Kim, Dennis Y. MD, MPH; Ridzon, Renee MD; Giles, Beverly RN, BSN; Mireles, Teresa MSN, APRN, BC
From the Epidemic Intelligence Service (Dr Kim); Centers for Disease Control and Prevention, Atlanta, Georgia (Dr Kim, Ms Ridzon); and Delaware Division of Public Health, Georgetown, Delaware (Ms Mireles, Ms Giles).
Address correspondence to: Dennis Kim, MD, MPH, Amgen Inc., One Amgen Way, MS: 17-2-C, Thousand Oaks, CA 91320-1799; e-mail: email@example.com
Dr. Kim is currently at Amgen Inc., Thousand Oaks, CA. Dr. Ridzon is currently at the Bill and Melinda Gates Foundation, Seattle, WA.
This article was written by employees of the U.S. Government as part of their duties, and therefore, is not subject to U.S. copyright.
In November 2000, the Centers for Disease Control and Prevention (CDC) received a request from the Delaware Division of Public Health for assistance with a suspected outbreak of TB among poultry plant workers in Sussex County, Delaware, in which three of four cases were reported to have meningeal disease. CDC and Delaware public health staff initiated an investigation to look for potential sources and epidemiologic links in this unusual cluster. This report describes an outbreak investigation in an occupational setting and demonstrates the use of molecular fingerprinting to help rule out the occurrence of an outbreak of TB.
Medical records of the four patients were reviewed. All available Mycobacterium tuberculosis isolates were sent to the National Tuberculosis Genotyping and Surveillance Network’s regional laboratory in Albany, NY, for DNA fingerprinting (genotyping) by a technique called spacer oligo nucleotide typing (spoligotyping 5).
Contact investigations of household members for each case were reviewed to search for epidemiologic links among the cases. In addition, contact investigations were conducted at the workplace for all cases. We were able to obtain country-of-origin data during the screening for one patient’s (patient 4) contacts. We defined a positive Tuberculin Skin Test (TST) was defined as induration ≥5 mm, and for the purposes of this contact investigation, a conversion as an increase in TST size of ≥5 mm within the past 2 years in someone with a previously documented negative TST.
Patient 1, a 31-year-old man born in Guatemala, worked at Plant A. On pre-employment screening in March 1998, he had a TST of 25 mm and his chest radiograph showed no active disease. He completed 6 months of isoniazid (INH) therapy at work with good adherence. In March 1999, he was hospitalized for symptoms of meningitis. Laboratory studies of his cerebrospinal fluid (CSF) were suggestive of meningitis, but the CSF was smear- and culture-negative for bacteria and acid-fast bacilli (AFB), and his serology for HIV was negative. In August 2000, he again developed symptoms of meningitis, was rehospitalized, and died. An autopsy revealed diffuse noncaseating granulomas throughout the meninges, pericardium, liver, lungs, bone marrow, and peritoneum, as well as old healed granulomas in the kidney, spleen, and dura. He was given a postmortem diagnosis of TB. However, at the time of autopsy, polymerase chain reaction testing of his specimens was negative for M. tuberculosis.
Patient 2, a 29-year-old HIV-infected man born in Mexico, worked in Plant B. His pre-employment TST was 12 mm in January 2000. His chest radiograph showed no active disease, and he denied respiratory symptoms. He started taking INH in April 2000 in a directly observed manner at the worksite. He was diagnosed with meningitis in July 2000, and in August, his CSF culture grew M. tuberculosis, demonstrating resistance to INH. He was treated with rifabutin, INH, pyrazinamide, and ethambutol; however, he died 2 months later from HIV-related illness.
Patient 3, a 22-year-old woman born in Mexico, worked in Plant B. In June 2000, her initial TST was negative. In October 2000, she was hospitalized with symptoms of meningitis. Her serology for HIV was negative. Her CSF was positive for AFB by smear and grew M. tuberculosis with resistance to streptomycin. Her chest radiograph revealed bilateral apical scarring. She refused sputum induction while hospitalized. Shortly after discharge, she returned to Mexico, where she received care in the Cure TB Program.
Patient 4, a 22-year-old man born in Guatemala, worked in Plant A. His pre-employment TST was 15 mm in April 2000. His chest radiograph was negative, and he denied any TB symptoms. Owing to elevated liver transaminases, he was not given treatment for latent TB infection. In October 2000, he was admitted to a local hospital and diagnosed with HIV infection with a CD4 count <20 cells/mL. His chest radiograph revealed bilateral diffuse patchy infiltrates. His sputum samples showed 1+ AFB, and a sputum culture grew M. tuberculosis susceptible to all first line anti-tuberculosis medications.
Table 1 summarizes the findings that suggested a work-related cluster.
Epidemiologic Study and Household Contact Investigation Review
Patients 1 and 4 worked at Plant A; patients 2 and 3 worked at Plant B. Patients 2 and 3 were reported to have social contact. There were no other cases of active disease among the household contacts of the cases with TB. Of the 11 close contacts of patient 1, four had previously positive TSTs; four had negative TSTs; and three had positive TSTs, two with skin test conversions. All five close contacts of patient 2 were TST negative. Of six close contacts of patient 3, four tested negative and two had positive TSTs; both had prior negative TSTs and demonstrated conversion. Of the nine contacts of patient 4, five were previously positive, three tested negative, and one tested positive and was a conversion.
Occupational Contact Investigation
TST results for work contacts of the four patients are summarized in Table 2. Only patients 3 and 4 had pulmonary disease and were thus potentially infectious. Because patient 2 had extrapulmonary disease only and there were no TB cases identified among contacts, the screening results obtained were used to serve as a baseline rate of positive TSTs in the population of poultry workers. There was no difference in the proportion of patient 3’s coworkers with a positive TST when compared with patient 2’s coworkers (RR = 1.1, 95% CI = 0.6–2.0) who worked at the same plant. Rates of positive TST were not higher in workers exposed to potentially infectious workers (patients 3 and 4) compared to those exposed to noninfectious workers (patients 1 and 2; RR = 0.49, 95% CI = 0.37–0.66).
Country-of-origin data were obtained for workers on the day shift at Plant A during the screening for patient 4. Of the 124 US-born workers, 11 (9%) were TST positive, compared with 25 (30%) of 82 foreign-born workers (RR of TST positivity among foreign born = 3.44 [95% CI = 1.79–6.60]).
Laboratory Specimen and Pathologic Review
The M. tuberculosis spoligotypes from isolates from patients 2, 3, and 4 did not demonstrate a matching pattern. No isolate was obtained from patient 1. The autopsy results from patient 1 were reviewed with the attending pathologist. There were no caseating granulomas, evidence of TB meningitis, or cavitation found in the lungs. Only noncaseating granulomas were identified, and no organisms were identified on special stains, leading to the conclusion that patient 1 did not have TB.
Poultry workers face numerous pulmonary occupational hazards. 6,7 TB has been reported in poultry workers previously, 8 and foreign-born poultry workers in particular make up a high-risk population for TB infection and disease. Birth in countries where TB is highly endemic, lack of access to health care facilities, crowded living conditions, and low income contribute to the higher rates of TB in this population.
The results of the investigation of a cluster of four cases of TB indicated that one was not a case of TB and that three other cases were unrelated because the strains of M. tuberculosis had different drug susceptibilities and patterns by spoligotyping. Although two of the patients had meningeal disease, their cases were not caused by a single pathogenic strain of M. tuberculosis.
Although these cases did not represent an outbreak, the high rate of positive TSTs and conversions among workers warrants explanation. The results from the workplace investigations indicate that rates of positive TSTs among coworkers of patients 3 and 4, the patients who were potentially infectious, were not higher than around patient 1, who did not have TB, and patient 2, whose disease was limited to the central nervous system. This suggests that the high rates of positive TSTs and conversions among workers were probably not the result of recent transmission of M. tuberculosis within the poultry plants. Foreign birth is a risk factor for having a TST conversion among these poultry plant workers. The conversion probably represents a boosted reaction to the TST from a prior old infection with M. tuberculosis or BCG vaccination rather than recent transmission. 9
Typically, DNA fingerprinting can be used to match M. tuberculosis isolates to confirm an outbreak of TB. 10 Here, we used molecular fingerprinting to help demonstrate that the cases of TB among poultry plant workers were unrelated to one another and did not represent an outbreak. Also, the epidemiologic investigation did not demonstrate evidence of transmission of M. tuberculosis in the workplace. Foreign-born workers were probably at higher risk for having a positive TST than US-born workers owing to prior M. tuberculosis infection and BCG vaccination. When conducting investigations, TST results need to be interpreted carefully, especially in high-risk populations. In this setting, there initially appeared to be a cluster of cases with transmission resulting in skin test conversions among workers. Case reviews, use of DNA fingerprinting techniques, and close scrutiny of the characteristics of those with skin test conversions allowed us to rule out a cluster of related cases and recent transmission in the workplace. This finding is important for a workplace investigation. First, we were able to demonstrate that there was not a workplace-based outbreak of TB, negating the need for workers’ compensation-related activities. Second, because the presence of positive TSTs appeared to be caused by old infections and possibly BCG vaccination rather than recent infection, we were able to focus efforts on detection and treatment of old infection in workers rather than investigation of ongoing contact investigation to detect infection.
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