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Background Body composition changes may explain the rapid increase in blood pressure (BP) in people with HIV (PWH) during the first year of antiretroviral therapy. Methods We analyzed data from a cohort of PWH and HIV-uninfected adults from the same communities in Mwanza, Tanzania. Blood pressure (BP, mm Hg) and body composition data were collected at baseline and 12-month follow-up. We used multivariable linear regression to compare BP changes in PWH and HIV-uninfected adults, and the relationship between changes in body composition and changes in BP. Results BP data were available for 640 PWH and 299 HIV-uninfected adults. Sixty-four percent were women and the mean age was 38 years. In PWH, systolic BP (SBP) increased (114–118) whereas SBP decreased (125–123) in HIV-uninfected participants. Fat mass increased by 1.6 kg on average in PWH and was strongly associated with the change in BP (P < 0.001). The greater increase in SBP in PWH was partly explained by the lower baseline SBP but PWH still experienced a 2.2 (95% CI: 0.3–4.2) greater increase in SBP after adjustment. Weight gain partially mediated the relationship between HIV and SBP increase in PWH; a 1-kg increase in fat mass accounted for 0.8 (95% CI: 0.6–1.1) increase in SBP. Conclusions Weight and fat mass increase rapidly in PWH during the first 12 months of antiretroviral therapy and contribute to a rapid increase in SBP. Interventions to prevent excessive increase in fat mass are needed for PWH.

Purpose of Review HIV testing is the critical first step to direct people living with HIV (PLWH) to treatment. However, progress is still being made towards the UNAIDS benchmark of 95% of PLWH knowing their status by 2030. Here, we discuss recent interventions to improve HIV testing uptake in global settings. Recent Findings Successful facility-based HIV testing interventions involve couples and index testing, partner notification, and offering of incentives. Community-based interventions such as home-based self-testing, mobile outreach, and hybrid approaches have improved HIV testing in low-resource settings and among priority populations. Partnerships with trusted community leaders have also increased testing among populations disproportionally impacted by HIV. Summary Recent HIV testing interventions span a breadth of facility- and community-based approaches. Continued research is needed to engage men in sub-Saharan Africa, people who inject drugs, and people who avoid biomedical care. Interventions should consider supporting linkage to care for newly diagnosed PLWH.

This study aimed to investigate sickle cell trait (SCT) associations with physical activity, markers of insulin secretion and resistance, and glucose among people living with HIV infection (PLWH), both antiretroviral therapy (ART) naïve and experienced, and HIV-uninfected adults. This was a cross-sectional study conducted in Mwanza, north-western Tanzania. We used data of 668 participants attained from two sub-studies of CICADA study. Mean age was 40 (SD 11.5) years, 402 (61.7 %) were females and 157 (24.1 %) had SCT. PLWH were 422 (64.7 %), of these, 80 (18.9 %) were on ART. People with SCT had higher risk of having an isolated β-cell dysfunction compared to those without SCT (RRR=1.82, CI: 1.10, 3.01, P=0.02). People with SCT but without HIV infection had lower average acceleration on the trunk longitudinal axis (ACCx) and higher level of self-reported physical activity. 30 min oral glucose tolerance test among PLWH on ART was higher in those with SCT compared to those without SCT. People with SCT are at higher risk of having β-cell dysfunction and those with SCT on ART are at more risk of developing diabetes. Future studies to investigate the interaction between SCT and HIV/ART on risk of diabetes should be considered.

OBJECTIVE Measuring internalized stigma is critical to understanding its impact on the health and quality of life of people living with HIV (PLHIV). The aim of this study was to assess the performance of the Internalized AIDS-Related Stigma Scale (IA-RSS). DESIGN Secondary analysis of the six-item IA-RSS was conducted using data from four cross-sectional surveys implemented in Cambodia (n = 1207), the Dominican Republic (n = 891), Uganda (n = 391) and Tanzania (n = 529) between 2018 and 2019. METHODS IA-RSS scale item distribution was described. Multivariate regression models measured correlations between the IA-RSS and depression, antiretroviral therapy (ART) use and viral suppression. Confirmatory factor analysis assessed IA-RSS reliability and performance through analysis of standardized factor loadings and conditional probabilities of scale items. Analysis of qualitative interviews with PLHIV explored acceptability of IA-RSS item content. RESULTS Mean IA-RSS scores (possible 0-6) ranged from 2.06 (Uganda) to 3.84 (Cambodia), and internal consistency was more than 0.70 in each country (Kuder-Richardson 20), ranging from 0.71 to 0.83. Higher IA-RSS scores were strongly correlated with depression in (P

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 (eGFR2) 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.

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

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 and categorized as: 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 7.8-11.1 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.

BackgroundThe 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.MethodsThis 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.ResultsOverall 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).ConclusionsThe 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.

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.

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 2were 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 (2H) diluted water (D2O) and air displacement plethysmography (ADP), and handgrip strength were determined at baseline and at 6 and 12 weeks post-ART, and effects of LNS-VMv.LNS at 6 and 12 weeks investigated. BIA data were available for 1461, D2O 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 D2O. 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 D2O 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.

Background\ud Cryptococcal meningitis (CM) causes 10-20% of HIV-related deaths in Africa. We performed a phase-II non-inferiority trial examining the Early Fungicidal Activity (EFA) of three short-course, high-dose liposomal amphotericin B (L-AmB) regimens for CM in Tanzania and Botswana.\ud Method\ud HIV-infected adults with CM were randomized to: (i) L-AmB 10mg/kg day 1 (single dose); (ii) L-AmB 10mg/kg day 1, 5mg/kg day 3 (two doses); (iii) L-AmB 10mg/kg day 1, 5 mg/kg days 3 and 7 (three doses); (iv) standard 14-day L-AmB 3mg/kg/day (control); all given with fluconazole 1200mg/day for 14 days. Primary endpoint was mean rate of clearance of cerebrospinal fluid (CSF) cryptococal infection (EFA). Non-inferiority was defined as an upper limit of the two-sided 95% confidence interval (CI) of difference in EFA between intervention and control less than 0.2 log10CFU/ml/day.\ud Results\ud 80 participants were enrolled. EFA for daily L-AmB was -0.41 (standard deviation 0.11, n=17) log10CFU/mL/day. Difference in mean EFA from control was -0.11 (95%CI -0.29,0.07) log10CFU/mL/day faster with single dose (n=16); -0.05 (95%CI -0.20,0.10) log10CFU/mL/day faster with two doses (n=18); and -0.13 (95%CI -0.35,0.09) log10CFU/mL/day faster with three doses (n=18). EFA in all short-course arms was non-inferior to control at the predefined non-inferiority margin. Overall 10-week mortality was 29% (n=23) with no statistical difference between arms. All arms were well tolerated.\ud Conclusions\ud Single dose 10mg/kg L-AmB was well tolerated and led to non-inferior EFA compared to 14 days of 3mg/kg/d L-AmB in HIV-associated CM. Induction based on single 10mg/kg L-AmB dose is being taken forward to a phase-III clinical endpoint trial.

IntroductionHemoglobin 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.MethodsBlood 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).ResultsThe 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.ConclusionsHbA1c 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.

INTRODUCTION: Contrasting findings have been published regarding the effect of human immunodeficiency virus (HIV) on tuberculosis (TB) drug pharmacokinetics (PK). OBJECTIVES: The aim of this systematic review was to investigate the effect of HIV infection on the PK of the first-line TB drugs (FLDs) rifampicin, isoniazid, pyrazinamide and ethambutol by assessing all published literature. METHODS: Searches were performed in MEDLINE (through PubMed) and EMBASE to find original studies evaluating the effect of HIV infection on the PK of FLDs. The included studies were assessed for bias and clinical relevance. PK data were extracted to provide insight into the difference of FLD PK between HIV-positive and HIV-negative TB patients. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and its protocol was registered at PROSPERO (registration number CRD42017067250). RESULTS: Overall, 27 studies were eligible for inclusion. The available studies provide a heterogeneous dataset from which consistent results could not be obtained. In both HIV-positive and HIV-negative TB groups, rifampicin (13 of 15) and ethambutol (4 of 8) peak concentration (Cmax) often did not achieve the minimum reference values. More than half of the studies (11 of 20) that included both HIV-positive and HIV-negative TB groups showed statistically significantly altered FLD area under the concentration-time curve and/or Cmax for at least one FLD. CONCLUSIONS: HIV infection may be one of several factors that reduce FLD exposure. We could not make general recommendations with respect to the role of dosing. There is a need for consistent and homogeneous studies to be conducted.

BACKGROUND: There is little information about serum phosphate levels among patients with pulmonary tuberculosis (TB) and HIV infection.OBJECTIVE: We aimed to assess the role of TB, HIV, inflammation and other correlates on serum phosphate levels.METHODS: A cross-sectional study was conducted among TB patients and age- and sex-matched non-TB controls. Pulmonary TB patients were categorized as sputum -negative and -positive, based on culture. Age- and sex-matched non-TB controls were randomly selected among neighbours to sputum-positive TB patients. Data on age, sex, alcohol and smoking habits were obtained. HIV status, serum phosphate, and the acute phase reactants C-reactive protein (serum CRP) and α1-acid glycoprotein (serum AGP) were determined. Linear regression analysis was used to identify correlates of serum phosphate.RESULTS: Of 1605 participants, 355 (22.1%) were controls and 1250 (77.9%) TB patients, of which 9.9% and 50.4% were HIV-infected. Serum phosphate was determined before start of TB treatment in 44%, and 1-14 days after start of treatment in 56%. Serum phosphate was up to 0.10 mmol/L higher 1-3 days after start of TB treatment, and lowest 4 days after treatment, after which it increased. In multivariable analysis, TB patients had 0.09 (95% CI: 0.05; 0.13) mmol/L higher serum phosphate than controls, and those with HIV had 0.05 (95% CI: 0.01; 0.08) mmol/L higher levels than those without. Smoking was also a positive correlate of serum phosphate, whereas male sex and age were negative correlates.CONCLUSION: While HIV and TB are associated with higher serum phosphate, our data suggest that TB treatment is followed by transient reductions in serum phosphate, which may reflect hypophosphataemia in some patients.

BACKGROUND/OBJECTIVES: Gains in fat mass and lean mass during tuberculosis (TB) treatment may determine functional recovery and survival; yet, data are scarce. We aimed to assess predictors of fat and fat-free mass during 2 months of intensive TB treatment in a cohort in Mwanza, Tanzania.SUBJECTS/METHODS: Fat and fat-free mass were determined at the start of TB treatment and repeated after 2 months using the deuterium dilution technique. Gains in fat and fat-free mass were determined and predictors assessed using regression analysis.RESULTS: Data for 116 patients were available at baseline and during follow-up. Of these, 38.8% were females, mean age was 37.3 (s.d. 13.5) years, 69% (81) had sputum-positive TB, 45.7% (53) were HIV infected and 25% (29) were current smokers. The mean weight gain was 3.3 kg (95% confidence interval: 2.7; 3.8), and it did not differ by sex. However, compared with females, males had 1.0 (0.4; 1.6) kg/m(2) lower fat mass but 0.7 (0.2; 1.3) kg/m(2) higher fat-free mass gain. Current smoking was associated with higher fat mass (0.7 kg/m(2), 0.04; 1.4) but lower fat-free mass (-0.5 kg/m(2), -1.2; 0.07) gain. Among HIV-infected patients, antiretroviral therapy (ART) led to a lower fat gain (-1.2 kg/m(2), -2.2; -0.2) but to a higher fat-free mass among sputum-negative (2.9 kg/m(2), 0.8; 5.1) but not sputum-positive patients.CONCLUSIONS: During intensive phase of TB treatment, sex, smoking and ART were predictors of body composition. Larger studies are needed to further understand predictors of body composition during recovery, to help design interventions to improve treatment outcomes.

BACKGROUND/OBJECTIVES: The effects of inflammation on nutritional rehabilitation after starting antiretroviral therapy (ART) are not well understood. We assessed the relationship between inflammation and body composition among patients enrolled in the Nutritional Support for African Adults Starting Antiretroviral therapy (NUSTART) trial in Tanzania and Zambia from 2011 to 2013. SUBJECTS/METHODS: HIV-infected, ART-eligible adults with body mass index (BMI) of

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

Objective Diabetes is associated with pulmonary tuberculosis (TB), possibly due to impaired immunity, and diabetes may exacerbate the clinical manifestations of TB. Our aim was to assess the role of diabetes in the clinical manifestations of TB. Methods We studied 1250 patients with pulmonary TB in an urban population in a cross-sectional study in Tanzania. All participants were tested for diabetes and HIV co-infection, and TB culture intensity was assessed. Levels of white blood cells, haemoglobin, acute phase reactants, CD4 count and HIV viral load were measured, and a qualitative morbidity questionnaire was used to identify the prevalence of disease-related symptoms. Results Tuberculosis patients with diabetes had a higher neutrophil count (B 0.5 × 109 cells/l, 95% CI 0.2; 0.9, P = 0.001) than non-diabetic TB patients. Serum C-reactive protein (B 18.8 mg/l, CI 95% 8.2; 29.4, P = 0.001) and alpha-1-acid glycoprotein (B 0.2 g/l, CI 95% 0.03; 0.3, P = 0.02) were similarly higher in patients with diabetes. Diabetes did not affect culture intensity or HIV status, but self-reported fever was three times higher among participants with diabetes than in those without diabetes (OR 2.9, CI 95% 1.5; 5.7, P = 0.002). Conclusion Diabetes is associated with small changes in the manifestations of TB, but may have little clinical significance. Objectif: L’association entre le diabete et la tuberculose (TB) pulmonaire est probablement liee a un deficit immunitaire et le diabete peut aggraver les manifestations cliniques de la TB. Notre objectif etait d’evaluer le role du diabete dans les manifestations cliniques de la TB. Methodes: Nous avons etudie 1250 patients atteints de TB pulmonaire dans une population urbaine dans le cadre d’une etude transversale en Tanzanie. Tous les participants ont ete testes pour le diabete et la coinfection VIH, et le rendement de la culture de TB a eteevalue. Les taux de globules blancs, l’hemoglobine, les reactants de phase aigue, la numeration des CD4 et la charge virale VIH ont ete mesures. Un questionnaire qualitatif sur la morbidite a ete utilise pour determiner la prevalence des symptomes lies a la maladie. Resultats: Les patients TB diabetiques avaient un nombre plus eleve de neutrophiles (B 0,5 x 109 cellules/L, IC95%: 0,2 - 0,9; p = 0,001) que les patients TB non-diabetiques. Le CRP (B 18,8 mg/L, IC95%: 8,2 - 29,4; p = 0,001) et AGP (B 0,2 g/L, IC95%: 0,03 - 0,3; p = 0,02) seriques etaient aussi plus eleves chez les patients diabetiques. Le diabete n’avait pas d’influence sur le rendement de la culture ou le statut VIH, mais la fievre auto-declaree etait trois fois plus elevee chez les patients atteints de diabete que chez ceux sans diabete (OR: 2,9, IC95%: 1,5 - 5,7; p = 0,002). Conclusion: Le diabete est associea de petits changements dans les manifestations de la TB, mais pourrait n’avoir que peu de signification clinique. Objetivo: La diabetes esta asociada con la tuberculosis (TB) pulmonar, posiblemente debido a una inmunidad comprometida, y puede exacerbar las manifestaciones clinicas de la TB. Nuestro objetivo era evaluar el papel de la diabetes en las manifestaciones clinicas de la TB. Metodos: Hemos estudiado a 1250 pacientes con TB pulmonar durante un estudio crosseccional en poblacion urbana de Tanzania. A todos los participantes se les realizaron pruebas para diabetes y VIH, y se evaluo la intensidad del cultivo de TB. Se midieron los niveles de leucocitos, hemoglobina, reactivos de fase aguda, conteo de CD4 y carga viral de VIH, y se utilizo un cuestionario cualitativo de morbilidad para identificar la prevalencia de los sintomas relacionados con la enfermedad. Resultados: Los pacientes con TB y diabetes tenian un mayor conteo de neutrofilos (B 0.5 × 109 celulas/L, 95% CI 0.2;0.9, p = 0.001) que los pacientes no diabeticos-TB. La proteina C-reactiva en suero (B 18.8 mg/L, IC 95% 8.2; 29.4, p = 0.001) y la alfa-1 glicoproteina acida (B 0.2 g/L, IC 95% 0.03;0.3, p = 0.02) eran igualmente altos en pacientes con diabetes. La diabetes no afectaba la intensidad de cultivo o el estatus de VIH, pero la fiebre autoreportada era tres veces mayor entre los participantes con diabetes que entre aquellos sin diabetes (OR 2.9, IC 95% 1.5; 5.7, p = 0.002). Conclusion: La diabetes esta asociada con pequenos cambios en las manifestaciones de la TB, pero pueden tener poco significado clinico.

Undernutrition is common among tuberculosis (TB) patients. The objective of this study was to assess the effect of multi-micronutrient supplementation during TB treatment on weight, body composition, and handgrip strength. A total of 865 patients with smear-positive (PTB+) or -negative (PTB-) pulmonary TB were randomly allocated to receive a daily biscuit with or without multi-micronutrients for 60 d during the intensive phase of TB treatment. Weight, arm fat area, arm muscle area, and handgrip strength were assessed at baseline and after 2 and 5 mo. At 2 mo, the multi-micronutrient supplementation led to a higher handgrip gain (1.22 kg; 95% CI = 0.50, 1.94; P = 0.001) but had no effects on other outcomes. The effects of multi-micronutrient supplementation were modified by HIV infection (P-interaction = 0.002). Among HIV- patients, multi-micronutrient supplementation increased weight gain by 590 g (95% CI = -40, 1210; P = 0.07) and handgrip strength by 1.6 kg (95% CI = 0.78, 2.47; P < 0.001), whereas among HIV+ patients, it reduced weight gain by 1440 g (95% CI = 290, 2590; P = 0.002) and had no effect on handgrip strength (0.07 kg; 95% CI = -1.30, 1.46; P = 0.91). The reduced weight gain among HIV+ patients receiving multi-micronutrient supplementation seemed to be explained by a higher proportion of patients reporting fever. At 5 mo, the effects on weight were sustained, whereas there was no effect on handgrip strength. In conclusion, multi-micronutrient supplementation given as a biscuit is beneficial among HIV- PTB patients and may be recommended to TB programs. More research is needed to develop an effective supplement for HIV+ PTB patients.

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.

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 ( C max ) and area under the concentration-time curve from 0 to 24 h (AUC 0–24 ) of 5.6 μg/ml and 28.6 μg · h/ml, respectively. HIV-coinfected patients on nutritional supplementation achieved higher C max and AUC 0–24 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.)

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.