncomplicated falciparum malaria. Children aged 6 months to 10 years and meeting the inclusion criteria were enrolled and treated with either ASAQ or DP. In each site, patients were enrolled sequentially; thus, enrolment of patients for the assessment of one artemisinin-based combination was completed before patients were recruited for assessment of the second drugs. Follow-up was done for 28 or 42 days for ASAQ and DP, respectively. The primary outcome was PCR corrected cure rates while the secondary outcome was occurrence of adverse events (AEs) or serious adverse events (SAEs)., Results: Of the 724 patients screened at both sites, 333 (46.0%) were enrolled and 326 (97.9%) either completed the 28/42 days of follow-up, or attained any of the treatment outcomes. PCR uncorrected adequate clinical and parasitological response (ACPR) for DP on day 42 was 98.8% and 75.9% at Kibaha and Ujiji, respectively. After PCR correction, DP's ACPR was 100% at both sites. For ASAQ, no parasite recurrence occurred giving 100% ACPR on day 28. Only one patient in the DP arm (1.1%) from Ujiji had parasites on day 3. Of the patients recruited (n = 333), 175 (52.6%) had AEs with 223 episodes (at both sites) in the two treatment groups. There was no SAE and the commonly reported AE episodes (with > 5%) included, cough, running nose, abdominal pain, diarrhoea and fever., Conclusion: Both artemisinin-based combinations had high cure rates with PCR corrected ACPR of 100%. The two drugs had adequate safety with no SAE and all AEs were mild, and not associated with the anti-malarials. Continued TES is critical to monitor the performance of nationally recommended artemisinin-based combination therapy and supporting evidence-based review of malaria treatment policies. Trial registration This study is registered at ClinicalTrials.gov, No. NCT03431714.

Background: The World Health Organization recommends regular therapeutic efficacy studies (TES) to monitor the performance of first and second-line anti-malarials. In 2016, efficacy and safety of artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria were assessed through a TES conducted between April and October 2016 at four sentinel sites of Kibaha, Mkuzi, Mlimba, and Ujiji in Tanzania. The study also assessed molecular markers of artemisinin and lumefantrine (partner drug) resistance., Methods: Eligible patients were enrolled at the four sites, treated with standard doses of AL, and monitored for 28 days with clinical and laboratory assessments. The main outcomes were PCR corrected cure rates, day 3 positivity rates, safety of AL, and prevalence of single nucleotide polymorphisms in Plasmodium falciparum kelch 13 (Pfk13) (codon positions: 440-600) and P. falciparum multi-drug resistance 1 (Pfmdr1) genes (codons: N86Y, Y184F and D1246Y), markers of artemisinin and lumefantrine resistance, respectively., Results: Of 344 patients enrolled, three withdrew, six were lost to follow-up; and results were analysed for 335 (97.4%) patients. Two patients had treatment failure (one early treatment failure and one recrudescent infection) after PCR correction, yielding an adequate clinical and parasitological response of > 98%. Day 3 positivity rates ranged from 0 to 5.7%. Common adverse events included cough, abdominal pain, vomiting, and diarrhoea. Two patients had serious adverse events; one died after the first dose of AL and another required hospitalization after the second dose of AL (on day 0) but recovered completely. Of 344 samples collected at enrolment (day 0), 92.7% and 100% were successfully sequenced for Pfk13 and Pfmdr1 genes, respectively. Six (1.9%) had non-synonymous mutations in Pfk13, none of which had been previously associated with artemisinin resistance. For Pfmdr1, the NFD haplotype (codons N86, 184F and D1246) was detected in 134 (39.0%) samples; ranging from 33.0% in Mlimba to 45.5% at Mkuzi. The difference among the four sites was not significant (p = 0.578). All samples had a single copy of the Pfmdr1 gene., Conclusion: The study indicated high efficacy of AL and the safety profile was consistent with previous reports. There were no known artemisinin-resistance Pfk13 mutations, but there was a high prevalence of a Pfmdr1 haplotype associated with reduced sensitivity to lumefantrine (but no reduced efficacy was observed in the subjects). Continued TES and monitoring of markers of resistance to artemisinin and partner drugs is critical for early detection of resistant parasites and to inform evidence-based malaria treatment policies. Trial Registration ClinicalTrials.gov NCT03387631.

Background: During the past six decades, remarkable success on malaria control has been made in China. The major experience could be shared with other malaria endemic countries including Tanzania with high malaria burden. Especially, China's 1-3-7 model for malaria elimination is one of the most important refined experiences from many years' efforts and key innovation measures for malaria elimination in China., Methods: The China-UK-Tanzania pilot project on malaria control was implemented from April, 2015 to June, 2018, which was an operational research with two communities receiving the proposed interventions and two comparable communities serving as control sites. The World Health Organization "Test, Treat, Track" (WHO-T3) Initiative, which calls for every suspected case to receive a diagnostic test, every confirmed case to be treated, and for the disease to be tracked, was integrated with Chinese experiences on malaria control and elimination for exploration of a proper model tailored to the local settings. Application of China's 1-3-7 model integrating with WHO-T3 initiative and local resources aiming at reducing the burden of malaria in terms of morbidity and mortality by 30% in the intervention communities in comparison with that at the baseline survey., Discussion: The China-UK-Tanzania pilot project on malaria control was that at China's first pilot project on malaria control in Africa, exploring the feasibility of Chinese experiences by China-Africa collaboration, which is expected that the strategies and approaches used in this project could be potential for scaling up in Tanzania and African countries, and contribute to the acceleration of malaria control and elimination in Africa.

Background: A nationwide, school, malaria survey was implemented to assess the risk factors of malaria prevalence and bed net use among primary school children in mainland Tanzania. This allowed the mapping of malaria prevalence at council level and assessment of malaria risk factors among school children., Methods: A cross-sectional, school, malaria parasitaemia survey was conducted in 25 regions, 166 councils and 357 schools in three phases: (1) August to September 2014; (2) May 2015; and, (3) October 2015. Children were tested for malaria parasites using rapid diagnostic tests and were interviewed about household information, parents' education, bed net indicators as well as recent history of fever. Multilevel mixed effects logistic regression models were fitted to estimate odds ratios of risk factors for malaria infection and for bed net use while adjusting for school effect., Results: In total, 49,113 children were interviewed and tested for malaria infection. The overall prevalence of malaria was 21.6%, ranging from < 0.1 to 53% among regions and from 0 to 76.4% among councils. The malaria prevalence was below 5% in 62 of the 166 councils and above 50% in 18 councils and between 5 and 50% in the other councils. The variation of malaria prevalence between schools was greatest in regions with a high mean prevalence, while the variation was marked by a few outlying schools in regions with a low mean prevalence. Overall, 70% of the children reported using mosquito nets, with the highest percentage observed among educated parents (80.7%), low land areas (82.7%) and those living in urban areas (82.2%)., Conclusions: The observed prevalence among school children showed marked variation at regional and sub-regional levels across the country. Findings of this survey are useful for updating the malaria epidemiological profile and for stratification of malaria transmission by region, council and age groups, which is essential for guiding resource allocation, evaluation and prioritization of malaria interventions.

Background: Artemisinin-based combination therapy (ACT) is the first-line anti-malarial treatment of uncomplicated malaria in most malaria endemic countries, including Tanzania. Unfortunately, there have been reports of artemisinin resistance and ACT failure from South East Asia highlighting the need to monitor therapeutic efficacy of ACT in these countries as recommended by World Health Organization., Methods: Open-label single arm studies in mainland Tanzania were conducted in nine sentinel sites in 2011, 2012 and 2015 to assess the efficacy and safety of artemether/lumefantrine (AL) and artesunate/amodiaquine (ASAQ) using 28 days follow-up and dihydroartemisinin/piperaquine (DHAPQ) using 42 days follow-up. Mutations in the propeller domain of the Plasmodium falciparum kelch 13 (k13) gene and amplification of the P. falciparum plasmepsin 2 (pm2) gene, associated with artemisinin and piperaquine (PQ) resistance, were also investigated., Results: Of the 428 patients enrolled, 328 patients provided study endpoint. For AL, the PCR corrected per-protocol analysis showed adequate clinical and parasitological response (ACPR) of 90.3% (n = 28; 95% CI 74.2-98.0) in Kyela 2012, 95.7% (n = 22; 95% CI 78.1-99.0) in Chamwino, 100% in Muheza (n = 29; 95% CI 88.1-100), 100% in Nagaga (n = 39; 95% CI 91.0-100) and Kyela 2015 (n = 60; 95% CI 94.0-100). For ASAQ, PCR corrected ACPR of 98% (n = 49; 95% CI 89.4-99.9) and 100% (n = 25; 95% CI 86.3-100) were observed in 2011 in Ujiji and Kibaha, respectively. For DHAPQ, the ACPR was 100% (n = 71; 95% CI 94.9-100). Of the 235 samples with genetic interpretable results, only 7 (3%) had non-synonymous k13 mutations. None of these are candidate or validated markers of artemisinin resistance and all patients carrying these alleles cleared the parasites on day 3. Of the DHAPQ group, 10% (3/29) of the samples with interpretable results had pm2 multiple copies and none of them was associated with treatment failure., Conclusion: All the tested ACT in mainland Tanzania were highly efficacious and none of validated k13 mutants associated with artemisinin resistance was observed. However, three isolates with multiple copy numbers of pm2 gene associated with PQ resistance among the limited samples tested successfully calls for further investigation. Trial registration Number ACTRN12615000159550. Registered 18th February 2015, https://www.anzctr.org.au/trial/MyTrial.aspx.

Background: Artemether-lumefantrine (AL) is the recommended first-line artemisinin-based combination therapy (ACT) for the treatment of uncomplicated falciparum malaria in most of the malaria-endemic countries, including Tanzania. Recently, dihydroartemisinin-piperaquine (DP) has been recommended as the alternative anti-malarial to ensure effective case management in Tanzania. This study assessed the parasite clearance rate and efficacy of AL and DP among patients aged 6 months to 10 years with uncomplicated falciparum malaria in two sites with different malaria transmission intensity., Methods: This was an open-label, randomized trial that was conducted at two sites of Muheza Designated District Hospital and Ujiji Health Centre in Tanga and Kigoma regions, respectively. Patients meeting inclusion criteria were enrolled, treated with either AL or DP and followed up for 28 (extended to 42) and 42 (63) days for AL and DP, respectively. Parasite clearance time was monitored in the first 72 h post treatment and the clearance rate constant and half-life were calculated using an established parasite clearance estimator. The primary outcome was parasitological cure on days 28 and 42 for AL and DP, respectively, while secondary outcome was extended parasitological cure on days 42 and 63 for AL and DP, respectively., Results: Of the 509 children enrolled (192 at Muheza and 317 at Ujiji), there was no early treatment failure and PCR uncorrected cure rates on day 28 in the AL group were 77.2 and 71.2% at Muheza and Ujiji, respectively. In the DP arm, the PCR uncorrected cure rate on day 42 was 73.6% at Muheza and 72.5% at Ujiji. With extended follow-up (to day 42 for AL and 63 for DP) cure rates were lower at Ujiji compared to Muheza (AL: 60.2 and 46.1%, p = 0.063; DP: 57.6 and 40.3% in Muheza and Ujiji, respectively, p = 0.021). The PCR corrected cure rate ranged from 94.6 to 100% for all the treatment groups at both sites. Parasite clearance rate constant was similar in the two groups and at both sites (< 0.28/h); the slope half-life was < 3.0 h and all but only one patient cleared parasites by 72 h., Conclusion: These findings confirm high efficacy of the first- and the newly recommended alternative ACT for treatments for uncomplicated falciparum malaria in Tanzania. The high parasite clearance rate suggests absence of suspected artemisinin resistance, defined as delayed parasite clearance. Trial registration This trial is registered at ClinicalTrials.gov under registration number NCT02590627.

Many sub-Saharan African countries have achieved substantial gains in insecticide treated bednet coverage since 2005. The Tanzania National Malaria Control Programme identified school-based net distribution as one potential 'keep-up' strategy for the purpose of maintaining long-lasting insecticidal net (LLIN) coverage after a nationwide mass campaign in 2011. The School Net Programme (SNP) was implemented in three regions of southern Tanzania and distributed one LLIN to each enrolled child attending schools in primary grades (standards) 1, 3, 5 and 7, and secondary grades (forms) 2 and 4 in 2013 and again with slightly modified eligibility criteria in 2014 and 2015. Household surveys in the programme area as well as in a control area were conducted after each of the SNP distributions to measure ownership and use of long-lasting insecticide treated nets. Ownership of at least one LLIN after the first distribution was 76.1% (95% CI 70.8-80.7) in the intervention area and 78.6% (95% CI 74.4-82.3) in the control area. After the second distribution, ownership of at least one LLIN had dropped significantly in the control area to 65.4% (95% CI 59.5-71.0) in 2015 (P < 0.001), while coverage in the intervention area was maintained at 79.3% (95% CI 75.4 × 82.6). Ownership of at least one LLIN in intervention area remained stable following the second round of net distribution. During the same period LLIN ownership, especially of enough nets to ensure all household member access, fell significantly in the control area. These results demonstrate that the SNP may be sufficient to maintain stable LLIN coverage following a mass distribution of LLINs., (© The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The Tanzania National Voucher Scheme (TNVS) was a public private partnership managed by the Ministry of Health that provided pregnant women and infants with highly subsidized (long-lasting) insecticide-treated nets between 2004 and 2014. It was implemented in the context of the National Insecticide Treated Nets (NATNETS) Programme and was the main keep up strategy for vulnerable populations., Case Description: The programme design was adjusted considerably over time to incorporate new evidence, shifting public health policies, and changing donor priorities. Three TNVS models can be distinguished: (1) the fixed discount; (2) the fixed top-up; (3) the hybrid voucher model. The changes improved equity and effectiveness, but also had a profound effect on how the programme was managed and implemented., Results: The TNVS reached the majority of beneficiaries with vouchers, and significantly increased household ownership and use of LLINs. While two mass distribution campaigns implemented between 2009 and 2011 achieved universal coverage and equity, the TNVS ensured continuous protection of the vulnerable populations before, during and after the campaigns. The TNVS stimulated and maintained a large national retail network which managed the LLIN supply chain., Discussion and Lessons Learned: The effectiveness of the TNVS was a function of several interdependent factors, including the supply chain of vouchers through the public health system; the supply chain of nets in the commercial sector; the demand for nets from voucher recipients; management and risk mitigation measures; and the influence of global and donor objectives., Conclusion: The TNVS was a highly innovative and globally influential programme, which stimulated the thinking around effectively and equitably distributing ITNs, and contributed directly to the evolution of global policy. It was a fundamental component of the NATNETS programme which protected a malaria-vulnerable population for over a decade.

Background: With more than half of Africa's population expected to live in urban settlements by 2030, the burden of malaria among urban populations in Africa continues to rise with an increasing number of people at risk of infection. However, malaria intervention across Africa remains focused on rural, highly endemic communities with far fewer strategic policy directions for the control of malaria in rapidly growing African urban settlements. The complex and heterogeneous nature of urban malaria requires a better understanding of the spatial and temporal patterns of urban malaria risk in order to design effective urban malaria control programs. In this study, we use remotely sensed variables and other environmental covariates to examine the predictability of intra-urban variations of malaria infection risk across the rapidly growing city of Dar es Salaam, Tanzania between 2006 and 2014., Methods: High resolution SPOT satellite imagery was used to identify urban environmental factors associated malaria prevalence in Dar es Salaam. Supervised classification with a random forest classifier was used to develop high resolution land cover classes that were combined with malaria parasite prevalence data to identify environmental factors that influence localized heterogeneity of malaria transmission and develop a high resolution predictive malaria risk map of Dar es Salaam., Results: Results indicate that the risk of malaria infection varied across the city. The risk of infection increased away from the city centre with lower parasite prevalence predicted in administrative units in the city centre compared to administrative units in the peri-urban suburbs. The variation in malaria risk within Dar es Salaam was shown to be influenced by varying environmental factors. Higher malaria risks were associated with proximity to dense vegetation, inland water and wet/swampy areas while lower risk of infection was predicted in densely built-up areas., Conclusions: The predictive maps produced can serve as valuable resources for municipal councils aiming to shrink the extents of malaria across cities, target resources for vector control or intensify mosquito and disease surveillance. The semi-automated modelling process developed can be replicated in other urban areas to identify factors that influence heterogeneity in malaria risk patterns and detect vulnerable zones. There is a definite need to expand research into the unique epidemiology of malaria transmission in urban areas for focal elimination and sustained control agendas.

Background: As malaria control interventions are scaled-up, rational approaches are needed for monitoring impact over time. One proposed approach includes monitoring the prevalence of malaria infection among pregnant women and children at the time of routine preventive health facility (HF) visits. This pilot explored the feasibility and utility of tracking the prevalence of malaria infection in pregnant women attending their first antenatal care (ANC) visit and infants presenting at 9-12 months of age for measles vaccination., Methods: Pregnant women attending first ANC and infants nine to 12 months old presenting for measles vaccination at a non-probability sample of 54 HFs in Tanzania's Lake Zone (Mara, Mwanza and Kagera Regions) were screened for malaria infection using a malaria rapid diagnostic test (RDT) from December 2012 to November 2013, regardless of symptoms. Participants who tested positive were treated for malaria per national guidelines. Data were collected monthly., Results: Overall 89.9 and 78.1 % of expected monthly reports on malaria infection prevalence were received for pregnant women and infants, respectively. Among 51,467 pregnant women and 35,155 infants attending routine preventive HF visits, 41.2 and 37.3 % were tested with RDT, respectively. Malaria infection prevalence was 12.8 % [95 % confidence interval (CI) 11.3-14.3] among pregnant women and 11.0 % (95 % CI 9.5-12.5) among infants, and varied by month. There was good correlation of the prevalence of malaria among pregnant women and infants at the HF level (Spearman rho = 0.6; p < 0.001). This approach is estimated to cost $1.28 for every person tested, with the RDT accounting for 72 % of the cost., Conclusions: Malaria infection was common and well correlated among pregnant women and infants attending routine health services. Routine screening of these readily accessible populations may offer a practical strategy for continuously tracking malaria trends, particularly seasonal variation. Positivity rates among afebrile individuals presenting for routine care offer an advantage as they are unaffected by the prevalence of other causes of febrile illness, which could influence positivity rates among febrile patients presenting to outpatient clinics. The data presented here suggest that in addition to contributing to clinical management, ongoing screening of pregnant women could be used for routine surveillance and detection of hotspots.

Tanzania successfully scaled up coverage of long-lasting insecticidal nets (LLINs) through mass campaigns. To sustain these gains, a school-based approach was piloted in the country's Southern Zone starting in 2013, called the School Net Program 1 (SNP1). We report on the design, implementation, monitoring, and outputs of the second round (SNP2) undertaken in 2014. SNP2 was conducted in all schools in Lindi, Mtwara, and Ruvuma regions, targeting students in primary (Standards 1, 3, 5, and 7) and secondary (Forms 2 and 4) schools and all teachers. In Lindi region, 2 additional classes (Standards 2 and 4) were targeted. LLIN distribution data were managed using an Android software application called SchoolNet. SNP2 included 2,337 schools, 473,700 students, and 25,269 teachers. A total of 5,070 people were trained in LLIN distribution (487 trainers and 4,583 distributors), and 4,392 (434 ward and 3,958 village) community change agents undertook sensitization and mobilization. A total of 507,775 LLINs were distributed to schools, with 464,510 (97.9% of those registered) students and 24,206 (95.8% of those registered) school teachers receiving LLINs. LLIN ownership and use is expected to have increased, potentially further reducing the burden of malaria in the Southern Zone of Tanzania., (© Lalji et al.)

Background: Long-lasting insecticidal nets (LLINs) are the first line choice for malaria vector control in sub-Saharan Africa, with most countries adopting universal coverage campaigns. However, there is only limited information on LLIN durability under user conditions. Therefore, this study aimed to assess the durability of Olyset(®) LLINs distributed during campaigns between 2009 and 2011 in Tanzania., Methods: A retrospective field survey was conducted in eight districts in Tanzania mainland to assess the durability of Olyset campaign nets. Household questionnaires were used to assess attrition, i.e. net loss. All nets remaining in households were collected. A sub-sample of 198 Olyset campaign nets was examined for bio-efficacy against Anopheles gambiae s.s. mosquitoes, permethrin content and physical integrity following standard World Health Organization (WHO) methods., Results: Of 6067 campaign nets reported to have been received between 2009 and 2011, 35% (2145 nets) were no longer present. Most of those nets had been discarded (84%) mainly because they were too torn (94%). Of the 198 sub-sampled Olyset LLINs, 61% were still in serviceable physical condition sufficient to provide personal protection while 39% were in unserviceable physical condition according to WHO proportionate Hole Index (pHI). More than 96% (116/120) of nets in serviceable condition passed WHO bioefficacy criteria while all nets in unserviceable condition passed WHO bioefficacy criteria. Overall mean permethrin content was 16.5 g/kg (95% CI 16.2-16.9) with 78% of the sub-sampled nets retaining recommended permethrin content regardless of their age or physical condition. Nets aged 4 years and above had a mean permethrin content of 14 g/kg (95% CI 12.0-16.0). The only statistically significant predictor of reduced physical net integrity was rats in the house., Conclusions: Two-to-four years after a mass campaign, only 39% of distributed nets remain both present and in serviceable physical condition, a functional survival considerably below WHO assumptions of 50% survival of a 'three-year' net. However, the majority of nets still retained substantial levels of permethrin and could still be bio-chemically useful against mosquitoes if their holes were repaired, adding evidence to the value of net care and repair campaigns.

Background: The increasing investment in malaria rapid diagnostic tests (RDTs) to differentiate malarial and non-malarial fevers, and an awareness of the need to improve case management of non-malarial fever, indicates an urgent need for high quality evidence on how best to improve prescribers' practices., Methods: A three-arm stratified cluster-randomised trial was conducted in 36 primary healthcare facilities from September 2010 to March 2012 within two rural districts in northeast Tanzania where malaria transmission has been declining. Interventions were guided by formative mixed-methods research and were introduced in phases. Prescribing staff from all facilities received standard Ministry of Health RDT training. Prescribers from facilities in the health worker (HW) and health worker-patient (HWP) arms further participated in small interactive peer-group training sessions with the HWP additionally receiving clinic posters and patient leaflets. Performance feedback and motivational mobile-phone text messaging (SMS) were added to the HW and HWP arms in later phases. The primary outcome was the proportion of patients with a non-severe, non-malarial illness incorrectly prescribed a (recommended) antimalarial. Secondary outcomes investigated RDT uptake, adherence to results, and antibiotic prescribing., Results: Standard RDT training reduced pre-trial levels of antimalarial prescribing, which was sustained throughout the trial. Both interventions significantly lowered incorrect prescribing of recommended antimalarials from 8% (749/8,942) in the standard training arm to 2% (250/10,118) in the HW arm (adjusted RD (aRD) 4%; 95% confidence interval (CI) 1% to 6%; P = 0.008) and 2% (184/10,163) in the HWP arm (aRD 4%; 95% CI 1% to 6%; P = 0.005). Small group training and SMS were incrementally effective. There was also a significant reduction in the prescribing of antimalarials to RDT-negatives but no effect on RDT-positives receiving an ACT. Antibiotic prescribing was significantly lower in the HWP arm but had increased in all arms compared with pre-trial levels., Conclusions: Small group training with SMS was associated with an incremental and sustained improvement in prescriber adherence to RDT results and reducing over-prescribing of antimalarials to close to zero. These interventions may become increasingly important to cope with the wider range of diagnostic and treatment options for patients with acute febrile illness in Africa.

Background: Long-Lasting Insecticidal Nets (LLINs) are one of the major malaria vector control tools, with most countries adopting free or subsidised universal coverage campaigns of populations at-risk from malaria. It is essential to understand LLIN durability so that public health policy makers can select the most cost effective nets that last for the longest time, and estimate the optimal timing of repeated distribution campaigns. However, there is limited knowledge from few countries of the durability of LLINs under user conditions., Methods/design: This study investigates LLIN durability in eight districts of Tanzania, selected for their demographic, geographic and ecological representativeness of the country as a whole. We use a two-stage approach: First, LLINs from recent national net campaigns will be evaluated retrospectively in 3,420 households. Those households will receive one of three leading LLIN products at random (Olyset®, PermaNet®2.0 or Netprotect®) and will be followed up for three years in a prospective study to compare their performance under user conditions. LLIN durability will be evaluated by measuring Attrition (the rate at which nets are discarded by households), Bioefficacy (the insecticidal efficacy of the nets measured by knock-down and mortality of mosquitoes), Chemical content (g/kg of insecticide available in net fibres) and physical Degradation (size and location of holes). In addition, we will extend the current national mosquito insecticide Resistance monitoring program to additional districts and use these data sets to provide GIS maps for use in health surveillance and decision making by the National Malaria Control Program (NMCP)., Discussion: The data will be of importance to policy makers and vector control specialists both in Tanzania and the SSA region to inform best practice for the maintenance of high and cost-effective coverage and to maximise current health gains in malaria control.

Background: To protect the most vulnerable groups from malaria (pregnant women and infants) the Tanzanian Government introduced a subsidy (voucher) scheme in 2004, on the basis of a public-private partnership. These vouchers are provided to pregnant women at their first antenatal care visit and mothers of infants at first vaccination. The vouchers are redeemed at registered retailers for a long-lasting insecticidal net against the payment of a modest top-up price. The present work analysed a large body of data from the Tanzanian National Voucher Scheme, focusing on interactions with concurrent mass distribution campaigns of free nets., Methods: In an ecologic study involving all regions of Tanzania, voucher redemption data for the period 2007-2011, as well as data on potential determinants of voucher redemption were analysed. The four outcome variables were: pregnant woman and infant voucher redemption rates, use of treated bed nets by all household members and by under- five children. Each of the outcomes was regressed with selected determinants, using a generalized estimating equation model and accounting for regional data clustering., Results: There was a consistent improvement in voucher redemption rates over the selected time period, with rates >80% in 2011. The major determinants of redemption rates were the top-up price paid by the voucher beneficiary, the retailer- clinic ratio, and socio-economic status. Improved redemption rates after 2009 were most likely due to reduced top-up prices (following a change in policy). Redemption rates were not affected by two major free net distribution campaigns. During this period, there was a consistent improvement in net use across all the regions, with rates of up to 75% in 2011., Conclusion: The key components of the National Treated Nets Programme (NATNETS) seem to work harmoniously, leading to a high level of net use in the entire population. This calls for the continuation of this effort in Tanzania and for emulation by other countries with endemic malaria.

Background: Tanzania achieved universal coverage with long-lasting insecticidal nets (LLINs) in October 2011, after three years of free mass net distribution campaigns and is now faced with the challenge of maintaining high coverage as nets wear out and the population grows. A process of exploring options for a continuous or "Keep-Up" distribution system was initiated in early 2011. This paper presents for the first time a comprehensive national process to review the major considerations, findings and recommendations for the implementation of a new strategy., Methods: Stakeholder meetings and site visits were conducted in five locations in Tanzania to garner stakeholder input on the proposed distribution systems. Coverage levels for LLINs and their decline over time were modelled using NetCALC software, taking realistic net decay rates, current demographic profiles and other relevant parameters into consideration. Costs of the different distribution systems were estimated using local data., Results: LLIN delivery was considered via mass campaigns, Antenatal Care-Expanded Programme on Immunization (ANC/EPI), community-based distribution, schools, the commercial sector and different combinations of the above. Most approaches appeared unlikely to maintain universal coverage when used alone. Mass campaigns, even when combined with a continuation of the Tanzania National Voucher Scheme (TNVS), would produce large temporal fluctuations in coverage levels; over 10 years this strategy would require 63.3 million LLINs and a total cost of $444 million USD. Community mechanisms, while able to deliver the required numbers of LLINs, would require a massive scale-up in monitoring, evaluation and supervision systems to ensure accurate application of identification criteria at the community level. School-based approaches combined with the existing TNVS would reach most Tanzanian households and deliver 65.4 million LLINs over 10 years at a total cost of $449 million USD and ensure continuous coverage. The cost of each strategy was largely driven by the number of LLINs delivered., Conclusions: The most cost-efficient strategy to maintain universal coverage is one that best optimizes the numbers of LLINs needed over time. A school-based approach using vouchers targeting all students in Standards 1, 3, 5, 7 and Forms 1 and 2 in combination with the TNVS appears to meet best the criteria of effectiveness, equity and efficiency.

Background: Since 2004, the Tanzanian National Voucher Scheme has increased availability and accessibility of insecticide-treated nets (ITNs) to pregnant women and infants by subsidizing the cost of nets purchased. From 2008 to 2010, a mass distribution campaign delivered nine million long-lasting insecticidal nets (LLINs) free-of-charge to children under-five years of age in Tanzania mainland. In 2010 and 2011, a Universal Coverage Campaign (UCC) led by the Ministry of Health and Social Welfare (MoHSW) was implemented to cover all sleeping spaces not yet reached through previous initiatives., Methods: The UCC was coordinated through a unit within the National Malaria Control Programme. Partners were contracted by the MoHSW to implement different activities in collaboration with local government authorities. Volunteers registered the number of uncovered sleeping spaces in every household in the country. On this basis, LLINs were ordered and delivered to village level, where they were issued over a three-day period in each zone (three regions). Household surveys were conducted in seven districts immediately after the campaign to assess net ownership and use., Results: The UCC was chiefly financed by the Global Fund to Fight AIDS, Tuberculosis and Malaria with important contributions from the US President's Malaria Initiative. A total of 18.2 million LLINs were delivered at an average cost of USD 5.30 per LLIN. Overall, 83% of the expenses were used for LLIN procurement and delivery and 17% for campaign associated activities. Preliminary results of the latest Tanzania HIV Malaria Indicator Survey (2011-12) show that household ownership of at least one ITN increased to 91.5%. ITN use, among children under-five years of age, improved to 72.7% after the campaign. ITN ownership and use data post-campaign indicated high equity across wealth quintiles., Conclusion: Close collaboration among the MoHSW, donors, contracted partners, local government authorities and volunteers made it possible to carry out one of the largest LLIN distribution campaigns conducted in Africa to date. Through the strong increase of ITN use, the recent activities of the national ITN programme will likely result in further decline in child mortality rates in Tanzania, helping to achieve Millennium Development Goals 4 and 6.

Background: There is no clear consensus on the most sustainable and effective distribution strategy for insecticide treated bed nets (ITNs). Tanzania has been a leader in social marketing but it is still not clear if this can result in high and equitable levels of coverage., Methods: A cluster-randomized survey of ITN and bed net ownership and use was conducted in a rural area exposed to intense Plasmodium falciparum transmission in NE Tanzania where ITN distribution had been subject to routine delivery of national strategies and episodic free distribution through local clinics. Data were collected on household assets to assess equity of ITN coverage and a rapid diagnostic test for malaria (RDT) was performed in all ages., Results: Among 598 households in four villages the use of any or insecticidal bed nets in children less than five years of age was 71% and 54% respectively. However there was a 19.8% increase in the number of bed nets per person (p < 0.001) and a 13.4% increase in the number of insecticidal nets per person (p < 0.001) for each quintile increase in household asset score. The odds of being RDT-positive were reduced by more than half in the least poor compared to the poorest households (OR 0.49, 95% CI 0.35-0.70). Poorer households had paid less for their nets and acquired them more recently, particularly from non-commercial sources, and bed nets in the least poor households were less likely to be insecticidal compared to nets in the poorest households (OR 0.44, 95% CI 0.26-0.74)., Conclusion: Marked inequity persists with the poorest households still experiencing the highest risk of malaria and the lowest ITN coverage. Abolition of this inequity within the foreseeable future is likely to require mass or targeted free distribution, but risks damaging what is otherwise an effective commercial market.

Background: Tanzania switched the antimalarial first line to sulphadoxine-pyrimethamine (SP) in 2001 from ineffective chloroquine (CQ). By 2003 higher levels of SP resistance were recorded, prompting an urgent need for replacing the first line drug with ACT, as currently recommended by the World Health Organization. Despite this recommendation country-specific evidence-based data to support efficacy and safety profile of ACT is still limited. A study on the efficacy and safety of artesunate plus amodiaquine (AS+AQ) and artemether plus lumefantrine (AL)(Coartem) was carried out in 2004 with the view of supporting the National Malaria Control Programme in the review of the policy in mainland Tanzania., Methods: An in vivo efficacy study was conducted at Ipinda and Mlimba health facilities between May and November 2004. The study recruited children aged 6-59 months presenting with symptoms of uncomplicated malaria, history of fever or an axillary temperature > or =37.5 degrees C; mono infection with Pasmodium falciparum (2,000-200,000 parasites/microl). Patients were randomized to received either SP or amodiaquine monotherapy or treated with standard doses of AS+AQ in Mlimba and Coartem in Kyela and followed-up for 28 days to assess treatment responses. This study reports results of the combination therapies., Results: A total of 157 children (76 in Mlimba and 99 in Kyela) who were enrolled in to the study and treated with either AL or AS+AQ were successfully followed-up. Both combinations were tolerated and effected rapid fever and parasite clearance. The crude ACPRs were 80 (87%) and 41 (63%) for AL and AS+AQ respectively. However, after PCR adjustments the corresponding figures raised to 100% (n = 86) and 93.8% (n = 45) in AL and AS+AQ groups, respectively. The mean haemoglobin improved moderately from day 0 to day 28 by 1 g/dl in AL and 0.4 g/dl in AS+AQ treatment group and was statistically significant (p < 0.001 both)., Conclusion: These findings provide substantial evidence that AL is highly efficacious in areas of high resistance of SP and supported the country's decision to switch from SP monotherapy to AL.