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
Sputum samples were examined to identify
clusters of infections. The investigators also constructed transmission
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
“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
Within the largest cluster of transmissions,
an epidemiological linkage could be established for 86% of men and 79% of
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
“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.”