Essen Regimen Research Articles

Rabies post-exposure prophylaxis vaccination with purified chick embryo cell vaccine (PCECV) and purified vero cell rabies vaccine (PVRV) in a four-site intradermal schedule (4-0-2-0-1-1): An immunogenic, cost-effective and practical regimen

Currently, two intradermal (ID) regimens for rabies post-exposure prophylaxis (PEP) are recommended by WHO and used in countries where approved by national authorities: the Thai Red Cross (TRC) two-site ID regimen and the eight-site ID regimen. Besides these WHO recommended schedules, a new economical four-site ID regimen was evaluated that reduces the cost of PEP by up to 80%, when compared with the standard intramuscular Essen regimen, reduces the number of visits required for the patients when compared with the TRC regimen, and is more convenient than the eight-site regimen. To determine the immunogenicity of the ID four-site PEP regimen (4-0-2-0-1-1), 180 healthy volunteers were randomized to receive 0.1 mL volumes of PCECV or PVRV administered ID over both left and right shoulders and both deltoid regions on day 0, both deltoid regions on day 7 and over one deltoid region on days 30 and 90. Regardless of the vaccine, every subject developed rabies virus neutralizing antibody (RVNA) titers above 0.5 IU/mL by day 14, as determined by rapid fluorescent focus inhibition test (RFFIT) using a homologous test system. Two weeks after the last dose of vaccine, RVNA titers were all above 0.5 IU/mL (day 104). Geometric mean titers were similar throughout the study period. Both vaccines were well tolerated. These results demonstrate that a new four-site ID PEP regimen is a cost-effective and convenient alternative to IM (Essen or Zagreb) or ID (TRC or eight-site) regimens, especially using a 1 mL vial of vaccine (PCECV).

Evaluation of a new five-injection, two-site,intradermal schedule for purified chick embryo cell rabies vaccine: A randomized, open-label, active-controlled trial in healthy adult volunteers in India

Background: Human rabies is an ongoing significant public health problem inmany developing countries, with India reporting the highest incidence of rabies-related deaths (∼20,000 per year). Many people living in India cannot afford the standard IM postexposure prophylaxis (PEP) with cell-culture vaccines, which are administered using a 5-dose regimen developed in Essen, Germany. A potentially less expensive intradermal (ID) regimen, based on the Essen regimen, has been developed at the Kempegowda Institute of Medical Sciences (KIMS), Bangalore, India. Objective: The objective of this study was to compare the immunogenicity and local and systemic tolerability of the KIMS-1D regimen with those of the standard Essen IM regimen in healthy adult volunteers in India. Methods: This randomized, open-label, active-controlled trial was conductedat the Antirabies Clinic, Medical College, KIMS. Healthy adult volunteers were randomly assigned to receive purified chick embryo cell vaccine (PCECV) using the KIMS-1D regimen (0.1 mL injected ID at 2 body sites on days 0, 3, 7, 14, and 28 [“2-2-2-2-2”]) or the Essen IM regimen (1 mL injected IM at 1 body site on the same days Subjects were followed up for 365 days by the treating physician and encouraged to voluntarily report any adverse events (AEs). Serum rabies virus-neutralizing antibody (RVNA) concentrations were measured before the first injection on day 0 (baseline) and on days 14, 28, 90, 180, and 365, using the rapid fluorescent focus inhibition test. Results: Ninety-one subjects were enrolled and included in the tolerabilityand immunogenicity analyses. The ID group comprised 45 subjects (26 men, 19 women; mean [SD] age, 20.84 [1.48] years); the IM group, 46 subjects (28 men, 18 women; mean [SD] age, 21.02 [1.16] years). The most common local AEs were pain at the injection site (2/225 [0.9%] in the ID group and 10/230 [4.3%] in the IM group; P < 0.006) and itching at the injection site (5/225 [2.2%] in the ID group and none in the IM group; P = 0.026). All of the AEs were transient and resolved without the need for medication. All subjects had serum RVNA concentrations ≥0.5 IU/mL—considered protective by the World Health Organization—at all follow-up visits. However, the mean RVNA concentrations in the IM group were significantly higher compared with those in the ID group from days 14 to 365 (all, P < 0.001). Conclusion: In this study in healthy volunteers, PEP with PCECV administered using the KIMS-ID regimen was well tolerated and immunologically efficacious for 365 days. Adequate RVNA levels were maintained with the KIMS-ID regimen from days 14 to 365, although these levels were significantly lower than those achieved in the group receiving the Essen IM regimen (all, P < 0.001).

Reducing the cost of post-exposure rabies prophylaxis: efficacy of 0.1 ml PCEC rabies vaccine administered intradermally using the Thai Red Cross post-exposure regimen in patients severely exposed to laboratory-confirmed rabid animals

Purified chick embryo cell rabies vaccine (PCECV) administered as 0.1 ml intradermally according to the Thai Red Cross (TRC) regimen could reduce the cost of PEP by up to 84% when compared to the traditional five-dose Essen regimen. To confirm the efficacy of 0.1 ml of PCECV using the TRC regimen, a clinical trial was conducted in 113 patients presenting with category III exposures from confirmed rabid animals at two bite referral centres in the Philippines. Patients were monitored monthly for 1 year after exposure. PCECV was well tolerated, no vaccine-related serious adverse events occurred and all patients were alive 1 year after their initial exposure.

Elimination of human rabies in a canine endemic province in Thailand: five-year programme.

A five-year project to prevent human deaths from rabies in Phetchabun Province, Thailand involved increasing accessibility of post-exposure treatment with the Thai Red Cross intradermal (2-2-2-0-1-1) regimen for humans exposed to potentially and confirmed rabid animals; intensifying documentation of post-exposure treatment; increasing educational awareness through advocacy in provincial schools, television programmes, and newspapers; reducing canine rabies by monitoring the dog population and implementing vaccination and sterilization programmes; increasing the cooperation between the Ministries of Public Health, Agriculture, and Education on a provincial level; and assessing the impact of the programme through intensified follow-up of patients exposed to suspected and laboratory-confirmed rabid animals. Between 1996 and 2001, 10350 patients received post-exposure treatment; 7227 of these received the Thai Red Cross intradermal regimen. Fewer than 3% of exposed patients received rabies immunoglobulin. Seventy-three percent of all patients presented with WHO category III exposures. In a retrospective study, 188 patients exposed to laboratory-confirmed rabid animals were followed to determine their health status. Of these patients, 20 received the intramuscular Essen regimen and 168 the Thai Red Cross intradermal regimen (148 received 0.1 ml purified chick embryo cell rabies vaccine, 10 received 0.1 ml purified vero cell rabies vaccine, and 10 received 0.2 ml purified duck embryo cell rabies vaccine). All patients were alive one year after exposure. Two human deaths occurred in the first two years of the programme - neither patient had received vaccine or rabies immunoglobulin after exposure. No deaths occurred during the last three years of the programme, which indicated that the programme was successful.