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ABSTRACT. Objective. Haemophilus influenzae type b causes severe disease in nonimmune infants and young children; other serotypes are uncommon pathogens and thought to have low virulence. Some have hypothesized that with the virtual elimination of H influenzae type b, other serotypes might acquire virulence traits and emerge as important pathogens of children. We describe the clinical, epidemiologic, and molecular biologic features of 5 cases of severe disease attributable to Haemophilus influenzae type a.Methods. After observing 4 cases of invasive disease caused by H influenzae type a, we reviewed microbiology records at 3 reference laboratories that perform all serotyping in Utah and surveillance databases. Strains of H influenzae type a and control strains were examined by Southern blotting with the use of the cap probe pUO38 and by pulsed-field gel electrophoresis. The putative virulence mutation, the IS1016-bexA deletion, was detected by polymerase chain reaction amplification and sequencing.Results. During a 10-month period, we observed 5 children with severe invasive disease caused by H influenzae type a. No isolates of H influenzae type a had been submitted to the reference laboratories between 1992 and 1998. The median age of patients was 12 months (range: 6 -48 months). Four of 5 had meningitis and bacteremia; 1 had purpura fulminans. Three isolates, representing 1 of 2 pulsed-field gel electrophoresis patterns, contained the IS1016-bexA deletion and were associated with particularly severe disease.Conclusions. We describe an unusual cluster of severe disease caused by H influenzae type a that resembles the clinical and epidemiologic features of H influenzae type b disease. Our data support the hypothesis that the IS1016-bexA deletion may identify more virulent strains of H influenzae. Pediatrics 2001;108(1). URL: http://www. pediatrics.org/cgi/content/full/108/1/e18; Haemophilus influenzae, epidemiology, virulence, serotyping, pathogenicity.

Background Because activation of T cells is associated with human immunodeficiency virus (HIV) pathogenesis, CD4 and CD8 activation levels in patients coinfected with HIV and hepatitis C virus (HCV) may explain conflicting reports regarding effects of HCV on HIV disease progression. Methods Kaplan-Meier and multivariate Cox regression models were used to study the risk of incident clinical AIDS and AIDS-related deaths among 813 HCV-negative women with HIV infection, 87 HCV-positive nonviremic women with HIV coinfection, and 407 HCV-positive viremic women with HIV coinfection (median follow-up time, 5.2 years). For 592 women, the percentages of activated CD4 and CD8 T cells expressing HLA-DR (DR) and/or CD38 were evaluated. Results HCV-positive viremic women had a statistically significantly higher percentage of activated CD8 T cells (P < .001) and a statistically significantly higher incidence of AIDS compared with HCV-negative women (P < .001 [log-rank test]). The AIDS risk was greater among HCV-positive viremic women in the highest tertile compared with the lowest tertile (>43% vs <26%) of CD8+CD38+DR+ T cells (hazard ratio, 2.94 [95% confidence interval, 1.50–5.77]; P =.001). This difference was not observed in the HCV-negative women (hazard ratio, 1.87 [95% confidence interval, 0.80–4.35]; P =.16). In contrast, CD4 activation predicted AIDS in both groups similarly. Increased percentages of CD8+CD38−DR+, CD4+CD38−DR−, and CD8+CD38−DR− T cells were associated with a >60% decreased risk of AIDS for HCV-positive viremic women and HCV-negative women. Conclusion HCV-positive viremic women with HIV coinfection who have high levels of T cell activation may have increased risk of AIDS. Earlier treatment of HIV and HCV infection may be beneficial.

Background-Coinfection with hepatitis C virus (HCV) is common among HIV-infected women.Objective-To further our understanding of the risk factors for HCV viremia and the predictors of HCV viral load among women.Study design-We investigated sociodemographic, immunologic, and virologic factors associated with presence and level of HCV viremia among 882 HIV-infected and 167 HIVuninfected HCV-seropositive women at entry into the Women's Interagency HIV Study.Results-Plasma HCV RNA was detected in 852 (81%) of these 1,049 women (range: 1.2-7.8 log 10 copies/ml). HCV-viremic women were more likely to have an HIV RNA level >100,000 copies/ml (P =0.0004), have reported smoking (P =0.01), or to be Black (P =0.005). They were less likely to have current or resolved hepatitis B infection. HCV RNA levels were higher in women who were >35 years old, or HIV-infected. Current smoking and history of drug use (crack/ freebase cocaine, marijuana, amphetamines, or heroin) were each associated with both presence and level of viremia. Conflict of interest Authors do not have conflicts of interest in relation to the present manuscript.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusions-Substance abuse counseling aimed at eliminating ongoing use of illicit drugs and tobacco may reduce clinical progression, improve response to treatment, and decrease HCV transmission by lowering levels of HCV viremia in women. NIH Public Access