EPIDEMIOLOGICAL OVERVIEW OF TUBERCULOSIS

1. EPIDEMIOLOGICAL OVERVIEW OF TUBERCULOSIS Gerardo de Cosio, MD, MPH Advisor, Prevention and Control of Diseases Pan American Health Organization/World Health Organization February 14, 2005 Montego Bay, Jamaica

2. Elements to Understanding TB Control Interventions Agent Individual Community

3. Remember these three concepts: • Infectivity • Pathogenicity • Virulence

4. The Burden of Tuberculosis,2004 • Overall, 1/3 of the world population is currently infected with M. tuberculosis • 16 million TB infected (246/100k) (including .38 TB/HIV) • 8.8 million new cases, 80% in 22 high-burden countries (141/100K) • 3.9 M New smear + • 2 million deaths • 98% of these deaths in the developing world • Countries: Developing -young adults/Developed - elderly • Over 1/4 million deaths due to TB/HIV • Multi-drug resistance (MDRTB) present in 102 of 109 countries surveyed from 1994-2003

6. Descriptive epidemiology • More common in developing countries. • Inadequate funding • In developed countries is more frequent among immigrants, drug users, HIV, homeless, and those living in inner cities. • HIV alone does not explain the increase of TB. • In developed countries more frequent in old age (shift in age)

7. Descriptive Epidemiology – Socioeconomic Status • Poverty • Crowding living conditions • Reduce access to health care • Race/ethnicity • Minorities • Migration • Population density (rural vs. urban) • Marital status • Substance abuse/alcoholism • Nutritional status

8. Descriptive epidemiology • Age-specific incidence varies over countries and socioeconomic conditions: • Elders in Developed countries • Young adults in developing countries* • Higher among males than females • Access to diagnosis • Health services notification process * Mainly those in their most productive years of life

9. Definitions: Patients with TB • TB infection • TB bacilli live inside the person, but the bacilli do not cause pathological destruction of organs • No signs or symptoms of disease • TB disease • TB bacilli progressively invade an organ(s) • Signs and symptoms of disease appear

10. Definitions: Patients with TB • Pulmonary TB • Disease involves the lung parenchyma • Smear-positive: visible TB bacilli in sputum • Smear-negative: no visible TB bacilli in sputum • Extra-pulmonary TB • Disease involving an organ other than the lung parenchyma • Includes pleural TB

11. Definitions: TB Epidemiology • Incidence • Number of persons that develop new TB disease within a specific time period, specific geographic area • Divided by number of persons at risk for TB disease (includes persons with and without TB infection) • Prevalence • Number of persons that develop new TB disease plus the number of persons that already have disease (existing cases + “incident” cases) • Divided by number of persons from which the population of cases arose

12. Definitions: TB Epidemiology • Annual risk of infection • Probability in a given year that a person will develop TB infection • Notification rate • Number of persons notified to a public health agency per 100,000 population • Most widely used statistic • Not the same as the incidence rate, because depends on persons who seek medical care, receive TB diagnosis, have public health report form complete, meet agency’s definition of a case

13. Risk of infection and infectious cases • Pre-chemotherapy era 1 infectious sources infected 20 persons during the 2-year period the case remained infectious before death or spontaneous bacteriological conversion. • When intervention introduced • Duration of infectiousness reduced • Transmission decreased • Relation between prevalence and incidence disturbed. • In countries with inadequate case management, the number of infectious patients may remain essentially the same after 2 years, because the principal impact of such an intervention lies with a reduction of case fatality at the expense of keeping infectious cases alive. • Infection increases with HIV and immunocompetent host

14. Risk of Infection from Exposure • Exposure to: • Persons who cough • Persons with sputum positive for acid-fast bacilli • Persons not on TB treatment • Persons just started on TB treatment • Persons with a poor response to TB treatment • Close contact, for long amounts of time, outside of natural sunlight (e.g., UV light) • Example: a slum dwelling with many persons living in a small space with very little sunlight

15. Definitions: TB Epidemiology • Treatment success rate • Number of new, smear-positive TB patients cured or completing treatment divided by all new, smear-positive TB patients enrolled in a DOTS program • International goal is >85% success rate • Case detection rate • Number of TB patients notified in public health surveillance divided by estimated TB incidence • Estimated TB incidence based on annual risk of infection and other studies • International goal is >70% case detection rate

16. Exposure to tubercule bacilli • Number of incident cases • Duration of infectiousness • Number of case-contact/time • Population density • Family size • Difference in climatic conditions • Age of sources of infection • Gender • Housing characteristics

17. Think TB Cough • Sputum • Haemoptysis • Fever • Loss of weight • Chest pain • Etc., etc., etc.

18. Steps in the pathogenesis of TB Risk factors Infectious Exposure Sub-clinical Infection Death Non-Infectious Risk factors

19. Infection with tubercle bacilli Probability of infection depends on: • Number of droplets nuclei in air • Duration of exposure of a susceptible individual to that droplet

20. Airborne transmission • Risk of infection is exogenous • To be transmissible through air, agent must remain buoyant in the air. • Velocity of a droplet falling to the ground depends on: surface and diameter. • For example: in moisture-saturated air droplets would fall to the ground from a height of 2 mts. in less than 10 sec. • Liquid droplets tend to evaporate, diminishing their size. • The duration of time droplets remain in unsaturated air is proportional to its size. • Very small droplets evaporate immediately • Large drops settle rapidly and reach ground without evaporation. • Droplets with a size less than 0.1 mm. are more likely to reach alveoli and then produce infection. • Droplets higher than 5 mm will not produce infection.

21. Droplet nuclei containing mycobacteria inhaled Usually deposited in the lower lobes TB Infection

22. Characteristics of an infectious patient • Patient must be able to produce airborne infectious droplets. • It requires some 5,000 bacilli in 1 ml. of sputum to yield positive a smear, and 10,000 to identify a smear as positive with a 95% probability. • Patients with a positive smear are by far more infectious than those with a negative one and positive culture. • Probability of becoming infected varies depending on the distance between source and receptor.

23. Air circulation and ventilation • Volume of air into which the bacilli are expelled determines the probability that a susceptible individual becomes infected • Ventilation dilutes the concentration of infectious droplets nuclei • Surgical masks are of low efficiency because they do not filter particles higher than 5 mm, and do not seal mouth and nose.

24. Reduction of Infection • Reducing expulsion of infectious materials from source cases such a covering the mouth and nose during coughing and the most efficient treatment. • Host immune response • Latent TB • Removed before infection through macrophages. • Other modes of transmission: M. bovis

25. Tuberculin • Tuberculin test • Sensitivity of test is well characterized • Specificity unpredictable. • The influence of BCG vaccination on the results of tuberculin skin testing is related to the time elapsed since vaccination.

26. Prevalence of infection • PPD predictive value is higher when the prevalence of infection is higher • Population density (urban vs. rural) • Socioeconomic indicators (crowding)

27. Etiologic epidemiology • The risk of becoming infected is largely exogenous in nature: • Characteristics of the source • Environment • Duration of exposure • (most likely young adults) • The risk of developing tuberculosis is largely endogenous, determined by the integrity of the cellular immune system most likely elders) • The importance of any risk factor in public health is determined by both the strength of the association and the prevalence of the risk factor in the population.

28. Etiologic epidemiology • Time elapsed since becoming infected (risk is elevated in the first years following infection, rapidly falls off and then remains low, but measurable for a prolonged period of time. • As a rule of the thumb is that the lifetime risk of a newly infected young child might be 10%, and that half of this risk falls within the first 5 years following infection (immune system). • The risk of development of disease in previously infected persons is not equally spread over the course of HIV infection.

29. Risk factors • Infection > 7 yr past or < year past • HIV • Fibrotic lesions • Silicosis • Carcinoma of head or neck • Hemophilia • Immuno uppresive treatment • Hemodialysis • Underweight • Diabetes • Gastrectomy • Jejunoileal bypass • Infecting dose

30. Age (adolescents and > 60) • Genetic factors • Sex (females vs. males) • Body build (low BMI, extra/pulmonary) • HLA types • Blood groups (higher in blood groups AB or B than O or A) • Hemophilia • Virgin population • Other genetic factors

31. Environmental • Smoking • Alcohol abuse • Injecting drug users • Nutrition • Malnutrition • Diet (vegetarian) • Vitamin D defficiency

32. Medical conditions • Silicosis (25 times Diabetes (3 times higher) • Malignant lymphomas (neck and head) ( • Renal failure (10-15 times higher) • Measles ??? • Gastrectomy (5 times higher) • Jejunoileal bypass (association reported but unknown prevalence) • Corticosteroid treatment (controversial)

33. Pregnancy • No solid evidence • However, there are indications that post-partum period might double the risk of progression to TB

34. Factors associated with the etiology of the agent • Infecting dose effect • Strain virulence associated to katG gene • Drug resistance • Infection with M. bovis.

35. Re-infection • All persons who have been treated can be re-infected • Immunologic memory wanes Note: It has been noted that those who already have been infected may have a lower risk of developing the disease than those who are not.

36. Mortality

37. TB mortality risk factors • Site (higher in positive smear) • Type of disease (association to…) • Timeliness of diagnosis • Appropriate diagnosis • Mistake in reading X-rays • Mistake in interpreting signs and symptoms • Delayed diagnosis • Quality of treatment • Each war and economic unrest usually results in an increase of mortality

38. Factors determining characteristics of mortality • Age-specific differences in mortality • Difference in mortality in each cohort group • Difference at particular periods or events

39. Impact of HIV infection • Endogenous re-activation of persons who became infected with HIV • Progression from infection in persons with pre-existing HIV infection • Transmission to the general population from persons who develop TB because of their HIV infection • The lifetime risk of dually infected persons to develop TB is about 30% • Higher probability of extra-pulmonary TB

40. The magnitude of TB mortality in the future will not so much depend on the epidemiology of tuberculosis as on the ability of effective treatment