Exam 4 Micro

Parvovirus

Parvovirus

• Small, non-enveloped linear ssDNA virus

• Mechanism:

  • Tropism for erythrocyte P Ag:

    • immature adult erythroid progenitor cells

    • placental trophoblasts, fetal liver, heart and myoblasts cells

  • Virus replicates in S-phase in rapidly dividing cells, causing S-phase arrest and cell death, reducing functional RBC

• Clinical Findings:

  • Fever, Chills, HA, Myalgias, Rash, Arthralgia

  • Decreased Reticulocytes, HgB

• Diseases:

  • Fifth Disease (Erythema Infectiosum)

    • Normal children: Low grade fever and malaise followed by rash during 2nd week

    • Rash seen first on cheeks, then progresses to reticular rash on trunk and limbs

      • Rash is result of Immune complexes that form after viral clearing

  • Arthropathy

    • Normal adults (+/- rash)

    • 50% have transient arthralgia/arthritis, usually women

      • Acute “RA-like” arthritis

      • Symmetric joint stiffness

      • Mostly in small joints (wrists, hands, feet)

    • Diagnosis: B-19 antibodies in plasma

  • Transient Aplastic Crisis

    • In patients with increased destruction of rbc and corresponding increased production, B19 infects the rbc precursors and results in a loss of rbcs

    • Decreased erythropoiesis with severe anemia in patients with:

      • Sickle cell, thalassemia, anemia, malaria

        Thrombocytopenia, neutropenia, pancytopenia

  • Persistent Anemia

    • Immunodeficient/Immunocompromised

    • Persistent infection because no Ab

      • Viruses aren’t cleared and continue infecting premature rbc

  • Hydrops Fetalis

    • Transplacental transmission from infected mother (may or may not have had mild cold symptoms)

    • Miscarriage and/or hydrops fetalis

    • 2nd trimester highest risk

      • 30% risk of infection if mother infected

      • 5-9% fetal loss

    • Presentation

      • Fluid accumulation in fetus

      • From severe anemia, possible myocarditis

      • Diagnosed on ultrasound

      • For all cases, 50%-90% fatality

      • 10-20% of cases due to B19

  • Congenital Anemia

Adenovirus

• Naked, ds linear, Icosahedral virus with its own DNA-dependent-DNA polymerase

• Attributes:

  • > 60 serotype, 7 subgroups (A-G)

  • 3 vaccines for military against serotypes 4,7, delivered in a coated capsule

  • Transmission via respiratory droplets, fecal oral route, direct contact, fomites and cervical secretions during birth

• Pathogenesis:

  • Replicates in dividing epithelial cells and kills

  • Immune evasion-interfere with MHC/peptide surface expression which results in decreased T cell recognition

  • Immunocompromised

    • more severe disease

    • Viremia spreads to kidneys, bladder, lymphatic system and causes inflammation

    • Pneumonia

      • Can remain in lymph nodes for 6-18 months

        Shed virus (even if carrier is not overtly sick)

• Clinical Presentation:

  • Accounts for 10% of acute febrile illness in the under 2 population

  • Acute Respiratory Distress (ARDs) in military recruits

• Diseases:

  • Exudative pharyngitis

    • Occasionally progresses to pneumonia or Acute Respiratory Disease

    • In late winter, spring

    • #1 cause of infectious conjunctivitis

      swimmer’s conjunctivitis from improperly maintained pools

  • #2 cause of diarrhea/gastroenteritis in kids

    Watery, non-bloody diarrhea, nausea, vomiting, cramps

    • Summer

    • Daycares

• Diagnosis

  • PCR or cell culture followed by Ab testing for epidemiology purposes

Human Papillomavirus

• naked icosahedral, circular dsDNA viruses

• Uses host DNA polymerases in nucleus

• Attributes:

  • > 250 genotypes

  • Plantar, cutaneous, flat, genital and palmar warts

  • Asymptomatic/unknown infections in which HPV remains dormant are common

  • Transmission:

    • Viruses on wart surfaces transmitted by skin-skin contact

    • Breaks in skin/mucus membranes necessary for spread

    • Cutaneous warts don’t spread easily

    • Mucus membranes more conducive

      • sex causes microlesions in skin/efficient transfer

    • Possible vertical transfer

• Pathogenesis:

  • Produced by low- and high-risk genotypes and needed for life cycle

  • Cells stimulated to enter S phase by E5, E6, E7

    • E5: binds EGF, stimulates mitosis, inhibits apoptosis

    • E6: degrades p53, blocks apoptosis

    • E7: inhibits RB, prevents cell cycle arrest

  • Persistent HPV infection can lead to cancer

    • Invasive cervical, intraepithelial neoplasia, anal, penile, oropharyngeal

    • DNA replication stress from entering cell cycle aberrantly - chromosome numerical and structural instabilities

    • E6 and E7 expression is deregulated leading to over-expression without productive virion production

      HPV genome integrates into host cell DNA at unstable loci

• Clinical Presentation:

• Diseases:

  • Common Cutaneous Warts

    • HPV2, HPV4

  • Flat Warts

    • HPV 3, HPV 10

  • Plantar and Palmar Warts

    • HPV 1, HPV 4

  • Anogenital Warts, Cervical Papillomas, Penile Warts, Respiratory Papillomatosis

    • High Risk Cancer Genotypes: 16, 18, 31, 33, 45, 52, 58

      • 16, 18, 31, 33, 45: 75% squamous cell carcinoma and 94% of all adenocarcinomas

    • Low Risk Cancer Genotypes: 6, 11

      • 6, 11: 90% of genital warts

• Diagnosis/Treatment

  • Verrucous: plates/debris that form thin fingerlike projections

    Mucosal, cervical lesions can be coated with 3-5% acetic acid and turn white

    Cervical intraepithelial neoplasia

    • Biopsy/Pap smear shows koilocytes with shrunken nucleus or multinucleated cells, and perinuclear halos

  • Vaccine

    • Gardasil 9, FDA licensed

      • Recombinant major capsid protein L1 (virus like particles)

      • Prevents infection: types 6, 11, 16, 18, 31, 33, 45, 52, 58

      • Recommended at 11-12, 13-26, 27-45

Polymavirus (John Cunningham)

• nonenveloped, circular, dsDNA, icosahedral

• Clinical Presentation:

  • Targets Immunocompromised

• Diseases:

  • Progressive Multifocal Leukoencephalopathy (PML)

    • Impaired memory, confusion, neurological signs (hemiparesis, visual impairment, coordination issues)

• Diagnosis/Treatment:

  • MRI/CT-white matter lesions, demyelination

  • Reduce immune suppression

    • Death 3-6 months after onset

Polymavirus (BK)

• nonenveloped, circular, dsDNA, icosahedral

• Clinical Presentation:

  • Associated with kidney, bone marrow transplants, immunocompromised

  • Slow progressive rise in BUN and Creatinine

• Diseases:

  • Hemorrhagic Cystitis

HSV 1

• Enveloped, dsDNA virus

• Attributes:

  • Has a primary, latency, and recurrence period

    • Latent Infection: Virus penetrates skin and replicates. It then enter the cutaneous neurons and migrates to a ganglion where it remains in a latent state.

    • Reactivation: Virus can subsequently be reactivated and travel through sensory neurons to the epidermis. A recurrent infection results.

• Pathogenesis:

  • Spread via direct contact with lesions (oral sex)

  • Cell-cell spread locally, including multinucleated giant cells of skin/mucus membranes

  • Causes clustered, painful, fluid-filled infectious vesicles

• Clinical Presentation:

  • Oral Sex transmission

• Diseases:

  • “Cold Sores” - Herpes Labialis

    • Painful grouped vesicles-scalloped border

    • Vesicles to pustules to erosions to ulcers

  • Gingivostomatitis

    • on gingiva and mucosa

    • primarily in children

    • Fever, oral lesions, irritability

    • Lesions: yellow, perioral, vesicular lesions that crust over

  • Herpetic Whitlow (Finger)

  • Herpes Meningitis/Encephalitis

    • Rare, HSV1 most common cause of sporadic fatal disease

      • primary or reactivated infection

      • *necrosis of one temporal lobe-CT and MRI/best diagnostic tool

  • Herpes Keratoconjunctivitis

    • Corneal ulcers in conjunctival epithelium

    • #1 for infectious blindness in developed countries

• Diagnosis/Treatment

  • Appearance/history/exposure

    • Tzanck smear: giant, multinucleated cells associated with HSV and VZV (can’t differentiate)

    • Cowdry type A inclusions with HSV and VZV

    • Direct Fluorescent Ab (DFA)

    • Indirect ELISA for IgM/IgG

    • PCR, NAAT

    • Culture

  • Acyclovir: guanine analog

    • Used for encephalitis, neonatal, disseminated infections

      (immunocompromised)

  • Famciclovir: prodrug metabolized in infected cells only to penciclovir

  • Not a cure-only works on replicating viruses not latent ones

    • Reduce shedding and recurrences

HSV 2

• Enveloped, dsDNA virus

• Attributes:

  • Transmission via sex, oral sex, childbirth

• Pathogenesis:

  • Spread via direct contact with lesions (oral sex)

  • Cell-cell spread locally, including multinucleated giant cells of skin/mucus membranes

  • Causes clustered, painful, fluid-filled infectious vesicles

• Clinical Presentation:

  • Primary infection includes fever and inguinal lymphadenopathy but recurrence does not

• Diseases:

  • “Cold Sores” - Herpes Labialis

    • Painful grouped vesicles-scalloped border

    • Vesicles to pustules to erosions to ulcers

  • Gingivostomatitis

    • on gingiva and mucosa

    • primarily in children

    • Fever, oral lesions, irritability

    • Lesions: yellow, perioral, vesicular lesions that crust over

  • Herpetic Whitlow (Finger)

  • Herpes Meningitis/Encephalitis

    • Rare, HSV1 most common cause of sporadic fatal disease

      • primary or reactivated infection

      • *necrosis of one temporal lobe-CT and MRI/best diagnostic tool

  • Herpes Keratoconjunctivitis

    • Corneal ulcers in conjunctival epithelium

    • #1 for infectious blindness in developed countries

  • Neonatal Herpes

    • contact during vaginal birth, prevented by C-section

    • asymptomatic to skin, eye, mouth and body-wide vesicles; to encephalitis w/ permanent neurological damage or death

• Diagnosis/Treatment

  • Acyclovir: guanine analog

    • Used for encephalitis, neonatal, disseminated infections

      (immunocompromised)

  • Famciclovir: prodrug metabolized in infected cells only to penciclovir

  • Not a cure-only works on replicating viruses not latent ones

    • Reduce shedding and recurrences

HSV3/VZV

• Enveloped, dsDNA virus

• Attributes:

  • Virus eliminated except for latent in ganglia-leads to shingles

• Diseases:

  • Chicken Pox (Children)

    • Mild, highly contagious

    • 10-21 day incubation period

    • No viral prodrome/fever

    • Asynchronous vesicular rash occurs on face, trunk, lesions blister, crust, itch

    • Infectious until all lesions crusted over

  • Chicken Pox (Adults)

    • 1° infection severe

    • Pneumonia, Liver failure, encephalitis, scarring

  • Shingles

    • Re-activation of latent VZV

    • Vesicles erupt along a dermatome-on skin along areas innervated by a particular dorsal root ganglion

    • Lesions identical to varicella zoster

    • Can lead to disseminated infections, post-herpetic neuralgia, Ramsay Hunt Syndrome

• Diagnosis/Treatment

  • Direct fluorescent Ag

  • PCR

  • Tzanck smear

  • Varicella (Chickenpox Vaccine)

    • 1st: 12-15mo

    • 2nd: 4-6yrs

  • Zoster Vaccine

HSV 4

• Enveloped, dsDNA virus

• Attributes:

  • Two types, 1 (A), 2 (B)

  • Lifelong, latent infection

  • 95% world infected

  • In immunocompromised patients with syphilis, syphilis can reactivate latent mono

• Pathogenesis:

  • Immunocompetent: Ab and T cells keep EBV under control; T cells kill EBV-infected B cells

    • Splenic rupture

  • Immunocompromised: loss of T cells lets EBV-infected B cells proliferate

  • EBV in B cells for life

• Clinical Presentation:

  • Developing countries

  • “Mono Rash”

    • If misdiagnosed and prescribed amoxicillin for Strep Throat--

      • Diffuse maculopapular rash…after about a week

• Diseases:

  • Infectious Mononucleosis

    • Pharyngitis, fatigue, malaise, photophobia, sore throat, atypical white blood cells

  • Nasopharyngeal Carcinoma

    • Host genetic backgrounds, EBV strains matter

    • Latent and lytic genes differentially expressed

    • Activate oncogenes, inhibit tumor suppressors

    • Mutations/deletions in latent/lytic genes affect interactions with host cells, increase chances for cancer

  • Endemic Burkitt Lymphoma

    • Due to chronic malaria

• Diagnosis/Treatment

  • CBC: high Lymphocyte count

    • >10% Atypical lymphocytes (Downey cells; reactive CD8+ T Lymphocytes)

  • MonoSpot (Heterophile Ab Test): No longer recommended by CDC as first test, needs CBC first

  • Serology

    • Elevated IgM, IgG = acute

    • Elevated IgG not IgM = chronic or reactivated

    • Anti-EBNA = older (remote), chronic

  • During an active EBV infection, EBV Antibodies in sera can (rarely) produce false positive results with

    • Lyme disease tests (B. burgdorferi Ag)

    • HIV test (HIV Ag)

    • VDRL Syphilis test

HSV 5

• Enveloped, dsDNA virus

• Clinical Presentation:

  • Abnormalities seen in utero for congenital CMV

    • Microcephaly, intracranial calcifications, occipital horn abnormalities, growth restriction, enlarged liver, pericardial effusion, placental inflammation, mortality, cerebral atrophy

    • Intracerebral calcifications (poor developmental prognosis)

• Diseases:

  • Mononucleosis

    • Fever, malaise, pharyngitis, rash, leukocytosis

  • Congenital CMV

    • Transplacental transmission risk

    • Most common intrauterine infection in U.S

    • Most common cause of non-genetic hearing loss

• Diagnosis/Treatment

  • NO heterophile antibodies

  • Biopsy cells to see Owl’s Eye Nuclei

    • Large, basophilic (dark) nuclear inclusion, perinuclear halo, cytoplasmic inclusions

  • Serological testing

  • Quantitative PCR

  • Treatment for Congenital: oral valganciclovir for 6 months if symptomatic

  • Diagnosis for Congenital: Consider TORCH

HSV 6/7

• Enveloped, dsDNA virus

• Clinical Presentation:

  • 6th Disease, 6 months to 3 years

    • 2 serogroups A, B

    • >90% of those> age 1 are seropositive

  • 7th Disease, ages 1-3

    • >90% seropositivity after age 3

• Diseases:

  • Roseola Infantum

    • Abrupt high fever for up to 5 days in child < 2-year-old

    • Irritable baby, lymphadenopathy, +/-rash

    • Fever breaks, maculopapular rash, starts on neck/trunk and spreads to face and limbs

    • Possible febrile seizures (unknown neurotropism)

    • Possible otitis, GI and/or respiratory distress

HSV 8

• Enveloped, dsDNA virus

• Attributes:

  • Lymphotropic, closely related to EBV

  • Lytic first then latent in B Cells

• Pathogenesis:

  • Infects/transforms endothelial cells

  • Pathogenesis related to ability to interfere with cell proliferation, apoptosis and host response

    • Inactivates tumor-suppressor genes

  • Inhibits viral polymerase

• Clinical Presentation:

  • Immunosuppressed, HIV/AIDS

  • Elderly men on lower extremities

  • Middle Eastern Descent

• Diseases:

  • Kaposi Sarcoma

    • Rapid tumor formation, often in the mouth and lower extremities

    • Infected lymph nodes

• Diagnosis/Treatment

  • High CD4 counts

  • Treated with Foscarnet, Famciclovir, Ganciclovir, Cidofovir

    Excision/removal

Variola: Smallpox

• Enveloped linear dsDNA virus

• Pox in a box: Complex, divides in cytoplasm

• Attributes:

  • Narrow host range (humans and monkeys)

  • WHO declared eradicated in 1980

  • Spread via respiratory droplets and fomites

  • Highly contagious

  • Bioterrorism threat

• Pathogenesis:

• Clinical Presentation:

• Diseases:

  • Smallpox

    • Fever

    • Tiredness

    • Muscle aches

    • Flat spots that appear on the body

    • Blisters that form before scabbing and falling off, which can leave scars

• Diagnosis/Treatment

  • Differential

  • PCR

  • DNA containing inclusion bodies in cytoplasm

  • JYNNEOS/IMVANEX/IMVAMUNE:

    • Modified Vaccinia Ankara (MVA) strain

    • highly attenuated, non-replicating

    • used for healthy and immunocompromised

    • Approved for Smallpox and MPX

    • Prophylaxis of MPX after exposure, high risk groups prior to exposure

  • ACAM2000:

    • Replication competent smallpox vaccine

    • Only for select patients and laboratory workers

    • More side effects than MVA

Monkeypox

• Enveloped linear dsDNA virus

• Pox in a box: Complex, divides in cytoplasm

• Attributes:

  • Spread through direct contact with infected people or animals

    • Skin to skin, body fluids, Not STI

• Pathogenesis:

• Clinical Presentation:

• Diseases:

  • Monkeypox

    • It's usually a self-limited infection with a painful rash that develops 5–21 days after exposure. Most people recover on their own after a few weeks. 

• Diagnosis/Treatment

  • JYNNEOS/IMVANEX/IMVAMUNE:

    • Modified Vaccinia Ankara (MVA) strain

    • highly attenuated, non-replicating

    • used for healthy and immunocompromised

    • Approved for Smallpox and MPX

    • Prophylaxis of MPX after exposure, high risk groups prior to exposure

  • ACAM2000:

    • Replication competent smallpox vaccine

    • Only for select patients and laboratory workers

    • More side effects than MVA

Vaccinia (Smallpox Strain)

• Enveloped linear dsDNA virus

• Pox in a box: Complex, divides in cytoplasm

• Attributes:

  • Smallpox vaccine strain

  • Close relative to cowpox

  • Infects wide host range

  • Natural reservoir unknown

• Diseases:

  • Lesions

    • inoculation causes small lesions with discharge, ulceration and necrosis

• Diagnosis/Treatment

  • Vaccine is successful if there is a venter pustule with red, raised area

Molluscum Contagiosum

• Enveloped linear dsDNA virus

• Pox in a box: Complex, divides in cytoplasm

• Attributes:

  • Transmission:

    • Skin/skin contact: roughhousing, wrestling, sex

    • Fomites-shared towels, toys, gym mats etc

  • Common in children and young adults

  • Incubation period 2 wks to 6 months

• Diseases:

  • Lesions

    • Pearly, umbilicated “flesh-colored dome” papule

      • “Central Dimple”

    • Itchy but often painless

    • Resembles chronic, localized miniature smallpox

    • Synchronous centripetal rash begins in mouth/face/arms/legs…then trunk within 24 hours

• Diagnosis/Treatment

  • Self-limiting-resolves in 6-12 months

  • YCANTH: new approved Tx

  • Cryosurgery, Cantharidin (beetle juice), Curettage, Pulsed dye laser (PDL), Imiquimod cream (topical at home)

  • TX patients who are immunocompromised, skin conditions, possibly others

HBV (Hepadnaviridae)

• Enveloped, circular, partially double stranded DNA

• Attributes:

  • Transmission

    • Body fluids, birth

  • Liver tropism: inflammation and replication

• Pathogenesis:

  • Acute Infections:

    • Binds liver-specific bile transporter, NCTP

    • Replication aided by host enzymes

    • Innate and adaptive responses (T cell and Abs) clears infection BUT also causes liver injury due to inflammation and destruction of infected cells by CD8+ T cells

    • Clearance; lifelong immunity to HBsAg

  • Chronic Infection

    • chronic when not cleared

    • 5% of infected adults/90% of infected newborns become carriers/chronically infected

    • Chromosomal integration-no replication

    • no cure; reactivated with loss of immune-competency

    • Extrahepatic: neuropathies, glomerulonephritis, vasculitis

  • Hepatocellular Carcinoma

    • Randomly integrated DNA: instability, disruption of genes, altered expression

    • Aberrantly expressed/mutated viral proteins interfere with gene expression and/or activate oncogenic signaling pathways

    • Expression of HBVx promotes proliferation by inactivating p53

    • Inflammation and speeding through cell cycle causes genetic damage (because T cells killed infected cells and liver trying to replace)

• Diseases:

  • Hep B Infection

    • Mild-acute

      • Asymptomatic

      • Mild flu-like symptoms

      • Fever, fatigue, abdominal discomfort

    • Severe acute

      • <1% Liver failure

      • Bilirubin accumulation-jaundice (test)

      • Encephalopathy (no detox)

      • Decreased clotting factors (test)

      • Elevated serum transaminases (ALT)

      • Swollen liver, wrinkled capsule due to parenchymal collapse, small regenerative nodules, no fibrosis.

• Diagnosis/Treatment

  • Acute—supportive

  • Possible antivirals:

    • nucleotide/nucleoside analogs

    • analogstenofovir

    • Entecavir

    • lamivudine

  • REST ON DIFF CARD CAUSE THERE IS TOO DAMN MUCH

Mono symptoms and negative heterophile antibody test strongly suggests

CMV

Difference between CMV and Rubella with newborn deafness

Smallpox vs Chickenpox vs Monkeypox

Explain what happens in the case of chronic hepatitis infection.

Progressive Disease:

Acute → chronic → cirrhosis → carcinoma

• Chronic serology and liver injury due to loss of cells caused by inflammation, destruction by T cells

• Ground glass cells in 50-75% chronic

• Stained for Hep B Surface Ag

• Contrast-enhanced CT scan- malignant hepatocellular lesions

Describe the relation between HBV structure and diagnostic tests that can be done.

HBsAg (Hepatitis B surface antigen): This is a protein present on the surface of the Hepatitis B virus. It is the earliest marker to appear in the blood after infection and can be detected during acute or chronic HBV infection. Detection of HBsAg indicates active HBV infection.

HBeAg (Hepatitis Be antigen): This is a marker of active viral replication. Its presence indicates that the virus is actively replicating in the liver and the patient is highly infectious.

HBcAg (Hepatitis B core antigen): This antigen is part of the Hepatitis B core and is not detectable in the blood. However, detection of antibodies against HBcAg (HBcAb) indicates prior exposure to the virus, whether acute or chronic, and does not confer immunity.

Hepatitis Diagnostic Chart

Hepatitis Treatment and Prevention

Calciviridae (Norovirus)

• Naked, (+) ssRNA virus

• Attributes:

  • Encodes RDRP but isn’t premade

  • Replication occurs in cytoplasm

  • Major capsid protein VP1 used for genotyping based on sequence

  • #1 cause of gastroenteritis worldwide

  • Fecal-Oral

• Pathogenesis:

  • Diarrhea: Abnormal absorption and secretion relating to changes in microvilli, crypt hypertrophy, disruption of barrier functions, apoptosis

• Diseases:

  • Gastroenteritis

    • Acute, watery, non-bloody diarrhea with projectile vomiting

    • Typically 3 days of vomiting, with non-inflammatory, negative fecal leukocytes

• Presentation:

  • Schools, ships, hospitals, nursing homes

• Diagnosis/Treatment

  • Clinical Presentation & RT-PCR

Echovirus (Picornaviridae)

• Nonenveloped, (+) ssRNA virus

• Attributes:

  • Spread via Fecal-Oral

• Diseases:

  • Aseptic Meningitis

    • Swallowed, 2-14 day incubation, multiplies peyer’s patches, viremia, organs infected, more viremia, possible CNS

Enteroviruses (Type of Picornaviridae, not Rhinovirus)

• Nonenveloped, (+) ssRNA virus

• Attributes:

  • Spread via Fecal-Oral

  • Seasonal

  • Primarily pediatric

  • Vertical transmission during birth

    • hepatic necrosis, meningoencephalitis, myocarditis, sepsis, death of neonate

• Pathogenesis:

  • Target and replicate in GI and URT

• Diseases:

  • Mild Case

    • Mild, febrile illness

    • Summer colds, diarrhea

  • Enterovirus D68

    • acute respiratory illness in summer, fall

    • respiratory secretions

    • Higher risk: young children that suffer from asthma, wheezing, or other breathing abnormalities

    • large outbreaks

    • associated with acute flaccid myelitis

  • Enterovirus A71

    • hand-foot-mouth disease

    • rarely: meningitis, encephalitis, acute flaccid paralysis

    • respiratory secretions, fecal-oral, contact, fomites

    • children in the late summer, fall

  • Enterovirus 70

    • Hemorrhagic conjunctivitis

Rhinovirus (Type of Picornaviridae, Enterovirus Genus)

• Nonenveloped, (+) ssRNA virus

• Attributes:

  • Spread via respiratory droplets

  • More severe in immunocompromised

• Pathogenesis:

  • Virus spreads to nasal epithelium

  • Replicates and sheds causing the infection to spread

  • Ab and interferons facilitate recovery. Infection will end and epithelium regenerates

• Diseases:

  • Primary cause of exacerbations of COPD and asthma

  • 50% Common Colds

    • Sneezing, sore throat, restlessness, coughing, fever, HA, myalgias

Coxsackievirus (Type of Picornaviridae, Enterovirus Genus)

• Nonenveloped, (+) ssRNA virus

• Attributes:

  • Worldwide distribution, summer and fall

  • Group A and B

    • Target:

      • A: skin and mucous membranes

      • B: invasive=heart, pleura, pancreas, liver

      • Both: meninges. motor neurons (anterior horn cells), paralysis

  • Transmitted by fecal-oral and respiratory secretions from human reservoirs

• Pathogenesis:

  • Replicate in oropharynx, GI tract

  • Enter blood stream

• Diseases:

  • Group A

    • Herpangina

      • high fever, sore throat, painful vesicles in oropharynx; summer

    • Hand-Foot-Mouth disease

      • rash on hands and feet, mouth ulcers, benign, self limiting, usually A16

    • Acute Hemorrhagic Conjunctivitis

      • only A24

  • Group B

    • Pleurodynia (Bornholm Disease)

      • “epidemic myalgia”: fever, severe pleuritic chest pain, inflammation of intercostal muscles

    • Myocarditis, Pericarditis

    • Pancreatitis

• Diagnosis/Treatment

  • Clinical findings, PCR, Ab

  • Supportive treatment

Poliovirus (Enterovirus C)

• Non-enveloped, (+) ssRNA virus

• Attributes:

  • three serotypes: 1, 2, 3

  • Fecal-oral route

  • 4-35 day incubation period possible, but usually 7-14 days

  • 95% of cases are asymptomatic

• Pathogenesis:

  • Infection enters intestine as passes through the blood and lymphatics

    • Could also pass straight through to the feces

  • Replicates in the oropharynx and small intestine

  • Febrile Illness (Day 3)

  • Meningitis (Day 6)

  • Paralysis (Day 8)

• Diseases:

  • Abortive Poliomyelitis

    • HA, Nausea, ST

  • Nonparalytic Poliomyelitis

    • Nearly identical to aseptic meningitis

  • Paralytic Poliomyelitis

    • Muscle paralysis follows myalgias, and asymmetric weakness. Respiratory paralysis may occur.

  • Post-Polio Syndrome

    • 40yrs post polio, develop new muscle pain, weakness, paralysis

• Diagnosis/Treatment

  • Iron lungs helped polio paralysis victims breathe, either temporarily or permanently.

  • Polio Vaccines

    • 1955 - Salk’s inactivated vaccine IPV against Type 1-no patent/free (USED IN US)

      • IgG response

      • Stopped disease but not transmission

    • 1959-1962 Sabin Oral live Polio Vaccine (OPV) against Type 1

      • stopped disease and transmission, IgA response

    • 1963-combined Type 1, 2, 3 OLPV vaccine

      • OLPV reverts to wild type = Vaccine-derived polioviruses

      • Can spread person to person and cause polio in unvaccinated (vaccine associated paralytic poliomyelitis)

      • Does not happen with IPV!!

Dengue Virus (Flavaviridae)

• Icosahedral, Enveloped, (+) ssRNA virus

• Attributes:

  • Vector: •Aedes aegypti and albopictus mosquitoes

• Pathogenesis:

  • Ab to other strains do not neutralize but enhance entry of viruses to immune cells with Fcγ receptors where they multiply

• Diseases:

  • “Breakbone Fever”

    • 1st infection

    • high fever, SEVERE muscle, joint, bone pain, enlarged lymph nodes, rash

    • Correlate with immune response, replication in lymph nodes and dissemination

    • Rarely fatal with few sequelae

    • Only a few strain-specific neutralizing Ab; most non-neutralizing

  • Severe-Dengue Hemorrhagic Fever

    • Usually 2nd infection with a 2nd strain

    • Initially classic then worsens due to ADE

    • High fever, rash from skin hemorrhages, Intestinal hemorrhages related to replication and immune system, shock and death likely

• Diagnosis/Treatment

  • Dengvaxia

    • live, attenuated, tetravalent (Yellow Fever virus vaccine base)

    • For 9-16 years only WITH a prior infection aka positive serology

    • Not for travelers

  • Serology, PCR, culture, ID proteins

  • Supportive, no antivirals

  • Eliminating mosquito breeding grounds and insecticides

    vaccine

Yellow Fever Virus (Flavaviridae)

• Icosahedral, Enveloped, (+) ssRNA virus

• Attributes:

  • Vector: Aedes mosquitoes during the rainy season

• Pathogenesis:

• Diseases:

  • “Yellow Fever”

    • 50% mortality due to internal bleeding within 2 weeks

    • HA, myalgias, lumbosacral pain, nausea, malaise, dizziness, conjunctival injection

    • Symptoms will abate and then progress and worsen 50% will lead to mortality due to internal bleeding within 2wks

    • Jaundice

• Diagnosis/Treatment

  • Difficult, confused with other viruses, malaria

  • PCR and NAAT

  • Later-serology and id proteins

  • No antivirals, symptomatic Tx

  • Prevention

    • Eradication

    • Avoidance

    • Live attenuated since 1935

    • YF-VAX in US

Vaccination dates for Polio

What is the issue with vaccine derived polio?

Problems:

• Decreased vaccination rates

• Use of OLPV, even newer versions, allows reversion and results in spread

Hepatitis A Vaccine Times

What is the difference between a reservoir host and an incidental host?

• Reservoir host - the natural host in which the virus lives and replicates and from which the vector can gain an adequate dose of the virus to spread it to another reservoir host

• Incidental host - a host that can be infected and become ill but is considered a “dead-end” because the vector can’t get enough virus out to spread to another host

Zika Virus

• Icosahedral, Enveloped, (+) ssRNA virus

• Attributes:

  • Many hosts

  • Tropical/Subtropical regions

  • Transmitted by  female Aedes aegypti, albopictus 

  • Sexual contact, body fluids, organ transplants, transplacental

• Pathogenesis:

  • Refer to image

• Diseases:

  • Self-resolving, asymptomatic or mild fever, rash, conjunctivitis, muscle and joint pain, malaise, and headache unless congenital

    • Possible GBS, arthritis (resolves in 2 weeks)

  • Fetal infection-microcephaly, birth defects, problems in pregnancy and/or partially collapsed skull

    • Decreased brain tissu

    • Eye damage, hearing issues

    • Joints with restricted motion

    • Developmental challenges

    • Seizures

    • Stops neural development, cell division in the fetus

      targets neural progenitors

• Diagnosis/Treatment

  • Symptomatic, supportive treatment

  • Diagnosis via PCR, serology, plaque reduction assasys in presence of IgM

Powassan Virus (Flavaviridae)

• Icosahedral, Enveloped, (+) ssRNA virus

• Attributes:

  • Transmission via:

    • Ixodes ick bites

    • I. cookei (groundhog tick)

    • I. marxi (squirrel tick)

    • I. scapularis (blacklegged deer tick)

  • Canada, Russia, US

• Diseases:

  • 4-6 week incubation

    • Most asymptomatic

    • Fever, headache, vomiting, weakness, rarely encephalitis and meningitis

• Diagnosis/Treatment

  • Serology, possibly RT-PCR

  • Supportive only

  • Variable appearances on MRI

St. Louis Encephalitis Virus (Flavaviridae)

• Icosahedral, Enveloped, (+) ssRNA virus

• Attributes:

  • Vector: Culex mosquito

• Diseases:

  • Mostly asymptomatic

  • CNS Disease

    • Headache, fever, agitation

    • Lymphocytic meningitis affects gray matter

    • Hypothalamus, cerebral and cerebellar cortex, basal ganglia, brainstem, spinal cord

    • CSF-elevated pressure, lightly increased lymphocytes, decreased protein, IgM; PCR

    • EEG-possible abnormalities

• Diagnosis/Treatment

  • Symptomatic → supportive

West Nile Virus (Flavaviridae, Arbovirus)

• Icosahedral, Enveloped, (+) ssRNA virus

• Attributes:

  • Vector: Culex mosquito

• Diseases:

  • Mostly asymptomatic, some develop fever and/or meningitis

  • CNS Disease

    • Acute inflammatory response causes headache, memory loss, disorientation

    • Meningoenceophalits

    • Destruction of neurons in spinal column and brain stem gray matter

    • CSF-elevated protein, leukocytes, normal glu, IgM; PCR

    • CT-no abnormalities for weeks

• Diagnosis/Treatment

  • Symptomatic → supportive

What is the purpose of sentinel chickens?

Monitoring the presence of arboviruses. They do not get sick when exposed but can generate antibodies.

Chinkungunya (Togaviridae, Family Arbovirus)

• Icosahedral, Enveloped, (+) ssRNA virus

• Attributes:

  • Vector: Aedes aegypti and albopictus mosquitoes

  • Can be spread during 2nd trimester of pregnancy and rarely but possible during birth

    • Spread by breast feeding

  • Old world

  • Anyone; young, old, immunocompromised at higher risk

• Pathogenesis:

• Diseases:

  • fever, polyarthralgia, joint pain, myalgia

  • debilitating pain can persist for months (1/1000)

• Diagnosis/Treatment

  • No NSAIDs unless it is not dengue

Venezuelan Equine Encephalitis

• Icosahedral, Enveloped, (+) ssRNA virus

• Attributes:

  • Vector: LOTS OF THEM, LOTS OF HOSTS

    • Mammals are not dead end 💀

  • Biological weapon

• Diseases:

  • 96% asymptomatic

  • 5% symptomatic

  • <5% flu like symptoms, then altered mental state and seizures indicating encephalitis

  • 1/3 of the 5% die

  • 2/3: neuro deficits, paralysis and other permanent neuro changes

• Diagnosis/Treatment

  • Horse vaccine 🐴 slayyy

Hepatitis A

Common Name: “Infectious”

Virus Structure: Picornavirus, capsid, (+) RNA

Transmission: Fecal-Oral

Onset: Abrupt

High-Risk groups: injection drug users, MSM, travelers to endemic regions, aid workers

Incubation Period (Days): 15-50

Severity: Mild

Symptoms: nausea, vomiting, fatigue, right upper abdominal discomfort, fever, poor appetite, jaundice, dark urine

Chronicity/Carrier State: No

Other Disease Associations: Rare Fulminant Hepatitis

Hepatitis B

Common Name: “Serum”

Virus Structure: Hepadnavirus; envelope, DNA

Transmission: Parenteral, sexual

Onset: Insidious

Incubation Period (Days): 45-160

Severity: Occasionally severe, 3%-10% chronicity in adults; 30%-90% in infants and children

Chronicity/Carrier State: Yes

Other Disease Associations: Primary Hepatocelluar carcinoma, cirrhosis

Hepatits C

Common Name: “Non-A, non-B posttransfusion”

Virus Structure: Flavivirus; envelope, (+) RNA

Transmission: Parenteral, sexual

• Percutaneous blood, needles risk

Onset: Insidious (Chronic Acute)

Symptoms: malaise, nausea, and right upper quadrant pain, dark urine and jaundice

Incubation Period (Days): 14-180+

Severity: Usually subclinical; 70% chronicity

Chronicity/Carrier State: Yes

• HCV viral loads, fibrosis and active liver inflammation, persistently elevated AST/ALT

Other Disease Associations: Primary Hepatocelluar carcinoma, cirrhosis, chronic hepatitis

Treatments:

• Direct Acting Antivirals for 12-24 weeks

• combination of 2nd generation protease inhibitors, inhibitors of structural proteins, polymerase inhibitors

• +/- ribavirin

• 95% success

Hepatitis D

Common Name: “Delta Agent”

Virus Structure: Viroid-like; envelope, circular RNA

Transmission: Parenteral, sexual

Onset: Abrupt

Incubation Period (Days): 15-64

Severity: Co-infection with HBV occasionally severe; superinfection with HBV often severe

Chronicity/Carrier State: Yes

Other Disease Associations: Cirrhosis, Fulminant hepatitis

Hepatitis E

Common Name: “Enteric non-A, non-B”

Virus Structure: Hepevirus capsid, (+), RNA

Transmission: Fecal-Oral, often in places with poor sanitation, undercooked deer and wild swine

Symptoms:

• 1-6 weeks of symptoms:

  • transient watery diarrhea, Jaundice, loss of appetite, enlarged liver, nausea and vomiting, fever, itching, rash, joint pain, dark urine, clay colored stool

• 1% fatality

  • fulminant hepatitis and liver failure

  • Acquiring during pregnancy increases risk of fulminant hepatitis and fetal mortality

Onset: Abrupt

Incubation Period (Days): 15-50

Severity: Severe in pregnant women, mild in adults

Chronicity/Carrier State: No

Other Disease Associations: None

Diagnosis: IgM Ab, PCR

Eastern Equine Encephalitis

• Icosahedral, Enveloped, (+) ssRNA virus

• Attributes:

  • Biological weapon

  • Found in the Eastern side of the US

• Pathogenesis:

• Diseases:

  • Fever, chills, aches, meningitis for 1-2 weeks, followed by encephalitis or recovery

  • 1/3 with encephalitis die

  • 2/3 recover; long-term physical or mental impairments and early death

  • 50-70% mortality

Rubivirus (Matonaviridae)

• Enveloped +ssRNA

• Attributes:

  • Human Reservoir, respiratory secretions

  • Highly contagious

  • Winter & Spring

• Pathogenesis:

  • URT, replicates, viremia, localizes to lymphoid tissues, skin, organs, rash, possible arthritis, due to immune complexes

  • Virus shed up to 8 days

  • 2-3 week incubation

• Diseases:

  • Congenital Rubella Syndrome

    • Congenital infection: placental infection, transplacental spread

    • Classic triad in newborn:

      • Deafness – Ears

      • Cataracts – Eyes

      • Cardiac disease (Patent ductus arteriosus = PDA)

      • PLUS: Blueberry muffin baby = extramedullary erythropoiesis

• Diagnosis:

  • TORCHeS infections: Toxoplasma, Others, Rubella, CMV, Herpes, Syphilis

Rubella Vaccine schedule

MMR or MMR II: attenuated live measles and rubella viruses for 12 months and over, non-pregnant

HTLV

• Enveloped, +ssRNA, retrovirus

• Attributes:

  • Use RT and incorporates into chromosome

  • Lifelong infection

  • 95% asymptomatic

  • Affects >5-10 million worldwide

  • 4 groups: I, II, III, IV

• Diseases:

  • HTLVI

    • Most oncogenic virus known

    • Breast feeding, blood transfusions prior to 1988, needles, sex

    • Adult T cell leukemia-lymphoma (ATL), HTLV-1-associated myelopathy (tropical spastic paraparesis)

    • Different subtypes in different regions

  • HTLVII

    • Hairy Cell Leukemia

What cells does HIV attack?

CD4 & CCR5

How does HAART therapy work?

• Antiretroviral drug combinations-Highly Active Anti Retroviral Therapy (HAART)

  • Nucleoside/tide Reverse Transcriptase Inhibitor (NRTI)

  • Integrase Inhibitors

  • Non-Nucleoside/tide Reverse Transcriptase Inhibitor (NNRTI)

  • Protease Inhibitors

  • CCR5 Inhibitors (Entry)

How does PrEP work for HIV?

1. Medication: PrEP involves taking a prescription medication called Truvada or Descovy. These medications contain a combination of two antiretroviral drugs: tenofovir and emtricitabine.

2. Mechanism of Action: When taken consistently, these drugs work to prevent HIV from establishing itself and replicating within the body. Tenofovir and emtricitabine interfere with HIV's ability to replicate by blocking an enzyme called reverse transcriptase, which the virus needs to multiply.

3. Preventative Effectiveness: When taken daily as prescribed, PrEP has been shown to significantly reduce the risk of HIV transmission. Studies have demonstrated that PrEP can reduce the risk of HIV infection by up to 99% when taken consistently.

4. Consistency is Key: It's important to emphasize that PrEP must be taken consistently and correctly to be effective. Missing doses can reduce its effectiveness in preventing HIV transmission.

5. Regular Testing and Monitoring: Individuals taking PrEP are typically recommended to undergo regular HIV testing and monitoring for other sexually transmitted infections (STIs) to ensure their ongoing health and the effectiveness of the treatment.

6. Combination Prevention Approach: PrEP is often used as part of a comprehensive HIV prevention strategy, which may include other preventive measures such as condom use, regular HIV testing, and access to comprehensive sexual health services.

CD4 count with HIV

Rotavirus (Sedoreoviridae)

• Attributes:

  • Use RT

  • Wheel-Shaped

  • 11 segments dsRNA

  • 3 layers of protein around RNA = very stable

  • Classification based on VP6 capsid

  • 8 groups (RVA to RVH)

  • Fecal-Oral

• Diseases:

  • Gastroenteritis (<5yrs)

    • Vomiting, diarrhea, and fever

    • Dehydration, loss of electrolytes

    • No blood or fecal leukocytes

• Presentation:

  • Most common in young infants and children.

• Treatment:

  • Rehydration

Rotavirus Vaccine Schedule

Coltivirus (Colorado Tick Fever Virus)

• Naked, dsRNA virus

  • 12 ds RNA segments with 3 capsids

  • RDRP

  • Replication cycle same as Reo

• Attributes:

  • Co-infections with Rickettsia

  • Dermacentor andersoni range

  • May-July

• Diseases:

  • Fever, chills, myalgias, headache

  • Can target CNS or liver

  • Self-limited with good prognosis

  • Rare deaths due to DIC (disseminated intracellular coagulation) and thrombocytopenia

What are the four keys to fungal pathogenesis in humans?

1. Thermal tolerance

2. Penetrating or circumventing host barriers to reach internal tissues

3. Digestion and absorption of human tissues

4. Withstand/resist the human immune system

Histoplasm Capsulatum

• Attributes:

  • Bat guano, bird droppings

  • Hot humid conditions

• Pathogenesis:

  • Spores are inhaled and morph into yeast in the lungs

  • 7-21 day incubation

  • Ingested by macrophages: prevent macrophage killing and multiply

  • Macrophages carry to other sites and establish infection

  • Dendritic cells engulf and produce pro-inflammatory cytokines

  • Cytokines finally activate macropahges to kill yeasts

• Clinical Presentation:

  • Mostly asymptomatic, self limiting

  • Symptomatic:

    • Slow onset

    • High fever, productive cough, chest pain

    • Dissemination possibly fatal: CNS, GI, anemia, bone marrow

  • Granulomas = relapsing, chronic

• Presentation:

  • Caves, poultry coops

  • Key indicators

  • History of high-risk exposure

  • Conditions:

    • HIV / AIDS

    • TNF-alpha inhibitors

  • Hepatosplenomegaly

  • Mouth and tongue ulcers

  • Pancytopenia (bone marrow involvement)

  • Often misdiagnosed as TB

• Diagnosis/Treatment:

  • Fungi in Monocytes

  • A. Lung Biopsy: Culture and staining, Histopathology/Cytopathology

  • B.Antigen Detection: Enzyme Immuno-Assay

  • C. Immune Reaction:

    • Immunodiffusion (Ab)

    • complement fixation (C’)

    • enzyme immunoassay (Ab)

    • skin test (Ab)

  • D. Molecular Methods: Not FDA approved yet

  • For severe cases treated with amphotericin B for 1-2wks followed by itraconozole for 12wks

Blastomycosis

• Attributes:

  • Endemic areas overlap with histoplasma

  • Can cause

    • Extrapulmonary disease

    • Verrucous (warts), pustules

    • Osteomyelitis

• Pathogenesis:

  • Inhaled w/ 21-106 days of incubation

  • Phagocytosed and killed by bronchopulmonary phagocytes.

    Some people eliminate better and remain asymptomatic

  • Converts to yeast, impairs innate and adaptive immunity

  • Yeast multiply and disseminate through blood and lymphatics

  • Eventually controlled by T cells, macrophages and antifungals

• Clinical Presentation:

  • Acute: fevers, chills, productive cough with or without sputum production

    severe cases progress to ARDS.

    • Slow onset pneumonia

    • Skin lesions with possible bone pain

  • Subacute/chronic: 2–6 months: fever, night sweats, cough, hemoptysis, weight loss

  • 20% extrapulmonary dissemination

    • more common in patients with chronic pulmonary illness or immunocompromised.

    • Depends on organ involved

• Diagnosis/Treatment:

  • Laboratory Tests

    • Histology

      • does not colonize so presence is confirmatory

    • Broad based budding yeast

    • Various stain

    • Culture

    • Serum/urine E1A Ag

    • Ab detection

  • Diff Diagnosis: Mimics acute pneumoccoccal pneumonia

  • Treatment

    • Depends on mild, moderate, severe, CNS

    • Complicated, 6-12 mo of tx

    • Amphotericin B and/or Azoles-Itraconazole

Coccidioidomycosis

• Attributes:

  • Generally, southwestern US

  • Washington State through Mexico, several locations in South America

  • Grows as mold beneath desert surface

  • Dry conditions causes mold to fracture into spores

  • Not spread person to person

• Pathogenesis:

  • Inhalation of spores, 10-50

  • Symptoms begin 1-4 weeks after inhalation

  • Spores enlarge to spherule

  • Spherules produce and release endospores

  • Each endospore produces another spherule, in lungs or other tissues

  • Macrophages carry endospores to other sites: bones, joints, soft tissues, CNS

• Clinical Presentation:

  • Most asymptomatic, transient lower respiratory infection

  • Symptoms of San Joaquin Valley Fever or Valley Fever (40%)

    • Cough, fever, malaise, dyspnea, headaches, night sweats, rash

    • Arthralgias

    • Erythema nodosum

    • Usually self limiting

  • Rarely disseminates 1%

    • Most dangerous is meningitis

    • Also bones, joints, soft tissues

• Presentation:

  • Clues: endemic area, pneumonia/URT disease that isn’t treatable with antibiotics, +/- rash and other symptoms

• Diagnosis/Treatment:

  • Most Common Dx methods:

    • Serology for Ab (IgM, IgA)

    • Ag in blood and urine

    • Culture and staining

    • Tissue Histology

      • Spherule: Classic pathology finding: Spherule filled with endospores “Cocci Cactus”

    • Imaging

  • Treatment

    • Africa American or Filipino descent-more likely to have extrapulmonary complications

    • Mild disease: no need to treat

    • Moderate disease:

      • Flucanazole (400 mg daily) for 6 to 12 weeks

    • Severe:

      • intravenous amphotericin B in combination with Flucanazole 400 to 800 mg daily until stable and transition to Flucanazole (400 mg daily) for 12 to 14 weeks

    • Immunocompromised (regardless of severity)

      • Same as above but with extended time or lifelong treatment

      • Consult with ID specialist regarding tx of immunocompromising condition with coccidioidomycosis for specific tailored treatments of multiple conditions

Paracoccidioidomycosis

• Attributes:

  • (Sub)Acute: famers, construction workers, generally males

  • Chronic: male, 30-60 years old (skin, mucus membranes, lymph nodes, spleen, liver, adrenals, more)

• Pathogenesis:

  • The saprophytic form of Paracoccidioides spp. are found in the soil as mycelium (25 °C). Conidia and hyphal fragments inhaled by mammalian hosts are the primary sources of infection. The propagules are inhaled and established in the lungs, which, at body temperature (37 °C), initiate the dimorphic transition to pathogenic yeast form. The immune cells present within the host, such as macrophages, neutrophils, and dendritic cells, recognize the pathogen and trigger defense mechanisms such as the production of reactive nitrogen and oxygen species (RNS/ROS).

• Clinical Presentation:

  • Cough, fever, malaise

  • granulomas form

  • Latent in granulomas

  • Reactivate decades later

  • Chronic, progressive pulmonary disease

• Diagnosis/Treatment:

  • Diagnosis

    • Skin test

    • Culture, staining (gold)

    • Tissue Histology (gold)

      • MICKEY MOUSE HEAD OR PILOT’S WHEEL

    • Serology to detect Ab

    • PCR

    • Differentiate from TB

  • Treatment

    • Severity, form, co-morbidities, immune state

    • Mild/moderate: Itraconazole 9-18 months

    • Severe: amphotericin B usually 2 to 4 weeks, followed by Itraconazole 9

    • 18 months

What are the four cutaenous implantation mycoses?

1. Sporotrichosis

2. Chromoblastomycosis

3. Mycetoma

4. Entomophthoramycosis

5. Lacaziosis

How do cutaenous implantation mycoses get in the body?

• Fungi enter thru cuts/punctures caused while working with soil, sphagnum moss, decaying wood, vegetation throughout the world

• Seen in people involved in farming, landscaping, and gardening

• Usually due to inoculation from thorn pricks and splinters but can be from other trauma

Sporotrichosis

• Attributes:

  • Sporothrix species

    • Some are human and animal pathogens and others are plant pathogens but not both

  • plant and organic matter, soil, wood, rose and other thorns

  • Dimorphic fungi

    • Sporothrix schenckii, S. schenckii, is a dimorphic fungus that can cause Sporotrichosis. S. schenckii exists in either a hyphal form at temperatures less than 37 degrees Celsius or as a budding yeast at 37 degrees Celsius or greater.

• Pathogenesis:

  • Skin, not systemic

  • Traumatic spore inoculation leads to papule formation after days/weeks

  • Travels up from site to lymphatics via macrophages “ascending lymphangitis”

  • Deep trauma = bone and joint infections

  • Other trauma leads to multiple sites

• Clinical Presentation:

  • Rose Gardener’s Disease

    • The first symptom of sporotrichosis is a small, painless bump that is pink, red, or purple and resembles an insect bite. The bump usually appears on the finger, hand, or arm where the fungus first entered through a break in the skin.

• Presentation:

  • Gardeners, potting soil

• Diagnosis/Treatment:

  • Most Common Dx methods:

    • Tissue histology and/or culture followed by staining and microscopy (yeasts)

    • Molecular ID (sequencing PCR)

    • serology

  • Treatment

    • Itraconazole, 3 to 6 months

    • Supersaturated potassium iodide (SSKI)

    • Bone/deep: Amphotericin B followed by Itraconazole for 1 year

Chromoblastomycosis

• Attributes:

  • chronic localized infection with different types of lesions

  • Multiple fungal species with same presentation

    Brazil, Mexico, southern China, Australia, and Madagascar

  • Present but not diagnosed/reported in Africa

  • Poor treatment outcomes, resistance a problem

• Clinical Presentation:

  • Verrucous Lesions

    • Lesions showing a keratotic exophytic surface composed of sharp or blunt epithelial projections with keratin-filled invaginations (plugging), but without obvious fibrovascular cores.

• Diagnosis/Treatment:

  • Treatment

    • Itraconazole or surgical removal

Mycetoma

• Attributes:

  • Can be bacteria (Actinomycetoma, eg Nocardia) or fungal (Eumycetoma-primarily Africa)

• Clinical Presentation:

  • Granulomatous infection of skin, subcutaneous, fascia, bone usually in hands or feet

    • Painless but debilitating

• Presentation:

  • Gardeners, potting soil

• Diagnosis/Treatment:

  • Diagnosis

    • Grains in biopsy

    • Hyphae in grains

  • Treatment

    • Itraconazole or surgical removal

Candida (General)

• Attributes:

  • Normal flora of the mouth, skin, vagina, gut

• Pathogenesis:

  • Adhere to epithelial cells

  • endocytose into cells or penetrate into cells

  • causes apoptosis and necrosis

  • forms biofilms

• Clinical Presentation:

  • Nail infection

  • Vulvovaginal candidasis

  • Oral thrust

  • Candidal Intertrigo

  • Diaper Dermatitis

  • Candidemia

    • Rare - Immunosuppressed patients

      • Most common fungal bloodstream infection in hospitalized patients

        • Neutropenic patients-chemotherapy

        • Patients with IVs and intravenous catheters

        • ICU / Central lines

        • Hyperalimentation/Total parenteral nutrition (TPN)

        • IV Drug Users

      • Can occur when gut Candida crosses intestinal epithelium and gains access to blood vessels

• Presentation:

  • opportunist of skin or mucus membranes

  • Diabetes (sugar/yeast connection)

  • Infections identified by body location

  • Infants or inhaled topical steroids (asthma)

  • Esophagitis – HIV/AIDS patients

• Diagnosis/Treatment:

  • Diagnosis

    • fungal detection in blood cultures

    • Detection of fungal Ag, Ab to Ag

    • PCR tests

  • Treatment

    • Nystatin, Clotrimazole, Amphotericin B, Miconazole

Candida Auris

• Attributes:

  • Nosocomial, MDR

  • Yeast, no germ tubes, rarely forms hyphae

• Clinical Presentation:

  • Fever and chills that don’t improve after antibiotic treatment for a suspected bacterial infection

• Diagnosis/Treatment:

  • Diagnosis

    • Culture, staining (CHROM AGAR)

    • Often misidentified in automated systems

    • MALDI TOF MS is best

    • NA methods including sequencing

  • Treatment

    • Problematic with MDR

    • Echinocandins preferred

      • Multiple drugs together for synergism

    • Remove catheters

    • Don’t treat non-invasive

    • 30-72% mortality rate

Aspergillus (Aspergillus Fumigatus)

• Attributes:

  • Environmental

• Pathogenesis:

  • Inhaled and reach alveoli

• Clinical Presentation:

  • Pneumonia

  • allergies

    • aspergilloma “fungus ball”

      • Commonly in pulmonary TB cavities

      • Cough, Coughing up blood, Shortness of breath, Possibly fatigue and weight loss if chronic

  • Allergic Bronchopulmonary Aspergillosis (ABPA)

    • Classical Presentation

      • Asthma or CF patient

      • Recurrent episodes of cough, fever, malaise

      • Hemoptysis

      • brownish mucus plugs/casts

• Diagnosis/Treatment:

  • Diagnosis

    • must see and ID the asexual conidium forming structure which is rare in vivo

  • Treatment

    • Steroids

Cryptococcosis (Neoformans & Gatti)

• Attributes:

  • 30 species, 2 pathogens

  • Environmental

  • Exposed in childhood, disease is reactivation of previous infections

  • NOT spread person to person

  • Chronic and Relapsing

  • Budding yeast with polysaccharide capsule

• Pathogenesis:

  • Latent infection in alveolar macrophages

  • Depressed immunity, grow, disseminate, replicate

  • >100 proteins help establish virulence and protect from immune system

  • Yeasts in macrophage or not in macrophage invade CNS

  • CD4+ T cells and cytokines are primary response

• Clinical Presentation:

  • Cough

  • Pulmonary: asymptomatic to visible on X-ray to life threatening pneumonia and ARDS

  • CNS: headache, fever, cranial neuropathies, altered mentation, lethargy, memory loss, and signs of meningeal irritation

  • Meningitis: neoformans

• Presentation:

  • Immunocompetent=low risk

  • associated with immunocompromised

  • CD4 T cell defects

    • HIV pts

• Diagnosis/Treatment:

  • Diagnosis

    • India ink

    • Latex agglutination test

    • Detects polysaccharide capsular antigens

    • Serum and CSF levels correlate with severity

  • Treatment

    • Amphotericin B formulations +/- flucytosine

Mucormycosis (Rhizopus & Mucor)

• Attributes:

  • 25% to 80% mortality

• Pathogenesis:

  • Inhalation leads to pneumonia or rhinocerebral zygomycosis in facial sinuses

    • May invade deeper: orbital cellulitis, vascular thrombosis, coma, death

    • Both thrive in high glucose environments and during ketoacidosis

• Clinical Presentation:

  • Severe sinusitis – fever, discharge, congestion, sinus pain

  • Necrosis of the palate

  • Erythema and cyanosis of skin over sinuses

  • Orbital pain and swelling

  • Black eschars

  • Facial numbness

  • Cavernous sinus thrombosis

• Presentation:

  • Neutropenic, diabetic ketoacidosis, cancer pts, extreme malnutrition, trauma

• Diagnosis/Treatment:

  • Treatment

    • Remedy underlying cause

    • Amphotericin B and Isavuconazole

    • Surgery

Pneumocystis Jirovecii

• Attributes:

  • Common fungi we breath in all the time

  • 25% to 80% mortality

• Pathogenesis:

  • Spores attach to alveoli and replicated unimpeded

  • Hypoxemia

  • Impaired gas exchange capacity

  • Changes in total lung capacity and vital capacity

• Clinical Presentation:

  • Diffuse bilateral infiltrates in the lung

  • Fever, Cough, Difficulty breathing, Chest pain, Chills, Fatigue

• Presentation:

  • Immunocompromised (HIV*, transplant, corticosteroids, Chronic lung diseases, cancer, inflammatory diseases, autoimmune diseases)

• Diagnosis/Treatment:

  • Diagnosis

    • Lung biopsy silver stain

  • Treatment

    • trimethoprim/sulfamethoxazole (TMP/SMX)

    • Fatal without Tx

Piedraia Hortae

Black Piedra-hair with nodules of hyphae around the hair shaft appearing black

Hortae Werneckii

Tinea nigra-dark brown to black discolorations on the palm occurring more commonly in warm coastal regions among young women

Trichosporon spp

White piedra: Piedra-hair with nodules of hyphae around the hair shaft appearing white

Pityriasis versicolor (Malassezia Furfur)

• discoloration or depigmentation and scaling of skin

• Dimorphic

• Infects as yeast, transforms into mycelia to spread

• Superficial so not a true tinea

• KOH prep shows hyphae and yeast

  • “Spaghetti and Meatballs”

• factors: pregnancy, heat/humidity, immunodeficiency, oil/lotions, genetics

• Multicolored hypopigmentation patches

• Degrades lipids, produces acids

• Damages melanocytes – causes hypopigmentation

• Triggers: Tropical vacation, Hot & humid weather, Increased sweating. Commercial tropical skin oils

  • Frequently seen in adolescents- increased sebum

Tineas

• Attributes:

  • fungal skin/hair/nail infection

  • Dermatophytes: Fungi that feed on keratin in skin, hair, and nails

    Scaling of skin, loss of hair, crumbling of nail

• Diagnosis/Treatment:

  • Diagnosis

    • Potassium hydroxide (KOH)

      • dissolves keratin & epidermal keratinocytes

      • Fungal elements visible in skin scrapings

    • Woods’ Lamp

  • Treatment

    • Depends on site/depth/seriousness

    • Topical treatment and/or systemic treatment

    • Azoles, amphotericin B and other polyenes, echinocandins

Tinea Pedis

Commonly known as athlete's foot, tinea pedis affects the feet, particularly the spaces between the toes and the soles. It can cause redness, itching, burning, scaling, and sometimes blisters and fissures.

Tinea Corporis

Also known as ringworm, tinea corporis affects the skin on the body, excluding the scalp, beard, groin, and feet. It presents as circular, red, scaly patches with a raised border that may be itchy or painful.

Tinea Capitis

This type of tinea affects the scalp and hair follicles. It is more common in children but can also occur in adults. Tinea capitis can cause hair loss, scaling, crusting, and sometimes swollen lymph nodes in the neck.

Tinea Cruris

Also called jock itch, tinea cruris affects the groin area, inner thighs, and buttocks. It presents as red, itchy, and often ring-shaped rashes with well-defined edges.

Tinea Unguium

Also known as onychomycosis, tinea unguium affects the nails, typically the toenails but can also affect fingernails. It can cause thickening, discoloration, crumbling, and deformity of the nails.

Lassa Fever Virus

• Attributes:

  • Negative sense  ssRNA viruses

  • 2 segments of -ssRNA

  • BSL-4 due to human-human transmission

  • Exposure via droppings, contaminated food

    1-3 week incubation

  • Vector: Mastomys Natalensis

• Pathogenesis:

• Clinical Presentation:

  • 80% mild with slight fever, malaise, weakness headache

  • 20% hemorrhaging, respiratory distress, facial swelling, pain, shock, neurological problems, encephalitis, multi-organ failure

  • 1% of total dies, 10% during epidemics

  • 3rd trimester pregnancies: 95% fetal mortality

    Deafness develops in mild and serious cases

• Presentation:

  • West Africa

• Diagnosis/Treatment:

  • Diagnosis and Treatment

    • Detect IgM and IgG

    • RT-PCR

    • Culture

    • Supportive care

    • Ribavirin

Hantavirus

• Attributes:

  • Negative sense  ssRNA viruses

  • New World

  • Vectors (different but overlapping habitats):  cotton rat, deer mouse, rice rat and white footed mouse

• Pathogenesis:

• Clinical Presentation:

  • Hantavirus Cardiopulmonary Syndrome (HCPS)

    • NEW WORLD

      • Rodent urine/feces/saliva

      • Flu-like symptoms, myalgia, cough, diarrhea,

      • Followed by rapid respiratory failure with pulmonary edema, cardiac shock

      • The Four corners (UT, CO, AZ, NM)

  • Hemorrhagic Fever with Renal Syndrome (HFRS) and NE (Nephropathia endemica)

    • Mortality 0.8% to 100%, dependent on virus, host genetics

    • Generally, mortality ranges up to 15%

    • OLD WORLD

• Presentation:

• Diagnosis/Treatment:

Crimean-Congo Hemorrhagic Fever

• Attributes:

  • Negative sense  ssRNA viruses

  • Most widely distributed hemorrhagic fever

  • Endemic in Africa, Europe, Asia, Mediterranean

  • Spread via contact with tick vector or from infected animals or humans via contaminated blood/body fluids

    • Hyalomma genus

• Pathogenesis:

• Clinical Presentation:

  • Incubation: 3-7 days (1-10 organisms!!)

    • Pre-hemorrhage: 4-5 days, headache, high fever, joint/back pain, vomiting, red eyes/throat, petechiae on palate, nonbloody diarrhea

    • Hemorrhage: petechiae, conjunctival hemorrhage, epistaxis, hematemesis, hemoptysis, and melena, possible hepatosplenomegaly

• Presentation:

• Diagnosis/Treatment:

Rift Valley Fever Virus

• Attributes:

  • (-) ss segmented RNA virus, enveloped

  • Virus in cattle, sheep, livestock in Africa

  • Transmitted primarily through handling meat but also mosquitos directly

  • Increased mosquitos during excess rainfall

  • Negative sense  ssRNA viruses

• Pathogenesis:

• Clinical Presentation:

  • Mild and self limiting with flu-like symptoms that can mimic meningitis

• Presentation:

• Diagnosis/Treatment:

California Encephalitis Disease

• Attributes:

  • Mosquito-borne viruses in north central US (rare in CA)

  • Negative sense  ssRNA viruses

• Pathogenesis:

• Clinical Presentation:

  • Primary viremia: Damages endothelial cells and lymphatic system, causes fever, drowsiness, disorientation

  • Secondary CNS localization: neurologic findings, seizures, encephalitis

• Presentation:

• Diagnosis/Treatment:

Nipah and Hendra Virus

• Attributes:

  • Negative sense  ssRNA viruses

  • Emerging zoonotic pathogens, outbreak frequency increasing

  • Transmitted from animals to humans via fruit bats, animal contact

  • Veterinary cross-protective vaccine under development, along with human vaccine

• Pathogenesis:

• Clinical Presentation:

  • Fever, headache, respiratory illness that can lead to encephalitis with seizures, coma and death

• Presentation:

• Diagnosis/Treatment:

Respiratory Syncital Virus

• Attributes:

  • Negative sense  ssRNA viruses

  • A and B subgroups worldwide

  • Shed between 5 days and 3 weeks, prior to symptom onset

  • Symptoms overlap other respiratory symptoms

    Problems for young and elderly

• Pathogenesis:

  • Coughs, sneezes, droplets, fomites

  • Lives for many hours in hard surfaces

  • Almost all infected by 2 yrs

  • Immunity not protective so reinfections occur

• Clinical Presentation:

  • mild URT to life threatening LRT

  • Infants/toddlers: most common cause of bronchiolitis

  • Young children: croup and tracheobronchitis

  • Elderly: tracheobronchitis, interstitial pneumonia

• Presentation:

  • Sept-Mid december

  • Predisposing factors: preterm birth, smoking, lung disease, immunodeficiency, congenital heart disease

• Diagnosis/Treatment:

  • Interstitial Lymphocytic Lung Infiltrates

  • Giant cells = Syncytia

  • No steroids or antibiotics

Rubulavirus (Mumps)

• Attributes:

  • (-) ss RNA virus, enveloped

• Pathogenesis:

• Clinical Presentation:

  • Parotitis: inflamed/tender “chipmunk” parotid glands

    30-40% of patients

    • Normally resolves in 1 week

  • Orchitis: exquisitely painful & inflamed testes

    May cause sterility in post-pubertal adolescent male

  • Aseptic Meningitis

    • pre-vaccine: 15%

    • Causes fever, meningitis

      Usually, self-limiting

• Presentation:

• Diagnosis/Treatment:

Morbillivirus (Measles)

• Attributes:

  • (-) ss RNA virus, enveloped

  • Spread via respiratory droplets, aerosols

  • Contagious 4 days before rash-4 days after

• Pathogenesis:

• Clinical Presentation:

  • flu-like illness, conjunctivitis, swelling of eyelids, photophobia

  • high fever (~105°F), hacking cough, coryza, fatigue

    Kopilik’s spots, rash

    • Red maculopapular (flat-to-bumpy) rapidly becomes confluent, spreads from head to face, to neck, to torso, to feet within 3 days

      Blanches initially but not later

      Rash disappears in same sequence it develops over 3-days

• Presentation:

• Diagnosis/Treatment:

  • No treatment

Influenza

• Attributes:

  • (-) ss RNA virus, enveloped

  • Animal reservoirs: humans, birds, pigs, whales, more

  • Flu A: animals, subtypes

  • Flu B: less widespread (humans)

  • Flu C: rare (humans)

  • Transmission:

    • respiratory secretions and droplets

      Survives 24-48 hours on hard surfaces but generally 4-9 hours

      less on non-porous surfaces

  • Virus Specificity: sialic acids of different species have different internal linkages; HA subtypes are specific for particular sialic acids

  • Uses RDRP

  • Glycoprotein Spikes

    • Hemagglutinin(HA) : attach to sialic acid

      •18 antigenic forms

    • Neuraminidase(NA): release/budding by cleaving sialic acid

      •11 antigenic forms

• Pathogenesis:

• Clinical Presentation:

  • Mild and self limiting with flu-like symptoms that can mimic meningitis

• Presentation:

• Diagnosis/Treatment:

  • Zofluza inhibits the RDRP

  • Rapivab, Relenza, Tamiflu, Permivir, Zanamivir, Oseltamivir —> Block release of virus via neuraminidase

Rhabdovirus

• Attributes:

  • (-) ss RNA virus, enveloped

  • Bullet Shape

  • There are no natural antibodies formed for rabies, so if you aren’t treated you will die

  • 99% dogs or wildlife

• Pathogenesis:

• Clinical Presentation:

  • 3 phases in humans:

    Prodromal phase: non-specific symptoms

    Excitation phase: hydrophobia, excitability,  abnormal sensation; CNS disease obvious

    Paralytic phase: apathy, stupor, coma, flaccid paralysis, vascular collapse and death

• Presentation:

• Diagnosis/Treatment:

  • Post-Mortem you will see Negri bodies

  • Two vaccines in US

    • RabAvert: GSK, chicken fibroblast culture, inactivated, processed, lyophilized

      Pre-exposure vaccination for high-risk groups

      Post exposure vaccination in all age groups

    • IMOVAX: human diploid cell vaccine, inactivated, processed, lyophilized

      Post-exposure prophylaxis

      Require 7-10 days to induce active immunity

  • Treatment

    • Exposed, early, no symptoms, never vaccinated:  vaccine on day 0, 3, 7, 14 PLUS immune globulin (HRIG) AND regardless of the length of time between the bite and the ER

    • Exposed, early, no symptoms, vaccinated: additional vaccine doses

    • Exposed, with symptoms, never vaccinated: vaccine won’t work, immune globulin increases symptoms

      •Palliative care because inevitably fatal…

Ebola Virus (Filoviridae)

• Attributes:

  • (-) ss linear RNA virus, enveloped

  • 6 strains: Zaire (80%), Sudan (60%), Tai Forest, Reston, Bombali, Bundibugyo

  • Pathogenic for humans, highly virulent

  • Hosts: chimpanzees, gorillas/African apes, monkeys, humans

  • Reservoir(s): unknown, possibly includes bats

• Pathogenesis:

• Clinical Presentation:

  • Hemorrhagic Fever

  • Persist in eye and testicles and likely other immune privileged sites

• Presentation:

• Diagnosis/Treatment:

  • rVSV-ZEBOV (Ervebo®)

    •Single dose vaccine (Zaire)

    •FDA approved in US: +18, Ebola responders, lab staff, treatment centers

    •Approved by African countries for outbreak use

  • Vaccine: Zabdeno

    •2-dose with 56-day booster (Zaire)

    •Not appropriate for outbreaks unless already have first dose

    •+>1 year old

Marburg Virus

• Attributes:

  • (-) ss RNA virus, enveloped

  • severe hemorrhagic virus of human and non-human primates

  • Reservoir-African fruit bat

  • Human to human spread via body fluids accessing broken skin or mucus or fomites with body fluids

• Pathogenesis:

• Clinical Presentation:

  • 2-21 day incubation

  • sudden fever, chills, headache, myalgia

  • 5th day-rash on trunk, nausea, vomiting, stomach pain, diarrhea

  • RECOVERY possible OR

  • increasingly severe jaundice, pancreatitis, weight loss, delirium, shock, liver failure, massive hemorrhages, multi-organ failure

• Presentation:

• Diagnosis/Treatment:

MMR vaccines