Nicholas D. Walter

Social Context of Work Injury Among Undocumented Day Laborers in San Francisco

AbstractOBJECTIVE: To identify ways in which undocumented day laborers’ social context affects their risk for occupational injury, and to characterize the ways in which these workers’ social context influences their experience of disability. DESIGN: Qualitative study employing ethnographic techniques of participant-observation, supplemented by semistructured in-depth interviews. SETTINGS: Street corners in San Francisco’s Mission District, a homeless shelter, and a nonprofit day labor hiring hall. PARTICIPANTS: Thirty-eight Mexican and Central American male day laborers, 11 of whom had been injured. PRIMARY THEMES: Anxiety over the potential for work injury is omnipresent for day laborers. They work in dangerous settings, and a variety of factors such as lack of training, inadequate safety equipment, and economic pressures further increase their risk for work injury. The day laborers are isolated from family and community support, living in a local context of homelessness, competition, and violence. Injuries tend to have severe emotional, social, and economic ramifications. Day laborers frequently perceive injury as a personal failure that threatens their masculinity and their status as patriarch of the family. Their shame and disappointment at failing to fulfill culturally defined masculine responsibilities leads to intense personal stress and can break family bonds. Despite the high incidence of work injuries and prevalence of work-related health conditions, day laborers are frequently reluctant to use health services due to anxiety regarding immigration status, communication barriers, and economic pressure. IMPLICATIONS: On the basis of these ethnographic data, we recommend strategies to improve ambulatory care services to day laborers in 3 areas: structural changes in ambulatory care delivery, clinical interactions with individual day laborers, and policymaking around immigration and health care issues.

Comparison of Laboratory Diagnostic Procedures for Detection of Mycoplasma pneumoniae in Community Outbreaks

BACKGROUND Mycoplasma pneumoniae continues to be a significant cause of community-acquired pneumonia (CAP). A more definitive methodology for reliable detection of M. pneumoniae is needed to identify outbreaks and to prevent potentially fatal extrapulmonary complications. METHODS We analyzed 2 outbreaks of CAP due to M. pneumoniae. Nasopharyngeal and/or oropharyngeal swab specimens and serum samples were obtained from persons with clinically defined cases, household contacts, and asymptomatic individuals. Real-time polymerase chain reaction (PCR) for M. pneumoniae was performed on all swab specimens, and the diagnostic utility was compared with that of 2 commercially available serologic test kits. RESULTS For cases, 21% yielded positive results with real-time PCR, whereas 81% and 54% yielded positive results with the immunoglobulin M and immunoglobulin G/immunoglobulin M serologic tests, respectively. For noncases, 1.8% yielded positive results with real-time PCR, whereas 63% and 79% yielded serologically positive results with the immunoglobulin M and immunoglobulin G/immunoglobulin M kits, respectively. The sensitivity of real-time PCR decreased as the duration between symptom onset and sample collection increased, with a peak sensitivity of 48% at 0-21 days. A specificity of 43% for the immunoglobulin M antibody detection assay was observed for persons aged 10-18 years, but the sensitivity increased to 82% for persons aged 19 years. DISCUSSION Thorough data analysis indicated that no single available test was reliable for the identification of an outbreak of CAP due to M. pneumoniae. A combination of testing methodologies proved to be the most reliable approach for identification of outbreaks of CAP due to M. pneumoniae, especially in the absence of other suspected respiratory pathogens.

Persistent Latent Tuberculosis Reactivation Risk in United States Immigrants

RATIONALE Current guidelines limit latent tuberculosis infection (LTBI) evaluation to persons in the United States less than or equal to 5 years based on the assumption that high TB rates among recent entrants are attributable to high LTBI reactivation risk, which declines over time. We hypothesized that high postarrival TB rates may instead be caused by imported active TB. OBJECTIVES Estimate reactivation and imported TB in an immigrant cohort. METHODS We linked preimmigration records from a cohort of California-bound Filipino immigrants during 2001-2010 with subsequent TB reports. TB was likely LTBI reactivation if the immigrant had no evidence of active TB at preimmigration examination, likely imported if preimmigration radiograph was abnormal and TB was reported less than or equal to 6 months after arrival, and likely reactivation of inactive TB if radiograph was abnormal but TB was reported more than 6 months after arrival. MEASUREMENTS AND MAIN RESULTS Among 123,114 immigrants, 793 TB cases were reported. Within 1 year of preimmigration examination, 85% of TB was imported; 6 and 9% were reactivation of LTBI and inactive TB, respectively. Conversely, during Years 2-9 after U.S. entry, 76 and 24% were reactivation of LTBI and inactive TB, respectively. The rate of LTBI reactivation (32 per 100,000) did not decline during Years 1-9. CONCLUSIONS High postarrival TB rates were caused by detection of imported TB through active postarrival surveillance. Among immigrants without active TB at baseline, reported TB did not decline over 9 years, indicating sustained high risk of LTBI reactivation. Revised guidelines should support LTBI screening and treatment more than 5 years after U.S. arrival.

Wound Healing after Trauma may Predispose to Lung Cancer Metastasis: Review of Potential Mechanisms

Inflammatory oncotaxis, the phenomenon in which mechanically injured tissues are predisposed to cancer metastases, has been reported for a number of tumor types, but not previously for histologically proven lung cancer. We review clinical and experimental evidence and mechanisms that may underlie inflammatory oncotaxis, and provide illustrative examples of two patients with squamous cell carcinoma of the lung who developed distant, localized metastatic disease at sites of recent physical trauma. Trauma may predispose to metastasis through two distinct, but not mutually exclusive, mechanisms: (1) physical trauma induces tissue damage and local inflammation, creating a favorable environment that is permissive for seeding of metastatic cells from distant sites; and/or (2) micrometastatic foci are already present at the time of physical injury, and trauma initiates changes in the microenvironment that stimulate the proliferation of the metastatic cells. Further exploration of post-traumatic inflammatory oncotaxis may elucidate fundamental mechanisms of metastasis and could provide novel strategies to prevent cancer metastasis.

Transcriptional adaptation of drug-tolerant Mycobacterium tuberculosis during treatment of human tuberculosis

BACKGROUND Treatment initiation rapidly kills most drug-susceptible Mycobacterium tuberculosis, but a bacterial subpopulation tolerates prolonged drug exposure. We evaluated drug-tolerant bacilli in human sputum by comparing messenger RNA (mRNA) expression of drug-tolerant bacilli that survive the early bactericidal phase with treatment-naive bacilli. METHODS M. tuberculosis gene expression was quantified via reverse-transcription polymerase chain reaction in serial sputa from 17 Ugandans treated for drug-susceptible pulmonary tuberculosis. RESULTS Within 4 days, bacterial mRNA abundance declined >98%, indicating rapid killing. Thereafter, the rate of decline slowed >94%, indicating drug tolerance. After 14 days, 16S ribosomal RNA transcripts/genome declined 96%, indicating slow growth. Drug-tolerant bacilli displayed marked downregulation of genes associated with growth, metabolism, and lipid synthesis and upregulation in stress responses and key regulatory categories-including stress-associated sigma factors, transcription factors, and toxin-antitoxin genes. Drug efflux pumps were upregulated. The isoniazid stress signature was induced by initial drug exposure, then disappeared after 4 days. CONCLUSIONS Transcriptional patterns suggest that drug-tolerant bacilli in sputum are in a slow-growing, metabolically and synthetically downregulated state. Absence of the isoniazid stress signature in drug-tolerant bacilli indicates that physiological state influences drug responsiveness in vivo. These results identify novel drug targets that should aid in development of novel shorter tuberculosis treatment regimens.

Prevalence and outcomes of cryptococcal antigenemia in HIV-seropositive patients hospitalized for suspected tuberculosis in Uganda.

Background:Cryptococcal infection occurs in HIV-seropositive patients and is associated with high mortality. However, limited information is available on the prevalence and outcomes of cryptococcal antigenemia among hospitalized HIV-seropositive patients in sub-Saharan Africa. Objectives:To determine the prevalence of and risk factors for cryptococcal antigenemia among HIV-seropositive patients presenting to Mulago Hospital (Kampala, Uganda) with unexplained cough ≥2 weeks and suspected tuberculosis (TB) and also to determine if antigenemia is associated with an increased mortality. Methods:Between September 2009 and September 2010, we enrolled consecutive HIV-seropositive adults hospitalized at Mulago Hospital with cough ≥2 weeks and suspected TB. Banked serum was tested for cryptococcal antigen. We compared demographic and clinical characteristics, and 2-month mortality in patients with and without cryptococcal antigenemia. Results:Of 563 HIV-seropositive patients, 32 (5.7%) were cryptococcal antigen (CrAg) positive. None had Cryptococcus neoformans detected on fungal culture of bronchoalveolar lavage fluid (n = 116). CrAg-positive patients had a lower median CD4 count compared with CrAg-negative patients (25 vs. 55 cells/&mgr;L, P = 0.02), and a substantial proportion of CrAg-positive patients also had concurrent TB (31%). A positive CrAg test was not associated with increased mortality during the 2-month follow-up period (hazard ratio: 0.99, 95% confidence interval: 0.63 to 1.54, P = 0.95) after adjusting for CD4 count and antiretroviral therapy use at enrollment and/or follow-up. Conclusions:Occult cryptococcal antigenemia occurs commonly among hospitalized HIV-seropositive patients with suspected TB. CrAg testing should be considered in hospitalized HIV-seropositive patients with CD4 count <50 cells/&mgr;L, coupled with longer follow-up to evaluate the diagnostic value of CrAg and therapeutic interventions in patients with asymptomatic cryptococcal antigenemia.

Update on tuberculosis biomarkers: From correlates of risk, to correlates of active disease and of cure from disease

Tuberculosis (TB) remains a devastating disease, yet despite its enormous toll on global health, tools to control TB are insufficient and often outdated. TB Biomarkers (TB‐BM) would constitute extremely useful tools to measure infection status and predict outcome of infection, vaccination or therapy. There are several types of TB‐BM: Correlate of Infection; Correlate of TB Disease; Correlate of Increased Risk of Developing Active TB Disease; Correlate of the Curative Response to Therapy; and Correlate of Protection (CoP). Most TB‐BM currently studied are host‐derived BM, and consist of transcriptomic, proteomic, metabolomic, cellular markers or marker combinations (‘signatures’). In particular, vaccine‐inducible CoP are expected to be transformative in developing new TB vaccines as they will de‐risk vaccine research and development (R&D) as well as human testing at an early stage. In addition, CoP could also help minimizing the need for preclinical studies in experimental animals.

Population-Level Impact of Same-Day Microscopy and Xpert MTB/RIF for Tuberculosis Diagnosis in Africa

Objective To compare the population-level impact of two World Health Organization-endorsed strategies for improving the diagnosis of tuberculosis (TB): same-day microscopy and Xpert MTB/RIF (Cepheid, USA). Methods We created a compartmental transmission model of TB in a representative African community, fit to the regional incidence and mortality of TB and HIV. We compared the population-level reduction in TB burden over ten years achievable with implementation over two years of same-day microscopy, Xpert MTB/RIF testing, and the combination of both approaches. Findings Same-day microscopy averted an estimated 11.0% of TB incidence over ten years (95% uncertainty range, UR: 3.3%–22.5%), and prevented 11.8% of all TB deaths (95% UR: 7.7%–27.1%). Scaling up Xpert MTB/RIF to all centralized laboratories to achieve 75% population coverage had similar impact on incidence (9.3% reduction, 95% UR: 1.9%–21.5%) and greater effect on mortality (23.8% reduction, 95% UR: 8.6%–33.4%). Combining the two strategies (i.e., same-day microscopy plus Xpert MTB/RIF) generated synergistic effects: an 18.7% reduction in incidence (95% UR: 5.6%–39.2%) and 33.1% reduction in TB mortality (95% UR: 18.1%–50.2%). By the end of year ten, combining same-day microscopy and Xpert MTB/RIF could reduce annual TB mortality by 44% relative to the current standard of care. Conclusion Scaling up novel diagnostic tests for TB and optimizing existing ones are complementary strategies that, when combined, may have substantial impact on TB epidemics in Africa.

Translating basic science insight into public health action for multidrug- and extensively drug-resistant tuberculosis.

Multidrug (MDR)‐ and extensively drug‐resistant (XDR) tuberculosis (TB) impose a heavy toll of human suffering and social costs. Controlling drug‐resistant TB is a complex global public health challenge. Basic science advances including elucidation of the genetic basis of resistance have enabled development of new assays that are transforming the diagnosis of MDR‐TB. Molecular epidemiological approaches have provided new insights into the natural history of TB with important implications for drug resistance. In the future, progress in understanding Mycobacterium tuberculosis strain‐specific human immune responses, integration of systems biology approaches with traditional epidemiology and insight into the biology of mycobacterial persistence have potential to be translated into new tools for diagnosis and treatment of MDR‐ and XDR‐TB. We review recent basic sciences developments that have contributed or may contribute to improved public health response.

Reaching the Limits of Tuberculosis Prevention among Foreign-Born Individuals: A Tuberculosis-Control Program Perspective

Analysis of whether assiduous implementation of American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America guidelines for targeted testing and treatment of latent tuberculosis infection could have prevented any of 223 cases of active tuberculosis in foreign-born persons in San Francisco during the period 2002-2003. We report that 62% of these cases were not preventable and conclude that a further reduction in the incidence of tuberculosis among foreign-born persons will be modest without modification of current guidelines.