Infectious disease Flashcards
What are the classes of human pathogens? Give an example of each and a disease it causes
Prions: prion protein, Creutzfeld-Jacob
Virus: poliovirus, poliomyelitis
bacteria: Streptococcus pneumoniae, pneumonia
fungi: Candida, thrush
protozoa: Trypanosoma cruzi, Chagas disease
helminths: trichinella spiralis, trichinosis
What histochemical stain highlights Histoplasma capsulatum?
Romanowsky/Giemsa
Which coccobacillus is negative for Gram staining but stains with silver (causes necrotizing bronchopneumonia)
Legionella pneumophila serogroup 1
What is the typical pattern of injury in a kidney bx from post-streptococcal kidney failure?
Diffuse proliferative glomerulonephritis
Name 4 viruses that can cause interstitial nephritis
CMV, EBV, BK, Hantavirus
Name 4 organisms other than TB that stain with acid fast stain
Nocardia sp.
Mycobacterium marinum
Legionella micdadei
Rhodococcus equi
What is the causative organism in cat scratch associated lymphadenitis?
Bartonella henselae
What intracerebral infection (ring enhancing lesion) in an HIV patient with a CD4 count of 50?
Toxoplasma gondii
What morphology do dimorphic fungi show in histology samples?
yeast structures
Negri bodies are seen in which condition?
Rabies encephalitis
What are 3 conditions associated with HHV8?
Kaposi sarcoma
Multicentric Castleman disease
Primary effusion lymphoma
Name 4 viruses causing hemorrhagic fevers
Lassa virus
Ebola virus
Marburg virus
Machupo virus
What are the histologic findings in a colon bx from a patient infected with Shigella?
Cryptitis, crypt abcess, pseudomembranes
Name 4 category A disease/bioterrorism agent as classified by the CDC?
Bacillus anthracis
Yersinia pestis
Clostridium botulinum toxin
Variola major virus (smallpox)
What is a finding in pseudomonas infections?
Necrotizing pneumonia
Name features of primary, secondary, tertiary syphilis
1: chancre on the penis/scrotum/vulva/cervix
2: diffuse rash (palmar)
3: endarteritis of proximal aorta, gummas of skin, bone, liver
Argyll0Robertson pupils
What is a cause of elephantitis?
Worms in the lymphatic system causing damage to lymphatics; aka filariasis. Includes Wuchereria bancrofti and Brugia sp.
What species of fungi are the most frequent cause of human infections?
Candida species
What does symbiosis imply?
Organisms that live on or in other organisms (hosts), with a mutually advantageous arrangement
Give 4 features of Whipple disease
- caused by gram-positive actinomycete Tropheryma whippelii
- histology shows dense accumulation of distended, foamy macrophages in the small intestinal lamina propria
- Ddx includles intestinal tuberculosis
- foamy macrophages are positive for PASD, but do not stain with acid fast stain
Name at least 4 human prion diseases
Creutzfeld-Jacob Variant Creutzfeld-Jacob Kuru Fatal familial insomnia Gerstmann-Straussler-Scheinker syndrome
What is the condition caused by prions?
Transmissible spongiform encephalopathies
What are prions, and how do they differ from other infectious organisms?
Infectious agents composed of misfolded proteins, that cause transmissible neurodegenerative disorders
They differ from others in that they do not contain nucleic acids
Describe the pathogenesis of prion disease
Normal prion protein (PrP), normally present in neurons undergoes a conformational change to abnormal form making it indigestible to proteases
Infectious (PrPsc) binds to normal (PrP) protein, catalyzing it into the abnormal form
- The new PrPsc continues to catalyze the transformation of more prion protein
- Abnormal prion protein accumulates in neural tissues, causing pathology
What are the 3 methods by which prion disease arises in humans?
- Acquired
- Familial
- Sporadic
What are the clinical presentations of prion diseases?
- Personality changes
- Psychiatric disorders (depression)
- Lack of coordination
- Ataxia
- Myoclonus
- Sensory changes
- Insomnia
- Confusion
- Memory deficits
- Dementia
- Paralysis
List 5 types of CJD
- Classic CJD
- Iatrogenic CJD
- Variant CJD
- Familial CJD
- Sporadic CJD
Compare and contrast classical and variant CJD
Classic:
age at death: 68
duration of illness: 4 months
s/s: dementia, neurologic
EEG with periodic short waves: present in 75%
florid plaques on histology: absent
IHC: variable accumulation
immunoblot for protease-resistant protein: not reported
detection of infective prion in lymphoid tissue: not detected
Variant: age at death: 28 yrs duration of illness: 13 months s/s: psychiatric, behavioural, sensory symptoms EEG periodic short waves: absent pulvinar sign on MRI: present florid plaques on histology PrP accumulation significant on IHC Significant PrP accumulation on immunoblot prion detected in lymphoid tissue
What are the microscopic features of CJD?
- Spongiform transformation of cerebral cortex, caudate, putamen
- Uneven distribution of variably sized small microscopic vacuoles within neuropil and perikaryon of neurons, expanding into cyst-like spaces
- Severe neuronal loss and reactive gliosis in advanced cases
- Kuru plaques (aggregates of PrPsc) frequently in cerebellum
- Kuru plaques also found in cerebral cortex in variant CJD
- Plaques are Congo red and PAS positive
Which prion disease does not show spongiform change? What are the characteristic histologic findings?
- Fatal familial insomnia
- Shows neuronal loss in anterior ventral and dorsomedial nuclei of thalamus, inferior olivary nuclei
- Reactive gliosis in anterior ventral and dorsomedial nuclei of thalamus
What four factors affect viral tropism?
- Host cell receptors
- Cellular transcription factors that respond to viral enhancers and promoter sequences
- Anatomic barriers
- Local environment including temperature, pH, host defenses
Through what 3 mechanisms do viruses cause damage to human hosts?
- Direct cytopathic effects
- Eliciting immune response that damages tissues
- Transforming infected cells into neoplastic cells
What are the three components of the viral particle?
- Envelope
- Capsid
- Core
List the Baltimore classification of viruses and give an example of each.
- dsDNA: herpesvirus
- ssDNA: parvovirus
- dsRNA: reovirus
- +ssRNA: West Nile virus
- -ssRNA: rabies virus
- ssRNA-RT: HIV
- dsDNA-RT: hepatitis B
What is the classification of viral hepatitis?
- can be classified by virus or by clinical syndrome
- clinical: acute symptomatic infection with recovery, acute symptomatic hepatitis with recovery, chronic hepatitis (+/- progression), fulminant hepatitis (massive/submassive hepatic necrosis)
- by virus type:
hepatotrophic: hepatitis A,B,C,D, E
non-hepatotrophic: CMV, EBV, herpes, adenovirus, HIV
What is the definition of chronic hepatitis?
Symptomatic, biochemical or serologic evidence of continuing/relapsing hepatic disease for greater than 6 months
What is the frequency of chronic liver disease for each hepatotrophic virus?
- Hep A: 0%
- Hep B: 10%
- Hep C: 80%
- Hep D (coinfection): 80% with HepB
- Hep E: 0%
What genotypes of HCV have the best response to treatment
- Genotypes 2 and 3
What defines the carrier state of HBV?
- Infected individual who can transmit the virus, but is asymptomatic (no liver disease or non-progressive damage)
- serologically have anti-HBe, normal AST/ALT, low serum HBV DNA
- do not have HBe-Ag
What are the laboratory and histologic findings in a healthy carrier of HBV?
- HBsAG+, HBeAG-
- AntiHBe+
- HBV-DNA low or negative
- ALT/AST normal
- bx: lack of inflammation or necrosis
What are the histologic findings in acute hepatitis
Hepatocyte ballooning degeneration
Cholestasis
Lymphocytic infiltrate, zone 3
Apoptotic hepatocytes with fragmented nuclei and eosinophilic cytoplasm
focal hepatocyte dropout w/ macrophages
Kupffer cell hypertrophy and hyperplasia with lipofuscin pigment
portal tract infiltrate with mixed inflammatory cells
What are some specific histologic features of acute HAV and HBV?
HAV: plasma-cell predominant inflammatory infiltrate of portal, periportal, lobular areas with perivenular cholestasis, extensive microvesicular steatosis
HBV: ground glass hepatocytes caused by cytoplasm packed with spheres of HBsAg
What are the histologic findings of chronic hepatitis?
- Lymphocytic portal infiltrate, +/- interface hepatitis
- varying degrees of necrosis/bridging necrosis
- varying degrees of fibrosis periportal–bridging
What are some specific histologic features of chronic HBV and HCV?
HBV: ground glass hepatocytes
HCV: lymphoid aggregates +/- germinal centres and reactive bile duct changes, focal macrovesicular steatosis esp. with genotype 3
What are the histologic findings in cirrhosis?
Hepatocytes divided into irregularly sized nodules separated by thick bands of fibrosis
What are several common grading/staging systems for viral hepatitis?
Hepatic activity index Ishak modification Scheuer classification Metavir classification Batts-Ludwig
What is reported in a grading/staging system for viral hepatitis
- Grade: degree of inflammation/necrosis
- Stage: degree of fibrosis
What is fulminant hepatic failure
Hepatic insufficiency that progresses from the onset of symptoms to hepatic encephalopathy in 2-3 weeks in an individual who does not have chronic liver disease
What are the morphologic features of fulminant hepatitis?
- Loss of liver mass
- Limp, red tissue
- Wrinkled capsule
- Necrotic red interior with hemorrhage
- Complete destruction of hepatocytes, with collapsed reticulin and preserved portal tracts
Describe transmission incubation period diagnostic investigations for the hepatotrophic viruses
A: F/O, 2-6 weeks anti-HAV (IgM)
B: parenteral, vertical, 6wks-6mo, HbSAg, HBVAg antibody
C: parenteral, 5-10wks, HCV RNA or anti-HCV (IgG/IgM)
D: parenteral, close contact; 6wks-6mo, Anti-HDV (IgG/IgM), HDV RNA, HDVAg in liver
E: F/O, 2-6wks, Anti HEV (IgG/IGM) or HEV RNA
What IHC stains are useful in HBV, and how are they used?
- HBV core antigen and HBV surface antigen
- can be negative in acute HBV
- positive in chronic, with decreased staining when +++Inflammation
- HBsAg stains cytoplasm
- HBcAg stains nucleus, represents active viral replication
- if HBsAG is membranous and HBcAg cytoplasmic=unopposed replication
Describe the serological/PCR findings of HBV in the following:
- Acute
- Chronic (high-infectivity)
- Chronic (low-infectivity)
- Recovered
- Immunized
Acute: HBsAG+, HBeAg+, Anti-HBC IgM, HBV DNA+
Chronic/infective: HBsAG+, HBeAg+, Anti-HBc IgG, HBV DNA+
Chronic/non-inf.: HBsAg+, HBeAg-, Anti-HBe+, Anti-HBC IgG, HBV DNA-
recovered: HBsAg-, AntiHBs+, HBeAg-, AntiHBe+, AntiHBc-IgG, HBV DNA-
immunized: Anti-HBs + (all the rest negative)
What are risk factors for HCV?
- IV drug use
- multiple sex partners
- recent surgery (6 mo)
- Needle stick injury
- Multiple contacts with HCV infected popuation
- employment in medical/dental fields
What is the natural history of HCV infection?
- Persistent infection/chronic hepatitis in 80%
- cirrhosis in 5-20 yrs in 1/3 of pts with persistent infection
Describe the morphology and IHC of HDV
- Same features as HBV
- HDAg
Describe HDV co-infection, superinfection and helper independant latent infection
- Acute co-infection: occurs on exposure to both HBV/HDV; HBV establised first, providing HBSAg necessary for HDV virions; hepatitis ranges from mild to fulminant (rarely chronic)
- Superinfection; occurs when chronic HBV exposed to new HDV; acute hepatitis 30-50d later, fequently develops into chronic disease/cirrhosis
- Helper independant: in liver transplants, HDV detected in nuclei of liver w/o HBV (prevented with HBV immunoglobulins)
What is hepatitis F
Various undesignated viruses causing hepatitis
some cause hemorrhagic hepatitis with toga-virus like particle on EM
Define Hepatitis G
Flavavirus related to HCV, transmitted by blood/sexual contact
- no known human disease, not hepatotrophic and no elevations in ALT/AST
What is relationship between HGV/HIV
- commonly co-infect
- dual infection protective against HIV
What should you do if you cut your finger during an autopsy?
- Follow facility’s procedures
- Wash wound with warm water/soap
- Hold affected limb down to get it to bleed
- Do not squeeze wound or soak in bleach
- apply antiseptic if necessary (poviodine-iodine 10%)
- contact occ heath or ED ASAP
What is the usual clinical presentation of infectious mononucleosis?
- Fever, generalized lymphadenopathy, splenomegally, sore throat, fatigue, atypical activated T lymphocytes (mononucleosis cells) in the blood
What are the uncommon complications of acute EBV infection?
splenic rupture, upper airway obstruction, hepatitis, encephalitis, pneumonitis, hemophagocytic lymphohistiocytosis
