Hospital exposure the source of XDR-TB infections, underlining the need for adequate infection control

Numerous hospital transmissions – rather than a single source – fuelled the outbreak of extensively drug-resistant tuberculosis (XDR-TB) at Tugela Ferry, South Africa, in 2005-06, research published in the online edition of the Journal of Infectious Diseases shows.

Epidemiological and molecular analysis left no doubt that transmission occurred within the hospital setting. There was a high degree of interconnectedness between the patients diagnosed with XDR-TB, allowing for “multiple generations of XDR-tuberculosis transmission over time”.

The investigators believe their findings have important implications for TB infection control, “especially in settings with high HIV infection and drug-resistant tuberculosis prevalence”.

Drug-resistant TB is a growing health problem. Strains of TB with resistance to second-line drugs (XDR-TB) have occurred worldwide and are associated with poor outcomes and high mortality.

One of the most publicised outbreaks of XDR-TB occurred at the Church of Scotland Hospital, a district hospital in Tugela Ferry, South Africa, between 2005 and 2009. A total of 516 cases were identified.

Investigators wanted to establish a clearer understanding of the role of hospital-acquired XDR-TB in the ongoing epidemic.

They therefore performed a retrospective study using epidemiology, molecular genotyping and social network analysis to characterise the initial outbreak at Tugela Ferry in 2005-06.

Care within the district hospital was provided in large, congregate wards, each accommodating between 30 and 40 people. Beds are in close proximity, approximately one metre apart. At the time of the outbreak, there were no mechanical air extractions fans, no isolation rooms and no airborne infection control procedures.

The investigators analysed the medical records of 148 people involved in the 2005-06 outbreak. Epidemiological links were established by looking at the dates of admission and discharge from the district hospital for each individual. Patients were considered epidemiologically linked if they met all the following criteria:

• They were hospitalised concurrently for at least one day.
• They were of the same sex (care in the hospital is provided on single-sex wards).
• One patient was infectious (infectiousness started two weeks before XDR-TB diagnosis and continued thereafter).
• The other patient was vulnerable to infection (exposure any time in the six weeks before diagnosis of XDR-TB).

Sputum samples were examined to identify clusters of infections. The investigators also constructed transmission networks.

Most of the patients (56%) were female and their median age was 34. Among the 126 patients tested for HIV, 98% were HIV-positive. Their median CD4 cell count was 64 cells/mm³.

Sputum-smear-positive TB was detected in 59% of patients.

The majority of patients (84%) had previously received first-line TB therapy, but only two individuals (1%) had received second-line treatment for multidrug-resistant TB (MDR-TB).

Previous exposure to anti-TB drugs was therefore not an explanation for the development of XDR-TB. Instead, transmission of the infection seemed a much more likely explanation.

Almost all the patients (93%) were admitted to hospital while infectious with XDR-TB. The median period of hospitalisation was 15 days. There was at least one infectious XDR-TB patient in the hospital during 91% of the study period.

Before diagnosis with XDR-TB, 113 (76%) of patients were hospitalised at least once and spent a median of 22 days in hospital. Of these people, 71% were exposed to one or more infectious XDR-TB patients during their stay in hospital. The median exposure was to five XDR-TB patients.

“We found that the majority of patients had been admitted to a single hospital and had experienced frequent, prolonged exposure to XDR-tuberculosis patients,” comment the authors.

Samples obtained from 86 patients were available for genetic analysis. Some 92% of cases were placed within a single transmission cluster.

Within the largest cluster of transmissions, an epidemiological linkage could be established for 86% of men and 79% of women.

Rather than originating in a single source patient, these transmissions occurred over a number of “generations”, suggesting that the outbreak was sustained over a period of time as new patients were exposed to XDR-TB on their admission to the hospital.

As the investigators explain: “There was a high-degree of interconnectedness that allowed for multiple generations of XDR-tuberculosis transmission over time.”

The author of an editorial accompanying the study believes its findings have important lessons for the control of drug-resistant TB.

“Patients with highly drug-resistant forms of TB must quickly receive their diagnosis, start an effective regimen…and [be] managed in settings where they are less likely to expose susceptible individuals until they initiate an effective treatment regime.”

Gandi NR et al. Nosocomial transmission of extensively drug-resistant tuberculosis in a rural hospital in South Africa. J Infect Dis, online edition. DOI: 10.1093/infdis/jis631, 2012.

Dharmadhikari AS Six degree of separation: use of social network analysis to better understand outbreaks of nosocomial transmission of extensively drug-resistant tuberculosis. J Infect Dis, online edition. DOI: 10.1093/infdis/jis634, 2012.

See the new edition of HIV & AIDS Treatment in Practice (HATIP) for an introduction to drug-resistant TB and its management.