WHO Guidelines on the Management of Latent TB Infection

Transcription

1 WHO Guidelines on the Management of Latent TB Infection 17th Wolfheze Workshops and 13th WHO National TB Programme Managers' meeting, The Hague, The Netherlands, 27 May 2015 Alberto Matteelli Global TB Programme, WHO

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4 Primary target countries for the WHO LTBI guidelines 113 high or upper middle income countries with an estimated TB incidence rate of less than 100 per 100,000 population

5 The guidelines target low burden high income countries WHO guidelines primarily target high-income or upper middle-income countries with an estimated TB incidence rate of less than 100 per population. Why low incidence? The higher the risk of re-infection the lower the individual benefit and the cost-effectiveness of the strategy Why high resources? The lower the available resources (financial, human) the lower LTBI management can compete with diagnosis and treatment of active disease

6 Transition to predominant reactivation Sutherland Adv Tuberc Res 1976;19:1 Recent transmission Reactivation of latent infection

7 Recommendations on: Guidelines content Target high-risk populations Diagnostic process Treatment options and seveal ancillary suggestions

8 Recommendations on at-risk populations Risk population groups People living with HIV Adult and child PTB contacts Patients initiating anti-tnf treatment Patients receiving dialysis Patients preparing for transplantation Patients with silicosis. Prisoners Health workers Immigrants from high burden countries Homeless persons Illicit drug user Strength of recommendation Strong: systematic testing and treatment should be performed (Low to very low quality of evidence) Conditional: Systematic testing and treatment should be considered (Low to very low quality of evidence) Patients with diabetes People with harmful alcohol use Tobacco smokers Under-weight people Conditional: systematic testing and treatment is not recommended unless they belong in the upper two groups (Very low quality of evidence)

9 How were at-risk populations selected? Three systematic reviews to prioritize at-risk population groups: 1. Risk of progression from LTBI to active TB 2. Increased incidence of active TB disease 3. Increased prevalence of LTBI Data available for 15 risk groups

10 Algorithmic approach to diagnosis and treatment of LTBI in at-risk populations Rule in LTBI Rule out active TB

11 Recommendation on ruling in LTBI Either TST or IGRA can be used to test for latent TB infection. IGRA should not replace TST in low and middle income countries 1. (Strong recommendation, very low quality of evidence) 1 Use of tuberculosis interferon-gamma release assays (IGRAS) in low- and middle-income countries. Policy statement. Geneva: World Health Organization; 2011.

12 How was evidence analyzed? Measure of outcome Risk ratio (RR) for test positives compared to test negatives (cohort studies) Selection of trials head-to-head studies (n=8), to minimize biases from heterogeneity of study setting and population

13 Pooled risk ratio for development of incident TB in 8 head to head studies

14 Recommendation on ruling out active TB Individuals should be asked about symptoms of TB and undergo chest radiography before initiating treatment of latent TB infection. Individuals with TB symptoms or abnormal radiological findings should be investigated further for active TB and other conditions. (Strong recommendation, low quality of evidence).

15 Algorithmic approach to diagnosis and treatment of LTBI in at-risk populations

16 Recommendation on LTBI treatment The following treatment options are recommended for the treatment of latent TB infection: 6 months isoniazid (6H) 9 months isoniazid (9H) 3 months weekly rifapentine plus isoniazid (3HP) 3 to 4 months isoniazid plus rifampicin (3-4HR)* 3 to 4 months rifampicin alone (3-4R)** (Strong recommendation, moderate to high quality of evidence) * Voted by 53% of panel and ** voted by 60% of panel as equivalent optionsfor 6H

17 Comparison of 6 months isoniazid with other regimens for the development of incident TB and hepatotoxicity

18 Risk of drug resistance following LTBI treatment No significant association of risk of drug resistance. INH RR (95%CI) = 1.45 (0.85,2.47) Rifamycin RR (95%CI) = 1.12 (0.41,3.08) However, Panel agreed on: Excluding active TB disease using all the possible investigations available Establishing national TB drug resistance surveillance systems along with LTBI management

19 Treatment of MDR-TB contacts No Recommendation, but Strict clinical observation and close monitoring for the development of active TB disease for at least two years is preferred over the provision of preventive treatment.

20 Contributors to the guidelines WHO Steering Group: Dennis Falzon, Nathan Ford, Haileyesus Getahun, Chris Gilpin, Christian Lienhardt, Knut Lonnroth, Alberto Matteelli, Lisa Nelson, Andreas Reis, Mukund Uplekar WHO Headquarters and Regional offices: Mohamed Abdel Aziz, Masoud Dara, Malgorzata Grzemska, Ernesto Jaramillo, Nobuyuki Nishikiori, Diana Weil, Karin Weyer Co-chairs of the WHO Guidelines Development Group: Holger Schünemann, Jay Varma. Consultants for Systematic Reviews: Saskia Den Boon, Esmee Doets, Enrico Girardi; Darshini Govindasamy, Ross Harris, Sandra Kik, Katharina Kranzer, Anouk Oordt-Speets, Molebogeng Rangaka, Monica Sane Schepisi, Giovanni Sotgiu, Helen Stagg, Femke van Kessel, Anja van t Hoog

21 Members of Guidelines Development Group Ibrahim Abubakar, Draurio Barreira, Susana Marta Borroto Gutierrez, Judith Bruchfeld, Erlina Burhan, Solange Cavalcante, Rolando Cedillos, Cynthia Bin-Eng Chee, Richard Chaisson, Lucy Chesire, Elizabeth Corbett, Justin Denholm,Gerard de Vries, Margaret Gale-Rowe, Un-Yeong Go, Alison Grant, Robert Horsburgh, Asker Ismayilov, Philippe LoBue, Guy Marks, Richard Menzies, Giovanni Battista Migliori, Davide Mosca, Ya Diul Mukadi, Alwyn Mwinga, Lisa Rotz, Andreas Sandgren, Holger Schünemann, Surender Kumar Sharma, Timothy Sterling, Tamara Tayeb, Marieke van der Werf, Wim Vandevelde, Jay Varma, Natalia Vezhnina, Constantia Voniatis, Robert John Wilkinson, Takashi Yoshiyama, Jean Pierre Zellweger

22 Members of Peer Reviewers Group Amy Bloom, Graham Bothamley, Gavin Churchyard, Daniela Maria Cirillo, Raquel Duarte, Michel Gasana, Stephen Graham, Connie Erkens, Brian Farrugia, Barbara Hauer, Diane Havlir, Einar Heldal, Rein Houben, Mohamed Akramul Islam, Jerker Jonsson, Michael Kimerling, Christopher Lange, Wang Lixia, Joan O Donnell, Anshu Prakash, Ejaz Qadeer, Lidija Ristic, Laura Sanchez-Cambronero, Martina Sester, Joseph Kimagut Sitienei, Alena Skrahina, Soumya Swaminathan, Ivan Solovic, Elena Suciliene, Maarten van Cleeff, Francis Varaine, Martina Vasakova, Irina Vasilyeva, Mercedes Vinuesa Sebastián, Brita Askeland Winje, Dalene von Delft, Dominik Zenner

23 Next steps LTBI task force, established in April 2015 Develop a Monitoring and Evaluation tool for LTBI activities Re-estimate the burden of LTBI, global and by at-risk population Implement a global survey on policies and practices for LTBI