Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in mainland Tanzania, 2019.

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

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 of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021.

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.

Microsatellites reveal high polymorphism and high potential for use in anti-malarial efficacy studies in areas with different transmission intensities in mainland Tanzania.

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 (RS = 7.48, range = 7.27-8.03, for an adjusted minimum sample size of 18 per site) and mean expected heterozygosity (He = 0.83, range = 0.80-0.85). Cluster analysis of haplotypes using STRUCTURE, principal component analysis, and pairwise genetic differentiation (FST) 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.

Efficacy of artesunate-amodiaquine for treatment of uncomplicated Plasmodium falciparum malaria in mainland Tanzania.

BACKGROUND: Diversification of artemisinin-based combination therapy (ACT) is suggested as one of the strategies that can be used to contain artemisinin resistance. Artesunate-amodiaquine (ASAQ) is one of the artemisinin-based combinations that can be used in the diversification strategy as an alternative first-line treatment for uncomplicated malaria in mainland Tanzania. There is however limited data on the efficacy of ASAQ in mainland Tanzania. This study assessed the efficacy of ASAQ for treatment of uncomplicated Plasmodium falciparum malaria in selected sentinel sites for therapeutic efficacy studies in mainland Tanzania. METHODS: Between December 2018 and March 2020, children aged between 6 months and 10 years, attending at Nagaga, Mkuzi, and Mlimba primary health facilities, and with suspected uncomplicated malaria infection were screened for eligibility to participate in the study. Malaria infection was screened using microscopy. Children with uncomplicated P. falciparum monoinfection and who fulfilled all other inclusion criteria, and had none of the exclusion criteria, according to the World Health Organization (WHO) guidelines, were treated with ASAQ. Follow-up visits were scheduled on days 0, 1, 2, 3, 7, 14, 21, and 28 or on any day of recurrent infection for clinical and laboratory assessment. Polymerase chain reaction (PCR)-corrected cure rate on day 28 was the primary outcome. RESULTS: A total of 264 children, 88 in each of the three study sites (Mlimba, Mkuzi and Nagaga health facilities) were enrolled and treated with ASAQ. The ASAQ PCR-corrected cure rate was 100% at all the three study sites. None of the participants had early treatment failure or late clinical failure. Furthermore, none of the participants had a serious adverse event. CONCLUSION: ASAQ was highly efficacious for the treatment of uncomplicated P. falciparum malaria in mainland Tanzania, therefore, it can be deployed as an alternative first-line treatment for uncomplicated malaria as part of diversification strategy to contain the spread of partial artemisinin resistance in the country.

Evaluation of Malaria Rapid Diagnostic Test Performance and pfhrp2 Deletion in Tanzania School Surveys, 2017.

As part of malaria nationwide monitoring and evaluation initiatives, there is an increasing trend of incorporating malaria rapid diagnostic tests (mRDTs) in surveys conducted within primary schools to detect malaria parasites. However, mRDTs based on the detection of histidine-rich protein 2 (HRP2) are known to yield false-positive results due to persistent antigenemia, and false-negative results may result from low parasitemia or Plasmodium falciparum hrp2/3 gene deletion. We evaluated diagnostic performance of an HRP2 and pan-parasite lactate dehydrogenase (HRP2/pLDH) mRDT against polymerase chain reaction (PCR) for detection of P. falciparum among 17,051 primary school-age children from eight regions of Tanzania in 2017. According to PCR, the prevalence of P. falciparum was 19.2% (95% CI: 18.6-19.8). Using PCR as reference, the sensitivity and specificity of mRDT was 76.2% (95% CI: 74.7-77.7) and 93.9% (95% CI: 93.5-94.3), respectively. Test agreement was lowest in low transmission areas, where true-positive mRDTs were outnumbered by false-negatives due to low parasitemia. Discordant samples (mRDT-negative but PCR-positive) were screened for pfhrp2/3 deletion by real-time PCR. Among those with a parasite density sufficient for analysis, pfhrp2 deletion was confirmed in 60 samples, whereas pfhrp3 deletion was confirmed in two samples; one sample had both pfhrp2 and pfhrp3 deletions. The majority of samples with gene deletions were detected in the high-transmission Kagera region. Compared with mRDTs, PCR and other molecular methods offer increased sensitivity and are not affected by pfhrp2/3 deletions, making them a useful supplement to mRDTs in schools and other epidemiological surveys.

Co-occurrence of Overweight, Stunting, and Anemia among Adolescents (10-19 Years) in Tanzania Mainland: A School-Based Cross-Sectional Study.

Background: Evidence on double and triple burdens of malnutrition among adolescents is an essential key to informing policy design, implementation, and tracking progress of adolescent nutritional programs. Tanzania has a scarcity of studies on the double and triple burden of malnutrition among adolescents. Objective: The aim of this study was to assess the co-occurrence of malnutrition (overweight, stunting, and anemia) among adolescents (10-19 y) in mainland Tanzania. Methods: A school-based cross-sectional study was conducted among 44,120 primary school adolescents aged 10 to 19 y in mainland Tanzania. Anthropometric assessments (weight, height, and body mass index), dietary assessments, and hemoglobin levels were used to calculate the single, double, and triple burden of malnutrition. Data were analyzed using Stata software 15. The chi-square test was used to test the association between the nutrition condition and social demographic variables, physical activity, and dietary quality. Log-binomial models were used to determine factors associated with stunting, overweight, and anemia. Multivariable log-binomial models were used to control confounders. All analyses were 2-tailed, and the significance level was set at 5%. Results: The prevalence of anemia was 34.1%, while stunting and overweight had a prevalence of 32% and 4.2%, respectively. Approximately 41.7%, 13.5%, and 0.3% had single, double, and triple burden malnutrition-related conditions, respectively. Females were found to have a higher risk of being overweight compared with males (relative risk [RR]: 1.33; 95% confidence interval [CI]: 1.21, 1.45), while engaging in moderate to low levels of physical activity was associated with a decreased risk of being overweight. Additionally, residing in urban areas was linked to a decreased risk of stunting (RR: 0.78; 95% CI: 0.75, 0.80) and a 27% lower risk of anemia when compared with participants from rural areas. Conclusion: The findings from this study suggest that the complex nature of malnutrition among school adolescents warrants consideration when designing policies and interventions to reduce the burden of malnutrition.

Accessibility of malaria commodities in Geita District Council, mainland Tanzania: the experiences from healthcare providers and clients.

Background: Access to essential malaria commodities is a cornerstone in malaria control. However optimal availability and access to essential malaria commodities remain a challenge in Tanzania. Therefore, this study aimed to explore the factors affecting the accessibility of malaria commodities in Tanzania. Methods: This was a mixed-method cross-sectional study using both quantitative and qualitative approaches. Data were collected between February and March 2023 from health facilities, health facility staff, and patients. Results: Availability of malaria commodities in government health facilities was 100% for all items while in the private and faith-based facilities, this ranged from 10% to 80%. The reasons for stockouts in Government facilities were related to delayed and inadequate quantity delivery while in private facilities the main reason was the lack of cash for procurement. Both private facilities' clients and healthcare providers concurred that most people do not access complete treatment due to the high costs of prescribed medicines and poor stocking levels. Conclusion: The availability, hence the accessibility, of malaria commodities in private and faith-based health facilities is still sub-optimal. Logistic management needs to be improved to eliminate stockouts and malaria commodities high costs need a permanent solution.

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.

Evidence of artemisinin partial resistance in North-western Tanzania: clinical and drug resistance markers study.

Background: Artemisinin-based combination therapies (ACTs) are the recommended antimalarial drugs for the treatment of uncomplicated malaria. The recent emergence of artemisinin partial resistance (ART-R) in Rwanda, Uganda and Eritrea is of great concern. In Tanzania, a nationwide molecular malaria surveillance in 2021 showed a high prevalence of the Kelch13 (K13) 561H mutation in Plasmodium falciparum from the north-western region, close to the border with Rwanda and Uganda. This study was conducted in 2022 to evaluate the efficacy of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) for the treatment of uncomplicated falciparum malaria and to confirm the presence of ART-R in Tanzania. Methods: This single-arm study evaluated the efficacy of AL and ASAQ in eligible children aged six months to 10 years at Bukangara Dispensary in Karagwe District, Kagera Region. Clinical and parasitological responses were monitored for 28 days according to standard WHO protocol. Mutations in K13 gene and extended haplotypes with these mutations were analysed using Sanger and whole genome sequencing data, respectively. Findings: 176 children (88 in each AL and ASAQ group) were enrolled and all achieved the defined outcomes. PCR-corrected adequate clinical and parasitological response (ACPR) was 98.3% (95% CI: 90.8-100) and 100.0% (95% CI: 95.8-100) for AL and ASAQ, respectively. Parasitaemia on day 3 was observed in 11/88 (12.5%) and 17/88 (19.3%) in the AL and ASAQ groups, respectively. The half-life of parasitaemia was significantly higher (>6.5 hrs) in patients with parasitaemia on day 3 and/or mutations in K13 gene at enrolment. Most patients with parasitaemia on day 3 (8/11 = 72.7% in the AL group and 10/17 = 58.8% in the ASAQ group) had 561H mutation at enrolment. The parasites with K13 mutations were not similar to those from south-east Asia and Rwanda, but had the same core haplotype of a new 561H haplotype reported in Kagera in 2021. Interpretation: These findings confirm the presence of ART-R in Tanzania. A context-specific strategy to respond to artemisinin partial resistance is urgently needed. Although both AL and ASAQ showed high efficacy, increased vigilance for reduced efficacy of these ACTs and detection of ART-R in other parts of the country is critical.

Country wide surveillance reveals prevalent artemisinin partial resistance mutations with evidence for multiple origins and expansion of high level sulfadoxine-pyrimethamine resistance mutations in northwest Tanzania.

Background: Emergence of artemisinin partial resistance (ART-R) in Plasmodium falciparum is a growing threat to the efficacy of artemisinin combination therapies (ACT) and the efforts for malaria elimination. The emergence of Plasmodium falciparum Kelch13 (K13) R561H in Rwanda raised concern about the impact in neighboring Tanzania. In addition, regional concern over resistance affecting sulfadoxine-pyrimethamine (SP), which is used for chemoprevention strategies, is high. Methods: To enhance longitudinal monitoring, the Molecular Surveillance of Malaria in Tanzania (MSMT) project was launched in 2020 with the goal of assessing and mapping antimalarial resistance. Community and clinic samples were assessed for resistance polymorphisms using a molecular inversion probe platform. Findings: Genotyping of 6,278 samples collected countrywide in 2021 revealed a focus of K13 561H mutants in northwestern Tanzania (Kagera) with prevalence of 7.7% (50/649). A small number of 561H mutants (about 1%) were found as far as 800 km away in Tabora, Manyara, and Njombe. Genomic analysis suggests some of these parasites are highly related to isolates collected in Rwanda in 2015, supporting regional spread of 561H. However, a novel haplotype was also observed, likely indicating a second origin in the region. Other validated resistance polymorphisms (622I and 675V) were also identified. A focus of high sulfadoxine-pyrimethamine drug resistance was also identified in Kagera with a prevalence of dihydrofolate reductase 164L of 15% (80/526). Interpretation: These findings demonstrate the K13 561H mutation is entrenched in the region and that multiple origins of ART-R, similar as to what was seen in Southeast Asia, have occurred. Mutations associated with high levels of SP resistance are increasing. These results raise concerns about the long-term efficacy of artemisinin and chemoprevention antimalarials in the region. Funding: This study was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health.

Community knowledge, attitude, practices and beliefs associated with persistence of malaria transmission in North-western and Southern regions of Tanzania.

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.

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.

The quality of malaria case management in different transmission settings in Tanzania mainland, 2017-2018.

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

Assessing the utility of pregnant women as a sentinel surveillance population for malaria in Geita, Tanzania, 2019 - 2021.

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

Spatio-temporal modelling of routine health facility data for malaria risk micro-stratification in mainland Tanzania.

As malaria transmission declines, the need to monitor the heterogeneity of malaria risk at finer scales becomes critical to guide community-based targeted interventions. Although routine health facility (HF) data can provide epidemiological evidence at high spatial and temporal resolution, its incomplete nature of information can result in lower administrative units without empirical data. To overcome geographic sparsity of data and its representativeness, geo-spatial models can leverage routine information to predict risk in un-represented areas as well as estimate uncertainty of predictions. Here, a Bayesian spatio-temporal model was applied on malaria test positivity rate (TPR) data for the period 2017-2019 to predict risks at the ward level, the lowest decision-making unit in mainland Tanzania. To quantify the associated uncertainty, the probability of malaria TPR exceeding programmatic threshold was estimated. Results showed a marked spatial heterogeneity in malaria TPR across wards. 17.7 million people resided in areas where malaria TPR was high (≥ 30; 90% certainty) in the North-West and South-East parts of Tanzania. Approximately 11.7 million people lived in areas where malaria TPR was very low (< 5%; 90% certainty). HF data can be used to identify different epidemiological strata and guide malaria interventions at micro-planning units in Tanzania. These data, however, are imperfect in many settings in Africa and often require application of geo-spatial modelling techniques for estimation.

Similar Prevalence of Plasmodium falciparum and Non-P. falciparum Malaria Infections among Schoolchildren, Tanzania1.

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

Malaria knowledge, attitude, and practice among communities involved in a seasonal malaria chemoprevention study in Nanyumbu and Masasi districts, Tanzania.

Background: Utilization of malaria interventions is influenced by, among other things, the level of knowledge and attitude that the community has toward the infection as well as the available interventions. This study assessed malaria knowledge, attitudes, and practices on malaria infection and interventions in Masasi and Nanyumbu districts, Tanzania. Methods: A community-based cross-sectional survey was conducted between August and September 2020, among the heads of households having at least one under-five child. Information on knowledge, attitudes, and practices on malaria infection and interventions was gathered from the heads of the households using a structured questionnaire. The knowledge level was classified into low, moderate, and high. Attitudes were classified into positive and negative, whereas the practices were classified into good and poor. Children aged between 3 and 59 months were screened for malaria infection using a malaria rapid diagnostic test (mRDT). The proportion of the households' heads with high level of knowledge was the primary outcome. Proportions were compared using Chi-square or fisher's test, and logistic regression analysis was used as appropriate. Results: A total of 1,556 household heads were interviewed, 1,167 (75.00%) were male, and according to marital status, 1,067 (68.57%) were couples. All the household heads had some knowledge of malaria, but 47.33% (736/1,555) and 13.83% (215/1,555) of them had moderate and high knowledge, respectively. The level of knowledge on malaria was significantly influenced by gender [adjusted odds ratio (aOR) = 0.72, 95.00% confidence interval (CI) = 0.56-0.94, p = 0.017], level of education (aOR = 1.50, 95.00% CI = 1.04-2.16, p = 0.03), and the occupation of the household head (aOR = 1.90, 95.00% CI = 1.22-2.96, p = 0.004). Majority of the households [83.87% (1,305/1,556)] had bed nets hanging on the sleeping spaces. Of the household heads possessing bed nets, 85.10% (514/604), 79.62% (586/736), and 95.35% (205/215) of them had a low, moderate, and high level of knowledge on malaria infection, respectively (trend x 2 = 31.53, p < 0.001). The majority [95.04% (1,474/1,551)] of the household heads perceived sleeping under the bed net to be beneficial. Furthermore, 15.56% (94/604), 14.67% (108/736), and 7.44% (16/215) of the household heads with low, moderate, and high knowledge, respectively, had children with malaria infection (trend x 2 = 9.172, p = 0.01). Conclusion: The study population had a good level of knowledge about malaria infection, and a good attitude toward malaria interventions, and the majority of them were using bed nets.

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.