Serologic response to hepatitis B vaccine in HIV infected and high-risk HIV uninfected adolescents in the REACH cohort. Reaching for Excellence in Adolescent Care and Health.

PURPOSE: To evaluate hepatitis B (HBV) vaccine response rates in HIV infected and high-risk HIV uninfected youth and examine associations with responsiveness in the HIV infected group. METHODS: Cohorts within the Reaching for Excellence in Adolescent Care and Health (REACH) study population were defined based on receipt of HBV vaccine both retrospectively and prospectively. Sero-responsiveness was determined by HBsAb measurements. Testing was done for HBsAg, HBsAb, and HBcAb. For HBsAb, a value of > 10 International Units per liter was considered a positive response, and the data were collected as either positive or negative from each of the reporting laboratories. Covariates of responsiveness were explored in univariate and multivariate models for each cohort. RESULTS: Sixty-one subjects had received a three-dose vaccination course at the time of entry into REACH. HIV uninfected subjects had significantly higher rates of response by serology compared with HIV infected subjects (70% vs. 41.1%; chi(2) = .05; RR = .586, 95% CI: .36-.96). By the time of an annual visit 43 subjects had received three vaccinations with at least one occurring in the study period. The rates of response were similar for the HIV infected and uninfected groups (37.1% vs. 37.5%) in this cohort. Univariate and multivariate analysis in the prospective HIV infected group (N = 35) found an association between elevated CD8(+)/CD38(+)/HLA-DR(+) T cells and lack of HBV vaccine responsiveness (6.7% vs. 60%; chi(2) = .03; RR = .12, 95% CI: .02- .55). CONCLUSIONS: The poor HBV vaccine response rate in the HIV uninfected high-risk adolescents was unexpected and suggests that HBV vaccination doses have not been optimized for older adolescents. This is the first report of decreased responsiveness in HIV infected subjects being associated with elevated CD8(+)/CD38(+)/HLA(-)DR(+) T cells and suggests that ongoing viral replication and concomitant immune system activation decreases the ability of the immune system in HIV infected subjects to respond to vaccination.

Early progression of disease in HIV-infected infants with thymus dysfunction.

BACKGROUND: Infants with congenital thymic deficiency (the DiGeorge syndrome) have immunodeficiency and a characteristic pattern of low CD4+ and CD8+ T-lymphocyte counts and low CD5+ B-lymphocyte counts. Because the thymus is essential for the generation of CD4+ cells, we sought evidence of thymus dysfunction in infants infected perinatally with the human immunodeficiency virus (HIV). METHODS: We studied the immunophenotypes of 59 infants with maternally transmitted HIV, 5 infants with the DiGeorge syndrome, and 168 infants exposed to HIV but not infected. The criteria for a presumed thymic defect were reductions in both the CD4+ and CD8+ T-cell subgroups during the first six months of life that were confirmed in a subgroup of infants by low counts of CD4+CD45RA+ and CD4+CD45RO+ T cells and CD5+ B cells. RESULTS: Of the 59 HIV-infected infants, 17 had immunophenotypes similar to those of infants with the DiGeorge syndrome. The risks of the acquired immunodeficiency syndrome (AIDS) by the ages of 12 and 24 months were 75 percent and 92 percent in these 17 infants, as compared with 14 and 34 percent in the other 42 infants (P<0.001). Nine of the HIV-infected infants with the DiGeorge-like immunophenotype (53 percent) died within six months of the progression to AIDS, as compared with only three of the other infants (7 percent, P=0.006). CONCLUSIONS: In some infants infected perinatally with HIV, a pattern of lymphocyte depletion develops that resembles the pattern in congenital thymic deficiency. Since HIV disease progresses rapidly in such infants, they may be candidates for early antiviral therapy and attempts at immune reconstitution.

A prospective population-based study of HIV perinatal transmission.

OBJECTIVE: To estimate the perinatal HIV transmission rate and describe the natural history of infant HIV infection in a situation in which HIV status is known in more than 95% of delivering women. DESIGN: A cohort of HIV-exposed infants born between 7 July 1987 and 30 June 1990, whose mothers were identified by routine voluntary universal HIV testing, were followed using clinical and laboratory measures. SETTING: Grady Memorial Hospital, a major health-care site for individuals of lower socioeconomic status in Atlanta, Georgia, USA, with approximately 7000 deliveries per year. PATIENTS: HIV-exposed infants (n = 165), 98% of whom were African American. RESULTS: Annual maternal HIV seroprevalence increased from 0.58 to 0.86%. The annual proportion of HIV-positive women having a second delivery increased from 4.3 to 25%. Clinical outcome was known for 132 out of 165 infants (22 infected and 110 uninfected), the transmission rate was 17% (confidence interval, 11-24%). The rate declined to 11% by the third year of the study. Gestational growth, prematurity and mode of delivery were unrelated to infant outcome. There was a trend for intravenous drug use to be more common in mothers of infected infants (P = 0.08). After 35 months median follow-up of infected infants, eight out of 22 (36%) had an opportunistic infection (seven Pneumocystis carinii pneumonia); three out of 22 (14%) had lymphocytic interstitial pneumonia, and 10 out of 22 (45%) were asymptomatic or had only nonspecific symptoms. Cumulative mortality in infected infants was 9, 32 and 32% by 1, 2 and 3 years of age, respectively. CONCLUSION: In this cohort of HIV-exposed infants, perinatal HIV transmission was 17% overall. Factors affecting the transmission rate and possible future changes in the rate require further study.

Bacterial diseases of the colon.

Acute diarrhea of bacterial origin is discussed for seven enteric pathogens, and specific antimicrobial therapy based on positive identification is stressed. Selection of patients with self-limited disease not requiring antimicrobial therapy is emphasized in order to avoid costly laboratory tests. The role of daycare facilities in the spread of enteric pathogens in this country is discussed. This article includes a review of newer methods for treating infants and children with oral rehydration and rapid refeeding.

Androstenedione metabolism by human lymphocytes.

Intact human lymphocytes were incubated with tritium-labeled androstenedione; after extraction and appropriate chromatographic separation, followed by crystallization to constant tritium to carbon-14 ratio to establish radiochemical homogeneity, the following metabolites were identified: testosterone, 5 alpha-androstane-3,17-dione, 5 alpha-dihydrotestosterone, androsterone and isoandrosterone. Neither estrogen nor 5 beta-reduced metabolites were found as products. The major androstenedione metabolizing activities in human lymphocytes were 5 alpha-reductase and 17 beta-hydroxysteroid oxidoreductase; in addition, 3 alpha-and 3 beta-hydroxysteroid oxidoreductase activities also were present in these cells. The rates of metabolite formation were linear with incubation time up to 4 h, and with cell number up to 2 x 10(7) lymphocytes per ml for the 5 alpha-reduced products and up to 1.6 x 10(7) lymphocytes per ml for testosterone. These findings are suggestive that, in the human, lymphocytes are a potential site of peripheral metabolism of androstenedione to potent adnrogens.

Recurrent infections and delayed separation of the umbilical cord in an infant with abnormal phagocytic cell locomotion and oxidative response during particle phagocytosis.

An 18-month-old infant with delayed separation of the umbilical cord and severe recurrent bacterial infections since the newborn period was found to have depressed polymorphonuclear leukocyte locomotion and oxidative metabolic response to particulate stimuli. Both her polymorphonuclear leukocytes and monocytes demonstrated a markedly delayed chemiluminescence response to zymosan, but there was a normal chemiluminescence response to soluble stimuli, phorbol myristate acetate and calcium ionophore A23187. The patient also had a marked delay in uptake of Staphylococcus aureus and Escherichia coli. The patient's polymorphonuclear leukocytes were normal morphologically, and myeloperoxidase was present in histochemical stains. The dichotomy between normal oxidative response to soluble stimuli and abnormal response to opsonized particulate stimuli, plus abnormal cell locomotion and phagocytosis, suggest an abnormality of cell membrane fluidity or contractility.

Renal responses of Australian lungfish to vasotocin, angiotensin II, and NaCl infusion.

The Australian lungfish (Neoceratodus forsteri) responds to intravenous injections of 0.63 ng/kg or more of arginine vasotocin with increased dorsal aortic blood pressure, inulin clearance, urine flow, and tubular rejection of Na+. Single injections of 1 ng/kg or more of angiotensin II or norepinephrine also increase dorsal aortic pressure but do not cause consistent diuresis and natriuresis, Continuous infusions of angiotensin II or repeated injections of norepinephrine produce sustained hypertension and more modest diuresis and natriuresis than are seen after injections of arginine vasotocin that cause less hypertension. Infusions of isosmolar or hyposmolar NaCl solutions increase blood pressure, inulin clearance, urine flow, and tubular Na+ rejection in a manner resembling the response to argininge vasotocoin injections. These data are consistent with the hypothesis that arginine vasotocin is released in response to volume expansion in lungfishes and that it may act on the kidney as a diuretic and natriuretic hormone. They do not rule out a more direct action of expansion on renal functions.