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Exposure to M. tuberculosis. o Etiologic epidemiology o Descriptive epidemiology o Predictive epidemiology. In just 30 years the median age of tuberculosis patients in Finland has moved from the generation of parents to that of grandparents.

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Exposure to

M. tuberculosis

o Etiologic epidemiology

o Descriptive epidemiology

o Predictive epidemiology


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In just 30 years the median age of tuberculosis patients in Finland has moved from the generation of parents to that

of grandparents.

People preferentially socialize with peers of the same age, thus interactions are intra-generational. In the case of parents, the important interactions are both inter- and intra-generational. In Europe, it is largely the parents (not the grandparents) who take care of the youngest. In other societies this might differ.

In any case, the age in which tuberculosis predominantly occurs, will have important repercussions on the risk of exposure for different population segments.


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Infection with Finland has moved from the generation of parents to that

M. tuberculosis

o Etiologic epidemiology

o Descriptive epidemiology

o Predictive epidemiology


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Risk of Infection Given Exposure: Finland has moved from the generation of parents to that

Largely Exogenous Factors

Particles

Volume

x

Exposure time

Particles:

Volume:

Exposure time:

Production of infectious droplet nuclei

Volume of air and ventilation

Time of inhaling air with droplet nuclei


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Production of Infectious Finland has moved from the generation of parents to that

Droplets and Droplet Nuclei

o Aerosolization

o Site and form of disease


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Clearance of Air Finland has moved from the generation of parents to that

o Dispersion of bacilli

o Survival of bacilli


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Extent of Contact Finland has moved from the generation of parents to that

o Proximity

o Length of contact



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Potential Transmitters of Proximity of ContactM. tuberculosis

Persons who cough

Persons with sputum positive for acid-fast bacilli

Persons not on chemotherapy

Persons just started on chemotherapy

Persons with a poor response to chemotherapy


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30 meters Proximity of Contact

Surgery

TB

Amb

District Hospital


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Advising the District Medical Officer Proximity of Contact

The number of infectious particles (tubercle bacilli) expelled into the air in this environment must be considered far above the average encountered in other areas of the city. While all patients are on treatment, some have commenced treatment only recently.

The volume of air into which these bacilli are expelled to is, however, infinite given a distance from the surgical ward of 30 meters (outdoors proximity matters).

The survival of bacilli outdoors in East Africa is likely to be limited because of frequent sunshine.

The length of exposure of surgical patients is by definition limited.

The District Medical Officer might be advised that the risk assessment allows construction of the ambulatory as planned.


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Infection with Proximity of Contact

M. tuberculosis

o Etiologic epidemiology

o Descriptive epidemiology

o Predictive epidemiology


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Descriptive epidemiology of Proximity of Contact

tuberculous infection

o Methodological issues in determining

prevalence of tuberculous infection

o Prevalence of tuberculous infection


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Milestones in the History of Tuberculin Proximity of Contact

1890

1907

1909

1909

1910

1924

1926

1934

1950ies

1958-65

1965-95

Koch Old Tuberculin

von Pirquet scratch test

Moro patch test

Mendel intradermal test

Mantoux intradermal test

Hastings no-lesion, reactor cattle

Crawford heterologous antigens

Seibert PPD-S

WHO surveys

US Navy recruit study

Korea surveys


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Standardization of the Proximity of Contact

Tuberculin Skin Test

o Standardization of tuberculin

o Standardization of administration

o Standardization of reading


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This slide is not available Proximity of Contact


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This slide is not available Proximity of Contact


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This slide is not available Proximity of Contact


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Sensitivity to Proximity of ContactM. intracellulare in the United States

Edwards LB, et al. Am Rev Respir Dis 1969;99:(No 4, part 2):13


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Example 1: Proximity of Contact

90% Sensitivity

90% Specificity

40% Prevalence

Example 1:

90% Sensitivity

90% Specificity

10% Prevalence

Example for the Dependence of the Predictive Value

of a Positive Test on the Prevalence

Condition

Test present absent total

pos 360 60 420

neg 40 540 580

tot 400 600 1000

Condition

Test present absent total

pos 90 90 180

neg 10 810 820

tot 100 900 1000

Predictive value of a positive test:

360 / 420 = 86%

Predictive value of a positive test:

90 / 180 = 50%


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With progress of the tuberculosis eradication program among cattle in the United States, the prevalence of tuberculous infection among cattle decreased.

As a result, the predictive value of a positive tuberculin skin test decreased: an increasing proportion of reactors had no tuberculous infection at necropsy.


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Summary Tuberculin Test cattle in the United States, the prevalence of tuberculous infection among cattle decreased.

o Standardized tuberculin

o Standardized technique

o Unpredictable specificity

o Weakness of cut-off points

o Mixture analysis promising


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Infection with cattle in the United States, the prevalence of tuberculous infection among cattle decreased.

M. tuberculosis

Prevalence of tuberculous infection

in different population segments


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Infection with cattle in the United States, the prevalence of tuberculous infection among cattle decreased.

M. tuberculosis

o Etiologic epidemiology

o Descriptive epidemiology

o Predictive epidemiology


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Epidemiologic uses of tuberculin skin test surveys cattle in the United States, the prevalence of tuberculous infection among cattle decreased.

o Predict course of the tuberculosis epidemic

o Estimate burden of tuberculosis


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Algebraic Derivation of the Average Annual Risk of Infection from Prevalence

Notation:

b Calendar year cohort was born

a Age of cohort at calendar time survey was conducted

Pb+a Prevalence of infection in cohort at time of survey

R Average annual risk of infection between calendar time b and calendar

time b+a

At birth: 1 – Pb = 1

At age = 1: 1 – Pb+1 = 1 (1 – R)1

At age = 2: 1 – Pb+2 = 1 (1 – R)1 (1 – R)2

At age = a: 1 – Pb+a = 1 (1 – R)1 (1 – R)2 … (1 – R)a

1 – Pb+a = (1 – R)a

(1 – Pb+a)1/a = (1 – R)

R = 1 – (1 – Pb+a)1/a


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Tuberculosis from Prevalence

o Etiologic epidemiology

o Descriptive epidemiology

o Predictive epidemiology


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Tuberculosis from Prevalence

o Etiologic epidemiology

o Descriptive epidemiology

o Predictive epidemiology


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Determinants for the Frequency of HIV-Associated Tuberculosis in a Community

Total population

Prevalence and incidence of infection with M. tuberculosis

Prevalence and incidence

of HIV infection

Overlap of the two respective

population segments

Infected with

M. tuberculosis

Infected with HIV


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Tuberculosis Tuberculosis in a Community

o Etiologic epidemiology

o Descriptive epidemiology

o Predictive epidemiology


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Tuberculosis Death Tuberculosis in a Community

o Etiologic epidemiology

o Descriptive epidemiology

o Predictive epidemiology


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Tuberculosis Death Tuberculosis in a Community

o Etiologic epidemiology

o Descriptive epidemiology

o Predictive epidemiology


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Tuberculosis Death Tuberculosis in a Community

o Etiologic epidemiology

o Descriptive epidemiology

o Predictive epidemiology


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