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Temporal Trends in Artemisinin Partial Resistance and Other Antimalarial Drug Mutations in <i>Plasmodium falciparum</i> from Kagera Region, Northwestern Tanzania, 2021–2023
) exhibiting marked spatial heterogeneity, peaking at 38.1% and 48.1%, respectively, in eastern districts. These findings reveal micro-geographic heterogeneity in resistance and ongoing spread, emphasizing the need for district-level surveillance to detect emerging hotspots and guide interventions. Sustained molecular monitoring is critical to inform treatment policy, preserve ACT efficacy, and mitigate the risk of widespread resistance in East Africa.
Implementation and effectiveness of intermittent preventive treatment in school aged children using dihydroartemisinin-piperaquine to reduce malaria burden: an implementation research of a cluster randomised trial in Tanzania
Background: In malaria endemic areas, malaria is a major contributor for half of the mortality in school-aged children (5-15 years old). Most infections are asymptomatic, contributing to anaemia, poor cognitive development, and reduced school performance. School-aged children often show low adherence to preventive and curative measures, and malaria control programs rarely target this group. We evaluated the pilot implementation of intermittent preventive treatment of malaria in schoolchildren (IPTsc) using Dihydroartemisinin-Piperaquine (DP) delivered by schoolteachers, to assess the implementation feasibility and effectiveness on asymptomatic and clinical malaria in a high endemic area in Tanzania. Methods: This study used a cluster-randomised design in which each ward (cluster) was assigned to implement IPTsc or serve as a control. All schoolchildren in primary schools under the intervention arm received three annual rounds of DP aligned with malaria transmission seasons. The primary implementation end point was IPTsc coverage, defined as the proportion of enrolled schoolchildren completing the full DP therapeutic course. For the effectiveness, 12 wards were randomly selected per arm, and one school per ward contributed outcome data. The primary effectiveness endpoints were (1) protective effectiveness of IPTsc on clinical malaria incidence and (2) reduction in parasite prevalence. Data were analysed using cluster-adjusted intention-to-treat (ITT) methods. The study was conducted from February 2020 to July 2021 and is registered with ClinicalTrials.gov (NCT04245033). Findings: Three rounds of DP dispensing covered 127 schools with more than 73,000 schoolchildren. IPTsc coverage reached 77% (range: 69-83%), 73% (64-81%), and 80% (76-85%) in August 2020, November 2020 and March 2021, respectively. DP was well tolerated. In the effectiveness evaluation, 1971 schoolchildren were enrolled in DP arm and 1781 in control arm. After one year, IPTsc reduced clinical malaria incidence by 41% overall (95% CI: 31-49; p < 0.001) and by 54% (95% CI: 44.2-62.6; p < 0.001) in high endemic strata (≥10% baseline prevalence). Parasite prevalence decreased by 81% overall (95% CI: 56.3-100; p < 0.001) ranging from 58% (95% CI: 10.9-100; p = 0.18) in low endemic to 83% (95% CI: 62.7-100; p < 0.001) in high endemic strata. Interpretation: Large scale implementation of IPTsc achieved impact comparable to randomised trials and was operationally feasible and well accepted by communities and teachers. This study sets a benchmark for school-based malaria chemoprevention in Tanzania and provides groundwork for national policy adoption. Funding: The Global Fund, through the Ministry of Health, Tanzania, funded the study.
Prevalence and risk factors associated with infections caused by Plasmodium parasites at micro-geographic level in three villages of Muheza district in Tanga region, north-eastern Tanzania
BACKGROUND: Malaria burden in Tanzania has recently become heterogeneous, with a higher burden in some regions than in others. This suggests that stratification of transmission intensities and predictors of risk factors associated with infections caused by Plasmodium parasites is critical to guide proper use of the current and future interventions. This study assessed the prevalence and predictors of /risk factors associated with Plasmodium parasite infections at micro-geographic levels in three villages of Muheza district, Tanga region, north-eastern Tanzania. METHODS: A cross-sectional community survey was conducted in June 2021 and covered three villages: Magoda, Mpapayu, and Mamboleo from Muheza district in Tanga region. Finger prick blood samples were taken for parasite detection using microscopy and rapid diagnostic tests (RDTs). A generalized estimating equation (GEE) was used to determine the association between the prevalence and predictors/risk factors of Plasmodium parasite infections. RESULTS: The survey recruited 1134 individuals from 380 households and most of them (95.2%) reported that they slept under bed nets the night before the survey. By both microscopy and RDTs, the prevalence of infections caused by Plasmodium parasite was 19.2% and 24.3%, respectively. The prevalence was significantly higher among school children (aged 5 to < 15 years, with 27.3% by microscopy and 37.6% by RDTs) compared to under-fives and adults (aged ≥ 15 years) (p < 0.001). Participants from households with closed eaves were less likely to be infected by Plasmodium parasites as detected by RDTs (AOR = 0.91; 95% CI, 0.85-0.97; p < 0.001). Among the three villages, the prevalence by microscopy ranged from 14.7% to 24.6% and varied significantly across villages, indicating high heterogeneity and random distribution of malaria at micro-geographic levels (p = 0.001). For RDTs, the prevalence ranged from 24.1% to 34.9%, but the differences of the prevalence in the three villages were not statistically significant (p = 0.422). CONCLUSION: The study villages had a high prevalence, and the risk of Plasmodium parasite infections was higher in school children (aged 5 to < 15 years). The prevalence and risk of infections varied significantly among the villages which are located next to each other suggesting high variations at micro-geographic levels. These findings will be useful in future planning of malaria stratification and targeting of interventions to high-risk groups and areas, as part of the strategies for malaria elimination by 2030.
Varying Malaria Rapid Diagnostic Test Accuracy by Regional Transmission Level and Demographics in Tanzania
Malaria remains a significant global health burden, with approximately 263 million cases across 83 countries. It's essential for malarial infection control to quickly and accurately detect cases. Given the widespread use of malaria rapid diagnostic testing (mRDTs) for case management and surveillance, it's essential to understand test reliability. Clarifying how mRDT results differ from qPCR results, and the nature of additional variance by test manufacturer, will be useful for reducing measurement bias. In comparing 3 national standard mRDTs and a research mRDT with qPCR results from a 2021 cross-sectional study in Tanzania, differences were found by age, gender and regional malaria transmission rate. The research test overall underperformed, with poor sensitivity across transmission strata. In comparing the research mRDT to standard mRDTs, odds ratios suggested transmission intensity may affect mRDT agreement and diagnostic performance. These results offer pertinent information on test accuracy and decrease outcome misclassification for malaria prevalence.
Performance of rapid diagnostic tests, microscopy, and qPCR for detection of Plasmodium parasites among community members with or without symptoms of malaria in villages located in North-western Tanzania
BACKGROUND: Despite the implementation of different control interventions, Plasmodium parasite infections in the communities (among asymptomatic and symptomatic individuals) still play a crucial role in sustaining malaria transmission. This study evaluated the performance of rapid diagnostic tests (RDTs), microscopy, and quantitative PCR (qPCR) in detecting Plasmodium parasites among community members in five villages of Kyerwa district, Kagera region in north-western Tanzania. METHODS: The study used samples and data collected during a community cross-sectional survey of asymptomatic and symptomatic participants (n = 4454) aged ≥ 6 months which was conducted in July and August 2023. Plasmodium parasites were detected using RDTs, microscopy, and qPCR (targeting 18S rRNA gene). The performance of RDTs and microscopy was assessed by sensitivity, specificity, and predictive values, using qPCR as the reference method. Factors affecting the accuracy of these methods were determined using a multivariate logistic regression model. RESULTS: The prevalence of Plasmodium parasite infections among 4454 participants was 44.4%, 32.1%, and 39.8% by RDTs, microscopy, and qPCR, respectively. The prevalence of Plasmodium falciparum, Plasmodium malariae and Plasmodium ovale mono-infection by microscopy was 28.7%, 0.2%, and 0.3%, while by qPCR it was 35.3%, 0.4% and 0.5%, respectively. The geometric mean parasite densities (GMPDs) by microscopy were 642 (95% confidence intervals (CI) = 570-723), 126 (95% CI = 98-162), and 124 (95% CI = 82-160) asexual parasites/µL for P. falciparum, P. ovale spp., and P. malariae, respectively. By qPCR, the GMPDs were 1180 (95% CI = 1032-1349) parasites/µL for P. falciparum, 44 (95% CI = 32-61) for P. ovale spp., and 50 (95% CI = 29-89) for P. malariae. The sensitivity and specificity of RDTs were 94.0% (95% CI = 92.8-95.1%) and 87.5% (95% CI = 86.2-88.7%), respectively, whereas those of microscopy were 74.6% (95% CI = 72.5-76.6%) and 95.2% (95% CI = 94.3-96.0%), respectively. The sensitivity of RDTs, and microscopy was low at very low parasitaemia (< 100 parasites/μL) but increased significantly with increasing parasitaemia, reaching ≥ 99.6% at > 10,000 parasites/μL (p < 0.001). CONCLUSION: High prevalence of Plasmodium parasites was detected, and the performance of RDTs and qPCR was comparable, but microscopy had lower performance. Higher sensitivity of RDTs compared to microscopy indicates that RDTs are effective for detection of infections caused by Plasmodium parasites in routine case management and surveillance in this area with confirmed artemisinin partial resistance (ART-R) and can be utilized in the ongoing plans to develop a response to ART-R.
Trends of malaria prevalence among individuals from rural communities in three regions with varying transmission intensities in Mainland Tanzania; Data from 2021 - 2023 community cross-sectional surveys
Abstract Background Recent reports showed the persistence of malaria transmission and disease burden in rural communities, which have limited the impact of ongoing control and elimination strategies. This study investigated the trends of malaria prevalence among community members from three regions of Mainland Tanzania with varying transmission intensities. Methods Community surveys were conducted from 2021 to 2023 and involved individuals aged ≥6 months in three regions Kigoma and Ruvuma (with high malaria transmission intensities) and Tanga (moderate transmission). Interviews were conducted using structured questionnaires, to collect anthropometric, clinical, parasitological (testing for malaria using rapid diagnostic tests (RDTs), type of house and socio-economic status (SES) data. Modified Poisson regression was used to identify factors associated with malaria infections and the results were presented as crude (cPR) and adjusted prevalence ratios (aPR). Results Malaria infections by RDTs were detected in 1,896 (23.2%, n=8,166) individuals, with significant variations across regions and years (22.9% in 2021, 20.6% in 2022, and 26.9% in 2023; p<0.001). The highest prevalence of malaria infections was in Kigoma in 2023 (35.6%) while the lowest was in Tanga in 2022 (10.5%). School children (5 – <15 years) had significantly higher prevalence (38.2% in 2021, 26.2% in 2022, and 34.4% in 2023 (p<0.001) as did males (26.7% in 2021, 25.4% in 2022 and 31.2% in 2023, p<0.001). Higher likelihood of malaria infections was in school children (aPR: 1.94, 95% CI: 1.67 – 2.25, p<0.001), males (aPR=1.24 95%CI: 1.14–1.34, p<0.001), individuals living in traditional houses (aPR=1.14, 95% CI: 1.01 – 1.28, p = 0.037), among individuals with moderate (aPR=1.27, 95% CI: 1.13 – 1.43, p<0.001) or low SES (aPR = 1.39, 95% CI: 1.24 – 1.55, p<0.001), and those with fever at presentation (axillary temperature ≥37.5°C; aPR = 1.34, 95% CI: 1.09 – 1.64, p = 0.005) or fever history within 48 hours before the survey (aPR = 3.55, 95% CI: 3.26–3.87, p<0.001). The likelihood of infections was also higher in Ruvuma (aPR=1.98, 95%CI: 1.77–2.21, p<0.001) and Kigoma (aPR=1.28, 95%CI: 1.15–1.42, p<0.001) regions compared to Tanga. The likelihood of malaria infections was similar among participants based on bed net ownership (aPR: 1.27, 95%CI: 0.80 – 2.01, p = 0.306) or use (aPR: 1.01, 95%CI: 0.64 – 1.50, p=0.920). Conclusion The study showed spatial and temporal variations of malaria prevalence, with the highest prevalence in 2023 and the lowest in 2022. Groups at higher risk of malaria infections included school children, males, participants with fever, low or moderate SES, and those who lived in traditional houses. Targeted interventions are urgently needed for areas with persistently high transmission and vulnerable groups, particularly in rural communities.
Genetic diversity of Plasmodium falciparum reticulocyte binding protein homologue-5, which is a potential malaria vaccine candidate: baseline data from areas of varying malaria endemicity in Mainland Tanzania
BACKGROUND: The limited efficacy of the two recently approved malaria vaccines, RTS,S/AS01 and R21/Matrix- M™, highlights the need for alternative vaccine candidate genes. Plasmodium falciparum Reticulocyte Binding Protein Homologue 5 (Pfrh5) is a promising malaria vaccine candidate, given its limited polymorphism, its essential role in parasite survival, a lack of immune selection pressure and higher efficacy against multiple parasites strains. This study evaluated the genetic diversity of Pfrh5 gene among parasites from regions with varying malaria transmission intensities in Mainland Tanzania, to generate baseline data for this potential malaria vaccine candidate. METHODS: ), Wright's inbreeding coefficient (Fws), Principal component analysis (PCA), nucleotide diversity (π), haplotype network, haplotype diversity (Hd), Tajima's D, and Linkage disequilibrium (LD) were used to assess the diversity of the gene. RESULTS: value was 0.015. Low nucleotide diversity values were observed across the study sites (mean π = 0.00056). A total of 27 haplotypes were observed among the 313 monoclonal samples and under-fives exhibited higher haplotype counts. The Pf3D7 was detected as Hap_1, which occurred in 16/313 (5.1%) monoclonal sequences. Negative Tajima's D values were observed among the parasite populations in all the study sites. CONCLUSION: Low levels of polymorphism in the pfrh5 gene were observed based on low nucleotide and haplotype diversity, a lack of population structure and negative Tajima's D values. This study provides essential data on the diversity of the Pfrh5 gene indicating that it can be considered in the development of the next generation malaria vaccines. Robust and intensive studies of this and other candidate genes are crucial to support the prioritization of the Pfrh5 gene for potential inclusion in a broadly cross-protective malaria vaccine.
Prevalence and drivers of malaria infection among asymptomatic and symptomatic community members in five regions with varying transmission intensity in mainland Tanzania
BACKGROUND: Despite implementation of effective interventions in the past two decades, malaria is still a major public health problem in Tanzania. This study assessed the prevalence and drivers of malaria infections among symptomatic and asymptomatic members of selected communities from five regions with varying endemicity in mainland Tanzania. METHODS: A cross-sectional community survey was conducted in five districts, including one district/region in Kagera, Kigoma, Njombe, Ruvuma and Tanga from July to August 2023. Participants aged ≥ 6 months were recruited and tested using rapid diagnostic tests (RDTs). Demographic, anthropometric, clinical, parasitological, type of house, and socio-economic status (SES) data were captured using structured questionnaires. Associations between parasite prevalence and potential drivers were determined by logistic regression, and the results were presented as crude (cOR) and adjusted odds ratios (aOR), with 95% confidence intervals (CIs). RESULTS: Among 10,228 individuals tested, 3515 (34.4%) had positive results by RDTs. The prevalence of malaria varied from 21.6% in Tanga to 44.4% in Kagera, and from 14.4% to 68.5% among the different villages (P < 0.001). The odds of malaria infections were higher in males (aOR = 1.32, 95% CI 1.19-1.48, P < 0.001), under-fives (aOR = 2.02, 95% CI 1.74-2.40, P < 0.001), schoolchildren [aged 5-9 years (aOR = 3.23, 95% CI 1.19-1.48, P < 0.001) and 10-14 years (aOR = 3.53, 95% CI 3.03-4.11, P < 0.001)], and non-bednet users (aOR = 1.49, 95% CI 1.29-1.72, P < 0.001). Individuals from households with low SES (aOR = 1.40, 95% CI 1.16-1.69, P < 0.001), or living in houses with open windows (aOR = 1.24, 95% CI 1.06-1.45, P < 0.001) and/or holes on the walls (aOR = 1.43, 95% CI 1.14-1.81, P < 0.001) also had higher odds. CONCLUSIONS: Malaria prevalence varied widely across regions and villages, and the odds of infections were higher in males, schoolchildren, non-bednet users, and individuals with low SES or living in houses with open windows and/or holes on the walls. The identified vulnerable groups and hotspots should be targeted with specific interventions to reduce the disease burden and support the ongoing malaria elimination efforts in Tanzania.
Mapping of the country-wide prevalence of non-malarial febrile illnesses in areas with varying malaria transmission intensities in Mainland Tanzania
Abstract Recent reports revealed a declining malaria burden, but non-malaria febrile illnesses (NMFIs) have either remained unchanged or increased. This study assessed the country-wide prevalence of NMFIs and their patterns across various malaria transmission settings in Mainland Tanzania. A cross-sectional study recruited patients aged ≥ 6 months from 86 health facilities in all 26 regions of Tanzania. All patients were tested for malaria using rapid diagnostic tests (RDTs) and the prevalence of NMFIs was determined for all patients with negative results. Logistic regression was used to determine factors associated with NMFIs. Of the 18,568 patients tested, 8,273 (44.6%) had NMFIs due to negative RDT results. Higher prevalence of NMFIs occurred in females (45.8%) than males (42.8%), adults (aged ≥ 15 years, with 50.6%) compared to under-fives (42.6%) and school children (aged 5 -< 15 years, 34.3%), and in very low (71.5%) compared to high transmission areas (33.9%). NMFIs were significantly more likely in females than in males (aOR = 1.14, 95% CI = 1.07–1.22), in very low transmission areas (aOR = 4.85, 95% CI = 4.42–5.33), adults (aOR = 1.60, 95% CI = 1.46–1.75) and under-fives (aOR = 1.60, 95% CI = 1.47–1.76). The findings show high prevalence of NMFIs overall, and higher prevalence and odds of NMFIs in females, under-fives and individuals from low and very low transmission areas. These groups should be targeted with appropriate point-of-care tests and treatment strategies.