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Postexposure Rabies Prophylaxis in a Patient With Lymphoma
To the Editor: Neither the US Advisory Committee on Immunization Practices (ACIP)1 nor the World Health Organization2 recommendations for rabies postexposure prophylaxis contain specific guidelines for treating immunosuppressed patients. We present the first case report of a patient with lymphoma who was bitten by a rabid animal.
Report of a Case
Three weeks after being diagnosed with stage IV lymphocytic B-cell lymphoma, a 55-year-old man was attacked by a jackal. The patient experienced multiple bites on his right index finger, hand, forearm, and elbow and abdomen. At that time, he had not yet begun chemotherapy. Treatment in the emergency department included cleansing of the wounds and infiltration of the lacerations and abrasions with human rabies immunoglobulin (HRIG) 20 IU/kg (Berirab P; Centeon Pharma GmbH, Germany), and intramuscular injection of rabies vaccine (Rabipur; Chiron Behring GmbH, Germany). Rabies was later diagnosed in the jackal by using fluorescent brain microscopic examination. The patient received active rabies vaccine on the 3rd, 7th, 14th and 28th days after the attack, and he was advised to refrain from chemotherapy until the end of the vaccination schedule.
Two days after the fifth and final dose, the patient's antirabies antibody titer was low, 0.2 IU/mL according to the rapid fluorescent focus inhibition test (protective level, 0.5 IU/mL). Because of his immunosuppressed state, we decided to administer a second course of rabies vaccine using double-dose vaccine and single intramuscular HRIG. Two days before the fourth double dose, the patient's antirabies antibody titer rose to 2.73 IU/mL. The patient was then advised to start chemotherapy immediately after the fifth double dose and to have his antibody titer measured every 3 months.
Eight weeks after the attack the patient received chemotherapy including fludarabine phosphate, mitoxantrone hydrochloride, dexamethasone, and sulfamethoxazole. He was found to have an acceptable antibody titer of 1.93 IU/mL 4 months after beginning chemotherapy, but this fell to 0.15 IU/mL 3 months later. The level remained nonprotective after 3 standard rabies vaccine doses given during 7 days, but increased to 3.84 IU/mL after a series of 3 double doses. Nearly 2 years later, the patient has no signs of rabies and his lymphoma is in remission.
Comment
The ACIP guidelines recommend postponing preexposure vaccination, if possible, in immunosuppressed patients and refraining from immunosuppressive agents, if possible, during postexposure rabies prophylaxis.1
Turner3 found that the ability to mount delayed-type hypersensitivity reactions in mice was restored 3 days after cyclophosphamide treatment, while antibody production to Escherichia coli antigen and rabies vaccine was restored only if the immunization of cyclophosphamide-treated mice was delayed for 7 to 10 days. Thisyakorn et al4 found significantly lower antirabies antibody levels in HIV (human immunodeficiency virus)-infected children compared with healthy subjects. Briggs et al5 found very low postexposure antirabies antibody titers in symptomatic HIV-infected patients in India, and protective antibody titer was achieved only on day 37. They concluded that HRIG should be given to immunocompromised patients and that symptomatic patients usually do not respond to rabies vaccine. These authors did not recommend doubling the vaccine dose because of a theoretical risk of increasing the viral load. Doubling the rabies vaccine dose was performed successfully in healthy Israeli soldiers who were exposed to bites of rabid animals and were given a higher HRIG dose than recommended.6
Our patient responded to a second double-dose series of vaccine, but his antibody titer decreased rapidly after chemotherapy. We suggest that the postexposure treatment schedule in such cases should include doubling the dose, close monitoring of antirabies antibody titers for at least 1 year, and postponing chemotherapy, whenever possible, until a protective antibody titer is achieved.
Emile Hay, MD;
Hashmonai Derazon, MD;
Natalia Bukish, MD
Department of Emergency Medicine
Shimon Scharf, MD
Hospital Director General
Barzilai Medical Center
Ashkelon, Israel
Shmuel Rishpon, MD,MPH
Haifa District Health Office
Haifa, Israel
1. Human rabies prevention—United States, 1999: recommedations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 1999;48:1-21.
PUBMED
2. WHO Recommendations on Rabies Post-Exposure Treatment and the Correct Technique of Intradermal Immunization Against Rabies. Geneva, Switzerland: World Health Organization; 1997. WHO publication WHO/EMC/ZOO.96.6.
3. Turner GS. Recovery of immune responsiveness to rabies vaccine after treatment of mice with cyclophosphamide. Arch Virol. 1979;61:321-325.
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4. Thisyakorn U, Pancharoen C, Ruxrungtham K, et al. Safety and immunogenicity of preexposure rabies vaccination in children infected with human immunodeficiency virus type 1. Clin Infect Dis. 2000;30:218-220.
PUBMED
5. Briggs DJ, Deshpande A, Banzhoff A, et al. Rabies vaccination in HIV-infected persons. In: Program and abstracts of the 2nd European Rabies Symposium; June 15-17, 1999; Sopron, Hungary.
6. Haviv J, Rishpon S, Gdalevich M, et al. Successful postexposure rabies prophylaxis after erroneous starting treatment. Prev Med. 1999;29:28-31.
PUBMED
Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.
JAMA. 2001;285:166-167.
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