Clinically Important Fungi and Protozoa (Chapters 21 - 26)

Dermatophytes

 fungi that invade keratinized tissue, leading to dermatomycoses

Dermatomycoses

the end product of dermatophytes

Ringworm

• Tinea corporis causes ringworm

• Tinea corporis has many names due to what gets infected: T.cruris, T.capitis, and T.unguinum

• They are all contagious fungal infections

• Transmission through unclean environment and fomites (inanimate objects, such as a cup or elevator rail)

• Because they are fungal infections, they can be treated with antifungal drugs. However, it takes weeks.

• If you have T.pedis (Athlete's foot), another name for Tinea corporis, you can get a secondary bacterial infection 

Candidiasis

• Candida albicans causes Candidiasis

• It is part of the normal flora (basically normal microbiota)

• Causes oral thrush, vaginitis, and is the most common nosocomial/hospital-borne fungal infection 

• Can cause a systemic infection in immunocompromised people

Candida auris

• Emerging fungal pathogen causing worldwide concern

• It causes serious infection in hospitalized patients, which is why it is an opportunistic infection 

• Transmission by the bloodstream, which spreads it throughout the body

• Highly resistant to antifungal drugs

• It needs special laboratory methods to identify it

Vulvovaginal Candidiasis

• Mostly caused by Candida albicans 

• Opportunistic infection 

• Can occur with uncontrolled diabetes, changes in pH, hormone changes, and long-term antibiotic therapy

Trichomoniasis

• Caused by protozoan (Trichomonas vaginalis) 

• Transmitted sexually (STD)

• Infect urogenital tract surfaces in both males and females

• Males rarely show symptoms (they are asymptomatic but can be carriers)

• T.hominis and T.tenax are normal commensals (one species gains/benefits while one species neither benefits nor loses) in the human body

Coccidioidomycosis

• Caused by Coccidioides immitis

• Common in the Southwest USA, obtaining the name “Valley Fever”. Also can be called “Darlings Disease”

• Transmitted through the inhalation of spores (molds)

• Inhalation of spores results in mild flu-like symptoms or no symptoms at all.

• In tissues, the organism can form spherules, thick walled-off body, filled with spores which helps with the diagnosis of the disease

• A significant issue for immunocompromised patients as it can spread to meninges or bones

Histoplasmosis

• Histoplasma capsulatum is commonly found in Central and Eastern US

• Transmitted through inhalation via soil fungal spores

• Soil fungal spores mature into an actively growing yeastlike form that can survive and multiply into macrophages

• Infection usually remains mild and is localized in the lungs in most cases

• Complications can arise such as pneumonia and an infection in the spleen, liver, and lymph nodes if the infection spreads

Pneumocystis pneumonia (PCP)

• Caused by Pneumocystis jiroveci, formerly known as P.carinii

• Invades lung cells

• An opportunistic pathogen, meaning that it doesn’t greatly affect healthy individuals. However, it greatly affects those who have a compromised immunity if it spreads to other organs

• Pneumocystis pneumonia (PCP) has a high fatality rate if people develop an infection and aren’t treated with antifungal agents

• Causes problems for people with AIDS

Blastomycosis

• Caused by Blastomyces dermatitidis

• Transmitted via wound or breathing spores into the lungs

• Spores mature into yeast cells which can get into circulation via macrophages and then spread to other organs

• Systemic blastomycosis can lead to extensive tissue damage

Aspergillosis

• Caused by Aspergilus fumigatus 

• It infects the lungs when the spores are inhaled

• The spores are often found in decaying vegetation

• Can become an invasive lung infection that leads to asphyxiation

• It is an opportunistic pathogen or in this case fungus, meaning that this is another fungal infection that causes problems for people with AIDS or an impaired immune system

Giardiasis

• Caused by Giardia duodenalis, also known as G.intestinalis or G.lamblia

• Cysts of the organism are ingested and go into the small intestine, developing into a trophozoite and sticking to the bowel wall. 

• They cause severe diarrhea with dehydration and can interrupt normal adsorption

• Only the cysts are not killed by chlorination, meaning that these are resistant to disinfectants

Amebiasis (Amoebic Dysentery)

• Caused by Entamoeba histolytica

• Can be an acute disease (severe, but short) or a chronic disease (long-lasting, or recurring)

• Cysts are ingested and develop into trophozoites in the colon

• Invade the intestinal mucosa and get into the bloodstream

• Intestinal lining damage can cause fecal material to get into the body cavity and cause “peritonitis”

• Cysts are not killed by normal chlorine concentrations in water, meaning that they are resistant to disinfectants

A small number of the population are asymptomatic carriers of E.histolytica

Cyclosporiasis

• More recently discovered protozoan causing intestinal disease

• Oocytes from Cyclospora cayetanesis are ingested and lead to watery diarrhea

• Oocytes are found in water or in foods like berries

Cryptosporidiosis

• Caused by genus Cryptosporidium

• The two main species infecting humans are C.hominis and C.parvum

• Oocysts are ingested and mature into sporozoites in the small intestine

• A significant issue for immunocompromised patients as immunodeficient individuals can have life-threatening diarrhea

• The usual source for the organism is contaminated diarrhea

Visceral Leishmaniasis

• Vectored by sand fly bite

• The Sand fly bite spreads the protozoan which enters the bloodstream

• A common disease in countries with a tropical climate

• While macrophages can ingest it, it can survive and continue to multiply within the organism

• While Visceral Leishmaniasis can have multiple forms, Leishmania donovani can cause extensive damage to the liver, spleen, and kidneys if left untreated, ultimately resulting in the organism's death

• Opportunistic pathogen associated with HIV

Malaria

• Common in tropical areas

• Vectored by an Anopheles mosquito infected with the organism

• The organism matures in three stages, labeled “sporozoite stage”, “merozoite stage”, and “trophozoite stage” in that order. 

• Individuals with the sickle cell trait actually possess some resistance to severe malaria due to the alteration of red blood cells caused by the sickle cell trait. This hinders the malaria parasite’s replication.

The three stages of Malaria

• Sporozoite stage - A female mosquito bites a human, carrying sporozoites which migrate through the bloodstream to the liver. They undergo schizogony in the liver cell, where trophozoites called merozoites are produced. This enters into the “Merozoite Stage”

• Merozoite stage - The liver cells rupture and merozoites invade the Red Blood Cells where they multiply. This enters into the “Trophozoite stage”

• Trophozoite state - The Red Blood Cells rupture periodically to release new merozoites. It also simultaneously raises the body temperature

  (Know the Asexual and Sexual stages of Malaria formation in the photograph)

Plasmodium falciparum

• While there are 4 species of Plasmodium, Plasmodium falciparum is the species that causes the most severe disease since it can lead to blood vessel obstruction.

• The protozoan has started to become more resistant to the chloroquine drug used to treat it

• The organism is best controlled by using pesticides against the mosquito population

• Recently, a mosquito has been developed with genetic manipulation that makes it resistant to infection with the organism. There are hopes that it will mate with the wild types and cause the wild mosquitos to no longer support the organisms.

Vaccine for Malaria

• Scientists are trying to develop a vaccine but it is hard to find the stage of the organism that protects against the infection 

• Pathogens can also further mutate many genes to evade the immune response

• However, the Mosquirix vaccine is now available for children which provides limited protection.

Chagas disease (American Trypanosomiasis)

• Caused by protozoan Trypanosoma cruzi and the infection usually occurs in southern USA. 

• Transmitted by the reduviid bug, or kissing bug

• The organism initially causes a fever and swollen glands, however, some people go on to a chronic form of the disease

• Nerves in various organs like the heart, skeletal muscles, and colon can be damaged

• An opportunistic pathogen, as if it infects pregnant women, can be passed onto the fetus (this means it can cross the placenta)

• It is difficult to treat at the chronic stage since the trypanosome can multiply inside host cells

Toxoplasmosis

• Caused by Toxoplasma gondii

• Can be found in the feces of cats as oocysts which can then infect a human

• Oocysts mature into trophozoites in host cells

• The organism can come from eating undercooked contaminated meat.

• Usually, the infection causes mild lymph node inflammation and is a self-limiting disease

• Can be transferred across the placenta, causing congenital defects

• An opportunistic pathogen, as it can cause problems for people with AIDS

• Research is being conducted to see if there is a connection between the organism and Schizophrenia

Cryptococcosis

• Caused by a budding yeast called Cryptococcus neoformans

• The primary route of infection seems to be airborne, as it occurs when the individual breathes in airborne Cryptococcus spores.

• These spores are commonly found in soil contaminated with bird droppings, leading to lung infection

• The fungus can spread to the central nervous system (CNS), and other parts of the body, leading to meningitis and systemic infections

• Primary causes problems for people with compromised immune systems, such as AIDS

Trypanosomiasis

• Trypanosomiasis is also known as the “African Sleeping Sickness”

• Caused by a protozoan (genus Trypanosoma) 

• Transmitted (vectored) by the bite of a tsetse fly

• The specific organism that infects humans is caused by either T.brucei rhodesiense or T. brucei gambiense

• The organism can infect all organs of the body and if left untreated, deterioration of the Central Nervous System (CNS) develops eventually leading to coma and death.

• It is hard to create a vaccine for Trypanosomiasis. This is because the organism constantly changes its membrane proteins to escape the host immune system making it hard to develop a vaccine with protecting antigens

Transmission routes

• Ringworm - Transmitted through unclean environment and fomites (inanimate objects, such as a cup or elevator rail)

• Trichomoniasis - Transmitted sexually (STD)

• Coccidioidomycosis - Transmitted through the inhalation of spores (molds)

• Histoplasmosis - Transmitted through the inflation of soil fungal spores

• Blastomycosis - Transmitted via wound or breathing spores into the lungs

• Aspergillosis - Transmitted through the inhalation of spores

• Giardiasis - Transmitted through the ingestion of cysts of the organism

• Amebiasis (Amoebic Dysentery) - Transmitted through the ingestion of cysts of the organism

• Cyclosporiasis - Transmitted through the ingestion of Cyclospora cayetanensis, leading to watery diarrhea

• Cryptosporidiosis - Transmitted through the ingestion of Oocysts, usually by contaminated water

• Toxoplasmosis - Transmitted through touching Oocysts found in the feces of cats 

• Cryptococcosis - Transmitted through the inhalation of budding yeast called Cryptococcus neoformans

Vectors

• Visceral Leishmaniasis - Vectored by sand fly bite

• Malaria - Vectored by Anopheles mosquito 

• Chagas disease (American Trypanosomiasis) - Vectored by reduviid bug, or kissing bug

• Trypanosomiasis - Vectored by tsetse fly

Vaccines and what they are

Malaria - Mosquirix vaccine

Ability to cross the placenta

• Chagas disease (American Trypanosomiasis) - If it infects pregnant women, it can infect the fetus

• Toxoplasmosis - Can be transferred across the placenta, causing congenital defects

Significant issues for immunocompromised patients, e.g. AIDS

• Candidiasis - Posibility of a systemic infection in immunocomproised people, like AIDS patients

• Candida auris - Causes a serious infection in hospitalized patients which often enters the bloodstream and spreads throughout the body

• Pneumocystis pneumonia (PCP) - It can cause complications if it spreads to other organs in individuals that have compromised immunity. The organism often causes problems for people with AIDS

• Aspergillosis - This is another fungal infection that causes problems for people with AIDS or with an impaired immune system

• Cryptosporidiosis - Immunodeficient individuals can have life threatening diarrhea

• Toxoplasmosis - The organism also causes a problem for people with AIDS

• Cryptococcosis - It primarily causes problems for people with compromised immune systems, e.g., AIDS

Developed resistance to drugs

• Candida auris - highly resistant to antifungal drugs

• Malaria - resistant towards the cloroquine drug used to treat it

Resistant to Disinfectants

• Giardiasis - Dormant form, the cysts, are resistant to chlorination(disinfection)

• Amebiasis (Amoebic Dysentery) - Dormant form, the cysts, are resistant to chlorination(disinfection)