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In 2021, nationwide malaria molecular surveillance revealed a high prevalence of a validated artemisinin resistance marker, the kelch13 (k13) Arg561His mutation, in the Kagera region of northwestern Tanzania. We aimed to investigate the efficacy of artemether–lumefantrine and artesunate–amodiaquine and to confirm the presence of artemisinin partial resistance (ART-R) in the Karagwe district of this region. This single-arm, therapeutic efficacy study was carried out at the Bukangara dispensary in the Karagwe district of the Kagera region in northwestern Tanzania. Eligible participants were aged between 6 months and 120 months, had confirmed Plasmodium falciparum asexual parasitaemia, and met other inclusion criteria according to WHO's standard protocol. Participants were enrolled, treated sequentially with either artemether–lumefantrine or artesunate–amodiaquine, and assessed clinically and parasitologically for 28 days as per WHO protocol. Parasitaemia was measured every 8 h until day 3, on day 7, and then during weekly follow-up visits until day 28. Mutations in the k13 gene and extended haplotypes with the mutations were analysed, and comparisons were made with previous samples collected in the same region of Kagera and in Rwanda and southeast Asia. The primary endpoint was PCR-corrected cure rate. Between April 29 and Sept 1, 2022, 343 patients were screened, of whom 176 were enrolled: 88 in each treatment group. The PCR-corrected cure rate was 98% (95% CI 91–100) in the artemether–lumefantrine group and 100% (96–100) in the artesunate–amodiaquine group. Persistent parasitaemia on day 3 occurred in 11 (13%) of 88 patients in the artemether–lumefantrine group and 17 (19%) of 88 patients in the artesunate–amodiaquine group. Arg561His mutations on day 0 and parasitaemia on day 3 were reported in eight (9%) of 87 patients in the artemether–lumefantrine group and ten (12%) of 86 patients in the artesunate–amodiaquine group. The median parasite clearance half-life in patients harbouring parasites with Arg561His mutation was 6·1 h in the artemether–lumefantrine group and 6·0 h in the artesunate–amodiaquine group. Parasites with the Arg561His mutation were not similar to those from southeast Asia and Rwanda but had similar haplotypes to parasites reported in the same Tanzanian region of Kagera in 2021. This study confirms the presence of ART-R in Tanzania, although artemether–lumefantrine and artesunate–amodiaquine showed high efficacy. A context-specific response strategy and vigilance to detect the reduced efficacy of current antimalarial treatments and ART-R in other parts of the country are urgently needed. The Bill & Melinda Gates Foundation and the US National Institutes of Health.

In Africa, children aged 5 to 15 years (school age) comprises more than 50% (>339 million) of the under 19 years population, and are highly burdened by malaria and anaemia that impair cognitive development. For the prospects of improving health in African citizens, understanding malaria and its relation to anaemia in school-aged children, it is crucial to inform targeted interventions for malaria control and accelerate elimination efforts as part of improved school health policy. We conducted a study to determine the risk factors for asymptomatic malaria and their association to anaemia. We explored the prevalence of antimalarial drug resistance as well as the association of asymptomatic malaria infection and anaemia on cognitive and psychomotor functions in school-aged children living in high endemic areas. This study was a comprehensive baseline survey, within the scope of a randomised, controlled trial on the effectiveness and safety of antimalarial drugs in preventing malaria and its related morbidity in schoolchildren. We enrolled 1,587 schoolchildren from 7 primary schools located in Muheza, north-eastern Tanzania. Finger-pricked blood samples were collected for estimation of malaria parasitaemia using a microscope, haemoglobin concentration using a haemoglobinometer, and markers of drug resistance processed from dried blood spots (DBS). Psychomotor and Cognitive functions were assessed using a ‘20 metre Shuttle run’ and a test of everyday attention for children (TEA-Ch), respectively. The prevalence of asymptomatic malaria parasitaemia, anaemia and stunting was 26.4%, 49.8%, and 21.0%, respectively with marked variation across schools. In multivariate models, asymptomatic malaria parasitaemia attributed to 61% of anaemia with a respective population attribution fraction of 16%. Stunting, not sleeping under a bednet and illiterate parent or guardian were other factors attributing to 7%, 9%, and 5% of anaemia in the study population, respectively. Factors such as age group (10–15 years), not sleeping under a bednet, low socioeconomic status, parents’ or guardians’ with a low level of education, children overcrowding in a household, and fewer rooms in a household were significantly attributed to higher malaria infection. There was no significant association between malaria infection or anaemia and performance on tests of cognitive function (sustained attention) or psychomotor function (VO2 max). However, a history of malaria in the past one month was significantly associated with decreased cognitive scores (aOR = -4.1, 95% CI -7.7–0.6, p = 0 . 02 ). Furthermore, stunted children had significantly lower VO2max scores (aOR = -1.9, 95% CI -3.0–0.8, p = 0 . 001 ). Regarding the antimalarial drug resistance markers, the most prevalent Pfmdr1 86-184-1034-1042-1246 haplotypes were the NFSND in 47% (n = 88) and the NYSND in 52% (n = 98). The wild type Pfcrt haplotypes (codons 72–76, CVMNK) were found in 99.1% (n = 219) of the samples. Malaria, stunting and parents’ or guardians’ illiteracy were the key attributable factors for anaemia in schoolchildren. Given malaria infection in schoolchildren is mostly asymptomatic; an addition of interventional programmes such as intermittent preventive treatment of malaria in schoolchildren (IPTsc) would probably act as a potential solution while calling for an improvement in the current tools such as bednet use, school food programme, and community-based (customised) health education with an emphasis on nutrition and malaria control.

Background WHO and the Lancet reported that malaria and malnutrition form a double health burden in low and middle-income countries. Despite the massive implementation of malaria control interventions, there is scarce evidence on the impact of intermittent preventive therapy (IPTsc) for malaria on the nutritional status of school-age children. In this study, we aimed to determine malnutrition risk factors and evaluate the impact of IPTsc for malaria on the nutritional status of school-age children in Muheza, Tanga, Tanzania. Methods We analysed secondary data from a cross-sectional baseline survey and a randomized controlled open-label trial conducted in Muheza, Tanga, Tanzania. Participants of our study were children of age 5–15 years. Baseline data collection was carried out between February-April 2019. The study continued through December 2020, during which participants were randomly assigned to one of the three groups: dihydroartemisinin-piperaquine (DP), artesunate-amodiaquine (ASAQ), or a control group, using a 3-arms balanced block design with a 1:1:1 allocation ratio. Intervention treatments were administered at recruitment, 4 months, and 8 months of the trial. Data were analysed using logistic regression and a linear mixed model. Findings At baseline, the prevalence of malaria was 27%. The prevalence of being underweight among children of ≤ 10 years was 23%. Among all children surveyed at baseline, 21% were stunted and 28% were either thin or severely thin. The odds of stunting were 78% higher (AOR = 1.78, 95%CI = [1.36, 2.33], P  < 0.001) among children who had malaria compared with those who did not have malaria. Children from low socioeconomic status (SES) had higher odds of being underweight (AOR = 1.50, 95%CI = [1.13,2.01], P  = 0.006) compared with their high SES counterparts. During the intervention, change in mean weight, height, and BMI over time as estimated from age-treatment interaction was not significantly different in the dihydroartemisinin-piperaquine (DP) and Artesunate amodiaquine (ASAQ) treatment groups compared with the control group. Conclusion Although substantial efforts to control malaria are ongoing in the study setting, the dual burden of malaria and malnutrition remains significant. Anti-malaria use for preventive purpose may not be sufficient to improve nutritional status, reinforcing that integrated interventions are required to address both malaria and malnutrition. Public health efforts should combine malaria control with nutrition programs, including community-driven strategies to enhance sustainable nutrition education and access to adequate food at home and school. Protocol for the parent study that generated these data was registered with ClinicalTrials.gov (NCT03640403) on Aug 21, 2018.

Malaria has remained persistently high in some regions of Tanzania despite increased control interventions. To address the burden of malaria in these regions, monitoring malaria vector dynamics is crucial to inform control interventions. This study assessed the composition and infectivity of malaria vectors in areas with varying levels of transmission. A cross-sectional study was conducted in five districts: Buhigwe, Kyerwa, Ludewa, Muheza, and Nyasa, from August to October 2023. In each district, one to five villages were selected for the study, and mosquitoes were collected indoors from 10 households per village using CDC light traps. Outdoor mosquitoes were collected from five households using Furvela tent traps. In all selected villages and trap types, mosquitoes were collected over three nights. Collected mosquitoes were sorted by species, and malaria vectors were sent to the laboratory for identification and screening for malaria parasites using polymerase chain reaction. A total of 19,898 mosquitoes were collected, and Anopheles gambiae complex, An. funestus group, other Anopheles species and culicine species accounted for 2.2%, 44.3%, 1.1% and 52.4%, respectively. An. funestus group was the predominant species, accounting for 95.3% of the malaria vectors. Sibling species identification revealed that An. arabiensis was the main species (75.0%) in An. gambiae complex, whereas An. funestus sensu stricto (s.s) was predominant (96.3%) in An. funestus group. A total of 1799 vectors were tested for infection with Plasmodium falciparum, and nine (0.5%) collected with CDC light traps were infected. The estimated annual entomological inoculation rate for An. funestus collected by light traps was 242.6, 66.5, and 13.0 infectious bites per person per year in Kyerwa, Nyasa, and Muheza, respectively. This study recorded a relatively high density of malaria vectors, particularly in Kyerwa district, despite being conducted during the dry season. An. funestus was the main vector, and interventions targeting it are urgently needed to achieve the national goal of malaria elimination by 2030.

Background Recent studies point to the need to incorporate the detection of non-falciparum species into malaria surveillance activities in sub-Saharan Africa, where 95% of the world’s malaria cases occur. Although malaria caused by infection with Plasmodium falciparum is typically more severe than malaria caused by the non-falciparum Plasmodium species P. malariae , P. ovale spp. and P. vivax , the latter may be more challenging to diagnose, treat, control and ultimately eliminate. The prevalence of non-falciparum species throughout sub-Saharan Africa is poorly defined. Tanzania has geographical heterogeneity in transmission levels but an overall high malaria burden. Methods To estimate the prevalence of malaria species in Mainland Tanzania, we randomly selected 1428 samples from 6005 asymptomatic isolates collected in previous cross-sectional community surveys across four regions and analyzed these by quantitative PCR to detect and identify the Plasmodium species. Results Plasmodium falciparum was the most prevalent species in all samples, with P. malariae and P. ovale spp. detected at a lower prevalence (< 5%) in all four regions; P. vivax was not detected in any sample. Conclusions The results of this study indicate that malaria elimination efforts in Tanzania will need to account for and enhance surveillance of these non-falciparum species. Graphical Abstract

The emergence of resistance against artemisinin combination treatment is a major concern for malaria control. ACTs are recommended as the rescue treatment, however, there is limited evidence as to whether treatment and re-treatment with ACTs select for drug-resistant P. falciparum parasites. Thus, the purpose of the present study is to investigate the impact of (re-)treatment using artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) on the selection of P. falciparum multidrug resistance-1 (Pfmdr1) alleles in clinical settings. P. falciparum positive samples were collected from children aged 12-59 months in a clinical trial in DR Congo and Uganda. Pfmdr1 single nucleotide polymorphisms (SNPs) analysis at codons N86Y, Y184F, and D1246Y were performed at baseline and post-treatment with either AL or ASAQ as a rescue treatment using nested PCR followed by restriction fragment length polymorphism (RFLP) assays. The pre-treatment prevalence of Pfmdr1 N86 and D1246Y varied significantly between the sites, (p>0.001) and (p = 0.013), respectively. There was borderline significant directional selection for Pfmdr1 184F in recurrent malaria infections after treatment with AL in Uganda site (p = 0.05). Pfmdr1 NFD haplotype did not significantly change in post-treatment infections after re-treatment with either AL or ASAQ. Comparison between pre-treatment and post-treatment recurrences did not indicate directional selection of Pfmdr1 N86, D1246 alleles in the pre-RCT, RCT and post-RCT phases in both AL and ASAQ treatment arms. Pfmdr1 86Y was significantly associated with reduced risk of AL treatment failure (RR = 0.34, 95% CI:0.11-1.05, p = 0.04) while no evidence for D1246 allele (RR = 1.02; 95% CI: 0.42-2.47, p = 1.0). Survival estimates showed that the Pfmdr1 alleles had comparable mean-time to PCR-corrected recrudescence and new infections in both AL and ASAQ treatment arms. We found limited impact of (re-)treatment with AL or ASAQ on selection for Pfmdr1 variants and haplotypes associated with resistance to partner drugs. These findings further supplement the evidence use of same or alternative ACTs as a rescue therapy for recurrent P.falciparum infections. Continued monitoring of genetic signatures of resistance is warranted to timely inform malaria (re-)treatment policies and guidelines.

Community-directed treatment with ivermectin (CDTi) is used to eliminate onchocerciasis. However, despite 25 years of annual CDTi in Mahenge, Tanzania, the prevalence of onchocerciasis and onchocerciasis-associated epilepsy remained high in certain rural villages. Therefore, in 2019, bi-annual CDTi was introduced in the area. This study assessed the impact of the programme on the incidence of epilepsy in four villages. Door-to-door epilepsy surveys were conducted prior to (2017/18) and after (2021) implementing a bi-annual CDTi program. All household members were screened for epilepsy symptoms using a validated questionnaire, and suspected cases were examined by a medical doctor to confirm/reject the diagnosis of epilepsy. The prevalence and annual incidence of epilepsy, including nodding syndrome, were calculated with 95% Wilson confidence intervals with continuity correction. The latter was also done for CDTi coverage in 2016 and 2021. Precisely 5,444 and 6,598 persons were screened for epilepsy before and after implementing the intervention. The CDTi coverage of the overall population was 82.3% (95%CI: 81.3-83.2%) in 2021 and sustained in both distribution rounds (81.5% and 76.8%). The coverage was particularly high in children and teenagers aged 6 to 18 years (93.2%, 95%CI: 92.1-94.2%). The epilepsy prevalence remained similar: 3.3% (95%CI: 2.9-3.9%) in 2017/18 versus 3.1% (95%CI: 2.7-3.5%) in 2021. However, the incidence of epilepsy declined from 177.6 (95%CI: 121.2-258.5) in 2015-2017 and 2016-2018 to 45.5 (95%CI: 22.2-89.7) in 2019-2021 per 100,000 persons-years. The incidence of probable nodding syndrome varied from 18.4 (95%CI: 4.7-58.5) to 5.1 (95%CI: 0.3-32.8). None of the nine incidence cases of epilepsy for which information on ivermectin intake was available took ivermectin in the year they developed their first seizures. A bi-annual CDTi programme should be implemented in areas with high prevalence of onchocerciasis and epilepsy. High CDTi coverage among children is particularly important to prevent onchocerciasis-associated epilepsy.

Background HIV and antiretroviral drugs, particularly protease inhibitors and nucleoside reverse transcriptase inhibitors, may increase the risk of Metabolic Syndrome (MetS) among people living with HIV (PLHIV). However, following the introduction of better drugs like dolutegravir, data on the burden of MetS are limited. This study aimed to assess the prevalence of MetS and associated factors among PLHIV on antiretroviral therapy (ART) in Tanzania. Methods This was a cross-sectional study among PLHIV aged ≥ 18 years on antiretroviral therapy for ≥ 1 year at Bugando Medical Centre in Mwanza conducted in 2020. Demographic and healthy-lifestyle-related non-communicable disease risk factors data were collected. Additionally, data on lipid profile, blood glucose, blood pressure, and waist circumference were collected for analysis of MetS according to the International Diabetes Federation criteria. Factors associated with MetS were assessed using logistic regression. A P  ≤ 0.05 was considered statistically significant. Results Data for 223 participants were analyzed. The mean (SD) age was 44 (± 12) years and 79.8% (178) were females. A majority 78% (174) were on a tenofovir, lamivudine,and dolutegravir regimen. About 12.1% (27) were either current or past smokers, 45.3% (101) were past alcohol drinkers, 22.9% (51) were current drinkers, 12.1% (27) reported taking ≥ 5 servings of vegetables and fruits per day and 5.8% (13) were physically inactive. The prevalence of MetS was 22.9%. The only factors that were associated with Mets were fat mass index and adequate intake of vegetables and fruits, (adjusted odds ratio (aOR) 2.9, 95% CI 1.0, 7.9, P =  0.04) and (aOR1.2, 95% CI 1.0, 1.3, P =  0.02), respectively). Conclusion The prevalence of MetS remains high among PLHIV. Adiposity and adequate fruit and vegetable intake increased the risk. The introduction of new ART regimens shows no effect on MetS prevalence. Research is needed to understand how lifestyle changes could reduce MetS in PLHIV.

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

Background 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).