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Background: Pre-vaccination monocyte-to-lymphocyte ratio was previously suggested as a marker for malaria vaccine effectiveness. We investigated the potential of this cell ratio as a marker for malaria vaccine efficacy and effectiveness. Effectiveness was investigated by using clinical malaria endpoint, and efficacy was investigated by using surrogate endpoints of Plasmodium falciparum prepatent period, parasite density, and multiplication rates in a controlled human malaria infection trial (CHMI). Methods: We evaluated the correlation between monocyte-to-lymphocyte ratio and RTS,S vaccine effectiveness using Cox regression modeling with clinical malaria as the primary endpoint. Of the 1704 participants in the RTS,S field trial, data on monocyte-to-lymphocyte ratio was available for 842 participants, of whom our analyses were restricted. We further used Spearman Correlations and Cox regression modeling to evaluate the correlation between monocyte-to-lymphocyte ratio and Whole Sporozoite malaria vaccine efficacy using the surrogate endpoints. Of the 97 participants in the controlled human malaria infection vaccine trials, hematology and parasitology information were available for 82 participants, of whom our analyses were restricted. Results: The unadjusted efficacy of RTS,S malaria vaccine was 54% (95% CI: 37%-66%, p <0.001). No correlation was observed between monocyte-to-lymphocyte ratio and RTS,S vaccine efficacy (Hazard Rate (HR):0.90, 95%CI:0.45–1.80; p = 0.77). The unadjusted efficacy of Whole Sporozoite malaria vaccine in the appended dataset was 17.6% (95%CI:10%-28.5%, p<0.001). No association between monocyte-to-lymphocyte ratio and the Whole Sporozoite malaria vaccine was found against either the prepatent period (HR = 1.16; 95%CI:0.51–2.62, p = 0.72), parasite density (rho = 0.004, p = 0.97) or multiplication rates (rho = 0.031, p = 0.80). Conclusion: Monocyte-to-lymphocyte ratio alone may not be an adequate marker for malaria vaccine efficacy. Further investigations on immune correlates and underlying mechanisms of immune protection against malaria could provide a clearer explanation of the differences between those protected in comparison with those not protected against malaria by vaccination. [ABSTRACT FROM AUTHOR]

Introduction: A serosurvey among health care providers (HCPs) and frontliners of an area previously affected by Ebola virus disease (EVD) in the Democratic Republic of the Congo (DRC) was conducted to assess the seroreactivity to Ebola virus antigens. Methods: Serum samples were collected in a cohort of HCPs and frontliners (n = 698) participants in the EBL2007 vaccine trial (December 2019 to October 2022). Specimens seroreactive for EBOV were confirmed using either the Filovirus Animal Nonclinical Group (FANG) ELISA or a Luminex multiplex assay. Results: The seroreactivity to at least two EBOV-Mayinga (m) antigens was found in 10 (1.4%: 95% CI, 0.7–2.6) samples for GP-EBOV-m + VP40-EBOV-m, and 2 (0.3%: 95% CI, 0.0–1.0) samples for VP40-EBOV-m + NP-EBOV-m using the Luminex assay. Seroreactivity to GP-EBOV-Kikwit (k) was observed in 59 (8.5%: 95%CI, 6.5–10.9) samples using FANG ELISA. Conclusion: In contrast to previous serosurveys, a low seroprevalence was found in the HCP and frontline population participating in the EBL2007 Ebola vaccine trial in Boende, DRC. This underscores the high need for standardized antibody assays and cutoffs in EBOV serosurveys to avoid the broad range of reported EBOV seroprevalence rates in EBOV endemic areas. [ABSTRACT FROM AUTHOR]

Introduction: Uganda has implemented lifelong antiretroviral therapy for the prevention of mother-to-child HIV transmission since September 2012. Implementation of this strategy has been met with health provider and client challenges which have persisted up to date. This study explored providers' perspectives on the challenges and countermeasures of the implementation and scale-up of lifelong ART among pregnant and breastfeeding women. Methods: A qualitative descriptive study was conducted whereby 54 purposively selected participants from six facilities in three districts of Central Uganda namely; Masaka, Mityana, and Luwero were recruited. A key informant interview guide was used to collect data from the study participants. The data were thematically analysed using Atlas-ti, Version 7. Results: Study participants reported challenges under the themes of 1) inadequacy of HIV service delivery (lack of relevant training, health provider shortages, inadequate counselling, stock-outs of essential HIV commodities); 2) Non-utilization of HIV services (Non-disclosure of HIV- positive results, denial of HIV positive results, fear to be followed up, unwillingness to be referred, large catchment area, lack of transport); and 3) Suboptimal treatment adherence (fear of ART side effects, preference for traditional medicines, low male partner involvement in care and treatment). Strategies such as on-job training, mentorship, task shifting, redistribution of HIV commodities across facilities, accompanying of women to mother-baby care points, ongoing counseling of women, peers, and family support groups were commonly used countermeasures. Conclusions: This study highlights key challenges that health providers face in implementing lifelong antiretroviral therapy services among pregnant and postpartum women. Context-specific, innovative, and multilevel system interventions are required at national, district, health facility, community and individual levels to scale up and sustain the lifelong antiretroviral therapy strategy among pregnant and breastfeeding women. [ABSTRACT FROM AUTHOR]

In Africa, children aged 5 to 15 years (school age) comprises more than 50% (>339 million) of the under 19 years population, and are highly burdened by malaria and anaemia that impair cognitive development. For the prospects of improving health in African citizens, understanding malaria and its relation to anaemia in school-aged children, it is crucial to inform targeted interventions for malaria control and accelerate elimination efforts as part of improved school health policy. We conducted a study to determine the risk factors for asymptomatic malaria and their association to anaemia. We explored the prevalence of antimalarial drug resistance as well as the association of asymptomatic malaria infection and anaemia on cognitive and psychomotor functions in school-aged children living in high endemic areas. This study was a comprehensive baseline survey, within the scope of a randomised, controlled trial on the effectiveness and safety of antimalarial drugs in preventing malaria and its related morbidity in schoolchildren. We enrolled 1,587 schoolchildren from 7 primary schools located in Muheza, north-eastern Tanzania. Finger-pricked blood samples were collected for estimation of malaria parasitaemia using a microscope, haemoglobin concentration using a haemoglobinometer, and markers of drug resistance processed from dried blood spots (DBS). Psychomotor and Cognitive functions were assessed using a '20 metre Shuttle run' and a test of everyday attention for children (TEA-Ch), respectively. The prevalence of asymptomatic malaria parasitaemia, anaemia and stunting was 26.4%, 49.8%, and 21.0%, respectively with marked variation across schools. In multivariate models, asymptomatic malaria parasitaemia attributed to 61% of anaemia with a respective population attribution fraction of 16%. Stunting, not sleeping under a bednet and illiterate parent or guardian were other factors attributing to 7%, 9%, and 5% of anaemia in the study population, respectively. Factors such as age group (10–15 years), not sleeping under a bednet, low socioeconomic status, parents' or guardians' with a low level of education, children overcrowding in a household, and fewer rooms in a household were significantly attributed to higher malaria infection. There was no significant association between malaria infection or anaemia and performance on tests of cognitive function (sustained attention) or psychomotor function (VO2 max). However, a history of malaria in the past one month was significantly associated with decreased cognitive scores (aOR = -4.1, 95% CI -7.7–0.6, p = 0.02). Furthermore, stunted children had significantly lower VO2max scores (aOR = -1.9, 95% CI -3.0–0.8, p = 0.001). Regarding the antimalarial drug resistance markers, the most prevalent Pfmdr1 86-184-1034-1042-1246 haplotypes were the NFSND in 47% (n = 88) and the NYSND in 52% (n = 98). The wild type Pfcrt haplotypes (codons 72–76, CVMNK) were found in 99.1% (n = 219) of the samples. Malaria, stunting and parents' or guardians' illiteracy were the key attributable factors for anaemia in schoolchildren. Given malaria infection in schoolchildren is mostly asymptomatic; an addition of interventional programmes such as intermittent preventive treatment of malaria in schoolchildren (IPTsc) would probably act as a potential solution while calling for an improvement in the current tools such as bednet use, school food programme, and community-based (customised) health education with an emphasis on nutrition and malaria control. [ABSTRACT FROM AUTHOR]

Background: High uptake and optimal adherence to Option B+ antiretroviral therapy (ART) increase effectiveness in averting mother-to-child transmission of HIV. Option B+ ART uptake, early adherence, and associated factors need to be evaluated in Central Uganda. Methods: A mixed approaches study was carried out in six health facilities in Masaka, Mityana, and Luwero districts from October 2013 to February 2016. Questionnaires were administered to 507 HIV positive pregnant females seeking antenatal care services. Key informant interviews were conducted with 54 health providers, and in-depth interviews (IDIs) with 57 HIV positive women on Option B+ ART. Quantitative data were analyzed using log-binomial regression model to determine factors associated with optimal adherence (taking at least 95% of the prescribed ART), while thematic analysis was used on qualitative data. Results: Ninety one percent of women (463/507) received a prescription of life long ART. Of these, 93.3% (432/463) started swallowing their medicines. Overall, 83% of women who received ART prescriptions (310/374) felt they were ready to initiate ART immediately. Main motivating factors to swallow ART among those who received a prescription were women's personal desire to be healthy (92.3%) and desire to protect their babies (90.6%). Optimal adherence to ART was achieved by 76.8% (315/410). Adherence was higher among females who were ready to start ART (adj. PR = 3.20; 95% CI: 1.15–8.79) and those who had revealed their HIV positive result to someone (adj. PR = 1.23; 95% CI: 1.04–1.46). Facilitators of ART uptake from qualitative findings included adequate counseling, willingness to start, and knowing the benefits of ART. Reasons for refusal to start ART included being unready to start ART, fear to take ART for life, doubt of HIV positive results, and preference for local herbs. Reasons for non-adherence were travelling far away from health facilities, fear of side effects, non-disclosure of HIV results to anyone, and perception that the baby is safe from HIV infection post-delivery. Conclusions: Uptake of Option B+ ART was very high. However, failure to start swallowing ART and sub-optimal adherence are a major public health concern. Enhancing women's readiness to start ART and encouraging HIV result revelation could improve ART uptake and adherence. [ABSTRACT FROM AUTHOR]

Background: Anemia has severe public health significance in sub-Saharan Africa. In Ethiopia, anemia has been increasing in the last two decades, reaching the highest national level in 2016, however, the geospatial distribution and determinants of anemia in children weren't well explored at a national level. Methods: We used the Ethiopian Demographic and Health Survey(EDHS) data from 2005–2016. The data consists of samples of households (HHs) obtained through a two-stage stratified sampling procedure. Our analysis included 19,699 children. Descriptive statistics, geospatial analysis, and Generalized Linear Mixed Model (GLMMs) were used. Results: The overall prevalence of anemia was 51.5%; the spatial distribution of anemia significantly different across clusters in each survey. Children from 6 to 11 months had higher odds of anemia compared to 24–59 months (Adjusted Odds ratio (AOR) = 3.4, 95%Confidence level (CI): 2.99–3.76). Children with the first and second birth order were less likely to be anemic compared to fifth and above (AOR = 0.60, 95%CI: 0.38–0.95, and AOR = 0.83, 95%C: 0.73–0.93) respectively. Mothers' age 15 to 24 years was associated with higher odds of anemia compared to 35 to 49 years (AOR = 1.37, 95%CI: 1.20–1.55). Children from HHs with the poorest and poorer wealth category showed a higher odds of anemia compared to the richest (AOR = 1.67, 95%CI: 1.45–1.93, and AOR = 1.25, 95%CI: 1.08–1.45) respectively. Moreover, children from HHs with one to two under-five children were less likely to be anemic compared to those three and more (AOR = 0.83, 95%CI: 0.76–0.91). Conclusions: The geospatial distribution of anemia among children varies in Ethiopia; it was highest in the East, Northeast, and Western regions of the country. Several factors were associated with anemia; therefore, interventions targeting the hotspots areas and specific determinant factors should be implemented by the concerned bodies to reduce the consequences of anemia on the generation. [ABSTRACT FROM AUTHOR]

In most low-resource settings, microscopy still is the standard method for diagnosis of cutaneous leishmaniasis, despite its limited sensitivity. In Ethiopia, the more sensitive molecular methods are not yet routinely used. This study compared five PCR methods with microscopy on two sample types collected from patients with a suspected lesion to advise on optimal diagnosis of Leishmania aethiopica. Between May and July 2018, skin scrapings (SS) and blood exudate from the lesion spotted on filter paper (dry blood spot, DBS) were collected for PCR from 111 patients of four zones in Southern Ethiopia. DNA and RNA were simultaneously extracted from both sample types. DNA was evaluated by a conventional PCR targeting ITS-1 and three probe-based real-time PCRs: one targeting the SSU 18S rRNA and two targeting the kDNA minicircle sequence (the 'Mary kDNA PCR' and a newly designed 'LC kDNA PCR' for improved L. aethiopica detection). RNAs were tested with a SYBR Green-based RT-PCR targeting spliced leader (SL) RNA. Giemsa-stained SS smears were examined by microscopy. Of the 111 SS, 100 were positive with at least two methods. Sensitivity of microscopy, ITS PCR, SSU PCR, Mary kDNA PCR, LC kDNA PCR and SL RNA PCR were respectively 52%, 22%, 64%, 99%, 100% and 94%. Microscopy-based parasite load correlated well with real-time PCR Ct-values. Despite suboptimal sample storage for RNA detection, the SL RNA PCR resulted in congruent results with low Ct-values. DBS collected from the same lesion showed lower PCR positivity rates compared to SS. The kDNA PCRs showed excellent performance for diagnosis of L. aethiopica on SS. Lower-cost SL RNA detection can be a complementary high-throughput tool. DBS can be used for PCR in case microscopy is negative, the SS sample can be sent to the referral health facility where kDNA PCR method is available. Author summary: Cutaneous leishmaniasis is a neglected tropical disease and causing a public health problem in Ethiopia. Microscopy is still the standard method for detection of the parasite in Ethiopia, and also in many other low resource settings. A more sensitive method is needed for timely diagnosis and treatment. In this study, we compared five molecular methods on samples collected from patients with a skin lesion suspected of cutaneous leishmaniasis to advice on optimal diagnosis of L. aethiopica. We collected two sample types from the same lesion (skin scrapings and lesion fluid on filter paper) and isolated both DNA and RNA of them. Majority (90.1%) of the samples from skin scrapings were positive in two or more methods and the molecular methods had a higher sensitivity than the conventional methods. Interestingly, we evaluated for the first time a new molecular method designed to improve L. aethiopica detection. Also, we showed that RNA detection performed well for samples that were collected under difficult field conditions. Samples collected on filter paper showed less positive results than skin scraped samples, but could still be the method of choice for easy sampling and transport in resource-limited settings as it performed better than microscopy. [ABSTRACT FROM AUTHOR]

Introduction: School-aged children become a highly vulnerable group for malaria, yet they are less likely to use malaria prevention interventions. Previous studies exploring perception on cause of malaria mainly focused on pregnant mothers or parents of children under age five years. Exploring parent's perception on cause of malaria and their experiences on the prevention of malaria and associated challenges among school-aged children is important to develop a malaria prevention education package for school-aged children to reduce malaria and malaria related morbidities among school-aged children. Methods: A descriptive qualitative study is conducted in Kutcha district by recruiting 19 parents of school-aged children for semi-structured interviews, 6 key informants and 6 focus group discussion which consists of parents, health development army and health extension workers. A semi-structured interview guide is used to guide the interview process. The collected data is analyzed thematically with a focus on the three major areas of concern: perceived cause of malaria, experience of malaria prevention and challenges of bed net use for prevention of malaria. Results: Five causes of malaria were identified, namely hunger, mosquito bite, exposure to hot sunshine, poor sanitation and hygiene and eating some sweet foods and unripe maize. Participants perceived that eating sweet foods and unripe maize lead to enlargement of the spleen that ends in malaria while poor hygiene and sanitation leads to either development of the ova of mosquito and the landing of the housefly to contaminate food for consumption. The experiences of malaria prevention were largely influenced by their perceived cause of malaria. The malaria prevention measures undertaken by parents were vectors control measures, homemade herbal remedies and restricting children from eating sweet foods. The challenges of malaria prevention by using bed nets were related to a negative attitude, sleeping behaviors of children; use of bed nets for unintended purposes, shortage of bed nets and delays in the distribution of bed nets. Conclusion: There were misconceptions about the cause of malaria and associated experiences of malaria prevention. Control of malaria among school-aged children need health education targeting the challenges and correcting identified misconceptions by parents in Kutcha district and in other similar settings. [ABSTRACT FROM AUTHOR]

Background: The Democratic Republic of the Congo (DRC) accounts for the majority of the reported gambiense human African trypanosomiasis (HAT) cases. Kongo Central province in the DRC reports a relatively low, yet steady number of cases, and forms a transboundary focus with Angola and the Republic of Congo. This paper describes an intervention aimed at reducing the case burden in Kongo Central by improving passive case detection, complemented with reactive screening. Methodology/Principal findings: At the initiation of this programme in August 2015, 620 health facilities were identified and equipped with Rapid Diagnostic Tests (RDTs) for HAT screening. Of these, 603 (97%) reported use of RDTs, and 584 (94%) that continued to use RDTs to the last quarter of 2016 were used in the analysis going forward. Among all health facilities involved, 23 were equipped to confirm HAT by microscopy, and 4 of the latter were equipped to perform molecular testing with loop-mediated isothermal amplification (LAMP). Patients clinically suspected of HAT were tested with an RDT and those with a positive RDT result were referred to the nearest microscopy facility for confirmatory testing. If RDT positive patients were negative by microscopy, they were tested by LAMP, either on fresh blood or blood that was dried on filter paper and transported to a facility performing LAMP. This network of diagnostic facilities reduced the median distance for a patient to travel to a screening facility from 13.7km when the classical card agglutination test for trypanosomiasis (CATT) was used as a screening test in the past, to 3.4km. As a consequence, passive case detection was improved by between 30% and 130% compared to the period before. Furthermore, the proportion of HAT cases detected in early stage disease by passive screening increased from 27% to 64%. Reactive screening took place in 20 villages where cases were reported by passive screening, and in 45 villages in the neighbourhood of these villages. Reactive screening was responsible for detection of 40% of cases, of which, 90% were in first stage of the disease. Conclusions: This programme has demonstrated that it is possible to deploy passive screening for HAT at sub-country or country levels in the DRC, and this is made more effective when supplemented with reactive screening. Results and achievements showed an increase in the number of HAT cases detected, the majority of them in early disease, demonstrating that this strategy enables better population coverage and early detection of cases, which is critical in removing the HAT reservoir and interrupting transmission, and could contribute to HAT elimination in regions where it is implemented. Author summary: A number of diagnostic tests for HAT have recently been developed, to improve case detection. We report on the use of these technologies in a strategy to increase coverage and early detection of HAT cases in Kongo Central province of DRC. All 620 health facilities in the focus were equipped with RDTs to test patients presenting with symptoms suggestive of HAT. Among these health facilities, 23 were upgraded to perform confirmatory testing, for a final diagnosis. This strategy has reduced the distance a patient travels to a facility screening for HAT, from 13.7km to 3.4km. From August 2015 to December 2016, the proportion of HAT cases detected, adjusted annually, increased by between 30% and 130% compared to the previous two years, and 64% of them were in early stage disease, compared to 27% previously. This strategy has enabled better population coverage, and when supplemented with reactive screening, the identification of local outbreaks and early detection of most cases, which is critical in removing the HAT reservoir and interrupting transmission, thus contributing to elimination of the disease. [ABSTRACT FROM AUTHOR]

Background: Malaria is endemic in all regions where gambiense or rhodesiense human African trypanosomiasis (HAT) is reported, and both diseases have similarities in their symptomatology. A combined test could be useful for both diseases and would facilitate integration of the screening for gambiense HAT (gHAT) and malaria diagnosis. This study aimed to evaluate a combined prototype rapid diagnostic test (RDT) for gHAT and malaria. Methods: Blood samples were collected in the Democratic Republic of the Congo and in Uganda to evaluate the performance of a prototype HAT/Malaria Combined RDT in comparison to an individual malaria RDT based on Plasmodium falciparum (P.f.) Histidine Rich Protein II (HRP-II or HRP2) antigen (SD BIOLINE Malaria Ag P.f. RDT) for malaria detection and an individual gHAT RDT based on recombinant antigens, the SD BIOLINE HAT 2.0 RDT for HAT screening. Due to the current low prevalence of gHAT in endemic regions, the set of blood samples that were collected was used to evaluate the specificity of the RDTs for gHAT, and additional archived plasma samples were used to complete the evaluation of the HAT/Malaria Combined RDT in comparison to the HAT 2.0 RDT. Results: Frozen whole blood samples from a total of 486 malaria cases and 239 non-malaria controls, as well as archived plasma samples from 246 gHAT positive and 246 gHAT negative individuals were tested. For malaria, the sensitivity and specificity of the malaria band in the HAT/Malaria Combined RDT were 96.9% (95% CI: 95.0–98.3) and 97.1% (95% CI: 94.1–98.8) respectively. The sensitivity and specificity of the SD BIOLINE malaria Ag P.f. RDT were 97.3% (95% CI: 95.5–98.6) and 97.1% (95% CI: 94.1–98.8) respectively. For gHAT, using archived plasma samples, the sensitivity and specificity were respectively 89% (95% CI: 84.4–92.6) and 93.5% (95% CI: 89.7–96.2) with the HAT /malaria Combined RDT, and 88.2% (95% CI: 83.5–92) and 94.7% (95% CI: 91.1–97.2) with the HAT 2.0 RDT. Using the whole blood samples that were collected during the study, the specificity of the HAT/malaria Combined RDT for gHAT was 95.8% (95% CI: 94.3–97.0). Conclusion: The HAT/Malaria Combined prototype RDT was as accurate as the individual malaria or gHAT RDTs. The HAT/Malaria Combined prototype RDT is therefore suitable for both malaria diagnosis and gHAT screening. However, there is a need to assess its accuracy using fresh samples in prospective clinical trials. Author summary: The annual number of reported cases of human African trypanosomiasis (HAT), also known as sleeping sickness (SS), is currently below 1,000 cases worldwide. The Democratic Republic of the Congo (DRC), the most affected country, and Uganda, which shares a border with DRC, are both endemic for gambiense HAT (gHAT). The main strategy to control gHAT is active screening of at-risk individuals, followed by diagnosis and treatment of confirmed cases. However, this strategy and even the passive screening as currently implemented become less efficient with declining incidence, justifying innovative strategies to efficiently detect the remaining cases. All areas where gHAT occurs are also endemic for malaria, presenting an opportunity to integrate gHAT screening activities within malaria control activities. This integration is warranted by the fact that in early disease stage, gHAT patients present with signs and symptoms strikingly similar to those of malaria. In order to use malaria diagnosis as an entry point to screen for gHAT, Standard Diagnostics (SD), Korea (now Abbott Diagnostics, Korea Inc–ADK) made a Combined prototype RDT for both malaria and gHAT, expected to be as accurate as the individual gHAT and malaria RDTs. In this study, we evaluated the accuracy of the Combined prototype RDT using whole blood samples collected in Uganda and DRC, and archived plasma samples collected in DRC, Angola and Central African Republic. We found that the Combined prototype performs just as well as individual RDTs. [ABSTRACT FROM AUTHOR]

Introduction: Artemisinin-based combination therapy is currently the best option for the treatment of uncomplicated malaria. Quinine is recommended as a rescue treatment. Safety information during repeated treatment with the same drug is scarce. We report safety data from the Quinact randomized clinical trial (RCT) that was designed to assess efficacy and safety of artesunate-amodiaquine (ASAQ), artemether-lumefantrine (AL) and quinine+clindamycin (QnC). Methodology: Males and females aged 12 to 59 months with uncomplicated malaria were treated with ASAQ and followed up during 42 days (preRCT). Clinical failures were randomized to one of the 3 treatments and followed up for 28 days (RCT). Subsequent failures were repeatedly treated with ASAQ several times as needed (postRCT1, postRCT2 and so on) until a 28-days follow up period without parasitaemia. Results: Eight hundred and sixty-five, 242 and 64 patients were recruited respectively in preRCT, RCT and postRCTs. In preRCT, 433 (50.0%) patients experienced at least one drug-related adverse event (AE). The most reported AEs were anorexia (22.9%), asthenia (19.4%), and abnormal behavior (14.6%). Twenty-nine AEs (3.5%) were reported to be severe. In RCT, at least one drug-related AE was reported in 54.7%, 21.5% and 40.0% of patient randomized respectively to ASAQ, AL and QnC (p<0.001). During postRCT1 (n = 64), postRCT 2 (n = 17) and postRCT3 (n = 7), respectively 32.8%, 35.3% and 71.4% of patients experienced at least one drug-related AE. Three serious adverse events occurred but not judged related to study medication. Conclusion: The proportion of AEs did not increase over the treatment courses with ASAQ. However, continuous monitoring is important. [ABSTRACT FROM AUTHOR]

Background: Pathogens causing acute fever, with the exception of malaria, remain largely unidentified in sub-Saharan Africa, given the local unavailability of diagnostic tests and the broad differential diagnosis. Methodology: We conducted a cross-sectional study including outpatient acute undifferentiated fever in both children and adults, between November 2015 and June 2016 in Kinshasa, Democratic Republic of Congo. Serological and molecular diagnostic tests for selected arboviral infections were performed on blood, including PCR, NS1-RDT, ELISA and IFA for acute, and ELISA and IFA for past infections. Results: Investigation among 342 patients, aged 2 to 68 years (mean age of 21 years), with acute undifferentiated fever (having no clear focus of infection) revealed 19 (8.1%) acute dengue–caused by DENV-1 and/or DENV-2 –and 2 (0.9%) acute chikungunya infections. Furthermore, 30.2% and 26.4% of participants had been infected in the past with dengue and chikungunya, respectively. We found no evidence of acute Zika nor yellow fever virus infections. 45.3% of patients tested positive on malaria Rapid Diagnostic Test, 87.7% received antimalarial treatment and 64.3% received antibacterial treatment. Discussion: Chikungunya outbreaks have been reported in the study area in the past, so the high seroprevalence is not surprising. However, scarce evidence exists on dengue transmission in Kinshasa and based on our data, circulation is more important than previously reported. Furthermore, our study shows that the prescription of antibiotics, both antibacterial and antimalarial drugs, is rampant. Studies like this one, elucidating the causes of acute fever, may lead to a more considerate and rigorous use of antibiotics. This will not only stem the ever-increasing problem of antimicrobial resistance, but will–ultimately and hopefully–improve the clinical care of outpatients in low-resource settings. Trial registration: ClinicalTrials.gov . [ABSTRACT FROM AUTHOR]

Background: Human papillomaviruses are the most important causative agents for invasive cervical cancer development. HPV type-specific vaccination and HPV cervical cancer screening methods are being widely recommended to control the disease but the epidemiology of the circulating HPV types may vary locally. The circulating HPV-strains have never been assessed in Burundi. This study determined the prevalence and genotype-specific distribution of HPV in four different strata in Burundi: HIV-infected or non-infected and women living in rural or urban areas. Implications for HPV diagnosis and vaccine implementation was discussed. Methods: Four cross-sectional surveys were conducted in Burundi (2013 in a rural area and 2016 in urban area) among HIV-infected and uninfected women living in rural and urban areas. Liquid-Based Cytology (LBC) and HPV genotyping were performed and risk factors for HPV infection and cervical pre-cancer lesions were determined using logistic regression model. Results: HPV prevalence was very high in urban area with significant differences between HIV-positive and negative women (p<0.0001). In fact, 45.7% of HIV-positive participants were infected with any HPV type and all were infected with at least one HR/pHR-HPV type. Among the HIV-negative participants, 13.4% were HPV-infected, of whom, only four women (2.7%) were infected with HR/pHR-HPV types. In rural area, HPV infection did not significantly differ between HIV-positive and negative women (30.0% and 31.3% respectively; p = 0.80). In urban area, multiple infections with HR/pHR-HPV types were detected in 13.9% and 2.7% among HIV-positive and negative women respectively (p<0.0001), whereas in rural area, multiple infections with HR/pHR-HPV types were detected in 4.7% and 3.3% of HIV-positive and negative women respectively (p = 0.56). The most prevalent HR/pHR-HPV types in HIV-positive women living in urban area were HPV 52, 51, 56, 18 and 16 types. In HIV-negative women living in urban area, the most prevalent HR/pHR-HPV types were HPV 66, 67, 18, 45 and 39 types. In HIV-positive women living in rural area, the most prevalent HR/pHR-HPV types were HPV 66, 16, 18 and 33 types. In HIV-negative women living in rural area, the most prevalent HR/pHR-HPV types were HPV 16, 66, 18, 35 and 45 types. Independent risk factors associated with cervical lesions were HPV and HIV infections. Conclusions: There is a high burden of HR and pHR-HPV infections, in particular among HIV-infected women living in urban area. The study points out the need to introduce a comprehensive cervical cancer control programme adapted to the context. This study shows that the nonavalent vaccine covers most of the HR/pHR-HPV infections in rural and urban areas among HIV-infected and uninfected women. [ABSTRACT FROM AUTHOR]

Background: The emergence of resistance against artemisinin combination treatment is a major concern for malaria control. ACTs are recommended as the rescue treatment, however, there is limited evidence as to whether treatment and re-treatment with ACTs select for drug-resistant P. falciparum parasites. Thus, the purpose of the present study is to investigate the impact of (re-)treatment using artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) on the selection of P. falciparum multidrug resistance-1 (Pfmdr1) alleles in clinical settings. Methods: P. falciparum positive samples were collected from children aged 12–59 months in a clinical trial in DR Congo and Uganda. Pfmdr1 single nucleotide polymorphisms (SNPs) analysis at codons N86Y, Y184F, and D1246Y were performed at baseline and post-treatment with either AL or ASAQ as a rescue treatment using nested PCR followed by restriction fragment length polymorphism (RFLP) assays. Results: The pre-treatment prevalence of Pfmdr1 N86 and D1246Y varied significantly between the sites, (p>0.001) and (p = 0.013), respectively. There was borderline significant directional selection for Pfmdr1 184F in recurrent malaria infections after treatment with AL in Uganda site (p = 0.05). Pfmdr1 NFD haplotype did not significantly change in post-treatment infections after re-treatment with either AL or ASAQ. Comparison between pre-treatment and post-treatment recurrences did not indicate directional selection of Pfmdr1 N86, D1246 alleles in the pre-RCT, RCT and post-RCT phases in both AL and ASAQ treatment arms. Pfmdr1 86Y was significantly associated with reduced risk of AL treatment failure (RR = 0.34, 95% CI:0.11–1.05, p = 0.04) while no evidence for D1246 allele (RR = 1.02; 95% CI: 0.42–2.47, p = 1.0). Survival estimates showed that the Pfmdr1 alleles had comparable mean-time to PCR-corrected recrudescence and new infections in both AL and ASAQ treatment arms. Conclusion: We found limited impact of (re-)treatment with AL or ASAQ on selection for Pfmdr1 variants and haplotypes associated with resistance to partner drugs. These findings further supplement the evidence use of same or alternative ACTs as a rescue therapy for recurrent P.falciparum infections. Continued monitoring of genetic signatures of resistance is warranted to timely inform malaria (re-)treatment policies and guidelines. [ABSTRACT FROM AUTHOR]

Over the last decades, malaria has declined substantially in The Gambia but its transmission has not been interrupted. In order to better target control interventions, it is essential to understand the dynamics of residual transmission. This prospective cohort study was conducted between June 2013 and April 2014 in six pairs of villages across The Gambia. Blood samples were collected monthly during the transmission season (June-December) from all residents aged ≥6 months (4,194 individuals) and then in April (dry season). Entomological data were collected monthly throughout the malaria transmission season. Ownership of Long-Lasting Insecticidal Nets was 71.5% (2766/3869). Incidence of malaria infection and clinical disease varied significantly across the country, with the highest values in eastern (1.7/PYAR) than in central (0.2 /PYAR) and western (0.1/PYAR) Gambia. Malaria infection at the beginning of the transmission season was significantly higher in individuals who slept outdoors (HR = 1.51, 95% CI: 1.02–2.23, p = 0.04) and in those who had travelled outside the village (HR = 2.47, 95% CI: 1.83–3.34, p <0.01). Sub-patent infections were more common in older children (HR = 1.35, 95% CI: 1.04–1.6, p <0.01) and adults (HR = 1.53, 95% CI: 1.23–1.89, p<0.01) than in younger children. The risk of clinical malaria was significantly higher in households with at least one infected individual at the beginning of the transmission season (HR = 1.76, p<0.01). Vector parity was significantly higher in the eastern part of the country, both in the south (90.7%, 117/129, p<0.01) and the north bank (81.1%, 227/280, p<0.01), than in the western region (41.2%, 341/826), indicating higher vector survival. There is still significant residual malaria transmission across The Gambia, particularly in the eastern region. Additional interventions able to target vectors escaping Long-Lasting Insecticidal Nets and indoor residual spraying are needed to achieve malaria elimination. [ABSTRACT FROM AUTHOR]

Introduction: Puerperal sepsis causes 10% of maternal deaths in Africa, but prospective studies on incidence, microbiology and antimicrobial resistance are lacking. Methods: We performed a prospective cohort study of 4,231 Ugandan women presenting to a regional referral hospital for delivery or postpartum care, measured vital signs after delivery, performed structured physical exam, symptom questionnaire, and microbiologic evaluation of febrile and hypothermic women. Malaria rapid diagnostic testing, blood and urine cultures were performed aseptically and processed at Epicentre Mbarara Research Centre. Antimicrobial susceptibility and breakpoints were determined using disk diffusion per EUCAST standards. Hospital diagnoses, treatments and outcomes were abstracted from patient charts. Results: Mean age was 25 years, 12% were HIV-infected, and 50% had cesarean deliveries. Approximately 5% (205/4176) with ≥1 temperature measurement recorded developed postpartum fever or hypothermia; blood and urine samples were collected from 174 (85%), and 17 others were evaluated clinically. Eighty-four (48%) had at least one confirmed source of infection: 39% (76/193) clinical postpartum endometritis, 14% (25/174) urinary tract infection (UTI), 3% (5/174) bloodstream infection. Another 3% (5/174) had malaria. Overall, 30/174 (17%) had positive blood or urine cultures, and Acinetobacter species were the most common bacteria isolated. Of 25 Gram-negatives isolated, 20 (80%) were multidrug-resistant and cefepime non-susceptible. Conclusions: For women in rural Uganda with postpartum fever, we found a high rate of antibiotic resistance among cultured urinary and bloodstream infections, including cephalosporin-resistant Acinetobacter species. Increasing availability of microbiology testing to inform appropriate antibiotic use, development of antimicrobial stewardship programs, and strengthening infection control practices should be high priorities. [ABSTRACT FROM AUTHOR]

Background: In the Democratic Republic of Congo, artesunate-amodiaquine (ASAQ) is the first-line medication recommended for uncomplicated malaria treatment. We conducted a study in Kinshasa to describe the clinical features of the disease and assess the efficacy of ASAQ and its impact on the multiplicity of infection in children with uncomplicated malaria. Methods: Children aged 12 to 59 months with uncomplicated P. falciparum malaria were treated with ASAQ and followed up passively for 42 days. To distinguish new infections from recrudescent parasites, samples were genotyped using a stepwise strategy with three molecular markers (GLURP, MSP2 and MSP1). We then assessed PCR-corrected and -uncorrected day-42 cure rates and multiplicity of infection (MOI). Results: In total, 2,796 patients were screened and 865 enrolled in the study. Clinical features were characterized by history of fever (100%), coryza (59.9%) and weakness (59.4%). The crude and PCR-corrected efficacies of ASAQ were 55.3% (95%CI: 51.8–58.8) and 92.8% (95%CI: 91.0–94.6) respectively, as 83.6% (95%CI: 79.1–87.2) of the recurrences were new infections. Compared to monoclonal infections, polyclonal infections were more frequent at enrollment (88.1%) and in recurrences (80.1%; p = 0.005; OR: 1.8, 95%CI: 1.20–2.8). The median MOI at enrollment (MOI = 3.7; IQR: 0.7–6.7) decreased to 3 (IQR: 1–5) in the recurrent samples (p<0.001). Patients infected with a single haplotype on day 0 had no recrudescence; the risk of recrudescence increased by 28% with each additional haplotype (HR: 1.3, 95%CI: 1.24–1.44). Conclusion: The PCR-corrected efficacy of ASAQ at day 42 was 92.8%, but crude efficacy was relatively poor due to high reinfection rates. Treatment outcomes were positively correlated with MOI. Continued monitoring of the efficacy of ACTs—ASAQ, in this case—is paramount. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: The burden of malaria in Vietnam has drastically reduced, prompting the National Malaria Control Program to officially engage in elimination efforts. Plasmodium vivax is becoming increasingly prevalent, remaining a major problem in the country's central and southern provinces. A better understanding of P. vivax genetic diversity and structure of local parasite populations will provide baseline data for the evaluation and improvement of current efforts for control and elimination. The aim of this study was to examine the population genetics and structure of P. vivax isolates from four communities in Tra Leng commune, Nam Tra My district in Quang Nam, Central Vietnam. Methodology/Principal Findings: P. vivax mono infections collected from 234 individuals between April 2009 and December 2010 were successfully analyzed using a panel of 14 microsatellite markers. Isolates displayed moderate genetic diversity (He = 0.68), with no significant differences between study communities. Polyclonal infections were frequent (71.4%) with a mean multiplicity of infection of 1.91 isolates/person. Low but significant genetic differentiation (FST value from -0.05 to 0.18) was observed between the community across the river and the other communities. Strong linkage disequilibrium ( = 0.113, p < 0.001) was detected across all communities, suggesting gene flow within and among them. Using multiple approaches, 101 haplotypes were grouped into two genetic clusters, while 60.4% of haplotypes were admixed. Conclusions/Significance: In this area of Central Vietnam, where malaria transmission has decreased significantly over the past decade, there was moderate genetic diversity and high occurrence of polyclonal infections. Local human populations have frequent social and economic interactions that facilitate gene flow and inbreeding among parasite populations, while decreasing population structure. Findings provide important information on parasites populations circulating in the study area and are relevant to current malaria elimination efforts. [ABSTRACT FROM AUTHOR]

Background: Characterizing the parasite dynamics and population structure provides useful information to understand the dynamic of transmission and to better target control interventions. Despite considerable efforts for its control, vivax malaria remains a major health problem in Peru. In this study, we have explored the population genetics of Plasmodium vivax isolates from Iquitos, the main city in the Peruvian Amazon, and 25 neighbouring peri-urban as well as rural villages along the Iquitos-Nauta Road. Methodology/ Results: From April to December 2008, 292 P. vivax isolates were collected and successfully genotyped using 14 neutral microsatellites. Analysis of the molecular data revealed a similar proportion of monoclonal and polyclonal infections in urban areas, while in rural areas monoclonal infections were predominant (p = 0.002). Multiplicity of infection was higher in urban (MOI = 1.5–2) compared to rural areas (MOI = 1) (p = 0.003). The level of genetic diversity was similar in all areas (He = 0.66–0.76, p = 0.32) though genetic differentiation between areas was substantial (PHIPT = 0.17, p<0.0001). Principal coordinate analysis showed a marked differentiation between parasites from urban and rural areas. Linkage disequilibrium was detected in all the areas ( = 0.08–0.49, for all p<0.0001). Gene flow among the areas was stablished through Bayesian analysis of migration models. Recent bottleneck events were detected in 4 areas and a recent parasite expansion in one of the isolated areas. In total, 87 unique haplotypes grouped in 2 or 3 genetic clusters described a sub-structured parasite population. Conclusion/Significance: Our study shows a sub-structured parasite population with clonal propagation, with most of its components recently affected by bottleneck events. Iquitos city is the main source of parasite spreading for all the peripheral study areas. The routes of transmission and gene flow and the reduction of the parasite population described are important from the public health perspective as well for the formulation of future control policies. [ABSTRACT FROM AUTHOR]

Background: The burden of chronic diseases is increasing in both low- and middle-income countries. However, healthcare systems in low-income countries are inadequately equipped to deal with the growing disease burden, which requires chronic care for patients. The aim of this study was to assess the capacity of health facilities to manage hypertension in two districts in Uganda. Methods: In a cross-sectional study conducted between June and October 2012, we surveyed 126 health facilities (6 hospitals, 4 Health Center IV (HCIV), 23 Health Center III (HCIII), 41 Health Center II (HCII) and 52 private clinics/dispensaries) in Mukono and Buikwe districts in Uganda. We assessed records, conducted structured interviews with heads of facilities, and administered questionnaires to 271 health workers. The study assessed service provision for hypertension, availability of supplies such as medicines, guidelines and equipment, in-service training for hypertension, knowledge of hypertension management, challenges and recommendations. Results: Of the 126 health facilities, 92.9% reported managing (diagnosing/treating) patients with hypertension, and most (80.2%) were run by non-medical doctors or non-physician health workers (NPHW). Less than half (46%) of the facilities had guidelines for managing hypertension. A 10th of the facilities lacked functioning blood pressure devices and 28% did not have stethoscopes. No facilities ever calibrated their BP devices except one. About a half of the facilities had anti-hypertensive medicines in stock; mainly thiazide diuretics (46%), beta blockers (56%) and calcium channel blockers (48.4%). Alpha blockers, mixed alpha & beta blockers and angiotensin II receptor antagonists were only stocked by private clinics/dispensaries. Most HCIIs lacked anti-hypertensive medicines, including the first line thiazide diuretics. Significant knowledge gaps in classification of patients as hypertensive were noted among respondents. All health workers (except 5, 1.9%) indicated that they needed additional training in hypertension management. Several provider and patient related challenges were also observed in this study. Conclusions: Health facilities in this setting are inadequately equipped to provide services for management of hypertension. Diagnostic equipment, anti-hypertensive drugs and personnel present great challenges. To address the increasing burden of hypertension and other chronic diseases, measures are needed to substantially strengthen the healthcare facilities, including training of personnel in management of hypertension and other chronic diseases, and improving diagnostic and treatment supplies. [ABSTRACT FROM AUTHOR]

Background: The emergence and spread of drug resistance represents one of the biggest challenges for malaria control in endemic regions. Sulfadoxine-pyrimethamine (SP) is currently deployed as intermittent preventive treatment in pregnancy (IPTp) to prevent the adverse effects of malaria on the mother and her offspring. Nevertheless, its efficacy is threatened by SP resistance which can be estimated by the prevalence of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) mutations. This was measured among pregnant women in the health district of Nanoro, Burkina Faso. Methods: From June to December 2010, two hundred and fifty six pregnant women in the second and third trimester, attending antenatal care with microscopically confirmed malaria infection were invited to participate, regardless of malaria symptoms. A blood sample was collected on filter paper and analyzed by PCR-RFLP for the alleles 51, 59, 108, 164 in the pfdhfr gene and 437, 540 in the pfdhps gene. Results: The genes were successfully genotyped in all but one sample (99.6%; 255/256) for dhfr and in 90.2% (231/256) for dhps. The dhfr C59R and S108N mutations were the most common, with a prevalence of 61.2% (156/255) and 55.7% (142/255), respectively; 12.2% (31/255) samples had also the dhfr N51I mutation while the I164L mutation was absent. The dhps A437G mutation was found in 34.2% (79/231) isolates, but none of them carried the codon K540E. The prevalence of the dhfr double mutations NI and the triple mutations I was 35.7% (91/255) and 11.4% (29/255), respectively. Conclusion: Though the mutations in the pfdhfr and pfdhps genes were relatively common, the prevalence of the triple pfdhfr mutation was very low, indicating that SP as IPTp is still efficacious in Burkina Faso. [ABSTRACT FROM AUTHOR]

Background: Unprotected sexual intercourse is a major risk factor for HIV transmission. Men who have sex with men (MSM) face challenges in accessing HIV prevention services, including condoms. However, there is limited in-depth assessment and documentation of the barriers to condom use among MSM in sub-Saharan Africa. In this paper, we examine the barriers to condom use among MSM in Uganda. Methods: The data for this study were extracted from a larger qualitative study conducted among 85 self-identified adult (>18 years) MSM in 11 districts in Uganda between July and December 2013. Data on sexual behaviours and access and barriers to condom use were collected using semi-structured interviews. All interviews were audio-recorded and transcribed verbatim. This paper presents an analysis of data for 33 MSM who did not use condoms at last sex, with a focus on barriers to condom use. Analysis was conducted using the content analysis approach. Results: Six major barriers to condom use were identified: Difficulties with using condoms, access challenges, lack of knowledge and misinformation about condom use, partner and relationship related issues, financial incentives and socio-economic vulnerability, and alcohol consumption. Conclusion: The findings suggest that several reasons account for lack of condom use among high-risk MSM. The findings are valuable to inform interventions needed to increase condom use among MSM. [ABSTRACT FROM AUTHOR]

Background: Little information exists on malaria burden, artemisinin-based combination therapy (ACT) use, and malaria care provided to infants under six months of age. The perception that malaria may be rare in this age group has led to lack of clinical trials and evidence-based treatment guidelines. The objective of this study was to identify malaria parasitemia positivity rate (MPPR) among patients under six months, and practices and predictors of malaria diagnosis and treatment in this population. Methods: Cross-sectional data collected from October 2010 to September 2011 on 25,997 individual outpatients aged <6 months from 36 health facilities across Uganda were analysed. Findings: Malaria was suspected in 18,415 (70.8%) patients, of whom 7,785 (42.3%) were tested for malaria. Of those tested, the MPPR was 36.1%, with 63.9% testing negative, of which 1,545 (31.1%) were prescribed an antimalarial. Among children <5kgs, off-label prescription of ACT was high (104/285, 36.5%). Younger age (1-6 days, aOR=0.47, p=0.01; 7-31 days, aOR=0.43, p<0.001; and 1-2 months, aOR=0.61, p<0.001), pneumonia (aOR=0.78, p=0.01) or cough/cold (aOR=0.65, p<0.001) diagnosis, and fever (aOR=0.56, p=0.01) reduced the odds of receiving a malaria test. Fever (aOR=2.22, p<0.001), anemia diagnosis (aOR=3.51, p=0.01), consulting midwives (aOR=3.58, p=0.04) and other less skilled providers (aOR=4.75, p<0.001) relative to medical officers, consulting at hospitals (aOR=3.31, p=0.03), visiting health facilities in a medium-high malaria transmission area (aOR=2.20, p<0.001), and visiting during antimalarial (aOR=1.82, p=0.04) or antibiotic (aOR=2.23, p=0.04) shortages increased the odds of prescribing an antimalarial despite a negative malaria test result. Conclusions: We found high malaria suspicion but low testing rates in outpatient children aged <6 months. Among those tested, MPPR was high. Despite a negative malaria test result, many infants were prescribed antimalarials. Off-label ACT prescription was common in children weighing <5kgs. Evidence-based malaria guidelines for infants weighing <5 kilograms and aged <6 months are urgently needed. [ABSTRACT FROM AUTHOR]

School-aged children suffer the most from schistosomiasis infection in sub Saharan Africa due to poverty and limited sanitary conditions. Mapping of disease burden is recommended and there is a need of updating prevalence data which is as old as 20 years in the Democratic Republic of Congo. An epidemiological and parasitological study was carried out in 2011 in the health zone of Kasansa. Six health areas (HA) were included in the study. In each health area, one primary school was selected. School-aged children were screened for S. mansoni infection using parallel Kato-Katz and direct microscopy techniques. A total of 335 school-aged children were screened. The average prevalence was 82.7% and ranged between 59.5–94.9%. Four of the six HAs had a prevalence level over 91%. Of all infected children, about half 112 (43.2%) had light parasite density. These results demonstrate that Schistosoma mansoni infection is a bigger problem than anticipated and there is an urgent need to implement effective control measures. Author Summary: Schistosomiasis (SCH) is a parasitic infection and one gets infected when bathing or in contact with contaminated fresh water bodies like rivers. It has been shown that people living in poor sanitary conditions and especially school-aged children suffer the most from this infection. Mapping is needed in order to control or prevent the disease. However, in the Democratic Republic of the Congo (DRC), surveillance of schistosomiasis is lacking. Previous data on distribution of schistosomiasis may have lost relevance since the disease was last mapped 20 years ago. This study was carried out in 2011 in the health zone of Kasansa, DRC. Six primary schools were visited and stool samples were collected from children attending the 3rd class. The stool samples were analyzed for S. mansoni infection. Up to 335 children were recruited and 82.7% were infected. Moreover, in 4 health areas over 91% of the children were infected. Of all infected children, almost half, 112 (43.2%) had light parasite density. These results demonstrate that Schistosoma mansoni infection is a bigger problem than anticipated and there is an urgent need to put effective control measures. [ABSTRACT FROM AUTHOR]

Background: Anaemia reduces cognitive potential in school children, retards their growth and predisposes them to other diseases. As there is a paucity of data on the current burden of P. falciparum, S. mansoni and soil transmitted helminths (STH) infections and their correlation with schoolchildren’s anemia in the Democratic Republic of Congo (DRC), we collect these data. Methods: This study reports baseline data collected from a randomized controlled trial investigating the impact of IPT with SP and SP-PQ on anemia and malaria morbidity in Congolese schoolchildren (Trial registration: NCT01722539; PACTR201211000449323). S. mansoni and STH infections were assessed using kato-katz technique. Malaria infection and hemoglobin concentration were assessed using Blood smear and Hemocontrol device, respectively. Results: A total of 616 primary schoolchildren from 4 to 13 years old were enrolled in the study. The prevalence of Plasmodium spp. infection was 18.5% (95%CI:15.6–21.9). Amongst those infected, 24 (21%), 40 (35.1%), 40 (35.1%), 10 (8.8%), had light, moderate, heavy, very high malaria parasite density, respectively. Above 9 years of age (p = 0.02), male and history of fever (p = 0.04) were both associated with malaria infection. The overall prevalence of S. mansoni infection was 6.4% (95%CI:4.4–9.1). Girls were associated with S. mansoni infection (p = 0.04). T. trichiura was the most prevalent STH infection (26.3%), followed by A. lumbricoides (20.1%). Co-infection with malaria-S. mansoni and malaria-STH was, respectively, 1.5% (CI95%:0.7–3.3) and 6.4% (CI95% 4.4–9.1). The prevalence of anemia was found to be 41.6% (95%CI:37.7–45.6) and anemia was strongly related with Plasmodium ssp infection (aOR:4.1; CI95%:2.6–6.5;p<0.001) and S. mansoni infection (aOR:3.3;CI95%:1.4–7.8;p<0.01). Conclusion: Malaria and S. mansoni infection were strongly associated with high prevalence of anemia in schoolchildren. Therefore, specific school-based interventions, such as intermittent preventive treatment or prophylaxis, LLITN distribution, anthelminthic mass treatment and micronutrient supplementation are needed to improve school children’s health. [ABSTRACT FROM AUTHOR]

Introduction: Antibiotic therapy during pregnancy may be beneficial and impacts positively on the reduction of adverse pregnancy outcomes. No studies have been done so far on the effects of daily Co-trimoxazole (CTX) prophylaxis on birth outcomes. A phase 3b randomized trial was conducted to establish that daily CTX in pregnancy is not inferior to SP intermittent preventive treatment (IPT) in reducing placental malaria; preventing peripheral parasitaemia; preventing perinatal mortality and also improving birth weight. To establish its safety on the offspring by measuring the gestational age and birth weight at delivery, and compare the safety and efficacy profile of CTX to that of SP. Methods: Pregnant women (HIV infected and uninfected) attending antenatal clinic were randomized to receive either daily CTX or sulfadoxine-pyrimethamine as per routine IPT. Safety was assessed using standard and pregnancy specific measurements. Women were followed up monthly until delivery and then with their offspring up to six weeks after delivery. Results: Data from 346 pregnant women (CTX = 190; SP = 156) and 311 newborns (CTX = 166 and SP = 145) showed that preterm deliveries (CTX 3.6%; SP 3.0%); still births (CTX 3.0%; SP 2.1%), neonatal deaths (CTX 0%; SP 1.4%), and spontaneous abortions (CTX 0.6%; SP 0%) were similar between study arms. The low birth weight rates were 9% for CTX and 13% for SP. There were no birth defects reported. Both drug exposure groups had full term deliveries with similar birth weights (mean of 3.1 Kg). The incidence and severity of AEs in the two groups were comparable. Conclusion: Exposure to daily CTX in pregnancy may not be associated with particular safety risks in terms of birth outcomes such as preterm deliveries, still births, neonatal deaths and spontaneous abortions compared to SP. However, more data are required on CTX use in pregnant women both among HIV infected and un-infected individuals. Trial Registration: Clinicaltrials.gov NCT00711906. [ABSTRACT FROM AUTHOR]

Background: The Integrated Infectious Diseases Capacity Building Evaluation (IDCAP) designed two interventions: Integrated Management of Infectious Disease (IMID) training program and On-Site Support (OSS). We evaluated their effects on 23 facility performance indicators, including malaria case management. Methodology: IMID, a three-week training with two follow-up booster courses, was for two mid- level practitioners, primarily clinical officers and registered nurses, from 36 primary care facilities. OSS was two days of training and continuous quality improvement activities for nine months at 18 facilities, to which all health workers were invited to participate. Facilities were randomized as clusters 1∶1 to parallel OSS “arm A” or control “arm B”. Outpatient data on four malaria case management indicators were collected for 14 months. Analysis compared changes before and during the interventions within arms (relative risk = RR). The effect of OSS was measured with the difference in changes across arms (ratio of RR = RRR). Findings: The proportion of patients with suspected malaria for whom a diagnostic test result for malaria was recorded decreased in arm B (adjusted RR (aRR) = 0.97; 99%CI: 0.82,1.14) during IMID, but increased 25% in arm A (aRR = 1.25; 99%CI:0.94, 1.65) during IMID and OSS relative to baseline; (aRRR = 1.28; 99%CI:0.93, 1.78). The estimated proportion of patients that received an appropriate antimalarial among those prescribed any antimalarial increased in arm B (aRR = 1.09; 99%CI: 0.87, 1.36) and arm A (aRR = 1.50; 99%CI: 1.04, 2.17); (aRRR = 1.38; 99%CI: 0.89, 2.13). The proportion of patients with a negative diagnostic test result for malaria prescribed an antimalarial decreased in arm B (aRR = 0.96; 99%CI: 0.84, 1.10) and arm A (aRR = 0.67; 99%CI: 0.46, 0.97); (aRRR = 0.70; 99%CI: 0.48, 1.00). The proportion of patients with a positive diagnostic test result for malaria prescribed an antibiotic did not change significantly in either arm. Interpretation: The combination of IMID and OSS was associated with statistically significant improvements in malaria case management. [ABSTRACT FROM AUTHOR]

Introduction: Cotrimoxazole (CTX) has been used for half a century. It is inexpensive hence the reason for its almost universal availability and wide clinical spectrum of use. In the last decade, CTX was used for prophylaxis of opportunistic infections in HIV infected people. It also had an impact on the malaria risk in this specific group. Objective: We performed a systematic review to explore the efficacy and safety of CTX used for P.falciparum malaria treatment and prophylaxis. Result: CTX is safe and efficacious against malaria. Up to 75% of the safety concerns relate to skin reactions and this increases in HIV/AIDs patients. In different study areas, in HIV negative individuals, CTX used as malaria treatment cleared 56%–97% of the malaria infections, reduced fever and improved anaemia. CTX prophylaxis reduces the incidence of clinical malaria in HIV-1 infected individuals from 46%–97%. In HIV negative non pregnant participants, CTX prophylaxis had 39.5%–99.5% protective efficacy against clinical malaria. The lowest figures were observed in zones of high sulfadoxine-pyrimethamine resistance. There were no data reported on CTX prophylaxis in HIV negative pregnant women. Conclusion: CTX is safe and still efficacious for the treatment of P.falciparum malaria in non-pregnant adults and children irrespective of HIV status and antifolate resistance profiles. There is need to explore its effect in pregnant women, irrespective of HIV status. CTX prophylaxis in HIV infected individuals protects against malaria and CTX may have a role for malaria prophylaxis in specific HIV negative target groups. [ABSTRACT FROM AUTHOR]

Background: Visceral Leishmaniasis (VL) is a vector-borne infectious disease, caused by the protozoan Leishmania donovani, which is transmitted by phlebotomine sand flies. In an earlier study in Bihar, India, we found an association between incidence of VL and housing conditions. In the current study we investigated the influence of housing structure and conditions in and around the house on the indoor abundance of Phlebotomus argentipes, the vector of VL in this area., Methods: In each of 50 study villages in Muzaffarpur district, we randomly selected 10 houses. Light traps were installed in each house for one night during three annual peaks of sand fly density over two successive years. Sand flies captured were morphologically identified and segregated by species, sex and feeding status. Data on housing conditions and socio-economic status were also collected. We fitted a linear mixed-effects regression model with log-transformed P. argentipes counts as outcome variable and village as random effect., Results: P. argentipes was found in all but four of the 500 households. There was considerable variability between the years and the seasons. On bivariate analysis, housing structure, dampness of the floor, keeping animals inside, presence of animal dung around the house, and socio-economic status were all significantly associated with sand fly density. Highest sand fly densities were observed in thatched houses. In the multivariate model only the housing structure and socio-economic status remained significant., Conclusions: Better housing conditions are associated with lower sand fly densities, independent of other socio-economic conditions. However, in this area in Bihar even in the better-built houses sand flies are present.

Introduction: Cotrimoxazole (CTX) has been used for half a century. It is inexpensive hence the reason for its almost universal availability and wide clinical spectrum of use. In the last decade, CTX was used for prophylaxis of opportunistic infections in HIV infected people. It also had an impact on the malaria risk in this specific group., Objective: We performed a systematic review to explore the efficacy and safety of CTX used for P.falciparum malaria treatment and prophylaxis., Result: CTX is safe and efficacious against malaria. Up to 75% of the safety concerns relate to skin reactions and this increases in HIV/AIDs patients. In different study areas, in HIV negative individuals, CTX used as malaria treatment cleared 56%-97% of the malaria infections, reduced fever and improved anaemia. CTX prophylaxis reduces the incidence of clinical malaria in HIV-1 infected individuals from 46%-97%. In HIV negative non pregnant participants, CTX prophylaxis had 39.5%-99.5% protective efficacy against clinical malaria. The lowest figures were observed in zones of high sulfadoxine-pyrimethamine resistance. There were no data reported on CTX prophylaxis in HIV negative pregnant women., Conclusion: CTX is safe and still efficacious for the treatment of P.falciparum malaria in non-pregnant adults and children irrespective of HIV status and antifolate resistance profiles. There is need to explore its effect in pregnant women, irrespective of HIV status. CTX prophylaxis in HIV infected individuals protects against malaria and CTX may have a role for malaria prophylaxis in specific HIV negative target groups.

Introduction: Malaria is re-emerging in most of the African highlands exposing the non immune population to deadly epidemics. A better understanding of the factors impacting transmission in the highlands is crucial to improve well targeted malaria control strategies., Methods and Findings: A conceptual model of potential malaria risk factors in the highlands was built based on the available literature. Furthermore, the relative importance of these factors on malaria can be estimated through "classification and regression trees", an unexploited statistical method in the malaria field. This CART method was used to analyse the malaria risk factors in the Burundi highlands. The results showed that Anopheles density was the best predictor for high malaria prevalence. Then lower rainfall, no vector control, higher minimum temperature and houses near breeding sites were associated by order of importance to higher Anopheles density., Conclusions: In Burundi highlands monitoring Anopheles densities when rainfall is low may be able to predict epidemics. The conceptual model combined with the CART analysis is a decision support tool that could provide an important contribution toward the prevention and control of malaria by identifying major risk factors.