Scientists have a new tool for unraveling the mysteries of how diseases
such as HIV move through a population, thanks to insights into
phylogenetics, the creation of an organism's genetic tree and
evolutionary relationships.
"It turns out that three different types of transmission histories are
possible between two persons who might have infected each other," said
Thomas Leitner of Los Alamos National Laboratory, the corresponding
author of a new paper out this week in the Proceedings of the National
Academy of Sciences. "Using phylogenetic inference in the
epidemiological investigations of HIV transmission, we've determined
that between two sampled, potentially epidemiologically linked persons,
we can now evaluate the possibility that an unsampled intermediary or
common source existed, even without a sample from that individual."
Like a detective inferring the existence of an unseen actor in a
sequence of events, the Los Alamos team used computational phylogenetic
analysis to examine how strains of HIV, both in computer modeling and
compared with real-life case studies, would be transmitted.
The team's research has broad implications. "The inference of
donor-recipient relationships we describe here is not restricted to HIV
transmissions; it applies to all situations when an original population
seeds a new population with a restricted random draw (a bottleneck) of
individuals. We use HIV transmission to illustrate the effects because
it helps trace contacts among people and untangle investigations into
outbreaks. Also, statistical guidelines are needed for interpreting
phylogenetic results in court."
Phylogenetic inference of who infected whom has great value in
epidemiological investigations, the authors point out, because it should
explain how transmission(s) occurred. Until now, however, there has not
been a systematic evaluation of which phylogeny to expect from
different transmission histories, and thus interpreting the meaning of
an observed phylogeny has remained elusive.
"Previously it was thought that it would be impossible to say who
infected whom and whether there were unsampled intermediary links in an
alleged transmission, or if both persons were infected by an
unsampled/unknown third party. We show that this is now possible in many
cases," Leitner said. "This will have large impact on future
epidemiological investigations, including forensics and outbreak
investigations."
In the paper, the team showed that certain types of phylogenies
associate with different transmission histories, which may make it
possible to exclude possible intermediary links or identify cases where a
common source was likely but not sampled. "Our systematic
classification and evaluation of expected topologies should make future
interpretation of phylogenetic results in epidemiological investigations
more objective and informative," Leitner said.
The paper is titled "Phylogenetically resolving epidemiologic linkage,"
by Ethan O. Romero-Severson, Ingo Bulla, and Thomas Leitner. The work
was supported by National Institute of Allergy and Infectious
Diseases/National Institutes of Health.
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