Cecelia Hutto

Survival in children with perinatally acquired Human Immunodeficiency Virus type 1 infection

Abstract We describe our experience at Jackson Memorial Hospital in Miami, Florida, with 172 children who were given diagnoses of perinatally acquired infection with human immunodeficiency virus ty...

Increased Rate of Cytomegalovirus Infection among Parents of Children Attending Day-Care Centers

We screened parents of children from three previously studied day-care centers where children have maintained high rates of cytomegalovirus (CMV) excretion, as well as parents of children not in day-care centers (controls), for antibody to CMV. Longitudinal serologic follow-up of seronegative parents revealed that 14 of 67 with children in the day-care centers acquired CMV, as compared with none of 31 controls (P less than 0.003). All 14 parents who seroconverted had a child who was shedding CMV in saliva or urine. Among the day-care group, acquisition of CMV occurred in 14 of 46 parents of children who shed CMV, as compared with none of 21 whose children did not excrete the virus (P less than 0.0001). There was no correlation between parental seroconversion and sex, race, age, number of years of education, marital status, occupation, or number of children in the home. CMV infection occurred in 9 of 20 parents (45 percent) with a child shedding CMV who was 18 months of age or less at enrollment. We conclude that children often transmit CMV to parents and could be an important source of maternal CMV infection during pregnancy.

Increased rate of cytomegalovirus infection among day care center workers.

Child care workers are potentially at risk for occupational exposure to cytomegalovirus, the leading cause of congenital infection in the United States. Preschool children often shed cytomegalovirus and commonly transmit virus to peers and parents. Workers from 32 day care centers were enrolled and tested for serum antibody to cytomegalovirus; 318 (62.5%) were seropositive. By logistic regression analysis the only variables significantly (P less than 0.05) associated with seropositivity at enrollment were older age and nonwhite race, though contact with younger children (less than 2 years of age) attained a P value of 0.06. Follow-up sera were obtained at 6-month intervals from 82 initially seronegative workers; 19 seroconverted in a median interval of 14 months, a rate of 20%/year, approximately 10-fold higher than the expected rate. The only demographic or employment variable associated with seroconversion was contact with children younger than 3 years of age for at least 20 hours per week (P = 0.03). Day care center workers have a markedly increased risk for acquisition of cytomegalovirus; those who could become pregnant should be appropriately counseled regarding prevention and consequences of cytomegalovirus infection during pregnancy.

A longitudinal assessment of autologous neutralizing antibodies in children perinatally infected with human immunodeficiency virus type 1

The evolution of autologous neutralizing antibodies to sequential human immunodeficiency virus type 1 (HIV-1) isolates was studied in a population of 16 children who were perinatally infected with human immunodeficiency virus type 1. The cohort included seven children with rapid disease progression (RP) and nine who had nonrapid disease progression (NRP). Four of the NRP after 6 months of age harbored viruses that could be neutralized by antibodies found in autologous contemporaneous plasma (titers up to 1:640) while the majority of longitudinally collected viruses from five NRP were resistant to neutralization with contemporaneous plasma. Because of their shorter survival, only five of the RP had studies after 6 months of age; three of the five had neutralizing antibodies to contemporaneous virus isolates and the highest titers were 1:20. The highest titers in RP (up to 1:160) occurred in specimens obtained prior to 6 months of age but these were most likely of maternal origin. Most isolates that were not neutralized by contemporaneous plasma could be neutralized using noncontemporaneous plasma obtained months to years after the virus isolates. These autologous noncontemporaneous neutralizing antibodies persisted for years, had titers that were higher to viruses isolated at younger ages, and were generally more potent in children with NRP than RP. Demonstration of neutralizing antibodies to viruses previously resistant to neutralization by contemporaneous plasma suggests a continuous evolution of virus variants in vivo that are able to escape the effect of neutralizing antibodies.

The natural history of human immunodeficiency virus 1 infection in Haitian infants.

OBJECTIVES The current study followed HIV-infected women through pregnancy and their infants through the first 2 years of life to determine the rate of vertical transmission of HIV infection from Haitian women, factors in maternal health and obstetrical history that might influence such transmission and the natural history of HIV infection in their affected offspring. STUDY DESIGN The medical histories of 81 infants born of HIV-infected women and of a control group of 88 infants born to uninfected women were documented with close clinical and serologic follow-up. In addition to standard tests for persistence of HIV antibodies, the use of acid-dissociated p24 assays enabled us to assign some additional infants to the HIV-infected cohort. RESULTS Transmission could be documented in 27% of infants born to HIV-infected women. Excess early deaths occurred in infants of HIV-infected women in Port-au-Prince with 60% of infected infants dead by 6 months of age. This is a more accelerated mortality than that in a group of 42 HIV-infected infants born of Haitian mothers living in Miami where 10% were dead at 6 months. Clinically, in 6 of 19 deaths in HIV-infected children in Haiti, failure to thrive and gastroenteritis lead to a systemic infection manifested as meningitis, sepsis or pneumonia as the immediate cause of death. CONCLUSIONS Early mortality attributable to perinatally acquired AIDS was identified in Haiti. The comparison of data from Miami and Port-au-Prince suggests that environmental exposures in developing countries may be more operative in this early mortality than viral strain or maternal host factors, both of which might be expected to be similar between the two groups of Haitian ethnicity.

Survival in children with perinatally acquired human immunodeficiency virus type 1 infection

We describe our experience at Jackson Memorial Hospital in Miami, Florida, with 172 children who were given diagnoses of perinatally acquired infection with human immunodeficiency virus type 1 (HIV-1). The 146 mothers of the children acquired HIV-1 through heterosexual contact (69 percent), intravenous drug use (30 percent), or blood transfusion (1 percent). The children presented with symptomatic disease at a median age of eight months; only 21 percent presented after the age of two years. The most common first manifestations of disease were lymphoid interstitial pneumonia (in 17 percent), encephalopathy (in 12 percent), recurrent bacterial infections (in 10 percent), and candida esophagitis (in 8 percent), for which the median survival times from diagnosis were 72, 11, 50, and 12 months, respectively. Nine percent of the children had Pneumocystis carinii pneumonia at a median age of five months and had a median survival of only one month. The median survival for all 172 children was 38 months from the time of diagnosis. Mortality was highest in the first year of life (17 percent), and by proportional-hazard analysis the probability of long-term survival is low. In multivariate analyses, early age at diagnosis and the first identifiable pattern of clinical disease were found to be independently related to survival. We conclude that children with perinatally acquired HIV-1 infection have a very poor prognosis and that most become symptomatic before one year of age. Early diagnosis is important, since there is only a short interval in which to initiate prophylactic or antiviral treatment before progressive disease begins.

IgE-based assay for early detection of HIV-1 infection in infants.

5Serum samples were collected from patients with HFRS in the Tula region during the outbreak and from convalescent patients (collected between 1 month and 4 years after disease) in the Tula and Ryazan regions. Initial serological screening by immunofluorescence assay (IFA) revealed higher antibody titres to Hantaan, Seoul, 5 and DOB (N Apekina, unpublished) antigens than to Puumala. These findings indicated that a hantavirus other than Puumala virus was the causative agent of the outbreak. In our study of 22 hantavirus-IgG-positive serum samples, as confirmed by ELISA with Puumala, DOB, and Hantaan antigens, 2 all showed the highest reactivities to DOB. However, since previous studies have identified high levels of crossreactive antibodies to several hantaviruses by IFA or ELISA analysis, the serum samples were further assayed by focus-reduction neutralisation test which allows precise serotyping. To avoid misleading crossreactivity of neutralising antibodies during the acute phase of HFRS, 2 only samples from convalescent patients obtained more than 1 month after onset of disease, were selected. Nine such samples were analysed against the hantaviruses known to cause HFRS and the putatively apathogenic Tula virus (table). All serum samples showed high specificities of neutralising antibodies to DOB, confirming its involvement in the Tula-Ryazan outbreak. Our results do not confirm the previously proposed involvement of Seoul virus in the outbreak because none of the serum samples showed significant titres to this hantavirus.