Promoting adverse drug reaction reporting: comparison of different approaches

ABSTRACT OBJECTIVE To describe different approaches to promote adverse drug reaction reporting among health care professionals, determining their cost-effectiveness. METHODS We analyzed and compared several approaches taken by the Northern Pharmacovigilance Centre (Portugal) to promote adverse drug reaction reporting. Approaches were compared regarding the number and relevance of adverse drug reaction reports obtained and costs involved. Costs by report were estimated by adding the initial costs and the running costs of each intervention. These costs were divided by the number of reports obtained with each intervention, to assess its cost-effectiveness. RESULTS All the approaches seem to have increased the number of adverse drug reaction reports. We noted the biggest increase with protocols (321 reports, costing 1.96 € each), followed by first educational approach (265 reports, 20.31 €/report) and by the hyperlink approach (136 reports, 15.59 €/report). Regarding the severity of adverse drug reactions, protocols were the most efficient approach, costing 2.29 €/report, followed by hyperlinks (30.28 €/report, having no running costs). Concerning unexpected adverse drug reactions, the best result was obtained with protocols (5.12 €/report), followed by first educational approach (38.79 €/report). CONCLUSIONS We recommend implementing protocols in other pharmacovigilance centers. They seem to be the most efficient intervention, allowing receiving adverse drug reactions reports at lower costs. The increase applied not only to the total number of reports, but also to the severity, unexpectedness and high degree of causality attributed to the adverse drug reactions. Still, hyperlinks have the advantage of not involving running costs, showing the second best performance in cost per adverse drug reactions report.

Passive haemagglutination test for human neurocysticercosis immunodiagnosis: II - Comparison of two standardized procedures for the passive haemagglutination reagent in the detection of anti-Cysticercus cellulosae antibodies in cerebrospinal fluids

A comparison of two different standardized reagent procedures for the passive haemagglutination test (PHA) in the detection of specific antibody to Cysticercus cellulosae in cerebrospinal fluid (CSF) was carried out. The formaldehyde-treated group O Rh-human red blood cells (HuRBC) and glutaraldehyde-treated sheep red blood cells (SRBC) were the supplies for the reagents preparation and, in the tests, they were designated as PHA-1 and PHA-2, respectively. For both reagents the cells were coated with the cysticerci total saline extract (TS) antigen. PHA-1 and PHA-2 were assessed in a total of 204 CSF from patients with neurocysticercosis, from non-related infections and from healthy individuals. The positivity and specificity indices obtained were respectively 81.7% and 94.4% for PHA-1 and for PHA-2, 88.7% and 96.6%. Since no significant differences were observed between the results provided by two reagents, at level of significance of 0.05, either processes of cell sensitization can alternatively be used according to the own laboratory convenience.

Natural Trypanosoma cruzi infection in dogs of endemic areas of the Argentine Republic

The population dynamics and the prevalence of chagasic infection of 352 dogs living in 108 rural houses infested by triatomines were studied. The region was divided into three sections according to increasing distances to an urban area. Each animal was identified by means of its particular characteristics and built, and its owners gave information about its habits. By means of xenodiagnosis, serology and ECG studies, prevalences of infection, parasitological-serological correlation, percentage of altered electrocardiographic outlines and percentage of houses with parasitemic dogs, were determined. The rural area showed a characteristic T. cruzi infection pattern and differences in the canine population parameters with respect to the other areas were observed: a higher proportion of puppies than adult dogs, a more sedentary population, higher prevalences of infection, as measured by xenodiagnosis, in dogs, and the highest proportion of bedroom insects infected with T. cruzi. It is assumed that the sedentary characteristics of the human population in that rural area impinge in the blood offer to the triatomine population, and the high percentage of parasitemic dogs of the area, contribute to the rise of "kissing ougs" infected with T. cruzi found in bedrooms.

Comparison of serum hepatitis B virus replication markers in patients with chronic hepatitis B: studies on HBeAg/Anti-HBe system, viral dna polymerase and HBV-DNA

The detection of HBV-DNA in serum by molecular hybridization is the most sensitive and specific marker of replication and infectivity of hepatitis B virus and currently is proposed as a routine diagnostic technique in the follow-up of HBV - related diseases. Comparing different techniques already described, we found that direct spotting of serum samples on nitrocellulose membranes under vacuum filtration, followed by denaturing and neutralizing washes is more practical, simple, sensible and reproducible. DNA polymerase assay using phosphonoformic acid as specific viral inhibitor has shown 86.8% of concordance with HBV-DNA detection, and so, it is an useful alternative in the follow-up of hepatitis B chronic patients. We found 19.2% HBeAg positive samples with no other markers of viral replication and no anti-HBe positive sample had detectable HBV-DNA. Discordance between the 2 systems have been extensively described, and we confirm this for the first time in our country. Molecular biological techniques are essential to determine the replication status of chronic hepatitis B patients.

Comparison of indirect immunofluorescence test for measles antibodies with haemagglutination inhibition and plaque neutralization tests

Indirect Immunofluorescence (IFA), Plaque Reduction Neutralization (PRN) and Haemagglutination Inhibition (HI) tests for measles antibodies were carried out in 197 sera obtained from umbilical cord and vaccinated children. The IFA was also applied to blood samples collected with filter paper. IFA results demonstrated that the test is relatively simple to perform, with good reproducibility for different antigen lots. Good correlation was obtained between IFA, PRN and HI antibody titers. Better correlation was demonstrated with IFA and PRN than with HI and PRN tests. Sensitivity of IFA in detecting antibody was less effective than PRN, however more effective than HI using rhesus monkey red blood cells. PRN antibody titers over 100 were detected by IFA but not by HI (9.7% with negative results). IFA may be of considerable practical use and able to substitute HI in Seroepidemiological surveys and to evaluate vaccine efficacy. It also can be simplified by employing filter paper collected samples.

Diagnosis of Helicobacter pylori: comparison of an urease test, histological visualization of curved bacteria and culture

Helicobacter pylori was investigated in 189 patients for culture, microscopic visualization of campylobacter-like organisms (CLO) and a ten minute urease test. In 136 (72%) the bacteria was isolated, and in 98 of them CLO were histologically detected. Specificity, sensitivity, positive and negative predictive values of microscopic visualization of CLO were: 0.77, 0.73, 0.97 and 0.51, respectively; 98 culture-positive patients were urease test positive. Specificity, sensitivity, positive and negative predictive values of the urease test were: 0.83, 0.72, 0.92 and 0.54, respectively. Comparing the urease test with culture of H. pylori combined with microscopic visualization of CLO, its specificity, sensitivity, positive and negative predictive values were: 0.95, 0.71, 0.98 and 0.48, respectively. Probably, these values are not real, since bacteria different from H. pylori could be misclassified as CLO.

Longitudinal study of acute respiratory diseases in Rio de Janeiro: occurrence of respiratory viruses during four consecutive years

The occurrence of different viruses in nasopharyngeal secretions from children less than 5 years old with acute respiratory infections (ARI) was investigated over a period of 4 years (1982-1985) in Rio de Janeiro. Of the viruses known to be associated with ARI, all but influenza C and parainfluenza types 1, 2 and 4 were found. Viruses were found more frequently in children attending emergency or pediatric wards than in outpatients. This was clearly related to the high incidence of respiratory syncytial virus (RSV) in the more severe cases of ARI. RSV positive specimens appeared mainly during the fall, over four consecutive years, showing a clear seasonal ocurrence of this virus. Emergency wards provide the best source of data for RSV surveillance, showing sharp increase in the number of positive cases coinciding with increased incidence of ARI cases. Adenovirus were the second most frequent viruses isolated and among these serotypes 1,2 and 7 were predominant. Influenza virus and parainfluenza virus type 3 were next in frequency. Influenza A virus were isolated with equal frequency in outpatient departments, emergency and pediatric wards. Influenza B was more frequent among outpatients. Parainfluenza type 3 caused outbreaks in the shanty town population annually during the late winter or spring and were isolated mainly from outpatients. Herpesvirus, enterovi-rus and rhinovirus were found less frequently. Other viruses than RSV and parainfluenza type 3 did not show a clear seasonal incidence.

Candidin: comparison of two antigens for cutaneous delayed hypersensitivity testing

A candidin, which is a suspension of killed yeast cells, is commonly used for intradermal tests of delayed hypersensitivity, to evaluate the immunological cellular competence of the patient, when the test is applied along with other similar tests. When working with a cellular antigen, the histopathology of positive skin tests reveals a cellular infiltrate which not only presents a characteristic hypersensitivity reaction but also a neutrophilic abscess in the central part. This research presents the results of a comparison between the yeast cell suspension and the polysaccharide antigens, both obtained from the same strains of Candida albicans. The results obtained by skin tests in one hundred individuals were 61.0% with the polysaccharide antigen and 69.0% with the yeast cell suspension antigen. Concordant results concerning the two antigens were observed in 82.0% of the individuals. The discussion section presents an assumption to explain the differences of positivity obtained with the two antigens. We conclude that the polysaccharide antigen can be utilized in the intradermal test of delayed hypersensitivity to Candida albicans.

Histoplasmin reaction. Comparison of a polysaccharide antigen to the filtrate antigen

This work was planned by taking into account all the knowledge accumulated from the immunological study of paracoccidioidomycosis. It aimed at comparing a polysaccharide antigen from Histoplasma capsulatum to a classic histoplasmin with the help of intradermal tests of delayed type of hypersensitivity. Tests were applied to 115 individuals in Santo Amaro, a town in the state of São Paulo. Positive results using classic histoplasmin were obtained in 46.0% cases whereas positive results using the polysaccharide antigen at its hightest concentration were obtained in 51.30% cases. The major conclusion in this investigation is that it is possible to use the polysaccharide antigen as histoplasmin instead of the filtrate antigen

REPRODUCIBILITY OF ALKALINE ANTIGENS OF Leishmania major-LIKE AND Leishmania (V.) braziliensis EVALUATED BY IgG-ELISA. COMPARISON OF ANTIGENS ADDED OF A PROTEIN INHIBITOR (PMSF) OR NOT

This paper deals with the analysis of 10 batches of L.major-like and L.(V.) braziliensis antigens added or not of a proteases inhibitor evaluated by means of an IgG-ELISA on three consecutive days using positive standard sera from patients with diagnosis of American Leishmaniasis previously tested for the presence of IgG antibodies by means of ELISA. The statistical analysis showed that for L. (V.) braziliensis the PMSF-containing antigen did not show any difference among batches or days of testing; the L.(V.) braziliensis antigen without PMSF showed statistical significance for differences among batches and a two-way ANOVA showed significant differences between antigens. L.major-like antigen prepared with or without PMSF showed differences among batches; all 3 days of testing displayed differences for the PMSF antigen but only for days 1 and 2 for the antigen without inhibitor. A two-way ANOVA showed differences among batches of the antigens but not for antigens with and without the protein inhibitor. According to the statistical analysis the L.major-like antigen added or not of PMSF has shown that it is the choice antigen for mucocutaneous leishmaniasis serology.

COMPARISON OF A COMMERCIAL ENZYME IMMUNOASSAY WITH PLAQUE REDUCTION NEUTRALIZATION FOR MATERNAL AND INFANT MEASLES ANTIBODY MEASUREMENT

The most practicable assay for measurement of measles IgG (mIgG) in large numbers of sera is an enzyme immunoassay (EIA). To assess how EIA results would agree with those by the gold standard method of plaque reduction neutralization (PRN) we compared the results from the two methods in 43 pairs of maternal and umbilical cord sera, and sera from the corresponding infants when aged 11 - 14 months. In maternal-cord sera, the differences between mean antibody levels by EIA or PRN were not statistically significant, though in individual sera, differences could be large. However, agreement was less good for infants sera, in which levels of mIgG were very low. The conclusions of a study of transplacental transport of mIgG would not be affected by the use of either technique. When studying waning immunity in infants, PRN should be the method of choice, while results from studies using EIA should be interpreted with caution.

Molecular characterization of Dengue viruses type 1 and 2 isolated from a concurrent human infection

In 2001, an autochthonous case of dual viremia, resulting from naturally acquired dengue virus DEN-1 and DEN-2 infections was detected during the dengue outbreak that occurred in Barretos, a city with about 105,000 inhabitants in the North region of São Paulo State. Serotype identification was based on virus isolation to C6/36 mosquito cells culture and immunofluorescence assays using type-specific monoclonal antibodies. The double infection was also confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). Comparative analysis of the 240-nucleotide sequences of E/NS1 gene junction region between the genome of DEN-1 and DEN-2 isolates of the corresponding reference Nauru and PR 159S1 strains, respectively, showed some nucleotide differences, mainly silent mutations in the third codon position. Results of maximum likelihood phylogenetic analysis of E/NS1 gene sequences indicated that both genotypes of DEN-1 and DEN-2 viruses recovered from double infection in Barretos belonged to genotypes I and III, respectively.

Incidence of respiratory viruses in preterm infants submitted to mechanical ventilation

The objectives of this study were to determine the incidence of infection by respiratory viruses in preterm infants submitted to mechanical ventilation, and to evaluate the clinical, laboratory and radiological patterns of viral infections among hospitalized infants in the neonatal intensive care unit (NICU) with any kind of acute respiratory failure. Seventy-eight preterm infants were studied from November 2000 to September 2002. The newborns were classified into two groups: with viral infection (Group I) and without viral infection (Group II). Respiratory viruses were diagnosed in 23 preterm infants (29.5%); the most frequent was respiratory syncytial virus (RSV) (14.1%), followed by influenza A virus (10.2%). Rhinorrhea, wheezing, vomiting and diarrhea, pneumonia, atelectasis, and interstitial infiltrate were significantly more frequent in newborns with nosocomial viral infection. There was a correlation between nosocomial viral infection and low values of C-reactive protein. Two patients with mixed infection from Group I died during the hospital stay. In conclusion, RSV was the most frequent virus in these patients. It was observed that, although the majority of viral lower respiratory tract infections had a favorable course, some patients presented a serious and prolonged clinical manifestation, especially when there was concomitant bacterial or fungal infection.