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Women enrolled in prenatal care at Grady Health System, Atlanta, GA, have routinely been offered HIV counseling and voluntary testing since 1987. Consistently >90% have accepted testing. With implementation of US Public Health Service guidelines for perinatal zidovudine prophylaxis in 1994, the mother-to-child HIV transmission rate rapidly decreased from 18% to 8% during the subsequent 2 years.

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Zidovudine (Zdv) is widely used to reduce maternal-infant human immunodeficiency virus transmission (HIV), but its consequences for disease progression among children infected despite Zdv exposure remain unknown. In a multicenter observational cohort study of 325 HIV-infected children born during 1986-1997, clinical progression was compared among infected children exposed or unexposed to Zdv during prenatal and perinatal periods. Zdv exposure was associated with 1.8-fold (95% confidence interval, 1.02-3.11) increased risk of progressing to AIDS or death after adjusting for year of birth, maternal CD4 cell count, maternal AIDS diagnosis, and subsequent antiretroviral therapy of the child. Mean log(10) viral copies at 7-12 weeks were higher among Zdv-exposed children (P=.004). No infected child treated early with multidrug therapy progressed to AIDS or died by 1 year, regardless of early Zdv exposure. More rapid disease progression was observed among infected children exposed during pregnancy or birth to Zdv if effective multidrug therapy was not initiated.

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BACKGROUND AND METHODS: Enteritis necroticans (pigbel), an often fatal illness characterized by hemorrhagic, inflammatory, or ischemic necrosis of the jejunum, occurs in developing countries but is rare in developed countries, where its occurrence is confined to adults with chronic illnesses. The causative organism of enteritis necroticans is Clostridium perfringens type C, an anaerobic gram-positive bacillus. In December 1998, enteritis necroticans developed in a 12-year-old boy with poorly controlled diabetes mellitus after he consumed pig intestines (chitterlings). He presented with hematemesis, abdominal distention, and severe diabetic ketoacidosis with hypotension. At laparotomy, extensive jejunal necrosis required bowel resection, jejunostomy, and ileostomy. Samples were obtained for histopathological examination. Polymerase-chain-reaction (PCR) assay was performed on paraffin-embedded bowel tissue with primers specific for the cpa and cpb genes, which code for the alpha and beta toxins produced by C. perfringens. RESULTS: Histologic examination of resected bowel tissue showed extensive mucosal necrosis, the formation of pseudomembrane, pneumatosis, and areas of epithelial regeneration that alternated with necrotic segments--findings consistent with a diagnosis of enteritis necroticans. Gram's staining showed large gram-positive bacilli whose features were consistent with those of clostridium species. Through PCR amplification, we detected products of the cpa and cpb genes, which indicated the presence of C. perfringens type C. Assay of ileal tissue obtained during surgery to restore the continuity of the patient's bowel was negative for C. perfringens. CONCLUSIONS: The preparation or consumption of chitterlings by diabetic patients and other chronically ill persons can result in potentially life-threatening infectious complications.

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OBJECTIVE: HIV infections in children are characterized by high viral load and, in some perinatally infected newborns, delayed appearance of viral markers. Both phenomena may be related to different levels of immune activation affecting viral replication. This study was designed to investigate the relationship between immune activation and viral replication in pediatric HIV infection, and the role of pre-existent immune activation in facilitating HIV transmission to the fetus/newborn. DESIGN: Plasma levels of soluble L-selectin (s-LS), an immune activation marker, were determined in 100 infants with perinatally transmitted HIV infection, compared with 106 age-matched HIV-exposed uninfected controls. Included in the analysis were samples from 31 HIV-infected (10 PCR+ and 21 PCR-) and 35 uninfected newborns aged < 2 days. METHODS: To determine s-LS levels, a solid phase ELISA was performed on plasma samples of patients and controls. RESULTS: s-LS levels in uninfected children were higher than those in normal adults. HIV-infected patients had more rapidly increasing values in the first 6 months of life compared with uninfected infants. Plasma s-LS levels correlated with HIV viral loads (r, 0.50). Among newborns in the first 2 days of life, s-LS levels were lowest in those with negative PCR tests, compared with PCR-positive or uninfected infants. CONCLUSIONS: These results suggest that higher immune activation in children contributes to higher viral loads, and that the level of pre-existent immune activation may have a role in determining which infants have detectable virus in peripheral blood at birth.

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Predictors and prognosis of intrauterine and intrapartum human immunodeficiency virus (HIV) transmission were investigated among 432 children of HIV-infected women in the Perinatal AIDS Collaborative Transmission Study. Timing of transmission was inferred from polymerase chain reaction or viral culture within 2 days of birth. Proportions of infections due to intrauterine transmission were similar among women using (29%) or not using zidovudine (30%). Preterm delivery was strongly associated with intrapartum transmission (relative risk, 3.7; 95% confidence interval [CI], 2.2-6.1), particularly among infants delivered longer after membrane rupture, but was not associated with intrauterine transmission. Progression to AIDS or death increased 2.5-fold (95% CI, 1.1-5.8) among intrauterine infected children, adjusting for preterm delivery, and maternal CD4 cell count. Early transmission appears unlikely to explain instances of zidovudine failure. Preterm infants may be more vulnerable to HIV acquisition at delivery, especially if membrane rupture is prolonged. Intrauterine infection does not appear to increase risk of preterm delivery.

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The effect of human immunodeficiency virus (HIV)-induced thymic dysfunction (TD) on mortality was studied in 265 infected infants in the CDC Perinatal AIDS Collaborative Transmission Study. TD was defined as both CD4 and CD8 T cell counts below the 5th percentile of joint distribution for uninfected infants within 6 months of life. The 40 HIV-infected infants with TD (15%) had a significantly greater mortality than did the 225 children without TD (44% vs. 9% within 2 years). Infants with TD infected in utero had higher mortality than did those infected intrapartum (70% vs. 37% within 2 years), while no significant difference was noted between infants without TD with either mode of transmission. The TD profile was independent of plasma virus load. Virus-induced TD by particular HIV strains and the time of transmission are likely to explain the variation in pathogenesis and patterns of disease progression and suggest the need for early aggressive therapies for HIV-infected infants with TD.

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Along with increasing knowledge of factors that put infants at risk for mother-to-infant HIV transmission (e.g., maternal-viral load, HIV-disease state, prematurity, and prolonged membrane rupture), there are new approaches to reducing the likelihood of such transmission (e.g., zidovudine treatment). Additional means of reducing transmission may become available in years to come. In this context, prenatal voluntary identification of HIV-infected women is vital. Finally, appropriate use of early diagnostic tests in HIV-exposed infants will allow effective use of prophylactic and therapeutic means.

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BACKGROUND: Little is known about whether a woman's risk of transmitting HIV perinatally increases over time and whether the infection outcome of a previous child affects the risk of transmitting HIV to subsequent children. METHODS: We analyzed data from 114 prospectively followed women who gave birth to at least 2 children after becoming infected with HIV to determine the risk for perinatal HIV transmission to these sibling pairs. RESULTS: The median interval between sibling births was 19 months. HIV infection occurred in 19 (17%) older siblings and 20 (18%) younger siblings (P = 0.87). Two (11%) of the 19 children with infected older siblings were infected compared with 18 (19%) of the 95 children with uninfected older siblings (P = 0.86). The risk for transmission to younger siblings was not associated with the interval between deliveries of the two siblings. CONCLUSIONS: These data do not demonstrate that an HIV-infected woman's risk of transmitting HIV perinatally increases with time, although the observed interpregnancy interval was relatively short. The risk for perinatal transmission does not appear to be affected by the infection outcome of previous children. These findings may be useful for counseling HIV-infected women about their risk of transmitting HIV perinatally.

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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.

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A 10-year retrospective study of age-frequency, sites of infection, and pre-existing conditions in 297 children with Hemophilus influenzae (HI) disease seen at Grady Memorial Hospital from 1974 through 1984 is described. The majority of the patients were black (73%) and of lower socioeconomic status and were less than 2 years of age. Manifestations of HI disease were similar to those described in reports from other centers, with meningitis being the most common (56.7%). Epiglottitis was much less common in the present study than is generally reported. The death rate of all patients was 1.8 percent. The results of this study indicate that HI disease continues to be a significant risk in children less than 2 years of age.

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