Jiehui Li

Relapse and Acquired Rifampin Resistance in HIV-Infected Patients with Tuberculosis Treated with Rifampin- or Rifabutin-Based Regimens in New York City, 1997–2000

BACKGROUND The relationship between rifamycin use and either relapse or treatment failure with acquired rifampin resistance (ARR) among human immunodeficiency virus (HIV)-infected patients with tuberculosis (TB) is not well understood. METHODS We conducted a retrospective cohort study of HIV-infected and HIV-uninfected persons with rifampin-susceptible TB, (1) to compare relapse rates, ARR, and treatment failure, according to HIV serostatus; and (2) to examine whether and how use of rifamycin was associated with clinical outcomes of interest among HIV-infected patients with TB. RESULTS HIV-infected patients were more likely to have ARR than were HIV-uninfected patients (0.9% vs. 0.1%; P = .007), and the association remained significant in multivariate analysis (adjusted odds ratio [OR], 5.5; 95% confidence interval [CI], 1.4-21.5). Among HIV-infected patients with TB, none of 57 patients treated with rifabutin-based regimens alone had ARR, and only 1 of 395 patients treated with rifabutin given in combination with a rifampin-based regimen had ARR, whereas 6 of 355 patients treated with a rifampin-based regimen alone had relapse and ARR. HIV-infected patients treated with rifampin-based regimens alone had a higher risk for relapse and development of rifampin resistance if intermittent dosing of rifampin was started during the intensive phase of treatment, compared with patients who did not receive intermittent dosing (hazard ratio [HR] for relapse, 6.7 [95% CI, 1.1-40.1]; HR for ARR, 6.4 [95% CI, 1.1-38.4]). This association remained when confined to patients with a CD4+ T lymphocyte count of < 100 lymphocytes/mm3. Intermittent dosing started only after the intensive phase of treatment did not increase the risks of relapse and ARR among HIV-infected patients with TB. CONCLUSION The risk for ARR among HIV-infected persons with TB did not depend on the rifamycin used but, rather, on the rifampin dosing schedule in the intensive phase of treatment.

Adherence to treatment of latent tuberculosis infection in a clinical population in New York City.

BACKGROUND Low adherence to treatment of latent tuberculosis infection (TLTBI) diminishes TB prevention efforts. This study examined the treatment completion rate among those who started TLTBI and factors associated with adherence to TLTBI. METHODS Patients who started TLTBI in New York City (NYC) Health Department chest clinics during January 2002-August 2004 were studied. TLTBI completion rate were described and compared according to patient demographic and clinical characteristics by regimen using univariate analysis and log-binomial regression. RESULTS A total of 15 035 patients started and 6788 (45.2%) completed TLTBI. Treatment completers were more likely than non-completers to be >or=35 years old (52.5%, adjusted relative risk (aRR)=1.2, 95% confidence interval (CI)=1.1, 1.2), contacts to pulmonary TB patients (57.4%, aRR=1.5, 95% CI=1.4, 1.7), treated by directly observed preventive therapy (DOPT) (71.4%, aRR=1.3, 95% CI=1.2, 1.3), and to have received the rifamycin-based regimen (60.0%, aRR=1.2, 95% CI=1.1, 1.3). The completion rate with an isoniazid regimen did not differ between HIV-infected and HIV-uninfected persons. Among those who failed to complete, 3748 (47.8%) failed to return for isoniazid and 59 (14.7%) for rifamycin after the first month of medication dispensing. CONCLUSIONS Shorter regimen and DOPT increased completion rates for LTBI. Though efforts to improve TLTBI completion need to address all groups, greater focus is needed for persons who are contacts and HIV-infected, as they have higher risk of developing TB.

Molecular Epidemiology of Multidrug-Resistant Tuberculosis, New York City, 1995–1997

From January 1, 1995, to December 31, 1997, we reviewed records of all New York City patients who had multidrug-resistant tuberculosis (MDRTB); we performed insertion sequence (IS) 6110-based DNA genotyping on the isolates. Secondary genotyping was performed for low IS6110 copy band strains. Patients with identical DNA pattern strains were considered clustered. From 1995 through 1997, MDRTB was diagnosed in 241 patients; 217 (90%) had no prior treatment history, and 166 (68.9%) were born in the United States or Puerto Rico. Compared with non-MDRTB patients, MDRTB patients were more likely to be born in the United States, have HIV infection, and work in health care. Genotyping results were available for 234 patients; 153 (65.4%) were clustered, 126 (82.3%) of them in eight clusters of >4 patients. Epidemiologic links were identified for 30 (12.8%) patients; most had been exposed to patients diagnosed before the study period. These strains were likely transmitted in the early 1990s when MDRTB outbreaks and tuberculosis transmission were widespread in New York.

Active Case Finding and Prevention of Tuberculosis Among a Cohort of Contacts Exposed to Infectious Tuberculosis Cases in New York City

BACKGROUND Tuberculosis contact investigation identifies individuals who may be recently infected with tuberculosis and are thus at increased risk for disease. Contacts with latent tuberculosis infection (LTBI) are offered chemoprophylaxis to prevent active disease; however, the effectiveness of this intervention is unclear as treatment completion is generally low. METHODS A retrospective cohort study of 30 561 contacts identified during investigation of 5182 cases of tuberculosis diagnosed in New York City, 1997-2003, was performed. We searched the NYC tuberculosis registry to identify contacts developing active tuberculosis within 4 years of follow-up. We estimated the following: number of contacts undergoing evaluation (ie, tuberculin skin test and/or chest radiograph) per prevalent case diagnosed; number of contacts with LTBI that need to be treated with standard chemoprophylaxis to prevent 1 active case. RESULTS Of 30 561 contacts, 27 293 (89%) were evaluated and 268 prevalent cases were diagnosed (102 contacts evaluated per prevalent case diagnosed, 95% confidence interval [CI], 90-115). LTBI was diagnosed in 7597 contacts, including 6001 (79%) who initiated chemoprophylaxis, 3642 (61%) who later completed treatment, and 2359 (39%) who did not complete treatment. During 4 years of follow-up, active tuberculosis was diagnosed in 46 contacts with LTBI, including 22 of 6001 (0.4%) who initiated chemoprophylaxis and 24 of 1596 (1.5%) who did not initiate treatment. The absolute risk reduction afforded by chemoprophylaxis initiation was 1.1% (95% CI, .6%-1.9%), leading to an estimated 88 contacts treated to prevent 1 tuberculosis case (95% CI, 53-164). CONCLUSIONS Contact investigation facilitates active case finding and tuberculosis prevention, even when completion rates of chemoprophylaxis are suboptimal.

Distinct clinical and epidemiological features of tuberculosis in New York City caused by the RD Rio Mycobacterium tuberculosis sublineage

BACKGROUND Genetic tracking of Mycobacterium tuberculosis is a cornerstone of tuberculosis (TB) control programs. The RD(Rio) M. tuberculosis sublineage was previously associated with TB in Brazil. We investigated 3847 M. tuberculosis isolates and registry data from New York City (NYC) (2001-2005) to: (1) affirm the position of RD(Rio) strains within the M. tuberculosis phylogenetic structure, (2) determine its prevalence, and (3) define transmission, demographic, and clinical characteristics associated with RD(Rio) TB. METHODS Isolates classified as RD(Rio) or non-RD(Rio) M. tuberculosis by multiplex PCR were further classified as clustered (≥2 isolates) or unique based primarily upon IS6110-RFLP patterns and lineage-specific cluster proportions were calculated. The secondary case rate of RD(Rio) was compared with other prevalent M. tuberculosis lineages. Genotype data were merged with the data from the NYC TB Registry to assess demographic and clinical characteristics. RESULTS RD(Rio) strains were found to: (1) be restricted to the Latin American-Mediterranean family, (2) cause approximately 8% of TB cases in NYC, and (3) be associated with heightened transmission as shown by: (i) a higher cluster proportion compared to other prevalent lineages, (ii) a higher secondary case rate, and (iii) cases in children. Furthermore, RD(Rio) strains were significantly associated with US-born Black or Hispanic race, birth in Latin American and Caribbean countries, and isoniazid resistance. CONCLUSIONS The RD(Rio) genotype is a single M. tuberculosis strain population that is emerging in NYC. The findings suggest that expanded RD(Rio) case and exposure identification could be of benefit due to its association with heightened transmission.

Trends in Drug-Resistant Mycobacterium tuberculosis in New York City, 1991–2003

BACKGROUND Two drug-resistance surveys showed a very high prevalence of drug resistance among isolates obtained from patients with tuberculosis in 1991 and 1994 in New York, New York. METHODS A cross-sectional survey in April 1997 and a survey of incident cases in April-June 2003 were conducted. The trend in the proportion of drug resistance in the 4 surveys was examined separately for prevalent and incident cases. Risk factors for drug resistance in incident cases were also assessed. RESULTS The number of patients was 251 in the 1997 survey and 217 in the 2003 survey. Among prevalent cases, the percentage of cases with resistance to any antituberculosis drug decreased from 33.5% in 1991 to 23.8% in 1994 and to 21.5% in 1997 (P < .001, by test for trend); cases of multidrug-resistant tuberculosis also decreased significantly, from 19% in 1991 to 6.8% in 1997 (P < .001, by test for trend). Among incident cases in the 4 surveys, the decrease in resistance to any antituberculosis drugs was not statistically significant; however, the decrease in multidrug-resistant tuberculosis (from 9% in 1991 to 2.8% in 2003) was statistically significant (P = .002, by test for trend). However, in 2003, a worrisome increase in incident cases of multidrug-resistant tuberculosis (an increase of 23%) was seen among previously treated patients with pulmonary tuberculosis not born in the United States. Human immunodeficiency virus infection, a strong predictor for drug resistance in 1991 and 1994, was not associated with drug resistance in subsequent surveys. CONCLUSIONS Intensive case management, including directly observed therapy, adherence monitoring, and periodic medical review to ensure appropriate treatment for each patient, should be sustained to prevent acquired drug resistance.

Changing Sociodemographic and Clinical Characteristics of Tuberculosis among HIV-Infected Patients, New York City, 1992–2005

BACKGROUND Although highly active antiretroviral therapy (HAART) has decreased human immunodeficiency virus (HIV)-related morbidity, tuberculosis remains an important disease among HIV-infected individuals. METHODS By use of surveillance data, sociodemographic and clinical changes among HIV-infected and HIV-uninfected tuberculosis patients in New York City were evaluated using the Cochran-Armitage trend test and multivariate logistic regression across 3 periods: 1992-1995 (pre-HAART), 1996-2000 (early HAART), and 2001-2005 (late HAART). RESULTS Among tuberculosis patients with known HIV status, 4345 (60%) of 7224 were HIV-infected in pre-HAART, 1943 (33%) of 5933 in early HAART, and 851 (22%) of 3815 in late HAART (P < .001 for trend). During the study period, the age of HIV-infected tuberculosis patients increased, and greater proportions were female, non-Hispanic black, Asian, and foreign born; the proportion that was non-Hispanic white decreased. The proportion that was culture-negative for Mycobacterium tuberculosis increased (from 7% pre-HAART to 21% late HAART; P < .001 for trend; early HAART vs pre-HAART adjusted odds ratio [aOR], 1.68; 95% confidence interval [CI], 1.38-2.04), and the proportion with extrapulmonary disease also increased (from 32% to 46%; P < .001 for trend). The proportion with multidrug-resistant tuberculosis decreased (from 16% to 4%; P < .001 for trend), especially from pre-HAART to early HAART (aOR, 0.31; 95% CI, 0.25-0.40). The proportion who died before tuberculosis treatment decreased (from 12% to 7%), and the proportion who died during tuberculosis treatment also decreased (from 29% to 11%) (both, P < .001 for trend). Over time, HIV-infected tuberculosis patients had AIDS longer before the diagnosis of tuberculosis (P < .001 for trend). Similar trends for culture, site of disease, and drug resistance were seen for HIV-uninfected tuberculosis patients. CONCLUSIONS The sociodemographic and clinical characteristics changed substantially among HIV-infected tuberculosis patients in New York City. Awareness of these changes may speed diagnosis of tuberculosis. Future studies should evaluate HAARTs effect on tuberculosis presentation among HIV-infected patients.

Risk factors for and consequences of persistent lower respiratory symptoms among World Trade Center Health Registrants 10 years after the disaster

Objectives The prevalence of persistent lower respiratory symptoms (LRS) among rescue/recovery workers, local area workers, residents and passers-by in the World Trade Center Health Registry (WTCHR) was analysed to identify associated factors and to measure its effect on quality of life (QoL) 10 years after 9/11/2001. Methods This cross-sectional study included 18 913 adults who completed 3 WTCHR surveys (2003–2004 (Wave 1 (W1)), 2006–2007 (Wave 2 (W2)) and 2011–2012 (Wave 3 (W3)). LRS were defined as self-reported cough, wheeze, dyspnoea or inhaler use in the 30 days before survey. The prevalence of three LRS outcomes: LRS at W1; LRS at W1 and W2; and LRS at W1, W2 and W3 (persistent LRS) was compared with no LRS on WTC exposure and probable mental health conditions determined by standard screening tests. Diminished physical and mental health QoL measures were examined as potential LRS outcomes, using multivariable logistic and Poisson regression. Results Of the 4 outcomes, persistent LRS was reported by 14.7%. Adjusted ORs for disaster exposure, probable post-traumatic stress disorder (PTSD) at W2, lacking college education and obesity were incrementally higher moving from LRS at W1, LRS at W1 and W2 to persistent LRS. Half of those with persistent LRS were comorbid for probable PTSD, depression or generalised anxiety disorder. Enrollees with persistent LRS were 3 times more likely to report poor physical health and ∼ 50% more likely to report poor mental health than the no LRS group. Conclusions LRS, accompanied by mental health conditions and decreased QoL, have persisted for at least 10 years after 9/11/2001. Affected adults require continuing surveillance and treatment.

Rising Number of Tuberculosis Cases Among Tibetans in New York City

Tuberculosis among Tibetans increased in New York City between 1995 and 1999. We examined characteristics of 68 Tibetan patients compared to 702 non-Tibetan patients from Nepal, India, or China, diagnosed between January 1995 and December 1999. The number of Tibetan patients increased each year after 1995 whereas non-Tibetans remained stable during the same period. Tibetans were younger (27 vs. 44 years), more likely to be infectious (63% vs. 46%), have multidrug resistance (7% vs. 2%) and shorter time to diagnosis after arrival (9 vs. 79 months, p < 0.01). For Tibetan patients, 68% of identified contacts were evaluated. The prevalence of tuberculosis infection was 65%. In contrast, among non-Tibetan patients 88.8% of contacts were evaluated and 45.2% were infected. Outreach efforts with community leaders and educational presentations at community events have been implemented in an effort to ensure continuity of care and completion of treatment.

Reproductive Outcomes Following Maternal Exposure to the Events of September 11, 2001, at the World Trade Center, in New York City

OBJECTIVES To estimate associations between exposure to the events of September 11, 2001, (9/11) and low birth weight (LBW), preterm delivery (PD), and small size for gestational age (SGA). METHODS We matched birth certificates filed in New York City for singleton births between 9/11 and the end of 2010 to 9/11-related exposure data provided by mothers who were World Trade Center Health Registry enrollees. Generalized estimating equations estimated associations between exposures and LBW, PD, and SGA. RESULTS Among 3360 births, 5.8% were LBW, 6.5% were PD, and 9% were SGA. Having incurred at least 2 of 4 exposures, having performed rescue or recovery work, and probable 9/11-related posttraumatic stress disorder 2 to 3 years after 9/11 were associated with PD and LBW during the early study period. CONCLUSIONS Disasters on the magnitude of 9/11 may exert effects on reproductive outcomes for several years. Women who are pregnant during and after a disaster should be closely monitored for physical and psychological sequelae. PUBLIC HEALTH IMPLICATIONS In utero and maternal disaster exposure may affect birth outcomes. Researchers studying effects of individual disasters should identify commonalities that may inform postdisaster responses to minimize disaster-related adverse birth outcomes.