European Respiratory Monographs
Respiratory epidemiology
Epidemaiology of tuberculosis
Donald A Enarson MD FRCP(c)
Nadia Ait-Khaled MD
･ Address correspondence: International Union Against Tuberculosis and Lung Disease, 68 boulevard Saint-Michel, Paris 75006 FRANCE. Tel: 33-1 44 32 03 60; Fax: 33-1 43 29 90 87; e-mail 101370.370@compuserve.com
The distribution and trend of tuberculosis both in the world and in Europe have been extensively described in other publications1 2 3 and will not be reiterated here. Tuberculosis is the most common cause of death in the world from a single agent among persons aged 15 to 49 years (variously estimated at 2.4 to 2.9 million deaths annually), there are an estimated 8 million new cases of tuberculosis appearing annually and there are said to be 1.7 billion persons infected with the causative agent, Mycobacterium tuberculosis4.
Tuberculosis was an extremely common cause of death in Europe in the nineteenth century. At the first international meeting of specialists of Internal Medicine, held in Paris in 1867, it was noted that the most frequent disease encountered by physicians was tuberculosis and, for this reason, a series of international meetings was commenced which culminated in the formation of what is now the International Union Against Tuberculosis and Lung Disease, the oldest international non-governmental organization dealing with health. Today,more than 90 per cent of cases and more than 95 per cent of deaths are reported to occur in low income countries5
The epidemiology of tuberculosis is, in some ways, unique in that it "bridges" the epidemiology of acute contagious diseases and that of chronic, mainly non-contagious, diseases6. Despite having been studied by a long list of eminent epidemiologists7 8 9 10 11 12 13 14 15 16 17 18, important aspects of the epidemiology of the disease are still not well understood.
A. "Components" of tuberculosis to be measured
Tuberculosis is a contagious disease, in that its cause is a micro organism of the Mycobacterium tuberculosis complex, consisting principally of three species, M. tuberculosis, M. bovis and M. africanum. It is a contagious disease in that it maintains itself in the population by transmission from person to person, from animal to person or from person to animal. It is the person to person transmission which accounts for most of the disease, is the focus of this chapter and will be what is meant by "tuberculosis" unless otherwise speciffied.
1. Transitions in tuberculosis
Understanding the epidemiology of tuberculosis is enhanced by a transition model which defines transition probabilities with the risk factors and effect modifiers which determine them. Figure 1 is an adaptation of such a model19 which encompasses the entire population vis a vis tuberculosis. It is not necessarily comprehensive, may be simplified or complicated, but includes the transitions essential for an understanding of tuberculosis and the interventions designed to control it.
Key transitions in the model are those from susceptible to exposure, from exposure to infection, from infection to becoming contagious, from being contagious to becoming no longer contagious and from being no longer contagious to becoming, once again, contagious. These transitions form a cycle which maintains the micro organism within the human population. When every contagious case produces a minimum of one more contagious case, the epidemic is maintained or enhanced; when it does not, the epidemic declines.
2. From Susceptible to Exposure
Biologically effective exposure is a function of contact, concentration and duraton of exposure20. It occurs when an individual breathes air containing micro organisms expelled from the lungs of another person who has micro organisms accessible to the airways. The number of such "cases" and their physical and temporal relations to susceptible individuals determine the nature of the contact21.
The concentratien of micro organisms in the air inhaled by a susceptible individual is determined, among other things, by the concentration expelled from the lungs of the source. Thus, the person with the highest concentration of bacilli on direct microscopic examination of sputum is the person who is most contagious. The rate of change of the air (ventilation) is another important determinant of the concentraton: good ventilation rapidly reduces the concentration of micro organisms and vice versa. In addition,the volume of enclosed space in which micro organisms are present is important in determining the concentration. Finally, the presence of direct sunshine affects the viability of the bacilli, reducing the concentration of viable bacilli capable of infecting an individual.
The duration of exposure is important in determining the effectiveness of exposure. Early diagnosis, isolation and chemotherapy reduce exposure by reducing the duration of contagiousness of a case13.
3. From Exposure to Infection
Characteristics of transmission22 23 and pathogenesis24 are key to this transition. The micro organisms are inhaled, implant themselves in the peripheral airways or alveoli, and multply there. Once inhaled,the micro organisms are phagocytosed by the alveolar macrophages in which they multiply, are carried to regional lymph nodes and may enter the blood stream in which they are disseminated throughout the body. This is the stage of infection and is usually accompanied by the development of an immune response which is the classic example of delayed type hypersensitivity or cell-mediated immunity indicated by a significant reaction to the tuberculin skin test. In most instances, this immune response is sufficient to cause the micro organisms to become quiescent in the sites to which they have been disseminated. The nature of this "quiescence" is not clearly understood at present.
The probability of becoming infected, given exposure, is relatively low (approximately one in six). This low probability is determined primarily by endogenous modifiers which have never been clearly delineated.
Unlike other organisms Mycobacterium tuberculosis does not prevent re-infection, although the probability of re-infection given exposure is reduced8 25.
