A Decade of Plague in Mahajanga, Madagascar: Insights into the Global Maritime Spread of Pandemic Plague

Abstract

A cluster of human plague cases occurred in the seaport city of Mahajanga, Madagascar, from 1991 to 1999 following 62 years with no evidence of plague, which offered insights into plague pathogen dynamics in an urban environment. We analyzed a set of 44 Mahajanga isolates from this 9-year outbreak, as well as an additional 218 Malagasy isolates from the highland foci. We 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 pathogens in Mahajanga suggests that, in this environment, the plague pathogen niche is tenuous at best. However, the temporary large pathogen population expansion provides the means for plague pathogens to disperse and become ecologically established in more suitable nonurban environments.

How old are bacterial pathogens?

“…However, Central Asia is underrepresented in modern analyses because its microbiological surveillance of rodent infections largely disappeared after the collapse of the Soviet Union in 1990. Fortunately, extensive historical collections of bacteria that were isolated during the twentieth century still exist at the Institut Pasteur in Paris [43] and Madagascar [44], the Beijing Institute of Microbiology and Epidemiology [16] and the Bundeswehr Institute of Microbiology in Munich [45]. These facilitated access to DNA from bacterial strains isolated from a variety of global sources, including Africa, the USA, the Middle East, South East Asia, China and Mongolia as well as a few strains from Central Asia.…”

Identification of Highly Pathogenic Microorganisms by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry: Results of an Interlaboratory Ring Trial

“…These pathogens may cause anthrax, tularemia, plague, brucellosis, glanders, melioidosis, and Q fever, respectively. In most parts of the world, the natural prevalence of these agents is low, even though some of these agents cause outbreaks in human and animal populations from time to time (5)(6)(7)(8). The intentional release of these agents, however, can result in severe public health consequences, as was shown in the Unites States in 2001 (9,10).…”

Lessons Learned from Historic Plague Epidemics: The Relevance of an Ancient Disease in Modern Times

“…Between the years 1967 to 1993, the World Health Organization (WHO) recorded an average of 1666 cases of human plague worldwide per year. Between 1991 and 1999, there was a nine-year outbreak of plague in Mahajanga, Madagascar [4,8,15,50,51]. Since its first introduction into South America (Paraguay 1899), numerous foci have been recorded over time in all countries in Central and South America [52].…”