Malaria Species Positivity Rates Among Symptomatic Individuals Across Regions of Differing Transmission Intensities in Mainland Tanzania.

BACKGROUND: Recent data indicate that non-Plasmodium falciparum species may be more prevalent than thought in sub-Saharan Africa. Although Plasmodium malariae, Plasmodium ovale spp., and Plasmodium vivax are less severe than P. falciparum, treatment and control are more challenging, and their geographic distributions are not well characterized. METHODS: We randomly selected 3284 of 12 845 samples collected from cross-sectional surveys in 100 health facilities across 10 regions of Mainland Tanzania and performed quantitative real-time PCR to determine presence and parasitemia of each malaria species. RESULTS: P. falciparum was most prevalent, but P. malariae and P. ovale were found in all but 1 region, with high levels (>5%) of P. ovale in 7 regions. The highest P. malariae positivity rate was 4.5% in Mara and 8 regions had positivity rates ≥1%. We only detected 3 P. vivax infections, all in Kilimanjaro. While most nonfalciparum malaria-positive samples were coinfected with P. falciparum, 23.6% (n = 13 of 55) of P. malariae and 14.7% (n = 24 of 163) of P. ovale spp. were monoinfections. CONCLUSIONS: P. falciparum remains by far the largest threat, but our data indicate that malaria elimination efforts in Tanzania will require increased surveillance and improved understanding of the biology of nonfalciparum species.

High prevalence and risk of malaria among asymptomatic individuals from villages with high prevalence of artemisinin partial resistance in Kyerwa district of Kagera region, north-western Tanzania.

BACKGROUND: Although Tanzania adopted and has been implementing effective interventions to control and eventually eliminate malaria, the disease is still a leading public health problem, and the country experiences heterogeneous transmission. Recent studies reported the emergence of parasites with artemisinin partial resistance (ART-R) in Kagera region with high prevalence (> 10.0%) in two districts of Karagwe and Kyerwa. This study assessed the prevalence and predictors/risk of malaria infections among asymptomatic individuals living in a hyperendemic area where ART-R has emerged in Kyerwa District of Kagera region, north-western Tanzania. METHODS: This was a community-based cross-sectional survey which was conducted in July and August 2023 and involved individuals aged ≥ 6 months from five villages in Kyerwa district. Demographic, anthropometric, clinical, parasitological, type of house inhabited and socio-economic status (SES) data were collected using electronic capture tools run on Open Data Kit (ODK) software. Predictors/risks of malaria infections were determined by univariate and multivariate logistic regression, and the results were presented as crude (cORs) and adjusted odds ratios (aORs), with 95% confidence intervals (CIs). RESULTS: Overall, 4454 individuals were tested using rapid diagnostic tests (RDTs), and 1979 (44.4%) had positive results. The prevalence of malaria infections ranged from 14.4% to 68.5% and varied significantly among the villages (p < 0.001). The prevalence and odds of infections were significantly higher in males (aOR = 1.28, 95% CI 1.08 -1.51, p = 0.003), school children (aged 5-≤10 years (aOR = 3.88, 95% CI 3.07-4.91, p < 0.001) and 10-≤15 years (aOR = 4.06, 95% CI 3.22-5.13, p < 0.001)) and among individuals who were not using bed nets (aOR = 1.22, 95% CI 1.03-1.46, p = 0.024). The odds of malaria infections were also higher in individuals with lower SES (aOR = 1.42, 95% CI 1.17-1.72, p < 0.001), and living in houses without windows (aOR = 2.08, 95% CI 1.46-2.96, p < 0.001), partially open (aOR = 1.33, 95% CI 1.11-1.58, p = 0.002) or fully open windows (aOR = 1.30, 95%CI 1.05-1.61, p = 0.015). CONCLUSION: The five villages had a high prevalence of malaria infections and heterogeneity at micro-geographic levels. Groups with higher odds of malaria infections included school children, males, and individuals with low SES, living in poorly constructed houses or non-bed net users. These are important baseline data from an area with high prevalence of parasites with ART-R and will be useful in planning interventions for these groups, and in future studies to monitor the trends and potential spread of such parasites, and in designing a response to ART-R.

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.

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.

Disability assessment among persons with epilepsy in Mahenge, an onchocerciasis-endemic area in Tanzania: A cross-sectional study.

BACKGROUND: A high prevalence of epilepsy has been observed in the onchocerciasis-endemic focus of Mahenge, Tanzania. This study sought to assess the degree of disability experienced by persons with epilepsy (PWE) in Mahenge and identify associations with sociodemographic and clinical features. METHOD: This cross-sectional study was conducted in Mahenge, Tanzania, between February and July 2020. PWE were recruited from the Mahenge epilepsy clinic and four neighbouring rural villages (Mdindo, Mzogezi, Mzelezi and Sali). Data were collected using the 36-item version of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) questionnaire for adults. For children aged 5-17 years, we used the Module on Child Functioning developed by UNICEF and the Washington Group. Questionnaires were administered by trained research assistants. Descriptive statistics were performed, and multivariable analyses (gamma and logistic regressions) were conducted. RESULTS: A total of 321 adults (45.5% males) and 48 children (55.3% males) with epilepsy participated. The overall median WHODAS 2.0 score was 4.8% (IQR: 0.9-18.9). The most affected disability domain was 'participating in the society' (median score: 12.5%, IQR: 0-29.2). Fifteen (31.3%) of the children with epilepsy had a disability in at least one domain of the child functioning module, with the 'accepting change' domain harbouring the highest proportion of disabled children (12.5%). Higher seizure frequency and longer epilepsy duration were associated with more disability. CONCLUSION: PWE in Mahenge experience variable degrees of disability. The affected domains indicate the need for societal rehabilitation of PWE in various community and/or social activities. Peer-support groups were instituted at the study sites to address these needs.

Metabolic syndrome among people living with HIV on antiretroviral therapy in Mwanza, Tanzania.

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.

A peer support group intervention to decrease epilepsy-related stigma in an onchocerciasis-endemic area in Mahenge, Tanzania: A pilot study.

A high burden of epilepsy has been reported in sub-Saharan Africa (SSA) particularly in onchocerciasis endemic areas. To improve the quality of life of persons with epilepsy (PWE) in Mahenge, an onchocerciasis-endemic area in Tanzania, we established peer support groups (PSG) in two out of four rural villages (Mdindo, Msogezi, Mzelezi and Sali). One year later (between February and July 2020), we carried out a cross-sectional survey among PWE and their caregivers in the four rural villages with the aim of comparing perceived stigma among PWE in study sites with and without PSG. Perceived stigma was measured using the validated Kilifi stigma scale of epilepsy (KSSE), whose total score ranges from 0-30. A generalized linear mixed regression model was used to identify factors associated with high stigma scores. A total of 161 PWE participated in the study; 76 (47.2%) resided in villages where a PSG intervention was implemented. The overall mean stigma score was 3.7 ±â€¯4.6, with no significant difference between villages with and without PSG (p = 0.537). Only one PWE (0.6%) scored above 20 (very high perceived stigma). Experiencing more seizures during the past week (Coef = 1.013 [0.568, 1.457]), having attended school (Coef = 1.821 0.345, 3.297], and a history of physical abuse (Coef = 3.200 [0.574, 5.827]) were associated with higher stigma scores. Perceived stigma in rural villages in Mahenge is a major public health problem. A follow-up study is needed to determine the medium- to long-term effect of the PSG intervention on perceived epilepsy-related stigma.

High cure rates and tolerability of artesunate-amodiaquine and dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Kibaha and Kigoma, Tanzania.

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

Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated malaria and prevalence of Pfk13 and Pfmdr1 polymorphisms after a decade of using artemisinin-based combination therapy in mainland Tanzania.

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

Pattern of all-causes and cause-specific mortality in an area with progressively declining malaria burden in Korogwe district, north-eastern Tanzania.

BACKGROUND: Although death records are useful for planning and monitoring health interventions, such information is limited in most developing countries. Verbal autopsy (VA) interviews are alternatively used to determine causes of death in places without or with incomplete hospital records. This study was conducted to determine all causes and cause-specific mortality in Korogwe health and demographic surveillance system (HDSS) undertaken in Korogwe district, northeastern Tanzania. METHODS: The study was conducted from January 2006 to December 2012 in 14 villages under Korogwe HDSS. Vital events such as births, deaths and migrations were routinely updated quarterly. A standard VA questionnaire was administered to parents/close relatives of the deceased to determine cause of death. RESULTS: Overall, 1325 deaths of individuals with median age of 46 years were recorded in a population with 170,471.4 person years observed (PY). Crude mortality rate was 7.8 per 1000 PY (95% CI 7.2-8.4) and the highest rate was observed in infants (77.9 per 1000 PY; 95% CI 67.4-90.0). The overall mortality increased between 2006 and 2007, followed by a slight decline up to 2011, with the highest decrease observed in 2012. Causes of deaths were established in 942 (71.1%) deaths and malaria (198 deaths, 21.0%) was the leading cause of death in all age groups except adults (15-59 years). HIV/AIDS (17.6%, n = 365) was the leading cause of death in individuals aged 15-59 years followed by malaria (13.9%) and tuberculosis. Non-communicable diseases (NCDs) including stroke, hypertension, cancer, and cardiac failure caused majority of deaths in elderly (60 years and above) accounting for 37.1% (n = 348) of all deaths, although malaria was the single leading cause of death in this group (16.6%). CONCLUSION: The study showed a significant decline of deaths in the Korogwe HDSS site and malaria was the main cause of death in all age groups (except adults, aged 15-59 years) while HIV/AIDS and NCDs were the main causes in adults and elderly, respectively. Further surveillance is required to monitor and document changes in cause-specific mortality as malaria transmission continues to decline in this and other parts of Tanzania.

Trends of Plasmodium falciparum prevalence in two communities of Muheza district North-eastern Tanzania: correlation between parasite prevalence, malaria interventions and rainfall in the context of re-emergence of malaria after two decades of progressively declining transmission.

BACKGROUND: Although the recent decline of malaria burden in some African countries has been attributed to a scale-up of interventions, such as bed nets (insecticide-treated bed nets, ITNs/long-lasting insecticidal nets, LLINs), the contribution of other factors to these changes has not been rigorously assessed. This study assessed the trends of Plasmodium falciparum prevalence in Magoda (1992-2017) and Mpapayu (1998-2017) villages of Muheza district, North-eastern Tanzania, in relation to changes in the levels of different interventions and rainfall patterns. METHODS: Individuals aged 0-19 years were recruited in cross-sectional surveys to determine the prevalence of P. falciparum infections in relation to different malaria interventions deployed, particularly bed nets and anti-malarial drugs. Trends and patterns of rainfall in Muheza for 35 years (from 1981 to 2016) were assessed to determine changes in the amount and pattern of rainfall and their possible impacts on P. falciparum prevalence besides of those ascribed to interventions. RESULTS: High prevalence (84-54%) was reported between 1992 and 2000 in Magoda, and 1998 and 2000 in Mpapayu, but it declined sharply from 2001 to 2004 (from 52.0 to 25.0%), followed by a progressive decline between 2008 and 2012 (to ≤ 7% in both villages). However, the prevalence increased significantly from 2013 to 2016 reaching ≥ 20.0% in 2016 (both villages), but declined in the two villages to ≤ 13% in 2017. Overall and age specific P. falciparum prevalence decreased in both villages over the years but with a peak prevalence shifting from children aged 5-9 years to those aged 10-19 years from 2008 onwards. Bed net coverage increased from < 4% in 1998 to > 98% in 2001 and was ≥ 85.0% in 2004 in both villages; followed by fluctuations with coverage ranging from 35.0 to ≤ 98% between 2008 and 2017. The 12-month weighted anomaly standardized precipitation index showed a marked rainfall deficit in 1990-1996 and 1999-2010 coinciding with declining prevalence and despite relatively high bed net coverage from 2000. From 1992, the risk of infection decreased steadily up to 2013 when the lowest risk was observed (RR = 0.07; 95% CI 0.06-0.08, P < 0.001), but it was significantly higher during periods with positive rainfall anomalies (RR = 2.79; 95% CI 2.23-3.50, P < 0.001). The risk was lower among individuals not owning bed nets compared to those with nets (RR = 1.35; 95% CI 1.22-1.49, P < 0.001). CONCLUSIONS: A decline in prevalence up to 2012 and resurgence thereafter was likely associated with changes in monthly rainfall, offset against changing malaria interventions. A sustained surveillance covering multiple factors needs to be undertaken and climate must be taken into consideration when relating control interventions to malaria prevalence.

Comparison of visual and automated Deki Reader interpretation of malaria rapid diagnostic tests in rural Tanzanian military health facilities.

BACKGROUND: Although microscopy is a standard diagnostic tool for malaria and the gold standard, it is infrequently used because of unavailability of laboratory facilities and the absence of skilled readers in poor resource settings. Malaria rapid diagnostic tests (RDT) are currently used instead of or as an adjunct to microscopy. However, at very low parasitaemia (usually < 100 asexual parasites/µl), the test line on malaria rapid diagnostic tests can be faint and consequently hard to visualize and this may potentially affect the interpretation of the test results. Fio Corporation (Canada), developed an automated RDT reader named Deki Reader™ for automatic analysis and interpretation of rapid diagnostic tests. This study aimed to compare visual assessment and automated Deki Reader evaluations to interpret malaria rapid diagnostic tests against microscopy. Unlike in the previous studies where expert laboratory technicians interpreted the test results visually and operated the device, in this study low cadre health care workers who have not attended any formal professional training in laboratory sciences were employed. METHODS: Finger prick blood from 1293 outpatients with fever was tested for malaria using RDT and Giemsa-stained microscopy for thick and thin blood smears. Blood samples for RDTs were processed according to manufacturers' instructions automated in the Deki Reader. Results of malaria diagnoses were compared between visual and the automated devise reading of RDT and microscopy. RESULTS: The sensitivity of malaria rapid diagnostic test results interpreted by the Deki Reader was 94.1% and that of visual interpretation was 93.9%. The specificity of malaria rapid diagnostic test results was 71.8% and that of human interpretation was 72.0%. The positive predictive value of malaria RDT results by the Deki Reader and visual interpretation was 75.8 and 75.4%, respectively, while the negative predictive values were 92.8 and 92.4%, respectively. The accuracy of RDT as interpreted by DR and visually was 82.6 and 82.1%, respectively. CONCLUSION: There was no significant difference in performance of RDTs interpreted by either automated DR or visually by unskilled health workers. However, despite the similarities in performance parameters, the device has proven useful because it provides stepwise guidance on processing RDT, data transfer and reporting.

Deployment and use of mobile phone technology for real-time reporting of fever cases and malaria treatment failure in areas of declining malaria transmission in Muheza district north-eastern Tanzania.

BACKGROUND: Early detection of febrile illnesses at community level is essential for improved malaria case management and control. Currently, mobile phone-based technology has been commonly used to collect and transfer health information and services in different settings. This study assessed the applicability of mobile phone-based technology in real-time reporting of fever cases and management of malaria by village health workers (VHWs) in north-eastern Tanzania. METHODS: The community mobile phone-based disease surveillance and treatment for malaria (ComDSTM) platform, combined with mobile phones and web applications, was developed and implemented in three villages and one dispensary in Muheza district from November 2013 to October 2014. A baseline census was conducted in May 2013. The data were uploaded on a web-based database and updated during follow-up home visits by VHWs. Active and passive case detection (ACD, PCD) of febrile cases were done by VHWs and cases found positive by malaria rapid diagnostic test (RDT) were given the first dose of artemether-lumefantrine (AL) at the dispensary. Each patient was visited at home by VHWs daily for the first 3 days to supervise intake of anti-malarial and on day 7 to monitor the recovery process. The data were captured and transmitted to the database using mobile phones. RESULTS: The baseline population in the three villages was 2934 in 678 households. A total of 1907 febrile cases were recorded by VHWs and 1828 (95.9%) were captured using mobile phones. At the dispensary, 1778 (93.2%) febrile cases were registered and of these, 84.2% were captured through PCD. Positivity rates were 48.2 and 45.8% by RDT and microscopy, respectively. Nine cases had treatment failure reported on day 7 post-treatment and adherence to treatment was 98%. One patient with severe febrile illness was referred to Muheza district hospital. CONCLUSION: The study showed that mobile phone-based technology can be successfully used by VHWs in surveillance and timely reporting of fever episodes and monitoring of treatment failure in remote areas. Further optimization and scaling-up will be required to utilize the tools for improved malaria case management and drug resistance surveillance.

Relationships between sickle cell trait, malaria, and educational outcomes in Tanzania.

BACKGROUND: Sickle Cell Trait (SCT) has been shown to be protective against malaria. A growing literature suggests that malaria exposure can reduce educational attainment. This study assessed the relationship and interactions between malaria, SCT and educational attainment in north-eastern Tanzania. METHODS: Seven hundred sixty seven children were selected from a list of individuals screened for SCT. Febrile illness and malaria incidence were monitored from January 2006 to December 2013 by community health workers. Education outcomes were extracted from the Korogwe Health and Demographic Surveillance system in 2015. The primary independent variables were malaria and SCT. The association between SCT and the number of fever and malaria episodes from 2006 to 2013 was analyzed. Main outcomes of interest were school enrolment and educational attainment in 2015. RESULTS: SCT was not associated with school enrolment (adjusted OR 1.42, 95% CI [0.593,3.412]) or highest grade attained (adjusted grade difference 0.0597, 95% CI [-0.567, 0.686]). SCT was associated with a 29% reduction in malaria incidence (adjusted IRR 0.71, 95% CI [0.526, 0.959]) but not with fever incidence (adjusted IRR 0.905, 95% CI [0.709-1.154]). In subgroup analysis of individuals with SCT, malaria exposure was associated with reduced school enrollment (adjusted OR 0.431, 95% CI [0.212, 0.877]). CONCLUSIONS: SCT appears to reduce incidence of malaria. Overall, children with SCT do not appear to attend more years of school; however children who get malaria despite SCT appear to have lower levels of enrolment in education than their peers.

Acceptability of malaria rapid diagnostic tests administered by village health workers in Pangani District, North eastern Tanzania.

BACKGROUND: Malaria continues to top the list of the ten most threatening diseases to child survival in Tanzania. The country has a functional policy for appropriate case management of malaria with rapid diagnostic tests (RDTs) from hospital level all the way to dispensaries, which are the first points of healthcare services in the national referral system. However, access to these health services in Tanzania is limited, especially in rural areas. Formalization of trained village health workers (VHWs) can strengthen and extend the scope of public health services, including diagnosis and management of uncomplicated malaria in resource-constrained settings. Despite long experience with VHWs in various health interventions, Tanzania has not yet formalized its involvement in malaria case management. This study presents evidence on acceptability of RDTs used by VHWs in rural northeastern Tanzania. METHODS: A cross-sectional study using quantitative and qualitative approaches was conducted between March and May 2012 in Pangani district, northeastern Tanzania, on community perceptions, practices and acceptance of RDTs used by VHWs. RESULTS: Among 346 caregivers of children under 5 years old, no evidence was found of differences in awareness of HIV rapid diagnostic tests and RDTs (54 vs. 46 %, p = 0.134). Of all respondents, 92 % expressed trust in RDT results, 96 % reported readiness to accept RDTs by VHWs, while 92 % expressed willingness to contribute towards the cost of RDTs used by VHWs. Qualitative results matched positive perceptions, attitudes and acceptance of mothers towards the use of RDTs by VHWs reported in the household surveys. Appropriate training, reliable supplies, affordability and close supervision emerged as important recommendations for implementation of RDTs by VHWs. CONCLUSION: RDTs implemented by VHWs are acceptable to rural communities in northeastern Tanzania. While families are willing to contribute towards costs of sustaining these services, policy decisions for scaling-up will need to consider the available and innovative lessons for successful universally accessible and acceptable services in keeping with national health policy and sustainable development goals.

A systematic review of risk factors associated with road traffic crashes and injuries among commercial motorcycle drivers.

To effectively reduce road traffic crashes (RTCs) and injuries interventions should be based on firm evidence regarding risk factors of RTCs and injuries in that specific population. Therefore, we undertook a systematic review to determine risk factors of RTCs and injuries among commercial motorcycle drivers. Searches were performed from inception to May 2022 in Medline, Embase, Cochrane Library, Web of Science Core Collection, PsycINFO and Cinahl, along with registers and reference lists. Inclusion criteria were commercial motorcycle drivers, quantitative observational studies, and RTCs and injuries. The search resulted in 1546 articles, of which 20 met the relevance and quality criteria. Of the 20 articles, 17 were cross-sectional, 2 were case-control studies, and one was a cohort study. Close to half of all articles (9) came from sub-Saharan Africa. Risk factors with consistent association with RTCs and injuries were young age, low education level, alcohol consumption, speeding, mobile phone use, non-helmet use, risky driving behaviours and long working hours. There was inconclusive evidence for driver's training, work schedules, motorcycle ownership, experience, dependents number, and marital status. More robust designs such as case-control or longitudinal studies are required to gain a comprehensive understanding of the antecedents of RTCs among commercial motorcycle drivers.

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.

Prevalence of non-falciparum malaria infections among asymptomatic individuals in four regions of Mainland Tanzania.

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.