Download Tuberculosis

Tuberculosis: Previous and
Present Millennium.
TB before advent
of chemotherapy
 TB in 1950 - 2000
 Morbidity,
Mortality &
Elimination of TB.
Censina R. Apap,
Pulmonologist.

Introducing Myself
Respiratory specialist since 1983
 Working in the Netherlands since 1977
 Special interests include Tuberculosis,
Asthma, COPD, and Oncology.
 Tuberculosis, a fascinating topic.

Introduction to the lecture
Natural history of TB
 Much morbidity and mortality before the
advent of antibiotics
 HIV, MDR-TB and relaxation of TB
control programs present new public health
problems

Tuberculosis in the past: Phtisis
Phtisis renamed Tuberculosis in 1837
 Congenital / infectious disease?
 Known to be infectious in 1865
 Cause of TB discovered by Koch in 1882
 Subdivision: open / closed TB

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?

“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.
1200
1000
800
Total patients
600
No of deaths
400
Total patie
% deaths
Sanatorium Hospital
Home /
1026
152
55
86
347
83
200
0
Total patients
No of deaths
Sanatorium
1026
565
From W.A. Griep
Hospital
152
131
Home R/
347
288
Deaths (fall off rate) due to TB.
% of deaths
After 1 year
Infectious TB Noninfectious TB
23.8%
0.9%
After 5 years
66.5%
After 10 years 74%
11.2%
16.5%
Active R/ of TB.

•
Collapse R/
 Artificial pneumothorax, Forlanini in
1888;
 Phrenicus paralysis;
 Thoracoplasty;
 Closed suction of lung cavities
(Monaldi);
Lung resection.
Complications of Thoracoplasty
Thorax cage instability with paravertebral
thoracoplasty
 Empyema and wound infections with
plombage
 In 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 infection

Mycobacteria inhaled -> phagocytosis by
alveolar macrophages-> 2 possibilities:
 No infection
 Infection (early / late)
Transmission 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 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.
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

Terminology
Rates are expressed per 100,000 inhabitants
TB mortality = number of deaths from TB
TB lethality = deaths from TB at a certain point of
time expressed as % of incidence
 TB prevalence = number of TB cases at a point in
time
 Infection prevalence = % of population infected
with TB
 TB incidence = number of TB cases infected in a
defined year
 Infection incidence = number of new cases (re-)
infected with TB in a certain year
 Tuberculin index = % of a defined age-group of a
defined population developing a positive
tuberculin test at a given point in time



Terminology




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?
TB is rare in industrialized countries
 If undetected, increased morbidity follows
 Outbreak to the general population may be
the result

Current situation in the
Netherlands (NL).
Mortality rate = 2 / 100,000
 Morbidity rate = 20 – 50 / 100,000
 1n 1987, 1229 cases recorded
 Current problems -> emergence of drug
resistance and HIV-infection.

100%
80%
60%
Total
Immigrants
Dutch
40%
20%
0%
1981 1984 1987 1990 1994
Prognostic factors.







Extent of the disease
Cavernous lung disease
Family history of tuberculosis
Social factors
Nutrition status
Immune state
R/
TB 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 TB
In 1990 -> 4%
 In 2000 -> 14%, of which 40% in subSaharan Africa, another 40% in South East
Asia
 Global mortality from TB associated with
HIV in 1990 -> 116,000

TB in HIV-positive subjects

M. Tuberculosis:
 Prevalence is higher than in HIVnegative subjects;
 Often preceeds the diagnosis of AIDS, is
commonly a reactivation of a latent
infection;
 Other mode of presentation than in HIVnegative individuals.
TB variance in HIV + and HIV subjects.
Features
Age incidence
Fever
Caseation
AFB’s
Tuberculin test
Calcification
Hilaradenopathy
Cavitation
Extrapulmonary
sites
HIV +
20 – 50 years
Common
Minimal
Present, often
extracellular
Negative in 60%
Absent
Bilateral
Rare
In 50%
HIV –
50 + years
Common
Present
Present, usually
intracellular
Positive in most
Present
Unilateral
Common
Rare
Atypical TB in HIV-postives.

Atypical TB:
 MAIS- complex, exposure difficult to
escape;
 Late manifestation of HIV disease, an
expression of severe immunosuppression;
 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 TB

2 basic strategies of paramount
importance:
 Timely identification and effective
treatment
 Effective and timely screening of close
contacts
Contact tracing
Ring 1 = high contact, 20% risk of
infection
 Ring 2 = moderate contact, 4% risk
 Ring 3 = little contact, 0,3% risk
 Positive case finding in an inner ring,
influences testing in an outer ring

Summary (1)
Past R/ ineffective -> high morbidity and
mortality
 Chemotherapy and improved socioeconomic conditions -> a radical change in
R/ -> ambulant and in out-patient setting
 Result -> TB, a rare disease in
industrialized countries

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 literature
Styblo K.
 Brudney et al
 Ryan Fr.
 Dolin PJ et al
 Gyselen A.

Recommended sites
New York’s Health department
 Global netwerk TB control
 Centers for disease control & prevention
 John Hopkin’s
 National Institute of Allergy & Infectious
Diseases
 Tuberculosis testing
 Discuss global TB program

Further links
Search for TB articles
 Personal stories, support groups
 National Library of Medicine
 World Health Organization
 Tuberculosis control in NL
 Tuberculosis control in Belgium
