Sequencing & Social-Network Analysis maybe a tool to look at outbreak of
communicable diseases in communities and may prove to be a useful tool in the
future. This combination was applied to study Tuberculosis outbreak in medium-sized community in
British Columbia, Canada.
Mycobacterium tuberculosis is an infectious
disease of grave significance. It is not confined to the poorer regions of the
world but is even found in developed countries that boast of extensive control
of tuberculosis occurred over a 3-year period in a medium-sized community in British
Columbia, Canada. This community has been struggling with severe challenges
of alcoholism, drug abuse, and transient- housing arrangements. A total of 41
TB cases were diagnosed between May 2006 and December 2008.It must be noted
that the 2007 incidence rate of 6.4 cases per 100,000 people, far exceeded the
national average of 4.7 cases per 1 lakh people.
In October 2006, the British Columbia Centre for
Disease Control (BCCDC) kick-started an epidemiologic investigation as
part of a public heath safe-guarding program.
of the patients studied were adults with a mean age of 36 years, who
presented with pulmonary tuberculosis
(68%) or pleural tuberculosis (24%). All the individuals studied were born
in Canada and none carried the HIV.
were recorded with a one-year minimum follow-up for all patients.
the patients had favorable outcomes.
contact tracing and Social-network analysis were employed in an effort to
identify key individuals, places and behaviors that contributed to the
spreading of the TB bacteria and to unravel the dynamics of the outbreak in a
Field epidemiologists were aware of the limitations
of contact tracing and hence used social-network analysis much early
during the outbreak.
A social-network questionnaire (SNQ) was
developed to identify shared
socialization patterns, and settings, and to prioritize case findings.
resulting data from the field investigations and case findings were fed into a
single network and could be visualized in Cytoscape software.
M. tuberculosis isolates from samples
were cultured at the BCCDC Public Health Microbiology and Reference Laboratory.
Restriction-fragment-length polymorphism (RFLP) analysis
(based on insertion sequence 6110) was performed on the first 13 outbreak
A 24-loci 'mycobacterial interspersed
repetitive unit-variable-number tandem-repeat' (MIRU-VNTR) genotyping analysis
was performed on all culture-positive, laboratory-confirmed isolates at the National Reference Centre
for Mycobacteriology of the National Microbiology Laboratory in Winnipeg,
The researchers carried also out a follow- up whole
genome sequencing of 32 Mycobacterium tuberculosis outbreak
isolates and 4 historical isolates. The latter were from the same region but
were collected before the outbreak.
Social Network Analysis, through structured
interviews, has been found to improve case finding in vulnerable populations.
The questionnaire focused on:
• Drug and alcohol use
• Residential history
• Travel history
• Places of social aggregation
• Identification of contacts and locations (in the context of high-risk
Social-network analysis was also found to be
far more efficient than contact tracing in identifying a probable source and
also in identifying cases or locations for follow-up.
Early field investigation suggested that the
outbreak was clonal because RFLP
and MIRU-VNTR genotyping of the outbreak isolates generated identical pattern.
follow-up whole genome sequencing
revealed this assumption to be untrue.
confirmed that the Conventional molecular
epidemiologic techniques such as RFLP is not
fully capable of capturing genetic diversity within a single genotype of M. tuberculosis.
Interesting highlights of the study were:
• The higher-resolution Social Network patterns aided by whole-genome
sequencing revealed that the TB outbreak was a coalescence of two outbreaks
and each of these had its own causative lineage
• Several transmission events and "superspreaders" were involved in the
• Historical isolates were associated with each
lineage and this suggested that divergence from a common ancestor occurred much earlier, before 2001
• If Social-network analysis and location-based screening had been
performed on the historical cases, rather than just resorting to contact
tracing, the recent outbreak could have been prevented
• The studies suggested that the trigger could be a social, rather than a
• Epidemiological studies also
revealed that the outbreak coincided with a significant increase in cocaine
use within the community
The study concludes that a socio-environmental
factor such as crack cocaine-use triggered the simultaneous expansion
of two lineages of M. tuberculosis among
It has also been concluded that epidemiological
inferences are greatly improved by the integrated use of bacterial whole-genome sequencing and
1. Jennifer L. Gardy, Ph.D., James C. Johnston,
M.D., Shannan J. Ho Sui, Ph.D., et al. NEJM, Vol
364( 8),pp 730-739, feb 2011.
"Whole-Genome Sequencing and Social-Network
Analysis of a Tuberculosis Outbreak"