The global burden of HIV-associated cryptococcal meningitis (CM) is estimated
at one million cases per year, causing up to a third of all AIDS-related
deaths. Cryptococcus neoformans variety grubii (Cng) is the most
ubiquitous cause of cryptococcal meningitis worldwide, however patterns of
molecular diversity are understudied across some geographical regions experiencing
significant burdens of disease. Cryptococcus species are notable
in the degree that virulence differs amongst lineages, and highly virulent
emerging lineages are changing patterns of human disease both temporally
and spatially. Molecular epidemiology constitutes the main methodology
for understanding the factors underpinning the emergence of this understudied,
yet increasingly important, group of pathogenic fungi. A multilocus
sequence typing (MLST) scheme was used to characterise a genetically
depauperate Cng population in Thailand, and a contrastingly highly diverse
Cng population in Cape Town, South Africa. Sequence types (STs)
from these populations were integrated into a dataset comprising global
STs of Cng and patterns of range expansion were traced. Evidence from
haplotypic networks and coalescent analyses revealed an ancestral African
population of molecular type VNB, from which emerged a VNI lineage. This
VNI lineage expanded globally out of Africa and led to the introduction of
a limited number of genotypes in novel regions, including Asia. Bayesian
inference estimated this spread of VNI to have occurred between 1 600 and
70 500 years ago, putatively vectored by the anthropogenically mediated
spread of domesticated pigeons, historically native African birds. Clinical
data collected from patients presenting with AIDS-associated CM showed
that infecting African Cng isolates were associated with poorer long-term
survival compared to Asian isolates. As mortality rates reported for these
patients in Sub-Saharan Africa are higher than those seen in Asia, supported
by a Galleria mellonella virulence model, this apparently elevated
virulence is postulated as being the result of recombinant progeny with diverse
phenotypes being created through frequent meiotic recombination
