Plague and other tick-borne diseases · The “Black Death” or Great Plague 14 th Century Modern...
Transcript of Plague and other tick-borne diseases · The “Black Death” or Great Plague 14 th Century Modern...
1/6/2016
1
Plague and other tick-borne diseases
Melina Braly, PharmD, BCPS
PGY-2 Critical Care Resident
Baptist Hospital of Miami
January 9, 2016
Objectives
� Define the locations and signs and symptoms of common tick-borne diseases.
� Understand the antibiotic treatments for common tick-borne diseases.
� Describe tick bite prevention and prophylaxis practices.
1/6/2016
2
The Plague in History1-9
Justinian Plague
6th Century
The “Black Death” or
Great Plague
14th Century
Modern Plague
19th Century
The Plague in History1-9
Justinian Plague
6th Century
The “Black Death” or
Great Plague
14th Century
Modern Plague
19th Century
The Plague in History1-9
Justinian Plague
6th Century
The “Black Death” or
Great Plague
14th Century
Modern Plague
19th Century
1/6/2016
3
The Plague in History1-9
Justinian Plague
6th Century
The “Black Death” or
Great Plague
14th Century
Modern Plague
19th Century
The Plague4
� Reported Plague Cases (2000-2009)
The Plague 4
� Plague cases/deaths, United States (2000- 2014)
1/6/2016
4
The Plague in 2015 4
� Fifteen people have been infected with bubonic plague in the U.S.
� 4 fatalities
� Locations include: Arizona, Colorado, New Mexico, Oregon, California, Utah, Georgia, Michigan
� Unknown reasons for the increase in cases
The Plague 1-9
� Causative agent: Yersina pestis
� Gram-negative coccobacillus
� Evolved from the enteric pathogen Y. pseudotuberculosis
� Bipolar staining with Giemsa, Wright’s, or Wayson staining
� Grows aerobically on most culture media
The Plague: Virulence Factors 1-9
Virulence Factors Function
Low calcium response V
antigen (LcrV)
Modulates host immune response,
essential for the production of Yops
Plasminogen activator
(Pla protease)
Dispersal within host and coagulase
and fibrinolytic activity
Yersinia outer proteins
(Yops) and pH 6 antigen
Involved in cytotoxic processes,
immune suppression, or survival within host phagocytes
Fraction 1 capsule (F1)
antigen
Enables resistance to phagocytosis,
expressed at higher temperatures
Murine toxin and pgm
locus
Responsible for pathogenicity in
mammals, and survival and transmission in vectors
1/6/2016
5
Resource #6
Resource #6
Resource #6
1/6/2016
6
Resource #6
The Plague 1-9
� Three main syndromes:
� Bubonic plague
• 80-95% of cases
� Septicemic plague
• 10-20% of cases
� Pneumonic plague
• Generally rare
• Primary or Secondary
� Other manifestations: pharyngitis, tonsillitis , meningitis
Bubonic Plague 1-9
� Transmission: flea bite
� May be overlooked
� Signs/Symptoms:
� Sudden onset of fever, chills, weakness, and headache, followed by intense pain and swelling in a lymph node bearing area (bubo)
� May become disseminated infection without treatment
1/6/2016
7
Septicemic Plague 1-9
� May be primary or secondary
� Signs/Symptoms:
� Febrile, nausea, vomiting, diarrhea and abdominal pain
� 40% mortality for treated cases
� 100% mortality for untreated cases
Pneumatic Plague 1-9
� May be primary or secondary
� Transmission: inhalation of respiratory secretions or aerosolized droplets
� Signs/Symptoms:
� Sudden onset of dyspnea, high fever, pleuritic chest pain, and cough
� 100% mortality if not treated within first 24 hours
The Plague: Diagnosis 1-9
� Clinical presentation
� High fever with lymphadenopathy
� Culture and staining
� Positive blood culture in 27-96%
� Gram-negative rods
� Serologic confirmation (F1 antigen)
� Requires acute and convalescent serum
� Single titer of >1:16 using the passive hemagglutination test is suggestive
� Rapid diagnostic test
� 100% sensitivity/specificity for F1 antigen
1/6/2016
8
The Plague: Treatment 1-9
Agent Dose Evidence
Doxycycline * 100 mg IV/PO Q12H Human data
Gentamicin * 5 mg/kg IV/IM QD OR2 mg/kg IV/IM LD, 1.7 mg/kg TID MD
Human data
Ciprofloxacin * 400 mg IVQ8-12H OR500mg PO BID
Animal dataLimited human data
Levofloxacin 500 mg IV/PO Q24H Animal data
Moxifloxacin 400 mg IV/PO Q24H Animal data
Chloramphenicol 25 mg/kg IV Q6H Human data for treatment of meningitis
* = Preferred agents in the United SatesLD = Loading doseMD = Maintenance dose
Treatment Duration = 10-14 days
Post-exposure Antibiotic Prophylaxis 1-9
� Naturally occurring plague
� Doxycycline is the preferred choice
� Alternative: Ciprofloxacin
� Biological weapon (pneumonic plague)
� Ciprofloxacin is the preferred choice
The Plague 1-9
� Resistance
� Case reports of plasmid-mediated antibiotic resistance strains
� Recent study of Y. pestis isolates in Mongolia showed naturally occurring, multi-drug resistant variants
� Vaccine
� Not available in Western world
� Recombinant vaccine in development
1/6/2016
9
Tick-Borne
Diseases
Lyme Disease Rocky
Mountain Spotted Fever
Ehrlichiosis
Tularemia
BabesiosisAnaplasmosis
Colorado tick
fever
PowassanDisease
Relapsing fever
Tick-Borne
Diseases
Lyme Disease Rocky
Mountain Spotted Fever
Ehrlichiosis
Tularemia
BabesiosisAnaplasmosis
Colorado tick
fever
PowassanDisease
Relapsing fever
Lyme Disease10,11,13
� Most common vector-borne infectious disease in the U.S.
� Causative agent: Borrelia burgdorferi
� Tick vector:
� Ixodes scapularis (“Deer tick”)
� Natural reservoirs: white-footed mouse and small mammals
1/6/2016
10
Lyme Disease: Presentation10,11,13
� Incubation period: 3-30 days
� Stage 1 (early localized):
� Erythema migrans rash at bite of bite, influenza-like symptoms, cough, lymphadenopathy
� Stage 2 (early disseminated):
� Secondary cutaneous annular lesions, fever, adenopathy, CNS symptoms
� Stage 3 (late chronic):
� Arthritis, CNS impairment, dermatitis, keratitis, and myocardial abnormalities
Lyme Disease10,11,13
� Diagnosis:
� Serologic testing insensitive within 2wks
� Two tier testing recommended:
• Enzyme immunoassay (EIA) or immunofluorescence assay (IFA)
• Western Blot
� Single positive serologic test results cannot distinguish between active and past infection
Lyme Disease: Treatment10,11,13
� Treatment of localized (early) disease
� Treatment of disseminated (late) disease
Antimicrobial Agent Dose Duration (Days)
Doxycycline 100 mg PO BID 14 (14-21)
Cefuroxime axetil 500 mg PO BID 14 (14-21)
Amoxicillin 500 mg PO BID 14 (14-21)
Late Disease with Neurologic/ Cardiac Involvement
Antimicrobial Agent Dose Duration (Days)
Ceftriaxone 2g IV QD 14-28
Cefotaxime 2g IV Q8H 14-28
Penicillin G 18-24 million units/day in divided doses (Q4H)
14-28
1/6/2016
11
Rocky Mountain Spotted Fever (RMSF)11,14
� Most common rickettsial disease in U.S.
� Causative agent: Rickettsia rickettsii
� Tick Vectors:
� Dermacentor variabilis ( “American dog tick”)
� Dermacentor andersoni (“Rocky Mountain wood tick”)
RMSF: Presentation 11,14
� Incubation: 2-14 days
� Signs/ Symptoms:
� Flu-like symptoms, GI symptoms, photophobia, focal neurological deficits
� Maculopapular rash
• Initially on extremities, then spread to trunk
� Petechial rash
• Considered a sign of progression
� Complications:
� DIC, ARF, gangrenous disorder, ARDS
RMSF: Diagnosis 11,14
� Laboratory findings:
� Thrombocytopenia, mildly elevated LFTs, hyponatremia
� Laboratory Confirmation:
� Gold standard: IFA on paired samples
• Four-fold change from week 1 to week 4 (3-5)
• Antibodies detectable 7-10 days after onset
� PCR or immunohistochemical (IHC) staining of skin biopsy
1/6/2016
12
RMSF: Treatment 11,14
� Presumed or confirmed RMSF:
� Doxycycline 100 mg PO Q12H
� Presumed Meningococcal Disease:
� Doxycycline 100 mg IV Q12H
AND
� Ceftriaxone 2g IV Q12H
� Duration:
� At least 3 days after fever subsides and until evidence of clinical improvement seen (minimum of 5-7 days, total course)
Babesiosis10,11
� Only tick-borne disease in U.S. that is caused by a protozoan
� Causative agent: Babesia microti
� Tick Vectors:
� Ixodes scapularis ticks
� Black-legged or deer ticks
Babesiosis: Presentation 10,11
� Incubation: 1-9+ weeks
� Signs and Symptoms:
� Flu-like symptoms, GI symptoms, dark urine
� Not all infected persons are symptomatic or febrile
1/6/2016
13
Babesiosis: Diagnosis 10,11
� Laboratory Findings:
� Hemolytic anemia, thrombocytopenia, elevated BUN and SCr, mildly elevated LFTs
� Laboratory Diagnosis:
� Identification of parasites within RBC
• “Maltese Cross” may be present
� Positive PCR analysis
� Isolation of parasites from a whole blood specimen
Babesiosis: Treatment10,11
� Mild disease:
� Symptomatic treatment only
� Severe disease:Regimen Drug Dose
1 Atovaquone 750 mg PO Q12H
Azithromycin Day 1: 500-1000mg PO (total dose)Subsequent days: 250-1000* mg in divided doses
2 Clindamycin 300-600 mg IV Q6H OR 600mg PO Q8H
Quinine 650 mg PO Q6-8H
* = Larger dose (600- 1000 mg) for immunocompromised patientsTreatment duration = 7-10 days
Anaplasmosis and Ehrlichiosis 10,11,15
1/6/2016
14
Anaplasmosis� Causative agent:
� Anaplasma
phagocytophilum
• Formerly known as human granulocytic anaplasmosis (HGA)
� Tick Vectors:
� Ixodes scapularis
• “Blacklegged tick”
� Ixodes pacificus
• “Western blacklegged tick “
Ehrlichiosis� Causative agents:
� Ehrlichia chaffeensis
• Human monocyticehrlichiosis (HME)
� Ehrlichia ewingii
• Human ewingiiehrlichiosis (HEE)
� Tick Vectors:
� Amblyomma
americanum
• “Lone star tick”
Resources: 10,11,15
Anaplasmosis and Ehrlichiosis 10,11,15
� Incubation:
� Anaplasmosis: 1-3 weeks
� Ehrlichiosis: 1-2 weeks
� Signs and Symptoms
� Fever, shaking, chills, headache, malaise, myalgia, GI symptoms, rash
� Conjunctival injection and confusion may occur in Ehrlichiosis
Anaplasmosis and Ehrlichiosis: Diagnosis 10,11,15
� Laboratory Findings:
� Anemia, thrombocytopenia, mildly elevated LFTs, leukopenia
� Visualization of morulae in granulocytes or monocytes
� Laboratory Diagnosis
� Gold standard: IFA on paired samples
• Four-fold change from week 1 to week 4 (3-5)
• Antibodies detectable 7-10 days after onset
� PCR of whole blood
1/6/2016
15
Anaplasmosis and Ehrlichiosis 10,11,15
� Treatment
� Doxycycline 100mg IV/PO Q12H
� Ceftriaxone may be added if meningococcal disease is suspected
� Duration
� 5 to 14 days, continuing for at least 3 to 5 days after the fever resolves
� In patients with anaplasmosis, coinfection with babesiosis or Lyme disease may occur
Flea and Tick Bite Prevention11
� Wear repellent containing at least 20% DEET or permethrin-treated clothing
� Treat dogs and cats for ticks
� Check for ticks daily, especially under the arms, in and around the ears, inside the belly button, behind the knees, between the legs, around the waist, and on the hairline and scalp
� Shower soon after being outdoors
Tick Removal11
� Use fine-tipped tweezers to grasp the tick as close to the skin’s surface as possible
� Pull upward with steady, even pressure. Don’t twist or jerk the tick; this can cause the mouth-parts to break off and remain in the skin
� After removing the tick, thoroughly clean the bite area and your hands
1/6/2016
16
Summary
� Y. pestis, Lyme disease, Rocky Mountain Spotted Fever, Babesiosis, Anaplasmosis and Ehrlichiosis have caused extensive morbidity and mortality prior to antibiotic use
� Early treatment is key in preventing morbidity and mortality from Y. pestis, Lyme disease, Rocky Mountain Spotted Fever, Babesiosis, Anaplasmosis and Ehrlichiosis
� Flea and tick bite prevention and management may also help in preventing morbidity and mortality
Assessment Questions
Assessment Questions
� Majority of tick-borne diseases occur in the Northeast United States.
� True/False
1/6/2016
17
Assessment Questions
� Majority of tick-borne diseases occur in the Northeast United States.
� True/False
Assessment Questions
� Majority of tick-borne diseases occur in the Northeast United States.
� True/False
� Ceftriaxone is the best choice for empiric treatment of a suspected tick-borne disease.
� True/False
Assessment Questions
� Majority of tick-borne diseases occur in the Northeast United States.
� True/False
� Ceftriaxone is the best choice for empiric treatment of a suspected tick-borne disease.
� True/False
1/6/2016
18
Assessment Questions
� Majority of tick-borne diseases occur in the Northeast United States.
� True/False
� Ceftriaxone is the best choice for empiric treatment of a suspected tick-borne disease.
� True/False
� Wearing repellent containing at least 20% DEET or permethrin-treated clothing can help to prevent tick bites.
� True/ False
Assessment Questions
� Majority of tick-borne diseases occur in the Northeast United States.
� True/False
� Ceftriaxone is the best choice for empiric treatment of a suspected tick-borne disease.
� True/False
� Wearing repellent containing at least 20% DEET or permethrin-treated clothing can help to prevent tick bites.
� True/ False
Resources
1. Lotfy WM. Plague in Egypt: Disease biology, history and contemporary analysis: A minireview. J Adv Res. 2015 Jul;6(4):549-54.
2. Perry RD, Fetherston JD. Yersinia pestis--etiologic agent of plague. Clin
Microbiol Rev. 1997 Jan;10(1):35-66.
3. Eisen RJ, Dennis DT, Gage KL. The Role of Early-Phase Transmission in the Spread of Yersinia pestis. J Med Entomol. 2015 Nov;52(6):1183-92.
4. CDC, Division of Vector-Borne Infectious Diseases: Plague.. CDC. Atlanta,
GA. 2003. Last updated: September 1, 2015
5. Feodorva VA, Motin VL. Plague vaccines: current developments and future perspectives. Emerg Microbes Infect. 2012 Nov;1(11):e36.
6. Gage KL, Kosoy MY. Natural history of the plague: perspectives
from more than a century of research. Annu Rev Entomol. 2005;50:505-28.
7. Stevens DL , Bisno AL , Chambers HF , et al: Practice guidelines for the
diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of america. Clin Infect Dis 2014; 59(2):e10-e52.
1/6/2016
19
Resources
8. Inglesby TV, Dennis DR, & Henderson DA: Plague as a biological weapon. JAMA 2000; 283:2281-2290.
9. Butler T: Yersinia species (including plague) In: Mandell GL, Bennett JE, & Dolin R (Eds): Principles and Practice of Infectious Diseases, 5th ed. Churchill Livingston, New York, NY, 2000, pp 2406-2414.
10. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006; 43: 1089–1134.
11. CDC, Division of Vector-Borne Infectious Diseases: Tickborne diseases of the United States. CDC. Atlanta, GA. 2015.
12. Dumler JS, Madigan JE, Pusterla N, et al: Ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment. Clin Infect Dis 2007; 45(Suppl 1):S45-S51.
13. Lyme Disease. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood Village, CO. Available at: http://www.micromedexsolutions.com. Accessed December, 2015.
14. Rocky Mountain Spotted Fever. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood Village, CO. Available at: http://www.micromedexsolutions.com. Accessed December, 2015.
15. Ehrlichiosis; Human anaplasmosis. Micromedex 2.0. Truven Health Analytics, Inc. Greenwood Village, CO. Available at: http://www.micromedexsolutions.com. Accessed December, 2015.
Questions and Discussion
Plague and other tick-borne diseases
Melina Braly, PharmD, BCPS
PGY-2 Critical Care Resident
Baptist Hospital of Miami
January 9, 2016