Impact of hepatitis B on mortality and specific causes of death in adults with and without HIV co-infection in NYC, 2000-2011.

High rates of immigration from endemic countries contribute to the high chronic hepatitis B (HBV) prevalence in New York City (NYC) compared to the United States overall, i.e. about 1 million individuals. We describe the impact of HBV infection on mortality and specific causes of death in NYC. We matched surveillance and vital statistics mortality data collected from 2000 to 2011 by the New York City Department of Health and Mental Hygiene (DOHMH) and analysed demographics and premature deaths (i.e. whether death occurred at <65 years) in persons with and without chronic HBV or HIV infection (excluding those with hepatitis C). From 2000 to 2011, a total of 588 346 adults died in NYC. Of all decedents, 568 753 (97%) had no report of HIV or HBV, and 4346 (0·7%) had an HBV report. Of HBV-infected decedents, 1074 (25%) were HIV co-infected. Fifty-five percent of HBV mono-infected and 95% of HBV/HIV co-infected decedents died prematurely. HBV disproportionately impacts two subgroups: Chinese immigrants and HIV-infected individuals. These two subgroups are geographically clustered in different neighbourhoods of NYC. Tailoring prevention and treatment messages to each group is necessary to reduce the overall burden of HBV in NYC.

Characteristics and TB treatment outcomes in TB patients with viral hepatitis, New York City, 2000-2010.

Literature surrounding the burden of and factors associated with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in persons with tuberculosis (TB) disease remains limited and focused on populations outside the USA. Cross-matched New York City (NYC) TB and viral hepatitis surveillance data were used to estimate the proportion of NYC adults diagnosed with TB from 2000 to 2010 with a report of viral hepatitis infection and to describe the impact of viral hepatitis infection on TB treatment completion and death. For 9512 TB patients, HCV infection was reported in 4.2% and HBV infection in 3.7%; <1% of TB patients had both HCV and HBV infection. The proportion of TB patients with HCV infection to die before TB treatment completion was larger than in TB patients without a viral hepatitis report (21% vs. 9%); this association remained when stratified by HIV status. There was no significant difference in death before treatment completion for TB patients with HBV infection compared to TB patients without a viral hepatitis report when stratified by HIV status. These findings reinforce the importance of hepatitis testing and providing additional support to TB patients with viral hepatitis infection.

HIV and viral hepatitis co-infection in New York City, 2000-2010: prevalence and case characteristics.

Using surveillance data, we describe the prevalence and characteristics of individuals in New York City (NYC) co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) and/or hepatitis C virus (HCV). Surveillance databases including persons reported to the NYC Department of Health and Mental Hygiene with HIV, HBV, and HCV by 31 December 2010 and not known to be dead as of 1 January 2000, were matched with 2000-2011 vital statistics mortality data. Of 140 606 persons reported with HIV, 4% were co-infected with HBV only, 15% were co-infected with HCV only, and 1% were co-infected with HBV and HCV. In all groups, 70-80% were male. The most common race/ethnicity and HIV transmission risk groups were non-Hispanic blacks and men who have sex with men (MSM) for HIV/HBV infection, and non-Hispanic blacks, Hispanics, and injection drug users for HIV/HCV and HIV/HBV/HCV infections. The overall age-adjusted 2000-2011 mortality was higher in co-infected than HIV mono-infected individuals. Use of population-based surveillance data provided a comprehensive characterization of HIV co-infection with HBV and HCV. Our findings emphasize the importance of targeting HIV and viral hepatitis testing and prevention efforts to populations at risk for co-infection, and of integrating HIV and viral hepatitis care and testing services.

Estimating the prevalence of hepatitis C infection in New York City using surveillance data.

Hepatitis C virus is the most common chronic blood-borne infection in the USA. Based on results of a serosurvey, national prevalence is estimated to be 1·3% or 3·2 million people. Sub-national estimates are not available for most jurisdictions. Hepatitis C surveillance data was adjusted for death, out-migration, under-diagnosis, and undetectable blood RNA, to estimate prevalence in New York City (NYC). The prevalence of hepatitis C infection in adults aged ⩾20 years in NYC is 2·37% (range 1·53-4·90%) or 146 500 cases of hepatitis C. This analysis presents a mechanism for generating prevalence estimates using local surveillance data accounting for biases and difficulty in accessing hard to reach populations. As the cohort of patients with hepatitis C age and require additional medical care, local public health officials will need a method to generate prevalence estimates to allocate resources. This approach can serve as a guideline for generating local estimates using surveillance data that is less resource prohibitive.

A recurring outbreak of Shigella sonnei among traditionally observant Jewish children in New York City: the risks of daycare and household transmission.

Dispersed community outbreaks of Shigella sonnei have occurred cyclically among traditionally observant Jews in the United States. In February 2000, we investigated a S. sonnei outbreak in one Jewish community in New York City. To determine risk factors for introduction of infection into households, we conducted a cohort study of households to compare risk factors for illness among primary subjects within households and age-matched well siblings. Isolates were subtyped by pulsed-field gel electrophoresis (PFGE). We used a random effects model to assess extra-household vs. intra-household transmission in households with multiple ill household members. Daycare or pre-school attendance [matched odds ratio (mOR) 16.1, P<0.001] and age <60 months (mOR 6.3, P<0.001) were independently associated with index subject illness. Outbreak isolates were closely related by PFGE analysis to the strain previously observed in Jewish community outbreaks. The random effects model strongly indicated that multiple illnesses in a single household are due to secondary transmission. Disease containment efforts should focus on reducing Shigella transmission in childcare settings and within homes.

Aging cohort of perinatally human immunodeficiency virus-infected children in New York City. New York City Pediatric Surveillance of Disease Consortium.

BACKGROUND: New York City (NYC) pediatricians are now caring for fewer HIV-infected infants and more school age children and adolescents than earlier in the epidemic. METHODS: Clinical, laboratory and demographic data were abstracted from medical records at 10 NYC centers participating in the CDC Pediatric Spectrum of HIV Disease project. Pediatric AIDS cases and HIV-related deaths reported to the NYC Department of Health were examined. RESULTS: Median age of HIV-infected children in care increased from 3 years in 1989 to 1991 to 6 years in 1995 to 1998. The number of HIV-infected women giving birth in NYC declined 50% from 1990 to 1997 (1630 to 831); increasing numbers were identified prenatally (14% in 1989; 78% after 1995); and most received prenatal zidovudine prophylaxis (73% in 1997). Estimated perinatal transmission decreased to 10% by 1997. Improved identification of seropositive status in infants was associated with an increased proportion of infected infants receiving Pneumocystis carinii pneumonia (PCP) prophylaxis, 84% in 1997. AIDS free survival was longer for children born 1995 to 1998 than for those born before 1995, P = 0.004. In 1998 among children with advanced immunosuppression (CDC category 3), 66% were prescribed 3 or more antiretroviral medicines and 88% received PCP prophylaxis. Citywide AIDS cases and HIV-related deaths fell precipitously beginning in 1996. CONCLUSIONS: Based on the observations of this study, the cohort of NYC HIV-infected children in care is aging, associated with a decline in new HIV infections, high rates of PCP prophylaxis and increased time to AIDS. Falling HIV-related deaths citywide support these observations.

Tuberculosis in human immunodeficiency virus-infected and human immunodeficiency virus-exposed children in New York City. The New York City Pediatric Spectrum of HIV Disease Consortium.

BACKGROUND: Tuberculosis disease incidence increased sharply in New York City (NYC) in the late 1980s in children and adults. The relationship of tuberculosis disease in adults with the coincident epidemic of immunosuppression caused by HIV disease has been well-documented. This paper examines the relationship of tuberculosis and HIV in children in NYC. METHODS: Information on tuberculosis was collected by retrospective chart abstraction in a cohort of HIV-exposed and infected children enrolled in a longitudinal study of HIV. Tuberculosis cases were ascertained by chart review or by matching HIV-infected and -exposed children to NYC Tuberculosis Registry cases. NYC Tuberculosis Registry data on children reported from 1989 to 1995, and not reported as HIV-infected, were used for comparison. RESULTS: Tuberculosis disease was found in 45 (3%) of 1426 HIV-infected children (0.61 per 100 child years of observation) and in 5 (0.5%) of 1085 HIV-exposed uninfected children (0.2 per 100 child years). 30% of children were evaluated for HIV only after presenting with tuberculosis. Children with tuberculosis and HIV were more likely than other age-matched HIV-infected children to have decreased CD4+ T lymphocyte counts (66% vs. 37%, P = 0.02) and more likely than other NYC children with tuberculosis to have culture-confirmed and extrapulmonary tuberculosis. In this series 8 of 21 deaths in HIV-infected children with tuberculosis appeared to be related to tuberculosis. CONCLUSIONS: During a period of high tuberculosis incidence in NYC, 3% of HIV-infected children in our cohort had tuberculosis, higher than the rate in uninfected children born to HIV-positive mothers in the same cohort. Because of this association, HIV-infected children with pulmonary illness should be tested for tuberculosis; and all children with tuberculosis should be tested for HIV.

Tissue-specific and developmental stage-specific DNA binding by a mammalian SWI/SNF complex associated with human fetal-to-adult globin gene switching.

SWI/SNF complexes in yeast and higher eukaryotes are thought to facilitate gene activation and transcription factor binding by disrupting repressive chromatin structures. Little is known, however, about how these complexes target specific genes for activation. We now have purified a specialized SWI/SNF-related complex (PYR complex) from murine erythroleukemia (MEL) cell nuclear extract that binds pyrimidine-rich elements at the human and murine beta-globin loci. PYR complex DNA-binding activity is restricted to definitive hematopoietic cells and is both DNA sequence- and length-dependent. Mass spectrometric identification of purified peptides and antibody supershift assays indicate that PYR complex contains at least four known mammalian SWI/SNF subunits: BAF57, INI1, BAF60a, and BAF170. PYR complex broadly footprints a 250-bp pyrimidine-rich element between the human fetal and adult beta-globin genes. A short intergenic deletion that removes this element from a human globin locus cosmid construct results in delayed human fetal-to-adult globin gene switching in transgenic mice. Taken together, the data suggest that PYR complex may act through this intergenic element to facilitate human fetal-to-adult globin gene switching, presumably by opening the locus in the region of the adult genes to permit the binding of beta-globin transcriptional activators.

The effect of maternal viral load on the risk of perinatal transmission of HIV-1. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To determine the effect of maternal viral load at delivery on the risk of perinatal transmission of HIV-1. DESIGN: A nested case-control study within a prospectively followed cohort of HIV-1-infected pregnant women and their infants. SETTING: The multicenter New York City Perinatal HIV Transmission Collaborative Study. PARTICIPANTS: Fifty-one women who gave birth to HIV-1 infected infants were frequency-matched within CD4+ cell count quintiles with 54 non-transmitting mothers. MAIN OUTCOME MEASURES: Maternal quantity of HIV-1 viral RNA was assayed in plasma obtained near delivery using the nucleic acid sequence-based amplification assay system. RESULTS: Viral RNA was detected in 73 (70%) out of 105 women and the median viral load was 16,000 RNA copies/ml in transmitters and 6,600 in non-transmitters (P < 0.01). When adjusted for maternal CD4+ count near delivery, women with measurable viral load were nearly sixfold more likely to transmit HIV-1 than women with viral load below detection [adjusted odds ratio (AOR), 5.8; 95% confidence interval (CI), 2.2 15.5]. The odds ratio for perinatal transmission of log10 viral load, adjusted for CD4 count was 2.7 (95% CI, 1.5-5.1). When stratified by the stage of HIV-1 disease, the only group with significant association between log10 viral load and transmission were AIDS-free women with CD4+ count > 500 x 10(6)/l (AOR, 9.1; 95% CI, 2.6-31.5). CONCLUSIONS: High maternal viral load increases the likelihood of perinatal transmission of HIV-1 in women without AIDS and advanced immunosuppression. HIV-1 infected pregnant women without advanced disease, shown by others to have the lowest risk of perinatal transmission, may benefit the most from efforts to identify and decrease viral load at delivery.

Expression of a cosmid containing the LCR, (A)gamma, delta, and beta globin genes in mouse erythroleukemia cells.

A novel method involving the packaging of phage particles was used to introduce cosmids containing components of the human beta-globin locus control region (LCR) and the human (A)gamma, delta, and beta globin genes into mouse erythroleukemia (MEL) cells. After stable transfection, MEL clones were selected and analyzed for expression of human genes. Both (A)gamma and beta globin mRNA were expressed in these clones, indicating that MEL cells do not suppress transcription of the human gamma globin gene. The variability of human (A)gamma vs. beta globin expression from clone to clone prevents a clear delineation of differences in the expression of these two genes with a cosmid in which a region potentially involved in gamma-to-beta switching has been deleted. The results suggest that MEL cells are capable of supporting human gamma expression, despite their predominantly adult phenotype.

A DNA-binding factor in adult hematopoietic cells interacts with a pyrimidine-rich domain upstream from the human delta-globin gene.

To date, DNA-binding factors with a developmental pattern of expression have not been described in human erythroid cells to explain the switch from fetal (gamma-) to adult (delta- and beta-) globin gene expression. Here we describe a factor present in nuclear extracts from adult mouse and human hematopoietic cells that binds to an oligopyrimidine repeat approximately 960 base pairs upstream from the human delta-globin gene. The binding site for the factor is within an unusual 250-base-pair domain that is greater than 95% pyrimidines on one strand. This domain is preferentially sensitive to S1 nuclease in supercoiled plasmids, indicating that it can adopt an alternative non-B-DNA conformation. A number of S1-sensitive sites within the domain, including the factor-binding site, have sequence characteristics associated with the formation of a triple helix (H-DNA). The position of the binding site between the fetal and adult beta-globin-like genes, its potential for adopting an unusual secondary structure, and the restricted activity of the binding factor to adult hematopoietic tissues suggest possible roles in hematopoietic cell development and hemoglobin switching.

A novel strategy for the generation of T cell lines lacking expression of endogenous alpha- and/or beta-chain T cell receptor genes.

Mutant T cell lines that do not express the endogenous alpha- and/or beta-chain genes of the TCR were generated from the alpha beta TCR/CD3+ tumor cell line C6VL with a combination of classical mutagenesis methods and selection of somatic hybrid variants. This novel strategy obviated the need for repeated mutagenesis and screening of a large number of individual clones. The loss of either the alpha- or the beta-chain expression in the mutant cells was associated with the loss of surface TCR/CD3 complex, which could be rescued by the transfection of appropriate exogenous alpha- and/or beta-chain gene constructs. Because these cells express a single TCR molecule on the cell surface, they are useful for the study of the assembly and function of the alpha beta TCR. This strategy is also generally applicable for the generation of homozygous mutant cell lines lacking other gene products.