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Respiratory infections III Fungal = Systemic mycoses y  Generally result from inhalation of air-borne spores in soil or plant material y  Most are caused by d imorphic fungi -  Saprophytic, vegetative mycelia form in nature and under ordinary laboratory conditions -  Pathogenic, unicellular yeast-like or spherule form in human and animal host tissues y  True pathogens -  Coccidiodomycosis -  Blastomycosis -  Histoplasmosis -  Paracoccidioidomycosis y  Opportunistic pathogens -  Aspergillosis -  Systemic candidosis -  Cryptococcosis -  Pneumocystis infection -  Zygomycosis (mucormycosis) -  Others INCIDENCE y  Systemic mycoses occur most frequently in those who work in the -  Agricultural sector -  Construction industry y  Before (I.e before the antibiotic era and the subsequent development in medicine) = Systemic mycoses was very rare -  Even though known since the end of 19 th century y  Often discovered post mortem y  However, since the advent of: -  Antibiotics (mid 1940s) -  Corticotherapy (1950s) -  Immunosuppressive therapy (1960s) -  Catheterization -  Prosthetic devices -  Organ and tissue ttranspolantation -  HIV/AIDS (late 1970s) y  Systemic mycoses started to: -  Develop new clinical aspects -  Occur with much higher frequency -  Begin to become important public health problems y  In fact several opportunistic infections have become nosocoial, hospital-acquired and invasive infections. HISTOPLASMOSIS

Respiratory Infections III (Updated)

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Respiratory infections III

Fungal = Systemic mycoses

y  Generally result from inhalation of air-borne spores in soil or plant material

y  Most are caused by dimorphic fungi

-  Saprophytic, vegetative mycelia form in nature and under ordinary laboratory conditions

-  Pathogenic, unicellular yeast-like or spherule form in human and animal host tissues

y  True pathogens

-  Coccidiodomycosis

-  Blastomycosis

-  Histoplasmosis

-  Paracoccidioidomycosis

y  Opportunistic pathogens

-  Aspergillosis

-  Systemic candidosis

-  Cryptococcosis-  Pneumocystis infection

-  Zygomycosis (mucormycosis)

-  Others

INCIDENCE

y  Systemic mycoses occur most frequently in those who work in the

-  Agricultural sector

-  Construction industry

y  Before (I.e before the antibiotic era and the subsequent development in medicine) =

Systemic mycoses was very rare-  Even though known since the end of 19

thcentury

y  Often discovered post mortem

y  However, since the advent of:

-  Antibiotics (mid 1940s)

-  Corticotherapy (1950s)

-  Immunosuppressive therapy (1960s)

-  Catheterization

-  Prosthetic devices

-  Organ and tissue ttranspolantation

-  HIV/AIDS (late 1970s)

y  Systemic mycoses started to:

-  Develop new clinical aspects

-  Occur with much higher frequency

-  Begin to become important public health problems

y  In fact several opportunistic infections have become nosocoial, hospital-acquired and

invasive infections.

HISTOPLASMOSIS

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y  Causative organism = H.capsulatum

y  Taxonomically H.capsulatum divided into 3 varieties; each with its own distinctive & defining

characteristics

a.  H. capsulatun var. capsulatum

-  Causes histoplasma capsulate

-  Cosmopolitan endemic in all continentsb.  H. capsulatum var. duboisii

-  Causes histoplasma duboisii

-  Liited to central Africa and Madagascar

-  Also called African histoplasmosis

c.  H. capsulatum var, farciminosum

-  Causes histoplasmosis

-  Africa, East Europe, Middle East, Asia, Far East

y  All 3 varieties are:

-  Saprophytes

-  Mitosporic moulds (fungi imperfecti) in nature or in laboratory at 25-30 C

-  Transformed into unicellular yeast-like budding organisms

-  In mammalian tissue

-  At 37 C in enriched media with cysteine in lab

Histoplasma Capsulati

y  Genus histoplasma established 1906 when Darling described first case

y  Usually either an asymptomatic or relatively mild and self-limiting pulmonary infection

y  But can be

-  Chronic

-

 Acute disseminated

y  Causative organism: fungus imperfecti histoplasma capsulatum var. capsulatum

-  An intracellular parasite

-  Found in soil enriched with bird and bat droppings (saprophyte)

-  Infection, inhalation of spores

-  Cosmopolitan [in USA Mississippi & Ohio river valleys (prevalence: 95%)]

-  Mould: fluffy, white or buff brown

-  Mycelium: Septate

-  2 types of unicellular asexual spores:

  Macroconidia (8-14 micrometer)

  Microconidia (2-4 micrometer)

-  Yest phase cell 2-3 x 3-4 mucrometer

y  Note: In birds not known to be infected. Only transitory infection in chicken (Gallus gallus)

and Pigeon (Columbia livia)

Pathogenesis

y  Infection usually asymptomatic or mild (skin test +)

y  Sometimes: acute influenza like

y  Fever with non-productive cough

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y  Although self-limiting, patient usually left with discrete, CALCIFIED lesions in the lungs

y  Chronic form: usually in adults develop large cavities directly from primary lesions or

reactivation of old lesions (c.f TB)

y  Occasionally patient develops acute PROGRESSIVE form with

-  Widespread infection of RES

-  Diseemination to other organs:-  Joints arhtralgia/arthritis

-  Skin erythema nodosum & erythema multiforme

-  Heart pericarditis

-  Liver }

-  Renal } failure -> death

-  Respiratory }

-  Meningitis, cerebritis or focal brain lesion

y  Usually in old aged, infancy and immunocompromised

Histoplasmosis(continued)

LABORATORY DIAGNOSIS

y  Microscopy

-  Sputum (Wright or Giemsa stain)

-  Pus (Wright or Giemsa stain)

-  Blood smear may be (+) especially in HIV cases

y  Biopsy

-  PAS stain

-  Methenamine-silver stain

[H. capsulatum: small oval teast cells packed within microorganisms and/or monocytes

y  Culture: Sabourauds agar

-  25-30 C for 1-4 weeks -> mycelium

-  Macro and microconidia visible under microscope

-  37 C in cysteine rich medium -> Yeast form

y  Serology

-  Precipitation test

-  Complement fixation test (CFT)

-  Latex particle agglutination test (LPA)

-  ELISA

TREATMENT

y  Mild

-  Ketaconazole

-  Itraconazole

y  Severe

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-  Amphotericin B (disseminated, HIV/AIDS patients)