Reduced schedule of human anti-rabies immunization with Fuenzalida & Palacios vaccine: additional data

It was reevaluated a reduced schedule for anti-rabies post-exposure immunization with newborn mice nervous tissue vaccine (Fuenzalida 8c Palacios) in a group of 30 non exposed volunteers. The vaccine was administered by intramuscular injections on days zero, 2, 4, 16 and 27, in the deltoid area. Antibody levels were determinated by a simplified serum neutralization microtest on days zero, 16 and 37. On days 16 and 37 the antibody levels of the whole group was >0.5 IU/ml and >1.0 IU/ml, respectively. The cell mediated immunity was precociously detected (on day 4) by the delayed type hipersensitivity skin test. Our results show that this reduced schedule elicited an early and effective humoral and cellular immune response. However it is necessary other studies with larger groups of vaccinees in order to obtain definitive conclusion.

Studies on human anti-rabies immunization in Brazil: II - Preliminary evaluation of the 2-1-1 schedule for human pre-exposure anti-rabies immunization, employing suckling mouse brain vaccine

This study reports preliminary results of virus neutralizing antibody (VNA) titers obtained on different days in the course of human anti-rabies immunization with the 2-1-1 schedule (one dose is given in the right arm and one dose in the left arm at day 0, and one dose is apllied on days 7 and 21), recommended by WHO for post-exposure treatment with cell culture vaccines. A variant schedule (double dose on day zero and another on day 14) was also tested, both employing suckling mouse brain vaccine. A complete seroconversion rate was obtained after only 3 vaccine doses, and almost all patients (11 of 12) presented titers higher than 1.0 IU/ml. Both neutralizing response and seroconversion rates were lower in the group receiving only 3 doses, regardless of the sample collecting day. Although our results are lower than those found with cell culture vaccines, the geometry mean of VNA is fully satisfactory, overcoming the lower limit recommended by WHO of 0.5 IU/ml. The 2-1-1 schedule could be an alternative one for pre exposure immunization, shorter than the classical 3+1 regimen (one dose on days 0, 2, 4 and 30) with only three visits to the doctor, instead of four.

Serological findings during a measles outbreak occurring in a population with vaccine coverage

From March 1991 to April 1992, serum samples for IgM detection were collected from 112 clinical measles cases reported to the Health Department of Niterói, State of Rio de Janeiro. The positivity exceeded 90% for specimens collected from the 5th to the 29th day after the onset of the disease. After day 30 a decline in IgM detection was observed, although positivity has been detected up to 90 days after the onset of the symptoms. Forty-four patients (48.9%) with an IgM response had a history of prior measles vaccination. In 5 of the 22 measles-IgM negative cases the infection was due to other agents (rubella: 4 cases, dengue: 1 case). These results show that sensitivity of the test employed for confirming suspected measles cases is high, even in vaccinated patients.

Temporal association between the isolation of Sabin-related poliovirus vaccine strains and the Guillain-Barré syndrome

Thirty eight paralysis cases classified as Guillain-Barré syndrome (GBS) in Brazil were analysed. In all these cases Sabin-related poliovirus vaccine strains were isolated. In most of the cases the last vaccine dose was given months or years before the onset of GBS, suggesting a persistent infection or the transmission of the Sabin-related strains to the patients. The isolation of Sabin-related strains from GBS cases some days or weeks after the onset of the disease, demonstrated a temporal association between the isolation of the strains and the disease. Although the isolates from the GBS cases may not be the etiological agent of the disease, this study strongly indicates that infections caused by Sabin-related vaccine strains can trigger the GBS in certain cases.

IMMUNOGENICITY OF LOW-DOSE INTRAMUSCULAR AND INTRADERMAL VACCINATION WITH RECOMBINANT HEPATITIS B VACCINE

The study is a randomized trial using recombinant DNA vaccine to determine whether an intramuscular 10 µg dose or intradermal 2 µg induces satisfactory anti-HBs levels compared to the standard dose of intramuscular 20 µg. participants were 359 healthy medical and nurse students randomly allocated to one of the three groups: Group I - IM 20 µg; Group II - IM 10 µg; Group III - ID 2 µg at 0, 1 and 6 months. Anti-HBs titres were measured after complete vaccine schedule by ELISA/Pasteur. Baseline variables were similar among groups and side effects were mild after any dose. Vaccinees in the IM-10 µg group had seroconversion rate and geometric mean titre (GMT 2344 IU L-1), not significant different from the IM-20 µg group (GMT 4570 IU L-1). On the contrary, 21.4% of the ID - 2 µg recipients mount antibody concentration below 10 IU L1 and GMT of 91 IU L-1, a statiscally significant difference compared with the standard schedule IM-20 µg (p < 0.001). A three dose regimen of half dosse IM could be considered an appropriate schedule to prevent hepatitis B in young health adults which is of relevance to the expansion of hepatitis B vaccine programme

PRELIMINARY REPORT OF THE USE ON ADULTS OF A RECOMBINANT YEAST-DERIVED HEPATITIS B VACCINE MANUFACTURED BY INSTITUTO BUTANTAN

Three 10 µg doses of the recombinant hepatitis B vaccine, manufactured by Instituto Butantan by original technology, were administered in a adult population, mean age 30 years old, following the 0, 1 and 6 months schedule immunization. The clinical trial was considered satisfactory in terms of immunogenicity (anti-HBs titers between 17.5-29500 IU/l, seroconversion 95.3%) and reactogenicity (no incapacitating side effects)

Massive shift in the pneumococcal nasopharyngeal flora after the 7-valent conjugate vaccine: epidemiological studies and testing pathogenic potential in animal models

Dissertation presented to obtain the PhD degree in Biology/Molecular Biology by Universidade Nova de Lisboa, Instituto de Tecnologia Química e Biológica

ADVERSE EFFECT VERSUS QUALITY CONTROL OF THE FUENZALIDA-PALACIOS ANTIRABIES VACCINE

We evaluated the components of the Fuenzalida-Palacios antirabies vaccine, which is till used in most developing countries in human immunization for treatment and prophylaxis. This vaccine is prepared from newborn mouse brains at 1% concentration. Even though the vaccine is considered to have a low myelin content, it is not fully free of myelin or of other undesirable components that might trigger adverse effects after vaccination. The most severe effect is a post-vaccination neuroparalytic accident associated with Guillain-Barré syndrome. In the present study we demonstrate how the vaccines produced and distributed by different laboratories show different component patterns with different degrees of impurity and with varying protein concentrations, indicating that production processes can vary from one laboratory to another. These differences, which could be resolved using a better quality control process, may affect and impair immunization, with consequent risks and adverse effects after vaccination. We used crossed immunoelectrophoresis to evaluate and demonstrate the possibility of quality control in vaccine production, reducing the risk factors possibly involved in these immunizing products.

AN ELISA SUITABLE FOR THE DETECTION OF RABIES VIRUS ANTIBODIES IN SERUM SAMPLES FROM HUMAN VACCINATED WITH EITHER CELL-CULTURE VACCINE OR SUCKLING-MOUSE-BRAIN VACCINE

An indirect ELISA for determination of post-vaccination rabies antibody was applied. Purified rabies virus was used as antigen to coat plates, and staphylococcal protein A linked with horseradish peroxidase was used for detecting IgG antibody in human sera. Sera from humans, vaccinated with cell-culture vaccine or suckling-mouse-brain vaccine, were examined. ELISA results were compared to those obtained from the virus neutralization test. The mean and standard deviation of OD were determined for 126 negative sera (pre-vaccination) and for 73 sera from vaccinated persons showing antibody titers lower than 0.5 IU/ml. Results were defined as ELISA -positive, -negative or -doubtful. Establishment of a doubtful region reduced the number of sera otherwise classified as positive (false-positive sera). In this way, the sensitivity, specificity and agreement values were respectively 87.5%, 92.4% and 88.5%. No significant differences were observed in these values when the group vaccinated with cell-culture vaccine and the group vaccinated with suckling-mouse-brain vaccine were compared. It was shown that much of the disagreement between the values obtained by neutralization test and ELISA occurred in sera obtained at the beginning of the immunization process, and was probably due to the presence of IgM in the serum samples, detected only by the former test. This ELISA method can be used as a screening test in rabies laboratories regardless of the kind of vaccine used for immunization.

Safety and immunogenicity of hepatitis B vaccine ButaNG in adults

Recombinant yeast-derived hepatitis B vaccine manufactured by Instituto Butantan was administered in two groups of adult volunteers (I, II) following two different schedules of immunization. In the first trial (10 mg doses and 0, 1, 3 months vaccination schedule) 106 individuals completed the full immunization program. The results of seroconversion by age group varied from 70 to 100% and the GMT from 46.5 to 124.9 mIU mL-1. In the second trial with 68 individuals (for dosage comparison and 0, 1, 6 months vaccination schedule) indicated that the vaccine formulated in 20 mg was more effective than in 10 mg. The adverse reactions observed in the vaccinees were less frequent than the ones previously found since the introduction of similar vaccines.

Hepatitis B vaccine in infants: a randomized controlled trial comparing gluteal versus anterolateral thigh muscle administration

A significantly diminished antibody response to hepatitis B vaccine has been demonstrated in adults when the buttock is used as the injection site. However, in Brazil, the buttock continues to be recommended as site of injection for intramuscular administration of vaccines in infants. In this age group, there are no controlled studies evaluating the immunogenicity of the hepatitis B vaccine when administered at this site. In the present study, 258 infants were randomized to receive the hepatitis B vaccine either in the buttock (n = 123) or in the anterolateral thigh muscle (n = 135). The immunization schedule consisted of three doses of hepatitis B vaccine (Engerix Bâ, 10 mug) at 2, 4 and 9 months of age. There were no significant differences in the proportion of seroconversion (99.3% x 99.2%), or in the geometric mean titer of ELISA anti-HBs (1,862.1 x 1,229.0 mIU/mL) between the two groups. This study demonstrates that a satisfactory serological response can be obtained when the hepatitis B vaccine is administered intramuscularly into the buttock.

Aseptic meningitis in a large MMR vaccine campaign (590,609 people) in Curitiba, Paraná, Brazil, 1998

The aseptic meningitis after Measles-Mumps-Rubella vaccine (MMR) is a well recognized complication, and different incidences have been observed in several studies. We retrospectively analyzed forty cases of aseptic meningitis, during a large public immunization campaign (1998) in Curitiba, Southern Brazil (590,609 people), admitted in our Service. The vaccine utilized was Leningrad-3-Zagreb mumps strain, Edmonston-Zagreb measles strain, and RA 27#3 rubella strain. In all county, a total number of 87 cases were reported, resulting in a incidence of 1.7 cases per 10,000 given doses . The mean age was 23.7 ± 12.8 years. The female:male ratio was 1.35:1. Severe headache with meningismus (92.5%), fever (87.5%), nausea/vomiting (82.5%) were the most common clinical findings. Three cases (7.5%) developed mild mumps. All patients underwent cerebrospinal fluid (CSF) tap with the following findings: mononuclear pleocytosis from 100 to 500 cells/mm³ in 17 cases (42.5%; 257.5 ± 260.6 cells/mm³); increased protein 28 cases (67.5%; 92.1 ± 76.9 mg/dL); glucose was normal in all cases (56.8 ± 11.2 mg/dL) except in 4 (10%) cases, which presented less than 44 mg/dL. All serological tests (latex to bacterial meningitis, Cryptococcus, cysticercosis, VDRL) and bacteriological cultures were negative. Virus identification were also negative in 8 samples. None of the patients had neurological deficits or related symptoms after one year of onset. We believe the benefit of vaccination clearly outweights the incidence of benign vaccine-associated meningitis.

Nutritional status in relation to the efficacy of the rhesus-human reassortant, tetravalent rotavirus vaccine (RRV-TV) in infants from Belém, Pará State, Brazil

The rhesus-human reassortant, tetravalent rotavirus vaccine (RRV-TV) was licensed for routine use in the United States of America but it was recently withdrawn from the market because of its possible association with intussusception as an adverse event. The protective efficacy of 3 doses of RRV-TV, in its lower-titer (4 x 10(4) pfu/dose) formulation, was evaluated according to the nutritional status of infants who participated in a phase III trial in Belém, Northern Brazil. A moderate protection conferred by RRV-TV was related to weight-for-age Z-scores (WAZ) greater than -1 only, with rates of 38% (p = 0.04) and 40% (p = 0.04) for all- and- pure rotavirus diarrhoeal cases, respectively. In addition, there was a trend for greater efficacy (43%, p = 0.05) among infants reaching an height-for-age Z-score (HAZ) of > -1. Taking WAZ, HAZ and weight-for-height Z-score (WHZ) indices <= -1 together, there was no significant protection (p > 0.05) if both placebo and vaccine groups are compared. There was no significant difference if rates of mixed and pure rotavirus diarrhoeal cases are compared in relation to HAZ, WAZ and weight-for-height Z-score (WHZ) indices. Although a low number of malnourished infants could be identified in the present study, our data show some evidence that malnutrition may interfere with the efficacy of rotavirus vaccines in developing countries.