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Malaria and anemia remain major public health challenges in Tanzania. Household socioeconomic factors are known to influence these conditions. However, it is not clear how these factors influence malaria transmission and anemia in Masasi and Nanyumbu Districts. This study presents findings on malaria and anemia situation in under-five children and its influencing socioeconomic factors in Masasi and Nanyumbu Districts, surveyed as part of an ongoing seasonal malaria chemoprevention operational study. A community-based cross-sectional survey was conducted between August and September 2020. Finger-prick blood samples collected from children aged 3-59 months were used to test for malaria infection using malaria rapid diagnostic test (mRDT), thick smears for determination of asexual and sexual parasitemia, and thin smear for parasite speciation. Hemoglobin concentration was measured using a HemoCue spectrophotometer. A structured questionnaire was used to collect household socioeconomic information from parents/caregivers of screened children. The prevalence of malaria was the primary outcome. Chi-square tests, t-tests, and logistic regression models were used appropriately. Overall mRDT-based malaria prevalence was 15.9% (373/2340), and was significantly higher in Nanyumbu (23.7% (167/705) than Masasi District (12.6% (206/1635), p<0.001. Location (Nanyumbu), no formal education, household number of people, household number of under-fives, not having a bed net, thatched roof, open/partially open eave, sand/soil floor, and low socioeconomic status were major risks for malaria infection. Some 53.9% (1196/2218) children had anemia, and the majority were in Nanyumbu (63.5% (458/705), p<0.001. Location (Nanyumbu), mRDT positive, not owning a bed net, not sleeping under bed net, open/partially open eave, thatched window, sex of the child, and age of the child were major risk factors for anemia. Prevalence of malaria and anemia was high and was strongly associated with household socioeconomic factors. Improving household socioeconomic status is expected to reduce the prevalence of the conditions in the area.

Nodding syndrome (NS) has been consistently associated with onchocerciasis. Nevertheless, a positive association between NS and a Mansonella perstans infection was found in South Sudan. We aimed to determine whether the latter parasite could be a risk factor for NS in Mahenge. Cases of epilepsy were identified in villages affected by NS in Mahenge, Tanzania, and matched with controls without epilepsy of the same sex, age and village. We examined blood films of cases and controls to identify M. perstans infections. The participants were also asked for sociodemographic and epilepsy information, examined for palpable onchocercal nodules and onchocerciasis-related skin lesions and tested for anti-Onchocerca volvulus antibodies (Ov16 IgG4) by ELISA. Clinical characteristics of cases and controls, O. volvulus exposure status and relevant sociodemographic variables were assessed by a conditional logistic regression model for NS and epilepsy status matched for age, sex and village. A total of 113 epilepsy cases and 132 controls were enrolled, of which, respectively, 56 (49.6%) and 64 (48.5%) were men. The median age in cases and controls was 28.0 (IQR: 22.0-35.0) and 27.0 (IQR: 21.0-33.3) years. Of the persons with epilepsy, 43 (38.1%) met the probable NS criteria and 106 (93.8%) had onchocerciasis-associated epilepsy (OAE). M. perstans infection was absent in all participants, while Ov16 seroprevalence was positively associated with probable NS (odds ratio (OR): 5.05, 95%CI: 1.79-14.27) and overall epilepsy (OR: 2.03, 95%CI: 1-07-3.86). Moreover, onchocerciasis-related skin manifestations were only found in the cases (n = 7, p = 0.0040), including persons with probable NS (n = 4, p = 0.0033). Residing longer in the village and having a family history of seizures were positively correlated with Ov16 status and made persons at higher odds for epilepsy, including probable NS. In contrast to O. volvulus, M. perstans is most likely not endemic to Mahenge and, therefore, cannot be a co-factor for NS in the area. Hence, this filaria is unlikely to be the primary and sole causal factor in the development of NS. The main risk factor for NS remains onchocerciasis.

Malnutrition and malaria are common co-morbidities in low-income countries, especially among under-fives children. But the malnutrition situation in Masasi and Nanyumbu districts, its interaction with malaria infection and the influence of socioeconomic factors are not well understood. Children aged between 3-59 months in Masasi and Nanyumbu were screened for nutritional status and malaria infection in the community. Nutritional status was determined using age and anthropometric parameters. Z-scores (weight for age (WAZ), height for age (HAZ) and weight for height (WHZ)) were calculated based on the World Health Organisation (WHO) growth reference curves. Malaria infection was determined using malaria rapid diagnostic test and microscopy. Hemoglobin concentration was assessed using HemoCue spectrophotometer, and anemia was classified as hemoglobin concentration < 11.0g/dL. Structured questionnaire was used to collect socio- demographic information electronically. A total of 2242 children, 1539 (68.6%) from Masasi and 1169 (52.1%) females were involved in the study. The mean z-scores (WAZ = -0.60 and HAZ = -1.56) were lower than the WHO reference population. The overall prevalence of malnutrition was 49%, and it was significantly higher in Nanyumbu (52.5%) than in Masasi (47.3%), (x2 = 5.045, p = 0.025). Prevalence of malnutrition was higher in boys (53.0%) than in girls (45.0%) (x2 = 13.9, p < 0.001). Stunting was the most prevalent component of undernutrition; it was slightly prevalent in Nanyumbu (46.5%) compared to Masasi (42.0%), (x2 = 3.624, p = 0.057) and in boys (48.2%) than in girls (39.1%), x2 = 17.44, p<0.001. Only 15.8% of the undernourished children had malaria infection. Sex, age group and anaemia were significantly associated with undernourishment (p<0.05), while district and malaria infection were marginally (p≤0.06) associated with undernourishment. None of the undernutrition indices was associated with malaria infection. Undernutrition was highly prevalent in the study population and was influenced sex, age, anaemia and malaria infection. More emphasis is needed to address the malnutrition problem especially stunting in Masasi and Nanyumbu districts.

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 Primaquine is a pro-drug and its active metabolite is potent against mature Plasmodium falciparum gametocytes. Primaquine is metabolized by a highly polymorphic cytochrome P450 2D6 (CYP2D6) enzyme. Mutations in the gene encoding this enzyme may lead to impaired primaquine activity. This study assessed if 0.25 mg/kg single-dose primaquine is safe and sufficient to reduce transmission of gametocytes in individuals with no, reduced, or increased CYP2D6 enzyme activity. Methods Between June 2019 and January 2020 children aged 1–10 years, attending at Yombo dispensary, Bagamoyo district, with confirmed microcopy-determined uncomplicated P. falciparum malaria were enrolled in the study. The enrolled patients were treated with a standard artemether-lumefantrine regimen plus 0.25 mg/kg single-dose primaquine and followed up for 28 days for clinical and laboratory assessment. Primaquine was administered with the first dose of artemether-lumefantrine. Safety assessment involved direct questioning and recording of the nature and incidence of clinical signs and symptoms, and measurement of haemoglobin (Hb) concentration. Blood samples collected from 100 patients were used for assessment of post-treatment infectiousness on day 7 using mosquito membrane feeding assays. Molecular methods were used to determine CYP2D6 and glucose-6-phosphate dehydrogenase (G6PD) status. The primary outcome was the safety of 0.25 mg/kg single-dose primaquine based on CYP2D6 status. Results In total, 157 children [median age 6.4 (Interquartile range 4.0–8.2) years] were recruited, of whom 21.0% (33/157) and 12.7% (20/157) had reduced CYP2D6 and deficient G6PD activity, respectively. Day 3 mean absolute Hb concentration reduction was 1.50 g/dL [95% confidence interval (CI) 1.10–1.90] and 1.51 g/dL (95% CI 1.31–1.71) in reduced and normal CYP2D6 patients, respectively ( t  = 0.012, p  = 0.990). The day 3 mean absolute Hb concentration reduction in G6PD deficient, G6PD normal and heterozygous female was 1.82 g/dL (95% CI 1.32–2.32), 1.48 g/dL (95% CI 1.30–1.67) and 1.47 g/dL (95% CI 0.76–2.18), respectively ( F  = 0.838, p  = 0.435). Sixteen percent (16/98) of the patients each infected at least one mosquito on day 7, and of these, 10.0% (2/20) and 17.9% (14/78) had reduced and normal CYP2D6 enzyme activity, respectively ( x 2  = 0.736, p  = 0.513). Conclusion Single-dose 0.25 mg/kg primaquine was safe and sufficient for reducing transmission of P. falciparum gametocytes regardless of CYP2D6 or G6PD status. Trial registration Study registration number: NCT03352843.

Effectiveness of dihydroartemisinin-piperaquine (DP) as seasonal malaria chemoprevention (SMC) was assessed in Nanyumbu and Masasi Districts. Between March and June 2021, children aged 3–59 months were enrolled in a cluster randomized study. Children in the intervention clusters received a monthly, 3-days course of DP for three consecutive months regardless of malaria infection status, and those in the control clusters received no intervention. Malaria infection was assessed at before the first-round and at 7 weeks after the third-round of DP in both arms. Malaria prevalence after the third-round of DP administration was the primary outcome. Chi -square tests and logistic regression model were used to compare proportions and adjust for explanatory variables. Before the intervention, malaria prevalence was 13.7% (161/1171) and 18.2% (212/1169) in the intervention and control clusters, respectively, p  < 004. Malaria prevalence declined to 5.8% (60/1036) in the intervention clusters after three rounds of DP, and in the control clusters it declined to 9.3% (97/1048), p  = 0.003. Unadjusted and adjusted prevalence ratios between the intervention and control arms were 0.42 (95%CI 0.32–0.55, p  < 0.001) and 0.77 (95%CI 0.53–1.13, p  = 0.189), respectively. SMC using DP was effective for control of malaria in the two Districts. Trial registration : NCT05874869, https://clinicaltrials.gov/ 25/05/2023.

Background Early diagnosis and timely treatment of malaria is recognized as a fundamental element to the control of the disease. Although access to health services in Tanzania is improved, still many people seek medical care when it is too late or not at all. This study aimed to determine factors associated with delay in seeking treatment for fever among children under five in Tanzania. Methods A three-stage cluster sampling design was used to sample households with children under five in Dodoma region, central Tanzania between October 2010 and January 2011. Information on illness and health-seeking behaviours in the previous four weeks was collected using a structured questionnaire. A multivariable logistic regression was used to investigate determinants of delay in treatment-seeking behaviour while accounting for sample design. Results A total of 287 under-five children with fever whose caretakers sought medical care were involved in the study. Of these, 55.4% were taken for medical care after 24 hours of onset of fever. The median time of delay in fever care seeking was two days. Children who lived with both biological parents were less likely to be delayed for medical care compared to those with either one or both of their biological parents absent from home (OR = 0.42, 95% CI: 0.24, 0.74). Children from households with two to three under-five children were more likely to be delayed for medical care compared to children from households with only one child (OR = 1.54, 95% CI: 1.04, 2.26). Also, children living in a distance ≥5 kilometres from the nearest health facility were about twice (95% CI: 1.11, 2.72) as likely to delay to be taken for medical care than those in the shorter distances. Conclusion Living with non-biological parents, high number of under-fives in household, and long distance to the nearest health facility were important factors for delay in seeking healthcare. Programmes to improve education on equity in social services, family planning, and access to health facilities are required for better healthcare and development of children.

Background The Plasmodium falciparum delayed clearance phenotype due to the emergence of partial artemisinin resistance has been documented in Asia and Africa, where it is associated with treatment failure of artemisinin-based combination therapy (ACT). The amplification of the Plasmodium falciparum plasmepsin2/3 gene ( pfpm2/3 ) has been shown to decrease the susceptibility of P. falciparum to piperaquine, leading to treatment failure among patients on dihydroartemisinin-piperaquine. The present systematic meta-analysis summarises the evidence of pfpm2/3 gene amplification in Asia and Africa. Methods The protocol for the review was registered at the PROSPERO (Reference number: CRD42024599774). Thirty-four studies conducted in Africa and Asia, reporting pfpm2/3 gene amplification among P. falciparum isolates, were identified through the Medline, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, and EMBASE online databases. The potential for publication bias was evaluated by examining asymmetry in funnel plots and using Egger’s test. Pooled proportions estimates were calculated using the random effects model, while heterogeneity was assessed through I 2 statistics. Sub-group analysis was performed based on the year of sample collection and continent. Results The heterogeneity among the studies included in the meta-analysis was high (I 2  > 95%, p  < 0.01). The funnel plot was asymmetrical, suggesting that publication bias affected the meta-analysis. However, Egger’s test and Begg’s (adjusted to Kendall’s) scores for the pooled proportions of the pfpm 2/3 gene confirmed no potential publication bias (p = 0.083 and 0.163, respectively). A total of 34 studies involving 4,005 P. falciparum isolates were included in this review. Of the 34 studies, 18 (53%) were conducted in Asia, and 16 (47%) were conducted in Africa. The samples for these studies were collected from 2009 to 2019. Among these studies, 15 (44%) were performed before 2016. The estimated pooled proportions of pfpm 2 /3 gene amplification via the random effects model were 16.0% (95% CI 8.0–26.0%). Subgroup analysis (per continent and year of sample collection) revealed that the pooled proportions estimates of pfpm2/3 gene amplification were greater in Asia (25.0%, 95% CI 9.0–45.0%) than in Africa (8.0%, 95% CI 2.0–15.0%) and lower before 2016 than 2016 to 2020 (11%, 95% CI 3.0–23% and 19%, 95% CI 7.0–36%, respectively). Conclusion The present review provides up-to-date evidence on the pfpm2/3 gene amplification. A substantial pooled proportion of pfpm2/3 gene amplification was reported, and many of the amplifications were observed in isolates from Asia rather than Africa. This calls for further efforts to monitor/control the emergence and spread of partner drug resistance in the regions to avoid the emergence of total ACT resistance, which will compromise global efforts toward eliminating malaria.

Nodding syndrome (NS) is a disabling childhood-onset epilepsy occurring in onchocerciasis-endemic regions. High Onchocerca volvulus microfilarial loads in childhood are a key risk factor, but not all heavily infected individuals develop NS, suggesting a possible role for host genetic susceptibility. Human leukocyte antigen (HLA) haplotypes have been implicated in susceptibility to various infectious and autoimmune diseases, including onchocerciasis. We investigated potential associations between HLA haplotypes and onchocerciasis-associated epilepsy (OAE), including NS, in Tanzania. A case-control study was conducted in an onchocerciasis-endemic area in the Mahenge area, Tanzania, including 98 persons with epilepsy and 112 controls. DNA was extracted from dry blood spots and HLA sequence-based typing was performed by Histogenetics (Ossining, USA). A total of 11 HLA loci (HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1) were exon sequenced. The HLA-typed dataset was analysed using pyHLA, including Bonferroni as multi-test adjustment, to test for associations with O. volvulus anti-Ov16 seropositivity, epilepsy, OAE and NS. Anti-Ov16 seropositivity was significantly higher in cases than controls (76.5% vs 58.9%; p = 0.01). No HLA alleles were significantly associated with epilepsy, OAE, NS, or anti-Ov16 seropositivity after correction. Before adjustment, HLA-C07:01 appeared to be a risk factor for epilepsy, HLA-DQB106:02 was associated with OAE, HLA-B35:01 with NS, and HLA-C08:02 and DRB1*03:01 with anti-Ov16 seropositivity. Post-hoc power analysis indicated that substantially larger sample sizes would be required to confirm these associations. This study did not identify statistically significant HLA associations with epilepsy, OAE, NS, or O. volvulus exposure. However, several alleles-particularly HLA-B*35:01, also reported in a previous South Sudanese study-emerged as potential candidates for further investigation. Larger, multi-country studies with sufficient power are needed to clarify whether host genetic factors contribute to susceptibility to OAE and NS. Strengthening onchocerciasis elimination programmes remains essential, as NS is a preventable disease.