By now you know, dear readers, that Cryptococcus gattii (CG), the deadly fungal pathogen and a native of tropical and subtropical regions of the world, has stealthily charted itself a course of world domination, starting with the Pacific Northwest of North America. I have also alerted you to the possibilities about its transmission – (a) that CG may have spread as a result of human activity, human and avian migration, and other natural means of dispersal; and (b) that slow, but sustained, elevation of global temperatures and corresponding changes in the long-term climate of different regions may have created micro-climates suitable for CG growth within zones with a temperate climate ordinarily considered inhospitable to the fungus.
Well, it is emerging that CG‘s plans are rather grandiose, total world domination – if possible.
But before I tell all, let me quickly introduce another key concept: genotype. In an earlier post, I had already mentioned immunological identification (based on specific antibody reactions to their surface structures) and grouping of CG isolates as Serotypes, B and C, to be precise. Various CG populations of the world can also be grouped based on certain common patterns of their genetic makeup, a kind of molecular signature. These groups are known as molecular subtypes, of which there are four for CG, namely, VGI, VGII (further subdivided into IIa, IIb and IIc), VGIII, and VGIV. Some European researchers, who use a different technique for genetic analysis, prefer the designations AFLP4 (=VGI), AFLP5 (=VGIII), AFLP6 (=VGII), and AFLP7 (=VGIV). The serotypes B and C are randomly distributed within these subtypes. Without going into details, suffice it to say that these molecular characterizations have been greatly helpful in tracking the clusters of CG found in different parts of the world.
The presence of CG has so far been well-known and documented in the environment (and causing disease in humans and animals) in Australia and New Zealand, Africa, South and Central America, parts of Asia (including the Indian subcontinent), and certain parts of North America and of Europe. More recently, it appears that its zone of incidence has greatly expanded in the temperate regions of the world, involving a large part of Europe.
Graphic image ©CDC. Used for the purpose of illustration and education; source: Springer DJ, Chaturvedi V. Emerg Infect Dis. 2010 January.
Massimo Cogliati, an Italian Microbiologist, has written a magnificent review (Disclaimer: I know Massimo personally; but this review is truly a monumental work.) on the molecular epidemiology of cryptococcal isolates of the world. In the following table, I have summarized some of his observations on the global prevalence of CG.
| Region of World | Countries | Animal source | Environmental Source | Notes |
|---|---|---|---|---|
| Europe | Denmark, Netherlands, Italy, Spain, Portugal, Greece, Switzerland | Ferrets, Goats AND Human |
Eucalyptus tree, Douglas fir, Carob tree, and Stone pine | VGI 3.4% VGII 0.3% VGIII 0.1% Molecular type identified in only about 15% of total cryptococcal isolates; CG appears less prevalent than CN. |
| Asia | China, India, Thailand (~80% of Asian isolates); also, Republic of Korea, Japan, Taiwan, Malaysia, Vietnam. Cryptococcal isolates found in Turkey, Iran, Nepal, Cambodia, Philippines, Singapore, Indonesia, Bangladesh, Pakistan, Saudi Arabia, Oman, Kuwait, Qatar, and so forth, but species/ serotype/ genotype identification data available are rather poor. |
Koala AND Human |
Portugese Plum (Jambul), Spanish Cherry (Maulsari), Neem, Acacia (gum Arabic/Babul), Golden Shower (Sonajhuri), Manilkara (Palai), Indian Mast tree (Debdaru), Eucalyptus, Tamarind, Cassia Rose/Red Shower (Laljhuri), and Mango; Bark and decaying wood in trunk hollows |
VGI 13.2% VGII 1.7% VGIII 0.1% VGIV 0.3% Of total cryptococcal isolates; CG lessprevalent than CN. Paucity of serotype and molecular identification data (11% and 8% respectively). |
| Africa | South Africa, Botswana, Malawi, Senegal, DR Congo; cryptococcal isolates found in 25 out of 58 countries (including Uganda, Rwanda, Tanzania, Zimbabwe, Egypt, Morocco, Tunisia, Algeria, Ghana, Mali, Ivory coast, Ethiopia, Nigeria et al.) but species, serotype, genotype info extremely sparse. |
Mainly Human | soil, Eucalyptus trees, and almond tree | VGI 1% VGII 0.25% VGIV 5% Of total cryptococcal isolates. CG appears to be relatively rare, and less prevalent than CN. Paucity of serotype and molecular identification data (11% and 2% respectively). |
| Central and South America | Guatemala, Honduras, Aruba, Cuba, Puerto Rico, Venezuela, Brazil, Peru, Colombia, Argentina, Uruguay; regional differences in genotype distribution: e.g. VGI major in Argentina, VGII in Brazil, Puerto Rico, and Colombia |
Cheetah, goat, some Psittacine (such as parrots) birds AND Human |
Eucalyptus, almond tree, kassod tree, pottery tree, jungle tree, Red flowering gum (Eucalypt family), a type of cactus, and soil, dust, and psittacine bird excreta |
VGI 4% VGII 17.5% VGIII 4% VGIV 1% Impressive 77% rate of identification of all cryptococcal isolates. |
| North America | US, Canada, Mexico; fair coverage, about 51% of total cryptococcal isolates have species, serotype, genotype info. |
Cat, dog, bird, ferret, llama, alpaca, elk, goat, sheep, horse, porpoise AND Humans |
Air, water, soil; Douglas Fir, Eucalyptus trees |
VGI 7% VGIIa 39% VGIIb 5% VGIIc (Note: 9 found in Oregon, % not reported) VGIII 4% VGIV 1% |
| Oceania | Australia, New Zealand, Papua New Guinea, and Hawaii Islands | kiwi, cat, dog, horse, sheep, cow, koala, quokka, cockatoo, ferret, long-nosed potoroo, echidna, African grey parrot, dolphin AND Humans |
Species of Eucalyptus, Turpentine tree, insect frass, olive seedlings, and plant debris | VGI 39% VGII 22% VGIII 3% Only 22% of 1328 CG isolates tested for serotype and genotype; more CG than CN. |
From the currently available epidemiological evidence, more than one CG clusters are criss-crossing the world, causing infections simultaneously in different parts. The CG VGIIa and VGIIb subtypes have been designated, respectively, the major and minor genotypes responsible for the outbreak in North America. However, the genetically distinct VGI, which is the predominant subtype in several parts of the world, has also been causing infections in parts of US, of Asia, of the Mediterranean region (Italy and Spain, for example), and in the Netherlands (which has the temperate climate of North Europe). Many of the clinical cases are ‘autochthonous’ (locally sourced CG, not travel related); for instance, in Netherlands, the CG recovered post mortem in 1957 from a woman’s lungs has been found to be VGI, and recent studies in the Berg en Dal forests have isolated the same genotype. VGI, same broad genotype but some with fine distinctions, have been found from patients in California, Southwest Georgia, Northern Florida, and Rhode Island in the US, whereas a VGIII cluster is known amongst HIV positive patients in Southern California since 2011. Delhi and Bangalore in India have recently reported VGIII and VGIV from patients and environment. Argentina and Colombia have both recently reported the first environmental isolation of VGIII.
Why is the knowledge of the genotypes and epidemiological patterns important? These CG genotypes are known to differ in their pathogenicity (‘ability to cause disease’) in human and animal hosts, as well as in virulence (‘degree of harm’) in hosts of different immune status, and in their susceptibility to available drugs. The globally-rising incidence of CG cryptococcosis cases underscores the urgent need for enhanced awareness, both in the affected regions, and in those that are at risk.
Further reading:
- Springer, D., & Chaturvedi, V. (2010). Projecting Global Occurrence of Cryptococcus gattii. Emerging Infectious Diseases, 16 (1), 14-20 DOI: 10.3201/eid1601.090369
- Cogliati, M. (2013). Global Molecular Epidemiology of Cryptococcus neoformans and Cryptococcus gattii: An Atlas of the Molecular Types Scientifica, 2013, 1-23 DOI: 10.1155/2013/675213
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