although the data are limited, appear to confer protection against reinfection in humans as well. Because M protein is the sole streptococcal antigen known to elicit protective antibodies, modern studies of streptococcal immunization have focused on development of a safe and immunogenic M protein preparation. Details of such studies are outlined below in the section on prospects for vaccine development. Although the pathogenesis of ARF remains unknown, most authorities believe that the disease results from host immune responses to certain streptococcal antigens that share antigenic determinants with human host tissues. For this reason, any putative M protein vaccine should consist of that portion of the M protein macromolecule that is responsible for eliciting type-specific immunity, while at the same time being free from antigens associated with M protein (so-called M associated proteins or non-type-specific M antigens) that might cross-react with host tissues.

Exact data on the geographic distribution of ARF and rheumatic heart disease are not available. However, the worldwide patterns of occurrence are clear. During this century, there has been a sustained and profound decline in rheumatic fever incidence in the developed countries of North America and Western Europe. Other highly developed countries, such as Japan, are also experiencing a marked drop in disease incidence. In contrast, ARF incidence is not declining, and may even be increasing, in many of the developing areas of the world. Such areas include the Indian subcontinent, the Arab countries of the Middle East, selected areas in sub-Saharan Africa and South America, and certain highly susceptible populations, such as the Maoris of New Zealand. The incidence of ARF tends to be highest in the thickly congested, low-income areas of the world’s major cities.

Although figures on the incidence of rheumatic fever are difficult to obtain and often unreliable, there is no doubt that rheumatic fever remains one of the major causes of cardiovascular morbidity and mortality in the developing nations of the world. As noted above, the disease is rampant in the Indian subcontinent, the Middle East, and many countries of Africa and South America. In Sri Lanka in 1978, for example, the morbidity rate of ARF was 47 per 100,000 population and over 140* for the 5 to 19 years age group (World Health Organization,