Michelle Aguirre, PharmD RABIES CASE PRESENTATION Medical Center Hospital September 8 th , 2017
PART I: CASE INTRODUCTION AND Michelle Aguirre, PharmD Medical Center Hospital DISEASE OVERVIEW September 8 th , 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 Home Medications Chronic active alcoholism 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 CO 2 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 • It then travels along the nerves towards the central nervous system Infection by bite • Rapid encephalitis develops and symptoms appear • The spinal cord may inflame producing myelitis Virus reaches 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):24-32
SIGNS 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 Death
SIGNS 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 symptoms
DIAGNOSIS 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 2017
EARLY 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
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