New Tuberculosis Guidelines Jason Stout, MD, MHS
Two New Sets of Guidelines Treatment of Drug-Susceptible Tuberculosis Clinical Infectious Diseases 2016; 63(7): e147-e195 Diagnosis of Tuberculosis in Adults and Children Clinical Infectious Diseases 2017; 64(2): 111-115 A lot of changes!
How Are the Guidelines Written? Panel of experts convened by the involved societies American Thoracic Society, CDC, Infectious Diseases Society of America GRADE methodology Evidence-based Does not consider cost explicitly Strong recommendation=almost all patients should get this Conditional recommendation=most patients should get this Organized around PICO (population, intervention, comparators, outcome) questions
TB Treatment Guidelines Focus on drug-susceptible disease Focus on pulmonary disease
TB Treatment Guidelines Impact for NC TB control: None (we do this already)
TB Treatment Guidelines Impact for NC TB control: None (we do this already)
TB Treatment Guidelines
TB Treatment Guidelines
TB Treatment Guidelines
TB Treatment Guidelines
TB Treatment Guidelines Preferred treatment frequency is daily In situations in which daily is not feasible, 3x/week preferred Twice-weekly is least preferred
TB Treatment Guidelines
TB Treatment Guidelines
TB Treatment Guidelines
TB Treatment Guidelines
TB Treatment Guidelines
TB Treatment Guidelines
TB Treatment Guidelines
TB Treatment Guidelines What is not changed: Case management recommended DOT recommended 6 months of treatment for most forms of disease recommended Steroids for TB meningitis recommended 4 months of treatment for culture-negative TB What is changed Frequency of meds No steroids for TB pericarditis INH/rifapentine once-weekly for active disease generally not recommended
NC TB Control Response Agree broadly with the evidence-based guidelines Most of these items are easy to implement Increased frequency of treatment is a challenge Emphasis on daily for first 8 weeks For many patients, 3x/week is OK after that Use video DOT, particularly in continuation phase NC TB Manual has been changed to reflect the guidelines
Diagnosis of TB in Adults and Children Guideline addressed both testing for LTBI and active TB 23 evidence-based recommendations provided
Diagnosis of TB in Adults and Children IGRAs recommended over TST for persons 5 years or older who Are likely to be infected with Mycobacterium tuberculosis Have a low or intermediate risk of disease progression Have a history of BCG vaccination Are unlikely to return to have the TST read TST is considered an acceptable alternative
Diagnosis of TB in Adults and Children No preference for TST or IGRA in individuals 5 years or older who are likely to be infected with M. tuberculosis and have a high risk of progression to disease
Diagnosis of TB in Adults and Children Do NOT test persons at low risk for M. tuberculosis infection and disease progression If testing is required for administrative/legal purposes, recommend an IGRA for persons 5 years and older If the test is positive in such persons, repeat the test and consider positive only if both tests are positive
Diagnosis of TB in Adults and Children For children under 5 years of age, TST is the preferred test Mention that some experts are willing to use IGRAs in children over 3 years of age
Diagnosis of TB in Adults and Children AFB smears should be done for all patients suspected of having pulmonary TB Caveats: Negative AFB smear does not exclude pulmonary TB Positive AFB smear does not confirm pulmonary TB Testing 3 specimens recommended Sputum volume of at least 3 ml recommended, 5-10 ml preferred Concentrated specimens and fluorescence microscopy preferred
Diagnosis of TB in Adults and Children Both solid and liquid media should be used for mycobacterial cultures (as opposed to either one alone) NAA testing (PCR) should be performed on the initial respiratory specimen from patients suspected of having pulmonary TB Positive test in patient with intermediate-high level of suspicion can be considered confirmatory Negative test cannot be used to exclude pulmonary TB
Diagnosis of TB in Adults and Children Rapid molecular testing for drug resistance should be performed on specimens from patients with positive AFB smear or NAA who: Have been treated for TB in the past Were born or have lived for at least 1 year in a country with at least moderate ( 20 per 100,000) TB incidence or a high ( 2%) rate of primary multidrug resistant TB Are contacts to patients with MDR TB Are HIV infected
Diagnosis of TB in Adults and Children Mycobacterial culture of respiratory specimens for all children suspected of having pulmonary TB is recommended Children identified in contact investigations and whose source case has drugsusceptible TB may not need cultures
Diagnosis of TB in Adults and Children Sputum induction is preferred over bronchoscopy as the initial respiratory sampling method for adults with suspected pulmonary TB who either cannot cough up sputum or who have AFB smear-negative sputum If induced sputum cannot be obtained, bronchoscopy is recommended Postbronchoscopy sputum specimens should be obtained from all adults with suspected pulmonary TB Bronchoscopy (especially with biopsy) is also recommended for suspected miliary TB if induced sputum is smear-negative or unobtainable
Diagnosis of TB in Adults and Children Cell counts and chemistries should be performed on fluid (pleural, CSF, pericardial, ascites, and joint fluid) obtained from suspected sites of extrapulmonary TB Adenosine deaminase should be measured in fluid collected from patients with suspected pleural, meningeal, peritoneal, or pericardial TB Free interferon-gamma levels should be measured in patients with suspected pleural and peritoneal TB AFB smears should be performed on specimens from suspected sites of extrapulmonary TB
Diagnosis of TB in Adults and Children The following routine tests should be performed on specimens collected from suspected sites of extrapulmonary TB: Mycobacterial cultures NAA for TB Histological examination
Diagnosis of TB in Adults and Children One culture isolate from each patient with culture-positive TB should be submitted for genotyping
NC Control Program Response IGRAs are too expensive for general use in health departments given limited resources In general, prefer IGRAs over TST for non-health department providers IGRAs are desirable in the health departments in specific situations: Large contact investigations (integrated with opt-out HIV testing) Situations in which patients are unlikely to return (e.g. homeless patients) Low-risk patients with positive TST
NC Control Program Response Emerging data support use of IGRAs in children <5 years Guidelines/recommendations may evolve Most of the recommendations for active TB diagnostics are things we already do Expensive tests (adenosine deaminase, interferon gamma) are conditional recommendations with low-quality evidence Not something we would routinely do in the health department setting Can be considered if patient is hospitalized Personally would rather they get a larger sample for AFB culture
Conclusions A lot of new information to absorb Extensive changes were made to the NC TB manual; this is all in there Memo summarizing these changes was sent to health departments and other relevant stakeholders Challenging to implement some of these recommendations in an era of declining resources Focus on how to provide best care in the most efficient way possible for both patient and providers