- Email: [email protected]
Intradermal Immunization for rabies Prophylaxis: Issues to be considered in India and other developing countries
Vaccine 21 (2003) 3095–3096
Letter to the Editor Intradermal Immunization for rabies Prophylaxis: Issues to be considered in India and other developing countries Dear Sir, This is with reference to the recently published article by Mary J. Warrell (Vaccine 2003;21:706–709) on the current issues related to intradermal (ID) administration of modern cell culture vaccines for post-exposure rabies prophylaxis. At the outset I would like to compliment Dr. Marry Warrell for comprehensively reviewing the problems facing clinicians in providing affordable post-exposure rabies treatment in developing countries. She has very rightly brought out the concern of the very low usage of RIG in category III exposures, in spite of the WHO recommendations. I agree with her findings that the immunogenicity of the 8-site Oxford intradermal schedule is better than the 2-site Thai Red Cross (TRC) schedule and we have also reported this observations [1]. However, in the setting of a busy anti-rabies clinic, the practically of administering the 8-site intradermal schedule routinely is tedious and difficult, particularly for women, and there is ample data on the good rabies virus neutralizing antibody titers developed following the TRC schedule with modern cell culture anti-rabies vaccines (CCV). I would differ however, with Dr. Warrell on two issues: 1. Dr. Warrell has commented that for the TRC regimen, there are two intradermal doses recommended, i.e. 0.1 or 0.2 ml. This statement needs to be examined in the context of current information. There is by now adequate clinical data for PCECV which demonstrates that 0.1 ml per ID site from a 1 ml reconstituted vaccine vial provides good immunogenicity when used as per the 2-site TRC regimen [2–5]. In fact, it has been clearly stated in the WHO Consultation Report of 2000 (WHO/CDS/CBR/APW-2000.5) which constitutes the minutes of the WHO Workshop on Intradermal applications of rabies vaccines, Bangkok, Thailand, 5–6 June 2000, that “the use of PCECV 0.1 ml per ID, site in a 2-2-2-0-1-1 regimen may be considered for use by national health authorities”. This regimen has been extensively used in the Phetchabum province in Thailand including 148 proven rabid dog bites and not a single case of vaccine failure has been observed [6]. 2. I do not quite understand in what context Dr. Warrell has stated that “if PVRV is the only vaccine available, should patients be denied the best logical treatment while awaiting the result of clinical trials which may take years
to implement”. I do not believe she could be inferring that PVRV is better than other cell culture rabies vaccines since there is absolutely no evidence to claim superiority. From perusing the previous few sentences, I wonder if she recommended that an intradermal dose of 0.05 ml of PVRV be given, which in practice has many pitfalls, or that a 4-site, unapproved regimen be adopted for general use, before the results of clinical trails are available and is approved by WHO and national health authorities. For us in India the primary concern is rapid phasing out of poorly immuongenic and highly reactogenic sample vaccine and replacing this with modern cell culture vaccines. As conventional five dose intramuscular (IM) regimens will not be cost effective for routine use (nearly 2 million post-exposure treatments annually) ID regimens should be approved and introduced as early as possible for which efforts are being made not only by government institutions but also by NGOs like Association for Prevention and Control of Rabies in India (APCRI). At this juncture, it is necessary that we follow some valid and approved schedules of ID administration and the currently approved WHO regimens should be adhered to. I have no objection to the statement that 8-site regimen is superior to 2-site regimen, but considering the decade old experience and the vast data on immunogenicity and efficacy generated with the 2-site regimen in countries like Thailand and Philippines, I would opt for 2-site regimen to be implemented routinely and 8-site regimen to be used only in special circumstances. As WHO has already recommended 0.1 ml ID dose with PCEC vaccine, I would suggest a uniform dosage schedule for both PVRV and PCEC vaccines that are currently approved by WHO.
References [1] Madhusudana SN, PremAnnad N, Shamsundar R. Evaluation of two intradermal vaccination regimens using purified chick embryo cell vaccine for post-exposure prophylaxis of rabies. Nat Med J India 2001;14:145–7. [2] Briggs DJ, Banzhoff A, Nicolay U, et al. Antibody responses of patients after post-exposure rabies vaccination with small intradermal doses of purified chick embryo cell vaccine or purified vero cell rabies vaccine. Bull WHO 2000;78:693–8. [3] Suntharasamai P, Chaiprasithikul C, Wasi W, et al. A simplified and economical intradermal regimen of purified chick embryo cell rabies vaccine for post-exposure prophylaxis. Vaccine 1994;12:508–12. [4] Wasi C, Chaiprasithikul P, Auewarakul P, Thongcharoen P. Kinetics of protective antibodies after small doses of purified chick embryo
0264-410X/03/$ – see front matter © 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0264-410X(03)00263-9
3096
Letter to the Editor / Vaccine 21 (2003) 3095–3096
cell rabies vaccinated intradermally for mld rabies post-exposure treatment. J Infect Dis Antimicrob Agent 1994;11:5–8. [5] Madhusudana SN, PremAnand N. Response to purified chick embryo cell vaccine administered intradermally for post-exposure prophylaxis. Nat Med J India 1997;10:115–7. [6] Kamoltham T. Experience with tissue culture rabies vaccines used intradermally in 7227 rabies exposed subjects at Phetchabun province, Thailand. In: Proceedings of the Presentation at the 10 International Congress on Infectious Diseases. Singapore; 11–14 March 2002.
S.N. Madhusudana Department of Neurovirology, National Institute of Mental Health and Neurosciences, Editor Association for Prevention and Control of Rabies in India (APCRI), P.O. Box 2900 Hosur Road, Bangalore 560029, India Tel.: +91-80-5995128; fax: +91-80-6564830. E-mail address: [email protected] (S.N. Madhusudana)
Letter to the Editor Intradermal Immunization for rabies Prophylaxis: Issues to be considered in India and other developing countries Dear Sir, This is with reference to the recently published article by Mary J. Warrell (Vaccine 2003;21:706–709) on the current issues related to intradermal (ID) administration of modern cell culture vaccines for post-exposure rabies prophylaxis. At the outset I would like to compliment Dr. Marry Warrell for comprehensively reviewing the problems facing clinicians in providing affordable post-exposure rabies treatment in developing countries. She has very rightly brought out the concern of the very low usage of RIG in category III exposures, in spite of the WHO recommendations. I agree with her findings that the immunogenicity of the 8-site Oxford intradermal schedule is better than the 2-site Thai Red Cross (TRC) schedule and we have also reported this observations [1]. However, in the setting of a busy anti-rabies clinic, the practically of administering the 8-site intradermal schedule routinely is tedious and difficult, particularly for women, and there is ample data on the good rabies virus neutralizing antibody titers developed following the TRC schedule with modern cell culture anti-rabies vaccines (CCV). I would differ however, with Dr. Warrell on two issues: 1. Dr. Warrell has commented that for the TRC regimen, there are two intradermal doses recommended, i.e. 0.1 or 0.2 ml. This statement needs to be examined in the context of current information. There is by now adequate clinical data for PCECV which demonstrates that 0.1 ml per ID site from a 1 ml reconstituted vaccine vial provides good immunogenicity when used as per the 2-site TRC regimen [2–5]. In fact, it has been clearly stated in the WHO Consultation Report of 2000 (WHO/CDS/CBR/APW-2000.5) which constitutes the minutes of the WHO Workshop on Intradermal applications of rabies vaccines, Bangkok, Thailand, 5–6 June 2000, that “the use of PCECV 0.1 ml per ID, site in a 2-2-2-0-1-1 regimen may be considered for use by national health authorities”. This regimen has been extensively used in the Phetchabum province in Thailand including 148 proven rabid dog bites and not a single case of vaccine failure has been observed [6]. 2. I do not quite understand in what context Dr. Warrell has stated that “if PVRV is the only vaccine available, should patients be denied the best logical treatment while awaiting the result of clinical trials which may take years
to implement”. I do not believe she could be inferring that PVRV is better than other cell culture rabies vaccines since there is absolutely no evidence to claim superiority. From perusing the previous few sentences, I wonder if she recommended that an intradermal dose of 0.05 ml of PVRV be given, which in practice has many pitfalls, or that a 4-site, unapproved regimen be adopted for general use, before the results of clinical trails are available and is approved by WHO and national health authorities. For us in India the primary concern is rapid phasing out of poorly immuongenic and highly reactogenic sample vaccine and replacing this with modern cell culture vaccines. As conventional five dose intramuscular (IM) regimens will not be cost effective for routine use (nearly 2 million post-exposure treatments annually) ID regimens should be approved and introduced as early as possible for which efforts are being made not only by government institutions but also by NGOs like Association for Prevention and Control of Rabies in India (APCRI). At this juncture, it is necessary that we follow some valid and approved schedules of ID administration and the currently approved WHO regimens should be adhered to. I have no objection to the statement that 8-site regimen is superior to 2-site regimen, but considering the decade old experience and the vast data on immunogenicity and efficacy generated with the 2-site regimen in countries like Thailand and Philippines, I would opt for 2-site regimen to be implemented routinely and 8-site regimen to be used only in special circumstances. As WHO has already recommended 0.1 ml ID dose with PCEC vaccine, I would suggest a uniform dosage schedule for both PVRV and PCEC vaccines that are currently approved by WHO.
References [1] Madhusudana SN, PremAnnad N, Shamsundar R. Evaluation of two intradermal vaccination regimens using purified chick embryo cell vaccine for post-exposure prophylaxis of rabies. Nat Med J India 2001;14:145–7. [2] Briggs DJ, Banzhoff A, Nicolay U, et al. Antibody responses of patients after post-exposure rabies vaccination with small intradermal doses of purified chick embryo cell vaccine or purified vero cell rabies vaccine. Bull WHO 2000;78:693–8. [3] Suntharasamai P, Chaiprasithikul C, Wasi W, et al. A simplified and economical intradermal regimen of purified chick embryo cell rabies vaccine for post-exposure prophylaxis. Vaccine 1994;12:508–12. [4] Wasi C, Chaiprasithikul P, Auewarakul P, Thongcharoen P. Kinetics of protective antibodies after small doses of purified chick embryo
0264-410X/03/$ – see front matter © 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0264-410X(03)00263-9
3096
Letter to the Editor / Vaccine 21 (2003) 3095–3096
cell rabies vaccinated intradermally for mld rabies post-exposure treatment. J Infect Dis Antimicrob Agent 1994;11:5–8. [5] Madhusudana SN, PremAnand N. Response to purified chick embryo cell vaccine administered intradermally for post-exposure prophylaxis. Nat Med J India 1997;10:115–7. [6] Kamoltham T. Experience with tissue culture rabies vaccines used intradermally in 7227 rabies exposed subjects at Phetchabun province, Thailand. In: Proceedings of the Presentation at the 10 International Congress on Infectious Diseases. Singapore; 11–14 March 2002.
S.N. Madhusudana Department of Neurovirology, National Institute of Mental Health and Neurosciences, Editor Association for Prevention and Control of Rabies in India (APCRI), P.O. Box 2900 Hosur Road, Bangalore 560029, India Tel.: +91-80-5995128; fax: +91-80-6564830. E-mail address: [email protected] (S.N. Madhusudana)