Fungal and Parasitic Infections/Antifungals

are fungi prokaryotes or eukaryotes?

eukaryotes (therefore, many aspects of the cellular physiology of fungal and human cells are very similar)

what are the few antifungals that are available?

• Fluconasole

  • Target: biosynthesis of ergosterol (cell membrane lipid)

• Caspofungin

  • Target: cell wall

• Amphotericin B

  • Target: cell membrane

  • Very toxic

Fungal Infections: Encounter

Typically, from the environment

• Exception: Candida albicans is a human commensal

Fungal Infections: Entry

• Inhalation

• Traumatic implantation

• Disruption of natural barriers (skin, mucosal surfaces)

Fungal Infections: spread/multiplication

• Fungal infections are usually mild and self-limiting

• Host response typically eliminates fungi

what is an important mechanism of the host response when eliminating fungi?

Phagocytosis by neutrophils

Fungal Infections: damage

• Indirect damage due to the inflammatory response

• Occlusion of organs

• If invasive, can cause destruction of host tissues

what are some examples of occlusion of organs caused by fungal infections?

• Fungus balls occlude bronchi in lung or tubules or ureters in kidney.

• Fungus mats growing on heart valves may break off and travel through blood causing arterial occlusion (Aspergillus)

The following statements about fungal infections are correct EXCEPT one. Which is the EXCEPTION?

A. Fungal infections are always acquired from the environment.

B. Fungal infections are usually mild and self-limiting.

C. Fungal pathogens are eukaryotes, which limits the targets for

antifungal drugs.

D. Immunosuppression can predispose to severe disease.

A. Fungal infections are always acquired from the environment.

Mortality due to fungal infection is high in what groups?

the immunocompromised

primary vs opportunistic fungal pathogens?

Primary → Can cause disease in immunocompetent host

Opportunistic → Typically, cause disease in the immunocompromised hosts

Coccidioides immitis is endemic to what region? and encounter?

Southwestern US, Mexico, parts of South America

encountered via soil/dust storms

Coccidioides immitis: entry

inhalation

Coccidioides immitis: disease

Coccidioidomycosis (aka Valley Fever)

Not contagious

Coccidioides immitis

what does it mean that Coccidioides immitis is a dimorphic fungus?

Symptoms of Coccidioidomycosis

• 60% – Asymptomatic or mild disease

  • None

  • Mild upper respiratory infection

• 35% – Symptomatic (symptoms within 1-3 weeks

  • resolves spontaneously

  • Cough, sputum, chest pain, fever, chills, night sweats, anorexia, weakness, arthralgia, rash (erythema nodosum)

• 1% – Disseminated disease

  • Risk: immunocompromised, pregnant, Black, Filipino

  • Skin, bones, joints, and brain

  • Ulcers, skin lesions

  • Meningitis (headache

Coccidioides immitis: treatment

oral itraconazole

For severe or disseminated infection, immunocompromised host: Amphotericin B until improved then oral itraconazole

Korean female, 74 years old

Visits daughter in Phoenix, Arizona for several months. Upon return home to Korea, develops a dry cough, night sweats.

Treated symptomatically. Symptoms resolve.

Several years later, routine chest radiograph shows pulmonary nodule.

Nodule is thought to be a malignancy and is removed. Fungal stain shows Coccidioides immitis.

Patient recovered from surgery and required no further treatment.

Diagnosis?

Pulmonary coccidioidomycosis without spread.

72 years old, resident of Ohio, spends winters in Arizona.

Presents to clinic in Ohio with hypothermia, dehydration, “generalized, pruritic maculopapular rash”.

A clear chest radiograph. Later, developed fever, cough, had left lower lobe infiltrate.

Given broad spectrum antibiotics but worsened. Required mechanical ventilation and received systemic steroids. Initially improved but then deteriorated rapidly. A bronchoalveolar specimen revealed Coccidioides immitis.

diganosis?

Disseminated coccidioidomycosis with atypical rash

The following statements about Coccidioides immitis are correct EXCEPT:

A. It can grow in the human body.

B. It is a dimorphic fungus.

C. It is found in the United States in a particular geographic area.

D. It only causes serious infection in immunocompromised people.

D. It only causes serious infection in immunocompromised people.

t/f: Immunosuppression predisposes to disseminated disease

true

what are predisposing factors to a candida albican infections?

Immunosuppression

Broad-spectrum antibiotics

what are predisposing factors to a cryptococcus neoformans infections?

AIDS

Immunosuppression

t/f: Disseminated disease can occur in immunocompetent people

true

characteristics of candida albicans

• commensal (oropharynx, gut, and skin)

• of endogenous origin

• opportunistic

• nosocomial

A 24 years old female partner of an IVDU presents with weight loss, pain on swallowing (odynophagia), and nausea

Superficial, raised white plaques on mucosal surface of esophagus viewed through endoscope.

Patient found to have HIV infection and advanced AIDS at presentation

Oropharyngeal/Esophageal candidiasis

what are some different forms of mucocutaneous candidiasis?

what does it mean that Candida albicans is a dimorphic fungus?

55 years old male was admitted to ICU after perforated duodenal ulcer. Underwent drainage of intraabdominal abscess and repair of ulcer 10 days ago. On IV nutrients and broad-spectrum antibiotics.

Develops fever of 39.9 C, hypotension

WBC = 18,200 with 90% neutrophils

Blood cultures in 2/4 bottles positive for “yeast”

Invasive candidiasis

mortality rate of Invasive candidiasis

40%

Predisposing factors for invasive candidiasis

• Cancer, organ and bone transplants, AIDS

• Burns, surgeries, trauma, long-term use of intravenous or intra-arterial catheters

• Treatment with broad-spectrum antibiotics

characteristics of invasive candidiasis?

• Critically ill or post-surgical patients

• Neutropenic (neutrophil deficient) hosts

• Dissemination

• Skin, Eyes, Bone

• Difficult to diagnose

Treatment strategies for Invasive Candidiasis

1. remove vascular catheter

2. reduce immunosuppression

3. treat with antifungal agent

A 25-year-old male patient has creamy white patches with a cottage- cheese-like appearance on his tongue. The patient notes that he has difficulty swallowing. The patient was healthy as a child and has not consulted a physician for several years. He is not currently taking any medications. Infection with what agents would you suspect?

A. Candida albicans and Streptococcus mutans

B. Candida albicans and Streptococcus pneumoniae

C. HIV and Candida albicans

D. HIV and Streptococcus mutans

C. HIV and Candida albicans

what is the most common cause of fungal meningitis?

Cryptococcus neoformans

what can cause reactivation and dissemination to CNS of Cryptococcus neoformans?

immunosuppression

what is the most common predisposing factor of reactivation/dissemination of Cryptococcus neoformans?

AIDS

Cryptococcus neoformans is ______ in the environment and is typically cleared but can cause…?

ubiquitous

latent infections

Cryptococcal meningitis: onset

acute or gradual

Cryptococcal meningitis disease correlates with

level of immunosuppression

In AIDS patients, there is often another site of infection → Skin, lung, blood

Cryptococcal meningitis disease symptoms

– Headache, lethargy, coma, personality changes, memory loss

– Fever sometimes present

32 years old male, HIV+.

Presents with papules, often umbilicated, on his face and body.

Sample obtained by curettage from one of the papules showed an encapsulated yeast.

Cultures of CSF, blood and skin grew Cryptococcus neoformans.

He was successfully treated with Amphotericin B, followed by daily oral fluconazole

Cryptococcal meningitis

what is an example primary fungal pathogen?

Coccidioides immitus

what is an example opportunistic fungal pathogen?

Candida albicans (colonize oropharynx, GI, skin)

Cryptococcus neoformans

parasites are prokaryotes/eukaryotes?

eukaryotes (therefore, they share many aspects of the cellular physiology with humans)

Unicellular parasites are called ..?

Multicellular parasites are called …?

protozoa

helminths (worms)

what are the different grwoth strategies of parasites?

• extracellularly

  • Some protozoa and all helminths

  • Often, fecal-oral transmission

• intracellularly

  • Some protozoa

  • Vector transmission (insect bite)

    • unstable in environment

what’s an example of a parasite that replicates extracellularly?

Giardia species (diarrhea) grow/multiply in lumen of GI tract

what’s an example of a parasite that replicates intracellularly?

Plasmodium species (malaria) grow/multiply in RBCs

Protozoa are unicellular organisms that typically, exist as two forms:

• trophozoite (active form that replicates)

• cyst (dormant form that is transmitted)

malaria infects 2 hosts:

humans and mosquitor=s

Malaria: encounter, entry, and multiplication

Encounter: infected mosquitoes

Entry: bite

Multiplication: inside red blood cells (RBCs)

malaria: disease/symptoms

• flu-like illness, fever, chills, headache, muscle aches, and tiredness

• nausea, vomiting, and diarrhea may also occur

• Ranges from very mild illness to severe disease and even death

malaria: treatment and prevention

Prevention: insect repellent, bed nets, drugs

Treatment: drugs

Leishmaniasis has 2 hosts:

humans and sand flies

Leishmaniasis: encounter, entry, and multiplication

Encounter: infected sand flies

Entry: bite

Multiplication: inside macrophages

Leishmaniasis: disease/symptoms

• Cutaneous: volcano-like skin sores

• Visceral: fever, enlarged spleen and liver, weight loss, low blood counts

• Asymptomatic

Leishmaniasis: prevention/treatment

Prevention: insect repellent

Treatment: drugs

Giardia: encounter, entry, and multiplication

Encounter: contaminated water, mountain streams

Entry: fecal-oral route

Multiplication: lumen of the GI tract

Giardia: disease, prevention, and treatment

Disease: diarrhea

Prevention: drinking clean water

Treatment: drugs

The following statements about protozoa are correct EXCEPT:

A. Despite being unicellular, protozoa can exist in multiple developmental stages.

B. Protozoa are prokaryotes, so their infections are treated with antibiotics.

C. Protozoa are single-celled, microscopic organisms that can perform all the necessary functions of metabolism and reproduction.

D. Protozoa are typically transmitted indirectly.

B. Protozoa are prokaryotes, so their infections are treated with antibiotics.

Helminths are multicellular organisms that grow and multiply _________ because of their large size

extracellularly

how many hosts do helminths infect?

Complex lifecycles with more than one host.

Often unable to complete their lifecycle in one host, so they cannot increase in number within that host.

what is the most common human helminthic infection globally?

Ascariasis

Ascariasis is transmitted via

fecal/oral route

Occurs in warm climates where untreated human feces are present

Ascariasis lifecycle

1. Ascaris eggs are excreted in stool

2. Eggs must mature into larvae in a warm environment

3. Larvae are ingested and grow into worms in different organs in the human host (GI and lung)

Ascariasis: encounter, entry, and multiplication

Encounter: untreated feces

Entry: ingestion

Multiplication: complex lifecycle

Ascariasis: disease and treatment

Disease: Abdominal pain, intestinal obstruction (Mild symptoms)

Treatment: drugs

Schistosomiasis infect 2 hosts:

humans and freshwater snails

Schistosomiasis: entry, encounter, and multiplication

Encounter: skin contact with contaminated water (grows in freshwater snails)

Entry: penetrates unbroken skin

Multiplication: complex lifecycle (Human→ liver, bowel, bladder)

Schistosomiasis: disease and treatment

Disease: rash, hepatic scarring that causes obstruction of blood flow and build up of fluid in the abdominal cavity

Treatment: drugs

Schistosomiasis lifecycle

1. Eggs in water infect snails and mature into cercariae (juveniles)

2. Cercariae leave the snail and penetrate the skin of a human, enter the blood, mature to worms in abdominal veins

3. Female worms produce eggs that migrate to the GI and the bladder

4. Eggs are excreted in stool and urine and end up in fresh water

Which of the following statements about the prevention and control of parasitic infections is TRUE?

A. Consumption of well-cooked beef reduces the risk of malaria.

B. Good oral hygiene protects against giardiasis.

C. Insect repellents and insecticide treated bed nets represent effective methods for the prevention of ascariasis.

D. Wearing of protective footwear in locations where humans have defecated protects against schistosomiasis.

D. Wearing of protective footwear in locations where humans have defecated protects against schistosomiasis.