Phase I safety and immunogenicity study of a Brazilian serogroup B vaccine.

Meningococcal disease by serogroup B has been a public health problem in Brazil in the last decades. The Brazilian Oswaldo Cruz Foundation has been working to develop a vaccine with detergent-treated outer membrane vesicles (OMV) and detoxified endotoxin (dLOS) from Neisseria meningitidis serogroup B prevalent strains. A phase I study, enrolling 26 adults (18-44 years of age) was performed using experimental vaccines combining B components and aluminum hydroxide as adjuvant. It was a dose escalation study testing vaccines made of 25, 50, and 100 µg OMV protein/mL (sum of both strains) and dLOS in half amount of total protein concentration, with three doses given two months apart. Adverse events were mild/moderate with frequency increasing with the amount of antigens. Pain in the site of injection was the most frequent reaction in all doses, reported in more than the 85% across vaccine groups. Considering all injections, cephalea was the most common systemic adverse event, detected in 11.1%, 17.2% and 32.1%, respectively with doses of 12.5 µg, 25 µg and 50 µg. High titers of total IgG (ELISA) were observed for the vaccine components before vaccination. Protective levels of bactericidal antibodies (titer ≥1:4) for both vaccine strains were also present. Considering a 4-fold increase of IgG titers compared to pre-immune values (seroconversion), 50%-70% of those who received intermediate and highest doses of antigens presented satisfactory response for OMV of N44/89 strain. The lowest dose vaccine induced no seroconversion for strain N44/89, and 11% for strain N603/95. For the three vaccines doses, 25% of seroconversion, in total IgG against LOS, was observed. Increased antibody bactericidal activity was observed for both strains in higher antigen concentrations. For IgG against LOS, all vaccine formulations showed 25% of seroconversion. In conclusion, MenB-Bio experimental vaccines were well tolerated and immunogenic, thus allowing phase II studies.

Effectiveness of pharmaceutical care for drug treatment adherence in women with lupus nephritis in Rio de Janeiro, Brazil: a randomized controlled trial.

OBJECTIVE: Studies have been conducted to determine the causal factors and clinical consequences of non-adherence to treatment in systemic lupus erythematosus (SLE). However, no interventions have been performed to increase drug adherence. Our objective was to assess the effectiveness of pharmaceutical care (PC) for drug treatment adherence in lupus nephritis (LN). METHODS: This was a randomized clinical trial (pragmatic trial) in patients with LN in Rio de Janeiro, Brazil, allocated in two groups: an intervention group (Dader Method for PC) and a control group (institution's usual care). Drug treatment adherence was measured by the combination of five questions normally used in clinical practice. RESULTS: A total of 131 patients were randomized, and 122 completed the study, with a mean follow-up of 12.7 months and use of six drugs per day and 10-12 doses per day. Low adherence was observed at baseline (intervention group: 30%; control group: 29%). PC showed 27% effectiveness (95% confidence interval (CI) -6% to 50%) in the intention to treat analysis and 31% (95% CI 0-52%) in per protocol analysis, considering all drugs. As for adherence to specific drugs for SLE, effectiveness of PC was 64% (95% CI 34-80%) with intention-to-treat analysis and 62% (95% CI 32-79%) in per protocol analysis. CONCLUSIONS: PC was effective for increasing drug treatment adherence in SLE. The detailed account provided by the Dader Method of the difficulties with patients' drug therapy proved invaluable to approach non-adherence.

Vaccination against hepatitis B with 4-double doses increases response rates and antibodies titers in HIV-infected adults.

BACKGROUND: Antibody responses to standard regimens of hepatitis B (HBV) vaccination are lower in HIV-infected subjects and the best hepatitis B vaccine schedule in this population is not known. OBJECTIVE: To assess the immunogenicity and to evaluate predictors of serologic response of a modified regimen of a HBV recombinant vaccine in a cohort of HIV-infected subjects. METHODS: HIV-infected subjects received 4 doses (40 µg) of a recombinant HBV vaccine at 0, 1, 2 and 6 months. Demographic information as well as CD4 cell count and plasma viral load were assessed at baseline. Protective and strong responses were defined as an anti-HBs titer ≥10 mIU/mL and ≥100 mIU/mL, respectively and were evaluated one month after the third and the fourth doses. RESULTS: 163 HIV-infected individuals were evaluated 67 (40%) were male and median age was 37 years. Median CD4 cell count was 385 cells/mm(3) and 113 (70%) had undetectable HIV-1 viral load. Protective antibody response was observed in 83 and 91% and a strong antibody response was observed in 62 and 80% of the subjects after 3 and 4 doses, respectively. In a multivariate logistic model undetectable HIV-1 viral load and higher CD4 cell counts were independent predictors of a strong antibody response after 4 doses. Patients with undetectable HIV viral load were almost 3 times more likely to have anti-HBs titers above 100 mIU/mL than those with detectable viral load. CONCLUSIONS: A 4-double-dose regimen of a recombinant HBV vaccine increased response rates and determined higher antibody titers which may translate in prolonged protection against HBV. Inclusion of a fourth dose of HBV vaccine for HIV-infected subjects should be considered in the public health setting.

Extensive Mycobacterium tuberculosis circulation in a highly endemic prison and the need for urgent environmental interventions.

Aimed at assessing the circulation of Mycobacterium tuberculosis in a highly endemic prison, this 13-month prospective study was performed on strains isolated from tuberculosis (TB) cases detected passively and actively. We used X-ray screening of newly admitted inmates and mass screening at the beginning of the study and again 1 year later. Of the 94 strains genotyped by restriction fragment-length polymorphism, 79 (84·0%) belonged to one of the 12 identified clusters (2-21 strains each), including two main clusters (18 and 21 cases, respectively). A history of TB treatment was reported in 22/79 (27·8%) clustered cases. Time-space distribution of clustered cases was predominantly consistent with transmission, in micro-epidemics. Given the dominant pattern of exogenous infection and the extensive strain circulation, effective TB control should emphasize reduction of overcrowding and improvement of environmental measures as a complement to detection and treatment of cases.

High rates of serological response to a modified hepatitis B vaccination schedule in HIV-infected adults subjects.

We evaluated a modified HBV regimen in a cohort of HIV-infected subjects in Rio de Janeiro, Brazil. HIV-infected subjects with no serologic evidences of previous hepatitis B infection were immunized with 4 doses (40 microg each) of recombinant hepatitis B vaccine given at 0, 1, 2 and 6 months. Blood samples were collected 1 month after the last dose and anti-HBs titers were measured. A protective antibody response was defined as an anti-HBs titer >or=10 mIU/mL. Forty-seven subjects (30 women, 17 men; mean age was 36 years, ranging from 21 to 58 years) were included in the final analysis. Median baseline CD4+ lymphocyte count was 402 cells/mm(3) and 33 subjects (70%) had an HIV viral load below 80 copies/mL. A protective antibody response was observed in 42 (89%) subjects. Thirty-seven (78%) and 28 (60%) patients developed anti-HBs titers higher than 100 mIU/mL and 1000 mIU/mL, respectively. 1 out of 5 non-responders (20%) had an HIV viral load below the detection limit, in contrast with 32 (76%) of those with an adequate serologic response (p=0.02). These findings suggest that 4-double dose alternative schedule may be considered to overcome the lower seroconversion rates observed with the standard regimens in HIV-infected subjects.

Effectiveness of BCG vaccination among leprosy contacts: a cohort study.

The study assessed the effectiveness of BCG vaccination against leprosy among the contacts of 1161 leprosy patients at the FIOCRUZ Leprosy Outpatient Clinic, RJ, Brazil, from June 1987 to December 2006. Following National Leprosy Program guidelines, the clinic has administered one-to-two doses to all healthy contacts since 1991. Among the 5680 contacts, 304 (5.4%) already had leprosy. Of the 5376 eligible healthy contacts, 3536 were vaccinated, 30 of whom were excluded due to previous or current tuberculosis, or HIV. In 18 years of follow up, 122 (2.15%) incident cases were diagnosed (58 vaccinated and 64 not), 28 occurring in the first year of follow up (21 vaccinated, 16 with no scar). The protection conferred by BCG was 56% and was not substantially affected by previous BCG vaccination (50% with a scar and 59% without). The risk of tuberculoid leprosy during the initial months was high among those vaccinated with no scar. However, it had substantially declined by the first year and in the following years, when the protection rate in this group reached 80%. Since Brazil is endemic for leprosy and the detection rate is not declining satisfactorily, vaccinating all contacts could be an effective means of substantially reducing the incidence of leprosy.

Risk of tuberculous infection in an indigenous population from Amazonia, Brazil.

SETTING: Suruí Indians, Amazonia, Brazil. OBJECTIVE: To estimate the prevalence and the annual risk of infection (ARI) of tuberculosis (TB) in an indigenous population in Brazil. METHODS: We applied a method to estimate the prevalence of TB infection in populations with high bacille Calmette-Guérin (BCG) vaccine coverage. The method consisted of comparing levels of skin test reactivity in individuals tested with purified protein derivative (PPD) before and after stimulation with intradermal BCG. Fieldwork was carried out among the Suruí Indians (n = 993) in two phases, 3 months apart. RESULTS: A total of 645 subjects were tested. In pre-BCG revaccination, tuberculin skin test (TST) indurations averaged 5.9 mm (33.5% > or =10 mm). In post-BCG revaccination TST, indurations averaged 9.4 mm (48.7% > or =10 mm). Conversion from non-reactor to reactor was 54.4%. The ARI ranged from 1.2% to 2.2%. In the logistic regression, age and history of TB were the strongest independent predictors of TB infection. BCG scar and the number of individuals per house were also associated with infection. CONCLUSION: Tuberculous transmission is very high in the Suruí, surpassing the ARI reported for Brazil (0.6%). The epidemiology of TB in this indigenous population is related to unfavourable social and economic conditions, as well as to deficient health care services.

Tuberculin reactivity and tuberculosis epidemiology in the Pakaanóva (Wari') Indians of Rondônia, south-western Brazilian Amazon.

OBJECTIVE: To investigate the characteristics of tuberculin skin test reactivity in the Pakaanóva Indians, in Amazonia, Brazil, after revaccination of all study participants with bacille Calmette-Guerin (BCG). METHODS: The investigation was designed as a post-BCG vaccination purified protein derivative (PPD) survey. Data included PPD readings, age, sex, nutritional status, place of residence, previous tuberculosis, physical examinations and BCG status. Bivariate and multivariate logistic regression analyses were conducted. RESULTS: About 90% (n = 505) of the total population participated. One third (32.1%) of the subjects presented induration > or = 10 mm at 72 h. Induration sizes showed weak linear correlation with age; differences between sexes were not observed. Skin reaction was not associated with nutritional status. Individuals with a history of tuberculosis were six times more likely to test positive. History of tuberculosis, age, and previous BCG vaccination were significantly associated with PPD reactivity in the multivariate analyses. CONCLUSION: The Pakaanóva showed a high proportion (58.4%) of non-reactors, even with a recent BCG booster. Sex differences in PPD reactivity were either not present or could not be demonstrated. The association between age and PPD reactivity resembles that observed in other Amazonian populations. The authors discuss the potential of PPD testing as a screening tool to enhance tuberculosis detection, especially in indigenous populations in Amazonia with limited access to health services.

Use of RT-PCR on oral fluid samples to assist the identification of measles cases during an outbreak.

This study investigated the occurrence of mild modified measles cases during an outbreak in Niterói, RJ, Brazil by using RT-PCR on oral fluid samples. From August to December 1997 a total of 76 patients with rash were seen at the study sites. Confirmed diagnosis by serology was achieved in 47 cases: measles (39.5%), rubella (13.2%), HHV-6 (3.9%), human parvovirus B19 (3.9%), dengue fever (3%). For 19 of the 29 patients without a conclusive diagnosis paired serum and saliva samples were available for further tests. In four of them, measles virus RNA was detected by RT-PCR in saliva samples in the absence of specific IgM in serum samples. Vaccination histories obtained from three of the RT-PCR positive cases showed that individuals previously immunized can still be infected and contribute to the circulation of measles virus. This study demonstrated the usefulness of RT-PCR on non-invasive clinical samples for the investigation of measles cases.