1. New WHO algorithm to prevent TB deaths in seriously ill patients with HIV
Yohhei Hamada
TB/HIV and Community Engagement

2. Seriously Ill Patients
Defined as patients with one or more of the
following danger signs:
Unable to walk unaided
Respiratory rate over 30/min
Fever of more than 39oC
Pulse rate of over 120/min

3. Challenges in early diagnosis
Low sputum bacillary load
Unable to provide sufficient and high quality sputum specimens
High rates of extrapulmonary TB

4. New tools to expedite TB diagnosis and treatment
Xpert MTB/RIF
Lateral flow urine lipoarabinomannan assay (LF-LAM)
Presumptive TB treatment ( ( (

5. Xpert MTR/RIF Automated and rapid assay (less than 2 hours)
Higher sensitivity than microscopy (79% for PLHIV)

6. Xpert MTR/RIF
Should be used as the initial diagnostic test in PLHIV to diagnose pulmonary TB and TB meningitis
May be used rather than conventional tests for testing other extrapulmonary specimens (lymph nodes and other tissues)

7. Lateral flow urine lipoarabinomannan assay (LF-LAM)
Urine-based point of care test
Results available in 25 minutes

8. Diagnostic characteristics of LF-LAM
Pooled sensitivity
Pooled specificity
By CD4 count
(5 studies)
<=100
56%
90%
<=200
49%
>200
15%
96%
By health care setting
Inpatients (6 studies)
54%
Outpatients (3 studies)
21%
97%
Sensitivity is higher with lower CD4 and higher severity of illness

9. LF-LAM associated with reduced deaths in HIV-positive inpatients suspected of having TB
Treatment given by trained nurses based on the positive LF-LAM

10. Lateral flow urine lipoarabinomannan assay (LF-LAM)
LF-LAM may be only used to assist in the diagnosis of active TB in HIV positive adults and children (both in-and out-patients), presumed to have TB who:
1) have a CD4 cell count<= 100 or
2) are seriously ill, regardless of CD4 cell count
LF-LAM should not be used as a screening test for TB
Detailed recommendations are available at:

11. Presumptive TB treatment
Operational definition Initiation of TB treatment for PLHIV in peripheral facilities based exclusively on clinical suspicion for “seriously ill patients” with respiratory distress based on the judgment of the clinician.

12. Presumptive TB treatment
Systematic review of presumptive TB treatment:
8 electronic databases up to March 2015.
2563 citations and 4 ongoing trials.
Identified one RCT (REMEMBER); but the study did not meet the operational definition of presumptive TB treatment.

13. This does not meet the operational definition of presumptive treatment
ACTG A REMEMBER trial
Multi-country RCT: Empirical TB tx vs IPT
Population: PLHIV with CD4<50 cells/mm2 without evidence of active TB
No evidence of reduced mortality as a result of presumptive TB treatment in PLHIV with CD4<50 in whom TB had been ruled out by extensive investigations and was not suspected.
This does not meet the operational definition of presumptive treatment
GLOBAL TB
PROGRAMME

14. This does not meet the operational definition of presumptive treatment
TB FAST TRACK Trial
Design: Cluster RCT
Population: Ambulatory PLHIV with CD4≤150
Intervention group:
Provide TB treatment for subjects with high TB probability (any of Hb <10g/dl, BMI ≤18.5 or a positive LF-LAM)
No reduction in mortality
This does not meet the operational definition of presumptive treatment
GLOBAL TB
PROGRAMME

15. 44% reduction in 8-week mortality among inpatients
Presumptive TB treatment associated with reduced deaths in PLHIV who are seriously ill and presumed to have TB

16. Presumptive TB treatment
In peripheral settings where TB investigations are not available, clinical assessment and judgment should be used to provide presumptive TB treatment for select individuals who are seriously ill

17. Xpert MTB/RIF-negative7 or no test available
HIV-positive or unknown and
Seriously ill, suspected of having TB and danger signs
Immediate referral to a higher level facility
Immediate referral not possible
Xpert MTB/RIF
Parenteral antibiotics for treatment of bacterial infections
Consider treatment for Pneumocystis pneumonia
Chest X-ray if available
Xpert MTB/RIF-positive
Xpert MTB/RIF-negative7 or no test available
LF-LAM may be used to assist in the diagnosis of active TB

18. Xpert MTB/RIF-negative7 or no test available
Clinical worsening or no improvement after 3-5 days
Improvement after 3-5 days
Start presumptive TB treatment
ART
Co-trimoxazole preventive therapy
Further investigations for TB and other diseases
Complete the course of parenteral antibiotics
TB unlikely
Reassess for other HIV-related diseases
ART assessment
Isoniazid preventive therapy
Co-trimoxazole preventive therapy
Complete the course of parenteral antibiotics

19. Conclusions
New WHO algorithm is likely to minimize delay in TB treatment initiation and prevent early mortality
Consider presumptive TB treatment among PLHIV who are seriously ill and presumed to have TB
Adopt rapid TB diagnostic tools (i.e. Xpert MTB/RIF and LF-LAM) to ensure early diagnosis of TB