Person:

Duggan, Christopher

Background: Experimental data suggest a role for iron in the course of tuberculosis (TB) infection, but there is limited evidence on the potential effects of iron deficiency or iron overload on the progression of TB disease in humans. The aim of the present analysis was to examine the association of iron status with the risk of TB progression and death. Methodology/Principal Findings: We analyzed plasma samples and data collected as part a randomized micronutrient supplementation trial (not including iron) among HIV-infected and HIV-uninfected TB patients in Dar es Salaam, Tanzania. We prospectively related baseline plasma ferritin concentrations from 705 subjects (362 HIV-infected and 343 HIV-uninfected) to the risk of treatment failure at one month after initiation, TB recurrence and death using binomial and Cox regression analyses. Overall, low (plasma ferritin<30 (\mu)g/L) and high (plasma ferritin>150 (\mu)g/L for women and>200 (\mu)g/L for men) iron status were seen in 9% and 48% of patients, respectively. Compared with normal levels, low plasma ferritin predicted an independent increased risk of treatment failure overall (adjusted RR = 1.95, 95% CI: 1.07 to 3.52) and of TB recurrence among HIV-infected patients (adjusted RR = 4.21, 95% CI: 1.22 to 14.55). High plasma ferritin, independent of C-reactive protein concentrations, was associated with an increased risk of overall mortality (adjusted RR = 3.02, 95% CI: 1.95 to 4.67). Conclusions/Significance: Both iron deficiency and overload exist in TB patients and may contribute to disease progression and poor clinical outcomes. Strategies to maintain normal iron status in TB patients could be helpful to reduce TB morbidity and mortality.

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

HIV infection can contribute to disturbances in both linear growth and weight gain in early childhood, with disturbances often apparent as early as 3 mo of age. There is little evidence for a difference in the early growth of HIV-exposed but uninfected children compared to healthy controls. Owing to the close association of growth with immune function and clinical progression, an understanding of growth patterns may be an important tool to ensure the provision of appropriate care to HIV-infected and exposed children. Timely growth monitoring may be used to improve the clinical course and quality of life of these children.

Prenatal iron supplementation may improve pregnancy outcomes and decrease the risk of child mortality. However, little is known about the importance of postnatal maternal iron status for child health and survival, particularly in the context of HIV infection. We examined the association of maternal anemia and hypochromic microcytosis, an erythrocyte morphology consistent with iron deficiency, with child health and survival in the first two to five years of life. Repeated measures of maternal anemia and hypochromic microcytosis from 840 HIV-positive women enrolled in a clinical trial of vitamin supplementation were prospectively related to child mortality, HIV infection, and CD4 T-cell count. Median duration of follow-up for the endpoints of child mortality, HIV infection and CD4 cell count was 58, 17 and 23 months, respectively. Maternal anemia and hypochromic microcytosis were associated with greater risk of child mortality (HR for severe anemia=2.58, 95% CI: 1.66-4.01, P trend<0.0001; HR for severe hypochromic microcytosis=2.36, 95% CI: 1.27-4.38, P trend=0.001). Maternal anemia was not significantly associated with greater risk of child HIV infection (HR for severe anemia=1.46, 95% CI: 0.91, 2.33, P trend=0.08) but predicted lower CD4 T-cell counts among HIV-uninfected children (difference in CD4 T-cell count/μL for severe anemia:-93, 95% CI: -204-17, P trend=0.02). The potential child health risks associated with maternal anemia and iron deficiency may not be limited to the prenatal period. Efforts to reduce maternal anemia and iron deficiency during pregnancy may need to be expanded to include the postpartum period.

BACKGROUND: We assembled a prospective cohort of 3144 children less than 15 years of age initiating antiretroviral therapy (ART) in Dar es Salaam, Tanzania. METHODS: The relationships of nutritional status and other baseline characteristics in relation to mortality were examined using Cox proportional hazards model. RESULTS: Compared with children with weight for age (WAZ) > -1, those with WAZ ≤ -2 to < -3 had a nearly double risk of death (relative risk [RR], 1.85; 95% confidence interval [CI], 1.10-3.11), and among those with WAZ ≤ -3, the risk more than tripled (RR, 3.36; 95% CI, 2.12-5.32). Other baseline risk factors for overall mortality included severe anemia (P < .001), severe immune suppression (P = .02), history of tuberculosis (P = .01), opportunistic infections (P < .001), living in the poorest district (P < .001), and advanced World Health Organization stage (P = .003). CONCLUSIONS: To sustain the obtained benefit of ART in this setting, interventions to improve nutritional status may be used as an adjunct to ART.

This paper examines predictors of breastfeeding cessation among a cohort of human immunodeficiency virus (HIV)-infected women. This was a prospective follow-up study of HIV-infected women who participated in a randomized micronutrient supplementation trial conducted in Dar es Salaam, Tanzania. 795 HIV-infected Tanzanian women with singleton newborns were utilized from the cohort for this analysis. The proportion of women breastfeeding declined from 95% at 12 months to 11% at 24 months. The multivariate analysis showed breastfeeding cessation was significantly associated with increasing calendar year of delivery from 1995 to 1997 [risk ratio (RR), 1.36; 95% confidence interval (CI) 1.13–1.63], having a new pregnancy (RR 1.33; 95% CI 1.10–1.61), overweight [body mass index (BMI) ≥25 kg m−2; RR 1.37; 95% CI 1.07–1.75], underweight (BMI <18.5 kg m−2; RR 1.29; 95% CI 1.00–1.65), introduction of cow’s milk at infant’s age of 4 months (RR 1.30; 95% CI 1.04–1.63). Material and social support was associated with decreased likelihood of cessation (RR 0.83; 95% CI 0.68–1.02). Demographic, health and nutritional factors among women and infants are associated with decisions by HIV-infected women to cease breastfeeding. The impact of breastfeeding counselling programs for HIV-infected African women should consider individual maternal, social and health contexts.