SBRC

MICROBIOLOG
Y
FALL 2022
REVIEW PART 4

CLAUDE-BERNARD ILIOU,
MD
 FUNGI/MOLDS

 Eukaryotic organisms

 Cell membranes contain Ergosterol

 Cell walls

 Sabouraud’s Agar

 Amphotericin B

 Triazoles & Imidazoles

 Capsofungins

 Flucytosine
 COMPARISION OF FUNGI AND BACTERIA
Feature Fungi Bacteria
Size Approximately 6 μm Approximately 1μm
(Candida) (Staphylococcus)
Nucleus Eukaryotic Prokaryotic
Cytoplasm Mitochondria and endoplasmic Mitochondria and
reticulum present endoplasmic reticulum
absent
Cell membrane Sterols present Sterols absent
(except Mycoplasma)
Cell wall content Chitin Peptidoglycan
Spores Sexual and asexual spores for Endospores for survival, not
reproduction for reproduction
Thermal Yes (some) No
dimorphism
Metabolism Require organic carbon; no Many do not require organic
obligate anaerobes carbon; many obligate
anaerobes
 TYPES OF FUNGI

 2 types :

1. Yeasts grow as single cells that reproduce by asexual budding

2. Molds grow as long filaments (hyphae) and form a mat (mycelium)
 Some hyphae form transverse walls (septate hyphae), whereas others do not (nonseptate hyphae)
 Nonseptate hyphae are multinucleated (coenocytic)

 The growth of hyphae occurs by extension of the tip of the hypha, not by cell division all along the filament
 DIMORPHISM

 Several medically important fungi are thermally dimorphic (ie,

they form different structures at different temperatures)
 They exist as molds in the environment at ambient temperature
(25oC) and as yeasts (or other structures) in human tissues at body
temperature (37oC)
 Histoplasma capsulatum, Sporothrix schenckii, Blastomyces
dermatitidis, Coccidioides immitis, Paracoccidioides brasiliensis,
Penicillium marneffei
 An important exception is Candida albicans, which is part of the
normal human flora
 TRANSMISSION AND GEOGRAPHIC
LOCATION OF SOME IMPORTANT FUNGI
Form of
Genus Habitat Organism Portal of Entry Endemic Geographic Location
Transmitted
Coccidioides Soil Arthrospores Inhalation into lungs Southwestern United States and
Latin America
Histoplasma Soil Microconidia Inhalation into lungs Mississippi and Ohio River valleys
(associated in United States; many other
with bird countries
feces)
Blastomyces Soil Microconidia Inhalation into lungs States east of Mississippi River in
United States; Africa

Paracoccidioides Soil Uncertain Inhalation into lungs Latin America

Cryptococcus Soil Yeast Inhalation into lungs Worldwide

(associated
with
pigeon feces)

Aspergillus Soil and Conidia Inhalation into lungs Worldwide

vegetation
Candida Human body Yeast Normal flora of skin, Worldwide
mouth, gastrointestinal
tract,
and vagina
 PATHOGENESIS
 Granulomas are produced due to cell mediated immune response in the major systemic
fungal diseases (eg, coccidioidomycosis, histoplasmosis, and blastomycosis)
 Acute suppuration, characterized by the presence of neutrophils in the exudate, also occurs
in certain fungal diseases such as aspergillosis and sporotrichosis
 Fungi do not have endotoxin in their cell walls and do not produce bacterial-type exotoxins

 A delayed hypersensitivity skin test response can be seen after injecting certain fungal
antigens intradermally
 Skin testing with Candida antigens can be used to determine whether cell-mediated
immunity is normal
 Amanitin and Phalloidin are potent hepatotoxins that inhibit host RNA polymerase and
depolymerization of actin, respectively
 Aflatoxins produced by Aspergillus can cause hepatotoxicity and are carcinogens (inducing
mutation in p53 tumor suppressor gene)
 MYCOSES (FUNGAL INFECTIONS)

 Medical mycoses can be divided into four categories:

1. Systemic
2. Opportunistic
3. Subcutaneous
4. Superficial mycoses (cutaneous)
 IMPORTANT FEATURES OF SYSTEMIC FUNGAL DISEASES
Form in Tissue
Geographic
Genus Seen by Important Clinical Findings Laboratory Diagnosis
Location
Microscopy
Coccidioides Spherule Southwestern United Valley fever in Culture at 20°C grows
States and Latin immunocompetent; mold with
America dissemination to bone and arthrospores; serologic
meninges in test for IgM and IgG
immunocompromised, pregnant
women, African Americans, and
Filipinos
Histoplasma Yeasts within Ohio and Mississippi Cavitary lung lesions; Culture at 20°C grows
macrophages River valleys; granulomas in liver and spleen; mold with tuberculate
worldwide; pancytopenia and tongue ulcer macroconidia;
associated with bird in immunocompromised serologic test for IgM
and bat guano and IgG; urinary
antigen

Blastomyces Yeasts with Central and Ulcerated lesions of the skin Culture at 20°C grows
single broad- southeastern United mold
based bud States; Africa

Paracoccidioides Yeasts with Latin America, Ulcerated lesions of the face Culture at 20°C grows
multiple buds especially Brazil and mouth mold; serologic test
for IgM and IgG
 HISTOPLASMOSIS

 Histoplasma capsulatum

 Found in soil, bat guano or bird droppings

 Causes pulmonary infection

 Can become disseminated in immunocompromised

 1-2 weeks after exposure, respiratory flu-like symptoms, hepatosplenomegaly,

lymphadenopathy, mediastinitis
 Treatment: Amphotericin B or Itraconazole

 Meningitis is treated with Fluconazole

 BLASTOMYCOSIS

 Blastomyces dermatitidis

 Large yeast with single bud - dimorphic

 Endemic to Central North America

 Causes pulmonary infection similar to TB

 Can be come disseminated involving skin, osteomyelitis, CNS involvement, etc.

 Treatment: Amphotericin B, Itraconazole, Fluconazole (for CNS involvement)

 COCCIDIODOMYCOSIS

 Coccidioides immitis or posadasii

 Endemic to Arizona, California, Nevada, New Mexico, Texas, Utah and Mexico.

 Most infected have no symptoms

 Causes a pneumonia in endemic areas (valley fever)

 Erythema Nodosum

 Grocott’s methenamine silver stain

 Treatment: Amphotericin B, Fluconazole, Posaconazole, Voriconazole

 PARACOCCIDIOIDOMYCOSIS

 Paracoccidioides brasiliensis causes

paracoccidioidomycosis, also known as South American
blastomycosis
 Properties:
 P brasiliensis is a dimorphic fungus
 Tissue form: round yeast with thick-double refractory walls Paracoccidioides brasiliensis Note
and multiple buds, in contrast to B dermatitidis, which has a the multiple buds of the yeast form
single bud of Paracoccidioides, in contrast to
the single bud of Blastomyces
 Treatment: Itraconazole or Amphotericin B
 OPPORTUNISTIC MYCOSES

 Fungal infections that occur in immunocompromised host is known as

opportunistic mycoses
 Opportunistic fungi fail to induce disease in most immunocompetent persons but
can do so in those with impaired host defenses
 There are five genera of medically important fungi: Candida, Cryptococcus,
Aspergillus, Mucor, and Rhizopus causing opportunistic mycoses, plus
Pneumocystis jiroveci
 IMPORTANT FEATURES OF
OPPORTUNISTIC FUNGAL DISEASES
Form in Tissue Seen Geographic
Genus Important Clinical Findings Laboratory Diagnosis
by Microscopy Location
Candida Yeast forms Worldwide Thrush in mouth and vagina; Gram-positive; culture grows
pseudohyphae endocarditis in intravenous yeast colonies; Candida
drug users albicans forms germ tubes

Cryptococcus Yeast with large Worldwide Meningitis India ink stain shows yeast with
capsule large capsule; culture grows very
mucoid colonies

Aspergillus Mold with septate Worldwide Fungus ball in lung; wound Culture grows mold with green
hyphae and burn infections; spores; conidia in radiating chains
indwelling catheter
infections; sinusitis

Mucor and Mold with Worldwide Necrotic lesion formed when Culture grows mold with black
Rhizopus nonseptate hyphae mold invades blood vessels; spores; conidia enclosed in a sac
predisposing factors are called a sporangium
diabetic ketoacidosis, renal
acidosis, and cancer
 CANDIDA ALBICANS

 Dimorphic oval yeast forming pseudohyphae

 Part of the normal flora

 Diseases:
 Oral Thrush/Esophagitis
 Septicemia
 Endocarditis in IVDA
 Cutaneous infection in diabetics and obesity
 Chronic mucocutaneous candidiasis

 Treatment: topical antifungals, clotrimazole, fluconazole, nystatin

 CRYPTOCOCCOSIS

 Cryptococcus neoformans

 Opportunistic Infection – CD4 < 100/μl

 Pulmonary Cryptococcosis spreads to CNS

 Cryptococcal meningitis

 Increased ICP (headache)

 Identified by India ink or mucicarmine in CSF or latex agglutination

 Treatment: Amphotericin B with Flucytosine or Fluconazole

 ASPERGILLUS

 Aspergillus species molds; monomorphic,

have septate hyphae that form V-shaped
(dichotomous) branches
 Diseases:
 Allergic Bronchopulmonary aspergillosis
 Fungal Balls in lung cavitations
 Disseminated aspergillosis in severe neutropenia
 Cellulitis in burn patients
 Aspergillus aflatoxins are carcinogenic

 Treatment: Voriconazole, Posaconazole, Liposomal Amphotericin B, Capsofungin

 MUCORMYCOSIS

 Mucor and Rhizopus are saprophytic molds fungi cause Mucormycosis

(zygomycosis, phycomycosis)
 These fungi are found widely in the environment
 They are nonseptate filamentous fungi
 Transmitted by airborne to patients with reduced host defenses, progressing
rapidly from sinuses into brain tissue
 Patients with diabetic ketoacidosis, and leukemia are particularly susceptible
 Treatment: Amphotericin B
 PNEUMOCYSTIS

 Pneumocystis jiroveci (formerly P carinii) is classified as a yeast on the

basis of molecular analysis, but it has many characteristics of a protozoan
 Obligate extracellular parasite

 Transmission: By inhalation of airborne organisms into the lungs

 Pathogenesis: An inflammatory exudate composed primarily of plasma
cells occurs, oxygen exchange is reduced, and dyspnea occurs
 A reduced number of CD 4-postive T lymphocytes, such as in AIDS,
predisposes to pneumonia
 Most immunocompetent people have asymptomatic infections
 Disease: interstitial pneumonia
 In AIDS patients, malnourished babies, premature neonates
 symptoms: fever, nonproductive cough, and dyspnea
 Rales are heard bilaterally and the chest X-ray shows a “ground-
glass” pattern
 Mortality of untreated Pneumocystis pneumonia is 100%

 Lab diagnosis
 Detection of cysts in bronchial alveolar lavage fluids or in biopsy

 Fluorescent antibody staining or PCR

 Treatment: TMP-SMX, Pentamidine or Dapsone

 SUBCUTANEOUS MYCOSES

 The fungi that cause subcutaneous mycoses normally reside in soil or

on vegetation
 They enter the skin or subcutaneous tissue by traumatic inoculation
with contaminated material
 The lesions become granulomatous and expand slowly from the area of
implantation
1. Sporotrichosis
2. Chromoblastomycosis (chromomycosis)
3. Mycetoma
 SPOROTRICHOSIS

 Caused by Sporothrix schenckii

 Rose gardener’s Disease
 Usually limited to skin infection causing papular lesions but may invade
other organs
 Treatment: Amphotericin B, Itraconazole, Fluconazole, Posaconazole,
Voriconazole
CHROMOBLASTOMYCOSIS (CHROMOMYCOSIS)

 A slowly progressive, granulomatous subcutaneous mycotic

infection
 Caused by several soil fungi, called dematiaceous fungi, having
melanized cell walls, dark-colored, either gray or black
 Phialophora verrucosa, Fonsecaea pedrosoi, Fonsecaea
compacta, Rhinocladiella aquaspersa, and Cladophialophora
carrionii
 Mode of transmission:
 Traumatic inoculation in the skin of legs of barefoot agrarian
workers mainly in the tropics
 Treatment: Surgical excision and flucytosine or itraconazole
 DERMATOPHYTOSES

 Caused by fungi (dermatophytes) that infect only superficial keratinized structures

(skin, hair, and nails)
 Classified in three genera: epidermophyton, trichophyton, and microsporum

 Spread from infected persons by direct contact

 Microsporum is also spread from animals such as dogs and cats

 This indicates that to prevent reinfection, the animal must be treated also

 Dermatophytoses (tinea, ringworm) are chronic infections often located in the

warm, humid areas of the body
 Typical ringworm lesions have an inflamed circular border containing papules and
vesicles surrounding a clear area of relatively normal skin
 The lesions are typically pruritic

 Broken hairs and thickened broken nails are often seen

 PROTOZOA

 Sterol membranes
 Endoplasmic reticula for protein acetylation and glycosylation
 Actin and Tubulin for motility
 Sporozoans (Plasmodium, Babesia and Toxoplasma) are non-motile
 Flagellates (Trichomonas, Trypanosoma and Leshmania) are motile
 PLASMODIUM

 Single celled eukaryote that causes malaria

 Plasmodium falciparum causes most serious disease
 Plasmodia falciparum and vivax are more common causes of malaria
 Plasmodium ovale is found in Africa
 Plasmodium Knowlesi is found in Southeast Asia
 Plasmodium malariae is found in Africa, Central and South America and the Caribbean
 Malaria infects 200 million worldwide
 Malaria causes > 1 million deaths/year
 Sickle cell, Thalassemia and G6PD protect against malaria
 Absence of Duffy blood group protects against P. vivax
 PLASMODIUM

 Organisms adopt several morphologies:

 Trophozoites [Erythrocytic]
 Bands
 Schizonts

 Merozoites

 Sporozoites [Exoerythrocytic]
 Hypnozoites

 Gametocytes [sexual form]

 PLASMODIUM

 Transmission: by mosquito bite (infected female anopheline mosquito),

that injects sporozoites present in the saliva
 Can be transmitted by transfusion, transplantation, trans-placental

 Life cycle:
 The sexual cycle is called sporogony
 Asexual cycle is called schizogony
 Sexual cycle in mosquitoes (definitive host)
 Asexual cycle in humans (intermediate hosts)
 MALARIA FEVER CYCLES

 P. malariae – 72 hours (quartan)

 P. vivax and ovale – 48 hours (tertian)

 P. knowlesi – 24 hours (quotidian)

 P. falciparum – variable

 Serious complications:
 Blackwater fever – renal damage
 Cerebral malaria – cerebral capillary occlusion
 Headaches, myalgias, arthralgias
 Hepatomegaly, Splenomegaly, Anemia
 Relapse is common with P. vivax and P. ovale
 PLASMODIUM

 Plasmodium vivax and ovale create intracytoplasmic granule called Schffner dots

 Treatment depends on species and endemic areas:

 Plasmodium malariae – Chloroquine
 Plasmodium vivax – Chloroquine + Primaquine
 Chloroquine-resistant Plasmodium falciparum – Fansidar, Malarone (Proguanil + Atovaquone),
Artesunate (artemisinin)
 LEISHMANIASIS

 Leishmania donovani, Leshmania braziliensis

 Transmitted by the bite of the Sand Fly

 Endemic areas include Africa, Middle East, Asia (India) and Central to South America

 12 million currently infected, 30,000 deaths/year

 Cutaneous Leishmaniasis – Skin lesion

 Mucotcutaneous Leishmaniasis – Face, nose

 Visceral Leishmaniasis (Kal-azar) – Hepatosplenomegaly

 Treatment – Miltefosine, Pentamidine, Paramomycin, Amphotericin B

 TRYPANOSOMIASIS
 Trypanosoma are flagellates:

 Trypanosoma cruzi - Chagas’ disease, American

trypanosomiasis
 Trypanosoma brucei (gambiense) – milder form
 Trypanosoma brucei (rhodesiense)- cause sleeping sickness,
African trypanosomiasis
 Transmission:

 Trypanosoma cruzi reduviid bug

 Typanosma brucei tsetse fly
 Treatment:
 Nifurtimox (cruzi)
 TOXOPLASMOSIS

 Toxoplasma gondi (obligate intracellular)

 Opportunistic or congenital transmission

 Protozoa reproduces in cats

 Immunocompetent have no symptoms

 Reactivation occurs at CD4+ < 200 cells/μl

 50% of world population have titers

 Immunocompromised: Coryza, headaches, fever, seizures, muscle pain,

lymphadenopathy
 Congenital infection: abortion, encephalitis, MR, chorioretinitis, microcephaly,
hepatosplenomegaly
 Treatment in pregnancy: spiramycin or pyrimethamine/sulfadiazine
 BABESIOSIS

 Babesia microti is a sporozoa causing a zoonosis

 Transmission - Female Ixodes scapularis tick (also Borrelia), blood transfusion,

transplacental
 Asplenic patients are especially at risk

 Malaria-like intemittent fver, sweating, hemolytic anemia, jaundice, hemoglobinuria

 Maltese cross intracellular shapes (no pigment)

 Treatment:

 Quinidine + Clindamycin

 Atovaquone + Azithromycin
 AMEBIASIS

 Amebic Dysentery caused by Entamoeba histolytica

 Exist in 2 forms: Cysts and Trophozoites

 50,000-100,000 deaths annually

 Luminal or Systemic Infection

 Diarrhea, colic, hematochezia, liver abscess

 Treatment: Metronidazole, Tinidazole, Chloroquine, Iodoquinoline, Diloxanide,

Paramomycin, Tetracycline kills bacteria on which they feed
 CRYPTOSPORIDIOSIS

 Protozoal infection cause by a variety of Cryptosporidium species

 Occurs in immunocompromised patients

 Recurrent Diarrhea containing mucus

 May disseminate to hepatobiliary system, lungs, pancreas, bladder

 Round, acid-fast oocysts

 Isospora are oval, acid fast oocysts

 Treatment: Nitazoxanide
 GIARDIASIS

 Giardia lamblia infects the small intestines

 280 million infected world-wide/year

 Most contract from contaminated water

 Weakness, diarrhea, cramps, flatulence, loss of appetite, lactose intolerance

 Treatment – Metronidazole or Tinidazole

 HELMINTHS
Trematodes Cestodes
Nematodes
 Acaris  Schistosoma  Taenia
 Necator  Diphyllobothrium
 Clonorchis
 Ancyclostoma  Echinococcus
 Strongyloides
 Paragonimus
 Enterobius  Segmented
 Dracunculus 
 Intermediate hosts – Undercooked meats
 Onchocerca
(intermediate hosts)
 Wurchereria fresh water snails  Treatment:
 Brugia  Definitive hosts- Praziquantel,
 Loa loa
humans Niclosamide,
 Toxocara Albendazole
 Trichinella
 Treatment -
 Treatment-Albendazole, DEC, Praziquantel
Ivermectin
 Location Species Common Name/disease Mode of Transmission Treatment

Intestines Enterobius Pinworm Ingestion of eggs Albendazole, mebendazole, or

pyrantel pamoate

Trichuris Whipworm Ingestion of eggs Albendazole

Ascaris Round worm Ingestion of eggs Albendazole, mebendazole, or
ivermectin
Ancylostoma and Hookworm Larval penetration of skin Albendazole, mebendazole, or
Necator pyrantel pamoate
Strongyloides Strongyloidiasis Larval penetration of skin, also Ivermectin
autoinfection
Trichinella Trichinosis Larvae in undercooked meat Albendazole plus prednisone
larvae;Mebendazole adult worm

Tissues Wuchereria Filariasis Mosquito bite Diethylcarbamazine

Onchocerca Onchocerciasis (river Blackfly bite Ivermectin

blindness)
Loa Loiasis Deer fly bite Diethylcarbamazine

Dracunculus Guinea worm Ingestion of copepods in water Gradual extraction of worm

Toxocara larvae Visceral larva migrans Ingestion of eggs Albendazole or mebendazole

Ancylostoma Cutaneous larva migrans Penetration of skin Albendazole or ivermectin

larvae