A 1-week intradermal dose-sparing regimen for rabies post-exposure prophylaxis (RESIST-2): an observational cohort study

• Published in: The Lancet infectious diseases Vol. 19; no. 12; pp. 1355 - 1362
• Main Authors: Cantaert, Tineke, Borand, Laurence, Kergoat, Lauriane, Leng, Chanthy, Ung, Sivlin, In, Sotheary, Peng, Yiksing, Phoeun, Chandara, Hing, Chanthy, Taing, Chun Navy, Saman, Manil, Ong, Sivuth, Mey, Channa, Choeung, Rithy, Ly, Sowath, Dussart, Philippe, Bourhy, Hervé, Tarantola, Arnaud
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01-12-2019; Elsevier Limited; New York, NY : Elsevier Science ; The Lancet Pub. Group, 2001
• Subjects: Adolescent; Adult; Age Factors; Animals; Antibodies; Antibodies, Neutralizing / immunology; Antibodies, Viral / immunology; Arm circumference; Child; Cohort analysis; Cohort Studies; Costs; Dogs; Drug dosages; Exposure; Female; Flow cytometry; Fluorescence; Human health and pathology; Humans; Immunization Schedule; Immunoglobulins; Immunology; Infectious diseases; Injection; Injections, Intradermal; Life Sciences; Lyssavirus; Male; Neutralization Tests; Nutrition; Observational studies; Patients; Post-Exposure Prophylaxis / methods; Prophylaxis; Rabies; Rabies / prevention & control; Rabies Vaccines / administration & dosage; Rabies virus / immunology; Studies; Systematic review; Vaccination; Vaccines; Viruses; Young Adult; Cambodia; France
• ISSN: 1473-3099; 1474-4457
• DOI: 10.1016/S1473-3099(19)30311-1

The international health authorities are backing an effort to eliminate canine-mediated rabies in humans by 2030. This effort will require improving access to adequate and timely rabies post-exposure prophylaxis as compliance is low with WHO-recommended regimens (given in four to five visits over 1 month). Access could be substantially improved by an abridged regimen to reduce doses, direct and indirect costs, and improve vaccine equity by better sharing of available vaccine. We aimed to compare rabies virus neutralising antibody titres before and after the fourth visit to determine whether that session was needed or the current regimen could be abridged.
In this observational cohort study, we measured rabies virus neutralising antibody titres using rapid fluorescent focus inhibition tests in 116 people bitten by dogs with laboratory-confirmed rabies and 20 control individuals. Percentages of circulating plasmablasts were determined by flow cytometry. All individuals had been referred to the rabies prevention clinic at Institut Pasteur in Cambodia and received two intradermal injections of post-exposure prophylaxis on days 0, 3, 7, and 28 (Thai Red Cross regimen) with or without equine rabies immunoglobulin, as per 2010 WHO recommendations.
All individuals had rabies virus neutralising antibody titres considered protective (≥0·5 IU/mL) and plasmablast activation on day 28 before the last injection. The median rabies virus neutralising antibody concentration in the group of individuals bitten by rabies virus-positive dogs was 1·08 IU/mL (IQR 0·37–3·09) on day 7, 26·86 (22·68–49·50) on day 28, and 26·74 (11·78–49·06) on day 42. No significant differences were observed in titres between days 28 and 42, after titres reached a plateau. These titres were reached notwithstanding equine rabies immunoglobulin use, age, sex, nutrition status as indicated by upper-arm circumference in children or BMI in adults, or dog infection status. Titres or plasmablast percentages did not increase between the day of the last injection and 2 weeks later. All patients were alive 1 year after post-exposure prophylaxis.
The fourth vaccine session on day 28 provides no additional benefit. Rabies post-exposure prophylaxis can be abridged to a two-dose, three-session, 1 week regimen to improve post-exposure prophylaxis coverage and equity at no risk to patients.
Institut Pasteur.