Altered Memory T-Cell Responses to Bacillus Calmette-Guerin and Tetanus Toxoid Vaccination and Altered Cytokine Responses to Polyclonal Stimulation in HIV-Exposed Uninfected Kenyan Infants.

Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU) infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU) infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42) and HU (n = 28) Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-α responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytokine responses were consistently lower than those seen in HU infants. Finally, reduced effector memory Th1 responses to vaccine antigens were observed in HEU infants at 3 and 12 months and higher central memory Th1 responses to M. tuberculosis antigens were observed at 3 months only. Long-term monitoring of vaccine efficacy and T-cell immunity in this vulnerable population is warranted.

The need for a reproductive health approach.

A reproductive health approach recognizes that the foundations of women's health are laid in childhood and adolescence, and are influenced by factors such as nutrition, education, sexual roles and social status, cultural practices, and the socioeconomic environment. Reproductive health care strategies to meet women's multiple needs include education for responsible and healthy sexuality, safe and appropriate contraception, and services for sexually transmitted diseases, pregnancy, delivery, and abortion.

Child spacing: impact on health.

PIP: The incidence and pattern of infant death and child illness and death are closely linked to fertility levels and birth intervals. Estimates from the World Fertility Survey data for all countries combined show that infant mortality is 60-70% higher for children born within 2 years or less of birth of an older sibling. Risk for the older child is 77% higher if a new baby is born within 1 year. About 1 in 7 of the 14 million deaths among children under 5 are associated with poor birth spacing. The detailed risk factors explaining these deaths include stopping breast feeding too soon, which increases likelihood of succumbing to diarrhea and respiratory infections. Breast feeding into the 2nd and 3rd years supplements nutrition where malnutrition is common. Since breast feeding has a natural contraceptive effect, early weaning may be a cause of rapid pregnancy as well as a result. A major advantage of longer birth intervals is reduced chance of low birth weight, a major contributing factor in infant deaths. Family health is another effect of longer child spacing because the mother has time to recover physically, to care for other young children, and give them time and attention. With fewer youngsters, change of infection passing between them is much lower. Women need access to family planning and education about the importance of breast feeding.^ieng

Farm background, socioeconomic status, and fertility: the two-generation hypothesis.

PIP: This paper examines whether the effects of farm background on socioeconomic differentials in fertility are diminished among nonfarm couples. The data are for a sample of white ever-married women belonging to the 1901-1910 birth cohorts. The research provides another test of the 2 generation-urbanite hypothesis 1st advanced by the Goldberg studies of Detroit and Indianapolis. Unlike a number of other studies, the findings do not support the hypothesis. Thus, a number of questions arise concerning the results obtained by previous investigators in support of this hypothesis. Different types of samples measuring farm background and socioeconomic status may be plausible explanations for the differing results. It is also important to note that both the Detroit and Indianapolis samples can hardly be considered representative of US urban populations in the 1940s and 1950s. A further difficulty with the Detroit study was that Goldberg aggregated the data of a relatively large number of cohorts. The Indianapolis sample was constrained by the eligibility requirements of the original study. The difficulties of adequately testing Goldberg's hypothesis may have been compounded by the extension of the hypothesis to nationally representative samples. Moreover, The hypothesis was not supported when education was used as a measure of socioeconomic status in the Detroit study. Until other studies can be carefully replicated, definitive answers to such questions as to whether fertility differentials by socioeconomic status will disappear or have become attenuated must remain an unanswered question.^ieng

Possible prevention and treatment of steroid-induced osteoporosis.

Patients with steroid-induced, juvenile and senile osteoporosis were studied using balance techniques. The changes in calciun and phosphorus balance associated with glucocorticoid therapy were corrected with vitamin D and bendrofluazide given in combination. No hypercalcaemia occurred in osteoporotic patients who continued to receive glucocorticoids. Calcium and phosphorus balance was also improved in the osteoporotic subjects not receiving steroids, but these patients became hypercalcaemic during treatment. It is suggested that vitamin D, bendrofluazide and steroids antagonize the actions of one another on the renal tubule, gut and bone and in this way prevent the increased calciuria which occurs with glucocorticoid therapy. Since the increased calciuria and negative calcium balance induced by glucocorticoids is considered to be the result of excessive bone resorption, an adequate dose of bendrofluazide and vitamin D in combination might prevent the development of, or even reverse, steroid-induced osteoporosis.

Treatment of Paget's disease of bone with mithramycin.

We report data from three patients with severe Paget's disease of bone who were treated with mithramycin.Mithramycin infusion resulted in a fall in plasma calcium, phosphate, alkaline phosphatase, and urinary hydroxyproline excretion. There was an improvement in calcium and phosphorus balance in two of the three subjects studied. A pronounced or complete relief of bone pain occurred in all three.We suggest that mithramycin exerts its beneficial effect in Paget's disease of bone by stimulating parathyroid hormone release. The parathyroid hormone released has a predominantly anabolic action on bone since its catabolic action is blocked by mithramycin, which inhibits bone resorption.

Defective intestinal phosphate absorption in familial and non-familial hypophosphataemia.

With an oral phosphate tolerance test a primary defect in intestinal phosphate absorption was found in patients with untreated familial and non-familial hypophosphataemia. It is suggested that this plays a major part in the aetiology of rickets and osteomalacia in these disorders. Vitamin D was shown to have a beneficial effect on intestinal transport of phosphate, though defective absorption was not completely corrected. If intestinal phosphate absorption is normal, oral phosphate supplements will maintain normal plasma phosphate levels even in the presence of a pronounced renal phosphate leak.In familial and non-familial hypophosphataemia the phosphate tolerance test may be a more sensitive index of genetic abnormality than a low plasma phosphate. It may be helpful in distinguishing several syndromes at present classified under non-familial hypophosphataemia, as well as assessing the response to treatment with vitamin D and in investigating intestinal transport of phosphate.