Vector-Borne & Zoonotic Disease Test 1

Question 1

Ticks in the US

Answer 1

Black Legged (I.scapularis) - Lyme, Babesiosis (Nymph stage), Ehrlichiosis, Anaplasmosis

Lone Star Ticks (Amblyomma americanum) - Anaplasmosis, Tularemia, Souther tick-associated rash illness, Ehrlichiosis

American dog tick (Dermacentor variabils) - Rocky Mountain Spotted Fever, Tularemia

Question 2

Lyme Disease

Answer 2

Tick Based - Bacterial Spirochete - (forested regions Primarily Borrelia Burgdorferi, NE US) I.scapularis NE, I.pacificus West Coast - Bimodal peaks 5-14 Y/O and 45-55 Y/O - Commonly contracted between June-Aug

Europe - Austria, Estonia, Lithuania, Netherlands, Slovenia - I.Ricinus, Asia - Russia, Japan, China - I.persulcatus

Transmission = Larva (rarely infected), Nymphal (25%), Adult (50%) must be attached 36-48 hours.

Clin Man = 3 Stages - Early Localized, Early Disseminated, Late Lyme

Question 3

Lyme Disease: Early Localized Disease - Clinical Manifestation

Answer 3

Only ~25% recall Tick bite

Erythema migrans (EM) - 79% of PTs - Presents within 7-14 days, but can present up to 30 days after.

Associated Viral Syndrom - Fatigue (79%), Anorexia (26%), Mild Headache (42%), Mild Neck Stiffness (44%), Myalgias and Arthralgias (44%), Regional Lymphadenopathy (23%), Fever (16%)

Question 4

Lyme Disease: Early Disseminated Disease - Clinical Manifestation

Answer 4

Usually present weeks-months after bite

Neurologic symptoms - Cranial nerve Palsies - especially facial nerve (Bells Palsy), Lymphocytic meningitis, Radiculopathy, Peripheral Neuropathy, Mononeuropathy, Cerebellar Ataxia, Encephalomyelitis

Neurological Lyme disease (Triad) - Cranial Neuropathy, Meningitis, Radiculoneurapathy

Carditis - AV Heart block, Pericarditis, Sudden Cardiac Death, Chronic Cardiomyopathy, Palpitations

Ocular Manifestation - Conjunctivitis (10%), Keratitis, Iridocyclitis, Retinal Vasculitis, Choroiditis, Optic Neuropathy, Uveitis

Question 5

Lyme Disease: Late LymeDisease - Clinical Manifestation

Answer 5

Occurs Months to years after onset of infection

Arthritis - Intermittent or persistent arthritis in a few large joints, especially the knee

Neurologic features - Lyme encephalopathy: Subtle cognitive disturbances, Polyneuropathy

Fibromyalgia

Question 6

Lyme Disease: Post Lyme Disease Syndrome- Clinical Manifestation

Answer 6

Used to describe the non-specific symptoms that may persist for a months after Tx of Lyme disease.

Headache, Fatigue, Arthralgia, Cognitive difficulties, Musculoskeletal pain

For the majority of PTs these symptoms improve gradually over 6-12 months.

Question 7

Lyme Disease Diagnostic Studies

Answer 7

Labs - CBC - Leukocytosis (5%), Leukopenia (4%), Anemia (3%), Thrombocytopenia (1.5%), Elevated ESR (24%), Elevated Creatine Phosphokinase (CPK) (12%), LFT - Elevated AST & ALT (37%)

Spirochetemia on blood culture - usually not preformed

Lyme Serologic Testing - ELISA testing (Most common initially) - IgM (early), IgG (late), and combined IgM/IgG. - THis or Immunoflourescense Assay (IFA) completed if Positive or equivocal -> IgM and IgG Western Blot (if Si/Sx <or>or= 30 days)</or>

Test if Recent travel to Endemic area/ Risk factor for exposure and symptoms consitant w/ Lyme

Question 8

Lyme Disease Treatment

Answer 8

First-line - Doxycycline

Alternatives - Amoxicillin/Ceftriaxone IV

Early Tx 10-21 days, otherwise 14-28 days

Prophylaxis - Not recommended, all must apply - Attached Tick identified as adult or nymph I.scapularis attached for >36 hrs, Prophylaxis can be started within 72 hrs of time tick removed, Ecologic info indicated local rate of infection of ticks is >or= to 20%, Doxycycline is not contraindicated. Administer single dose of Doxycycline to adults and children >or= 8 Y/O

Question 9

Babesiosis

Answer 9

Nymph stage I.scapularis carry B. microti - transmitted via Tick Bites, blood transfusions, and congenitally (rare) - Cannot be transmitted from person to person - Primarily in NE and Upper MW, often Co-infected w/ Lyme.

Clin Man = Asymptomatic to progressively fatal - Flu-like symptoms - Hemolytic Anemia (Jaundice, Dark Urine) - Rash Uncommon

Life-threatening in Asplenic, weakened immune systems, liver or kidney disease, and the elderly.

Complications - Sepsis, Hemolytic Anemia, thrombocytopenia, Disseminated Intravascular Coagulation (DIC), multi-organ failure, and death.

Diag = High Index of suspicion (due to non-specific presentation), CBC/hemolytic anemia labs (Thrombocytopenia and anemia), Peripheral smear (may look similar to malaria “Maltese cross”), IFA and PCR can be utilized.

Tx = Atovaquone+Azithromycin or Clindamycin+Quinine, Antipyretics, Vasopressors, Blood transfusions (supporting anemia), Exchange transfusions (critically ill), Ventilation, Dialysis.

Educate PT, no blood donation!

Only Tick Bonre Illness not to get Doxycycline

Question 10

Ehrlichiosis

Answer 10

Name to describe disease caused by multiple parasites - Spread through bite of infected Tick or Blood transfussion - Human granulocytic anaplasmosis (HGA), Human monocytic ehrlichiosis (HE).

9 day incubation period - Majority cases June/July, Only adult and Nymphal ticks spread - Missouri, Arkansas, New York, and Virginia >50% of cases followed by SE and South Central US - Men > Women - 60-69 Y/O - Compromised immune system more susceptible.

Si/Sx = 1-2 weeks post bite - Malaise, rigors, nausea, high fevers, headache, Rash (infrequent if present consider co-infection) - Immunocompromised PTs can have Severe presentations.

Dx = CBC (Leukopenia, thrombocytopenia), CMP (abnormal LFTs), Peripheral Smear (Bacteria in the Leukocytes), Polymerase Chain Reaction (PCR) - Identify specific genes unique to Ehelichiosis - mostly sensitive in the first week, Indirect Fluorescent Antibody (IFA) - not commonly used - Measure antibody to the bacteria - can take 3 weeks for result.

Tx = First-line: Doxycycline 100mg PO BID 10-14 days or until 3 days after defervescence, Rifampin approved for pregnant women.

Do not wait for confirmation if you have high suspicion, lack of improvement after 48 Hrs suggest alternative Dx.

Complications = Confusion/seizures/coma, Hemorrhage, Heart Failure, Respiratory Failure, Kidney Failure, Septic Shock

Question 11

Anaplasmosis

Answer 11

Majority of cases Summer June/July - VT, ME, RI, MN, WI, NH, NY 90% of cases - Often misdiagnosed as ehrlichiosis - Spread via Tick Bite, Blood transfusion (rare) - Males >40 Y/O - Weakened Immune System - Residence or time spent in tick habitats (contact with white tail deer/white foot mouse)

Si/Sx = 1-2 weeks after bite - Warly illness 1-5 days: Fevers, Chills, Severe Headache, Myalgia, Nausea, Vomiting, Diarrhea, Anorexia - Late Illness: Respiratory Failure, Bleeding Problems, Organ Failure, Death (rare <1%)

Dx = CBC (Leukopenia, THrombocytopenia), CMP (abnormal LFTs), Peripheral Smear (bacteria in the monocytes, don’t confuse with ehrlichiosis), PCR - Identify specific genes unique to Anaplasmosis- mostly sensitive in the first week, IFA - not commonly used - Measure antibody to the bacteria - can take 3 weeks for result.

Tx = Doxyxycline (new evidence supports use in all ages?) 100mg PO BID and Rifampin in pregnant and Doxycycline allergy.

**Same Treatment as Ehrlichiosis

Question 12

Rocky Mountain Spotted Fever (RMSF)

Answer 12

Most cases outside the Rocky Mountains - Obligate gram neg coccobacilli which multiplies within eukaryotic cells - Tropism for Vascular endothelial cells - Direct Vascular injury - INC vascular permeability - activation of Clotting factor - Hypovolemia, Hyponatremia, Reduced Tissue Perfusion.

Transmission after attached for 6-10 hrs - incubation 2-14 days - Occurs throughout the US, Mexico, central/south America - SE and South Central US - Spring and early summer (April thru September) - Fatality highest in <4 and >or= 60 Y/O

Risk = INC incidence in <10 and 40-60 Y/O, Frequent exposure to dogs, reside near wooded/high grass areas, Amer Indian.

Question 13

Rocky Mountain Spotted Fever (RMSF): Clinical Manifestations, Signs, and Symptoms

Answer 13

Clin Man = Blanching erythematous rash w/ macules 1-4 mm in size that become petechial (bleeding under the skin) over time, onset 3-5th day of illness - 88-90% of PTs have a rash - Spotless RMSF may be severe and have fatal outcomes.

Si/Sx = appear 2-14 days after the bite, rash appears 3-5th day, is left untreated RMSF can cause severe multiorgan dysfunction and fatality rates of 73% - Rash initially involves wrist and ankles, spreading centrally to arms/legs/trunk, involves palms/soles - Facial flushing, conjunctival injection, and hard palate lesions may occur - ARDS and necrotizing vasculitis are signs of concern.

Early non-specific symptoms = Fever (often severe), Headache, Malaise, Myalgias, Arthralgias, Nausea +/- vomiting, Abdominal pain - Other symptoms = Cough, Bleeding, Edema (especially children), Confusion, Focal Nuero signs, Seizures, Conjunctivitis, Retinal abnormalities (rare).

Question 14

Rocky Mountain Spotted Fever (RMSF): Major complications and PE findings.

Answer 14

Major complications = Encephalitis, noncardiogenic pulmonary edema, Adult Respiratory distress syndrome, Cardiac arythmias, Coagulopathy, GI Bleeding, Skin necrosis

Physical Exam Findings = Rash (common in 90% of PTs), Pedal Edema (especially in children), Confusion, Conjunctival erythema, Retinal abnormalities, Meningismus, Abnormal mentation, Focal Neuro Deficits, Gangrene of the digits/ears/scrotum

Question 15

Rocky Mountain Spotted Fever (RMSF): Diagnostic studies, Differential

Answer 15

Labs :Normal WBC at presentation - As disease progresses Thrombocytopenia/Low fibrinogen/elevated fibrin sl=plit products (FSP)/Hypernatremia/Elevated serum aminotransferases and bilirubin/Azotemia/Prolonged PTT and PT

Chest X-ray: Interstitial infiltrates consistent with early pulmonary edema

Echocardiographic studies: Minimal myocardial dysfunction and normal pulmonary wedge pressure measurements during intensive care monitoring

Differential = Nonspecific viral illness/Other tick-borne illness/Meningococcal meningitis (rash looks similar)/Est nile virus meningitis or encephalitis/meningitis/thrombotic thrombocytopenic purpura (TTP)/Measles/Infectious Mononucleosis/Primary HIV

Question 16

Rocky Mountain Spotted Fever (RMSF): Diagnosis and Treatment

Answer 16

Dx = Presumptive based on clinical signs/symptoms (difficult with long differential) - IFA assay for IgG Rickettsii antigen (Not present during the initial weeks of the illness)- IgM only available through some labs (not as specific) - Positive PCR helpful but deosn’t rule out negative as may not have large amounts of DNA in blood as it is invasive of endothelial - Special stain on biopsy specimen.

Tx = Therapy should be initiated w/in 5 days of symptom onset - Nonpregnant adults (Doxyxyxline/Chloramphenicol) - Pregnant Women (Chloramphenicol if not 3rd trimester) - Continue antibiotics for 3 days after PT becomes afebrile - Supportive care for critically ill

Doxycycline 100 mg PO BID for 10-14 days

Chloramphenicol 50-100mg/kg/day in 4 divided doses for 4-10 days

Response to therapy typically quick, Mild illness - typically defervesce w/in 48-72 Hrs, Severe Illness - may remain critically ill and febrile for up to 5 days after therapy initiation.

Mortality 3-5% in treated - Older native Americans w delay in antibiotics at higher risk of death. PTs who survive initial episode generally recover completely and gain immunity.

Question 17

Rabies: Etiology, Epidemiology

Answer 17

Spread through saliva - Bites to head/face have greatest risk of infection - Can be transmitted w/out bite in some cases - Most common infected animals Bats/Racoons/Skunks/Foxes

Epidemiology = Worldwide with following exceptions - Antarctica/New Zealand/Japan/Sweden/Norway/Spain/Some Caribbean Island/Hawaii

Question 18

Rabies: Transmission

Answer 18

Through Saliva, often in a bite - Virus multiplies locally in myocytes at wound site - Virus binds to nicotinic AcH receptors at NMJ - Virus travels w/in axons in PNS to the CNS - Virus replicates in motor neurons of the spinal cord and local dorsal root ganglia rapidly ascending to brain - Virus infects brain’s neurons - Virus spreads to salivary glands/skin/cornea/other organs, saliva infectious for up to 2 weeks before symptoms appear.

Question 19

Rabies Clinical Manifestations

Answer 19

Incubation between 1-3 months - Prodromal symptoms few days to a week (Lowgrade Fever/Chills/Malaise/Myalgias/weakness/Fatigue/Anorexia/Sore throat/Vomiting/Headache/Photophobia

Disease evolves into Encephalatic (furious Rabies) 80% or Paralytic (dumb) <20%

Furious Rabies - Fever, Hydrophobia (33-50%), Pharyngeal spasms, Hyperactivity of muscle subsiding to paralysis, Autonomic instability (Hypersalivation/lacrimation/sweating/“goose flesh“/dilation of pupil), Agitation and combativeness, Coma, Death, Aerophobia (9%)

Dumb Rabies - Ascending paralysis (mimics Guilain barre syndrome), Flaccid paralysis starting in bitten limb then spreading, Headache, Pain, Nuchal rigidity, Cranial Nerve Palsies

Question 20

Rabies Physical Exam, Studies

Answer 20

Physical Exam = Bite (infected w/erythema/pus), Mental Status Change (Agitation), Increased muscular tone, Increased Tendon Reflexes with extensor plantar response and fasciculations (will be seen in encephalitis), Nuchal rigidity, Flaccid Paralysis w/ generalized areflexia and loss od deep tendon reflexes (will be seen in paralytic), Tachycardia, Dilated Pupils, Increased lacrimation

Studies = Clinical suspicion, no one test (multiple tests required involve CDC)

• Rabies serum antibody titer (won’t be positive until later in course)
• Spinal Tap: elevated protein, normal glucose, anti-rabies antibodies
• Skin Biopsy
• Saliva

CT Head (Cerebral Edema)

Post Mortem Testing

Question 21

Rabies Treatment, Prognosis

Answer 21

Tx = Pre-exposure Vacc: 3 IM injections given at days 0,7, and 21 or 28

Post Exposure Vacc: Wound should be cleaned immediately

Persons not previously immunized:

• Immunocompetent: 4 IM injections given at days 0, 3, 7, and 14
• Immunocompromised: 5 IM injections given at days 0, 3, 7, 14, and 28

Persons who have been vaccinated prior should receive the pre-exposure series again

Prognosis = If not treated most Pts die w/in 2 weeks after coma - Since april 2019 there have only been 25 documented cases of survival

Treatment choices:

• Palliative care
• Immunotherapies (rabies vaccine or human rabies immune globulin)
• Antiviral therapies
• Neuroprotective therapies

Question 22

Malaria Epidemiology, Etiology

Answer 22

Endemic through most of the tropics (most cases occur in Subsaharan Africa/SE Asia and Indian subcontinent), May thru Dec - Vector is mosquito (usually between dusk and dawn) - Rarely (congenital /blood transfusion/contaminated needle sharing/organ transplant)

Bite deposits Sporozoites which collect in the liver where they can remain dormant for years - RBCs infected in Liver go into circulation - PT can be asymptomatic 12-35 days

Question 23

Malaria Uncomplicated/Severe Clinical presentation, Physical Exam

Answer 23

Uncomplicated: Cycle of cold, hot, sweating occurring every 2 or 3 days

Fever/Tachycardia/Tachypnea/Chills/Malaise/Fatigue/Diaphoresis/Head Ache/Cough/Anorexia/NVD/Arthralgias and Myalagias/Anemia

Severe: “Cerebral Malaria” - Confusion/Obtunded/Seizures/Coma - Hemolysis/Hemoglobinuria - ARDS: Inflammation in lungs which impairs O2 exchange - Coagulopathy - Hypotension - AKI - Hyperparasitemia >5% of RBCs infected (palpable spleen) - Metabolic acidosis - Hypoglycemia (especially in pregnant females)

Physical Exam = Diaphoreses, Tachycardia, Tachypnea, Palpable Spleen, Hepatomegaly, Pale from anemia/Jaundice, Weakness

Question 24

Malaria Diagnosis, Treatment

Answer 24

Suspect with febrile illness + travel to endemic region

Rapid diagnostic test (RDT): if + blood smear evidence of hemozoin-breakdown products

Smear for speciation & degree of parasitemia, if negative at first continue testing each day for 2 more days.

Uncomplicated: Parasitemia <5% & no organ dysfunction

Complicated: Parasitemia >10% w.organ dysfunction

Anemia/Thrombocytopenia/Elevated (Transaminases/BUN/Creatinine)

Tx = Depends on Species of Plasmodium, the area of inoculation, drug resistance, clinical status of PT, Medical Comorbidities, pregnancy and G6PD

Chloroquine, Malarone (Atovaquone + Proguanil), Coartem (artemether + Lomefantone), Mefloquine, Quinine (+Doxycycline, Clindamycin or Tetracycline), Artesunate (must get through the CDC), Primoquine and Tafenoquine are active against the dormant liver forms and prevent relapses

Usually Complete cure after Tx; however some forms lay dormant in liver for years and can have multiple relapses, Immunity after being infected several times.

Question 25

Tularemia

Answer 25

Occurs in NA, Europe, Asia, and Middle east - South Central states in US. Spread through direct/indirect animal/insect bites - Most common in children <15 and in middle-aged adults

Transmission = Ticks/Mosquitos/Horse flies/Fleas/Lice, Animal Contact (Hunting/skinning, Animal pelts, Bites), Contaminated food/water, or airborne transmission.

Clinical Manifestation = ABrubt & rapid onset of non-specific symptoms between 3-5 days after exposure - Fever/Chills/Anorexia/Malaise/Headache/Fatigue/Soreness in the chest or muscles/Abdominal pain/VD

If not treated, disease progresses to specific manifestation (skin/lymphadenopathy/Eye/Mouth or throat/Lungs/systemic)

Severe complications - Meningitis/Endocarditis

Dx = Clinical Suspicion (Lab data can take a while), F. tularensis Serology (Initial presentation and 2-4 weeks after), Culture and gram stain (rarely positive)

Tx = Mild:Doxycycline 100mg BID for 14-21 days or Ciprofloxacin 500-750mg BID for 10-14 days

Severe: Streptomycin 10mg/kg IM every 12 hours for 7-10 days or Gentamicin 5mg/kg or IV divided into TID dosing for 7-10 days

Question 26

Plague

Answer 26

Transmitted by Rodent Fleas, Scratches/Bites from infected cats, Direct handling of infected animal tissue, Inhalation of respiratory secretions from animals, Inhalation of respiratory droplets from humans, Contaminated food, Lab exposure

Common areas: SW and Pacific Coastal US, Former USSR, Africa, Asia, South America - Incubation usually 2-8 days (except respiratory which may be just a few hours)

Clinical manifestations = Bubonic Plague (80-95%) - Skin lesions (eschars, pustules, necrotic lesions), Purpura with associated intravascular coag, Intense pain and swelling of lymph node (bubo), sudden onset of fever, Chills, weakness, headache - If untreated can progress to disseminated infection (sepsis), meningitis, or secondary pneumonic plague

Septicemic Plague (10-20%) - Extremely Ill, Fever, GI Symptoms (NVD), Abdominal pain, Hypotension, DIC, Multi-Organ failure

Pneumonic Plague - Sudden Dyspnea, High Fever, Pleuritic chest pain, Cough +/- blood sputum - Rapidly fatal unless appropriate treatment is started within the first day.

Question 27

Plague: Diagnostics, Diagnosis, Treatment

Answer 27

CBC: Elevated WBC or Leukopenia, Thrombocytopenia - CXR: Bronchopneumonia, Consolidation, Cavities, Pleural effusions - Culture and staining - Blood Serology - Rapid Test

Dx = High index of suspicion needed to make timely Dx and start Tx - Any PT w/ Fever and painful lymphadenopathy should be questioned about travel/common vectors

3 Important diagnostic clues: Fever w/ dead rodent contact/travel to plague-endemic area, Fever/Hypotension and unexplained lymphadenitis, Pneumonia/hemoptysis, and sputum containing Gram- Rods

Tx = Streptomycin 30mg/kg IM divided into BID for 7-14 days - or - Doxycycline/Tetracycline

ISOLATION

Bubonic Plague - Mortality rate 50-90% untreated, and 10-20% if treated

Pneumonic Plague - Mortality rate of 100% if untreated, and 50% if treated