WHO guidelines & operational handbook:

Module 2:
Systematic screening for
TB disease
Overview of guidelines

Released March 2021, composed of

17 recommendations covering two major areas:

1. Who to screen – what populations and

groups should be screened for TB disease
2. How to screen – what tools should be used
for TB screening

https://extranet.who.int/
tbknowledge/en/node/1274
Module 2: Systematic screening for TB disease 2
Background: Definition
Definition: Systematic screening for TB disease
“The systematic identification of people at risk for TB disease, in a pre-
determined target group, by assessing symptoms and using tests,
examinations, or other procedures that can be applied rapidly.”
Key features:
• Should be done systematically in a selected
population
• Should be done using a highly sensitive tool to
distinguish people with a higher probability of TB
• Should be followed with a diagnostic evaluation
using a test with high accuracy to confirm a diagnosis
• Should follow ethical principles specific to screening

Module 2: Systematic screening for TB disease 3

Background: Objectives of TB screening
• Benefit individuals by detecting TB early or preventing TB
• Improve access to diagnosis and treatment or preventive
care
• Reduce delays in diagnosis
• Improve treatment outcomes
• Reduce costs of TB care for people with TB
• Improve TB epidemiology at the community level
• Increase detection of people with TB and treat them
• Reduce transmission of TB
• Reduce prevalence over time

Module 2: Systematic screening for TB disease 4

Background: Role of TB screening in overall TB care

• Addressing the case detection gap

The “missing millions” of people who develop Case
TB each year and are not diagnosed, notified, detection
gap
started on treatment

• Reaching the most vulnerable groups

Those with highest risk for TB often have the
least access to care

• Enabling initiation of TB preventive treatment

Systematic screening for TB disease is essential
first step in initiating TPT in eligible populations

Module 2: Systematic screening for TB disease 5

Background: principles of screening

Module 2: Systematic screening for TB disease 6

 Evidence: populations at risk for TB
Relative risk of TB or prevalence of TB among risk
groups: Risk groups Relative Risk (RR) or Prevalence of TB
Strongly recommended risk groups Contacts of TB patients Prevalence = 3.6%

People living with HIV RR = 16

Prisoners Prevalence = 1.4%

Miners RR = 3.8

Clinical risk factors Diabetes mellitus RR = 1.5

Chronic lung disease RR = 2.5

Smoking RR = 1.6

Alcohol use disorders RR = 3.3

Drug use disorders Varies

Malnourishment RR = 3.2

Healthcare workers RR = 2.9

Community-based screening groups Urban poor communities RR = 3.0

Homeless communities Prevalence = 1.1%

Migrants/refugees/IDPs Varies

Module 2: Systematic screening for TB disease 7

Evidence: accuracy of screening tools
For people aged 15 years and older across high-risk
groups
(not including people living with HIV):
Screening tool Sensitivity Specificity

Prolonged cough 42% 94%

Any cough 51% 88%

Any TB symptom (cough, haemoptysis, fever, night sweats, weight loss) 71% 64%

Chest X-ray (any abnormality) 94% 89%

Chest X-ray (suggestive of TB) 85% 96%

Molecular WHO-recommended rapid diagnostic test 69% 99%

* Culture is reference standard

Module 2: Systematic screening for TB disease 8

 Evidence: accuracy of tests in people living with HIV

WHO-recommended 4 C-Reactive Protein Chest X-ray mWRDs

symptom screen Cut off >5 mg/L / 10mg/L
Population
Sensitivity Specificity Sensitivity Specificity Sensitivity Specificity Sensitivity Specificity

All people 83% 38% 90% / 83% 50% / 65% 93% 20% 69% 98%
living with
HIV
Inpatients 96% 11% 98% / 97% 12% / 21% 90% 7% 77% 93%

Outpatients 53% 70% 40% / 20% 80% / 90% 85% 33% 54% 99%
on ART
Outpatients 84% 37% 89% / 82% 54% / 67% 94% 19% 72% 98%
not on ART
≤ 200 CD4 86% 30% 93% / 90% 40% / 54% 94% 14% 76% 97%
cells/μL
Pregnant 61% 58% 70% / 70% 41% / 54% 75% 56% 55% 99%
women living
with HIV *Culture is reference standard

Module 2: Systematic screening for TB disease 9

Evidence: accuracy of screening tools
For screening children

Population Screening tool Sensitivity Specificity

Symptom screening 89% 69%

Child contacts <15 years
Chest X-ray 84% 91%

Children <10 years Symptom screening 61% 94%

living with HIV

*Composite reference standard

Module 2: Systematic screening for TB disease 10

Recommendations: populations to be screened
TB screening is strongly recommended
for:

Household People Miners

and close living with exposed to Prisoners
contacts HIV silica dust
These populations should always be screened in all
global settings.

Module 2: Systematic screening for TB disease 11

Recommendations: populations to be screened

TB screening is strongly recommended

for:

Child contacts
Children living
of people with
with HIV
TB
• Very high risk of TB
• Higher risk of rapid progression from
infection to disease

Module 2: Systematic screening for TB disease 12

Recommendations: populations to be screened
TB screening is conditionally
• recommended for:
People with risk factors for
TB seeking health-care • People with structural risk
service in settings with factors for TB and limited
≥0.1% TB prevalence access to health care
 Malnourishment  Urban poor
 Diabetes  Homeless
 History of previous TB  Refugees
 Chronic lung disease  Migrants
 Health care workers  Other vulnerable, marginalized
 Those with other risk factors groups
for TB
• People with untreated • People in settings with 0.5%
fibrotic lesions on chest X-ray TB prevalence
Module 2: Systematic screening for TB disease 13
Recommendations: tools for screening (>15 years)

Symptom • Feasible and easy to implement

screening: • Low resource requirements
• Cough
• Not highly accurate
• Multiple
• Does not detect everyone with TB
symptom

• Highly sensitive for TB disease

• Chest X-ray • Can detect TB before onset of
• Computer-aided symptoms
detection (CAD) • CAD approved in place of human
reading of CXR for adults (>15 y)

• Less sensitive as screening tool

Rapid molecular
but highly specific
tests
• Still requires a follow-up test

Module 2: Systematic screening for TB disease​ 14

Recommendations: tools for screening - HIV
For adults & adolescents (>10 years) living with HIV:
C-Reactive Protein
WHO 4-symptom screen • A general marker of
(W4SS) inflammation, can be
• used as a point-of-care
Any one of cough, fever,
test
night sweats, weight loss
• Increases specificity of
• Recommended to be done at
screening, particularly
every health visit
among those not yet on
ART

Rapid molecular tests

Chest X-ray & CAD • Can be used for
• Improves the sensitivity of screening all people
screening, particularly living with HIV
among those in regular ART • Strongly recommended
care for acutely ill and
• CAD only recommended for hospitalized patients in
those 15 years & older a “test and treat”
strategy directly to
guide treatment

Module 2: Systematic screening for TB disease 15

Recommendations: tools for screening children

For child contacts of TB patients (≤ 15 years)

• Symptom screening (cough, fever, weight
loss/lack of weight gain, reduced
playfulness)
• Chest X-ray

For childen living with HIV (≤ 10 years)

• Symptom screening (cough, fever, weight
loss/lack of weight gain, reduced
playfulness)
• Contact with TB patient

Module 2: Systematic screening for TB disease 16

Operational handbook
The handbook provides
• Support on developing context-specific screening
approaches
• A sound basis for national guidelines based on TB
epidemiology in different risk groups and the health
care system in the country
Target audience:
• Staff in national TB programmes and national
HIV/AIDS programmes
• Other health programmes involved in screening in
public and private sectors
• Communities and implementing partners

https://extranet.who.int/
tbknowledge/en/node/1275
Module 2: Systematic screening for TB disease 17
Operational handbook
How to create, implement, and update a national TB screening strategy?
Setting goals
Assessing the
and specific
situation
objectives
1
Monitoring, 2
evaluation,
and modifying 6 Identifying and
the programme prioritizing risk
3 groups

Planning, 5
budgeting and 4 Choosing
algorithms for
implementing prioritized risk
Module 2: Systematic screening for TB disease groups 18
Operational handbook
What are different screening models, and what are the pros and cons of them?

Mobile
Residential, Communit outreac
occupationa y events h
Health
l, and screenin Home
facilities
penitentiary gathering g
settings s campaig
Institution-based screening
approaches
n
Community-based screening approaches
• Can increase reach and coverage
• Can increase efficiency
• Higher resource requirements
• Will note reach remote or
isolated populations

Module 2: Systematic screening for TB disease 19

Operational handbook
What is a single screening test algorithm?
• Utilizes one screening test to distinguish
between people who possibly have TB and
are referred for TB diagnostic evaluation and
people in whom TB has been ruled out and
who can be assess for TPT

Why use this algorithm?

• Straightforward to understand
• Can be very effective if using screening and
diagnostic tests of sufficient accuracy

Examples
• Cough screening for all clinic attendees
• Community chest X-ray screening via a
mobile van

Module 2: Systematic screening for TB disease 20

Operational handbook
What is a parallel screening algorithm?
• Utilizes two screening tests together
– a positive or abnormal on either or
both test is an indication for
diagnostic evaluation

Why use this algorithm?

• More sensitive than a single screening
test approach – will detect more
prevalent TB ​
• However, less specific – will result
in diagnostic evaluation for
more people who do not have TB​,
higher cost implications
If either or both are Example
positive • Prevalence survey
screening algorithm – CXR and
symptom screening for all
participants

Module 2: Systematic screening for TB disease 21

Operational handbook
What is a positive sequential screening algorithm?
• Uses two screening tests - only those
positive on the first test going on to a
second screen, and only those positive on
both screens go on for diagnosis

Why use this algorithm?

• More specific than a single or parallel
screening approach – more efficient at
selecting people with the highest risk of
TB
• However, less sensitive – will not detect
all prevalent TB cases

Example
• Screening for symptoms, followed by
chest X-ray to select who should go on for
diagnostic testing

Module 2: Systematic screening for TB disease 22

Operational handbook
What is a negative sequential screening algorithm?
• Uses two screening tests - those positive on
the first test go straight to diagnostic
evaluation, those negative on the first test
go on to a second screen – thus those
positive on either screen go on for diagnosis

Why use this algorithm?

• High sensitivity but saves resources – the
more expensive screening test is conducted
only among those who do not already
screen positive with the less expensive
screening test
Example
• Screening for symptoms first, then
screening with chest X-ray only among
those who don’t report symptoms

Module 2: Systematic screening for TB disease 23

 Operational handbook
How to monitor and
evaluate TB screening? # people eligible for TB
screening
# people screened for TB
Acceptability (B/A) # people with presumptive
TB identified
Screened positive (C/B) # people evaluated for TB
Testing retention (D/C) disease
NNS and number necessary to # people diagnosed with TB
treat (E/B) and tested (E/D)
# people initiated on TB treatment
Linkage to care (F/E)
# people successfully completing TB
Treatment success (G/F) treatment
Global Indicators By 2025
Contact investigation coverage
Number of contacts of people with bacteriologically confirmed TB who were ≥ 90%
evaluated for TB, divided by the number eligible (%)
Treatment coverage
Number of people that developed TB, and were notified and treated, out of the total ≥ 90%
Module 1:
estimated number of incident TB preventive
cases treatment
in the same year (%). 24
Useful tools – ScreenTB online tool
ScreenTB
• Web-based tool to assist countries with
prioritization of risk groups for screening
and selection of screening tools and
algorithms
• Harnesses data from a variety of sources –
WHO Global TB Report, UN HIV data,
published literature
• Produces estimates of yield and cost of
screening, allowing for comparison
between risk groups and across algorithm
options within groups
• Creates figures to allow for easy visual
analysis

ScreenTB.org

Module 2: Systematic screening for TB disease 25

Useful tools – CAD calibration toolkit
What tools and resources are available?
CAD for TB Calibration
• A toolkit to assist countries with
calibration and implementation of
CAD
• Includes a protocol for gathering data
and a web-based tool for data
analysis to support decision-making
https://tdr.who.int/activities/calibrating
-computer-aided-detection-for-tb

Module 2: Systematic screening for TB disease 26

Useful tools – PreventTB application
What tools and resources are available?
PreventTB
• A mobile application that enables digital data recording and
reporting, analysis, monitoring and evaluation when implementing
TB screening and TPT

https://www.who.int/activities/preventing-tb/
Module 2: Systematic screening for TB disease 27
Useful tools – KSP website

Module 2: Systematic screening for TB disease 28

Main messages
• TB screening is a key intervention to find missing people with TB who are often the
most vulnerable, and enables initiation of TPT in those at highest risk of TB
• Chest X-ray is the preferred screening tool due to high sensitivity and ability to
detect
• Computer-aided detection (CAD) software using artificial intelligence can now be
used to automatically interpret digital chest X-rays for TB screening
• New screening tools also include rapid molecular tests and C-Reactive Protein for
people living with HIV
• A process of prioritization, planning, and careful monitoring and evaluation is
necessary when implementing screening in order to ensure that :
• The appropriate risk groups are chosen for screening interventions
• The best screening algorithms are chosen for each risk group, to maximize yield,
cost-effectiveness, efficiency of screening

Module 2: Systematic screening for TB disease 29

Acknowledgements

Cecily Miller, Saskia den Boon, Dennis Falzon at WHO Global TB Programme
Other WHO staff at Headquarters, Regional, and Country Offices
Patients and participants who contributed to evidence presented here
Evidence Reviewers
National TB and HIV Programmes
Guideline Development Group, External Review Group
FIND, Stop TB Partnership, IoM
TAG, civil society
Global Fund, USAID
Other experts and funding agencies

Module 2: Systematic screening for TB disease 30

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