Publications by authors named "George Praygod"

49 Publications

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.

AIDS Care 2021 Dec 10:1-8. Epub 2021 Dec 10.

National Institute for Medical Research (NIMR) -Mwanza Centre, Mwanza, 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.
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http://dx.doi.org/10.1080/09540121.2021.2012555DOI Listing
December 2021

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

BMC Nephrol 2021 Oct 29;22(1):355. Epub 2021 Oct 29.

Mwanza Intervention Trials Unit/National Institute for Medical Research, Mwanza, 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 m) and impaired renal function (eGFR< 60 mL/min/1.73 m) 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 m but 111.2 mL/min/1.73 m in HIV-uninfected, 109.7 mL/min/1.73 m in ART-naive HIV-infected and 129.5 mL/min/1.73 m 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.
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http://dx.doi.org/10.1186/s12882-021-02563-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555220PMC
October 2021

Prevalence of Mycobacterium tuberculosis infection as measured by the QuantiFERON-TB Gold assay and ESAT-6 free IGRA among adolescents in Mwanza, Tanzania.

PLoS One 2021 7;16(6):e0252808. Epub 2021 Jun 7.

Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.

Background: The prevalence of latent tuberculosis infection (LTBI) is vastly higher than that of tuberculosis (TB) disease and this enormous reservoir of individuals with LTBI impacts the global TB control strategy. Adolescents are at greatest risk of TB infection and are thus an ideal target population for a potential effective TB vaccine to be added to the current BCG programme as it could reduce the number of latent infections and consequently the number of adults with TB disease. However, LTBI rates are often unknown for this population. This study aims to estimate the magnitude of LTBI and to determine if Tanzanian adolescents would be a good population for a prevention of TB infection trial.

Methods: This was a descriptive cross-sectional study that recruited 193 adolescents aged 12 and 16 years from government schools and directly from the community in Mwanza Region, Tanzania. Socio-demographic characteristics were collected for all enrolled participants. Blood was drawn and tested using QuantiFERON-TB Gold In-Tube (QFT-GIT), and Early Secretory Antigenic Target-6-Free Interferon-gamma Release Assay (ESAT-6 free IGRA). Concordance between QFT-GIT and ESAT-6 free IGRA was evaluated using the McNemar's test.

Results: Overall estimates of LTBI prevalence were 19.2% [95%CI, 14.1; 25.2] and 18.6% [95%CI, 13.6; 24.6] as measured by QFT-GIT IGRA and ESAT-6 free IGRA, respectively. The 16-year-old cohort had a higher LTBI prevalence (23.7% [95%CI, 16.1; 32.9]) as compared to 12-year-old cohort (14.6% [95%CI, 8.6; 22.7]) as measured by QFT-GIT IGRA. When measured by ESAT-6 Free IGRA, LTBI prevalence was 24.7% (95%CI, 16.9; 34.0) for the 16-year-old cohort and 12.5% (95%CI, 7.0; 20.3) among the 12-year-old cohort. According to both tests the prevalence of TB infection and the corresponding annual risk of tuberculosis infection (ARTI) and force of infection were high and increased with age. Of all enrolled participants, 97.4% had concordant results for QFT-GIT IGRA and ESAT-6 free IGRA (p = 0.65).

Conclusions: The prevalence of LTBI and the associated ARTI and force of infection among adolescents is high and increases with age in Mwanza Region. There was a high concordance between the QFT-GIT and the novel ESAT-6 free IGRA assays. These findings suggest Mwanza is a promising area to conduct novel TB vaccine research prevention of infection (POI) studies targeting adolescents.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252808PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183982PMC
November 2021

Prior undernutrition and insulin production several years later in Tanzanian adults.

Am J Clin Nutr 2021 06;113(6):1600-1608

University of Copenhagen, Copenhagen, Denmark.

Background: The prevalence, pathology, and existence of malnutrition-associated diabetes remain uncertain, especially with respect to adult-acquired undernutrition.

Objective: The aim was to investigate the association of prior undernutrition (low BMI, in kg/m2), acquired in adulthood and insulin during an oral glucose tolerance test (OGTT).

Methods: We followed up 630 adults recruited 7-14 y previously for other studies. Plasma insulin was measured fasting and at 30 and 120 min during an OGTT. The main exposure was BMI measured 7-14 y prior. The main outcome of interest was plasma insulin, controlling for time during the OGTT using generalized estimating equations, and exploratory outcomes were early insulin response (relative change in insulin and glucose from 0-30 min) and relative insulin and glucose AUCs from 0 to 120 min. Current confounding factors were age, sex, BMI, HIV, socioeconomic status, and physical activity.

Results: In unadjusted analyses, increasing severity of prior malnutrition was associated with lower insulin concentration. In multivariate adjusted analyses, only current BMI was a strong predictor of overall insulin concentration. Associations with prior BMI of insulin responses accounting for glucose were also seen in unadjusted but not adjusted analyses. For insulin concentration but not the outcomes accounting for glucose, there was a sex interaction with prior BMI such that only men had lower insulin if previously malnourished: insulin (pmol/L) at 120 min was 311 (95% CI: 272, 351) for prior BMI ≥18.5, 271 (95% CI: 221, 321) for prior BMI 17.0-18.5, and 237 (95% CI: 194, 297) for prior BMI <17.0; P = 0.03. HIV status showed limited and variable associations with insulin.

Conclusions: Insulin concentration, fasting and during an OGTT, was normalized in women more than in men several years after adult malnutrition. Chronic malnutrition, as indicated by low prior and current BMI, may contribute to diabetes through low insulin secretion.
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http://dx.doi.org/10.1093/ajcn/nqaa438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168356PMC
June 2021

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

Trop Med Int Health 2021 04 27;26(4):435-443. Epub 2021 Jan 27.

Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.

Objective: Studies on phenotypes of diabetes in Africa are inconsistent. We assessed the role of β-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 β-cell dysfunction and insulin resistance which was categorised as follows: normal β-cell function and insulin sensitivity, isolated β-cell dysfunction, isolated insulin resistance, and combined β-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 β-cell dysfunction and insulin resistance with outcome measures.

Results: β-cell dysfunction, insulin resistance, and combined β-cell dysfunction and insulin resistance were associated with higher pre-diabetes risk. Similarly, isolated β-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 β-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 β-cell dysfunction, insulin resistance, and combined β-cell dysfunction and insulin resistance, respectively.

Conclusions: β-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.
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http://dx.doi.org/10.1111/tmi.13545DOI Listing
April 2021

Influence of hemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency on diagnosis of diabetes by HbA1c among Tanzanian adults with and without HIV: A cross-sectional study.

PLoS One 2020 31;15(12):e0244782. Epub 2020 Dec 31.

Vanderbilt Institute for Global Health and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.

Introduction: Hemoglobin A1c (HbA1c) is recommended for diagnosing and monitoring diabetes. However, in people with sickle cell disease (SCD), sickle cell trait (SCT), α-thalassemia or glucose-6-phosphate dehydrogenase (G6PD) deficiency, HbA1c may underestimate the prevalence of diabetes. There are no data on the extent of this problem in sub-Saharan Africa despite having high prevalence of these red blood cell disorders.

Methods: Blood samples from 431 adults in northwestern Tanzania, randomly selected from the prospective cohort study, Chronic Infections, Comorbidities and Diabetes in Africa (CICADA), were analysed for SCT/SCD, α-thalassemia and G6PD deficiency and tested for associations with the combined prevalence of prediabetes and diabetes (PD/DM) by HbA1c, using the HemoCue 501 HbA1c instrument, and by 2-hour oral glucose tolerance test (OGTT).

Results: The mean age of the participants was 40.5 (SD11.6) years; 61% were females and 71% were HIV-infected. Among 431 participants, 110 (25.5%) had SCT and none had SCD. Heterozygous α-thalassemia (heterozygous α+ AT) was present in 186 (43%) of the participants, while 52 participants (12%) had homozygous α-thalassemia (homozygous α+ AT). Furthermore, 40 (9.3%) participants, all females, had heterozygous G6PD deficiency while 24 (5.6%) males and 4 (0.9%) females had hemizygous and homozygous G6PD deficiency, respectively. In adjusted analysis, participants with SCT were 85% less likely to be diagnosed with PD/DM by HbA1c compared to those without SCT (OR = 0.15, 95% CI: 0.08, 0.26, P < 0.001). When using OGTT, in adjusted analysis, SCT was not associated with diagnosis of PD/DM while participants with homozygous α+ AT and hemizygous G6PD deficiency were more likely to be diagnosed with PD/DM.

Conclusions: HbA1c underestimates the prevalence of PD/DM among Tanzanian adults with SCT. Further research using other HbA1c instruments is needed to optimize HbA1c use among populations with high prevalence of hemoglobinopathies or G6PD deficiency.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244782PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775052PMC
March 2021

Does adipose tissue have a role in tuberculosis?

Authors:
George PrayGod

Expert Rev Anti Infect Ther 2020 09 25;18(9):839-841. Epub 2020 May 25.

Mwanza Research Centre, National Institute for Medical Research , Mwanza, Tanzania.

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http://dx.doi.org/10.1080/14787210.2020.1770597DOI Listing
September 2020

Diabetes prevalence by HbA1c and oral glucose tolerance test among HIV-infected and uninfected Tanzanian adults.

PLoS One 2020 8;15(4):e0230723. Epub 2020 Apr 8.

Mwanza Research Centre, National Institute for Medical Research, Mwanza, Tanzania.

Background: The burden of diabetes is increasing in sub-Saharan Africa, including among people living with HIV. We assessed the prevalence of diabetes and the roles of HIV, antiretroviral therapy (ART) and traditional risk factors among adults in Tanzania.

Methods: We analysed diabetes-relevant baseline data from 1,947 adult participants in the CICADA study in Mwanza, Tanzania: 655 HIV-uninfected, 956 HIV-infected ART-naïve, and 336 HIV-infected persons on ART. WHO guidelines for haemoglobin A1c (HbA1c) and oral glucose tolerance test (OGTT) were used to define diabetes and prediabetes. Risk factors were evaluated using multinomial logistic regression analysis. Relative risk ratios (RRR) were generated comparing participants with diabetes and prediabetes against the reference of those with no diabetes.

Results: Mean age was 41 (SD 12) years; 59% were women. The prevalence of diabetes was 13% by HbA1c and 6% by OGTT, with partial overlap among participants identified by the two tests. Relative to HIV-uninfected, HIV-infected ART-naïve persons had increased relative risks of diabetes (HbA1c: RRR = 1.95, 95% CI 1.25-3.03; OGTT: RRR = 1.90, 95% CI 0.96-3.73) and prediabetes (HbA1c: RRR = 2.89, 95% CI 1.93-4.34; OGTT: RRR = 1.61, 95% CI 1.22-2.13). HIV-infected participants on ART showed increased risk of prediabetes (RRR 1.80, 95% CI 1.09, 2.94) by HbA1c, but not diabetes. CD4 count < 200 cell/μL at recruitment increased risk and physical activity decreased risk of diabetes by both HbA1c and OGTT.

Conclusions: The prevalence of diabetes was high, especially among HIV-infected ART-naïve adults. Being more physically active was associated with lower risk of diabetes. HbA1c and OGTT identified different participants as having diabetes or prediabetes. Overall, the finding of high burden of diabetes among HIV-infected persons suggests that health systems should consider integrating diabetes screening and treatment in HIV clinics to optimize the care of HIV patients and improve their health outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230723PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141607PMC
July 2020

Complementary Feeding of Sorghum-Based and Corn-Based Fortified Blended Foods Results in Similar Iron, Vitamin A, and Anthropometric Outcomes in the MFFAPP Tanzania Efficacy Study.

Curr Dev Nutr 2019 Jun 10;3(6):nzz027. Epub 2019 Apr 10.

Departments of Food, Nutrition, Dietetics and Health, Kansas State University, Manhattan, KS.

Background: Fortified blended foods (FBFs) are micronutrient-fortified food aid products containing cereals and pulses. It has been suggested to reformulate FBFs to include whey protein concentrate, use alternative commodities (e.g., sorghum and cowpea), and utilize processing methods such as extrusion to produce them. The Micronutrient Fortified Food Aid Pilot Project (MFFAPP) efficacy study was designed to test the efficacy of complementary feeding of newly formulated FBFs.

Objectives: The aim of this study was to test the effectiveness of 5 newly formulated FBFs in combating iron deficiency anemia and vitamin A deficiency compared with traditionally prepared corn-soy blend plus (CSB+) and no intervention. A secondary aim was to determine the impact on underweight, stunting, wasting, and middle-upper arm circumference.

Methods: A 20-wk, partially randomized cluster study was completed. Two age groups (aged 6-23 and 24-53 mo) with hemoglobin status <10.3 g/dL, and weight-for-height scores >-3 were enrolled and assigned to diet groups. Biochemical and anthropometric measurements were collected at 0, 10, and 20 wk.

Results: Both hemoglobin concentrations and anemia ORs were significantly improved in all intervention groups except for CSB+ and the no-intervention groups at week 20. Only extruded corn-soy blend 14 and the no-intervention age groups failed to significantly decrease vitamin A deficiency risk ( < 0.04). There were no consistent significant differences among groups in anthropometric outcomes.

Conclusions: FBFs reformulated with sorghum, cowpea, corn, and soy significantly improved anemia and vitamin A deficiency ORs compared with week 0 and with no intervention. Although newly formulated FBFs did not significantly improve vitamin A deficiency or anemia compared with CSB+, CSB+ was the only FBF not to significantly improve these outcomes over the study duration. Our findings suggest that newly formulated sorghum- and cowpea-based FBFs are equally efficacious in improving these micronutrient outcomes. However, further FBF refinement is warranted. This trial was registered at clinicaltrials.gov as NCT02847962.
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http://dx.doi.org/10.1093/cdn/nzz027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535421PMC
June 2019

Effects on body composition and handgrip strength of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy: a randomised controlled trial.

J Nutr Sci 2019 16;8:e19. Epub 2019 May 16.

Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.

Lipid-based nutrient supplements (LNS) may be beneficial for malnourished HIV-infected patients starting antiretroviral therapy (ART). We assessed the effect of adding vitamins and minerals to LNS on body composition and handgrip strength during ART initiation. ART-eligible HIV-infected patients with BMI <18·5 kg/m were randomised to LNS or LNS with added high-dose vitamins and minerals (LNS-VM) from referral for ART to 6 weeks post-ART and followed up until 12 weeks. Body composition by bioelectrical impedance analysis (BIA), deuterium (H) diluted water (DO) and air displacement plethysmography (ADP), and handgrip strength were determined at baseline and at 6 and 12 weeks post-ART, and effects of LNS-VM LNS at 6 and 12 weeks investigated. BIA data were available for 1461, DO data for 479, ADP data for 498 and handgrip strength data for 1752 patients. Fat mass tended to be lower, and fat-free mass correspondingly higher, by BIA than by ADP or DO. At 6 weeks post-ART, LNS-VM led to a higher regain of BIA-assessed fat mass (0·4 (95 % CI 0·05, 0·8) kg), but not fat-free mass, and a borderline significant increase in handgrip strength (0·72 (95 % CI -0·03, 1·5) kg). These effects were not sustained at 12 weeks. Similar effects as for BIA were seen using ADP or DO but no differences reached statistical significance. In conclusion, LNS-VM led to a higher regain of fat mass at 6 weeks and to a borderline significant beneficial effect on handgrip strength. Further research is needed to determine appropriate timing and supplement composition to optimise nutritional interventions in malnourished HIV patients.
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http://dx.doi.org/10.1017/jns.2019.15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522867PMC
January 2020

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.

J Infect Dis 2019 06;220(1):46-56

London School of Hygiene and Tropical Medicine, London, United Kingdom.

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.
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http://dx.doi.org/10.1093/infdis/jiz070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548900PMC
June 2019

Growth Status, Inflammation, and Enteropathy in Young Children in Northern Tanzania.

Am J Trop Med Hyg 2019 01;100(1):192-201

International Food Policy Research Institute (IFPRI), Dakar, Senegal.

Recent evidence suggests that enteropathy of the gut due to environmental conditions (i.e., environmental enteropathy [EE]) in young children is negatively associated with linear growth. Using a case-control study design, we examined the potential determinants of stunting in stunted and non-stunted children 22-28 months of age. Potential determinants included inflammation biomarkers C-reactive protein, alpha-1-acid glycoprotein (AGP), and endotoxin-core antibody (EndoCAb) measured in serum samples; enteropathy markers alpha-1-antitrypsin, neopterin, myeloperoxidase (MPO) measured in stools samples; and demographic, health, feeding, and household characteristics. We also explored the determinants of EE by testing associations of composite EE scores and individual biomarkers with potential risk factors. Fifty-two percent of children ( = 310) were found to be stunted, and mean height-for-age scores (HAZ) were -1.22 (standard deviation [SD] ± 0.56) among non-stunted (control) children and -2.82 (SD ± 0.61) among stunted (case) children. Child HAZ was significantly ( < 0.05) and inversely associated with AGP, and child stunting was significantly positively associated ( < 0.05) with low dietary diversity, severe household hunger, and absence of soap in the household. Alpha-1-acid glycoprotein and EndoCAb concentrations were also significantly higher ( < 0.05) among children in households with no soap. Our study documented a seemingly localized cultural practice of young children (25%) being fed their dirty bathwater, which was associated with significantly higher concentrations of MPO ( < 0.05). Alpha-1-acid glycoprotein showed the most consistent associations with child growth and hygiene practices, but fecal EE biomarkers were not associated with child growth. The lack of retrospective data in our study may explain the null findings related to fecal EE biomarkers and child growth.
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http://dx.doi.org/10.4269/ajtmh.17-0720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335920PMC
January 2019

HIV treatment is associated with a two-fold higher probability of raised triglycerides: Pooled Analyses in 21 023 individuals in sub-Saharan Africa.

Glob Health Epidemiol Genom 2018 8;3. Epub 2018 May 8.

HART (Hypertension in Africa Research Team), North-West University, Potchefstroom, South Africa.

Background: Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TG) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations.

Methods: Pooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models.

Findings: Among 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51-2.77, I=45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies.

Interpretation: Evidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SSA.
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http://dx.doi.org/10.1017/gheg.2018.7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985947PMC
May 2018

Nutritional support to reduce mortality in patients with HIV?

Lancet HIV 2018 05 10;5(5):e202-e204. Epub 2018 Apr 10.

Department of Population Health, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.

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http://dx.doi.org/10.1016/S2352-3018(18)30047-XDOI Listing
May 2018

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.

Br J Nutr 2017 Mar 10;117(6):814-821. Epub 2017 Apr 10.

1London School of Hygiene & Tropical Medicine,London WC1E 7HT,UK.

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.
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http://dx.doi.org/10.1017/S0007114517000721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426318PMC
March 2017

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

BMC Infect Dis 2017 01 30;17(1):103. Epub 2017 Jan 30.

London School of Hygiene and Tropical Medicine, London, UK.

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/m) 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/m, 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.
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http://dx.doi.org/10.1186/s12879-017-2209-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282875PMC
January 2017

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

BMC Infect Dis 2016 10 12;16(1):562. Epub 2016 Oct 12.

Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.

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/m) 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.
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http://dx.doi.org/10.1186/s12879-016-1894-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062813PMC
October 2016

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

J Infect Dis 2016 Oct;214 Suppl 2:S75-82

Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, United Kingdom.

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.
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http://dx.doi.org/10.1093/infdis/jiw286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021242PMC
October 2016

Indoor Air Pollution and Delayed Measles Vaccination Increase the Risk of Severe Pneumonia in Children: Results from a Case-Control Study in Mwanza, Tanzania.

PLoS One 2016 10;11(8):e0160804. Epub 2016 Aug 10.

Department of Medicine, University of Cambridge, Cambridge, United Kingdom.

Background: Mortality due to severe pneumonia during childhood in resource-constrained settings is high, but data to provide basis for interventions to improve survival are limited. The objective of this study was to determine the risk factors for severe pneumonia in children aged under five years old in Mwanza, Tanzania.

Methods: We conducted a case-control study of children aged 2 to 59 months at Sekou-Toure regional hospital in Mwanza City, north-western, Tanzania from May 2013 to March 2014. Cases were children with severe pneumonia and controls were children with other illnesses. Data on demography, social-economical status, nutritional status, environmental factors, vaccination status, vitamin A supplementation and deworming, and nasopharyngeal carriage were collected and analysed using logistic regression.

Results: 117 patients were included in the study. Of these, 45 were cases and 72 controls. Cases were younger than controls, but there were no differences in social-economic or nutritional status between the two groups. In multiple regression, we found that an increased risk of severe pneumonia was associated with cooking indoors (OR 5.5, 95% CI: 1.4, 22.1), and delayed measles vaccination (OR 3.9, 95% CI: 1.1, 14.8). The lack of vitamin A supplementation in the preceding six month and Enterobacter spp nasopharyngeal carriage were not associated with higher risk of severe pneumonia. Age ≥24 months (OR 0.2, 95% CI: 0.04, 0.8) and not receiving antibiotics before referral (OR 0.3, 95% CI 0.1, 0.9) were associated with lower risk for severe pneumonia.

Conclusions: Indoor air pollution and delayed measles vaccination increase the risk for severe pneumonia among children aged below five years. Interventions to reduce indoor air pollution and to promote timely administration of measles vaccination are urgently needed to reduce the burden of severe pneumonia in children in Tanzania.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0160804PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979871PMC
August 2017

Pharmacokinetics of Isoniazid, Pyrazinamide, and Ethambutol in Newly Diagnosed Pulmonary TB Patients in Tanzania.

PLoS One 2015 26;10(10):e0141002. Epub 2015 Oct 26.

Department of Infectious Diseases, Odense University Hospital, Odense, Denmark; Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.

Exposure to lower-than-therapeutic levels of anti-tuberculosis drugs is likely to cause selection of resistant strains of Mycobacterium tuberculosis and treatment failure. The first-line anti-tuberculosis (TB) regimen consists of rifampicin, isoniazid, pyrazinamide, and ethambutol, and correct management reduces risk of TB relapse and development of drug resistance. In this study we aimed to investigate the effect of standard of care plus nutritional supplementation versus standard care on the pharmacokinetics of isoniazid, pyrazinamide and ethambutol among sputum smear positive TB patients with and without HIV. In a clinical trial in 100 Tanzanian TB patients, with or without HIV infection, drug concentrations were determined at 1 week and 2 months post initiation of anti-TB medication. Data was analysed using population pharmacokinetic modelling. The effect of body size was described using allometric scaling, and the effects of nutritional supplementation, HIV, age, sex, CD4+ count, weight-adjusted dose, NAT2 genotype, and time on TB treatment were investigated. The kinetics of all drugs was well characterised using first-order elimination and transit compartment absorption, with isoniazid and ethambutol described by two-compartment disposition models, and pyrazinamide by a one-compartment model. Patients with a slow NAT2 genotype had higher isoniazid exposure and a lower estimate of oral clearance (15.5 L/h) than rapid/intermediate NAT2 genotype (26.1 L/h). Pyrazinamide clearance had an estimated typical value of 3.32 L/h, and it was found to increase with time on treatment, with a 16.3% increase after the first 2 months of anti-TB treatment. The typical clearance of ethambutol was estimated to be 40.7 L/h, and was found to decrease with age, at a rate of 1.41% per year. Neither HIV status nor nutritional supplementations were found to affect the pharmacokinetics of these drugs in our cohort of patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0141002PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621059PMC
June 2016

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.

Br J Nutr 2015 Aug 16;114(3):387-97. Epub 2015 Jul 16.

Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine,Keppel Street,LondonWC1E 7HT,UK.

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.
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http://dx.doi.org/10.1017/S0007114515001920DOI Listing
August 2015

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

Appl Environ Microbiol 2015 Aug 15;81(15):4965-75. Epub 2015 May 15.

Department of Microbiology and Immunology, The University of Western Ontario, London, Ontario, Canada Department of Surgery, The University of Western Ontario, London, Ontario, Canada Canadian Centre for Human Microbiome and Probiotics, Lawson Health Research Institute, London, Ontario, Canada

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.
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http://dx.doi.org/10.1128/AEM.00780-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495201PMC
August 2015

Height as a prognostic marker for survival during antituberculous therapy.

Infect Dis (Lond) 2015 Jul 26;47(7):515-6. Epub 2015 Feb 26.

From the Department of Nutrition, Exercise and Sports, University of Copenhagen , Frederiksberg , Denmark.

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http://dx.doi.org/10.3109/00365548.2015.1006676DOI Listing
July 2015

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

BMC Med 2015 Jan 28;13:17. Epub 2015 Jan 28.

Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.

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.
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http://dx.doi.org/10.1186/s12916-014-0253-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4308881PMC
January 2015

Effects on anthropometry and appetite of vitamins and minerals given in lipid nutritional supplements for malnourished HIV-infected adults referred for antiretroviral therapy: results from the NUSTART randomized controlled trial.

J Acquir Immune Defic Syndr 2015 Apr;68(4):405-12

*Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom; †Mwanza Research Centre, National Institute for Medical Research, Mwanza, Tanzania; ‡University Teaching Hospital, Lusaka, Zambia; §Vanderbilt University School of Medicine, Nashville, TN; ‖Department of Gastroenterology, Queen Mary University of London, London, United Kingdom; and ¶Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.

Background: The evidence base for effects of nutritional interventions for malnourished HIV-infected patients starting antiretroviral therapy (ART) is limited and inconclusive.

Objective: We hypothesized that both vitamin and mineral deficiencies and poor appetite limit weight gain in malnourished patients starting ART and that vitamin and mineral supplementation would improve appetite and permit nutritional recovery.

Design: The randomized controlled Nutritional Support for Africans Starting Antiretroviral Therapy trial was conducted in Mwanza, Tanzania, and Lusaka, Zambia. ART-naive adults referred for ART and with body mass index <18.5 kg/m received lipid-based nutritional supplements either without (LNS) or with added vitamins and minerals (LNS-VM), beginning before ART initiation. Participants were given 30 g/d LNS from recruitment until 2 weeks after starting ART and 250 g/d from weeks 2 to 6 of ART.

Results: Of 1815 patients recruited, 365 (20%) died during the study and 813 (45%) provided data at 12 weeks. Controlling for baseline values, anthropometric measures were consistently higher at 12-week ART in the LNS-VM than in the LNS group but statistically significant only for calf and mid-upper arm circumferences and triceps skinfold. Appetite did not differ between groups. Using piecewise mixed-effects quadratic models including all patients and time points, the main effects of LNS-VM were seen after starting ART and were significant for weight, body mass index, and mid-upper arm circumference.

Conclusions: Provision of high levels of vitamins and minerals to patients referred for ART, delivered with substantial macronutrients, increased nutritional recovery but did not seem to act through treatment group differences in appetite.
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http://dx.doi.org/10.1097/QAI.0000000000000483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337586PMC
April 2015

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

BMC Infect Dis 2014 Jun 5;14:309. Epub 2014 Jun 5.

Department of Clinical Science, Infection, Faculty of Medicine and Dentristry, University of Bergen, Bergen, Norway.

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 (β = 0.4, P = 0.02; 95% CI [0.06-0.66]) and neutrophil counts (β = 0.9, P = 0.02; 95% CI [0.12-1.64]) and had lower BMI score (β = -1.0, P = 0.04; 95% CI[-1.89 - (-0.03)]). LAM11_ZWE ('modern') isolates induced higher levels of CRP (β = 24.4, P = 0.05; 95% CI[0.24-48.63]) and neutrophil counts (β = 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.
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http://dx.doi.org/10.1186/1471-2334-14-309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057905PMC
June 2014

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

Public Health Nutr 2015 Mar 1;18(4):742-51. Epub 2014 May 1.

1Faculty of Epidemiology and Population Health,London School of Hygiene and Tropical Medicine,Keppel Street,London WC1E 7HT,UK.

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.
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March 2015

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

Antimicrob Agents Chemother 2014 Jun 7;58(6):3468-74. Epub 2014 Apr 7.

Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.

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.).
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http://dx.doi.org/10.1128/AAC.02307-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068463PMC
June 2014

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

Scand J Infect Dis 2014 May 12;46(5):384-91. Epub 2014 Mar 12.

Department of Nutrition, Exercise and Sports, University of Copenhagen , Denmark.

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.
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http://dx.doi.org/10.3109/00365548.2014.885657DOI Listing
May 2014
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