Infectious Diseases 2: Fungal Infections (V1) LECTURE NOTES PDF

PATHOLOGY | TRANS #4E LE Infectious Diseases 2: Fungal Infections DR. CARINA P. VILLAMAYOR, FPSP | Lecture Date (09...

PATHOLOGY | TRANS #4E LE Infectious Diseases 2: Fungal Infections DR. CARINA P. VILLAMAYOR, FPSP | Lecture Date (09/27/2024) | Version #1 02 OUTLINE Hyphae grow by apical elongation and produce round I. Introduction III. Mold Infections cells at the tip called conidia which become airborne. A. Fungi A. Aspergillosis Fungal infections: B. Major Types of Fungal B. Zygomycosis → Diagnosed by histologic examination Infection (Mucormycosis) → Definitive identification of some species requires II. Yeast Infections IV. Review Questions culture. A. Candidiasis V. References B. Cryptococcosis VI. Formative Quiz MORPHOLOGY OF YEAST C. Pneumocystis Infection Must Lecturer Book Previous Youtube ❗️ Know 💬 📖 📋 Trans 🔺 Video SUMMARY OF ABBREVIATIONS GMS Gomori Methenamine Silver H&E Hematoxylin and Eosin Figure 1. Yeast Morphology [Lecture PPT] PAS Periodic Acid Schiff This depicts round to oval shaped yeasts that mainly ✔ LEARNING OBJECTIVES Classify fungi and parasites according to the division where it belongs. 📋 reproduce by budding into daughter cells. Small daughter cells that bud and elongate become pseudohyphae structures ✔ Specify the characteristic tropism of fungi and parasites as to the primary organ affected. MORPHOLOGY OF HYPHAE ✔ Identify the disease and discuss the epidemiology of these infectious agents. ✔ Demonstrate knowledge and understanding of etio-pathogenesis of the infectious disease. ✔ Demonstrate knowledge and understanding of the pathology of the infectious disease by identifying and describing the gross lesion and microscopic findings. ✔ Evaluate the diagnostic procedures to be used given the expected results. I. INTRODUCTION A. FUNGI Fungi are eukaryotes with cell walls. They can either grow as: → Molds: multicellular filaments → Yeast: individual cells or chains Table 1. Comparison of Mold and Yeast Figure 2. Hyphae Morphology [Lecture PPT] MOLD YEAST Mold hyphae grow and divide at their tips which produce 📋 round cells called conidia. Can be septated or non-septated; tangled masses of hyphae are called mycelium B. MAJOR TYPES OF FUNGAL INFECTION Superficial and cutaneous mycoses → Common and limited to very superficial and Multicellular and consists of Unicellular keratinized layers of the skin, hair and nails threadlike or filamentous → E.g. Dermatophytosis (ringworm) colonies Subcutaneous mycoses Filamentous Growth Most reproduce by budding → Skin, subcutaneous tissues, and lymphatics and rarely HYPHAE: Branching, Spherical to ellipsoidal; disseminate systemically. cylindrical tubules; vary in vary in diameter (3 - 15 μm) Endemic mycoses diameter (2 - 10 μm) → Caused by dimorphic fungi that can produce serious Mycelium: mass of Pseudohyphae: buds that systemic disease even in healthy individuals. intertwined hyphae that has fail to detach become Opportunistic mycoses accumulated during active elongated yeast cells → Life-threatening systemic diseases in individuals who growth are immunosuppressed, prosthesis, on chemotherapy Form at room temperature Form at human body or those with transplants. temperature LE 2 TG 4 | Perolina, Pescasio, Pico, J. Pinlac, TE | A. Reyes, Serrano AVPAA | J. Tudtud PAGE 1 of 11 TRANS 4E Piñon VPAA | D. Patajo PATHOLOGY | LE 2 Infectious Diseases 2: Fungal Infections | Dr. Carina P. Villamayor, FPSP OPPORTUNISTIC MYCOSES ETIOLOGY Yeast infections: Candidiasis, Cryptococcosis, Most Candida infections originate when the normal Pneumocystis infections commensal flora breach the skin or mucosal barriers Mold infections: Aspergillosis, Zygomycosis → Usually live as benign commensals that seldom (Mucormycosis) produce disease in healthy people → Found in the skin, mucous membranes, mouth, GIT and II. YEAST INFECTIONS vagina A. CANDIDIASIS Disease: Candidiasis or Moniliasis CASE SCENARIO → Most frequent cause of human fungal infection A 22-year-old pregnant female, who just finished a course of antimicrobial therapy for urinary tract 💬 caused by Candida albicans Opportunistic fungal infection → Healthy individuals may experience vaginitis or diaper infection (UTI), complains of intense vulvovaginal pruritus with white, thick, curd-like discharge. Her rash. OB-Gyne did a Pap Smear. → Candida is capable of spreading to the bloodstream in individuals with severe neutropenia and other underlying factors Figure 3. Case 1 [Lecture PPT] Figure 5. Pseudohyphae and Budding Yeast Cells[Lecture PPT] Risk/Predisposing Factors → Severe neutropenia → Prolonged antibiotic treatment → Prolonged steroid administration → Pregnancy → Underlying diseases (Diabetes mellitus) → Altered immunity → Polyendocrine disturbance Figure 4. Pap smear of the patient [Lecture PPT] PATHOLOGIC FINDINGS Clinical Impression: Vaginal Candidiasis → Cellular elements: Skewered squamous cells Pseudohyphae Speared by Chain of budding yeast pseudohyphae (shish formed by elongated kebab appearance) budding, few budding yeasts can also be seen 💬 Papanicolaou smear (Pap smear) 💬 Routinely done to screen for cervical cancer Can also detect fungal and protozoal infections as well as bacterial vaginosis Figure 6. Branching budding yeast cells with pseudohyphae in Gram Stain F [Lecture PPT] Successful either as a commensal or a pathogen Able to shift between different phenotypes and this ability involves coordinated regulation of phase-specific genes that allows it to adapt to changes in the environment Candida has the capacity to grow in biofilms → Increases resistance to immune response and Figure 5. Pathology of Vulvovaginitis & Cervicitis antifungal drugs caused by Candida [Lecture PPT] Neutrophils, macrophages, and Th17 cells are natural protection against Candida infections PATHOLOGY Infectious Diseases 2: Fungal Infections PAGE 2 of 11 PATHOLOGY | LE 2 Infectious Diseases 2: Fungal Infections | Dr. Carina P. Villamayor, FPSP → Microscopic Findings: appears as matted fungal pseudohyphae and inflammatory debris in the superficial epithelial cell layer. → Figure 7. Pseudohyphae and budding yeasts of Candida [Lecture PPT] Figure 10. Microscopic findings of Oral Thrush [Lecture PPT] INVASIVE CANDIDIASIS Invasive candidiasis is caused by blood-borne dissemination of organisms to various tissues or organs. Common patterns include: → Renal abscesses → Myocardial abscesses and endocarditis → Brain microabscesses and meningitis → Hepatic abscesses Depending on the immune status of the patient, this fungi Figure 8. Silver Stain of esophageal candidiasis [Lecture PPT] may evoke little inflammation to cause the usual ❗ Pseudohyphae: Candidiasis most important clue in the diagnosis of suppurative granulomas. response and occasionally cause Candida can appear as yeast-like forms, pseudohyphae CASE SCENARIO and rarely as true hyphae together in the same tissue A 38-year-old Systemic Lupus Erythematosus (SLE) Usually seen in routine hematoxylin and eosin (H&E) patient complaining of worsening headache and altered Specials stains are also used to visualize them: mental status. She has been a chronic steroid user for → Gomori Methenamine Silver (GMS) five years. She underwent lumbar tap and CSF findings → Periodic Acid Schiff (PAS) showed decreased glucose, increased pressure, CLINICAL MANIFESTATIONS variable pleocytosis and budding encapsulated fungus SUPERFICIAL INFECTIONS (CUTANEOUS / cells as seen on India ink preparation. What is your MUCOCUTANEOUS) clinical impression? Oral Thrush → Most commonly, Candidiasis can take the form of a superficial infection of the mucosal surface of the oral cavity (thrush) → Usually present in newborns, debilitated patients, individuals on oral steroids or antibiotics that destroy competing normal flora. → HIV is a major consideration in people presenting with oral thrush for no obvious reasons. → Gross appearance: creamy white pseudomembrane or patches covering the tongue or the buccal mucosa ▪ Easily detached to reveal a reddened & inflamed Figure 11. Clinical Manifestation of Cryptococcosis surface ▪ Made out of matted fungal organisms and inflammatory debris 💬 💬 Infection [Lecture PPT] This is a case of Cryptococcosis by C. neoformans. When you do lumbar tap, you get cerebrospinal fluid 📋 (CSF) from the patient. In cases of CSF infections, high opening pressure or signs of increased intracranial pressure, lumbar tap is 📋 done. Usually in the hospital, when the CSF findings show decreased glucose levels, this pertains to an infection caused by fungal elements that are present within the system. → This test result, along with the presence of budding encapsulated fungal cells with the use of India ink preparation is a sure case of Cryptococcosis. Figure 9. Macroscopic findings of Oral thrush [Lecture PPT] PATHOLOGY Infectious Diseases 2: Fungal Infections PAGE 3 of 11 PATHOLOGY | LE 2 Infectious Diseases 2: Fungal Infections | Dr. Carina P. Villamayor, FPSP ❗️ REMEMBER PATHOLOGY OF CRYPTOCOCCOSIS When you hear of a patient with immunocompromised state such as SLE, chronic steroid use, neurologic symptoms, and use of India ink stain, Cryptococcosis should come to mind B. CRYPTOCOCCOSIS Causative agent: Cryptococcus neoformans Two species are known to cause disease in humans, which grow as encapsulated yeasts: → Cryptococcus neoformans → Cryptococcus gattii Cryptococcus neoformans can cause the following: → Meningoencephalitis in healthy individuals → Opportunistic infections in immunocompromised individuals with the following conditions: ▪ AIDS Figure 12. Cryptococcus in India Ink Preparation [Lecture PPT] ▪ Leukemia India Ink Preparation ▪ Lymphoma → Thick polysaccharide capsules appear as a clear halo ▪ SLE ▪ Sarcoidosis ▪ Transplant patients on high-dose steroids 💬 within a dark background These preparations create a negative image PATHOGENESIS OF CRYPTOCOCCOSIS C. neoformans is present in the soil and in bird droppings most specifically pigeons and infects people when inhaled. Mode of transmission: inhalation → It affects primarily the lungs and brain. → When it affects the lungs, it only presents with mild symptoms. C. gattii is more likely to cause infection in immunologically healthy individuals → Presents with large lesions that could mimic neoplasms. It is associated with certain species of trees and also found in soil. VIRULENCE FACTORS Major virulence factor: thick & gelatinous polysaccharide capsule → Made up of Glucuronoxylomannan → Inhibits phagocytosis by alveolar macrophages, leukocyte migration, and recruitment of inflammatory cells. Cryptococcus neoformans can undergo phenotypic switching like Candida. → Can lead to changes in the structure and size of the capsule polysaccharide providing a means to escape immune responses. Figure 13. (Top) Mucicarmine Stain in a Virchow-Robin Melanin production with the help of laccase enzyme perivascular space & (bottom) Periodic Acid Schiff (PAS) ▪ Catalyzes formation of a melanin which acts as an of Cryptococcus spp. [Lecture PPT] antioxidant and counteracts the effect of antifungal Mucicarmine stain & Periodic Acid Schiff (PAS) drugs, binds irons and provides cell wall integrity → The cryptococcus polysaccharide capsule stains an Presence of enzymes intense red in both mucicarmine and PAS. → Serine proteinase Lung is a primary site for infection ▪ Includes fibronectin which aid tissue invasion → Pulmonary involvement is mild and asymptomatic, even → Basement membrane proteins while the fungus is spreading to the CNS. ▪ Aids in tissue invasion Space intentionally left blank Space intentionally left blank PATHOLOGY Infectious Diseases 2: Fungal Infections PAGE 4 of 11 PATHOLOGY | LE 2 Infectious Diseases 2: Fungal Infections | Dr. Carina P. Villamayor, FPSP PATHOLOGY OF CRYPTOCOCCAL MENINGITIS Gross appearance: irregularly-shaped yellow nodules Histologic appearance: lesions can be seen as numerous organisms with a large mucoid capsule appearing as a clear zone around a faint, round nucleus In immunosuppressed persons, it may disseminate to skin, liver, spleen, adrenal glands and bones. In those with non-immunosuppressed state, the fungi can cause a chronic granulomatous reaction composed of macrophages, lymphocytes and foreign body-type giant cells looking much like tuberculosis → Occasionally, a tuberculous-like caseating granuloma is Figure 14. Gross Appearance of Cryptococcal Meningitis formed [Lecture PPT] Major lesions of cryptococcosis are in the CNS involving the meninges, cortical gray matter and basal nuclei. Grossly, they may appear as microcysts Host response may be variable depending on immune resistance → In immunosuppressed people, it may evoke virtually no inflammatory reaction Gelatinous masses of fungi grow in the meninges or expand in the Virchow-Robin spaces within the gray matter giving off a soap-bubble lesion appearance [Lecture PPT] Figure 18. TB - Like Caseating Granuloma C. PNEUMOCYSTIS INFECTION Significant opportunistic infection seen in AIDS patients Caused by Pneumocystis jirovecii → Originally goes by the name Pneumocystic carinii → Originally classified as protozoan parasite, and descriptions of developmental forms reflect this historical classification → Yeast-like fungus which primarily causes lung infections → Causes rapidly progressive, bilateral pneumonia Figure 15. Soap-bubble Lesion [Lecture PPT] → Its nucleus and mitochondria are visible with CRYPTOCOCCOSIS OF THE LUNGS Wright-Giemsa stain Transmission is believed to be airborne Three forms of the organism include: → Trophozoites → Sporocytes → Cysts Clusters of the organism in bronchoalveolar lavage fluid may reach 200 μm in diameter Figure 16. Gross Appearance of Cryptococcosis in the Lungs [Lecture PPT] Figure 17. Histologic Appearance of Cryptococcosis in the Lungs [Lecture PPT] PATHOLOGY Infectious Diseases 2: Fungal Infections PAGE 5 of 11 PATHOLOGY | LE 2 Infectious Diseases 2: Fungal Infections | Dr. Carina P. Villamayor, FPSP III. MOLD INFECTIONS 📋 A. ASPERGILLOSIS Aspergillus is a ubiquitous mold that can cause: → Allergies in, otherwise, healthy individuals → Serious sinusitis, pneumonia and invasive disease 📋 in immunosuppressed individuals Neutropenia and use of corticosteroids can predispose to Aspergillosis Pulmonary aspergillosis can be caused by 3 species: → Aspergillus fumigatus: most common species Figure 19. Pneumocystis Infection [Lecture PPT] pathogenic for humans On tissue sections they can appear as cysts with a → Aspergillus niger cup-shaped appearance with a central dot → Aspergillus flavus Histopathologic findings: Can be isolated from vegetation, especially nuts and → Alveolar interstitial thickening grains during their growth and storage, and from decaying → Eosinophilic honeycombed exudate in the lumen of matter, soil, and air the lung PATHOGENESIS Fluorescein-conjugated antibody stains are commonly Aspergillus is transmitted by airborne Conidia used to diagnose these infections → Conidia germinate into hyphae, which invades tissues They may also register as elevated Beta D-glucan levels, Major portal of entry: Lung although this is not specific for Pneumocystis spp. → The small size of A. fumigatus spores (approx. 2-3 μm) Sensitive and specific PCR tests can also be used enables them to reach the alveoli No environmental source or external reservoir outside of 3 forms of Pulmonary Aspergillosis: humans has been identified for P. jirovecii. → Allergic bronchopulmonary aspergillosis The lack of a continuous in vitro culture method has ▪ Hypersensitivity reaction to spores hindered research of this pathogenesis. → Colonizing aspergillosis (Aspergilloma) ▪ Formation of aspergilloma or fungus balls: growth of fungus in preexisting pulmonary cavities ▪ Patients usually present with hemoptysis → Invasive Aspergillosis ▪ Opportunistic infection wherein there can also be hematogenous dissemination with involvement of the heart valves and brain aside from pulmonary lung lesion ▪ Pulmonary lesion takes the form of a necrotizing pneumonia: with sharply delineated, rounded, and gray foci and hemorrhagic borders PATHOLOGIC FINDINGS Figure 21. Aspergillus fungus ball within a dilated bronchus [Lecture PPT] Figure 20. Cup-shaped appearance with central dot Proliferating masses of hyphae form brownish “fungal cysts of Pneumocystis infection [Lecture PPT] balls” lying free within the cavities The surrounding inflammatory reaction may be sparse, or there may be chronic inflammation and fibrosis People with aspergillomas usually have recurrent hemoptysis PATHOLOGY Infectious Diseases 2: Fungal Infections PAGE 6 of 11 PATHOLOGY | LE 2 Infectious Diseases 2: Fungal Infections | Dr. Carina P. Villamayor, FPSP Figure 24. (L) Aspergillus on GMS stain; (R) Fungal hyphae on H&E stain [Lecture PPT] Figure 22. Invasive aspergillosis of the lung in a bone Gomori methenamine silver stain (GMS Stain) marrow transplant patient [Lecture PPT] → Shows the characteristic septate hyphae with parallel ‘ walls and acute angle branching The usual form of Aspergillus is hyphae H&E Stain → Aspergillus forms septate filaments, 5-10 μm thick, → Show radiating arrangement of fungal hyphae branching at acute angles of 40 degrees invading through the arterial wall → Aspergillus hyphae cannot be distinguished from the following species by morphology alone: ▪ Pseudallescheria boydii spp. ▪ Fusarium spp Figure 25. Radiating arrangement of fungal hyphae of Aspergillus (HPO) [Lecture PPT] B. ZYGOMYCOSIS (MUCORMYCOSIS) Figure 23. Aspergillus septate filaments [Lecture PPT] Conidial heads form rarely when the organism is exposed to air It may also exhibit Splendore-Hoeppli phenomenon → Radiating eosinophilic material is seen at the edges of fungal masses Aspergillus likes to invade blood vessels and surrounding tissues → Areas of hemorrhage and infarction are usually superimposed on the necrotizing, inflammatory tissue reactions STAINING Figure 26. Zygomycosis [Lecture PPT] Caused by Mucoromycotina → Widely distributed in nature → Usually cause no harm in immunocompetent individuals, but may cause mucormycosis in immunosuppressed individuals PATHOLOGY Infectious Diseases 2: Fungal Infections PAGE 7 of 11 PATHOLOGY | LE 2 Infectious Diseases 2: Fungal Infections | Dr. Carina P. Villamayor, FPSP Opportunistic infection caused by the following bread mold Mucormycetes form broad, non-septate hyphae with fungi: frequent near right angle branching of the hyphae → Mucor spp. → Variable width of hyphae (6-50 micrometers) → Rhizopus spp. Three primary sites of invasion: → Cunninghamella spp. (belongs to subphylum → Nasal Sinuses (Rhinocerebral mucormycosis) Mucoromycotina) ▪ Spreads from the nasal sinuses to the orbit and Major predisposing factors: brain → Neutropenia ▪ Can cause local tissue necrosis, invade arterial walls, → Corticosteroid use and penetrate the periorbital tissues and cranial vault → Diabetes Mellitus → Lungs (Thoracic mucormycosis) → Iron overload ▪ May be secondary to rhinocerebral disease or → Breakdown of cutaneous barriers (e.g. burns, wounds, trauma) PATHOGENESIS 📋 primary in immunosuppressed individuals Lung lesions combine areas of hemorrhagic pneumonia with vascular thrombi and distal infection Similar to Aspergillus, zygomycetes fungi are transmitted → Gastrointestinal Tract (GIT mucormycosis) by airborne asexual spores ▪ If the spores were ingested → Most commonly, inhaled spores produce infection in the sinuses and lungs Percutaneous exposure or ingestion can also lead to infection Macrophages provide the initial defense by phagocytosis 📋 and non-oxidative killing of germinating sporangiophores Neutrophils have a key role in killing hyphae after 📋 germination by directly damaging hyphae walls The availability of free iron increases the probability of infection → Free iron is a promoter of Mucoromycotina growth → Seen in people with: ▪ Diabetes: increased free iron due to ketoacidosis and/or glycosylation-induced poor iron affinity ▪ Chronic iron chelation treatment, where deferoxamine act as a siderophore within the fungi Figure 28. Rhinocerebral mucormycosis [Lecture PPT] PATHOLOGIC FINDINGS IV. REVIEW QUESTIONS 1. A 44-year-old female veterinarian working in a bird aviary complained of headache and neurologic symptoms. She was worked up in a hospital and was diagnosed to have meningitis. Which finding will support a diagnosis of cryptococcosis? a. Accompanying necrotizing pneumonia b. Fungus balls within dilated bronchi c. Presence of microcysts within the meninges d. Punctate hemorrhages within the cerebrum 2. The following fungi can undergo phenotypic switching to evade host defenses, EXCEPT: a. Candida spp. b. Cryptococcus spp. c. Aspergillus spp. d. None of the above 3. Infection by ingestion is an alternative route of transmission for these fungi: a. Aspergillus spp. b. Mucor spp. c. Candida spp. d. Pneumocystis spp. 4. A biologist tries to grow fungi using dextrose agar. He places this at 37oC. He notes growth of spherical to ellipsoidal cells. He most likely grew: a. Molds and yeasts Figure 27. (L) Meningeal blood vessels with angioinvasive b. Fungi won’t grow at this temperature Mucor species, with irregular width and near right-angle c. Molds branching of hyphae; (R) Broad, non-septate hyphae of d. Yeast variable width with frequent near right-angle branching of hyphae [Lecture PPT] PATHOLOGY Infectious Diseases 2: Fungal Infections PAGE 8 of 11 PATHOLOGY | LE 2 Infectious Diseases 2: Fungal Infections | Dr. Carina P. Villamayor, FPSP ANS: 1. C. Major lesions of cryptococcosis are in the CNS, V. REFERENCES involving the meninges, cortical gray matter, and basal Batch 2026 Trans. Infectious Diseases 2: Fungal Infections. nuclei. They grossly appear as microcysts. Dr. Carina Vilamayor’s Lecture: Infectious Diseases, Fungi and Parasites 2. C. Candida spp. and Cryptococcus spp. undergo phenotypic switching, only Aspergillus spp. does not. 3. B. Mucor spp. are transmitted by airborne asexual spores, percutaneous exposure, or ingestion. 4. D. Spherical and ellipsoidal from 3-5 μm, they form pseudohyphae that fail to detach and become elongated yeast cells. VI. FORMATIVE QUIZ Question & Choices Answer & Rationale 1. 4 Pics 1 word Left Upper Pic - Branching at acute angles of 40 degrees Right Upper Pic - Formation of aspergilloma or fungus balls Aspergillosis Left Lower Pic - Radiating arrangement of fungal hyphae Right Lower Pic - Aspergillus likes to invade blood vessels or angioinvasion 2. 4 Pics 1 word Left Upper Pic - C. neoformans is present in the soil and in bird droppings most specifically pigeons and infects people when inhaled. Cryptococcosis Right Upper Pic - Taj Mahal found in India. India Ink Preparation. Left Lower Pic - soap-bubble lesion appearance Right Lower Pic - Crypto-currency PATHOLOGY Infectious Diseases 2: Fungal Infections PAGE 9 of 11 PATHOLOGY | LE 2 Infectious Diseases 2: Fungal Infections | Dr. Carina P. Villamayor, FPSP 3. 4 Pics 1 word Left Upper Pic - blackwater fever Right Upper Pic - banana-shaped gametocytes Malaria Left Lower Pic - ring forms Right Lower Pic - kulambo prevents Malarial infection from mosquitoes CHOICES FOR THE QUESTIONS BELOW (includes questions on parasitic and fungal infections): A. Aspergillus spp. B. Kissing bug C. Parthenogenesis D. Genotypic mutations E. Mucor spp. F. P. falciparum G. C. gatti H. E. granulosus I. P. vivax J. Tsetse fly K. Cercaria L. Camouflage M. Microfilaria N. Blood smear O. Fission P. Phenotypic switching Q. Taenia solium R. Fecalysis S. C. neoformans T. Metacercaria 1. Infective stage of Schistosomiasis K Schistosomiasis larvae (Cercariae) swim through the freshwater and penetrate human skin with the aid of proteolytic enzymes that degrade the keratinized layer. 2. Ability of S. stercoralis to produce eggs asexually C Female worms reside in the mucosa of the small intestine where they produce the eggs asexually (Parthenogenesis) 3. Diagnostic lab exam for Babesiosis N Blood smear of patients with Babesiosis has maltese crosses or tetrads. 4. Diagnostic stage for Filariasis M The diagnosis of filariasis depends on the nocturnal periodicity of the microfilariae found in the blood. 5. Tapeworm that causes hydatid cyst H Echinoccoccus granulosus has an inner, nucleated germinative cell layer and outer, opaque, non-nucleated layer. Humans are accidental intermediate hosts, infected by ingestion of food contaminated with ova from dogs or foxes. PATHOLOGY Infectious Diseases 2: Fungal Infections PAGE 10 of 11 PATHOLOGY | LE 2 Infectious Diseases 2: Fungal Infections | Dr. Carina P. Villamayor, FPSP 6. Ability of Candida spp. to adapt to changes in P Able to shift between different phenotypes and environment this ability involves coordinated regulation of phase-specific genes that allows it to adapt to changes in the environment. 7. Species that can cause cryptococcosis in G C. gatti is more likely to cause infection in immunologically normal patients immunologically healthy or normal individuals - Presents with large lesions that mimic neoplasms - Associated with soil and certain species of trees - Acquired by inhalation In contrast, the severity of symptoms from C. neoformans infections will depend on the immune status of the patient. Associated with soil and bird droppings, specifically pigeons. Infects people through inhalation leading to infection in the lungs and CNS. 8. Causes Benign Tertian Malaria I Fever recurrence according to the species of Malaria Species Type Fever Occurrence P. falciparum Malignant Every 48 hours Tertian Malaria P. vivax Benign Tertian Every 48 hours Malaria P. ovale Ovale Malaria Every 48 hours P. malariae Quartan Malaria Every 72 hours 9. Insect vector that can cause Sleeping Sickness J African trypanosomes are transmitted via the bite of an infected tsetse fly (genus Glossina) which can manifest as intermittent fever, splenomegaly, lymphadenopathy, progressive brain dysfunction (sleeping sickness), cachexia, and death. 10. Fungi that has the GIT as a site of invasion E Mucor spp. Is the only fungal infection that can be transmitted via ingestion of spores that can lead to GIT mucormycosis. Other primary sites of invasion include the nasal sinuses (rhinocerebral mucormycosis). PATHOLOGY Infectious Diseases 2: Fungal Infections PAGE 11 of 11