Hepatitis D
HDV cannot cause disease without HBV. Hepatitis D is an enveloped (-)sense RNA virus with a circular genome.
HDV requires HepB Surface antigen (HBsAg) to cause infection.
Co-infection: both HepB and HepD are transmitted simultaneously.
Superinfection: HepD is transmitted ontop of existing HepB infection. Associated with worse outcomes.
Most acute infections clear without treatment.
Pregnant women and people with chronic infections should receive treatment. Treatment does not eradicate disease, only reduces damage by preventing replication.
Tx includes antivirals (Lamivudine) and nucleoside reverse transcriptase inhibitors (NRTIs) and IFN-
These drugs (except IFN-can be given to pregnant women prior to delivery.
If mother is HepB positive, baby must be treated with immunoglobulin and HepB vaccine (passive and active immunization).
FUNGI
Chapter 1: Systemic Mycoses
Histoplasma capsulata (The Historian’s Cave)
Systemic fungi can spread to other organ systems (typically originate in the lung). Systemic fungi have specific geographic distributions.
Histoplasma capsulata causes histoplasmosis.
Histoplasma is most commonly associated with bird or bat
droppings. It typically presents in people who were inside a cave, spelunkers, or farmers inside chicken coups.
Histoplasma is endemic in the Midwest and Central US along the Mississippi and Ohio River Valleys.
Transmission occurs via the respiratory systems. Spores in bird or bat droppings are inhaled and travel to the lungs, where they are ingested by macrophages.
Diagnosis of Histoplasma:
Macrophages from tissue samples or respiratory prep are stained with a KOH prep. Visualization of macrophages filled with small, intracellular oval bodies suggests Histoplasma.
Histoplasma is much smaller than a RBC and numerous
Histoplasma can be seen within a single RBC (macrophages are only slightly larger than RBCs). A single macrophage can contain 10 to 100 Histoplasma.
Histoplasma can also be cultured, but this is time intensive.
Rapid Histoplasma serum or urine antigen test is also used.
Histoplasma is dimorphic, which means that the form of the fungus is dependent upon the temperature of its surroundings (this feature is shared among all of the systemic fungi).
Mold in the cold and yeast in the heat.
In the soil (cold), the fungus is in the mold form.
In the body (heat or 37C), the fungus is in the yeast form.
Systemic fungi are generally asymptomatic or subclinical in most people. They can cause granuloma formation in some people, which results in pneumonia with cough. The granulomas of the lungs will eventually calcify, which leads to pulmonary issues.
Chronic Histoplasma can mimic TB with cavitary lesions in the upper lobes and calcified nodules with fibrotic scarring. Hilar Calcifications
Histoplasma can also cause erythema nodosum, which are painful red nodules that are usually found on the shins.
Systemic fungi are especially associated with the
immunocompromised. Immunocompromised persons can have disseminated Histoplasma. Dissemination to the liver and spleen results in hepatosplenomegaly with gross calcifications.
Fungus disseminates to the liver and spleen because the fungus targets the reticuloendothelial system, which has
abundant macrophages.
Dissemination can also produce some skin and neurological findings.
Systemic fungi can cause local infections or can progress to systemic infections. Treatment is dependent on the status of the infection.
Local infections and mild infections should be treated with – conazole drugs, such as Fluconazole or Ketoconazole.
Systemic infections should be treated with Amphotericin B (much stronger). Amphotericin is associated with numerous side effects and should be reserved for disseminated infections.
Blastomycosis dermatitidis (The Blast of the Cannons)
Blastomycosis dermatitidis causes blastomycosis.
Blastomycosis is endemic to the Great Lakes and Ohio River Valley (Southern and Eastern US). The distribution of Blastomycosis has some overlap with Histoplasma.
Blastomycosis is a dimorphic fungus that changes forms
depending on the temperature (mold in the cold, yeast in the heat).
Fungus lives in the dirt and has potential to become aerosolized. Spores are inhaled and are converted to the yeast form as it colonizes the lungs.
Blastomycosis replicates via broad based budding.
Blastomycosis is very large and appears roughly the same size as a RBC.
Blastomycosis causes the lungs to have a patchy alveolar
infiltrate (haziness) on CXR. Lesions or cavities may also be present on imaging.
This pneumonia can be acute or chronic and it is considered a local lung infection. The infection can spread to other organs, especially in the immunocompromised. The majority of infections are subclinical or asymptomatic.
Systemic infection typically only occurs in the immunocompromised.
Dissemination of Blastomycosis is most likely to occur in the skin and bones.
Chronic Blastomycosis infection with bone involvement can cause osteomyelitis.
Diagnosis can be achieved via KOH prep or culture.
KOH prep will show round yeast with a single broad based bud.
Blastomycosis can also be detected using a urine antigen test.
Treatment
Local infections are treated with –conazoles, such as Itraconazole.
Systemic or disseminated infections are treated with Amphotericin B.
Coccidioides immitis (Presidio San Joaquin)
Coccidioidomycosis is endemic to the Southwestern US.
Transmission occurs via inhalation of a single arthroconidium (spore). Spores normally reside within dust and transmission is greatly increased when large amounts of dust are dispersed into the air (dust storms and earthquakes are risk factors for spread of infection).
Frequent dust storms in San Joaquin Valley of California cause high incidence of Coccidioidomycoses San Joaquin Valley Fever is another name for Coccidioidomycosis.
Coccidioides is a dimorphic fungus that changes forms depending on the temperature.
In the cold, the fungus is in the mold form.
In the body, the fungus exists as spherules of endospores.
Spherules rupture and release endospores, which spread throughout the lungs and possibly throughout the body.
Cocci spherules are larger than a RBC (Cocci > Blasto = RBC >
Histo).
Coccidioidomycosis is asymptomatic or subclinical. In some it can present as a self-limited acute pneumonia with fevers, sweats, and arthralgias (lasts a couple weeks).
Radiographic imaging can be unremarkable in the majority of patients, but others may show cavities or nodules (or both).
Coccidioidomycosis can also cause erythema nodosum, which is an inflammatory condition that leads to the formation of red,
extremely tender nodules that are usually located over the shins.
Erythema nodosum is present in both Histoplasmosis and Coccidioidomycosis, but it is more commonly present in Coccidioidomycosis.
Erythema nodosum symbolizes a robust immune response and is typically only seen in healthy individuals.
In immunocompromised persons, the infection can disseminate.
Skin and lungs are common sites of infection in the immunocompromised.
Coccidioidomycosis may also disseminate to the bone in immunocompromised persons.
The fungus can also disseminate into the meninges, which results in a fungal meningitis (associated with headache and stiff neck).
Definitive diagnosis is achieved via a KOH stain or a culture.
Serology for antibody titers can be used for diagnosis (serology can be used for all systemic mycoses). IgM for Coccidioidomycosis would indicate recent infection.
Treatment is dependent on the status of the infection.
Local lung infections should be treated with –azole drugs, such as Ketoconzaole.
Systemic infections should be treated with Amphotericin B.
Paracoccidioides brasiliensis (Piratas del Sur)
Paracoccidioidomycosis is distributed in Brazil and other parts of South America. It is sometimes referred to as the Brazilian
Blastomycosis.
Geographic distribution = South America
Paracocci in yeast form has a distinct form, which consists of
multiple buds that radiate out from a central vacuole. This pattern is described as looking like a “Captain’s Wheel” with round and bulb shaped handles.
Paracocci is a dimorphic fungus. (Mold in the cold [environment], yeast in the heat [body]).
Paracocci yeast are very large; they are larger than a RBC (Paracocci and Cocci are roughly the same size).
Paracoccidioidomycosis is transmitted via respiratory droplets.
After inhalation, the fungus disseminates and causes
lymphadenopathy (cervical, axillary, and inguinal). As the disease progresses, it moves downwards to affect the lungs and upper respiratory system. In the lungs, the disease cause granuloma formation.
Mucosal ulcers can develop in the upper respiratory tract, especially in the mouth. The ulcers are often in the gum in the mouth with ragged borders and small spots of hemorrhage.
Mucocutaneous lesions and cervical lymphadenopathy are the most important defining clinical features of the fungus.
Treatment includes Itraconazole (mild infections) or Amphotericin (severe infections).