Systemic mycosis

1. SYSTEMIC MYCOSIS
Dr. Dinesh Jain
Assistant Professor
Deptt. of Microbiology
SMS MC Jaipur

2. Systemic Mycosis
 Fungal infection of internal organs.
 Primarily involve the respiratory system.
 Infection occurs by inhalation of air- borne
conidia.
 More than 95% are self limiting &
asymptomatic.
 Rest are symptomatic & disseminate by
hematogenous route.

3. Systemic Mycosis
 Caused by dimorphic fungi which infect healthy &
immunocompetent individuals.
 Other systemic infections found in
immunocompromised patients are called as
opportunistic mycotic infections.
 Includes :
Histoplasma capsulatum
Blastomyces dermatitidis
Coccidioides immitis
Paracoccidioides brasiliensis

4. HISTOPLASMOSIS
 Intracellular infection of the RES caused by
Histoplasma capsulatum. Endemic in parts of USA
 Also called Darling’s disease; 1st described by
Samuel Darling.
“histio” within histiocytes
“plasma” resembled plasmodium.
 Present in soil, rotting areas and in feces of
chicken, bats & other birds. (high N2 content)

5. Pathogenesis & Pathology
Inhalation of conidia or mycelial fragments
Converted into yeast in alveolar macrophages
Localized granulomatous inflammation
Granuloma with or assist in
without caseation dissemination to RES
 Involves all phagocytic cells of RES, cytoplasm
being studded with fungal cells.

6. Clinical features
 Resembles TB – mainly asymptomatic
 Clinical types –
1. Pulmonary
2. Cutaneous & mucocutaneous
3. Disseminated histoplasmosis – commonly
seen in children below 2 yrs & adolescents
- individuals with HIV are at a greater risk.

7. Laboratory Diagnosis
Specimen – sputum, BM, LNs, scrapings from
lesions, biopsy & peripheral blood.
Direct Examination
 Blood smear – Giemsa or Wright stains.
- small, oval yeast like cells, 2-4µ within mononuclear
or polymorphonuclear cells, narrow neck budding.
 Fluorescent Ab technique.

8. Fungal Culture
 SDA , BHI at 25° & 37°C.
 LPCB - White cottony mycelia with large (8-
20µ) thick walled, spherical spores with
tubercles or finger
like projections –
Tuberculate
Macroconidia.

9. Immunodiagnosis
 Histoplasmin skin test – I.D. test with 0.1
ml histoplasmin Ag – DTH response.
 Serological tests – LA
* titer of 1:32 or higher or 4-fold
increase in titer of Abs is significant.

10. Treatment & Prophylaxis
 Amphotericin B – disseminated & other
severe forms.
 Oral Itraconazole
 Regular cleaning of farm buildings,
chicken houses for prevention.

11. BLASTOMYCOSIS
 Also called as Gilchrist’s disease or Chicago
disease due to its endemicity in N.America
(N.American blastomycosis)
 Caused by Inhalation of the spores of
Blastomyces dermatitidis
 Causes suppurative & granulomatous infection

12. Clinical features
 1° infection resembles TB or histoplasmosis.
 Clinical types:
1. Pulmonary
2. Cutaneous – commonest form, hence the name
“dermatitidis”.
- seen over exposed parts like face, neck &
hands.
3. Disseminated type – form multiple abscesses in
different parts like bone, genitourinary system,
breast etc

13. Laboratory Diagnosis
Specimen – sputum, BAL, biopsy or pus
from abscesses, urine.
Direct Examination
 Wet mount – KOH, CFW : double contoured,
thick walled,
multinucleate giant
yeast cells with
broad base budding
daughter cells.

14. Fungal Culture
 Very slow growth – 2 to 4 weeks.
 Tissue & cultures at 37°C shows budding yeast
cells.
 At 25°C - fine, branched septate hypha with
conidia measuring 2-10µ located on short
terminal or lateral branches.

15. Diagnosis
 Immunodiffusion precipitation bands.
 EIA / RIA
 Skin test using blastomycin
Treatment & Prophylaxis
 Initial phase - Oral Ketoconazole &
Itraconazole
 Life threatening infections - AMB

16. COCCIDIOIDOMYCOSIS
 Infection of the respiratory system caused by
Coccidioides immitis.
 Most virulent of all the fungal pathogens but not
contagious.
 More prevalent in western hemisphere.
 Fungus present in soil & in rodents.
 Infection occurs by
- inhalation of arthroconidia or
- reactivation of latent infection in
immunocompromised patients.

17. Clinical features
 Many develop influenza like fever – Valley
fever or Desert Rheumatism
 < 1% develop chronic progression
disseminated disease –
- skin (commonest) : granuloma, cold abscess.
- osteomyelitis & synovitis
- CNS (meningitis)

18. Laboratory Diagnosis
Specimen – sputum, gastric contents, CSF,
exudate or pus.
Direct Examination
 Presence of doubly refractile thick walled
globular spherules
(30-60µ in dia)
filled with endospores
 Tissue – HE, PAS & GMS

19. Fungal Culture
 Different from other dimorphic fungi – grows as mold
at 25° & 37°C under standard conditions.
 Growth in 3 - 5 days at 25°C
 LPCB of culture shows branching septate hypha &
chains of thick walled rectangular arthroconidia.
 Arthroconidia are mature
infectious propagules
that develop from
alternate cells on hypha.

20. Immunodiagnosis
 Skin tests – I.D. inoculation of
coccidioidin: positive is >5mm in 24-48
hours.
 Serology – detection of Abs
Treatment & Prophylaxis
 Rapidly progressive disease – AMB
 Chronic, mild to moderate - azoles

21. PARACOCCIDIOIDOMYCOSIS
 Acute or chronic, granulomatous
infection
1. primarily of lungs &
2. disseminates to skin, mucosa, LNs &
other internal organs.
 Caused by Paracoccidioides brasiliensis.
 Confined to S.America (S.American
blastomycosis).

22. Laboratory Diagnosis
Specimen – sputum, BAL, pus & crusts from
granulomatous lesions, biopsy
Direct Examination
 Wet mount - KOH, CFW
- round refractile yeast
cells 2-10 to 30µ
- single or chain of cells
 Tissue stains – HE, GMS

23. Fungal Culture
 SDA, BHIA & BA incubated at 25° & 37°C.
 At 25°C – colonies are white to tan in colour,with a
yellowish-brown reverse
LPCB - mycelia bearing conidia & numerous
intercalary chlamydospores.
 37°C – off-white to cream,
rough to pasty.
LPCB- spherical mother cell
surrounded by multiple
thin-necked daughter cells:
“Mariner’s wheel”

24. Treatment & Prophylaxis
 Long term therapy
 Reviewed periodically as relapses are
frequent
 AMB combined with sulfonamides
 Oral Itraconazole

25. CANDIDIASIS
 Commonest fungal disease in humans
 Affects mucosa, skin, nails & internal organs -
superficial and deep infections
 Caused by yeast- like fungi of genus candida.
 Candida albicans : commonest pathogenic
species.
 Normal flora of skin, GIT & female genital
tract.
 Commonest fungal infection in HIV+ve
individuals

26. Epidemiology
 Predisposing factors
1. Natural receptive states like infancy, old age,
pregnancy.
2. Changes in local bacterial flora 2º to antibiotics.
3. Endocrine diseases like DM
4. Severe chronic underlying debilitated conditions
5. Malignancy
6. Drugs – steroids, immunosuppressants &
chemotherapeutic agents.
7. Trauma, burns or injury.

27. Pathogenesis & Pathology
 Adhesion – entry into host as yeast cell
 Local colonization & invasion into deeper
tissues
 Hyphal form - phospholipase at tip -
invasion
large size - resistant to
phagocytosis
 Biofilm formation around cells – facilitates
survival of organisms.

28. Clinical Classification of Candidiasis

29. Mucocutaneous Manifestations
 Oral candidiasis or oral thrush – commonest
form: - Creamy white patches on tongue or
buccal mucosa
- 90% of AIDS pt.
 Vaginitis
- Young & middle – aged females, during active
reproductive life.
- Acidic discharge, itching & burning sensation

30. Cutaneous Manifestations
 Intertriginous – skin folds
 Paronychia – nail folds
 Diaper dermatitis – in babies
- maceration & wet diapers
Systemic Candidiasis
 Gastrointestinal candidiasis
- follow oral antibiotic therapy
- in leukemia & hematological
malignancy: ulcerations, peritonitis

31. Clinical forms of Candidiasis in
HIV patients
 Asymptomatic oral carriage
 Oropharyngeal thrush
 Angular cheilitis
 Leukoplakia
 Oesophagitis
 Laryngitis
 Vulvovaginitis, balanitis
 Acute atrophic erythema
 Hematogenous dissemination

32. Laboratory Diagnosis
 Clinical specimens are collected depending on
the site of involvement.
Direct Examination
 Wet mount – KOH
- Yeast cells, 4-8
with budding &
pseudohyphae
 Gram’s stain – gram
+ve budding yeast cells

33. Fungal Culture
 SDA & other bacteriological
media
 Colonies appear in 2-3 days.
 Creamy white, smooth &
pasty.
Identification of species
using
 Tetrazolium reduction
medium (TRM)
 CHROM agar

34. C.tropicalis
C.krusei
C.albicans
CHROM Agar

35. Germ tube test
 Culture is treated with sheep or normal human
serum.
 Incubated at 370C for 2 to 4 hrs.
 Wet mount : shows long tube – like projections
extending from the yeast cells, called GERM
TUBE.
 Positive for - C. albicans
- C. dubliniensis
- C. tropicalis (sometimes)
 Also known as Reynolds – braude phenomenon.

36. CANDIDA – GERM TUBE

37. Chlamydospore formation
 Cornmeal agar or Rice starch agar
 Incubated at 250c
 Large, highly refractive, thick – walled
chlamydospores after 2-3 days of
incubation.
Biochemical tests
 Sugar fermentation
 Sugar assimilation

38. Treatment & Prophylaxis
 Correct the underlying condition
 Oral & Mucocutaneous – 1% Gentian violet
 Resistant mucosal lesions – Nystatin
 Vaginal candidiasis – oral fluconazole (single
dose), suppositories & creams
 Systemic lesions – AMB
 Oral antifungals