Hospital acquired infections are never a good thing, usually there is simply lapse in care, resources or common sense behind most occurrence. The normal kinds of infection you “expect” to see being acquired in hospitals are MRSA, Norovirus or Clostridium difficile. However sometimes outbreaks can be a real mystery to solve. I have had to deal with an unusual outbreak of hospital acquired fungal infection myself, so I was intrigued to “read on” when I saw this week’s headlines that “a strange outbreak had occurred in a Scottish hospital”.
This outbreak occurred at the Queen Elizabeth University Hospital in Glasgow and sadly patients have died as a result. An outbreak is defined when there are two or more cases linked in time, place or person. A single infection can constitute an outbreak if the infection is significantly rare or unlikely in the particular situation. The Glasgow outbreak is unusual in that it is not the normal kind of infection you expect to see being acquired in hospitals, this was cryptococcosis.
Cryptococcosis is a fungal infection caused by yeast like organisms of the family Cryptococcus spp. There are three main subspecies which infect humans:
Cryptococcus spp. are found worldwide and throughout the environment; C. gatii is mainly found in the tropics whereas C. neoformans is more common and widespread. C. neoformans is principally found in pigeon droppings and pigeon nests as well as soil whereas C. gatii tends to be found in the bark of trees as well as soil. Other animals have been known to carry Cryptococcus spp. including cats, dogs, horses and even camels, llamas and alpacas!
This outbreak occurred at the Queen Elizabeth University Hospital in Glasgow and sadly patients have died as a result. An outbreak is defined when there are two or more cases linked in time, place or person. A single infection can constitute an outbreak if the infection is significantly rare or unlikely in the particular situation. The Glasgow outbreak is unusual in that it is not the normal kind of infection you expect to see being acquired in hospitals, this was cryptococcosis.
Cryptococcosis is a fungal infection caused by yeast like organisms of the family Cryptococcus spp. There are three main subspecies which infect humans:
- Cryptococcus neoformans var. neoformans
- Cryptococcus neoformans var. grubii
- Cryptococcus gatii
Cryptococcus spp. are found worldwide and throughout the environment; C. gatii is mainly found in the tropics whereas C. neoformans is more common and widespread. C. neoformans is principally found in pigeon droppings and pigeon nests as well as soil whereas C. gatii tends to be found in the bark of trees as well as soil. Other animals have been known to carry Cryptococcus spp. including cats, dogs, horses and even camels, llamas and alpacas!
What is the source of the outbreak in Glasgow?
It appears that the likely source of cryptococcosis in the Glasgow outbreak is not one of the usual suspects of cleanliness of the wards, or a problem with staffing, but contamination of an air handling room. Often the air supply of large public buildings, like hospitals, can be very complex and in order to refresh air in parts of the building air is usually drawn in and pumped through air ducts. This requires large “turbines” known as air handling units, but the principle is essentially the same as smaller air-conditioning units. Bird droppings on air-conditioning units is a familiar sight!
It appears that the likely source of cryptococcosis in the Glasgow outbreak is not one of the usual suspects of cleanliness of the wards, or a problem with staffing, but contamination of an air handling room. Often the air supply of large public buildings, like hospitals, can be very complex and in order to refresh air in parts of the building air is usually drawn in and pumped through air ducts. This requires large “turbines” known as air handling units, but the principle is essentially the same as smaller air-conditioning units. Bird droppings on air-conditioning units is a familiar sight!
Pigeon guano is a common sight on air-conditioning units
From the online media reports (which have to be read cautiously as many news channels now sensationalise “facts” to “sell a story”) it seems that pigeons have got into the room containing the air handling unit and their droppings have contaminated the environment and hence the source of Cryptococcus spp. One way to remember the type of microorganism is “pigeon poo is grubii”. The air handling unit has then blown the Cryptococcus spp. into the hospitals patient areas resulting in a number of frail and young patients developing cryptococcosis.
How does cryptococcosis present?
Most infections in patients with a normal immune system are either asymptomatic or a mild respiratory infection with non-productive cough and fever. This isn’t really surprising as in order to acquire this infection you usually have to inhale fungal spores, which then settle in the lungs.
However, in immunosuppressed patients the infection can disseminate via the bloodstream from the lungs to other parts of the body, in particular the CSF to cause meningitis. Cryptococcal meningitis is usually slow in onset when compared to other forms of meningitis. Cryptococcus spp. can spread to the kidneys, prostate, bone and skin (pustules, ulcers and subcutaneous masses) but this is rare. The most common form of immunosuppression associated with cryptococcosis is HIV infection; cryptococcosis is an AIDS defining illness and represents a profound reduction in immune function. Without treatment cryptococcal meningitis is fatal.
The incubation period for cryptococcosis is unknown; it may be days or weeks but has been described as being as long as 1 year. Added to this, dissemination from the lungs may occur months or years after the initial pulmonary infection if the patient has remained chronically colonised and then becomes immunosuppressed for some other reason.
How is cryptococcosis diagnosed?
The mainstay of diagnosis is usually clinical suspicion. In the context of meningitis the yeast can often be seen in the counting chamber used to calculate the white blood cell count (an untrained eye can mistake them for lymphocytes) and on the Gram film. Further confirmation can be done by adding India ink to the CSF which demonstrates a characteristic large capsular halo around the microorganism.
How does cryptococcosis present?
Most infections in patients with a normal immune system are either asymptomatic or a mild respiratory infection with non-productive cough and fever. This isn’t really surprising as in order to acquire this infection you usually have to inhale fungal spores, which then settle in the lungs.
However, in immunosuppressed patients the infection can disseminate via the bloodstream from the lungs to other parts of the body, in particular the CSF to cause meningitis. Cryptococcal meningitis is usually slow in onset when compared to other forms of meningitis. Cryptococcus spp. can spread to the kidneys, prostate, bone and skin (pustules, ulcers and subcutaneous masses) but this is rare. The most common form of immunosuppression associated with cryptococcosis is HIV infection; cryptococcosis is an AIDS defining illness and represents a profound reduction in immune function. Without treatment cryptococcal meningitis is fatal.
The incubation period for cryptococcosis is unknown; it may be days or weeks but has been described as being as long as 1 year. Added to this, dissemination from the lungs may occur months or years after the initial pulmonary infection if the patient has remained chronically colonised and then becomes immunosuppressed for some other reason.
How is cryptococcosis diagnosed?
The mainstay of diagnosis is usually clinical suspicion. In the context of meningitis the yeast can often be seen in the counting chamber used to calculate the white blood cell count (an untrained eye can mistake them for lymphocytes) and on the Gram film. Further confirmation can be done by adding India ink to the CSF which demonstrates a characteristic large capsular halo around the microorganism.
Adding India ink to Cryptococcus spp. shows characteristic large capsular halo
Cryptococcus spp. will usually grow on most laboratory media but it may take a few days. The organism can be further identified using biochemical or mass spectrometry methods (MaldiTOF).
The other test available to aid the diagnosis of cryptococcosis is cryptococcal antigen (CrAg). This test detects fragments of the yeast and can be done on blood or CSF. It has good sensitivity and specificity but is usually a reference laboratory test so can take a few days or up to a week to give an answer.
For other forms of disseminated cryptococcosis histopathological examination of tissue can usually identified the yeast.
How is cryptococcosis treated?
Treatment of cryptococcosis is dependent on the type of infection. Cryptococcal pneumonia is treated with 6-12 months of PO Fluconazole but meningitis has a much more complicated treatment regimen.
Cryptococcal meningitis:
The other test available to aid the diagnosis of cryptococcosis is cryptococcal antigen (CrAg). This test detects fragments of the yeast and can be done on blood or CSF. It has good sensitivity and specificity but is usually a reference laboratory test so can take a few days or up to a week to give an answer.
For other forms of disseminated cryptococcosis histopathological examination of tissue can usually identified the yeast.
How is cryptococcosis treated?
Treatment of cryptococcosis is dependent on the type of infection. Cryptococcal pneumonia is treated with 6-12 months of PO Fluconazole but meningitis has a much more complicated treatment regimen.
Cryptococcal meningitis:
Induction phase |
IV Liposomal Amphotericin B PLUS PO Flucytosine |
Consolidation phase |
High dose PO Fluconazole |
Maintenance phase |
Low dose PO Fluconazole |
Duration
Induction – 2-6 weeks depending on improvement of symptoms and repeat lumbar puncture at 2 weeks; if CSF still culture positive then continue induction antimicrobials
Consolidation – 8 weeks
Maintenance – 1 year
Note: If the patient is immunosuppressed then every effort should also be made to try and reduce the amount of immunosuppression wherever possible.
Can cryptococcosis be prevented?
Maintenance Fluconazole in the treatment of cryptococcosis reduces the relapse rate from up to 25% within 6 months to almost zero. Patients with HIV infection and low CD4 counts are usually given Fluconazole prophylaxis which reduces the incidence of cryptococcosis as well as oesophageal candidiasis.
Tracking down a source of contamination can be challenging, however once it is found it might be a blindingly obvious lapse in care. Knowing the microorganisms helps identify potential sources in which to investigate. Until the microorganism was grown and identified, it would have been unlikely the Doctors, Microbiologists or Estates staff in Glasgow’s hospital would have thought of Cryptococcus spp. and gone looking for a source. There are many flaws in our crumbling NHS infrastructure; they will be evident if we look for them. It may seem obvious that letting animals get in to parts of a hospital which have the potential to spread any diseases those animals may carry to the rest of the hospital, and vulnerable patients, is going to be a bad thing but unfortunately these problems are often not addressed until something goes wrong. It appears that the Glasgow Hospital’s air handling room has now been cleaned and the pigeons evicted.
I suspect that the reasons two patients have died is because they were immunocompromised, young or frail and the Doctors looking after them didn’t think of cryptococcosis when they became unwell… why would they… it’s very rare in the UK and not usually seen as a healthcare associated infection. I wouldn’t have thought of it either…
Another fine mess Mr Bevan… sorry!
Induction – 2-6 weeks depending on improvement of symptoms and repeat lumbar puncture at 2 weeks; if CSF still culture positive then continue induction antimicrobials
Consolidation – 8 weeks
Maintenance – 1 year
Note: If the patient is immunosuppressed then every effort should also be made to try and reduce the amount of immunosuppression wherever possible.
Can cryptococcosis be prevented?
Maintenance Fluconazole in the treatment of cryptococcosis reduces the relapse rate from up to 25% within 6 months to almost zero. Patients with HIV infection and low CD4 counts are usually given Fluconazole prophylaxis which reduces the incidence of cryptococcosis as well as oesophageal candidiasis.
Tracking down a source of contamination can be challenging, however once it is found it might be a blindingly obvious lapse in care. Knowing the microorganisms helps identify potential sources in which to investigate. Until the microorganism was grown and identified, it would have been unlikely the Doctors, Microbiologists or Estates staff in Glasgow’s hospital would have thought of Cryptococcus spp. and gone looking for a source. There are many flaws in our crumbling NHS infrastructure; they will be evident if we look for them. It may seem obvious that letting animals get in to parts of a hospital which have the potential to spread any diseases those animals may carry to the rest of the hospital, and vulnerable patients, is going to be a bad thing but unfortunately these problems are often not addressed until something goes wrong. It appears that the Glasgow Hospital’s air handling room has now been cleaned and the pigeons evicted.
I suspect that the reasons two patients have died is because they were immunocompromised, young or frail and the Doctors looking after them didn’t think of cryptococcosis when they became unwell… why would they… it’s very rare in the UK and not usually seen as a healthcare associated infection. I wouldn’t have thought of it either…
Another fine mess Mr Bevan… sorry!
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