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Medicine review course Animal bites (dogs, cats, monkeys)

8/7/17 Assessment of a bite (the crude history)

1) Where (the circumstances) did the bite occur? 2) Where (on the body) did the bite occur? 3) Time from bite to presentation? 4) Extent of wound? 5) immunocompetence? 6) Host vaccination history?

The answers to these questions will provide…….

Assessment of a bite (the refined history)

1) The potential organisms (from the animal’s surroundings, from the animal’s flora, from the patient’s skin)

2) The need to image deeper tissues and activate more than the ID-on-call (Ortho, GS, vascular, ….)

3) The maximal potential extent of this injury

4) Wound treatment, , vaccination and follow-up required. Dogs and cats 1) Potential organisms -Consider rabies in wild dogs, in non-rabies free countries, in unprovoked attacks. -Consider soil derived organisms( tetanus, melioidosis) in wild dogs -Consider anthracis in farm dogs -Consider capnocytophaga carnimorsus and pasteurella species in exams!

2) Deeper tissues imaging -Consider bone and joint involvement if wound is deep -Look out for presence of prosthetic joints. -cats can bite deep. Small wound can be deeply punctured 3) Maximal potential -Melioidosis in poorly controlled DM -Deeper in breast cancer patients post axillary clearance -Disseminated capnocytophaga carnimorsus in asplenia -Tetanus and rabies in bites close to face Rabies Duration (% of Stage Associated Findings Cases) <30 d (25%) 30-90 d (50%) Incubation period None. 90 d to 1 y (20%) >1 y (5%)

Paresthesias or pain at the Prodrome and early wound site; ; malaise; 2-10 d symptoms anorexia; nausea and vomiting. Hallucinations; bizarre behavior; anxiety; agitation; Acute neurologic disease; biting; hydrophobia; Furious rabies (80% of 2-7 d autonomic dysfunction; cases) syndrome of inappropriate antidiuretic hormone (SIADH). Myocarditis Paralytic rabies (20% of 2-7 d Ascending . cases) Coma, death* 0-14 d — Diagnosis of rabies 1) Clinical 2) for rabies antibodies (RFFIT: rapid fluorescent focus inhibition test) -50% positive by day 8 and 100% positive by day 15 3) RT-PCR of CSF or saliva for rabies virus 4) MRI Brain is not specific. No pathogmnemonic findings.

Treatment of rabies

RISK CATEGORY NATURE OF RISK TYPICAL POPULATIONS PREEXPOSURE REGIMEN

Continuous Virus present continuously, Rabies research Primary course; often in high concentrations laboratory serologic testing every 1 Specific exposures likely to workers, rabies 6 months; booster go unrecognized biologics production vaccination if antibody Bite, nonbite, or aerosol workers titer is below exposure acceptable level

Frequent Exposure usually episodic Rabies diagnostic Primary course; with source recognized, but laboratory serologic testing every 1 exposure might also be workers, cavers, 2 years; booster unrecognized veterinarians and staff, vaccination if antibody Bite, nonbite, or aerosol and animal control and titer is below exposure possible wildlife workers in acceptable level areas where rabies is (0.5IU/ml OR complete enzootic. All people neutralization at 1:5 in who frequently handle the RFFIT) bats. RISK CATEGORY NATURE OF RISK TYPICAL POPULATIONS PREEXPOSURE REGIMEN Infrequent Exposure nearly always Veterinarians and animal Primary course; no (greater than episodic with source control staff working with serologic testing or general recognized terrestrial carnivores in booster vaccination population) Bite or nonbite exposure areas where rabies is uncommon to rare; veterinary students; and travelers visiting areas where rabies is enzootic and immediate access to medical care, including biologics, is limited

Rare (general Exposure always US population at large, No preexposure population) episodic, with source including individuals in immunization recognized rabies-epizootic areas necessary Bit or nonbite exposure Types of contact are: category I – touching or feeding animals, licks on the skin category II - nibbling of uncovered skin, minor scratches or abrasions without bleeding, licks on broken skin category III – single or multiple transdermal bites or scratches, contamination of mucous membrane with saliva from licks; exposure to bat bites or scratches

Vaccine details 1) IM rabies vaccines are given in deltoid not gluteus. 2) Rabies immune globulin should be given within 7 days of start of active immunization. 3) Different IM formulations are interchangeable. 4) Different ID formulations are interchangeable. 5) IM and ID formulations are NOT interchangeable. 6) Excess of immune globulins are injected into patient at a site distant from active immunization. 7) Missed doses in pre-exposure vaccination? Resume without repeating previous dose 8) Missed doses in post-exposure vaccination? Resume without repeating previous dose. If unsure, check antibodies levels 1-2 weeks after last dose Efficacy

Anderson LJ, Sikes RK, Langkop CW, et al. Postexposure trial of a human diploid cell strain rabies vaccine. J Infect Dis 1980;142:133--8. Bahmanyar M, Fayaz A, Nour-Salehi S, Mohammadi M, Koprowski H. Successful protection of humans exposed to rabies infection. Postexposure treatment with the new human diploid cell rabies vaccine and anti-rabies serum. JAMA 1976;236:2751--4. Aoki FY, Rubin ME, Fast MV. Rabies neutralizing antibody in serum of children compared to adults following postexposure prophylaxis. Biologicals 1992;20:283--7. Benjavongkulchai M, Kositprapa C, Limsuwun K, et al. An immunogenicity and efficacy study of purified chick embryo cell culture rabies vaccine manufactured in Japan. Vaccine 1997;15:1816--9. Bijok U, Vodopija I, Smerdel S, et al. Purified chick embryo cell (PCEC) rabies vaccine for human use: clinical trials. Behring Inst Mitt 1984:155--64. Wasi C, Chaiprasithikul P, Auewarakul P, Puthavathana P, Thongcharoen P, Trishnananda M. The abbreviated 2-1-1 schedule of purified chick embryo cell rabies vaccination for rabies postexposure treatment. Southeast Asian J Trop Med Public Health 1993;24:461--6. Tanphaichitra D, Siristonpun Y. Study of the efficacy of a purified chick embryo cell vaccine in patients bitten by rabid animals. Intern Med J 1987;3:158--60

Total >222 patients. 0 deaths from rabies 5 bitten given active vaccine without antiserum3 died 12 bitten given active vaccine with antiserum1 died

Fangtao L, Shubeng C, Yinzhon W, Chenze S, Fanzhen Z, Guanfu W. Use of serum and vaccine in combination for prophylaxis following exposure to rabies. Rev Infect Dis 1988;10:S766--70. 0/23 with IVIg died, 3/3 without died

Who should receive abx prophylaxis? Without treatment, 16% of dog bites become infected.1 With treatment, RR 0.56 (95% confidence interval, 0.38 to 0.82) Prophylaxis to be considered within 24 hours of injury.2 Preemptive early antimicrobial therapy for 3–5 days is recommended for patients who3 1) Are immunocompromised 5) Hang injuries 2) Are asplenic 6) Bone and joint involvement 3) Have advanced liver disease 7) Moderate and severe injuries 4) Edematous in the biten limb

1) Antibiotics to prevent infection in patients with dog bite wounds: a meta-analysis of randomized trials Cummings P. Ann Emerg Med 1994; 23:535–40. 2) A comparative double blind study of amoxycillin/clavulanate vs placebo in the prevention of infection after animal bites Brakenbury PH, Muwanga C Arch Emerg Med. 1989;6(4):251 3) Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue : 2014 Update by the Infectious Diseases Society of America Stevens et al CID June: 2014 Common organisms isolated

Principle and Practice of Infectious Disease 7th edition Mandell et al Treatment Same antibiotics choice as prophylaxis Duration to be determined by extent of infection.

Remember tetanus toxoid: Tetanus toxoid should be administered to patients without toxoid vaccination within 5 years.

Wound care

Primary wound closure is not recommended for wounds with the exception of those to the face, which should be managed with copious irrigation, cautious , and preemptive antibiotics (strong, low). Other wounds may be approximated (weak, low).

*lack of good controlled studies, heterogeneity in wounds undermine stregth of recommendation

Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America Stevens et al CID June: 2014 Capnocytophaga carnimorsus or cynodegni Gram negative bacillus. Normal oral flora of dogs and cats. -more with dog bites 3 days from bite Risk factors: asplenia, alcohol Septicemia and meningitis prominent Mortality for septicemia: 30% Mortality for meningitis: 5% Prolonged blood cultures needed -3-7 days to grow.

Augmentin, 3 and 4th generation usually useful. Consider brain penetration when dosing

Retiform purpura

-occurs in about 20-40% of C. carnimorsus bacteremia. -clotted superficial veins in a background of purpura fulminans.

Pasteurella multocida Gram negative bacillus. Normal oral flora of dogs and cats. More with cat bites.

Skin and soft tissue infections Upper respiratory tract infection Lower respiratory tract infection in COPD and bronchiectasis Bacteremia in cirrhotic, immunocompromised host1 -mortality is 31% in this cohort b-lactam-b-lactamase inhibitor, penicillin, cefazolin, cefuroxime ceftriaxone, fluoroquinolones, doxycyclines active. Anti-staphylococcal penicillins not active.

Scandinavian journal of infectious diseases 1987;19(4):385-93.: bacteremia: report of thirteen cases over twelve years and review of the literature.

Cat scratch disease: henselae Gram negative bacillus Cats are reservoirs. Cats may be persistently bacteremic Incubation period 3-10 days. Primary papule or pustule -lasting 1-3 weeks Then 1-7 weeks later, regional lymph- adenopathy

Myalgia and arthralgia in about 10% Can be complicated by ↑Ca2+

Typical presentation

Bartonella henselae: atypical presentations

Parinaud oculoglandular syndrome Neuroretinitis

Encephalitis -headache, restlessness, seizures, coma. Endocarditis -notable agent of culture negative endocarditis. -Bartonella quintata more common the henselae. : atypical presentations

Bacillary peliosis hepatis

Usually in HIV positive patients with CD4<100 cells/mm3 Diagnosis Histology: granulomatous inflammation with stellate necrosis. Gram negative but stains poorly. Stains with silver stains. Culture: slow-growing, detectable only after 7 days. Fastidious organism PCR of issue samples. Serology: from serum. Might not be detectable for up to 6 weeks in immunocompetent and 25% of HIV negative patients may be false negative.

Treatment Cat-scratch disease: azithromycin 500mg om x 1 day then 250mg om X 4 days Neuroretinits: ( 100mg bd + rifampcin 300mg bd) X 6 weeks Bacillary angiomatosis or peliosis hepatits: doxycycline 100mg bd x 3-4 months Endocarditis: 3mg/kg/day x 2 weeks + doxycycline 100mg bd x 6 weeks

Minireview: Recommendations for the treatment of Human infections caused by Bartonella Speices J.M. Rolain et al Antimicrobial Agents and Chemotherapy June 2004 p1921-1933

Herpes simiae, herpes B virus Acquired from monkey bites, scratches, mucosal contact. Only found in Old world monkeys. Herpes B virus not found in New World monkeys. Sheds herpes B virus like human shed herpes simplex virus. About 0.4-2% chance that an exposure will carry viral particles -yet very low number of disease described. -risk higher if wounds are deep or near head Incubcation period: 5 days to 3 weeks. 3 patterns of disease 1) Vesicles 2) Fever, myalgia-viral illness. Progressing to CNS symptoms 3) CNS symptoms from the outset

Evaluation

Post-exposure: PCR, serology not routinely done.

Suspected disease 1) Swabs of vesicles for PCR 2) B virus serology 3) LP for B virus PCR and serology 4) MRI brain: brainstem encephalitis

Prognosis without treatment: 80% mortality

Treatment of disease

Key point #1: B virus IC50 for acyclovir is higher than herpes simplex virus Key point #2: Ganciclovir is better than aciclovir for treatment and prophylaxis in ANIMAL models.

Hence, …. For disease with neurological involvement: IV ganciclovir 5mg/kg bd X at least 2-3 weeks AND until symptoms resolves AND culture negative, FOLLOWED by 1 year of Valacyclovir 1g tds or Acyclovir 800mg 5x/day, +/- followed by lifelong Valacyclovir 0.5g bd or Acyclovir 400mg bd -initial IV phase can be replaced by IV acyclovir 12.5-15mg/kg tds

Post-exposure prophylaxis Valacyclovir 1g tds or acyclovir 800mg 5x/day for 2 weeks within 5 days of exposure (because this worked in rabbits)

Assessment of a bite (the refined history)

1) The potential organisms (from the animal’s surroundings, from the animal’s flora, from the patient’s skin)

2) The need to image deeper tissues and activate more than the ID-on-call (Ortho, GS, vascular, ….)

3) The maximal potential extent of this injury

4) Wound treatment, antibiotics, vaccination and follow-up required.