Variation in breastmilk HIV-1 viral load in left and right breasts during the first 3 months of lactation.

The mechanism and risk factors associated with mother-to-child transmission of HIV-1 through breastfeeding remain unclear; breastmilk viral load may be an important determinant of transmission. Analysis of breastmilk cell-free viral load in samples taken from each breast at 1, 6 and 14 weeks postpartum showed that HIV-1 is shed intermittently and load may differ considerably between breasts of an individual woman at any given time. Breastmilk HIV-1 load was undetectable in approximately one-third of samples.

The effect of antenatal vitamin A and beta-carotene supplementation on gut integrity of infants of HIV-infected South African women.

BACKGROUND: Vitamin A is important for protection against diarrhea, and supplements may benefit gut function of infants of HIV-infected mothers. METHODS: We studied 238 infants of HIV-infected South African women participating in a randomized, double-blind, placebo-controlled trial of vitamin A during pregnancy (1.5 mg retinyl palmitate and 30 mg beta-carotene daily) plus 60 mg retinyl palmitate at delivery. The placebo group received identical placebo capsules at the same times. When infants were 1, 6, and 14 weeks of age, lactulose/mannitol dual sugar intestinal permeability tests were performed. RESULTS: Maternal vitamin A supplementation did not significantly affect infant gut permeability in the group as a whole at any time. By multiple regression analysis, HIV infection of the infant by 14 weeks was significantly associated with increased gut permeability at both 6 and 14 weeks. After controlling for birth weight, gestational age, current weight, feeding mode and recent morbidity, there was a trend toward an interaction between vitamin A supplementation and HIV infection (P = 0.086) at 14 weeks. Vitamin A made no difference to gut permeability of uninfected infants (lactulose/mannitol ratio for vitamin A group: 0.11, 95% confidence interval [CI] 0.08, 0.15, n = 73 and for placebo group: 0.09, 95% CI 0.06, 0.12, n = 76), but largely prevented the increase in the ratio of HIV-infected infants (vitamin A group: 0.17, 95% CI 0.13, 0.23, n = 23; placebo group: 0.50, 95% CI 0.37, 0.68, n = 20). The effects on the lactulose/mannitol ratio were related to changes in lactulose, not mannitol, excretion. Vitamin A supplementation was associated with significantly lower lactulose excretion at 1 and 14 weeks, suggesting the major effect of vitamin A was on maintaining the integrity of gut tight junctions. CONCLUSIONS: Vitamin A supplementation of HIV-infected pregnant women may prevent the deterioration in gut integrity in the subgroup of their infants who themselves become infected. Improving vitamin A status of HIV-infected infants may decrease their gastrointestinal morbidity.

Subclinical mastitis as a risk factor for mother-infant HIV transmission.

Subclinical mastitis, as diagnosed by an elevated sodium/potassium ratio in milk accompanied by an increased milk concentration of the inflammatory cytokine, interleukin-8 (IL8), was found to be common among breast feeding women in Bangladesh and Tanzania. Subclinical mastitis results in leakage of plasma constituents into milk, active recruitment of leukocytes into milk, and possible infant gut damage from inflammatory cytokines. Therefore, we wished to investigate whether subclinical mastitis was related to known risk factors for postnatal mother-to-child HIV transmission, that is, high milk viral load or increased infant gut permeability. HIV-infected South African women were recruited at the antenatal clinic of McCord's Hospital, Durban. Risks and benefits of different feeding strategies were explained to them and, if they chose to breast feed, they were encouraged to do so exclusively. Women and infants returned to the clinic at 1, 6 and 14 weeks postpartum for an interview about infant health and current feeding pattern, a lactulose/mannitol test of infant gut permeability, and milk sample collection from each breast separately for analysis of Na/K ratio, IL8 concentration and viral load in the cell-free aqueous phase. Only preliminary cross-sectional analyses from an incomplete database are available at this point. Moderately (0.6-1.0) or greatly (>1.0) raised Na/K ratio was common and was often unilateral, although as a group right and left breasts did not differ. Considering both breasts together, normal, moderately raised or greatly raised Na/K was found, respectively, in 51%, 28%, 21% of milk samples at 1 week (n=190); 69%, 20%, 11% at 6 weeks (n=167); and 72%, 16%, 12% at 14 weeks (n=122). IL8 concentration significantly correlated with both Na/K and viral load at all times. Na/K correlated with viral load at 1 and 14, but not 6 weeks. At 1 and 14 weeks, geometric mean viral loads in samples with Na/K > 1.0 were approximately 4 times those in samples with Na/K < 0.6. At 1 week but not later times, exclusive breast feeding was associated with lower milk viral load than was mixed feeding. Gut permeability was unrelated to milk Na/K ratio or IL8 concentration and was not significantly increased by inclusion of other foods than breast milk in the infant's diet. The results suggest that subclinical mastitis among HIV-infected women may increase the risk of vertical transmission through breast feeding by increasing milk viral load. The importance of various causes of subclinical mastitis, which likely differ at 1 week from at later times and may include local infection or sterile inflammation, systemic infection, micronutrient deficiencies, or poor lactation practices, needs to be further clarified so that appropriate interventions can be implemented.

Use of the retinol-binding protein: transthyretin ratio for assessment of vitamin A status during the acute-phase response.

The ratio plasma retinol-binding protein (RBP):transthyretin (TTR) has been proposed as a means to improve the assessment of vitamin A status of individuals with concurrent infection or inflammation. We have measured RBP and TTR in stored sera from South African children who had accidentally ingested kerosene. Samples were collected from these children in hospital when suffering acute inflammation and respiratory distress, and from them and neighbourhood control children 3 months later. Vitamin A status was defined by modified relative dose response (MRDR) tests of liver retinol stores at 3 months and by serum retinol concentration both when children were ill and when they were well. Illness was defined as either being in hospital or, at follow-up, as having a raised plasma alpha 1-acid glycoprotein (AGP) level. The RBP:TTR value was significantly decreased by both illness and low liver retinol stores. When the effects on RBP:TTR of illness and vitamin A stores were considered together for the 3-month follow-up samples, only vitamin A status significantly decreased the value. We calculated sensitivity and specificity of the RBP:TTR ratio against established measures of vitamin A status using a cut-off value of 0.3 for RBP:TTR and standard cut-off values for MRDR (0.06) and plasma retinol (0.7 mumol/l). Compared with MRDR, RBP:TTR had sensitivities of 76% and 43% and specificities of 22% and 81% to detect vitamin A deficiency in hospitalized and well children respectively. Compared with plasma retinol, sensitivities were 88% and 44% and specificities were 55% and 64% in hospitalized and well children respectively. Only for the case of clinically well children with biochemical evidence of subclinical inflammation did sensitivity (62% and 100% against MRDR and plasma retinol respectively) and specificity (100% and 60% against MRDR and retinol) approach useful levels for an assessment tool. Overall, although a trend supporting the theory behind the use of the RBP:TTR for assessment of vitamin A status in infection was observed in the current study, the ratio did not provide adequate sensitivity and specificity to be a useful assessment tool.

Breast milk immune factors in Bangladeshi women supplemented postpartum with retinol or beta-carotene.

BACKGROUND: Vitamin A supplementation of mothers postpartum may improve infant health, not only by increasing vitamin A delivery to the infant through breast milk but also by increasing delivery of milk immune factors. Our hypothesis was that postpartum supplementation with vitamin A increases milk concentrations of certain soluble immune factors. DESIGN: In a double-blind trial conducted in Matlab, Bangladesh, women at 1-3 wk postpartum were randomly assigned to receive until 9 mo postpartum 1) a single dose of 60 mg retinol as retinyl palmitate followed by daily placebos (n = 69), 2) daily doses of 7.6 mg beta-carotene (n = 72), or 3) daily placebos (n = 71). Milk samples collected at baseline and 3 mo postpartum were analyzed by enzyme-linked immunosorbent assay for secretory immunoglobulin A, lactoferrin, lysozyme, and interleukin 8; by HPLC for total retinol; and by atomic absorption spectroscopy for sodium and potassium. RESULTS: After mammary epithelial permeability (defined as an elevated Na:K) and baseline immune factor concentrations were controlled for, there were no significant treatment effects on immune factors at 3 mo. Increased mammary permeability was common (25% of women at baseline and 12% at 3 mo) and was associated with higher concentrations of milk immune factors. Low body vitamin A stores at baseline, as assessed by the modified-relative-dose-response test, were associated with a higher Na:K, but neither retinol nor beta-carotene supplementation affected the prevalence of increased mammary permeability. CONCLUSIONS: Postpartum vitamin A supplementation does not increase milk concentrations of immune factors. The causes of increased mammary epithelial permeability in this population require further study.

Toxic damage to the respiratory epithelium induces acute phase changes in vitamin A metabolism without depleting retinol stores of South African children.

Whereas there is much information concerning the effects of vitamin A status on response to infectious challenge, the effects of infection or trauma on vitamin A metabolism and status are less well documented. These relationships need to be understood to optimize clinical and public health programs to improve vitamin A status and health of children in less-developed countries. We measured acute changes in retinol and retinol-binding protein in 57 young South African children hospitalized following respiratory epithelial damage resulting from accidental ingestion of kerosene. In addition, vitamin A status, as measured by the modified relative dose response test, of these children 3 mo later was compared with that of neighborhood control children to determine whether their illness had depleted retinol stores. Plasma retinol was already significantly below control levels when children were admitted [geometric mean (95% CI): 0.57 micromol/L (0.48-0.67) compared with 1.15 micromol/L (1.02-1.30) for controls] and decreased further the following morning [0.38 micromol/L (0.31-0.46)]. Significant differences in retinol-binding protein were not detected until the next morning [5.99 mg/L (4.70-7.63) compared with 14.0 mg/L (11.8-16.6) for controls] and were not as large as the relative differences in retinol. This dissociation between changes in retinol and its binding protein suggests that there may be increased retinol uptake by certain tissues during the acute phase response. The proportion of case children (37/46, 80%) with inadequate liver retinol stores 3 mo after the illness was slightly, but not significantly (chi2 = 2.16, P = 0.14), greater than the proportion of control children (28/42, 67%). Acute respiratory illness therefore did not further deplete retinol stores in this population in which stores were already frequently inadequate.

Dietary management of acute diarrhoea in children: effect of fermented and amylase-digested weaning foods on intestinal permeability.

BACKGROUND: There is a strong relationship between diarrhoea, malnutrition, and intestinal integrity. To investigate the effect of different dietary-treatment on intestinal permeability during acute diarrhoea, 87 Tanzanian children aged 6-25 months were recruited to this study when admitted to hospital. METHODS: Children with acute diarrhoea were rehydrated and then randomly assigned to one of three dietary treatment groups: a conventional low-energy density porridge, a high-energy density amylase digested porridge (AMD), or a high-energy density amylase digested and then fermented porridge (FAD). Lactulose/mannitol permeability tests were performed on admission, at 3 days, and at follow-up 2 and 4 weeks after discharge. The lactulose/mannitol (L/M) ratios were compared between dietary treatment groups and to a group of age-matched, healthy control subjects. RESULTS: Children with diarrhoea had higher L/M ratios (geometric mean 0.85, 95% CI 0.68-1.05) compared with control subjects (0.14, 0.12-0.17) on admission. There was a significant difference in the change in L/M ratio between admission and 3 days between dietary treatment groups in favour of the FAD group (p < 0.05). CONCLUSIONS: Dietary treatment and intestinal damage at admission explain 13.5% of the variation in L/M ratio, but when age at admission and age at weaning are included as covariants, 21.9% is explained. FAD porridge seems to be more effective in the treatment of intestinal permeability than AMD or conventional porridge. Urinary lactose concentrations in spot urine samples taken prior to the permeability test were also measured. There was a significant correlation with the L/M ratio (correlation coefficient = 0.62, p < 0.001).

PIP: The effect of three dietary treatments on intestinal permeability during acute diarrhea was compared in 86 Tanzanian children 6-25 months of age admitted to Muhimbili Medical Center's Pediatric Diarrhea Treatment Unit in Dar es Salaam in 1992. 55 children (64%) had received foods other than breast milk during the first week of life. After rehydration, children were randomly assigned to receive a conventional low-energy density porridge (n = 33), a high-energy density amylase digested (AMD) porridge (n = 28), or AMD porridge followed by fermented amylase digested (FAD) porridge (n = 25). Lactulose/mannitol (L/M) permeability tests were performed at admission, after 3 days, and at 2 and 4 weeks after hospital discharge. Children with diarrhea had higher L/M ratios (geometric mean, 0.85; 95% confidence interval (CI), 0.68-1.05) at admission than the 30 age-matched healthy controls (mean, 0.14; 95% CI, 0.12-0.17). The L/M ratio of study children fell over time and approached values recorded among healthy controls by the first follow-up visit. The change in L/M ratio between admission and day 3 of hospitalization was significantly greater in the FAD group (89%) than the conventional or AMD groups (44% and 75%, respectively). Dietary treatment and intestinal damage at admission explained 13.5% of the variation in this L/M ratio, while age at admission and age at weaning explained an additional 8.4%. These findings suggest that a porridge that has been both amylase digested and fermented effectively repairs mucosal damage through trophic effects on intestinal epithelium and should be administered to children with acute diarrhea to prevent malnutrition.