Our data point to important differences in the epidemiology of two large TB genotype clusters in NYC. While genotype clustering is generally thought to reflect recent transmission, characteristics of cases in the largest cluster caused by a common strain (Cs30) seen for more than 15 years in NYC (1
; NYC DOHMH, unpublished data) suggest that disease was due to remote infection compared to cases with the BEs75 strain. The cluster of the BEs75 strain, a more recent strain first identified in NYC in 1997, was associated with a larger proportion of patients that were infectious and HIV infected. Respiratory AFB smear positivity is associated with increased TB transmission, while HIV infection is associated with higher risk of progression to disease. AFB smear positivity increases the likelihood of transmission, since TB cases with a positive AFB smear are more likely to be infectious than respiratory smear-negative cases (4
). A study of close contacts in Finland showed a higher risk of secondary cases among contacts to AFB smear-positive cases than AFB smear-negative cases (19
). Based on respiratory smear results, patients with the BEs75 strain were significantly more infectious than patients with the Cs30 strain, which increases the likelihood of transmission. In addition, 53% of patients with the BEs75 strain had epidemiologic links compared to 26% among patients with the Cs30 strain, which indicates that patients with the BEs75 strain were in recent contact with another infectious patient with the BEs75 strain. Once infected with the TB bacteria, HIV is the greatest single risk factor for progressing to active disease (7
). Since patients with the BEs75 strain were more likely to be HIV infected than patients with the Cs30 strain, it is likely that patients with the BEs75 strain progressed rapidly to disease after recent infection. For these reasons, TB disease in patients with the Cs30 strain was more likely caused by reactivation of latent TB infection acquired during the epidemic years of the early 1990s, while disease in patients with the BEs75 strain was more likely the result of very recent transmission.
Even though these two strains have few IS6110
copies (Cs30 has three and BEs75 has one), they have been shown to be clonal through various strain typing methods: inverse PCR, polymorphic guanine- and cytosine-rich repetitive sequence, and variable number tandem repeat (10
). Furthermore, the high proportion of patients with the BEs75 strain that were linked epidemiologically also suggests that all of these cases were due to a single strain.
Molecular information, in conjunction with conventional epidemiologic methods in our study, provided insight into TB transmission patterns reported by others (8
). Many investigators have examined the differences between clustered cases and nonclustered cases (18
). However, few studies have examined characteristics of specific clusters (10
). Our results suggest that cluster-specific differences may provide important information that is lost in aggregate analysis of clustered cases.
The high rate of tuberculosis among individuals in homeless settings is likely due to several factors that increase the risk of development of disease or transmission. First, while homeless persons have a high risk of latent TB infection (LTBI), it is difficult to screen unstably housed individuals for LTBI, which is present without symptoms. Even once LTBI is diagnosed among individuals in this population, it is often difficult to initiate and complete LTBI treatment, which usually requires taking medications for 9 months (NYC DOHMH, unpublished data). Second, when an individual has LTBI, factors such as drug abuse (29
) and HIV infection increase the risk of progression to active disease (11
). And finally, there is increased opportunity for transmission among homeless persons in congregate settings once a case is present due to the increased number and proximity of contacts.
Other investigators have recommended focusing on locations of TB exposure rather than traditional contact identification for contact tracing among homeless persons (2
). Housing records are an excellent source of information for location-based contact investigation. Information obtained from DHS and HASA housing histories and address matching have been useful in NYC for making additional epidemiologic links over those obtained from traditional interviews among the homeless. Furthermore, once a genotype cluster is known to be associated with transmission at a particular location, future patients having the same strain can be asked whether they frequented that location prior to diagnosis.
Our investigation was limited by several factors. Since the number of cases in these clusters was relatively small, there may have been other factors associated with having the Cs30 strain that were not detected due to limited power. As genotyping of additional culture-confirmed TB isolates is obtained, additional differences between clusters may become evident. Second, many patients in the Cs30 and BEs75 groups could not be reinterviewed to identify potential locations of common exposure; thus, epidemiologic links between cases were likely underascertained.
The health department and the DHS are collaborating to improve detection of TB among persons with a history of homelessness. Matches of the TB case registry and the DHS database are conducted at regular intervals to determine whether suspected or confirmed TB patients reside in a DHS facility. Once homelessness in a TB patient is recognized, the housing history is reviewed to ascertain the need for additional contact investigation among shelter residents. The health department also works with DHS to find homeless persons who were exposed to a TB case at one facility but moved prior to the contact investigation. Finally, our collaboration with the DHS has facilitated tracking of nonadherent patients residing in any of the DHS facilities, thereby ensuring completion of treatment among patients and contacts.
In summary, TB genotyping was useful in identifying transmission among HIV-infected homeless persons. Differences among cases in two large genotype clusters suggest differences in the dynamics of transmission of these clusters. While continuing transmission from common TB strains may occur, reactivation of TB from strains transmitted during epidemic periods is also a source of genotype clustering. All cases in a cluster do not necessarily represent recent transmission; they may represent reactivation of infection acquired more remotely. To determine if clusters of TB patients are the result of recent transmission, additional investigations are often required.