Alzheimer's disease: is a vaccine possible?

The cause of Alzheimer's disease is still unknown, but the disease is distinctively characterized by the accumulation of β-amyloid plaques and neurofibrillary tangles in the brain. These features have become the primary focus of much of the research looking for new treatments for the disease, including immunotherapy and vaccines targeting β-amyloid in the brain. Adverse effects observed in a clinical trial based on the β-amyloid protein were attributed to the presence of the target antigen and emphasized the relevance of finding safer antigen candidates for active immunization. For this kind of approach, different vaccine formulations using DNA, peptide, and heterologous prime-boost immunization regimens have been proposed. Promising results are expected from different vaccine candidates encompassing B-cell epitopes of the β-amyloid protein. In addition, recent results indicate that targeting another protein involved in the etiology of the disease has opened new perspectives for the effective prevention of the illness. Collectively, the evidence indicates that the idea of finding an effective vaccine for the control of Alzheimer's disease, although not without challenges, is a possibility.

A glycoprotein E gene-deleted bovine herpesvirus 1 as a candidate vaccine strain

A bovine herpesvirus 1 (BoHV-1) defective in glycoprotein E (gE) was constructed from a Brazilian genital BoHV-1 isolate, by replacing the full gE coding region with the green fluorescent protein (GFP) gene for selection. Upon co-transfection of MDBK cells with genomic viral DNA plus the GFP-bearing gE-deletion plasmid, three fluorescent recombinant clones were obtained out of approximately 5000 viral plaques. Deletion of the gE gene and the presence of the GFP marker in the genome of recombinant viruses were confirmed by PCR. Despite forming smaller plaques, the BoHV-1△gE recombinants replicated in MDBK cells with similar kinetics and to similar titers to that of the parental virus (SV56/90), demonstrating that the gE deletion had no deleterious effects on replication efficacy in vitro. Thirteen calves inoculated intramuscularly with BoHV-1△gE developed virus neutralizing antibodies at day 42 post-infection (titers from 2 to 16), demonstrating the ability of the recombinant to replicate and to induce a serological response in vivo. Furthermore, the serological response induced by recombinant BoHV-1△gE could be differentiated from that induced by wild-type BoHV-1 by the use of an anti-gE antibody ELISA kit. Taken together, these results indicated the potential application of recombinant BoHV-1 △gE in vaccine formulations to prevent the losses caused by BoHV-1 infections while allowing for differentiation of vaccinated from naturally infected animals.

Dengue in the South-eastern region of Brazil: historical analysis and epidemiology

The aim of the study is an historical analysis of the work undertaken by the Public Health organizations dedicated to the combat of the Aedes aegypti, as well as an epidemiolocal study of persons with unexplained fever, with a view to evaluating the ocurrence of dengue within the population. The Mac-Elisa, Gac-Elisa, hemaglutination inhibition, isolation and typage tests were used. Organophosphate intoxication in agricultural workers was also assessed by measuring concentrations of serie cholinesterase. A sera samples of 2,094 were collected in 23 towns, and the type 1 dengue virus was detected in 17 towns and autochthony was confirmed in 12 of them. The cholinesterase was measured in 2,391 sera samples of which 53 cases had abnormal levels. Poisoning was confirmed in 3 cases. Results reveal an epidemic the gravity of which was not officially know. The relationshipe between levels of IgM and IgG antibodies indicates the outbreak tendency. The widespread distribution of the vector is troubling because of the possibility of the urbanization of wild yellow fever, whereas the absence of A. aegypti in 2 towns with autochthony suggests the existence of another vector. Since there is no vaccine against dengue, the combat of the vector is the most efficient measure for preventing outbreaks. The eradication of the vector depends on government decisions which depend, for their execution, on the organization of the Health System and the propagation of information concerning the prevention of the disease using all possible means because short and long term results depend on the education and the active participation of the entire population.

Age transition of tuberculosis incidence and mortality in Brazil

OBJECTIVE: Before the Aids pandemic, demographic transition and control programs prompted a shift in the age of incidence of tuberculosis from adults to older people in many countries. The objective of the study is to evaluate this transition in Brazil. METHODS: Tuberculosis incidence and mortality data from the Ministry of Health and population data from the Brazilian Bureau of Statistics were used to calculate age-specific incidence and mortality rates and medians. RESULTS: Among reported cases, the proportion of older people increased from 10.5% to 12% and the median age from 38 to 41 years between the period of 1986 and 1996. The smallest decrease in the incidence rate occurred in the 30--49 and 60+ age groups. The median age of death increased from 53 to 55 years between 1980 and 1996. The general decline in mortality rates from 1986 to 1991 became less evident in the 30+ age group during the period of 1991 to 1996. A direct correlation between age and mortality rates was observed. The largest proportion of bacteriologically unconfirmed cases occurred in older individuals. CONCLUSIONS: The incidence of tuberculosis has begun to shift to the older population. This shift results from the decline in the annual risk of infection as well as the demographic transition. An increase in reactivation tuberculosis in older people is expected, since this population will grow from 5% to 14% of the Brazilian population over the next 50 years. A progressive reduction in HIV-related cases in adults will most likely occur. The difficulty in diagnosing tuberculosis in old age leads to increased mortality.

Cytomegalovirus seroepidemiology in an urban community of São Paulo, Brazil

INTRODUCTION: After the era of rubella vaccine, cytomegalovirus (CMV) infection is one of the most frequently causes of mental retardation and congenital deafness. Seroepidemiological studies are necessary to understand the transmission dynamics of the disease. The purpose of the study was to quantify the transmission rate of CMV disease in a community in the state of São Paulo, Brazil. METHODS: Using ELISA test (IgG), a retrospective serological survey looking for CMV antibodies was performed in an non-immunized community. Frozen sera from 443 individuals, randomly selected by cluster sampling technique in the town of Caieiras, São Paulo, were collected from November 1990 to January 1991. Seroprevalence was stratified by age (0-40 years). Mathematical techniques were applied to determine the age-dependent decay function of maternal antibodies during the first year of life, the age-dependent seroprevalence function and the force of infection for CMV in this community. RESULTS: It was observed a descending phase of seropositivity in the first 9 months, but changes in antibody titration were observed between 8 months old and one year of age. The average age of the first infection was 5.02 months of age and 19.84 years, when the age-dependent seroprevalence and the force of infection were analyzed between 10 months of age and 10 years of age and from 10 to 40 years old, respectively. CONCLUSION: CMV infection is highly prevalent among the population studied and infection occurs in the first year of life. This study shows that most women at reproductive age are vulnerable to the first infection, increasing the risk for congenital infection.

Epidemiology of bacterial meningitis among children in Brazil, 1997-1998

OBJECTIVE: To document the incidence and the descriptive epidemiology of bacterial meningitis among individuals under age 20 in a geographically defined region in Brazil during the two-year period immediately preceding the introduction of Haemophilus influenzae type b (Hib) vaccines into the national immunization program of Brazil. METHODS: Population-based epidemiological study of all cases of bacterial meningitis reported among residents of Campinas, Brazil, under age 20 (n=316,570) during the period of 1997-98, using comprehensive surveillance records compiled by the Campinas Health Department from cases reported among hospital inpatients, outpatients, emergency room visits, death certificates, and autopsy reports. RESULTS: The incidence of bacterial meningitis (n=274) was 334.9, 115 and 43.5 cases/10(5) person-years (pys) for residents of Campinas under age 1, 5 and 20, respectively. All cases were hospitalized, with an average length of stay of 12 days. Documented prior antibiotic use was 4.0%. The case-fatality rate of bacterial meningitis in individuals under age 20 was 9% (24/274) with 75% of deaths occurring in children under the age of five. The incidence of Hib meningitis (n=26) was 62.8 and 17 cases/10(5) pys in children age <1 and <5, respectively. CONCLUSIONS: The incidence of Hib meningitis in children under the age of 5 in Campinas during 1997-98 was similar to that reported in the US, Western Europe, and Israel prior to widespread Hib vaccine use in those regions. This study provides a baseline for later studies to evaluate changes in the etiology and incidence of bacterial meningitis in children after introduction of routine Hib vaccination in Brazil.

Rash after measles vaccination: laboratory analysis of cases reported in São Paulo, Brazil

OBJECTIVE: The clinical differential diagnosis of rash due to viral infections is often difficult, and misdiagnosis is not rare, especially after the introduction of measles and rubella vaccination. A study to determine the etiological diagnosis of exanthema was carried out in a group of children after measles vaccination. METHODS: Sera collected from children with rash who received measles vaccine were reported in 1999. They were analyzed for IgM antibodies against measles virus, rubella virus, human parvovirus B19 (HPV B19) using ELISA commercial techniques, and human herpes virus 6 (HHV 6) using immunofluorescence commercial technique. Viremia for each of those viruses was tested using a polimerase chain reaction (PCR). RESULTS: A total of 17 cases of children with exanthema after measles immunization were reported in 1999. The children, aged 9 to 12 months (median 10 months), had a blood sample taken for laboratory analysis. The time between vaccination and the first rash signs varied from 1 to 60 days. The serological results of those 17 children suspected of measles or rubella infection showed the following etiological diagnosis: 17.6% (3 in 17) HPV B19 infection; 76.5% (13 in 17) HHV 6 infection; 5.9% (1 in 17) rash due to measles vaccine. CONCLUSIONS: The study data indicate that infection due to HPV B19 or HHV 6 can be misdiagnosed as exanthema due to measles vaccination. Therefore, it is important to better characterize the etiology of rash in order to avoid attributing it incorrectly to measles vaccine.

Dengue and the risk of urban yellow fever reintroduction in São Paulo State, Brazil

OBJECTIVE: To propose a mathematical method for the estimation of the Basic Reproduction Number, R0, of urban yellow fever in a dengue-infested area. METHODS: The method is based on the assumption that, as the same vector (Aedes aegypti) causes both infections, all the quantities related to the mosquito, estimated from the initial phase of dengue epidemic, could be applied to yellow fever dynamics. It is demonstrated that R0 for yellow fever is, on average, 43% lower than that for dengue. This difference is due to the longer dengue viremia and its shorter extrinsic incubation period. RESULTS: In this study the analysis was expanded to the epidemiological situation of dengue in São Paulo in the year 2001. The total number of dengue cases increased from 3,582 in 2000 to 51,348 in 2001. It was then calculated R0 for yellow fever for every city which have shown R0 of dengue greater than 1. It was also estimated the total number of unprotected people living in highly risky areas for urban yellow fever. CONCLUSIONS: Currently there is a great number of non-vaccinated people living in Aedes aegypti infested area in the state of São Paulo.