Heterogeneity of Rabies Vaccination Recommendations across Asia
Abstract
:Highlights
- The recommended practices for rabies pre- and post-exposure prophylaxis vary widely from country to country in Asia.
- Overall, the WHO recommendations for wound management are consistent in national guidelines. The post-exposure prophylaxis (PEP) 5-dose Essen and 4-dose Zagreb intramuscular (IM) regimens are uniformly recommended.
- The value of intradermal (ID) administration in reducing costs is not considered in several country guidelines.
- In the majority of the national recommendations, concurrent administration of rabies immunoglobulin (RIG) in category III exposures is recommended; however, there are concerns regarding availability and cost.
- Booster recommendations are not included in all guidelines, with limited clarity on booster requirement across the spectrum of risk of rabies exposure.
- Limited recommendations are available for special populations including pregnant women, aged population, and immunocompromised patients.
1. Introduction
2. Methods
3. Findings
3.1. Overall Findings
3.2. Post-Exposure Prophylaxis (PEP)
3.2.1. Wound Care
3.2.2. RIG
3.2.3. PEP Vaccination Schedules
- The 5-dose Essen, 4-dose Zagreb, or both schedules were the regimens of choice for IM administration. The Essen is used in Bhutan, Cambodia, China, India, Philippines, Sri Lanka, Taiwan, Thailand, Vietnam; and Zagreb in Bangladesh, Cambodia, China, Indonesia, Pakistan, Philippines, Sri Lanka (Table 2). The 4-dose shortened Essen was the regimen of choice in the Malaysian recommendations, and was also recommended in the guidelines of Philippines (Table 2 and Table 3).
- We found recommendation for ID administration in 9 of the 13 retrieved national guidelines; the guidelines of China, Indonesia, Malaysia, and Taiwan do not include such recommendation (Table 2 and Table 3). Also in the official documents retrieved for Japan and Lao PDR we did not find ID recommendations (Table 2 and Table 3). All guidelines with ID recommendation suggested the updated Thai Red Cross regimen (Table 2 and Table 3).
- The Japanese guidelines recommend only subcutaneous (SC) administration as shown in Table 2.
3.2.4. PEP Vaccination for Re-Exposed Individuals
3.3. Pre-Exposure Prophylaxis (PrEP)
3.3.1. PrEP Vaccination Schedules
3.3.2. Booster after PrEP Vaccination
3.4. Vaccination Recommendations for Special Populations
- Pregnant and lactating women: The guidelines of Bangladesh, Bhutan, Cambodia, India, Pakistan, Philippines, and Sri Lanka state that there is no contraindication for vaccination in this population. The Chinese guidelines do not directly state whether PEP should be given or not, however they make reference to studies demonstrating that rabies vaccines are safe for pregnant women and for the fetus.
- Aged population and individuals with comorbidities: the same as above in the guidelines of Bangladesh, India, Pakistan, Philippines, and Sri Lanka.
- Immunocompromised population: full PEP and IM route is recommended in the guidelines of Bangladesh, Bhutan, India, Malaysia, Philippines, and Sri Lanka. There is no special reference to this population in the guidelines of Cambodia and Pakistan. Chinese guidelines indicate that passive immunization can be administered in patients with immunodeficiency disorder and that the antibody response should be closely monitored.
- Individuals on treatment for malaria taking chloroquine: ID is contraindicated and IM is recommended in the guidelines of Bangladesh, Cambodia, India, Malaysia, Pakistan, Philippines, and Sri Lanka.
- Other populations: Philippine’s guidelines also note that IM is contraindicated for individuals with hematologic conditions, for whom the ID route should be chosen and that ID is contraindicated for individuals with chronic liver disease.
4. Discussion
4.1. Characteristics of Human Rabies Burden
4.2. Rabies: An Unjustified Disease Burden
4.3. Rabies Vaccination Schedules Across Asia: Current Situation
PEP Recommendations
4.4. PrEP Recommendations
4.5. Country-Specific Information for Countries Whose National Guidelines Were Not Retrieved
4.6. Future Perspective
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
Ab | antibody |
APCRI | Association for Prevention and Control of Rabies in India |
CCEEV | cell culture vaccine and embryonated egg-based vaccines |
CCV | cell culture vaccine |
ERIG | equine immunoglobulin |
FAO | Food and Agriculture Organization |
GARC | Global Alliance for Rabies Control |
HDCV | human diploid cells vaccine |
HIV | human immunodeficiency virus |
HRIG | human immunoglobulin |
IAP | Indian Academy of Pediatrics |
ID | intradermal |
IM | intramuscular |
NTD | Neglected Tropical Diseases |
OIE | World Organization for Animal Health |
PAHO | Pan American Health Organization |
PCECV | purified chick embryo cell vaccine |
PDEV | purified duck embryo vaccine |
PEP | post-exposure prophylaxis |
PHKCV | primary hamster kidney cell vaccine |
PrEP | pre-exposure prophylaxis |
PVRV | purified Vero rabies vaccine |
RIG | rabies immunoglobulin |
RVNA | rabies virus neutralizing antibodies |
SAGE | Strategic Advisory Group of Experts |
SC | subcutaneous |
SDG | Sustainable Development Goals |
SEARS | South-East Asia Rabies Strategy |
UN | United Nations |
WHO | World Health Organization |
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Categories of Exposure to Suspected or Confirmed Rabid Animal and Actions Required | |
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Category I |
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Action required: not regarded as exposures, no post-exposure prophylaxis is required | |
Category II |
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Action required: thorough local wound care and vaccine injection as soon as possible | |
Category III |
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Action required: thorough local wound care and administration of vaccine and RIG as soon as possible | |
Passive Immunization: Rabies Immunoglobulin (RIG) | |
Target population |
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Type, dose |
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Time and site |
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Active Immunization: Vaccines | |
Types | Cell culture vaccine (CCV) and embryonated egg-based vaccines (CCEEVs): |
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and | |
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Potency | ≥2.5 IU per single IM |
Route of administration, dose, vaccine type, and injection sites |
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Sites: | |
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Sites: | |
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Pre-Exposure Prophylaxis | |
Indication |
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IM vaccination regimen | 3 doses, one IM dose on each of days 0, 7, and 21 or 28 |
ID vaccination regimen | 3 doses, one ID injection of 0.1 mL on each of days 0, 7, and 21 or 28 * |
Booster injections | Only for those working under continuous or frequent risk of exposure †, if rabies-virus neutralizing antibody titers is <0.5 IU/mL |
Post-Exposure Prophylaxis | |
Indication |
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Wound care |
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IM vaccination regimen § | 5-dose, Essen regimen (1-1-1-1-1): |
one dose on each of days 0, 3, 7, 14, and 28 | |
4-dose, Zagreb regimen (2-0-1-0-1 or 2-1-1): | |
2 doses on day 0 (one in each of the two deltoid or thigh sites) followed by one dose on each of days 7 and 21 | |
4-dose shortened Essen regimen (1-1-1-1-0) for fully immunocompetent, exposed people who received wound care + high quality RIG + WHO prequalified rabies vaccine: | |
One dose on each of days 0, 3, 7, and 14 | |
For immunocompromised individuals including patients with HIV/AIDS: | |
5-dose CCEEV regimen + wound care + local infiltration with human RIG. Evaluation of the rabies-virus neutralizing antibody 2–4 weeks after vaccination and administration of an additional vaccine dose if needed. | |
ID vaccination regimen § | The updated Thai Red Cross regimen (2-2-2-0-2): |
Injections of 0.1 mL at two sites (deltoid and thigh) on each of days 0, 3, 7, and 28 | |
Short Post-Exposure Prophylaxis for Previously Vaccinated Individuals | |
Exposed or re-exposed individuals, or individuals with rabies-virus neutralizing antibody titers of ≥0.5 IU/mL: | |
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Individuals exposed or re-exposed three months after complete vaccination: | |
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Individuals with category III re- exposure who were vaccinated with a vaccine of unproven potency, or have received an incomplete course of vaccination: | |
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Country | Document Title | Published by, (Year) | Available Vaccine Types (Route) | PEP Vaccination Schedule | PrEP Vaccination Schedule |
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Bangladesh | National Guideline for Rabies Prophylaxis and Intra-dermal Application of Cell Culture Rabies Vaccines [23] | Disease Control Unit, Ministry of Health & Family Welfare (2010) | PVRV (IM, ID) PCECV (IM, ID) ID administration is recommended as cost-effective and the technique is thoroughly described (not indicated for immunocompromised individuals) | IM: 4-dose Zagreb (Essen schedule described but not favored by the government) | IM: 3 doses, one injection on each of days 0, 7, and 21 or 28 |
ID: Updated Thai Red Cross | ID: 3 doses, one injection on each of days 0, 7, and 21 or 28 | ||||
Re-exposed previously vaccinated: 2 doses, one injection (IM or ID) on each of days 0 and 3, if re-exposure was ≤5 years after full PEP + wound washing (RIG not necessary) | Booster: 1 dose when titers <0.5 IU/mL, for individuals working under risk for rabies exposure, monitoring Ab titers every 6 months | ||||
Bhutan | National Guideline for Management of Rabies [24] | Ministry of Health, Department of Public Health Zoonotic Disease Program (2014) | HDCV (IM) PVRV (IM, ID) | IM: 5-dose Essen | IM: 3 doses, one injection on each of days 0, 7, and 21 or 28 |
ID: Updated Thai Red Cross | ID: 3 doses, one injection on each of days 0, 7, and 21 or 28 | ||||
Re-exposed previously vaccinated: 2 doses (IM or ID), each on days 0 and 3, for those who have documented previous full vaccination. | Booster: 1 site ID at 1 year and every 3 years to lab staff, veterinarians, animal handlers, dog catchers, wildlife workers. Regular (exact timing not specified) monitoring of Ab titers and administration of a booster dose when titers <0.5 IU/mL. | ||||
Cambodia | Rabies Vaccine Procedure SOP-OPD-02-004 [25] | National Institute of Public Health, National Public Health Laboratory (2012) | PDEV (IM) PCECV (IM, ID) HDCV (IM) PVRV (IM, ID) | IM: 5-dose Essen 4-dose Zagreb | IM: 3 doses, one injection on each of days 0, 7, 21–28 |
ID: The updated Thai Red Cross 8-site Oxford (8-0-4-0-1-1 injection sites on days 0, 7, 28 and 90) | ID: 3 doses, one injection on each of days 0, 7, 21–28 | ||||
Re-exposed previously vaccinated: 2 doses, one injection on each of days 0 and 3, in individuals who had receive at least 3 doses of any PEP regimen | |||||
China | Technical Guidelines for Human Rabies Control and Prevention [26] | Chinese Center for Disease Control and Prevention (2016) | PVRV, (IM) HDCV, (IM) PHKCV, (IM) PCECV, (IM) | IM: 5-dose Essen 4-dose Zagreb | IM: 3 doses, one injection on each of days 0, 7, and 21 or 28 |
Re-exposed previously vaccinated: 2 injections each on days 0 and 3 if >3 months have passed from previous full vaccination, if <3 months have passed, booster may be deferred if animal is healthy, vaccinated and accessible for observation | Booster: 1 booster dose when titers <0.5 IU/mL, for individuals working under risk for rabies exposure (monitoring every 6 months for lab workers and every 24 months for veterinarians/animal health officers) | ||||
Hong Kong | Web page: Rabies [37] | Center for Health Protection, Department of Health (2017) | (not specified) | Thorough wound cleansing Vaccination if necessary | Travelers to endemic areas |
Web page: Vaccine and Prophylaxis—Rabies Vaccination [39] | Travel Health Service, Department of Health (2012) | (not specified) | (not specified) | For Travelers to endemic areas, one month before the trip: 3 doses, one injection on each of days 0, 7, and 21 or 28 (Route is not specified) | |
Scientific Committee on Emerging and Zoonotic Diseases — Prevention and Control of Rabies [38] | Center for Health Protection (2005) | (not specified) | (not specified) | (not specified) | |
India | National Guidelines on Rabies Prophylaxis [27] | National Center for Disease Control (2015) | PCECV (IM, ID) PVRV (IM, ID) HDCV (IM) PDEV (IM) | IM: 5-dose Essen | IM: 3 doses, one injection on each of days 0, 7, and 21 or 28 |
ID: Updated Thai Red Cross | Booster: 1 booster dose when Ab titers <0.5 IU/mL, for individuals working under risk for rabies exposure (monitoring every 6 months for the first 2 years and every 24 months thereafter) | ||||
Re-exposed previously vaccinated: 2 doses (IM or ID), each on days 0 and 3, for those who have received full vaccination and re-exposed | |||||
Indian Academy of Pediatrics (IAP) Recommended Immunization for Children Aged 0 through 18 years—India, 2016 and Updates on Immunization [28] | Indian Pediatrics (2016) | HDCV (IM) PCECV (IM) PDEV (IM) PVRV (IM) ID not in individual practice | IM: 5 doses, one dose on each day 0, 3, 7, 14, and 30, and for individuals with severe debility or immunosuppressed, and optional 6th dose on day 90 | IM: 3 doses, one injection on each of days 0, 7, 21, or 28 (day 28 is preferred) | |
Re-exposed previously vaccinated: 2 doses for those who have received full vaccination and re-exposed | |||||
Indonesia | National Guidelines for Rabies Vaccination [29] | Center for Disease Control, Ministry of Health (2011) | PVRV (IM) PCECV (IM) | IM: 4-dose Zagreb | IM: 3 doses, one injection on each of days 0, 7, 21, or 28 |
Re-exposed previously vaccinated: 1 dose if re-exposure occurred 3–12 months from full vaccination, no vaccination below 3 months, full vaccination over 12 months | |||||
Japan | Questions and answers on rabies [40] | Ministry of Health (2017) | (not specified) ID is not approved RIG is not approved | SC: 6 doses on days 0, 3, 7, 14, 30, and 90 | SC: week 0, 4 and month 6–12 |
Re-exposed previously vaccinated: 2 injections for those who have received full vaccination, on days 0 and 3 | |||||
Lao People’s Democratic Republic | Intradermal application of rabies vaccines. Report of a WHO consultation. Bangkok, Thailand 2000 [41] | WHO, Communicable Disease Surveillance and Control (2000) | PVRV (IM) PCECV (IM) ID not yet used, RIG is rarely used due high cost The ID route is not used | (not specified) | (not specified) |
Malaysia | Interim guideline for human rabies prevention & control [30] | Ministry of Health, Disease Control Division (2015) | PVRV (IM) | IM: 4-dose shortened Essen | (not specified) |
Re-exposed previously vaccinated: 2 doses on days 0 and 3 | |||||
Pakistan | Country Guidelines for Prevention of Rabies. Pakistan Rabies Control Programme [31] | WHO in consultation with Provincial Health Departments (2013) | PVRV (IM, ID) PCECV (IM, ID) PDEV (IM) | IM: 4-dose Zagreb | IM: 3 doses, one injection on each of days 0, 7, 21, or 28 |
ID: The updated Thai Red Cross | ID: 3 doses, one injection on each of days 0, 7, 21, or 28 | ||||
Re-exposed previously vaccinated: 2 injections (IM or ID), for those who have received full vaccination, on days 0 and 3 | |||||
Philippines | New Guidelines on the Management of Rabies Exposure [32] | Republic of Philippines. Department of Health (2014) | PVRV (IM, ID) PCECV (IM, ID) Among the first countries that adopted ID | IM: 5-dose Essen 4-dose Zagreb 4-dose shortened Essen | IM: 3 doses, one injection on each of days 0, 7, 21, or 28 |
ID: The updated Thai Red Cross | ID: 3 doses, one injection on each of days 0, 7, 21, or 28 | ||||
Re-exposed previously vaccinated: 2 injections (IM or ID), each on days 0 and 3 if the re-exposed individual had previously receive full vaccination, and full vaccination if he/she had not receive full vaccination course | Booster: Routine booster for individual with occupational risk: 1 dose after one year from full vaccination and one more thereafter in case of Ab titers <0.5 IU/mL | ||||
Republic of Korea | Recommended Adult Immunizations for Foreign Travel [42] | Korea Society of Infectious Disease (2012) | (not specified) | 3 doses | |
Sri Lanka | Protocol for anti-rabies post exposure therapy [33] | Director General of Health Services (2016) | PVRV (IM, ID) PCECV (IM, ID) | IM: 5-dose Essen 4-dose Zagreb | IM: 3 doses, one injection on each of days 0, 7, 21, or 28 |
ID: Updated Thai Red Cross Modified 4-site ( 4-2-2-0-2): one dose at 4 sites on day 0 and one dose at 2 sites on days 3, 7, and 30 | ID: 3 doses, one injection on each of days 0, 7, 21, or 28 | ||||
Re-exposed previously vaccinated: 2 injections (IM or ID), one on each of day 0 and 3, OR 4 ID at four sites on the same visit | Booster: One injection on the 1st year following full vaccination, and one more every five years | ||||
Taiwan | Post-exposure guidelines [34] | Centers for Disease Control (2016) | (not specified, ID not recommended) | IM: 5-dose Essen | IM: one dose, on day 0, 7, 21 or 28 (3 doses) |
Booster: For individuals at high risk (e.g., laboratory workers): 2 injections, one on each day 0 and 4 when Ab titers <0.5 IU/mL, For workers in animal health: One booster dose one year following full vaccination and every 3–5 years thereafter | |||||
Thailand | Thai rabies management guidelines [35] | Queen Saovabha Memorial Institute (2015) | PCEVC (IM, ID) PVRV (IM, ID) PDEV (IM) | IM: 5-dose Essen | IM: 3 doses, one injection on each of days 0, 7, 21, or 28 |
ID: Updated Thai Red Cross | ID: 3 doses, one injection on each of days 0, 7, 21, or 28 Only for PVRV: 2 doses, one injection on each of days 0 and 28 | ||||
Re-exposed previously vaccinated: (a) 2 injections, each on day 0 and 3 if exposure occurred within 6 months from vaccination, no RIG; (b) same as previous or 4-site ID on a single visit if >6 months have elapsed from previous vaccination to exposure | Booster: For individuals at continuous or frequent risk of exposure: One booster vaccination if Ab titers <0.5 IU/mL | ||||
Vietnam | Guidelines on human rabies surveillance and prevention [36] | Ministry of Health (2014) | Cell culture vaccines (not specified) | IM: 5-dose Essen | IM: 3 doses, one injection on each of days 0, 7, 21, or 28 One repeated injection every year |
ID: Updated Thai Red Cross | Booster: One injection on 1st year from previous full vaccination and every year thereafter | ||||
Re-exposed previously vaccinated: (a) 2 injections, each on days 0 and 3 if time from previous full vaccination <5 years; (b) Full vaccination if previous was not completed or >5 years have elapsed from previous full vaccination |
Country | 5-Dose Essen (1-1-1-1-1) | 4-Dose Zagreb (2-0-1-0-1 or 2-1-1) | 4-Dose Essen (1-1-1-1-0) | Updated Thai Red Cross (2-2-2-0-2) |
---|---|---|---|---|
Bangladesh | X | X | X | |
Bhutan | X | X | ||
Cambodia | X | X | X | |
China | X | X | ||
India | X | X | ||
Indonesia | X | |||
Malaysia | X | |||
Pakistan | X | X | ||
Philippines | X | X | X | X |
Sri Lanka | X | X | X | |
Taiwan | X | |||
Thailand | X | X | ||
Vietnam | X | X |
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Buchy, P.; Preiss, S.; Singh, V.; Mukherjee, P. Heterogeneity of Rabies Vaccination Recommendations across Asia. Trop. Med. Infect. Dis. 2017, 2, 23. https://doi.org/10.3390/tropicalmed2030023
Buchy P, Preiss S, Singh V, Mukherjee P. Heterogeneity of Rabies Vaccination Recommendations across Asia. Tropical Medicine and Infectious Disease. 2017; 2(3):23. https://doi.org/10.3390/tropicalmed2030023
Chicago/Turabian StyleBuchy, Philippe, Scott Preiss, Ved Singh, and Piyali Mukherjee. 2017. "Heterogeneity of Rabies Vaccination Recommendations across Asia" Tropical Medicine and Infectious Disease 2, no. 3: 23. https://doi.org/10.3390/tropicalmed2030023