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OPPORTUNISTIC MYCOSES
       CLASSIFICATION      ORGANISMS

       Yeast               Candida
                           Cryptococcus
                           Torulopsis
                           Trichosporon
                           Rhodotorula
                           Geotrichium


       Molds               Aspergillus
                           Pseudoallescheria
                           Zygomycetes (Rhizopus, Mucor, and Absidia


Monday, January 16, 2012
OPPORTUNISTIC MYCOSES
                           True Pathogenic Fungi    Opportunistic Fungi

       Diseases            Histoplasmosis           Aspergillosis
                           Blastomycosis            Candidiasis
                           Paracoccidioidomycosis   Mucormycosis
                           Coccidioidomycosis       Cryptococcosis


       Host                Normal                   Abrogated/
                                                      Compromised

       Portal of           Primary infection is     Various
         Entry                pulmonary


Monday, January 16, 2012
OPPORTUNISTIC MYCOSES
                           True Pathogenic Fungi          Opportunistic Fungi

       Prognosis           99% spontaneous resolution     Recovery depends on the
                                                             severity of impairment of
                                                             host defenses
       Immunity            Resolution results to strong   No specific resistance to
                              specific immunity               infection

       Host Response       Tuberculoid granuloma,         Depends on degree of
                              mixed pyogenic                 impairment necrosis to
                                                             pyogenic to
                                                             granulomatous

       Morphology in       All agents showed              No change in morphology
          Tissue               dimorphism to a tissue
                               form

       Distribution        Geographically restricted      Ubiquitous


Monday, January 16, 2012
CANDIDIASIS
            C. albicans is the most common (4-6 um;
           budding)

           Multiplication: blastospore formation
           producing either pseudohyphae or
           septate hyphae

           Identification: assimilation and
           fermentation of CHOs; physiologic and
           morphologic responses they exhibit
           when grown under controlled
           nutritional conditions                     “germ tubes”

Monday, January 16, 2012
CANDIDIASIS



                                 “chlamydoconidia”




Monday, January 16, 2012
FACTORS THAT AFFECT CANDIDA
               NORMAL POPULATION


            poor oral hygiene

           use of antibiotics

           use of oral contraceptives

           diet

           presence of antagonistic inhibitory bacteria


Monday, January 16, 2012
Candida albicans is a resident flora of the
          skin, mouth, vagina and stool!


             Imbalance will lead to infection....HOW?

                 Changes in the Physiology: e.g.
                 pregnancy, use of steroids and diabetes

                 Prolonged administration of antibiotics

                 Immunocompromised patients

Monday, January 16, 2012
MUCOCUTANEOUS CANDIDIASIS
                 (MC)
            a condition caused by a fungus from
           the candida family (lives on the
           surface of skin) that develops a
           diffuse and persistent type of
           infection of the mouth, nails, skin, and
           at times other organs

           affects infants (starts before age 3) and
           young adults, is rarely seen in adults
           with other diseases

           including chronic mucocutaneous
           candidaisis or CMCC

Monday, January 16, 2012
SYMPTOMS: ORAL




           “thrush”               “glossitis”        “stomatitis”




                 “cheilitis”            “perleche”

Monday, January 16, 2012
SYMPTOMS: VAGINITIS &
                                BALANITIS




        “VAGINITIS = female”

          “BALANITIS = male”

Monday, January 16, 2012
SYMPTOMS: ALIMENTARY




                                “Esophageal growth”

     OTHERS: gastritis, peritonitis, enteric and perianal disease
Monday, January 16, 2012
CANDIDIASIS IN NAILS




Monday, January 16, 2012
CANDIDIASIS IN DIAPER RASH




                           “Candida may come from fecal origin”


Monday, January 16, 2012
SYSTEMIC INVOLVEMENT

            Urinary tract

           Endocarditis

           Meningitis

           Septicemia

           Latrogenic candidemia

           Dissemination to other organ systems
Monday, January 16, 2012
DISSEMINATED CANDIDIASIS

                           originate at a gastrointestinal site

                           CA enters epithelial microvilli through persorption of yeast cells
                           or by germination (a,c)

                              In both cases, organisms enter the vasculature (b,d) for
                              dissemination into tissues such as the kidney (e)

                              localizes in the cortex (f) where it grows as hyphae/
                              pseudohyphae

                           A vigorous host response occurs at this site consisting of both
                           mononuclear and polymorphonuclear leukocytes

                           Virulence factors (adhesins, morphogenesis, switch phenotypes,
                           antioxidant proteins and invasive enzymes) promote the invasion
                           of the organism

Monday, January 16, 2012
ALLERGIC CANDIDIASIS



                     Eczema
                     Asthma
                     Gastritis

Monday, January 16, 2012
LABORATORY DIAGNOSIS:
                                CADIDIASIS

             Direct microscopic
           examination

           Specimen for examination can
           be sputum, skin scrapings,
           vaginal swabs, biopsy material,
           from any types of organs or
           even in blood.

           The specimen is treated with
           1-2 drops of 10-20% KOH.

Monday, January 16, 2012
LABORATORY DIAGNOSIS:
                                CADIDIASIS


             The presence of the capsule
            and budding yeast cells are
            considered as the positive
            results.

            Aside from KOH, other
            stains can be used such as
            India ink and Papanicolaou
            stain.


Monday, January 16, 2012
GERM TUBE TEST



              Most isolates of
            C. albicans produce a
            hyphal growth from
            blastospores when
            they are suspended in
            serum at 37°C for 2-3
            hours.

Monday, January 16, 2012
IN CULTURE...



              SDA at either room temperature or at 37°C

            Colonies: usually develop in 2-3 days as
            white, typical yeast colonies

            In vitro: monomorphic, growing as non
            encapsulated yeast cells at any temperature

Monday, January 16, 2012
IN CULTURE...




Monday, January 16, 2012
FROM CORN MEAL AGAR




Monday, January 16, 2012
TREATMENT OF CANDIDIASIS


              Most localized, cutaneous, candidiasis infections may
            be treated with any number of topical antifungal
            agents (eg, clotrimazole, econazole, ciclopirox,
            miconazole, ketoconazole, nystatin).

            For Candida onychomycosis, oral itraconazole
            (Sporanox)

            For Genitourinary tract candidiasis, VVC can be
            managed with either topical antifungal agents or

Monday, January 16, 2012
TREATMENT OF CANDIDIASIS



              Caspofungin acetate (Cancidas) as a 70-mg
            loading dose is followed by 50 mg/d IV for a
            minimum of 2 weeks after improvement or
            after blood cultures have cleared.

            Chronic mucocutaneous candidiasis is treated
            with oral azoles, either fluconazole (Diflucan)

Monday, January 16, 2012
ASPERGILLOSIS


              One of the largest of the fungal genera

            Hundred of species have been recorded

            The most important species:

                  A. fumigatus

                  A. flavus

                  A. niger

Monday, January 16, 2012
ASPERGILLUS FUMIGATUS


            Aspergillus fumigatus

                  identified according to
                  the pattern of
                  conidiophore
                  development,
                  morphologic features
                  and color of the
                  conidia

Monday, January 16, 2012
IMPORTANT PARTS




Monday, January 16, 2012
SPECTRA OF ASPERGILLOSIS


             Toxicity due to ingestion of contaminated foods

            Allergy and sequelae to the presence of conidia or transient
            growth of the organism in body orifices

            Colonization without extension in preformed cavities and
            debilitated tissues

            Invasive, inflammatory, granulomatous, necrotizing disease of
            lungs and other organs

            Systemic and fatal disseminated disease

Monday, January 16, 2012
ALLERGIC ASPERILLOSIS


              Allergic aspergillosis maybe benign early on and
            severe as the patient grows older

            In secondary colonization, a chronic clinical
            situation may exist with little distress except
            occasional bout of hemoptysis and some
            pathological changes in the lungs that may lead to
            the formation of fungus ball.

Monday, January 16, 2012
ALLERGIC ASPERILLOSIS




                            SKIN        FUNGAL SPECIMEN
                                          IN THE TISSUE


Monday, January 16, 2012
SYSTEMIC ASPERGILLOSIS




              An extreme serious disorder that is usually
            rapidly fatal unless diagnosed early and treated
            aggressively

            The status of the host’s immune system
            contributes to the prognosis of the patient



Monday, January 16, 2012
SYSTEMIC ASPERGILLOSIS




                      FUNGUS BALL/
                     ASPERGILLOMA


Monday, January 16, 2012
Disease              Etiologic Factors

      Mycotoxicoses        Ingestion of contaminated food
                             products
      Hypersensitivity     Allergic bronchopulmonary
        peumonitis           disease

      Secondary            Colonization of preexisting
        colonization         cavity (pulmonary abscess)
                             without invasion into
                             contiguous tissue

      Systemic disease Invasive disease involving
                         multiple organs

Monday, January 16, 2012
DISSEMINATED ASPERGILLOSIS

                           Aerosols of Aspergillus fumigatus conidia are inhaled and
                           travel to the alveoli

                           In the healthy host, alveolar macrophages (AM) phagocytose
                           and kill the organism after swelling of the conidium, an
                           essential pre-germination stage

                              The production of reactive oxygen intermediates by AM is
                              required to eliminate the organism, but
                              polymorphonuclear cells (PMNs) also contribute

                           In the immunosuppressed patient, reduced numbers of PMNs
                           and inefficient AM allow growth of the fungus

                           Consequently, the conidia germinate and escape from the AM


Monday, January 16, 2012
LABORATORY DIAGNOSIS


              Aspergillosis is easy to isolate and identify....BUT!

                  also important to distinguish a true pathogen
                  from a contaminant

            If sputum sample is to be collected, it is expected
            to be thick and gelatinous

            In invasive sampling, lung aspirates or tissue
            biopsy is used
Monday, January 16, 2012
LABORATORY DIAGNOSIS



              Direct microscopic examination will show
            hyaline, dichotomously branched and septate
            hyphae

            Occasionally in sputum, in cases of pulmonary
            aspergillosis, one may also sees very small, rough
            walled spores (3-4 um in diameter).


Monday, January 16, 2012
PULMONARY ASPERGILLOSIS




Monday, January 16, 2012
TREATMENT



              Amphotericin B was used
            for many years BUT!!! with
            disappointing results

            In 1990 itraconazole was
            introduced as a new broad
            spectrum anti-fungal agent.


Monday, January 16, 2012
ZYGOMYCOSIS/PHYCOMYSIS


              Class Phycomycetes

                  Rhizopus

                  Absidia

                  Mucor

            They formed coenocytic hyphae and reproduce
            asexually by producing sporangiosphores within
            which develops sporangiospores
Monday, January 16, 2012
ZYGOMYCOSIS/PHYCOMYSIS


              Repeated isolation of the
            organisms from consecutive
            specimens provides strong
            evidence that the organisms
            may be relevant, even though
            coenocytic hyphal elements
            are not seen in
            histopathologic examination
            of tissue.

Monday, January 16, 2012
MUCORMYCOSIS (ORAL CAVITY)




Monday, January 16, 2012
CATEGORIES           COMMENTS
      Rhinocerebral        It is the most frequent presentation overall and classically affects diabetics with
                                 ketoacidosis.

                               Usually presents with facial and/or eye pain, proptosis and progressive signs of
                               involvement of orbital structures (muscles, nerves and vessels).

                               Common complications include cavernous sinus and internal carotid artery
                               thrombosis.

      Pulmonary            It occurs most frequently among neutropenic patients.

                               It presents with nonspecific symptoms such as fever, cough and dyspnea;
                               hemoptysis may occur with vascular invasion.

                               Radiological presentation includes segmental consolidation that progresses to
                               contiguous areas of the lung, with occasional cavitation.

      Gastrointestinal     Usually affects patients with severe malnutrition

                               May involve the stomach, ileum, and colon

                               Clinical picture mimics intra-abdominal abscess. The diagnosis is often made at
                               autopsy.
      Cutaneous            It has been reported with minor trauma, insect bites, no sterile dressing, wounds, and
                                burns.

                               The necrotic lesions progressively evolve from the epidermis into dermis and even
                               muscle.
      Others               Heart, bone, kidneys, bladder, trachea, and mediastinum


Monday, January 16, 2012
DIRECT EXAMINATION: ZYGOMYCOSIS


             A rapid diagnosis is critical

            Fungal elements are usually not numerous in discharges

            Scrapings from the upper turbinates, aspirated material
            from sinuses, sputum in pulmonary disease, and biopsy
            material mounted in 10% KOH typically contain thick-
            walled, refractile hyphae 6-15 um in diameter

            Swollen cells (up to 50 um) and distorted hyphae may be
            present

Monday, January 16, 2012
IN CULTURE...

              Sabouraud dextrose agar:
            Incubate at 30°C

            DON’T: cycloheximide =
            sensitive

            Sterile bread:

                  for recovery of Zygomycetes
                  when other media fail

                  WHY bread???
Monday, January 16, 2012
TREATMENT




              Control of the diabetes

            Aggressive surgical
            debridement of involved tissue

            High doses of amphotericin B
            are recommended



Monday, January 16, 2012

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Opportunistic mycoses

  • 1. OPPORTUNISTIC MYCOSES CLASSIFICATION ORGANISMS Yeast Candida Cryptococcus Torulopsis Trichosporon Rhodotorula Geotrichium Molds Aspergillus Pseudoallescheria Zygomycetes (Rhizopus, Mucor, and Absidia Monday, January 16, 2012
  • 2. OPPORTUNISTIC MYCOSES True Pathogenic Fungi Opportunistic Fungi Diseases Histoplasmosis Aspergillosis Blastomycosis Candidiasis Paracoccidioidomycosis Mucormycosis Coccidioidomycosis Cryptococcosis Host Normal Abrogated/ Compromised Portal of Primary infection is Various Entry pulmonary Monday, January 16, 2012
  • 3. OPPORTUNISTIC MYCOSES True Pathogenic Fungi Opportunistic Fungi Prognosis 99% spontaneous resolution Recovery depends on the severity of impairment of host defenses Immunity Resolution results to strong No specific resistance to specific immunity infection Host Response Tuberculoid granuloma, Depends on degree of mixed pyogenic impairment necrosis to pyogenic to granulomatous Morphology in All agents showed No change in morphology Tissue dimorphism to a tissue form Distribution Geographically restricted Ubiquitous Monday, January 16, 2012
  • 4. CANDIDIASIS C. albicans is the most common (4-6 um; budding) Multiplication: blastospore formation producing either pseudohyphae or septate hyphae Identification: assimilation and fermentation of CHOs; physiologic and morphologic responses they exhibit when grown under controlled nutritional conditions “germ tubes” Monday, January 16, 2012
  • 5. CANDIDIASIS “chlamydoconidia” Monday, January 16, 2012
  • 6. FACTORS THAT AFFECT CANDIDA NORMAL POPULATION poor oral hygiene use of antibiotics use of oral contraceptives diet presence of antagonistic inhibitory bacteria Monday, January 16, 2012
  • 7. Candida albicans is a resident flora of the skin, mouth, vagina and stool! Imbalance will lead to infection....HOW? Changes in the Physiology: e.g. pregnancy, use of steroids and diabetes Prolonged administration of antibiotics Immunocompromised patients Monday, January 16, 2012
  • 8. MUCOCUTANEOUS CANDIDIASIS (MC) a condition caused by a fungus from the candida family (lives on the surface of skin) that develops a diffuse and persistent type of infection of the mouth, nails, skin, and at times other organs affects infants (starts before age 3) and young adults, is rarely seen in adults with other diseases including chronic mucocutaneous candidaisis or CMCC Monday, January 16, 2012
  • 9. SYMPTOMS: ORAL “thrush” “glossitis” “stomatitis” “cheilitis” “perleche” Monday, January 16, 2012
  • 10. SYMPTOMS: VAGINITIS & BALANITIS “VAGINITIS = female” “BALANITIS = male” Monday, January 16, 2012
  • 11. SYMPTOMS: ALIMENTARY “Esophageal growth” OTHERS: gastritis, peritonitis, enteric and perianal disease Monday, January 16, 2012
  • 12. CANDIDIASIS IN NAILS Monday, January 16, 2012
  • 13. CANDIDIASIS IN DIAPER RASH “Candida may come from fecal origin” Monday, January 16, 2012
  • 14. SYSTEMIC INVOLVEMENT Urinary tract Endocarditis Meningitis Septicemia Latrogenic candidemia Dissemination to other organ systems Monday, January 16, 2012
  • 15. DISSEMINATED CANDIDIASIS originate at a gastrointestinal site CA enters epithelial microvilli through persorption of yeast cells or by germination (a,c) In both cases, organisms enter the vasculature (b,d) for dissemination into tissues such as the kidney (e) localizes in the cortex (f) where it grows as hyphae/ pseudohyphae A vigorous host response occurs at this site consisting of both mononuclear and polymorphonuclear leukocytes Virulence factors (adhesins, morphogenesis, switch phenotypes, antioxidant proteins and invasive enzymes) promote the invasion of the organism Monday, January 16, 2012
  • 16. ALLERGIC CANDIDIASIS Eczema Asthma Gastritis Monday, January 16, 2012
  • 17. LABORATORY DIAGNOSIS: CADIDIASIS Direct microscopic examination Specimen for examination can be sputum, skin scrapings, vaginal swabs, biopsy material, from any types of organs or even in blood. The specimen is treated with 1-2 drops of 10-20% KOH. Monday, January 16, 2012
  • 18. LABORATORY DIAGNOSIS: CADIDIASIS The presence of the capsule and budding yeast cells are considered as the positive results. Aside from KOH, other stains can be used such as India ink and Papanicolaou stain. Monday, January 16, 2012
  • 19. GERM TUBE TEST Most isolates of C. albicans produce a hyphal growth from blastospores when they are suspended in serum at 37°C for 2-3 hours. Monday, January 16, 2012
  • 20. IN CULTURE... SDA at either room temperature or at 37°C Colonies: usually develop in 2-3 days as white, typical yeast colonies In vitro: monomorphic, growing as non encapsulated yeast cells at any temperature Monday, January 16, 2012
  • 22. FROM CORN MEAL AGAR Monday, January 16, 2012
  • 23. TREATMENT OF CANDIDIASIS Most localized, cutaneous, candidiasis infections may be treated with any number of topical antifungal agents (eg, clotrimazole, econazole, ciclopirox, miconazole, ketoconazole, nystatin). For Candida onychomycosis, oral itraconazole (Sporanox) For Genitourinary tract candidiasis, VVC can be managed with either topical antifungal agents or Monday, January 16, 2012
  • 24. TREATMENT OF CANDIDIASIS Caspofungin acetate (Cancidas) as a 70-mg loading dose is followed by 50 mg/d IV for a minimum of 2 weeks after improvement or after blood cultures have cleared. Chronic mucocutaneous candidiasis is treated with oral azoles, either fluconazole (Diflucan) Monday, January 16, 2012
  • 25. ASPERGILLOSIS One of the largest of the fungal genera Hundred of species have been recorded The most important species: A. fumigatus A. flavus A. niger Monday, January 16, 2012
  • 26. ASPERGILLUS FUMIGATUS Aspergillus fumigatus identified according to the pattern of conidiophore development, morphologic features and color of the conidia Monday, January 16, 2012
  • 28. SPECTRA OF ASPERGILLOSIS Toxicity due to ingestion of contaminated foods Allergy and sequelae to the presence of conidia or transient growth of the organism in body orifices Colonization without extension in preformed cavities and debilitated tissues Invasive, inflammatory, granulomatous, necrotizing disease of lungs and other organs Systemic and fatal disseminated disease Monday, January 16, 2012
  • 29. ALLERGIC ASPERILLOSIS Allergic aspergillosis maybe benign early on and severe as the patient grows older In secondary colonization, a chronic clinical situation may exist with little distress except occasional bout of hemoptysis and some pathological changes in the lungs that may lead to the formation of fungus ball. Monday, January 16, 2012
  • 30. ALLERGIC ASPERILLOSIS SKIN FUNGAL SPECIMEN IN THE TISSUE Monday, January 16, 2012
  • 31. SYSTEMIC ASPERGILLOSIS An extreme serious disorder that is usually rapidly fatal unless diagnosed early and treated aggressively The status of the host’s immune system contributes to the prognosis of the patient Monday, January 16, 2012
  • 32. SYSTEMIC ASPERGILLOSIS FUNGUS BALL/ ASPERGILLOMA Monday, January 16, 2012
  • 33. Disease Etiologic Factors Mycotoxicoses Ingestion of contaminated food products Hypersensitivity Allergic bronchopulmonary peumonitis disease Secondary Colonization of preexisting colonization cavity (pulmonary abscess) without invasion into contiguous tissue Systemic disease Invasive disease involving multiple organs Monday, January 16, 2012
  • 34. DISSEMINATED ASPERGILLOSIS Aerosols of Aspergillus fumigatus conidia are inhaled and travel to the alveoli In the healthy host, alveolar macrophages (AM) phagocytose and kill the organism after swelling of the conidium, an essential pre-germination stage The production of reactive oxygen intermediates by AM is required to eliminate the organism, but polymorphonuclear cells (PMNs) also contribute In the immunosuppressed patient, reduced numbers of PMNs and inefficient AM allow growth of the fungus Consequently, the conidia germinate and escape from the AM Monday, January 16, 2012
  • 35. LABORATORY DIAGNOSIS Aspergillosis is easy to isolate and identify....BUT! also important to distinguish a true pathogen from a contaminant If sputum sample is to be collected, it is expected to be thick and gelatinous In invasive sampling, lung aspirates or tissue biopsy is used Monday, January 16, 2012
  • 36. LABORATORY DIAGNOSIS Direct microscopic examination will show hyaline, dichotomously branched and septate hyphae Occasionally in sputum, in cases of pulmonary aspergillosis, one may also sees very small, rough walled spores (3-4 um in diameter). Monday, January 16, 2012
  • 38. TREATMENT Amphotericin B was used for many years BUT!!! with disappointing results In 1990 itraconazole was introduced as a new broad spectrum anti-fungal agent. Monday, January 16, 2012
  • 39. ZYGOMYCOSIS/PHYCOMYSIS Class Phycomycetes Rhizopus Absidia Mucor They formed coenocytic hyphae and reproduce asexually by producing sporangiosphores within which develops sporangiospores Monday, January 16, 2012
  • 40. ZYGOMYCOSIS/PHYCOMYSIS Repeated isolation of the organisms from consecutive specimens provides strong evidence that the organisms may be relevant, even though coenocytic hyphal elements are not seen in histopathologic examination of tissue. Monday, January 16, 2012
  • 42. CATEGORIES COMMENTS Rhinocerebral It is the most frequent presentation overall and classically affects diabetics with ketoacidosis. Usually presents with facial and/or eye pain, proptosis and progressive signs of involvement of orbital structures (muscles, nerves and vessels). Common complications include cavernous sinus and internal carotid artery thrombosis. Pulmonary It occurs most frequently among neutropenic patients. It presents with nonspecific symptoms such as fever, cough and dyspnea; hemoptysis may occur with vascular invasion. Radiological presentation includes segmental consolidation that progresses to contiguous areas of the lung, with occasional cavitation. Gastrointestinal Usually affects patients with severe malnutrition May involve the stomach, ileum, and colon Clinical picture mimics intra-abdominal abscess. The diagnosis is often made at autopsy. Cutaneous It has been reported with minor trauma, insect bites, no sterile dressing, wounds, and burns. The necrotic lesions progressively evolve from the epidermis into dermis and even muscle. Others Heart, bone, kidneys, bladder, trachea, and mediastinum Monday, January 16, 2012
  • 43. DIRECT EXAMINATION: ZYGOMYCOSIS A rapid diagnosis is critical Fungal elements are usually not numerous in discharges Scrapings from the upper turbinates, aspirated material from sinuses, sputum in pulmonary disease, and biopsy material mounted in 10% KOH typically contain thick- walled, refractile hyphae 6-15 um in diameter Swollen cells (up to 50 um) and distorted hyphae may be present Monday, January 16, 2012
  • 44. IN CULTURE... Sabouraud dextrose agar: Incubate at 30°C DON’T: cycloheximide = sensitive Sterile bread: for recovery of Zygomycetes when other media fail WHY bread??? Monday, January 16, 2012
  • 45. TREATMENT Control of the diabetes Aggressive surgical debridement of involved tissue High doses of amphotericin B are recommended Monday, January 16, 2012