Contribution of Food from Market Purchases and Home Production to Child Nutrient Intake: Evidence from the EFFECTS Study Baseline Data.

BACKGROUND: Child undernutrition is prevalent in Tanzania, and households rely primarily on local markets and home production as food sources. However, little is known about the contribution of food market purchases to nutrient intakes among children consuming complementary foods. OBJECTIVES: To quantify the relationships between diversity of foods purchased and produced by households and adequate child nutrient intake in Mara, Tanzania. METHODS: Cross-sectional baseline dietary and household food source data from the Engaging Fathers for Effective Child Nutrition and Development in Tanzania study were collected from mothers of 586 children aged 9-23 mo clustered in 80 villages in Mara, Tanzania. We conducted mixed effects linear regressions to quantify the association between the diversity of foods consumed at home, from market purchases and home production, and nutrient intake adequacy (based on 24-h food recalls). RESULTS: Children had inadequate diets, with fewer than half of children consuming adequate amounts of vitamin A, vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B9 (folate), calcium, iron, and zinc. Breastfeeding was associated with higher overall mean adequacy (b = 0.15-0.19 across models, P < 0.001). Diversity of foods purchased was positively associated with the intake of vitamin B12 and calcium (both P < 0.001); this effect was attenuated among breastfed children. Among nonbreastfed children, production diversity was positively associated with vitamin A intake (b=0.04; P < .05) but not with intake of other nutrients. CONCLUSIONS: Both household food purchase and food production diversities were positively associated with children's nutrient intake in rural Mara, Tanzania. Nutrition programming should consider the role of food markets in addition to home food production to improve child diets. This trial was registered at clinicaltrials.gov as NCT03759821, https://clinicaltrials.gov/study/NCT03759821.

Effects of engaging fathers and bundling parenting and nutrition interventions on early child development and maternal and paternal parenting in Mara, Tanzania: a factorial cluster-randomized controlled trial.

BACKGROUND: Multicomponent interventions are needed to address the various co-occurring risks that compromise early child nutrition and development. We compared the independent and combined effects of engaging fathers and bundling parenting components into a nutrition intervention on early child development (ECD) and parenting outcomes. METHODS: We conducted a 2×2 factorial cluster-randomized controlled trial across 80 villages in Mara Region, Tanzania, also known as EFFECTS (Engaging Fathers for Effective Child Nutrition and Development in Tanzania; ClinicalTrials.gov, NCT03759821). Households with children under 18 months of age residing with their mother and father were enrolled. Villages were randomly assigned to one of five groups: a nutrition intervention for mothers, a nutrition intervention for couples, a bundled nutrition and parenting intervention for mothers, a bundled intervention for couples, and a standard-of-care control. Interventions were delivered by trained community health workers through peer groups and home visits over 12 months. Mothers, fathers, and children were assessed at baseline, midline, and endline or postintervention. We used a difference-in-difference approach with intention-to-treat analysis to estimate intervention effects on ECD (Bayley Scales of Infant and Toddler Development, third edition) and maternal and paternal parenting and psychosocial well-being. RESULTS: Between October 29, 2018, and May 24, 2019, 960 households were enrolled (n = 192 per arm). Compared to nutrition interventions, bundled interventions improved children's cognitive (ß = .18 [95% CI: 0.01, 0.36]) and receptive language development (ß = .23 [0.04, 0.41]). There were no differences between interventions for other ECD domains. Compared to nutrition interventions, bundled interventions achieved additional benefits on maternal stimulation (ß = .21 [0.04, 0.38]) and availability of home learning materials (ß = .25 [0.07-0.43]) and reduced paternal parenting distress (ß = -.34 [-0.55, -0.12]). Compared to interventions with mothers only, interventions that engaged fathers improved paternal stimulation (ß = .45 [0.27, 0.63]). CONCLUSIONS: Jointly bundling parenting components into nutrition interventions while also engaging both mothers and fathers is most effective for improving maternal and paternal parenting and ECD outcomes.

HIV Positive status disclosure to sexual partners: a qualitative study to explore experiences and challenges among clients attending HIV care services in North-Western Tanzania.

HIV status disclosure rates to sexual partners are low in Tanzania, despite the benefits it confers to both partners. This qualitative study drew on the Disclosure Decision Model to explore the decision by people living with HIV (PLHIV) to disclose, or not, their HIV status to their partner. Six focus group discussions and thirty in-depth interviews were conducted in Mwanza, Tanzania in 2019 with PLHIV. Topics covered decision-making around disclosure and disclosure experiences. Thematic content analysis was conducted. Most respondents reported having disclosed their status to their partners. Disclosure was reported to facilitate or hinder the attainment of social goals including having intimate relationships, raising a family, relief from distress and accessing social support. Decisions made by PLHIV about whether to disclose their status were made after weighing up the perceived benefits and risks. The sense of liberty from a guilty conscious, and not "living a lie" were perceived as benefits of disclosure, while fears of stigma, family break-up or abandonment were perceived as risks. Many participants found disclosure was beneficial in promoting their adherence to treatment and clinic appointments. Interventions to support PLHIV with disclosure should include enhanced counselling, strengthening HIV support groups and enhanced assisted partner notification services.

Metabolic syndrome among people living with HIV on antiretroviral therapy in Mwanza, Tanzania.

BACKGROUND: HIV and antiretroviral drugs, particularly protease inhibitors and nucleoside reverse transcriptase inhibitors, may increase the risk of Metabolic Syndrome (MetS) among people living with HIV (PLHIV). However, following the introduction of better drugs like dolutegravir, data on the burden of MetS are limited. This study aimed to assess the prevalence of MetS and associated factors among PLHIV on antiretroviral therapy (ART) in Tanzania. METHODS: This was a cross-sectional study among PLHIV aged ≥ 18 years on antiretroviral therapy for ≥ 1 year at Bugando Medical Centre in Mwanza conducted in 2020. Demographic and healthy-lifestyle-related non-communicable disease risk factors data were collected. Additionally, data on lipid profile, blood glucose, blood pressure, and waist circumference were collected for analysis of MetS according to the International Diabetes Federation criteria. Factors associated with MetS were assessed using logistic regression. A P ≤ 0.05 was considered statistically significant. RESULTS: Data for 223 participants were analyzed. The mean (SD) age was 44 (± 12) years and 79.8% (178) were females. A majority 78% (174) were on a tenofovir, lamivudine,and dolutegravir regimen. About 12.1% (27) were either current or past smokers, 45.3% (101) were past alcohol drinkers, 22.9% (51) were current drinkers, 12.1% (27) reported taking ≥ 5 servings of vegetables and fruits per day and 5.8% (13) were physically inactive. The prevalence of MetS was 22.9%. The only factors that were associated with Mets were fat mass index and adequate intake of vegetables and fruits, (adjusted odds ratio (aOR) 2.9, 95% CI 1.0, 7.9, P = 0.04) and (aOR1.2, 95% CI 1.0, 1.3, P = 0.02), respectively). CONCLUSION: The prevalence of MetS remains high among PLHIV. Adiposity and adequate fruit and vegetable intake increased the risk. The introduction of new ART regimens shows no effect on MetS prevalence. Research is needed to understand how lifestyle changes could reduce MetS in PLHIV.

Perceptions, facilitators and barriers of physical activity among people living with HIV: a qualitative study.

BACKGROUND: People living with HIV (PLWH) have low levels of physical activity. Using the social ecological model to understand perceptions, facilitators and barriers of physical activity in this population is of importance for developing contextualised interventions to improve physical activity in PLWH. METHOD: This was a qualitative sub-study conducted between august and November 2019 as part of a cohort study on diabetes and associated complications in HIV infected in Mwanza, Tanzania. Sixteen in-depth interviews and three focus groups with nine participants in each were conducted. The interviews and focus groups were audio recorded, transcribed and translated into English. The social ecological model was considered during the coding and interpretation of the results. Transcripts were discussed, coded and analyzed using deductive content analysis. RESULTS: Forty-three PLWH aged 23-61 years participated in this study. The findings showed that most PLWH perceived physical activity as beneficial to their health. However, their perceptions of physical activity were rooted within existing gender stereotypes and roles in the community. Running and playing football were perceived as activities for men while household chores activities were for women. Further, men were perceived to do more physical activity than women. For women, household chores and income-generating activities were perceived as sufficient physical activity. Social support and engagement of family members and friends in physical activity were reported as facilitators of physical activity. Reported barriers of physical activity were lack of time, money, availability of physical activity facilities and social support groups, and poor information on physical activity from health care providers in HIV clinics. Human-immunodeficiency virus (HIV) HIV infection was not perceived by PLWH as a barrier for doing physical activity but most family members did not support them to do physical activity, fearing that it might worsen their condition. CONCLUSION: The findings demonstrated differing perceptions, facilitators and barriers of physical activity among PLWH. Interventions addressing awareness, gender stereotypes and roles related to physical activity from individual to community level are needed. Supportive environment and infrastructures are needed to improve physical activity levels in PLWH in Tanzania.

ß-cell dysfunction and insulin resistance in relation to pre-diabetes and diabetes among adults in north-western Tanzania: a cross-sectional study.

OBJECTIVE: Studies on phenotypes of diabetes in Africa are inconsistent. We assessed the role of ß-cell dysfunction and insulin resistance on pre-diabetes and diabetes. METHODS: We included 1890 participants with mean age of 40.6 (SD11.9) years in a cross-sectional study among male and female adults in Tanzania during 2016 to 2017. Data on C-reactive protein (CRP), alpha-acid glycoprotein (AGP), HIV, oral glucose tolerance test (OGTT), body composition and insulin were collected. Insulinogenic index and HOMA-IR were used to derive an overall marker of ß-cell dysfunction and insulin resistance which was categorised as follows: normal ß-cell function and insulin sensitivity, isolated ß-cell dysfunction, isolated insulin resistance, and combined ß-cell dysfunction and insulin resistance. Pre-diabetes and diabetes were defined as 2-hour OGTT glucose between 7.8-11.0 and ≥ 11.1 mmol/L, respectively. Multinomial regression assessed the association of ß-cell dysfunction and insulin resistance with outcome measures. RESULTS: ß-cell dysfunction, insulin resistance, and combined ß-cell dysfunction and insulin resistance were associated with higher pre-diabetes risk. Similarly, isolated ß-cell dysfunction (adjusted relative risk ratio (aRRR) 4.8 (95% confidence interval (CI) 2.5, 9.0), isolated insulin resistance (aRRR 3.2 (95% CI 1.5, 6.9), and combined ß-cell dysfunction and insulin resistance (aRRR 35.9 (95% CI 17.2, 75.2) were associated with higher diabetes risk. CRP, AGP and HIV were associated with higher diabetes risk, but fat mass was not. 31%, 10% and 33% of diabetes cases were attributed to ß-cell dysfunction, insulin resistance, and combined ß-cell dysfunction and insulin resistance, respectively. CONCLUSIONS: ß-cell dysfunction seemed to explain most of diabetes cases compared to insulin resistance in this population. Cohort studies on evolution of diabetes in Africa are needed to confirm these results.

Risk factors for impaired renal function in HIV-infected and HIV-uninfected adults: cross-sectional study in North-Western Tanzania.

BACKGROUND: Although the burden of impaired renal function is rising in sub-Saharan Africa (SSA), little is known about correlates of impaired renal function in the region. We determined factors associated with estimated glomerular filtration rate (eGFR) and impaired renal function in HIV-infected and HIV-uninfected adults. METHODS: We undertook cross-sectional analysis of data from 1947 adults at enrolment for a cohort study on diabetes and associated complications in HIV patients in Mwanza, north-western Tanzania. A structured questionnaire was used to collect data on sociodemography, smoking, alcohol, physical activity, antiretroviral therapy (ART) and anthropometry. We measured blood pressure, tested blood samples for creatinine, glucose and HIV, and performed Kato Katz for Schistosoma mansoni. Correlates of eGFR (mL/min/1.73 m2) and impaired renal function (eGFR< 60 mL/min/1.73 m2) were determined using linear regression and logistic regression, respectively. RESULTS: 655 (34%) participants were HIV-uninfected, 956 (49%) were ART-naive HIV-infected and 336 (17%) were HIV-infected adults on ART. The mean age was 41 years (SD12) and majority (59%) were females. Overall, the mean eGFR was 113.6 mL/min/1.73 m2 but 111.2 mL/min/1.73 m2 in HIV-uninfected, 109.7 mL/min/1.73 m2 in ART-naive HIV-infected and 129.5 mL/min/1.73 m2 in HIV-infected ART-experienced adults, and respective prevalence of impaired renal function was 7.0, 5.7, 8.1 and 6.3%. Correlates of lower eGFR were increasing age, higher socioeconomic status, unhealthy alcohol drinking, higher body mass index and diabetes mellitus. Anaemia was associated with 1.9 (95% Confidence Interval (CI):1.2, 2.7, p = 0.001) higher odds of impaired renal function compared to no anaemia and this effect was modified by HIV status (p value 0.02 for interaction). CONCLUSION: Impaired renal function is prevalent in this middle-aged study population. Interventions for prevention of impaired renal function are needed in the study population with special focus in HIV-infected adults and those with high socioeconomic status. Interventions targeting modifiable risk factors such as alcohol and weight reduction are warranted.

Safety and Immunogenicity of a 2-Dose Heterologous Vaccination Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1 Randomized Clinical Trial in Uganda and Tanzania.

BACKGROUND: Ebola vaccine development was accelerated in response to the 2014 Ebola virus infection outbreak. This phase 1 study (VAC52150EBL1004) assessed safety, tolerability, and immunogenicity of heterologous 2-dose Ad26.ZEBOV, MVA-BN-Filo vaccination regimens in the Lake Victoria Basin of Tanzania and Uganda in mid-level altitude, malaria-endemic settings. METHODS: Healthy volunteers aged 18-50 years from Tanzania (n = 25) and Uganda (n = 47) were randomized to receive placebo or active vaccination with Ad26.ZEBOV or MVA-BN-Filo (first vaccination), followed by MVA-BN-Filo or Ad26.ZEBOV (second vaccination) dose 2, respectively, with intervals of 28 or 56 days. RESULTS: Seventy-two adults were randomized to receive vaccine (n = 60) or placebo (n = 12). No vaccine-related serious adverse events were reported. The most frequent solicited local and systemic adverse events were injection site pain (frequency, 70%, 66%, and 42% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively) and headache (57%, 56%, and 46%, respectively). Adverse event patterns were similar among regimens. Twenty-one days after dose 2, 100% of volunteers demonstrated binding antibody responses against Ebola virus glycoprotein, and 87%-100% demonstrated neutralizing antibody responses. Ad26.ZEBOV dose 1 vaccination induced more-robust initial binding antibody and cellular responses than MVA-BN-Filo dose 1 vaccination. CONCLUSIONS: Heterologous 2-dose vaccination with Ad26.ZEBOV and MVA-BN-Filo against Ebola virus is well tolerated and immunogenic in healthy volunteers. CLINICAL TRIALS REGISTRATION: NCT02376400.

Changes in serum phosphate and potassium and their effects on mortality in malnourished African HIV-infected adults starting antiretroviral therapy and given vitamins and minerals in lipid-based nutritional supplements: secondary analysis from the Nutritional Support for African Adults Starting Antiretroviral Therapy (NUSTART) trial.

Malnourished HIV-infected patients starting antiretroviral therapy (ART) are at high risk of early mortality, some of which may be attributed to altered electrolyte metabolism. We used data from a randomised controlled trial of electrolyte-enriched lipid-based nutritional supplements to assess the association of baseline and time-varying serum phosphate and K concentrations with mortality within the first 12 weeks after starting ART. Baseline phosphate results were available from 1764 patients and there were 9096 subsequent serum phosphate measurements, a median of 6 per patient. For serum K there were 1701 baseline and 8773 subsequent measures, a median of 6 per patient. Abnormally high or low serum phosphate was more common than high or low serum K. Controlling for other factors found to affect mortality in this cohort, low phosphate which had not changed from the previous time interval was associated with increased mortality; the same was not true for high phosphate or for high or low K. Both increases and decreases in serum electrolytes from the previous time interval were generally associated with increased mortality, particularly in the electrolyte-supplemented group. The results suggest that changes in serum electrolytes, largely irrespective of the starting point and the direction of change, were more strongly associated with mortality than were absolute electrolyte levels. Although K and phosphate are required for tissue deposition during recovery from malnutrition, further studies are needed to determine whether specific supplements exacerbate physiologically adverse shifts in electrolyte levels during nutritional rehabilitation of ill malnourished HIV patients.

Dysglycemia associations with adipose tissue among HIV-infected patients after 2 years of antiretroviral therapy in Mwanza: a follow-up cross-sectional study.

BACKGROUND: Data on the burden of dysglycemia among HIV-infected patients on antiretroviral therapy (ART) in Africa are limited. We determined the prevalence of pre-diabetes and diabetes among HIV-infected patients who started ART when malnourished 2 to 3 years previously and investigated the association of dysglycemia with body composition. METHODS: Malnourished (body mass index (BMI) < 18.5 kg/m2) HIV-infected patients who were enrolled in the Nutritional Support for Africans Starting Antiretroviral Therapy (NUSTART) trial from 2011 to 2013 were followed-up from March to August 2015. Anthropometric, fat mass and fat-free mass by bioelectrical impedance, and C-reactive protein (CRP) data were collected at baseline and follow-up. At follow-up, we defined fasting glucose of 6.1-6.9 mmol/L as impaired fasting glucose (IFG) and 2-h oral glucose tolerance test (OGTT) glucose of ≥7.8 to <11.1 mmol/L as impaired glucose tolerance (IGT). Both of these were considered pre-diabetes. Fasting glucose of ≥7.0 mmol/L or impaired glucose tolerance of ≥11.1 mmol/L was defined as diabetes mellitus. The relation of pre-diabetes and diabetes with body composition was assessed using logistic regression. RESULTS: Two hundred seventy-three (57%) of 478 patients who were alive at trial conclusion were followed-up. The mean age was 41.5 (SD 9.8) years and 65.2% (178) were females. The mean follow-up BMI was 19.9 (SD 2.8) kg/m2, 12 (4.4%) were either overweight or obese, and 61 (22.3%) patients had pre-diabetes or diabetes. In multiple regression, upper tertiles of baseline hip circumference (OR: 0.41, 95% CI: 0.2, 0.8) and fat mass index (OR: 0.20 (0.1, 0.5), and upper tertiles of follow-up waist circumference (OR: 0.22 (0.1, 0.5), BMI (OR: 0.32 (0.1, 0.7), fat mass index (OR: 0.19 (0.1, 0.5) and the middle tertile of follow-up fat-free mass (OR: 0.36, 95% CI: 0.1, 0.8) were associated with lower risk of pre-diabetes and diabetes (P < 0.05 for all). Baseline and follow-up CRP were not predictors. CONCLUSIONS: Low rather than high measures of adipose tissue were associated with increased risk of pre-diabetes and diabetes. Additional studies are needed to further investigate the role of body composition and control of glucose metabolism in the pathogenesis of diabetes among persons living with HIV in Africa.

From Wasting to Obesity: The Contribution of Nutritional Status to Immune Activation in HIV Infection.

The impact of human immunodeficiency virus (HIV) infection on innate and adaptive immune activation occurs in the context of host factors, which serve to augment or dampen the physiologic response to the virus. Independent of HIV infection, nutritional status, particularly body composition, affects innate immune activation through a variety of conditions, including reduced mucosal barrier defenses and microbiome dysbiosis in malnutrition and the proinflammatory contribution of adipocytes and stromal vascular cells in obesity. Similarly, T-cell activation, proliferation, and cytokine expression are reduced in the setting of malnutrition and increased in obesity, potentially due to adipokine regulatory mechanisms restraining energy-avid adaptive immunity in times of starvation and exerting a paradoxical effect in overnutrition. The response to HIV infection is situated within these complex interactions between host nutritional health and immunologic function, which contribute to the varied phenotypes of immune activation among HIV-infected patients across a spectrum from malnutrition to obesity.

Risk factors for mortality among malnourished HIV-infected adults eligible for antiretroviral therapy.

BACKGROUND: A substantial proportion of HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa are malnourished. We aimed to increase understanding of the factors affecting their high mortality, particularly in the high-risk period before ART initiation. METHODS: We analysed potential risk factors for mortality of Zambian and Tanzanian participants enrolled in the NUSTART clinical trial. Malnourished adults (n = 1815; body mass index [BMI] <18.5 kg/m2) were recruited at referral to ART and randomised to receive different nutritional supplements. Demographics, measures of body composition, blood electrolytes and clinical conditions were investigated as potential risk factors using Poisson regression models. RESULTS: The mortality rate was higher in the period from referral to starting ART (121 deaths/100 person-years; 95 % CI 103, 142) than during the first 12 weeks of ART (66; 95 % CI 57, 76) and was not affected by trial study arm. In adjusted analyses, lower CD4 count, BMI and mid-arm circumference and raised C-reactive protein were associated with an increased risk of mortality throughout the study. Male sex and lower hand-grip strength carried an increased risk in the pre-ART period. Participants on tuberculosis treatment at referral had a lower mortality rate (adjusted Rate Ratio 0.44; 95 % CI 0.31, 0.63). CONCLUSION: Among malnourished ART-eligible adults, pre-ART mortality was twice that in the early post-ART period, suggesting many early ART deaths represent advanced HIV disease rather than treatment-related events. Therefore, more efforts are needed to promote earlier diagnosis and immediate initiation of ART, as recently recommended by WHO for all persons with HIV worldwide. The positive effect of tuberculosis treatment suggests undiagnosed tuberculosis is a contributor to mortality in this population. TRIAL REGISTRATION: Pan African Clinical Trials Registry, PACTR201106000300631 ; registered on 1st June 2011.

Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy: a randomised controlled trial.

BACKGROUND: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality. METHODS: The study was an individually-randomised phase III trial conducted in ART clinics in Mwanza, Tanzania, and Lusaka, Zambia. Participants were 1,815 ART-naïve non-pregnant adults with body mass index (BMI) <18.5 kg/m² who were referred for ART based on CD4 count <350 cells/µL or WHO stage 3 or 4 disease. The intervention was a lipid-based nutritional supplement either without (LNS) or with additional vitamins and minerals (LNS-VM), beginning prior to ART initiation; supplement amounts were 30 g/day (150 kcal) from recruitment until 2 weeks after starting ART and 250 g/day (1,400 kcal) from weeks 2 to 6 after starting ART. The primary outcome was mortality between recruitment and 12 weeks of ART. Secondary outcomes were serious adverse events (SAEs) and abnormal electrolytes throughout, and BMI and CD4 count at 12 weeks ART. RESULTS: Follow-up for the primary outcome was 91%. Median adherence was 66%. There were 181 deaths in the LNS group (83.7/100 person-years) and 184 (82.6/100 person-years) in the LNS-VM group (rate ratio (RR), 0.99; 95% CI, 0.80-1.21; P = 0.89). The intervention did not affect SAEs or BMI, but decreased the incidence of low serum phosphate (RR, 0.73; 95% CI, 0.55-0.97; P = 0.03) and increased the incidence of high serum potassium (RR, 1.60; 95% CI, 1.19-2.15; P = 0.002) and phosphate (RR, 1.23; 95% CI, 1.10-1.37; P <0.001). Mean CD4 count at 12 weeks post-ART was 25 cells/µL (95% CI, 4-46) higher in the LNS-VM compared to the LNS arm (P = 0.02). CONCLUSIONS: High-dose vitamin and mineral supplementation in LNS, compared to LNS alone, did not decrease mortality or clinical SAEs in malnourished African adults initiating ART, but improved CD4 count. The higher frequency of elevated serum potassium and phosphate levels suggests high-level electrolyte supplementation for all patients is inadvisable but the addition of micronutrient supplements to ART may provide clinical benefits in these patients. TRIAL REGISTRATION: PACTR201106000300631, registered on 1st June 2011.

Microbiota at Multiple Body Sites during Pregnancy in a Rural Tanzanian Population and Effects of Moringa-Supplemented Probiotic Yogurt.

The nutritional status of pregnant women is vital for healthy outcomes and is a concern for a large proportion of the world's population. The role of the microbiota in pregnancy and nutrition is a promising new area of study with potential health ramifications. In many African countries, maternal and infant death and morbidity are associated with malnutrition. Here, we assess the influence of probiotic yogurt containing Lactobacillus rhamnosus GR-1, supplemented with Moringa plant as a source of micronutrients, on the health and oral, gut, vaginal, and milk microbiotas of 56 pregnant women in Tanzania. In an open-label study design, 26 subjects received yogurt daily, and 30 were untreated during the last two trimesters and for 1 month after birth. Samples were analyzed using 16S rRNA gene sequencing, and dietary recalls were recorded. Women initially categorized as nourished or undernourished consumed similar calories and macronutrients, which may explain why there was no difference in the microbiota at any body site. Consumption of yogurt increased the relative abundance of Bifidobacterium and decreased Enterobacteriaceae in the newborn feces but had no effect on the mother's microbiota at any body site. The microbiota of the oral cavity and GI tract remained stable over pregnancy, but the vaginal microbiota showed a significant increase in diversity leading up to and after birth. In summary, daily micronutrient-supplemented probiotic yogurt provides a safe, affordable food for pregnant women in rural Tanzania, and the resultant improvement in the gut microbial profile of infants is worthy of further study.

Minimal impact of an iron-fortified lipid-based nutrient supplement on Hb and iron status: a randomised controlled trial in malnourished HIV-positive African adults starting antiretroviral therapy.

Anaemia, redistribution of Fe, malnutrition and heightened systemic inflammation during HIV infection confer an increased risk of morbidity and mortality in HIV patients. We analysed information on Fe status and inflammation from a randomised, double blind, controlled phase-III clinical trial in Lusaka, Zambia and Mwanza, Tanzania. Malnourished patients (n 1815) were recruited at referral to antiretroviral therapy (ART) into a two-stage nutritional rehabilitation programme, randomised to receive a lipid-based nutrient supplement with or without added micronutrients. Fe was included in the intervention arm during the second stage, given from 2 to 6 weeks post-ART. Hb, serum C-reactive protein (CRP), serum ferritin and soluble transferrin receptor (sTfR) were measured at recruitment and 6 weeks post-ART. Multivariable linear regression models were used to assess the impact of the intervention, and the effect of reducing inflammation from recruitment to week 6 on Hb and Fe status. There was no effect of the intervention on Hb, serum ferritin, sTfR or serum CRP. A one-log decrease of serum CRP from recruitment to week 6 was associated with a 1.81 g/l increase in Hb (95% CI 0.85, 2.76; P< 0.001), and a 0.11 log decrease in serum ferritin (95% CI - 0.22, 0.03; P= 0.012) from recruitment to week 6. There was no association between the change in serum CRP and the change in sTfR over the same time period (P= 0.78). In malnourished, HIV-infected adults receiving dietary Fe, a reduction in inflammation in the early ART treatment period appears to be a precondition for recovery from anaemia.

Appetite testing in HIV-infected African adults recovering from malnutrition and given antiretroviral therapy.

OBJECTIVE: The Nutritional Support for Africans Starting Antiretroviral Therapy (NUSTART) trial was designed to determine whether nutritional support for malnourished HIV-infected adults starting antiretroviral therapy (ART) can improve early survival. Appetite is related to health outcomes in this population, but the optimal appetite metric for field use is uncertain. We evaluated two measures of appetite with the goal of improving understanding and treatment of malnutrition in HIV-infected adults. DESIGN: Longitudinal cohort study embedded in a clinical trial of vitamin and mineral-fortified, v. unfortified, lipid-based nutritional supplements. SETTING: HIV clinics in Mwanza, Tanzania and Lusaka, Zambia. SUBJECTS: Malnourished (BMI<18.5 kg/m2) HIV-infected adults starting ART. RESULTS: Appetite measurements, by short questionnaire and by weight of maize porridge consumed in a standardized test, were compared across time and correlated with changes in weight. Appetite questionnaire scores, from polychoric correlation, and porridge test results were normally distributed for Tanzanians (n 187) but clustered and unreliable for Zambians (n 297). Among Tanzanian patients, the appetite score increased rapidly from referral for ART, plateaued at the start of ART and then increased slowly during the 12-week follow-up. Change in appetite questionnaire score, but not porridge test, correlated with weight change in the corresponding two-week intervals (P=0.002) or over the whole study (P=0.05) but a point estimate of hunger did not predict weight change (P=0.4). CONCLUSIONS: In Tanzania change in appetite score correlated with weight change, but single point measurements did not. Appetite increases several weeks after the start of ART, which may be an appropriate time for nutritional interventions for malnourished HIV-infected adults.

Nutritional supplementation increases rifampin exposure among tuberculosis patients coinfected with HIV.

Nutritional supplementation to tuberculosis (TB) patients has been associated with increased weight and reduced mortality, but its effect on the pharmacokinetics of first-line anti-TB drugs is unknown. A cohort of 100 TB patients (58 men; median age, 35 [interquartile range {IQR}, 29 to 40] years, and median body mass index [BMI], 18.8 [17.3 to 19.9] kg/m(2)) were randomized to receive nutritional supplementation during the intensive phase of TB treatment. Rifampin plasma concentrations were determined after 1 week and 2 months of treatment. The effects of nutritional supplementation, HIV, time on treatment, body weight, and SLCO1B1 rs4149032 genotype were examined using a population pharmacokinetic model. The model adjusted for body size via allometric scaling, accounted for clearance autoinduction, and detected an increase in bioavailability (+14%) for the patients in the continuation phase. HIV coinfection in patients not receiving the supplementation was found to decrease bioavailability by 21.8%, with a median maximum concentration of drug in serum (Cmax) and area under the concentration-time curve from 0 to 24 h (AUC0-24) of 5.6 µg/ml and 28.6 µg · h/ml, respectively. HIV-coinfected patients on nutritional supplementation achieved higher Cmax and AUC0-24 values of 6.4 µg/ml and 31.6 µg · h/ml, respectively, and only 13.3% bioavailability reduction. No effect of the SLCO1B1 rs4149032 genotype was observed. In conclusion, nutritional supplementation during the first 2 months of TB treatment reduces the decrease in rifampin exposure observed in HIV-coinfected patients but does not affect exposure in HIV-uninfected patients. If confirmed in other studies, the use of defined nutritional supplementation in HIV-coinfected TB patients should be considered in TB control programs. (This study has the controlled trial registration number ISRCTN 16552219.).

Increased level of acute phase reactants in patients infected with modern Mycobacterium tuberculosis genotypes in Mwanza, Tanzania.

BACKGROUND: There is increasing evidence to suggest that different Mycobacterium tuberculosis lineages cause variations in the clinical presentation of tuberculosis (TB). Certain M. tuberculosis genotypes/lineages have been shown to be more likely to cause active TB in human populations from a distinct genetic ancestry. This study describes the genetic biodiversity of M. tuberculosis genotypes in Mwanza city, Tanzania and the clinical presentation of the disease caused by isolates of different lineages. METHODS: Two-hundred-fifty-two isolates from pulmonary TB patients in Mwanza, Tanzania were characterized by spoligotyping, and 45 isolates were further characterized by mycobacterium interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR). The patients' level of the acute phase reactants AGP, CRP and neutrophil counts, in addition to BMI, were measured and compared to the M. tuberculosis lineage of the infectious agent for each patient. RESULTS: The most frequent genotype was ST59 (48 out of 248 [19.4%]), belonging to the Euro-American lineage LAM11_ZWE, followed by ST21 (CAS_KILI lineage [44 out of 248 [17.7%]). A low degree of diversity (15.7% [39 different ST's out of 248 isolates]) of genotypes, in addition to a high level of mixed M. tuberculosis sub-populations among isolates with an unreported spoligotype pattern (10 out of 20 isolates [50.0%]) and isolates belonging to the ST53 lineage (13 out of 25 [52%]) was observed. Isolates of the 'modern' (TbD1-) Euro-American lineage induced higher levels of α1-acid glycoprotein (ß = 0.4, P = 0.02; 95% CI [0.06-0.66]) and neutrophil counts (ß = 0.9, P = 0.02; 95% CI [0.12-1.64]) and had lower BMI score (ß = -1.0, P = 0.04; 95% CI[-1.89 - (-0.03)]). LAM11_ZWE ('modern') isolates induced higher levels of CRP (ß = 24.4, P = 0.05; 95% CI[0.24-48.63]) and neutrophil counts (ß = 0.9, P = 0.03; 95% CI[0.09-1.70]). CONCLUSION: The low diversity of genotypes may be explained by an evolutionary advantage of the most common lineages over other lineages combined with optimal conditions for transmission, such as overcrowding and inadequate ventilation. The induction of higher levels of acute phase reactants in patients infected by 'modern' lineage isolates compared to 'ancient' lineages may suggest increased virulence among 'modern' lineage isolates.

Diabetes is associated with lower tuberculosis antigen-specific interferon gamma release in Tanzanian tuberculosis patients and non-tuberculosis controls.

BACKGROUND: Diabetes is increasingly common in TB endemic regions and plays a role as a possible risk factor for increased progression from latent TB infection (LTBI) to active TB disease. Although the pathophysiological mechanisms are not fully understood, the immune system is weakened in diabetes patients and therefore the validity of interferon gamma release assays (IGRA) may be compromised. The aim of the present study was to assess the association between diabetes and Mycobacterium tuberculosis (Mtb) antigen-specific interferon gamma (IFN-γ) release in a TB endemic area among culture-confirmed TB patients and non-TB controls. METHODS: Culture-confirmed pulmonary TB patients (n = 187) and healthy non-TB neighbourhood controls (n = 190) from Mwanza, Tanzania were tested for the presence of circulating T cells recognizing Mtb antigens using an IGRA. The diabetes status of all participants was assessed using a standard oral glucose tolerance test. The impact of diabetes on the performance of the IGRA was estimated using robust linear and logistic regression. RESULTS: Compared to normal glucose tolerance, diabetes was associated with reduced levels of Mtb-specific IFN-γ. Increasing levels of fasting blood glucose (B - 0.3, 95% confidence interval - 0.6 to - 0.03, p = 0.033) was negatively associated with IFN-γ. Although TB patients had higher specific and lower unspecific mitogen IFN-γ responses compared to non-TB controls, the association between diabetes and IFN-γ did not depend on TB status. CONCLUSION: Diabetes is associated with lower levels of Mtb antigen-specific IFN-γ, and the validity of IFN- γ tests for LTBI may be questionable in individuals with diabetes.

Developing a context-relevant psychosocial stimulation intervention to promote cognitive development of children with severe acute malnutrition in Mwanza, Tanzania.

More than 250 million children will not meet their developmental potential due to poverty and malnutrition. Psychosocial stimulation has shown promising effects for improving development in children exposed to severe acute malnutrition (SAM) but programs are rarely implemented. In this study, we used qualitative methods to inform the development of a psychosocial stimulation programme to be integrated with SAM treatment in Mwanza, Tanzania. We conducted in-depth interviews with seven caregivers of children recently treated for SAM and nine professionals in early child development. We used thematic content analysis and group feedback sessions and organised our results within the Nurturing Care Framework. Common barriers to stimulate child development included financial and food insecurity, competing time demands, low awareness about importance of responsive caregiving and stimulating environment, poor father involvement, and gender inequality. Caregivers and professionals suggested that community-based support after SAM treatment and counselling on psychosocial stimulation would be helpful, e.g., how to create homemade toys and stimulate through involvement in everyday chores. Based on the findings of this study we developed a context-relevant psychosocial stimulation programme. Some issues identified were structural highlighting the need for programmes to be linked with broader supportive initiatives.