Vitamin D deficiency (VDD) is common in women with and without polycystic ovary syndrome (PCOS) and may be associated with metabolic and endocrine disorders in PCOS. The aim of this meta-analysis is to assess the associations of serum vitamin D levels with metabolic and endocrine dysregulations in women with PCOS, and to determine effects of vitamin D supplementation on metabolic and hormonal functions in PCOS patients. The literature search was undertaken through five databases until 16 January 2015 for both observational and experimental studies concerning relationships between vitamin D and PCOS. A total of 366 citations were identified, of which 30 were selected (n = 3182). We found that lower serum vitamin D levels were related to metabolic and hormonal disorders in women with PCOS. Specifically, PCOS patients with VDD were more likely to have dysglycemia (e.g., increased levels of fasting glucose and homeostatic model assessment-insulin resistance index (HOMA-IR)) compared to those without VDD. This meta-analysis found no evidence that vitamin D supplementation reduced or mitigated metabolic and hormonal dysregulations in PCOS. VDD may be a comorbid manifestation of PCOS or a minor pathway in PCOS associated metabolic and hormonal dysregulation. Future prospective observational studies and randomized controlled trials with repeated VDD assessment and better characterization of PCOS disease severity at enrollment are needed to clarify whether VDD is a co-determinant of hormonal and metabolic dysregulations in PCOS, represents a consequence of hormonal and metabolic dysregulations in PCOS or both.

Evidence of an adverse influence of soil transmitted helminth (STH) infections on cognitive function and educational loss is equivocal. Prior meta-analyses have focused on randomized controlled trials only and have not sufficiently explored the potential for disparate influence of STH infection by cognitive domain. We re-examine the hypothesis that STH infection is associated with cognitive deficit and educational loss using data from all primary epidemiologic studies published between 1992 and 2016. Medline, Biosis and Web of Science were searched for original studies published in the English language. Cognitive function was defined in four domains (learning, memory, reaction time and innate intelligence) and educational loss in two domains (attendance and scholastic achievement). Pooled effect across studies were calculated as standardized mean differences (SMD) to compare cognitive and educational measures for STH infected/non-dewormed children versus STH uninfected /dewormed children using Review Manager 5.3. Sub-group analyses were implemented by study design, risk of bias (ROB) and co-prevalence of Schistosoma species infection. Influential studies were excluded in sensitivity analysis to examine stability of pooled estimates. We included 36 studies of 12,920 children. STH infected/non-dewormed children had small to moderate deficits in three domains—learning, memory and intelligence (SMD: -0.44 to -0.27, P<0.01–0.03) compared to STH-uninfected/dewormed children. There were no differences by infection/treatment status for reaction time, school attendance and scholastic achievement (SMD: -0.26 to -0.16, P = 0.06–0.19). Heterogeneity of the pooled effects in all six domains was high (P<0.01; I² = 66–99%). Application of outlier treatment reduced heterogeneity in learning domain (P = 0.12; I² = 33%) and strengthened STH-related associations in all domains but intelligence (SMD: -0.20, P = 0.09). Results varied by study design and ROB. Among experimental intervention studies, there was no association between STH treatment and educational loss/performance in tests of memory, reaction time and innate intelligence (SMD: -0.27 to 0.17, P = 0.18–0.69). Infection-related deficits in learning persisted within design/ROB levels (SMD: -0.37 to -52, P<0.01) except for pre-vs post intervention design (n = 3 studies, SMD = -0.43, P = 0.47). Deficits in memory, reaction time and innate intelligence persisted within observational studies (SMD: -0.23 to -0.38, all P<0.01) and high ROB strata (SMD:-0.37 to -0.83, P = 0.07 to <0.01). Further, in Schistosoma infection co-prevalent settings, associations were generally stronger and statistically robust for STH-related deficits in learning, memory and reaction time tests(SMD:-0.36 to -0.55, P = 0.003–0.02). STH-related deficits in school attendance and scholastic achievement was noted in low (SMD:-0.57, P = 0.05) and high ROB strata respectively. We provide evidence of superior performance in five of six educational and cognitive domains assessed for STH uninfected/dewormed versus STH infected/not-dewormed school-aged children from helminth endemic regions. Cautious interpretation is warranted due to high ROB in some of the primary literature and high between study variability in most domains. Notwithstanding, this synthesis provides empirical support for a cognitive and educational benefit of deworming. The benefit of deworming will be enhanced by strategically employing, integrated interventions. Thus, multi-pronged inter-sectoral strategies that holistically address the environmental and structural roots of child cognitive impairment and educational loss in the developing world may be needed to fully realize the benefit of mass deworming programs. Previous systematic reviews of the effect of STH infection on cognitive and educational performance were either inconclusive or found little to no evidence of associated benefit. Lack of consensus in prior reviews and their narrow emphasis on randomized controlled trials prompted this comprehensive assessment of whether educational and cognitive benefits are associated with the common practice of preventive chemotherapy among children in STH-endemic regions. This literature synthesis included all relevant epidemiologic studies regardless of design and investigated associations between STH infections and two outcomes: i) educational loss (attendance and scholastic achievement) and ii) psychometrically performance in four neurocognitive domains—memory, learning, reaction time and intelligence. Pooled results across 36 observational and intervention studies suggest that STH infection/non-treatment is associated with deficits in five of six domains evaluated and provide evidence in support of a cognitive and educational benefit of deworming for STH infections. This overall finding was sensitive to study design and risk of bias across studies.

By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits. This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains—learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5–19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits in scholastic achievement was sensitive to ROB. Schistosoma infection-related deficits in learning and memory tests were invariant by ROB and study design. Schistosoma infection/non-treatment was significantly associated with educational, learning, and memory deficits in SAC. Early treatment of children in Schistosoma-endemic regions could potentially mitigate these deficits. ClinicalTrials.gov CRD42016040052 Empirical evidence for cognitive or educational benefits of anti-Schistosoma treatment is currently uncertain, despite the recommended practice of wide-scale deworming with praziquantel. We addressed this knowledge gap by synthesizing information from 30 relevant epidemiologic studies reporting on 38,992 children between 5–19 years old from 14 countries. In those studies, Schistosoma infection or non-dewormed status was associated with educational loss and cognitive deficits. Specifically, there were small to moderate deficits in both school attendance and scholastic achievement. Similarly, Schistosoma infection or non-dewormed status was associated with deficits in learning and memory domains of psychometrically tested cognitive function. However, there was no evidence of Schistosoma infection- or non-deworming-associated deficits on tests of innate intelligence or reaction-time. Overall, compared to Schistosoma-uninfected or to dewormed children, the presence of Schistosoma infection or non-dewormed status was associated with educational, learning, and memory deficits in school-aged children. The combined evidence suggests that early treatment of children in Schistosoma-endemic regions could mitigate these deficits.

Cytopenias are the most common HIV-associated hematological abnormality. Cytopenias have been associated with several factors including sex, race/ethnicity, geographical location and comorbidities such as tuberculosis, hepatitis B infection, fever and oral candidiasis. Cytopenias become more prevalent as HIV progresses and are often fatal. Data from resource-limited settings about the prevalence and correlates of cytopenia are limited. Therefore we conducted this cross-sectional study to assess the prevalence and correlates of cytopenia among adult AIDS patients at initiation of HAART in Uganda. 400 HIV-infected subjects who were HAART-naïve or on HAART for ≤ 6 months were enrolled into the Multivitamins, HAART and HIV/AIDS Trial. Anemia was defined according to WHO guidelines as any hemoglobin concentration < 12 g/dl for non-pregnant females and < 13 g/dl for males. Leucopenia and thrombocytopenia were defined using study site laboratory reference ranges for lack of generally accepted definitions for these 2 cell lines as leucopenia if white blood cell count < 2.75 × 109 cells/litre and thrombocytopenia if platelets < 125 × 109 cells/litre for females and < 156 × 109 cells/litre for males. Univariate and bivariate analyses were done to describe the patient population and log-binomial regression was used to quantify the correlates of cytopenia. Sixty five percent of the 400 subjects had at least one form of cytopenia. Anemia occurred in 47.8%, leucopenia in 24.3%, thrombocytopenia in 8.3%, bicytopenia in 21.9% and only 2 had a pancytopenia. Cytopenia was more prevalent in females (prevalence ratio [PR]:1.33, 95% confidence interval [CI]:1.12-1.59); CD4 count category 50 to <200 (PR: 0.75, 95% CI: 0.64 -0.88) and CD4 count category 200 to <350 (PR: 0.74, 95% CI: 0.59 - 0.92) compared to CD4 count category <50; normal BMI (PR: 0.82, 95% CI:0.68-1.00) and overweight BMI (PR: 0.64, 95% CI:0.50- 0.82) compared to underweight BMI and those with a history or presence of oral candidiasis. Cytopenias are a frequent complication in HIV-infected adults at initiation of HAART in Uganda. The presence of any cytopenia was associated with female sex, decreasing CD4 count and decreasing body mass index. Prospective studies in resource-limited settings on the trend in HIV-related cytopenias are needed.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in 2008 to answer strategic questions about schistosomiasis control. For programme managers, a high-priority question is: what are the most cost-effective strategies for delivering preventive chemotherapy (PCT) with praziquantel (PZQ)? This paper describes the process SCORE used to transform this question into a harmonized research protocol, the study design for answering this question, the village eligibility assessments and data resulting from the first year of the study. Beginning in 2009, SCORE held a series of meetings to specify empirical questions and design studies related to different schedules of PCT for schistosomiasis control in communities with high (gaining control studies) and moderate (sustaining control studies) prevalence of Schistosoma infection among school-aged children. Seven studies are currently being implemented in five African countries. During the first year, villages were screened for eligibility, and data were collected on prevalence and intensity of infection prior to randomisation and the implementation of different schemes of PZQ intervention strategies. These studies of different treatment schedules with PZQ will provide the most comprehensive data thus far on the optimal frequency and continuity of PCT for schistosomiasis infection and morbidity control. We expect that the study outcomes will provide data for decision-making for country programme managers and a rich resource of information to the schistosomiasis research community. The trials are registered at International Standard Randomised Controlled Trial registry (identifiers: ISRCTN99401114 , ISRCTN14849830 , ISRCTN16755535 , ISRCTN14117624 , ISRCTN95819193 and ISRCTN32045736 ).

Nearly one third of the world is infected with latent tuberculosis infection (LTBI) and a vast pool of individuals with LTBI persists in developing countries, posing a major barrier to global TB control. The aim of the present study was to determine the prevalence of LTBI and the associated risk factors among adults in Kampala, Uganda. We performed a secondary analysis from a door-to-door cross-sectional survey of chronic cough conducted from January 2008 to June 2009. Urban residents of Rubaga community in Kampala aged 15 years and older who had received Tuberculin skin testing (TST) were included in the analysis. The primary outcome was LTBI defined as a TST with induration 10 mm or greater. Multivariable logistic regression analyses were used to assess the risk factors associated with LTBI. A total of 290 participants were tested with TST, 283 had their tests read and 7 didn’t have the TST read because of failure to trace them within 48–72 hours. Of the participants with TST results, 68% were female, 75% were 15–34 years, 83% had attained at least 13 years of education, 12% were smokers, 50% were currently married, 57% left home for school or employment, 21% were HIV positive and 65% reported chronic cough of 2 weeks or longer. The overall prevalence of LTBI was 49% [95% CI 44–55] with some age-and sex-specific differences. On multivariable analysis, leaving home for school or employment, aOR = 1.72; [95%CI: 1.05, 2.81] and age 25–34, aOR = 1.94; [95%CI: 1.12, 3.38]; 35 years and older, aOR = 3.12; [95%CI: 1.65, 5.88] were significant risk factors of LTBI. The prevalence of LTBI was high in this urban African setting. Leaving home for school or employment and older age were factors significantly associated with LTBI in this setting. This suggests a potential role of expansion of one’s social network outside the home and cumulative risk of exposure to TB with age in the acquisition of LTBI. Our results provide support for LTBI screening and preventive treatment programs of these sub-groups in order to enhance TB control.