Progress in the development of influenza vaccines: Memorandum from a WHO Meeting

Although influenza remains an important disease causing high levels of morbidity in many countries, the impact of epidemics can be reduced by immunoprophylaxis with available inactivated or cold-adapted live attenuated influenza vaccines. In closed or semi-closed communities, maximum benefit from immunization is likely to be achieved when more than 75% of the population are immunized. Other strategies to reduce the impact of influenza include mass immunization of certain populations to protect them as well as to reduce illness in the overall community. Adequate studies have not yet been undertaken to confirm whether the desired reduction in community-wide illnesses results from such target mass immunization programmes. Well-controlled studies to assess further the efficacy of influenza vaccines in not only protecting the vaccinee but also reducing the impact of influenza epidemics in the community should be encouraged.     

Role of non-human primates in malaria vaccine development: Memorandum from a WHO Meeting

This Memorandum discusses the coordination and standardization of malaria vaccine research in non-human primates to encourage optimum use of the available animals in experiments that are fully justified both scientifically and ethically. The requirements for experimentation in non-human primates, the availability of suitable animals for malaria vaccine studies, and the criteria for testing candidate vaccines are considered. The policy and legislation relevant to the use of non-human primates in biomedical research are also briefly discussed. The Memorandum concludes with eight recommendations.     

Development of vaccines against shigellosis: Memorandum from a WHO Meeting

Endemic shigellosis is a worldwide problem, with a high morbidity rate in most developing countries; substantial mortality may also occur, especially with disease caused by Shigella dysenteriae serotype 1. The limited efficacy of current measures to control this infection makes the development of vaccines for the prevention of shigellosis particularly important. This Memorandum describes the clinical features of and immunity to shigellosis, summarizes the present status of efforts to develop suitable vaccines, and lists the topics that should be given priority in research.     

Principles of malaria vaccine trials: Memorandum from a WHO Meeting

The Scientific Working Groups on Immunology of Malaria and on Applied Field Research in Malaria of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases held a joint meeting at WHO headquarters in Geneva, Switzerland, on 4-8 February 1985 to consider the current status of malaria vaccine research. Although experience with vaccines against bacterial and viral infections provides valuable information, the advanced stages of development of malaria vaccines pose entirely new problems calling for the elaboration of guidelines for preclinical studies and vaccine trials. The principal purpose of this meeting was to establish such guidelines.     

Recent advances in cholera research: Memorandum from a WHO Meeting

Vibrio cholerae O1 is an important cause of diarrhoeal disease in large parts of Asia and Africa. The seventh pandemic of cholera is still continuing (92 countries have so far been affected), and other organisms related to V. cholerae O1 are being reported increasingly frequently as the cause of diarrhoeal outbreaks as well as endemic diarrhoea.     

Development of malaria vaccines: Memorandum from a USAID/WHO meeting

The fifth meeting of the Scientific Working Group on the Immunology of Malaria evaluated studies of the production and analysis of defined malarial antigens. Rapid progress has been made in the study of protective antigens on the surface of sporozoites and it is likely that a family of analogous polypeptides occurs in several species of Plasmodium. New assays have been developed for the detection of these antigens and for the detection of infected mosquitos. Exoerythrocytic stages of several parasite species can be cultivated in vitro, providing an assay system for antibody and allowing the characterization of exoerythrocytic stage antigens. Progress has also been made in the identification of species- and stage-specific antigens of the asexual blood stages of rodent, simian, and human malaria parasites. In some instances, protective immunity has been shown to be directed against polypeptides (with a high relative molecular mass) synthesized at a late stage of schizont development. Messenger RNA (mRNA) species from P. knowlesi and P. yoelii have been successfully translated in vitro to give polypeptides with a high relative molecular mass (M_r). Monoclonal antibodies have been used to identify and to purify important parasite antigens and purified P. yoelii antigens induced protective immunity. Monoclonal antibodies reactive with merozoite surface antigens have been used, as well as S-antigens, to distinguish between different isolates of P. falciparum. Recombinant DNA technology is being applied to Plasmodium: differences were found between repetitive DNA sequences from the genome of two isolates of P. falciparum; the genes for ribosomal RNA of P. falciparum and P. yoelii, and sequences homologous to the actin gene were identified in fragments of Plasmodium DNA cloned in prokaryotic vectors; by means of hybrid selection, complementary DNA (cDNA) probes were used to purify mRNAs encoding proteins of P. knowlesi of up to 100 000 M_r.     

New approaches to vaccine development: Memorandum from a WHO Meeting

Recent advances in immunology and cell biology may make it possible to improve existing vaccines and even, in future, to obtain vaccines against complex organisms, such as parasites.     

The epidemiology of drug resistance of malaria parasites: Memorandum from a WHO Meeting

This Memorandum presents current knowledge concerning the epidemiology of drug resistance of malaria parasites and outlines 33 research proposals which could lead to a better understanding of that epidemiology and to a better management of the problem.     

The use of DNA probes for malaria diagnosis: Memorandum from a WHO Meeting

Current progress in the development and potential application of DNA probes for malaria diagnosis was reviewed at an informal WHO Consultation in Geneva in October 1985. The development and use of such probes for malaria diagnosis is based on the premise that within any organism there are unique DNA sequences which differentiate that organism from closely related organisms. DNA probes specific for Plasmodium falciparum have been developed in several laboratories. Their major characteristic is that they are highly repeated within the P. falciparum genome. Their reported sensitivity in laboratory studies of from 5-10 pg to 1 ng DNA, which is equivalent to 10²-10⁴ ring-stage parasites in a single sample, appears to be well within the range of that obtained by standard microscopical diagnosis. The technique, therefore, apparently has potential for operational use. A test based on use of the complete genome of P. falciparum has also been developed, and studies have recently been initiated on the diagnostic application of RNA probes and DNA probes specific for the human malaria parasites.     

Immunodiagnosis simplified: Memorandum from a WHO Meeting

Technologies suitable for the development of simplified immunodiagnostic tests were reviewed by a Working Group of the WHO Advisory Committee on Medical Research in Geneva in June 1983. They included agglutination tests and use of artificial particles coated with immunoglobulins, direct visual detection of antigen-antibody reactions, enzyme-immunoassays, and immunofluorescence and fluoroimmunoassays. The use of monoclonal antibodies in immunodiagnosis and of DNA/RNA probes to identify viruses was also discussed in detail. The need for applicability of these tests at three levels, i.e., field conditions (or primary health care level), local laboratories, and central laboratories, was discussed and their use at the field level was emphasized.     

Malaria diagnosis: Memorandum from a WHO Meeting

This Memorandum reviews (1) the diagnostic requirements for malaria control within the primary health care system; (2) the current methods of malaria diagnosis used both in the clinic and in epidemiological studies; (3) the status of research on alternative methods to microscopy for the diagnosis of malaria; and (4) the application of new diagnostic methods in individual cases, in the community, and in the mosquito and their possible integration into existing epidemiological studies and control programmes. It also identifies priorities for the development and validation of new and reliable diagnostic techniques, and makes recommendations for the improvement, standardization, and utilization of current methodology.     

AIDS and the WHO Collaborating Centres: Memorandum from a WHO Meeting

The important role of WHO Collaborating Centres in international cooperation and action to control and prevent the acquired immunodeficiency syndrome (AIDS) in the affected countries, and eventually worldwide, was emphasized at a meeting in Geneva on 25-26 September 1985. The participants reviewed the progress that had been made in the past few months and recognized that WHO activities related to the control of LAV/HTLV-III infections and associated diseases, particularly AIDS, are likely to increase rapidly during the next few years. They therefore recommended the assignment of responsibility within WHO to ensure optimal coordination of activities involving the Collaborating Centres, the Organization, and the countries.     

Hepatitis B vaccines prepared from yeast by recombinant DNA techniques: Memorandum from a WHO Meeting

A meeting of experts was convened on 19-21 November 1984 in Geneva, Switzerland, to advise the World Health Organization on the production of hepatitis B vaccine prepared from yeast (Saccharomyces cerevisiae), using recombinant DNA technology. This vaccine development follows the advances in molecular genetics that have permitted genes coding for biologically active substances to be identified, analysed with fine precision, transferred within and between host organisms, and expressed under controlled conditions so as to obtain efficient synthesis of the product which they encode. The gene for hepatitis B surface antigen (HBsAg, the coat protein of the virus) has been cloned and inserted into several expression vectors. These recombinants have been introduced into and have been expressed in yeast cells. The meeting, which included representatives from seven manufacturers, presented preliminary guidelines for the control and testing of hepatitis B vaccine produced in yeast.     

Control of antibiotic-resistant bacteria: Memorandum from a WHO Meeting

Control of the prevalence of antibiotic-resistant bacteria is essential for the appropriate use of antibiotics for prophylaxis and treatment of infections. Hospitals are regarded as the place where antibiotic-resistant bacteria might often develop. Control of antibiotic use in hospitals is therefore one of the most important measures for effective control of antibiotic resistance. Another effective means to control antibiotic resistance is to develop a surveillance programme on a national, and international scale. This would be of great assistance, especially for forecasting future changes in the resistance of bacteria. The prevention of disease by measures other than the use of antibiotics could also reduce antibiotic resistance.     

Molecular epidemiology of influenza viruses: Memorandum from a WHO Meeting

This Memorandum summarizes recent information on influenza viruses of non-human hosts, discussed at the WHO Consultation on Molecular Epidemiology of Influenza Viruses, Athens, Georgia, USA, in September 1986. It was noted that a wide variety of antigenic variants of influenza viruses have been isolated from non-human hosts, especially birds. Of particular epidemiological interest in recent years has been the isolation of H7N7 influenza viruses from epidemics of disease in seals, the isolation of an H10N7 virus from outbreaks of disease among domestic mink, and the occurrence of pathogenic avian influenza viruses in Australia, Ireland and the USA.     

Progress in the control of viral hepatitis: Memorandum from a WHO Meeting

Viral hepatitis is a major public health problem in all parts of the world, with hepatitis B (HB) as the most important of all the viral hepatitides. It is estimated that worldwide there are nearly 300 million carriers of HB markers of active infection. More than 40% of persistently infected persons who survive into adult life will die of the consequences of HB, such as cirrhosis and hepatocellular carcinoma. The vaccines available against HB have an impressive record of safety and efficacy, and the best means of controlling the infection on a global scale, including the reduction of mortality due to its sequelae, will be by mass immunization of infants. In areas where most infections are acquired early in life the vaccine should be administered shortly after birth, and HB immunization should be integrated into the Expanded Programme on Immunization.     

Haemorrhagic fever with renal syndrome: Memorandum from a WHO Meeting

Haemorrhagic fever with renal syndrome (HFRS) is a public health problem throughout most of the European and Asian land mass. Although predominantly associated with rural areas, it is now being recognized as an urban problem in some countries, and also presents a particular hazard to laboratory staff who use rodents for biomedical research. In wild rodents (rats, mice and voles) the infection is asymptomatic. Human infection with the HFRS agent(s) is sporadic, but under special circumstances epidemics occur; the infection may be completely silent, or associated with mild or severe disease. Severe cases are usually seen in the Far East. The epidemiological features of the disease vary from country to country and depend upon a variety of factors, the elucidation of which requires a multidisciplinary approach. The recently discovered Hantaan virus is the etiologic agent of HFRS in Asia. It is now possible to detect Hantaan virus antigen by immunofluorescence using either infected mouse lung or infected human cells as substrate. Prevention measures to date have concentrated on rodent control; the role played by the ectoparasites of rodents, if any, has still to be elucidated. Antigens have been detected in rodents captured in HFRS-endemic areas in China, Finland, Japan, Sweden, and the Soviet Union. None of these have been cultured as yet, but preliminary results with the Puumala agent detected in Finland indicate a relationship with the Hantaan virus. Sera collected from Scandinavian patients react to a high titre with both Puumala and Hantaan agents, whereas sera collected from patients in East Asia have much higher titres against the homologous antigen. Surveillance is very important and further research on the virus is needed, especially to identify the virus in the West and to determine strain differences.     

Prevention of avoidable mutational diseases: Memorandum from a WHO Meeting

About 1% of children are born with a serious disorder which is the direct result of a mutational event in a parent or a more distant ancestor. These disorders, of which several thousand are known, mainly afflict the blood, bone, brain, ear, eye or muscle and the changes are usually irrevocable by the time of diagnosis. Another 1% of individuals will develop a serious genetic disease some time after birth. In addition to these direct consequences of a mutant event, far higher proportions will suffer from the indirect effects of one or several mutations.     

Essential drugs for cancer chemotherapy: Memorandum from a WHO Meeting

Essential drugs for cancer chemotherapy were reviewed in a consultation convened by WHO in Geneva. General principles regarding the proper role of cancer chemotherapeutic agents in relation to other established treatment modalities and the classification of tumours with respect to curative potential are discussed. Curable cancers and those cancers where the cost-benefit ratio clearly favours drug treatment can be managed appropriately using only 14 drugs.     

Facts about an implantable contraceptive: Memorandum from a WHO Meeting

This Memorandum reviews the results of research undertaken in animals and human subjects on the implantable contraceptive, Norplant, and where relevant, its components, levonorgestrel and Silastic. Results from clinical trials, including effectiveness and side-effects, are evaluated and service delivery aspects commented on. The Memorandum concludes with a statement regarding the use of Norplant as an option for long-term reversible contraception.