Douglas Proops

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.

Mycobacterium tuberculosis cluster with developing drug resistance, New York, New York, USA, 2003-2009.

In 2004, identification of patients infected with the same Mycobacterium tuberculosis strain in New York, New York, USA, resulted in an outbreak investigation. The investigation involved data collection and analysis, establishing links between patients, and forming transmission hypotheses. Fifty-four geographically clustered cases were identified during 2003–2009. Initially, the M. tuberculosis strain was drug susceptible. However, in 2006, isoniazid resistance emerged, resulting in isoniazid-resistant M. tuberculosis among 17 (31%) patients. Compared with patients with drug-susceptible M. tuberculosis, a greater proportion of patients with isoniazid-resistant M. tuberculosis were US born and had a history of illegal drug use. No patients named one another as contacts. We used patient photographs to identify links between patients. Three links were associated with drug use among patients infected with isoniazid-resistant M. tuberculosis. The photographic method would have been more successful if used earlier in the investigation. Name-based contact investigation might not identify all contacts, particularly when illegal drug use is involved.

Moxifloxacin Prophylaxis against MDR TB, New York, New York, USA

Contacts of persons infected with multidrug-resistant tuberculosis (MDR TB) have few prophylaxis options. Of 50 contacts of HIV- and MDR TB–positive persons who were treated with moxifloxacin, 30 completed treatment and 3 discontinued treatment because of gastrointestinal symptoms. Moxifloxacin was generally well-tolerated; further research of its efficacy against MDR TB is needed.

Long-term Mortality of Patients With Tuberculous Meningitis in New York City: A Cohort Study

Background Tuberculous meningitis (TBM) is the most devastating clinical presentation of infection with Mycobacterium tuberculosis; delayed initiation of effective antituberculosis therapy is associated with poor treatment outcomes. Our objective was to determine the relationship between drug resistance and 10-year mortality among patients with TBM. Methods We conducted a retrospective cohort study of 324 patients with culture-confirmed TBM, susceptibility results reported for isoniazid and rifampin, and initiation of at least 2 antituberculosis drugs, reported to the tuberculosis registry in New York City between 1 January 1992 and 31 December 2001. Date of death was ascertained by matching the tuberculosis registry with death certificate data for 1992-2012 from the New York Office of Vital Statistics. Human immunodeficiency virus (HIV) status was ascertained by medical records review, matching with the New York City HIV Surveillance registry, and review of cause of death. Results Among 257 TBM patients without rifampin-resistant isolates, isoniazid resistance was associated with mortality after the first 60 days of treatment when controlling for age and HIV infection (adjusted hazard ratio, 1.94 [95% confidence interval, 1.08-3.94]). Death occurred before completion of antituberculosis therapy in 63 of 67 TBM patients (94%) with rifampin-resistant disease. Conclusions Among patients with culture-confirmed TBM, we observed rapid early mortality in patients with rifampin-resistant isolates, and an independent association between isoniazid-resistant isolates and death after 60 days of therapy. These findings support the continued evaluation of rapid diagnostic techniques and the empiric addition of second-line drugs for patients with clinically suspected drug-resistant TBM.

Increasing the efficiency and yield of a tuberculosis contact investigation through electronic data systems matching.

BACKGROUND Electronic health data may improve the timeliness and accuracy of resource-intense contact investigations (CIs) in healthcare settings. METHODS In September 2013, we initiated a CI around a healthcare worker (HCW) with infectious tuberculosis (TB) who worked in a maternity ward. Two sources of electronic health data were employed: hospital-based electronic medical records (EMRs), to identify patients exposed to the HCW, and an electronic immunization registry, to obtain contact information for exposed infants and their providers at two points during follow-up. RESULTS Among 954 patients cared for in the maternity ward during the HCWs infectious period, the review of EMRs identified 285 patients (30%) who interacted with the HCW and were, thus, exposed to TB. Matching infants to the immunization registry offered new provider information for 52% and 30% of the infants in the first and second matches. Providers reported evaluation results for the majority of patients (66%). CONCLUSION Data matching improved the efficiency and yield of this CI, thereby demonstrating the usefulness of enhancing CIs with electronic health data.

Confirming Mycobacterium tuberculosis transmission from a cadaver to an embalmer using molecular epidemiology

Genotyping results and epidemiologic investigation were used to confirm tuberculosis transmission from a cadaver to an embalmer. This investigation highlights the utility of genotyping in identifying unsuspected epidemiologic links and unusual transmission settings. In addition, the investigation provides additional evidence for the occupational risk of tuberculosis among funeral service workers and indicates a need for education about tuberculosis risk and the importance of adhering to appropriate infection control measures among funeral service workers.

Using QuantiFERON-TB Gold In-Tube for field-based tuberculosis contact investigations in congregate settings.

Contact investigations are crucial to controlling tuberculosis in the United States. In these investigations, the tuberculin skin test has been the primary test to detect tuberculosis infection. Interferon-γ release assays, such as the QuantiFERON-TB Gold In-Tube test, were recently introduced and are intended to address limitations of the tuberculin skin test. However, there are limited data on the use of these tests in contact investigations in congregate settings. We present 2 field-based investigations to highlight potential advantages, limitations, and feasibility of using the QuantiFERON-TB Gold In-Tube test in congregate setting investigations.

Exploring genotype concordance in epidemiologically linked cases of tuberculosis in New York City.

Comparing genotype results of tuberculosis (TB) isolates from individuals diagnosed with TB can support or refute transmission; however, these conclusions are based upon the criteria used to define a genotype match. We used a genotype-match definition which allowed for variation in IS6110 restriction fragment length polymorphism (RFLP) to support transmission between epidemiologically linked persons. Contacts of individuals with infectious TB (index cases) diagnosed in New York City from 1997 to 2003 who subsequently developed TB (contact cases) from 1997 to 2007 were identified. For each contact case and index case (case-pair), isolate genotypes (spoligotype and RFLP results) were evaluated. Isolates from case-pairs were classified as exact or non-exact genotype match. Genotypes from non-exact match case-pairs were reviewed at the genotyping laboratory to determine if the isolates met the near-genotype-match criteria (exactly matching spoligotype and similar RFLP banding patterns). Of 118 case-pairs identified, isolates from 83 (70%) had exactly matching genotypes and 14 (12%) had nearly matching genotypes (supporting transmission), while the remaining 21 (18%) case-pairs had discordant genotypes (refuting transmission). Using identical genotype-match criteria for isolates from case-pairs epidemiologically linked through contact investigation may lead to underestimation of transmission. TB programmes should consider the value of expanding genotype-match criteria to more accurately assess transmission between such cases.

Contact Investigations Around Mycobacterium tuberculosis Patients Without Positive Respiratory Culture.

OBJECTIVE To evaluate the yield and effectiveness of contact investigations conducted around potentially infectious tuberculosis (TB) patients with no positive respiratory culture for Mycobacterium tuberculosis in New York City (NYC). DESIGN All TB patients without a positive respiratory culture from 2003 to 2012 were extracted from the NYC TB registry, and all patients eligible for contact investigation and their contacts were evaluated. Patients without a positive respiratory culture were defined as eligible for contact investigation if they had a respiratory nucleic acid amplification result positive for M tuberculosis, a cavitary chest radiograph, or a positive respiratory acid-fast bacilli smear. SETTING NYC, New York. MAIN OUTCOME MEASURES To evaluate the yield of the investigations, the number of contacts identified and the outcome of testing was quantified. Potential transmission was defined on the basis of whether active TB patients were detected among the contacts and if a contact had a TB test conversion. RESULTS From 2003 to 2012, there were 2191 TB patients without a positive respiratory culture in NYC, 374 (17%) of which were considered eligible for contact investigation. A total of 11 096 contacts were identified around 300 (80%) eligible patients, 136 of whom had a diagnosis of TB infection; of those with TB infection who initiated preventive treatment, 66% completed treatment. Potential transmission was identified around 14 patients, with the identification of 2 additional cases of active TB and 15 contacts with TB infection test conversion. CONCLUSIONS Conducting contact investigations around patients without a positive respiratory culture yielded evidence of possible transmission and led to the identification and treatment of new TB cases and those with TB infection. These findings suggest that these investigations should be conducted in settings where resources permit.