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Fungal Infections and Antifungal Treatments Ringworm Candida Aspergillus Histoplasmosis

August 12, 2019


Distinguished future physicians welcome to
Stomp on Step 1 the only free videos series that helps you study more efficiently by focusing
on the highest yield material. I’m Brian McDaniel and I will be your guide on this
journey through Fungi. This is the 1st video in my playlist covering all of Microbiology
for the USMLE Step 1 Medical Board Exam. We are going to review Opportunistic Mycoses,
Systemic Mycoses, Superficial Fungal infections and Antifungal medications. This info isn’t very high yield for the
exam, but I want to give us a little bit of a foundation to build on. Fungi are a group
of eukaryotic organisms that present as either a unicellular organism (Yeast) or a multicellular
organism (Mold). They are nearly everywhere in nature, but only a small percentage can
cause disease in humans. Most of the infections that occur are asymptomatic or so mild that
that are not detected. Many of the pathogenic Fungi are dimorphic, meaning that they are
present in the form of a mold in colder temperatures and present in the form of yeast at warmer
temperatures (such as body temperature after infecting a human). A way to remember this
is the mnemonic “Mold in the Cold, Yeast in the Heat.” Fungi have a complex reproductive
life cycle that includes formation of Spores which can live in the environment in a vegetative
state. Humans usually contract fungal infections by acquiring these spores from environmental
sources such as soil. Most fungal infections do not have a person to person spread. Mold form hyphae while Yeast form budding
yeast and psuedohyphae. Both hyphae and Psuedohyphae are branching filamentous vegetative structures
of fungi and each form spores. True hyphae have septae or cell walls between sections
while psuedohyphae are formed by budding without a true cell wall/septae between sections. The high yield fungal infections can primarily
be broken down into two groups, Systemic and Opportunistic. Fungi in the systemic category
have a higher virulence and can infect health individuals. While these fungi can infect
immunocompetent individuals the infections are usually mild and localized to the respiratory
system. In immunocompromised individuals the infections can more commonly spread from the
lungs and disseminate to the rest of the body. Systemic fungi are found in specific geographic
regions so when a question stem mentions a specific state that should be a buzzword to
consider these fungi. Opportunistic Fungi are lower virulence and have to “wait for
the right opportunity” to infect a host. Opportunistic infections usually only occur
in immunocompromised patients such as those with AIDs, transplanted organs or cancer.
For both systemic and Opportunistic Mycoses infections the route of infections is most
often inhalation of a spore from an environmental source. This first leads to a respiratory
infection, and then given the right circumstances the infection may then spread to other parts
of the body. Candida is the exception as it is normal skin flora. We all have Candida
present on our skin and it only causes a problem when factors lead to an overgrowth of the
fungi. The highest yield systemic mycoses are histoplasmosis,
blastomycosis & Coccidioidomycosis. The highest yield Opportunistic Mycoses are Candida, aspergillus,
cryptococcus, mucormycosis & Pneumocystis Jiirovecii. For the most part, these different fungal
infections cannot be differentiated based only on the signs and symptoms. Most of the
fungi present like pneumonia with vague flu like symptoms. Therefore, the different fungi
are primarily differentiated based on histologic examination of the sputum, biopsy or swab.
A stain such as PAS or silver stain is usually needed to visualize the fungi. You should
be able to identify the histology of each fungus via a pictures and a text description
of the findings as you can be presented with either in the question. Coccidioidomycosis is one of the Systemic
Mycoses. I give it a high yield rating of 3. If you would like to learn more about that
rating system please go to my website. Coccidio tends to be found in the southwestern part
of the US. Question stems for Coccidioidomycosis may also mention a recent earthquake or an
occupation such as construction which can help spread spores from soil into the air.
Appears as “Spherule full of endospores” on sputum culture. Here you can see the larger spherule with
the smaller endospores inside of it. Eventually the spherule will rupture releasing the smaller
endospores. Histoplasmosis is another Systemic Mycoses.
It is found primarily in the Mississippi and Ohio River Valley. Histoplasmosis questions
may make mention of the patient being in caves or cleaning bird cages as it can be found
in sole contaminated with bat or bird droppings. On histology you find “macrophages filled
with many ovoid cells” since this fungi is intracellular. Here is a picture of that histology, which
could be better but I’m limited by copyrights with what pictures I can show you. If you
want better pictures just google it Blastomycosis is also a Systemic Mycoses.
It is found east of the Mississippi River and is often associated with exposure to bodies
of water like ponds and riverbanks. Histologically it appears as a large yeast with “Broad
Based Budding” which you can remember with the mnemonic “All Bs” for blastomycosis,
broad, based and budding. Here are a couple pictures of that histology. Here is a map I made that shows roughly where
you can get the different systemic infections in the United States. You have coccidio in
the southwest. Histo in the eastern part of the country from the Mississippi River over
to the coast. And Blasto is sort of in the middle of the country around the Mississippi
and Ohio rivers. Note that there is an overlap between Histoplasmosis and Blastomycosis. Cryptococcus Neoformans is an opportunistic
mycoses infection associated with exposure to pigeon droppings. Following inhalation
and infection of the respiratory system, Cryptococcus has a predilection for spreading to the meninges
and causing Meningitis. Cryptococcus is monomorphic and not present as a mold. Its main virulence
factor is an antiphagocytic polysaccharide capsule which can be seen with India Ink stain.
Histologically it appears as singular budding yeast with a “halo.” Here is just a gram stain so you can’t see
the capsule. Here is a picture of india ink staining where
you can see the capsule halo Aspergillus Fumigatus is an Opportunistic
Mycoses with a number of different high yield presentations. Allergic Bronchopulmonary Aspergillosis
is when the fungus colonizes the airway of patients with CF or asthma leading to a hypersensitivity
reaction. It presents with asthma like symptoms and migratory pulmonary infiltrates. It can
be identified with an aspergillus skin test. An Aspergilloma (AKA “Fungus Ball”) is
when the fungus fills up a cavitary lung lesions previously formed by a TB infection or other
lung injury. Here is a picture of a fungus ball filling
up a cavity in the lung Aspergillus is also associated with hepatocellular
carcinoma as the fungus produces a carcinogenic Aflatoxin. Histologically aspergillus presents
with “V-shaped” hyphae branching at acute angle Here is a picture of the branching hyphae
with acute angle of roughly 45 degrees or less Pneumocystis Jiroveci is an opportunistic
infection that primarily presents as Pneumocystis Pneumonia (PCP) in patients with AIDs. PCP
usually has diffuse bilateral interstitial infiltrates in patients with CD4 T Cell counts
below 200. Once counts are below 200 AIDs patients should be given Trimethoprim/Sulfamethoxazole
prophylaxis to prevent PCP. Previously known as Pneumocystis Carinii. Mucormycosis & Rhizopus (AKA Zygomycosis)
are opportunistic mycoses that are usually seen in diabetics (most often during ketoacidosis).
It results in an infection of paranasal sinuses or the eye that can extend into the brain.
The fungi infect the vessels and can form a clot leading to a necrotic black eschar.
Histologically it has “ribbon like” hyphae without septae branching at a wide angle (about
90 degree). Here are a couple examples And here is one more example where you can
see the ribbon like hyphae without septae We have already discussed the more serious
fungal infections which can spread through the body. Now we will move onto the less serious
infections which are localized to the skin, mouth and/or vagina. Tineae is a group of common fungal infections
that are primarily localized to the skin, hair and/or nails.
Dermatophytes cause Tinea Corporis (AKA Ringworm), Tinea Pedis (AKA Atheletes Foot), Tinea Capitis
(a superficial scalp infection) & Tinea Unguium (infection of the nails). Scrapes of these
superficial fungal infections can be shown on KOH prep to have a “spaghetti and meatball”
pattern of hyphae and yeast balls. Athlete’s foot is a scaly pruritic erythematous lesion
of the feet most common in young adults. Ringworm usually presents as a scaly erythematous
circular lesion with central clearing. Tinea Capitus is a scaly area on the scalp
which may have localized alopecia (or hair loss). Infections of the nails (AKA Onchomychosis)
are more commonly in elderly individuals, are very tough to treat and present with thickened
opacified nails. Tinea Versicolor is caused my Malassezia Furfur
and leads to well demarcated areas of hyperpigmentation or hypopigmentation. It is more common in
young adults especially in hot weather and occurs on the trunk more than other regions. Candida is part of normal skin flora and the
most common cause of fungal infection worldwide. It is an opportunistic infection that most
often effects the vagina (AKA “Yeast Infection”), mouth/tongue (AKA “Thrush”), and genital
area (AKA “Diaper Rash”). However, it can also occur in the esophagus (particularly
in HIV patients), between skin folds (primarily in the obese), and heart valve (IV drug users).
Infections can arise soon after antibiotic treatment as the removal of “good” bacteria
allows for overgrowth of the fungal flora. Histologically it presents with oval budding
yeast and psuedohyphae. It forms germ tubes (true hyphae) when incubated at 37 degree
Celsius for a few hours. And I also have a picture of oral thrush here.
I’m going to do an entire video on vulvovaginal infections so I will save the details of that
type of candida infection for that video. Sporotrichosis is seen when spores on a thorn
get introduced under the skin by a thorn prick. Question stems usually mention a rose gardener.
In immunocompetent individuals it causes a localized subcutaneous nodule and/or an ulcer
at the site of skin breakage. That brings us to the antifungal medications.
The Azoles (Fluconazole/Diflucan, Ketoconazole, Miconazole, Itraconazole …) inhibit the
cytochrome P450 Lanosterol 14 Alpha Demethylase enzyme which is necessary to convert Lanosterol
into ergosterol. Ergosterol is important for fungal function as it acts in the cell membrane
similar to cholesterol in our cells. Mutations that encode for the enzyme can prevent the
drug from binding to the enzyme and lead to drug resistance. This class of drugs has a
wide range of antifungal uses, from serious to mild. Some are even available over the
counter. Amphotericin B & Nystatin bind to ergosterol
in fungal cell membranes creating pores. Nystatin is most commonly used in the form of “Swish
and Swallow” mouthwash for thrush. Amphotericin B is used only for serious systemic fungal
infections or fungal meningitis due to its severe side effects. Soon after it is administered
Ampho B can cause fever, chills & hypotension (AKA “Shake and Bake”). The drug is also
nephrotoxic.

9 Comments

  • Reply Kat K March 19, 2016 at 4:17 am

    Your videos are wonderful.

  • Reply Musa Absi June 29, 2016 at 12:56 am

    very helpful thank you

  • Reply Hanadi Nasser July 24, 2016 at 3:04 pm

    Is this information enough?

  • Reply David Rose October 16, 2016 at 10:32 pm

    does hydrogen peroxide kill fungi?

  • Reply John Foley April 18, 2017 at 7:10 pm

    THANK YOU !

  • Reply DARLENE GAUDAS April 24, 2017 at 8:46 am

    FUNGUS. Merde!:))

  • Reply motasim ghassab February 10, 2018 at 11:12 pm

    spaghetti and meatballs are for tineae versicolor not dermatophyte..and thanks for the great video

  • Reply Slay Step 1 August 28, 2018 at 4:59 am

    Uh Malassezia furfur is not a dermatophyte.

  • Reply Jack Salvatierra January 22, 2019 at 6:18 pm

    Hi there, Whats is the difference between the cryptococcosis and the other???

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