Dengue vaccines: what we know, what has been done, but what does the future hold?

Dengue, a disease caused by any of the four serotypes of dengue viruses, is the most important arthropod-borne viral disease in the world in terms of both morbidity and mortality. The infection by these viruses induces a plethora of clinical manifestations ranging from asymptomatic infections to severe diseases with involvement of several organs. Severe forms of the disease are more frequent in secondary infections by distinct serotypes and, consequently, a dengue vaccine must be tetravalent. Although several approaches have been used on the vaccine development, no vaccine is available against these viruses, especially because of problems on the development of a tetravalent vaccine. Here, we describe briefly the vaccine candidates available and their ability to elicit a protective immune response. We also discuss the problems and possibilities of any of the vaccines in final development stage reaching the market for human use.

Reproductive isolation between different forms of Lutzomyia longipalpis (Lutz & Neiva), (Diptera: Psychodidae), the vector of Leishmania donovani chagasi Cunha & Chagas and its significance to kala-azar distribution in South America

The males of the sandfly Lutzomyia longipalpis occur in two forms, one which bears a single pair of pale spots on tergite 4 and another in which an additional pair of spots characterizes tergite 3. In crosses between laboratory reared stocks of the two forms originating from allopatric and sympatric sites in Brazil nearly all males of one form fail to inseminate females of the other. In addition, insemination failure between some allopatric populaytions of Lu. longipalpis with similar tergal spot patterns is recorded, indicating the existence of additional forms in an apparent species complex. The possibility that Lu. longipalpis sensu latu represents more than a single taxon is discussed and the relevance of these findings to future epidemiological studies on kala-azar is considered.

Ki-67 is expressed in multiplying forms of Schistosoma mansoni, but not in snail host tissues

Ki-67 is a protein expressed in the nucleus of several species during cell-division, being absent during the GO resting phase of the cellular cycle. During attempts to disclose mitosis in the so-called " amebocyte-producing organ " in Biomphalaria glabrata infected with Schistosoma mansoni, the parasite multiplying forms appeared strongly marked for Ki-67, while the snail tissues were completely negative. These data are worth registering to complement general data on Ki-67, and to help future studies on the relationship of the parasite and of its intermediate host.

Towards an uncertain future? The strengthening of Japan's autonomy in Asia-Pacific

Recently, Japan has been increasing tensions with China regarding the Pinnacle Senkaku/Diaoyu islands. Due to the Chinese military development, Japan has been working on its political and military strengthening in Asia. This essay presents two possible scenarios for Japan.

Mortality problems in Brazil and in Germany: past-present-future. Learning from each other?

This article was written by a Swiss-German historical demographer after having visited different Brazilian Universities in 1984 as a guest-professor. It aims at promoting a real dialog between developed and developing countries, commencing the discussion with the question: Can we learn from each other? An affirmative answer is given, but not in the superficial manner in which the discussion partners simply want to give each other some "good advice" or in which the one declares his country's own development to be the solely valid standard. Three points are emphasized: 1. Using infant mortality in S. Paulo from 1908 to 1983 as an example, it is shown that Brazil has at its disposal excellent, highly varied research literature that is unjustifiably unknown to us (in Europe) for the most part. Brazil by no means needs our tutoring lessons as regards the causal relationships; rather, we could learn two things from Brazil about this. For one, it becomes clear that our almost exclusively medical-biological view is inappropriate for passing a judgment on the present-day problems in Brazil and that any conclusions so derived are thus only transferable to a limited extent. For another, we need to reinterpret the history of infant mortality in our own countries up to the past few decades in a much more encompassing "Brazilian" sense. 2. A fruitful dialog can only take place if both partners frankly present their problems. For this reason, the article refers with much emprasis to our present problems in dealing with death and dying - problems arising near the end of the demographic and epidemiologic transitions: the superanuation of the population, chronic-incurable illnesses as the main causes of death, the manifold dependencies of more and more elderly and really old people at the end of a long life. Brazil seems to be catching up to us in this and will be confronted with these problems sooner or later. A far-sighted discussion already at this time seems thus to be useful. 3. The article, however, does not want to conclude with the rather depressing state of affairs of problems alternatingly superseding each other. Despite the caution which definitely has a place when prognoses are being made on the basis of extrapolations from historical findings, the foreseeable development especially of the epidemiologic transition in the direction of a rectangular survival curve does nevertheless provide good reason for being rather optimistic towards the future: first in regards to the development in our own countries, but then - assuming that the present similar tendencies of development are stuck to - also in regard to Brazil.

Two-year follow-up study of elderly residents in S. Paulo, Brazil: methodology and preliminary results

INTRODUCTION: Previous cross-sectional studies have shown a high prevalence of chronic disease and disability among the elderly. Given Brazil’s rapid aging process and the obvious consequences of the growing number of old people with chronic diseases and associated disabilities for the provision of health services, a need was felt for a study that would overcome the limitations of cross-sectional data and shed some light on the main factors determining whether a person will live longer and free of disabling diseases, the so-called successful aging. The methodology of the first follow-up study of elderly residents in Brazil is presented. METHOD: The profile of the initial cohort is compared with previous cross-sectional data and an in-depth analysis of nonresponse is carried out in order to assess the validity of future longitudinal analysis. The EPIDOSO (‘Epidemiologia do Idoso’) Study conducted a two-year follow-up of 1,667 elderly people (65+), living in S. Paulo. The study consisted of two waves, each consisting of household, clinical, and biochemical surveys. RESULTS AND CONCLUSIONS: In general, the initial cohort showed a similar profile to previous cross-sectional samples in S. Paulo. There was a majority of women, mostly widows, living in multigenerational households, and a high prevalence of chronic illnesses, psychiatric disturbances, and physical disabilities. Despite all the difficulties inherent in follow-up studies, there was a fairly low rate of nonresponse to the household survey after two years, which did not actually affect the representation of the cohort at the final household assessment, making unbiased longitudinal analysis possible. Concerning the clinical and blood sampling surveys, the respondents tended to be younger and less disabled than the nonrespondents, limiting the use of the clinical and laboratory data to longitudinal analysis aimed at a healthier cohort. It is worth mentioning that gender, education, family support, and socioeconomic status were not important determinants of nonresponse, as is often the case.

Trypanosoma cruzi prevalence and clinical forms in blood donor candidates in Brazil

The prevalence and clinical forms of Trypanosoma cruzi were evaluated among blood donor candidates attended at a general hospital in Rio de Janeiro, Brazil, from January 1997 to April 1999. The investigation was done by means of the indirect hemagglutination test and was confirmed via ELISA. Data were collected from clinical examinations, conventional electrocardiogram, chest radiography and echocar-diography. The results showed that despite Trypanosoma cruzi prevalence of 1.17% (128 patients), mainly in males aged 40 years or over, 70.8% of these patients, mainly males aged 19 to 39 years, demonstrated abnormalities that allowed the diagnosis of cardiopathy and/or esophagopathy. This once again corroborates the importance of Trypanosoma cruzi infection in urban centers.

Lytic antibodies elicited by Trypanosoma cruzi infection recognize epitopes present on both bloodstream trypomastigote and epimastigote forms of parasite

Sera of Chaga's disease patients containing anti-T. cruzi lytic antibodies were submitted to affinity chromatography using Sepharose 4B conjugated with antigen extracted from epimasiigote or trypomasiigote forms of the parasite. Epimastigotes were obtained from culture at the exponential growth phase and the trypomastigotes from blood of infected and immunosuppressed mice. Antigen of both parasite forms was obtained by sonication of the parasites followed by centrifugation. Both antigens were then conjugated to activated Sepharose 4B. Affinity chromatography was performed by passing sera from chagasic patients through an immunoadsorbent column containing either epimasiigote or trypomasiigote antigens. Antibodies bound to the column were eluted with cold 0,2 M glycine buffer pH 2,8. The eluted antibodies were analysed regarding their isotype and lytic activity. The results showed that anti-T. cruzi lytic antibodies present in sera from chagasic patients are mainly located in the IgG isotype and recognize epitopes present in both trypomasiigote and epimastigote forms. A brief report of this work has already been published12.

Chagas' disease: IgA, IgM and IgG antibodies to T. cruzi amastigote, trypomastigote and epimastigote antigens in acute and in different chronic forms of the disease

In an attempt to find a better T. cruzi antigen and possible immunological markers for the diagnosis of different clinical forms of Chagas' disease, amastigote and trypomastigote antigens obtained from immunosuppressed mice infected with T. cruzi (Y strain) were assessed in comparison with conventional epimastigote antigens. A total of 506 serum samples from patients with acute and with chronic (indeterminate, cardiac and digestive) forms, from nonchagasic infections, and from healthy individuals were assayed in immunofluorescence (IF) tests, to search for IgG, IgM and IgA antibodies. Amastigote proved to be the most convenient antigen for our purposes, providing higher relative efficiency indexes of 0.946, 0.871 and 0.914 for IgG, IgM and IgA IF tests, respectively. Anti-amastigote antibodies presented higher geometric mean titers (GMT) than anti-trypomastigote and anti-epimastigote. Anti-amastigote IgG antibodies were found in all forms of Chagas' disease, and predominantly IgA antibodies, in chronic digestive and in acute forms, as well as IgM antibodies, in latter forms. Thus, tests with amastigote antigen could be helpful for screening chagasic infections in blood banks. Practical and economical aspects in obtaining amastigotes as here described speak in favour of its use in developing countries, since those from other sources require more complex system of substruction, specialized personnel or equipment.

In vitro action of some disinfectants on Paracoccidioides brasiliensis yeast forms

The fungicidal action of sodium hypochlorite (0.3, 1, 2.5, 5 and 10%); formaldehyde (2, 5, and 10%); and ethyl alcohol (70%) on yeast forms of Paracoccidioides brasiliensis Pb 18 and a newly-isolated Goiana strain was described. Contact between the fungus and the disinfectants was maintained for 1, 2, 24, 48 and 72 hours at room temperature. Viability was evaluated by the fluorescein diacetate-ethidium bromide treatment, culture in solid and liquid media (36ºC and 26ºC); yeast to mycelial germination at room temperature; and radiometric study of metabolic activity. All concentrations of disinfectants were found to be effective in inactivating Pb 18 and Goiana strains, except for the 1-hour contact with 2% formaldehyde, in which fluorescein diacetate-ethidium bromide treatment was found to reveal 40 and 27% of viable cells, respectively. The yeast to mycelial germination method was considered to reveal faster and similar results as compared to culture in solid and liquid media.