Communicable diseases: a major burden of morbidity and mortality.

A brief overview of the present situation regarding some of the world's most important diseases is given. Particular mention is made of dengue, yellow fever, malaria and parasitic diseases. Vaccination is concluded to have a major role in combating these diseases.

WHO's vaccine development programme.

The World Health Organization is playing a major international role in encouraging, coordinating, and where appropriate commissioning, research and development activities relevant to the control of high priority infectious diseases. The Expanded Programme on Immunization would be the vehicle for the introduction of new or improved vaccines. In many parts of the developing world the health infrastructure is strained to breaking point by the heavy load of disease. It has failed to make the best use of the already available technology. Immunization provides the simplest, least expensive and most effective intervention technology. Every effort is therefore needed to extend immunization coverage and lighten the burden on the health infrastructure and accelerate the overall development of the vast rural and peri-urban communities in the developing world. WHO has, on the one hand, to call on the most eminent scientists to give effective and simple interventions, and on the other, on the politicians, social leaders, economic managers, medical profession and all public health workers to build up the infrastructure to put intervention technologies into action.

Studies on the congenitally goitrous sheep. Iodoproteins of the goitre.

1. Congenitally goitrous thyroid tissue was obtained from South Australian Merino sheep. Ultrastructural studies of the secretory cells in this tissue showed active cells of normal appearance, containing apical protein droplets. 2. (125)I-labelling in vivo of goitre tissue was used to investigate the iodoproteins, in which the major proportion of (125)I appeared in the cell protein fraction soluble in 0.9% sodium chloride (average 62% in goitres from untreated sheep). 3. Ammonium sulphate fractionation showed two clear peaks of iodoprotein precipitation, one at 35-40% saturation and the other at 50-55% saturation. Both iodoprotein fractions contained iodotyrosines and iodothyronines, which were identified chromatographically after enzymic hydrolysis of the protein. 4. Polyacrylamide-gel electrophoresis at pH9.4, at either 7.5 or 5.0% acrylamide concentration, was used to characterize the iodoproteins. Two major fractions were observed, the fastest-migrating fraction coincident with serum albumin, and a slower-migrating, less-well-defined zone. This fraction migrated in 7.5% acrylamide gel, which excluded normal thyroglobulin. 5. Density-gradient (10-40% sucrose) centrifugation was used to determine the approximate sedimentation coefficients of the iodoproteins, which showed major components at s(20,w) 8-9S and s(20,w)<5S. 6. Immunoprecipitation with rabbit anti-(sheep thyroglobulin) failed to sediment (125)I-labelled proteins from goitre extracts. 7. Ouchterlony-type double diffusion in agar plates demonstrated immunoprecipitation lines between rabbit anti-(sheep thyroglobulin) and both the concentrated goitre extract and its Sephadex G-200-excluded fraction, which were confluent with that obtained on reaction with purified normal thyroglobulin. 8. It was concluded that both major iodoprotein fractions were capable of supplying thyroid hormones to the animal, and that the fraction of s(20,w)<5S was iodinated serum albumin. As (125)I-labelled thyroglobulin was not detected in goitre tissue from untreated or thyroxine-treated animals, it was possible that the genetic defect causing goitre resulted in an abnormal thyroglobulin, incapable of being iodinated but immunologically reactive.

Hidden' IgG antiglobulins in normal human serum.

Hidden antiglobulins reacting with whole rabbit immunoglobulin were found by radioassay or indirect haemagglutination after gel filtration or ultracentrifugation of normal serum. Suprisingly, both the IgM and IgG antiglobulins were present in the same macroglobulin fractions. The IgG antiglobulins could be dissociated into 7S components by separating the serum under acid conditions. Antiglobulin activity was a function of the Fab region.

Virus-associated immunopathology: animal models and implications for human disease. 1. Effects of viruses on the immune system, immune-complex diseases, and antibody-mediated immunologic injury.

The tissue damage caused by virus infection has been traditionally explained by the ability of viruses to multiply in cells and thereby injure or destroy them. Recent evidence suggests, however, that lesions may also be caused by the host's immune response to viral antigens and that the immune system itself may be perturbed by some viruses. This memorandum reviews recent developments in viral immunopathology, with special reference to animal model systems, and indicates the possible relevance of the new concepts and techniques for certain diseases of man. Certain viruses, notably the leukaemia viruses and some of those causing persistent infections, depress the host's ability to mount an antibody response to antigens, while other viruses may enhance the antibody response. Cell-mediated immunity may also be depressed. Another immunopathological manifestation of virus infection is immune-complex disease. When viruses or their antigens persist in the circulation they combine with specific antibody, and the resulting complexes lodge in various sites, especially the kidney. Further combination with complement leads to the release of tissue-damaging substances. A third condition associated with virus infection is antibody-mediated immunologic injury. Both oncogenic and non-oncogenic viruses frequently induce new antigens on the surface of the cells they invade. When antibody attaches to these antigens in the presence of complement, the cells are destroyed.

Virus-associated immunopathology: animal models and implications for human disease. 2. Cell-mediated immunity, autoimmune diseases, genetics, and implications for clinical research.

Part 2 of this memorandum describes further mechanisms whereby the interaction of a virus with the host's immune system may lead to tissue damage. Cell-mediated immunity plays a vital role in promoting recovery from virus infections, but under some circumstances tissue damage may be caused by the reaction of immune cells with viral antigens. When mice are infected with lymphocytic choriomeningitis virus neonatally or as adults while receiving immunosuppressive drugs, widespread invasion of cells is seen but there is little overt disease. If, however, normal adults are infected or if immune cells are transfused into tolerant mice, cell injury and death follow. Viruses have long been suspected of contributing to the pathogenesis of autoimmune diseases. Antibodies directed against normal cell constituents have been reported in several virus infections. Viruses may conceivably unmask or release host antigens, alter host antigens and act as "helper determinants", or perhaps in other ways provoke immune responses against normal body constituents. The immunopathological manifestations caused by viruses may also be influenced by the host's genetic makeup. Certain observations indicate that, in addition to controlling susceptibility to virus infection, genetic factors partly determine the effectiveness of the immune response. The memorandum calls attention to the possible implications of these concepts and findings for clinical research. Some of the diseases of animals and man that serve as models for studies of virus-associated immunopathology are briefly described.