Celine Hanson

HIV-1 genotypic zidovudine drug resistance and the risk of maternal-infant transmission in the women and infants transmission study.

ObjectivesAlthough the treatment of pregnant women and their infants with zidovudine (ZDV) has been remarkably effective in preventing the perinatal transmission of human HIV-1, many potentially preventable infections still occur. To examine whether the risk of perinatal infection is increased among women who carry ZDV-resistant HIV-1, the role of genotypic ZDV resistance in perinatal transmission was evaluated. MethodsThe reverse transcriptase (RT) region of clinical isolates from culture supernatants of 142 HIV-1-infected women enrolled in the Women and Infants Transmission Study (WITS), who had been treated with ZDV during pregnancy was sequenced. Results from genotypic sequencing were linked to demographic, laboratory, and obstetrical databases, and the magnitude of association of having consensus drug-resistant HIV-1 RT mutations with transmission was estimated. ResultsTwenty-five per cent (34/142) of maternal isolates had at least one ZDV-associated resistance mutation. A lower CD4 cell percentage and count (P  = 0.0001) and higher plasma HIV-1 RNA (P  = 0.006) were associated with having any ZDV resistance mutation at delivery. Having any RT resistance mutation [odds ratio (OR): 5.16; 95% confidence interval (CI): 1.40, 18.97; P  = 0 0.01], duration of ruptured membranes [OR: 1.13 (1.02, 1.26) per 4 h duration; P  = 0.02], and total lymphocyte count [OR: 1.06 (1.01, 1.10) per 50 cells higher level; P  = 0.009] were independently associated with transmission in multivariate analysis. ConclusionMaternal ZDV resistant virus was predictive of transmission, independent of viral load, in these mothers with moderately advanced HIV-1 disease, many of whom had been treated with ZDV before pregnancy.

Human Immunodeficiency Virus (HIV) Type 1 Antibodies in Perinatal HIV-1 Infection: Association with Human HIV-1 Transmission, Infection, and Disease Progression

Anti -human immunodeficiency virus (HIV) type 1 antibodies in 242 pregnant women and 238 infants were measured at birth and at 1, 2, 4, and 6 months after birth, to estimate their association with perinatal transmission and infant disease progression. Maternal anti-p24 (P = .01) and anti-gp120 (P = .04) antibodies were inversely associated with vertical transmission rates, independent of maternal percentage of CD4 cells, hard drug use, duration of ruptured membranes, serum albumin levels, serum vitamin A levels, and quantitative HIV-1 peripheral mononuclear blood cell culture, but not with maternal plasma immune complex dissociated p24 or HIV-1 RNA copy number, both of which were highly correlated with antibodies. From ages 1-2 months, anti-gp120, -gp41, -p31, and -p66 decayed to a greater extent in infected than in uninfected infants. Infected infants produced anti-p24 antibody by age 2 months, anti-p17 by 4 months, and anti-p41 and anti-gp120 by 6 months. As early as birth, infants with rapid disease progression had lower levels of anti-p24 than did infants whose disease did not rapidly progress, but not independently of HIV-1 RNA levels.

Pathology of the kidney in childhood immunodeficiency: AIDS-related nephropathy is not unique.

Clinical and nephropathologic findings in autopsy material from 7 children with acquired immune deficiency syndrome (AIDS), 13 with severe combined immune deficiency (SCID), and 6 with a variety of other congenital immune deficiencies were reviewed in an effort to understand better the pathophysiology of the AIDS-related nephropathy. Non-HIV viral infection seemed to be associated with the development of the pathologic changes considered to be components of the AIDS-related nephropathy, and these changes, including focal segmental glomerulosclerosis (FSGS) and tubular epithelial cell injury and ectasia, were not limited to the kidneys of children with AIDS but were present in many of the congenital immune deficiencies. Of the 5 children with congenital AIDS, only the 3 who survived longer than a year developed AIDS-related nephropathy, whereas the two children with transfusion-acquired AIDS did not develop renal disease despite surviving for several years after initial infection.

Control lymphocyte subsets: can one country's values serve for another's?

Lymphocyte subsets can be affected by host and environmental factors, yet direct comparisons of their patterns across continents are lacking. This work compares proportions and counts of lymphocyte subsets between healthy children from Thailand, Malawi and the USA. We analyzed subsets of 1,399 healthy children aged between 0 and 15 years: 281 Thai, 397 Malawian and 721American children. Existing data for five subsets were available for all three cohorts (Total T, CD4+ T, CD8+ T, natural killer (NK) and B cells), with data for another six subsets from the Thai and American cohorts (naive, memory and activated CD4+ and CD8+ T cells). Cellular patterns between cohorts differed mainly in children under two years. Compared to American children, Thai children had higher median numbers of total T cells, CD8+ T cells and NK cells while Malawian children under 18 months, on average, had more CD8+ T cells and B cells. Both Thai and Malawian children had lower median CD4+ T cell percentages and CD4/CD8 ratios than American children. Thai children had more memory and activated CD8+ T cells than American children. Approximately one-fifth of Thai and Malawian HIV-uninfected healthy children aged 0-3 years met WHO-defined CD4+ count criteria for immune-deficiency in HIV-infected children. Healthy children from Thailand, Malawi and the USA have differences in lymphocyte subsets that are likely to be due to differences in ethnicity, exposure to infectious diseases and environmental factors. These results indicate the need for country-specific reference ranges for diagnosis and management of immunologic disorders.

Rare Duplication or Deletion of Exons 6, 7 and 8 in CYBB Leading to X-Linked Chronic Granulomatous Disease in Two Patients from Different Families

Chronic granulomatous disease (CGD) is a rare congenital disorder in which phagocytes cannot generate superoxide (O2−) and other microbicidal oxidants due to mutations in one of the five components of the O2−-generating NADPH oxidase complex. The most common form is caused by mutations in CYBB on the X chromosome, encoding gp91phox, the enzymatic subunit of the phagocyte NADPH oxidase. Here, we report two rare cases of male X-linked CGD patients, one caused by a 5.7-kb duplication of a region containing CYBB exons 6 to 8 and the other caused by a deletion of this same region. We found both the duplication in patient 1 and the deletion in patient 2 to be bordered by a GT repeat. Indeed, in control DNA, the 3′ part of CYBB intron 5 contains a GT repeat and the 5′ part of intron 8 also contains such a repeat. Duplication of exons 6, 7 and 8 in patient 1 was probably caused by a non-homologous crossing over between the two GT repeats. The deletion found in patient 2 probably arose from a similar misalignment. The results found in these patients were confirmed by multiplex ligation-dependent probe amplification. The clinical profile of XCGD is severe in both patients.

Annatto seed hypersensitivity in a pediatric patient

cause because it is often given with cyclophosphamide. Although the positive and negative predictive values of skin testing for cyclophosphamide and mesna are not well defined, it may still be worth pursuing, particularly when the culprit medication is uncertain. A 12-step desensitization protocol can be successfully implemented if there are limited options for treatment, including the pediatric population with underlying autoimmune and renal disease.