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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. Elements to Understanding TB. Control. Interventions.
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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
Elements to Understanding TB Control Interventions Agent Individual Community
Remember these three concepts: • Infectivity • Pathogenicity • Virulence
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
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)
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
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
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
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
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
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
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
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
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
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
Think TB Cough • Sputum • Haemoptysis • Fever • Loss of weight • Chest pain • Etc., etc., etc.
Steps in the pathogenesis of TB Risk factors Infectious Exposure Sub-clinical Infection Death Non-Infectious Risk factors
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
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.
Droplet nuclei containing mycobacteria inhaled Usually deposited in the lower lobes TB Infection
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.
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.
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
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.
Prevalence of infection • PPD predictive value is higher when the prevalence of infection is higher • Population density (urban vs. rural) • Socioeconomic indicators (crowding)
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.
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.
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
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
Environmental • Smoking • Alcohol abuse • Injecting drug users • Nutrition • Malnutrition • Diet (vegetarian) • Vitamin D defficiency
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)
Pregnancy • No solid evidence • However, there are indications that post-partum period might double the risk of progression to TB
Factors associated with the etiology of the agent • Infecting dose effect • Strain virulence associated to katG gene • Drug resistance • Infection with M. bovis.
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.
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
Factors determining characteristics of mortality • Age-specific differences in mortality • Difference in mortality in each cohort group • Difference at particular periods or events
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
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