Cryptococcus, the Silent Menace: A Primer

Sir Arthur Conan Doyle (1859-1930), the celebrated author of Sherlock Holmes and the Sci-Fi Professor Challenger series, was also a physician and prone to poetry. In his second poetry collection, called Songs of the Road (published in 1911), he included several of his narrative verses and songs, as well as philosophical verses - some of which stand testaments to his abiding interest in the field of Medical Mycology, the study of clinically-relevant fungi. One particularly poignant poem, titled Mind and Matter, details his awe about spore-bearing pathogenic fungi and related systemic fungal infections, which were - in the early 20th century - probably almost always fatal. (Broad spectrum antifungals of today didn't appear until the 60s.)

Mind and Matter

Great was his soul and high his aim,
He viewed the world, and he could trace
A lofty plan to leave his name
Immortal 'mid the human race.
But as he planned, and as he worked,
The fungus spore within him lurked.

Though dark the present and the past,
The future seemed a sunlit thing.
Still ever deeper and more vast,
The changes that he hoped to bring.
His was the will to dare and do;
But still the stealthy fungus grew.

Alas the plans that came to nought!
Alas the soul that thrilled in vain!
The sunlit future that he sought
Was but a mirage of the brain.
Where now the wit? Where now the will?
The fungus is the master still.

Powerful imagery, right? To me, no fungus brings home this sense of foreboding and inevitability more, than does the yeast-like pathogen, Cryptococcus neoformans (let's call it CN). (I admit I have a bias towards this microbe, having worked on it for the longest time in my academic career.)

Why Cryptococcus, you may well ask. Surely there are other sporulating (spore-forming) fungal pathogens that fit the bill? There are, of course. But I think, it was the mention of the brain in the third last line, that settled CN firmly in my mind. You see, CN is known to have a peculiar predilection for the brain and the central nervous system, even though the microbe - in form of spores (technical term: infectious propagules) - comes into the body from the environment most likely via the nose and the respiratory pathway, depositing itself into the lungs.

In healthy people, the body can usually fight off this invasion, with the aid of various components of the immune armamentarium - such as alveolar Macrophages, residents of the lungs and the first line of defence - cells that engulf the microbe and kill it internally; helper T-lymphocytes (a.k.a. CD4+ T-cells) which recognize fragments of the microbe and help B-lymphocytes to produce more and specific antibodies; immune effector cells, cytotoxic T-lymphocytes (a.k.a. CTL, or CD8+ T-cells) and Natural Killer (NK) cells; and so forth.

However, sometimes, and especially those who have a suppressed or compromised immunity for any reason, the microbe can overwhelm this defence and escape the lungs. One of the major systems it primarily attacks is the central nervous system (CNS), the brain and the spinal cord. Immune-compromised patients lie within a wide spectrum; suppression of immune defences may be secondary to HIV infection and AIDS, aggressive chemotherapy for cancer, therapeutic immune suppression for the purpose of organ or tissue transplants, or even metabolic immune-suppression that may result from chronic disorders such as diabetes. In these patients, the microbe CN is able to evade the sub-optimal immune defences and reach the CNS to cause a serious inflammatory condition called meningitis or meningoencephalitis. This is why CN is primarily considered to be an 'Opportunistic Pathogen', one that causes disease only in the context of suppressed immunity. This distinction is no longer strictly correct, because there are well-documented instances of cryptococcal infection of apparently-healthy individuals, too. However, a majority of the cases of cryptococcal meningitis occur in immunocompromised patients; in fact, cryptococcal disease of any organ other than the lung (a.k.a. extra-pulmonary cryptococcosis) is considered an AIDS-defining illness in an HIV infected individual, according to the Centers for Disease Control and Prevention’s (CDC) guidelines.

In the next few posts, I would describe more of the importance of this micro-organism, especially in the context of the United States. Stay tuned for part deux!

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