Studies of the optimal case management of acute respiratory infections, appropriate for aid posts, health centres and hospitals, and investigations of the most relevant clinical signs, and the capacity of health staff to elicit them, have been undertaken over many years in close collaboration with doctors and nurses working in the Goroka Base Hospital. These studies have influenced the standard management of acute respiratory infection (ARI) in PNG and, through the World Health Organization (WHO), elsewhere in the tropical world.

A multivalent pneumococcal polysaccharide vaccine is available against 23 serotypes of pneumococcus. Previous studies in Tari had shown that pneumococcal vaccine reduced the mortality from pneumonia in adults.

One of the first aims of the pneumonia research program was therefore to test the pneumococcal vaccine in children and mothers, in an attempt to reduce the serious morbidity and mortality from pneumonia in young children. The trial in children was carried out in Tari and the Asaro Valley. The trial demonstrated the efficacy of the vaccine in preventing death from pneumonia in children under 5 years of age, with a 59% reduction in mortality. In children aged less than 2 years the efficacy was 50% and there was a 25% reduction in all deaths in this age group. Analysis of the effect on morbidity has shown a reduction in severe (but not mild) disease by the vaccine, clearly demonstrated during epidemic periods of acute respiratory infection. The immune responses to pneumococcal polysaccharides in young children were shown to increase with age and to be serotype dependent; there was no general threshold at 18 months or any other age and with the most immunogenic serotypes responses were detected as early as 6 months of age.

The major needs now are to evaluate the vaccine in other communities within Papua New Guinea, especially in coastal areas, with epidemiological characteristics which would predict a similar impact of the vaccine, and to work towards securing the vaccine at a unit cost which we can afford. For this to be achieved it will be necessary for the study to be replicated in other tropical countries. The campaign to promote these results in international meetings and through the World Health Organization has been a long one and still continues.

Evaluation of the effectiveness of the vaccine when distributed through the health services and further immunogenicity studies have been conducted in Tari. Conjugate pneumococcal vaccines (in which each serotypic polysaccharide is conjugated to a protein carrier), which are more immunogenic in infants, are being developed overseas and should eventually become available; but they will be made for only a limited number of serotypes and will be very expensive. Nevertheless, it is hoped to undertake studies on these vaccines in the future. Since pneumonia is such a serious and common disease, worldwide, even a vaccine of modest efficacy can have a profound effect in terms of the number of lives saved; furthermore, the cost of an effective vaccine should be subsidized by the international programs and agencies which promote the immunization of the world's children.

An alternative approach to protecting young infants from pneumonia is to immunize mothers with the 23-valent pneumococcal vaccine in the third trimester of pregnancy. A study to evaluate this approach has been carried out in Tari; preliminary analysis of the serological immune status of the children of vaccinated mothers compared to controls supports the idea of maternal immunization and justifies a trial of its efficacy. The laboratory assays of the breastmilk samples from the study have recently been started.

Haemophilus influenzae is the other major cause of pneumonia in children; the aetiological studies in Goroka have shown that many invasive strains are non-serotypable (non-capsulated). Nevertheless, an effective vaccine against type b organisms alone would protect against the most serious forms of Haemophilus infection, especially meningitis, and conjugate vaccines against Haemophilus influenzae type b (Hib) are available. Immunogenicity studies of two types of Hib vaccine carried out in Goroka have shown that the vaccines are immunogenic and safe in Papua New Guinean children. The campaign to promote the use of Hib vaccine in PNG and obtain it through WHO at an affordable price continues.

Longitudinal studies have been conducted in village communities on the respiratory carriage of pathogenic bacteria and viruses and on the factors which enhance the severity of acute respiratory infection. The organisms are known to be widespread, and one of the major questions is why certain individuals develop severe or fatal pneumonia. Studies on host factors, immunological, nutritional and genetic, have been undertaken in the study populations. Poor nutritional status and low levels of pneumococcal antibody have been shown to increase the risk of children getting moderate or severe pneumonia; and malnourished children have an increased chance of dying of the disease. The immune status of young children and the generally low level of cell-mediated immune responses in the population have been investigated. Transmission studies are planned which will investigate the ecology of the organisms in the village environment in more detail. Studies on chronic lung disease in adults have shown that patients have very heavy carriage loads of pathogenic bacteria and this provides an obvious source of infection for young children living in the same household. An oral haemophilus vaccine has given encouraging results in reducing morbidity and bacterial carriage when tested in these adult patients; and preliminary evidence suggests that its use might also reduce household transmission of respiratory bacteria. Many patients with chronic lung disease have a hyperreactive component as well as obstruction and infection, and their symptoms are helped to some extent by the bronchodilating treatment given for asthma.

A study of neonatal infections (which have a different aetiology from those in older infants) has been conducted in the Goroka Base Hospital, with funding from the World Health Organization, as part of a coordinated global study. Preliminary results indicate the importance of pneumococcus, other streptococci, staphylococcus, respiratory syncytial virus and chlamydia (for both conjunctivitis and pneumonia) as causes of infection in young infants.

The pneumonia research program exemplifies the general approach taken by the Institute to the study of a major disease. An epidemiological study in a well-defined community is supported by laboratory studies of the aetiology and pathogenesis of the disease; both the causative organisms (together with vectors and intermediate hosts, if any) and the human host factors are considered, with an investigation of the place of these organisms and factors in the local ecosystem; and a novel intervention is evaluated as soon as possible in the course of the study. At the same time the health care sought, both traditional and western, is documented, and the effectiveness of such care in handling the disease problem under study is evaluated. Such a research program is multifaceted and requires careful integration; it also needs a relatively large staff, hard work, good funding - and time. We believe that all these are required in studying the major diseases of the tropical world if we are ever to achieve the desired practical outcomes. Moreover, if the results of such research are to be applied generally within Papua New Guinea - as is the intention - then the conditions under which particular causes operate or an intervention program proves successful must be known in detail, so that the new methods can be modified in appropriate ways when they are applied in different areas.

Another respiratory disease which the Institute is studying is asthma. Asthma was a new disease to the highlands of Papua New Guinea in 1970 when the first case in the Okapa area was diagnosed. It has since become highly prevalent in adults in some, but by no means all, parts of the rural highlands. It is being investigated to determine its nature and cause in the hope that this knowledge will lead to methods of preventing the disease, which is severe and often fatal. Reduction in exposure to house dust mite through spraying of blankets has been shown to reduce episodes of asthma and improve lung function. This may also be achieved through the regular airing and washing of blankets, though paradoxically it is hard to maintain compliance with such a simple intervention. Studies on the best method of treatment of asthma in village communities have also been undertaken; unfortunately, it has proved difficult for the health services to provide a sufficient supply of metered aerosol treatment to those living in the more remote places where the disease is prevalent. A new finding of considerable interest has been the fall in incidence of the disease in the study area in the last few years, for which there is no ready explanation. In contrast to the increasing asthma associated with expanding urbanization in PNG, which characteristically begins in childhood, the rural asthma of the highlands has been confined to adults.

Measles is a common respiratory infection in children and evaluation of a heat-stable measles vaccine was conducted by the Institute before measles vaccination was introduced into routine childhood immunizations in Papua New Guinea. Maternally derived immunity to measles has been shown in PNG to have declined significantly by the age of 4 months, when many infants become both susceptible to severe and fatal measles and capable of making a good response to vaccination. As a result of these studies it has now become national policy to vaccinate against measles from the age of 6 months. After a disturbingly high incidence of subacute sclerosing panencephalitis (SSPE), the delayed, `slow virus' form of measles, was found in a number of provincial hospitals, its epidemiology was investigated in Goroka. The disease can only be prevented by early immunization with a potent measles vaccine. The responsibility for the surveillance of SSPE has now been handed over to the Central Public Health Laboratory. Further molecular studies of SSPE, which in PNG has now unfortunately reached the highest reported incidence in the world, are continuing in collaboration with colleagues in Japan.

Another respiratory virus of importance is influenza. The Institute is the National Reference Centre for Influenza, but lack of resources and the failure of other centres to send in samples have made its function dormant; however, it could readily be stirred to action if a new epidemic arose.

The Institute is not carrying out research on tuberculosis, for which methods of control and treatment regimens have been well established. However, because of its public health importance as a cause of mortality, and its association with AIDS, new approaches to the prevention and treatment of tuberculosis developed elsewhere are being kept under close scrutiny.