Exam 5 Flashcards
Fungi pathogens are most associated with:
Superficial Infections
Allergic Reactions
Are fungi thermotolerant?
No, optimal growth temperatures are well below body temperature
Fungal Pathogens two major growth forms:
Yeast
Mold
Ability to grow as yeast or hyphae
Dimorphism
Are Fungi Eukaryotes or Prokaryotes?
Eukaryotes
Glucan is a part of the Fungal Cell Wall. What are the two major types of glucan?
- B (1,3) glucan
- B (1,6) glucan
An important component for immune recognition by the host.
B (1,3) glucan and B (1,6) glucan are both synthesized by
B-(1,3)-glucan synthase enzyme
Chitin is also a part of the fungal cell. What is its importance?
Structural Component of the wall
Do Fungi produce ergosterol or cholesterol?
Ergosterol
Ergosterol is located where in the cell?
Fungal Plasma Membrane
Polyenes, Imidazoles, Triazoles, and Allylamines targets what?
Ergosterol and Ergosterol Synthesis in Plasma Membrane
_____ binds to ergosterol to form pores.
Polyenes
Amphotericin B and Nystatin are types of
Polyene
_______ and ______ inhibit fungal lanosterol 14-a-dmethylase to inhibit ergosterol synthesis. Toxic intermediate back up and increased membrance permeability.
Imidazoles and Triazoles
Ketoconazole, Itraconazole, Fluconazole, and Voriconazole are types of
Imidazoles and Triazoles
_______ inhibit fungal squalene epoxidase to inhibit ergosterol synthesis.
Allylamines
Terbinafine is a type of
Allylamine
Echinocandines targets
Cell Wall - B-(1,3) glucan synthase
__________ inhibits activity of B-(1,3)-glucan synthase depletion of glucans, decreased cell wall integrity.
Echinocandins
Caspofungin, Micafungin, and Anidulofungin are types of
Echinocandiin
Yeast can cause what disease?
Candidiasis, Cryptococcosis, and Pneumocytosis
Is Candididasis endogenous or exogenous?
Endogenous
Most common cause of candidemia?
C. albicans
Candida is a colonizer where?
GI tract, vaginal mucosa, and skin
Is Candidiasis opportunistic? (Needs Conditions (DM, Malnutrition, Immunosuppressive, Trauma) to infect)
Yes
Candidemia is
bloodstream infection of candida
Manifestations of Candidiasis
In immunocompetent hosts:
Thrush, Vaginitis, Cutaneous Lesions
In immune suppressed hosts
Esophagitis, Chronic Mucocutaneous Candidiasis (CMCC), Disseminated
Candidiasis virulence and pathogenesis
Adherence factors - allows yeast and hyphae to attach to tissues
“Yeast-to-hyphal” transition - phenotypic switching
Treatment of Candida species
Triazole (static)
Echinocandins (Cidal)
C. glabrata is resistant to what class of drugs?
Triazoles
Clinical Manifestations of Cryptococcosis
Subacute to Chronic Meningitis, Pneumonia, Skin Ulcers, and Bone Lesions
Can occur during defective T-lymphocyte function (AIDS, carcinoma, leukemia, Hodgkin’s lymphoma
Emerging Cryptococcosis pathogen
Cryptococcus gattii
Clinical Manifestations of Cyptococus gattii
Causes tumor-like lesions “cryptococcomas” in lungs, brain, and soft tissue.
More tolerant to antifungal compounds
Virulence and Pathogenesis of Cryptococcosis
Polysaccharide Capsule
Melanin deposited in cell wall (provides stress protection for intracellular survival)
Cyptococcus species are susceptible to
Triazoles
Pneumocystosis predisposing agents
AIDS, Pulmonary Infections
Pneumocystosis virulence an pathogenesis
Major Surface Glycoprotein (MSG) - acts as an attachment factor to several host proteins
Histologically - alveoli are filled with foamy exudate
Clinical manifestations of Pneumocystosis
Pneumonitis
Lesions outside the lung are common in AIDS patients
Treatment of Pneumocystis
Bactrim and Clindamycin
Bactrim and Clindamycin are treatment options for Pneumocystis but which drug has a higher incidence of adverse effects in AIDS patients?
TMP-SMX (Bactrim)
Are fungi opportunistic or true pathogens?
True Pathogens
Fungi are also thermal dimorphism
Body Temp = Yeast
Room Temp = Mold
Type of ENDEMIC Thermal Dimorphic Mycoses
Blastomyces dermatitidis
Coccidioides immitis
Histoplasma capsulatum
Endemic Dimorphic Mycoses: Pathogen for Histoplasmosis
H. capsulatum, endemic to the eastern US, near MS and OH river valleys
Endemic Dimorphic Mycoses: H. capsulatum and B. dermatitidis transmission
inhalation of airborne conidia (spores)
Endemic Dimorphic Mycoses: Histoplasmosis Virulence and Pathogenesis
Inhaled Conidia/spores convert to yeast phase at body temperature
Initial infection is pulmonary
Reticuloendothelial system is the focus of the infection (lymph nodes, spleen, bone marrow)
Endemic Dimorphic Mycoses: Histoplasmosis Clinical manifestations
Dependent on intensity of exposure and immune status of host
Low inoculum = asymptomatic
Heavy inoculum = primary pulmonary infection
Progressive (chronic) pulmonary histoplasmosis
Dissemination - higher incidence in children and immunocompromised
Calcified Nodules, Granuloma
Endemic Dimorphic Mycoses: Blastomycosis Clinical Manifestations
Respiratory Infection - asymptomatic or mild, resolves spontaneously
Systemic Blastomycosis - Defects in CMI are predisposing
Chronic Cutaneous Blastomycosis - ulcerated lesions, exposed or mucocutaneous tissues
Endemic Dimorphic Mycoses: Coccidioidomycosis pathogen
Coccidioides Immitis
Located to the desert southwest US, Mexico, and Guatemala
Endemic Dimorphic Mycoses: Coccidioides immitis initiates
Infectious Arthroconida
Endemic Dimorphic Mycoses: Coccidioidomycosis Virulence and Pathogenesis
Arthroconidia - highly infectious, but NOT highly virulent
Endemic Dimorphic Mycoses: Coccidioidomycosis Clinical Manifestations
Respiratory Infections
- Symptomatic Patients - VALLEY FEVER with malaise, cough, chest pain, fever
- Filipinos, African/Native Americans & Hispanics are at greatest risk of dissemination
Treatment of Endemic Dimorphic Pathogens
Blastomyces dermatitidis
Coccidioides immitis
Histoplasma capsulatum
Triazoles
Endemic Dimorphic Mycoses: Pathogen of Sporotrichosis
Sporothrix schenckii
Endemic Dimorphic Mycoses: Sporotrichosis is associated with
Decaying Vegetation.. Enters blood via splinter, thorn pricks (gardeners and landscapers)
Endemic Dimorphic Mycoses: Sporotrichosis is widely present in
Soil
Endemic Dimorphic Mycoses: Clinical Manifestation of Sporotrichosis
Skin Lesion begins as a painless papule (normally on hand or finger)
Papule larges and slowly ulcerates
Primary pulmonary Sporotrichosis
Treatment of Sporotrichosis
Triazoles
Characteristics of opportunistic mold
Monomorphic (produce hyphae in vitro and vivo, regardless of temperature
Opportunistic Mold can cause what diseases?
Aspergillosis
Mucormycosis (Zygomycosis)
Opportunistic Mold: Pathogen for Aspergillosis
Aspergillus fumigatus
Opportunistic Mold: Aspergillus fumigatus is present
Air vents and Construction and Remodeling efforts can aerosolize
Common contaminant in clinical laboratories
Opportunistic Mold: Clinical Manifestations of Aspergillosis
Allergic bronchopulmonary aspergillosis (ABPA)
- Elevated serum IgE
- Asthma type response
Aspergilloma
*colonization of paranasal sinuses and the lower airways
Occurs in pre-formed cavitary lesions (CF, Chronic Bronchitis, TB)
ASYMPTOMATIC
Invasive Aspergillosis
- Requires pre-existing pulmonary disease or immunosuppression
- Colonization of airways leads to localized tissue invasion by hyphae
Disseminated Disease
- Requires immunocompromised host
- Acute Pneumonia
Opportunistic Mold: Treatment of Aspergillus spp
Triazoles and Echinocandins
Opportunistic Mold: Mucormycosis (Zygomycosis) pathogenesis
Rapidly growing hyphae invade tissue
Opportunistic Mold: Mucormycosis (Zygomycosis) Clinical Manifestations
Pulmonary Mucorcycosis
Rhinocerebral Mucorcycosis
Primary Cutaneous Mucorcycosis (Contaminated Bandages)
Disseminated
What constitutes a parasite?
Protozoans: single cell organism
Helminths: Multicellular flatworms and roundworms
How do we become infected by parasites?
Fecal-Oral
Food-Borne
Vector-Borne
Skin-penetrators
What kind of hosts do parasites use?
Definitive - contains the sexually mature stages
Intermediate - maturational stage
Reservoir - an animal which can substitute for humans in a parasite’s life cycle
Paratenic - maintains the parasite through space and time
- *Some parasites use more than 1 host
- *Some parasites can convert one type of host to another
KEY Parasite Concepts
Parasitic Infection Tend To Be Chronic
EXCEPT: Malaria
Travel History is often very important to diagnosis
Elevated eosinophilia with contributing history may indicate parasitic infection
*IgE responses to worm infections attract eosinophils
The protozoan parasites
Malaria: Plasmodium spp
Blood-Borne Flagellates: Trypanosoma
Protozoan infections in AIDS patient: Toxoplasma gondii
Sexually Transmitted: Trichomonas Vaginalis
Properties of Protozoans
Single Celled, Eukaryotic Organism
May be intracellular or extracellular
Can live in GI, tissues, or vasculature
How do Protozoan exert their effects?
Interfering with nucleic acid synthesis orrrr carbohydrate metabolism
This pathogen causes Malaria
Plasmodium spp
In Malaria, a parasite growing within RBCs can cause
High Fever, Chills, and Profuse Sweating Fever Anemia Tissue Hypoxia Renal Failure Lung Edema Coma
The Plasmodium pathogen is carried by what?
Female Anopheles Mosquito and Human
*Different species burst RBC at different times
P. vivax and P. ovale Q48H = Tertian malaria
P. malariae Q 72 H = Quartan Malaria
P. falciparum Q 36-48 H
Plasmodium Life Cycle
Mosquito takes a blood meal injects sporozodes
After Infection of Liver Cell becomes Schzont
Malaria - Immunity
Host quickly mounts an immune response
Limits multiplication without eliminating infection = premunition
Leads to prolonged recovery period marked by recurrent exacerbations
Recovery likely requires the concerted effort of T- and B- lymphocytes
Which Malaria strands can form intrahepatic cysts that are dormant and survive the host’s immunologic attack?
P. vivax and P. ovale
P. vivax and P. ovale only infects
immature cells (reticulocytes)
P. malariae infects
Senescent Cells
P. falciparum infects
Mature RBC (most aggressive infection)
Parasites degrade hemoglobin within an acidic food vacuole for
Protein Requirements and Synthesize folate de novo
For Malaria, Chloroquine is used for treatment how?
Inhibits heme utilization by erythrocyte forms and ONLY KILLS ERYTHROCYTE FORM (Schizonts)
For Malaria, Primaquine is used for treatment and kills what Pathogen?
Liver schizonts of P. vivax and P. ovale
Prevention Protocols for Malaria
Prevent mosquito bit with pesticides, repellants
Mefloquine can be used for Malaria Chemoprophylaxis > 2 weeks before, weekly while in country , and 4 weeks after return, what is the MOA?
Inhibition of Lipid Trafficking and Nutrient Uptake
Doxycycline can be used Malaria chemoprophylaxis 1-2 days before, daily while in country, 4 weeks after return and normally least expensive, What is the MOA?
Inhibition of Mitochondrial Protein Synthesis
Atovaquone-Proguanil can be used for Malaria chemoprophylaxis 1-2 days before, daily while in county, 7 days after return, what is the MOA?
Combo electron transport chain and DHFR inhibitor
\_\_\_\_\_\_\_\_\_ and \_\_\_\_\_\_\_\_\_ can be used for Malaria prophylaxis and pregnancy. Atovaquone-proguanil Chloroquine Mefloquine Doxycycline
Mefloquine
Chloroquine
Blood-Borne Flagellates: Chagas’ Disease (Trypanosoma cruzi) can be transmitted by
Reduviid bug (“kissing bug”)
Feeds on sleeping human and defalcates near wound which then Chagoma develops
Pathogen for Chagas’ Disease
Trypanosoma cruzi
Chagas’ Disease ranges from what regions?
Texas, Mexico, Central America, South America
Chagas’ Disease survives in
wild animal reservoirs like rodents, opossums, armadillos
Systemic spread of Chagas Disease causes
acute phase with fever, malaise, swollen lymph nodes (can spread to heart and CNS)
Intermediate phase has no symptoms, but parasite remains for life
Chronic Disease for Chagas can develop years later and cause
Cardiac Arrhythmia, Increase Heart Size
Dilation of Esophagus and Colon, dysfunction
Treatment of Chagas’ Disease
Nifutimox - produces oxidative stress in parasite
Benznidazole - DNA binder
Both reduce severity of acute disease, but no activity in chronic infections
Toxoplasmosis pathogen
Toxoplasma gondii
Toxoplasma gondii is acquired through
interaction with infected cat, ingestion of contaminated pork, transfusions, transplacental
Cat is the definitive host where sexual reproduction occurs in the GI
Toxoplasmosis Common Manifestations
Reactivation of latent infection upon immunosuppression
- AIDS, immunosuppressive regimens for cancer or transplantation
- Leads to disseminated infection with myocarditis and encephalitis
- Fatal
Primary Infection in Pregnant Woman
- Risk of transmission is highest in the third trimester
- Abortion, stillbirth, microcephaly, psychomotor retardation
Treatment of Toxoplsmosis for Trophozoites
Pyrimethamine/sulfadiazine
Interferes with the regeneration of tetrahydrofolic acid from dihydrofolate by competitively inhibiting the enzyme dihydrofolate reductase
Treatment of Toxoplasmosis for Cysts
Atovaquone
Block pyrimidine biosynthesis
Pathogen for Trichomoniasis
Trichomonas vaginalis
- Trophozoite form is flagellated
- Lacks a cyst form, but can survive a few hours outside of host
Primary Manifestation for Trichomoniasis
Vaginits
- Discharge, Vulvar itching, burning sensation, dysuria
- Lasts weeks to month
- Can increase the risk of preterm birth and enhance susceptibility to HIV infections
Treatment of Trichomoniasis (T. vaginalis)
Metronidazole
*likely effective through alkylation of DNA
Nematodes are also called
Nonsegmented, Roundworms
Cestodes are also called
Tapeworms
Trematodes
Flukes
Nemotodes are covered by a
Flexible, Durable outer cuticle that is resistant to chemicals
Females are reproductive factories
Most females release shelled eggs, some release live larvae
Key Players in the Infection
Infective Ovum (microscopic)
- Contains single larva
- Eggshell is chemically resistant
Larvae (microscopic)
- Eosinophilic pneumonitis after extravasation
- MOST SYMPTOMATIC Phase
Adult Males & Females
- Inhibit Duodenum
- Mate about 2x per year
- Each female produces 200,000 ova per day
- Ova released into fecal stream
Helminths: Pathogenesis of Ascariasis
Pulmonary Phase
* Eosinophil-rich pneumonitis (cough, bloody sputum)
Intestinal Phase
- Symptoms proportional to adult worm burden
- Significant cause of malnourishment
- Small children have intestinal or biliary obstruction, leading to perforation
Helminths: Treatment of Ascariasis
Mebendazole or Albendazole
* Both inhibit sugar absorption in the parasite, energy loss
In light infections, when females use up their stored sperm, they can wander
- into the biliary/pancreatic duct system
- Up on out of the GI system
- Fever or pressurized airplane cabins also causes seeking behavior
Intestinal Nematodes
Ascaris lumbricoides
Toxocara canis
Strongyloides stercoralis
Enterobius vermicularis (pinworm)
Helminths: Types of Larva Migrans (COMES FROM ANIMALS)
CLM = Cutaneous Larva Migrans (Dog Hookworm) VLM = Visceral Larva Migrans (Toxocara canis - dog Ascaris - Toxocariasis) - COMMON IN SE US! OLM = Ocular Larva Migrans
Routes of Transmission for Toxocara
Fecal - Oral
Intrauterine
Transmammary
Predation - animal eat infected animal
T. Canis Life Cycle
Adult Helminths live in dog and cat small intestine
Animals eat embroyonated eggs
Eggs pass in feces and embroyonate in soil (Eggs are ingested)
Larvae hatch in small intestin, and penetrate wall
Larvae migrate to all organs via bloodstream
EYE, CNS, LIVER
Helminths: Clinical Manifestation of VLM
- Typical Patient is < 5 years old and heavily infected
- Presents with fever, hepato(spleno)megaly, lower respiratory symptoms
- Host response to T. Canis is characterized by eosinophil-rich granulomas encapsulating migrating larvae
- Pulmonary response includes bronchospasm, cough, wheezing, pneumonia
Helminth: Clinical Manifestation of OLM
Typical Patient 5 - 10 yearso ld
Presents with unilater vision impairment
Retinal granuloma formation can lead to blindness
Treatment of Larva Migrans (VLM & OLM)
Albendazole
Mebendazole
Pathogen for Strongyloidiasis
S. Stercoralis
Infection Route For Stronglyoides
Autoinfection
Direct Cycle
Indirect Cycle
Strongyloidiasis Clinical Manifestations
Acute Strongyloidiasis
- Pruritic Rash at larval penetration site
- Trachea irritation with a dry cough
- Diarrhea and constipation, abdominal pains and anorexia
Chronic Stronglyoidiasis (asymptomatic)
* Most Common are GI and cutaneous
* Diarrhea and constipatin, postpradial fullness, heartburn, and epigastric pain
LARVA CURRENS along buttock, perineum, and thigh
*Chronic Urticaria (Hives)
Hyperinfection Syndrome and Disseminated Strogyloidiasis
* Occurs in subclinical patients receiving hi-dose corticosteroids
–> Asthma, COPD exacerbation, organ transplantation
Hyperinfection: Larvae invade GI and Pulmonary
Disseminated: Larvae invade numerous organ systems
Basis of Hyperinfection (Strongyloidiasis)
Under normal condition, T cell-mediated immunity limits the intestinal worm burden to relatively small number of adult females. (With time, adults will die and be digested)
Immunosuppresion allows a greater number of females to establish in the gut
- Increased number of eggs and hatched larvae
- Larvae mature and reintiate the migration patten through lungs and GI
Treatment and Prevention of Strongylodiasis
Acute or Chronic Strongloidiasis - Ivermectin
Hyperinfection Syndrome and/or Disseminated
* Discontinue or taper steroids if possible and Ivermectin
PREVENTION
- Wear shoes when walking on soil
- Avoid contact with feces and/or sewage
Pinworm or Enterobius vermicularis is a pathogen for
Enterbiasis
Lifecycle for Enterbiasis
Female migrates to perianal area (usually at night) to lay eggs
Eggs are infectious within 4-6 hours
Causes severe itching
Ingested by humans
Treatment of Enterbiasis
Albendazole
This Cestodes (tapeworms) causes cysticercosis
Taenia solium (pork)
What does Cestodes inhabit? What is the head and body referred to?
Inhabit in the GI lumen
Head is called scolex
Body is called a strobila consisting of proglottids
Are Cestodes Asexual, Heterosexual, or Hermaphodites?
Hermaphodites
Outer Surface of Cestodes are called?
Tegument
Treatment of Cestodes
Rx Niclosamide
Taeniasis is aquired by
ingesting undercooked, contaminated meat.
Starts by human release of eggs or proglottids
Forms Cysticerci
What is Cysticercosis?
Acquired when human play the part of the pig, ingesting eggs rather than encysted larvae
Eggs hatch in small intestine, larvae migrate through body and encyst in brain and skeletal muscle
Cysticercosis causes Neurocysticercosis which can lead to
Seizures, Obstructive Hydrocephalus, and Focal Neurologic Deficits. Cysts will grow slowly for up to 10 years before dying. Antigenic contents lead to local inflammation and enhanced seizures.
Treatment of Neurocysticercosis
Albendazole
