Downloaded 65 times
More Related Content
Similar to Diagnostic modalities in tuberculosis
Diagnostic modalities in tuberculosis
- 1. Dr Biplave Karki Resident InternalMedicine Diagnostic modalities in tuberculosis Pulmonary and Extrapulmonary
- 2. Mycobacterium tuberculosis Rodshaped Non-spore forming Aerobic bacterium 0.5 ×3 µm Neutral on gram staining Acid fast Mycolic acid Long chain crosslinked fatty acids
- 3. Global Burden Morethan two billion people (about one-third of the world population) are estimated to be latently infected with Mycobacterium tuberculosis . In 2015, approximately 10.4 million individuals became ill with tuberculosis (TB), and 1.8 million died Prompt diagnosis of active TB facilitates timely therapeutic intervention and minimizes community transmission
- 4.
- 5. Extra-pulmonary TB 10-40% ofTB Lymph nodes 35% Pleura 20% Genitourinary tract 10-15% Bones and joints 10% Spine 40% Hip 13% Knee 10% Meninges 5% Peritonium 3.5% Pericardium
- 6. Overview Sputum smearmicroscopy Culture Phenotypic drug susceptibility tests (DST) Molecular techniques Automated real time PCR (Xpert MTB/RIF) Line probe assays (LPA) Radiology X-rays Ultrasound Tuberculin skin test (TST) Interferon gamma release assays (IGRAs) Biopsies and fine needle aspirate cytology (FNAC) Laboratory tests on body fluids Other biological examinations
- 7. Sputum smear microscopy Rapid and reliable identification of patients with pulmonary tuberculosis (PTB) where there are more than 5000 bacilli/ml of sputum Low sensitivity(40-60%), non-specificity At least two sputum specimens about 80% of sputum smear-positive patients are found during the first sputum examination and over 15% more during the second First sample at the time of the consultation when the patient is identified as a suspected TB case Second sample early morning the day after
- 8. Sputum smear microscopy contd.. In order to limit the number of visits to the health facility, “frontloaded microscopy” ('same day' or 'spot-spot' microscopy) can be performed. Two sputum specimens are collected one hour apart. This strategy has shown similar results to the standard strategy over two days (spot- morning-spot).
- 9. Sputum specimen collection, storage Collect at least 3 ml Smears should be performed within three-four days of collection and in the meanwhile stored refrigerated (2 to 8°C) and protected from light Use Falcon tubes and add 1% CPC to preserve the specimen for up to 2 weeks. Specimens with CPC should not be refrigerated Sputum induction (3% or 5% hypertonic saline) Gastric aspiration (children) Bronchoscopy with washings or BAL
- 10. Satisfactory sample Criteriaof good quality sputum Physical appearance of sputum sample should be thick, purulent and/or bloodstained Sufficient quantity of at least 3-5 ml Contains no food particles or other remnants Unsatisfactory sample Saliva or upper aerodigestive tract secretion 24 hr sample Excessive food comtamination Very bloody specimen Absence of alveolar
- 11. Methods of staining Ziehl-Neelsen staining Auramine staining More rapid slide reading It is recommended in laboratories with a high workload defined as ≥ 20 slides per reader per day It requires trained, experienced technicians and a fluorescent microscope.
- 12. Ziehl-Neelsen staining Carbolfuchsin Steam for 5 min Rinse with distilled or filtered water 3% acid-alcohol (ethanol + hydrochloric acid) 3min 3 times Rinse with distilled or filtered water 0.3% methylene blue 1min Rinse with distilled or filtered water Air dry
- 13. Grading AFB scale(WHO- IUATLD) Examine at least 300 fields (15 minutes on average) before giving a negative result.
- 14. Grading AFB scale(CDC-ATS)
- 15. Auramin O staining 0.1% auramin O solution for15min Rinse with distilled or filtered water 0.5 % acid alcohol for 2 min Rinse with distilled or filtered water 0.5% potassium permanganate solution for 2 min Rinse with distilled or filtered water Air dry
- 16. Auramin O staining Readone length of the smear (about 40 fields)
- 17. Concentration techniques Centrifugation Increase the sensitivity of sputum smear microscopy and fluorescence (up to 20% in some settings with high HIV prevalence)
- 18. Culture More sensitivethan microscopy (10-100 bacilli/ml) 1. Confirmation of failures 2. Diagnosis of EPTB 3. Confirmation of smear negative TB when the diagnosis is in doubt 4. Distinction between M. tuberculosis complex and NTM 5. Monitoring treatment and outcome evaluation for patients on second-line anti-TB drugs
- 19. Culture contd.. InHIV-infected patients (CD4<100 cells/mm3) , cultures of blood and urine should also be performed in addition to culture of bodily secretions (sputum, BAL, pleural fluid). Once there is growth on either a solid or liquid media, the organism must be identified. Phenotypic Genotypic
- 20. Culture contd.. Othermethods of species identification High pressure liquid chromatography of mycolic acid Low cost, rapid immuno-chromatographic lateral flow assay (MTP64 Ag) Microscopic growth indicator tube
- 21. Drug susceptibility tests(DST) Phenotypic DST determines if a strain is resistant to an anti-TB drug by evaluating the growth (or metabolic activity) in the presence of the drug Genotypic DST Detect drug resistance through identifying genetic mutations (drug-resistant alleles) in the bacterium Also useful for Diagnosis of TB through the amplification of nucleic acids DNA or RNA (Nucleic acid amplification test NAAT)
- 22. Molecular techniques 1. Automatedreal time PCR (Xpert MTB/RIF) 2. Line probe assays (LPA)
- 23. Automated real timePCR (Xpert MTB/RIF) Based on hemi-nested real time PCR for simultaneous detection of M. tuberculosis (MTB) and rifampicin (RIF) resistance (rpoB gene) Minimum 1.5 ml sputum Highly automated test (only 3 manual steps required) run in a closed system with one cartridge per sample Each instrument can process 4 samples at one time processing time of just under 2 hours
- 24. Procedure for XpertMTB/RIF
- 25. Xpert MTB/RIF contd.. Sensitivities of assay 98% for smear-positive, culture-positive samples 72% for smear-negative, culture-positive samples (sensitivity can reach 90% if the test is repeated 3 times). 80% sensitivity and > 98% specificity when performed on cerebrospinal fluid, lymph node material and gastric fluid. Used as an initial diagnostic test (both adults and children) HIV-infected patients Suspected Multidrug-resistant TB (MDR-TB) or TB meningitis As the sensitivity of the Xpert test in pleural fluid
- 26. Xpert MTB/RIF contd.. Xpert with RIF positive Repeat the test Second Xpert MTB/RIF test does not show rifampicin resistance susceptible TB shows rifampicin resistance confirmed by a phenotypic DST or a different genotypic DST method
- 27. Xpert MTB/RIF Ultra(Xpert Ultra) Same molecular assay that detects Mycobacterium tuberculosis and rifampin resistance with increased sensitivity. Uses the same analyzer as Xpert but employs a new specimen cartridge and software WHO has recommended Xpert Ultra as a replacement for Xpert in all settings (where available) Sensitivity Culture positive sputum Culture positive but Smear negative Xpert 83 % 46% Xpert Ultra 88% 63% Source: Lancet Infect Dis. 2018;18(1):76.
- 28. Line probe assays(LPA) Conventional Nucleic Acid Amplification (NAA) amplifies M. tuberculosis-specific nucleic acid sequences with a nucleic acid probe, enabling direct detection of the bacillus lower sensitivity than culture and not recommended Two molecular techniques are commercially available: 1) Hain assays (Germany) GenoType® MTBDRplus GenoType®MTBDRsl 2) INNO-LiPA Rif. TB® line probe assay (Belgium)
- 29. GenoType® MTBDRplus assay Good at detecting rifampicin resistance but less so for isoniazid resistance among smear positive patients Mutation on KatG gene resistance to high-dose isoniazid Mutation on InhA gene resistance to both isoniazid and ethionamide, but not necessarily to high-dose isoniazid. Sensitivity Specificity Rifampicin 95.3% 95.5% Isoniazid 89.9% 87.1%
- 30. GenoType®MTBDRsl assay Detectsthe resistance to Fluoroquinolones (gyr A gene) and injectables drugs (rrs gene) with a good sensitivity but a lower specificity Triage test on smear-positive patients to guide the initial treatment in extensively drug- resistant TB (XDR-TB) suspects while awaiting confirmatory results from conventional phenotypic testing
- 31. Other Inexpensive DST Methods Microscopically observed drug suceptibility (MODS) Nitrate reduction assays Colorimetric redox indicator assays
- 32. Microscopically observed drug suceptibility(MODS) Microcolonies detected on solid media (7H11 agar) Light microscopy Identifies characteristics strings and tangles of M.tb Sensitivity 92%
- 33.
- 34. Indications for DST Ideally, genotypic DST is indicated for all patients at the start of TB treatment At the very least, the following patients should have DST performed to isoniazid and rifampicin, or rifampicin alone: 1. Previously treated patients; 2. Persons who develop active TB after exposure to a patient with documented MDR-TB 3. Patients who remain smear-positive after two months of therapy 4. New patients in countries with high prevalence of MDR-TB
- 35. Indications for DST(second-line drugs) 1. Resistance to at least rifampicin 2. Resistance to at least isoniazid and another Group 1 drug 3. Culture positive on or after Month 4 of an MDR- TB treatment 4. Active TB after exposure to a patient with documented MDR-TB.
- 36. Reliability of DST 1st line drugs very reliable for rifampicin and isoniazid less reliable for pyrazinamide much less for ethambutol Injectable and 2nd line drugs relatively good reliability and reproducibility for aminoglycosides, polypeptides and fluoroquinolones much less reliable for other second-line drugs (para-aminosalicylic acid, ethionamide and cycloserine
- 37. Radiology Chest X-ray Non-specific investigation for TB Not routinely indicated in sputum smear-positive patients Recommended smear microscopy results are negative suspected TB in children Particularly useful where the proportion of bacteriologically unconfirmed TB is likely to be high (populations with a high incidence of HIV) Pleural and pericardial effusions Miliary TB.
- 38. Chest X-ray Less common manifestations oPneumothorax oARDS ocorpulmonale olocalised emphysema
- 39. Radiology contd.. Bonesand joints (Xray and CT-scan) Ultrasound pleural and pericardial effusions abdominal TB multiple enlarged lymph nodes, bowel wall thickening (ileocaecal region)
- 40. Latent TB Heaftest Montoux test IGRAs
- 41. Heaf test Readat 3–7 days Multipuncture method Grade 1: 4–6 papules Grade 2: Confluent papules forming ring Grade 3: Central induration Grade 4: >10 mm induration
- 42. Tuberculin skin test(TST)-Montoux test 5 IU of tuberculin (PPD) injected intradermally on the ventral surface of the forearm and read after 48 to 72 hours The diameter of induration is measured with a ruler in mm across the forearm Positive TST ≥ 5 mm HIV infected Immunocompromised patients prednisolone therapy of ≥ 15 mg/day for ≥ 1 month Malnourished children ≥ 10 mm all other adults or children (BCG vaccinated or not).
- 43. Tuberculin skin test(TST) contd.. Role of TST Diagnosis of TB in children Identification of candidates for Isoniazid prophylaxis Highly positive (> 20 mm) or phlyctenular reaction can be considered as an argument in favour of active TB
- 44. False positive TST SevereTB (25% of cases negative) Newborn and elderly HIV (if CD4 count < 200 cells/mL) Malnutrition Recent infection (e.g. measles) or immunisation Immunosuppressive drugs Malignancy Sarcoidosis False negative TST BCG vaccination Average diameter after1 year is 10 mm (4 to 20 mm) Expected to disappear by 5 to 10 years. Non-tuberculous mycobacteria
- 45. Interferon gamma releaseassays (IGRAs) no cross reactivity with prior BCG vaccination and with most environmental mycobacteria less sensitive test in HIV co-infected expensive
- 46. Principles of IGRAs A sampleof either purified T cells or whole blood is incubated in the presence of antigens specific to Mycobacterium tuberculosis (ESAT-6, CEP-10) The release of interferon- gamma (IFN-γ) by the cells is measured by enzyme- lined immunosorbent assay (ELISA) ESAT (early secretory T-SPOT.TB® test QuantiFERON® – TB Gold test
- 47. Biopsies and fineneedle aspirate cytology (FNAC) Lymph nodes, bone and pleural lining Specific granulomatous tissue, the presence of giant Langhans' cells, and/or caseous necrosis strongly correlate with TB. AFBs are not always present Molecular tests can be used on the specimens obtained from FNAC of lymph nodes
- 48. Biopsies and fineneedle aspirate cytology (FNAC) contd.. Two smears with Giemsa stain Caseous necrosis, granuloma, giants cells, and epithelioid cells or histocytes 1 or 2 with Ziehl- Neelsen (ZN) stain acid-fast bacilli (AFB) G ranulomatous inflammation characterised by large numbers of macrophages and multinucleate giant cells (white arrow). The central area of this focus shows caseous degeneration (black arrow).
- 49. Biopsies and fineneedle aspirate cytology (FNAC) contd Biopsy and culture of bone marrow and liver tissue good diagnostic yield in disseminated (miliary)TB particularly in HIV infected patients, who also tend to have positive blood culture
- 50. Fluid Colour CellsAlbumin ∆, Glucose ADA (U/L) AFB stain Ascitic fluid Translucen t yellow > 300/mm3, lymphocytic Protein ≥ 30 g/L SAAG < 1.1 g/dl Revalta test positive >39 Negativ e (<2%) Pleural fluid Straw 1,000-2,500/mm3), predominant lymphocytes, L/N ratio >0.75 Protein ≥ 30 g/L Revalta test positive >50 Negativ e Pericardia l fluid Sero- sanguinou s Lymphocytes/monocyt es L/N ratio≥1 High protein >30 Positive (40- 60%) CSF Clear, concentrat ed 100 -1,000/mm3, 80% Lymphocytes Proteins>0.40g/L (Pandy test) Glucose<60mg/L, CSF/blood glucose<0.5 >10 Positive (<10%) Laboratory tests on body fluids
- 51. Role of ADAin diagnosis of TB Fluid ADA value (U/L) Sensitivity specificity Ascitic fluid 39 100% 97% Pleural fluid 50 92% 90% Pericardial fluid 30 94% 68% CSF 10 79% 91%
- 52. Xpert MTB/RIF inbody fluids Not recommedded in pleural fluid Has moderate sensitivity in CSF that can be increased following centrifugation Has modereate sensitivity in urine, specially recommended in those with CD4 <50
- 53. Other biological tests LAM assay based on detecting lipo-arabino-mannan (LAM) a carbohydrate cell wall antigen that is excreted in the urine of TB patients The sensitivity of the LAM urine assay for most populations are poor An exception is the sensitivity of the LAM assay in patients with CD4 counts < 200. Sedimentation rate almost always higher but very non-specific normal sedimentation rate makes TB less likely but still possible. C-reactive protein increased but very non-specific Rapid blood tests for “serological diagnosis of TB” Not very reliable in diagnosing active TB Not recommended by WHO
- 54. References Davidsons Principlesand Practice of Medicine 22ed Harrison's Principles of Internal Medicine 19th Ed Kumar and Clarks Clinical Medicine 9th ed Tuberculosis: Practical guide for clinicians, nurses, laboratory technicians and medical auxiliaries. 2014 Edition.
- 55.
Editor's Notes
- #8 Non-specificity, such that M. tuberculosis appears the same as non tuberculous mycobacteria (NTM)
- #10 CPC cethylpyrodinium chloride, not compatible with MGIT
- #11 A sputum Gram's stain specimen is considered satisfactory for interpretation when Neutrophil count >25 and epithelial cells <10 per low-power field.
- #12 Light microscope for ZN staining Fluorescence microscope with mercury vapor light sources/light emitting diode (LED) for Auramine staining.
- #14 Word Health Organization and the International Union against Tuberculosis and Lung Disease (WHO-IUATLD)
- #15 US Centre of Disease Control and American Thoracic Society (CDC-ATS)
- #16 Potassium permaganate or Acridine Orange
- #19 Egg based (Lowenstein-Jensen), Agar based (Middlebrook 7H10 or 7H11), Liquid (Middlebrook 7H12, MGIT 960) Rapid culture techniques Mycobacteria Growth Indicator Tube (MGIT) Microscopic Observation Drug Susceptibility (MODS) assay. Sputum culture has sensitivity 80% and specificity 98%.
- #20 Conventional method of species identification (growth time, colony pigmentation and morphology, and varieties of biochemical tests).
- #21 MGIT The fluorescent compound is sensitive to the presence of oxygen dissolved in the broth. Initially, the large amount of dissolved oxygen quenches emissions from the compound and little fluorescence can be detected. Later, actively respiring microorganisms consume the oxygen and allow the fluorescence to be detected.
- #24 Types of PCR Long PCR: Used to amplify DNA over the entire length up to 25kb of genomic DNA segments cloned. Nested PCR: Involves two consecutive PCR reactions of 25 cycles. The first PCR uses primers external to the sequence of interest. The second PCR uses the product of the first PCR in conjunction with one or more nested primers (as they lie/are nested within the first fragment) to amplify the sequence within the region flanked by the initial set of primers. Inverse PCR: Used to amplify DNA of unknown sequence that is adjacent to known DNA sequence. Quantitative PCR: Product amplification w r t time, which is compared with a standard DNA. Hot start PCR: Used to optimize the yield of the desired amplified product in PCR and simultaneously to suppress nonspecific amplification. Multiplex PCR: is a variant of PCR which enabling simultaneous amplification of many targets of interest in one reaction by using more than one pair of primer Reverse Transcriptase PCR(RT-PCR): Based on the process of reverse transcription, which reverse transcribes RNA into DNA and was initially isolated from retroviruses Real-time PCR: monitors the fluorescence emitted during the reaction as an indicator of amplicon production at each PCR cycle (in real time) as opposed to the endpoint detection Application of PCR DNA fingerprinting Drug discovery Genetic matching Genetic engineering Pre-natal diagnosis Classification of organisms Genotyping Molecular archaeology Mutagenesis Mutation detection Sequencing Cancer research
- #28 Xpert MTB/RIF Ultra (Xpert Ultra) approved in december 2017 The Xpert Ultra is available in the United States for research use only.
- #34 TLA (thin layer agar) MODS (microscopically observed drug susceptibility)
- #39 CXR in TB Infiltrates, nodules with or without cavitation in the upper lobes and in the superior segments of the lower lobes Pleural effusions Adenopathy in the mediastinum or hila (rare in TB in adults and adolescents) Miliary disease
- #42 Montoux induration 5–14 mm (equivalent to Heaf grade 2) and > 15 mm (Heaf grade 3–4)
- #46 IGRA is preferred in age more than 5 years but TST is preferred in age less than 5 years due to the lack of studies of IGRA in age less than 5 years.
- #47 QuantiFERON®–TB Gold In-Tube assay (also contains another specific Ag, TB 7.7)
- #49 The golden standard of diagnosis for TB on tissue samples is hematoxylin-eosin stain, but Giemsa stain can be used as an alternative in remote areas with limited equipment.
- #51 Pandy test Add 3 drops of CSF to 1 ml of Pandy reagent (saturated phenol solution) in centrifuge tube and look for white cloud The normal range of protein in CSF is 0.20-0.45 g/litre. The Pandy test is positive when protein is superior to 0.45 g/litre. Rivalta test Add 3 drops of pleural fluid/ascites to 2 ml of Revalta reagent (glacial acetic acid) in centrifuge tube and look for white cloud The test is positive when the proteins are superior to 30 g/litre The sensitivity of AFB smear and mycobacterial culture ascites fluid is low (less than 2 percent and less than 20 percent, respectively) The yield of mycobacterial culture may be increased (up to 83 percent) if 1 L of ascitic fluid (concentrated by centrifugation) is cultured SAAG is >1.1 in TB with cirrhosis The sensitivity of ascites fluid ADA in patients with cirrhosis is lower(30%), likely due to poor humoral and T cell–mediated response, in such cases, it may be a helpful supportive diagnostic tool if lower thresholds are used (21 to 30 international units/L) HIV-infected patients and patients already on TB medications may have lower levels of ADA ADA is generally not a good test in cerebrospinal fluid
- #55 a. When the patient’s serological status is unknown, this algorithm should be used in settings with HIV prevalence < 5%. b. Patients are considered to be at low risk of multidrug-resistant TB (MDR-TB) if they do not meet one of the following criteria: resident in areas with high MDR-TB prevalence; all retreatment categories; exposure to a known MDR-TB case; patient remaining smear + at 2 months; exposure to institutions with high risk of MDR-TB (e.g. prisons). c. Danger signs: respiratory rate > 30/min and/or fever > 39°C and/or pulse rate > 120/min and/or unable to walk. d. Smear microscopy: two sputum examinations performed on the same day. e. Broad spectrum ATB: • If no danger signs: amoxicillin for 7 days (NO fluoroquinolones); • If danger signs: parenteral ATB (e.g. ceftriaxone). f. Clinical response to a broad spectrum antibiotic does not rule out TB. Patient should be informed to return for reassessment if symptoms recur. g. According to setting: • Xpert MTB/RIF available: two sputum smear microscopy on the same day and one Xpert MTB/RIF from one of the samples collected for smear microscopy; • Xpert MTB/RIF not available: two sputum smear microscopy on the same day. h. In groups of patients with high level of resistance to isoniazid (> 10%) it is recommended to perform a conventional DST at baseline (and/or a line probe assay) in order to provide adequate treatment.
- #56 i. According to setting: • Prevalence of MDR-TB < 10%, patients seriously ill should immediately be initiated under empiric MDR-TB treatment. H and R will be included in the regimen until confirmation of MDR-TB by conventional methods. If the patient is stable, the clinician may choose to wait for confirmation before initiating a MDR treatment. • Prevalence of MDR-TB ≥ 10%, patients should be initiated under empiric MDR-TB treatment. Consider adding H in settings where mono-resistance to R is not uncommon. j. Clinical signs and chest X-ray (CXR) findings tend to be more typical in those who are HIV-negative having active TB
- #57 a. When the patient’s serological status is unknown, this algorithm should be used in settings with HIV prevalence > 5%. b. TB suspect is defined as: cough for more than 2 weeks or any cough with at least one of the following signs: loss of weight, night sweats, fever, and suspicion based on clinical judgment. c. Danger signs: respiratory rate > 30/min and/or fever > 39°C and/or pulse rate > 120/min and/or unable to walk. d. According to setting: • Xpert MTB/RIF available: two sputum smear microscopy on the same day AND one Xpert MTB/RIF from one of the samples collected for smear microscopy; • Xpert MTB/RIF not available: two sputum smear microscopy on the same day. e. In patients groups with high level of resistance to isoniazid (> 10%) it is recommended to perform a conventional DST at baseline (and/or a line probe assay) in order to provide adequate treatment. f. When possible a culture should be performed. A positive culture result at any point in time in the algorithm should lead to a full TB treatment. g. TB treatment should be started when clinical signs AND chest X-ray (CXR) are suggestive of TB. h. Broad spectrum ATB/PCP: • If no danger signs: amoxicillin for 7 days (or recommended oral agent for community-acquired pneumonia in the area). Do NOT use fluoroquinolones; • If danger signs: parenteral ATB (e.g. ceftriaxone) AND high dose cotrimoxazole. i. If no danger signs: patient should be re-assessed after 7 days. If danger signs: patient should be assessed daily and if no response, TB treatment should be considered after 3 to 5 days. Clinical response to broad-spectrum ATB does not rule out TB. Patient should be informed to return for reassessment if symptoms recur. j. Differential diagnosis of a coughing HIV-infected adult/adolescent: bacterial (including atypical) pneumonia, PCP, fungal infection, non-tuberculous mycobacteria, nocardiosis, Kaposi sarcoma and lymphoma. k. The diagnosis should be based on clinical assessment, CXR and CD4 results, whether cotrimoxazole preventive therapy (CPT) was used, and other treatment already used in the patient. If the index of suspicion for active TB is high, empiric TB treatment should be initiated without waiting for diagnosis confirmation. Other treatments such as broad-spectrum ATB or therapy for PCP may be needed in addition to TB treatment.
- #58 l. In the absence of any improvement of clinical signs (no weight gain, persistent cough, pain, etc.) AND no improvement on CXR after 2 months of a well conducted TB treatment, diagnosis and treatment should be reconsidered. MDR-TB should also be considered. m. In addition to the differential diagnosis in Note k above, DR-TB should be considered. n. Immediately start empiric MDR treatment, even if positive predictive value of Xpert MTB/RIF for R resistance is low (this is done to avoid the rapid and high mortality due to untreated MDR-TB in HIV patients). H and R should be included in the regimen until confirmation of MDR-TB by conventional methods if the patient comes from a group with less than a prevalence of MDR-TB < 10%. In groups of patients with prevalence of MDR-TB ≥ 10%, patients should be initiated under an empiric MDR treatment without H or R, although one can consider adding H in settings where mono-resistance to R is not uncommon.
- #59 a.The following patients are considered to be at high risk of MDR-TB: resident in areas with high MDR-TB prevalence; all retreatment categories; exposure to a known MDR-TB case; patient remaining smear-positive at 2 months; exposure to institutions with high risk of MDR-TB (e.g. prisons). b.Groups of patients at risk of MDR-TB are also at risk of other types of DR-TB as well. DST to the first-line should be performed in order to provide adequate treatment for possible mono- or poly-drug resistance. c.In populations with a prevalence < 10% of MDR-TB, the resistance to R diagnosed by Xpert MTB/RIF must be confirmed by conventional methods. Drug sensitivity testing (DST) to both first-line drugs and second line TB drugs should be performed if possible. d.In groups of patients with prevalence of MDR-TB < 10%, the decision to start the MDR-TB treatment will be made on clinical presentation of the patient and immunological status. Patients seriously ill and/or HIV+ should be initiated immediately under empiric MDR-TB treatment. H and R will be included in the regimen until confirmation by conventional methods. In groups of patients with prevalence of MDR-TB ≥ 10%, the patient should be initiated using an empiric MDR-TB treatment. Consider adding H in settings where mono-resistance to R is not uncommon. e. Baseline sputum smear microscopy result on 1 specimen in order to: 1) allow patient follow-up with microscopy; 2) take immediate decisions related to TB infection control.