L21 - A Carmichael - Systemic fungal infections Flashcards
describe infectious diseases
multiply at site of entry (eg lungs) then spread through blood or lymphatics to rest of body - esp in immunocompromised host
2 types of deep fungal infections
picutre
describe systemic pathogens
These are microscopic saprotrophs that live in the environment.
Infection of humans is accidental, and is not required for the maintenance of the fungus in nature.
The consequences of an infection are determined by the strain, infectious dose and resistance of the host.
describe how a human may accidently be infected with histoplasma capsulatum?
e.g. Histoplasma capsulatum, a dimorphic fungus that lives in soil or bat droppings in Mississippi & Ohio valleys; the filamentous mould releases air-borne spores which are inhaled by bats, and sometimes accidentally inhaled by humans who venture into caves.
describe how Histoplasma switches from filamenous mould to budding yeast?
dimorphic
the temperature-sensitive dimorphism regulating kinases DRK1 and RYP1 induce a different pattern of gene expression that equips the yeast for a life of persistent infection within mammalian macrophages.
which arsenal of warm genes does histoplasma equip for mamallian host survival
urface α- 1,3-glucan which is not recognized by host pattenn recognition receptors (= camofluage); fungal hsp60 which binds to CD11/CD18 on the surface of human macrophages; and a secreted protease-resistant calcium binding protein CBP that facilitates fungal growth within macrophage vacuoles.
label histoplasma infection slide
In most people, does Histoplasma infection cause symptoms?
no
in most people how is histoplasma infection controlled?
the persistent intracellular infection of macrophages is controlled by host T cells which activate macrophages leading to the formation of granulomas.
how can you test to see whether someone has had histolpasma before
One can identify a person who has previously been infected with Histoplasma by using a skin test in which dead Histoplasma antigen is injected into the skin where it evokes a delayed-type IV hypersensitivity reaction (skin inflammation) due to the presence of Histoplasma-specific memory CD4+ T cells.
when does histoplasma become a problem?
Histoplasma yeast cells persist for decades in an asymptomatic host under the control of cell-mediated immunity;
if subsequently the host becomes immunocompromised (e.g. because of HIV or immunosuppressive drug treatment following a kidney transplant), the infection can re-activate and multiplying yeasts invade into the surrounding tissues.
outcomes for histoplasmosis disease
whats this?
whats this?
describe systemic oppertunists
- fungi of low intrinsic virulence
- cause disease in only a minority of individuals whose defences are compromised
- high density of organisms
- relative lack of host inflammatory response
- prolonged anti-fungal treatment is often needed to eradicate the infection
- it is important to restore the impaired host defence e.g. by stopping immunosuppressant drugs or by treating HIV with anti-HIV drugs
T or F
When a person develops a systemic opportunistic fungal infection, in addition to treating the infection with anti-fungal drugs, it is essential to identify and if possible correct the underlying host defect (e.g. in AIDS, by starting anti-HIV treatment).
T
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give 4 systemic oppertunists
Candida albicans
Pneumocystis jiroveci
Cryptococcus neoformans
Aspergillus fumigatus
Candida albicans is a _______ yeast on moist mucosal surfaces,
Candida albicans is a commensal yeast on moist mucosal surfaces,
what usually restrains candida albicans>
by host defences and competition with bacterial flora.
Candida albicans – a budding yeast
which can form ______ when it invades tissue
Candida albicans – a budding yeast
which can form pseudo-hyphae when it invades tissue
whast this
candida albicans
describe biofilm formation
large structured communities of organisms
embedded in a sticky extracellular matrix
on a solid/liquid interface (e.g. the surface of a plastic cannula)
does candida albicans secrete a toxin?
yep
what toxin does candida albicans secrete?
Candidalysin: secreted 31 amino acid peptide toxin which damages epithelial cells, important for virulence in animal models of mucosal Candida infection
whats this
Superficial Candida albicans infection
whats this?
Candida endophthalmitis (white spots in retina and vitreous)
treatmenst for candida albicans
Candida auris is resistant to Fluconazole, so it requires treatment with a different anti-fungal drug such as _______,
Candida auris is resistant to Fluconazole, so it requires treatment with a different anti-fungal drug such as Caspofungin,
describe the oxford outbreak of candida auris
describe Pneumocystis jirovecii
Pneumocystis is a yeast which is an obligate parasite of humans;
during its co-evolution with humans it has lost many genes needed for amino acid synthesis, and at present Pneumocystis cannot be cultured in vitro.
is Pneumocystis a fission or fusion yeast?
fission yeast
Pneumocystis jirovecii - does it have ergosterol
no
The infection is acquired by _______ and transmission is from human-to-human through…..
The infection is acquired by inhalation and transmission is from human-to-human through the air
Most children develop antibodies against Pneumocystis by the age of 3, suggesting……
Most children develop antibodies against Pneumocystis by the age of 3, suggesting that asymptomatic infection occurs early in life in almost everyone
Host defence against Pneumocystis depends on….
Host defence against Pneumocystis depends on T cells and not antibodies.
how do we diagnose Pneumocystis jirovecii
PCR amplification of Pneumocystis DNA
Pneumocystis jirovecii:
can it reinfect? where have utbreaks occured? hospitals perhaps?
In individuals who have impaired T cell immunity, lung disease can occur following re-acquisition of Pneumocystis by inhalation later in life. Outbreaks have occurred in hospitals as a result of airborne transmission of Pneumocystis from one immunocompromised patient to another in the same ward
Pneumocystis jirovecii:
give the type of infection, and when it mght occur
describe The disease Pneumocystis pneumonia (abbreviated to PCP)
The disease Pneumocystis pneumonia (abbreviated to PCP) is a diffuse inflammation of lung alveoli, with clusters of oval fungal organisms in the alveolar airspaces and injury to alveolar epithelial cells; instead of being full of air, the alveoli become filled with a foamy protein-rich exudate.
physiological issues with Pneumocystis pneumonia (abbreviated to PCP)
and clinical features
impairment of gas diffusion that causes arterial hypoxaemia that is worse during exercise.
The clinical features are a dry cough, worsening breathlessness, fever and weight loss; the chest X-ray shows widespread hazy opacification of lung alveoli.
treatment for Pneumocystis pneumonia (abbreviated to PCP)
The treatment is high-dose Co-trimoxazole (= Sulphamethoxazole + Trimethoprim) which inhibits fungal folic acid synthesis, combined with short-term anti-inflammatory treatment with corticosteroid Prednisolone so as to reduce the pattern recognition receptor-mediated inflammatory response to fungal polysaccharides that are released by dying organisms in the lung.
In high-risk immunocompromised patients, Pneumocystis pneumonia can to a large extent be prevented by….
In high-risk immunocompromised patients, Pneumocystis pneumonia can to a large extent be prevented by regular low-dose preventive treatment with either Co-trimoxazole or inhaled Pentamidine.
whats shown
Pneumocystis pneumonia (PCP) summary
where does Cryptococcus neoformans occur?
worldwide
Cryptococcus is a yeast that occurs worldwide, is abundant in….s
Cryptococcus is a yeast that occurs worldwide, is abundant in bird droppings
Cryptococcus is a yeast that occurs worldwide, is abundant in bird droppings, and possesses a thick ,…..
Cryptococcus is a yeast that occurs worldwide, is abundant in bird droppings, and possesses a thick polysaccharide capsule that is an important virulence determinant.
how do you aquire a Cryptococcus neoformans infection?
inhalation
Cryptococcus neoformans has a tendancy to spread from the lungs to where?
strong tendency to spread from the lung through the circulation to the central nervous system.
crytococcus neoformans infection disease may occur when?
disease occurs when T cell immunity is impaired
Cryptococcus neoformans - disease caused in teh brain?
- spreads from the lung through the blood to the brain
- chronic meningo-encephalitis +/- hydrocephalus
- 20% fatality; survivors may have neurological disability
Cryptococcus neoformans infection types and conditions it may accompany
Cryptococcus neoformans brain disease info in people with HIV or organ transplants
In HIV infection or organ transplant recipients, Cryptococcus typically causes a slowly worsening meningo-encephalitis, with progressively worsening headache, fever, confusion, hydrocephalus (excessive accumulation of cerebrospinal fluid due to impaired CSF reabsorption) and finally coma.
treatment for Cryptococcus neoformans?
Treatment – Amphotericin plus Flucytosine, followed by long-term high-dose Fluconazole.
Despite treatment, 20% fatality rate; survivors may have persistent neurological disability including blindness
whats this?
Cryptococcus neoformans causes hydrocephalus - how may this look on a head CT
enlarged cerebral ventricels
describe Aspergillus fumigatus
Aspergillus is an environmental filamentous mould that occurs worldwide and produces abundant air-borne spores which are inhaled by people every day (e.g. mouldy hay, compost heaps, hospital re-building work).
is Aspergillus an oppertunistic mould?
yep
Aspergillus fumigatus
fatality rate of Invasive Aspergillus infection
Invasive Aspergillus infection has a very high fatality rate
Invasive Aspergillus infection has a very high fatality rate – typically it occurs in patients who have ….
Invasive Aspergillus infection has a very high fatality rate – typically it occurs in patients who have a serious underlying disease that compromises the immune system.
Treatment of invasive aspergillus infection?
Treatment – Amphotericin or Voriconazole, surgery if possible.
summary of Aspergillus fumigatus
whats this
Aspergilloma in a lung cavity previously caused by tuberculosis
can this happen?
acute lung infarction caused by hyphae invading & blocking arteries
yessss
whats this
describe Mucor
Mucor is an environmental filamentous mould, acquired by inhalation of air-borne spores or occasionally by direct contamination of wounds (e.g. following a tornado or tsunami) .
what disease does mucor cause?
The disease Mucormycosis is rare but very serious.
what happens regarding a mucor infection in pateints with badly ontrolled fiabetes or leukaemia?
the mould invades aggressively through para-nasal sinuses or lungs, with a very high fatality rate
treatment of Mucormycosis - caused by mucorreatment – urgent surgery to remove dead tissue plus intravenous Amphotericin.
Treatment – urgent surgery to remove dead tissue plus intravenous Amphotericin.
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