Bugs Flashcards
Measles Virus
morbillivirus, Paramyxoviridae family, “new” human virus
How is the Measles Virus different that other paramyxoviruses?
1) Lacks neuraminidase activity (protein H, not HN)
2) Forms intracellular inclusion bodies
Measles Illness
- Childhood infection spread by respiratory route.
- Latent: 10-14 days
- 2-3 day prodrome of fever, cough, conjunctivitis
- maculopapular rash, T cell response, virus clearance
Measles Clinical Case Definition
1) Rash >3 days
2) Temp > 38.3/101
3) Cough, rhinorhea, conjunctivitis
* If more than 1 case, contact health department.
Measles: Early Infection Stage
1) First, virus replication restricted to tracheal and bronchial epithelium.
2) After 2-4 days, spreads to lymph nodes
( appearance of reticuloendothelial giant cells-warthin-Finkeldy cells)
3) Amplification of lymph nodes leads to viremia, causes infection of other tissues/organs
Measles Virus Viremia/Disease Progression
1) Symptoms soon after onset of viremia
2) Patient is infectious 1-2 days before symptoms
(10-20 days after exposure)
3) Symptoms:maculopapular (morbilliform) rash and Koplik spots
Measles Virus Complications
1) Immune suppression during infection
-suppression of delayed type hypersensitivity
skin test response
-Antibody/cellular immune responses to new antigens are impaired
2) Acute Disseminated Encephalomyelitis - Autoimmune demyelination disease
- immune response to myelin basic protein
- mechanism unknown/not restricted to measles
3) Measles Inclusion Body Encephalitis/Subacute Scleerosing Panencephalitis
-establishment of perisistent infections in the
brain
-mechanism of entry not understood
Measles Prevention/Control
1) Vaccine (MMR) at 12-15 months and 4-6 years
- live-attenuated provides “life-long” protection
2) Virus is antigenically stable monotypic
- once recovered, individual is immune for life
- different strains (AA different in H or HN) but
Ab to one protects from all
Why is measles ideal to eradicate through Immunization?
1) 1 serotype
2) Cases are clinically identifiable
3) No animal reservoir
4) Eradication requires herd immunity-98% population is immune
What limits measles vaccine?
1) Pregnancy statue
2) Immune status/illness
Mumps Virus
rubulavirus, Paramyxoviridae family
Mumps Illness
1) Initially Infects nasal mucosa/upper respiratory tract epithelium
- incubation is ~18 days
- spreads to draining lymph nodes
- sheds in saliva for ~6 days before clinical onset
2) 1st clinical sign: infection of parotid gland (95%)
Mumps Complications
- CNS involvement: Aseptic meningitis, deafness
- post-pubertal men: symptomatic gonadal issues
- mumps with type 1 insulin-dep diabetes
- MI occurs frequently
- Fetal wastage leading to spontaneous abortion in first trimester of pregnancy.
Mumps Prevention/Control
Vaccine - Live-attenuated, safe, effective, few adverse effects
Rubella Virus
-small, enveloped, nonsegmented, + strand RNA
-Togaviridae family
- alpha virus: western equine encephalitis, EEE,
VEE, arthropod-borne
- rubiviruses: rubella, distinguished from alpha
by limited (human) host range
Rubella Virus Replication Cycle
1) Entry: receptor mediated endocytosis, viral envelope fuses with endosomal membrane in pH dependent manner
2) Genome serves as mRNA for translation of viral polymerase - polymerase makes 1 sense antigenome to make:
-subgenomic mRNA encoding viral capsid and
envelope proteins
-more full-length + strand genomic RNA
Rubella Virus Transmission
By aerosols: initial replication in mucosa of upper respiratory tract and nasopharyngeal lymph nodes
Rubella Illness
mild disease low-grade fever occasional conjunctivitis sore throat lymphadenopathy morbilliform rash- starts on face and spreads
Rubella Disease Progression
~7-9 incubation before virus in in serum, then it starts shedding, isolated from nasopharynx and stool
- rash at 16-21 days after exposure
- virus still shed after rash disappears (up to a month from exposure)
Rubella: worst effect
Congenital Birth Defects (congenital rebella syndrome)
-highest risk in 1st/2nd trimester
1st month-spontaneous abortion/mental retardation/motor disabilities/hearing loss/congenital heart disease/ cataracts
Rubella Prevention/Treatment
- Vaccine in 1969 - before there were epidemics every 3-9 years
- Developed to protect the fetus, not illness in kids/adults
- No antiviral treatment needed b/c mild disease
Leprosy
Hansen’s Disease
Chronic Granulomatous - affecting peripheral nerves and superficial tissues (nasal mucosa)
Caused by Mycobacterium leprae (like MTB)
Can’t grow on agar media/cell culture
Humans and Armadillos
1) Tuberculoid
2) Lepromatous
Leprosy Transmission
- via small droplets from nasal secretions of lepromatous leprosy patients
- low infectivity, prolonged close contact with infected
- 2-7 years incubation
- most common in India and Braxil
About M. leprae
- obligate intracellular parasite, primarily of macrophages and Schwann cells
- also invade peripheral neurons
- Lepromatous causes lack of TH1 mediators
- disease extent determined by T cell-mediatated immunity
Leprosy Disease
- single skin lesions on face, limbs, buttocks
- peripheral nerve involvement can leave lesions anesthetic (not normally facial)
- low # of organisms in lesions, not normally contagious
- Tuberculoid heal and prognosis is good
Lepromatous Leprosy Progression
1st - edema and rhinitis
Lesions on face, buttocks, limbs
Infiltration notable on ear lobes (acid fast bacilli)
Severe Damage - perforation of nasal septum
- collapse of nose (cartilage loss)
- finger loss, neurotrophic atrophy
- atrophy of testicles
Spread to reticuloendothelial system
Leprosy Diagnosis/Treatment
- skin biopsies, acid-fast bacilli
- abx resistance is a problem, multiple drugs
- sulfone (inhibits para-aminobenzoic acid metabolism) + rifampin (cure tuberculoid leprosy in 6 months)
- with lepromatous form +clofazimine and 2 years
- prophylaxis for kids: sulfones
- early diagnosis/treatment is key
Herpesviruses
Linear, ds DNA genome of 150-250 kbp
Icosahedral capsid
enveloped
dozen glycoproteins
DNA replicated/virus assembled in nucleus
*normally self-limiting, but can be life-thretening in immunocompromised host
Herpesvirus Classifications
-Alpha: herpes simplex virus type 1 (HSV-1)
HSV-2
Varcella-zoster virus (VZV)
-Beta: Cytomegalovirus (CMV)
Human herpesvirus 6 (HHV-6)
HHV-7
-Gamma: Epstein-Barr virus (EBV)
HHV-8 (Kaposi's Sarcoma-asscoiated herpies)Herpes Virus Latency
-occurs soon after initial infection
-no virus particles produced (entire genome is extrachromosomally maintained), few viral genes expressed
3 stages: establishment, maintenance, reactivation
Herpes Virus Neurotrophic Latency
HSV-1
HSV-2
VZV
Herpes Virus Lymphotrophic Latency
CMV EBV HHV-6 HHV-7 KSHV
Varicella-Zoster Virus
-Primary infection: Chicken pox
-Highly communicable, aerosol
-Late winter/early spring
-Fever, itchy rash starting on scalp/trunk
-Adult cases more sever-pneumonia
-Reactivation: shingles - sudden onset of pain, rash along thoracic dermatome or forehead
rash last 2-4 weeks, pain longer, postherpetic neuralgia
Varicella-Zoster Virus - Diagnosis/Treatment
Diagnosis is clinical
FDA approved attenuated vaccine (MMR regimen)
Treat chickenpox itchiness and aches
Adult pneumonia require VSV Ig
Zoster treated with oral ACV and steroids
Vaccine designed to boost immunity to or lessen zoster
HHV-6 and HHV-7
Cause roseola (exanthem subitum)
- mild respiratory illness followed by high fever
- after fever, 25% children will exhibit rash on face and body that lasts 2-3 days
- affect 3months-6 years of age
- > 90% US is seropositive
Parvovirus B19
autonomous replication
Genus: Parvovirus
Adeno-associated virus
Genus: Dependovirus
require helper virus
Family Parvoviridae Structure
- linear, ssDNA, 5.6kbp
- icosahedral capsid, no envelop
- or - strand
- replication/assembly in nucleus
- replicate in rapidly dividing cells-providing replication function
Parvo B19: Epidemiology
Erythema infectiosum- “slapped cheek” rash
- “lacy red rash”
“fifth disease” - resolve in 7-10 days
mild, common childhood rash
-50% of population seropositive
1)conversion after school age
2)Ab offer protective immunity
Parvo B19: Pathogenesis
Can spread before rash shows-respiratory secretions!
Biphasic- 4 of 5 will show symptoms
1) initial viremia - may have flu-like symptoms
2) second phase is rash
3) symptoms are immune mediated
-Adults have joint pain/swelling “polyarthritis”, flu-like symptoms
Parvo B19 in certain populations?
Sickle Cell- transient aplastic crisis-B19 infects and lyses erythroid precursor cells
-results in loss of red blood cell production during infection (7-10 days)
-shortened life span of RBC in sickle cell patients, get anemia
Immune compromised: chronic anemia-hard to clear
Transplacentally Transmitted: normally not concerning, 5% fetal anemia, hydrops fetalis, miscarriage-most common in first 1/2 of pregnancy
Parvo B19 Diagnosis
Rash, serological and viral DNA testing of blood
Parvo B19 Treatment
treat flu-like symptoms and itchy rash
anemia patients may need blood transfusion
Parvo B19 Prevention
hard-infectious period before rash
- no vaccine
- genreal hygiene may limit spread
Family Poxviridae
1) Variola (small pox)
2) Vaccinia (small pox vaccine)
-molluscum contagiosum
Non-ocosahedral complex structure- virus can be seen in light microscope “brick-shaped”
-intracellular virus has core & lateral bodies surround by envelope, extracellular virus has additional envelope
-large, double-strand linear DNA genomes that are complexed with proteins
Family Poxviridae Replication
Cytoplasmic replication
makes everything by ribosomes
Variola
Small Pox
-Variola Major (25% fatality)
-Variola Minor (1% fatality)
Systemic disease with generalized rash
Variola Spread
Inhalation from virus being released from ruptured mouth lesions
Variola Virus
Small Pox (eradicated in 1977)
Molluscum Contagiosum
nodular skin lesions
Childhood: lesions-face,trunk, limbs
skin to skin spread
tropical
Young Adult: lower abdomen
sexual transmission
disappear spontaneous in 2 to 12 months
LARGE CYTOPLASMIC INCLUSIONS in eosinophils of affected areaVariola Virus symptoms
prodrome of high fever, malaise, body aches, viremia
-red spots in mouth/tongue: contagious when rupture
Second viremia: infected macrophages go to epidermis-lesions (toxemic)
Variola Virus second viremia
-skin lesion is raised bump with depression in middle
-become pustules (BB inside)
-pustules scab, pitted scar
-contagious until last scab is gone
ALL LESIONS IN SAME STAGE
Variola Virus prognosis
Death or Recovery (complete clearance)
Smallpox vaccine
disease know 2000, Jenner milkmaids (cowpox not bad, provide immunity to all)-1789
- then in 1950s, use vaccinia -live, enoculate in epidermis (local lesion that heals in 2 weeks)
- not effective after 20 years
What key features let smallpox be eradicated?
1) Humans only reservoir
2) No healthy carriers
3) No sub-clinical infections
4) Effective vaccine
Smallpox vaccine effects
- not safe
- NO: pregnant women, immune suppression, eczema, atopic dermatitis, acne, <18, heart disease patients
1 million: 50-1000 severe, 15 life-threatening,
1-3 die
can give VIG: Vaccine immune globlin
can give Cidofovir
Vector-borne/Zoonotic
rare "flu-like" initially rapid treatment critical human to human is rare -have animal/insect reservoir
Vector Borne Transmission
tick, flea, louse
transmit during blood meal
Zoonotic Transmission
aerosol, fluid, direct contact
Rickettsia
gram - rods, obligate intracellular bacteria
Can’t culture on media
3 phyla: rickettsia (vector-borne), ehrlichia (vector)
coxiella (non-vector)
-diagnosis relies heavily on patient presentation & travel
-confirm by serology
all responsive to doxycycline
Rickettsia Symptoms
Classic: fever-headache-rash (rash 3-5 days)
- replicate in cytoplasm of endothelial & muscle cells of small blood vessels
- Hemorrhage & edema
- Vasculitis leading to rash & headache
R. Rickettsia
“Rocky Mountain Spotted Fever”
-ticks
2000 cases a year, seasonal, in NC, SC, AR, MO, OK
endemic in TN
R. Rickettsia symptoms
Initial: flu with severe headache, then rash
- spreads from ankles & wrists to soles, palms, trunks
- calf muscle tenderness
- Septicemia, DIC
R. Rickettsia Diagnosis
-presentation/history
-Weil-Felix serologic test (non-specific)
Indirect Fluorescent Antibody (need early blood draw, then one several weeks later) -need 4 fold increase in titers
-25% mortality if untreated
R. prowazekii
Epidemic Typhus
- Human to human by body lice (flying squirrels?)
- Historical - poverty & wars
- Rash similar to Rocky, but spreads from trunk to extremities, not palms/soles
- Not in US
- 10-60% mortality rate- myocarditis, CNS
R. typhi
Endemic (murine) typhus
-southern Texas, southern California, Hawaii
Rat flea to human
less severe than epidemic typhus, less mortality
Ehrlichia
southern tick borne disease 1,400/year
E. chaffeensis
Human Monocytic ehrlichiosis Transmitted by Lone Star deer tick replicates in monocytes ***form inclusions called morulae*** (wright/Giemasa stain) -treat with doxycycline
A. phagocytophilia
Human granulocytic anaplasmosis "rocky moutain spotless fever" Ixodes deer tick -wright/giemsa stian - morulae in granulocytes -serology treat with doxycycline
Borrelai
Spirochetes
- most to thin for gram staining (use Wright/Giemsa)
- antigenic variation (1 in 1000 change surface antigens)
B. burgdorferi
Lyme Disease
Ixodes deer tick nymph to humans-prevented if removed in 24 hours
-most common tick disease (22,000)
-Endemic New England, Mid-Atlantic, Upper Midwest, TN
B. burgdorferi Symptoms
Early: flue-like Classic Bull's Eye Rash at sight of tick Secondary: disseminated -weeks/months after initial infection -arthritis, facial palsy, peripheral neuropathy Tertiary: chronic -months/years -erosive arthritis (knees) -numbness, Bell palsy
B. burgdorferi Diagnose/ Treatment
2 step seriological test: ELISA
Western Blot
-PCR-based NAATs
Treat: early (doxy or amoxicilllin)
chronic (IV cephalosporines extended)
B. hermsii
B. recurrentis
“relapsing fever”
tick-hemsii, endemic in high, dry west US
louse-recurrentis
-3 day on, 1 week off,(antigenic variation) rash uncommon
microbes in wright/giemsa stain
serology needed to confirm
Treat: doxycycline
Leptospira interrogans
Spirochetes-Leptospirosis
- water with animal urine (break in skin)
- NO skin lesions
- flu-like, jaundice/renal (Weil’s disease), meningitis
DDX: serologic
Treat: Penicillin
-vaccine cattle & pets
Bartonella henselae
Cat Scratch can reservoir (no symptoms) -mostly kids (24,000) swollen lymph glands near scratch Adults: flu-like, Both: disseminated disease involving CNS in immune compromised DDX: presentation, history (scratch) most clear on own, immunocomprised
Anthrax
eschar at site
Plague
swollen gland (bubo) in groin/axilla
Tularemia
ulcer at infection site
