Tuberculosis: PTuberculosis: Previousrevious and and Present MillenniumPresent Millennium. .

TB before advent of chemotherapy

TB in 1950 - 2000 Morbidity,

Mortality & Elimination of TB.

Censina R. Apap, Pulmonologist.

Introducing MyselfIntroducing Myself

Respiratory specialist since 1983Working in the Netherlands since 1977Special interests include Tuberculosis,

Asthma, COPD, and Oncology.Tuberculosis, a fascinating topic.

Introduction to the lectureIntroduction to the lecture

Natural history of TBMuch morbidity and mortality before the

advent of antibiotics HIV, MDR-TB and relaxation of TB

control programs present new public health problems

TTuberculosis in the past: Phtisisuberculosis in the past: Phtisis

Phtisis renamed Tuberculosis in 1837 Congenital / infectious disease?Known to be infectious in 1865Cause of TB discovered by Koch in 1882 Subdivision: open / closed TB

TB R/ in the pre-antibiotica era.TB R/ in the pre-antibiotica era.

Conservative, directed at relief of symptoms. Sanatorium R/ introduced in Germany by

Brehmer resulted in 25% sputum conversion within 6 mo. 50% of smear positive cases died of disease within 5 years.

How was TB treated in 1937?How was TB treated in 1937?

“Upon the permanence of closure of a tuberculous cavity depends the future development of the disease.The tuberculous cavity is the disease itself, the one feature which controls and regulates the course and outcome of the pulmonary lesion and the fate of the patient.”

Coryllos.

0

200

400

600

800

1000

1200

Total patients

No of deaths

Sanatorium Hospital Home /Total patie 1026 152 347% deaths 55 86 83

Sanatorium Hospital Home R/Total patients 1026 152 347 No of deaths 565 131 288 From W.A. Griep

Deaths (fall off rate) due to TB.Deaths (fall off rate) due to TB.

% of deaths Infectious TB Non-infectious TB

After 1 year 23.8% 0.9%

After 5 years 66.5% 11.2%

After 10 years 74% 16.5%

Active R/ of TB.Active R/ of TB.

Collapse R/ Artificial pneumothorax, Forlanini in

1888; Phrenicus paralysis; Thoracoplasty; Closed suction of lung cavities

(Monaldi);• Lung resection.

Results of active R/- Active treatment gives an additional sputum

conversion of 6%.N.B. Lung resection only possible with required

appropriate intratracheal anaesthetic techniques.

Complications of ThoracoplastyComplications of ThoracoplastyThorax cage instability with paravertebral thoracoplastyEmpyema and wound infections with plombageIn the case of selective thoracoplasty and resection of

first rib: Air emboli Trauma to the brachial plexus and thoracic duct

• Postoperative complications included:• Shock Aspiration pneumonia, atelectasis Cardiac complications

Natural course of TB infectionNatural course of TB infection

Mycobacteria inhaled -> phagocytosis by alveolar macrophages-> 2 possibilities: No infection Infection (early / late)

Transmission of TBTransmission of TB

Source case with open TB of lungs / larynx -> transmission through cough /sneeze ->

infection: early 5-10%, late in 5%.-> result: recovery (possible morbidity) / death. Positive tuberculin test reflects infected

contacts. Progression to early / late infection Possible new source cases provided

Introduction of Antibiotics 1944Introduction of Antibiotics 1944

In 1944, Waksman makes Streptomycin.PAS is available in 1946, INH in 1952 and

Rifampicin in 1965. Improved socio-economic factors and

availability of effective chemotherapy-> radical change in R/

Ambulant and in outpatient setting, unless otherwise indicated.

TB R/ in the antibiotic era.TB R/ in the antibiotic era.

Role of chemotherapy: permanent cure without development of resistance

Lack of success herein due to various factors:

- Improper use of antibiotics- Increased transmission- Priority of disease control less imminent Risk -> outbreak

TerminologyTerminology Rates are expressed per 100,000 inhabitants TB mortality = number of deaths from TBTB lethality = deaths from TB at a certain point of time

expressed as % of incidenceTB prevalence = number of TB cases at a point in timeInfection prevalence = % of population infected with TB TB incidence = number of TB cases infected in a defined

yearInfection incidence = number of new cases (re-) infected

with TB in a certain yearTuberculin index = % of a defined age-group of a

defined population developing a positive tuberculin test at a given point in time

TerminologyTerminology

Bacterial resistance = 1% of TB bacilli population insensitive to chemotherapy

Resistance: mono / multiple INH = 5-10%, RMP rare Resistance: primary / secondary MDR-TB -> resistant to both INH + RMP

Blessing or threat?Blessing or threat?

TB is rare in industrialized countriesIf undetected, increased morbidity followsOutbreak to the general population may be

the result

Current situation in the Current situation in the Netherlands (NL).Netherlands (NL).Mortality rate = 2 / 100,000 Morbidity rate = 20 – 50 / 100,0001n 1987, 1229 cases recordedCurrent problems -> emergence of drug

resistance and HIV-infection.

0%

20%

40%

60%

80%

100%

1981 1984 1987 1990 1994

Total

Immigrants

Dutch

Prognostic factors.Prognostic factors.

Extent of the disease Cavernous lung disease Family history of tuberculosis Social factors Nutrition status Immune state R/

TB in the year 2000TB in the year 2000

TB -> still a leading cause of death in developing countries

TB -> kills 3 million people a year worldwide

3 current epidemics -> HIV, resurgence of TB, MDR-TB

AIDS + MDR-TB (super bug) -> alliance of error

HIV attributable TBHIV attributable TB

In 1990 -> 4%In 2000 -> 14%, of which 40% in sub-

Saharan Africa, another 40% in South East Asia

Global mortality from TB associated with HIV in 1990 -> 116,000

TB in HIV-positive subjectsTB in HIV-positive subjects

M. Tuberculosis: Prevalence is higher than in HIV-

negative subjects; Often preceeds the diagnosis of AIDS,

is commonly a reactivation of a latent infection;

Other mode of presentation than in HIV-negative individuals.

TB variance in HIV + and HIV - subjects.FeaturesAge incidenceFeverCaseationAFB’s

Tuberculin testCalcificationHilaradenopathyCavitationExtrapulmonary

sites

HIV +20 – 50 yearsCommonMinimalPresent, often extracellularNegative in 60%AbsentBilateralRareIn 50%

HIV –50 + yearsCommonPresentPresent, usually intracellularPositive in mostPresentUnilateralCommonRare

Atypical TB in HIV-postives.

Atypical TB: MAIS- complex, exposure difficult to

escape; Late manifestation of HIV disease, an

expression of severe immuno-suppression; Is usually widely disseminated, lung is not

the primary organ affected; Heaps of intracellular AFB’s; Is to be seen as a harbinger of death.

Prevention and control of TBPrevention and control of TB

2 basic strategies of paramount importance: Timely identification and effective

treatment Effective and timely screening of close

contacts

Contact tracingContact tracing

Ring 1 = high contact, 20% risk of infection

Ring 2 = moderate contact, 4% riskRing 3 = little contact, 0,3% riskPositive case finding in an inner ring,

influences testing in an outer ring

Summary (1)Summary (1)

Past R/ ineffective -> high morbidity and mortality

Chemotherapy and improved socio-economic conditions -> a radical change in R/ -> ambulant and in out-patient setting

Result -> TB, a rare disease in industrialized countries

Summary (2)Summary (2)

In 1980+ : relaxation / dismantling of TB control network

HIV epidemic causes TB resurgence Drug resistance leads to MDR-TB in

Sub-Saharan Africa and South East Asia Some states of the USA Might become a problem in W. Europe

A 3rd epidemic with MDR-TB should be avoided at all costs

Recommended literatureRecommended literature

Styblo K. Brudney et al Ryan Fr. Dolin PJ et al Gyselen A.

Recommended sitesRecommended sites

New York’s Health departmentGlobal netwerk TB controlCenters for disease control & preventionJohn Hopkin’s National Institute of Allergy & Infectious

DiseasesTuberculosis testingDiscuss global TB program

Further linksFurther links

Search for TB articles Personal stories, support groups National Library of MedicineWorld Health OrganizationTuberculosis control in NLTuberculosis control in Belgium