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ABSTRACT: BACKGROUND: The development of low-cost point-of-care technologies to improve HIV treatment is a major focus of current research in resource-limited settings. OBJECTIVE: We assessed associations of body mass index (BMI; in kg/m(2)) at antiretroviral therapy (ART) initiation and weight change after 1 mo of treatment with mortality, morbidity, and CD4 T cell reconstitution. DESIGN: A prospective cohort of 3389 Tanzanian adults initiating ART enrolled in a multivitamin trial was followed at monthly clinic visits (median: 19.7 mo). Proportional hazard models were used to analyze mortality and morbidity associations, whereas generalized estimating equations were used for CD4 T cell counts. RESULTS: The median weight change at 1 mo of ART was +2.0% (IQR: -0.4% to +4.6%). The association of weight loss at 1 mo with subsequent mortality varied significantly by baseline BMI (P = 0.011). Participants with ≥2.5% weight loss had 6.43 times (95% CI: 3.78, 10.93 times) the hazard of mortality compared with that of participants with weight gains ≥2.5%, if their baseline BMI was <18.5 but only 2.73 times (95% CI: 1.49, 5.00 times) the hazard of mortality if their baseline BMI was ≥18.5 and <25.0. Weight loss at 1 mo was also associated with incident pneumonia (P = 0.002), oral thrush (P = 0.007), and pulmonary tuberculosis (P < 0.001) but not change in CD4 T cell counts (P > 0.05). CONCLUSIONS: Weight loss as early as 1 mo after ART initiation can identify adults at high risk of adverse outcomes. Studies identifying reasons for and managing early weight loss are needed to improve HIV treatment, with particular urgency for malnourished adults initiating ART. The parent trial was registered at clinicaltrials.gov as NCT00383669.
American Journal of Clinical Nutrition 05/2013; · 6.67 Impact Factor
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ABSTRACT: Vitamin D is essential for bone development and may also play an integral role in control of intracellular pathogens. Serum 25-hydroxyvitamin D levels were assessed at 6 months of age for 191 HIV-exposed uninfected infants enrolled in a trial of multivitamins (not including vitamin D) in Tanzania. A total of 66 infants (34.6%) were classified as vitamin D deficient (<20 ng/ml), 93 (48.7%) as vitamin D insufficient (20-30 ng/ml) and 32 (16.8%) as vitamin D sufficient (≥30 ng/ml). Independent risk factors for vitamin D deficiency were sampling during the rainy season and infant wasting. Infant breastfeeding, maternal CD4 T-cell count, maternal wasting status and maternal receipt of antiretroviral therapy were not associated with vitamin D deficiency. Low levels of vitamin D were highly prevalent among HIV-exposed uninfected infants in Tanzania, and longitudinal studies and clinical trials of supplementation are needed to assess the impact on child health.
Journal of Tropical Pediatrics 04/2013; · 1.39 Impact Factor
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ABSTRACT: Growth faltering and micronutrient deficiencies commonly coexist in HIV-exposed children in sub-Saharan Africa, and correcting deficiencies, such as those of vitamins B-complex, C, and E, may improve HIV-related endpoints and child growth. We therefore examined the effect of daily oral supplementation of vitamins B-complex, C, and E on growth among 2341 children born to HIV-infected mothers in Tanzania. HIV-infected women pregnant at ≤32 wk of gestation were enrolled in the study. Children were randomized at age 6 wk to receive multivitamins or placebo until age 104 wk. All women received the same types of vitamins pre- and postnatally. At 6 wk, 256 children (11.1%) were HIV infected and the mean (SD) Z-scores for length for age (LAZ), weight for length (WLZ), and weight for age (WAZ) were -0.39 ± 1.20, -0.21 ± 1.23, and -0.52 ± 1.11, respectively. There was no overall treatment effect on LAZ, WLZ, or WAZ profiles during the follow-up (P ≥ 0.15). There was no treatment effect from 6 to 104 wk on LAZ [(95% CI: -0.14, 0.13); P = 0.94], WLZ [(95% CI: -0.17, 0.13); P = 0.78], or WAZ [(95% CI: -0.15, 0.16); P = 0.97] or on the incidence of growth failure, defined as respective Z-scores < -2 (P ≥ 0.29). Among the subgroup of HIV-uninfected children, there was no treatment effect from 6 to 104 wk on LAZ, WLZ, and WAZ (P ≥ 0.71) or on the incidence of growth failure (P ≥ 0.16). Multivitamin supplements had no effect on growth among children born to HIV-infected women who were themselves receiving multivitamins.
Journal of Nutrition 03/2013; · 3.92 Impact Factor
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ABSTRACT: We prospectively determined the association between undernutrition and incidence of acute respiratory infections (ARIs) among 711 children born to HIV-infected women. Overall, underweight was associated with a 58% increased risk of ARI. Similarly, wasting (54%), very low birth weight (88%) and child HIV infection (62%) were significantly associated with increased risk of ARI during the first 2 years. Breastfeeding was associated with 52% reduction in risk of ARI only during the first 12 months of life. Among HIV-exposed, but uninfected, children, underweight, wasting and stunting were associated with 73%, 61% and 33% increased risk of ARI, respectively. Very low birthweight and advanced maternal disease stage were also associated with increased risk of ARI. Similar results were observed among HIV-infected children, except for stunting and very low birth weight. Prevention of child undernutrition could have major impact in reducing child ARI morbidity in settings of high HIV prevalence.
Journal of Tropical Pediatrics 02/2013; · 1.39 Impact Factor
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ABSTRACT: Background. Prospective studies of serum albumin as a low-cost predictor of HIV progression are needed for individuals initiating ART in resource-limited settings.Methods. Serum albumin was measured at ART initiation for 2,145 adults enrolled in a trial of multivitamins in Tanzania. Participants were prospectively followed for mortality, morbidity, and anthropometric outcomes at monthly visits (median follow-up=21.2 months). Proportional hazard models were utilized to analyze mortality, morbidity, and nutritional outcomes; while generalized estimating equations were used for CD4 T-cell counts.Results. Individuals with hypoalbuminemia (<35 g/L) at ART initiation had 4.52 (95% CI: 3.37-6.07; p<0.001) times the hazard of death as compared to individuals with concentrations ≥35 g/L, after multivariate adjustment. Hypoalbuminemia was also independently associated with incidence of pulmonary tuberculosis (p<0.001), severe anemia (p<0.001), wasting (p=0.002), and >10% weight loss (p=0.012). Secondary analyses suggest serum albumin concentrations <38 g/L are associated with increased mortality and incident pulmonary TB. There was no association of serum albumin with change in CD4 T-cell count (p=0.121).Conclusions. Serum albumin can identify adults initiating ART at high risk for mortality and selected morbidities. Future research is needed to identify and manage conditions reducing serum albumin.
The Journal of Infectious Diseases 01/2013; · 6.41 Impact Factor
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ABSTRACT: Background. Maintaining vitamin D sufficiency may decrease the incidence of pulmonary tuberculosis (TB) and other infectious diseases. We present the first prospective study of vitamin D among HIV-infected adults receiving antiretrovirals in sub-Saharan Africa.Methods. Serum 25-hydroxyvitamin D (25(OH)D) was assessed at ART initiation for 1103 HIV-infected adults enrolled in a trial of multivitamins (not including vitamin D) in Tanzania. Participants were prospectively followed at monthly visits at which trained physicians performed a clinical examination and nurses took anthropometric measurements and assessed self-reported symptoms. Cox proportional hazards models estimated hazard ratios of morbidity outcomes.Results. After multivariate adjustment, vitamin D deficiency (<20 ng/mL) was significantly associated with incident pulmonary TB as compared to vitamin D sufficiency (HR 2.89; 95% CI: 1.31-7.41; p=0.027), but no association was found for insufficiency (20-30 ng/mL) (p=0.687). Deficiency was also significantly associated with incident oral thrush (HR: 1.96; 95% CI: 1.01-3.81; p=0.046), wasting (HR: 3.10; 95% CI: 1.33-7.24; p=0.009), and >10% weight loss (HR: 2.10; 95% CI: 1.13-3.91; p=0.019). Wasting results were robust to exclusion of individuals experiencing pulmonary TB. Vitamin D status was not associated with incident malaria, pneumonia, or anemia.Conclusions. Vitamin D supplementation trials for adults receiving ART appear to be warranted.
The Journal of Infectious Diseases 11/2012; · 6.41 Impact Factor
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ABSTRACT: BACKGROUND: Multiple micronutrients (vitamin B complex and vitamins C and E) were effective at reducing infectious disease morbidity, HIV disease progression, and poor pregnancy outcomes in HIV-infected women. OBJECTIVE: The objective was to evaluate whether direct supplementation of these micronutrients to HIV-exposed infants reduces mortality and morbidity. DESIGN: Infants born to HIV-infected women from Dar es Salaam, Tanzania, were randomly assigned to receive daily oral supplementation of multiple multivitamins (vitamin B complex and vitamins C and E) or placebo from age 6 wk for 24 mo. All-cause mortality, hospitalizations, and unscheduled clinic visits were recorded. Morbidities were recorded during monthly follow-up visits. All mothers received multiple micronutrients throughout the study. RESULTS: A total of 1193 infants were randomly assigned to receive micronutrients and 1194 to receive placebo. There were 138 child deaths in the multivitamin group and 124 deaths in the placebo group (HR: 1.13; 95% CI: 0.88, 1.44; P = 0.33). Hospitalizations (RR: 0.83; 95% CI: 0.62, 1.13; P = 0.23), unscheduled clinic visits (RR: 0.97; 95% CI: 0.85, 1.10; P = 0.59), and maternal reports of diarrhea (RR: 0.97; 0.87, 1.10; P = 0.64) were not significantly different between the 2 groups. Fever (P = 0.02) and vomiting (P = 0.007) were significantly lower in the multivitamin group. Among 429 children whose mothers received antiretroviral (ARV) therapy, multivitamin use had no effect on mortality but was associated with a significant reduction in hospitalizations (P = 0.035), episodes of fever (P = 0.005), and episodes of fever and cough (P = 0.019). CONCLUSIONS: In the setting of maternal micronutrient supplementation, supplementation of HIV-exposed infants with vitamin B and vitamins C and E does not reduce mortality. Studies of nutrition supplementation in ARV-exposed infants may be warranted. This trial was registered at clinicaltrials.gov as NCT00197730.
American Journal of Clinical Nutrition 11/2012; · 6.67 Impact Factor
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ABSTRACT: Large randomized trials have previously shown that high-dose micronutrient supplementation can increase CD4 counts and reduce human immunodeficiency virus (HIV) disease progression and mortality among individuals not receiving highly active antiretroviral therapy (HAART); however, the safety and efficacy of such supplementation has not been established in the context of HAART.
To test the hypothesis that high-dose multivitamin supplementation vs standard-dose multivitamin supplementation decreases the risk of HIV disease progression or death and improves immunological, virological, and nutritional parameters in patients with HIV initiating HAART.
A randomized, double-blind, controlled trial of high-dose vs standard-dose multivitamin supplementation for 24 months in 3418 patients with HIV initiating HAART between November 2006 and November 2008 in 7 clinics in Dar es Salaam, Tanzania. INTERVENTION The provision of daily oral supplements of vitamin B complex, vitamin C, and vitamin E at high levels or standard levels of the recommended dietary allowance.
The composite of HIV disease progression or death from any cause.
The study was stopped early in March 2009 because of evidence of increased levels of alanine transaminase (ALT) in patients receiving the high-dose multivitamin supplement. At the time of stopping, 3418 patients were enrolled (median follow-up, 15 months), and there were 2374 HIV disease progression events and 453 observed deaths (2460 total combined events). Compared with standard-dose multivitamin supplementation, high-dose supplementation did not reduce the risk of HIV disease progression or death. The absolute risk of HIV progression or death was 72% in the high-dose group vs 72% in the standard-dose group (risk ratio [RR], 1.00; 95% CI, 0.96-1.04). High-dose supplementation had no effect on CD4 count, plasma viral load, body mass index, or hemoglobin level concentration, but increased the risk of ALT elevations (1239 events per 1215 person-years vs 879 events per 1236 person-years; RR, 1.44; 95% CI, 1.11-1.87) vs standard-dose supplementation. CONCLUSION In adults receiving HAART, use of high-dose multivitamin supplements compared with standard-dose multivitamin supplements did not result in a decrease in HIV disease progression or death but may have resulted in an increase in ALT levels.
Clinicaltrials.gov Identifier: NCT00383669.
JAMA The Journal of the American Medical Association 10/2012; 308(15):1535-44. · 30.03 Impact Factor
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ABSTRACT: Despite the benefits of exclusive breastfeeding (EBF), exposure to HIV from breast milk has relegated EBF to an option only when formula feeding is not affordable, feasible, safe, and sustainable. Mixed feeding remains the norm in sub-Saharan Africa.
We evaluated whether the duration of EBF was associated with mortality and HIV infection in children followed to ≤5 y of age. Methods: A total of 690 mother-infant pairs from the Trial of Vitamins with information on infant feeding, HIV status, and at least one visit in the first year were included in the analysis. The duration of EBF was defined in months as a time-varying covariate at each follow-up visit. Associations of the duration of EBF with mortality, HIV infection, and HIV infection or death were estimated by using Cox proportional hazards models and Kaplan-Meier survival curves.
A 1-mo increase in EBF was associated with a 49% reduction in early infant mortality in the first 6 mo of life (RR: 0.51; 95% CI: 0.28, 0.93) and a nonsignificant 15% reduction in risk of HIV infection or death (RR: 0.85; 95% CI: 0.71, 1.01; P = 0.07) over the first 5 y of life. EBF was not associated with HIV infection (RR: 0.93; 95% CI: 0.76, 1.15).
Longer EBF by HIV-positive mothers was associated with reduced mortality in the first 6 mo of life without increased HIV infection, which makes EBF the best option for women who cannot sustain exclusive formula feeding. This trial was registered at clinicaltrials.gov as NCT00197743.
American Journal of Clinical Nutrition 10/2012; 96(5):1071-8. · 6.67 Impact Factor
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Amara E Ezeamama,
Donna Spiegelman,
Ellen Hertzmark,
Ronald J Bosch,
Karim P Manji,
Christopher Duggan,
Roland Kupka,
Melanie W Lo,
James O Okuma,
Rodrick Kisenge, Said Aboud,
Wafaie W Fawzi
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ABSTRACT: To determine whether human immunodeficiency virus (HIV) infection is associated with increased risk of malaria incidence and recurrence in children.
Newborn infants of HIV-infected mothers were enrolled at 6 weeks and followed for 2 years. HIV status was assessed by enzyme-linked immunosorbant assay and confirmed by HIV DNA polymerase chain reaction. Malaria was defined as (1) physician-diagnosed clinical malaria; (2) probable malaria, in which laboratory testing is requested for parasitemia; and (3) blood smear-confirmed malaria. Cox proportional hazards models estimated hazard ratios (HRs) for development of first and second malaria episodes, and generalized estimating equation models estimated malaria rate differences per 100-child-years in relation to time-updated HIV status.
Child HIV infection was associated with clinical (HR, 1.34; 95% confidence interval [CI], 1.12-1.61), probable (HR, 1.47; 95% CI, 1.19-1.81), and confirmed (HR, 1.67; 95% CI, 1.18-2.36) malaria episodes. Per 100 child-years, HIV-infected children experienced 88 (95% CI, 65-113), 36 (95% CI, 19-53), and 20 (95% CI, 9-31) more episodes of clinical, probable, and confirmed malaria episodes, respectively, than HIV-uninfected children. Among children with ≥1 malaria episodes, those with HIV infection developed second clinical (HR, 1.28; 95% CI, 1.04-1.57), probable (HR, 1.60; 95% CI, 1.26-2.14), and confirmed (HR, 2.27; 95% CI, 1.06-3.89) malaria sooner than HIV-uninfected children.
HIV infection is a risk factor for the development of malaria. Proactive malaria disease prevention and treatment is warranted for all children, particularly those with HIV infection in settings of coendemicity.
The Journal of Infectious Diseases 03/2012; 205(10):1486-94. · 6.41 Impact Factor
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ABSTRACT: This study aimed to determine the magnitude of nasopharyngeal carriage, antimicrobial resistance and serotype distribution of Streptococcus pneumoniae in healthy children under 5 years of age in Tanzania. Nasopharyngeal swabs were obtained from 300 healthy children attending a child health clinic at Muhimbili National Hospital in Dar es Salaam, Tanzania. S. pneumoniae was isolated and identified using conventional methods. Antimicrobial susceptibility testing was performed using the Kirby-Bauer disc diffusion method. Penicillin MICs and serotypes were determined by an agar gradient diffusion method and the Quellung reaction, respectively. A total of 105 samples (35 .0%) were positive for S. pneumoniae and 115 serotypes were detected (ten specimens yielded two serotypes each). Overall, 78 of 115 isolates (67.8 %) were penicillin-non-susceptible pneumococci (PNSP). The resistance levels of S. pneumoniae to trimethoprim-sulfamethoxazole, tetracycline, erythromycin, chloramphenicol and ceftriaxone were 82.6, 10.4, 6.0, 3.5 and 0.0 %, respectively. Multidrug resistance was detected in 19 isolates (16.5 %). The most prevalent serotypes were 19F (n = 25, 21.7 %), 6B (n = 15, 13.0 %), 9V (n = 14, 12.2 %) and 13 (n = 14, 12.2 %). Of the 64 pneumococcal isolates potentially covered by the seven-valent pneumococcal conjugate vaccine (PCV7), 44 (68.8 %) were PNSP. A high prevalence of PNSP, common pneumococcal serotypes circulating worldwide, was found, and many of the resistant pneumococci strains are covered by the PCV7. These findings indicate that the carriage rate of such resistant strains could be influenced by an appropriate vaccination programme in the study setting and by reinforcing regulations on the rational use of antimicrobial agents.
Journal of Medical Microbiology 03/2012; 61(Pt 7):952-9. · 2.50 Impact Factor
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ABSTRACT: 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 human immunodeficiency virus (HIV)-infected women.
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 excluding vitamin D) in Tanzania. Information on child morbidities, anemia and hypochromic microcytosis, and anthropometry was recorded through monthly clinic visits. Generalized estimating equations and Cox proportional hazards models were used to assess the relationships of outcomes with maternal vitamin D status.
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 (relative risk [RR], 1.11; 95% confidence interval [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 being underweight (weight-for-age z score, <-2; RR, 1.33; 95% CI, 1.03-1.71).
Maternal vitamin D status may be important for preventing respiratory infections and ensuring optimal growth in HIV-exposed children.
The Pediatric Infectious Disease Journal 02/2012; 31(2):171-5. · 3.58 Impact Factor
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ABSTRACT: Prenatal iron supplementation may improve pregnancy outcomes and decrease the risk of child mortality. However, little is known about the importance of post-natal maternal iron status for child health and survival, particularly in the context of HIV infection. We examined the association of maternal anaemia 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 anaemia 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 anaemia and hypochromic microcytosis were associated with greater risk of child mortality [hazard ratio (HR) for severe anaemia = 2.58, 95% confidence interval (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 anaemia was not significantly associated with greater risk of child HIV infection (HR for severe anaemia = 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 anaemia: -93, 95% CI: -204-17, P trend = 0.02). The potential child health risks associated with maternal anaemia and iron deficiency may not be limited to the prenatal period. Efforts to reduce maternal anaemia and iron deficiency during pregnancy may need to be expanded to include the post-partum period.
Maternal and Child Nutrition 01/2012; 8(3):287-98. · 1.61 Impact Factor
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ABSTRACT: 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.
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 µg/L) and high (plasma ferritin>150 µg/L for women and>200 µg/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).
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.
PLoS ONE 01/2012; 7(5):e37350. · 4.09 Impact Factor
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ABSTRACT: There is growing evidence of an association between low vitamin D and HIV disease progression; however, no prospective studies have been conducted among adults receiving antiretroviral therapy (ART) in sub-Saharan Africa.
Serum 25-hydroxyvitamin D (25(OH)D) levels were assessed at ART initiation for a randomly selected cohort of HIV-infected adults enrolled in a trial of multivitamins (not including vitamin D) in Tanzania during 2006-2010. Participants were prospectively followed at monthly clinic visits for a median of 20.6 months. CD4 T-cell measurements were obtained every 4 months. Proportional hazard models were utilized for mortality analyses while generalized estimating equations were used for CD4 T-cell counts.
Serum 25(OH)D was measured in 1103 adults 9.2% were classified as vitamin D deficient (<20 ng/ml), 43.6% insufficient (20-30 ng/mL), and 47.2% as sufficient (>30 ng/mL). After multivariate adjustment, vitamin D deficiency was significantly associated with increased mortality as compared to vitamin D sufficiency (HR: 2.00; 95% CI: 1.19-3.37; p = 0.009), whereas no significant association was found for vitamin D insufficiency (HR: 1.24; 95% CI: 0.87-1.78; p = 0.24). No effect modification by ART regimen or change in the associations over time was detected. Vitamin D status was not associated with change in CD4 T-cell count after ART initiation.
Deficient vitamin D levels may lead to increased mortality in individuals receiving ART and this relationship does not appear to be due to impaired CD4 T-cell reconstitution. Randomized controlled trials are needed to determine the safety and efficacy of vitamin D supplementation for individuals receiving ART.
PLoS ONE 01/2012; 7(6):e40036. · 4.09 Impact Factor
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ABSTRACT: Anaemia is common during pregnancy, and prenatal Fe supplementation is the standard of care. However, the persistence of anaemia despite Fe supplementation, particularly in HIV infection, suggests that its aetiology may be more complex and warrants further investigation. The present study was conducted to examine predictors of incident haematological outcomes in HIV-infected pregnant women in Tanzania.
Prospective cohort study. Cox proportional hazards and binomial regression models were used to identify predictors of incident haematological outcomes: anaemia (Hb < 110 g/l), severe anaemia (Hb < 85 g/l) and hypochromic microcytosis, during the follow-up period.
Antenatal clinics in Dar es Salaam, Tanzania.
Participants were 904 HIV-infected pregnant women enrolled in a randomized trial of vitamins (1995-1997).
Malaria, pathogenic protozoan and hookworm infections at baseline were associated with a two-fold increase in the risk of anaemia and hypochromic microcytosis during follow-up. Higher baseline erythrocyte sedimentation rate and CD8 T-cell concentrations, and lower Hb concentrations and CD4 T-cell counts, were independent predictors of incident anaemia and Fe deficiency. Low baseline vitamin D (<32 ng/ml) concentrations predicted a 1.4 and 2.3 times greater risk of severe anaemia and hypochromic microcytosis, respectively, during the follow-up period.
Parasitic infections, vitamin D insufficiency, low CD4 T-cell count and high erythrocyte sedimentation rate were the main predictors of anaemia and Fe deficiency in pregnancy and the postpartum period in this population. A comprehensive approach to prevent and manage anaemia, including micronutrient supplementation and infectious disease control, is warranted in HIV-infected women in resource-limited settings - particularly during the pre- and postpartum periods.
Public Health Nutrition 10/2011; 15(5):928-37. · 2.17 Impact Factor
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Muhammad Bakari, Said Aboud,
Charlotta Nilsson,
Joel Francis,
Deus Buma,
Candida Moshiro,
Eric A Aris,
Eligius F Lyamuya,
Mohamed Janabi,
Karina Godoy-Ramirez, [......],
Victoria R Polonis,
Andreas Bråve,
Patricia Earl,
Merlin Robb,
Mary Marovich,
Britta Wahren,
Kisali Pallangyo,
Gunnel Biberfeld,
Fred Mhalu,
Eric Sandström
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ABSTRACT: We conducted a phase I/II randomized placebo-controlled trial with the aim of exploring whether priming with a low intradermal dose of a multiclade, multigene HIV-1 DNA vaccine could improve the immunogenicity of the same vaccine given intramuscularly prior to boosting with a heterologous HIV-1 MVA among healthy adults in Dar es Salaam, Tanzania.
Sixty HIV-uninfected volunteers were randomized to receive DNA plasmid vaccine 1mg intradermally (id), n=20, or 3.8mg intramuscularly (im), n=20, or placebo, n=20, using a needle-free injection device. DNA plasmids encoding HIV-1 genes gp160 subtype A, B, C; rev B; p17/p24 gag A, B and Rtmut B were given at weeks 0, 4 and 12. Recombinant MVA (10(8)pfu) expressing HIV-1 Env, Gag, Pol of CRF01_AE or placebo was administered im at month 9 and 21.
The vaccines were well tolerated. Two weeks after the third HIV-DNA injection, 22/38 (58%) vaccinees had IFN-γ ELISpot responses to Gag. Two weeks after the first HIV-MVA boost all 35 (100%) vaccinees responded to Gag and 31 (89%) to Env. Two to four weeks after the second HIV-MVA boost, 28/29 (97%) vaccinees had IFN-γ ELISpot responses, 27 (93%) to Gag and 23 (79%) to Env. The id-primed recipients had significantly higher responses to Env than im recipients. Intracellular cytokine staining for Gag-specific IFN-γ/IL-2 production showed both CD8(+) and CD4(+) T cell responses. All vaccinees had HIV-specific lymphoproliferative responses. All vaccinees reacted in diagnostic HIV serological tests and 26/29 (90%) had antibodies against gp160 after the second HIV-MVA boost. Furthermore, while all of 29 vaccinee sera were negative for neutralizing antibodies against clade B, C and CRF01_AE pseudoviruses in the TZM-bl neutralization assay, in a PBMC assay, the response rate ranged from 31% to 83% positives, depending upon the clade B or CRF01_AE virus tested.
This vaccine approach is safe and highly immunogenic. Low dose, id HIV-DNA priming elicited higher and broader cell-mediated immune responses to Env after HIV-MVA boost compared to a higher HIV-DNA priming dose given im. Three HIV-DNA priming immunizations followed by two HIV-MVA boosts efficiently induced Env-antibody responses.
Vaccine 08/2011; 29(46):8417-28. · 3.77 Impact Factor
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ABSTRACT: 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.
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.
Dar es Salaam, Tanzania.
The sample consisted of 666 children born to HIV-infected women.
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.
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.
Public Health Nutrition 02/2011; 14(7):1251-8. · 2.17 Impact Factor
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ABSTRACT: CD4(+) T-lymphocyte count (CD4 count) is a standard method used to monitor HIV-infected patients during anti-retroviral therapy (ART). The World Health Organization (WHO) has pointed out or recommended that a handheld, point-of-care, reliable, and affordable CD4 count platform is urgently needed in resource-scarce settings.
HIV-infected patient blood samples were tested at the point-of-care using a portable and label-free microchip CD4 count platform that we have developed. A total of 130 HIV-infected patient samples were collected that included 16 de-identified left over blood samples from Brigham and Women's Hospital (BWH), and 114 left over samples from Muhimbili University of Health and Allied Sciences (MUHAS) enrolled in the HIV and AIDS care and treatment centers in the City of Dar es Salaam, Tanzania. The two data groups from BWH and MUHAS were analyzed and compared to the commonly accepted CD4 count reference method (FACSCalibur system).
The portable, battery operated and microscope-free microchip platform developed in our laboratory (BWH) showed significant correlation in CD4 counts compared with FACSCalibur system both at BWH (r = 0.94, p<0.01) and MUHAS (r = 0.49, p<0.01), which was supported by the Bland-Altman methods comparison analysis. The device rapidly produced CD4 count within 10 minutes using an in-house developed automated cell counting program.
We obtained CD4 counts of HIV-infected patients using a portable platform which is an inexpensive (<$1 material cost) and disposable microchip that uses whole blood sample (<10 µl) without any pre-processing. The system operates without the need for antibody-based fluorescent labeling and expensive fluorescent illumination and microscope setup. This portable CD4 count platform displays agreement with the FACSCalibur results and has the potential to expand access to HIV and AIDS monitoring using fingerprick volume of whole blood and helping people who suffer from HIV and AIDS in resource-limited settings.
PLoS ONE 01/2011; 6(7):e21409. · 4.09 Impact Factor
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ABSTRACT: Children with tuberculosis often have underlying nutritional deficiencies. Multivitamin supplementation has been proposed as a means to enhance the health of these children; however, the efficacy of such an intervention has not been examined adequately.
255 children, aged six weeks to five years, with tuberculosis were randomized to receive either a daily multivitamin supplement or a placebo in the first eight weeks of anti-tuberculous therapy in Tanzania. This was only 64% of the proposed sample size as the trial had to be terminated prematurely due to funding constraints. They were followed up for the duration of supplementation through clinic and home visits to assess anthropometric indices and laboratory parameters, including hemoglobin and albumin.
There was no significant effect of multivitamin supplementation on the primary endpoint of the trial: weight gain after eight weeks. However, significant differences in weight gain were observed among children aged six weeks to six months in subgroup analyses (n=22; 1.08 kg, compared to 0.46 kg in the placebo group; 95% CI=0.12, 1.10; p=0.01). Supplementation resulted in significant improvement in hemoglobin levels at the end of follow-up in children of all age groups; the median increase in children receiving multivitamins was 1.0 g/dL, compared to 0.4 g/dL in children receiving placebo (p<0.01). HIV-infected children between six months and three years of age had a significantly higher gain in height if they received multivitamins (n=48; 2 cm, compared to 1 cm in the placebo group; 95% CI=0.20, 1.70; p=0.01; p for interaction by age group=0.01).
Multivitamin supplementation for a short duration of eight weeks improved the hematological profile of children with tuberculosis, though it didn't have any effect on weight gain, the primary outcome of the trial. Larger studies with a longer period of supplementation are needed to confirm these findings and assess the effect of multivitamins on clinical outcomes including treatment success and growth failure. CLINICALTRIALS.GOV IDENTIFIER: NCT00145184.
Nutrition Journal 01/2011; 10:120. · 2.48 Impact Factor
