Identification of Mycobacterium tuberculosis Peptides in Serum Extracellular Vesicles from Persons with Latent Tuberculosis Infection.

Identification of biomarkers for latent infection and risk of progression to tuberculosis (TB) disease are needed to better identify individuals to target for preventive therapy, predict disease risk, and potentially predict preventive therapy efficacy. Our group developed multiple reaction monitoring mass spectrometry (MRM-MS) assays that detected peptides in serum extracellular vesicles from TB patients. We subsequently optimized this MRM-MS assay to selectively identify 40 peptides from 19 proteins that most commonly copurify with serum vesicles of patients with TB.

A Clinical Predictor Score for 30-Day Mortality among HIV-Infected Adults Hospitalized with Pneumonia in Uganda.

Background: Pneumonia is a major cause of mortality among HIV-infected patients. Pneumonia severity scores are promising tools to assist clinicians in predicting patients' 30-day mortality, but existing scores were developed in populations infected with neither HIV nor tuberculosis (TB) and include laboratory data that may not be available in resource-limited settings. The objective of this study was to develop a score to predict mortality in HIV-infected adults with pneumonia in TB-endemic, resource-limited settings.

Association between diabetes mellitus and tuberculosis in United States-born and foreign-born populations in San Francisco.

Setting: The impact of diabetes on tuberculosis in United States and foreign-born populations in San Francisco has not been studied.

Objective: To determine the characteristics, prevalence and temporal trends of diabetes in US and foreign-born persons attending the San Francisco Tuberculosis Clinic.

Design: We analyzed data from individuals seeking medical attention at the San Francisco Tuberculosis Clinic.

Childhood tuberculosis in northern Viet Nam: a review of 103 cases.

Background: Childhood tuberculosis causes significant morbidity and mortality in Southeast Asia, yet little is known about the epidemiology and clinical characteristics of this disease in Viet Nam.

Objectives: To determine the demographics, clinical presentations, radiographic and microbiologic findings, treatment regimens, and outcomes of children admitted with tuberculosis (TB) to a national referral hospital in Viet Nam.

Methods: We conducted a retrospective case series study of children ≤ 15 years old with bacteriologically confirmed or clinically diagnosed TB admitted to a national referral hospital in Ha Noi, Viet Nam from January through December 2007.

Non-tuberculous mycobacterial infections at San Francisco General Hospital.

Background And Aims: The epidemiology of non-tuberculous mycobacteria (NTM) infection is not well defined. We evaluated the trends in incidence of NTM infections at San Francisco General Hospital (SFGH), a large metropolitan county hospital.

Methods: We performed a retrospective review of microbiologic and clinical records of all patients with a positive NTM culture reported from 1993 to 2001.

Pyrazinamide resistance, Mycobacterium tuberculosis lineage and treatment outcomes in San Francisco, California.

Background: Pyrazinamide (PZA) is a first line agent for the treatment of active tuberculosis. PZA is also considered a potent companion drug for newer regimens under development. There are limited data on the demographic, clinical, and pathogen characteristics of PZA resistant tuberculosis.

The lung microbiome of Ugandan HIV-infected pneumonia patients is compositionally and functionally distinct from that of San Franciscan patients.

Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco).

Aptamer-based proteomic signature of intensive phase treatment response in pulmonary tuberculosis.

Background: New drug regimens of greater efficacy and shorter duration are needed for tuberculosis (TB) treatment. The identification of accurate, quantitative, non-culture based markers of treatment response would improve the efficiency of Phase 2 TB drug testing.

Methods: In an unbiased biomarker discovery approach, we applied a highly multiplexed, aptamer-based, proteomic technology to analyze serum samples collected at baseline and after 8 weeks of treatment from 39 patients with pulmonary TB from Kampala, Uganda enrolled in a Centers for Disease Control and Prevention (CDC) TB Trials Consortium Phase 2B treatment trial.

Procalcitonin predicts mortality in HIV-infected Ugandan adults with lower respiratory tract infections.

Background And Objective: In low and middle-income countries where HIV infection is prevalent, identifying patients at high risk of dying from lower respiratory tract infections is challenging and validated prognostic models are lacking. Serum procalcitonin may be a useful prognostic tool in these settings. We sought to determine if elevated serum procalcitonin is associated with increased in-hospital mortality and to combine serum procalcitonin with available clinical characteristics to create a clinically useful prognostic model.

Ambient air pollution associated with suppressed serologic responses to Pneumocystis jirovecii in a prospective cohort of HIV-infected patients with Pneumocystis pneumonia.

Background: Ambient air pollution (AAP) may be associated with increased risk for Pneumocystis pneumonia (PCP). The mechanisms underlying this association remain uncertain.

Objectives: To determine if real-life exposures to AAP are associated with suppressed IgM antibody responses to P.

Antibody responses against Pneumocystis jirovecii in health care workers over time.

In a previous cross-sectional study, we showed that clinical staff working in a hospital had significantly higher antibody levels than nonclinical staff to Pneumocystis jirovecii. We conducted a longitudinal study, described here, to determine whether occupation and self-reported exposure to a patient with P. jirovecii pneumonia were associated with antibody levels to P.

Molecular epidemiology of tuberculosis in foreign-born persons living in San Francisco.

Rationale: In San Francisco, 70% of the tuberculosis cases occur among foreign-born persons, mainly from China, the Philippines, and Mexico. We postulate that there are differences in the characteristics and risk factors for tuberculosis among these populations.

Objectives: To determine the clinical, epidemiological and microbiological characteristics of tuberculosis caused by recent infection and rapid evolution in the major groups of foreign-born and the U.

Dihydropteroate synthase mutations in Pneumocystis pneumonia: impact of applying different definitions of prophylaxis, mortality endpoints and mutant in a single cohort.

Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations are well-reported. Although sulfa prophylaxis generally is associated with DHPS mutant infection, whether mutant infection is associated with poorer clinical outcomes is less clear. The differing definitions of sulfa prophylaxis and the different mortality endpoints used in these studies may be one explanation for the conflicting study results.

Serologic responses to recombinant Pneumocystis jirovecii major surface glycoprotein among Ugandan patients with respiratory symptoms.

Background: Little is known about the serologic responses to Pneumocystis jirovecii major surface glycoprotein (Msg) antigen in African cohorts, or the IgM responses to Msg in HIV-positive and HIV-negative persons with respiratory symptoms.

Methods: We conducted a prospective study of 550 patients, both HIV-positive (n = 467) and HIV-negative (n = 83), hospitalized with cough ≥2 weeks in Kampala, Uganda, to evaluate the association between HIV status, CD4 cell count, and other clinical predictors and antibody responses to P. jirovecii.

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Background: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB.

Methods And Findings: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB.

Beijing sublineages of Mycobacterium tuberculosis differ in pathogenicity in the guinea pig.

The Beijing family of Mycobacterium tuberculosis strains is part of lineage 2 (also known as the East Asian lineage). In clinical studies, we have observed that isolates from the sublineage RD207 of lineage 2 were more readily transmitted among humans. To investigate the basis for this difference, we tested representative strains with the characteristic Beijing spoligotype from four of the five sublineages of lineage 2 in the guinea pig model and subjected these strains to comparative whole-genome sequencing.

Racial differences in tuberculosis infection in United States communities: the coronary artery risk development in young adults study.

Previously reported associations between race/ethnicity and tuberculosis infection have lacked sufficient adjustment for socioeconomic factors. We analyzed race/ethnicity and self-reported tuberculosis infection data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a well-characterized cohort of 5115 black and white participants, and found that after adjusting for sociodemographic and clinical factors, black participants were more likely to report tuberculosis infection and/or disease (odds ratio, 2.0; 95% confidence interval, 1.

Factors associated with mortality in patients with drug-susceptible pulmonary tuberculosis.

Background: Tuberculosis is a leading cause of death worldwide, yet the determinants of death are not well understood. We sought to determine risk factors for mortality during treatment of drug-susceptible pulmonary tuberculosis under program settings.

Methods: Retrospective chart review of patients with drug-susceptible tuberculosis reported to the San Francisco Tuberculosis Control Program from 1990-2001.

A randomized controlled trial to evaluate the effectiveness of a distance asthma learning program for pediatricians.

Objectives: To assess provider acceptability of a distance learning program for pediatric asthma and pilot test its effects on physician knowledge, attitudes and treatment practices.

Design: Randomized controlled trial.

Setting: Louisville and the surrounding central Kentucky region.

Comparison of restriction fragment length polymorphism with the polymorphic guanine-cytosine-rich sequence and spoligotyping for differentiation of Mycobacterium tuberculosis isolates with five or fewer copies of IS6110.

The use of IS6110 as a marker for molecular epidemiological studies is limited when a Mycobacterium tuberculosis isolate has five or fewer copies of IS6110. Restriction fragment length polymorphism analysis with a highly polymorphic GC-rich repetitive sequence located in the plasmid pTBN12 (PGRS RFLP) and spoligotyping (based on the polymorphism of the DR region) are two frequently used secondary typing methods. The aim of this study was to compare the performance of these two methods in a population-based study in San Francisco.

Healthcare worker occupation and immune response to Pneumocystis jirovecii.

The reservoir and mode of transmission of Pneumocystis jirovecii remain uncertain. We conducted a cross-sectional study of 126 San Francisco General Hospital staff in clinical (n = 103) and nonclinical (n = 23) occupations to assess whether occupational exposure was associated with immune responses to P. jirovecii.

Severity and outcomes of Pneumocystis pneumonia in patients newly diagnosed with HIV infection: an observational cohort study.

It is unclear whether patients who are unaware of their HIV infection have different severity or outcomes of Pneumocystis pneumonia (PCP) compared to patients who have been previously diagnosed with HIV. In this retrospective observational cohort study of consecutive HIV-infected patients with microscopically diagnosed PCP at San Francisco General Hospital between 1997 and 2006, 121 of 522 patients (23%) were unaware of their HIV infection prior to their diagnosis of PCP. The proportion of patients with concurrently diagnosed HIV and PCP each year remained unchanged during the study period.

Clinical characteristics and treatment outcomes of patients with isoniazid-monoresistant tuberculosis.

Background: Risk factors and treatment outcomes under program conditions for isoniazid (INH)-monoresistant tuberculosis have not been well described.

Methods: Medical charts were retrospectively reviewed for all cases of culture-confirmed, INH-monoresistant tuberculosis ( n = 137) reported to the San Francisco Department of Public Health Tuberculosis Control Section from October 1992 through October 2005, and those cases were compared with a time-matched sample of drug-susceptible tuberculosis cases (n = 274)

Results: In multivariate analysis, only a history of treatment for latent tuberculosis (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.

At what age do children start taking daily asthma medicines on their own?

Objective: Use of daily controller medications is a critical task in management of persistent asthma. Study aims were to examine (1) the association between child age and extent of daily controller-medication responsibility in a sample aged 4 to 19 years, (2) parent, child, and disease predictors of child daily controller-medication responsibility and overall daily controller-medication adherence, and (3) the association between child daily controller-medication responsibility and overall daily controller-medication adherence.

Methods: We conducted a cross-sectional telephone survey of 351 parents of children who were prescribed daily controller medication.

Selective provision of asthma self-management tools to families.

Objective: Providing asthma education in a primary care setting can be challenging because of time and resource constraints. The purpose of this work was to determine factors associated with the provision of different asthma self-management tools.

Methods: We conducted a cross-sectional survey with 896 parents of children with asthma (age 2-12 years).