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Background: Severe falciparum malaria is a medical emergency characterised by potentially lethal vital organ dysfunction. Patient fatality rates even with parenteral artesunate treatment remain high. Despite considerable research into adjuvant therapies targeting organ and tissue dysfunction, none have shown efficacy apart from renal replacement therapy. Understanding the causal contributions of clinical and laboratory abnormalities to mortality is essential for the design and evaluation of novel therapeutic interventions.Methods and Findings: We used a structural model causal inference approach to investigate causal relationships between epidemiological, laboratory, and clinical variables in patients with severe falciparum malaria enrolled in clinical trials and their in-hospital mortality. Under this causal model, we analysed records from 9,040 hospitalised children (0-12 years, n = 5,635) and adults (n = 3,405, 12-87 years) with severe falciparum malaria from 15 countries in Africa and Asia who were studied prospectively over the past 35 years. On admission, patient covariates associated with increased in-hospital mortality were severity of acidosis (odds ratio [OR] 2.10 for a 7-mEq/L increase in base deficit [95% CI 1.93-2.28]), renal impairment (OR 1.71 for a 2-fold increase in blood urea nitrogen [95% CI 1.58, 1.86]), coma (OR 3.59 [95% CI 3.07-4.21]), seizures (OR 1.40 [95% CI 1.16-1.68]), shock (OR 1.51 [95% CI 1.14-1.99]), and presumed pulmonary oedema (OR 1.58 [95% CI 1.04-2.39]). Lower in-hospital mortality was associated with moderate anaemia (OR 0.87 for a decrease of 10 percentage points in haematocrit [95% CI 0.80-0.95]). Circulating parasite density was not associated with mortality (OR 1.02 for a 6-fold increase [95% CI 0.94-1.11]), so the pathological effects of parasitaemia appear to be mediated entirely by the downstream effects of sequestration. Treatment with an artemisinin derivative decreased mortality compared with quinine (OR 0.64 [95% CI 0.56-0.74]). These estimates were consistent across children and adults (mainly representing African and Asian patients, respectively). Using inverse probability weighting, transfusion was not estimated to be beneficial in children with admission haematocrit values between 15% and 25% (OR 0.99 [95% CI 0.97-1.02]). Except for the effects of artemisinin treatment and transfusion, causal interpretations of these estimates could be biased by unmeasured confounding from severe bacterial sepsis, immunity, and duration of illness.Conclusion: These data suggest that moderate anaemia is associated with a reduced risk of death in severe falciparum malaria. This is possibly a direct causal association. The severe anaemia threshold criteria for a definition of severe falciparum malaria should be reconsidered. [ABSTRACT FROM AUTHOR]

Typhoid fever is endemic across sub-Saharan Africa. However, estimates of the burden of typhoid are undermined by insufficient blood volumes and lack of sensitivity of blood culture. Here, we aimed to address this limitation by exploiting pre-enrichment culture followed by PCR, alongside routine blood culture to improve typhoid case detection. We carried out a prospective diagnostic cohort study and enrolled children (aged 0–4 years) with non-specific febrile disease admitted to a tertiary hospital in Blantyre, Malawi from August 2014 to July 2016. Blood was collected for culture (BC) and real-time PCR after a pre-enrichment culture in tryptone soy broth and ox-bile. DNA was subjected to PCR for invA (Pan-Salmonella), staG (S. Typhi), and fliC (S. Typhimurium) genes. A positive PCR was defined as invA plus either staG or fliC (CT<29). IgM and IgG ELISA against four S. Typhi antigens was also performed. In total, 643 children (median age 1.3 years) with nonspecific febrile disease were enrolled; 31 (4.8%) were BC positive for Salmonella (n = 13 S. Typhi, n = 16 S. Typhimurium, and n = 2 S. Enteritidis). Pre-enrichment culture of blood followed by PCR identified a further 8 S. Typhi and 15 S. Typhimurium positive children. IgM and IgG titres to the S. Typhi antigen STY1498 (haemolysin) were significantly higher in children that were PCR positive but blood culture negative compared to febrile children with all other non-typhoid illnesses. The addition of pre-enrichment culture and PCR increased the case ascertainment of invasive Salmonella disease in children by 62–94%. These data support recent burden estimates that highlight the insensitivity of blood cultures and support the targeting of pre-school children for typhoid vaccine prevention in Africa. Blood culture with real-time PCR following pre-enrichment should be used to further refine estimates of vaccine effectiveness in typhoid vaccine trials. [ABSTRACT FROM AUTHOR]

Background: The Madagascar National Strategic Plan for Malaria Control 2018 (NSP) outlines malaria control pre-elimination strategies that include detailed goals for mosquito control. Primary surveillance protocols and mosquito control interventions focus on indoor vectors of malaria, while many potential vectors feed and rest outdoors. Here we describe the application of tools that advance our understanding of diversity, host choice, and Plasmodium infection in the Anopheline mosquitoes of the Western Highland Fringe of Madagascar. Methodology/Principal findings: We employed a modified barrier screen trap, the QUadrant Enabled Screen Trap (QUEST), in conjunction with the recently developed multiplex BLOOdmeal Detection Assay for Regional Transmission (BLOODART). We captured a total of 1252 female Anopheles mosquitoes (10 species), all of which were subjected to BLOODART analysis. QUEST collection captured a heterogenous distribution of mosquito density, diversity, host choice, and Plasmodium infection. Concordance between Anopheles morphology and BLOODART species identifications ranged from 93–99%. Mosquito feeding behavior in this collection frequently exhibited multiple blood meal hosts (single host = 53.6%, two hosts = 42.1%, three hosts = 4.3%). The overall percentage of human positive bloodmeals increased between the December 2017 and the April 2018 timepoints (27% to 44%). Plasmodium positivity was frequently observed in the abdomens of vectors considered to be of secondary importance, with an overall prevalence of 6%. Conclusions/Significance: The QUEST was an efficient tool for sampling exophilic Anopheline mosquitoes. Vectors considered to be of secondary importance were commonly found with Plasmodium DNA in their abdomens, indicating a need to account for these species in routine surveillance efforts. Mosquitoes exhibited multiple blood feeding behavior within a gonotrophic cycle, with predominantly non-human hosts in the bloodmeal. Taken together, this complex feeding behavior could enhance the role of multiple Anopheline species in malaria transmission, possibly tempered by zoophilic feeding tendencies. [ABSTRACT FROM AUTHOR]

Background: In the face of the rising burden of non-communicable diseases like diabetes mellitus (DM) and hypertension in sub-Saharan Africa, where infectious diseases like Tuberculosis (TB) are still endemic, the double burden of communicable and non-communicable diseases appears to be increasing rapidly. However, the size of the problem and what is the proper health system approach to deal with the double burden is still unclear. The aim of this project was to estimate the double burden of DM hypertension and TB and to pilot the integration of the screening for DM and hypertension in the TB national programs in six TB centers in Luanda, Angola. Methods: All newly diagnosed pulmonary TB (PTB) patients accessing six directly observed treatment (DOT) centers in Luanda were screened for diabetes and hypertension. TB diagnosis was made clinically and/or with sputum microscopy DM diagnosis was made through estimation of either fasting plasma glucose (FPG) (considered positive if ≥ 7∙0mmol/l) or random plasma glucose (considered positive if ≥ 11∙1mmol/l). Uncontrolled hypertension was defined as systolic blood pressure (SBP) of ≥ 140 mm of Hg and/or diastolic blood pressure (DBP) of ≥ 90 mm of Hg, irrespective of use of antihypertensive drug. Results: Between January 2015 and December 2016, a total of 7,205 newly diagnosed patients with PTB were included in the analysis; 3,598 (49∙9%) were males and 3,607 females. Among 7,205 PTB patients enrolled, blood pressure was measured in 6,954 and 1,352 (19∙4%) were found to have uncontrolled hypertension, more frequently in females (23%) compared to males (16%). In multivariate logistic regression analysis uncontrolled hypertension was associated with increasing age and BMI and ethnic group. The crude prevalence of DM among TB patients was close to 6%, slightly higher in males (6∙3%) compared to females (5∙7%). Age adjusted prevalence was 8%. Impaired fasting glucose (>6∙1 to <7∙0 mmol/L) was detected in 414 patients (7%). In multivariate logistic regression analysis DM prevalence was higher in males and increased with increasing age and BMI. Interpretation: TB patients have a considerable hypertension and diabetes co-morbidity. It is possible to screen for these conditions within the DOTs centres. Integration of health services for both communicable and non-communicable diseases is desirable and recommended. [ABSTRACT FROM AUTHOR]

Background: Little is known on how the interaction between Sickle Cell Disease (SCD) and renal insults caused by other coexisting conditions in Sub Saharan Africa such as urinary schistosomiasis, malnutrition and HIV affect the prevalence of renal dysfunction in children with SCD. Objectives: To determine the prevalence and factors associated with renal dysfunction among children with SCD aged 6 months to 12 years attended at a tertiary hospital in Northwestern Tanzania. Methods: A cross sectional hospital-based study with a short follow up component of 3 months for 153 children with SCD was done to document demographics, clinical characteristics and features of renal dysfunction including urine dipstick albuminuria (>20mg/l) and eGFR (<60ml/ml/min/1.73m2). Other potential renal insults such as HIV infection and Schistosomiasis were also evaluated. Results: At enrollment, 48/153(31.37%) children had renal dysfunction declining to 31(20.3%) at 3 months follow up. Acute chest syndrome (OR 3.04, 95% CI [1.08–8.96], p = 0.044), severe anemia (OR 0.44, 95% CI [0.26–0.76],p = 0.003), urinary schistosomiasis (OR 7.43, 95% CI [2.10–26.32] p<0.002) and acute malnutrition (OR 4.92, 95% CI [1.29–18.84], p = 0.020). were associated with renal dysfunction. Conclusion: Where prevalent, urinary schistosomiasis and acute malnutrition increase the risk for renal dysfunction in children with SCD. We recommend albuminuria routine screening in children with SCD especially those presenting with acute chest syndrome, severe anemia and features of acute malnutrition for early detection of renal dysfunction among children with SCD. [ABSTRACT FROM AUTHOR]

Background: HIV prevalence in Mozambique is estimated to be 13.2%. Routine viral load for HIV monitoring was first implemented in the rural area of Tete in 2014. Programmatic data showed an unexpected high proportion of high viral load results, with up to 40% of patients having a viral load above 1000 copies/ml. Objectives: This qualitative study aimed to explore perceptions about virological failure and viral load monitoring from the perspective of HIV positive patients on first-line antiretroviral therapy (ART) and health-care workers. Methods: The study was conducted in seven rural communities in Changara-Marara district, Tete province, Mozambique. A total of 91 participants took part in in-depth interviews (IDIs) and focus group discussions (FGDs), including health-care workers (n = 18), patients on ART in individual care or Community Adherence Groups (CAGs) who experienced virological failure and virological re-suppression (n = 39) and CAG focal points (n = 34). Purposive sampling was used to select participants. Interviews and FGDs were conducted in Nhuengue and Portuguese. IDIs and FGDs were translated and transcribed before being coded and thematically analysed. Results: Emergent themes showed that patients and health-care workers attributed great importance to viral load monitoring. A supressed viral load was viewed by participants as a predictor of good health and good adherence. However, some patients were confused and appeared distressed when confronted with virological failure. Viral load results were often little understood, especially when virological failure was detected despite good adherence. Inadequate explanations of causes of virological failure, delayed follow-up viral load results, repeated blood tests and lack of access to second-line ART resulted in reduced confidence in the effectiveness of ART, challenged the patient-provider relationship and disempowered patients and providers. Conclusion: In this rural context undetectable viral load is recognized as a predictor of good health by people living with HIV and health-care workers. However, a lack of knowledge and health system barriers caused different responses in patients and health-care workers. Adapted counselling strategies, accelerated viral load follow-up and second-line ART initiation in patients with virological failure need to be prioritized. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is the 9th leading cause of death from a single infectious agent. Patients live in a complex health care system with both formal and informal providers, and it is important that a TB diagnosis is not missed at the first interaction with the health care system. In this study, we highlight the health seeking behavior of patients and missed opportunities for early TB diagnosis for which interventions could be instituted to ensure early TB diagnosis and prompt TB treatment initiation. Methods: This study was nested in a cross-sectional study that assessed the accuracy of different Xpert MTB/Rif implementation strategies in programmatic settings at the referral hospitals in Uganda. We documented the symptom profile of presumptive TB patients and assessed the health seeking behavior of those with chronic cough by calculating proportion of patients that visited each type of health facility and further calculated the odds of being TB positive given the type of health facility initially visited for consultation. Results: A total of 1,863 presumptive TB patients were enrolled of which 979 (54.5%) were male, and 1795 (99.9%) had chronic cough. A total of 1352 (75.4%) had previously sought care for chronic cough, with 805 (59.6%) seeking care from a public health facility followed by private health facility (289; 21.4%). Up to 182 (13.5%) patients visited a drug store for chronic cough. Patients whose first contact was a private health facility were more likely to have a positive GeneXpert test (adjOR 1.4, 95% CI: 1.0–1.9; p = 0.047). Conclusions: Chronic cough is a main symptom for many of the presumptive TB patients presenting at referral hospitals, with several patients having to visit the health system more than once before a TB diagnosis is made. This suggests the need for patients to be thoroughly evaluated at first interface with the health care system to ensure prompt diagnosis and treatment initiation. Improved TB diagnosis possibly with the GeneXpert test, at first contact with the health care system has potential to increase TB case finding and break the transmission cycle in the community. [ABSTRACT FROM AUTHOR]

Background: Although the success of HIV treatment programs depends on retention and viral suppression, routine program monitoring of these outcomes may be incomplete. We used data from the national electronic medical record (EMR) system in Zambia to enumerate a large and regionally representative cohort of patients on treatment. We traced a random sample with unknown outcomes (lost to follow-up) to document true care status and HIV RNA levels.Methods and Findings: On 31 July 2015, we selected facilities from 4 provinces in 12 joint strata defined by facility type and province with probability proportional to size. In each facility, we enumerated adults with at least 1 clinical encounter after treatment initiation in the previous 24 months. From this cohort, we identified lost-to-follow-up patients (defined as 90 or more days late for their last appointment), selected a random sample, and intensively reviewed their records and traced them via phone calls and in-person visits in the community. In 1 of 4 provinces, we also collected dried blood spots (DBSs) for plasma HIV RNA testing. We used inverse probability weights to incorporate sampling outcomes into Aalen-Johansen and Cox proportional hazards regression to estimate retention and viremia. We used a bias analysis approach to correct for the known inaccuracy of plasma HIV RNA levels obtained from DBSs. From a total of 64 facilities with 165,464 adults on ART, we selected 32 facilities with 104,966 patients, of whom 17,602 (17%) were lost to follow-up: Those lost to follow-up had median age 36 years, 60% were female (N = 11,241), they had median enrollment CD4 count of 220 cells/μl, and 38% had WHO stage 1 clinical disease (N = 10,690). We traced 2,892 (16%) and found updated outcomes for 2,163 (75%): 412 (19%) had died, 836 (39%) were alive and in care at their original clinic, 457 (21%) had transferred to a new clinic, 255 (12%) were alive and out of care, and 203 (9%) were alive but we were unable to determine care status. Estimates using data from the EMR only suggested that 42.7% (95% CI 38.0%-47.1%) of new ART starters and 72.3% (95% CI 71.8%-73.0%) of all ART users were retained at 2 years. After incorporating updated data through tracing, we found that 77.3% (95% CI 70.5%-84.0%) of new initiates and 91.2% (95% CI 90.5%-91.8%) of all ART users were retained (at original clinic or transferred), indicating that routine program data underestimated retention in care markedly. In Lusaka Province, HIV RNA levels greater than or equal to 1,000 copies/ml were present in 18.1% (95% CI 14.0%-22.3%) of patients in care, 71.3% (95% CI 58.2%-84.4%) of lost patients, and 24.7% (95% CI 21.0%-29.3%). The main study limitations were imperfect response rates and the use of self-reported care status.Conclusions: In this region of Zambia, routine program data underestimated retention, and the point prevalence of unsuppressed HIV RNA was high when lost patients were accounted for. Viremia was prevalent among patients who unofficially transferred: Sustained engagement remains a challenge among HIV patients in Zambia, and targeted sampling is an effective strategy to identify such gaps in the care cascade and monitor programmatic progress. [ABSTRACT FROM AUTHOR]

Iodine deficiency (ID) during pregnancy results in pregnancy losses, intrauterine growth retardation, and lower IQ in the offspring. Even after two decades of universal salt iodization (USI) implementation, the efficacy of USI has not been reported in high risk groups in vulnerable regions in Ghana. We aimed to assess and improve ID status in childbearing age women (all lactating women) and their toddlers in northern Ghana, a geographically and socioeconomically vulnerable region. We provided weekly supply of household iodized salt and community-based feeding of native Hibiscus Sabdariffaa leaves meal (HSM) prepared with iodized salt to women and their toddlers in intervention (n = 60) vs. control group (n = 60). At baseline, ID was prevalent in women (36%) and their toddlers (29%). For women, both median UIC values for intervention (57.4 ug/l) and control group (65.1 ug/l) were below the recommended UIC value of 100 ug/l with no significant differences between the two groups (p = 0.2778). At the endpoint, median UIC for the intervention group (123.6 ug/l) was significantly higher (p = 0.008) than the control group (59.7 ug/l). Our results suggest that weekly supply of iodized salt along with the feeding HSM is an effective channel for improving iodine status of economically disadvantaged groups in communities remote from coastal lands. Furthermore, our results suggest that decreased median UIC among lactating mothers does not necessarily imply lower iodine status for their breastfed toddlers. And finally, the observed median UIC<100 ug/l may point to a non-improvement in iodine status for the past decade for Ghana. There is a need to revisit, assess, and ascertain the challenges in preventing populations from attaining the intended benefits of the USI policy in Ghana. [ABSTRACT FROM AUTHOR]

Background: A single co-administered dose of ivermectin (IVM) plus diethylcarbamazine (DEC) plus albendazole (ALB), or triple-drug therapy, was recently found to be more effective for clearing microfilariae (Mf) than standard DEC plus ALB currently used for mass drug administration programs for lymphatic filariasis (LF) outside of sub-Saharan Africa. Triple-drug therapy has not been previously tested in LF-uninfected individuals from Africa. This study evaluated the pharmacokinetics (PK), safety, and efficacy of triple-drug therapy in people with and without Wuchereria bancrofti infection in West Africa. Methods: In this open-label cohort study, treatment-naïve microfilaremic (>50 mf/mL, n = 32) and uninfected (circulating filarial antigen negative, n = 24) adults residing in Agboville district, Côte d’Ivoire, were treated with a single dose of IVM plus DEC plus ALB, and evaluated for adverse events (AEs) until 7 days post treatment. Drug levels were assessed by liquid chromatography and mass spectrometry. Persons responsible for assessing AEs were blinded to participants’ infection status. Findings: There was no difference in AUC0-inf or Cmax between LF-infected and uninfected participants (P>0.05 for all comparisons). All subjects experienced mild AEs; 28% and 25% of infected and uninfected participants experienced grade 2 AEs, respectively. There were no severe or serious adverse events. Only fever (16 of 32 versus 4 of 24, P<0.001) and scrotal pain/swelling in males (6 of 20 versus 0 of 12, P = 0.025) were more frequent in infected than uninfected participants. All LF positive participants were amicrofilaremic at 7 days post-treatment and 27 of 31 (87%) remained amicrofilaremic 12 months after treatment. Conclusions: Moderate to heavy W. bancrofti infection did not affect PK parameters for IVM, DEC or ALB following a single co-administered dose of these drugs compared to uninfected individuals. The drugs were well tolerated. This study confirmed the efficacy of the triple-drug therapy for clearing W. bancrofti Mf and has added important information to support the use of this regimen in LF elimination programs in areas of Africa without co-endemic onchocerciasis or loiasis. Trial registration: ClinicalTrials.gov . [ABSTRACT FROM AUTHOR]

Background: Incidence of Acute Kidney Injury (AKI) among Type 2 diabetic patients is significantly increasing. But, earlier studies has focused on the admitted patients which may hide the true nature of the Acute Kidney Injury among Type 2 Diabetic (T2D) patients. So, this study was conducted to determine the time to Acute Kidney Injury and its predictors among Type 2 Diabetic patients in Harari Region, East Ethiopia. Methods: We conducted a retrospective cohort study among type 2 diabetic patients who had been receiving treatment at government hospitals of Harari region, Ethiopia from 2013 to 2017. We extracted data from patients’ medical records. We estimated incidence rate and compared survival curves between different exposure groups using Kaplan-Meier and log-rank test. Weibull regression model was fitted to the data to identify the predictor variables. Variables with p-value <0.05 were considered statistically significant. Results: Overall, 14.5% (95%CI: 11.7–17.9) of the study population developed acute kidney injury, with median survival time of 57 months. The significant predictors were physical activity [Adjusted Time Ratio (ATR):95%CI; 0.6 (0.49–0.75)], congestive heart failure [ATR:95%CI; 0.84 (0.71–0.99)], chronic kidney disease [ATR:95%CI; 0.77(0.65–0.91)], hypertension [ATR:95%CI; 0.78(0.65–0.91)], obesity [ATR:95%CI; 0.84(0.74–0.96)], diabetic nephropathy [ATR:95%CI; 0.80(0.65–0.98)], diuretics & beta blockers [ATR:95%CI; 0.85(0.74–0.97)], and delay of follow-up [ATR:95%CI; 0.97(0.96–0.98)]. Conclusions: Incidence of acute kidney injury was high in our study area. Hence, identification and controlling of comorbidities along with regular monitoring of kidney function are needed to prevent or delay the risk of acute kidney injury in type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Mothers are recommended to exclusively breastfeed their infants for the first six months of their lives. Also, after the sixth month, breastfeeding should continue with added complementary foods to the diets of children. Studies designed to sought the views of mothers on breastfeeding practices are limited. The aim of this study was to explore challenges to breastfeeding practices by considering spatial, societal and maternal characteristics in Ghana. Twenty mothers aged 15–49 years were interviewed purposively in selected communities within two regions of the country. Thematic content analytical procedures were applied to interpret and present findings. Challenges (to both exclusive breastfeeding and complementary feeding) spanned across spatial (home and work places), societal, and maternal characteristics. Key themes identified were in relation to household chores, work schedules, family influence, low breast milk production, swollen breasts or sore nipples, access to food items and preparation or giving foods. Addressing these challenges would require co-creation of supportive environments between couples and significant others as well as tackling institutional barriers that obstruct adequate breastfeeding among mothers. On complementary feeding, there is the need to form community health volunteers help educate mothers more on how to appropriately use local foods to feed their children. [ABSTRACT FROM AUTHOR]

Rift Valley fever virus (RVFV) is a zoonotic phlebovirus that can be transmitted to humans or livestock by mosquitoes or through direct contact with contaminated bodily fluids and tissues. Exposure to bodily fluids and tissues varies by types of behaviors engaged for occupational tasks, homestead responsibilities, or use in dietary or therapeutic capacities. While previous studies have included milk exposures in their analyses, their primary focus on livestock exposures has been on animal handling, breeding, and slaughter. We analyzed data from multiple field surveys in Kenya with the aim of associating RVFV infection to raw milk exposures from common animal species. Of those with evidence of prior RVFV infection by serology (n = 267), 77.2% engaged in milking livestock compared to 32.0% for 3,956 co-local seronegative individuals (p < 0.001), and 86.5% of seropositive individuals consumed raw milk compared to 33.4% seronegative individuals (p < 0.001). Individuals who milked and also consumed raw milk had greater odds of RVFV exposure than individuals whose only contact to raw milk was through milking. Increased risks were associated with exposure to milk sourced from cows (p < 0.001), sheep (p < 0.001), and goats (p < 0.001), but not camels (p = 0.98 for consuming, p = 0.21 for milking). Our data suggest that exposure to raw milk may contribute to a significant number of cases of RVFV, especially during outbreaks and in endemic areas, and that some animal species may be associated with a higher risk for RVFV exposure. Livestock trade is regulated to limit RVFV spread from endemic areas, yet further interventions designed to fully understand the risk of RVFV exposure from raw milk are imperative. [ABSTRACT FROM AUTHOR]

While access to safe sanitation is a global issue, there are large disparities in access. Women living in informal settlements, in particular, are disproportionately affected by lack of access to sanitation. Without adequate sanitation, these women may resort to unsafe strategies to manage their sanitation needs, but limited research has focused specifically on this issue. Qualitative and quantitative data were collected from women in the Mathare informal settlement in Nairobi, Kenya in 2016. A latent class analysis (LCA) using the quantitative data yielded five distinct sanitation profiles (SP) among women in Mathare. In-depth interviews and sanitation walks with women added further detail about the characteristics of and motivations underlying each profile. Women's sanitation profiles in these settlements are complex. A majority of women in this study utilized an unsafe method of disposal at least once in a 24-hour period that increased their risk of direct exposure to waste and harmful pathogens. [ABSTRACT FROM AUTHOR]

Currently, malaria rapid diagnostic tests (RDTs) are widely used for malaria diagnosis, but test performance and the factors that lead to failure of Plasmodium ovale detection are not well understood. In this study, three pLDH-based RDTs were evaluated using cases in China that originated in Africa. The sensitivity of Wondfo Pf/Pan, CareStart pLDH PAN and SD BIOLINE Pf/Pan in P. ovale detection was 70, 55 and 18%, respectively. CareStart was worse at detecting P. o. curtisi (36.5%) than at detecting P. o. wallikeri (75.0%), and SD could not detect P. o. curtisi. The overall detection ratio of all three RDTs decreased with parasite density and pLDH concentration. Wondfo, CareStart and SD detected only 75.0, 78.1 and 46.9% of the P. ovale cases, respectively, even when the parasitemia were higher than 5000 parasites/μL. Subspecies of P. ovale should be considered while to improve RDT quality for P. ovale diagnosis to achieve the goal of malaria elimination. [ABSTRACT FROM AUTHOR]

Agricultural sector plays a key role towards achieving healthier diets that are deemed critical for improving health and nutritional outcomes. To what extent the current food supply systems support healthy diets remains unknown. Using annual and nationally representative data on crop and livestock production in Ethiopia, we assess the national agricultural sector from a nutrition lens and its role in supporting healthy diets in the country. We do so by converting the agricultural production into energy and nutrients for the period of 2011–2015. These data show that the national food production has increased dramatically over the 5-year period to supply more than 3,000 calories per capita in 2015. Moreover, nutrient production gaps have substantially decreased (2011–15), but deficits in energy (5%), vitamin C (16%), and calcium (9%) production remained in 2015. However, this production growth–coming primarily from the cereal sector and at the expense of other food groups–led to a decrease in production diversity as reflected by a drop in the Shannon index between 2011 and 2015. Together these findings imply that the production increases in Ethiopia would need to be sustained to feed the rapidly growing population but more emphasis should be given to diversification to support healthy and nutritionally diversified diets. [ABSTRACT FROM AUTHOR]

Background: Mapping of lymphatic filariasis (LF) caused by Wuchereria bancrofti largely relies on the detection of circulating antigen using ICT cards. Several studies have recently shown that this test can be cross-reactive with sera of subjects heavily infected with Loa loa and thus mapping results in loiasis endemic areas may be inaccurate. Methodology/Principal findings: In order to develop an LF mapping strategy for areas with high loiasis prevalence, we collected day blood samples from 5,001 subjects residing in 50 villages that make up 6 health districts throughout Cameroon. Antigen testing using Filarial Test Strip (FTS, a novel platform that uses the same reagents as ICT) revealed an overall positivity rate of 1.1% and L. loa microfilaria (Mf) rates of up to 46%. Among the subjects with 0 to 8,000 Mf/ml in day blood, only 0.4% were FTS positive, while 29% of subjects with >8,000 Mf/ml were FTS positive. A Mf density of >8,200 Mf/ml was determined as the cut point at which positive FTS results should be excluded from the analysis. No FTS positive samples were also positive for W. bancrofti antibodies as measured by two different point of care tests that use the Wb123 antigen not found in L. loa. Night blood examination of the FTS positive subjects showed a high prevalence of L. loa Mf with densities up to 12,710 Mf/ml. No W. bancrofti Mf were identified, as confirmed by qPCR. Our results show that high loads of L. loa Mf in day blood are a reliable indicator of FTS positivity, and Wb123 rapid test proved to be relatively specific. Conclusions/Significance: Our study provides a simple day blood-based algorithm for LF mapping in loiasis areas. The results indicate that many districts that were formerly classified as endemic for LF in Cameroon are non-endemic and do not require mass drug administration for elimination of LF. [ABSTRACT FROM AUTHOR]

Background: Infection of bones and joints remains one of the most commonly described complications of brucellosis in humans and is predominantly reported in all ages and sexes in high-risk regions, such as the Middle East, Asia, South and Central America, and Africa. We aimed to systematically review the literature and perform a meta-analysis to estimate the global prevalence of osteoarticular brucellosis. Methodology: Major bibliographic databases were searched using keywords and suitable combinations. All studies reporting the incidence and clinical manifestations of osteoarticular brucellosis in humans, and demonstrated by two or more diagnostic methods (bacteriological, molecular, serological, and/or radiographic) were included. Random effect model was used, and statistical significance was set at 0.5% Principal findings: A total of 56 studies met the inclusion criteria and were included in the systematic review and meta-analysis. There was an evidence of geographical variation in the prevalence of osteoarticular disease with estimates ranging from 27% in low-risk regions to 36% in high-risk regions. However, the difference was not significant. Thus, brucellosis patients have at least 27% chance of developing osteoarticular disease. Conclusions: The prevalence of OAB is not dependent on the endemicity of brucellosis in a particular region. Hence, further research should investigate the potential mechanisms of OAB, as well as the influence of age, gender, and other socioeconomic factor variations in its global prevalence, as this may provide insight into associated exposure risks and management of the disease. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer survival rates in Africa are low as many cases are diagnosed late. Currently, there are no inexpensive, non-invasive and simple techniques that can be employed in poor resource settings for early case detection. In this study, we explored the possibility using blood in gastric juice as a screening tool to identify patients requiring referral for endoscopy. Methods: The study was conducted at the University Teaching Hospital endoscopy unit in Lusaka, Zambia. During esophagogastroduodenoscopy, gastric juice was aspirated and the pH determined using pH paper test strips. The presence of blood was tested using urinalysis reagent strips. Results: We enrolled 276 patients; 147(53%) were female and median age was 49 years (IQR 40–64 years). The presence of blood was associated with mucosal lesions, [OR 2.1; 95% CI 1.2–3.7, P = 0.004]. It was also associated with gastric cancer, [OR 6.7; 95% CI 2–35, P = 0.0005], even at 1:10 and 1:100 dilutions, [OR 5.4; 95% CI 2.3–13.8, P<0.0001] and [OR 9.1; 95% CI 3.5–23, P<0.0001] respectively. The sensitivity for gastric cancer detection using blood in gastric juice was 91% and the specificity was 41%. Analysis using the intensity of blood in gastric juice yielded an area under the receiver operating characteristic curve of 0.78; 95% CI 0.71–0.86 with a sensitivity of 79% and a specificity of 77%. Conclusions: The presence of blood in gastric juice is associated with gastric mucosal lesions. It has a high sensitivity but low specificity for gastric cancer detection. [ABSTRACT FROM AUTHOR]

Background: Rapid diagnostic test (RDT) kits have been useful tools to screen for the presence of infection with malaria parasites. Despite the improvement, false results from RDTs present a greater challenge. The need for quality test kits is desirable. We evaluated the diagnostic accuracy of three malaria RDTs. Method: The team consented and enrolled 754 participants from the two major public hospitals in Kintampo districts of Ghana from June 2014 to August 2014. Venous blood samples were obtained by trained personnel and samples were screened for malaria using CareStart and SD Bioline HRP2 and HRP2 with pLDH based RDTs with blood slides for malaria microscopy as “gold standard”. Geometric mean parasite densities were estimated and parasite densities were used to estimate the quantitative limits of the RDTs. The sensitivities, specificities and other performance criteria were calculated using statistical analytical software. Result: The median age of participants was 21 (range 5–31) years. There were 28.6% (215/752) were males and 71.4% (537/752) were females. Comparing with microscopy, the sensitivity, specificity, positive predictive value, negative predictive value and the ROC were for CareStart (HRP2), 98.2%, 66.5%, 82.6%, 95.6%, 0.82; for CareStart (HRP2/pLDH) 98.2%, 66.5%, 82.6%, 95.6%, 0.82 and for SD-Bioline (HRP2/pLDH) RDTs 98.2%, 69.2%, 84.2%, 96.0%, 0.84 respectively. The performance for all the kits were acceptable at a cut-off of 25 or more parasites/μl of blood. Conclusions: The diagnostic performance of the three malaria RDTs was acceptable, according to the World Health Organisation criteria, to detect densities ≥25 parasite/μl of blood. The RDTs with HRP2/pLDH targets were comparable to those with only HRP2 and could successfully substitute current and commonly used HRP2-based RDTs. [ABSTRACT FROM AUTHOR]

Introduction: Effective point-of-care testing (POCT) is reliant on optimal specimen collection, quality assured testing, and expedited return of results. Many of the POCT are designed to be used with fingerstick capillary blood to simplify the blood collection burden. However, fingerstick blood collection has inherent errors in sampling. An evaluation of the use of capillary and venous blood with CD4 POCT was conducted. Methods: Three different specimen collection methods were evaluated for compatibility using the Alere Pima CD4 assay at 5 HIV/AIDS healthcare sites in Dar es Salaam, Tanzania. At each site, whole blood specimens were collected from enrolled patients by venipuncture and fingerstick. Pima CD4 testing was performed at site of collection on venipuncture specimens (Venous) and fingerstick blood directly applied to a Pima CD4 cartridge (Capillary-Direct) and collected into an EDTA microtube (Capillary-Microtube). Venous blood was also tested at the laboratory by the reference CD4 method and Pima for comparison analysis. Results: All three specimen collection methods were successfully collected by healthcare workers for use with the Pima CD4 assay. When compared to the reference CD4 method, Pima CD4 testing with the Capillary-Microtube method performed similarly to Venous, while Pima CD4 counts with the Capillary-Direct method were slightly more biased (-20 cells/μL) and variable (-229 to +189 cells/μL limit of agreement). Even though all three collection methods had similar invalid Pima testing rates (10.5%, 9.8%, and 8.3% for Capillary-Direct, Capillary-Microtube, and Venous respectively), the ability to perform repeat testing with Capillary-Microtube and Venous specimens increased the likelihood of acquiring a valid CD4 result with the Pima assay. Conclusions: Capillary blood, either directly applied to Pima CD4 cartridges or collected in an EDTA microtube, and venous blood are suitable specimens for Pima CD4 testing. The advantages of capillary blood collection in an EDTA microtube are that it uses fingerstick collection which mimics venous blood and allows extra testing without additional blood collection. [ABSTRACT FROM AUTHOR]

Objective: To assess changes and equity in antiretroviral therapy (ART) use in Kenya and South Africa. Methods: We analysed national population-based household surveys conducted in Kenya and South Africa between 2007 and 2012 for factors associated with lack of ART use among people living with HIV (PLHIV) aged 15–64 years. We considered ART use to be inequitable if significant differences in use were found between groups of PLHIV (e.g. by sex). Findings: ART use among PLHIV increased from 29.3% (95% confidence interval [CI]: 22.8–35.8) to 42.5% (95%CI: 37.4–47.7) from 2007 to 2012 in Kenya and 17.4% (95%CI: 14.2–20.9) to 30.3% (95%CI: 27.2–33.6) from 2008 to 2012 in South Africa. In 2012, factors independently associated with lack of ART use among adult Kenyan PLHIV were rural residency (adjusted odds ratio [aOR] 1.98, 95%CI: 1.23–3.18), younger age (15–24 years: aOR 4.25, 95%CI: 1.7–10.63, and 25–34 years: aOR 5.16, 95%CI: 2.73–9.74 versus 50–64 years), nondisclosure of HIV status to most recent sex partner (aOR 2.41, 95%CI: 1.27–4.57) and recent recreational drug use (aOR 2.50, 95%CI: 1.09–5.77). Among South African PLHIV in 2012, lack of ART use was significantly associated with younger age (15–24 years: aOR 4.23, 95%CI: 2.56–6.70, and 25–34 years: aOR 2.84, 95%CI: 1.73–4.67, versus 50–64 years), employment status (aOR 1.61, 95%CI: 1.16–2.23 in students versus unemployed), and recent recreational drug use (aOR 4.56, 95%CI: 1.79–11.57). Conclusion: Although we found substantial increases in ART use in both countries over time, we identified areas needing improvement including among rural Kenyans, students in South Africa, and among young people and drug users in both countries. [ABSTRACT FROM AUTHOR]

In 2011, an unusually large number of independent Hendra virus outbreaks were recorded on horse properties in Queensland and New South Wales, Australia. Urine from bat colonies adjacent to the outbreak sites were sampled and screened for Hendra and other viruses. Several novel paramyxoviruses were also isolated at different locations. Here one of the novel viruses, named Hervey virus (HerPV), is fully characterized by genome sequencing, annotation, phylogeny and in vitro host range, and its serological cross-reactivity and neutralization patterns are examined. HerPV may have ecological and spatial and temporal patterns similar to Hendra virus and could serve as a sentinel virus for the surveillance of this highly pathogenic virus. The suitability of HerPV as potential sentinel virus is further assessed by determining the serological prevalence of HerPV antibodies in fruit-eating bats from Australia, Indonesia, Papua New Guinea, Tanzania and the Gulf of Guinea, indicating the presence of similar viruses in regions beyond the Australian border. [ABSTRACT FROM AUTHOR]

Background: Congenital talipes equino-varus (CTEV), also known as clubfoot, is one of the most common congenital musculoskeletal malformations. Despite this, considerable variation exists in the measurement of deformity correction and outcome evaluation. This study aims to determine the criteria for successful clubfoot correction using the Ponseti technique in low resource settings through Africa. Methods: Using the Delphi method, 18 experienced clubfoot practitioners and trainers from ten countries in Africa ranked the importance of 22 criteria to define an ‘acceptable or good clubfoot correction’ at the end of bracing with the Ponseti technique. A 10cm visual analogue scale was used. They repeated the rating with the results of the mean scores and standard deviation of the first test provided. The consistency among trainers was determined with the intra-class correlation coefficient (ICC). From the original 22 criteria, ten criteria with a mean score >7 and SD <2 were identified and were rated through a second Delphi round by 17 different clubfoot treatment trainers from 11 countries in Africa. The final definition consisted of all statements that achieved strong agreement, a mean score of >9 and SD<1.5. Results: The consensus definition of a successfully treated clubfoot includes: (1) a plantigrade foot, (2) the ability to wear a normal shoe, (3) no pain, and (4) the parent is satisfied. Participants demonstrated good consistency in rating these final criteria (ICC 0.88; 0.74,0.97). Conclusions: The consistency of Ponseti technique trainers from Africa in rating criteria for a successful outcome of clubfoot management was good. The consensus definition includes basic physical assessment, footwear use, pain and parent satisfaction. [ABSTRACT FROM AUTHOR]

Schistosomiasis is one of the major Neglected Tropical Diseases (NTDs) in sub-Saharan Africa. In sub-Saharan Africa, two major human schistosome species namely Schistosoma mansoni and S. haematobium often occur sympatrically largely affecting children. Recognizing the public health impact of Schistosomiasis, the World Health Organization (WHO) is urging member states to regularly treat at least 75% and up to 100%, of all school-aged children at risk of morbidity. For control strategies based on targeted mass drug administration (MDA) to succeed it is essential to have a simple and sensitive test for monitoring the success of these interventions. Current available diagnostic tests, such as egg detection in stool by Kato-Katz (KK) for S. mansoni and detection of eggs or blood (hematuria) in urine for S. haematobium have reduced sensitivity in low intensity settings. The objective of the study was to evaluate active single or duo schistosome infections in school children following MDA using molecular diagnostics (PCR) on filtered urine samples and comparing that against traditional diagnostic tests. This cross-sectional study was conducted among 111 school children aged 7–15 years in Chongwe and Siavonga Districts in Zambia. Species-specific cell-free repeat DNA fragment were amplified from 111 filtered urine samples. Our approach detected eight times more positive cases (total 77) than by KK (9) for S. mansoni and six times more (total 72) than by hematuria (11) for S. haematobium and even more against urine filtration (77 compared to only 6). The same pattern was observed when stratified for age group and sex specific analysis with 100% sensitivity and specificity devoid of any cross amplification. In addition, 69 individuals (62%) were co-infected by both parasites. We have demonstrated a significantly higher prevalence of both species than indicated by the traditional tests and the persistent maintenance of reservoir of infection after MDA. Our approach is an effective means of detecting low intensity infection, which will enhance the effectiveness of surveillance and assess the impact of MDA control programs against schistosomiasis. [ABSTRACT FROM AUTHOR]

Nontyphoidal Salmonellae commonly cause invasive disease in African children that is often fatal. The clinical diagnosis of these infections is hampered by the absence of a clear clinical syndrome. Drug resistance means that empirical antibiotic therapy is often ineffective and currently no vaccine is available. The study objective was to identify risk factors for mortality among children presenting to hospital with invasive Salmonella disease in Africa. We conducted a prospective study enrolling consecutive children with microbiologically-confirmed invasive Salmonella disease admitted to Queen Elizabeth Central Hospital, Blantyre, in 2006. Data on clinical presentation, co-morbidities and outcome were used to identify children at risk of inpatient mortality through logistic-regression modeling. Over one calendar year, 263 consecutive children presented with invasive Salmonella disease. Median age was 16 months (range 0–15 years) and 52/256 children (20%; 95%CI 15–25%) died. Nontyphoidal serovars caused 248/263 (94%) of cases. 211/259 (81%) of isolates were multi-drug resistant. 251/263 children presented with bacteremia, 6 with meningitis and 6 with both. Respiratory symptoms were present in 184/240 (77%; 95%CI 71–82%), 123/240 (51%; 95%CI 45–58%) had gastrointestinal symptoms and 101/240 (42%; 95%CI 36–49%) had an overlapping clinical syndrome. Presentation at <7 months (OR 10.0; 95%CI 2.8–35.1), dyspnea (OR 4.2; 95%CI 1.5–12.0) and HIV infection (OR 3.3; 95%CI 1.1–10.2) were independent risk factors for inpatient mortality. Invasive Salmonella disease in Malawi is characterized by high mortality and prevalence of multi-drug resistant isolates, along with non-specific presentation. Young infants, children with dyspnea and HIV-infected children bear a disproportionate burden of the Salmonella-associated mortality in Malawi. Strategies to improve prevention, diagnosis and management of invasive Salmonella disease should be targeted at these children. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis affects 218 million people worldwide, with most infections in Africa. Prevalence studies suggest that people with chronic schistosomiasis may have higher risk of HIV-1 acquisition and impaired ability to control HIV-1 replication once infected. We hypothesized that: (1) pre-existing schistosome infection may increase the odds of HIV-1 acquisition and that the effects may differ between men and women, and (2) individuals with active schistosome infection at the time of HIV-1 acquisition may have impaired immune control of HIV-1, resulting in higher HIV-1 viral loads at HIV-1 seroconversion. Methology/Principal findings: We conducted a nested case-control study within a large population-based survey of HIV-1 transmission in Tanzania. A population of adults from seven villages was tested for HIV in 2007, 2010, and 2013 and dried blood spots were archived for future studies with participants’ consent. Approximately 40% of this population has Schistosoma mansoni infection, and 2% has S. haematobium. We tested for schistosome antigens in the pre- and post-HIV-1-seroconversion blood spots of people who acquired HIV-1. We also tested blood spots of matched controls who did not acquire HIV-1 and calculated the odds that a person with schistosomiasis would become HIV-1-infected compared to these matched controls. Analysis was stratified by gender. We compared 73 HIV-1 seroconverters with 265 controls. Women with schistosome infections had a higher odds of HIV-1 acquisition than those without (adjusted OR = 2.8 [1.2–6.6], p = 0.019). Schistosome-infected men did not have an increased odds of HIV-1 acquisition (adjusted OR = 0.7 [0.3–1.8], p = 0.42). We additionally compared HIV-1 RNA levels in the post-seroconversion blood spots in HIV-1 seroconverters with schistosomiasis versus those without who became HIV-infected in 2010, before antiretroviral therapy was widely available in the region. The median whole blood HIV-1 RNA level in the 15 HIV-1 seroconverters with schistosome infection was significantly higher than in the 22 without schistosomiasis: 4.4 [3.9–4.6] log10 copies/mL versus 3.7 [3.2–4.3], p = 0.017. Conclusions/Significance: We confirm, in an area with endemic S. mansoni, that pre-existing schistosome infection increases odds of HIV-1 acquisition in women and raises HIV-1 viral load at the time of HIV-1 seroconversion. This is the first study to demonstrate the effect of schistosome infection on HIV-1 susceptibility and viral control, and to differentiate effects by gender. Validation studies will be needed at additional sites. [ABSTRACT FROM AUTHOR]

Introduction: Neurological involvement is one of the most important clinical manifestations of syphilis and neurological disease occurs in both early and late syphilis. The impact of HIV co-infection on clinical neurosyphilis remains unclear. The highest prevalence of both syphilis and HIV is in Africa. Therefore it might be expected that neurosyphilis would be an important and not uncommon manifestation of syphilis in Africa and frequently occur in association with HIV co-infection; yet few data are available on neurosyphilis in Africa. The aim of this study is to review data on neurosyphilis in Africa since the onset of the HIV epidemic. Methods: We searched the literature for references on neurosyphilis in Africa for studies published between the 1st of January 1990 and 15th February 2017. We included case reports, case series, and retrospective and prospective cohort and case-control studies. We did not limit inclusion based on the diagnostic criteria used for neurosyphilis. For retrospective and prospective cohorts, we calculated the proportion of study participants who were diagnosed with neurosyphilis according to the individual study criteria. Depending on the study, we assessed the proportion of patients with syphilis found to have neurosyphilis, and the proportion of patients with neurological syndromes who had neurosyphilis. Due to heterogeneity of data no formal pooling of the data or meta-analysis was undertaken. Results: Amongst patients presenting with a neurological syndrome, three studies of patients with meningitis were identified; neurosyphilis was consistently reported to cause approximately 3% of all cases. Three studies on stroke reported mixed findings but were limited due to the small number of patients undergoing CSF examination, whilst neurosyphilis continued to be reported as a common cause of dementia in studies from North Africa. Ten studies reported on cases of neurosyphilis amongst patients known to have syphilis. Studies from both North and Southern Africa continue to report cases of late stage syphilis, including tabes dorsalis and neurosyphilis, in association with ocular disease. Discussion: This is the first systematic review of the literature on neurosyphilis in Africa since the beginning of the HIV epidemic. Neurosyphilis continues to be reported as a manifestation of both early and late syphilis, but the methodological quality of the majority of the included studies was poor. Future well-designed prospective studies are needed to better delineate the incidence and clinical spectrum of neurosyphilis in Africa and to better define interactions with HIV in this setting. [ABSTRACT FROM AUTHOR]

The global prevalence of malaria has decreased over the past fifteen years, but similar gains have not been realized against Plasmodium vivax because this species is less responsive to conventional malaria control interventions aimed principally at P. falciparum. Approximately half of all malaria cases outside of Africa are caused by P. vivax. This species places dormant forms in human liver that cause repeated clinical attacks without involving another mosquito bite. The diagnosis of acute patent P. vivax malaria relies primarily on light microscopy. Specific rapid diagnostic tests exist but typically perform relatively poorly compared to those for P. falciparum. Better diagnostic tests are needed for P. vivax. To guide their development, FIND, in collaboration with P. vivax experts, identified the specific diagnostic needs associated with this species and defined a series of three distinct target product profiles, each aimed at a particular diagnostic application: (i) point-of-care of acutely ill patients for clinical care purposes; (ii) point-of-care asymptomatic and otherwise sub-patent residents for public health purposes, e.g., mass screen and treat campaigns; and (iii) ultra-sensitive not point-of-care diagnosis for epidemiological research/surveillance purposes. This report presents and discusses the rationale for these P. vivax-specific diagnostic target product profiles. These contribute to the rational development of fit-for-purpose diagnostic tests suitable for use the clinical management, control and elimination of P. vivax malaria. [ABSTRACT FROM AUTHOR]

This study systematically reviews the literature on the occurrence, incidence and case fatality rate (CFR) of invasive nontyphoidal Salmonella (iNTS) disease in Africa from 1966 to 2014. Data on the burden of iNTS disease in Africa are sparse and generally have not been aggregated, making it difficult to describe the epidemiology that is needed to inform the development and implementation of effective prevention and control policies. This study involved a comprehensive search of PubMed and Embase databases. It documents the geographical spread of iNTS disease over time in Africa, and describes its reported incidence, risk factors and CFR. We found that Nontyphoidal Salmonella (NTS) have been reported as a cause of bacteraemia in 33 out of 54 African countries, spanning the five geographical regions of Africa, and especially in sub-Saharan Africa since 1966. Our review indicates that NTS have been responsible for up to 39% of community acquired blood stream infections in sub-Saharan Africa with an average CFR of 19%. Salmonella Typhimurium and Enteritidis are the major serovars implicated and together have been responsible for 91%% of the cases of iNTS disease, (where serotype was determined), reported in Africa. The study confirms that iNTS disease is more prevalent amongst Human Immunodeficiency Virus (HIV)-infected individuals, infants, and young children with malaria, anaemia and malnutrition. In conclusion, iNTS disease is a substantial cause of community-acquired bacteraemia in Africa. Given the high morbidity and mortality of iNTS disease in Africa, it is important to develop effective prevention and control strategies including vaccination. [ABSTRACT FROM AUTHOR]

Background: There are limited data on the performance of the use of fixed-dose combination (FDC) TB drugs when used under programmatic settings in high TB-endemic countries. We evaluated the efficacy and safety of FDC versus loose formulation (LF) TB treatment regimens for treatment of pulmonary TB (PTB) in the context of actual medical practice in prevailing conditions within programmatic settings in five sites in two high TB-burden African countries. Methods: A two-arm, single-blind, randomized clinical trial comparing FDCs with separate LFs involving 1000 adults newly diagnosed with culture positive PTB was conducted at five sites in two African countries between 2007 and 2011. Participants were randomized to receive daily treatment with anti-TB drugs given as either FDC or separate LFs for 24 weeks (intensive phase– 8 weeks of isoniazid, rifampicin, ethambutol and pyrazinamide; continuation phase– 16 weeks of rifampicin and isoniazid). Primary outcome measures were microbiological cure and safety at the end of six months’ treatment; pre-specified non-inferiority margin for difference in cure rate was 4%. The primary efficacy analysis was based on the modified intent to treat (mITT) cohort comprising all randomized patients with a positive baseline culture result for TB and who received at least one dose of study treatment. Patients missing end of treatment culture results were considered failures. Further analyses were done in which mITT patients without an end of treatment (EOT) culture were excluded in a complete case analysis (mITTcc) and a per protocol cohort analysis defined as mITTcc patients who received at least 95% of their intended doses and had an EOT culture result. Results: In the mITT analysis, the cure rate in the FDC group was 86.7% (398/459) and in the LF group 85.2% (396/465) (difference 1.5-% (90% confidence interval (CI) (-2.2%– 5.3%)). Per Protocol analysis showed similar results: FDC 98.9% (359/363) versus LF 96.9% (345/356), (difference 2.0% (90% CI: 0.1%– 3.8%)). The two arms showed no significant differences in terms of safety, early culture conversion and patient adherence to treatment. Interpretation: The comparison of the two drug regimens satisfied the pre-specified non-inferiority criterion. Our results support the WHO recommendations for the use of FDC in the context of actual medical practice within health services in high TB-endemic countries. Trial Registration: ISRCTN Registry [ABSTRACT FROM AUTHOR]

Background: Diarrheal disease is the second leading cause of disease in children less than 5 y of age. Poor water, sanitation, and hygiene conditions are the primary routes of exposure and infection. Sanitation and hygiene interventions are estimated to generate a 36% and 48% reduction in diarrheal risk in young children, respectively. Little is known about whether the number of households sharing a sanitation facility affects a child's risk of diarrhea. The objective of this study was to describe sanitation and hygiene access across the Global Enteric Multicenter Study (GEMS) sites in Africa and South Asia and to assess sanitation and hygiene exposures, including shared sanitation access, as risk factors for moderate-to-severe diarrhea (MSD) in children less than 5 y of age.Methods/findings: The GEMS matched case-control study was conducted between December 1, 2007, and March 3, 2011, at seven sites in Basse, The Gambia; Nyanza Province, Kenya; Bamako, Mali; Manhiça, Mozambique; Mirzapur, Bangladesh; Kolkata, India; and Karachi, Pakistan. Data was collected for 8,592 case children aged <5 y old experiencing MSD and for 12,390 asymptomatic age, gender, and neighborhood-matched controls. An MSD case was defined as a child with a diarrheal illness <7 d duration comprising ≥3 loose stools in 24 h and ≥1 of the following: sunken eyes, skin tenting, dysentery, intravenous (IV) rehydration, or hospitalization. Site-specific conditional logistic regression models were used to explore the association between sanitation and hygiene exposures and MSD. Most households at six sites (>93%) had access to a sanitation facility, while 70% of households in rural Kenya had access to a facility. Practicing open defecation was a risk factor for MSD in children <5 y old in Kenya. Sharing sanitation facilities with 1-2 or ≥3 other households was a statistically significant risk factor for MSD in Kenya, Mali, Mozambique, and Pakistan. Among those with a designated handwashing area near the home, soap or ash were more frequently observed at control households and were significantly protective against MSD in Mozambique and India.Conclusions: This study suggests that sharing a sanitation facility with just one to two other households can increase the risk of MSD in young children, compared to using a private facility. Interventions aimed at increasing access to private household sanitation facilities may reduce the burden of MSD in children. These findings support the current World Health Organization/ United Nations Children's Emergency Fund (UNICEF) system that categorizes shared sanitation as unimproved. [ABSTRACT FROM AUTHOR]

Objectives: To describe the variation in household crowding and social mixing patterns in the African meningitis belt and to assess any association with self-reported recent respiratory symptoms. Methods: In 2010, the African Meningococcal Carriage Consortium (MenAfriCar) conducted cross-sectional surveys in urban and rural areas of seven countries. The number of household members, rooms per household, attendance at social gatherings and meeting places were recorded. Associations with self-reported recent respiratory symptoms were analysed by univariate and multivariate regression models. Results: The geometric mean people per room ranged from 1.9 to 2.8 between Ghana and Ethiopia respectively. Attendance at different types of social gatherings was variable by country, ranging from 0.5 to 1.5 per week. Those who attended 3 or more different types of social gatherings a week (frequent mixers) were more likely to be older, male (OR 1.27, p<0.001) and live in urban areas (OR 1.45, p<0.001). Frequent mixing and young age, but not increased household crowding, were associated with higher odds of self-reported respiratory symptoms (aOR 2.2, p<0.001 and OR 2.8, p<0.001 respectively). A limitation is that we did not measure school and workplace attendance. Conclusion: There are substantial variations in household crowding and social mixing patterns across the African meningitis belt. This study finds a clear association between age, increased social mixing and respiratory symptoms. It lays the foundation for designing and implementing more detailed studies of social contact patterns in this region. [ABSTRACT FROM AUTHOR]