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Background: Anaemia in sickle cell disease (SCD) is a significant cause of morbidity and mortality, but few studies have reported on the burden and outcome of very severe anaemia. This study described the epidemiology of very severe anaemia by determining the prevalence and incidence, investigating associated clinical and laboratory factors, and assessing outcomes in SCD., Methods: A 10-year prospective cohort study involving SCD patients of all ages was conducted at Muhimbili National Hospital in Tanzania between 2004 and 2013. SCD included Homozygous SS-Sickle cell anaemia and Sβ 0 thalassemia at clinics and during hospitalization visits. Very severe anaemia was defined as Haemoglobin <5 g/dL at steady-state which was a period when a patient was stable with no blood transfusion in past 3 months or accute pain report in the previous month., Findings: There were 28,293 (92.9%) clinic visits and 2158 hospitalisations amongst 3586 patients. Mean haemoglobin concentration at clinic was 7.4 g/dL, (95% CI: 7.4-7.5) compared to hospitalisation [6.4 g/dL, 95% CI: 6.3-6.5], p < 0.001. Prevalence of very severe anaemia at the clinic was 4.1%, and 23.8% during hospitalization, while the overall incidence was 114.1 (95% CI: 108.2-120.2) events per 1000 person years. Risk ratio of dying for patients with very severe anaemia was 4.78 times higher (95% CI: 3.65-6.25, p < 0.001) than in individuals without very severe anaemia. The risk ratio for mortality was highest in children aged <2 years, and was decreasing steadily with increase in age, from HR = 0.73 (95% CI: 0.39-1.35) in children aged 2-4 years to HR of 0.38 (95% CI: 0.20-0.71) in patients in age group 10-17 years when compared to those aged 0-1 years. Mortality risk ratio was higher (HR = 6.76 [95% CI: 4.31-10.62, p < 0.001]) in patients with steady-state haemoglobin <5 g/dL and presenting with very severe anaemia before death compared to those with steady state haemoglobin ≥5 g/dL and haemoglobin ≥5 g/dL before death., Interpretation: The burden of very severe anaemia in SCD was high, especially during hospitalization, and was independent predictor of mortality. There is an urgent need to improve prevention, diagnosis, and interventions for very severe anaemia in SCD in Africa. More research to elucidate the aetiology and mechanisms of anaemia in this population is required., Funding: Government of the United Republic of Tanzania, Wellcome Trust, United Kingdom (JKM 072064; Project grant 080025, Strategic award 084538)., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: Epilepsy remains a significant public health concern in Tanzania, with affected individuals enduring stigma, whether through actions or perceptions. Myths, misunderstandings, and misconceptions about epilepsy have persisted due to a multitude of factors. Here, we assessed attitudes and perceptions toward epilepsy in Mahenge., Methods: A cross-sectional study utilising a mixed-methods approach was undertaken in eight villages in the Ulanga district of Mahenge, integrating a semi-structured questionnaire and focus group discussions (FGDs). The questionnaire involved 778 community members, and 15 FGDs were conducted (seven groups with people with epilepsy and eight without). Descriptive statistics, chi-square, and logistic regression were used for quantitative analysis, while we used NVivo version 14 for thematic analysis of qualitative data., Results: Of 778 participants, over half were women (425, 54.6%) with a median age of 41 years (IQR: 30-55) and most had completed primary education (79.9%). The majority of participants were aware of epilepsy (96.8%), yet they displayed low knowledge (51%), negative attitudes (45.5%), and perceptions (42.1%) towards the disorder. A low level of understanding was significantly associated with negative attitudes (Adjusted Odds Ratio [AOR] = 1.89, 95%CI: 1.41-2.53) and perceptions (AOR = 3.22, 95%CI: 2.05-5.04) towards epilepsy. In the qualitative analysis, often hereditary factors and infections were named as causes of epilepsy, along with misconceptions involving witchcraft and divine punishment. There was also a misconception about the contagiousness of epilepsy. Traditional healers were often the initial point of treatment. Epilepsy-related stigma was evident, with individuals with epilepsy facing derogatory labels, social isolation, and barriers to education. Lastly, there was a lack of understanding regarding a possible association between epilepsy and onchocerciasis., Conclusions: Despite high awareness of epilepsy, there is insufficient understanding, negative attitudes, and perceptions, including misconceptions and stigma about this neurologic condition. Community-based education programmes are essential for promoting proper healthcare-seeking behaviour and dispelling myths., (© 2024. The Author(s).)

Introduction: Epidemiological evidence suggests that Onchocerca volvulus is associated with epilepsy, although the exact pathophysiological mechanism is unknown. Mahenge is an endemic focus of onchocerciasis, with the longest-running ivermectin treatment intervention in Tanzania. We assessed the prevalence of onchocerciasis and epilepsy after 25 years of control using ivermectin., Methods: This was a population-based cross-sectional study in 34 villages in Mahenge in 2021. Community health workers conducted door-to-door household surveys to enumerate the population and screen for individuals suspected of epilepsy using a standardised questionnaire. Trained physicians confirmed epilepsy. Children aged 6-11 years were screened for onchocerciasis antibodies using the Ov16 rapid test. Villages were stratified into three altitude levels (low [<400], medium [400-950], and high [>950 meters above sea level]) as a proxy for rapids, which black flies favour for breeding sites. Incidence of epilepsy was estimated as a ratio of new cases in the year preceding the survey per 100,000 population., Results: 56,604 individuals (median age 20.2 years, 51.1% females) were surveyed. Onchocerciasis prevalence in children was 11.8% and was highest in villages at medium (21.7%) and lowest in low altitudes (3.2%), p<0.001. Self-reported use of ivermectin was 88.4%. Epilepsy prevalence was 21.1 (95%CI: 19.9-22.3) cases per 1000 persons and was highest in medium (29.5%) and lowest in the lowlands (12.7%). The odds ratio (OR) of having epilepsy was significantly higher in females (OR = 1.22, 95%CI: 1.08-1.38), middle altitudes (OR = 2.34 [95%CI: 2.04-2.68]), and in individuals positive for OV16 (OR = 1.98 [95%CI:1.57-2.50]). The incidence of epilepsy a year before the survey was 117 (95%CI: 99.7-160.4) cases per 100,000 person-years., Conclusion: Despite ivermectin use for 25 years, the prevalence of onchocerciasis and epilepsy remains high. It is crucial to strengthen bi-annual ivermectin treatment and initiate interventions targeting vectors to control onchocerciasis and epilepsy in the area., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mushi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Sickle cell anemia (SCA) prevalence remains high in sub-Saharan Africa. Long-term treatment with hydroxyurea (HU) increases survival, however, poor adherence to treatment could limit effectiveness. Whilst HU treatment adherence is currently high, this might decrease over time., Methods: We conducted a single-center, randomized, open-label, parallel group phase 2 controlled clinical trial to determine whether mobile Directly Observed Therapy (m-DOT) increases HU treatment adherence (NCT02844673). Eligible participants were adults with homozygous SCA. People on a chronic blood transfusion program, with hemoglobin (Hb) A levels greater than 20% of the total Hb, total Hb less than 4 g/dL, pregnant or HIV positive were excluded. After a 3-month pre-treatment period participants were randomized to either m-DOT or standard monitoring arm. All participants received smart mobile phones and were treated with HU (15 mg/kg) daily for three months. In the m-DOT arm, drug intake was video recorded on cell phone by the participant and the video sent to the study team. The primary objective was to evaluate the effect of m-DOT on adherence to HU treatment by medication possession ratio (MPR)., Results: Of the 86 participants randomized, 76 completed the trial (26.13 ± 6.97 years, 63.5 % female). Adherence was high (MPR > 95 %) in both groups, 29 (80.6 %) in m-DOT versus 37 (94.9 %) in the standard monitoring arm (P = 0.079). No HU treatment was withheld from participants due to safety concerns., Conclusions: m-DOT did not increase adherence to HU treatment. We recommend that further testing in larger trials with a longer follow up period be undertaken., (© 2024. The Author(s).)

Competing Interests: The authors have declared that no competing interests exist.

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)., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

COVID-19 vaccination remains to be the most important intervention in the fight against the pandemic. The immunity among the vaccinated population and its durability can significantly vary due to various factors. This study investigated the humoral immune responses among individuals who received any of the COVID-19 vaccines approved for use in Tanzania. A total of 1048 randomly selected adults who received COVID-19 vaccines at different time points were enrolled and humoral immune responses (IR) were tested at baseline and three months later (960, 91.6%). The level of SARS-CoV-2 anti-spike/receptor binding domain (RBD) IgG, anti-nucleocapsid IgG, and IgM antibodies were determined using a commercially available chemiluminescent microparticle immunoassay. Descriptive data analysis was performed using STATA version 18 and R. At baseline, serum IgG against anti-spike/RBD was detected in 1010/1048 (96.4%) participants (95%CI: 94.9-97.5) and 98.3% (95%CI: 97.3-99) three months later. The IgG against the SARS-CoV-2 nucleocapsid proteins were detected in 40.8% and 45.3% of participants at baseline and follow-up, respectively. The proportion of seroconverters following vaccination and mean titers of anti-spike/RBD antibodies were significantly more among those who had past SARS-CoV-2 infection than in those with no evidence of past infection, ( p < 0.001). Only 0.5% of those who had detectable anti-spike/RBD antibodies at baseline were negative after three months of follow-up and 1.5% had breakthrough infections. The majority of participants (99.5%) had detectable anti-spike/RBD antibodies beyond 6 months post-vaccination. The proportion of Tanzanians who mounted humoral IR following COVID-19 vaccination was very high. Seroconversions, as well as the mean titers and durability of humoral IR, were significantly enhanced by exposure to natural SARS-CoV-2 infection. In view of the limited availability of COVID-19 vaccines as well as challenges to completing subsequent doses, booster doses could only be suggested to high-risk groups.

Background: Epilepsy is estimated to affect 50 million people globally, with 80% living in sub-Saharan Africa (SSA). Children with epilepsy (CWE) in SSA are often socially isolated, and many do not get access to school. This study aimed to explore the barriers hindering accessibility to formal education among CWE in Mahenge, Tanzania., Methods: The study was conducted in June 2022 in four villages (Mdindo, Msogezi, Mzelezi and Sali) using quantitative and qualitative methods. The quantitative included 203 persons with epilepsy (PWE), while the qualitative involved six focus group discussions and 17 in-depth interviews. Quantitative and qualitative data were analyzed using Stata and Nvivo software, respectively., Results: Of the 203 PWE, 62 (30.5%) had never enrolled in school, while 77 (54.6%) of those enrolled dropped-out before completing it. The perceived barriers to accessing education were categorized as individual barriers (such as frequent seizures, learning difficulties, anti-seizure medication side effects and perceived stigma), Community barriers (such as stigma and discrimination, negative beliefs and misconceptions, relocation to farms and poor socio-economic status), and Institutional barriers (including lack of knowledge about epilepsy among stake-holders, topography and distance to schools)., Conclusion: There is a high rate of dropouts and non-enrolment of CWE in schools within the Mahenge area. Negative beliefs and low awareness of the community about epilepsy and formal education contribute to this issue. This calls for more advocacy to raise community awareness on epilepsy. The government should enforce an inclusive education policy and provide free and uninterrupted anti-seizure medication for seizure control., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Despite significant decline in the past two decades, malaria is still a major public health concern in Tanzania; with over 93% of the population still at risk. Community knowledge, attitudes and practices (KAP), and beliefs are key in enhancing uptake and utilization of malaria control interventions, but there is a lack of information on their contribution to effective control of the disease. This study was undertaken to determine KAP and beliefs of community members and service providers on malaria, and how they might be associated with increased risk and persistence of the disease burden in North-western and Southern regions of Tanzania., Methods: This was an exploratory study that used qualitative methods including 16 in-depth interviews (IDI) and 32 focus group discussions (FGDs) to collect data from health service providers and community members, respectively. The study was conducted from September to October 2017 and covered 16 villages within eight districts from four regions of mainland Tanzania (Geita, Kigoma, Mtwara and Ruvuma) with persistently high malaria transmission for more than two decades., Results: Most of the participants had good knowledge of malaria and how it is transmitted but some FGD participants did not know the actual cause of malaria, and thought that it is caused by bathing and drinking un-boiled water, or consuming contaminated food that has malaria parasites without warming it. Reported barriers to malaria prevention and control (by FGD and IDI participants) included shortage of qualified health workers, inefficient health financing, low care-seeking behaviour, consulting traditional healers, use of local herbs to treat malaria, poverty, increased breeding sites by socio-economic activities and misconceptions related to the use of bed nets and indoor residual spraying (IRS). Among the misconceptions, some participants believed that bed nets provided for free by the government came with bedbugs while others reported that free bed nets caused impotence among men., Conclusion: Despite good knowledge of malaria, several risk factors, such as socio-economic and behavioural issues, and misconceptions related to the use of bed nets and IRS were reported. Other key factors included unavailability or limited access to health services, poor health financing and economic activities that potentially contributed to persistence of malaria burden in these regions. Relevant policies and targeted malaria interventions, focusing on understanding socio-cultural factors, should be implemented to reduce and finally eliminate the disease in the study regions and others with persistent transmission., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have seemed to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This study investigated the quality of life (QoL) of adults with epilepsy living in Mahenge, an onchocerciasis-endemic area in Tanzania with a high prevalence of onchocerciasis-associated epilepsy (OAE)., Methods: Between February and December 2020, persons with epilepsy (PWE) were recruited from four rural villages in Mahenge: Mdindo, Msogezi, Mzelezi, and Sali. For PWE who could not answer the questionnaire due to their mental or physical disability, a family member was asked to answer the questions instead. The Quality of Life in Epilepsy Inventory-31 (QOLIE-31) questionnaire used contained seven domains. The raw domain scores were transformed to 0-100% subscales, with higher scores indicating better QoL. The global QoL was calculated from the subscales using the overall QOLIE-31 score formula., Results: In total, 96 PWE were enrolled in the study with a median age of 28 (range: 18-60) years, of whom 45 (47%) were male. The questionnaires were answered by PWE (54.8%) or one of their family members (45.2%). Most PWE were single (81%), and half never attended school. About two-thirds (65%) of PWE were suspected of having OAE, and a third (31%) had a history of head nodding seizures. Most PWE were treated with phenobarbital (85.4%) and had high treatment adherence (96.9%). Still, the number of seizures per week ranged from 0 to 7, with a median of one. The mean global QOLIE-31 score was 66.9 (range: 38.3-92.1) out of 100.0. Predictors of lower QoL were living in Sali Village and experiencing seizures the week before the interview. In contrast, completing primary school and switching to second-line anti-seizure medication were predictors of higher QoL., Conclusion: In order to improve the QoL of PWE in Mahenge, it is vital to optimize anti-seizure medication regimens to decrease the frequency of seizures and to increase the schooling of PWE., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: 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., Methodology: 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., Results: 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., Conclusion: 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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bhwana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: 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., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Amaral et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Utilization of malaria interventions is influenced by, among other things, the level of knowledge and attitude that the community has toward the infection as well as the available interventions. This study assessed malaria knowledge, attitudes, and practices on malaria infection and interventions in Masasi and Nanyumbu districts, Tanzania., Methods: A community-based cross-sectional survey was conducted between August and September 2020, among the heads of households having at least one under-five child. Information on knowledge, attitudes, and practices on malaria infection and interventions was gathered from the heads of the households using a structured questionnaire. The knowledge level was classified into low, moderate, and high. Attitudes were classified into positive and negative, whereas the practices were classified into good and poor. Children aged between 3 and 59 months were screened for malaria infection using a malaria rapid diagnostic test (mRDT). The proportion of the households' heads with high level of knowledge was the primary outcome. Proportions were compared using Chi -square or fisher's test, and logistic regression analysis was used as appropriate., Results: A total of 1,556 household heads were interviewed, 1,167 (75.00%) were male, and according to marital status, 1,067 (68.57%) were couples. All the household heads had some knowledge of malaria, but 47.33% (736/1,555) and 13.83% (215/1,555) of them had moderate and high knowledge, respectively. The level of knowledge on malaria was significantly influenced by gender [adjusted odds ratio (aOR) = 0.72, 95.00% confidence interval (CI) = 0.56-0.94, p = 0.017], level of education (aOR = 1.50, 95.00% CI = 1.04-2.16, p = 0.03), and the occupation of the household head (aOR = 1.90, 95.00% CI = 1.22-2.96, p = 0.004). Majority of the households [83.87% (1,305/1,556)] had bed nets hanging on the sleeping spaces. Of the household heads possessing bed nets, 85.10% (514/604), 79.62% (586/736), and 95.35% (205/215) of them had a low, moderate, and high level of knowledge on malaria infection, respectively (trend x 2 = 31.53, p < 0.001). The majority [95.04% (1,474/1,551)] of the household heads perceived sleeping under the bed net to be beneficial. Furthermore, 15.56% (94/604), 14.67% (108/736), and 7.44% (16/215) of the household heads with low, moderate, and high knowledge, respectively, had children with malaria infection (trend x 2 = 9.172, p = 0.01)., Conclusion: The study population had a good level of knowledge about malaria infection, and a good attitude toward malaria interventions, and the majority of them were using bed nets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ngasala, Mwaiswelo, Chacky, Molteni, Mohamed, Lazaro, Samuel and Mmbando.)

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 3 rd 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., (© 2023. The Author(s).)

Onchocerciasis is known to cause skin lesions and blindness, but there is also epidemiological evidence that onchocerciasis is associated with epilepsy, including nodding syndrome. We carried out ocular exams in persons with epilepsy in Mahenge, an onchocerciasis endemic area with a high prevalence of epilepsy in Tanzania. We recruited 278 consecutive persons with epilepsy attending the epilepsy clinic at Mahenge hospital and satellite clinics in rural villages. They underwent a general physical and a detailed ocular examination and were tested for onchocerciasis Ov16 IgG4 antibodies. Glaucoma was defined by a raised intraocular pressure above 21 mmHg with evidence of typical glaucomatous disc changes in one or both eyes. Among the 278 participants, median age 27 (IQR 21-38) years, 55.4% were female; 151/210 (71.9%) (95% CI: 65.3-77.9) were Ov16 positive. The most frequent ophthalmic lesions were glaucoma (33.1%), vitreous opacities (6.5%) and cataracts (2.9%). In multivariate analysis, glaucoma (adjusted IRR = 1.46; 95% CI: 1.24-1.70) and age (adjusted IRR = 1.01; 95% CI: 1.01-1.02) were significantly associated with onchocerciasis. In conclusion, a high prevalence of glaucoma was observed among Ov16 positive persons with epilepsy. Persons with epilepsy with O. volvulus infection should undergo screening for glaucoma to prevent one of the causes of preventable blindness.

Background: Despite 20 years of ivermectin mass distribution in the Mahenge area, Tanzania, the prevalence of onchocerciasis and epilepsy has remained high in rural villages., Objectives: We investigated the efficacy of ivermectin in reducing Onchocerca volvulus microfilariae and predictors for parasitic load following ivermectin treatment in persons with (PWE) and without epilepsy (PWOE)., Methods: Between April and September 2019, 50 PWE and 160 randomly selected PWOE from Msogezi and Mdindo villages participated in a follow-up study. Skin snips were obtained pre (baseline) and three months post-ivermectin treatment., Results: The overall prevalence of O. volvulus positive skin snips at baseline was 49% (103/210), with no significant difference between PWE (58.0%) and PWOE (46.3%); p=0.197. The overall mean microfilarial density was significantly higher at baseline 1.45(95%CI:0.98-2.04)) than three-month post-ivermectin treatment (0.23(95%CI:0.11-0.37), p<0.001. Three months after ivermectin, the microfilarial density had decreased by ≥80% in 54 (81.8%, 95%CI: 72.3-91.4) of the 66 individuals with positive skin snips at baseline. High microfilarial density at baseline was the only significant predictor associated with higher microfilarial density in the post-ivermectin skin snips., Conclusion: Our study reports a decrease in microfilarial density following ivermectin treatment in most individuals. Optimizing ivermectin coverage will address the ongoing onchocerciasis transmission in Mahenge., (© 2022 Bhwana D et al.)

Ivermectin and albendazole (IA) combination preventive chemotherapy to all at-risk populations is deployed to eliminate lymphatic filariasis. Although safety monitoring is imperative, data from Sub-Saharan Africa is scarce. We conducted a large-scale active safety surveillance of adverse events (AEs) following IA mass drug administration (MDA) to identify the type, incidence, and associated risk factors in Tanzania. After recording sociodemographic, clinical, and medical histories, 9640 eligible residents received single-dose IA combination preventive chemotherapy. Treatment-associated AEs were actively monitored through house-to-house visits on day 1, day 2, and day 7 of MDA. Events reported before and after MDA were cross-checked and verified to identify MDA-associated AEs. 9288 participants (96.3%) completed the seven-day safety follow-up, of whom 442 reported 719 MDA-associated AEs. The incidence of experiencing one or more type of MDA-associated AE was 4.8% (95% CI = 4.3−5.2%); this being significantly higher among those with Pre-MDA clinical events than those without (8.5% versus 4.1%, p < 0.001). AEs were mild (83.8%), moderate (15.9%), and severe (0.3%), and most resolved within 72 h. The incidence of experiencing one, two, ≥ three types of AEs were 2.8%, 1.3%, and 0.6%, respectively. The most common AEs were headache (1.23%), drowsiness (1.15%), fever (1.12%), and dizziness (1.06%). A chronic illness, or clinical manifestation of lymphatic filariasis, or being female or pre-existing clinical symptoms were independent significant predictors of AEs. IA combination preventive chemotherapy is safe and tolerable, and associated AEs are mild-to-moderate and transient, with few severe AEs. Safety monitoring during MDA campaigns in individuals with underlying clinical conditions is recommended for timely detection and management of AEs.

Background: 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., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: The authors have declared that no competing interests exist.

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., (© 2022. The Author(s).)

Background: Throughout Africa, epilepsy is a highly stigmatized condition. It is often considered to be contagious. This study aimed to assess community knowledge, attitude, and practices toward epilepsy in four villages namely Mdindo, Msogezi, Mzelezi, and Sali within Mahenge division, in Morogoro region, Tanzania. These villages are located in an onchocerciasis-endemic area with a high prevalence of epilepsy., Methods: A qualitative cross-sectional study was conducted between June and July 2019 within the framework of a multi-disciplinary research project investigating the association between onchocerciasis and epilepsy. Focus group discussions (FGDs) and in-depth interviews (IDIs) were held with persons with epilepsy (PWE) and their caretakers, community resource persons, and program coordinators of the neglected tropical diseases program., Results: The main symptoms of epilepsy were well described by all participants in all villages. PWE and caretakers in all villages considered epilepsy to be a major health problem and some participants ranked it second in importance after malaria. The reported perceived causes of epilepsy included febrile seizures during childhood (locally known as degedege), heredity, evil spirits, and inhaling flatus or touching secretions from PWE, especially during seizures. Knowledge about the association between epilepsy and onchocerciasis was low. People with epilepsy are disregarded, stigmatized, and marginalized from various opportunities such as conjugal rights, schooling, leadership roles, and property inheritance. Traditional healers are often the first contact when seeking care after a person develops epilepsy., Conclusion: Epilepsy is a major health burden and public health concern in the Mahenge area. The negative attitudes toward PWE and misconceptions about the causes of epilepsy contribute to delays in seeking care at health facilities. Findings from this study will be used to optimize the comprehensive community-based epilepsy treatment program that was recently initiated in the area., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

To eliminate onchocerciasis-associated morbidity, it is important to identify areas where there is still high ongoing Onchocerca volvulus transmission. Between 2015 and 2021, door-to-door surveys were conducted in onchocerciasis-endemic villages in Cameroon, the Democratic Republic of Congo (DRC), Nigeria, South Sudan, and Tanzania to determine epilepsy prevalence and incidence, type of epilepsy and ivermectin therapeutic coverage. Moreover, children aged between six and 10 years were tested for anti- Onchocerca antibodies using the Ov16 IgG4 rapid diagnostic test (RDT). A mixed-effect binary logistic regression analysis was used to assess significantly associated variables of Ov16 antibody seroprevalence. A high prevalence and incidence of epilepsy was found to be associated with a high Ov16 antibody seroprevalence among 6-10-year-old children, except in the Logo health zone, DRC. The low Ov16 antibody seroprevalence among young children in the Logo health zone, despite a high prevalence of epilepsy, may be explained by a recent decrease in O. volvulus transmission because of a decline in the Simulium vector population as a result of deforestation. In the Central African Republic, a new focus of O. volvulus transmission was detected based on the high Ov16 IgG4 seropositivity among children and the detecting of nodding syndrome cases, a phenotypic form of onchocerciasis-associated epilepsy (OAE). In conclusion, Ov16 IgG4 RDT testing of 6-10-year-old children is a cheap and rapid method to determine the level of ongoing O. volvulus transmission and to assess, together with surveillance for OAE, the performance of onchocerciasis elimination programs.

Background: 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., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: The authors have declared that no competing interests exist.

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 ± 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., Competing Interests: Conflicts of Interest The authors declare no competing interests. The study sponsor was neither involved in performing the research nor in the writing of the paper., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Sickle cell disease is a genetic disease with a predisposition to infections caused by encapsulated organisms, especially Streptococcus pneumoniae. Pneumococcal vaccines and prophylactic penicillin have reduced the rate of this infection and mortality in sickle cell disease. However, implementation of these interventions is limited in Africa. The objectives of the study were to assess health care providers' behaviors with the implementation of pneumococcal vaccination and penicillin prophylaxis and to identify barriers to their use. A 25-item online questionnaire was administered through SickleinAfrica: a network of researchers, and healthcare providers, in Ghana, Nigeria, and Tanzania, working to improve health outcomes of sickle cell disease in Africa. Data was collected and managed using the Research Electronic Data Capture (REDCap), tools and data analysis was done using STATA version 13 and R statistical software. Eighty-two medical practitioners responded to the questionnaire. Only 54.0 and 48.7% of respondents indicated the availability of published guidelines on sickle cell disease management and pneumococcal vaccine use, respectively, at their facilities. The majority (54.0%) perceived that the vaccines are effective but over 20.0% were uncertain of their usefulness. All respondents from Ghana and Tanzania affirmed the availability of guidelines for penicillin prophylaxis in contrast to 44.1% in Nigeria. Eighty-five percent of respondents affirmed the need for penicillin prophylaxis but 15.0% had a contrary opinion for reasons including the rarity of isolation of Streptococcus pneumoniae in African studies, and therefore, the uncertainty of its benefit. Lack of published guidelines on the management of sickle cell disease and doubts about the necessity of prophylactic measures are potential barriers to the implementation of effective interventions.

Patients with sickle cell disease (SCD) with high fetal haemoglobin (HbF) tend to have a lower incidence of complications and longer survival due to inhibition of deoxyhaemoglobin S (HbS) polymerisation by HbF. HbF-containing cells, namely F cells, are strongly influenced by genetic factors. We measured the percentage of F cells (Fcells%) in 222 patients with SCD to evaluate the association of (i) Fcells% with genetic HbF-modifier variants and (ii) Fcells% with haematological parameters. There was a different distribution of Fcells% in females compared to males. The association of the B-cell lymphoma/leukaemia 11A (BCL11A) locus with Fcells% (β = 8·238; P < 0·001) and with HbF% (β = 2·490; P < 0·001) was significant. All red cell parameters except for Hb and mean corpuscular Hb concentration levels in males and females were significantly different. The Fcells% was positively associated with mean cell Hb, mean cell volume and reticulocytes. To explain the significant gender difference in Fcells%, we tested for associations with single nucleotide polymorphisms on the X chromosomal region Xp22.2, where a genetic determinant of HbF had been previously hypothesised. We found in males a significant association with a SNP in FERM and PDZ domain-containing protein 4 (FRMPD4) and adjacent to male-specific lethal complex subunit 3 (MSL3). Thus, we have identified an X-linked locus that could account for a significant fraction of the Fcells% variation in patients with SCD., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

There is growing epidemiological evidence that onchocerciasis may induce epilepsy. High prevalence of onchocerciasis has been reported in onchocerciasis-meso and hyper-endemic regions. We aimed to determine the OV16 antibody prevalence in persons with epilepsy (PWE) in four onchocerciasis-endemic regions. PWE were identified during studies in Mahenge area (Tanzania), Kitgum and Pader districts (Uganda), the Mbam and Sanaga river valleys (Cameroon), and the Logo health zone (Democratic Republic of Congo). Exposure to Onchocerca volvulus was assessed by testing PWE for OV16 IgG4 antibodies using a rapid diagnostic test. The OV16 seroprevalence among PWE in the four onchocerciasis-endemic study sites ranged from 35.2% to 59.7%. OV16 seroprevalence increased with age until the age of 39 years, after which it decreased drastically. Our study suggests that, in onchocerciasis-endemic regions, epilepsy in young people is often associated with onchocerciasis, while epilepsy in older persons seems unrelated to O. volvulus exposure.

Despite a long history of community-directed treatment with ivermectin (CDTI), a high ongoing Onchocerca volvulus transmission is observed in certain onchocerciasis-endemic regions in Africa with a high prevalence of epilepsy. We investigated factors associated with higher microfilarial (mf) density after ivermectin treatment. Skin snips were obtained from O. volvulus- infected persons with epilepsy before, and 3 to 5 months after ivermectin treatment. Participants were enrolled from 4 study sites: Maridi (South Sudan); Logo and Aketi (Democratic Republic of Congo); and Mahenge (Tanzania). Of the 329 participants, 105 (31.9%) had a post-treatment mf density >20% of the pre-treatment value. The percentage reduction in the geometric mean mf density ranged from 69.0% (5 months after treatment) to 89.4% (3 months after treatment). A higher pre-treatment mf density was associated with increased probability of a positive skin snip after ivermectin treatment ( p = 0.016). For participants with persistent microfiladermia during follow-up, a higher number of previous CDTI rounds increased the odds of having a post-treatment mf density >20% of the pre-treatment value ( p = 0.006). In conclusion, the high onchocerciasis transmission in the study sites may be due to initially high infection intensity in some individuals. Whether the decreasing effect of ivermectin with increasing years of CDTI results from sub-optimal response mechanisms warrants further research.

Background: Extended artemisinin-based combination therapy (ACT) for treatment of uncomplicated Plasmodium falciparum malaria with already existing drug regimens, such as artemether-lumefantrine, might be effective in tackling the emerging ACT resistance. However, given the history of cardiotoxicity among anti-malarial drugs structurally similar to lumefantrine, the potential effect of extended artemether-lumefantrine treatment on the electrocardiographic (ECG) QTc interval is of high concern., Methods: Male and non-pregnant females aged 1-65 years, diagnosed with uncomplicated P. falciparum malaria in Bagamoyo district, Tanzania, were randomized into two arms. The intervention arm received an extended, i.e. 6-day, course of artemether-lumefantrine and an additional single low-dose primaquine (0.25 mg/kg) administered together with the last artemether-lumefantrine dose. The control arm received the standard weight-based 3-day course. ECGs were performed at day 0 and 4-5 h after the last dose at day 5. QT intervals were read manually using the tangent method and automatically. Bazett's (QTcB) and Fridericia's (QTcF) formulae were used for correction for heart rate. Descriptive statistics were used to calculate baseline characteristics and the number of supra-thresholds QTc intervals (QTc prolongation > 500, change in QTc interval (ΔQTc) > 60 ms). The mean change in QTc interval in and between the two arms was compared using the paired t-test and independent samples t-test, respectively., Results: A total of 195 patients were enrolled, 103 and 92 in the intervention and control arm, respectively. No patient experienced QTc intervals > 500 ms on day 5 by both formulae. Patients with ΔQTc > 60 ms, for QTcF were 6/103 (5.8%) vs 2/92 (2.2%) and for QTcB 2/103 (1.9%) vs 1/92 (1.1%) in the intervention and control arms, respectively. The mean difference in ΔQTc interval was statistically significant between the two arms with both correction formulae, 11.4 ms (95% CI 2.7-20.0, p = 0.010) and 13.4 ms (95% CI 5.3-21.5, p = 0.001), for QTcB and QTcF, respectively., Conclusion: The extended 6-day course of artemether-lumefantrine did not reveal clinically relevant QTc prolonging effects. However, significant QTcF prolongation and presence of patients with supra-threshold QTc values observed in the intervention arm underscore the importance of further monitoring of QTc parameters in extended artemether-lumefantrine treatment. Trial registration ClinicalTrials.gov, NCT03241901. Registered July 27, 2017. https://clinicaltrials.gov/show/NCT03241901.

Background: Artemisinin-based combination therapy (ACT) resistant Plasmodium falciparum represents an increasing threat to Africa. Extended ACT regimens from standard 3 to 6 days may represent a means to prevent its development and potential spread in Africa., Methods: Standard 3-day treatment with artemether-lumefantrine (control) was compared to extended 6-day treatment and single low-dose primaquine (intervention); in a randomized controlled, parallel group, superiority clinical trial of patients aged 1-65 years with microscopy confirmed uncomplicated P. falciparum malaria, enrolled in Bagamoyo district, Tanzania. The study evaluated parasite clearance, including proportion of PCR detectable P. falciparum on days 5 and 7 (primary endpoint), cure rate, post-treatment prophylaxis, safety and tolerability. Clinical, and laboratory assessments, including ECG were conducted during 42 days of follow-up. Blood samples were collected for parasite detection (by microscopy and PCR), molecular genotyping and pharmacokinetic analyses. Kaplan-Meier survival analyses were done for both parasite clearance and recurrence., Results: A total of 280 patients were enrolled, 141 and 139 in the control and intervention arm, respectively, of whom 121 completed 42 days follow-up in each arm. There was no difference in proportion of PCR positivity across the arms at day 5 (80/130 (61.5%) vs 89/134 (66.4%), p = 0.44), or day 7 (71/129 (55.0%) vs 70/134 (52.2%), p = 0.71). Day 42 microscopy determined cure rates (PCR adjusted) were 97.4% (100/103) and 98.3% (110/112), p = 0.65, in the control and intervention arm, respectively. Microscopy determined crude recurrent parasitaemia during follow-up was 21/121 (17.4%) in the control and 14/121 (11.6%) in the intervention arm, p = 0.20, and it took 34 days and 42 days in the respective arms for 90% of the patients to remain without recurrent parasitaemia. Lumefantrine exposure was significantly higher in intervention arm from D3 to D42, but cardiac, biochemical and haematological safety was high and similar in both arms., Conclusion: Extended 6-day artemether-lumefantrine treatment and a single low-dose of primaquine was not superior to standard 3-day treatment for ACT sensitive P. falciparum infections but, importantly, equally efficacious and safe. Thus, extended artemether-lumefantrine treatment may be considered as a future treatment regimen for ACT resistant P. falciparum, to prolong the therapeutic lifespan of ACT in Africa. Trial registration ClinicalTrials.gov, NCT03241901. Registered July 27, 2017 https://clinicaltrials.gov/show/NCT03241901.

Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as public health problem through morbidity management and preventive annual mass drug administration (MDA). This cross-sectional community-based surveillance assessed the prevalence and correlates of LF infection in Mkinga district, Tanga-region, Tanzania. A total of 4115 individuals (49.7% males, 35.2% children) were screened for circulating filarial antigens (CFA), microfilaremia (mf) and disease manifestations in 15 villages between November 2018 and January 2019. MDA uptake in the previous year was assessed. Overall prevalence of CFA-positivity was 5.8% (239/4115; 95% CI: 5.1-6.6), with significant heterogeneity between villages (range 1.2% to 13.5%). CFA-positivity was higher in males (8.8%) than females (3.3%), and correlated with increasing age ( p < 0.001). Prevalence of mf among CFA-positives was 5.2%. Only 60% of eligible inhabitants in the study area took MDA in the previous year, and CFA-positivity was 2-fold higher in those who missed MDA ( p < 0.0001). Prevalence of scrotal enlargement, hydrocele, arms or legs swelling, lymphoedema and lymphadenopathy was 6.4%, 3.7%, 1.35%, 1.2% and 0.32%, respectively. Compared to baseline data, 16 years of MDA intervention significantly reduced LF transmission and morbidity, although the intended elimination target of <1% mf and <2% antigenemia to level where recrudescence is unlikely to occur by the year 2020 may not be attained. The finding of hotspots with ongoing transmission calls for intensified control measures.

During door-to-door surveys in onchocerciasis-endemic regions in Africa, the age-specific ivermectin coverage in 29 722 individuals was assessed. Children 5-6 y of age had significantly lower coverage compared with older participants. Insufficient ivermectin intake among young children could prolong onchocerciasis elimination prospects, as they may serve as human reservoirs of Onchocerca volvulus; moreover, it increases the risk of developing onchocerciasis-associated epilepsy (OAE). The causes of the low ivermectin coverage observed among children 5-6 y of age need to be explored. Integrating ivermectin distribution into chemoprophylaxis strategies for other neglected diseases could increase coverage in a cost-effective manner., (© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Coinfections with malaria and soil-transmitted helminths (STHs) has been common among school-aged children in Tanzania. However, after a countrywide scaling up of interventions for malaria and STHs, there are limited data on the prevalence of malaria-STH coinfections and its effect on anemia in schoolchildren in Tanzania. We assessed the distribution and risk factors for malaria, STHs, and malaria-STH coinfections, and its relation to anemia among 445 primary schoolchildren in Muheza district. A semi-structured questionnaire was used to collect demographic characteristics of the children. Malaria rapid diagnostic test (mRDT) was used to diagnose malaria infection. Soil-transmitted helminths were diagnosed using the Kato-Katz technique. Primary outcome was anemia, defined as hemoglobin concentration < 11 g/dL. Chi-square (χ 2 ) or Fisher's exact tests, Kruskal-Wallis or t -test, and logistic models were used as appropriate. Overall, the prevalence of malaria, STHs, malaria-STH coinfection, and anemia were 18.4%, 6.1%, 1.6%, and 19.8%, respectively. Anemic children were more likely to have malaria (adjusted odds ratio [aOR] = 4.538, 95% CI: 2.189-9.409), whereas frequent use of bed nets was associated with reduced risk of malaria (aOR = 0.234, 95% CI: 0.130-0.42). On the other hand, not always using latrines and eating raw uncooked food increased the risk of STH infection. The prevalence of anemia was high and was associated with both malaria and malaria-STH infections, therefore calling for more integrated malaria-STH control approaches to target school-aged children.

Microscopy-determined Plasmodium falciparum positivity rates exceeding 10% on day 3 after initiation of artemisinin-based combination therapy (ACT) is an important indicator of artemisinin resistance. However, microscopy does not detect low-density parasitemia, contrary to molecular tools such as loop-mediated isothermal amplification (LAMP) and polymerase chain reaction (PCR). We compared microscopy, LAMP, and PCR for detection of P. falciparum on day 3 after ACT in 256 patients with uncomplicated malaria in Bagamoyo District, Tanzania. Day 3 positivity rates were 0%, 84.8%, and 84.4% for each method, respectively. The sensitivity and specificity of LAMP against PCR was 100% (95% CI, 96.1-100) and 77.4% (95% CI, 58.9-90.4) when quantitative PCR-determined parasite densities were ≥ two parasites/µL. Loop-mediated isothermal amplification had comparable diagnostic accuracy to PCR and could potentially represent a field-friendly tool for determining day 3 positivity rates. However, what day 3 P. falciparum positivity determined using molecular methods represents needs to be further elucidated.

To describe the clinical manifestations of epilepsy and access to antiseizure treatment in Mahenge in Central Tanzania, an onchocerciasis endemic area with a high prevalence of epilepsy. A door-to-door epilepsy prevalence survey was conducted in four rural and two sub-urban villages. Trained community workers used five screening questions to identify persons suspected to have epilepsy. Such individuals were interviewed and examined by a neurologist or a medical doctor with additional training in epilepsy, and were tested for Onchocerca volvulus antibodies. A total of 221 out of 8,062 (2.74%) surveyed individuals were confirmed to have epilepsy. The median age at seizure onset was 12 years (interquartile range: 7-16). Seventy-nine persons with epilepsy (PWE) (36.1%) had a family member with epilepsy, which was a sibling in 52.1%. Tonic-clonic seizures (142 individuals; 64.2%) were the most common seizure type. Nodding seizures were reported in 12.7% of PWE; the majority of them living in rural villages. Persons with nodding seizures reported more frequent seizures, presented with more psychiatric symptoms, and more often had onchocerciasis antibodies than those with other seizure types. The high rate of individuals with a seizure onset at between seven and 16 years is characteristic of onchocerciasis-associated epilepsy (OAE). Of the PWE, 77.9% met the criteria for the clinical case definition of OAE. Eighty-three PWE (37.6%) were not taking any antiepileptic medication. Phenobarbital was the antiepileptic drug most commonly prescribed in 76.1% of treated PWE. The high prevalence of epilepsy in rural villages in Mahenge most likely is related to the high prevalence of OAE. To prevent children developing OAE, strengthening the onchocerciasis elimination programme in Mahenge is urgently needed. Moreover, a decentralised epilepsy treatment programme is also needed to provide uninterrupted access to affordable antiepileptic drugs for the many PWE living in rural villages in the Mahenge area.

Background: The distribution of human parvovirus B19 (HPV B19) infection is ubiquitous and occurs worldwide. The virus has high tropism to red blood cells progenitor's cells leading to temporary infection of bone marrow and transient arrest of erythropoiesis. People with frequent episodes of hemolytic anemia including sickle cell disease (SCD) and thalassemia are at increased risk of infection. This study aimed at assessing prevalence and factors associated with HPV B19 infections among hospitalized SCD patients., Methodology: This was a cross-sectional hospital-based study among SCD patients hospitalized at Muhimbili National Hospital. HPV B19 was detected using RT-PCR. Hematological and Chemistry tests were done using Sysmex XT2000i and Chemistry analyzer respectively., Results: A total of 329 SCD patients, median age 15 years (interquartile range 7-22 years) were tested for HPV B19. The prevalence of HPV B19 was 29%. In multivariate logistic regression model, HPV B19 infection was associated with pain (OR=4.28, 95%CI: 1.20-15.19; p=0.025), low neutrophil counts (OR=0.57, 95%CI: 0.35-0.92, p=0.022) and MCH (OR=0.92, 95%CI: 0.85-0.99; p=0.033). Individuals infected with HPV B19 had slightly higher prevalence of severe anaemia (30.4% vs. 20.3%, p=0.054) and HIV infection (6.0% vs. 2.1%, p=0.083) in the univariate analysis. Considering the effect of HPV B19 virus on spleen, aplastic anemia and platelet counts in SCD patients, our study did not find any association with these parameters (p=0.244; p= 0.205 and p=0.567 respectively)., Conclusion: The prevalence of HPV B19 among hospitalized SCD patients at MNH was high. SCD patients with HPV B19 were more likely to present with pain, low neutrophils levels, and MCH. HIV infection might be associated with a high risk of HPV infection in SCD patients; however, this requires further investigation., Competing Interests: Competing interests: The authors have declared that no competing interests exist.

Prevalence of and risk factors associated with polymerase chain reaction (PCR)-determined Plasmodium falciparum positivity were assessed on day 3 after initiation of treatment, pre-implementation and up to 8 years post-deployment of artemether-lumefantrine as first-line treatment for uncomplicated malaria in Bagamoyo district, Tanzania. Samples originated from previously reported trials conducted between 2006 and 2014. Cytochrome b-nested PCR was used to detect malaria parasites from blood samples collected on a filter paper on day 3. Chi-square and McNemar chi-squared tests, logistic regression models, and analysis of variance were used as appropriate. Primary outcome was based on the proportion of patients with day 3 PCR-determined P. falciparum positivity. Overall, 256/584 (43.8%) of screened patients had day 3 PCR-determined positivity, whereas only 2/584 (0.3%) had microscopy-determined asexual parasitemia. Day 3 PCR-determined positivity increased from 28.0% (14/50) in 2006 to 74.2% (132/178) in 2007-2008 and declined, thereafter, to 36.0% (50/139) in 2012-2013 and 27.6% (60/217) in 2014. When data were pooled, pretreatment microscopy-determined asexual parasitemia ≥ 100,000/µL, hemoglobin < 10 g/dL, age < 5 years, temperature ≥ 37.5°C, and year of study 2007-2008 and 2012-2013 were significantly associated with PCR-determined positivity on day 3. Significant increases in P. falciparum multidrug resistance gene 1 N86 and P. falciparum chloroquine resistant transporter K76 across years were not associated with PCR-determined positivity on day 3. No statistically significant association was observed between day 3 PCR-determined positivity and PCR-adjusted recrudescence. Day 3 PCR-determined P. falciparum positivity remained common in patients treated before and after implementation of artemether-lumefantrine in Bagamoyo district, Tanzania. However, its presence was associated with pretreatment characteristics. Trials registration numbers: NCT00336375, ISRCTN69189899, NCT01998295, and NCT02090036.

Background: Africa has the highest burden of Sickle cell disease (SCD) but there are few large, systematic studies providing reliable descriptions of the disease spectrum. Tanzania, with 11,000 SCD births annually, established the Muhimbili Sickle Cell program aiming to improve understanding of SCD in Africa. We report the profile of SCD seen in the first 10 years at Muhimbili National Hospital (MNH)., Methods: Individuals seen at MNH known or suspected to have SCD were enrolled at clinic and laboratory testing for SCD, haematological and biochemical analyses done. Ethnicity was self-reported. Clinical and laboratory features of SCD were documented. Comparison was made with non-SCD population as well as within 3 different age groups (< 5, 5-17 and ≥ 18 years) within the SCD population., Results: From 2004 to 2013, 6397 individuals, 3751 (58.6%) SCD patients, were enrolled, the majority (47.4%) in age group 5-17 years. There was variation in the geographical distribution of SCD. Individuals with SCD compared to non-SCD, had significantly lower blood pressure and peripheral oxygen saturation (SpO 2 ). SCD patients had higher prevalence of severe anemia, jaundice and desaturation (SpO 2  < 95%) as well as higher levels of reticulocytes, white blood cells, platelets and fetal hemoglobin. The main causes of hospitalization for SCD within a 12-month period preceding enrolment were pain (adults), and fever and severe anemia (children). When clinical and laboratory features were compared in SCD within 3 age groups, there was a progressive decrease in the prevalence of splenic enlargement and an increase in prevalence of jaundice. Furthermore, there were significant differences with monotonic trends across age groups in SpO2, hematological and biochemical parameters., Conclusion: This report confirms that the wide spectrum of clinical expression of SCD observed elsewhere is also present in Tanzania, with non-uniform geographical distribution across the country. Age-specific analysis is consistent with different disease-patterns across the lifespan., Competing Interests: Approval was by MUHAS ethical committee (MU/RP/AEC/VOL XI/33) and permission given by MNH. Written informed consent was obtained from all participants. For individuals 18 years or above, while for minors, a parent/guardian consented and signed the consent on behalf of the patient; adolescents provided assent.Not applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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.

Background: Epilepsy is a neurological disorder with a multitude of underlying causes, which may include infection with Onchocerca volvulus, the parasitic worm that causes human onchocerciasis. A survey carried out in 1989 revealed a high prevalence of epilepsy (1.02% overall, ranging from 0.51 to 3.71% in ten villages) in the Mahenge area of Ulanga district, an onchocerciasis endemic region in south eastern Tanzania. This study aimed to determine the prevalence and incidence of epilepsy following 20 years of onchocerciasis control through annual community directed treatment with ivermectin (CDTI)., Methods: The study was conducted in January 2017 in two suburban and two rural villages in the Mahenge area. Door-to-door household visits were carried out by trained community health workers and data assistants to screen for persons suspected of having epilepsy, using a standardised questionnaire. Persons with suspected epilepsy were then interviewed and examined by a neurologist for case verification. Onchocerciasis associated epilepsy was defined as epilepsy without an obvious cause, with an onset of seizures between the ages of 3-18 years in previously healthy children. In each village, fifty males aged ≥20 years were tested for onchocerciasis antibodies using an OV16 rapid test and were examined for presence of onchocerciasis nodules. Children aged 6-10 years were also tested using OV16 tests., Results: 5117 individuals (median age 18.5 years, 53.2% female) from 1168 households were screened. 244 (4.8%) were suspected of having epilepsy and invited for neurological assessment. Prevalence of epilepsy was 2.5%, with the rural villages having the highest rate (3.5% vs 1.5%), P < 0.001. Overall incidence of epilepsy was 111 cases (95% CI: 73-161) per 100 000 person-years, while that of onchocerciasis associated epilepsy was 131 (95% CI: 70-223). Prevalence of OV16 antibodies in adult males and among children 6-10 years old was higher in rural villages than in suburban villages (76.5% vs 50.6, and 42.6% vs 4.7% respectively), (P < 0.001), while overall prevalence of onchocerciasis nodules was 1.8%., Conclusions: This survey revealed a high prevalence and incidence of epilepsy in two rural onchocerciasis endemic villages in the Mahenge area. Despite 20 years of CDTI, a high prevalence of OV16 antibodies in children aged 6-10 years suggests on-going O. volvulus transmission. Reasons for the persistence of on-going parasite transmission in the Mahenge area need to be investigated.

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.

Fetal hemoglobin (HbF) and peripheral hemoglobin oxygen saturation (SpO 2 ) both predict clinical severity in sickle cell disease (SCD), while reticulocytosis is associated with vasculopathy, but there are few data on mechanisms. HbF, SpO 2 and routine clinical and laboratory measures were available in a Tanzanian cohort of 1175 SCD individuals aged≥5years and the association with SpO 2 (as response variable transformed to a Poisson distribution) was assessed by negative binomial model with age and sex as covariates. Increase in HbF was associated with increased SpO 2 (rate ratio, RR=1.19; 95% confidence intervals [CI] 1.04, 1.37 per natural log unit of HbF; p=0.0004). In univariable analysis, SpO 2 was inversely associated with age, reticulocyte count, and log (total bilirubin) and directly with pulse, SBP, hemoglobin, and log(HbF). In multivariable regression log(HbF) (RR 1.191; 95%CI 1.04, 1.37; p=0.013), pulse (RR 1.01; 95%CI 1.00, 1.01; p=0.026), SBP (RR 1.008; 95%CI 1.00, 1.02; p=0.014), and hemoglobin (1.120; 95%CI 1.05, 1.19; p=0.001) were positively and independently associated with SpO 2 while reticulocyte count (RR 0.985; 95%CI 0.97, 0.99; p=0.019) was independently inversely associated with SpO 2 . In SCD, improving SpO 2 , in part through cardiovascular compensation and associated with reduced reticulocytosis, may be a mechanism by which HbF reduces disease severity., (Copyright © 2017. Published by Elsevier B.V.)

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.