tickborne illnesses and hematologic consequences - Stillwell

Question 1

spotted fevers

Answer 1

1. Rocky Mountain spotted fever

2. American tick bite fever

Question 2

tick borne illnesses

Answer 2

• triad of disease –> fever, headache, myalgia**
• any month of the year in western AR**
• don’t always get a rash
• serologies take forever, treat 1st***

Question 3

doxycycline/tetracycline**

Answer 3

-the only antimicrobial antibiotics that treat all tick-borne bacterial illnesses**

Question 4

Rocky Mountain spotted fever (RMSF)

Answer 4

• organism: rickettsia rickettsia ** (intracellular)
• attacks vascular endothelial cells –> permeability and petechia**
• where?: north, central, South America; AR, OK, TN, NC in the US
• ticks: dermacentor variabilis (American dog tick), dermacentor Andersoni (Rocky Mountain wood tick), Rhipicephalus sanguineus (brown dog tick)
• transmission 6 hr after tick bite from salivary glands**
• incubation (5-7 days) after bite** (usual for most ticks)
• high fever, headache, myalgia**
• spotless rash in 80-90% of cases**
• nausea, vomiting, diarrhea, ab pain early**
• rash on wrists/ankles spreading to palms/soles/trunk** –> progress to petechia, necrosis, gangrene, edema
• 1/3 with hepatitis (elevated liver enzymes) and jaundice**
• diagnosis: weil-felix agglutination test for antigens, serology with IgM/IgG (most common; takes 2 weeks to become +), PCR (not sensitive)
• elevated transaminase (liver enzyme) –> indicate damage**
• normal WBC count
• “shoot 1st” –> give doxycycline/tetracycline**

Question 5

why should you not wait to treat people until antibodies are +?

Answer 5

• take awhile to become +

- need to treat immediately or it may be too late

Question 6

American tick bite fever

Answer 6

• organism: rickettsia parkeri
• where?: south/southeastern US
• ticks: Amblyomma maculatum (gulf coast tick); A. americanum (lone star tick - dot in center of back)**
• less severe than RMSF
• unlike RMSF, eschar seen at tick bite 90% of time***
• may see vesiculopapular rash**
• treat: doxycycline*

Question 7

what is the most common tick bite around here?

Answer 7

• amblyomma americanum (lone star tick)**

- dot in the center of back

Question 8

Ehrlichiosis (Human monocytes ehrlichiosis - HME)

Answer 8

• organism: ehrlichia chaffeensis** –> bacteria that lives in vacuoles (morulae) of monocytes and Macs**
• where?: worldwide, south/southeast US
• tick: amblyomma americanum (lone star tick)** ; also Ixodes pacificus (western black legged tick) and Ixodes scapularis (deer tick)
• invades bloodstream and evades host defenses, but no endothelial injury like RMSF**
• may lead to toxic shock, high liver enzymes, or granulomas
• only 1/3 have clinical illness (usually cleared)**
• 1/3 people get rash (mild, palms/soles) - children common
• severe in elderly, immunosuppressed –> multi organ failure
• leukopenia, thrombocytopenia, elevated transaminase, blood smear showing morulae in monocytes/Macs**
• patchy infiltrates on chest X ray
• serology (antibody) - takes 2-3 weeks to become +**
• treat: doxycycline/tetracycline

Question 9

Anaplasmosis (human granulocytic anaplasmosis HGA and human granulocytic ehrlichiosis HGE)

Answer 9

• organism: anaplasma phagocytophilum**; also ehrlichia ewingii (canine granulocytic ehrlichiosis)
• bacteria living in morula of granulocytes**
• E. ewingii usually in immunocompromised
• where?: north/northeast US, California, Europe
• tick: ixodes scapularis (deer tick)** and ixodes pacificus (western blacklegged tick)**
• similar to HME in symptoms (except no rash), labs, and treatment

Question 10

tularemia

Answer 10

• organism: francisella tularensis (originally bacterium tularense) and F. holarctica
• won’t grow on gram neg. media like MacConkey**
• makes endotoxin, no exotoxin
• if it grows in lab –> treat everyone with doxycycline bc it gets aerosolized and inhaled**
• where?: worldwide, AR, OK, KS, MO
• ticks: 13 strains; American dog, rocky mountain wood, pacific coast dog, lone star
• passed by ticks east of Rocky Mountains**
• passed by tabanids (deer/horse flies) in western states**
• also passed by mosquitos
• reservoir: many animals (rabbits, rodents, squirrels, deer)**
• replicate in macrophages (protection against reinfection once recovered by cell-mediated immunity)
• sudden fever, headache, myalgia/arthralgia –> relapsing fever**
• pulse-temp dissociation (Faget’s sign)***
• skin lesions at inoculation site that ulcerate with black eschars, slow healing –> can progress to lymphadenopathy**
• diagnosis: serology antibodies (main) - takes weeks, remain + for years, can cross react with brucellosis and RMSF
• labs: granulomas, leukocytosis, thrombocytosis, elevated transaminase and ESR, CSR***

Question 11

tularemia types**

Answer 11

1. ulceroglandular and glandular** (80%) –> localized lymphadenopathy
2. typhoidal - multisystem symptoms (sepsis)
3. pneumonic - atypical pneumonia
4. oropharyngeal and GI
5. oculoglandular (inoculated by conjunctiva)

Question 12

tularemia treatment

Answer 12

1. quinolones - good intracellular activity**
2. doxycycline - low relapse rate**
3. chloramphenicol - high relapse rate
4. aminoglycosides (for serious infection) - Gentamicin**

Question 13

Q fever

Answer 13

• organism: coxiella burnetii**
• biphasic antigen presentation** (phase 1 antigen when infected; phase 2 antigen in non-infective)
• resistant to environmental stress; can be inhaled
• where?: zoonosis worldwide (except Antarctica), AR, OK
• exposure to birth products (ex. placenta, amniotic fluid), urine, feces, milk***
• ticks: lone star, rocky mountain wood, brown dog
• loves low pH of phagolysosomes of Macs/monocytes
• elevated transaminase 85% of time**; also high ESR, CRP
• low Na+ with SIADH
• diagnose: serology antibody by 3rd week** (phase II IgG/M/A develop more than a year; phase I develop later with chronic disease)** –> OPPOSITE of normal in acute Q fever; normal with chronic Q fever
• treat: doxycycline/tetracycline; double drug coverage for chronic Q fever (doxy/hydroxychloroquine or doxy/quinolone)
• need surgical debridement
• sulfa drugs + folic acid during pregnancy
• QVAX (killed vaccine) for abbatoir workers

Question 14

acute Q fever

Answer 14

• asymptomatic
• self-limited febrile illness
• if symptomatic –> atypical pneumonia, acute granulomatous hepatitis (“doughnut like”), high liver enzymes, spontaneous abortion/premature birth***
• no intracellular growth, but high inflammatory response
• phase II antibodies higher than phase I

Question 15

chronic Q fever

Answer 15

• infective endocarditis/prosthetic infection (think about heart murmur)
• hepatitis, osteomyelitis, lymphadenopathy
• persistent intracellular growth in Macs/monocytes, decreased T cell response, little inflammation
• phase I antibodies higher than phase II

Question 16

STARI (southern tick associated rash illness)

Answer 16

• similar to Lyme disease, but a different organism and less sever (no inflammatory arthritis or cardiac/neurologic deficits)
• organism: Borrelia lonestari??
• where?: south and Southeast US
• tick: amblyomma americanum (lone star tick)***
• targetoid erythema chronicum migrans (ECM) skin lesion**
• smaller lesions and less multiple than lyme**
• treat: doxycycline

Question 17

heartland virus

Answer 17

• organism: phlebovirus - RNA)
• tick: amblyomma americanum (lone star tick)
• flu-like illness with anorexia
• leukopenia, thrombocytopenia, elevated transaminase

Question 18

Bourbon virus

Answer 18

• organism: thogotovirus (RNA)

- thrombocytopenia, leukopenia, elevated transaminase

Question 19

Powassan virus**

Answer 19

• organism: flavivirus (RNA), yellow fever virus, dengue virus, zika virus
• meningitis and encephalitis type syndromes
• where?: only MN, WI, and northeastern states***
• tick: ixodes scapularis (deer tick)***
• 15 min. for attachment
• neurologic symptoms (confusion, seizure, memory loss, coordination)***
• fequent meningoencephalitis***

Question 20

bartonella (bartonellosis)

Answer 20

• organism: bartonella henselae (cat scratch)**
• infect erythrocytes and endothelial cells
• tick: ixodes scapularis (deer tick) and I. pacificus (western blacklegged tick)
• localized lymphadenopathy***, retinitis, splenomegaly
• warthin starry stain on tissue**

Question 21

babesiosis

Answer 21

• malaria like parasite that infects RBCs - Babesia microti (divergens)***
• tick: ixodes scapularis (deer tick)*** -same as lyme
• can get both Lyme disease and babesiosis by same tick bite**
• cases in long/fire/shelter/Nantucket Island and Martha’s vineyard in US**
• malaria found in Costa Rica**
• hemolytic anemia** with neutropenia or thrombocytopenia
• severe hemolytic anemia –> low Hb/hematocrit/haptoglobin, elevated bilirubin/reticulocyte/LDH, hemoglobinuria, schistocytes***
• severe sepsis with splenectomy, older age, cancer, or immunosuppressed**
• diagnosis: similar to malaria on thick/thin smears
• see parasites in RBCs or Maltese cross***
• treat: atovaquone/azithromycin

Question 22

Lyme disease**

Answer 22

• organism: Borrelia burgdorferi*** sensu lato (spirochetes)
• B. burgdoferi sensu stricto in US
• ticks: ixodes scapularis (deer tick) in northeast and upper midwest; ixodes pacificus in CA and OR
• reservoir for spirochetes: white foot mice and chipmunks**
• spirochetes**
• diagnose: ECM rash** - think STARI if outside geographic area
• serology: ELISA 1st then western blot (20% risk of getting IgM false + if western blot is 1st)

Question 23

stages of Lyme disease

Answer 23

1. stage I (localized infection) - papule –> targetoid lesion called erythema chronicum migrans (ECM)***
   - ECM always indicative of Lyme disease (don’t always have + serologies)
2. stage II (disseminated infection) - spirochete spreads hematogenously
   - get malaise, fatigue, conjunctivitis/iritis, keratitis, lymphadenopathy, meningitis/encephalitis, Bell’s palsy**, radiculopathy, myelitis, heart block, myocarditis
3. stage III (late, persistent infection) - months after onset of infection**
   - get oligoarticular arthritis, CNS problems, acrodermatitis chronica (skin disorder - red/blue on back of hands/feet)
4. stage IV (post-lyme syndrome) - acquire chronic fatigue syndrome or fibromyalgia**
   - no proof that it is related to chronic infection, and antibiotics may not even help (side effects instead)***
   - don’t treat with antimicrobial therapy
5. congenital Lyme disease - rare transplacental transmission
6. co-infection*** - ixodes ticks carry other organisms (ex. anaplasma, babesia, powassan virus)

Question 24

difference between Lyme disease and erythema multiform

Answer 24

• erythema multiform –> targetoid lesions all over body

- Lyme disease –> targetoid lesions few

Question 25

Lyme disease treatment

Answer 25

1. postexposure prophylaxis - doxycycline is good 2. early disease/ECM - doxycycline, amoxicillin, erythromycin 3. carditis - certain antibiotics for AV blocks 4. facial nerve paralysis antibiotics 5. meningitis/encephalitis antibiotics 6. arthritis antibiotics 7. post lyme syndrome - no treatment

Question 26

relapsing fever (tick-borne)

Answer 26

- organism: borrelia hermsii - tick: ornithodoros soft ticks - recurring fever, myalgia, headache, myalgia - relapsing due to recurrent bacteremias after changing antigen*** - diagnose: spirochetes on blood smear** - treat: doxycycline

Question 27

colorado tick fever

Answer 27

- organism: coltivirus - tick: dermacentor andersoni (rocky mountain wood tick) - where?: western US and Canada - virus infects RBCs - biphasic illness*** - triad of symptoms plus retro-orbital pain - treat: tick removal

Question 28

typical rickettsial infection

Answer 28

- like RMSF** --> present with symptoms 1-2 weeks after bite - maculopapular/morbilliform rash

Question 29

African tick bite fever

Answer 29

- organism: rickettsia africa** - passed by ticks (amblyomma ticks) - MULTIPLE red/black eschars (tache noire)***

Question 30

epidemic typhus

Answer 30

- organism: rickettsia prowazekii** - vector: body lice - disease is silent for months/years after acute illness resolves --> reactivate into milder form called Brill-zinsser disease**

Question 31

murine typhus

Answer 31

- organism: R. typhi and R. felis - vector: fleas - where?: TX, CA, Hawaii*** - milder than RMSF***

Question 32

scrub typhus

Answer 32

- organism: Orientia tsutsugamushi, formerly R. tsutsugamushi - black eschar - where?: Southeast Asia and pacific islands***

Question 33

Boutonneuse or Mediterranean fever

Answer 33

- organism: R. conorii ** - vector: tick - SINGLE, large tache noire (black eschar)****

Question 34

rickettsialpox

Answer 34

- organism: R. akari - vector: mites - maculopapular rash with vesicle, spares palms/soles (unlike RMSF)****

Question 35

Tick paralysis (noninfectious)

Answer 35

- caused by neurotoxin* made in salivary glands of ticks (ex. dermacentor variabilis and andersoni) - ascending paralysis (peripheral --> central) - mimic Guillain-Barre syndrome

Question 36

alpha-gal (noninfectious)

Answer 36

- allergic rxn to red meat* after tick bite from amplyomma americanum (lone star) - lone star transmits alpha-gal sugar to human --> delayed immune IgE response --> anaphylaxis, hives - treat: avoid red meat

Question 37

Queensland tick typhus

Answer 37

-organism: rickettsia australis

Question 38

target lesions everywhere (even palms/soles)?**

Answer 38

- think erythema multiforme*** (immune rxn to HSV, drug, or autoimmune) - STARI and Lyme disease only have FEW target lesions**

Question 39

single or just a few target lesions?**

Answer 39

- think lyme or STARI disease** | - ECM (erythema chronicum migrans)

Question 40

when to consider tick-borne illnesses?

Answer 40

- fever, myalgia, headache at any time of year with leukopenia, thrombocytopenia, or elevated transaminase** - use doxycycline early on