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)

EUROPEINDUSTRIAL REVOLUTION:

1800 - 1900

Annual Incidence of Tuberculosis

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

“The White Plague”

TB TREATMENT pre-chemotherapy

BC

(Hippocrates)

Venesection, leeches, emetics, blistering agents on the skin

AD

(Middle Ages)

Monarch’s touch for scrofula

Laennec – seaweed

AD 1840

(Sanatorium)

Fresh air, good diet, rest,

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

Entered human population in 1930s HIV-1 HIV-2

Sooty-Mangabey Monkeys Chimpanzees

1930s 1940s

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-HIVINTERACTION

Risk of TB in persons withMycobacterium tuberculosis

Not HIV Infected

Life time risk = 5-15%

HIV Infected

Annual risk = 5-15%

TB risk in HIV-infected person

Weeks Years

CD

4 C

ell

Co

un

t (

cell

s/m

m3)

0 3 6 9 12 1 2 3 4 5 6 7 8 9 10 11

1200

1100

1000

900

800

700

600

500

400

300

200

100

0

DeathAIDS

TB risk increases as CD4 count declines

TB risk doubles in first year of HIV

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

0

100

200

300

400

500

600

700

1980 1985 1990 1995 2000 2005

Re

po

rte

d T

B c

as

es

/10

0,0

00

/ye

ar

Malawi

Botswana

Kenya

S Africa

Zimbabwe

Estimated HIV prevalence in new adult TB cases

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

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

0 - 45 - 1920 - 4950 or moreNo estimate

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

Southern Africa: 60-80% TB cases HIV infected

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 contacts5-10% 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

• increased TB cases• hot spots of transmission• stigma • illness in health staff

Patient management

• difficult TB diagnosis• increased mortality • increased recurrent TB• spread of MDR- XDR-TB

Poverty

MalnutritionImmune deficiency

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]

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

Activities

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

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

Activities

Step 3: Build monitoring and evaluation and accountability into the new activity

1999 - 2002

6-monthly meetings between NTP and Prison Medical Staff with minutes

Incorporate supervision for prison TB control into quarterly NTP activities

Invite prison medical staff to annual TB meetings and training sessions

Invite NGOs to assist with Prison TB control

Support the new programme work through routine activities

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