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.

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

Objective

To describe the burden of pediatric tuberculosis (TB) in a human immunodeficiency virus (HIV)-infected population and explore the demographic and clinical factors associated with the occurrence of pediatric TB.

Design

Longitudinal analysis of a cohort of HIV-infected children.

Methods

The endpoint of the study was clinically diagnosed TB. Cox proportional hazard regression was used to explore the predictors of incident TB among HIV-infected children under age 15 years after enrollment into the HIV program.

Results

The cohort comprised of 5040 children [median age: 5 years, interquartile range (IQR): 1–9 years]. During a median follow-up of 0.8 (IQR: 0.1–2.5) years, 376 out of 5040 children met the case definition for TB. The overall incidence of TB was 5.2/100 person-years. In multivariate analyses, older age at enrollment [relative risk (RR): 1.7, 95%, confidence interval (CI): 1.5–1.8], severe wasting (RR: 1.8, 95% CI: 1.3 –2.5), severe immune-suppression (RR: 2.6, 95% CI: 1.8–3.8), anemia (RR: 1.4, 95% CI: 1.0–1.9) and World Health Organization (WHO) stage IV (RR: 4.5, 95% CI: 2.4–8.5) were all independently associated with a higher risk of TB. In addition, the use of antiretroviral drugs for more than 180 days reduced the risk of TB by 70% (RR: 0.3, 95% CI: 0.2–0.4).

Conclusions

ART use is strongly associated with a reduced risk of tuberculosis among HIV-infected children, and should therefore be included in HIV care and treatment programs. Trials of interventions designed to improve the nutritional and hematologic status of these children should also be performed.

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.

Introduction: Anaemia is prevalent among children born to HIV-positive women, and it is associated with adverse effects on cognitive and motor development, growth, and increased risks of morbidity and mortality. Objective: To examine the effect of daily multivitamin supplementation on haematologic status and mother-to-child transmission (MTCT) of HIV through breastfeeding. Methods: A total of 2387 infants born to HIV-positive women from Dar es Salaam, Tanzania were enrolled in a randomized, double-blind, placebo-controlled trial, and provided a daily oral supplement of multivitamins (vitamin B complex, C and E) or placebo at age 6 weeks for 24 months. Among them, 2008 infants provided blood samples and had haemoglobin concentrations measured at baseline and during a follow-up period. Anaemia was defined as haemoglobin concentrations<11 g/dL and severe anaemia<8.5 g/dL. Results: Haemoglobin concentrations among children in the treatment group were significantly higher than those in the placebo group at 12 (9.77 vs. 9.64 g/dL, p=0.03), 18 (9.76 vs. 9.57 g/dL, p=0.004), and 24 months (9.93 vs. 9.75 g/dL, p=0.02) of follow-up. Compared to those in the placebo group, children in the treatment group had a 12% lower risk of anaemia (hazard ratio (HR): 0.88; 95% CI: 0.79–0.99; p=0.03). The treatment was associated with a 28% reduced risk of severe anaemia among children born to women without anaemia (HR: 0.72; 95% CI: 0.56–0.92; p=0.008), but not among those born to women with anaemia (HR: 1.10; 95% CI: 0.79–1.54; p=0.57; p for interaction=0.007). One thousand seven hundred fifty three infants who tested HIV-negative at baseline and had HIV testing during follow-up were included in the analysis for MTCT of HIV. No association was found between multivitamin supplements and MTCT of HIV. Conclusions: Multivitamin supplements improve haematologic status among children born to HIV-positive women. Further trials focusing on anaemia among HIV-exposed children are warranted in the context of antiretroviral therapy.

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.

Background

Vitamin D may help prevent adverse pediatric outcomes, including infectious diseases and growth failure, based on its role in immune and metabolic functions. We examined the association of maternal vitamin D status and pediatric health outcomes in children born to HIV-infected women.

Methods

Vitamin D status was determined in 884 HIV-infected pregnant women at 12 to 27 weeks of gestation in a trial of vitamin supplementation (not including vitamin D) in Tanzania. Information on child morbidities, anemia and hypochromic microcytosis, and anthropometry was recorded through monthly clinic visits. Generalized estimated equations and Cox proportional hazards models were used to assess the relationships of outcomes with maternal vitamin D status.

Results

A total of 39% of women had low vitamin D levels (<32 ng/mL). Children born to women with low vitamin D status were 1.11 times more likely to report cough during follow-up (RR: 1.11; 95% CI: 1.02-1.21). No significant associations were noted for other respiratory symptoms, diarrhea, or anemia outcomes. Low maternal vitamin D status was associated with significantly increased risk of stunting (height-for-age z-score <-2; RR: 1.29; 95% CI: 1.05-1.59) and underweight (weight-for-age z-score <-2; RR: 1.33; 95% CI: 1.03-1.71).

Conclusions

Maternal vitamin D status may be an important risk factor for respiratory infections, and ensuring optimal growth in HIV-exposed children.

Objective

We examined the relationships between exclusive breast-feeding and the risks of respiratory, diarrhoea and nutritional morbidities during the first 2 years of life among children born to women infected with HIV-1.

Design

We prospectively determined the incidence of respiratory illnesses, diarrhoea, fever, hospitalizations, outpatient visits and nutritional morbidities. Generalized estimating equations were used to estimate the relative risks for morbidity episodes and Cox proportional hazards models to estimate the incidence rate ratios of nutritional morbidities.

Setting

Dar es Salaam, Tanzania.

Subjects

The sample consisted of 666 children born to HIV-infected women.

Results

The 666 children were followed for 2 years. Exclusive breast-feeding was associated with lower risk for cough (rate ratio (RR) = 0·49, 95 % CI 0·41, 0·60, P < 0·0001), cough and fever (RR = 0·44, 95 % CI 0·32, 0·60, P < 0·0001) and cough and difficulty breathing or refusal to feed (RR = 0·31, 95 % CI 0·18, 0·55, P < 0·0001). Exclusive breast-feeding was also associated with lower risk of acute diarrhoea, watery diarrhoea, dysentery, fever and outpatient visits during the first 6 months of life, but showed no effect at 6–24 months of life. Exclusive breast-feeding did not significantly reduce the risks of nutritional morbidities during the first 2 years of life.

Conclusions

Exclusive breast-feeding is strongly associated with reductions in the risk of respiratory and diarrhoea morbidities during the first 6 months of life among children born to HIV-infected women.