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Microscopy
Acid-fast bacilli (AFB) Ziehl andNeelsen (1892)
Tuberculin-Skin Test
Robert Koch 1890 (Tuberculin) Mendel (1909), Mantoux (1910)
Diagnosis of active TB
Today
Microscopy remains the frontline tool for diagnosing active TB But New and exciting developments
Microscopy
o Certain amount of bacilli needed for visibility Diagnostic delay Morbidity
Transmission
Microscopy
Advantages o Can be used at district level o Simple and inexpensive o Rapid detection of infectious cases Disadvantages
o Diagnostic delay: 5000-10,000 bacilli/ml o Sensitivity 60-70% in HIVuninfected adults o Suboptimal in
o HIV-infected o Children 20% o Extrapulmonary TB (EPTB)
o Cannot distinguish
o M. tuberculosis versus NTM o Dead or live M. tuberculosis o Drug-sensitive or resistant
Symptoms
o Non-remitting cough o Night sweats o Fever o Fatigue o Organ-specific symptoms
Symptoms
Advantages o Cheap o Can be done anywhere Disadvantages o Unspecific o No diagnosis BUT: index of suspicion
Chest radiography
Advantages o Diagnosis of extent of disease and complications o o o o Disadvantages Unspecific Often difficult to access Equipment and personnel Training in interpretation
= Indirect assays Detection of the host response to M. tuberculosis o Cannot differentiate between active TB and M. tuberculosis infection (LTBI)
Bacteriologic confirmation
Advantages Disadvantages
o Gold standard o Increases case-finding (3050%) o Earlier detection than microscopy (10-100 bacteria/ml)
o o o o o o
Time (incl. DST) Cost Lab and HR requirements Biosafety requirements Training Maintenance of equipment
Conclusion
o Existing diagnostic tools are suboptimal
o Accuracy (microscopy)
o HIV-infected o Children
NDWG 2009
Sophistication of diagnostic
Health clinic
Needs assessment
o Depends on the epidemiologic setting and health system context o Add-on or replacement? Each of these indications has different needs for a test no one-fits all solution
Desirable: o High accuracy in all patient groups (smear positive, smear negative, HIV-infected, children, EPTB) o Easy to perform
o Little training, user-friendly o Biosafety o Close to the patient point of care
Improved microscopy
o Fluorescent microscopy
o 10% increased yield o Recommended for intermediate level laboratories (100+ smears)
MODS
o Simple o Less expensive o Modest training requirements o Combines detection of M. tuberculosis and DST o Not standardized o Local variations in methodology o Quality assurance o Biosafety WHO 2011: Recommended for MDR suspects as interim alternative
o based on DNA strip technology. Three steps: DNA extraction, PCR and reverse hybridization Recommended for detection of MDR TB on smear+ samples
Xpert MTB/RIF
Xpert MTB/RIF
Potential for point of care test? Cost Electric supply WHO policy statement: Xpert MTB/RIF as initial diagnostic test in MDR suspects or HIV-infected TB suspects Follow-on test to microscopy in MDR or HIV lowburden settings, further testing of smear negative samples District, Sub-district Level
Conclusions
Exciting development in the area of new diagnostics Challenges:
Cost Adoption at country level Implementation and scale up
43 % 24 %
Children 57-85%
15 %
5-10 %
modified from Sharma SK Lancet Infect Dis 2005; Marais Int J Tuberc Lung Dis 2004
TB diagnosis in children
Diagnostic challenges: o Different disease presentation o Difficulty to produce sputum
Alternative: gastric acid
o Paucibacillary TB
Urine LAM
Volatile organic compounds
No data
NDWG 2009
WHO
Little information on
o Functioning of new tool in different epidemiologic settings o Functioning of new tool within diagnostic algorithms o Cost effectiveness o Impact on health system and patients o Operational issues: training, maintenance, , supply chains, storage, waste management
o Question remains: which tool or which combination of new tools o Will there be another, better tool soon?
vanKampen PLoS One 2010
Research
o Delay policy process? o Accompanying implementation process
o Optimize implementation o Inform national and global policy
What are the human resource implications of introducing the test? (training, number and cadre of staff) What are the infrastructure implications? (equipment, lab layout, safety installations) What are the procurement implications? (reagents, consumables, documentation) What are the implications for quality assurance? (internal and external)
What are the projected impacts of going to scale with the test? eg a) cost savings to patients in relation to income b) cost savings to health providers / the health system d) Effects on transmission of improved infection control as a result of test introduction What other similar technologies are available or likely to become available? How do similar existing or emerging technologies compare in their projected performance within each of the layers above? Bertie Squire and Gillian Mann, Liverpool School of Tropical Medicine
Layer 4: Layer 4: SCALE UP SCALE UP ANALYSIS ANALYSIS Layer 5: Layer 5: POLICY ANALYSIS POLICY ANALYSIS
Conclusions
o Exciting new diagnostics have been developed o Many open questions remain as to
o how these new diagnostics work in health systems o how they influence patient outcomes
Thank you!