|By Admin1 (admin) on Thursday, November 01, 2001 - 9:53 am: Edit Post|
Read this article on the results of a study of rabies using Peace Corps Volunteers in high risk areas:
Rabies: Risks, recognition, and prophylaxis
Oct 1, 2001 - Formulary Author(s): C, Alan
Rabies and its relationship to the bite of a "mad dog" have been recognized and feared for many centuries.1 The disease was mentioned in early written records from the Middle East, Greece, Rome, and China,2 including a legal code prepared in Mesopotamia more than 4000 years ago, in which rabies was identified as a cause of "wrongful death."3
Rabies encephalomyelitis (inflammatory disorder of the brain and spinal cord) develops after invasion of the victim's central nervous system (CNS) by rabies virus, which belongs to the Lyssavirus genus.4,5 The disease is generally transmitted to humans by the bite of an infected animal, which deposits virus-containing saliva into the wound; transmission by aerosol inhalation or via transplantation of a cornea from an infected donor has been reported in extremely rare cases.4
The reputation of the disease is based on its horrific clinical features and unusual clinical course, which include:
* A long incubation period: 20 to 60 days on average6 but occasionally more than 1 year7
* The distinctive features of the classic, or "furious," form: hydrophobia (severe spasms of the pharynx, larynx, and diaphragm after attempts to drink); periods of hyperactivity, agitation, and confusion followed by lucid intervals; and hypersalivation'
* Rapid progression to paralysis, coma, and death8
* The absence of any effective treatment after the onset of clinical disease.9
Once the disease becomes clinically apparent, rabies is virtually always fatal. Therapy for rabies has been successful in only four reported cases, in which rabies vaccination was completed before the onset of the disease.9 However, rabies is preventable when appropriate prophylaxis is given in a timely fashion before symptoms emerge. The prophylactic regimens in use today are based on highly effective cell culture vaccines. In fact, these vaccines are uniformly effective when properly applied.4 No postexposure vaccine failures have occurred in the United States (US) since these vaccines came into routine use.4
In the US today, the annual number of human rabies cases is very low. Between 1980 and 2000, only 42 cases of human rabies were reported, and there were only 2 years in which 5 or more human cases were reported (1994, 6 cases; 2000, 5 cases).10-12 This admirable public health achievement has been made possible by highly successful animal vaccination campaigns in the US that have virtually eliminated rabies among dogs, the traditional source of human rabies, and the availability of highly efficacious cell culture rabies vaccines for humans.11
Since 1990, however, a new challenge has become apparent in the prevention of human rabies. Bats have emerged as the major agent of transmission in human rabies cases in the US, causing 75% (24) of the 32 cases reported during this period.10 Bat bites may cause minimal trauma,13 and victims may not seek medical attention and therefore may not receive postexposure prophylaxis. When symptoms of rabies develop, clinicians may not ask about bat exposure, and the patient may not recall the exposure or even realize that an exposure occurred. The number of human rabies cases is likely tq rise unless there is greater awareness of the risk of rabies following contacts with bats or other wildlife species, including raccoons, skunks, and foxes, that coexist successfully with humans and are also reservoirs for rabies virus.14
In the US, Canada, and much of Europe, wild animal populations form the main reservoirs for rabies virus.9,11,15 As the incidence of dog rabies declined throughout the US, the number of human rabies cases attributed to dog bites also decreased, and in the 1960s and 1970s, most human rabies cases acquired in the US were associated with exposures to wildlife species.16 In most human cases reported in the US that were attributed to dogs, rabies was acquired when the victim was living in or visiting a country where dog rabies is endemic.17 Only 2 of the 42 cases of human rabies reported in the US since 1980 have been attributed to exposure to dogs living in the US.10 12 Currently, the number of dogs in the US confirmed to be rabid is approximately 100 per year,11 owing to spillover from wild animals rather than dog-to-dog transmission, and has been overshadowed by the rise in rabies cases among wild animals (Figure 1)10-12,18-25
In the US, rabies is epidemic or endemic among a number of wild animal populations, including raccoons, skunks, bats, and foxes.10,11,18-25 Confirmed rabies cases diagnosed in raccoons exceed those among other wild species, but rabies virus variants circulating in bats have been responsible for all but three of the indigenously acquired cases of human rabies in the US since 1980.10-12
Bats: Predominant Vector of Human Rabies in the US
Bats have been the source of 62% (26) of the 42 cases of human rabies eported in the US since 1980 and 75% (24) of the 32 cases reported since 1990.10-12 A number of different bat species and rabies virus variants have been implicated in human rabies cases in the US. Some bat species migrate over wide areas, whereas others have a fairly well-defined home territory. Similar rabies virus variants are usually isolated from migratory species such as the Mexican free- tailed bat (Tadarida brasiliensis) or the silver-haired bat (Lasionycteris noctivagans) in all locations, whereas virus variants obtained from nonmigratory bats such as the big brown bat (Eptesicus fuscus) may differ by location, as is true for terrestrial mammals.1 Since 1980, four virus variants obtained from five bat species have been associated with human rabies cases in the US: Lasionycteris noctivagans/Pipistrellus subflavus (eastern pipistrelle) (18 cases; 69%), Tadarida brasiliensis (5 cases; 19%), Myotis sp.
(2 cases; 8%), and Eptesicus fuscus (1 case; 4%).10-13
Transmission and Exposure History
All mammal bites represent a potential risk of rabies transmission. Less frequently, the virus may be transmitted through nonbite exposures by contamination of open wounds, abrasions, mucous membranes, or scratches with saliva (or other potentially infectious material). Exposure to rabies does not occur through petting a rabid animal or contact with blood, urine, or feces, and other modes of transmission are extremely rare.4
Prior to the 1980s, most cases of human rabies in the US were associated with a documented bite from a rabid animal.26,27 Since 1980, bite histories have been obtained for only 2 of 26 cases of human rabies caused by virus variants isolated from bats; a history of contact with bats was found in approximately half of the cases.10 12 In several cases, victims were reported to have handled bats,10,28- 30 or to have had a bat strike or land on them,10,29,31 but no wounds or scratches were subsequently recalled. Certain types of bat encounters are associated with an increased risk of exposure to the rabies virus (Table 1).32 However, medical advice should be sought after all encounters with a bat that might represent a potential exposure.
Although the rabies virus variant circulating predominantly in silver-haired and eastern pipistrelle bats differs genetically from dog rabies virus variants, the human and animal rabies vaccines available in the US are protective against rabies virus variants in dogs and bats as well as other wildlife.33
After the rabies virus is deposited into muscle in saliva from an infected animal, it is believed to bind to nicotinic acetylcholine binding sites on the plasma membrane of muscle cells at neuromuscular junctions? The virus may replicate in muscle cells or other cell types prior to binding at the neuromuscular junction.34 The length of the incubation period before the onset of clinical disease depends on a number of factors, including the site of the exposure, viral variant, and amount of virus inoculated into the wound.15 Bites on the head are typically associated with shorter incubation periods than those on extremities.5
The development of clinical disease may be prevented by vaccination, along with proper wound care and administration of rabies immune globulin (RIG), during the incubation period, but vaccination is likely to be poorly effective after the virus enters the sensory and motor axons of peripheral nerves.17 The virus is actively transported along the axons of peripheral nerves until it reaches the spinal cord and sensory ganglia, where it multiplies.9- 34 At this point, the first neurologic symptom of rabies-pain or paresthesias at the site of the bite wound-may appear.17 The virus then disseminates rapidly throughout the CNS by axonal transport with cell-to-cell transfer at synaptic junctions.9,34 Dissemination of the virus within the brain is associated with development of a rapidly progressive encephalitis.
17 The virus then spreads centrifugally (outward) along autonomic and sensory nerves throughout the body, infecting many organs and tissues, including the salivary glands, from which it is released into saliva.2
The clinical presentation of rabies is highly variable. During a prodromal period lasting 2 to 10 days, the initial presenting symptoms (malaise, fatigue, headache, anorexia, fever, cough, chills, sore throat, abdominal pain, nausea, vomiting, and diarrhea) are often nonspecific and mimic those of many respiratory or gastrointestinal infections." Pain or paresthesias at the site of the healed wound \may be the first symptom suggestive of rabies. Anxiety, agitation, irritability, nervousness, insomnia, and depression may also be present.
In the acute neurologic period, which generally lasts 2 to 7 days,17 symptoms may follow one of two patterns. In the classic (or furious) form of rabies, initial neurologic symptoms include hyperactivity, disorientation, hallucinations, and bizarre behavior.8 As the disease progresses, the hyperactive phases alternate with periods of calm. Hyperthermia, tachycardia, hypersalivation, and priapism may be present. In about 50% of patients, attempts to drink cause spasms of the pharynx, larynx, and diaphragm (hydrophobia), and choking and gagging develop; similar symptoms may be elicited by blowing air on the patient's face (aerophobia).2 Other symptoms include hyperventilation and hyperpyrexia.8
The paralytic form of rabies is marked by the early onset of paralysis with progression to quadriparesis.6 Hyperactivity and behavioral changes are normally absent. Mental status is generally intact at first but later deteriorates to confusion and disorientation, and then stupor.
In the final phase of the disease, coma develops.6 In both clinical forms of rabies, death may occur abruptly from cardiac or respiratory arrest or may be caused by secondary complications, including multisystem organ failure and secondary infections.
Few health care professionals in the US have ever seen a patient with rabies. It is not surprising, therefore, that rabies is sometimes not included in the differential diagnosis of encephalitis even when clinical signs or symptoms are suggestive. The failure to consider rabies in the differential diagnosis of encephalitis is especially likely in the absence of a history of animal bite or bat exposure. In 8 of 38 human rabies cases reported in the US from 1960 to 1979(16) and in 12 of 32 cases reported from 1980 to 1996,35 the diagnosis of rabies was made only after death. The presence of hydrophobia, aerophobia, or three or more signs typical of rabies was found to increase the likelihood of a diagnosis before death.35 Rabies should be included in the differential diagnosis of acute, rapidly progressing encephalitis, even in the absence of a history of animal bite or bat exposure.35 Rabies must be distinguished from other, treatable causes of viral encephalitis, such as that caused by herpes simplex virus, and from tetanus, which causes more prolonged muscle spasms in the absence of mental status changes.17 The paralytic form of rabies may be difficult to distinguish from Guillain-Barre syndrome or transverse myelitis.17
The course of the illness, additional history, and laboratory tests for other, more common etiologies will determine if samples specific for rabies should be collected. Before samples are collected, consultation with state health departments or with the Rabies Laboratory at the Centers for Disease Control and Prevention (CDC) is suggested.
Antemortem diagnosis may be established by a direct fluorescent antibody test for rabies virus antigen in a nuchal skin biopsy specimen or by a reverse transcriptase-polymerase chain reaction assay for rabies viral RNA in a nuchal skin biopsy specimen, cerebrospinal fluid, or saliva.9
Early diagnosis does not affect the clinical course of rabies. However, it does ensure that standard safety precautions will be followed, thus reducing the number of health care personnel requiring postexposure treatment, which is recommended following exposure of mucous membranes or nonintact skin to body fluids potentially infected with rabies virus.4
Non-Cell Culture Vaccines
Prevention is the only effective form of treatment for rabies. Rabies vaccines were initially developed more than 100 years ago by Louis Pasteur and Emile Roux.17,36 The first use of crude rabies vaccine, composed of a suspension of dried rabbit spinal cord infected with live rabies virus, was reported in 1885 in a 9-year- old boy bitten by a rabid dog.2 Today, unpurified nerve tissue vaccines of sheep brain and suckling mouse brain origin are still used in many developing countries.6,17 These vaccines are inexpensive, but they produce an unacceptable number of postvaccination complications.17
Cell Culture Vaccines
The rabies vaccines with the best records of safety and efficacy are those produced in cell culture and then highly purified.4 The Food and Drug Administration requires cell culture rabies vaccines to contain >=2.5 international units (IU) of rabies virus antigen per single 1-mL intramuscular (IM) dose. All cell culture vaccines available for clinical use in the US are considered to be equally safe and effective when used as recommended. Since they have been routinely used, these vaccines have not been associated with any postexposure vaccine failures in the US.
Two cell culture human rabies vaccines are widely available in the US: RabAvert(TM), a primary purified chick embryo cell vaccine (PCECV) distributed by Chiron Corporation, and Imovax(R) Rabies, a
human diploid cell vaccine (HDCV) distributed by Aventis Pasteur, Inc. (A third vaccine, Rabies Vaccine Adsorbed [RVA], manufactured by BioPort Corporation, has limited availability.)
RabAvert was introduced abroad in 1984 as Rabipur(R) and was approved for clinical use in the US in 1997.37 It is available for IM injection and may be used for both pre-exposure and post-- exposure prophylaxis against rabies.38 Imovax Rabies, initially approved for clinical use in the US in 1980,39 was available for IM and intradermal (ID) injection 40,41 ; the ID formulation, which had been approved for pre-exposure immunization only, was recently withdrawn.
As shown in Figure 2, a rapid and lasting rabies virus neutralizing antibody response follows primary vaccination with either PCECV or HDCV (IM or ID). In a study of antibody titers following primary vaccination, as measured by the rapid fluorescent focus inhibition test (RFFIT), differences in antibody titers between the ID and the IM regimens were statistically significant (p<=0.05) at most time points.42 However, all regimens produced antibody titers above the CDC-accepted level (complete neutralization of the rabies virus at a 1:5 serum dilution4).
The interchangeability of approved rabies vaccines may be important in situations in which the vaccine used initially may not be available for subsequent or booster doses. In a recent study, booster vaccination with PCECV following primary pre-exposure vaccination with either HDCV or PCECV produced satisfactory and equivalent antibody titers (>=0.5 IU/mL by day 7), indicating that switching from HDCV to PCECV does not
compromise the efficacy of booster vaccination.43
Adverse reactions to cell culture rabies vaccines are significantly less common and less serious than those observed following administration of previously available vaccines.4 Local adverse reactions may include pain, erythema, swelling, and itching at the injection site, and localized lymphadenopathy, while systemic adverse reactions may include headache, nausea, abdominal pain, muscle aches, and dizziness.38,40 In a study of normal volunteers, pain at the injection site was the most common local adverse reaction to both HDCV (45% of recipients) and PCECV (34% of recipients), followed by localized lymphadenopathy (15% of each group).40 The most common systemic adverse reactions were malaise (25% and 15% for HDCV and PCECV, respectively), headache (20% and 10%, respectively), and dizziness (10% and 15%, respectively).40 Serious systemic anaphylactic reactions and neuroparalytic events have been reported in rare cases in temporal association with the administration of cell culture vaccines.38,40 In approximately 6% of persons given a booster dose of HDCV, a type III hypersensitivity, or "immune complex-- like," reaction developed 2 to 21 days after the booster dose.4.40 This non-life-threatening reaction is characterized by a generalized urticaria and sometimes includes arthralgia, arthritis, angioedema, nausea, vomiting, and fever.4,40
In US cohorts of subjects who received HDCV between June 1980 and March 1984, 87 cases of presumed type III hypersensitivity reactions were reported to the CDC: 6 (7%) occurred during primary vaccination (after two or more doses) and 81 (93%) occurred following booster immunization.39 In about half of the known cohorts that received booster doses between January 1982 and March 1984, 67 (7%) of 962 persons experienced a type III hypersensitivity reaction. Most patients improved after treatment with antihistamines; a few required systemic corticosteroids and epinephrine. Systemic allergic reactions related to HDCV rarely required hospitalization.
Type III hypersensitivity reactions following HDCV booster administration may be related to the presence of human serum - albumin (used as a stabilizers) that has been rendered allogeneic by beta-propiolactone (used to inactivate infectious rabies virus).44 Systemic allergic reactions were not observed following booster vaccination with HDCV subjected to an additional purification step." HDCV IM and ID formulations contain <100 mg and <15 mg of human serum albumin, respectively, per dose of vaccine.40,41 No type III hypersensitivity reactions following booster vaccination have been reported with PCECV, which contains <0.3 (mu)g of human serum albumin per dose.38
The most recent Advisory Committee on Immunization Practices (ACIP) recommendations for rabies postexposure prophylaxis reflect the current epidemiology of rabies in the US.4 They note that postexposure prophylaxis is a medical urgency but not a medical emergency Physicians should evaluate each possible exposure and, if necessary, consult with local or state public health officials about the need for rabies prophylaxis.
Routine delivery of health care to a patient with rabies is not an indication \for postexposure treatment unless mucous membranes or nonintact skin of health care workers has been exposed to potentially infectious body fluids.4 However, such exposure is often difficult to exclude in a critical care setting unless precautions are taken.
Exposure to Wild and Domestic Animals
Postexposure treatment is recommended for all persons with bite, scratch, or mucous membrane exposure to a bat unless the bat is tested and is confirmed to be negative for the presence of rabies virus.4 Postexposure treatment should be considered when direct contact between a bat and a human has occurred unless the exposed person can be certain that a bite, scratch, or mucous membrane exposure did not occur. If a bat is found indoors and is unavailable for testing, postexposure treatment should be considered for persons who were present in the same room as the bat but might have been unaware of physical contact with the bat.
Such persons include sleeping individuals, unattended children, mentally disabled persons, and incapacitated or intoxicated persons.
All bites by raccoons, skunks, foxes, and coyotes should be considered possible exposures to the rabies virus, and postexposure treatment should be initiated immediately.4 If the animal subsequently tests negative for the presence of rabies virus, vaccination can be discontinued. Postexposure treatment must never be withheld while these animals are observed for signs of rabies.
A healthy domestic do& cat, or ferret that has bitten a person may be confined and observed for 10 days for signs of rabies.4 Confinement and observation of animals should be supervised by local
health authorities. If an animal shows clinical signs of rabies, a physician should be contacted immediately and postexposure prophylaxis should be initiated. The animal should be euthanized and the head submitted to a laboratory for rabies diagnosis.
The essential components of rabies postexposure treatment are immediate wound care and prompt immunization.4 They should be initiated as soon as feasible after exposure, but if a delay occurs, they should be started at any time before symptoms appear. The recommended immunization regimen depends on the patient's previous vaccination status. Recommendations for postexposure treatment are summarized in Table 2.
Since cell culture vaccines have been routinely used in the US, no postexposure vaccine failures have occurred.4 The rare cases of rabies postexposure treatment failure reported outside the US have been attributed to deviations from the World Health Organization recommended regimens (eg, lack of proper wound toilet, failure to administer RIG).
The ACIP recommends pre-exposure rabies prophylaxis for persons with continuous or frequent risk of exposure to the rabies virus (high-risk groups) as well as for those with infrequent but episodic exposure (Table 3).4 Pre-exposure prophylaxis is particularly advantageous for persons who may not be able to gain quick access to cell culture vaccines or purified RIG after a rabies exposure and for those at risk of unrecognized exposures.4 Vaccination against rabies is not recommended for the general population.
The rabies pre-exposure vaccination schedule recommended by the ACIP is shown in Table 4. Persons at continuous or frequent risk should receive a primary course of vaccination with a cell culture vaccine. Determination of antibody titers following the primary course is not required unless immunosuppression is suspected. Antibody titers should be determined every 6 months for those in the continuous-risk category and every 2 years for those in the
frequent-risk category. The rabies antibody titer is considered adequate if a serum sample completely neutralizes a challenge virus at a 1:5 serum dilution as measured by RFFIT If the serum antibody titer falls below this level, one routine booster dose is required. Postexposure treatment for an exposure to an animal known or suspected to be rabid requires two booster doses, as indicated in Table 2.
A primary course of a cell culture vaccine without serologic testing or booster vaccination is recommended for persons in the infrequent-risk category.4 This category includes travelers to areas of the world in which dog rabies is endemic and immediate access to medical care and appropriate rabies biologics might be limited.
Dog rabies is endemic in many countries in South America, Africa, and Asia and is highly endemic in parts of Brazil, Bolivia, Colombia, Ecuador, El Salvador, Guatemala, India, Mexico, Nepal, Peru, the Philippines, Sri Lanka, Thailand, and Vietnam.46 Travelers whose plans include outdoor activities such as bicycling and camping, those whose professional activities may expose them to the rabies virus, and those who believe they may be unable to obtain immediate access to appropriate medical care should consider preexposure vaccination. Children, who are typically at higher risk for dog bites than adults, may have a higher risk of rabies during stays in areas where dog rabies is endemic and immediate access to medical care is limited.47 Travelers receiving rabies pre-exposure prophylaxis generally do not require serologic testing unless their immune response might be diminished by drug therapy or disease.46
Although the ID formulation of HDCV has been withdrawn, it is important to understand certain issues regarding rabies immunization via the ID route. The ID formulation was developed in response to concerns about the cost of cell culture vaccines. The per-dose cost of the ID formulation was reduced, because each dose contains only
0.1 mL of vaccine as opposed to 1.0 mL of vaccine per dose of an IM cell culture vaccine.
In clinical trials, both the IM formulation of PCECV and the ID and IM formulations of HDCV produced acceptable rabies antibody titers after primary vaccination and booster vaccination.42,43,48-52 Following a review of the results of HDCV ID primary vaccination among 1500 subjects, the ACIP recommended in 1982 that primary vaccination with ID formulations be considered an alternative to IM vaccination for pre-exposure prophylaxis.53
Around this time, the Peace Corps began to vaccinate volunteers with HDCV ID in areas where it was available; acceptable antibody titers were achieved in 567 of the first 570 volunteers vaccinated.54 In 1983, however, a Peace Corps volunteer in Kenya who had been vaccinated with HDCV ID while in Kenya contracted rabies.55 Serologic testing was subsequently performed on volunteers in other Peace Corps cohorts immunized outside the US with HDCV ID, and many volunteers were found to have rabies antibody titers below the acceptable level.55
A subsequent investigation found that the three-- dose HDCV ID regimen given to six groups in the US between 1980 and 1984 produced acceptable antibody titers, which were significantly higher than those in native Kenyan subjects immunized with the same regimen (p<=0.0001), and these titers were, in turn, significantly higher than those in Peace Corps volunteers immunized in Kenya (p<=0.0001).56 Many factors may have been involved in the diminished serologic response to ID vaccination, including the immunosuppressive effects of multiple vaccinations and concomitant administration of the antimalarial chloroquine.53
The duration of response following primary vaccination may be a consideration in selecting an appropriate vaccine for persons in the continuous-- risk or frequent-risk group who may require booster vaccinations) if the rabies antibody titer falls below the acceptable level. The duration of the response to primary vaccination with HDCV ID or HDCV IM,,as measured by acceptable antibody titer by RFFIT, was evaluated in a retrospective study of 875 serum samples analyzed at the Department of Veterinary Diagnosis, Kansas State University, between 1984 and 1989.57 This study included samples from 381 Peace Corps volunteers and 494 non-Peace Corps volunteers collected at various time points after pre-exposure or postexposure vaccination; 834 of the subjects contributing samples had received pre-exposure prophylaxis.
Because many factors not typically present in US populations undergoing pre-exposure vaccination may have influenced antibody titers in the Peace Corps samples,55.56 the duration of antibody response in the non-Peace Corps group is probably more representative of the experience in the US. In this group, the duration of response, calculated by Kaplan-Meier survival estimates, was significantly greater among those receiving HDCV IM (n = 180) than among those immunized with HDCV ID (n = 314) (p-<0.0001).57 At all time points, the percentage of patients having an acceptable antibody titer was higher among those receiving HDCV IM than among those who were immunized with HDCV ID (Figure 3).57
The response to booster vaccination has generally been similar and satisfactory among those receiving primary vaccination by the IM or ID route.42,43,58 In one study, however, the response to booster vaccination was slower to develop among those who had received primary vaccination with an ID formulation rather than an IM formulation.59
|By Admin1 (admin) on Thursday, November 01, 2001 - 9:53 am: Edit Post|
For persons in the continuous-risk or frequent-risk group, the recommended pre-exposure prophylaxis regimen includes repeated serologic testing every 6 months or 2 years, respectively, followed by booster vaccination if a rabies antibody titer falls below the acceptable level.4 The anticipated duration of response may therefore be a consideration in selecting a cost-effective dose for primary vaccination.37 In a recent decision-based cost analysis of the most economical route for pre-exposure prophylaxis, the IM and ID routes of administration were compared. For persons in the continuous-risk group, the cost of primary vaccination using the IM route, as compared with the ID route, was calculate\d to provide a cost savings of more than $1000 over a 30-year period.42 A reduction in the number of booster doses required during this period reduces not only vaccine costs but also the potential risk (and costs) of complications associated with booster vaccination, including the type III hypersensitivity reactions that have been observed after booster doses of HDCV.40,41
SUMMARY AND CONCLUSIONS
Rabies in humans most often results from the bite of an infected animal; other modes of transmission are extremely rare. There is a long incubation period, and once the disease becomes clinically apparent, with signs and symptoms that may include hydrophobia, hyperactivity, and hypersalivation, it is virtually always fatal.
In the US today, human rabies is relatively rare, owing in part to highly successful vaccination and animal control campaigns that have virtually eliminated the disease among dogs. However, as rabies among dogs, the traditional source of rabies in humans, has declined, rabies among wildlife, including raccoons, skunks, bats, and foxes, has risen.11,12,18-25 Rabies among bats has had the greatest impact on humans: Since 1980, rabies virus variants circulating in bats have been identified in 26 of the 42 cases of human rabies reported in the US and in all but three cases of human rabies acquired in the US.10- 12 Greater public awareness of the potential risk of rabies following contact with bats and other wildlife will be an important step in further reducing the incidence of rabies among humans.
Highly effective cell culture vaccines for preexposure and postexposure prophylaxis have been major weapons in the fight against rabies among humans. Although all cell culture rabies vaccines available in the US today are considered equally effective when used correctly,4 duration and magnitude of the antibody response, unit cost of the vaccine, frequency and cost of booster vaccination, and the potential for adverse reactions must be considered in the selection of a vaccine. Booster vaccinations with HDCV have been associated with a risk of type III hypersensitivity reactions,40,41 whereas booster doses of PCECV have not.38 Therefore, PCECV has advantages for persons at high risk of exposure to the rabies virus.
1. Smith JS. New aspects of rabies with emphasis on epidemiology, diagnosis, and prevention of the disease in the United States. Clin Microbiol Rev 1996;9:166-76.
2. Jackson AC. Rabies. In: Nathanson N, Ahmed R, Gonzalez-Scarano F, et at, eds. Viral Pathogenesis. Philadelphia: Lippincott-Raven Publishers; 1997;575-91.
3. Rosner F Rabies in the Talmud. Med Hist 1974;18:198-200.
4. Centers for Disease Control and Prevention. Human rabies prevention-- United States, 1999. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1999;48:RR-1.
S. Plotkin SA. Rabies. Clin Infect Dis 2000;30:4-12.
6. Hattwick MAW. Human rabies. Pub Health Rev 1974;3:229-74.
7 Smith IS, Fishbein DB, Rupprecht CE, Clark K. Unexplained rabies in three immigrants in the United States. A virologic investigation. N Engl [ Med 1991;324:205-11.
8. Warren DA. The clinical picture of rabies in man, Trans R Soc Trop Med Hyg 1976;70:188-95.
9. Jackson AC. Rabies. Can I Neurol Sci 2000;27:278-83.
10. Centers for Disease Control and Prevention. Human rabies- California, Georgia, Minnesota, and Wisconsin, 2000. MMWR Morb Mortal Wkly Rep 2000;49:1111-5.
It. Krebs JW, Rupprecht CE, Childs IFE. Rabies surveillance in the United States during 1999. 1 Am Vet Med Assoc 2000;217:1799-811.
12. Krebs JW, Strine TW, Smith IS, et al. Rabies surveillance in the United States during 1995. J Am Vet Med Assoc 1996;209:2031-44.
13. Jackson AC, Fenton MB. Human rabies ard bat bites [letter]. Lancet 2001;357:1714.
14. Hanlon CA, Childs JE, Nettles VF, National Working Group on Rabies Prevention and Control. Recommendations of a national working group on prevention and control of rabies in the United States. Article Ill: Rabies in wildlife. I Am Vet Med Assoc 1999;215:1612-8.
15. World Health Organization. World survey of rabies No. 34 for the year 1998. Available at www.who.org. Accessed 9/13/2001.
16. Anderson L, Nicholson K, Tauxe R, Winkler W Human rabies in the United States, 1960 to 1979: epidemiology, diagnosis, and prevention. Ann Intern Med 1984;100:728-35.
17 Fishbein DB, Bernard KW. Rabies virus. In: Mandell G, Bennett JE, Dolin R, eds. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 4th ed. New York: Churchill Livingstone; 1995;1527-43.
18. Krebs JW, Holman RC, Hines U, et al. Rabies surveillance in the United States during 1991.1 Am Vet Med Assoc 1992;201:836-48.
19. Krebs JW, Strine TW, Smith IS, Rupprecht C, Childs J. Rabies surveillance in the United States during 1993. 1 Am Vet Med Assoc 1994;205:1695-709. 20. Uhaa 11, Mandel EJ, Whiteway R, Fishbein DB. Rabies surveillance in the
United States during 1990. 1 Am Vet Med Assoc 1992;200:920-9.
21. Krebs JW, Strine TW, Childs JE. Rabies surveillance in the United States during 1992. 1 Am Vet Med Assoc 1993;203:18-31.
22. Krebs JW, Strine TW, Smith IS, et al. Rabies surveillance in the United States during 1994. J Am Vet Med Assoc 1995;207:562-75.
23. Krebs [W, Smith 15, Rupprecht CE, Childs JE. Rabies surveillance in the United States during 1996. 1 Am Vet Med Assoc 1997;211:525-39.
24. Krebs IW, Smith IS, Rupprecht CE, Childs JE. Rabies surveillance in the United States during 1997 J Am Vet Med Assoc 1998; 213:713-28. 25. Krebs JW, Smith IS, Rupprecht CE, Childs JE. Rabies surveillance in the
United States during 1998. J Am Vet Med Assoc 1999;215:1786-98. 26. Fishbein DB, Dobbins IG, Bryson JH, et al. Rabies surveillance, United States, 1987 MMWR Morb Mortal Wkly Rep 1988;37:1-7
27. Rupprecht CE, Smith IS, Fekadu M, et al. The ascension of wildlife rabies: a cause for public health concern or intervention? Emerg Infect Dis 1995;1:107-14.
28. Centers for Disease Control and Prevention. Human rabies- Alabama, Tennessee, and Texas, 1994. MMWR Morb Mortal Wkly Rep 1995;44:269-72.
29. Centers for Disease Control and Prevention. Human rabies- Texas and New Jersey, 1997 MMWR Morb Mortal Wkly Rep 1998;47:1-5.
30. Centers for Disease Control and Prevention. Human rabies-West Virginia, 1994. MMWR Morb Mortal Wkly Rep 1995;44:86-7, 93.
31. Centers for Disease Control and Prevention. Human rabies- California, 1995. MMWR Morb Mortal Wkly Rep 1996;45:353-6.
32. Pape WI, Fitzsimmons TD, Hoffman RE Risk for rabies transmission from encounters with bats, Colorado, 1977-1996. Emerg Infect Dis 1999;5:433-7. 33. Dietzschold B, Hooper D. Human diploid cell culture rabies vaccine
(HDCV) and purified chick embryo cell culture rabies vaccine (PCECV) both confer protective immunity against infection with the silver-haired bat rabies virus strain (SHBRV). Vaccine 1998; 16:1656- 9.
34. Charlton KM. The pathogenesis of rabies. In: Campbell IB, Charlton KM, eds. Rabies. Boston: Kluwer Academic Publishers; 1988;102-50.
35. Noah D, Drenzek C, Smith IS, et al. Epidemiology of human rabies in the United States, 1980 to 1996. Ann Intern Med 1998;128:922-30.
36. Geison GL. The Private Science of Louis Pasteur. Princeton, NJ: Princeton University Press; 1995.
37 Murray KO, Arguin PM. Decision-based evaluation of recommendations for preexposure rabies vaccination. I Am Vet Med Assoc 2000;216:188-91. 38. RabAvert'. Physicians Desk Reference. Montvale, NJ: Medical Economics Company; 2001; 1100-3.
39. Centers for Disease Control and Prevention. Systemic allergic reactions following immunization with human diploid cell rabies vaccine. MMWR Morb Mortal Wkly Rep 1984;33:185-7.
40. [Imovax Rabies'. Physicians' Desk Reference. Montvale, NJ: Medical Economics Company; 2001;776-8.
41. Imovax(R) Rabies' LD. [package insert]. Swiftwater, PA: Aventis Pasteur, Inc, 2001. Available at http:// www.us.aventispasteur.com/PROD UCT/ PDFFILES/Imovax(R)%201D.pdf Accessed 8/22/01.
42. Dreesen DW, Fishbein DB, Kemp DT, Brown 1. Two-year comparative trial on the immunogenicity and adverse effects of purified chick embryo cell rabies vaccine for pre-exposure immunization. Vaccine 1989;7:397-400.
43. Briggs DJ, Dreesen DW, Nicolay U, et al. Purified chick embryo cell cut ture rabies vaccine: interchangeability with human diploid cell culture rabies vaccine and comparison of one versus two-dose post-exposure booster regimen for previously immunized persons. Vaccine
44. Swanson MC, Rosanoff E, Gurwith M, et al. IgE and IgG antibodies to beta-propiolactone and human serum albumin associated with urticarial reactions to rabies vaccine. J Infect Dis 1987;155:909-13.
45. Fishbein D, Dreesen D, Holmes D, et al. Human diploid cell rabies vaccine purified by zonal centrifugation: a controlled study of antibody response and side effects following primary and booster pre-exposure immunizations. Vaccine 1989;7:437-42.
46. Centers for Disease Control and Prevention. Rabies: Health Information for International Travel, 2001=2002. Available at http:// www.cdc.gov/travel/-disea ses/rabies.htm. Accessed 8/22/01.
47 LeGuerrier P, Pilon PA, Deshaies D, Allard R. Pre-exposure rabies prophylaxis for the international traveller: a decision analysis. Vaccine 1996; 14:167-76.
48. Bernard K, Mallonee J, Wright J, et al. Preexposure immunization with intradermal human diploid cell rabies vaccine. Risks and benefits of primary and booster vaccination. JAMA 1987;257:1059-63.
49. Dreesen D, Brown W, Kemp D, et al. Pre-exposure rabies prophylaxis: efficacy of a new packaging and delivery system for intradermal administration of human diploid cell vaccine. Vaccine 1984;2:185-8.
50. Nicholson KG, Farrow PR, Bijok U, Barth R. Pre-exposure studies with purified chick embryo cell culture rabies vaccine and human diploid cell vaccine: serological and clinical responses in man. Vaccine 1987;5208-10.
51. Rodrigues F, Mandke V, Roumiantzeff M, et al\. Persistence of rabies antibody 5 years after pre-exposure prophylaxis with human diploid cell antirabies vaccine and antibody response to a single booster dose. Epidemiol Infect 1987;99:91-5.
52. Turner G, Nicholson K, Tyrrell D, Aoki F Evaluation of a human diploid cell strain rabies vaccine: final report of a three year study of pre-exposure immunization. I Hyg (Lond) 1982;89:101-10.
53. Centers for Disease Control and Prevention. Recommendation of the Immunization Practices Advisory Committee supplementary statement on pre-exposure rabies prophylaxis by the intradermal route, MMWR Morb Mortal Wkly Rep 1982;31:279-80, 285.
54. Rosa F Pre-exposure prophylaxis in Peace Corps volunteers with intradermal human diploid cell rabies vaccine. I Trop Med Hyg 1983;86:81-4.
55. Centers for Disease Control and Prevention. Field evaluations of preexposure use of human diploid cell rabies vaccine. MMWR Morb Mortal Wkly Rep 1983;32:601-3.
56. Bernard K, Fishbein D, Miller K, et al. Pre-exposure rabies immunization with human diploid cell vaccine: decreased antibody responses in persons immunized in developing countries. Am I Trop Med Hyg 1985;34:633-47
57. Briggs D, Schwenke JR. Longevity of rabies antibody titre in recipients of human diploid cell rabies vaccine. Vaccine 1992; 10:125- 9.
58. Burridge M, Summer J, Baer G. Intradermal immunization with human diploid cell rabies vaccine: serological and clinical responses of immunized persons to intradermal booster vaccination. Am I Public Health 1984;74:503-5.
59. Jaijaroensup W, Limusanno S, Khawplod P, et al. Immunogenicity of rabies postexposure booster injections in subjects who had previously received intradermal preexposure vaccination. I Travel Med 1999;6:234-50.
Alan C. Jackson, MD, FRCPC, Editor
Professor of Medicine (Neurology)
Associate Professor of Microbiology and Immunology
Kingston, Ontario, Canada
Copyright Advanstar Communications, Inc. Oct 2001
|By kong on Tuesday, February 18, 2003 - 1:08 am: Edit Post|
I want to ask for the safety and sterility of PCEC rabies vaccine that manufactured in India (Rabipur)
please let me know.
I hope to hear from you soon.
Thankyou for your kindness.
kong, thailand. (18/2/2006)
E-mail : firstname.lastname@example.org
|By dr k kant bhoi on Friday, July 18, 2003 - 11:28 am: Edit Post|
what antemortem test available in india [nicd delhi/niv pune] for