TB control in a sea of TB/HIV

Upstream and Downstream Interventions.

Linda-Gail Bekker
The Desmond Tutu HIV Centre
Webinar WAD 2017

1
 Global TB in
2016

9th leading cause of death globally

Leading cause from single infectious agent
6.3 million new cases of TB globally in 2016
10% co-infected with HIV (74% in Africa).
1.3 million deaths (374 000 deaths in HIV/TB)
56% of TB in 5 countries
490 000 cases of MDR TB
16% of cases die from TB.
WHO 2017 TB Report
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HIV targets.....

3
 African regions are the most affected by the HIV epidemic &
behind in reaching the first 90-90-90 target: diagnosis of HIV
status
Western & Central Europe &
North America 90-90-90 Progress, 2015

Eastern & Southern Africa 90-90-90 Progress, 2015

Territory size
scaled by HIV
prevalence
(Benjamin Hennig,
Source: UNAIDS Gap Report, 2016
4
Worldmapper, 2003)
TB

5
6
7
8
 TB infection and disease
PTB

0.1% ARI 10% per lifetime

10% per lifetime

TB

TB Infection

9
35000

30000
Annual TB notifications
25000

20000

15000

10000

5000

0
Cape Town United Switzerland
Kingdom
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 NEW YORK 1910 CAPE TOWN 2010

City Population: 3.5 Million City Population: 3.5 Million

11
New York & Cape Town TB rates: 1910- 100 Years of TB
2010 900 New York TB notification rate
New York TB notification rate
800
Annual tuberculosis notification rate per 100,000

700

600

500

400

300

200

100

12
 New York : 1910-50, 1950-80 & 1980-2010

900 900 900

A B C
Annual tuberculosis incidence rates per 100,000

800 800 800

700 700 700

600 600 600

500 500 500

400 400 400

A : Generalised
300 300 300

C: Individualised
200 200
B : Localised 200

100 100 100

0 0 0
1910 1920 1930 1940 1950 1950 1960 1970 1980 1980 1990 2000 2010
13
New York & Cape Town TB rates: 1910- 100 Years of TB
2010 900
New York TB notification rate

Cape Town TB notification rate

800
Annual tuberculosis notification rate per 100,000

700

600

500

400

300

200

100

14
 High Force of Infection : HIV neg
PTB

20% per lifetime

10-14% ARI

30% per lifetime

TB

TB Infection

15
TST Status, Accumulated TB Disease & Infections
by Age in HIV-ve Population
School Sexual Peak HIV
entry debut Prevalence
1 20% 60% 75%

0.8
Proportion of population

TB disease
& infection

0.6
TB infected

0.4

0.2
Accumulated
TB disease

0
0 5 10 15 20 25 30 35 40
Age (Years)
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 HIV hyperendemic : HIV pos
15% per annum PTB

10-14% ARI

30% per annum

TB

TB Infection

HIV infection
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 CAPE TOWN NOTIFICATIONS (2010) : HIV infected and uninfected
800
800 HIV-positive new TB cases
HIV-negative new TB cases
HIV-positive retreatment TB cases
HIV-negative retreatment TB cases 700
700

Annual TB case notification rate per 100,000

600
Annual TB case notification rate per 100,000

600

500
500

400
400

300
300

200 200

100 100

0 0

Age strata (5-years) Age strata (5-years)

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 Primary Health care setting

HIV CT Referral to ART

TB clinic
services

TB Referral to TB
HIV/ART clinic
ACTIVE CF services

Missed opportunities: HCT, ACF, IPT, CTX

Inherent DELAYS and LOSS TO FOLLOW UP
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 The primary health care setting

HIV only HIV/TB TB only

TB treatment for TB treatment for

6-9 months 6-9 months

Overburdened clinics
and overburdened
ART for life ART for life patients 20
By integrating services (the 4th I)
Tackle the 3 Is in HIV+:
Intensified case finding (delay freeTB Rx)
(INH) Prophylaxis
Infection control
But other advantages in TB suspects and
patients:
Test all for HIV
Offer ART without delays
Streamline services to provide both medications
hassle free- quality of services (DSD=reduce LTFU).
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 TB + HIV: cont
Screen efficiently for TB
Diagnose drug resistance
More treatment options for MDR TB
TB treatments that are:
compatible with antiretroviral therapy
Well tolerated and safe

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 Systematic Review: 2013
Integrating TB and HIV services in low and
middle income countries
63 peer-reviewed articles and 70 Models of Integration:
abstracts describing models of 1. Entry via TB service, with
integration referral to HIV testing and
Referral-based models were the easiest care
to implement but referral failure 2. Entry via TB service with on-
remained a key risk. site HIV testing and referral
Further integration efforts require for care
more staff training and additional 3. Entry via HIV service with
infrastructure referral for TB screening
and treatment
Most reported outcomes (i.e. TB patients 4. Entry via HIV service with
tested for HIV), but few reported on site TB screening and
downstream impacts (such as referral for diagnosis and
ultimate outcomes of therapy) treatment
Few studies address the 5. TB and HIV services
Perspectives of service users or staff provided in a single facility
Costs and cost-effectiveness
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Legido-Quigley et al., 2013, Trop Med & Int Health.
Models for HIV/TB Integration

Legido-Quigley et al., 2013, Trop Med & Int Health. 24

 900
Cape Town TB notification rate

New York TB notification rate

Annual tuberculosis notification rate per 100,000
800

700
localised
Epidemic
600

500

Generalised Epidemic
400

300
The Whom and the Where to drive ECN down..

200

100

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Bekker, Wood (Royal Transactions 2016)
 1910 Edinburgh TB management
scheme
1. Dispensary, diagnosis & triage 1997 DOTS.
2. Sanatorium, early cases directly
3. Hospitalization, advanced observed
cases therapy
1948-1994 Mass Radiography
Total 3,3 million radiographs 1988 Fixed dose
2,58 milliom in fixed screening units TB combination
737,000 in mobile services therapy

1959 BCG vaccination

1912 Tuberculin therapy of all newborns

1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010

1924 Nelspoort 1983 Rifampin-based 2002 Public sector

Sanatorium short course antiretroviral
chemotherapy therapy

1904 Compulsory notification 1953 INH for TB meningitis

of TB deaths and new TB cases 1954 Combination Strep/PAS/INH

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Cape Town TB Combination Chemotherapy 1953-2009

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TB case fatality New York & Cape Town 1910-2010
0.7

New York TB case fatality

0.6
Cape Town TB case fatality

0.5
Tuberculosis case fatality

0.4

0.3
Streptomycin 1944

PAS 1947
0.2
Isoniazid 1952

0.1
Rifampicin 1967

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New York & Cape Town TB rates: 1910- 100 Years of TB
2010 900
New York TB notification rate

Cape Town TB notification rate

800

Anti-TB therapy
Annual tuberculosis notification rate per 100,000

700

600

500

400

300

200

100

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Bekker, Wood; Royal Transactions 2016
 Approach to TB

DISEASED INDIVIDUALS
Management

POPULATION CONTROL
Management
SUSCEPTIBLE INDIVIDUALS

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 TB Prevention strategies.

Susceptibles
Force of
infection

1

TB Infection TB Disease TB Case TB Cure
2

Death Death

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 TB transmission
Volume of shared air = ventilation

Prevalence of case Susceptability

and Infectiousness

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Annual Risk of TB Infection is Determined by
Number of Inhaled TB Infectious Quanta per Year
Annual Risk of TB Infection

Pinf = 1-e-(ftp*tbi**df)
Generalised version of
Wells & Riley Equation
C=S(1-e-iptq/Q)

Volume of Prevalence of Infectious quanta

shared air TB cases concentration
f*t*p TBI* **f

Social mixing & TB control TB case

environment programme infectiousness 33
Annual Risk of TB Infection is Determined by
Number of Inhaled TB Infectious Quanta per Year
Annual Risk of TB Infection

Pinf = 1-e-(ftp*tbi**df)
Generalised version of
Wells & Riley Equation
C=S(1-e-iptq/Q)

Volume of
Reduce Targeted caseof
Prevalence Infectious
Reduce quanta
shared
Exposure air finding
TB cases concentration
infectiousness
f*t*p TBI* **f

Social mixing & TB control TB case

environment programme infectiousness 34
 TB Risk and shared air

Shared Air: A Renewed Focus on

Ventilation for the Prevention of
Tuberculosis Transmission.
Richardson ET et al Plos One 2014.

Modeling the Role of Public

Transportation in Sustaining
Tuberculosis Transmission in
South Africa.
Andrews JR et al. Am J Epi
2012.
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 TB Control: Upstream
TB is still endemic and generalised
We need to tackle our generalised epidemic:
Primary Prevention
Turn our attention further upstream to tackle
transmission
Need to understand WHERE, WHOM and HOW
Transmission Driver is within the HIV Negative
population

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 TB Control: Downstream
With more than 6 million cases per annum
We have a treatment imperative
Earlier diagnosis, earlier sterilisation and
sustained cure
Reduced morbidity and mortality
Enhance adherence for cure and reduced
recurrence rates
Reduced TB drug resistance
Realise 2ndary prevention benefits
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 TB Control: innovation
Better understanding of the aerobiology
Where and when to interrupt TB
Improved mass active case finding
New drugs ART compatible, tolerable, single
dose
Better vaccine- pre-infection?
More options for MDR TB
Ways to prevent lung damage and improve
outcomes 38
TB Targets

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 TB Control : HIV co-infection
The localised epidemic in HIV infected population reflects an
ongoing generalised TB epidemic
Important to reduce mortality in TB/HIV population.
Must intensify case finding- TB testing in HIV/ HIV testing in TB/ Both
offered at health screening
Offer IPT but not at the expense of rapid ART commencement
Reduce further contamination of suceptibles.
Delays in treatment of both HIV and TB leads to increased
morbidity and mortality.
Pragmatic to co-locate and move toward integration (paying
attention to infection control).
More research required that measures outcomes including TB
cure, viral control and any risks (IC).
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 Acknowledgments
Robin Wood and Aerobiology Unit, DTHC
Carey Pike

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