RABIES CASE PRESENTATION - Michelle Aguirre, PharmD Medical Center Hospital September 8th, 2017 - Medical Center Health ...
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Michelle Aguirre, PharmD
RABIES CASE PRESENTATION Medical Center Hospital
September 8th, 2017
PART I: CASE INTRODUCTION AND Michelle Aguirre, PharmD
Medical Center Hospital
DISEASE OVERVIEW September 8th, 2017
CASE INTRODUCTION Chief complaint Unobtainable at the moment History of present illness JC is a 49-year-old male who was walking down the street and was drinking one liter of vodka roaming exhibiting signs of confusion. He was called by his neighbor to go back to his house, as it was hot in the day. The patient refused to go back to this home and had recurrent falls on his head and sustained multiple injuries on his limbs and left knee. Along his journey, a dog came and bit him on his left knee and then ran away. Afterwards, one of the neighbors called the ambulance and the patient was transferred to the ER for further care.
CASE INTRODUCTION
PMH Allergies
Hypertension Sulfa (reaction unknown)
Bipolar disorder
Chronic active alcoholism
Home Medications
Seroquel 400 mg PO daily
Family history Lithium 300 mg PO TID
Unknown Lisinopril 20 mg PO daily
Social history
Drinks about one liter of vodka
every day for the last 20 years
and has multiple admissions for
alcohol withdrawal symptoms
CASE INTRODUCTION Review of systems: General appearance: Patient was awake and alert and in severe acute distress Head: Normocephalic. No raccoon’s eyes or battle signs Neck: Mild tenderness in the upper cervical spine/posterior scalp Eyes: PERRLA, extraocular muscles intact Respiratory: Lungs clear to auscultation bilaterally, no respiratory distress Cardiovascular: Regular rate and rhythm, no murmurs, rubs, or gallops Abdomen: Soft, nontender, nondistended Neuro: GCS 15, awake alert, and oriented x4 Skin: Multiple bruises noted from patient’s posterior shoulder to his right flank; There is a large bruise over the patient’s left knee with good range of motion. Also, presence of dog bite with minor skin abrasions Extremities: Left knee bruise, normal range of motion
CASE INTRODUCTION Vital Signs HR: 77 RR: 13 BP: 58/25 Temp: 101F Weight: 91kg Height: 6’6’’ Labs Na 129 L Glucose 76 WBC 14.8 H K 4.0 Mg Hgb 9.2 Cl 75 L Albumin 3.6 Plts 124 L CO2 16 L AST 42 H Lact. Acid 3.1 H BUN 112 H ALT 38 PT 18.0 H SCr 20.6 H Bili 0.9 INR 1.53 H
CASE INTRODUCTION JC is admitted to the ICU where the admitting physician decides to start this patient on a rabies vaccine schedule The whole ICU team is now on the case and will follow the patient clinically and make adjustments as necessary
RABIES: BACKGROUND Rabies is a zoonotic disease caused by RNA viruses in the family Rhabdoviridae, genus Lyssavirus Virus is transmitted in the saliva of rabid mammals via a bite After entry to the central nervous system, these viruses cause an acute progressive encephalomyelitis The incubation period usually ranges from 1 to 3 months after exposure, but can range from days to years The vast majority of rabies cases reported to the Centers for Disease Control and Prevention (CDC) each year occur in wild animals like raccoons, skunks, bats, and foxes
EPIDEMIOLOGY Over the last 100 years, rabies in the United States has changed dramatically More than 90% of all animal cases reported annually to CDC now occur in wildlife (before 1960, the majority were domestic animals) The principal rabies hosts today are wild carnivores and bats The number of rabies-related human deaths in the United states has declined from more than 100 annually at the turn of the century to one or two per year in the 1990’s Prompt wound care and the administration of rabies immune globulin (RIG) and vaccine are highly effective in preventing human rabies following exposure
TRANSMISSION The route of infection is usually, but not necessarily, by a bite In many cases the affected animal is exceptionally aggressive, may attack without provocation, and exhibits otherwise uncharacteristic behavior Transmission may also occur via an aerosol through mucous membranes (transmission in this form may have happened in people exploring caves populated by rabid bats) Transmission between humans is extremely rare, although it can happen through transplant surgery, or, eve, more rarely through bites or kisses Various routes of transmission have been documented and include contamination of mucous membranes (i.e., eyes, nose mouth), aerosol transmission, and corneal transplantations
PATHOPHYSIOLOGY: OVERVIEW
• The virus directly or indirectly enters the peripheral nervous system
Infection by • It then travels along the nerves towards the central nervous system
bite
• Rapid encephalitis develops and symptoms appear
Virus reaches • The spinal cord may inflame producing myelitis
brain
• Lymphocytes, polymorphonuclear leukocytes, and plasma cells may
leak throughout the entire CNS
Perivascular • Virus enters salivary glands and other organs of victim
infiltration
Am J Vet Res. 1966 Jan;27(116):24-32SIGNS AND SYMPTOMS When a person contracts rabies, they do not show symptoms immediately The disease takes a period of time to manifest in the body which is known as its period of incubation Once symptoms arise, the patients condition deteriorates rapidly
FIVE STAGES OF RABIES
Incubation period: 5 days to > 2 years
U.S. median ~ 35 days
Pro-dome State: 0-10 days
Early flu-like symptoms
Acute neurologic period: 2-7 days
Neurologic symptoms begin
Coma: 5-14 days
Requires mechanical ventilation
DeathSIGNS AND SYMPTOMS
Early Symptoms Late Symptoms
• Fever • Insomnia
• Headache • Anxiety
• Generalized weakness • Confusion
• Generalized discomfort • Slight or partial paralysis
• Excitation
• Hallucinations
• Agitation
• Hypersalivation
• Difficulty swallowing
• Hydrophobia
*Death usually occurs within day of the onset of late symptomsDIAGNOSIS In animals, rabies is diagnosed using the direct fluorescent antibody (DFA) test, which looks for the presence of rabies virus antigens in brain tissue Several tests are required in humans to diagnose rabies ante-mortem (before death); no single test is sufficient Saliva can be tested by virus isolation or reverse transcription followed by polymerase chain reaction (RT-PCR) Serum and spinal fluid are tested for antibodies to rabies virus Skin biopsy specimens are examined for rabies antigen in the cutaneous nerves at the base of hair follicles
Schizophrenia Final
PART II: DRUG THERAPY DISCUSSION Presentation
Michelle Aguirre, PharmD
Candidate 2017EARLY MANAGEMENT Wash any wounds immediately One of the most effective ways to decrease the chance for infection is to wash the wound thoroughly with soap and water Refer to a doctor For attention for any trauma due to the animal attack before considering the need for rabies vaccination The doctor, possibly in consultation with state or local health department, will decide on the need of rabies vaccination Decisions to start vaccination, known as post-exposure prophylaxis (PEP) are up to the discretion of the physician, but two organizations have developed recommendations: Advisory Committee on Immunization Practices (ACIP) schedule for rabies vaccine (2010) World Health Organization (WHO) pre- and post-exposure prophylaxis 2010
EARLY MANAGEMENT
Post-exposure prophylaxis (PEP)
CDC recommends following ACIP 2010 vaccination schedule
Consists of one dose of immune globulin and four doses of rabies vaccine over a 14-
day period
Rabies immune globulin and the first dose of rabies vaccine should be given by a
health care provider as soon as possible after exposure
Additional doses or rabies vaccine should be given on days 3, 7, and 14 after the
first vaccination
Current vaccines are relatively painless and are given in the arm, like a flu vaccine
Rabies immunoglobulin is referred to as “passive immunization” while rabies vaccine is
referred to as “active immunization”
*Recommendations for PEP schedules are based on vaccination status: not
previously vaccinated vs. previously vaccinated*POST-EXPOSURE PROPHYLAXIS Goal: To neutralize the virus at the site of infection before it can enter the human nervous system generally ensures survival Rabies Immune Globulin The administration of RIG provides immediate virus-neutralizing antibodies until protective antibodies are generated in response to vaccine HRIG has a half-life of approximately three weeks Two preparations of HRIG are licensed and available in the U.S. Rabies Vaccines Rabies vaccine induces the production for protective virus-neutralizing antibodies within approximately 7 to 10 days that persist for several years Two licensed vaccines are currently available in the U.S.
DYNAMICS OF RABIES AND PEP Figure 1. Schematic of dynamics of rabies virus pathogenesis in the presence and absence of PEP-mediated immune responses
NOT PREVIOUSLY VACCINATED
Intervention Regimen
Wound cleansing All PEP should begin with immediate thorough
cleansing of all wounds with soap and water. If
available, a virucidal agent (e.g., povidine-iodine
solution) should be used to irrigate the wounds
Human rabies Administer 20 IU/kg body weight on day 0. If
immune globulin anatomically feasible, the full dose should be
(HRIG) infiltrated around and into the wound(s), and any
remaining volume should be administered
intramuscularly at an anatomical site distant from the
vaccine administration
Vaccine Human diploid cell vaccine (HDCV) or purified chick
embryo cell vaccine (PCECV) 1.0 mL, IM (deltoid
area), 1 each on days 0, 3, 7 and 14PREVIOUSLY VACCINATED
Intervention Regimen
Wound cleansing All PEP should begin with immediate thorough
cleansing of all wounds with soap and water. If
available, a virucidal agent (e.g., povidine-iodine
solution) should be used to irrigate the wounds
Human rabies HRIG should not be administered
immune globulin
(HRIG)
Vaccine Human diploid cell vaccine (HDCV) or purified chick
embryo cell vaccine (PCECV) 1.0 mL, IM (deltoid
area), 1 each on days 0 and 3POST-EXPOSURE PROPHYLAXIS FOR
UNVACCINATED PERSONS
1. The combination of RIG and vaccine is recommended for both bite
and non-bite exposures, regardless of the time interval between
exposure and initiation of PEP
2. If PEP has been initiated and appropriate laboratory diagnostic
testing (i.e., the direct fluorescent antibody test) indicates that the
animal that caused the exposure was not rabid, PEP may be
discontinued
3. If HRIG was not administered when vaccination was begun on day
0, it can be administered up to and including day 7 of the PEP
series
4. Even when PEP is administered imperfectly or not according to the
schedule, it might generally be effectiveOTHER KEY POINTS HRIG is not administered in the same syringe or at the same anatomic site as the first vaccine dose The gluteal area should not be used because administration of vaccine in this area may result in diminished immunologic response Children should receive the same vaccine dose (i.e., vaccine volume) as recommended for adults
SEROLOGIC TESTING All healthy persons tested in accordance with ACIP guidelines after completion of at least a 4-dose regimen of rabies PEP should demonstrate an adequate antibody response against rabies virus No routine testing of healthy patients completing PEP is necessary to document seroconversion When titers are obtained, serum specimens collected 1-2 weeks after prophylaxis should completely neutralize challenge virus The titers will decline gradually since the last vaccination
ADVERSE REACTIONS AND PRECAUTIONS Adverse effects with modern human rabies vaccination are uncommon Pregnancy and infancy are not contraindications Immunosuppression All rabies vaccines licensed in the United States are inactivated cell-culture vaccines that can be administered safely to persons with altered immunocompetence Use of corticosteroids, other immunosuppressive agents, antimalarials, and immunosuppressive illnesses might reduce immune responses to rabies vaccines and should receive a 5-dose vaccine regimen
PRICING AND AVAILABILITY Rabies Immune Globulin Injection (HyperRAB S/D Intramuscular) 150 units/mL (2mL): $852.14 Injection (Imogam Rabies-HT Intramuscular) 150 units/mL (2mL): $867.05 Rabies Virus Vaccine Injection (Imovax Rabies Intramuscular) 2.5 units/mL (1): $386.76 Location at Medical Center Hospital Immunoglobulin is stored in Gloria’s office in the first refrigerator Vaccines are dispensed from the central pharmacy
WHO VACCINE RECOMMENDATIONS
Definition of categories of exposure and use of rabies biologicals
from the World Health Organization (2010)
Immune Transdermal bites or scratches, licks on
globulin + broken skin, contamination of mucous
vaccine membrane with saliva, or contact with bats
Vaccine Minor scratches or abrasions without
bleeding or and nibbling of uncovered
only skin
No Touching, feeding of animals, or licks on
prophylaxis intact skinINFECTIOUS DISEASES SOCIETY OF
AMERICA
Skin and Soft Tissue Infection Guidelines (2014)
Specific recommendations are made for dog bites, including indications for
antimicrobials
IDSA briefly mention PEP in their guidelines
Therapy Recommendation
Post-exposure • May be indicated; consultation with local health officials
prophylaxis is recommended to determine if vaccination should be
initiatedPART III: CLINICAL COURSE Michelle Aguirre, PharmD
Candidate 2017CLINICAL COURSE Day 1: JC received the following regimen on day 0: No documentation of wound care was found Dog that bit patient was presumably killed by neighbor who owned dog
CLINICAL COURSE
Was this treatment appropriate?
Correct treatment
The recommendation is to administer:
Immune globulin 20 IU/kg x 91 kg = ~18,000 units
Chick embryo cell vaccine 2.5 mL/mL x 2.5 mg = 1 mL
Both should be given intramuscularly on day 0!
However, we do not know if he received proper wound care…CLINICAL COURSE
Days that followed:
Day 0
RIG and Day 7 Day 14
vaccine 1 Vaccine 3 Scheduled vaccine
1 mL 1 mL never given
Day 4 Day 12
Vaccine 2 Patient
1 mL discharged
Is this regimen appropriate?PATIENT COURSE CONCLUSION
JC received the correct doses for RIG and vaccines
ACIP recommends immune globulin + vaccines (CDC
preferred); WHO classification is difficult to determine
but likely recommends vaccine only for this patient
Wound care was never documented in the patient chart
± Although the treatment plan did not follow the vaccine schedule
days exactly and the patient did not receive the last vaccine,
he is expected to have some general immunityQUESTIONS?
REFERENCES
1. CDC. Rabies. Centers for Disease Control and Prevention [cited
September 1, 2017]. Available from
[https://www.cdc.gov/rabies/index.html].
2. CDC. Rabies prevention – Unites States, 2010: recommendations
of the Immunization Practices Advisory Committee (ACIP). Y40(No.
RRR-3)
3. Dietzschold B, Schnell M, Koprowski H. Pathogenesis of rabies. Curr
Top Microbiol Immunol. 2005;292:45-56.
4. 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):147-59.You can also read
