Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in mainland Tanzania, 2018.

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.

Trends in retail sales of insecticide-treated nets and untreated nets in Tanzania: cross-section surveys.

BACKGROUND: The commercial sector plays a vital role in mosquito net ownership and access in Tanzania. The National Malaria Strategic Plan (NMSP) includes long-lasting insecticidal nets (LLIN) delivery through the commercial sector as a complementary mechanism. The NMSP aims to increase LLIN sales while decreasing untreated mosquito net sales. This survey aimed to track quantities, market share of different net categories, prices, and origins of mosquito nets in retail markets and to engage stakeholders to analyse market trends. METHODS: This mixed-method mosquito net retail outlet survey was conducted in mid-2021 in six and in mid-2022 in eight regions. Field teams identified net-selling outlets in major urban and peri-urban markets and used snowball sampling to identify additional outlets. A structured questionnaire was used, and photos of available mosquito net products were taken. Key informant interviews were conducted with wholesalers and retailers. The relative market share of a product was calculated by using the mean of each sales category as frequency weights. Qualitative data analysis was undertaken by summarizing common themes and observations based on the research question. RESULTS: A total of 394 and 1139 outlets were surveyed in 2021 and 2022, respectively. More than 96% of distributed brands in both years were untreated nets. The market share for untreated mosquito nets was 99.2% in 2021 and 88.3% in 2022. Bed net sales were seasonal, peaking in the rainy season and at the start of the school year. Leaked LLINs from the public sector comprised 0.3% of the market share in 2021 and 8.3% in 2022. Kigoma markets had the most significant frequency of leaked LLIN products. Legitimate LLINs were rare in 2021 (n = 2) and not found in 2022, despite the presence of a local LLIN manufacturer. A small number (n = 3) of untreated nets fabricated in China claiming to be LLINs were observed in 2022. CONCLUSIONS: Despite NMCP's strategic approach to increasing retail market share for legitimate LLINs, significant challenges remain. Efforts are needed to change the current situation given the context of large-scale public sector distributions of LLINs, the higher consumer cost of LLINs, the lack of bed net varieties. Improvement of registration process is recommended.

Estimating population ITN access at council level in Tanzania.

BACKGROUND: Since 2013, the National Malaria Control Programme in mainland Tanzania and the Zanzibar Malaria Elimination Programme have implemented mass insecticide-treated net (ITN) distribution campaigns, routine ITN distribution to pregnant women and infants, and continuous distribution through primary schools (mainland) and community leaders (Zanzibar) to further malaria control efforts. Mass campaigns are triggered when ITN access falls below 40%. In this context, there is a need to monitor ITN access annually to assess whether it is below threshold and inform quantification of ITNs for the following year. Annual estimates of access are needed at the council level to inform programmatic decision-making. METHODS: An age-structured stock and flow model was used to predict annual net crops from council-level distribution data in Tanzania from 2012 to 2020 parameterized with a Tanzania-specific net median lifespan of 2.15 years. Annual nets-per-capita (NPC) was calculated by dividing each annual net crop by mid-year council projected population. A previously fit nonparametric conditional quantile function for the proportion of the population with access to an ITN (ITN access) as a function of NPC was used to predict ITN access at the council level based on the predicted NPC value. These estimates were compared to regional-level ITN access from large household surveys. RESULTS: For regions with the same ITN strategy for all councils, predicted council-level ITN access was consistent with regional-level survey data for 79% of councils. Regions where ITN strategy varied by council had regional estimates of ITN access that diverged from the council-specific estimates. Predicted ITN access reached 60% only when "nets issued as a percentage of the council population" (NPP) exceeded 15%, and approached 80% ITN access when NPP was at or above 20%. CONCLUSION: Modelling ITN access with country-specific net decay rates, council-level population, and ITN distribution data is a promising approach to monitor ITN coverage sub-regionally and between household surveys in Tanzania and beyond.

Implementation research of a cluster randomized trial evaluating the implementation and effectiveness of intermittent preventive treatment for malaria using dihydroartemisinin-piperaquine on reducing malaria burden in school-aged children in Tanzania: methodology, challenges, and mitigation.

BACKGROUND: It has been more than 20 years since the malaria epidemiologic shift to school-aged children was noted. In the meantime, school-aged children (5-15 years) have become increasingly more vulnerable with asymptomatic malaria prevalence reaching up to 70%, making them reservoirs for subsequent transmission of malaria in the endemic communities. Intermittent Preventive Treatment of malaria in schoolchildren (IPTsc) has proven to be an effective tool to shrink this reservoir. As of 3rd June 2022, the World Health Organization recommends IPTsc in moderate and high endemic areas. Even so, for decision-makers, the adoption of scientific research recommendations has been stifled by real-world implementation challenges. This study presents methodology, challenges faced, and mitigations used in the evaluation of the implementation of IPTsc using dihydroartemisinin-piperaquine (DP) in three councils (Handeni District Council (DC), Handeni Town Council (TC) and Kilindi DC) of Tanga Region, Tanzania so as to understand the operational feasibility and effectiveness of IPTsc on malaria parasitaemia and clinical malaria incidence. METHODS: The study deployed an effectiveness-implementation hybrid design to assess feasibility and effectiveness of IPTsc using DP, the interventional drug, against standard of care (control). Wards in the three study councils were the randomization unit (clusters). Each ward was randomized to implement IPTsc or not (control). In all wards in the IPTsc arm, DP was given to schoolchildren three times a year in four-month intervals. In each council, 24 randomly selected wards (12 per study arm, one school per ward) were chosen as representatives for intervention impact evaluation. Mixed design methods were used to assess the feasibility and acceptability of implementing IPTsc as part of a more comprehensive health package for schoolchildren. The study reimagined an existing school health programme for Neglected Tropical Diseases (NTD) control include IPTsc implementation. RESULTS: The study shows IPTsc can feasibly be implemented by integrating it into existing school health and education systems, paving the way for sustainable programme adoption in a cost-effective manner. CONCLUSIONS: Through this article other interested countries may realise a feasible plan for IPTsc implementation. Mitigation to any challenge can be customized based on local circumstances without jeopardising the gains expected from an IPTsc programme. Trial registration clinicaltrials.gov, NCT04245033. Registered 28 January 2020, https://clinicaltrials.gov/ct2/show/NCT04245033.

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

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

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.

Understanding Antenatal Care Service Quality for Malaria in Pregnancy through Supportive Supervision Data in Tanzania.

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