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D. INFECTIOUS DISEASES

As the WHO generally followed the operational priorities set by the First World Health Assembly, an extensive research program gradually emerged.

The inevitability with which research followed the development of control programs was epitomized by the malaria program, discussed in the preceding part.

In the pages which follow, selected WHO research activities are described in order to illustrate the variety of research approaches followed, the general areas of concentration of research, the cooperative arrangements that typify the program, the major disease areas covered, and the various relationships between disease control programs and research. The section is not, however, a complete catalog of WHO's research activities.

1. Tuberculosis

As was true of malaria, the tuberculosis control programs immediately encountered difficulties calling for research. For example, the BCG vaccine for tuberculosis is generally regarded as valuable under certain conditions, and WHO developed mass vaccination campaigns. Precise evaluation of the effects of these campaigns was, however, difficult because the extent and duration of protection conferred by the vaccine could not be precisely measured.

WHO set up a Tuberculosis Research Office in Copenhagen to solve this and and other problems relating to tuberculosis. This office. developed methods for evaluating the results of mass BCG vaccination campaigns in terms of allergy production, a useful index for assessing both the vaccines and the techniques used in these projects.

As another example of TB research there is some evidence of several types of tuberculosis micro-organisms other than the well-known human, bovine, and avian. Investigations are currently being undertaken in Africa and India into the types of tubercle baccilli isolated from human and animal populations. Field teams collect sputum specimens from randomly selected population groups in various countries for the laboratories participating in this research program, coordinated by WHO. This work illustrates both the need for a world approach in dealing with many medical research problems, and the experience which WHO has gained in the practical problems of organizing and carrying out such studies.

2. Trachoma

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Trachoma, a blinding eye disease now known to be carried by a virus, and infectious conjunctivitis affect no less than 400 million people (see p. 52, "The Status of World Health"). They present a grave social problem because of the high percentage of blindness. Trachoma may reach very high percentages of infection among children, and in some territories of North Africa the percentage is often as high as 70-90 and may even reach 100 percent. In other territories of Africa, evidence during the last years has shown that trachoma is a more important problem than it was hitherto believed to be in certain areas of French territories in west and Equatorial Africa, Ghana, Kenya, and South Africa. A very high incidence has been detected in several areas of the Middle East as well as of Iran, India, Indonesia, and China, in Asia.

The bacterial types of conjunctivitis which may cause blindness and other complications in themselves, produce yearly epidemics and are associated in varying frequency with trachoma in the different countries. This association prolongs and makes the evolution of trachoma more severe.

The WHO Expert Committee on Trachoma which met in 1955 recommended that the Organization stimulate research with a view to establishing the identity of the trachoma virus and the bacteriology of the associated conjunctivitis. A long-term program of coordinated research in this field has since been established among institutions in the United States, United Kingdom, and Italy, Switzerland, and Tunisia. It is planned to extend this research to include laboratories in Ethiopia, Japan, Vietnam, India, Turkey, Morocco, and Australia. The Lister Institute in London has isolated a virus and bas indicated its readiness to circulate the strain to other collaborating institutes. Meanwhile, among those receiving a WHO grant-in-aid are the Institute Pasteur (Tunisia) which has published its work on the isolation of a virus which it is willing to circulate for further study.

With the recent isolation of the virus of trachoma, the disease is now ripe for an intensive research effort using modern techniques of virology.

3. Yaws and syphilis

Some 50 million people are infected with yaws, but elimination is now practical (p. 50, "The Status of World Health"). Active WHO projects are now in operation in the Cameroons, French West Africa, Ghana, Liberia, Nigeria, Sierra Leone, and Togoland in Africa; India, Indonesia, Laos, Malaya, and Thailand in Asia; and also in some of the Caribbean Islands, Haiti, the Philippine Islands, a number of Pacific islands, and west New Guinea.

Control campaigns-mass treatment with penicillin-have already achieved a substantial decrease in the prevalence of clinical yaws. Nearly 90 million persons have been examined, and 22 million have been treated as active cases or contacts. At resurveys of these populations it has been found that clinically active yaws has fallen from an average prevalence of about 10-12 percent, to 1 percent, and in some areas no active cases at all have been discovered. This means that the transmission of the disease has largely come to an end. Thus, while the progress of the disease has been checked in persons infected when the campaign was begun, new infections have been very few. Thereby, the health of the country has greatly benefited both now and in time to come.

The future extension of the campaign against yaws, now that most areas of high prevalence have been covered, will carry it into the less affected districts where some adaptation of technical policy will no doubt be required. The importance of adequate provision of rural health centers in the supervision of yaws, until eradication is complete, is apparent.

The battle against endemic syphilis is proceeding in Bechuanaland, Iraq, Syria, and other countries. It has achieved almost complete success in Yugoslavia. The prevalence of venereal syphilis has for some years been relatively low in the more developed countries. In fact, the reduction in antisyphilitic measures in some of these countries has led to a recent increase in the disease.

The research prerequisite to the control of syphilis and yaws was done some years ago with the development of penicillin. Now the problem is primarily one of applying the research findings effectively. But research is still needed. Investigations into problems in this field with which WHO has been concerned have been partly initiated by the Expert Committee on Venereal Diseases and the Treponematoses and the Subcommittee on Serology and Laboratory aspects or have arisen from the needs of the field program of the Organization. The work was carried out at certain designated centers in cooperation with other laboratories and clinics in many parts of the world and was coordinated by WHO. In some cases grants were also awarded.

At the International Treponematosis Center at Baltimore, Md., the mutual relationships of the treponemes of yaws and endemic and venereal syphilis and their unchanged susceptibility to penicillin have been investigated. Immunological studies have indicated important developments in serological tests for the treponematoses using treponemal antigens.

At the WHO serological Reference Laboratories in Copenhagen (1950) and Chamblee, Ga. (1954), investigations on the standardization of antigens and on the preparation of standard freeze-dried reactive sera for the reagin tests for syphilis have made possible improved techniques.

The observation that certain batches of penicillin did not appear as effective as others led to coordinated study which resulted in recommendations of certain criteria, especially the duration of blood level in human volunteers, which has made possible the use of single and relatively small doses of penicillin in mass campaigns against yaws and endemic syphilis.

Other investigations have been concerned with the introduction and dosage of penicillin in mass campaigns against endemic syphilis and with the treatment that should be adopted with different prevalences of clinically active yaws. Inquiries have also been made in the dosage of penicillin in use throughout the world.

E. NONINFECTIOUS DISEASES AND SPECIAL PROBLEMS

While WHO's research efforts have been concentrated on problems related to infectious diseases, noninfectious diseases and special problems have been the subject of research efforts. UNICEF and FAO have been particularly active in this connection.

1. NUTRITIONAL RESEARCH

Millions of people throughout the world suffer from nutritional diseases, and elimination of these is a major public health problem of the world. A brief discussion of some of them will indicate how research is related to disease control measures in various ways. Of the deficiency diseases, kwashiorkor, or protein deficiency, is the most serious from the public health point of view.

The first complete clinical account of this disease was given in Ghana, but the prevalence in the world is not known. The condition is associated with insufficient total protein intake, or a lack of balance of certain compounds called amino acids, especially around the period

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of weaning. The majority of sufferers are between 9 and 36 months old.

The prevention of the disease involves fundamental changes in the way of life of the people and requires cooperative efforts on the part of health, agricultural, economic, fisheries, and education departments. Disorders connected with insufficient or unbalanced food have to be approached from an educational point of view, because it is difficult. to persuade people to change traditional food habits, quite apart from any question of cost or technique. The most effective channel is possibly education in nutrition through the maternal and child health

centers.

New protein sources *

A great deal of research of both the laboratory and the field type is going on. Most of it is devoted to discovering ways of feeding children and providing sufficient protein without using relatively costly foods such as milk, eggs, etc. Research is now underway in India, Africa, and Central America to find suitable vegetable and fish sources of protein. It is helped by WHO and the Pan-American Health Organization through small grants to participating institutions.

In collaboration with the Josiah Macy, Jr., Foundation and FAO, a meeting was convened of biochemists engaged in the experimental feeding of animals, scientists studying the most efficient methods of feeding stock, as well as of pediatricians and general medical nutritionists. A small protein advisory group has also been formed, the members of which conduct tests on different foodstuffs in their own laboratories.

The Rockefeller Foundation has generously donated a sum of $250,000 to further research in this field by grants to institutions in Japan, Taiwan, India, south, east, and west Africa, Mexico, Guatemala, United States, United Kingdom, and France, whose work is coordinated by WHO. A great deal of progress has been made in this extensive research, and there are now some protein-rich vegetable foods on trial. Special work has been done in Uganda, Coonoor (India), and Guatemala, and recently in other centers of investigation, especially in the Institute for Nutrition of Central America and Panama (INCAP).

Coping with pellagra

Efforts have been made recently to control and eradicate pellagra. Studies were carried out in Yugoslavia, Egypt, and Basutoland. Epidemiologically the disease is most frequently associated with grossly restricted intake of food with little variety and with a predominance of maize in the diet. The reduction of pellagra is not a gigantic problem and no research is needed on the disease itself. The solution is a social problem essentially dependent on altering the diet pattern rather than providing any specific treatment. This may mean a change in agricultural policy with the addition of certain special techniques. Some demonstration programs indicated that the enrichment of maize with niacin in the small mills was an effective measure which could sometimes be introduced without difficulty. Deficiency diseases

Other nutritional diseases include the deficiency group of which beriberi is one of the most important. It is well known that it usually

See pt. V, sec. C (2) and (3) for discussion of nutrition activities in conjunction with FAO and UNICEF.

occurs among those who consume a diet composed mainly of highly milled rice, and it is rare with any other cereal. The research needed here is social-how to alter diet patterns.

Endemic goiter

Endemic goiter is another deficiency disease which bears much responsibility for poor social and economic conditions as well as ill health. It has been estimated that there are some 5 million persons suffering from goiter in India alone.

It is generally admitted that endemic goiter can be prevented by the administration of appropriate amounts of iodine. Nonetheless, the practical difficulties the less-developed areas have to face are serious. No method had been devised for the iodization of crude saltgenerally used in underdeveloped countries-which would be comparable in effectiveness to the iodization of refined table salt by the addition of iodine in a certain form-iodides. Iodides added to crude salt have proved unstable.

Research which the Chilean Iodine Educational Bureau of London undertook, at the request of WHO, produced a simple technique for the iodization of crude salt and showed that another sort of iodine compounds-iodates were more stable than iodides in crude salt under tropical conditions. Further research work carried out in the United Kingdom and the United States ruled out the danger of toxicity of these iodates. Meanwhile their efficiency was established through field experiments in Latin America and studies in London. As a result of the research, programs of prevention are now going ahead in Latin America, and in India and other countries in Asia.

Anemia

Anemia constitutes a public health problem of great magnitude, particularly in the underdeveloped and tropical areas of the world. Malnutrition underlies most of these anemias-particularly an anemia caused by or linked with a deficiency of iron in the dietwhich affect particularly certain vulnerable groups in the population, i.e. expectant and lactating mothers, infants, and young children. The high rates of maternal mortality in some countries are unquestionably influenced by the prevalence of anemia. Since it is usually a chronic condition, anemia impairs health and working capacity and hence leads to economic loss. WHO is planning a coordinated world research program on iron deficiency anemia.

In summary, extensive research is in progress both on causes of nutritional diseases and also into simple and cheap methods of pre

vention.

2. DRUG ADDICTION

The multiplicity of paths by which WHO is led into research, and the political, social, and economic questions that sometimes surround research are illustrated by WHO activity relating to khat.

The plant Catha edulis (khat) grows wild or is cultivated in many areas of east Africa and in some parts of the Arabian Peninsula. Its leaves are chewed or consumed in the form of an infusion. It has been reported that in some regions of east Africa and in Aden and Yemen many people have become habituated to the consumption of khat, with very serious consequences to their health, earning capacity, and family life, thus creating a grave social problem.

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