Welcome to I-TECH Nurse Clinical Seminar Series 19 August 2010 2010 WHO Recommendations for TB...

Welcome to I-TECH Nurse Clinical Seminar Series

19 August 2010

2010 WHO Recommendations for TB Screening and

IPT among People Living with HIV

Stacie C. Stender

Objectives

• Review the WHO 12 point policy package• Describe the evolution of global IPT policy and

implementation, including WHO guideline development processes

• Identify evidence-based recommendations for TB screening and IPT in adults and children

• Determine who is eligible for isoniazid preventive therapy

WHO 12 point TB/HIV policy package

8. HIV testing and counselling9. HIV preventive methods10. Cotrimoxazole preventive therapy11. HIV/AIDS care and support12. Antiretroviral therapy to TB patients.

5. Intensified TB case finding6. Isoniazid preventive therapy7. Infection control for TB

1. TB/HIV coordinating bodies2. HIV surveillance among TB patient3. TB/HIV planning4. TB/HIV monitoring and evaluation

Three Is

A . Establish the mechanism for collaboration

B . Decrease the burden of TB among PLHIV

C. Decrease burden of HIV among TB patient

Review: Steps in TB Disease

EXPOSURE

INFECTION

DISEASE

DEATH

10% of general population

What is the lifetime risk of developing active TB if you have a competent immune system?

What is the risk of developing active TB in an individual with HIV and latent TB

IPT 50% of HIV infected individuals

Multiple stakeholders in international IPT policy

WHO/IUATLD. Tuberculosis preventive therapy in HIV-infected

individuals. A Joint Statement of the WHO

Tuberculosis Programme and the Global Programme

on AIDS, and the International Union

Against Tuberculosis and Lung Disease (IUATLD).

Wkly Epidemiol Rec 1993,68:361-364.

1993 1998 2004

WHO & Union

WHO & UNAIDS

WHO

Key IPT recommendations (1993-2009)

• IPT should be provided to TST positives• If TST is not feasible IPT should be given to:

– PLHIV in areas >30% MTB infection in population– Health workers, prisoners, contacts, miners

• CXR to exclude active TB until the validity of different screening algorithms established

• Self administered for 6 months

TB screening among PLHIV, 2003-2008

1384458

728929

364261

0

200000

400000

600000

800000

1000000

1200000

1400000

South Africa Africa region Global

2003

2004

2005

2006

2007

2008

7%

3%

4%

Poor TB/HIV Integration

48120

25553

7359

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

50000

South Africa Africa region Global

200320042005200620072008

Gap between policy & implementation of IPT

IPT provision among PLHIV, 2003-2008

2010, the year of…

New IPT Guidelines!

? Proper TB/HIV Integration?

Uganda example (2006)

Human resources:• Medical Officer• Laboratory assistant• Trained counselor• Pharmacy technician• Adherence supporters

Equipment and logistics:• Facilities for TB microscopy• Facilities for skin testing (mantoux)• Cold chain system• Facilities for HIV testing• Sustainable supply of anti-TB

drugs including isoniazid• Sustainable supply of HIV test kits

Eligibility criteria for an institution to offer IPTThe following are the minimum requirements for an organization/institution to offer IPT

Infrastructure:• Functional Laboratory• X-ray or access to x-ray

services• Counseling room/space• Consultation room

Other key issues:• If an organization has a TB default

rate of greater than 5% it will not be eligible to provide IPT

?

WHO GRADE Quality Assessment Criteria

Quality of Evidence

Study Design Lower if* Higher if*

High Randomized trial

Study quality:-1 Serious limitations-2 Very serious limitations-1 Important inconsistency

Directness:-1 Some uncertainty-2 Major uncertainty

-1 Sparse data

-1 High probability of reporting bias

Strong association: +1 Strong, no plausible confounders, consistent and direct evidence**+2 Very strong, no major threats to validity and direct evidence***

+1 Evidence of a dose response gradient

+1 All plausible confounders would have reduced the effect

Moderate

Low Observational study

Very Low Any other evidence

* 1=move up or down one grade (for example from high to intermediate) 2=move up or down two grades (for example from high to low)** A statistically significant relative risk of >2 (<0.5), based on consistent evidence from two or more observational studies, with no plausible confounders.*** A statistically significant relative risk of >5 (<0.2) based on direct evidence with no major threats to validity.

Strength of Recommendations

Strong: the desirable effects of a recommendation outweigh the undesirable effects.

Conditional: the desirable effects probably outweigh the undesirable effects. However,– Data are scant or– Only applicable to specific group/population or setting or– New evidence may change risk to benefit balance or– Benefits may not warrant the cost or resources required

Recommendation 1 : TB screening

Adults and adolescents living with HIV should be screened with a clinical algorithm and those who do not report any one of– current cough, – fever, – weight loss or – night sweats

are unlikely to have active TB and should be offeredIPT.

Strong recommendation, moderate quality evidence

Recommendation 2 : TB screening

Adults and adolescents living with HIV screened with a clinical algorithm and reported one of the following; – current cough, – fever, – weight loss or – night sweats

may have active TB and should be evaluated for TB and other diseases.


Evidence: individual patient data meta-analysis

Inclusion criteria for studies• Collected sputum specimens from PLHIV regardless of

signs or symptoms;

• Used mycobacterial culture of at least one specimen to diagnose TB and;

• Collected data about signs and symptoms.

What is the most sensitive clinical algorithm to screen for culture-confirmed TB in people living with HIV?

12 studies

Total patients in the 12 datasets (n=29,523)

HIV-uninfected patients or those with unknown HIV status (n=19,466)

HIV-infected patients (n=10,057)

Patients not receiving TB treatment (n=9,870)

Patients receiving TB disease or TB infection treatment at screening (n=187)

Patients with sputum smear results (n=9,710)

Patients with known TB status (n=9,626)

Patients with TB (n=557)

Patients without TB (n=9,069)

Unknown smear results or sputum smear positive with no culture or negative culture or culture grew NTM (n=160)

Patients with unknown TB status (n=84)

29,523

10,057

9,626

Top five best performing rules in all subjects

Combination rule

Sen(%)

Spe (%)

LR-

NPV (95% CI)

5% TB prevalence

CC, F, NS, WL 85 53 0.29 98.5 (98.1-98.8)

H, F, NS, WL 82 56 0.32 98.4 (97.9-98.7)

CC, F, WL 81 57 0.33 98.3 (97.9-98.6)

CC, NS, WL 81 57 0.34 98.3 (97.8-98.6)

CC, F, NS 81 62 0.31 98.4 (98.0-98.7)

CC: cough in the last 24 hours; F: Fever; H: Haemoptysis; NS: Night sweats; WL: Weight loss

Top five best performing rules in all subjects with abnormal CXR

Combination rule

Sen(%)

Spe (%)

LR-

NPV (95% CI)

5% TB prevalence

CC, F, NS, WL, X 93 40 0.17 99.1 (98.4-99.5)

CC, F, NS, X 92 50 0.16 99.2 (98.5-99.5)

CC, F, WL, X 92 43 0.20 99.0 (98.2-99.4)

H, F, NS, WL, X 91 44 0.20 99.0 (98.2-99.4)

CC, NS, W,L X 91 45 0.20 99.0 (98.2-99.4)


Performance of the best rule (one of current cough, fever, night sweats or weight loss)

SettingSen (%)

Spe (%)

LR- (%)

NPV (95% CI)

5% TB prevalence

Community 76 61 0.39 98.0 (97.4-98.4)

Clinical 89 30 0.38 98.0 (96.7-98.8)

CD4 < 200 94 22 0.29 98.5 (95.8-99.5)

CD4> 200 83 34 0.49 97.5 (95.3-98.7)


Recommendation 3

Adults and adolescents who are living withHIV and:

– have unknown or positive TST status and;– unlikely to have active TB

should receive IPT for at least 6 months

Strong recommendation, high quality evidence

Recommendation 4

Adults and adolescents who are living withHIV in settings with higher TB transmissionand:

– have unknown or positive TST status and;– unlikely to have active TB

should receive IPT for at least 36 months

Conditional recommendation, low quality evidence

Recommendation 5

Tuberculin skin test is not a requirement for initiating IPT for people living with HIV

Where feasible, TST can be used as people with a positive test benefit more from IPT than those with a negative test

Strong recommendation

Evidence for recommendations 3, 4 and 5

Outcome Studies

Patients RR (95% CI)

Probable, confirmed or possible TB

8 4136 0.67 (0.51,0.87)

- TST positive 4 1311 0.36 (0.22,0.61)

- TST negative 7 2490 0.86 (0.59,1.26)

- TST unknown 2 335 0.86 (0.48,1.52)

Confirmed TB 4 2063 0.72 (0.47,1.11)

- TST positive 1 112 0.13 (0.01, 2.32)

- TST negative 3 1021 0.76 (0.36,1.61)

- TST unknown 2 930 0.79 (0.46,1.36)

The effect of IPT is more in TST positives than TST negatives and unknowns

(Akollo et al 2010 Cochrane Review)

GRADE analysis table: 36 vs. 6 month IPT

RR for Probable TB (95% CI) = 0.50 (0.29 to 0.84) RR for Confirmed TB (95% CI) = 0.48 (0.26 to 0.9)

Samanadari et al, unpublished, 2010Martinson et al, unpublished, 2010

Settings for 36 month should be determined by national guidelines• Local context (feasibility, resources, safety and relevance) • Higher TB prevalence and transmission

Recommendation 6

Providing IPT to people living with HIV does not increase the risk of developing INH resistant TB. Therefore concerns regarding the development of INH resistance shouldnot be a barrier to providing IPT.


IPT and drug resistance RR 95% CI 1.45 (0.85-2.47)

(Balcell's et al, 2006)

Concomitant use of IPT with ART

• No study directly address the issue• Contrasting results on immune status and IPT effect

– No difference by HIV stage at baseline (Gordin, 1997)– Greater effect when TLC >2/L (Mwinga, 1998)– Not affected by CD4 count (Churchyard, 2003)– IPT+ART= TB IRR 0.20 (0.09–0.91) (Golub, 2007-Brazil)– IPT+ART= TB IRR 0.15 (0.004–0.85) (Golub, 2009-SA)

Strong recommendation, low quality evidence

TB screening and IPT algorithm

No Yes

Not TB TBYesNo Other Dx

Screen for TB (any one of the following): Current cough, fever, weight loss, night sweats

Investigate for TB and other DxAssess IPT contraindications

Person living with HIV

Treat for TB

Appropriate rx & consider IPTDefer IPTGive IPT Follow up &

consider IPT

Screen for TB regularly

?

Recommendations for Children: TB screening

• Children living with HIV who do not have poor weight gain*, fever or current cough are unlikely to have active tuberculosis TB.


• Children living with HIV who have any one of poor weight gain, fever, current cough or contact history with a TB case may have TB and should be evaluated for TB and other conditions. If the evaluation shows no TB, children should be offered IPT regardless of their age.


*Poor weight gain is defined as reported weight loss, or very low weight (weight-for-age less than -3 z-score), or underweight (weight-for-age less than -2 z-score), or confirmed weight loss (>5%) since the last visit, or growth curve flattening

Recommendations for children: IPT

Children over 12 months of age who are living with HIV and who are unlikely to have active TB on symptom based screening and have no contact with a TB case should receive 6 months of INH preventive therapy (10mg/kg)


In children less than 12 months of age, only those children who have contact with a TB case and who are evaluated for TB (using investigations) should receive 6 months IPT if the evaluation shows no TB disease


Summary changes in 2010

• Screening for TB only by using symptom based algorithm is sufficient to start IPT for PLHIV

• No mandatory CXR and TST requirement for IPT

• Regular screening of those on IPT at every visit

• Pregnant women, children, those on ART and those who completed TB treatment should receive IPT

• Conditional recommendation of 36 months IPT for settings with high TB transmission among PLHIV

3Is case: ICF & IPT

• Mrs. Z, a 26 year old HIV positive pregnant woman comes to the HIV clinic in your hospital for routine care with her 2 year old who is also HIV positive – How would you rule out active TB in Mrs. Z and

her child? – Is this considered active or passive case finding?– Would a tuberculin skin test (TST) be done as

part of the initial evaluation at your site?– If symptom negative, what dose of INH would

you offer Mrs. Z?

Thank You

[email protected]

mailto:[email protected]

Thank you!Next session: Sept 16, 2010

Listserv: [email protected]: [email protected]

Welcome to I-TECH Nurse Clinical Seminar Series

Next session:

TBD

Welcome to I-TECH Nurse Clinical Seminar Series 19 August 2010 2010 WHO Recommendations for TB...

Documents

Transcript of Welcome to I-TECH Nurse Clinical Seminar Series 19 August 2010 2010 WHO Recommendations for TB...