Plasma zinc concentrations are depressed during the acute phase response in children with falciparum malaria

Plasma concentrations of some micronutrients are altered in the setting of acute infectious or inflammatory stress. Previous studies have provided conflicting evidence concerning the extent and direction of changes in plasma zinc concentrations during the acute phase response. We carried out an observational cohort study in 689 children enrolled in a randomized trial of zinc supplementation during acute falciparum malaria in order to evaluate the relation between plasma zinc concentration and the acute phase response. Plasma zinc was measured by atomic absorption spectrophotometry. On admission, 70% of all subjects had low plasma zinc (\u3c9.2 μmol/L). Multivariate analysis of predictors of admission plasma zinc showed that admission C-reactive protein (CRP), parasite density, and study site were the most important predictors. Predictors of changes in plasma zinc from admission to 72 h included baseline CRP, change in CRP, treatment group, study site, and baseline zinc concentration. In children with acute malaria infection, baseline plasma zinc concentrations were very low and were inversely correlated with CRP (r = -0.24, P \u3c 0.0001) and the degree of parasitemia (r = -0.19, P \u3c 0.0001). Even when CRP and time were taken into account, zinc supplementation increased plasma zinc concentration from admission to 72 h. When available, plasma zinc concentrations should be interpreted with concurrent measures of the acute phase response such as CRP. In children whose age, diet, and/or nutritional status place them at risk of zinc deficiency, those with low plasma zinc levels should be supplemented with oral zinc and followed for clinical and/or biochemical response. © 2005 American Society for Nutritional Sciences

Age, temperature, and parasitaemia predict chloroquine treatment failure and anaemia in children with uncomplicated Plasmodium falciparum malaria

The prevalence of chloroquine-resistant Plasmodium falciparum malaria has been increasing in sub-Saharan Africa and parts of South America over the last 2 decades, and has been associated with increased anaemia-associated morbidity and higher mortality rates. Prospectively collected clinical and parasitological data from a multicentre study of 788 children aged 6-59 months with uncomplicated P. falciparum malaria were analysed in order to identify risk factors for chloroquine treatment failure and to assess its impact on anaemia after therapy. The proportion of chloroquine treatment failures (combined early and late treatment failures) was higher in the central-eastern African countries (Tanzania, 53%; Uganda, 80%; Zambia, 57%) and Ecuador (54%) than in Ghana (36%). Using logistic regression, predictors of early treatment failure included younger age, higher baseline temperature, and greater levels of parasitaemia. We conclude that younger age, higher initial temperature, and higher baseline parasitaemia predict early treatment failure and a higher probability of worsening anaemia between admission and days 7 or 14 post-treatment

Associations of Suboptimal Growth with All-Cause and Cause-Specific Mortality in Children under Five Years: A Pooled Analysis of Ten Prospective Studies

Background: Child undernutrition affects millions of children globally. We investigated associations between suboptimal growth and mortality by pooling large studies. Methods: Pooled analysis involving children 1 week to 59 months old in 10 prospective studies in Africa, Asia and South America. Utilizing most recent measurements, we calculated weight-for-age, height/length-for-age and weight-for-height/length Z scores, applying 2006 WHO Standards and the 1977 NCHS/WHO Reference. We estimated all-cause and cause-specific mortality hazard ratios (HR) using proportional hazards models comparing children with mild (-2≤Z<-1), moderate (-3≤Z<-2), or severe (Z<-3) anthropometric deficits with the reference category (Z≥-1). Results: 53809 children were eligible for this re-analysis and contributed a total of 55 359 person-years, during which 1315 deaths were observed. All degrees of underweight, stunting and wasting were associated with significantly higher mortality. The strength of association increased monotonically as Z scores decreased. Pooled mortality HR was 1.52 (95% Confidence Interval 1.28, 1.81) for mild underweight; 2.63 (2.20, 3.14) for moderate underweight; and 9.40 (8.02, 11.03) for severe underweight. Wasting was a stronger determinant of mortality than stunting or underweight. Mortality HR for severe wasting was 11.63 (9.84, 13.76) compared with 5.48 (4.62, 6.50) for severe stunting. Using older NCHS standards resulted in larger HRs compared with WHO standards. In cause-specific analyses, all degrees of anthropometric deficits increased the hazards of dying from respiratory tract infections and diarrheal diseases. The study had insufficient power to precisely estimate effects of undernutrition on malaria mortality. Conclusions: All degrees of anthropometric deficits are associated with increased risk of under-five mortality using the 2006 WHO Standards. Even mild deficits substantially increase mortality, especially from infectious diseases

The timing of mother-to-child transmission of human immunodeficiency virus infection and the neurodevelopment of children in Tanzania

OBJECTIVE: To determine the association between the timing of mother-to-child transmission of human immunodeficiency virus (HIV)-1 and neurodevelopment among children born to HIV-1 infected mothers in Tanzania.METHODS: Bayley Scales of Infant Development (2nd edition) were administered at 6, 12 and 18 months to a subset of children (N = 327). Linear regression models and Cox proportional hazard models were separately fitted for the mental development index (MDI) and the psychomotor development index (PDI).RESULTS: Children who tested HIV-1-positive at birth had significantly higher decreases per month in MDI and PDI than HIV-1-negative children; 1.1 [95% confidence interval (95% CI), 0.4, 1.8] for MDI and 1.4 (95% CI 0.0, 2.7] for PDI. Children who tested HIV-1-positive after birth had an additional 0.6 (95% CI 0.1, 1.1) point decrease in MDI per month and a 0.6 (95% CI 0.0, 1.1) higher decrease in PDI each month than HIV-1-negative children. Testing HIV-1-positive at birth was associated with a 14.9 (95% CI 5.0, 44.7) times higher rate of becoming developmentally delayed in mental function, while testing HIV-1-positive after birth was associated with a 3.2 (95% CI 1.6, 6.4) times higher rate than in uninfected children.CONCLUSIONS: HIV-1 infected infants performed worse on tests of neurodevelopment and were significantly more likely to be identified as developmentally delayed in the first 18 months of life than HIV-1-negative children. The effect of HIV-1 infection on neurodevelopment scores and the risk of developmental delay may be highest among those who are already HIV-1 infected at birth

Socio-economic and demographic factors associated with prevalence of HIV infection among pregnant women in Dar es Salaam, Tanzania

BACKGROUND: HIV/AIDS epidemic has become generalised in low resource settings in sub-Saharan Africa where 90% of all maternal-foetal transmission of HIV infection occurs. Global effort to scale-up pMTCT is underway, however, mechanisms to maximise screening of HIV- 1 positive women for Nevirapine treatment and other interventions, are not clear.OBJECTIVE: To identify socioeconomic and demographic characteristics associated with the prevalence of HIV- 1 infection among Tanzanian women.DESIGN: Cross-sectional study.SETTING: Four antenatal clinics in Dar es Salaam.RESULTS: HIV prevalence rate was 13.1 (95% confidence interval (CI): 12.7% - 13.5%) and it increased with increasing maternal age. Older age than 25, mid-arm circumference less than 25cm, geographic location, working in a public house, and partner's occupation were independently associated with higher prevalence of infection. Women in monogamous marriages were 77% less likely to be HIV infected compared to women with no regular partner. Similarly, women with more than five persons per household, and those who spent less on food had a significantly lower HIV prevalence.CONCLUSION: HIV infection is sufficiently widespread among women in Dar es Salaam suggesting that screening based on socioeconomic and demographic characteristics would miss a large proportion of the positives. There is need to increase facilities for counselling and testing using an opt-out approach for testing in all antenatal clinics in the city

L’hypertension pendant la grossesse chez les femmes séropositives en Afrique subsaharienne : Prévalence et les résultats infantiles.

This analysis was performed to determine the prevalence of hypertension and association of MAP (mean arterial pressure) with birth outcomes among HIV-infected pregnant women not taking antiretrovirals. HIV-infected pregnant women, enrolled into the HPTN024 trial in Tanzania, Malawi and Zambia were followed up at 26-30, 36 weeks, and delivery. The prevalence of hypertension was <1% at both 20-24 weeks and 26-30 weeks and 1.7% by 36 weeks. A 5 mm Hg elevation in MAP increased the risk of stillbirth at 20-24 weeks by 29% (p=0.001), 32% (p=0.001) at 26-30 weeks and of low birth weight (LBW) at 36 weeks by 26% (p=0.001). MAP was not associated with stillbirth at 36 weeks, LBW prior to 36 weeks, preterm birth, neonatal mortality or the risk of maternal to child transmission (MTCT) of HIV (Afr J Reprod Health 2009; 13[4]:25-36).On a fait cette analyse pour déterminer la prévalence de l’hypertension et l’association de la PAM (Pression Artérielle Moyenne) avec les résultats de naissance chez les femmes séropositives enceintes qui ne prennent pas des médicaments antirétroviraux. Les femmes séropositives enceintes inscrites pour l’essai PHTNO24 en Tanzanie, au Malawi et en Zambie ont été suivies à 26 – 30, 36 semaines et à l’accouchement. La prévalence de l’hypertension était <1% à la fin de 20 – 24 semaines et à la fin de 26 – 30 semaines et 1,7% à la fin de 36 semaines. Une hausse de 5mm Hg de la PAM a augmente le risque de la mortinatalité à la fin de 20 – 24 semaines de 29% (p = 0,001), 32% (p = 0,001) à la fin de 26 – 30 semaines et de la faible poids de naissance (FPN) à la fin de 36 semaines de 26% (p = 0,001). La PAM n’était pas liée à la mortinatalité à la fin de 36 semaines, à la FPN avant 36 semaines, à la naissance avant-terme, à la mortalité néonatale ou au risque de la transmission de la mère à l’enfant (TME) du VIH (Afr J Reprod Health 2009; 13[4]:25-36)

Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania

BACKGROUND: In HIV-1-infected women, poor micronutrient status has been associated with faster progression of HIV-1 disease and adverse birth outcomes. We assessed the effects of vitamin A and multivitamins on birth outcomes in such women.METHODS: In Tanzania, 1075 HIV-1-infected pregnant women at between 12 and 27 weeks' gestation received placebo (n=267), vitamin A (n=269), multivitamins excluding vitamin A (n=269), or multivitamins including vitamin A (n=270) in a randomised, double-blind, placebo-controlled trial with a 2x2 factorial design. We measured the effects of multivitamins and vitamin A on birth outcomes and counts of T lymphocyte subsets. We did analyses by intention to treat.RESULTS: 30 fetal deaths occurred among women assigned multivitamins compared with 49 among those not on multivitamins (relative risk 0.61 [95% CI 0.39-0.94] p=0.02). Multivitamin supplementation decreased the risk of low birthweight (&lt;2500 g) by 44% (0.56 [0.38-0.82] p=0.003), severe preterm birth (&lt;34 weeks of gestation) by 39% (0.61 [0.38-0.96] p=0.03), and small size for gestational age at birth by 43% (0.57 [0.39-0.82] p=0.002). Vitamin A supplementation had no significant effect on these variables. Multivitamins, but not vitamin A, resulted in a significant increase in CD4, CD8, and CD3 counts.INTERPRETATION: Multivitamin supplementation is a low-cost way of substantially decreasing adverse pregnancy outcomes and increasing T-cell counts in HIV-1-infected women. The clinical relevance of our findings for vertical transmission and clinical progression of HIV-1 disease is yet to be ascertained.PIP: Poor micronutrient status has been associated, in HIV-positive women, with faster progression of HIV disease and adverse birth outcomes. This randomized, double-blind, placebo-controlled study assessed the effects of vitamin A and multivitamins on birth outcomes in 1075 HIV-positive pregnant women at 12-27 weeks' gestation from Dar es Salaam, Tanzania. There were no differences in baseline plasma vitamin concentrations between groups. 267 women received a placebo, 269 were given vitamin A, 269 were administered a multivitamin excluding vitamin A, and 270 received a multivitamin including vitamin A. There were 30 fetal deaths in the group of women who received multivitamins (with and without vitamin A) compared with 49 among those not given multivitamins (relative risk (RR), 0.61; 95% confidence interval (CI), 0.39-0.94). Multivitamin supplementation decreased the risk of low birth weight (2500 g) by 44% (RR, 0.56; 95% CI, 0.38-0.82), of preterm birth (prior to 34 weeks gestation) by 39% (RR, 0.61; 95% CI, 0.38-0.96), and of small size for gestational age at birth by 43% (RR, 0.57; 95% CI, 0.39-0.82). Vitamin A had no significant effect on these variables. Multivitamins, but not vitamin A, were associated with significant increases in CD4, CD8, and CD3 counts. The clinical relevance of multivitamin supplementation for vertical transmission of HIV and the progression of disease remain unknown. However, these results indicate such supplementation is a low-cost means of substantially decreasing adverse pregnancy outcomes and increasing T cell counts in HIV-infected women. The observed beneficial effects of multivitamins on birth outcomes may have been mediated through improved maternal immune status

Níveis plasmáticos de vitamina A, carotenóides e proteína ligadora de retinol em crianças com infecções respiratórias agudas e doenças diarréicas Plasma levels of vitamin A, carotenoids and retinol binding protein in children with acute respiratory infections and diarrhoeal diseases

Planejou-se um estudo com o objetivo de se avaliar os níveis plasmáticos de vitamina A, carotenóides e proteína ligadora de retinol (RBP) em 311 crianças, de 7 meses a onze anos de idade, com história de infecções das vias aéreas superiores (IVAS), pneumonia e diarréia, residentes na área urbana da Cidade de São Paulo, Brasil, e atendidas no serviço de pediatria de um hospital-escola. As dosagens de vitamina A e carotenóides realizaram-se pelo método de Neeld-Pearson e o RBP pelo método de Mancini. Os níveis plasmáticos de vitamina A (µg/dl) e RBP (mg/dl) foram mais baixos (p<0,05) nos grupos diarréia e pneumonia (15,2 µg/dl e 1,7 µg/dl; 15,2 µg/dl; 2,6 mg/dl, respectivamente), quando comparados com os grupos IVAS e testemunha (19,0 µg/dl; 2,4µg/dl e 18,8µg/dl; 2,6mg/dl, respectivamente. Os níveis de carotenóides foram mais baixos nos três grupos de estudo em relação ao grupo testemunha (p<0,05). Os baixos níveis de vitamina A verificados nas crianças estudadas estão em concordância com outras pesquisas que encontraram diminuição dos níveis de vitamina A durante as infecções.<br>The present study was carried out in order to assess the plasma levels of vitamin A, carotenoids and retinol binding protein (RBP) of three-hundred and eleven children aged from seven months to eleven years, who had a history of upper respiratory infection (URI), pneumonia and diarrhoea. The children were resident in the urban area of the Municipality of S. Paulo, Brazil, and were seen at the pediatric service of the one school-hospital. The data show that plasma vitamin A (µg/dl) and RBP (mg/ dl) levels in the diarrhoea (15.2 µg/dl; 1.7 mg/dl) and pneumonia (15.2 µg/dl; 0.7 mg/dl) groups were lower (p<0.05) than those observed in the control (18.8 µg/dl; 2.6 mg/dl) and URI (19.0 µg/dl; 2.4 mg/dl) groups. The plasma carotenoid levels were lower in all groups than in the control group (p<0.05). These findings corroborate the results that show low levels of vitamin A in circulation during period of infection