Community acquired bacterial meningitis in Cuba: a follow up of a decade.

BACKGROUND: Community acquired Bacterial Meningitis (BM) remains a serious threat to global health. Cuban surveillance system for BM allowed to characterize the main epidemiological features of this group of diseases, as well as to assess the association of some variables with mortality. Results of the BM surveillance in Cuba are presented in this paper. METHODS: A follow up of BM cases reported to the Institute "Pedro Kourí" by the National Bacterial Meningitis Surveillance System from 1998 to 2007 was completed. Incidence and case-fatality rate (CFR) were calculated. Univariate analysis and logistic regression were used to elucidate associated factors to mortality comparing death versus survival. Relative Risk (RR) or odds ratio and its 95% confidence interval (CI 95%) were estimated, using either a Chi-squared Test or Fisher's Exact Test as appropriate. A Holt-Winters model was used to assess seasonality. RESULTS: 4798 cases of BM (4.3 per 100,000 population) were reported, with a decreasing trend of the incidence. Highest incidence was observed in infants and elderly. Overall CFR reached 24.1% affecting mostly older adults. S. pneumoniae (23.6%), N. meningitidis (8.2%) and H. influenzae type b (6.0%) were the main causative agents. Males predominate in the incidence. Highest incidence and CFR were mainly clustered in the centre of the island. The univariate analysis did not show association between delayed medical consultation (RR = 1.20; CI = 1.07-1.35) or delayed hospitalization (RR = 0.98; CI = 0.87-1.11) and the fatal outcome. Logistic regression model showed association of categories housewife, pensioned, imprisoned, unemployed, S. pneumoniae and other bacteria with mortality. Seasonality during September, January and March was observed. CONCLUSIONS: The results of the National Program for Control and Prevention of the Neurological Infectious Syndrome evidenced a reduction of the BM incidence, but not the CFR. Multivariate analysis identified an association of mortality with some societal groups as well as with S. pneumoniae.

Safety and preliminary immunogenicity of MenC/P64k, a meningococcal serogroup C conjugate vaccine with a new recombinant carrier.

This study reports the preliminary assessment of the safety and immunogenicity of the first serogroup C conjugate vaccine candidate that includes meningococcal P64k recombinant protein as the carrier (MenC/P64k). Twenty volunteers were recruited for a double-blind, randomized, controlled phase I clinical trial, receiving a single dose of MenC/P64k (study group) and a single dose of the commercial polysaccharide vaccine AC (control group). Only mild reactions were observed. No statistical differences were detected between the antipolysaccharide C IgG responses of both groups as well as between bactericidal serum titre (P > 0.05). The MenC/P64k vaccine was found to have a good safety profile, to be well tolerated and immunogenic.

Bacterial meningitis in children and adolescents: an observational study based on the national surveillance system.

BACKGROUND: Bacterial meningitis is a group of life threatening infections that mostly affect children and adolescents, and may be the cause of severe neurological sequelae. Cuba has implemented massive vaccination programmes against both Neisseria meningitidis (serogroup C in 1979 and B in 1987), and Haemophilus influenzae type b (1999), two of the main causal pathogens. We described and discussed some epidemiological aspects of the current status of bacterial meningitis to learn from the Cuban experience. METHODS: A nationwide observational study on children and adolescents from 1 to 18 years old was carried out from 1998 to 2003, estimating the incidence and case-fatality rate by age group and causal pathogens, as well as the seasonality and frequency of overcrowded dormitories. The association between disease and attendance to day care centres or boarding schools was estimated by using relative risk (Chi-squared test and Fisher Exact Test). RESULTS: The overall number of cases was 1023; the incidence ranged from 3.4 to 8.5 per 100,000 population, with the higher figures in children 1-5 years old (16.8 per 100,000 population). Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis serogroup B were the main identified agents. The average case-fatality rate was 10.5% and the most lethal agents were Streptococcus pneumoniae (27%) and Haemophilus influenzae type b (10.7%). Overall percentage of cases who slept in overcrowded dormitories was 15%, reaching 30.6% in adolescents. Seasonality was only evident among meningococcal meningitis cases between September-October. The attendance to boarding high school showed an association with disease only in 1998 and 1999 (RR = 2.1; p > 0.05). CONCLUSION: The highest incidence of bacterial meningitis was observed among children from 1-5 years old. Pneumococcus was both the leading causal and the most lethal agent. Sleeping in overcrowded dormitories was more frequent among adolescents. No strong association was observed between the bacterial meningitis and attendance to day care centres or boarding schools. The incidence of bacterial meningitis in Cuba is declining after massive vaccination programmes against Neisseria meningitidis serogroup B and C and Haemophilus influenzae type b through a national immunisation program.

Meningococcal disease serogroup C.

Despite current advances in antibiotic therapy and vaccines, meningococcal disease serogroup C (MDC) remains a serious threat to global health, particularly in countries in North and Latin America, Europe, and Asia. MDC is a leading cause of morbidity, mortality, and neurological sequelae and it is a heavy economic burden. At the individual level, despite advances in antibiotics and supportive therapies, case fatality rate remains nearly 10% and severe neurological sequelae are frequent. At the population level, prevention and control of infection is more challenging. The main approaches include health education, providing information to the public, specific treatment, chemoprophylaxis, and the use of vaccines. Plain and conjugate meningococcal C polysaccharide vaccines are considered safe, are well tolerated, and have been used successfully for over 30 years. Most high-income countries use vaccination as a part of public health strategies, and different meningococcal C vaccination schedules have proven to be effective in reducing incidence. This is particularly so with conjugate vaccines, which have been found to induce immunogenicity in infants (the age group with the highest incidence rates of disease), stimulate immunologic memory, have longer effects, not lead to hyporesponsiveness with repeated dosing, and decrease acquisition of nasopharyngeal carriage, inducing herd immunity. Antibiotics are considered a cornerstone of MDC treatment and must be administered empirically as soon as possible. The choice of which antibiotic to use should be made based on local antibiotic resistance, availability, and circulating strains. Excellent options for a 7-day course are penicillin, ampicillin, chloramphenicol, and third-generation cephalosporins (ceftriaxone and cefotaxime) intravenously, although the latter are considerably more expensive than the others. The use of steroids as adjunctive therapy for MDC is still controversial and remains a topic of debate. A combination of all of the aforementioned approaches is useful in the prevention and control of MDC, and each country should tailor its public health policy to its own particular needs and knowledge of disease burden.

Impacto de la vacunación contra haemophilus influenzae tipo b en Cuba / Impact of vaccination against haemophilus influenzae type b in Cuba

Objetivo. Determinar el impacto de la vacunación de menores de 2 años en Cuba contra Haemophilus influenzae tipo b (Hib), principal agente causal de la meningitis bacteriana en ese país. Métodos. La disponibilidad de vacunas conjugadas eficaces contra Hib motivó la vacunación nacional en 1999 de niños menores de 2 años, que alcanzó una cobertura de 97%. El impacto se evaluó mediante el Sistema Nacional de Vigilancia de Meningoencefalitis Bacterianas (SNVMEB). Resultados. La eficacia global de la vacunación se estimó en 99% y la incidencia general de la meningoencefalitis por Hib disminuyó de 1,3 a 0,6 por 100 000 habitantes (46,1%), observándose la mayor reducción en niños menores de 5 años (56,1%). En los menores de 1 año se redujo 70,5% y en el resto de los grupos de menores de 5 años disminuyó entre 25,9 y 49,6%. En el grupo diana para la vacunación, la incidencia se redujo 61,1%; entre los niños de este grupo que contrajeron la meningoencefalitis por Hib, solamente 8 (24,2%) estaban vacunados, 7 de ellos con una sola dosis, aplicada 1 mes antes de enfermar. Conclusiones. Se ha demostrado que la vacunación a gran escala de los niños menores de 2 años contra Hib en Cuba a través del SNVMEB ha logrado disminuir notablemente la incidencia de meningoencefalitis por Hib.

Objective. To assess the effectiveness of mass vaccination in Cuba of children under 2 years of age against Haemophilus influenzae type b (Hib), the most common causative pathogen of bacterial meningitis. Methods. The availability of effective Hib conjugate vaccines led to a nationwide vaccination program in 1999 targeting all children under 2 years of age, with a 97% coverage rate achieved. To assess the program's impact, data from 1998 and 1999 from the National Bacterial Meningitis Reporting System were used. Results. Vaccination efficacy was estimated at 99%. The overall incidence of Hib meningitis declined 46.1%, from 1.3 to 0.6 cases per 100 000 population. The greatest overall reduction, of 56.1%, occurred among children under 5 years of age. Among children under 1 year of age, the reduction was 70.5%, and among the rest of the age groups of children under 5, incidence decreased between 25.9% and 49.6%. In the group targeted for vaccination, incidence decreased 61.1%. Among children in the target group who contracted Hib meningitis, only 8 cases (24.2%) had been vaccinated, most with a single dose applied 1 month before becoming ill. Conclusions. Hib vaccination of all children under 2 years of age in Cuba greatly reduced the incidence of Hib meningitis, as measured by the National Bacterial Meningitis Reporting System