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19-Jun-20 (c) PIOA 1 Spinal TB John Ferguson, Infectious Diseases Physician & Microbiologist, Newcastle, Australia Addendum: DR-TB Catherine Berry
19-Jun-20 (c) PIOA 1
Spinal TB
John Ferguson, Infectious Diseases Physician & Microbiologist, Newcastle, Australia
Addendum: DR-TB Catherine Berry
19-Jun-20 (c) PIOA 2
OVERVIEW
• Epidemiology
• Diagnosis and confirmation
• Medical management
Drug regimes
Dealing with failed treatment
Epidemiology
Epidemiology
• 1.7 billion latently infected worldwide – 10% lifetime risk of reactivation
• 10 million active cases in 2018- 5.7 million men, 3.2 million women and 1.1 million children (overall 0.86 million with HIV)• 30 high TB burden countries accounted for 87% of new TB
cases.
• Deaths 1.5 million in 2018 – case mortality without rx –45% (non HIV) and 100% (HIV)
• Globally, TB incidence is falling at about 2% per year
https://www.who.int/news-room/fact-sheets/detail/tuberculosis
https://www.who.int/news-room/fact-sheets/detail/tuberculosis
Risk factors
• Primary disease: • poverty, malnutrition, overcrowding, poor housing, limited
access to healthcare
• Reactivation (most occurring first 2 years post infection):• Old age• Immunosuppressive therapy -steroids, chemotherapy• alcohol use and smoking (17% of TB cases attributable to
either disease in 2018), • HIV (CD4
HIV and TB
In HIV:
• TB is a most important opportunistic disease
• TB causes severe illness and increases progression to AIDS;
• TB kills – it is the number one killer in HIV.
In TB:
• HIV is the main risk factor for progression from latent TB infection to active disease
• HIV increases adverse drug reactions to TB treatment
• HIV increases TB case fatality
• HIV increases recurrent TB.
All newly diagnosed TB patients must be screened for HIV.
https://www.who.int/tb/publications/global_report/en/
https://www.who.int/tb/publications/global_report/en/
TB Incidence rates – per 100,000: 2018
PNG 432 - rising
Tuvalu 270 - rising
Solomons 74 – stable
Fiji 54 - rising
Tonga 10 – falling
Samoa 6 – stable
Australia 6 – stable
http://data.worldbank.org/indicator/SH.TBS.INCD/countries?display=default
http://data.worldbank.org/indicator/SH.TBS.INCD/countries?display=default
Pott’s disease
• Vertebral osteomyelitis– Thoracic spine – most common– Back pain most common and earliest presenting
symptom – Progressive neurologic deficits and spinal deformity – Some patients lack clinical symptoms even in the
presence of active spinal disease. – Constitutional symptoms present in only 20%-30% of
cases– Cold abscess formation 50% –> discharging sinus
• Endemic countries – older children, young adults• Developed countries – older adults
Diagnosis
Diagnostic evaluation
• Clinical pointers - wider constitutional symptoms
• Radiology - include CT if possible; screen entire spine
• Exclude coexisting pulmonary TB or disseminated: symptoms, CXR, sputum examinations, induced sputum if cannot produce or HIV positive. Rapid testing with rif res is gold standard for diagnosis
• HIV antibody testing for all
• Spinal biopsy via needle or open surgery – Xpert-TB direct testing possible
• ESR/CRP non specific, insensitive- raised in 25-30%. WCC often normal.
• Baseline liver function tests if available
• Mantoux or Quantiferon-TB gold assay NOT of use – does not distinguish latent from active TB
Approach to TB diagnosis in HIV situation
• Sputum smear microscopy often negative in late HIV infection; atypical respiratory findings/radiology often
• Induced sputum and direct molecular detection is the current standard of care for HIV positive patients with abnormal CXR or symptoms c/w TB
• Consider in all HIV patients with suspected/proven bone/joint TB
• Urine TB-LAM (lipoarabinomannan) antigen testing likely to be used in future
• https://erj.ersjournals.com/content/erj/43/1/185.full.pdf (Inducted sputum• https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30001-5/fulltext
(TB-LAM)
https://erj.ersjournals.com/content/erj/43/1/185.full.pdfhttps://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30001-5/fulltext
Molecular TB detection platforms
• Xpert MTB/RIF
• Xpert Ultra
• GeneXpert® Omni® and Edge®
• Truenat MTB, MTB Plus and MTB-RIF Dx
• TB-LAMP® assay
• Fujifilm SILVAMP TB LAM antigen test (urine)
Detect smear negative, culture positive cases
Detect rifampicin resistance – indicates that MDR TB likely – early MDR treatment essential.
https://idmic.net/2018/04/09/recent-update-on-tb-diagnostic-techniques-genxpert-mtb-rif-ultra/
https://www.who.int/publications/i/item/9789240000339 January 2020
https://idmic.net/2018/04/09/recent-update-on-tb-diagnostic-techniques-genxpert-mtb-rif-ultra/https://www.who.int/publications/i/item/9789240000339
WHO evaluations of molecular testing evidence 2020
• High diagnostic accuracy and improved patient outcomes confirmed for Xpert MTB/RIF and Xpert Ultra as initial test to diagnose pulmonary TB (i.e. replacing smear microscopy) and to simultaneously detect rifampicin resistance
• Use of Xpert MTB/RIF and Xpert Ultra to diagnose TB and detect rifampicin resistance in children from sputum, stool, nasopharyngeal and gastric specimens: sensitivity varied by specimen type (46% for nasopharyngeal specimens; 61% for stool; 65% for sputum; and 73% for gastric specimens). Specificity for all specimens varied from 98% to 100%.
• Use of Xpert MTB/RIF and Xpert Ultra to diagnose TB and detect rifampicin resistance in adults with extra-pulmonary TB – LN, pleural fluid and other tissues
https://www.who.int/publications/i/item/9789240000339 January 2020
https://www.who.int/publications/i/item/9789240000339
Drug susceptibility testing
• Rapid testing: patients likely to have acquired TB in settings where the risk of multidrug resistance (resistant to isoniazid and rifampicin) is significant, the detection of rifampicin resistance by Xpert MTB/RIF highly predictive of MDR-TB
• Conventional DST: BACTEC 960 MGIT liquid culture system usual. First line DST (isoniazid, rifampicin, ethambutol, streptomycin and pyrazinamide). Drug resistant strains receive supplementary DST to the second line agents. Each requires 10-14 days for a result.
• Rapid detection of resistance from culture isolates and direct from specimens
• Line probe assays
• Sequencing
PMGH CPHL Lab has culture and DST (MIGIT) validated for rollout
NB. MDR-TB needs active detection and management approach; otherwise it expands to replace/ add to existing TB burden
https://pubmed.ncbi.nlm.nih.gov/27003160/
https://pubmed.ncbi.nlm.nih.gov/27003160/
Medical management
Treatment principles: drug susceptible TB
• 6-month rifampicin-based regimen 2HRZE/4HR remains the recommended regimen; fixed-dose combination tablets are recommended
• thrice-weekly dosing is not recommended in both the intensive and continuation phases of therapy and daily dosing remains the recommended dosing frequency
• ART should be started in all TB patients living with HIV regardless of their CD4 cell count within 8 weeks (2 weeks for patients with CD4 < 50
• Health education and counselling on the disease and treatment adherence should be provided to patients
• Directly observed therapy is the standard of care
GUIDELINES FOR TREATMENT OF DRUG-SUSCEPTIBLE TUBERCULOSIS AND PATIENT CARE - 2017 UPDATE WHO
MDR (rifampicin-R) treatment
Local expertise needs to be developed (supported as necessary from local or foreign expert clinician(s). Get support from an experienced clinician.
Treatment is usual standardised but recommended to be individualised on receipt of 2nd line DST
2020 WHO guidelines:
Option 1 – 9 – 11 months (fluoroquinolone sensitive only)
- 4 -6 month HEZ, ethionamide, moxi, clofazimine; 5 months E/Z/Mfx/Cfz
- Plus - 6 months Bedaquiline
Option 2 – 18 months
- 4-5 drugs including linezolid, bedaquiline, clofazimine, cycloserine & moxifloxacin
NB. Infectivity is guided by time to appropriate treatment – essential that MDR cases with pulmonary disease are isolated separately with appropriate protection for healthcare staff and relatives
MDR-TB regimens
https://www.who.int/publications/i/item/WHO-CDS-TB-2018.18
https://www.who.int/publications/i/item/WHO-CDS-TB-2018.18
Side effects (1)
https://www.health.qld.gov.au/clinical-practice/guidelines-procedures/diseases-infection/diseases/tuberculosis/guidance/guidelines
Queensland TB Guidelines 2015
https://www.health.qld.gov.au/clinical-practice/guidelines-procedures/diseases-infection/diseases/tuberculosis/guidance/guidelines
Side effects (2)
Immune reconstitution inflammatory syndrome
• Reconstitution of immune system– Worsening of symptoms– ~6-8 weeks following Rx commencement– Median 2 months– Self-limiting
• Corticosteroids – symptom control
– Mortality – rare except in CNS disease
• Incidence– 2%– 36% HIV positive patient
Duration: Bone and joint TB
Conventional wisdom: 9-12 months
QLD: “Standard short course therapy (2EHRZ, 4 HR) is sufficient in most cases where TB is known to be susceptible to first line drugs.
QLD: “Continuation phase is sometimes extended to 7 or 10 months but this regimen is not supported by published evidence unless:
• HIV infected
• infection is disseminated
• treatment interruption
• drug resistance suspected or proven.
Judging response to treatment
• Symptoms
• Deformity
• +/-ESR if abnormal prior to treatment
• Radiology
All patients should be followed clinically for at least two years following cessation of planned therapy.
Treatment failure
• Compliance major issue
• Relapse 2-5%
• Potential for re-infection – hospital infection control; infectious cases in household
• Mechanical failure of spine; neurological complications
• Drug resistance – emergence during treatment unusual provided compliant; failure to respond may indicate undiagnosed resistance
19-Jun-20 (c) PIOA 34
Take home messages• Epidemiology
• High burdens of latent TB infection in Pacific Nations
• Need for clinical vigilance for active TB, especially in those with risk factors (HIV, smokers, alcohol, diabetes, vitamin D deficiency (active treatment of latent TB optimal)
• Drug resistant TB is emerging and already at a significant level in PNG
• Diagnosis and confirmation
• Direct molecular detection (sputum and other) of TB and MDR is now the standard of care
• Special considerations for children and those with HIV
• Medical management
• Local clinical expertise required – patient education, close monitoring and drug management (side effects, MDR)
• Don’t neglect MDR-TB management- must embrace local detection & control
• Emerging shortened course management for MDR
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Questions
http://idmic.net for a range of PRIDA materials dealing with infection and antibiotic management (below) References will be listed there.
http://[email protected]
http://idmic.net/http://pridanetwork.org/mailto:[email protected]
