Estimates of disease incidence in women based on antenatal or neonatal seroprevalence data: HIV in new york city

Piecewise constant incidence models were developed to estimate the force of infection in women from age-and time-specific antenatal or neonatal seroprevalence data. Differential inclusion of infected women in sero-surveys compared to uninfected women was taken into account, with respect to both changes in inclusion rate following infection, and changes in relative inclusion rate over calendar time. These models were applied to anonymous HIV seroprevalence data collected from neonates born to black and Hispanic women in New York City 1988-1992, with incidence and fertility parameters estimated by maximum likelihood. Estimates of inclusion rate parameters accorded well with what is known about the natural history of HIV. The data could not distinguish between additive and multiplicative combination of the effects of age and time on incidence. Incidence was strongly dependent on age with the highest incidence in women aged 20-34 years. There was strong evidence that incidence had been falling in Hispanic women since 1982-1984. The results illustrate the extent to which trends in incidence over time may be confounded by changes in the relative inclusion rate of infected and uninfected women.     

Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

"In vivo effects of rIL-2 pretreatment on chemotherapeutically induced in vivo natural cytolytic hyporesponsiveness"

Chemotherapeutics have been shown to have detrimental effects on immune response, hence, pretreatment or concurrent use of an immune augmentation substance could lead to reconstitution of an immune response such as cytolytic activity after administration of chemotherapeutic agent. Previously, in an in vitro system, we have demonstrated IL-2 pretreatment reconstituted drug induced immunosuppression as well as altered differential sensitivities to chemotherapeutic agents. This study presents evidence that in vivo functional cytolytic potential can be retained by IL-2 pretreatment on chemotherapeutically-induced natural cytolytic hyporesponsiveness.     

Protective effect(s) of rIL-2 modulation. I. The effects of chemotherapeutic/cytotoxic agents on human natural killer cells and lymphokine-activated killer cells

This study investigated whether in vitro immunotherapy with rIL-2 which augments human natural cytotoxicity and generation of lymphokine-activated killer cells diminished or inhibits the severity of therapeutically induced human in vitro NK immunosuppression. We demonstrate that rIL-2 induces a rapid and potent enhancement of cytolytic killing and that pretreatment of effector cells for one hour with rIL-2 yields effector cells which are more resistant to drug-induced immunosuppression. Additionally, we demonstrate cells pretreated for 24 hours with rIL-2 were less sensitive to drug inhibitory effects than rIL-2 non-treated or one hour pretreated effector cells. Our data suggest prophylactic treatment with IL-2 for drug induced immunosuppression is feasible.     

Age-related reference ranges: Significance tests for models and confidence intervals for centiles

A method of fitting age-related reference ranges using maximized likelihood is presented. The method is illustrated using CD4 counts of uninfected children born to HIV-1 infected women. The likelihood incorporates exponential functions to describe the Box-Cox transformation parameter that induces Normality and the mean and standard deviation of the transformed data, at all ages in the range. This guarantees that the centiles are asymptotic to notional adult values and avoids edge effects. Likelihood ratio tests were used to assess the significance of the model parameters, and profile likelihood confidence intervals were constructed around the fitted centiles. The asymptotes of the resulting CD4 reference range for the childhood dataset were compared with CD4 counts available from a group of uninfected adults. The proposed approach limits the need for arbitrary decisions about grouping of the data, degree of smoothing or choice of model.     

Obstetric and perinatal consequences of human immunodeficiency virus (HIV) infection: a review

Pediatric acquired immune deficiency syndrome (AIDS) was known to be a new disease that could be acquired from the mother even before human immunodeficiency virus (HIV) was identified. The suggested routes of transmission of infection are intrauterine, perinatal--from contact with infected maternal genital secretions, or through breastfeeding. At this time the problem in Europe concerns primarily women in high-risk groups: intravenous drug abusers, prostitutes, women from countries where the prevalence of HIV is high, and women whose sexual partners are in a high-risk group. In the future, the infection may extend beyond women in high-risk groups as the disease becomes more prevalent in the community. It has been claimed that pregnancy accelerates symptoms in women who are HIV positive, yet this is based on only a series of case reports of severe infection in pregnancy and on the development of AIDS in asymptomatic women in pregnancy subsequent to the birth of an AIDS child. The only data capable of shedding some light on this issue would be a prospective followup of both pregnant and nonpregnant HIV-positive women from similar high-risk groups. Such a study is ongoing in the US. An increasing number of case reports suggest intrauterine transmission of infection. The following 3 case reports provide clear evidence of intrauterine transmission. Sprecher et al. (1986) detected HIV antigen in amniotic fluid and fetal tissues from a pregnancy termination at 15 weeks gestation in a woman with stage IV AIDS and Kaposi sarcoma. Lapointe et al. (1985) reported an infant born by cesarean section at 28 weeks gestation to a mother with terminal aids. A new dysmorphic syndrome recently has been described in children with symptomatic HIV infection (Marion et al., 1986). HIV has been isolated from cervical secretions (Fogt et al., 1986; Wofsy et al., 1986), which suggests that this cold be another source of infection. There is 1 report of isolation of HIV from the noncellular fraction of breast milk (Thirty et al., 1985). Several case reports have described acquired immunodeficiency in infants for whom the only known risk factor was neonatal transfusion from an individual later found to be suffering from AIDS. The risk of transmission from an infected mother to her infant is unknown, but the best available evidence comes from a study of children born to women who had previously given birth to a child with AIDS (Scott et al, 1985). Of 12 children, 4 developed AIDS or Aids-related complex. Clinical problems among children with AIDS or AIDS-related complex have been fully described. The fatality rate of children with AIDS is high, but the ultimate progress of children with less severe disease or who have asymptomatic infection is known.     

Decreased serum levels of nutritional biochemical indices in healthy children with marginally delayed physical growth

Biochemical markers of nutritional status (albumin, transthyretin, insulin-like growth factor-I and zinc) were measured in slowly growing two- to five-year-old, low-income Parisian children whose weight-for-height or height-for-age z scores (WHZ or HAZ) were between — 1 and — 2 SD of the NCHS median. The results were compared to controls who were matched for age, sex, and ethnic origin with WHZ and HAZ between — 1 and + 2 SD. Mean serum levels of transthyretin, albumin and insulin-like growth factor-I and mean plasma zinc concentrations were significantly lower in the growth-impaired children than in the controls ( p = 0.002, p = 0.006, p = 0.015, and p = 0.035, respectively). While the height-retarded children had low mean serum insulin-like growth factor-I values, the weight-retarded subjects had decreased levels of albumin, transthyretin and zinc when compared to controls. Lower mean levels of nutritional markers in healthy, slowly growing children suggest that inadequate dietary intakes of zinc, protein and/or energy may result in marginal delays in weight and height gains.     

Evidence for superantigenic activity during murine malaria infection

TCR V beta usage was examined in C57BL/6 mice infected with Plasmodium yoelii. In addition to a polyclonal T cell activation, already described, a superantigenic-like activity was observed during the acute infection. This superantigenic activity induces a preferential deletion without prior expansion of CD4+ and CD8+ T cells bearing the TCR V beta 9 segment. The superantigen could be released by the parasite at different stages of its development since the deletion of V beta 9+ T cells was observed in blood and lymph nodes of mice infected either with sporozoites or with erythrocytic stages. Injection of sporozoite or parasitized erythrocytes to newborn mice led to a deletion and anergy of peripheral V beta 9+ T cells, without affecting thymic T cell populations. These observations suggest that the superantigen is released at very low concentrations during parasite development. The role of such parasite superantigenic activity in infectivity can be underlined by the observation that congenic BALB.D2 Mis1a mice lacking V beta 9 T cells are more susceptible to infection by P. yoelii.