Week 6 and 7 Flashcards
Mycoplasma Pneumoniae:
Main features:
- gram stain?
- membrane contains ______
- transmission?
No cell wall (does NOT gram stain)
Membrane contains cholesterol
Transmitted via inhalation of respiratory droplets (highly contagious)
Exclusively human pathogen
Mycoplasma Pneumoniae:
Pathogenesis
Inhaled → adheres to respiratory epithelium → inhibit ciliary motion and destroy mucosa → inflammation WITHOUT invasion into mucosa
Mycoplasma Pneumoniae:
Virulence factors (1)
P1 adhesin → allows cytotoxic effects on cilia
Mycoplasma Pneumoniae:
Diseases
1) Atypical pneumonia (walking pneumonia)
2) *Hemolytic anemia
3) Tracheobronchitis
4) Wheezing in infants
5) Pharyngitis
6) Rhinitis
Mycoplasma Pneumoniae: atypical pneumonia presentation
typically effects who?
Atypical pneumonia (walking pneumonia)
Symptoms: fever, headache, myalgia, tracheobronchitis, non-productive cough
Vague ill-defined or patchy opacities
Typically affects: young people - those in close quarters (prisons, military bases)
Mycoplasma Pneumoniae:
treatment (3)
Macrolide (erythromycin, azithromycin)
Tetracycline (doxycycline)
Fluoroquinolone
Mycoplasma Pneumoniae:
Diagnosis (3 ways)
Serology
Cold serum agglutination test
PCR
Cold serum agglutination test
non specific test for Mycoplasma Pneumoniae
autoimmune response involving cold hemagglutinins of IgM antibodies (molecular mimicry) and blood group antigen I of human RBCs → activates complement
Legionella Pneumophila:
Main features:
- oxidase?
- intra/extracellular?
- gram stain? shape?
- grows on what?
- what special stain?
Facultative intracellular
Oxidase positive
Gram negative bacillus
Grows on charcoal yeast extract with iron and cysteine
Weak gram stain → SILVER STAIN
Legionella Pneumophila:
Transmission
Transmission via aerosols from environmental water sources (air conditioning systems, hot water tanks)
Legionella Pneumophila:
Disease
Legionnaire’s Disease
Pontiac Fever
Legionella Pneumophila:
Treatment
Macrolides (azithromycin)
Fluoroquinolones (levofloxacin)
Legionnaire’s Disease
severe, lobar pneumonia
Nonproductive cough
Confusion, diarrhea
Signs of kidney damage (proteinuria, microscopic hematuria)
Hyponatremia (due to SIADH and/or renal tubulointerstitial disease impairing sodium reabsorption)
Pontiac fever
mild flu-like illness (fever, chills, fatigue, malaise, headache) without respiratory symptoms
Legionella Pneumophila
Diagnosis
Presence of antigen in URINE
C. Diphtheriae:
Main features
-anaerobe, aerobe?
-spore forming?
-gram? shape?
-motility?
-appearance on microscopy?
Culture on what agar? appears what color?
Aerobic
Non-spore forming
Gram positive bacillus
Non-motile
“Chinese letter” appearance on microscopy
Culture on cystine-tellurite agar → BLACK colonies
C. Diphtheriae
colonizes where?
transmitted how?
Transmitted via respiratory droplets
Colonize nasopharynx
C. Diphtheriae
Virulence factors
AB exotoxin
C. Diphtheriae
AB exotoxin
catalyzes ADP ribosylation of EF-2 → inhibit EF2 and prevent tRNA translocation from ribosomal A-sites to P-sites
Encoded by bacteriophage
Causes cardiac (arrhythmia and myocarditis) and nervous (cranial/peripheral nerve palsy) effects
C. Diphtheriae
Disease
Grayish-white pseudomembranes in oropharynx (can cause suffocation)
Cervical lymphadenopathy (“Bulls neck”)
Myocarditis (if left untreated)
Progressive deterioration of myelin sheaths in CNS and PNS → blurry vision, pharyngeal/diaphragmatic paralysis
C. Diphtheriae
Diagnosis (2 ways)
1) visualization of gram (+) bacilli with metachromatic (blue and red) granules on specialized media (Loeffler’s)
2) Presence of toxin production via positive Elek test
C. Diphtheriae
Treatment
penicillin or erythromycin (for local colonization)
Antitoxin for toxin neutralization
DTaP booster to prevent recolonization
B. Pertussis:
Main features
- gram? shape?
- capsule?
- oxidase?
- aerobe/anaerobe?
- culture on what two media?
Gram negative, coccobacillus Encapsulated Oxidase positive Strict aerobe Cultured on Regan-Lowe or Bordet-Gengou (potato) agar
B. Pertussis
Transmission?
Humans are only reservoir of Bordetella pertussis
Transmitted via respiratory droplets
B. Pertussis
Virulence factors (3)
Pertussis toxin (AB toxin)
Adenylate cyclase toxin
Tracheal toxin
B. Pertussis
Pertussis toxin (AB toxin) - A component
ADP ribosylates Gi (remove ADP-ribosyl group from NAD and covalently attaches it to Gi) → Gi inactivation → increased cAMP
→ increased secretion of Na+, Cl-, H2O from cells → edema, neutrophil dysfunction
B. Pertussis
Pertussis toxin (AB toxin) - B component
Facilitates endocytosis
B. Pertussis
Adenylate cyclase toxin
increases intracellular cAMP → inhibit leukocyte chemotaxis and phagocytosis
B. Pertussis
Tracheal toxin
inhibits DNA synthesis in ciliated epithelial cells → cell death → loss of ciliated epithelial cells → debris accumulates in lungs → coughing fits
B. Pertussis
Disease
Whooping cough: “whoops” on inspiration, coughs on expiration
Incubation period = 2 weeks → 3 major phases
Cough lasting > 2 weeks
Highly contagious acute respiratory infection
B. Pertussis
major phases of whooping cough
Catarrhal phase: mild coughing and sneezing
- Highly contagious
- Mild clinical course
Paroxysmal phase: classic whooping cough, can induce post tussive vomiting
Convalescent phase: gradual reduction in severity and frequency of cough
B. Pertussis
Diagnosis (2 main things)
Absolute lymphocytosis (due to pertussis toxin)
Hypoglycemia (due to increased insulin secretion from increased cAMP)
B. Pertussis
Treatment
-when should it be given?
Macrolides (given during catarrhal stage)
- Also used for prophylaxis in close contacts
- Can decrease bacterial shedding, but does NOT alter disease course if given during paroxysmal stage
Supportive care
Sepsis
-what is the early predictor of bad outcome?
life threatening organ dysfunction due to dysregulated host immune response
Abnormalities of cognitive dysfunction are among most sensitive early predictors of bad outcome with sepsis
In a THIRD of patients with sepsis, an infectious organism is NEVER found…how is that possible?
endogenous antigens may also trigger sepsis
Noninfectious diseases can mimic sepsis:
-Acute MI, acute PE, acute pancreatitis, acute GI bleeding, adverse drug reactions, accidents (major trauma), severe burns
Common pathway of sepsis:
Sepsis → endothelial injury due to inflammation, oxidant stress and then increased coagulation/decreased fibrinolysis → organ failure → death
Maladaptive immune response is what causes disease
- Young → hyperimmune
- Old, malnourished, DM → deplete immune response, hypoimmune
Primary sepsis mediators (5)
IL-1, TNF-a, IL-10, ROS, lipids
Early cellular and molecular events during infection: (3)
1) Vasodilation and endothelial activation
2) Leukocyte recruitment and activation
3) Coagulation and NET formation → block microcirculation
Sepsis is a viscous cycle of…
hypoperfusion, vasodilation, capillary leak, endothelial damage, microvascular obstruction, myocardial depression, ischemia, microcirculatory shunts and acidosis
VASODILATION, ENDOTHELIAL DAMAGE→not enough circulating volume
In sepsis, alterations in microcirculatory blood flow → ?
abnormal microcirculation with inflammatory response
Decrease number of functional capillaries and blood is diverted → unable to extract O2 → anaerobic metabolism and production of lactate
Cytopathic mitochondrial dysoxia
Responsible for pathogenesis of septic organ failure
oxygen utilization by mitochondria is DYSFUNCTIONAL but oxygen delivery is PRESERVED
ATP not effectively generated
Due to cytokines
Resuscitation bundle used in sepsis
start immediately, complete within 3 hours
Blood and respiratory cultures
Broad spectrum abx - within 1 hr
- Mortality increased by 7.5%/hr beyond first hr of shock
- Must select CORRECT abx
IV N/S (30mL/kg in 1st 2 hr) + add albumin
Normalize serum lactate
Vasopressors
Yersinia Pestis
Transmission (3)
1) Flea bite (flea carries Y. pestis from infected animal to human host)
2) Respiratory droplets (from infected host)
3) Direct contact (with infected tissue or fluid from human or animal host)
Yersinia Pestis
Main features:
- staining?
- gram? shape?
- motility?
- intra or extracellular?
- Bipolar “safety-pin” staining on Wayson stain
- Wright-Giemsa staining
- Gram negative bacillus
- Pleomorphic
- Nonmotile
- Facultative intracellular
Yersinia Pestis
Virulence factors: (2)
Capsular F1 antigen
Type III secretion system
Yersinia Pestis
Capsular F1 antigen
prevent phagocytosis, generates antibody response
Yersinia Pestis
Type III secretion system
allows organism to inject Yops (yersinia outer proteins) → inhibit phagocytosis and cell signaling
Yersinia Pestis
3 types of plague?
1) Bubonic plague
2) Septicemic plague
3) Pneumonic plague
Bubonic plague
sudden onset fever, chills, weakness, headache → intense pain and swelling of lymph gland (BUBOES) resulting from bite of flea 2-5 days earlier → 60-90% mortality if untreated
Uncontrolled spread can cause organ abscess, cutaneous hemorrhage, and tissue necrosis
Septicemic plague
invasion of almost all organs, no significant evidence of prior disease
Nonspecific fever, GI illness and pain
Buboes are NOT present
Death occurs in 12-24 hours
Pneumonic Plague
primary or secondary lung infection which is infectious and 100% fatal if untreated - most infectious
Acquired by inhaling droplets or hematogenous spread
Sudden onset dyspnea, fever, pleuritic chest pain, cough, bloody sputum
Yersinia Pestis
Treatment (2)
1) Streptomycin, Gentamicin
2) Doxycycline, Tetracycline
Prophylaxis: doxy or tetracycline
Francisella Tularensis
Main features
- gram? shape?
- where in the US it occurs?
- intra or extracellular
- immune evasion?
Gram negative coccobacilli
Occurs in Missouri and Arkansas
Pleomorphic
Facultative intracellular
Can undergo phase variation to avoid immune response
Francisella Tularensis
Transmission (3)
Bite by tick (Dermacentor variabilis) or deerfly
Handling infected animals (primarily rabbits)
Inhalation of aerosol
Francisella Tularensis can/cannot be spread person to person?
Yersinia pestis can/cannot be spread person to person?
Francisella Tularensis CANNOT be spread from person to person
Yersinia pestis CAN be spread from person to person (pneumonic plague)
Francisella Tularensis
Treatment (2)
1) streptomycin, gentamicin
2) levofloxacin and doxycycline
Francisella Tularensis
Tularemia
site-specific infection and lymphadenopathy
Painful ulcer at site of infection + regional lymphadenopathy
Can cause granulomas with caseating necrosis in reticuloendothelial system (lymph nodes, spleen)
Borrelia Burgdorferi
Transmission
Ixodes tick bite - mostly in summer in NE United States
Most infections in late spring and summer
Tick must feed for 48-72 hours to transmit sufficient bug
Ixodes tick also vector for Anaplasma and Babesia
Borrelia Burgdorferi
Primary (natural) RESERVOIR are _________
________acts as intermediate HOST (food source for adult ticks)
Primary (natural) RESERVOIR are rodents (white-footed mouse)
White-tailed deer acts as intermediate HOST (food source for adult ticks)
Borrelia Burgdorferi
Lyme disease - STAGE 1
Stage 1 = Early-Localized Lyme Disease: Erythema migrans +/- viral-like syndrome - occurs in 1-4 weeks after bite
Begins as homogenous erythema that may spread to develop central clearing = Bull’s-eye rash
Borrelia Burgdorferi
Lyme disease - STAGE 2
Stage 2 = Early-Disseminated Lyme Disease: acute neural or cardiac involvement - weeks to months after tick bite
- Lymphocytic meningitis
- Facial nerve (Bell’s) Palsy
- Peripheral neuropathy
- AV heart block
- Migratory arthralgias
Borrelia Burgdorferi
Lyme disease - STAGE 3
Stage 3 = Late Lyme disease: chronic arthritis of large joints (knee) and encephalopathy
Borrelia Burgdorferi
Lyme disease - Diagnosis
Empirical abx treatment without testing if pt has erythema migrans
Serologic testing + Western blot → abx treatment if positive
Do NOT treat if serologic treatment negative
Borrelia Burgdorferi
Lyme disease - Treatment?
Doxycycline (early disease)
Ceftriaxone for neurologic disease
Rickettsiae
main characteristics
- motility? spores?
- gram? shape?
- intra/extracellular?
- stain?
- what carries disease?
Non-motile, non-spore forming
Weakly gram negative coccobaccili
Highly pleomorphic
Obligate intracellular bacteria
Stain with Giemsa stain
Have animal reservoirs - arthropod transmitted, humans are incidental hosts (except louse borne typhus fever
Rickettsiae
Pathogenesis
Invade endothelial cells → disseminate through vascular system → anemia, hypovolemia, ischemia and rash
→ causes VASCULITIS and RASH
Rickettsiae
Clinical presentation
Abrupt onset headache, fever, petechial rash
Rickettsia Rickettsii
disease?
Rocky Mountain Spotted Fever (RMSF)
Rocky Mountain Spotted Fever (RMSF)
- infection where?
- transmission?
Infection of endothelial cells
Transmitted to humans from bite of Dermacentor tick
Typically in North Carolina
Humans are an incidental host
Rocky Mountain Spotted Fever (RMSF)
Symptoms?
acute onset fever, headache, myalgias → petechial rash that starts on ankles and wrists and spreads to trunk
RASH: appears on PALMS and SOLES then spreads
**STARTS on extremities and moves to trunk (CENTRIPETAL)
Can get thrombocytopenia and hyponatremia
Treatment of Rocky Mountain Spotted fever?
Doxycycline
Rickettsia Typhi
Disease?
Endemic (murine) Typhus
Endemic (murine) Typhus
Transmission?
Carried by rats and transmitted to humans from feces of fleas
Endemic (murine) Typhus
Symptoms?
hills, high fever, headache, myalgias
Maculopapular RASH: starts on trunk and moves to extremities (CENTRIFUGAL) sparing face, palms, and soles
8-16 day incubation
Rickettsia Prowazekii
Disease? (2)
Epidemic Typhus
Brill’s Disease
Epidemic Typhus
Transmission?
Transmitted from feces of lice
Tick bites, and defecates → spread to blood by itching
Epidemic Typhus
Symptoms
encephalitis, confusion, myalgias, arthralgias, pneumonia, RASH that spreads from trunk out to extremities
Ehrlichia and Anaplasma
Main features?
gram? shape?
intra/extracellular?
-infects what kind of cells?
-trasmission?
Gram-negative bacilli
Obligate intracellular - enter cell, prevent fusion of lysosomes, inhibits host cell apoptosis
Infect phagocytic cells and multiple inside vacuoles
Transmitted by ticks, reservoir is deer
Ehrlichia and Anaplasma
Clinical presentation?
fever, headache, malaise WITHOUT rash
→ Leukopenia and thrombocytopenia
Elevated AST and ALT
Erhlichiosis
- transmitted by what?
- found where?
- infection of what cell type?
Morulae (intracytoplasmic inclusions) within monocytes
Transmitted by Lone Star Tick → infection of monocytes and macrophages
Found in Mid-Atlantic, Southeastern, and South Central states
Anaplasmosis
- transmitted by what?
- found where?
- infection of what cell type?
Morulae within granulocytes
Transmitted by Ixodes Tick → infection of neutrophils
Found in NE and upper Midwest
Oxygen and Anaerobes:
Oxygen is TOXIC for anaerobes - why?
- Direct oxidation of cellular components
- Production of H2O2 and O2- → Strict anaerobes lack catalase and SOD
Anaerobes that cause disease are usually AEROTOLERANT → may produce catalase and/or SOD
Anaerobic Normal Flora:
Anaerobes are THE predominant component of human microbial flora → oral cavity, colon, female genital tract, skin
ANY of these can cause infections in adjacent tissue
Abscess formation of anaerobes - acute vs. chronic stage?
Mixed (polymicrobial) infection with anaerobes plus facultative or aerobic organisms
Acute stage: aerobes and facultative organisms predominate → hypotensive
Chronic stage: formation of fibrin-encased abscess
Anaerobes predominate - polymicrobial
Bacteroides fragilis
Frequent isolate from anaerobic abscesses (BELOW the diaphragm) - Minor component of gut flora, BUT isolated from 80% of abdominal abscesses
Bacteroides fragilis
Virulence factors? (3)
Aerotolerant (catalase and SOD production)
Extracellular enzymes (phospholipase, collagenase)
Capsule - abscess formation
C. Tetani
In feces and soil
Spores introduced into wounds → germinate and devitalized tissue → locally produce tetanospasmin → transported to CNS via retrograde axonal transport along peripheral motor neurons
→ block release of inhibitory neurotransmitters (GABA, glycine)
Disease: Tetanus
C. Botulinum - spores
Spores in soil and water, commonly contaminate food and wounds
Pressure sterilization required to kill SPORES
TOXIN is heat-labile and destroyed by cooking
Botulism
Botulinum toxin blocks ACh transmission at neuromuscular junctions → “DESCENDING flaccid paralysis”
Babies ingest honey with SPORES → form TOXIN in gut
Adults ingest PREFORMED TOXIN
Pathogenesis of Foodborne Botulism:
Spores from soil/water contaminate food → spores germinate, grow, and produce toxin (WITHOUT signs of spoilage)
Food (toxin) consumed (uncooked) and enters bloodstream → synapses at NMJ
Zoonotic Viruses
viruses that normally exist within animal reservoirs and cause disease when transmitted to humans
Rabies Virus
Main features:
- genome?
- symmetry, capsid?
- enveloped or non-enveloped?
- virus family?
Linear, nonsegmented negative ssRNA
- Bullet shaped helical capsid symmetry
- Enveloped
- Rhabdovirus
Rabies Virus
Transmission
- ONLY ANIMAL –> HUMAN
- Transmitted from animals to humans, but do NOT exhibit human to human transmission under natural conditions
Bite from a rabid animal
Highest risk with canine rabies virus (eliminated in USA), so mostly due to bats (overall), skunks (west, and racoons/foxes (east)
Virus shed into saliva and secretions of other organs (virus travels down peripheral nerves) → spread via aerosols or bites
Pathogenesis of Rabies Infection
Rabies virus glycoprotein binds nicotinic ACh receptors in postsynaptic muscle membrane of NMJ and enters → infection and replication within striated muscle cell at site of wound
Eventually virions cross synaptic cleft → bind neural cell adhesion molecules (NCAMs) and enter motor and sensory neurons → retrograde axonal transport to CNS
Negri Bodies
- where are they?
- what do they look like?
- what is going on here?
eosinophilic cytoplasmic inclusions, where replication and transcription of rabies virus occurs
Located in neuron cell bodies in spinal cord and CNS (especially Purkinje cells in cerebellum and pyramidal cells of hippocampus)
Rabies virus Incubation period
weeks to months (PROLONGED)
Longer incubation when bite on lower extremities (longer distance for virus to travel before it can get to CNS and replicate)
→ allows for POSTEXPOSURE PROPHYLAXIS
Disease caused by Rabies virus?
Flu-like prodrome (fever, malaise, anorexia, headache, nausea, vomiting)
→ Acute neurologic syndrome: hydrophobia, aerophobia, photophobia, autonomic instability, hallucinations
Dysphagia due to pharyngeal muscle spasms
Generalized flaccid paralysis and coma after acute neurologic phase
Rapidly fatal encephalitis (travels to brain)
Without treatment, is uniformly fatal
Treatment: Rabies post-exposure prophylaxis (3)
1) Wash wound
2) Give rabies vaccine (killed virus) (4 doses - given at different site than immune globulin)
3) Human rabies immune globulin (passive immunity)
Hantavirus (Sin Nombre) Virus
Main features:
- enveloped or non enveloped?
- shape, capsid?
- genome?
- virus family?
Enveloped, helical capsid virus
Negative sense segmented sdsRNA
Bunyavirus
Hantavirus (Sin Nombre) Virus
Transmission
Rodent borne virus (primary reservoir is deer mouse)
-Transmitted from animals to humans, but do NOT exhibit human to human transmission under natural conditions (similar to rabies)
Inhalation of aerosol of virus shed by rodent hosts in feces and urine
Two diseases caused by Hantavirus?
Hemorrhagic fever with renal syndrome (HFRS)
Hantavirus cardiopulmonary syndrome (HCPS)
Hemorrhagic fever with renal syndrome (HFRS):
Fever, hemorrhage, hypotension, renal failure
Hantavirus cardiopulmonary syndrome (HCPS)
Rapid onset (12-24 hours)
Capillary leak into pulmonary bed after flu-like prodrome
Fever + bilateral diffuse interstitial edema (resembles ARDS)
How do you diagnose hantavirus?
serology
Disease caused by west nile virus? (2)
1) WNV neuroinvasive disease
2) WNV fever
WNV fever
rapid onset of low grade fever, headache, malaise, back pain and myalgias
WNV neuroinvasive disease
Risk for severe disease with OLDER age
→ fever + meningitis, encephalitis, and flaccid paralysis
West Nile virus transmission
vector?
host?
-non-vector transmission?
Birds act as major host (also horses)
Mosquitos = VECTOR for transmission
Transmitted from animals to humans, but do NOT exhibit human to human transmission under natural conditions
Can also get NON-VECTOR transmission of WNV (organ transplant, blood transfusion - check with RT-PCR)
Ebola Virus
Main features:
- virus family?
- envelope?
- genome?
- capsid, shape?
Filovirus
Enveloped
Nonsegmented negative sense ssRNA
Helical capsid
Thread-like filamentous structure
Ebola:
Pathogenesis of infection:
Ebola enters body → infects and lyses endothelial cells, hepatocytes, macrophages, and dendritic cells → spread to regional lymph nodes → dissemination to lymphoid tissue
Causes consumptive coagulopathy triggered by aberrant production of TISSUE FACTOR by virally infected macrophages
Ebola:
Disease?
acute hemorrhagic fever with high mortality rate
Incubation period of 5-7 days and up to two weeks
Ebola
Transmission?
Transmit from animals to humans and can cause limited cycles of human to human transmission - requires close contact with bodily fluids for transmission
Lassa Fever Virus:
Main features:
- virus family?
- envelope?
- genome?
- shape?
Arenavirus
Enveloped
Helical
Segmented (ambisense) ssRNA
Lassa Fever Virus:
Disease
causes acute hemorrhagic fever
Restricted to West Africa
Lassa Fever Virus:
Transmission
Transmit from animals to humans and can cause limited cycles of human to human transmission
Transmission to humans via rodent urine and feces or through close contact with infected individuals
ANIMALS –> HUMANS and LIMITED HUMAN –> HUMAN
3 Main families of arboviruses
Bunyaviruses
Flaviviruses
Togaviruses
Bunyaviruses
Main features of genome?
Segmented, enveloped, helical negative sense ssRNA
Flaviviruses
Main features of genome, envelope, capsid?
Includes what 5 viruses?
Main features:
-Non-segmented, enveloped, icosahedral, positive sense ssRNA
Arthropod borne:
1) Dengue fever - most common
2) Yellow fever
3) Japanese encephalitis
4) St. Louis encephalitis
5) West Nile Virus
Togaviruses
Main features of genome, envelope, capsid?
Includes what 1 virus?
Main features:
-Non-segmented, enveloped, icosahedral, positive sense ssRNA
Chikungunya
Outcome of Arbovirus Infection in Humans: (6)
**All cause encephalitis and fever
1) Asymptomatic
Dengue virus, WNV, and Zika → Majority asymptomatic
Chikungunya virus → Majority symptomatic
2) Febrile illness: abrupt onset fever, chills, muscle pain
3) Neurologic disease: *encephalitis, meningitis, AFP
Mortality or long term neurological sequelae in survivors
4) Arthritis/MSK: *fever, intense pain in peripheral joints, inflammation in joints, muscle, tendons → can develop chronic disease
5) Hemorrhagic fever
6) Congenital disease (e.g. Zika)
Transmission cycle of arboviruses:
VECTOR?
Arthropod VECTORS
Primarily mosquitoes, but also ticks, biting flies
Infected vectors transmit virus to vertebrate hosts during feeding
Mosquito and virus cycle of infection? (5 steps)
1) Female mosquito ingests blood from viremic vertebrate
2) Virus replicates in mosquito midgut
3) Systemic spread in mosquito
4) Virus replicates and accumulates in salivary glands
5) Mosquito injects saliva/virus into skin during next blood meal
Transmission cycle of arboviruses:
HOSTS? 2 kinds of hosts
1) Those that do not serve as reservoirs, but have overt disease
2) Those that serve as main source for infections of vectors = RESERVOIRS
Arbovirus reservoirs?
Those that serve as main source for infections of vectors = RESERVOIRS
May or may not develop disease
Presence of high titer serum viremia of long duration required to infect adequate number of vectors
Humans are often DEAD END HOSTS (not high enough titer serum viremia)
Humans are NOT dead end hosts for…(4)
Dengue
Yellow Fever
Zika
Chikungunya
Dengue Virus:
Most common arbovirus worldwide
Four serotypes of virus
Dengue Virus:
Disease? 3 possible outcomes
Majority of infections are asymptomatic (75%)
Dengue Fever
Dengue hemorrhagic fever
Dengue hemorrhagic fever
mainly in SE Asia and S. America
Circulatory failure and shock
Increased vascular permeability, marked thrombocytopenia, fever for 2-7 days, hemorrhagic tendency
Dengue Fever
Headache, retro-orbital pain
Marked muscle and joint pain (“break bone fever”)
Bleeding of skin and nose
Pathogenesis of multiple infections with Dengue Fever:
what happens after the 1st infection?
what does this mean for the 2nd infection?
1st infection → ab response to 1st infection
- Protects from second infection with SAME serotype
- Provides some initial protection for cross-reactive serotypes that decline and becomes sub neutralizing over time
2nd infection → cross-reactive sub-neutralizing antibodies generated during first infection mediates enhanced infection of specific cells → increased viral replication and immune activation (increased cytokines)
**Preexisting, subclinical protection → MORE severe disease
Chikungunya Virus
Part of what virus family?
genome?
Togavirus (alphavirus)
Non-segmented, enveloped, icosahedral, positive sense ssRNA
Chikungunya Virus
Causes what disease?
Re-emerged recently
Endemic to West Africa, but has spread to Caribbean
High grade fever
Bilateral polyarthralgia
Macular or maculopapular rash
Can have chronic phase with chronic inflammatory rheumatism and MSK disorders
Zika Virus
Part of what virus family?
Genome?
Flavivirus
Non-segmented, enveloped, icosahedral, positive sense ssRNA
Zika virus
Disease?
Majority asymptomatic
Recent re-emergence
Fever, muscle/joint pain, conjunctivitis
Linked to severe fetal disease and Guillain-Barre Syndrome in adults
