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Abstract Background Reactive case detection (RACD) for malaria control has been found effective in low transmission settings, but its impact and cost-effectiveness in moderate-to-high transmission settings are unknown. We conducted an economic evaluation alongside an empirical trial of a modified RACD strategy (1,7-mRCTR) in three moderate-to-high malaria transmission districts in Tanzania. Methods The costs and cost savings associated with the intervention relative to passive case detection alone were estimated in the study sites of Kilwa, Kibiti, and Rufiji districts in Tanzania from 2019–2021. Empirical cost data were collected using household surveys. The incremental costs of the intervention were calculated from under a societal perspective. Costs are reported in 2022 US dollars. Trial data and malaria registers from health facilities were used to calculate the number of malaria cases detected. We simulated unobserved and distal health effects of the intervention to assess cost-effectiveness in terms of incremental cost-effectiveness ratios (ICERs). Propagated uncertainty was assessed via second-order Monte Carlo simulation, including bootstrapping of empirical data distributions. Incremental costs per disability-adjusted life year (DALY) averted were compared to a willingness-to-pay threshold based on estimated opportunity costs of healthcare spending in Tanzania. Results The programmatic cost of the 1,7-mRCTR intervention was 5327 United States Dollars (USD) per 1000 population. The combination of reactive and passive case detection in the intervention arm resulted in an additional 445 malaria cases detected per 1000 compared to passive detection alone, yielding an incremental cost per additional case detected of 12.0 USD. Based on modelling results, for every percentage point decline in malaria prevalence, the intervention averted 95.2 cases and 0.04 deaths per 1000 population. On average, the 1,7-mRCTR intervention averted 19.1 DALYs per 1000 population. Compared to passive malaria detection, the ICERs for the 1,7-mRCTR intervention were 7.3 USD per case averted, 16,884 USD per death averted, and 163 USD per DALY averted. Conclusions Our analysis demonstrates that the 1,7-mRCTR intervention appears to be cost-effective under a willingness-to-pay threshold of 417 USD per DALY averted, showing that modified RACD strategies can provide value for money in moderate-to-high transmission settings. Graphical Abstract

ABSTRACT Piperaquine tetraphosphate (PQP), a long‐acting antimalarial, is being considered in a combination for chemoprevention. Dihydroartemisinin‐piperaquine tablets (hard and dispersible) approved for the treatment of acute uncomplicated malaria should be administered in a fasted state, as PQP bioavailability increases with food. A new taste‐masked dispersible granules PQP formulation aims to minimize the impact of food on drug exposure. This randomized, open label, parallel group, Phase I pilot study was conducted between 24th July 2023, and 3rd January 2024, at the Ifakara Health Institute, Bagamoyo, Tanzania in 60 healthy African adults (five cohorts of 12). Single‐dose pharmacokinetics and relative systemic exposure of the oral PQP dispersible granules formulation prototype (320 mg) was compared to the hard tablet when fasted and PQP granules in three different fed conditions. In the fasted state, the relative exposure of PQP granules versus the tablet was 73.9% (90% CI 48.3, 113.0) for Cmax and 86.5% (68.2, 109.6) for AUC0‐t. Following a typical East African low‐fat meal, a standard high‐fat meal, or 250 mL whole milk, the relative exposure of PQP granules versus the fasted state was 202% (90% CI 132, 311), 275% (193, 391), and 294% (203, 425) for Cmax and 164% (124, 217), 184% (148, 228), and 195% (147, 259) for AUC0‐t, respectively. Both formulations were well tolerated with one drug‐related adverse event (moderate migraine). No severe or serious adverse events or clinically relevant laboratory or electrocardiograph changes were observed. PQP dispersible granules had lower systemic exposures versus the tablet when fasted, whereas various meals increased drug exposure.

Abstract Background Soil-transmitted helminth (STH) infection control remains a priority in endemic regions where local epidemiological data are needed for sustainable control strategies, particularly regarding population knowledge, attitudes, and practices (KAP). Our work assessed KAP toward STH infection and associated factors among residents of Bata district, Equatorial Guinea. Methods A community-based cross-sectional study was conducted among 14 randomly selected communities in the Bata district. Eligible participants were interviewed face-to-face using a standardized questionnaire. Participants aged under 18 years were interviewed in the presence of their parents or legal guardians. For participants aged less than ten, a simplified version of the main questionnaire was developed focusing on children’s practices toward STH and was administered to their parents or legal guardians. Results A total of 399 participants were included in the present analysis. Among them, 58% responded to the main questionnaire. The mean (± SD) age of participants aged 10 and over was 37.5 (± 22.2) years, and 60% of them were females, while the mean (± SD) age of those aged less than ten was 5.0 (± 2.5) years. The respondents’ overall knowledge, attitudes, and practices to STH were rated as bad (33%), very good (77%), and good (55%), respectively. Knowledge was significantly associated with education level (p = 0.04) with the knowledge level lower for participants with no formal education than for those with secondary/university education (β = -0.56, 95% CI: -1.00 – -0.12, p = 0.01); Appropriate attitudes level was significantly associated with occupation (p = 0.02) and education levels (p = 0.049) with the appropriate attitude level lower for students than for farmers/fishers (β = -1.24, 95% CI: -2.17—-0.32, p = 0.01) and for primary-level participants than for those with secondary/university education (β = -0.68, 95% CI: -1.23—-0.13, p = 0.02); while appropriate practice level were significantly associated with age (p = 0.01), occupation (p = 0.01), and education (p = 0.02), with the appropriate practices level increasing with age (β = 0.03, 95% CI: 0.005 – 0.05, p = 0.01) and lower in participants with no formal education than in those with secondary/university education (β = -1.19, -2.05 – -0.32, p = 0.007). Conclusion The present study revealed a lack of knowledge about STH in the study population, particularly regarding disease causes and transmission ways, highlighting the need for the implementation of integrated health education strategies, both at the community and school levels.

Summary: Background: PfSPZ Vaccine, a promising pre-erythrocytic stage malaria vaccine candidate based on whole, radiation-attenuated Plasmodium falciparum (Pf) sporozoites (SPZ), has proven safe and effective in mediating sterile protection from malaria in malaria-naïve and exposed healthy adults. Vaccine-induced protection presumably depends on cellular responses to early parasite liver stages, but humoral immunity contributes. Methods: On custom-made Pf protein microarrays, we profiled IgG and IgM responses to PfSPZ Vaccine and subsequent homologous controlled human malaria infection (CHMI) in 21 Tanzanian adults with (n = 12) or without (n = 9) HIV infection. Expression of the main identified immunogens in the pre-erythrocytic parasite stage was verified by immunofluorescence detection using freshly purified PfSPZ and an in vitro model of primary human hepatocytes. Findings: Independent of HIV infection status, immunisation induced focused IgG and IgM responses to circumsporozoite surface protein (PfCSP) and merozoite surface protein 5 (PfMSP5). We show that PfMSP5 is detectable on the surface and in the apical complex of PfSPZ. Interpretation: Our data demonstrate that HIV infection does not affect the quantity of the total IgG and IgM antibody responses to PfCSP and PfMSP5 after immunization with PfSPZ Vaccine. PfMSP5 represents a highly immunogenic, so far underexplored, target for vaccine-induced antibodies in malaria pre-exposed volunteers. Funding: This work was supported by the Equatorial Guinea Malaria Vaccine Initiative (EGMVI), the Clinical Trial Platform of the German Center for Infection Research (TTU 03.702), the Swiss Government Excellence Scholarships for Foreign Scholars and Artists (grant 2016.0056) and the Interdisciplinary Center for Clinical Research doctoral program of the Tübingen University Hospital. The funders had no role in design, analysis, or reporting of this study.

Abstract A pilot implementation of the rapid diagnostic test program was performed to collect evidence of the feasibility, acceptability, and uptake of the COVID-19 AgRDT in Tanzania. We conducted a prospective cross-sectional study in the community to provide quantitative details of the pilot implementation of the antigen rapid diagnostic test (AgRDT) in Tanzania. This study was undertaken between March 2022 and September 2022. The pilot was implemented by distributing and offering test kits to people suspected of having COVID-19 in Dar es Salaam through community health workers. A total of 1039 participants consented to participate in the survey. All the participants reported having heard about the disease. The radio was the main source (93.2%) of information on COVID-19. With regard to prevention measures, approximately 930 (89.5%) of the respondents thought that COVID-19 could be prevented. Approximately 1035 (99.6%) participants reported that they were willing to have a COVID-19 AgRDT test and wait for 20 min for the results. With regard to the participants’ opinions on the AgRDT device, the majority 907 (87.3%) felt comfortable with the test, and 1,029 (99.0%) were very likely to recommend the AgRDT test to their friends. The majority of participants 848 (83.1%) mentioned that they would be willing to pay for the test if it was not available for free. The results suggest overall good acceptance of the COVID-19 AgRDT test. It is evident that the use of trained community healthcare workers allows easy screening of all possible suspects and helps them receive early treatment.

BackgroundParasitic infectious agents rarely occur in isolation. Epidemiological evidence is mostly lacking, and little is known on how the two common parasites Plasmodium and soil transmitted helminths (STH) interact. There are contradictory findings in different studies. Synergism, antagonism and neutral effect have been documented between Plasmodium and STH. This study investigated the impact of STH on clinical malaria presentation and treatment outcome.MethodsA matched case control study with a semi longitudinal follow up according to World Health Organization (WHO) antimalarial surveillance guideline was done among children aged 2 months to 9 years inclusively living in western rural areas of Bagamoyo, coastal region of Tanzania. Cases were children with uncomplicated and severe malaria enrolled from the health facilities while controls were children with asymptomatic Plasmodium parasitemia enrolled from the same community.ResultsIn simple conditional regression analysis there was a tendency for a protective effect of STH on the development of clinical malaria [OR = 0.6, 95% CI of 0.3-1.3] which was more marked for Enterobius vermicularis species [OR = 0.2, 95% CI of 0.0-0.9]. On the contrary, hookworm species tended to be associated with increased risk of clinical malaria [OR = 3.0, 95% CI of 0.9-9.5]. In multiple conditional regression analysis, the overall protective effect was lower for all helminth infection [OR = 0.8, 95% CI of 0.3-1.9] but remained significantly protective for E. vermicularis species [OR = 0.1, 95% CI of 0.0-1.0] and borderline significant for hookworm species [OR = 3.6, 95% CI of 0.9-14.3]. Using ordinal logistic regression which better reflects the progression of asymptomatic Plasmodium parasitemia to severe malaria, there was a 50% significant protective effect with overall helminths [OR = 0.5, 95% CI of 0.3-0.9]. On the contrary, hookworm species was highly predictive of uncomplicated and severe malaria [OR = 7.8, 95% (CI of 1.8-33.9) and 49.7 (95% CI of 1.9-1298.9) respectively]. Generally, children infected with STH had higher geometric mean time to first clearance of parasitemia.ConclusionThe findings of a protective effect of E. vermicularis and an enhancing effect of hookworms may explain the contradictory results found in the literature about impact of helminths on clinical malaria. More insight should be gained on possible mechanisms for these opposite effects. These results should not deter at this stage deworming programs but rather foster implementation of integrated control program for these two common parasites.

Abstract Background Progress in malaria control has stalled in recent years and innovative surveillance and response approaches are needed to accelerate malaria control and elimination efforts in endemic areas of Africa. Building on a previous China-UK-Tanzania pilot study on malaria control, this study aimed to assess the impact of the 1,7-malaria Reactive Community-Based Testing and Response (1,7-mRCTR) approach implemented over two years in three districts of Tanzania. Methods The 1,7-mRCTR approach provides community-based malaria testing via rapid diagnostic tests and treatment in villages with the highest burden of malaria incidence based on surveillance data from health facilities. We used a difference-in-differences quasi-experimental design with linear probability models and two waves of cross-sectional household surveys to assess the impact of 1,7-mRCTR on malaria prevalence. We conducted sensitivity analyses to assess the robustness of our results, examined how intervention effects varied in subgroups, and explored alternative explanations for the observed results. Results Between October 2019 and September 2021, 244,771 community-based malaria rapid tests were completed in intervention areas, and each intervention village received an average of 3.85 rounds of 1-7mRCTR. Malaria prevalence declined from 27.4% at baseline to 11.7% at endline in the intervention areas and from 26.0% to 16.0% in the control areas. 1,7-mRCTR was associated with a 4.5-percentage-point decrease in malaria prevalence (95% confidence interval: − 0.067, − 0.023), equivalent to a 17% reduction from the baseline. In Rufiji, a district characterized by lower prevalence and where larviciding was additionally provided, 1,7-mRCTR was associated with a 63.9% decline in malaria prevalence. Conclusions The 1,7-mRCTR approach reduced malaria prevalence. Despite implementation interruptions due to the COVID-19 pandemic and supply chain challenges, the study provided novel evidence on the effectiveness of community-based reactive approaches in moderate- to high-endemicity areas and demonstrated the potential of South-South cooperation in tackling global health challenges. Graphical Abstract

Abstract A field experiment was carried out during the agricultural season 2021-2022 in two locations within the administrative borders of Nineveh Governorate, the first location in the Gleokhan area within the borders of Mosul Center and the second location within the administrative borders of Namrod district, which is 45 km from the center of Mosul district, in order to know the effect of the balanced NPK 20:20:20 compound fertilizer nano the growth and yield of four varieties of bread wheat. The global experiment was carried out, which consisted of two factors, a randomized complete block design, and three replications. The first factor was fertilizer levels with four levels (1, 2, and 3 gm.L-1) added in two phases. The first is in the tillers stage (Z 2-1) and the second stage is at the beginning of the boating stage (Z 4-0) on the Zadoks scale, in addition to the comparison treatment, which was the traditional farmer’s method of fertilization (adding urea and dab fertilizer according to the times and quantities recommended by the Ministry Iraqi Agriculture), the second factor, four varieties of local bread wheat (Bhoth 22, Abu Ghraib, Rashid and Jihan), the following characteristics were studied: plant height, number of tillers, flag leaf area, total chlorophyll content of flag leaf, number of days up to 50% flowering, number of spikes, spike length, number of grains per spike, grain yield, weight of 1000 grains. The most important results of the study were as follows: The comparison treatment (the traditional farmer's method) excelled in the total chlorophyll content of the Gleokhan site and in the number of spikes and weight of 1000 grains in the Namrod site, with values of (28.41 Spad, 267.75 spikes.m-2, and 44.91 g), respectively. The 1 g spray treatment excelled in the characteristics of the number of tillers, number of spikes, length of spike, grain yield, and weight of 1000 grains at the Gleokhan site, and in the two characteristics of leaf area and spike length at the Namrod site, with averages of (178.17 tiller.m-2, 100.08 spikes.m-2, 8.58 cm , 128.83 g.m-2, 35.20 g, 34.46 cm2 and 10.85 cm) in the aforementioned order. The 3 g spray treatment was superior in the characteristics of plant height for both sites, the number of days up to 50% flowering, and grain yield of the Namrod site, with rates of (54.42 cm, 80.77 cm, 135.83 days, and 332.17 g.m-2), respectively. No significant differences were recorded between the levels of fertilizer in terms of flag leaf area and number of days up to 50% flowering for Gleokhan site and number of grains per spike for both sites. The cultivar Bhoth 22 excelled in terms of total chlorophyll content and the weight of 1000 grains at the Gleokhan site, and for the characteristics of the number of tillers, number of days up to 50% flowering, number of spikes, and grain yield of the Namrod site, as averages were recorded (27.29 Spad, 34.23 g, 302.75 tiller.m-2, 134.92 days, 290.17 spike.m-2 and 405.42 g m-2) respectively. The Abu Ghraib cultivar achieved superiority in the number of grains per spike at Al-Namrod site, with an average of (46.43 grains.spike-1). The cultivar Rashid excelled in the characteristics of the number of tillers, number of spikes, and spike length at the Gleokhan site, and for the two characteristics of the flag leaf area and spike length at the Namrod site, where the rates were recorded (169.08 tiller.m-2, 104.58 spike.m-2, 8.56 cm, 34.55 cm2 and 12.98 cm), respectively. The cultivar Jihan achieved superiority in the two characteristics of the number of days up to 50% flowering and grain yield at Gleokhan site, with values of (131 days and 108.08 g.m-2), respectively. No significant differences were recorded between the cultivars included in the study in the characteristics of plant height, flag leaf area, number of grains per spike for Gleokhan site, and for the two characteristics of total chlorophyll content and weight of 1000 grains for Namrod site. The interaction of 1 g spray treatment with Jihan cultivar recorded the highest average grain yield at Gleokhan site, and the 3 g spray treatment with Bhoth 22 cultivar had the highest average grain yield at Namrod site with values of (301 and 487.67 g.m-2), respectively.

Introduction Malaria, a devastating febrile illness caused by protozoan parasites, sickened 247,000,000 people in 2021 and killed 619,000, mostly children and pregnant women in sub-Saharan Africa. A highly effective vaccine is urgently needed, especially for Plasmodium falciparum (Pf), the deadliest human malaria parasite. Areas covered Sporozoites (SPZ), the parasite stage transmitted by Anopheles mosquitoes to humans, are the only vaccine immunogen achieving > 90% efficacy against Pf infection. This review describes > 30 clinical trials of PfSPZ vaccines in the U.S.A., Europe, Africa, and Asia, based on first-hand knowledge of the trials and PubMed searches of ‘sporozoites,’ ‘malaria,’ and ‘vaccines.’ Expert opinion First generation (radiation-attenuated) PfSPZ vaccines are safe, well tolerated, 80-100% efficacious against homologous controlled human malaria infection (CHMI) and provide 18-19 months protection without boosting in Africa. Second generation chemo-attenuated PfSPZ are more potent, 100% efficacious against stringent heterologous (variant strain) CHMI, but require a co-administered drug, raising safety concerns. Third generation, late liver stage-arresting, replication competent (LARC), genetically-attenuated PfSPZ are expected to be both safe and highly efficacious. Overall, PfSPZ vaccines meet safety, tolerability, and efficacy requirements for protecting pregnant women and travelers, with licensure for these populations possible within five years. Protecting children and mass vaccination programs to block transmission and eliminate malaria are long-term objectives.

Abstract World Health Organization (WHO) certified China malaria-free on June 30, 2021, which brightens the goal of global malaria elimination efforts. China contributed its unique innovations to the global community: Artemisinin, discovered by Tu Youyou, has saved millions of lives globally; the “1-3-7” norm developed in 2012, has been adapted in the local contexts of countries in the Southeast Asia and Africa. How to the targets of Global Technical Strategy for Malaria (GTS) 2016−2030. By looking into the malaria control phase, towards elimination phase from 1960 to 2011 in sub-Saharan Africa and China, we found that the gap in malaria burden will widen unless the interventions in Africa are enhanced. It is imperative to identify the key China–Africa cooperation areas on malaria control and elimination, so that synergized efforts could be pooled together to help African countries achieve the elimination goal. The practices from China malaria control and elimination efforts could be leveraged to fast-track malaria elimination efforts in Africa, which makes it possible that the China’s journey of malaria elimination extends to Africa. Graphical Abstract

BackgroundSoil transmitted Helminths (STH) infections remain a public health concern worldwide, particularly in tropical and subtropical areas where these diseases are highly endemic. Knowing the prevalence and risk factors of the disease is crucial for efficient STH control strategies in endemic areas. The scarcity of epidemiological data on STH for Equatorial Guinea has motivated the decision to perform the present study.MethodsA cluster-based cross-sectional study was carried out in Bata district from November 2020 to January 2021. Stool samples were collected for the diagnostic of STH infections using Kato-Katz technique. Descriptive statistics was performed for determination of STH prevalence and intensity, while logistic regression models were used to assess the risk factors associated with STH infections.ResultsA total of 340 participants were included in the study with a mean age of 24 years (SD = 23.7) and 1.2 female-to-male sex-ratio. The overall prevalence of any STH was 60% (95%CI: 55-65). The most prevalent species were Ascaris lumbricoides (43%, 95%CI: 37-48) and Trichuris trichiura (40%, 95%CI: 35-46). Intensity of infection were mainly light to moderate. A trend of association was observed between age and any STH infection (overall p-value = 0.07), with a significant difference observed between children aged 5-14 years as compared to those aged 1-4 (aOR 2.12; 95%CI: 1.02-4.43, p-value = 0.04), while locality was significantly associated with STH infection (overall p-valueConclusionBata district is a high STH transmission area, where school-aged children and peri-urban areas are associated with a higher risk of any STH infection. This situation calls for a full implementation of the WHO recommendations for STH control; mass drug administration of anthelminthic twice a year to the whole population with great attention to school age children, and prioritizing peri-urban areas where safe water, improve sanitation, and hygiene education should be implemented to achieve a better control.

Abstract Background Progress towards malaria elimination has stagnated, partly because infections persisting at low parasite densities comprise a large reservoir contributing to ongoing malaria transmission and are difficult to detect. This study compared the performance of an ultrasensitive rapid diagnostic test (uRDT) designed to detect low density infections to a conventional RDT (cRDT), expert microscopy using Giemsa-stained thick blood smears (TBS), and quantitative polymerase chain reaction (qPCR) during a controlled human malaria infection (CHMI) study conducted in malaria exposed adults (NCT03590340). Methods Blood samples were collected from healthy Equatoguineans aged 18–35 years beginning on day 8 after CHMI with 3.2 × 103 cryopreserved, infectious Plasmodium falciparum sporozoites (PfSPZ Challenge, strain NF54) administered by direct venous inoculation. qPCR (18s ribosomal DNA), uRDT (Alere™ Malaria Ag P.f.), cRDT [Carestart Malaria Pf/PAN (PfHRP2/pLDH)], and TBS were performed daily until the volunteer became TBS positive and treatment was administered. qPCR was the reference for the presence of Plasmodium falciparum parasites. Results 279 samples were collected from 24 participants; 123 were positive by qPCR. TBS detected 24/123 (19.5% sensitivity [95% CI 13.1–27.8%]), uRDT 21/123 (17.1% sensitivity [95% CI 11.1–25.1%]), cRDT 10/123 (8.1% sensitivity [95% CI 4.2–14.8%]); all were 100% specific and did not detect any positive samples not detected by qPCR. TBS and uRDT were more sensitive than cRDT (TBS vs. cRDT p = 0.015; uRDT vs. cRDT p = 0.053), detecting parasitaemias as low as 3.7 parasites/µL (p/µL) (TBS and uRDT) compared to 5.6 p/µL (cRDT) based on TBS density measurements. TBS, uRDT and cRDT did not detect any of the 70/123 samples positive by qPCR below 5.86 p/µL, the qPCR density corresponding to 3.7 p/µL by TBS. The median prepatent periods in days (ranges) were 14.5 (10–20), 18.0 (15–28), 18.0 (15–20) and 18.0 (16–24) for qPCR, TBS, uRDT and cRDT, respectively; qPCR detected parasitaemia significantly earlier (3.5 days) than the other tests. Conclusions TBS and uRDT had similar sensitivities, both were more sensitive than cRDT, and neither matched qPCR for detecting low density parasitaemia. uRDT could be considered an alternative to TBS in selected applications, such as CHMI or field diagnosis, where qualitative, dichotomous results for malaria infection might be sufficient.

Abstract Background Understanding the age patterns of disease is necessary to target interventions to maximise cost-effective impact. New malaria chemoprevention and vaccine initiatives target young children attending routine immunisation services. Here we explore the relationships between age and severity of malaria hospitalisation versus malaria transmission intensity. Methods Clinical data from 21 surveillance hospitals in East Africa were reviewed. Malaria admissions aged 1 month to 14 years from discrete administrative areas since 2006 were identified. Each site-time period was matched to a model estimated community-based age-corrected parasite prevalence to provide predictions of prevalence in childhood (PfPR2–10). Admission with all-cause malaria, severe malaria anaemia (SMA), respiratory distress (RD) and cerebral malaria (CM) were analysed as means and predicted probabilities from Bayesian generalised mixed models. Results 52,684 malaria admissions aged 1 month to 14 years were described at 21 hospitals from 49 site-time locations where PfPR2–10 varied from

Abstract Background Primaquine is a gametocytocidal drug recommended by the World Health Organization (WHO) in a single-low dose combined with artemisinin-based combination therapy (ACT) for the treatment and prevention of Plasmodium falciparum malaria transmission. Safety monitoring concerns and the lack of a universal validated and approved primaquine pharmacovigilance tool is a challenge for a national rollout in many countries. This study aimed to explore the acceptance, reliability and perceived effectiveness of the primaquine roll out monitoring pharmacovigilance tool (PROMPT). Methods This study was conducted in three dispensaries in the Coastal region of Eastern Tanzania. The study held six in-depth interviews with healthcare providers and six participatory focus group discussions with malaria patients (3) and parents/guardians of sick children (3). Participants were purposively sampled. Thematic analysis was conducted with the aid of NVivo qualitative analysis software. Results The respondents’ general acceptance and perceived effectiveness of the single-low dose primaquine and PROMPT was good. Screening procedure for treatment eligibility and explaining to patients about the possible adverse events was considered very useful for safety reasons. Crushing and dissolving of primaquine tablet to get the appropriate dose, particularly in children, was reported by all providers to be challenging. Transport costs and poor access to the health facility were the main reasons for a patient failing to return to the clinic for a scheduled follow-up visit. Treatment was perceived to be safe by both providers and patients and reported no case of a severe adverse event. Some providers were concerned with the haemoglobin drop observed on day 7. Conclusion Single-low dose primaquine was perceived to be safe and acceptable among providers and patients. PROMPT demonstrated to be a reliable and user-friendly tool among providers. Further validation of the tool by involving the National Malaria Control Programme is pivotal to addressing key challenges and facilitating primaquine adoption in the national policy.

BackgroundWhile prior research has shown differences in the risk of malaria infection and sickness between males and females, little is known about sex differences in vaccine-induced immunity to malaria. Identifying such differences could elucidate important aspects of malaria biology and facilitate development of improved approaches to malaria vaccination.MethodsUsing a standardized enzyme-linked immunosorbent assay, IgG antibodies to the major surface protein on Plasmodium falciparum (Pf) sporozoites (SPZ), the Pf circumsporozoite protein (PfCSP), were measured before and two weeks after administration of a PfSPZ-based malaria vaccine (PfSPZ Vaccine) to 5-month to 61-year-olds in 11 clinical trials in Germany, the US and five countries in Africa, to determine if there were differences in vaccine elicited antibody response between males and females and if these differences were associated with differential protection against naturally transmitted Pf malaria (Africa) or controlled human malaria infection (Germany, the US and Africa).ResultsFemales ≥ 11 years of age made significantly higher levels of antibodies to PfCSP than did males in most trials, while there was no indication of such differences in infants or children. Although adult females had higher levels of antibodies, there was no evidence of improved protection compared to males. In 2 of the 7 trials with sufficient data, protected males had significantly higher levels of antibodies than unprotected males, and in 3 other trials protected females had higher levels of antibodies than did unprotected females.ConclusionImmunization with PfSPZ Vaccine induced higher levels of antibodies in post-pubertal females but showed equivalent protection in males and females. We conclude that the increased antibody levels in post-pubertal females did not contribute substantially to improved protection. We hypothesize that while antibodies to PfCSP (and PfSPZ) may potentially contribute directly to protection, they primarily correlate with other, potentially protective immune mechanisms, such as antibody dependent and antibody independent cellular responses in the liver.

Abstract Background Vaccination with radiation-attenuated Plasmodium falciparum sporozoites is known to induce protective immunity. However, the mechanisms underlying this protection remain unclear. In this work, two recent radiation-attenuated sporozoite vaccination studies were used to identify potential transcriptional correlates of vaccination-induced protection. Methods Longitudinal whole blood RNAseq transcriptome responses to immunization with radiation-attenuated P. falciparum sporozoites were analysed and compared across malaria-naïve adult participants (IMRAS) and malaria-experienced adult participants (BSPZV1). Parasite dose and method of delivery differed between trials, and immunization regimens were designed to achieve incomplete protective efficacy. Observed protective efficacy was 55% in IMRAS and 20% in BSPZV1. Study vaccine dosings were chosen to elicit both protected and non-protected subjects, so that protection-associated responses could be identified. Results Analysis of comparable time points up to 1 week after the first vaccination revealed a shared cross-study transcriptional response programme, despite large differences in number and magnitude of differentially expressed genes between trials. A time-dependent regulatory programme of coherent blood transcriptional modular responses was observed, involving induction of inflammatory responses 1–3 days post-vaccination, with cell cycle responses apparent by day 7 in protected individuals from both trials. Additionally, strongly increased induction of inflammation and interferon-associated responses was seen in non-protected IMRAS participants. All individuals, except for non-protected BSPZV1 participants, showed robust upregulation of cell-cycle associated transcriptional responses post vaccination. Conclusions In summary, despite stark differences between the two studies, including route of vaccination and status of malaria exposure, responses were identified that were associated with protection after PfRAS vaccination. These comprised a moderate early interferon response peaking 2 days post vaccination, followed by a later proliferative cell cycle response steadily increasing over the first 7 days post vaccination. Non-protection is associated with deviations from this model, observed in this study with over-induction of early interferon responses in IMRAS and failure to mount a cell cycle response in BSPZV1.

Abstract Background Extensive malaria control measures have been implemented on Bioko Island, Equatorial Guinea over the past 16 years, reducing parasite prevalence and malaria-related morbidity and mortality, but without achieving elimination. Malaria vaccines offer hope for reducing the burden to zero. Three phase 1/2 studies have been conducted successfully on Bioko Island to evaluate the safety and efficacy of whole Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccines. A large, pivotal trial of the safety and efficacy of the radiation-attenuated Sanaria® PfSPZ Vaccine against P. falciparum is planned for 2022. This study assessed the incidence of malaria at the phase 3 study site and characterized the influence of socio-demographic factors on the burden of malaria to guide trial design. Methods A cohort of 240 randomly selected individuals aged 6 months to 45 years from selected areas of North Bioko Province, Bioko Island, was followed for 24 weeks after clearance of parasitaemia. Assessment of clinical presentation consistent with malaria and thick blood smears were performed every 2 weeks. Incidence of first and multiple malaria infections per person-time of follow-up was estimated, compared between age groups, and examined for associated socio-demographic risk factors. Results There were 58 malaria infection episodes observed during the follow up period, including 47 first and 11 repeat infections. The incidence of malaria was 0.25 [95% CI (0.19, 0.32)] and of first malaria was 0.23 [95% CI (0.17, 0.30)] per person per 24 weeks (0.22 in 6–59-month-olds, 0.26 in 5–17-year-olds, 0.20 in 18–45-year-olds). Incidence of first malaria with symptoms was 0.13 [95% CI (0.09, 0.19)] per person per 24 weeks (0.16 in 6–59-month-olds, 0.10 in 5–17-year-olds, 0.11 in 18–45-year-olds). Multivariate assessment showed that study area, gender, malaria positivity at screening, and household socioeconomic status independently predicted the observed incidence of malaria. Conclusion Despite intensive malaria control efforts on Bioko Island, local transmission remains and is spread evenly throughout age groups. These incidence rates indicate moderate malaria transmission which may be sufficient to support future larger trials of PfSPZ Vaccine. The long-term goal is to conduct mass vaccination programmes to halt transmission and eliminate P. falciparum malaria.

Abstract Background Diverse vaccination outcomes and protection levels among different populations pose a serious challenge to the development of an effective malaria vaccine. Co-infections are among many factors associated with immune dysfunction and sub-optimal vaccination outcomes. Chronic, asymptomatic viral infections can contribute to the modulation of vaccine efficacy through various mechanisms. Human Pegivirus-1 (HPgV-1) persists in immune cells thereby potentially modulating immune responses. We investigated whether Pegivirus infection influences vaccine-induced responses and protection in African volunteers undergoing whole P. falciparum sporozoites-based malaria vaccination and controlled human malaria infections (CHMI). Methods HPgV-1 prevalence was quantified by RT-qPCR in plasma samples of 96 individuals before, post vaccination with PfSPZ Vaccine and after CHMI in cohorts from Tanzania and Equatorial Guinea. The impact of HPgV-1 infection was evaluated on (1) systemic cytokine and chemokine levels measured by Luminex, (2) PfCSP-specific antibody titers quantified by ELISA, (3) asexual blood-stage parasitemia pre-patent periods and parasite multiplication rates, (4) HPgV-1 RNA levels upon asexual blood-stage parasitemia induced by CHMI. Results The prevalence of HPgV-1 was 29.2% (28/96) and sequence analysis of the 5′ UTR and E2 regions revealed the predominance of genotypes 1, 2 and 5. HPgV-1 infection was associated with elevated systemic levels of IL-2 and IL-17A. Comparable vaccine-induced anti-PfCSP antibody titers, asexual blood-stage multiplication rates and pre-patent periods were observed in HPgV-1 positive and negative individuals. However, a tendency for higher protection levels was detected in the HPgV-1 positive group (62.5%) compared to the negative one (51.6%) following CHMI. HPgV-1 viremia levels were not significantly altered after CHMI. Conclusions HPgV-1 infection did not alter PfSPZ Vaccine elicited levels of PfCSP-specific antibody responses and parasite multiplication rates. Ongoing HPgV-1 infection appears to improve to some degree protection against CHMI in PfSPZ-vaccinated individuals. This is likely through modulation of immune system activation and systemic cytokines as higher levels of IL-2 and IL17A were observed in HPgV-1 infected individuals. CHMI is safe and well tolerated in HPgV-1 infected individuals. Identification of cell types and mechanisms of both silent and productive infection in individuals will help to unravel the biology of this widely present but largely under-researched virus.

Abstract Background In 2015, a China-UK-Tanzania tripartite pilot project was implemented in southeastern Tanzania to explore a new model for reducing malaria burden and possibly scaling-out the approach into other malaria-endemic countries. The 1,7-malaria Reactive Community-based Testing and Response (1,7-mRCTR) which is a locally-tailored approach for reporting febrile malaria cases in endemic villages was developed to stop transmission and Plasmodium life-cycle. The (1,7-mRCTR) utilizes existing health facility data and locally trained community health workers to conduct community-level testing and treatment. Methods The pilot project was implemented from September 2015 to June 2018 in Rufiji District, southern Tanzania. The study took place in four wards, two with low incidence and two with a higher incidence. One ward of each type was selected for each of the control and intervention arms. The control wards implemented the existing Ministry of Health programmes. The 1,7-mRCTR activities implemented in the intervention arm included community testing and treatment of malaria infection. Malaria case-to-suspect ratios at health facilities (HF) were aggregated by villages, weekly to identify the village with the highest ratio. Community-based mobile test stations (cMTS) were used for conducting mass testing and treatment. Baseline (pre) and endline (post) household surveys were done in the control and intervention wards to assess the change in malaria prevalence measured by the interaction term of ‘time’ (post vs pre) and arm in a logistic model. A secondary analysis also studied the malaria incidence reported at the HFs during the intervention. Results Overall the 85 rounds of 1,7-mRCTR conducted in the intervention wards significantly reduced the odds of malaria infection by 66% (adjusted OR 0.34, 95% CI 0.26,0.44, p

BackgroundThe success of any randomized clinical trial relies on the willingness of people to be recruited in the trial. However, 90% of all clinical trials worldwide have been reported to have failed to recruit the required number of trial participants within the scheduled time. This study aimed to qualitatively explore the motivations and barriers for healthy participants to participate in herbal remedy clinical trials in Tanzania.Materials and methodsThis study used a qualitative descriptive research design based on the theory of planned behaviour. A total of five Focus Group Discussions (FGD) were conducted at Bagamoyo Clinical Trial Facility from 29 to 30 May 2021. Each group consisted of 5 to 10 participants. The participants of the study were 30 healthy males aged 18 to 45 male who participated in the clinical trial that evaluated the safety, tolerability, and efficacy of Maytenus Senegalensis. The focus group discussions were recorded audio-recorded. Verbatim transcription and thematic analysis were performed on the data.ResultsThe prominent motivations mentioned were the opportunity for self-development, altruism, flexible study visit schedule, and financial compensation. Furthermore, the Participants' mothers and friends were reported as those most likely to approve of participation in an herbal remedy. The most mentioned barriers were inconvenience related to time commitment requirements, possible side effects, inflexible study visit schedule, and having other commitments. Moreover, the participants' father was reported to be more likely to disapprove of participation in a clinical trial of herbal remedy clinical trial.ConclusionsThe results of this study showed that the motivations and barriers of healthy participants to participate in clinical trials of herbal remedies are varied and that participants are motivated by more than financial gains. The identified motivations and barriers can be used as a guideline to improve the design of recruitment and retention strategies for herbal remedy clinical trials.

Abstract Background Primaquine is an important gametocytocidal drug that is combined with conventional malaria treatment for prevention of Plasmodium falciparum malaria transmission. Primaquine has been administered together on the first or the last day of conventional treatment but the impact of primaquine timing has never been examined. This study aimed to assess safety, efficacy and optimal timing of single full-dose (0.75 mg/kg) primaquine when added to a standard 6-dose regimen of artemether–lumefantrine (AL). Methods In an individual-level randomized controlled trial, enrolled participants who were G6PD normal and had uncomplicated P. falciparum malaria were randomly assigned to receive: AL only; AL and a single 0.75 mg/kg primaquine dose on the first day of AL (day 1); or AL and single 0.75 mg//kg primaquine on the last day of AL (day 3). On days 2, 3, 4, 8, 11 and 15, gametocytes were assessed and quantified by microscope and quantitative nuclear acid sequence based quantification (QT-NASBA). Results Overall, 111 participants aged between 3 and 17 years were randomly allocated to receive AL only (36) or combined with primaquine on day 1 (38), or primaquine on day 3 (37). Day 4 gametocyte prevalence in AL + day 1 primaquine was half the level seen in either AL + day 3 primaquine or AL only arm (11% [4/35] vs 26% [8/31] and 27% [8/30], respectively) albeit not statistically significant. A similar trend of lower gametocyte in the AL + day 1 primaquine verses AL + day 3 primaquine or AL only arm was observed in mean gametocyte density. Mean (sd) haemoglobin level in AL + day 3 primaquine arm recovered from -0.42(1.2) g/dl on day 2 to 0.35 (1.5) g/dl on day 15 of follow up. This was not the case in AL only and AL + day 1 primaquine arms during the same follow-up period, although the difference was not statistically significant (p = 318). No serious adverse events reported in the study. Across arms, 23% (26/111) of participants reported a total of 31 mild adverse events and the difference was not statistically significant (p = 0.477). Conclusion Primaquine administration on the first day of AL is well tolerated and as safe as later administration. Whilst the World Health Organization currently recommends a lower dose of primaquine (0.25 mg/kg), the findings are supportive of early primaquine administration when combined with artemisinin-combination therapy. ClinicalTrials.gov Registration NCT01906788

Pregnant women constitute a promising sentinel group for continuous monitoring of malaria transmission. To identify antibody signatures of recent Plasmodium falciparum exposure during pregnancy, we dissected IgG responses against VAR2CSA, the parasite antigen that mediates placental sequestration. We used a multiplex peptide-based suspension array in 2,354 samples from pregnant women from Mozambique, Benin, Kenya, Gabon, Tanzania, and Spain. Two VAR2CSA peptides of limited polymorphism were immunogenic and targeted by IgG responses readily boosted during infection and with estimated half-lives of

RTS,S/AS01E has been tested in a phase 3 malaria vaccine trial and has shown partial efficacy in children and infants. Here, the authors analyze IgG concentration and avidity to CSP in ~1000 participants and show that IgG avidity to the C-terminus of CSP is significantly associated with vaccine-mediated protection.

Abstract Background Malaria is endemic in Tanzania with majority of clinical cases caused by Plasmodium falciparum. Additionally, Plasmodium malariae and Plasmodium ovale spp. are also present and clinical manifestations caused by these infections are not well described. Clinical episodes caused by P. malariae infections are often characterized by a relatively mild illness with a low number of parasites, which can persist for long periods. In this report, two cases of P. malariae infections that were identified during a clinical trial evaluating the P. falciparum malaria vaccine candidate, PfSPZ Vaccine are described. The two participants were followed up and monitored for clinical and laboratory parameters to assess vaccine safety providing the opportunity to study clinical manifestations of P. malariae over 4 months. Case presentation Two young, healthy Tanzanian men infected with low density asexual blood stage P. malariae diagnosed by quantitative polymerase chain reaction (qPCR) are described. Retrospective analysis of collected and stored blood samples revealed that the two volunteers had constant asexual blood stage parasitaemia for more than 4 months. During the 132 days of infection, the volunteers’ vital signs, body temperature and serum biochemistry all remained within normal ranges. Haematological abnormalities, which were transiently outside normal ranges, were regarded as not clinically significant. During this time period, four consecutive evaluations of blood samples by thick blood smear microscopy conducted by an experienced microscopist were all negative, indicating the presence of low-density sub-microscopic infections. Conclusions The two cases of P. malariae infections presented here confirm the ability of this Plasmodium species to persist at low density in the human host for extended time periods without causing clinical symptoms. The presented data also demonstrate that clinical study sites in malaria endemic regions need to have a strong malaria diagnostic infrastructure, including the ability of capturing sub-microscopic parasitaemia and differentiation of Plasmodium species. Trial registration ClinicalTrials.gov: NCT02613520, https://clinicaltrials.gov/ct2/show/NCT02613520, Registered: November 24th 2015, Enrolment of the first participant to the trial: December 15th 2015, Trial was registered before the first participant was enrolled

Background: Though Maytenus senegalensis is one of the medicinal plants widely used in traditional medicine to treat infectious and inflammatory diseases in Africa, there is a lack of safety data regarding its use. Therefore, the study aimed to asselss the safety and tolerability of the antimalarial herbal remedy M. senegalensis. Material and Methods: The study design was an open-label, single-arm, dose-escalation. Twelve eligible male healthy Tanzanians aged 18 to 45 years were enrolled in four study dose groups. Volunteers’ safety and tolerability post-investigational-product administration were monitored on days 0 to 7,14, and 56. Results: There were no deaths or serious adverse events in any of the study groups, nor any adverse events that resulted in premature discontinuation. The significant mean changes observed in WBC (p = 0.003), Neutrophils (p = 0.02), Lymphocytes (p = 0.001), Eosinophils (p = 0.009), Alanine aminotransferase (p = 0.002), Creatinine (p = 0.03) and Total bilirubin (p = 0.004) laboratory parameters were not associated with any signs of toxicity or clinical symptoms. Conclusions: M. senegalensis was demonstrated to be safe and tolerable when administered at a dose of 800 mg every eight hours a day for four days. This study design may be adapted to evaluate other herbal remedies.

Tanzanian adult male volunteers were immunized by direct venous inoculation with radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum (Pf) sporozoites (PfSPZ Vaccine) and protective efficacy assessed by homologous controlled human malaria infection (CHMI). Serum immunoglobulin G (IgG) responses were analyzed longitudinally using a Pf protein microarray covering 91% of the proteome, providing first insights into naturally acquired and PfSPZ Vaccine-induced whole parasite antibody profiles in malaria pre-exposed Africans. Immunoreactivity was identified against 2239 functionally diverse Pf proteins, showing a wide breadth of humoral response. Antibody-based immune ‘fingerprints’ in these individuals indicated a strong person-specific immune response at baseline, with little changes in the overall humoral immunoreactivity pattern measured after immunization. The moderate increase in immunogenicity following immunization and the extensive and variable breadth of humoral immune response observed in the volunteers at baseline suggest that pre-exposure reduces vaccine-induced antigen reactivity in unanticipated ways.

Abstract Background During the past six decades, remarkable success on malaria control has been made in China. The major experience could be shared with other malaria endemic countries including Tanzania with high malaria burden. Especially, China’s 1–3-7 model for malaria elimination is one of the most important refined experiences from many years’ efforts and key innovation measures for malaria elimination in China. Methods The China-UK-Tanzania pilot project on malaria control was implemented from April, 2015 to June, 2018, which was an operational research with two communities receiving the proposed interventions and two comparable communities serving as control sites. The World Health Organization “Test, Treat, Track” (WHO-T3) Initiative, which calls for every suspected case to receive a diagnostic test, every confirmed case to be treated, and for the disease to be tracked, was integrated with Chinese experiences on malaria control and elimination for exploration of a proper model tailored to the local settings. Application of China’s 1–3-7 model integrating with WHO-T3 initiative and local resources aiming at reducing the burden of malaria in terms of morbidity and mortality by 30% in the intervention communities in comparison with that at the baseline survey. Discussion The China-UK-Tanzania pilot project on malaria control was that at China's first pilot project on malaria control in Africa, exploring the feasibility of Chinese experiences by China-Africa collaboration, which is expected that the strategies and approaches used in this project could be potential for scaling up in Tanzania and African countries, and contribute to the acceleration of malaria control and elimination in Africa.

Introduction Epidemiological data about diabetes mellitus (DM) for sub-Saharan Africa (SSA) are scarce and the utility of glycated hemoglobin (HbA1c) to diagnose DM is uncertain in African populations with a high proportion of anemia.Research design and methods In a cross-sectional study, age-adjusted prevalence rates and predictors for DM and pre-DM were prospectively assessed by HbA1c in a semirural walk-in population of Tanzania (n=992). Predictors for DM were calculated by logistic regression. Correlations between HbA1c, hemoglobin, and blood glucose levels were done by Pearson’s correlation.Results Overall, DM and pre-DM prevalence rates were 6.8% (95% CI 5.3 to 8.5) and 25% (95% CI 22.8 to 28.3), respectively. There was an increase in DM prevalence in patients 50–59 (14.9%; 95% CI 9.1 to 22.5), ≥60 years old (18.5%; 95% CI 12.2 to 26.2) and in patients with overweight (9.3%; 95% CI 5.9 to 13.7), obesity (10.9%; 95% CI 6.9 to 16) compared with patients 18–29 years old (2.2%; 95% CI 0.9 to 4.4) (p

Abstract Background Plasmodium falciparum prevalence (PfPR) is a widely used metric for assessing malaria transmission intensity. This study was carried out concurrently with the RTS,S/AS01 candidate malaria vaccine Phase III trial and estimated PfPR over ≤ 4 standardized cross-sectional surveys. Methods This epidemiology study (NCT01190202) was conducted in 8 sites from 6 countries (Burkina Faso, Gabon, Ghana, Kenya, Malawi, and Tanzania), between March 2011 and December 2013. Participants were enrolled in a 2:1:1 ratio according to age category: 6 months–4 years, 5–19 years, and ≥ 20 years, respectively, per year and per centre. All sites carried out surveys 1–3 while survey 4 was conducted only in 3 sites. Surveys were usually performed during the peak malaria parasite transmission season, in one home visit, when medical history and malaria risk factors/prevention measures were collected, and a blood sample taken for rapid diagnostic test, microscopy, and haemoglobin measurement. PfPR was estimated by site and age category. Results Overall, 6401 (survey 1), 6411 (survey 2), 6400 (survey 3), and 2399 (survey 4) individuals were included in the analyses. In the 6 months–4 years age group, the lowest prevalence (assessed using microscopy) was observed in 2 Tanzanian centres (4.6% for Korogwe and 9.95% for Bagamoyo) and Lambaréné, Gabon (6.0%), while the highest PfPR was recorded for Nanoro, Burkina Faso (52.5%). PfPR significantly decreased over the 3 years in Agogo (Ghana), Kombewa (Kenya), Lilongwe (Malawi), and Bagamoyo (Tanzania), and a trend for increased PfPR was observed over the 4 surveys for Kintampo, Ghana. Over the 4 surveys, for all sites, PfPR was predominantly higher in the 5–19 years group than in the other age categories. Occurrence of fever and anaemia was associated with high P. falciparum parasitaemia. Univariate analyses showed a significant association of anti-malarial treatment in 4 surveys (odds ratios [ORs]: 0.52, 0.52, 0.68, 0.41) and bed net use in 2 surveys (ORs: 0.63, 0.68, 1.03, 1.78) with lower risk of malaria infection. Conclusion Local PfPR differed substantially between sites and age groups. In children 6 months–4 years old, a significant decrease in prevalence over the 3 years was observed in 4 out of the 8 study sites. Trial registration Clinical Trials.gov identifier: NCT01190202:NCT. GSK Study ID numbers: 114001

Abstract Background Malaria remains one of the most important infectious diseases. Treatment options for severe malaria are limited and the choline analogue SAR97276A is a novel chemical entity that was developed primarily as treatment for severe malaria. Before starting clinical investigations in severely ill malaria patients, safety and efficacy of SAR97276A was studied in patients with uncomplicated malaria. Here, we summarize two open-label, multi-center phase 2 trials assessing safety and efficacy of parenterally administered SAR97276A in African adults and children with falciparum malaria. Results Study 1 was conducted in Burkina Faso, Gabon, Benin and Tanzania between August 2008 and July 2009 in malaria patients in an age de-escalating design (adults, children). A total of 113 malaria patients received SAR97276A. Adults were randomized to receive a single dose SAR97296A given either intramuscularly (IM) (0.18 mg/kg) or intravenously (IV) (0.14 mg/kg). If a single dose was not efficacious a second adult group was planned to test a three dose regimen administered IM once daily for 3 days. Single dose SAR97276A showed insufficient efficacy in adults (IM: 20 of 34 cured, 59%; and IV: 23/30 cured, 77%). The 3-day IM regimen showed acceptable efficacy in adults (27/30, 90%) but not in children (13/19, 68%). SAR97276A was well tolerated but no further groups were recruited due lack of efficacy. Study 2 was conducted between October 2011 and January 2012 in Burkina Faso, Gabon and Kenya. SAR97276A administered at a higher dose given IM was compared to artemether–lumefantrine. The study population was restricted to underage malaria patients to be subsequently enrolled in two age cohorts (teenagers, children). Rescue therapy was required in all teenaged malaria patients (8/8) receiving SAR97276A once daily (0.5 mg/kg) for 3 days and in 5 out of 8 teenaged patients treated twice daily (0.25 mg/kg) for 3 days. All patients (4/4) in the control group were cured. The study was stopped, before enrollment of children, due to lack of efficacy but the overall safety profile was good. Conclusions Monotherapy with SAR97276A up to twice daily for 3 days is not an efficacious treatment for falciparum malaria. SAR97276A will not be further developed for the treatment of malaria. Trial registration at clinicaltrials.gov: NCT00739206, retrospectively registered August 20, 2008 for Study 1 and NCT01445938 registered September 26, 2011 for Study 2.

Abstract Clonal clusters and gene repertoires of Staphylococcus aureus are essential to understand disease and are well characterized in industrialized countries but poorly analysed in developing regions. The objective of this study was to compare the molecular-epidemiologic profiles of S. aureus isolates from Sub-Saharan Africa and Germany. S. aureus isolates from 600 staphylococcal carriers and 600 patients with community-associated staphylococcal disease were characterized by DNA hybridization, clonal complex (CC) attribution, and principal component (PCA)-based gene repertoire analysis. 73% of all CCs identified representing 77% of the isolates contained in these CCs were predominant in either African or German region. Significant differences between African versus German isolates were found for alleles encoding the accessory gene regulator type, enterotoxins, the Panton-Valentine leukocidin, immune evasion gene cluster, and adhesins. PCA in conjunction with silhouette analysis distinguished nine separable PCA clusters, with five clusters primarily comprising of African and two clusters of German isolates. Significant differences between S. aureus lineages in Africa and Germany may be a clue to explain the apparent difference in disease between tropical/(so-called) developing and temperate/industrialized regions. In low-resource countries further clinical-epidemiologic research is warranted not only for neglected tropical diseases but also for major bacterial infections.

Abstract Background Malnutrition has long been associated with poverty, poor diet and inadequate access to health care, and it remains a key global health issue that both stems from and contributes to ill-health, with 50 % of childhood deaths due to underlying undernutrition. The purpose of this study was to determine the prevalence of malnutrition among children under-five seen at Bagamoyo District Hospital (BDH) and three rural health facilities ranging between 25 and 55 km from Bagamoyo: Kiwangwa, Fukayosi, and Yombo. Methods A total of 63,237 children under-five presenting to Bagamoyo District Hospital and the three rural health facilities participated in the study. Anthropometric measures of age, height/length and weight and measurements of mid-upper arm circumference were obtained and compared with reference anthropometric indices to assess nutritional status for patients presenting to the hospital and health facilities. Results Overall proportion of stunting, underweight and wasting was 8.37, 5.74 and 1.41 % respectively. Boys were significantly more stunted, under weight and wasted than girls (p-value

Background: Semiquantitative dipstick tests are utilized for albuminuria screening. Methods: In a prospective cross-sectional survey, we analyzed the diagnostic test validity of the semiquantitative colorimetric indicator-dye-based Combur9-Test® and the albumin-specific immunochromatographic assay Micral-Test® for the detection of albuminuria, the distribution of the semiquantitative measurements within the albuminuria stages according to KDIGO, and the utility for albuminuria screening compared with an albumin-to-creatinine ratio (ACR) in a walk-in population. Results: In 970 subjects, albuminuria (≥30 mg/g) was detected in 12.7% (95% CI 85.6–96.3%) with the ACR. Sensitivity was 82.9% (95% CI 75.1–89.1%) and 91.9% (95% CI 88.7–96.9%) and specificity 71.5% (95% CI 68.4–74.6%) and 17.5% (95% CI 15.0–20.2%) for the Combur9-Test® and Micral-Test®, respectively. Correct classification to KDIGO albuminuria stages A2/A3 with the Combur9-Test® was 15.4%, 51.4%, and 87.9% at cut-offs of 30, 100, and ≥300 mg/dL, and with the Micral-Test® it was 1.8%, 10.5%, and 53.6% at cut-offs of 2, 5, and 10 mg/dL, respectively. Overall, disagreement to KDIGO albuminuria was seen in 27% and 73% with the Combur9-Test® and Micral-Test®, respectively. From the total population, 62.5% and 15.3% were correctly ruled out and 2.2% and 1% were missed as false-negatives by the Combur9-Test® and Micral-Test®, respectively. Conclusion: Compared to the Combur9-Test®, the utility of the Micral-Test® is limited, because the fraction of correctly ruled out patients is small and a large proportion with a positive Micral-Test® require a subsequent ACR conformation test.

In sub-Saharan Africa (SSA), epidemiological data for chronic kidney disease (CKD) are scarce. We conducted a prospective cross-sectional study including 952 patients in an outpatient clinic in Tanzania to explore CKD prevalence estimates and the association with cardiovascular and infectious disorders. According to KDIGO, we measured albumin-to-creatinine ratio and calculated eGFR using CKD-EPI formula. Factors associated with CKD were calculated by logistic regression. Venn diagrams were modelled to visualize interaction between associated factors and CKD. Overall, the estimated CKD prevalence was 13.6% (95% CI 11-16%). Ninety-eight patients (11.2%) (95% CI 9-14%) were categorized as moderate, 12 (1.4%) (95% CI 0-4%) as high, and 9 (1%) (95% CI 0-3%) as very high risk according to KDIGO. History of tuberculosis (OR 3.75, 95% CI 1.66-8.18; p = 0.001) and schistosomiasis (OR 2.49, 95% CI 1.13-5.18; p = 0.02) were associated with CKD. A trend was seen for increasing systolic blood pressure (OR 1.02 per 1 mmHg, 95% CI 1.00-1.03; p = 0.01). Increasing BMI (OR 0.92 per 1kg/m2, 95% CI 0.88-0.96; p =

BACKGROUND:At times, ultrasound is not readily available in low resource countries in Africa for accurate determination of gestational age, so using alternative methods is pivotal during pregnancy. These assessments are used to aid the risk analysis for an infant and management strategies for premature delivery, if necessary. Currently, date of last menstrual period, fundal height measurements, and the New Ballard Score are commonly used in resource-limited settings. However, concordance of these measures is unknown for sub-Saharan Africa. We obtained data from an open-label randomized controlled trial, to assess the concordance of these alternative assessment methods. The purpose of our study was to determine the agreement between these alternative methods when used in sub-Saharan African populations. METHODS:A total of 4,390 pregnant women from Benin, Gabon, Mozambique and Tanzania were included in our analysis. The assessment methods compared were: 1) reported last menstrual period, 2) symphysis-fundal height measurement, and 3) the New Ballard Score. The Bland-Altman method and intraclass correlation coefficient (ICC) were used to test the degree of agreement. Survival range gestational age, used as an inclusion criterion for further analysis, was from 22 to 44 weeks. FINDINGS:Plots showed a lack of agreement between methods and the 95% limits of agreement too wide to be clinically useful. ICC = 0.25 indicated poor agreement. A post-hoc analysis, restricted from 32 to 42 weeks, was done to check for better agreement in this near-term population. The plots and ICC = 0.16 still confirmed poor agreement. CONCLUSION:The alternative assessments do not result in comparable outcomes and discrepancies are far beyond the clinically acceptable range. Last menstrual period should not be used as the only estimator of gestational age. In the absence of reliable early ultrasound, symphysis-fundal height measurements may be most useful during pregnancy for fetal risk assessment and the New Ballard Score after delivery as a confirmation of these estimations and for further neonatal management. However, promotion of portable ultrasound devices is required for accurate assessment of gestational age in sub-Sahara Africa.

Malaria continues to be one of mankind's most devastating diseases despite the many and varied efforts to combat it. Indispensable for malaria elimination and eventual eradication is the development of effective vaccines. Controlled human malaria infection (CHMI) is an invaluable tool for vaccine efficacy assessment and investigation of early immunological and molecular responses against Plasmodium falciparum infection. Here, we investigated gene expression changes following CHMI using RNA-Seq. Peripheral blood samples were collected in Bagamoyo, Tanzania, from ten adults who were injected intradermally (ID) with 2.5x104 aseptic, purified, cryopreserved P. falciparum sporozoites (Sanaria® PfSPZ Challenge). A total of 2,758 genes were identified as differentially expressed following CHMI. Transcriptional changes were most pronounced on day 5 after inoculation, during the clinically silent liver phase. A secondary analysis, grouping the volunteers according to their prepatent period duration, identified 265 genes whose expression levels were linked to time of blood stage parasitemia detection. Gene modules associated with these 265 genes were linked to regulation of transcription, cell cycle, phosphatidylinositol signaling and erythrocyte development. Our study showed that in malaria pre-exposed volunteers, parasite prepatent period in each individual is linked to magnitude and timing of early gene expression changes after ID CHMI.

Background: Malaria transmission is measured using entomological inoculation rate (EIR), number of infective mosquito bites/person/unit time. Understanding heterogeneity of malaria transmission has been difficult due to a lack of appropriate data. A comprehensive entomological database compiled by the Malaria Transmission Intensity and Mortality Burden across Africa (MTIMBA) project (2001–2004) at several sites is the most suitable dataset for studying malaria transmission–mortality relations. The data are sparse and large, with small-scale spatial–temporal variation. Objective: This work demonstrates a rigorous approach for analysing large and highly variable entomological data for the study of malaria transmission heterogeneity, measured by EIR, within the Rufiji Demographic Surveillance System (DSS), MTIMBA project site in Tanzania. Design: Bayesian geostatistical binomial and negative binomial models with zero inflation were fitted for sporozoite rates (SRs) and mosquito density, respectively. The spatial process was approximated from a subset of locations. The models were adjusted for environmental effects, seasonality and temporal correlations and assessed based on their predictive ability. EIR was calculated using model-based predictions of SR and density. Results: Malaria transmission was mostly influenced by rain and temperature, which significantly reduces the probability of observing zero mosquitoes. High transmission was observed at the onset of heavy rains. Transmission intensity reduced significantly during Year 2 and 3, contrary to the Year 1, pronouncing high seasonality and spatial variability. The southern part of the DSS showed high transmission throughout the years. A spatial shift of transmission intensity was observed where an increase in households with very low transmission intensity and significant reduction of locations with high transmission were observed over time. Over 68 and 85% of the locations selected for validation for SR and density, respectively, were correctly predicted within 95% credible interval indicating good performance of the models. Conclusion: Methodology introduced here has the potential for efficient assessment of the contribution of malaria transmission in mortality and monitoring performance of control and intervention strategies.

OBJECTIVE: To determine why health workers fail to follow integrated management of childhood illness (IMCI) guidelines for severely ill children at first-level outpatient health facilities in rural areas of the United Republic of Tanzania. METHODS: Retrospective and prospective case reviews of severely ill children aged < 5 years were conducted at health facilities in four districts. We ascertained treatment and examined the characteristics associated with referral, conducted follow-up interviews with parents of severely ill children, and gave health workers questionnaires and interviews. FINDINGS: In total, 502 cases were reviewed at 62 facilities. Treatment with antimalarials and antibiotics was consistent with the diagnosis given by health workers. However, of 240 children classified as having "very severe febrile disease", none received all IMCI-recommended therapies, and only 25% of severely ill children were referred. Lethargy and anaemia diagnoses were independently associated with referral. Most (91%) health workers indicated that certain severe conditions can be managed without referral. CONCLUSION: The health workers surveyed rarely adhered to IMCI treatment and referral guidelines for children with severe illness. They administered therapy based on narrow diagnoses rather than IMCI classifications, disagreed with referral guidelines and often considered referral unnecessary. To improve implementation of IMCI, attention should focus on the reasons for health worker non-adherence.

BackgroundLittle is known about the effects of intermittent preventive treatment of malaria in pregnancy (IPTp) on the health of sub-Saharan African infants. We have evaluated the safety of IPTp with mefloquine (MQ) compared to sulfadoxine-pyrimethamine (SP) for important infant health and developmental outcomes.Methods and findingsIn the context of a multicenter randomized controlled trial evaluating the safety and efficacy of IPTp with MQ compared to SP in pregnancy carried out in four sub-Saharan countries (Mozambique, Benin, Gabon, and Tanzania), 4,247 newborns, 2,815 born to women who received MQ and 1,432 born to women who received SP for IPTp, were followed up until 12 mo of age. Anthropometric parameters and psychomotor development were assessed at 1, 9, and 12 mo of age, and the incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were determined until 12 mo of age. No significant differences were found in the proportion of infants with stunting, underweight, wasting, and severe acute malnutrition at 1, 9, and 12 mo of age between infants born to women who were on IPTp with MQ versus SP. Except for three items evaluated at 9 mo of age, no significant differences were observed in the psychomotor development milestones assessed. Incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were similar between the two groups. Information on the outcomes at 12 mo of age was unavailable in 26% of the infants, 761 (27%) from the MQ group and 377 (26%) from the SP group. Reasons for not completing the study were death (4% of total study population), study withdrawal (6%), migration (8%), and loss to follow-up (9%).ConclusionsNo significant differences were found between IPTp with MQ and SP administered in pregnancy on infant mortality, morbidity, and nutritional outcomes. The poorer performance on certain psychomotor development milestones at 9 mo of age in children born to women in the MQ group compared to those in the SP group may deserve further studies.Trial registrationClinicalTrials.gov NCT00811421.

The antimalarial drug piperaquine is associated with delayed ventricular depolarization, causing prolonged QT interval (time taken for ventricular de-polarisation and re-polarisation). There is a lack of safety data regarding dihydroartemisinin/piperaquine (DHA/PPQ) for the treatment of uncomplicated malaria, which has limited its use. We created a platform where electrocardiograms (ECG) were performed in public hospitals for the safety assessment of DHA/PPQ, at baseline before the use of dihydroartemisinin/piperaquine (Eurartesim®), and on day 3 (before and after administration of the final dose) and day 7 post-administration. Laboratory analyses included haematology and clinical chemistry. The main objective of the ECG assessment in this study was to evaluate the effect of administration of DHA/PPQ on QTc intervals and the association of QTc intervals with changes in blood biochemistry, full and differential blood count over time after the DHA/PPQ administration. A total of 1315 patients gave consent and were enrolled of which 1147 (87%) had complete information for analyses. Of the enrolled patients 488 (42%), 323 (28%), 213 (19%) and 123 (11%) were from Ghana, Burkina Faso, Tanzania and Mozambique, respectively. Median (lower-upper quartile) age was 8 (5-14) years and a quarter of the patients were children under five years of age (n = 287). Changes in blood biochemistry, full and differential blood count were temporal which remained within clinical thresholds and did not require any intervention. The mean QTcF values were significantly higher than on day 1 when measured on day 3 before and after administration of the treatment as well as on day 7, four days after completion of treatment (12, 22 and 4 higher, p < 0.001). In all age groups the values of QT, QTcF and QTcB were highest on day 3 after drug intake. The mean extreme QTcF prolongation from baseline was lowest on day 3 before drug intake (33 ms, SD = 19) and highest on day 3 after the last dose (60 ms, SD = 31). There were 79 (7%) events of extreme mean QTcF prolongation which were not clinically significant. Nearly a half of them (n = 37) were grade 3 and mainly among males (33/37). Patients in Burkina Faso, Mozambique and Tanzania had significantly lower mean QTcF than patients in Ghana by an average of 3, 4 and 11 ms, respectively. We found no evidence that Eurartesim® administered in therapeutic doses in patients with uncomplicated malaria and no predisposing cardiac conditions in Africa was associated with adverse clinically significant QTc prolongation.

BACKGROUND:Plasmodium and soil transmitted helminth infections (STH) are a major public health problem, particularly among children. There are conflicting findings on potential association between these two parasites. This study investigated the Plasmodium and helminth co-infections among children aged 2 months to 9 years living in Bagamoyo district, coastal region of Tanzania. METHODS:A community-based cross-sectional survey was conducted among 1033 children. Stool, urine and blood samples were examined using a broad set of quality controlled diagnostic methods for common STH (Ascaris lumbricoides, hookworm, Strongyloides stercoralis, Enterobius vermicularis, Trichuris trichura), schistosoma species and Wuchereria bancrofti. Blood slides and malaria rapid diagnostic tests (mRDTs) were utilized for Plasmodium diagnosis. RESULTS:Out of 992 children analyzed, the prevalence of Plasmodium infection was 13% (130/992), helminth 28.5% (283/992); 5% (50/992) had co-infection with Plasmodium and helminth. The prevalence rate of Plasmodium, specific STH and co-infections increased significantly with age (p < 0.001), with older children mostly affected except for S. stercoralis monoinfection and co-infections. Spatial variations of co-infection prevalence were observed between and within villages. There was a trend for STH infections to be associated with Plasmodium infection [OR adjusted for age group 1.4, 95% CI (1.0-2.1)], which was more marked for S. stercoralis (OR = 2.2, 95% CI (1.1-4.3). Age and not schooling were risk factors for Plasmodium and STH co-infection. CONCLUSION:The findings suggest that STH and Plasmodium infections tend to occur in the same children, with increasing prevalence of co-infection with age. This calls for an integrated approach such as using mass chemotherapy with dual effect (e.g., ivermectin) coupled with improved housing, sanitation and hygiene for the control of both parasitic infections.

Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended in HIV-negative women to avert malaria, while this relies on cotrimoxazole prophylaxis (CTXp) in HIV-positive women. Alternative antimalarials are required in areas where parasite resistance to antifolate drugs is high. The cost-effectiveness of IPTp with alternative drugs is needed to inform policy.The cost-effectiveness of 2-dose IPTp-mefloquine (MQ) was compared with IPTp-SP in HIV-negative women (Benin, Gabon, Mozambique and Tanzania). In HIV-positive women the cost-effectiveness of 3-dose IPTp-MQ added to CTXp was compared with CTXp alone (Kenya, Mozambique and Tanzania). The outcomes used were maternal clinical malaria, anaemia at delivery and non-obstetric hospital admissions. The poor tolerability to MQ was included as the value of women's loss of working days. Incremental cost-effectiveness ratios (ICERs) were calculated and threshold analysis undertaken.For HIV-negative women, the ICER for IPTp-MQ versus IPTp-SP was 136.30 US$ (2012 US$) (95%CI 131.41; 141.18) per disability-adjusted life-year (DALY) averted, or 237.78 US$ (95%CI 230.99; 244.57), depending on whether estimates from Gabon were included or not. For HIV-positive women, the ICER per DALY averted for IPTp-MQ added to CTXp, versus CTXp alone was 6.96 US$ (95%CI 4.22; 9.70). In HIV-negative women, moderate shifts of variables such as malaria incidence, drug cost, and IPTp efficacy increased the ICERs above the cost-effectiveness threshold. In HIV-positive women the intervention remained cost-effective for a substantial (up to 21 times) increase in cost per tablet.Addition of IPTp with an effective antimalarial to CTXp was very cost-effective in HIV-positive women. IPTp with an efficacious antimalarial was more cost-effective than IPTp-SP in HIV-negative women. However, the poor tolerability of MQ does not favour its use as IPTp. Regardless of HIV status, prevention of malaria in pregnancy with a highly efficacious, well tolerated antimalarial would be cost-effective despite its high price.ClinicalTrials.gov NCT 00811421; Pan African Trials Registry PACTR2010020001429343 and PACTR2010020001813440.

BackgroundIntermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by WHO to prevent malaria in African pregnant women. The spread of SP parasite resistance has raised concerns regarding long-term use for IPT. Mefloquine (MQ) is the most promising of available alternatives to SP based on safety profile, long half-life, and high efficacy in Africa. We evaluated the safety and efficacy of MQ for IPTp compared to those of SP in HIV-negative women.Methods and findingsA total of 4,749 pregnant women were enrolled in an open-label randomized clinical trial conducted in Benin, Gabon, Mozambique, and Tanzania comparing two-dose MQ or SP for IPTp and MQ tolerability of two different regimens. The study arms were: (1) SP, (2) single dose MQ (15 mg/kg), and (3) split-dose MQ in the context of long lasting insecticide treated nets. There was no difference on low birth weight prevalence (primary study outcome) between groups (360/2,778 [13.0%]) for MQ group and 177/1,398 (12.7%) for SP group; risk ratio [RR], 1.02 (95% CI 0.86-1.22; p=0.80 in the ITT analysis). Women receiving MQ had reduced risks of parasitemia (63/1,372 [4.6%] in the SP group and 88/2,737 [3.2%] in the MQ group; RR, 0.70 [95% CI 0.51-0.96]; p=0.03) and anemia at delivery (609/1,380 [44.1%] in the SP group and 1,110/2743 [40.5%] in the MQ group; RR, 0.92 [95% CI 0.85-0.99]; p=0.03), and reduced incidence of clinical malaria (96/551.8 malaria episodes person/year [PYAR] in the SP group and 130/1,103.2 episodes PYAR in the MQ group; RR, 0.67 [95% CI 0.52-0.88]; p=0.004) and all-cause outpatient attendances during pregnancy (850/557.8 outpatients visits PYAR in the SP group and 1,480/1,110.1 visits PYAR in the MQ group; RR, 0.86 [0.78-0.95]; p=0.003). There were no differences in the prevalence of placental infection and adverse pregnancy outcomes between groups. Tolerability was poorer in the two MQ groups compared to SP. The most frequently reported related adverse events were dizziness (ranging from 33.9% to 35.5% after dose 1; and 16.0% to 20.8% after dose 2) and vomiting (30.2% to 31.7%, after dose 1 and 15.3% to 17.4% after dose 2) with similar proportions in the full and split MQ arms. The open-label design is a limitation of the study that affects mainly the safety assessment.ConclusionsWomen taking MQ IPTp (15 mg/kg) in the context of long lasting insecticide treated nets had similar prevalence rates of low birth weight as those taking SP IPTp. MQ recipients had less clinical malaria than SP recipients, and the pregnancy outcomes and safety profile were similar. MQ had poorer tolerability even when splitting the dose over two days. These results do not support a change in the current IPTp policy.Trial registrationClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001429343 Please see later in the article for the Editors' Summary.

BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs). METHODS AND FINDINGS: A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27-0.82]; p=0.008), placental malaria (RR, 0.52 [95% CI 0.29-0.90]; p=0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37-0.95]; p=0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p=0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14-3.33]; p=0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis. CONCLUSIONS: An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need to find alternatives with better tolerability to reduce malaria in this particularly vulnerable group. MQ was associated with an increased risk of mother to child transmission of HIV, which warrants a better understanding of the pharmacological interactions between antimalarials and antiretroviral drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001813440 Please see later in the article for the Editors' Summary.

BACKGROUND: Throughout Africa, many people seek care for malaria in private-sector drug shops where diagnostic testing is often unavailable. Recently, subsidized artemisinin-based combination therapies (ACTs), a first-line medication for uncomplicated malaria, were made available in these drug shops in Tanzania. This study assessed the prevalence of malaria among and purchase of ACTs by drug shop clients in the setting of a national ACT subsidy program and sub-national drug shop accreditation program. METHOD AND FINDINGS: A cross-sectional survey of drug shop clients was performed in two regions in Tanzania, one with a government drug shop accreditation program and one without, from March-May, 2012. Drug shops were randomly sampled from non-urban districts. Shop attendants were interviewed about their education, training, and accreditation status. Clients were interviewed about their symptoms and medication purchases, then underwent a limited physical examination and laboratory testing for malaria. Malaria prevalence and predictors of ACT purchase were assessed using univariate analysis and multiple logistic regression. Amongst 777 clients from 73 drug shops, the prevalence of laboratory-confirmed malaria was 12% (95% CI: 6-18%). Less than a third of clients with malaria had purchased ACTs, and less than a quarter of clients who purchased ACTs tested positive for malaria. Clients were more likely to have purchased ACTs if the participant was 5 years, experience (aOR: 2.8; 95% CI: 1.2-6.3). Having malaria was only a predictor of ACT purchase in the region with a drug shop accreditation program (aOR: 3.4; 95% CI: 1.5-7.4). CONCLUSION: Malaria is common amongst persons presenting to drug shops with a complaint of fever. The low proportion of persons with malaria purchasing ACTs, and the high proportion of ACTs going to persons without malaria demonstrates a need to better target who receives ACTs in these drug shops.

Accelerated development and use of decision-making technology, including the analytical hierarchy process (AHP) which has a high reliability to solve most of the uncertainty problems and meet their practical requirements, which enabled it to be used in a number of engineering and administrative applications. Statistical design of experiments technology is considered essential keys to deal with random data. Their important features enables us to combine them in a appropriate scenario to predict the prospects and rates of random factors and determine the extent of their impact on the delay for the implementation of a project. This research verified and reach the possibility of using these two techniques in the development of mutual influence between each of random factors, a very high correlation has been proved among such factors, where the correlation coefficient between them is equal to the value (1), a mathematical models that govern random factors effects was built by using of Statistical analysis of variance (Anova) and multiple linear regression to find mathematical models that found to be had a high resolution through R2 and F tests which gave (R2 = 1, F > = 1.18E +32) results. These models are used to build a scenario to predict the expectations of potential for the disposal of these factors during the annual monthly plan, and treatment to avoid random effects on the implementation of the project and the planned completion time.

This trial was conducted to evaluate the safety and immunogenicity of two virosome formulated malaria peptidomimetics derived from Plasmodium falciparum AMA-1 and CSP in malaria semi-immune adults and children.The design was a prospective randomized, double-blind, controlled, age-deescalating study with two immunizations. 10 adults and 40 children (aged 5-9 years) living in a malaria endemic area were immunized with PEV3B or virosomal influenza vaccine Inflexal®V on day 0 and 90.No serious or severe adverse events (AEs) related to the vaccines were observed. The only local solicited AE reported was pain at injection site, which affected more children in the Inflexal®V group compared to the PEV3B group (p = 0.014). In the PEV3B group, IgG ELISA endpoint titers specific for the AMA-1 and CSP peptide antigens were significantly higher for most time points compared to the Inflexal®V control group. Across all time points after first immunization the average ratio of endpoint titers to baseline values in PEV3B subjects ranged from 4 to 15 in adults and from 4 to 66 in children. As an exploratory outcome, we found that the incidence rate of clinical malaria episodes in children vaccinees was half the rate of the control children between study days 30 and 365 (0.0035 episodes per day at risk for PEV3B vs. 0.0069 for Inflexal®V; RR = 0.50 [95%-CI: 0.29-0.88], p = 0.02).These findings provide a strong basis for the further development of multivalent virosomal malaria peptide vaccines.ClinicalTrials.gov NCT00513669.

Retail pharmaceutical products are commonly used to treat fever and malaria in sub-Saharan African countries. Small scale studies have suggested that poor quality antimalarials are widespread throughout the region, but nationwide data are not available that could lead to generalizable conclusions about the extent to which poor quality drugs are available in African communities. This study aimed to assess the quality of antimalarials available from retail outlets across mainland Tanzania.We systematically purchased samples of oral antimalarial tablets from retail outlets across 21 districts in mainland Tanzania in 2005. A total of 1080 antimalarial formulations were collected including 679 antifol antimalarial samples (394 sulfadoxine/pyrimethamine and 285 sulfamethoxypyrazine/pyrimethamine), 260 amodiaquine samples, 63 quinine samples, and 51 artemisinin derivative samples. A systematic subsample of 304 products was assessed for quality by laboratory based analysis to determine the amount of the active ingredient and dissolution profile by following the published United States Pharmacopoeia (USP) monogram for the particular tablet being tested. Products for which a published analytical monogram did not exist were assessed on amount of active ingredient alone. Overall 38 or 12.2% of the samples were found to be of poor quality. Of the antifolate antimalarial drugs tested 13.4% were found to be of poor quality by dissolution and content analysis using high-performance liquid chromatography (HPLC). Nearly one quarter (23.8%) of quinine tablets did not comply within the tolerance limits of the dissolution and quantification analysis. Quality of amodiaquine drugs was relatively better but still unacceptable as 7.5% did not comply within the tolerance limits of the dissolution analysis. Formulations of the artemisinin derivatives all contained the stated amount of active ingredient when analysed using HPLC alone.Substandard antimalarial formulations were widely available in Tanzania at the time of this study. No products were detected that did not contain any amount of the stated active ingredient. Quinine and sulfadoxine/pyrimethamine products were the most widely available and also the most likely to be of poor quality. Substandard products were identified in all parts of the country and were labeled as made by both domestic and international manufacturers. With the expansion of the retail pharmaceutical sector as a delivery channel for antimalarial formulations the need for regular nationwide monitoring of their quality will become increasingly important.

BackgroundThe Roll Back Malaria strategy recommends a combination of interventions for malaria control. Zanzibar implemented artemisinin-based combination therapy (ACT) for uncomplicated malaria in late 2003 and long-lasting insecticidal nets (LLINs) from early 2006. ACT is provided free of charge to all malaria patients, while LLINs are distributed free to children under age 5 y ("under five") and pregnant women. We investigated temporal trends in Plasmodium falciparum prevalence and malaria-related health parameters following the implementation of these two malaria control interventions in Zanzibar.Methods and findingsCross-sectional clinical and parasitological surveys in children under the age of 14 y were conducted in North A District in May 2003, 2005, and 2006. Survey data were analyzed in a logistic regression model and adjusted for complex sampling design and potential confounders. Records from all 13 public health facilities in North A District were analyzed for malaria-related outpatient visits and admissions. Mortality and demographic data were obtained from District Commissioner's Office. P. falciparum prevalence decreased in children under five between 2003 and 2006; using 2003 as the reference year, odds ratios (ORs) and 95% confidence intervals (CIs) were, for 2005, 0.55 (0.28-1.08), and for 2006, 0.03 (0.00-0.27); p for trend < 0.001. Between 2002 and 2005 crude under-five, infant (under age 1 y), and child (aged 1-4 y) mortality decreased by 52%, 33%, and 71%, respectively. Similarly, malaria-related admissions, blood transfusions, and malaria-attributed mortality decreased significantly by 77%, 67% and 75%, respectively, between 2002 and 2005 in children under five. Climatic conditions favorable for malaria transmission persisted throughout the observational period.ConclusionsFollowing deployment of ACT in Zanzibar 2003, malaria-associated morbidity and mortality decreased dramatically within two years. Additional distribution of LLINs in early 2006 resulted in a 10-fold reduction of malaria parasite prevalence. The results indicate that the Millennium Development Goals of reducing mortality in children under five and alleviating the burden of malaria are achievable in tropical Africa with high coverage of combined malaria control interventions.