Respiratory infections III

Fungal = Systemic mycoses

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

 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
 True pathogens
- Coccidiodomycosis
- Blastomycosis
- Histoplasmosis
- Paracoccidioidomycosis
 Opportunistic pathogens
- Aspergillosis
- Systemic candidosis
- Cryptococcosis
- Pneumocystis infection
- Zygomycosis (mucormycosis)
- Others

INCIDENCE

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

- Agricultural sector
- Construction industry
 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
 Often discovered post mortem
 However, since the advent of:
- Antibiotics (mid 1940’s)
- Corticotherapy (1950’s)
- Immunosuppressive therapy (1960’s)
- Catheterization
- Prosthetic devices
- Organ and tissue ttranspolantation
- HIV/AIDS (late 1970’s)
 Systemic mycoses started to:
- Develop new clinical aspects
- Occur with much higher frequency
- Begin to become important public health problems
 In fact several opportunistic infections have become nosocoial, hospital-acquired and
invasive infections.

HISTOPLASMOSIS
  Causative organism = H.capsulatum
 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 continents
b. 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
 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

 Genus histoplasma established 1906 when Darling described first case

 Usually either an asymptomatic or relatively mild and self-limiting pulmonary infection
 But can be
- Chronic
- Acute disseminated
 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
 Note: In birds – not known to be infected. Only transitory infection in chicken (Gallus gallus)
and Pigeon (Columbia livia)

Pathogenesis

 Infection usually asymptomatic or mild (skin test +)

 Sometimes: acute influenza like
 Fever with non-productive cough
  Although self-limiting, patient usually left with discrete, CALCIFIED lesions in the lungs
 Chronic form: usually in adults develop large cavities directly from primary lesions or
reactivation of old lesions (c.f TB)
 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
 Usually in old aged, infancy and immunocompromised

Histoplasmosis(continued)

LABORATORY DIAGNOSIS

 Microscopy
- Sputum (Wright or Giemsa stain)
- Pus (Wright or Giemsa stain)
- Blood smear may be (+) especially in HIV cases
 Biopsy
- PAS stain
- Methenamine-silver stain

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

 Culture: Sabouraud’s agar

- 25-30 C for 1-4 weeks -> mycelium
- Macro and microconidia visible under microscope
- 37 C in cysteine rich medium -> Yeast form

 Serology
- Precipitation test
- Complement fixation test (CFT)
- Latex particle agglutination test (LPA)
- ELISA

TREATMENT

 Mild
- Ketaconazole
- Itraconazole

 Severe
- Amphotericin B (disseminated, HIV/AIDS patients)