Diagnosis of Smear negative pulmonary TB in high HIV settings: RESEARCH PRIORITIES Haileyesus...
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Transcript of Diagnosis of Smear negative pulmonary TB in high HIV settings: RESEARCH PRIORITIES Haileyesus...
Diagnosis of Smear negative pulmonary TB in
high HIV settings:
RESEARCH PRIORITIESHaileyesus Getahun, Stop TB, WHO.
Expert consultation on TB/HIV research priorities,14-15 February 2005, Geneva, Switzerland
Smear negative pulmonary TB
• At least three negative sputum specimens for AFB
AND
• Radiographic abnormalities consistent with active TB
AND
• No response to a course of broad spectrum antibiotics
AND
• Clinician decision to treat with a full course of TB drugs
Differential diagnoses in PLWHA
• Bacterial pneumonia• Kaposis sarcoma• Pneumocystis carinii pneumonia• Cryptococossis • Nocardiosis• Penicilliosis• Melioidosis• Histoplasmosis • Etc..
Magnitude of SN- pulmonary TB in PLWHA
• Significant increase in incidence in HIV+
• Inferior treatment outcomes than HIV-
• In published data SN- in PLWHA ranges from 24-61% ( 28% in 7763 patients)
• However,– Institution based (poor health coverage)
studies– Biased towards smear positives– In autopsy TB causes 14-54% of PWA deaths
Global TB data end of 2003
SS+
SS+
SS+
SS+
SS+
SS+
SS-
SS-
SS-
SS-
SS-
EP
EP
EPEP
EP
EP
SS-
0%
10%
20%
30%
40%
50%
60%
70%
India
Mya
nmar
Thaila
nd
Cambod
ia
China
Viet N
am
Global TB data, end 2003
SS+
SS+
SS+
SS+
SS+
SS+
SS+
SS-
SS-SS-
SS-
SS-
SS-
SS-
EPEP
EP
EP
EP
EPEP
0%
10%
20%
30%
40%
50%
60%
70%
Kenya
Moz
ambiq
ue
Niger
ia
South
Afri
ca
UR Tan
zani
a
Zambia
Zimba
bwe
Global TB data, end 2003
SS+
SS+
SS+
SS+
SS+
SS+
SS-SS-
SS-
SS-
SS-
SS-EP EP
EP
EP
EP
EP
0%
10%
20%
30%
40%
50%
USA
Germ
any
Portu
gal
Japan
Singa
pore
Nethe
rlands
Global TB data, end 2003
SS+
SS+
SS+
SS+
SS+
SS+
SS-
SS-
SS-
SS-
SS-
SS-
EP
EP
EP
EP EP
EP
0
10
20
30
40
50
60
AFR AMR EMR EUR SEA WPR
Regions
Per
cen
t
Proportion smear negative of all pulmonary cases with HIV
prevalence in selected sub-Sahara African countries, 2003.
R2 = 0.1601
2.0
2.5
3.0
3.5
4.0
4.5
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0
% HIV Prevalence in Adult (log)
Pro
po
rtio
n s
mea
r n
eag
ativ
e o
f al
l p
ulm
on
ary
case
s (l
og
)
SN- pulmonary TB in NTP
• Diagnosis of smear negative pulmonary TB in resource constrained settings is difficult.
• Less attention by NTP to document treatment outcome of SN- cases.
• SN- is an important component of TB that needs more urgent attention by NTP
WHO-Diagnostic Algorithm
Diagnostic algorithm
• Algorithm adapted from WHO• Key parameters include
– AFB sputum smear examinations– Diagnostic antibiotic trial (s)– CXR– Medical officer's judgement– Group discussion of the case (peer review)
• Best scenario assumption= 11-34 days• Few studies address delay in diagnosis among
PLWHA (Thailand and Zimbabwe)• Other suggested clinical predictors include
weight loss and anaemia.
Sputum smear microscopy
• If sensitivity improved-it is more valuable tool
• Positive threshold– Reported as 1+-3+ when >10 AFB/100 HPF– < 10 AFB/HPF reported in exact numbers– Scanty:" competent authority" to decide (c.f)
• Fluorescence microscopy – Increase ZN yield (15% and 18%)– 15X more field scanned in the same period than ZN– Reduce time needed (4 mt vs 10 mts)– Cost effective- $40 (on 2 sputa) vs $57(ZN 3 sputa)– Limitations: Economic, require electricity, naturally
fluorescent particles
Bleach method
• Most widely studied method
• Centrifugation and sedimentation
Bleach method95% CI of relative improvement of sensitivity
Bleach method
• Most widely studied method
• Centrifugation and sedimentation
• Used in 3 countries under routine NTP
• Additional processing time is the limitation
• Sensitivity 38→50% among PLWHA
• Most studies in hospital or research settings
• Technique is not standardised.
Sputum Culture
• 5-10 x more expensive• Selective recommendation (? Underutilised)• Sophisticated facilities and expertise• Contamination (1-4%) • Takes 6-8 weeks• MGIT
– 8-20 vs 20-26 days– The same facilities – Expensive– More contamination
Intensified TB case finding
• Early detection of cases through intensive case detection
• Practical Approach to Lung Health (PAL) improves efficiency of resp services and improves TB case detection
• Involvement of community members is very important
Conclusion
• Expedite the search for new and rapid tools
However, in the meantime• Research should be focused
– To immediately inform changes in policy and practice (e.g. rapid and effective diagnostic algorithm)
– To hasten the expansion and utility of existing diagnostic methods (e.g. bleach, culture facilities in peripheral settings)
– To inform the development of appropriate technologies for resource constrained settings (e.g. culture facility using solar energy)