Mosquito Net Use in Early Childhood and Survival to Adulthood in Tanzania.

BACKGROUND: It has been hypothesized that in high-transmission settings, malaria control in early childhood (<5 years of age) might delay the acquisition of functional immunity and shift child deaths from younger to older ages. METHODS: We used data from a 22-year prospective cohort study in rural southern Tanzania to estimate the association between early-life use of treated nets and survival to adulthood. All the children born between January 1, 1998, and August 30, 2000, in the study area were invited to enroll in a longitudinal study from 1998 through 2003. Adult survival outcomes were verified in 2019 through community outreach and mobile telephones. We used Cox proportional-hazards models to estimate the association between the use of treated nets in early childhood and survival to adulthood, adjusting for potential confounders. RESULTS: A total of 6706 children were enrolled. In 2019, we verified information on the vital status of 5983 participants (89%). According to reports of early-life community outreach visits, approximately one quarter of children never slept under a treated net, one half slept under a treated net some of the time, and the remaining quarter always slept under a treated net. Participants who were reported to have used treated nets at half the early-life visits or more had a hazard ratio for death of 0.57 (95% confidence interval [CI], 0.45 to 0.72) as compared with those who were reported to have used treated nets at less than half the visits. The corresponding hazard ratio between 5 years of age and adulthood was 0.93 (95% CI, 0.58 to 1.49). CONCLUSIONS: In this long-term study of early-life malaria control in a high-transmission setting, the survival benefit from early-life use of treated nets persisted to adulthood. (Funded by the Eckenstein-Geigy Professorship and others.).

Indigenous emergence and spread of kelch13 C469Y artemisinin-resistant Plasmodium falciparum in Uganda.

Artemisinin-based combination therapies (ACTs) were introduced as the standard of care for uncomplicated malaria in Africa almost two decades ago. Recent studies in East Africa have reported a gradual increase in kelch13 (k13) mutant parasites associated with reduced artesunate efficacy. As part of the Community Access to Rectal Artesunate for Malaria project, we collected blood samples from 697 children with signs of severe malaria in northern Uganda between 2018 and 2020, before and after the introduction of rectal artesunate (RAS) in 2019. K13 polymorphisms were assessed, and parasite editing and phenotyping were performed to assess the impact of mutations on parasite resistance. Whole-genome sequencing was performed, and haplotype networks were constructed to determine the geographic origin of k13 mutations. Of the 697 children, 540 were positive for Plasmodium falciparum malaria by PCR and were treated with either RAS or injectable artesunate monotherapy followed in most cases by ACT. The most common k13 mutation was C469Y (6.7%), which was detected more frequently in samples collected after RAS introduction. Genome editing confirmed reduced in vitro susceptibility to artemisinin in C469Y-harboring parasites compared to wild-type controls (P < 0.001). The haplotypic network showed that flanking regions of the C469Y mutation shared the same African genetic background, suggesting a single and indigenous origin of the mutation. Our data provide evidence of selection for the artemisinin-resistant C469Y mutation. The realistic threat of multiresistant parasites emerging in Africa should encourage careful monitoring of the efficacy of artemisinin derivatives and strict adherence to ACT treatment regimens.

Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study.

BACKGROUND: For a full treatment course of severe malaria, community-administered pre-referral rectal artesunate (RAS) should be completed by post-referral treatment consisting of an injectable antimalarial and oral artemisinin-based combination therapy (ACT). This study aimed to assess compliance with this treatment recommendation in children under 5 years. METHODS AND FINDINGS: This observational study accompanied the implementation of RAS in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda between 2018 and 2020. Antimalarial treatment was assessed during admission in included referral health facilities (RHFs) in children under 5 with a diagnosis of severe malaria. Children were either referred from a community-based provider or directly attending the RHF. RHF data of 7,983 children was analysed for appropriateness of antimalarials; a subsample of 3,449 children was assessed additionally for dosage and method of ACT provision (treatment compliance). A parenteral antimalarial and an ACT were administered to 2.7% (28/1,051) of admitted children in Nigeria, 44.5% (1,211/2,724) in Uganda, and 50.3% (2,117/4,208) in DRC. Children receiving RAS from a community-based provider were more likely to be administered post-referral medication according to the guidelines in DRC (adjusted odds ratio (aOR) = 2.13, 95% CI 1.55 to 2.92, P < 0.001), but less likely in Uganda (aOR = 0.37, 95% CI 0.14 to 0.96, P = 0.04) adjusting for patient, provider, caregiver, and other contextual factors. While in DRC, inpatient ACT administration was common, ACTs were often prescribed at discharge in Nigeria (54.4%, 229/421) and Uganda (53.0%, 715/1,349). Study limitations include the unfeasibility to independently confirm the diagnosis of severe malaria due to the observational nature of the study. CONCLUSIONS: Directly observed treatment was often incomplete, bearing a high risk for partial parasite clearance and disease recrudescence. Parenteral artesunate not followed up with oral ACT constitutes an artemisinin monotherapy and may favour the selection of resistant parasites. In connection with the finding that pre-referral RAS had no beneficial effect on child survival in the 3 study countries, concerns about an effective continuum of care for children with severe malaria seem justified. Stricter compliance with the WHO severe malaria treatment guidelines is critical to effectively manage this disease and further reduce child mortality. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03568344).

Correction: Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study.

[This corrects the article DOI: 10.1371/journal.pmed.1004189.].

Pre-referral rectal artesunate is no "magic bullet" in weak health systems.

Severe malaria is a potentially fatal condition that requires urgent treatment. In a clinical trial, a sub-group of children treated with rectal artesunate (RAS) before being referred to a health facility had an increased chance of survival. We recently published in BMC Medicine results of the CARAMAL Project that did not find the same protective effect of pre-referral RAS implemented at scale under real-world conditions in three African countries. Instead, CARAMAL identified serious health system shortfalls that impacted the entire continuum of care, constraining the effectiveness of RAS. Correspondence to the article criticized the observational study design and the alleged interpretation and consequences of our findings.Here, we clarify that we do not dispute the life-saving potential of RAS, and discuss the methodological criticism. We acknowledge the potential for confounding in observational studies. Nevertheless, the totality of CARAMAL evidence is in full support of our conclusion that the conditions under which RAS can be beneficial were not met in our settings, as children often failed to complete referral and post-referral treatment was inadequate.The criticism did not appear to acknowledge the realities of highly malarious settings documented in detail in the CARAMAL project. Suggesting that trial-demonstrated efficacy is sufficient to warrant large-scale deployment of pre-referral RAS ignores the paramount importance of functioning health systems for its delivery, for completing post-referral treatment, and for achieving complete cure. Presenting RAS as a "magic bullet" distracts from the most urgent priority: fixing health systems so they can provide a functioning continuum of care and save the lives of sick children.The data underlying our publication is freely accessible on Zenodo.

Assessing caregivers' perceptions of treatment-seeking for suspected severe malaria in the Democratic Republic of the Congo.

BACKGROUND: Malaria remains a major public health issue in the Democratic Republic of the Congo (DRC), accounting for 44% deaths among outpatient visits in children < 5 years of age, and 22% of facility deaths. Understanding determinants of caregivers' treatment-seeking patterns and decision-making is crucial in reducing the malaria burden. METHODS: In the frame of the Community Access to Rectal Artesunate for Malaria (CARAMAL) project, cross-sectional household surveys that randomly sampled villages and households were carried-out in three rural DRC health zones prior to the rollout of pre-referral Rectal Artesunate (RAS) and then 9 and 19 months after RAS rollout (post-RAS). Data were captured electronically through face-to-face interviews with the main caregivers of children < 5 years. Capillary blood samples of the children were tested for malaria and anaemia. The main study outcome was whether caregiver "sought treatment outside home" when the child had fever. Multilevel mixed effects logistic regression models using village as random effect and health zone as a fixed effect was performed to assess treatment-seeking predictors. RESULTS: 2439 household interviews were completed (pre-RAS 888 and post-RAS 1551), including 316 and 653 treatment-seeking interviews. Overall, 3499 children < 5 years were tested for malaria and anaemia (pre-RAS 1,315 and post-RAS 2184). Caregiver's recognition of severe malaria signs was poor, while knowledge of symptoms of uncomplicated malaria seemed high. Despite this, danger signs significantly increased the odds of seeking treatment (aOR = 2.12, 95%CI 1.03-4.38), the same was found for the "least poor" quintile (aOR = 3.01, 95%CI 1.03-8.82), as well as residents of Kingandu (aOR = 2.78, 95%CI 1.01-7.65). "Doing something at home" against fever negatively affected treatment-seeking in both study phases. RAS acceptance was high, at almost 100%. Malaria prevalence was higher post-RAS (45.2%) compared to pre-RAS (34.4%), p = 0.003, but anaemia, although high (≥ 75%), was similar in both study phases (p = 0.92). CONCLUSION: In remote communities with high malaria prevalence in the DRC, malaria remains a major problem. Improving the recognition of danger signs of severe disease and introducing pre-referral RAS may improve treatment-seeking and contribute to reducing malaria-related mortality among children-if quality of care can be guaranteed.

Key Contributions by the Swiss Tropical and Public Health Institute Towards New and Better Drugs for Tropical Diseases.

Thanks to its expertise in clinical research, epidemiology, infectious diseases, microbiology, parasitology, public health, translational research and tropical medicine, coupled with deeply rooted partnerships with institutions in low- and middle-income countries (LMICs), the Swiss Tropical and Public Health Institute (Swiss TPH) has been a key contributor in many drug research and development consortia involving academia, pharma and product development partnerships. Our know-how of the maintenance of parasites and their life-cycles in the laboratory, plus our strong ties to research centres and disease control programme managers in LMICs with access to field sites and laboratories, have enabled systems for drug efficacy testing in vitro and in vivo, clinical research, and modelling to support the experimental approaches. Thus, Swiss TPH has made fundamental contributions towards the development of new drugs - and the better use of old drugs - for neglected tropical diseases and infectious diseases of poverty, such as Buruli ulcer, Chagas disease, food-borne trematodiasis (e.g. clonorchiasis, fascioliasis and opisthorchiasis), human African trypanosomiasis, leishmaniasis, malaria, schistosomiasis, soil-transmitted helminthiasis and tuberculosis. In this article, we show case the success stories of molecules to which Swiss TPH has made a substantial contribution regarding their use as anti-infective compounds with the ultimate aim to improve people's health and well-being.

Effectiveness of rectal artesunate as pre-referral treatment for severe malaria in children under 5 years of age: a multi-country observational study.

BACKGROUND: To prevent child deaths from severe malaria, early parenteral treatment is essential. Yet, in remote rural areas, accessing facilities offering parenteral antimalarials may be difficult. A randomised controlled trial found pre-referral treatment with rectal artesunate (RAS) to reduce deaths and disability in children who arrived at a referral facility with delay. This study examined the effectiveness of pre-referral RAS treatment implemented through routine procedures of established community-based health care systems. METHODS: An observational study accompanied the roll-out of RAS in the Democratic Republic of the Congo (DRC), Nigeria and Uganda. Children <5 years of age presenting to a community-based health provider with a positive malaria test and signs of severe malaria were enrolled and followed up during admission and after 28 days to assess their health status and treatment history. The primary outcome was death; covariates of interest included RAS use, referral completion, and post-referral treatment. RESULTS: Post-roll-out, RAS was administered to 88% of patients in DRC, 52% in Nigeria, and 70% in Uganda. The overall case fatality rate (CFR) was 6.7% (135/2011) in DRC, 11.7% (69/589) in Nigeria, and 0.5% (19/3686) in Uganda; 13.8% (865/6286) of patients were sick on day 28. The CFR was higher after RAS roll-out in Nigeria (16.1 vs. 4.2%) and stable in DRC (6.7 vs. 6.6%) and Uganda (0.7 vs. 0.3%). In DRC and Nigeria, children receiving RAS were more likely to die than those not receiving RAS (aOR=3.06, 95% CI 1.35-6.92 and aOR=2.16, 95% CI 1.11-4.21, respectively). Only in Uganda, RAS users were less likely to be dead or sick at follow-up (aOR=0.60, 95% CI 0.45-0.79). Post-referral parenteral antimalarials plus oral artemisinin-based combination therapy (ACT), a proxy for appropriate post-referral treatment, was protective. However, in referral health facilities, ACT was not consistently administered after parenteral treatment (DRC 68.4%, Nigeria 0%, Uganda 70.9%). CONCLUSIONS: Implemented at scale to the recommended target group, pre-referral RAS had no beneficial effect on child survival in three highly malaria-endemic settings. RAS is unlikely to reduce malaria deaths unless health system issues such as referral and quality of care at all levels are addressed. TRIAL REGISTRATION: The study is registered on ClinicalTrials.gov : NCT03568344.

Sub-national tailoring of malaria interventions in Mainland Tanzania: simulation of the impact of strata-specific intervention combinations using modelling.

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.

Key factors predicting suspected severe malaria case management and health outcomes: an operational study in the Democratic Republic of the Congo.

BACKGROUND: Evidence suggests that pre-referral Rectal Artesunate (RAS) can be a life-saving intervention for severe malaria in remote settings in Africa. Recognition of danger signs indicative of severe malaria is critical for prompt and appropriate case management. METHODS: This was an observational study conducted in three Health Zones of the Democratic Republic of the Congo to determine the distribution of dangers signs for severe malaria and assess their impact on RAS use, referral completion, injectable treatment and ACT provision, and health outcomes including death. An individual-level analysis was carried out, using multilevel-mixed effects logistic regression models. Severely ill febrile children < 5 years seeking care from community-based healthcare providers were recruited into a patient surveillance system based on the presence of key danger signs. Clinical and case management data were collected comprehensively over a 28 days period. Treatment seeking was elicited and health outcomes assessed during 28 days home visits. RESULTS: Overall, 66.4% of patients had iCCM general danger signs. Age of 2-5 years and iCCM general danger signs predicted RAS use (aOR = 2.77, 95% CI 2.04-3.77). RAS administration positively affected referral completion (aOR = 0.63, 95% CI 0.44-0.92). After RAS rollout, 161 children died (case fatality ratio: 7.1%, 95% CI 6.1-8.2). RAS improved the health status of the children on Day 28 (aOR = 0.64, 95% CI 0.45-0.92) and there was a non-significant trend that mortality was higher in children not receiving RAS (aOR = 1.50, 95% CI 0.86-2.60). Full severe malaria treatment at the RHF including injectable anti-malarial and a course of ACT was highly protective against death (aOR = 0.26, 95% CI 0.09-0.79). CONCLUSIONS: The main findings point towards the fact that danger signs are reasonably well recognized by health provider at the primary care level, and that RAS could influence positively health outcomes of such severe disease episodes and death. Its effectiveness is hampered by the insufficient quality of care at RHF, especially the provision of a full course of ACT following parenteral treatment. These are simple but important findings that requires urgent action by the health system planners and implementers.

The use of routine health facility data for micro-stratification of malaria risk in mainland Tanzania.

BACKGROUND: Current efforts to estimate the spatially diverse malaria burden in malaria-endemic countries largely involve the use of epidemiological modelling methods for describing temporal and spatial heterogeneity using sparse interpolated prevalence data from periodic cross-sectional surveys. However, more malaria-endemic countries are beginning to consider local routine data for this purpose. Nevertheless, routine information from health facilities (HFs) remains widely under-utilized despite improved data quality, including increased access to diagnostic testing and the adoption of the electronic District Health Information System (DHIS2). This paper describes the process undertaken in mainland Tanzania using routine data to develop a high-resolution, micro-stratification risk map to guide future malaria control efforts. METHODS: Combinations of various routine malariometric indicators collected from 7098 HFs were assembled across 3065 wards of mainland Tanzania for the period 2017-2019. The reported council-level prevalence classification in school children aged 5-16 years (PfPR5-16) was used as a benchmark to define four malaria risk groups. These groups were subsequently used to derive cut-offs for the routine indicators by minimizing misclassifications and maximizing overall agreement. The derived-cutoffs were converted into numbered scores and summed across the three indicators to allocate wards into their overall risk stratum. RESULTS: Of 3065 wards, 353 were assigned to the very low strata (10.5% of the total ward population), 717 to the low strata (28.6% of the population), 525 to the moderate strata (16.2% of the population), and 1470 to the high strata (39.8% of the population). The resulting micro-stratification revealed malaria risk heterogeneity within 80 councils and identified wards that would benefit from community-level focal interventions, such as community-case management, indoor residual spraying and larviciding. CONCLUSION: The micro-stratification approach employed is simple and pragmatic, with potential to be easily adopted by the malaria programme in Tanzania. It makes use of available routine data that are rich in spatial resolution and that can be readily accessed allowing for a stratification of malaria risk below the council level. Such a framework is optimal for supporting evidence-based, decentralized malaria control planning, thereby improving the effectiveness and allocation efficiency of malaria control interventions.

Acceptability of pre-referral rectal artesunate for severe malaria in children under 5 years by health workers and caregivers in the Democratic Republic of the Congo, Nigeria and Uganda.

BACKGROUND: For children below 6 years with suspected severe malaria attending a health care provider unable to provide parenteral malaria treatment, pre-referral rectal artesunate (RAS) is recommended by the World Health Organization to prevent death and disability. A number of African countries are in the process of rolling out quality-assured RAS for pre-referral treatment of severe malaria at community-level. The success of RAS depends, among other factors, on the acceptability of RAS in the communities where it is being rolled-out. Yet to date, there is limited literature on RAS acceptability. This study aimed to determine the acceptability of RAS by health care providers and child caregivers in communities where quality assured RAS was rolled out. This study was nested within the comprehensive multi-country observational research project Community Access to Rectal Artesunate for Malaria (CARAMAL), implemented in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda between 2018 and 2020. Data from three different sources were analysed to understand RAS acceptability: interviews with health workers during three health care provider surveys (N = 341 community health workers and 467 primary health facility workers), with caregivers of children < 5 years of age during three household surveys (N = 9332 caregivers), and with caregivers of children < 5 years of age who were treated with RAS and enrolled in the CARAMAL Patient Surveillance System (N = 3645 caregivers). RESULTS: RAS acceptability was high among all interviewed stakeholders in the three countries. After the roll-out of RAS, 97-100% heath care providers in DRC, 98-100% in Nigeria and 93-100% in Uganda considered RAS as very good or good. Majority of caregivers whose children had received RAS for pre-referral management of severe malaria indicated that they would want to get the medication again, if their child had the same illness (99.8% of caregivers in DRC, 100% in Nigeria and 99.9% in Uganda). In three household surveys, 67-80% of caregivers whose children had not previously received RAS considered the medication as useful. CONCLUSION: RAS was well accepted by health workers and child caregivers in DRC, Nigeria and Uganda. Acceptability is unlikely to be an obstacle to the large-scale roll-out of RAS in the studied settings.

Prevalence and risk factors for malaria in pregnancy in Vanga, Democratic Republic of Congo.

The Democratic Republic of Congo (DRC) is the second most malarious country in the world, but little information is available on malaria control measures in pregnancy. We conducted a longitudinal study among 395 women pregnant with singletons in the Vanga and Mayoko health facilities, Vanga Health Zone, Kwilu Province. We recruited 406 pregnant women between April and October 2019. Malaria prevalence at recruitment was 18.8% in Vanga and 30.1% in Mayoko (difference p<0.01). At delivery, malaria prevalence in placental samples was 9.7% in Vanga and 17.7% in Mayoko (difference p=0.04). The overall prevalence of anemia (< 11 g/dl hemoglobin) in both sites was high at recruitment (68.8%) and at delivery (62.9%). Malaria infection rates in the mother were high but decreased between first ANC contact and delivery - from 24.2% to 13.6%. It is unclear whether regular use of ITNs and uptake of IPTp-SP have contributed to that decrease.

Applied mathematical modelling to inform national malaria policies, strategies and operations in Tanzania.

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.

Sub-national stratification of malaria risk in mainland Tanzania: a simplified assembly of survey and routine data.

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.

Sustaining LLIN coverage with continuous distribution: the school net programme in Tanzania.

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.

The potential of pregnant women as a sentinel population for malaria surveillance.

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.

Towards improved health service quality in Tanzania: contribution of a supportive supervision approach to increased quality of primary healthcare.

BACKGROUND: Universal Health Coverage only leads to the desired health outcomes if quality of health services is ensured. In Tanzania, quality has been a major concern for many years, including the problem of ineffective and inadequate routine supportive supervision of healthcare providers by council health management teams. To address this, we developed and assessed an approach to improve quality of primary healthcare through enhanced routine supportive supervision. METHODS: Mixed methods were used, combining trends of quantitative quality of care measurements with qualitative data mainly collected through in-depth interviews. The former allowed for identification of drivers of quality improvements and the latter investigated the perceived contribution of the new supportive supervision approach to these improvements. RESULTS: The results showed that the new approach managed to address quality issues that could be solved either solely by the healthcare provider, or in collaboration with the council. The new approach was able to improve and maintain crucial primary healthcare quality standards across different health facility level and owner categories in various contexts. CONCLUSION: Together with other findings reported in companion papers, we could show that the new supportive supervision approach not only served to assess quality of primary healthcare, but also to improve and maintain crucial primary healthcare quality standards. The new approach therefore presents a powerful tool to support, guide and drive quality improvement measures within council. It can thus be considered a suitable option to make routine supportive supervision more effective and adequate.

Towards improved health service quality in Tanzania: appropriateness of an electronic tool to assess quality of primary healthcare.

BACKGROUND: Progress in health service quality is vital to reach the target of Universal Health Coverage. However, in order to improve quality, it must be measured, and the assessment results must be actionable. We analyzed an electronic tool, which was developed to assess and monitor the quality of primary healthcare in Tanzania in the context of routine supportive supervision. The electronic assessment tool focused on areas in which improvements are most effective in order to suit its purpose of routinely steering improvement measures at local level. METHODS: Due to the lack of standards regarding how to best measure quality of care, we used a range of different quantitative and qualitative methods to investigate the appropriateness of the quality assessment tool. The quantitative methods included descriptive statistics, linear regression models, and factor analysis; the qualitative methods in-depth interviews and observations. RESULTS: Quantitative and qualitative results were overlapping and consistent. Robustness checks confirmed the tool's ability to assign scores to health facilities and revealed the usefulness of grouping indicators into different quality dimensions. Focusing the quality assessment on processes and structural adequacy of healthcare was an appropriate approach for the assessment's intended purpose, and a unique key feature of the electronic assessment tool. The findings underpinned the accuracy of the assessment tool to measure and monitor quality of primary healthcare for the purpose of routinely steering improvement measures at local level. This was true for different level and owner categories of primary healthcare facilities in Tanzania. CONCLUSION: The electronic assessment tool demonstrated a feasible option for routine quality measures of primary healthcare in Tanzania. The findings, combined with the more operational results of companion papers, created a solid foundation for an approach that could lastingly improve services for patients attending primary healthcare. However, the results also revealed that the use of the electronic assessment tool outside its intended purpose, for example for performance-based payment schemes, accreditation and other systematic evaluations of healthcare quality, should be considered carefully because of the risk of bias, adverse effects and corruption.

Nationwide school malaria parasitaemia survey in public primary schools, the United Republic of Tanzania.

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.