Vector Borne and Animal Associated Infections Kimberly Martin, DO, MPH Assistant Professor of Pediatrics Pediatric Infectious Diseases 1
Conflict of Interest I have no relevant financial relationships or affiliations with commercial interests to disclose I do intend to discuss unapproved/investigative uses of commercial products in my presentation 2
Learning Objectives Review the epidemiology, diagnosis and treatment of tick-borne infections Describe the infectious complications of animal bites and their management Recognize the risk factor for Rabies and the necessary post-exposure management 3
What this talk with cover Rickettsial infections Rocky Mountain Spotted Fever (RMSF) Ehrlichiosis Anaplasmosis Borrelia infections Lyme disease STARI Animal bite wound infections Rabies 4
Photo credit: CDC 5
Rocky Mountain Spotted Fever (RMSF) Caused by Rickettsia rickettsii Reservoir: ticks and small mammals In ticks, organism is passed: Transstadially (from one life stage to next) Transvarially (from one generation to next) Principal recognized tick vectors: Southeastern/central US: American dog tick (Dermacentor variabilis) Rocky Mountains: Rocky Mountain wood tick (Dermacentor andersoni) Arizona, Mexico: Brown dog tick (Rhipicephalus sanguineus) Central and South America: Cayenne tick (Amblyomma cajennense) 6
Photo credit: CDC 7
RMSF: Epidemiology Geography: confined to the Americas Endemic to nearly all of the continental US Highest incidence in southeastern, south-central US Five states (North Carolina, Oklahoma, Arkansas, Tennessee, and Missouri) account for over 60% of RMSF cases In the last decade: increased incidence in Arizona Majority of cases occur April September but cases can occur year- round (even with cold winters) Risk factors for infection: close contact with animals, outdoor activities 50% of patients don t recall previous tick bite 8
Reported Cases of RMSF, 2013 Photo credit: CDC 9
RMSF: Clinical Manifestations Incubation period: 2 to 14 days (median 4 days) Initial symptoms are nonspecific: fever, headache, myalgia, nausea, vomiting, abdominal pain Rash: Begins 2-5 days after onset of fever May be absent in 20% of adults and <5% in children Typically starts on wrists and ankles and spreads centrally Initially erythematous and becomes petechial in 60% Involves palms and soles in 2/3 of patients 10
Early Onset Maculopapular Rash Photo credit: CDC 11
Late Onset Petechial Rash Photo credit: CDC 12
RMSF: Clinical Manifestations Multisystem vasculitis : any organ can be affected Disease can be severe: approximately 1/3 require ICU CNS involvement 33% have altered mental status 10-20% with meningismus, photophobia, seizures, coma Other findings include: conjunctivitis, peripheral edema, periorbital edema, hepatosplenomegaly Classic triad: not very sensitive in children Fever, rash, history of tick bite (~60%) Fever, rash, headache (~50%) 13
RMSF: Laboratory findings WBC: can be low or high but usually normal Platelets: usually low (<150,000 in 60%) Hyponatremia in half of patients Less common labs: mildly elevated transaminases, anemia, elevated BUN/Cr, elevated bilirubin, low albumin, prolonged PT/PTT 14
RMSF: Prognosis Mortality rate in children: < 5% Prior to tetracycline antibiotics, fatality rate 20-80% Mortality risk factors: male sex, age 5-9 y or > 50 y, no history of tick attachment, delayed diagnosis, delayed doxycycline therapy Risk of mortality increases 4-fold if started after day 5 of illness Factors contributing to delayed diagnosis: absence of rash, initial presentation to HCP before 4 th day of illness, illness outside of peak tick activity months 15
RMSF: Diagnosis Suspect RMSF based on clinical picture! Serum antibodies aren t detected until 7-10 days into the disease Therapy should NOT be delayed while awaiting serology results Delay in therapy increases mortality Confirm diagnosis : Serology : 4-fold rise in IgG titer Indirect immunofluorescence assay (IFA) is gold standard Cross reaction with other rickettsiae occur 16
RMSF: Management Doxycycline (regardless of age) Start as soon as RMSF suspected Switch to PO as soon as oral therapy tolerated Treat 3 days after defervescence (usual course 7-10d) No evidence that doxycycline stains permanent teeth (even with numerous short courses) Supportive care as indicated No proven role for prophylactic antibiotics after recognized tick bite/ attached tick 17
Ehrlichiosis and Anaplasmosis 4 member of the family Anaplasmatacae cause human disease in the US Ehrlichia chaffeensis (ehrlichiosis) Anaplasma phagocytophilum (anaplasmosis) Ehrlichia ewingii Ehrlichia muris-like agent Generally, clinical features of these illnesses are similar All systemic, febrile illness with some similarities to RMSF Vectors and geography vary 18
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Ehrlichia: Epidemiology Ehrlichiosis- caused by E. chaffeensis Also called human monocytic ehrlichiosis (HME) Vector: Amblyomma americanum (Lone Star tick) Most prominent in southeast/south-central/ eastern seaboard Three states (Oklahoma, Missouri, Arkansas) account for 35% of all reported E. chaffeensis infections. White tailed deer is likely natural reservoir 20
Ehrlichia: Epidemiology Emerging agents of ehrlichiosis: E. ewingii Vector : Amblyomma americanum (Lone Star Tick) Most prominent in southeast and south-central US Clinical findings similar to anaplasmosis E. muris-like agent Cases reported from states in the Upper Midwest Tick vector unknown 21
Photo credit: CDC 22
Reported Cases of Ehrlichia, 2013 Photo credit: CDC 23
Anaplasmosis: Epidemiology Anaplasmosis- caused by A. phagocytophilum Also called human granulocytic anaplasmosis (HGA) Formerly human granulocytic ehrlichiosis (HGE) Vector : Ixodes scapularis (blacklegged tick), Ixodes pacificus (Western blacklegged tick) Occurs in northeastern US, upper Midwest Small rodents are natural reservoir 24
Reported Cases of Anaplasmosis, 2013 Photo credit: CDC 25
Ehrlichiosis and Anaplasmosis: Clinical Manifestations Clinical manifestations: similar to RMSF Incubation period 5-10 days (median 9 days) Most common symptoms: fever, headache, rash, myalgia, nausea, abdominal pain, altered mental status Meningitis or meningoencephalitis may occur late in illness Rash Occurs in 60% of children and 30% of adults Rash appears similar to RMSF but appears later in illness (day 4-5), less frequently petechial, less frequently on palms and soles Rarely occurs in patients with anaplasmosis or E. ewingii infection 26
Ehrlichiosis and Anaplasmosis: Lab findings, Diagnosis and Treatment Laboratory findings: Thrombocytopenia, leukopenia, elevated transaminases Hyponatremia in half of patients Disease can be severe but generally less severe than RMSF Mortality rate: 1-3% Ehrlichia; <1% Anaplasmosis Diagnosis : 4-fold rise in titer by IFA Treatment: Doxycycline (regardless of age) Start therapy presumptively Continue 3 days after defervescence 27
Lyme Disease: Epidemiology Caused by Borrelia burgdorferi Ixodes species tick vectors in US I. scapularis : Northeast, upper Midwest I. pacificus: West Coast Reservoirs-small mammals including white footed mouse, western gray squirrel White-tailed deer: important food source/habitat for Ixodes ticks, but not a reservoir for B. burgdorferi B. burgdorferi is NOT found in southern US ticks (Ixodes ticks in the South feed on reptiles, which do not serve as a reservoir) 28
Photo credit: CDC 29
Lyme Disease: Epidemiology 95% of cases occur in northeastern or upper Midwestern states, less often Pacific Northwest Cases reported from other parts result from : Returning travelers from endemic regions False positive testing in patients without epidemiologic risk factors Cases of STARI > 50% of cases in the summer Incidence highest in 5-9 y, 55-59 years 30
Reported Cases of Lyme Disease, 2013 Photo credit: CDC 31
Lyme Disease: Diagnosis Early localized: diagnosis based on appearance of erythema migrans rash (bulls-eye) Antibodies are only detectable in 1/3 of patient with solitary EM lesions Early disseminated with multiple EMs : clinical diagnosis Early disseminated disease without rash or late disease: diagnosed based on clinical presentation + 2 step serology 1 st step: ELISA or IFA 2 nd step: Confirmatory Western Blot need 2/3 IgM+ bands or 5/10 IgG+ bands to be considered a positive WB 32
Photo credit: CDC 33
Lyme Disease: Diagnosis Key point: Don t perform serology unless clinical AND epidemiological factors suggest Lyme disease Positive serology does not necessarily indicate that the illness is Lyme disease False positives are frequent (even with 2 step serology) Do not perform serial serologic testing to monitor for response to treatment 34
Lyme Disease: Treatment Antibiotics are indicated for all stages of Lyme Disease Treatment is not indicated for positive serology without clinical symptoms Oral regimens: doxycycline, amoxicillin or cefuroxime Doxycycline: adults and children 8 years Amoxicillin: children 8 years Cefuroxime: alternative regimen Parenteral regimens: ceftriaxone, PCN G, cefotaxime 35
Lyme Disease: Treatment Localized erythema migrans/multiple erythema migrans: oral regimen x 14 days Isolated facial palsy: oral regimen x 14-21 days Arthritis: oral regimen x 28 days Heart block or carditis: oral or parenteral x 14-21 days Meningitis: parenteral regimen x 14-21 days (or PO doxycycline x 14-21 days if 8 years) Late neurologic disease: parenteral regimen x 14-28 days 36
Southern Tick-Associated Rash Illness (STARI) Associated with bite of Amblyomma americanum (lone star tick) Unknown etiologic agent Characterized by a mild illness: fatigue, myalgia, headache and fever Often with EM like rash that develops within 7 days of tick bite Has not been linked to arthritis, neurologic disease, or chronic symptoms Unclear if treatment is necessary or beneficial but many will treat with oral antibiotic (same as Lyme disease) 37
Photo credit: CDC 38
Distribution of the Lone Star Tick Photo credit: CDC 39
Photo credit: CDC 40
Animal Bites: Epidemiology Dogs responsible for about 90% of bite wounds Estimated animal incidence in US 1-2 million dog bites 400,000 cat bites 250,000 human bites 45,000 snake bites Rabbits, skunks, squirrels, horses, rats, hogs, and monkeys account for about 1% of all bites Children are the most frequent victims (50-75% of all dog bites) 41
Bite Wound Infections Puncture wounds: high risk for infection Hand wounds: more likely to be infected than wounds on arms, legs or face Delayed care > 24 hrs & primary closure: increases risk of infection Rate of infection depends on biting animal: Cat: 20-50% Dog: 3-20% Human: 10-30% Other mammals: Rare, except monkeys 42
Clean the wound Bite Wound Management Remove visible dirt and superficial devitalized tissue Irrigate with normal saline using high pressure Cleanse but don t irrigate puncture wounds Insufficient data to make specific recommendations on which wounds can be safely sutured after cleaning In general, don t suture wounds that are Apparently infected More than 8 hours old Puncture wounds On hands or feet (consult surgical specialist) Always review need for tetanus or rabies prophylaxis 43
Antimicrobial prophylaxis Limited data to base recommendations Usually prescribed for 3-5 days Reasonable indications for prophylaxis: Moderate or severe wounds < 8 hours old Dog bites > 8 hours old Bites to the hands, feet, face or genital region Puncture wounds (ex: cat bites) Immunocompromised or asplenic patients Usual empiric choice: amoxicillin/clavulanate 44
Management of Infected Bite Wounds Obtain aerobic and anaerobic cultures, final regimen based on culture results Reasonable choices for empiric therapy (or prophylaxis) of mammal bites (including human bites) PO: amoxicillin/clavulanate IV: ampicillin/sulbactam For PCN allergic patients: PO: Extended spectrum cephalosporin or TMP/SMX PLUS clindamycin IV: Same as oral OR meropenem 45
Reptile Bite Wounds Gram negative enteric flora more prominent Need for prophylaxis not well defined Reasonable choices for empiric therapy/prophylaxis: PO: same as used for mammal bites IV: ampicillin/sulbactam + gentamicin OR clindamycin+ gentamicin OR meropenem 46
Animal Rabies in the US All mammals are believed to susceptible to rabies Rabies is endemic in wild animals in all US states except Hawaii Animal rabies cases reported to CDC in 2013: Wild animals 5398 cases (92%) Raccoons (32%), bats ( 27%), skunks (25%), foxes (6%), rabbits/lagomorphs (0.7%) Domestic animals 467 cases (8%) Cats (4%), dogs (2%), cattle (1%), horses/mules (0.5%), sheep/goats ( 0.2%) 47
Human Rabies in the US Most human cases result from animal bites ANY penetration of skin by teeth constitutes exposure (bite may be undetectable) 2003-2013: 34 cases of confirmed human rabies 24 (70%) of these cases acquired in US or Puerto Rico 5/24 were secondary to organ transplantation 12/19 (63%) non-organ transplant cases were associated with bats Finding a bat in the dwelling of a sleeping child or incapacitated individual is significant 48
Rabies: Clinical Manifestations First symptoms are vague and insidious (prodrome) Prodrome last 2-10 days Symptoms: unwell feeling, depression, anxiety, fever, nausea, itching, pain or tingling at bite site Secondary phase (acute neurologic phase) Lasts 2-10 days Furious rabies (agitation, nuchal rigidity, hydrophobia) vs. paralytic rabies (flaccid paralysis starts in limb with bite then spreads to body) Death may occur from cardiac or respiratory collapse Final stage: coma and death 49
Almost always fatal in humans Rabies: Survival 3 unimmunized patients have survived in the US 1 received the Milwaukee protocol (coma induction, ketamine, midazolam, ribavirin, amantadine) 2 cases of apparent spontaneous recovery Rare cases of recovery have been documented among patients who received some post-exposure prophylaxis Nearly all surviving patients are left with significant neurologic sequelae 50
Rabies: Immunization Rabies Immune Globulin (RIG) Gamma globulin prepared from plasma of persons immunized with rabies vaccines Used for passive immunization in exposed patients Rabies vaccines licensed and available in US: Human diploid cell vaccine (HDCV) Purified chick embryo vaccines (PCECV) 51
Rabies Prophylaxis: Points to Consider Consider Type of Exposure Break in skin caused by teeth of rabid animal Contamination of wound or mucous membrane by saliva or neural tissue of rabid animal Bat exposures are often unrecognized Geographic area (urban vs. rural vs. developing country) Circumstances surrounding bite Unprovoked attacks considered more suggestive of rabid animal Feeding or handling wild animals is considered provocative 52
Post-Exposure Prophylaxis by Biting Animal Dog, cat, ferret: If animal is healthy and can be observed for 10 days, then HOLD prophylaxis unless animal demonstrates signs of rabies If suspected to be rabid: START prophylaxis (can discontinue if proven not rabid) If status is unknown (escaped), consult public health officials Skunks, raccoons, bats, foxes and most other carnivores: START prophylaxis (can discontinue if proven not rabid) Livestock, rodents, other mammals: consider individually Squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, other small rodents, rabbits and hares almost never require prophylaxis 53
Rabies: Post-Exposure Management Flush the wound thoroughly: clean with soap and water Give rabies vaccine ( HDCV or PCECV) Start as soon as possible, preferably within 24 hours after bite If not available immediately, give vaccine as soon as available regardless of interval since bite Give on days 0, 3, 7, and 14 Administer RIG (20 IU/kg) with first dose of vaccine Infiltrate as much as possible around the wound (give the rest IM) If RIG not available: give vaccine and then RIG within 7 days 54
Questions? 55
References American Academy of Pediatrics. RMSF. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30 th ed. Elk Grove Village, IL: American Academy of Pediatrics ; 2015: 682-684. American Academy of Pediatrics. Ehrlichia, Anaplasma, and Related Infections. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30 th ed. Elk Grove Village, IL: American Academy of Pediatrics ; 2015: 329-333. American Academy of Pediatrics. Lyme Disease. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30 th ed. Elk Grove Village, IL: American Academy of Pediatrics ; 2015: 516-525. Southern Tick- Associated Rash Illness. (2015, October 22). Retrieved December 21, 2015, from http://www.cdc.gov/stari/index.html Tickborne Diseases of the United States : A Reference Manual for Healthcare Providers, Third Edition, 2015. (2015). Retrieved December 20, 2015, from www.cdc.gov/lyme/resources/tickbornediseases.pdf American Academy of Pediatrics. Bite Wounds. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30 th ed. Elk Grove Village, IL: American Academy of Pediatrics ; 2015: 205-210. American Academy of Pediatrics. Rabies. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30 th ed. Elk Grove Village, IL: American Academy of Pediatrics ; 2015: 658-666. Dyer, et al. Rabies surveillance in the United States during 2013. J Am Vet Med Assoc 2014; 10: 1111-1123. 56