Strep/Mono/Vectors Flashcards

1
Q

Streptococcus Pyogenes (Group A Strep): most common diseases

A

Pharyngitis
Scarlet Fever
Impetigo
Necrotizing Fascitis
Acute rheumatic fever*
Poststreptococcal glomerulonephritis*

*more important in terms of morbidity and mortality worldwide

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2
Q

S. pyogenes characteristics in Micro

A

Gram positive coccus

Beta-hemolytic

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3
Q

S. pyogenes: less common diseases

A

Otitis media in children
Sinusitis in adults
Osteomylitis
Septic arthritis
Neonatal septicemia
Pneumonia (rare)

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4
Q

Necrotizing Fasciitis

A

S. pyogenes

“flesh eating bacteria”

Rare, destroys skin and soft tissue, including fat and tissues surrounding muscles (fascia)

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5
Q

S. pyogenes morphological characteristics

A

Classified based on immunologic action of cell wall carbohydrates. Lancefield serogroups A-H, K & O.

Fimbriae
-structures near plasma membrane, project through cell wall and capsule, contain important
-EX: M Protein is a major virulence factor, found in association with hyaluronic capsule, it inhibit phagocytosis. Antibody against M protein provides type specific immunity

Lipoteichoic Acid
-important to adherence to human epithelium and initiation of infection

(Margin notes: S. pyogenes contains many antigenic structural components and produces several antigenic enzymes, which of which may elicit a specific antibody response from the infected host)

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6
Q

S. pyogenes Extracellular Products - Two Hemolysins

A

Streptolysin O (SLO): oxygen labile enzyme, binds to RBC membranes, allows submicroscopic holes in membranes and Hgb diffuses from cells. Antibody response to SLO is the most commonly used indicator of recent strep infection.

Streptolysin S: oxygen-stable, responsible for beta-hemolysis of blood agar, disrupts RBC membrane selective permeability (causing osmotic lysis), not antigenic

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7
Q

S. pyogenes extracellular products (non-hemolysins, facilitate rapid spread)

A

Hyaluronidase “spreading factor”: breaks down hyaluronic acid found in connective tissue

DNases A, B, C & D (immunologically distinct)

Streptokinase: enzyme that dissolves clots by coverting plasminogen to plasmin

Erythrogenic toxin: elaborated by scarlet fever associated strains (characteristic rash)

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8
Q

S. pyogenes Epidemiology

A

One of the most common human pathogens

Found in respiratory tract, spread by contact with large droplets, crowding increases spread (Upper resp. infections common in school age kids)

Some asymptomatic carriers

Rheumatic fever a major complication of infection (decreased in US due to early treatments)

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9
Q

S. pyogenes - Upper Respiratory Infection, Viral Pharyngitis symptoms

A

Both have age dependent manifestations

Infant/young child: rhinorrhea, coughing fever, vomit, anorexia

Kids >3 years: classic strep pharyngitis

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10
Q

S. pyogenes - Impetigo/Cellulitis signs and symptoms

A

Skin infection begins as papule

Lesion may itch, eventually crusting over and healing

Cellulitis - subq infection, warm, tender

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11
Q

S. pyogenes - Scarlet Fever signs & symptoms

A

Result of pharyngeal infection with a strain of group A that produces erythrogenic toxin

Rash along with regular signs and symptoms

After 1 week, face begins to peel

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12
Q

S. pyogenes infection complications

A

notallinfections

Upper respiratory infections may become acute rheumatic fever

Pharyngitis or skin infections may become poststreptococcal glomerulonephritis

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13
Q

S. pyogenes: Diagnostic Eval

A

Throat culture
Rapid antigen test on throat swab
Molecular test for GAS

Serological tests
-demonstrate Abs & extracellular products
-Antistreptolysin O (ASO) and anti-deoxyribonuclease B (anti-Dnase B) standard
-Specimen pairing: compare acute and convalescent sera collected 3 weeks apart

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14
Q

S. pyogenes - Antistreptolysin O (serological test)

A

Ability of patient serum to neutralize erythrocyte-lysing capability of SLO

Titer rises ~7 days after infection onset, maxes out ~4-6 weeks (can have elevated titer for up to a year)

The rise in the titer over 1-2 weeks more significant than one titer

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15
Q

S. pyogenes - Deoxyribonuclease B (serological test)

A

Dnase B produced by S. pyogenes, not other streps.

Reliable Ab test for skin & throat infections.

50% patients with S. pyogenes acute glomerulonephris will have elevated Dnase B with normal ASO titer

LESS SUSCEPTIBLE TO FALSE POSITIVES THAN ASO due to bacterial growth in specimen, liver disease and oxidation of the antigen

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16
Q

S. pyogenes Toxic Shock Syndrome (STSS) - Etiology

A

Portal of entry unknown in 50% of cases

Has been associated with use of super tampons

Appears after cocci have invaded areas of injured skin

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17
Q

S. pyogenes Toxic Shock Syndrome (STSS) - Immunological Mechanisms

A

Pyrogenic exotoxins cause fever and help induce shock by lowering the threshold to exogenous endotoxin

Induction of cytokines in vivo is likely the cause of shock

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18
Q

S. pyogenes Toxic Shock Syndrome (STSS) - Epidemiology

A

Highest rates in young children and older adults

50+ % have underlying chronic illness

up to 70% mortality

rare infection, ~300 cases per year

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19
Q

S. pyogenes Toxic Shock Syndrome (STSS) - Signs & Symptoms

A

Fever, blotchy rash, red/swollen/pain on infected skin

Average incubation time 2-3 days

80% cases have clinical signs of soft tissue infection

20% have influenze like symptoms

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20
Q

S. pyogenes Toxic Shock Syndrome (STSS) - Laboratory Findings

A

Serological confirmation shows 4x rise against SLO(ASO) & Dnase B

Milk leukocytosis, immature neutrophils 40-50%

Positive blood cultures in 60% of cases

Hemoglobinuria & serum creatinine 2.5x normal (renal involvment)

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21
Q

S. pyogenes Toxic Shock Syndrome (STSS) - Treatment

A

IV fluids, blood pressure maintenance medication

Can be deadly, requires immediate treatment

Skin may peel as rash heals, may need to debride with surgery

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22
Q

Streptococcus agalactiae (Group B Strep) Disease - Epidemiology

A

Fatality rates 26-70% for men & non-pregnant women

30+% women asymptomatic carriers in genitourinary tract. Leading cause of early-onset neonatal sepsis in US

Universal screening at 35-37 weeks pregnancy, intrapartum antibiotics reduce GBS disease in newborns.

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23
Q

Streptococcus agalactiae (Group B Strep) Disease - Etiology

A

Gram positive

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24
Q

Streptococcus agalactiae (Group B Strep) Disease - Laboratory Data

A

Mostly isolated from blood

Latex test not as effective as culture or molecular
PCR assay from culture broth (commonly used)

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25
Streptococcus agalactiae (Group B Strep) Disease - Signs & Symptoms
Skin & soft tissue infections Neonatal infection during birth
26
Epstein-Barr Virus (EBV) - Etioilogy
Human herpes virus that infects B lymps Causes infectious mononucleosis, burkitt lymphoma, neoplasms of thymus/parotid gland/supraglottic larynx Can compicate cardio, ocular, respiratory, hematologic, digestive, renal & neurologic symtoms (so everything)
27
Epstein-Barr Virus (EBV) - Epidemiology
~95% world population has been exposed Herpes DNA virus that infects B lymphs Variant lymphs produced have T cell characteristics (mononucleosis from large effector CD8 Tc cell reponse against EBV infection of circulating B cells) Transmitted by oral-pharyngeal secretions touching *smooch*. Can also be trasmitted by blood transfusion or transplacental route (not common).
28
Epstein-Barr Virus (EBV) & Immunocompromised folks
Major concern! Infectious mononucleosis postperfusion syndrome -blood transfusion from immune donor to nonimmune recipient -may be from CMV rather than EBV Maintain EBV as chronic, latent infection Low % of patients experience symptomatic reactivation
29
Epstein-Barr Virus (EBV) - Signs & Symptoms
Asymptomatic for most infants (they ain't got no B cells lieutenant dan) Typical illness in teens Incubation 10-50 days Extreme fatigue, malaise, sore throat, fever, cervical lymphadenopathy. Splenomegaly in 50% of cases. Rare jaundice. Lasts 1-4 weeks. Significant # of patients do not manifest cassic signs (cool cool cool)
30
Epstein-Barr Virus (EBV) - Laboratory Diagnostic Eval
High leukocytes in most cases (10-20 x 10^9). 10% of patients leukopenic. Relative lymph counts 60-90% (with 5-30% of those being mono/varient lymphs) Increase in virus specific CD8+ T cells (important for life-long control of EBV disease) Serologic antibody testing for non-classic symptoms. Abs present are heterophile & EBV.
31
Epstein-Barr Virus (EBV) - Heterophile Antibodies
Broad class, may be present in low concentrations in healthy person. Titer of > 1:56 clinically significant for suspected mono. IgM appears in acute phase (IgM reacts with horse/ox/sheep RBCs, absorbed by beef RBCs, not absorbed by guinea pig kidney cells, does not react with EBV specific antigens)
32
Epstein-Barr Virus (EBV) - Serology
10-20% of adults don't produce heterophile antibodies 50%+ of kids younger than 4 with mono are heterophile negative EBV serology recommended for people without classic symptoms, heterophile negative, immunosuppressed EBV infected B cells express new antigens encorded by virus Viral capsid antigen, early antigen & nuclear antigen all corresponding antibody responses -assays for IgM & IgG antibodies to these EBV antigens are available
33
Epstein-Barr Virus (EBV) - Viral Capsid Antigen
produced by infected B cells & found in cytoplasm Anti-VCA IgM detectable, but low concentration, in early infection. Desappears ~2-4 months. Anti-VCA IgG detectable within 4-7 days and persis for a long time, possibly forever
34
Epstein-Barr Virus (EBV) - Early Antigen
Early antigen-diffuse (EA-D) -found in nucleus & cytoplasm of B cells -IgG type (indicative of acute infection) Early antigen-restriced (EA-R) -Found as a mass only in cytoplasm -IgG usually only seen in young children Neither consistent indicators of disease stage
35
Epstein-Barr Nuclear Antigen (EBNA, NA)
Found in nucleus of all EBV infected cells Anti-EBNA IgG doesn't appear until patient has entered convalescence Titers gradually increase and reach plateau 3-12 months after infection Most healthy individuals with previous exposures have titers ranging from 1:10 - 1:160 Should be taked in combination with patient symptoms, history & Ab response patterns
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VCA IgG Antibody Formation (blue chart)
No previous exposure: negative Recent acute infection: positive Past infection (convalescent): positive Reactivation of latent infecgtion: positive
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EBNA IgG Antibody Formation (blue chart)
No previous exposure: negative Recent acute infection: negative Past infection (convalescent): positive Reactivation of latent infecgtion: positive
38
Epstein-Barr Virus (EBV) - Immunofluorescence
Common method for EBV serology Antigen substrate slide containing EBV infected cells incubate with serum Fluorescein-conjugated antihuman IgG or IgM Cons: time consuming, difficult to interpret, prone to interference from other serum components
39
Vector-Borne Diseases (overview)
Bacterial/viral diseases transmitted by mosquitoes, ticks & fleas Travelers & military at highest risk Discovery and surveillance often done with serologic testing
40
Lyme Disease - Etiology
Spirochete Borrelia burgdorferi Transmitted by Ixodes ticks. Can be carried into household on dogs & cats. White footed mouse for larval and nymphal stages. White tailed deer for adult stages.
41
Lyme Disease - Epidemiology
Most common vector-borne illness in US (95%!). But found worldwide. NE and upper midwest.
42
Lyme Disease - Signs & Symptoms
After tick bite, spirochetes migrate outwardly into skin (skin lesions, erthema chronicum migrans (ECM)) 60-80% begin with flu like symptoms, evolves through stages. Bullseye rash. Most patients have ECM (50% of these patients develop secondary lesions), .25% have arthritis. Rarely, neurologic & cardiac issues.
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Lyme Disease - Stage 1
~4 weeks afater infection ECM or other skin eruptions, flulike symptoms, neurologic symptoms
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Lyme Disease - Stage 2
Variable latent period Nervous system, heart, eyes, skin can all manifest abnormalities
45
Lyme Disease - Stage 3
Weeks to years later Arthritis, late neurologic complications, acrodermatitis chronica atrophicans
46
Lyme Disease - Arthritis
Common sign of early Lyme May be associated with long-standing infiltration of the joints by spirochetes along with local inflammatory response
47
Lyme Disease - Cardiac Manifestations
Lyme carditis in ~8% of untreated patients within 1-2 months Lightheadedness, syncope, dyspnea, palpitations, chest pain Usually self-limited and mild course
48
Lyme Disease - Neurologic Manifestations
~15% of untreated patients 2-8 weeks after onset Aseptic meningitis, cranial nerve palsies, peripheral radiculoneuitis, peripheral neuropathy Severe headache, mild neck stiffness Maybe chronic encephalopathy
49
Lyme Disease - Pregnancy
Transplancental transmission possible Infant dies shortly after birth, mother acquired infection early in pregnancy with no treatment
50
Lyme Disease - Immunologic Manifestations
Cellular immune responses begin concurrent with early clinical illness Increase in spontaneous suppressor cell activity and reduction in NK cell activity Mononuclear cell, Ag specific responsese develop during spirochete dissemination and humoral respones soon follow Serodiagnostic tests insensitive during first several weeks After 1 month, most patients have IgG antibodies - both IgM & IgG can persist for years Ab formed: cryoglobulins, immune complexes, antibodies to B. burgdorferi, anticardiolipin antibodies
51
Lyme Disease - Diagnostic Eval
Culter is definitive diagnosis, but rare. Usually from biopsy samples, less often from plasma or CSF. Usually based on clinical findings, history of exposure, antibody response to B. burgdorferi Might find spirochetes in a blood smear! But very transient, will be there one day, gone the next
52
Lyme Disease - Antibody detection
CDC recommends two step process EIA or IFA, then Western blot Only positive if BOTH tests are positive
53
Lyme Disease - Western Blot Analysis
Verifies reactivity of antibody to surface/flagellar protein of B. burgdorferi Helpful in borderline results More definitive test later in disease
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Lyme Disease - ELISA
Standard test method Low sensitivity, lengthy processing time
55
Lyme Disease - PCR
Detects spirochetes in synovial fluid from joints, other samples Directly IDs pathogen, useful when patient is seronegative
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Lyme Disease - CSF for Ab Detection
Not recommended unless patied has pronouced neurological manifestations
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Lyme Disease - Treatment
How long tick was attached, probability of tick being a carrier, risk of antibiotic reactions all influence treatment decisions Antibiotics -tetracyclines (bacteriostatic unless in high doses) -amoxicillin (more effective than penicillin) -unclear if antimicrobial treatment will prevent Lyme disease
58
Lyme Disease - Prevention
None really! No vaccine. Check for ticks, wear light-colored clothes, tuck socks into pants
59
Human Ehrlichiosis - Etiology
First described in US in 1986 Can be fatal, needs prompt treatment! Tick-borne rickettsiae, genus Ehrlichia Ehrlichia chaffeensis - agent of human monocytic ehrlichiosis in us
60
Human Ehrlichiosis - Epidemiology
Prevelance in low, primarily southern Mid-Atlantic & south central states during spring and summer Lone Star Tick main vector for E. chaffeensis. White tailed deer principle reservoir. In easern US, maybe white-footed mouse.
61
Human Ehrlichiosis - Signs & Symptoms
'Ehrlichiosis' is the general term for human granulocytic ehrlichiosis (now called anaplasmosis) and human monocytic ehrlichiosis (HME) Most patients not suspected of having rickettsial infection. Symptoms nonspecific: fever, chills, headache
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Human Ehrlichiosis - Three Developmental Stages
Elementary bodies enter leukocyte by phagocytosis, multiply rapidly 3-5 days later, tightly packed elementary bodies visible Over 7-12 days, initial bodies developp into morular (mulberry) forms
63
Human Ehrlichiosis - Diagnostic Eval
Direct observation on Wright-Giemsa stain (rapid, inexpensive) PCR test of skin biopsy of rash or EDTA whole blood Specific immunohistochemical detection In anaplasmosis: diagnosis by seroconversion or by single titer higher than 1:80 w/ supporting systems
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Human Ehrlichiosis - Treatment & Prevention
Doxycycline (no guideline for long term therapy) Prevention/reducing tick exposures
65
Rocky Mountain Spotted Fever - Etiology
RMSF - tick-borne disease caused by bacterium Rickettsia rickettsii found in N & S America Transmitted by American dog tick , Rocky Mountain wood tick, brown dog tick
66
Rocky Mountain Spotted Fever - Epidemiology
Reported since 1920 in every state except Vermont & Maine Geographic distribution tied to location of various tick species Most illness reported in June and July
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Rocky Mountain Spotted Fever - Signs & Symptoms
First symptoms 2-14 days after bite, often go unnoticed Sudden onset of fever and headache, 90% have rash, some nausea & vomiting
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Rocky Mountain Spotted Fever - Diagnostic Eval
If rash present: PCR on biopsy or immunohistochemical staining Ab detected within 7-10 days (85% negative during first week) IFA with 2 paired specimens with four-fold increase in titers the gold standard. First sample asap, second 2-4 weeks later both IgM & IgG remain elevated for months
69
Rocky Mountain Spotted Fever - Treatment & Prevention
Earlier treatment corresponds to quicker recovery. Doxycycline first line of treatment, most effective if started before 5th day of symptoms. Durations of treatment 7-14 days. IV antibiotics, prolonged hospitilization, intensive care for more sever course
70
Babesiosis - Etiology
Rare, severe, sometimes fatal Tick-borne, caused by Babesia (microscopic parasite that infects RBCs)
71
Babesiosis - Epidemiology
Reportable in 37 states Transmitted by I. scapularis tick. Larvae feed on white-footed mouse, nymphs and adults feed on white-tailed deer Most common in older individuals, splenectomized patients, immunocompromised
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Babesiosis - Signs & Symptoms
Incubation period 7-21 days—may take 1-8 weeks for symptoms to appear Clinical presentation is variable: ranges from asymptomatic to rapidly progressive and sometime fatal Disease can cause fever, fatigue, and hemolytic anemia lasting several days to months
73
Babesiosis - Diagnostic Eval
Observation of parasites in blood (symptomatic people) Difficult to distinguish from malaria, can used PCR No test is approved for blood donors :)
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Babesiosis - Treatment & Prevention
No standardized treatments have been developed Some drugs used for malarial treatment have shown effectiveness Antibiotic therapy recommended for splenectomized or immunodeficient patients Combo of azithromycin and oral quinine Exchange transfusion for patients with high level of parasites (>10%), severe disease, or massive hemolysis Prevention requires diligence in tick infested areas
75
Chikungunya Disease - Etiology & Epidemiology
Chikungunya virus is transmitted through mosquito bites Outbreaks in Africa, Asia, Europe, and the Indian and Pacific Oceans U.S. cases from returning travelers
76
Chikungunya Disease - Signs & Symptoms
Symptoms begin 3-7 days after bitten by infected mosquito Fever, joint pain, headache, rash, joint swelling
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Chikungunya Disease - Diagnostic Eval
IgM and IgG antibody testing by ELISA method IgM suggests new, active infection IgG suggests current or past infection Parallel testing of acute and convalescent together suggested
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Chikungunya Disease - Treatment & Prevention
No vaccine! Prevent mosquito bites Treatment to relieve fever/pain only option...
79
Dengue Virus - Etiology
Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) Caused by 4 related viruses (1-4 serotypes) Transmitted by mosquitos
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Dengue Virus - Epidemiology
Endemic in at least 100 countries Most cases in U.S. acquired by travelers
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Dengue Virus - Signs & Symptoms (without warning signs)
Fever and Two of the following: nausea, vomiting, rash, aches and pains, leukopenia, positive tourniquet test
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Dengue Virus - Signs & Symptoms (with warning signs)
Can include any of the following: abdominal pain and tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy, restlessness, liver enlargement >2 cm, lab finding of increases hct, red cell mass concurrent with rapid decrease in platelet count
83
Dengue Virus - Signs & Symptoms (severe dengue)
Must include dengue symptoms with at least one of: Severe plasma leakage leading to shock (DSS) or fluid accumulations with respiratory distress; severe bleeding; severe organ involvement: Liver- AST or ALT >1000, CNS-impaired consciousness, failure of heart and other organs
84
Dengue Virus - Diagnostic Eval
CDC: Testing is divided into confirmatory testing and testing for probably or suspected dengue infection Probable testing (Detection on IgM anti-DENV) Suspected testing (Absence of IgM anti-DENV) Dengue infection results in long-lasting immunity with a specific serotype—crossreactive protection is shortlived (1-3 years)
85
Dengue Virus - Treatment & Prevention
No vaccines available—prevent mosquito bites Treatment is consistent with classification of disease
86
West Nile Virus - Etiology & Epidemiology
WNV-member of Japanese encephalitis virus group of flaviviruses Mosquito-borne pathogen Has been in the U.S. since at least summer of 1999
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West Nile Virus - Signs & Symptoms
Fever, headache, fatigue, aches, sometimes a rash Can last a few days to several weeks
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West Nile Virus - Diagnostic Eval
Serologic tests or virus isolation IgM antibody—7-8 days after symptom onset IgG antibody 3-4 weeks Some FDA approved ELISA kits available—need confirmation by CDC or state health lab
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West Nile Virus - Treatment & Prevention
No specific treatment—mild cases resolve over time More severe cases with hospitalization—supportive treatment including IVs Prevent mosquito bites
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Zika Virus - signs & symptoms
Infection during pregnancy—can cause microencephaly—incomplete brain development and other severe fatal brain defects; also have eye defects, hearing defects, impaired growth Many people won’t have symptoms or only mild: fever, rash, joint pain, conjunctivitis—can last for several days to a week
90
Zika Virus - Etiology & Epidemiology
Spread primarily by the bite of an infected Aedes spp. Mosquito Pregnant women can transmit to fetus Sexual contact Typically tropical areas; Puerto Rico and Florida High point in 2016—5168 symptomatic cases in U.S. 2018– 74 Zika cases
91
Zika Virus - Diagnostic Eval
Based on person’s recent travel history, symptoms, and test results Molecular Assay -rRT-PCR for RNA performed on paired serum and urine samples Serologic Test -IgM typically develop at end of first week of illness Zika MAC-ELISA -Used for qualitative detection of IgM antibodies in serum or CSF -Has some nonspecific cross-reactivity