Transmision, Infection,Disease

Transmision, Infection,Disease - Tuberculosis is a rare disease, whose prevalence is measured or estimated in cases per 100,000 population. TB is also a slow-moving disease – the time scale of epidemics is decades rather than weeks or years. The natural history of TB helps us understand the driving forces behind these ‘slow epidemics of a rare disease’,1 and the temporal and geographical patterns in its distribution. In Fig. 3.1, arrows represent the processes by which individuals enter and leave each of the states represented by the boxes. An individual can be uninfected, latently infected, or can have primary or post-primarydisease.

Pulmonary tuberculosis

Tuberculosis

Infection with Mycobacterium tuberculosis, the causative agent of TB, results from inhaling droplets containing the bacilli, which are produced when a person with infectious TB coughs, talks, or sneezes (see Chapter 14 for a more detailed discussion). A widely used rule of thumb in TB epidemiology is that each untreated, infectious TB case infects, on average, about another 10 individuals each year.2,3 

The estimated prevalence of smearpositive disease was just under 0.1% (90 per 100,000) in 2005,4 which corresponds to an annual risk of infection of just under 1%. A recent assessment of new infections caused by all infectious TB cases (treated and untreated) suggests an average of six new infections per case, which would imply an even lower annual risk of infection.5 Of infected individuals, only about 5% (in the absence of other predisposing conditions) develop ‘progressive primary’ disease following infection.6 Progression is typically slow, with time to development

of primary disease averaging 3–4 years.

For the remainder, who enter the pool of ‘latently infected’ individuals, there is a low annual risk of developing TB by ‘reactivation’ of infection. Whether latent bacteria remain viable for the full lifespan of all infected people is unknown, but the risk of reactivation certainly persists into old age for many. Infection is associated with only partial immune protection from reinfection.7–9 Thus, particularly in areas where infection transmission is high, infected persons remain at risk of disease resulting from reinfection. At the population level, the relative importance of primary disease, of post-primary disease resulting from reactivation and of post-primary disease following reinfection varies according to past and current patterns of transmission and breakdown to disease. 

The majority of individuals infected with M. tuberculosis (but not with HIV) do not develop TB disease; the lifetime risk of pulmonary disease among infected individuals has been estimated at 12% for England and Wales in the second half of the twentieth century.8 It is this large pool of infected, healthy individuals and the typically long interval from acquiring infection to developing disease which give the slow-moving epidemics of TB their momentum, and mean that they generally respond slowly to control efforts.

While the low rate of infection and breakdown to disease make TB a relatively rare disease, it is principally the high case-fatality rate which makes it one of major public health significance. Left untreated, and in the absence of HIV, about two-thirds of smearpositive cases will die, mostly within 2 years.3 For untreated smear-negative cases, case fatality rates are lower: 10–15%.10,11 Even on treatment, over 10% of smear-positive patients die in settings where adherence to treatment is low, or rates of HIV infection or drug resistance are high, although in other settings as few as 2% of smear-positive patients die while on treatment.