TUBERCULOSIS:

THE PAST AND THE PRESENT

“The captain of all these men of death”
5800 BC Italy TB spondylitis
(female skeleton)
1000 BC Egypt TB spine /psoas abscess
(Nespharan mummy)
400 BC Greece “Phthisis”
(Hippocrates)
1300 AD Europe “Scrofula
(Arnold of Villanova)
1650 AD London “Consumption”
(London Bill of Mortalities)
 EUROPE
INDUSTRIAL REVOLUTION:
1800 - 1900

Annual Incidence of Tuberculosis

800 / 100,000
[compare Malawi at 230 / 100,000]

“The White Plague”

 TB TREATMENT
pre-chemotherapy
BC Venesection, leeches, emetics,
(Hippocrates) blistering agents on the skin

AD Monarch’s touch for scrofula

(Middle Ages) Laennec – seaweed
AD 1840 Fresh air, good diet, rest,
(Sanatorium) graded exercise
Robert Koch

1882: Described the tubercle

bacillus and linked it to
cause of TB

1882: Ehrlich developed a

more rapid stain “AFB”

1882: Ziehl and Neelsen

developed the currently used
“Z-N” stain
Tuberculosis is an air-borne disease

It can be transmitted by cough

It is associated with poverty and

crowding
The Chest X-ray: 1895 Conrad Roentgen
 TB CHEMOTHERAPY
1944 Streptomycin (S)
1945 Para-amino salicylic acid (PAS)
1952 Isoniazid (H)
1954 Pyrazinamide (Z)
1960 Thiacetazone (T) for use in developing world
1962 Ethambutol (E)
1969 Rifampicin
1960s - Standard treatment: 12-24 months
1970s- Short course treatment: 6 – 8 months
 1970s – 1980s

“TB is a conquered disease”

 BUT:
sharp increase in global TB in 1980s
• Disease flourished in the developing world, but no
visibility because subsumed into primary health care

• TB control neglected everywhere

• Dissolution of the Soviet Union

• Advent of HIV and AIDS

 Sooty-Mangabey Monkeys
Chimpanzees

1930s 1940s

HIV-1 HIV-2
Entered human population in 1930s
By December 2007 (26 years after
AIDS was first recognised)
• 25 million people worldwide had died of the
disease
• 33.2 million people worldwide living with the
virus (HIV) in 2007
• 2.5 million people in 2007 were newly infected
with the virus
• 2.1 million people in 2007 died from AIDS
 THE TB-HIV
INTERACTION
 Risk of TB in persons with
Mycobacterium tuberculosis

Not HIV Infected HIV Infected

Life time risk = 5-15% Annual risk = 5-15%

 TB risk in HIV-infected person

1200 TB risk doubles in first year of HIV

1100

1000
CD4 Cell Count (cells/mm3)

900
TB risk increases as CD4 count declines
800

700

600

500

400

300

200

100
AIDS Death
0
0 3 6 9 12 1 2 3 4 5 6 7 8 9 10 11
Weeks Years
 DUAL INFECTION

• 14 million people co-infected with HIV and

M.TB in the world

• 11 million people co-infected with HIV and

M.TB in sub-Saharan Africa (80%)
 Growth in TB incidence in Eastern and
Southern Africa, 1980-2004
700
Reported TB cases/100,000/year

Malawi
600 Botswana
500 Kenya
S Africa
400 Zimbabwe

300

200

100

0
1980 1985 1990 1995 2000 2005
 Estimated HIV prevalence in new adult TB cases

HIV prevalence in TB
cases, 15-49 years (%)

0-4
5 - 19
20 - 49
50 or more
No estimate

Sub-Saharan Africa: 35% TB cases HIV-infected

Southern Africa: 60-80% TB cases HIV infected

The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the
legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.
Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.
 WHO 2005. All rights reserved
1990:
• Global TB incidence
= 8 million
• Global TB deaths
= 1-2 million

1993:
WHO (Dr Arata Kochi)
declared “TB a global
emergency”
 Framework for TB Control
“DOTS”
• Sustained political commitment

• Case detection with smear microscopy

• Standardised short-course treatment

• Uninterrupted supplies of drugs

• Standardised monitoring and evaluation

Dr. Karel Styblo
Director of IUATLD

Pioneered the “DOTS” TB

Control Framework in the
1980s in Tanzania,
Malawi, and Mozambique
Find TB suspects
through passive
case finding

Obtain sputum for

smear microscopy
Get sputum to the
laboratory

Sputum prepared
with Z-N stain or
fluorescence and
examined by light
microscopy
Z-N stain: AFB on the slide = smear-positive PTB
 Algorithms for diagnosing
smear-negative PTB and EPTB
Get the patient registered and on TB Treatment as soon as possible

Implement directly observed treatment (DOT)

 Standardised TB Treatment

New Cases:

2RHZE/ 4RH is standard first line treatment

WHO recommended regimens - 2009

Systems in place to ensure uninterrupted TB drug supplies
Standardised monitoring, recording and reporting
 Quarterly supervision / monitoring of all TB
Registration centres and collation of national data
 Targets for TB Control:
set for 2000, then deferred to 2005
• To detect 70% of estimated smear-positive PTB cases
• To cure 85% of detected smear-positive PTB cases

• In the absence of HIV, target achievement will lead to:-

40% decrease in infected contacts

5-10% decrease in TB incidence
 GLOBAL PROGRESS:
Twelve years of DOTS

• 1995: DOTS Programmes initiated worldwide

• 2007: 180 countries used DOTS

37 million patients treated under DOTS
Global TB incidence rate falling slightly
Global TB case detection rate = 63%
Global TB treatment success rate = 85%
WHO Global Tuberculosis Report 2009
PROGRESS IN AFRICA REGION:

By 2007:

• TB case detection rate = 47%

• TB treatment success rate = 75%

WHO Global Tuberculosis Report 2009

 EFFECT OF HIV ON TB
CONTROL IN AFRICA
Programme delivery Patient management

• increased TB cases • difficult TB diagnosis

• hot spots of transmission • increased mortality
• stigma • increased recurrent TB
• illness in health staff • spread of MDR- XDR-TB
 Poverty

Immune deficiency Malnutrition

Tuberculosis
 Malnutrition and low body weight

Immune deficiency and low CD4 cell count

Tuberculosis
In the TB patient:
• Wasting
• Vitamin A deficiency
• Trace element deficiency
• Low levels of protein

Micronutrient deficiencies
are worse in those with
the lowest BMI
Nutrition - clinical outcomes
• study in Malawi -1181 patients
• risk factors for early death =
age >35, HIV, low BMI

In first 4 weeks of TB therapy:

• BMI<17 = 11% death
• BMI >17 = 6.5% death

Zachariah et al, 2002

 BUT……

No evidence that nutritional

supplementation on its own can improve
TB treatment outcomes
 Poverty and TB…
• The poor are at greater risk for TB

• The poor face barriers to accessing care:-

– Financial – user fees, diagnostic tests, transport
– Geographic - distance to health services
– Cultural – stigma, poor education, traditional
– Health system – poor treated worse than the rich
 Household characteristics of 770 smear-
positive Pulmonary TB patients in Malawi

• Live in mud-built houses 36%

• No piped water in house 75%
• No electricity in house 92%

• Household income (<$10/m) 45%

Claessens et al, IJTLD, 2002

 TB in Prisons

• High risk of TB transmission

• Overcrowding and poor conditions

• Poor people

• High HIV prevalence

 Zomba Central Prison
May and July 1996

Aim:
To determine prevalence of PTB in the prison

Method :
Active screening of prisoners in cells
 Zomba Central Prison
• Screened for TB 914 (70%)
• On TB treatment 14
• Interviewed about cough 900
• Cough > 1 week 238
• Gave sputum samples 222
• Diagnosis smear+ve PTB 18
• Diagnosis smear-ve PTB 15
 Zomba Central Prison

PREVALENCE OF PTB

47 / 914 (5%)

[75% of TB patients tested were HIV-positive]

 Conclusion

• High prevalence of TB in the central prison

• Strong association with HIV

• No TB control system in prison

Four main steps towards change
in policy and practice
 Step 1: write up and disseminate findings

August 1996 Study completed

November 1996 Study written up as report and as

draft paper
December 1996 Report presented to Chief
Commissioner of Prisons; agreement
to allow publication; instructions to
improve TB control in Malawi
prisons
November 1997 Paper published in Lancet
[1997; 350: 1284-1287]
 Activities

Move fast at the end of the study with

writing up

 Ensure dissemination to the people who

make decisions

Publish in a peer-reviewed journal –

improves credibility of the findings
Step 2: ensure TB prison control is an important
part of TB Programme Objectives

Jan-Jun 1997 •TB Prison control part of the

Objectives of TB control under
“improving equity”
•Identify specific budget line for
Prison TB control
Nov 1997 First meeting of NTP and Prison
Medical Staff. Minutes copied to
Chief Commissioner of Prisons and
Secretary for Health
 Activities

 Ensure topic is integrated into Disease

Programme planning and objectives

 Identify funding lines to support activities

 Ensure there is leadership and clarity at all

levels so that the new programme work
commences well
 Step 3: Build monitoring and evaluation
and accountability into the new activity
6-monthly meetings between NTP and
Prison Medical Staff with minutes
Incorporate supervision for prison TB
control into quarterly NTP activities
1999 - 2002 Invite prison medical staff to annual TB
meetings and training sessions
Invite NGOs to assist with Prison TB
control
 Activities

Support the new programme work

through routine activities
 Step 4: publicise the new programme work
at meetings and in papers
Number of New Prisoners 130,588
Number (%) with cough > 1 week 11,863 (9%)
Number Smear-positive PTB 516
Number Smear-negative PTB 603
Number EPTB 71
Cure rate (%) in smear-positive PTB 62%

Int J Tuberc Lung Dis 2003; 8: 614-617

Summary of the basic steps for getting
research into policy and practice
Before you start the research, think ahead
to…
 What you would like to see happen
 How you think your vision can be made
sustainable
 Who you will need for support
 Who you will need to validate any policy
changes
 Who will need to put policy changes into
practice
 Then, after the study….

1. Write up and disseminate findings

2. Ensure the topic becomes an important
part of TB programme objectives
3. Build monitoring and evaluation, and
accountability into the new activity
4. Publicise new programme work in
meetings and as articles