Nosocomial transmission of extensively drug-resistant tuberculosis in a rural hospital in South Africa

Abstract

Background: Extensively drug-resistant tuberculosis (XDR-tuberculosis) is a global public health threat, but few data exist elucidating factors driving this epidemic. The initial XDR-tuberculosis report from South Africa suggested transmission is an important factor, but detailed epidemiologic and molecular analyses were not available for further characterization.

Methods: We performed a retrospective, observational study among XDR-tuberculosis patients to identify hospital-associated epidemiologic links. We used spoligotyping, IS6110-based restriction fragment-length polymorphism analysis, and sequencing of resistance-determining regions to identify clusters. Social network analysis was used to construct transmission networks among genotypically clustered patients.

Results: Among 148 XDR-tuberculosis patients, 98% were infected with human immunodeficiency virus (HIV), and 59% had smear-positive tuberculosis. Nearly all (93%) were hospitalized while infectious with XDR-tuberculosis (median duration, 15 days; interquartile range: 10-25 days). Genotyping identified a predominant cluster comprising 96% of isolates. Epidemiologic links were identified for 82% of patients; social network analysis demonstrated multiple generations of transmission across a highly interconnected network.

Conclusions: The XDR-tuberculosis epidemic in Tugela Ferry, South Africa, has been highly clonal. However, the epidemic is not the result of a point-source outbreak; rather, a high degree of interconnectedness allowed multiple generations of nosocomial transmission. Similar to the outbreaks of multidrug-resistant tuberculosis in the 1990s, poor infection control, delayed diagnosis, and a high HIV prevalence facilitated transmission. Important lessons from those outbreaks must be applied to stem further expansion of this epidemic.

Figure 1.

Epidemic curve of new cases of extensively drug-resistant tuberculosis (XDR-tuberculosis), by month of sputum collection, January 2005 to December 2006.

Figure 2.

Daily hospital census of patients with infectious extensively drug-resistant tuberculosis (XDR-tuberculosis), 1 January 2005–31 December 2006.

Figure 3.

A, Spoligotype pattern and classifications for extensively drug-resistant tuberculosis Mycobacterium tuberculosis isolates [24]. B, KZN M. tuberculosis IS6110–based restriction fragment–length polymorphism (RFLP) profile. Lanes 2–17 and 19–20 show RFLP patterns from 18 unique patients analyzed in this study. Lanes 1 and 18 show a molecular weight standard.

Figure 4.

Network relationship of male (A) and female (B) patients with extensively drug-resistant tuberculosis (XDR-tuberculosis) due to Mycobacterium tuberculosis isolates with the ST60/KZN genotype. Squares represent XDR-tuberculosis patients. Lines represent inpatient overlap. Numbers represent the duration of inpatient overlap. Circles and lines depict examples of multiple generations of potential nosocomial transmission. (Note: Although convention for such graphics dictates that patients seen earlier are on the left, and patients seen later are on the right, this representation of time has been violated here for clarity in several instances, to avoid numerous overlapping lines).