A cluster of human plague cases over a 10-year period in the seaport city of Mahajanga, Madagascar after a 62-year plague-free period provided researchers from Arizona and Madagascar with an opportunity to study plague dynamics in an urban environment, especially since historically plague entered new geographic areas through port cities such as this.
Most of the isolates found during the outbreak were very closely related, suggesting that a single introduction became established in Mahajanga and then underwent local cycling and differential.
Researchers analyzed 44 Mahajanga isolates from the outbreak, as well as an additional 218 Malagasy isolates from the highland foci, and sequenced the genomes of four Mahajanga strains, performed whole-genome sequence single-nucleotide polymorphism (SNP) discovery on those strains, screened the discovered SNPs, and performed a high-resolution 43-locus multilocus variable-number tandem-repeat analysis of the isolate panel. Twenty-two new SNPs were identified and defined a new phylogenetic lineage among the Malagasy isolates.
Phylogeographic analysis suggests that the Mahajanga lineage likely originated in the Ambositra district in the highlands, spread throughout the northern central highlands, and was then introduced into and became transiently established in Mahajanga. Although multiple transfers between the central highlands and Mahajanga occurred, there was a locally differentiating and dominant subpopulation that was primarily responsible for the 1991-to-1999 Mahajanga outbreaks. Phylotemporal analysis of this Mahajanga subpopulation revealed a cycling pattern of diversity generation and loss that occurred during and after each outbreak. This pattern is consistent with severe interseasonal genetic bottlenecks along with large seasonal population expansions.
The ultimate extinction of plague in Mahajanga suggests that although plague pathogens' ability to invade port cities has been essential for intercontinental spread, these regions are not a suitable long-term niche. However, the temporary large pathogen population expansion provides the means for plague pathogens to disperse and become ecologically established in more suitable non-urban environments.
Citation: Amy J. Vogler, Fabien Chan, Roxanne Nottingham, Genevieve Andersen, Kevin Drees, Stephen M. Beckstrom-Sternberg, David M. Wagner, Suzanne Chanteaub, Paul Keim, 'A Decade of Plague in Mahajanga, Madagascar: Insights into the Global Maritime Spread of Pandemic Plague', doi: 10.1128/mBio.00623-12 12 February 2013 mBio vol. 4 no. 1 e00623-12