Large outbreak of isoniazid-monoresistant tuberculosis in London, 1995 to 2006: case-control study and recommendations.

We conducted a case­control study to examine risk factors for isoniazid-monoresistant Mycobacterium tuberculosis in an ongoing outbreak in London. Cases were defined as individuals with an isoniazid-monoresistant strain diagnosed from 1995 to the third quarter of 2006 with an indistinguishable restriction fragment length polymorphism (RFLP) or mycobacterial interspersed repetitive unit (MIRU)-variable number tandem repeats (VNTR) pattern who were resident in or had epidemiological links with London. Controls were all other individuals reported with tuberculosis to the Health Protection Agency London regional epidemiology unit or the HPA London TB Register during 2000 to 2005. Of 293 cases, 153 (52%) were sputum smear-positive compared with 3,266 (18%) of controls. Cases were more likely to be young adults (aged between 15 and 34 years), born in the United Kingdom (OR: 2.4; 95% CI: 1.7­3.4) and of white (OR: 2.9; 95% CI: 1.8­4.8) or black Caribbean (OR: 12.5; 95% CI: 7.7­20.4) ethnicity, a prisoner at the time of diagnosis (OR: 20.2; 95% CI: 6.7­60.6), unemployed (OR: 4.1; 95% CI: 3.0­5.6), or a drug dealer or sex worker (OR: 187.1; 95% CI: 28.4­1,232.3). A total of 113 (39%) of cases used drugs and 54 (18%) were homeless. Completion of treatment gradually improved in cases from 55% among those diagnosed up to the end of 2002 compared with 65% by the end of 2006. Treatment completion increased from 79% to 83% in controls from 2000 to 2005. There are complex social challenges facing many cases in this outbreak that need to be addressed if medical interventions are to be successful.

Distribution and epitope analysis of the cell membrane glycoprotein (HPCA-1) associated with human hemopoietic progenitor cells.

Monoclonal antibodies My10, BI.3C5, 12.8, and ICH3 identify a monomeric cell surface glycoprotein (HPCA-1) of 100-120 kD, which is selectively expressed on human hemopoietic progenitor cells. Other tissues are nonreactive with the exception of capillary endothelia and basement membrane in some sites. In addition, the antigen can be detected on cell lines that exhibit characteristics associated with early T cell precursors. HPCA-1 is therefore associated with myeloid, B, and T lineage precursors. Sequential immunoprecipitation and Western blotting studies demonstrate that BI.3C5, ICH3, My10, and an antibody directed against endothelial cells, 188.27, all react with the same glycoprotein species, although the epitopes involved may be distinct. The epitope recognized by BI.3C5 is sialic acid dependent, whereas that recognized by ICH3 is not. The My10 epitope has partial sensitivity to neuraminidase. Competitive/additive binding experiments suggest that these epitopes, although probably distinct, may be closely associated.

Epidemiology of tuberculosis in children in London, 2009-2011: are opportunities for prevention being missed?

SETTING: London, United Kingdom. OBJECTIVE: To explore missed opportunities (MO) for the prevention of tuberculosis (TB) in children aged 0-15 years. DESIGN: Parents/guardians of children aged <15 years diagnosed with TB and reported through surveillance were interviewed about bacille Calmette-Guérin vaccination (MO-V) or contact tracing and screening for TB (MO-C) via an algorithm reflecting eligibility. RESULTS: Annual TB incidence was 12 per 100,000 (65/100,000 in Black Africans, 20/100,000 in Indian or Pakistani children). The response rate was 36% (145/405). About 20% of UK-born children had not been vaccinated. MO-V was not associated with any particular factor. Contact with a known TB case before illness had occurred in 71 children (49%; 71% in those aged 0-1 years vs. 30% in those aged 11-15 years), of whom 64 (91%) were diagnosed through contact tracing. MO-C had been conducted in six (4% overall). Children with MO-C were all of Black ethnic origin. Their index cases were family members (within their household) or relatives or family friends from abroad (outside their household). MO-C was not associated with any other factor. CONCLUSION: Although overall few missed opportunities for prevention had occurred, we recommend increased rigour when performing contact tracing in any case where a child may have been exposed.

Divergent molecular phenotypes of KG1 and KG1a myeloid cell lines.

The cell line KG1 derived from a patient with erythroleukemia in myeloblastic relapse has the composite phenotype and functional repertoire of myeloblasts. In marked contrast, its subline KG1a has lost myeloid features, acquired new karyotypic markers, and has three characteristics associated with immature T cells: low-level expression of the T cell receptor beta mRNA (but not alpha) transcribed from a germline gene; high-level expression of T3 delta mRNA and intracellular, but not cell surface, T3 protein; and expression of the CD7/gp40 T cell-associated membrane antigen. Both KG1 and KG1a transcribe unrearranged IgH genes. These data suggest that either the KG1 cell line was derived from a common myeloid-lymphoid progenitor or that the KG1a subline phenotype is aberrant.