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Several interventional strategies have been implemented in malaria endemic areas where the burden is high, that include among others, intermittent preventive treatment (IPT), a tactic that blocks transmission and can reduce disease morbidity. However, the implementation IPT strategies raises a genuine concern, intervening the development of naturally acquired immunity to malaria which requires continuous contact with parasite antigens. This study investigated whether dihydroartemisinin-piperaquine (DP) or artesunate-amodiaquine (ASAQ) IPT in schoolchildren (IPTsc) impairs IgG reactivity to six malaria antigens. An IPTsc trial in north-eastern Tanzania administered three doses of DP or ASAQ at four-monthly intervals and the schoolchildren were followed up. This study compared IgG reactivity against GLURP-R2, MSP1, MSP3, and CIDR domains (CIDRa1.1, CIDRa1.4, and CIDRa1.5) of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP-1) in intervention and control groups using enzyme linked immunosorbent assay (ELISA) technique. During the study, 369 schoolchildren were available for analysis, 119, 134 and 116 participants in the control, DP and ASAQ groups, respectively. Breadth of malaria antigen recognition increased significantly during and after the intervention phases and did not differ between the study groups (Trend test: DP, z-score = 5.92, p < 0.001, ASAQ, z-score = 6.64, p < 0.001 and control, z-score = 5.85, p < 0.001). There were no differences between the control and ASAQ group in the recognition of any of the tested antigens at all visits. In the DP group, however, during the intervention period IPTsc did not impair antibody against MSP1, MSP3, CIDRa1.1, CIDRa1.4 and CIDRa1.5, but it did impair against GLURP-R2. The current study has shown that effective IPTsc with DP or ASAQ does not interfere with the development of antibodies against malaria antigens of the blood stages, suggesting that the advancement of naturally acquired immunity to malaria is not impeded by IPTsc interventions.

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

To determine time and cost differences between one- and two-step injectable artesunate formulations for treatment of severe malaria and compare their safety and treatment outcomes. We conducted an open-label randomized clinical trial at hospitals in Kinshasa, Democratic Republic of the Congo and Korogwe, United Republic of Tanzania in patients aged 3 months to 16 years with severe malaria. We randomly allocated patients to a new one-step injectable artesunate formulation or the conventional two-step formulation. After discharge, patients were followed for 4 weeks. The main outcomes evaluated were time and cost of administering treatment, and clinical and pharmacodynamic effects. Between 7 June 2022 and 11 August 2023, 200 patients were randomized (1:1) to either the one-step or two-step arm. Mean time to administer artesunate was 2 min 22 s (standard deviation, SD: 50 s) in the one-step arm and 3 min 41 s (SD: 95 s) in the two-step ( -value: < 0.0001). Mean cost of syringes and needles used per patient was 0.53 (SD: 0.13) United States dollars (US$) in the one-step arm versus US$ 0.84 (SD:  0.22) in the two-step ( -value: 0.0001). Parasite clearance half-lives were 2.1 h (SD: 0.9) in the one-step arm and 2.0 h (SD: 0.8) in the two-step (  -value: 0.173). Severe adverse events occurred in one patient in each arm (  -value: 1.000), while 242 and 229 ungraded adverse events occurred in the one- and two-step arms, respectively (  -value: 0.549). In children with severe malaria, one-step injectable artesunate was quicker and cheaper to administer and had equivalent safety and efficacy compared with the conventional formulation.

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.

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

Background Asymptomatic malaria infections largely remain undetected and act as a reservoir for continuous transmission. The study assessed the prevalence of submicroscopic asymptomatic malaria infections and anaemia in two rural low (300 m above sea level) and highland (700 m asl) settings of Korogwe District north-eastern Tanzania. Methods A cross-sectional malariometric survey involving individuals aged 0–19 years was conducted in June 2018 in the two rural villages. Venous blood was collected from eligible study participants for estimation of haemoglobin level, detection of malaria by rapid diagnostic test (RDT), quantification of malaria parasitaemia by microscopy, as well as dried blood spot (DBS) for determining submicroscopic infections by PCR targeting the small subunit of the ribosomal ribonucleic acid (ssrRNA) of human Plasmodium. Results Out of 565 individuals tested, 211 (37.3%) were malaria positive based on RDT, whereas only 81 (14.3%) were positive by microscopy. There was no significant difference in the prevalence between the highland and the lowland village, p = 0.19 and p = 0.78 microscopy and RDT, respectively. Three out of 206 (1.5%) RDT/microscopy negative samples were P. falciparum positive by PCR. Of the 211 RDT and 81 microscopy positive, 130 (61.6%) and 33 (40.7%), respectively, were defined as being asymptomatic. Of the 565 individuals, 135 (23.9%) were anaemic (haemoglobin < 11 g/dL) out of which 5.2% were severely anaemic. The risk of being anaemic was significantly higher among individuals with asymptomatic malaria as compared to those without malaria as confirmed by RDT (AOR = 2.06 (95% CI 1.32–3.20) while based on microscopic results there was no significant differences observed (AOR = 2.09, 95% CI 0.98–4.47). Age and altitude had no effect on the risk of anaemia even after adjusting for asymptomatic malaria. Conclusions Asymptomatic malaria is associated with an increased risk of having anaemia in the study communities. The findings highlight the need for targeted interventions focusing on asymptomatic infections which is an important risks factor for anaemia in the community and act as a source of continued transmission of malaria in the study area.

The efficacy of RTS,S/AS01 as a vaccine for malaria is being tested in a phase 3 clinical trial. Early results show significant, albeit partial, protection against clinical malaria and severe malaria. To ascertain variations in vaccine efficacy according to covariates such as transmission intensity, choice of adjuvant, age at vaccination, and bednet use, we did an individual-participant pooled analysis of phase 2 clinical data. We analysed data from 11 different sites in Africa, including 4453 participants. We measured heterogeneity in vaccine efficacy by estimating the interactions between covariates and vaccination in pooled multivariable Cox regression and Poisson regression analyses. Endpoints for measurement of vaccine efficacy were infection, clinical malaria, severe malaria, and death. We defined transmission intensity levels according to the estimated local parasite prevalence in children aged 2–10 years (PrP2–10), ranging from 5% to 80%. Choice of adjuvant was either AS01 or AS02. Vaccine efficacy against all episodes of clinical malaria varied by transmission intensity (p=0·001). At low transmission (PrP2–10 10%) vaccine efficacy was 60% (95% CI 54 to 67), at moderate transmission (PrP2–10 20%) it was 41% (21 to 57), and at high transmission (PrP2–10 70%) the efficacy was 4% (−10 to 22). Vaccine efficacy also varied by adjuvant choice (p<0·0001)—eg, at low transmission (PrP2–10 10%), efficacy varied from 60% (95% CI 54 to 67) for AS01 to 47% (14 to 75) for AS02. Variations in efficacy by age at vaccination were of borderline significance (p=0·038), and bednet use and sex were not significant covariates. Vaccine efficacy (pooled across adjuvant choice and transmission intensity) varied significantly (p<0·0001) according to time since vaccination, from 36% efficacy (95% CI 24 to 45) at time of vaccination to 0% (−38 to 38) after 3 years. Vaccine efficacy against clinical disease was of limited duration and was not detectable 3 years after vaccination. Furthermore, efficacy fell with increasing transmission intensity. Outcomes after vaccination cannot be gauged accurately on the basis of one pooled efficacy figure. However, predictions of public-health outcomes of vaccination will need to take account of variations in efficacy by transmission intensity and by time since vaccination. Medical Research Council (UK); Bill & Melinda Gates Foundation Vaccine Modelling Initiative; Wellcome Trust.

Intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin–piperaquine is more effective than IPTp with sulfadoxine–pyrimethamine at reducing malaria infection during pregnancy in areas with high-grade resistance to sulfadoxine–pyrimethamine by Plasmodium falciparum in east Africa. We aimed to assess whether IPTp with dihydroartemisinin–piperaquine, alone or combined with azithromycin, can reduce adverse pregnancy outcomes compared with IPTp with sulfadoxine–pyrimethamine. We did an individually randomised, double-blind, three-arm, partly placebo-controlled trial in areas of high sulfadoxine–pyrimethamine resistance in Kenya, Malawi, and Tanzania. HIV-negative women with a viable singleton pregnancy were randomly assigned (1:1:1) by computer-generated block randomisation, stratified by site and gravidity, to receive monthly IPTp with sulfadoxine–pyrimethamine (500 mg of sulfadoxine and 25 mg of pyrimethamine for 1 day), monthly IPTp with dihydroartemisinin–piperaquine (dosed by weight; three to five tablets containing 40 mg of dihydroartemisinin and 320 mg of piperaquine once daily for 3 consecutive days) plus a single treatment course of placebo, or monthly IPTp with dihydroartemisinin–piperaquine plus a single treatment course of azithromycin (two tablets containing 500 mg once daily for 2 consecutive days). Outcome assessors in the delivery units were masked to treatment group. The composite primary endpoint was adverse pregnancy outcome, defined as fetal loss, adverse newborn baby outcomes (small for gestational age, low birthweight, or preterm), or neonatal death. The primary analysis was by modified intention to treat, consisting of all randomised participants with primary endpoint data. Women who received at least one dose of study drug were included in the safety analyses. This trial is registered with ClinicalTrials.gov, NCT03208179. From March-29, 2018, to July 5, 2019, 4680 women (mean age 25·0 years [SD 6·0]) were enrolled and randomly assigned: 1561 (33%; mean age 24·9 years [SD 6·1]) to the sulfadoxine–pyrimethamine group, 1561 (33%; mean age 25·1 years [6·1]) to the dihydroartemisinin–piperaquine group, and 1558 (33%; mean age 24·9 years [6.0]) to the dihydroartemisinin–piperaquine plus azithromycin group. Compared with 335 (23·3%) of 1435 women in the sulfadoxine–pyrimethamine group, the primary composite endpoint of adverse pregnancy outcomes was reported more frequently in the dihydroartemisinin–piperaquine group (403 [27·9%] of 1442; risk ratio 1·20, 95% CI 1·06–1·36; p=0·0040) and in the dihydroartemisinin–piperaquine plus azithromycin group (396 [27·6%] of 1433; 1·16, 1·03–1·32; p=0·017). The incidence of serious adverse events was similar in mothers (sulfadoxine–pyrimethamine group 17·7 per 100 person-years, dihydroartemisinin–piperaquine group 14·8 per 100 person-years, and dihydroartemisinin–piperaquine plus azithromycin group 16·9 per 100 person-years) and infants (sulfadoxine–pyrimethamine group 49·2 per 100 person-years, dihydroartemisinin–piperaquine group 42·4 per 100 person-years, and dihydroartemisinin–piperaquine plus azithromycin group 47·8 per 100 person-years) across treatment groups. 12 (0·2%) of 6685 sulfadoxine–pyrimethamine, 19 (0·3%) of 7014 dihydroartemisinin–piperaquine, and 23 (0·3%) of 6849 dihydroartemisinin–piperaquine plus azithromycin treatment courses were vomited within 30 min. Monthly IPTp with dihydroartemisinin–piperaquine did not improve pregnancy outcomes, and the addition of a single course of azithromycin did not enhance the effect of monthly IPTp with dihydroartemisinin–piperaquine. Trials that combine sulfadoxine–pyrimethamine and dihydroartemisinin–piperaquine for IPTp should be considered. European & Developing Countries Clinical Trials Partnership 2, supported by the EU, and the UK Joint-Global-Health-Trials-Scheme of the Foreign, Commonwealth and Development Office, Medical Research Council, Department of Health and Social Care, Wellcome, and the Bill-&-Melinda-Gates-Foundation.

Background The demand for herbal medicines continues to increase globally. However, community perceptions on their effectiveness and factors influencing their use have not been extensively investigated, notably in the Tanga Region, North-eastern Tanzania, where their use in treating various diseases, including paediatric diarrhoea, has flourished. According to studies, Tanga Region has a high prevalence of diarrhoea among under-five children. This study explored community perceptions on the effectiveness of herbal medicines and factors associated with their use in managing diarrhoea among under-five children in North-eastern Tanzania. Methods A qualitative approach and a narrative design were employed by the present study since they had the potential to reveal unrecognized or unreported research problems. Focus group discussions and in-depth interviews were used to facilitate data collection from June 2022 to February 2023. The methods were chosen since they are the most common sources of qualitative data in health research. Purposive sampling method was used to select 247 participants, which included 171 caretakers, 52 traditional healers, and 24 paediatric health workers. Interviews were conducted until the saturation point was reached. The purposive technique was considered since it was a method that enabled the researcher to select participants who were knowledgeable about the study topic. Data analysis was performed using thematic analysis. Results Economic hardship, culture and heritage, superstitious beliefs, failure to recover after receiving hospital medication, easy accessibility of herbal medicines, and long distance to the health facility were the factors perceived to be potentially associated with persistent use of herbal medicines among caretakers. The majority of participants believed that herbal treatments were harmless and effective in treating diarrhoea. Conclusion Superstitious beliefs, culture, and heritage were the primary justifications for using herbal medicines. It is vital for the relevant authority to educate the community on the risk of using unproven herbal medicines in order to diminish the effects that may arise from using uninvestigated herbs. As things stand, the use of herbal medications will continue owing to their relevance to the lives of people in the study setting.

Background Effective malaria vector control in endemic areas requires understanding the distribution and composition of Anopheles species, as shifts in malaria vector species and composition can influence the efficacy of control interventions and transmission patterns. The current study explored the temporal and spatial distribution of Anopheles species and their infection with Plasmodium in different transmission settings in Tanga region and Unguja, Zanzibar, United Republic of Tanzania. Methods From September 2021 to December 2023, monthly entomological surveys were conducted in 11 villages in Tanga and four Shehias in Unguja. Anopheles mosquitoes were sampled every month in each of 11 villages in Tanga and four Shehias in Unguja, 10 households were consented to participate in each village or Shehia. Mosquitoes were collected indoors and outdoors using CDC light traps, Furvela tent traps, Indoor and Outdoor prokopack. Species identification was performed using PCR, and Plasmodium infections were detected using TaqMan real-time PCR assay. Results A total of 4771 Anopheles mosquitoes collected (3,766 and 905 in Tanga and Unguja respectively), PCR amplification failed in 100 samples. Among successfully identified specimens, An. gambiae s.s. (43.8%) and An. merus (37.1%) were predominant. In Unguja, An. arabiensis (55.7%) and An. merus (41.9%) were most common. Seasonal variations were observed, with An. gambiae s.s . and An. funestus s.s. peaking in the short rainy season, An. arabiensis peaking in both dry and long rainy seasons, and An. merus peaked during both the wet and dry seasons, suggesting relatively stable occurrence throughout the year. Plasmodium infection rates for An. gambiae s.s ., An. funestus s.s ., An. arabiensis , and An. merus were 3.0% in Tanga and 1.2% in Unguja but only found in An. arabiensis . In Tanga, An. gambiae s.s., An. merus , and An. funestus s.s. were more abundant in upland and lowland areas than in the highlands, with urbanization limiting An. merus occurrence. In Unguja, An. arabiensis and An. merus were less common in semi-urban areas but showed a sharp increase during the wet season. Conclusions The study indicates a shift in  An. gambiae   s.l.  sibling species composition has taken place in the study areas compared to previous reports. In the past, An. merus was not considered an important vector in Tanzania. However, in this study An. merus was observed as the second most abundant species across coastal and inland areas of Tanga and Unguja during both wet and dry season. Combined with its observed infection with P. falciparum , the findings suggest An. merus may contribute to perennial transmission of malaria in the region. This presents a new challenge to malaria vector surveillance and control including the need for a year-round multi-strategic approach.