are an important source of new tuberculosis (TB) cases in people living with HIV, according to a study conducted in a South African township published
in the online edition of the Journal of
examined TB isolates obtained from sputum samples to see if cases were
reactivation of latent disease, unique cases, index cases within clusters, or
secondary transmissions within clusters. Cluster index cases were significantly
more likely to be HIV-negative and secondary cases within clusters were
significantly more likely to involve people living with HIV, including people on
antiretroviral therapy (ART).
showed that HIV-positive and HIV-negative TB disease are not independent of one
another,” write the authors. “Cluster index patients had nearly twice the odds
of being HIV-negative suggesting that HIV-negative patients may be
disproportionally responsible for transmission in the community.”
TB remains an
important cause of serious illness and death in resource-limited settings. The
burden of TB disease is especially high in countries with serious HIV
understanding of the dynamics of TB transmission is required so that more
effective infection control strategies can be developed. A technique called
molecular epidemiology can be used to trace the dynamics of TB transmissions. It
involves the genetic analysis of isolates obtained from patients to see if
their infection can be linked to other cases.
team of investigators used molecular epidemiology to explore the interaction
between TB disease in HIV-positive and HIV-negative patients, and also to
examine the impact of antiretroviral therapy programmes on the dynamics of TB
TB isolates were
collected from people living in a South African township. Approximately a
quarter of adults resident in the township are living with HIV. TB
notification rates are extraordinarily high at over 2000 cases per 100,000 and
the annual risk of TB infection is 4%.
Analysis of TB
genotypes from isolates enabled the investigators to determine if cases were
reactivation of latent disease, unique cases, index cases in clusters, or
secondary transmissions within clusters.
population comprised 710 people who received care between 2001 and 2010. The median
age was 32 years. Most (91%) patients were tested for HIV and 64% were
HIV-positive, with 23% taking ART at the time of TB diagnosis.
provided 718 isolates from which 318 TB genotypes were identified.
The dominant TB
strains were W-Beijing (32%), CC-related (30%) and BM (5%). Comparison with
other strains showed that W-Beijing strain was associated with HIV infection (p
Of the 718 TB
isolates, 31% were unique strains, 67% were clustered and 2% were reactivation
disease. There were a total of 87 clusters within the community, their size
ranging from 2 to 85 patients.
The majority of
cluster index patients (66%) were HIV negative, whereas two-thirds (63%) of
secondary cases within clusters were HIV positive. At least 61% of clusters
involved both HIV-positive and HIV-negative patients, with a further 9%
possibly including patients with and without HIV.
substantial evidence that HIV-negative individuals were the source of new TB
infections in people living with HIV. Index
cases were almost twice as likely to be HIV negative compared with other TB
cases (OR = 1.9; 95% CI, 1.2-31.) Reactivation cases were also more likely to
occur in HIV-negative patients (OR = 1.7; 95% CI, 1.2-2.4). Secondary cluster
cases were more likely to involve HIV-positive patients (p = 0.001) and patients on ART (p = 0.04).
transmission was responsible for as much as 54% of the overall TB disease and
60% among HIV-positive patients,” comment the investigators. “HIV-negative
patients accounted for a disproportionally high number of cluster index cases.”
suggest their findings have important implications for TB control. “Our
attention and interventions need to expand beyond HIV-positive patients, and
include reducing transmission from HIV-negative patients,” they conclude. “Such
efforts may be guided by the identification of the factors and locations
associated with transmission in these settings.”