Vibrio cholerae 638 is a living candidate cholera vaccine strain attenuated by deletion of the CTX⌽ prophage from C7258 (O1, El Tor Ogawa) and by insertion of the Clostridium thermocellum endoglucanase A gene into the hemagglutinin/protease coding sequence. This vaccine candidate was previously found to be well tolerated and immunogenic in volunteers. This article reports a randomized, double-blind, placebo-controlled trial conducted to test short-term protection conferred by 638 against subsequent V. cholerae infection and disease in volunteers in Cuba. A total of 45 subjects were enrolled and assigned to receive vaccine or placebo. The vaccine contained 10 9 CFU of freshly harvested 638 buffered with 1.3% NaHCO 3 , while the placebo was buffer alone. After vaccine but not after placebo intake, 96% of volunteers had at least a fourfold increase in vibriocidal antibody titers, and 50% showed a doubling of at least the lipopolysaccharide-specific immunoglobulin A titers in serum. At 1 month after vaccination, five volunteers from the vaccine group and five from the placebo group underwent an exploratory challenge study with 10 9 CFU of ⌬CTX⌽ attenuated mutant strain V. cholerae 81. Only two volunteers from the vaccine group shed strain 81 in their feces, but none of them experienced diarrhea; in the placebo group, all volunteers excreted the challenge strain, and three had reactogenic diarrhea. An additional 12 vaccinees and 9 placebo recipients underwent challenge with 7 ؋ 10 5 CFU of virulent strain V. cholerae 3008 freshly harvested from a brain heart infusion agar plate and buffered with 1.3% NaHCO 3 . Three volunteers (25%) from the vaccine group and all from the placebo group shed the challenge agent in their feces. None of the 12 vaccinees but 7 volunteers from the placebo group had diarrhea, and 2 of the latter exhibited severe cholera (>5,000 g of diarrheal stool). These results indicate that at 1 month after ingestion of a single oral dose (10 9 CFU) of strain 638, volunteers remained protected against cholera infection and disease provoked by the wild-type challenge agent V. cholerae 3008. We recommend that additional vaccine lots of 638 be prepared under good manufacturing practices for further evaluation.

In the present study the dynamics of antigenemia and coproantigens were studied in patients withFasciola hepatica infection during an outbreak occurring in La Palma, Pinar del Rı́o, in the West Province of Cuba. Stool and serum samples were collected from 67 patients and 40 healthy subjects. Stool samples were studied by a simple gravity sedimentation technique and an ES78 sandwich enzyme-linked immunosorbent assay (ELISA) for observation of eggs and detection of parasite coproantigens, respectively. Serum samples were also studied by the ES78 sandwich ELISA and an indirect ELISA to detect circulating antigens and antibodies, respectively. At the beginning of the study, 8 of 67 patients had patent infections and 59 had prepatent infections, which was determined by the recent consumption of lettuce contaminated with metacercariae of F. hepatica, the presence of clinical symptoms, and the absence of Fasciolaeggs in their stools. Patients with prepatent infections were monitored by all techniques until patency. Circulating antigens were not detected in patients with patent infections. However, coproantigens were clearly detected in all patients with patent infections. On the other hand, 28.8% of patients with prepatent infections tested positive for circulating antigens and 81.4% tested positive for coproantigens in the first stool sample studied. Only two other coproantigen determinations were necessary to diagnose 93.2% of the patients. While circulating antigen levels diminished in all patients during the infection, coproantigen levels increased. The present study demonstrates that the ES78 sandwich ELISA is a better tool than parasitological examination for diagnosis of active early infection, since by the combination of the circulating-antigen detection assay and the coproantigen detection assay 91% of patients were able to be diagnosed at the beginning of the study. In contrast, a coprologic analysis repeated over several weeks was necessary to diagnose 100% of the patients.

BackgroundCommunity 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.MethodsA 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.Results4 798 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. influenzaetype 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. peumoniae and other bacteria with mortality. Seasonality during September, January and March was observed.ConclusionsThe 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. peumoniae.

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.

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.