Universal test and treat in relation to HIV disease progression: results from a stepped-wedge trial in Eswatini.

OBJECTIVES: Universal test and treat (UTT) is recommended for people living with HIV (PLHIV) to reduce morbidity/mortality and minimize transmission. However, concerns exist that this strategy may lead to more crowded hospitals, longer wait times and poorer service, adversely impacting health outcomes for clients with severe disease. We assessed how UTT was related to markers of disease progression in PLHIV overall and specifically among clients with low CD4 count/high World Health Organization (WHO) stage. METHODS: The analysis was conducted using data from a stepped-wedge trial of UTT in 14 government-managed health facilities in Eswatini from 2014 to 2017. Disease progression was defined as CD4 count falling below 200 cells/µL or baseline value, > 10% weight loss, body mass index (BMI) dropping below 18.5, incident tuberculosis (TB) or HIV-related death; these outcomes also were assessed individually. We assessed multivariate Cox proportional hazard models overall and specifically among clients with CD4 count < 350 cells/µL or WHO stage 3-4 at enrolment. RESULTS: Eight hundred and seven of 3176 clients demonstrated at least one marker of disease progression over 2339 person-years of follow-up. Overall, 62.4% of clients were female; 57.2% were < 35 years old. Compared to clients not exposed to UTT, those exposed to UTT had a lower rate of disease progression overall [adjusted hazard ratio (aHR) 0.60; 95% confidence interval (CI) 0.46-0.78] and a lower rate of CD4 decline (aHR 0.40; 95% CI 0.27-0.58). When the analysis was limited to clients with CD4 count < 350 cells/µL or WHO stage 3-4, UTT was not associated with disease progression (aHR 0.92; 95% CI 0.66-1.29). CONCLUSIONS: UTT reduced HIV disease progression overall and was not detrimental for clients with more severe disease.

Mortality under early access to antiretroviral therapy vs. Eswatini's national standard of care: the MaxART clustered randomized stepped-wedge trial.

OBJECTIVES: Current WHO guidelines recommend the treatment of all HIV-infected individuals with antiretroviral therapy (ART) to improve survival and quality of life, and decrease infection of others. MaxART is the first implementation trial of this strategy embedded within a government-managed health system, and assesses mortality as a secondary outcome. Because primary findings strongly supported scale-up of the 'treat all' strategy (hereafter Treat All), this analysis examines mortality as an additional indicator of its impact. METHODS: MaxART was conducted in 14 Eswatinian health clinics through a clinic-based stepped-wedge design, by transitioning clinics from then-national standard of care (SoC) to the Treat All intervention. All-cause, disease-related, and HIV-related mortality were analysed using the Cox proportional hazards model, censoring SoC participants at clinic transition. Median follow-up time among study participants was 292 days. There were 36/2034 deaths in SoC (1.77%) and 49/1371 deaths in Treat All (3.57%). RESULTS: Between September 2014 and August 2017, 3405 participants were enrolled. In SoC and Treat All interventions, respectively, the multivariable-adjusted 12-month all-cause mortality rates were 1.42% [95% confidence interval (CI): 0.66-2.17] and 1.60% (95% CI: 0.78-2.40), disease-related mortality rates were 1.02% (95% CI: 0.40-1.64) and 1.10% (95% CI: 0.46-1.73), and HIV-related mortality rates were 1.03% (95% CI: 0.40-1.65) and 0.99% (95% CI: 0.40-1.58). Treat All had no impact on all-cause [hazard ratio (HR) = 1.12, 95% CI: 0.58-2.18, P = 0.73], disease-related (HR = 1.04, 95% CI: 0.52-2.11, P = 0.90), or HIV-related mortality (HR = 0.93, 95% CI: 0.46-1.87, P = 0.83). CONCLUSION: There was no immediate benefit of the Treat All strategy on mortality, nor evidence of harm. Longer follow-up of participants is needed to establish long-term consequences.

On the analysis of two-phase designs in cluster-correlated data settings.

In public health research, information that is readily available may be insufficient to address the primary question(s) of interest. One cost-efficient way forward, especially in resource-limited settings, is to conduct a two-phase study in which the population is initially stratified, at phase I, by the outcome and/or some categorical risk factor(s). At phase II detailed covariate data is ascertained on a subsample within each phase I strata. While analysis methods for two-phase designs are well established, they have focused exclusively on settings in which participants are assumed to be independent. As such, when participants are naturally clustered (eg, patients within clinics) these methods may yield invalid inference. To address this, we develop a novel analysis approach based on inverse-probability weighting that permits researchers to specify some working covariance structure and appropriately accounts for the sampling design and ensures valid inference via a robust sandwich estimator for which a closed-form expression is provided. To enhance statistical efficiency, we propose a calibrated inverse-probability weighting estimator that makes use of information available at phase I but not used in the design. In addition to describing the technique, practical guidance is provided for the cluster-correlated data settings that we consider. A comprehensive simulation study is conducted to evaluate small-sample operating characteristics, including the impact of using naïve methods that ignore correlation due to clustering, as well as to investigate design considerations. Finally, the methods are illustrated using data from a one-time survey of the national antiretroviral treatment program in Malawi.

Substituting brown rice for white rice on diabetes risk factors in India: a randomised controlled trial.

India has the second largest number of people with type 2 diabetes (T2D) globally. Epidemiological evidence indicates that consumption of white rice is positively associated with T2D risk, while intake of brown rice is inversely associated. Thus, we explored the effect of substituting brown rice for white rice on T2D risk factors among adults in urban South India. A total of 166 overweight (BMI ≥ 23 kg/m2) adults aged 25-65 years were enrolled in a randomised cross-over trial in Chennai, India. Interventions were a parboiled brown rice or white rice regimen providing two ad libitum meals/d, 6 d/week for 3 months with a 2-week washout period. Primary outcomes were blood glucose, insulin, glycosylated Hb (HbA1c), insulin resistance (homeostasis model assessment of insulin resistance) and lipids. High-sensitivity C-reactive protein (hs-CRP) was a secondary outcome. We did not observe significant between-group differences for primary outcomes among all participants. However, a significant reduction in HbA1c was observed in the brown rice group among participants with the metabolic syndrome (-0·18 (se 0·08) %) relative to those without the metabolic syndrome (0·05 (se 0·05) %) (P-for-heterogeneity = 0·02). Improvements in HbA1c, total and LDL-cholesterol were observed in the brown rice group among participants with a BMI ≥ 25 kg/m2 compared with those with a BMI < 25 kg/m2 (P-for-heterogeneity < 0·05). We observed a smaller increase in hs-CRP in the brown (0·03 (sd 2·12) mg/l) compared with white rice group (0·63 (sd 2·35) mg/l) (P = 0·04). In conclusion, substituting brown rice for white rice showed a potential benefit on HbA1c among participants with the metabolic syndrome and an elevated BMI. A small benefit on inflammation was also observed.

There is no impact of exposure measurement error on latency estimation in linear models.

Identification of the latency period for the effect of a time-varying exposure is key when assessing many environmental, nutritional, and behavioral risk factors. A pre-specified exposure metric involving an unknown latency parameter is often used in the statistical model for the exposure-disease relationship. Likelihood-based methods have been developed to estimate this latency parameter for generalized linear models but do not exist for scenarios where the exposure is measured with error, as is usually the case. Here, we explore the performance of naive estimators for both the latency parameter and the regression coefficients, which ignore exposure measurement error, assuming a linear measurement error model. We prove that, in many scenarios under this general measurement error setting, the least squares estimator for the latency parameter remains consistent, while the regression coefficient estimates are inconsistent as has previously been found in standard measurement error models where the primary disease model does not involve a latency parameter. Conditions under which this result holds are generalized to a wide class of covariance structures and mean functions. The findings are illustrated in a study of body mass index in relation to physical activity in the Health Professionals Follow-Up Study.

The GBA p.Trp378Gly mutation is a probable French-Canadian founder mutation causing Gaucher disease and synucleinopathies.

Biallelic GBA mutations cause Gaucher disease (GD), and heterozygous carriers are at risk for synucleinopathies. No founder GBA mutations in French-Canadians are known. GBA was fully sequenced using targeted next generation and Sanger sequencing in French-Canadian Parkinson disease (PD) patients (n = 436), rapid eye movement (REM)-sleep behavior disorder (RBD) patients (n = 189) and controls (n = 891). Haplotype, identity-by-descent (IBD) and principal component analyses (PCA) were performed using single nucleotide polymorphism-chip data. Data on GD patients from Toronto and Montreal were collected from patients' files. A GBA p.Trp378Gly mutation was identified in two RBD and four PD patients (1% of all patients combined), and not in controls. The two RBD patients had converted to DLB within 3 years of their diagnosis. Haplotype, IBD and PCA analysis demonstrated that this mutation is from a single founder. Out of 167 GD patients screened, 15 (9.0%) carried the p.Trp378Gly mutation, all in trans with p.Asn370Ser. Three (20%) of the GD patients with the p.Trp378Gly mutation had developed Parkinsonism, and 11 patients had family history of PD. The p.Trp378Gly mutation is the first French-Canadian founder GBA mutation to be described, which leads to synucleinopathies and to GD type 1 when in compound heterozygosity with p.Asn370Ser.

Rare susceptibility variants for bipolar disorder suggest a role for G protein-coupled receptors.

Bipolar disorder (BD) is a prevalent mood disorder that tends to cluster in families. Despite high heritability estimates, few genetic susceptibility factors have been identified over decades of genetic research. One possible interpretation for the shortcomings of previous studies to detect causative genes is that BD is caused by highly penetrant rare variants in many genes. We explored this hypothesis by sequencing the exomes of affected individuals from 40 well-characterized multiplex families. We identified rare variants segregating with affected status in many interesting genes, and found an enrichment of deleterious variants in G protein-coupled receptor (GPCR) family genes, which are important drug targets. Furthermore, we showed targeted downstream GPCR dysregulation for some of the variants that may contribute to disease pathology. Particularly interesting was the finding of a rare and functionally relevant nonsense mutation in the corticotropin-releasing hormone receptor 2 (CRHR2) gene that tracked with affected status in one family. By focusing on rare variants in informative families, we identified key biochemical pathways likely implicated in this complex disorder.

A prospective cohort study of endometriosis and subsequent risk of infertility.

STUDY QUESTION: Is there a temporal relationship between endometriosis and infertility? SUMMARY ANSWER: Endometriosis is associated with a higher risk of subsequent infertility, but only among women age <35 years. WHAT IS KNOWN ALREADY: Endometriosis is the most commonly observed gynecologic pathology among infertile women undergoing laparoscopic examination. Whether endometriosis is a cause of infertility or an incidental discovery during the infertility examination is unknown. STUDY DESIGN, SIZE, DURATION: This study included data collected from 58 427 married premenopausal female nurses <40 years of age from 1989 to 2005, who are participants of the Nurses' Health Study II prospective cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our exposure was laparoscopically confirmed endometriosis. Multivariate Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for infertility risk (defined as attempting to conceive for >12 months) among women with and without endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 4612 incident cases of infertility due to any cause over 362 219 person-years of follow-up. Compared with women without a history of endometriosis, women with endometriosis had an age-adjusted 2-fold increased risk of incident infertility (HR = 2.12, 95% CI = 1.76-2.56) that attenuated slightly after accounting for parity. The relationship with endometriosis was only observed among women <35 years of age (multivariate HR <35 years = 1.77, 95% CI = 1.46-2.14; multivariate HR 35-39 years = 1.20, 95% CI = 0.94-1.53; P-interaction = 0.008). Risk of primary versus secondary infertility was similar subsequent to endometriosis diagnosis. Among women with primary infertility, 50% became parous after the endometriosis diagnosis, and among all women with endometriosis, 83% were parous by age 40 years. LIMITATIONS, REASONS FOR CAUTION: We did not have information on participants' intentions to conceive, but by restricting the analytic population to married women we increased the likelihood that pregnancies were planned (and therefore infertility would be recognized). Women in our cohort with undiagnosed asymptomatic endometriosis will be misclassified as unexposed. However, the small proportion of these women are diluted among the >50 000 women accurately classified as endometriosis-free, minimizing the impact of exposure misclassification on the effect estimates. WIDER IMPLICATIONS OF THE FINDINGS: This study supports a temporal association between endometriosis and infertility risk. Our prospective analysis indicates a possible detection bias in previous studies, with our findings suggesting that the infertility risk posed by endometriosis is about half the estimates observed in cross-sectional analyses. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Institutes of Health (grant numbers: UM1 CA176726, HD52473, HD57210, T32DK007703, T32HD060454, K01DK103720). We have no competing interests to declare.

Sugar-sweetened beverage consumption and age at menarche in a prospective study of US girls.

STUDY QUESTION: Is sugar-sweetened beverage (SSB) consumption associated with age at menarche? SUMMARY ANSWER: More frequent SSB consumption was associated with earlier menarche in a population of US girls. WHAT IS KNOWN ALREADY: SSB consumption is associated with metabolic changes that could potentially impact menarcheal timing, but direct associations with age at menarche have yet to be investigated. STUDY DESIGN, SIZE, DURATION: The Growing up Today Study, a prospective cohort study of 16 875 children of Nurses' Health Study II participants residing in all 50 US states. This analysis followed 5583 girls, aged 9-14 years and premenarcheal at baseline, between 1996 and 2001. During 10 555 person-years of follow-up, 94% (n = 5227) of girls reported their age at menarche, and 3% (n = 159) remained premenarcheal in 2001; 4% (n = 197) of eligible girls were censored, primarily for missing age at menarche. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cumulative updated SSB consumption (composed of non-carbonated fruit drinks, sugar-sweetened soda and iced tea) was calculated using annual Youth/Adolescent Food Frequency Questionnaires from 1996 to 1998. Age at menarche was self-reported annually. The association between SSB consumption and age at menarche was assessed using Cox proportional hazards regression. MAIN RESULTS AND THE ROLE OF CHANCE: More frequent SSB consumption predicted earlier menarche. At any given age between 9 and 18.5 years, premenarcheal girls who reported consuming >1.5 servings of SSBs per day were, on average, 24% more likely [95% confidence interval (CI): 13, 36%; P-trend: <0.001] to attain menarche in the next month relative to girls consuming ≤2 servings of SSBs weekly, adjusting for potential confounders including height, but not BMI (considered an intermediate). Correspondingly, girls consuming >1.5 SSBs daily had an estimated 2.7-month earlier menarche (95% CI: -4.1, -1.3 months) relative to those consuming ≤2 SSBs weekly. The frequency of non-carbonated fruit drink (P-trend: 0.03) and sugar-sweetened soda (P-trend: 0.001), but not iced tea (P-trend: 0.49), consumption also predicted earlier menarche. The effect of SSB consumption on age at menarche was observed in every tertile of baseline BMI. Diet soda and fruit juice consumption were not associated with age at menarche. LIMITATIONS, REASONS FOR CAUTION: Although we adjusted for a variety of suspected confounders, residual confounding is possible. We did not measure SSB consumption during early childhood, which may be an important window of exposure. WIDER IMPLICATIONS OF THE FINDINGS: More frequent SSB consumption may predict earlier menarche through mechanisms other than increased BMI. Our findings provide further support for public health efforts to reduce SSB consumption. STUDY FUNDING/COMPETING INTERESTS: The Growing up Today Study is supported by grant R03 CA 106238. J.L.C. was supported by the Breast Cancer Research Foundation; Training Grant T32ES007069 in Environmental Epidemiology from the National Institute of Environmental Health Sciences, National Institutes of Health; and Training Grant T32HD060454 in Reproductive, Perinatal and Pediatric Epidemiology from the National Institute of Child Health and Human Development, National Institutes of Health. A.L.F. is supported by the American Cancer Society, Research Scholar Grant in Cancer Control. K.B.M. was supported in part by the National Cancer Institute at the National Institutes of Health (Public Health Service grants R01CA158313 and R03CA170952). There are no conflicts of interest to declare.

Clinical malaria diagnosis in pregnancy in relation to early perinatal mother-to-child transmission of HIV: a prospective cohort study.

OBJECTIVES: We prospectively investigated fever symptoms and maternal diagnosis of malaria in pregnancy (MIP) in relation to child HIV infection among 2368 pregnant HIV-positive women and their infants, followed up from pregnancy until 6 weeks post-delivery in Tanzania. METHODS: Doctors clinically diagnosed and treated MIP and fever symptoms during prenatal health care. Child HIV status was determined via DNA polymerase chain reaction (PCR). Multivariable logistic regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for HIV mother-to-child transmission (MTCT) by the 6th week of life. RESULTS: Mean gestational age at enrolment was 22.2 weeks. During follow-up, 16.6% of mothers had at least one MIP diagnosis, 15.9% reported fever symptoms and 8.7% had both fever and MIP diagnosis. Eleven per cent of HIV-exposed infants were HIV-positive by 6 weeks. The RR of HIV MTCT was statistically similar for infants whose mothers were ever vs. never clinically diagnosed with MIP (RR 1.24; 95% CI 0.94-1.64), were diagnosed with one vs. no clinical MIP episodes (RR 1.07; 95% CI 0.77-1.48) and had ever vs. never reported fever symptoms (RR 1.04; 95% CI 0.78-1.38) in pregnancy. However, the HIV MTCT risk increased by 29% (95% CI 4-58%) per MIP episode. Infants of women with at least two vs. no MIP diagnoses were 2.1 times more likely to be HIV infected by 6 weeks old (95% CI 1.31-3.45). CONCLUSIONS: Clinical MIP diagnosis, but not fevers, in HIV-positive pregnant women was associated with an elevated risk of early HIV MTCT, suggesting that malaria prevention and treatment in pregnant HIV-positive women may enhance the effectiveness of HIV prevention in MTCT programmes in this setting. Future studies using a laboratory-confirmed diagnosis of malaria are needed to confirm this association.

Micronutrient supplementation and T cell-mediated immune responses in patients with tuberculosis in Tanzania.

Limited studies exist regarding whether incorporating micronutrient supplements during tuberculosis (TB) treatment may improve cell-mediated immune response. We examined the effect of micronutrient supplementation on lymphocyte proliferation response to mycobacteria or T-cell mitogens in a randomized trial conducted on 423 patients with pulmonary TB. Eligible participants were randomly assigned to receive a daily dose of micronutrients (vitamins A, B-complex, C, E, and selenium) or placebo at the time of initiation of TB treatment. We found no overall effect of micronutrient supplements on lymphocyte proliferative responses to phytohaemagglutinin or purified protein derivatives in HIV-negative and HIV-positive TB patients. Of HIV-negative TB patients, the micronutrient group tended to show higher proliferative responses to concanavalin A than the placebo group, although the clinical relevance of this finding is not readily notable. The role of nutritional intervention in this vulnerable population remains an important area of future research.

Determinants of anemia in postpartum HIV-negative women in Dar es Salaam, Tanzania.

OBJECTIVE: The determinants of anemia during both pregnancy and postpartum recovery remain incompletely understood in sub-Saharan African women. SUBJECTS/METHODS: In a prospective cohort study among pregnant women, we assessed dietary, biochemical, anthropometric, infectious and sociodemographic factors at baseline. In multivariate Cox proportional hazards models, we examined predictors of incident anemia (hemoglobin <11 g/dl) and iron deficiency anemia (anemia plus mean corpuscular volume <80fL), and recovery from anemia and iron deficiency anemia through 18 months postpartum at antenatal clinics in Dar es Salaam, Tanzania between 2001 and 2005. A total of 2364 non-anemic pregnant women and 4884 anemic women were enrolled between 12 and 27 weeks of gestation. RESULTS: In total, 292 women developed anemia during the postpartum period and 165 developed iron deficiency anemia, whereas 2982 recovered from baseline anemia and 2044 from iron deficiency anemia. Risk factors for postpartum anemia were delivery complications (RR 1.6, 95% confidence interval (CI) 1.13, 2.22) and low postpartum CD4 cell count (RR 1.73, 95% CI 0.96, 3.17). Iron/folate supplementation during pregnancy had a protective relationship with the incidence of iron deficiency anemia. Absence of delivery complications, education status and iron/folate supplementation were positively associated with time to recovery from iron deficiency. CONCLUSION: Maternal nutritional status during pregnancy, prenatal iron/folate supplementation, perinatal care, and prevention and management of infections, such as malaria, are modifiable risk factors for the occurrence of, and recovery from, anemia.

Predictors of stunting, wasting and underweight among Tanzanian children born to HIV-infected women.

BACKGROUND/OBJECTIVES: Children born to human immunodeficiency virus (HIV)-infected women are susceptible to undernutrition, but modifiable risk factors and the time course of the development of undernutrition have not been well characterized. The objective of this study was to identify maternal, socioeconomic and child characteristics that are associated with stunting, wasting and underweight among Tanzanian children born to HIV-infected mothers, followed from 6 weeks of age for 24 months. SUBJECTS/METHODS: Maternal and socioeconomic characteristics were recorded during pregnancy, data pertaining to the infant's birth were collected immediately after delivery, morbidity histories and anthropometric measurements were performed monthly. Multivariate Cox proportional hazards methods were used to assess the association between potential predictors and the time to first episode of stunting, wasting and underweight. RESULTS: A total of 2387 infants (54.0% male) were enrolled and followed for a median duration of 21.2 months. The respective prevalence of prematurity (<37 weeks) and low birth weight (<2500 g) was 15.2% and 7.0%; 11.3% of infants were HIV-positive at 6 weeks. Median time to first episode of stunting, wasting and underweight was 8.7, 7.2 and 7.0 months, respectively. Low maternal education, few household possessions, low infant birth weight, child HIV infection and male sex were all independent predictors of stunting, wasting and underweight. In addition, preterm infants were more likely to become wasted and underweight, whereas those with a low Apgar score at birth were more likely to become stunted. CONCLUSIONS: Interventions to improve maternal education and nutritional status, reduce mother-to-child transmission of HIV, and increase birth weight may lower the risk of undernutrition among children born to HIV-infected women.

Elevated alanine aminotransferase in antiretroviral-naïve HIV-infected African patients: magnitude and risk factors.

BACKGROUND: Alanine aminotransferase (ALT) is commonly used to measure liver injury in resource-limited settings. Elevations in ALT are predictive of increased mortality from liver disease and may influence the choice of first-line antiretroviral therapy (ART). METHODS: A cross-sectional analysis of the prevalence and predictors of elevated ALT (defined as >40 IU/L) was conducted. ART-naïve, HIV-infected adults with a baseline ALT measurement who were enrolled in any of the 18 HIV Care and Treatment Clinics in Dar es Salaam, Tanzania between November 2004 and December 2009 were included in the study. Median values were calculated and log-binomial regression models were used to examine predictors of elevated ALT. RESULTS: During the study period, 41891 adults had a baseline ALT measurement performed. The prevalence of ALT >40, >120 and >200 IU/L was 13, 1 and 0.3%, respectively. In multivariate analyses, male sex, CD4 T lymphocyte count <200 cells/µL and higher World Health Organization (WHO) clinical stages were associated with a significantly higher risk of ALT >40 IU/L (all P<0.01). Hypertryglyceridaemia, hyperglycaemia and hepatitis B virus (HBV) coinfection (positive for HBV surface antigen) were significantly associated with a higher risk of elevated ALT. Pregnancy, anaemia, low-density lipoprotein cholesterol >130 mg/dL and current tuberculosis treatment were associated with a significantly reduced risk for elevated ALT. CONCLUSIONS: In this HIV-infected, ART-naïve Tanzanian population, extreme elevations in ALT were infrequent but minor elevations were not uncommon. Antiretrovirals with potentially hepatotoxic side effects should be initiated with caution in male patients, and in patients with HBV coinfection, advanced immunosuppression and components of the metabolic syndrome.

Cohort studies around the world: methodologies, research questions and integration to address the emerging global epidemic of chronic diseases.

With ageing populations, increased economic prosperity and the ensuing lifestyle changes, there has been a dramatic increase in the burden of chronic non-communicable diseases in countries of the developing world. The distribution of risk factors for chronic diseases among populations in developing countries has traditionally been very different from that in their Western counterparts, thus resulting in considerable variation in disease distribution in these settings. However, with the increase in globalization along with rapid advancements in technology, many developing countries are now faced with the challenge of a dual disease burden, battling existing communicable infectious diseases as well as the emerging epidemic of non-communicable chronic diseases. This paper highlights the need for multiple cohort studies on chronic diseases around the world, and explores some of the challenges in establishing and maintaining these studies in resource-constrained settings.

PREDICTORS OF INCIDENT TUBERCULOSIS IN HIV-EXPOSED CHILDREN IN TANZANIA.

OBJECTIVE: To examine the predictors of tuberculosis infection in HIV-exposed children. DESIGN: A longitudinal cohort study nested within a randomised controlled trial. SETTING: Antenatal clinics in Dar-es-Salaam, Tanzania. SUBJECTS: Children born to 875 HIV-infected women in Tanzania. RESULTS: A total of 82 children developed tuberculosis during the follow-up period. In multivariate analyses, HIV infection was associated with a six-fold increase in risk of tuberculosis. Breastfeeding duration, child mid-upper arm circumference, and maternal CD4 T-cell counts were inversely related to risk of tuberculosis. In HIV-infected children, greater number of people eating at the same household meal and child CD8 T-cell counts were associated with increased risk of tuberculosis; higher maternal lymphocyte counts, increased duration of breastfeeding, and lower vitamin E levels were associated with reduced risk of tuberculosis. In HIV-uninfected children, breastfeeding duration and increased child mid-upper arm circumference were associated with reduced risk of tuberculosis. CONCLUSION: Breastfeeding duration, HIV status, maternal and child nutritional and immunological status were important predictors of child tuberculosis. Appropriate infant feeding and nutritional interventions could represent important adjuncts to prevent tuberculosis in children born to HIV-infected women in sub-Saharan Africa.

Nutritional and sensory profile of two Indian rice varieties with different degrees of polishing.

Traditional hand-pounded rice has been replaced today with highly polished white rice in the Asian Indian diets. The study aimed to evaluate the nutritional as well as the sensory differences between the brown (0% polish) and the rice milled to different degrees of polish (2.3, 4.4 and 8.0%). Bapatla and Uma (red pigmented) varieties in both raw and parboiled forms were used. The protein, fat, dietary fibre, γ-oryzanol, polyphenols, vitamin E, total antioxidant activity and free radical scavenging abilities of the brown rice decreased while the available carbohydrates increased with polishing. Sensory attributes of the cooked rice samples (whiteness, grain intactness, fluffiness, firmness, stickiness, chewiness and the cooked rice aroma) were evaluated by trained panelists. Scores for branny taste and chewiness decreased with polishing. On the whole, brown rice of both the varieties was readily accepted by the well-informed sensory trained panelists.

Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia.

Autism spectrum disorder (ASD) and schizophrenia (SCZ) are two common neurodevelopmental syndromes that result from the combined effects of environmental and genetic factors. We set out to test the hypothesis that rare variants in many different genes, including de novo variants, could predispose to these conditions in a fraction of cases. In addition, for both disorders, males are either more significantly or more severely affected than females, which may be explained in part by X-linked genetic factors. Therefore, we directly sequenced 111 X-linked synaptic genes in individuals with ASD (n = 142; 122 males and 20 females) or SCZ (n = 143; 95 males and 48 females). We identified >200 non-synonymous variants, with an excess of rare damaging variants, which suggest the presence of disease-causing mutations. Truncating mutations in genes encoding the calcium-related protein IL1RAPL1 (already described in Piton et al. Hum Mol Genet 2008) and the monoamine degradation enzyme monoamine oxidase B were found in ASD and SCZ, respectively. Moreover, several promising non-synonymous rare variants were identified in genes encoding proteins involved in regulation of neurite outgrowth and other various synaptic functions (MECP2, TM4SF2/TSPAN7, PPP1R3F, PSMD10, MCF2, SLITRK2, GPRASP2, and OPHN1).