At the beginning of the century, urban rabies was adequately controlled in European countries through the use of vaccines obtained from the nervous tissue of various animal species infected with the rabies virus (Pasteur, Fermi, Semple). However, these vaccines contained myelin and other foreign protein residues and frequently produced neurological-type adverse reactions.

In 1956, Fuenzalida and Palacios developed a vaccine produced in suckling mouse brain, dramatically reducing the myelin content, but not the presence of other proteins foreign to humans. Later, the duck embryo vaccine, whose side effects decreased at the expense of immunogenicity, was produced. Finally, in the 1970s vaccines produced for human use in cell cultures were developed that in addition to preserving immunogenicity, eliminated the majority of the adverse effects produced by the myelin content and other foreign proteins. The VERO cell vaccine and the human diploid cell vaccine belong to this group.

The cell line used in the production of the latter vaccine is the diploid cell MRC-5, which avoids the appearance of undesirable mutations. It is, therefore, not considered as oncogenic, differing from vaccines used in animals. However, there should be continued periodic testing on vaccines produced in these cells to confirm the absence of their oncogenic ability.

The prevention of human rabies in Mexico continues to be an important goal for the health sector. Although the rate of human rabies has fallen significantly during the last 2 years, there are still cases of human rabies registered. Between 1990 and 1995, a total of 238 cases of human rabies were registered (an average of 40 cases annually), with a mean annual incidence of 0.04 cases per 100,000 inhabitants and a mortality rate of almost 100%. During 1998, 15 cases of human rabies were reported in Mexico, for a rate of 0.012 cases per 100,000 inhabitants, exhibiting an important decrease when compared to previous yearly rates of 0.02 (1996) and 0.02 (1997).

Based on data from the Panamerican Center for Zoonosis (CEPANZO) from 1985 to 1989, Mexico and Brazil were the countries registering the greatest number of deaths due to human rabies (rates of 0.092 and 0.03 per 100,000 inhabitants, respectively).

The official epidemiologic data for Mexico has annually reported between 70,000 and 80,000 persons hurt by animals potentially infected with the rabies virus, of whom approximately 30,000 receive vaccinations. In taking this into consideration, it is important to have highly effective vaccines with minimal side effects.

Side effects were generally much more troublesome with vaccine obtained from nervous tissue of animals than vaccine produced in cell cultures. Nevertheless, some signs related to human diploid cell antirabies vaccine consisting of urticarial rash and fever have been reported.

The objectives set forth for this study were to evaluate seroconversion to the human diploid cell antirabies vaccine through the measurement of vaccine-induced antibody levels achieved by subjects exposed to rabies who received or did not receive antirabies hyperimmune gamma globulin, to ascertain tolerance to this vaccine by measuring the type and frequency of adverse reactions after its application.

This is a comparative transverse study carried out between December 1, 1989 and June 30, 1995 in two tertiary-level pediatric hospitals located in Mexico City.

Forty children and adults were included with diverse histories of exposure to animals suspected of having rabies. These persons requested the antirabies vaccine application from the Preventive Medicine Department at one of the hospitals mentioned previously. Some patients came from other second-level hospitals, from health centers, or from direct physician referrals from the private sector. The administration of human hyperimmune gamma globulin was used following the criteria for a severe exposure. Hyperimmune gamma globulin was not, however, administered to all severe cases because on some occasions the product was not obtainable.

All subjects treated for post-exposure prophylaxis after contact with animals positive for rabies or suspected of having the disease were included. All subjects previously vaccinated with any other type of rabies vaccine or those who were immunosuppressed were excluded.

All patients received a complete scheme (five doses) of the human diploid cell vaccine, applied i.m. on days 0, 3, 7, 14, and 28 post-exposure. All of the previously mentioned treatments were performed after obtaining written informed consent from the patient or legal guardian.

Initially, general identification data were recorded for each patient and an interview was conducted 3 days after the application of each dose in order to assess the presence of any adverse post-vaccine effects, including induration, erythema, heat, pain at the application site, itching, fever, headaches, regional adenopathy, or anaphylactic reaction.

Two blood samples were taken (at baseline and at the end of the vaccination scheme). Antibody titers against the rabies virus were measured using a commercial ELISA diagnostic kit (Platelia r rage, Pasteur Diagnostic, Paris, France). This kit is an immuno-enzyme technique for the detection of rabies virus antiglycoprotein antibodies in human serum or plasma. The test is based on the use of a solid phase prepared with the glycoprotein extracted from the inactivated, purified virus membrane and an enzymatic conjugate (protein A from Staphylococcus aureus coupled with peroxidase). Comparison with a control serum titrated in international units IU/mL provided the titer of the unknown serum in equivalent units (the unit equivalent to the international units defined by seroneutralization).

Written authorization and consent were requested from each participating patient. Based on previously mentioned data, a specific format was designed in which the central objective of the study was explained, including data on the type of biological information to be used, days and dates of application, number of doses, and the potential side effects in the taking of blood samples—one at baseline (previous to the beginning of the vaccination scheme) and a second at the end. The patient’s signature or that of the parent or guardian, in the cases of minors, was included in addition to the principal investigator’s signature.

Simple frequencies, central tendency, and dispersion measures were estimated. For the comparison between the occurrence of adverse effects produced by the diploid cell vaccine and that reported in the literature for the Fuenzalida vaccine, a Z approximation to the binomial distribution was used, in addition to estimating the p value. Data are shown in tables and graphs, as well as on a histogram.

A total of 40 patients were included, 12 adults (30%) and 28 minors (70%), with an average age of 12.7 years (SD 11.1 years). The time between the exposure and the application of the first vaccine dose ranged between 1 and 15 days, with an average of 3.9 days.