Mother-to-child transmission of the human immunodeficiency virus in Texas.

BACKGROUND: The Pediatric Spectrum of HIV Diseases (PSD) project has been collecting data on HIV-exposed children in Texas since 1989. These data have now been analyzed to describe mother-to-child transmission in Texas and to provide much needed information on the magnitude of the pediatric HIV epidemic in the state. METHODS: We examined trends in the numbers of perinatally exposed children and perinatally acquired cases of HIV in the Texas PSD cohort. We calculated transmission rates and relative risks for 656 children born from January, 1995, to July, 1998, that received all or part of the ACTG 076 regimen. RESULTS: Only a small proportion (38%) of pairs of an HIV-infected mother and her HIV-exposed child received the full AIDS Clinical Trial Group 076 (ACTG 076) regimen; only 73% of the mothers received at least some prenatal care. In recent years, however, the numbers of perinatally exposed children and perinatally acquired cases of HIV have decreased in Texas. Univariate analyses showed that a reduction in the vertical transmission of HIV was associated with receipt of a full ACTG 076 regimen, receipt of a partial ACTG 076 regimen and residence in Dallas County. CONCLUSIONS: Findings identify a gap in meeting the health care needs of pregnant HIV-infected women and suggest missed opportunities to prevent mother-to-child transmission of HIV. At the same time this study confirms progress in prevention efforts to reduce mother-to-child transmission of HIV in Texas.

Concerns of pregnant women about bing tested for HIV: a study in a predominately Mexican-American population.

More than 90% of pediatric acquired immune deficiency syndrome (AIDS) cases are due to mother-to-child (vertical) transmission. Medical intervention can reduce the risk of vertical transmission human immunodeficiency virus (HIV) from 25% to less than 8%. However, studies have suggested that approximately one-fourth of women may refuse HIV testing as part of routine prenatal care. The purpose of this study was to identify concerns that pregnant women might have that would impact their decision to undergo HIV testing in pregnancy. The study is a cross-sectional survey of 413 pregnant women in south Texas. A survey questionnaire was used to assess reasons why subjects might avoid HIV testing and to assess their risks for HIV infection. The reasons for not wanting HIV testing grouped around four themes: (1) fear of being stigmatized as sexually promiscuous or as an injecting drug user; (2) denial about the possibility of being infected; (3) fatalism; and (4) of rejection leading to loss of emotional and financial support. Overall, 15% of subjects who had not been previously tested (5% of all subjects) indicated that they would refuse HIV testing, a rate which is below rates of 20%-24% in previous studies. The lower rate of refusal for HIV testing in our study may reflect a downward trend nationally in the rate of refusal for prenatal testing. Many women have concerns about HIV testing, although these concerns may not necessarily prevent them from undergoing testing. Physicians and policy makers need to be aware of women's concerns and fears when implementing HIV testing policies.

False-positive and indeterminate human immunodeficiency virus test results in pregnant women.

Guidelines from the Centers for Disease Control and Prevention, Atlanta, Ga, recommend that all pregnant women be offered human immunodeficiency virus (HIV) testing to ensure that they have the opportunity to use currently available therapeutic interventions to reduce the risk infecting their offspring with HIV. These recommendations have resulted in an increased number of low-risk women being tested and a significant rise in the percentage of false-positive results from HIV antibody screening tests and ambiguous (indeterminate) findings from confirmatory tests. Women receiving such results are generally in emotional turmoil yet must make treatment choices if they prove to be infected. This article provides guidelines to help general medical practitioners to understand the nature of HIV testing, to assess a woman's infection status when initial tests are ambiguous, and to determine when treatment is appropriate.

The role of Citrobacter in clinical disease of children: review.

Various species of Citrobacter may cause infections in neonates and immunocompromised hosts. Citrobacter koseri (formerly Citrobacter diversus) is best known as the cause of sepsis and meningitis leading to central nervous system (CNS) abscesses in neonates and young infants. Early onset and late-onset infections occur as for other neonatal bacterial infections. The majority of cases are sporadic, with no clear source of infection. A few have been confirmed to be vertically transmitted, and nosocomial outbreaks have occurred in neonatal care units. The pathophysiology is not well understood, but a surface protein has been identified as a possible virulence factor among strains that cause citrobacter brain abscesses in neonates. Despite improvements in diagnostic imaging techniques, surgery, and antibiotic therapy, approximately one-third of infants with abscesses die, and one-half sustain CNS damage. In this article, the taxonomy, epidemiology, pathogenesis, diagnosis, treatment, and outcome of citrobacter disease in children are reviewed.

Factors contributing to delayed diagnosis of HIV-infected women and their children in south Texas.

Preliminary results from a previous study at a family human immunodeficiency virus (HIV) clinic in South Texas indicated that HIV-positive (HIV+) children from small communities were usually infected and often symptomatic at the time of referral. The current study evaluated rates of vertical transmission and factors that contributed to delayed diagnosis of HIV for 82 children born to HIV-infected women in South Texas. Children from smaller metropolitan statistical areas (MSAs) were infected more often (70.4% vs. 33.3%), identified later (average 9.7 vs. 3.2 months) and were less often known to be HIV+ at birth (51.4% vs. 64.4%), than those from the largest MSA. In addition, children whose mothers were infected sexually were infected more often (52.8% vs. 32.0%), tested later (average 7.6 vs. 1.6 months), and were less often known to be HIV+ at birth (46.8% vs. 85.2%), than those children whose mothers were injecting drug users (IDU). Children followed from birth were infected less often (34.3%) than those identified later (65.5%). In South Texas, children born to HIV+ mothers were at higher risk for missed or delayed diagnosis if they were from small MSAs and had mothers who were infected sexually. Early diagnosis of HIV+ women and children is increasingly important because of advances in treatment of HIV and prevention of vertical transmission of HIV.

A conformationally defined 6-s-trans-retinoic acid isomer: synthesis, chemopreventive activity, and toxicity.

A conformationally defined retinoic acid analog (1) which contains a dimethylene bridge to maintain the 6-s-trans orientation for two terminal double bonds in the polyene chain was synthesized. A Reformatsky reaction was utilized to extend the polyene chain of the starting enone, which provided exclusively the 9Z-configuration for the intermediate aldehyde. A Horners-Emmons condensation with this aldehyde then produced retinoic acid analogs with both 9Z- and 9Z,13Z-configurations. An I2-catalyzed isomerization of the intermediate 9Z-aldehyde yielded the all-E-aldehyde, which was olefinated as above to yield the (all-E)- and (13Z)-retinoic acid analogs of 1. Each configurational isomer of 1 was evaluated for its ability to inhibit the binding of retinoic acid to CRABP (chick skin) and to inhibit the chemical induction of ornithine decarboxylase in mouse skin. In each assay (all-E)-1 was the most active isomer, and this activity was comparable to or better than that for (all-E)-retinoic acid. (all-E)-1 and (13Z)-1 were both shown to be equally effective as (13Z)-retinoic acid in suppressing the proliferation of human sebaceous cells in vitro. (all-E)-1 was further evaluated for its ability to prevent the induction of mouse skin papillomas and to induce signs of vitamin A toxicity in mice. The cancer chemopreventive activity of (all-E)-1 was comparable to that of (all-E)-retinoic acid, and the toxicity was comparable to or slightly better than that of the natural vitamin.

Characterization of human sebaceous cells in vitro.

Human sebaceous cells, isolated from adult human skin, were cultured on either bovine type I collagen or mitomycin-C-treated 3T3 fibroblasts. Sebaceous cells, termed "sebocytes", were determined to be epithelial in nature by positive staining with monoclonal antikeratin antibodies BG2 and BG12. However, sebocyte colonies were also negative for keratins found in differentiated cells of keratinocyte colonies, as defined by monoclonal antikeratin antibodies CC2 and CC6. Sebocytes did not produce cornified envelopes in vitro and could only be induced to produce small quantities (less than 5%) of envelopes with a calcium ionophore. Sebocyte growth characteristics in a variety of serum, dexamethasone, and hydrocortisone combinations were significantly different from those of human facial keratinocytes. Sebocytes also displayed a growth curve and plating efficiency that were different from those of keratinocytes. Large lipid droplets within growing sebocytes could be visualized with oil red o staining. Additionally, squalene and wax/cholesterol esters were made by sebocytes in vitro in greater amounts than by facial keratinocytes, as determined by thin-layer chromatography of organic extracts of 3H2O-labeled sebocytes. Sebocytes synthesized greater quantities of lipid, on a per-cell and protein basis, than did keratinocytes.

Human biliary metabolites of isotretinoin: identification, quantification, synthesis, and biological activity.

1. The metabolites of isotretinoin (13-cis-retinoic acid, Accutane) were investigated in the bile of two patients with biliary T-tube drainage after administration of a single, oral, 80-mg dose of 14C-isotretinoin. Radioactivity measurements showed that the two patients excreted 22.7 and 17.1% of the dose in their bile in 4 days. 2. The two major drug-related components in the bile were identified as the glucuronide conjugates of 4-oxo-isotretinoin and 16-hydroxy-isotretinoin. Two minor components were identified as the glucuronide conjugates of isotretinoin and 18-hydroxy-isotretinoin. 3. H.p.l.c. analyses of Glusulase-treated bile samples indicated that the glucuronides of isotretinoin and the two major metabolites accounted for about 48% and 44% of the total radioactivity in the bile of the two patients. 4. Racemic 16-hydroxy-isotretinoin was synthesized and evaluated for its effect on human sebocytes in vitro. This metabolite and the other major metabolites of isotretinoin were less active than isotretinoin in inhibiting the proliferation of the sebocytes.

Retinoid effects on sebocyte proliferation.

The human sebocyte model offers several advantages over the current animal models. Foremost among these is the correlation of in vitro activity with clinical results, which was not true for arotinoids in the animal models. It is also possible to study several parameters (total cell number, [3H]thymidine uptake, protein and lipid composition/synthesis, hormone response, receptor regulation, etc.) in the same system. The proliferation of isolated sebocytes is inhibited by retinoids, such as isotretinoin and tretinoin, which are known to be clinically active in human acne. Sebocytes are not responsive to the arotinoid temarotene, which is active in the aforementioned animal models and against dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinoma but inactive clinically in acne. Additionally, this model is not responsive to etretinate, a compound known to be active in psoriasis but inactive in acne. The in vitro model is, therefore, more predicative of clinical efficacy than the animal models alone.

Association of type- and group-specific antigens with the cell wall of serotype III group B streptococcus.

The type-specific antigens (TSA) of group B streptococcus (GBS) represent the primary virulence factors for these organisms, yet little is known about their relationship to the cell surface of GBS. Crude cell walls of serotype III GBS strain 110 were purified by extraction with sodium dodecyl sulfate, LiCl, and urea, which removed essentially all of the protein associated with the cell wall as determined by amino acid analysis. Only those amino acids found in peptidoglycan were present, which included alanine, lysine, and glutamate (3.5:1:1 molar ratio). In contrast, these procedures resulted in the release of only 4.6% of the wall-associated TSA, indicating that protein was not the primary means by which TSA was bound to the cell surface. Mutanolysin (20 micrograms/ml) treatment of purified cell walls resulted in the release of 95% of the wall-associated TSA. The covalent association of TSA, the group B polysaccharide, and the peptidoglycan was demonstrated by the presence of N-acetylmuramic acid, rhamnose, alanine, glutamate, and lysine in mutanolysin-extracted TSA material purified by DEAE-Sephacel anion exchange and Sepharose 4B gel chromatography. Chemical analysis of purified cell walls revealed that group B antigen and peptidoglycan comprised 37.4 and 36.5%, respectively, whereas TSA accounted for 22.1 to 24.5% of the weight of the purified walls. Of the total 283.5 mg of TSA produced per 10-liter culture of GBS strain 110, 8.4% was released into the supernatant fluid. The remainder (249 mg) comprised the cell wall antigen. As described above, 4.6% of the cell wall antigen was extractable by nonenzymatic methods, which represented 3.8% of the total TSA, whereas 87.8% of the total TSA produced appeared to be covalently attached to the cell wall.

Correlation between the production of extracellular substances by type III group B streptococcal strains and virulence in a mouse model.

Twelve strains of serotype III group B streptococci (8 isolated from cases of neonatal disease, 3 isolated from asymptomatically colonized infants, and 1 laboratory reference strain) were examined for the vitro production of three potential extracellular virulence products: type-specific antigen, neuraminidase, and protease. In addition, virulence in a mouse model, expressed as 50% lethal dose, was determined for the 12 strains to determine whether a relationship existed between the production of any of the three extracellular products and virulence. Only production of extracellular type-specific antigen showed a correlation with virulence in the mouse model. The high producers of extracellular type-specific antigen were an average of 166-fold more virulent for mice than low producers of the same component. There was no correlation between virulence and either neuraminidase or protease production, nor was there a correlation between either of these two extracellular products and the levels of extracellular type-specific antigen. When levels of group B streptococci of each type (a high and low producer of extracellular type-specific antigen) in organs of infected mice were examined, comparable levels of organisms were found in the brain, spleen, and lungs of mice near death regardless of the initial inoculum. However, the high producer of extracellular type-specific antigen caused death in mice with a 2 to 3 log lower inoculum than the low producer, suggesting that these strains may be more invasive.

Characterization of populations of promastigotes of Leishmania donovani.

Promastigotes of Leishmania donovani cultured for either 3 or 10 days in vitro and inoculated intracardially into golden hamsters with an equal number of organisms from either population showed a 7-fold difference in infectivity when compared at both 10 and 16 days post-infection. Reproducible histochemical staining for the promastigote enzymes glucose-6-phosphate dehydrogenase (G6PDH) and peptidase after polyacrylamide gel electrophoresis showed two isoelectric variants of G6PDH (Bands 1 and 2) that displayed a 45% decrease (Band 1) and a 60% increase (Band 2) in total activity when 3- and 10-day-old promastigotes were compared. Peptidase activity, present in a single band, increased 7-fold in 10-day-old promastigotes. A decrease in the lectin-induced agglutination of promastigotes by castor bean agglutinin (RCA60), specific for D-galactose and N-acetyl-D-galactosamine, was seen when 3- and 10-day-old promastigotes are compared. Antisera raised against sonicated 10-day-old promastigotes showed a unique precipitin band between the antiserum and sonicated 10-day-old promastigotes not found between the antiserum and sonicated 3-day-old promastigotes.

Factors influencing release of type III antigens by group B streptococci.

The release of serotype III group B streptococcal polysaccharides into the supernatant fluid was examined under a variety of physiological conditions. Release of both high- and low-molecular-weight type III antigens was fairly constant throughout exponential growth, but increased markedly upon entering the stationary phase of growth. Increased glucose and decreased phosphate concentrations both caused a large increase in release of antigens. Inhibition of protein synthesis in exponentially growing cells by chloramphenicol (10 micrograms/ml) caused a condition of unbalanced growth in which antigen release was increased greatly over control values. Strain variability in antigen release was also observed. Strains which are known to be high neuraminidase producers released elevated levels of both low- and high-molecular-weight type III antigens. Non-neuraminidase-producing strains released considerably less high-molecular-weight antigen, but similar levels of the low-molecular-weight antigen compared with the high neuraminidase producers. Strain D136C, a type III non-neuraminidase producer, released negligible quantities of the high-molecular-weight antigen in the supernatant fluid. These results indicate that both the physiological environment and the type III strain are important in determining the quantity of type-specific antigen released into the culture fluid.

Extracellular antigens of serotype III group B streptococci.

Two sialic acid-containing type III group B streptococcal antigens were obtained from a supernatant growth medium, purified by anion exchange or gel filtration, and found to be free of group B reactivity. Quantitation of the high-molecular-weight extracellular type III antigen indicated that approximately 20-fold more antigen was recoverable from the growth medium than could be obtained by neutral buffer extraction of whole cells.

Protease production by clinical isolates of type III group B streptococci.

Six strains of serotype III group B streptococci isolated from confirmed cases of neonatal disease were examined for their ability to produce proteolytic enzymes. Three neuraminidase-producing strains and three non-neuraminidase-producing strains were employed in this study. Protease production was examined in 1,000-fold concentrated filtrates of stationary-phase cells with an insoluble substrate derived from horse hide powder labeled covalently with Remazol brilliant blue. Protease activity was not detected in any cultural supernatant fluids until they were fractionated on Sephadex G-100. After fractionation, the neuraminidase-producing strains were shown to elaborate approximately sixfold more protease than the non-neuraminidase-producing strains. The finding that clinical isolates of group B streptococci that elaborated high levels of neuraminidase also produced elevated levels of extracellular protease may indicate that the production of several different factors may determine the virulence of these organisms.

Growth and amino acid requirements of various strains of group B streptococci.

A chemically defined medium (FMC; B. Terleckyj, N. P. Willett, and G. D. Shockman, Infect. Immun. 11:649-655, 1975) was used to compare the growth and amino acid requirements of 16 strains of group B streptococci, consisting of both laboratory-passaged organisms and fresh clinical isolates from adult and neonatal infections. The 5 standard Lancefield immunizing strains of group B streptococci, 090 (Ia), H36B (Ib), A909 (Ic), 18RS21 (II), and D136C (III), had doubling times in FMC (28 to 36 min) similar to those observed in Todd-Hewitt glucose broth (24 to 30 min). Similar doubling times were obtained with 11 clinical isolates growing in Todd-Hewitt glucose broth and FMC. The optimum buffering capacity of FMC was provided by 0.06 M sodium phosphate, and 1% glucose gave maximum cell yield. The group B streptococci, with minor exceptions, were very homogeneous in their amino acid requirements under both aerobic and anaerobic growth conditions. Phenylalanine, tyrosine, tryptophan, glutamate, arginine, valine, leucine, lysine, methionine, isoleucine, cystine, and histidine were required by all 16 strains under both aerobic and anaerobic growth conditions. In addition, threonine was required by all strains under aerobic growth conditions, whereas only 9 strains required threonine under anaerobic conditions. Serine was required by only 3 type III fresh clinical isolates aerobically, but not anaerobically. A requirement for glycine varied from strain to strain, apparently influenced by the oxidation-reduction potential of the growth medium.