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WORLD HEALTH O RG AN IZATION ORGANISATION MONDIAL E DE LA SANTE DOTS Expansion Working Group Annual meeting of the Childhood TB Subgroup La Maison des Polytechniciens Paris, France, 14 October 2008 Meeting Report Background Despite recent developments in childhood TB and issuing the international policy guidelines on the management of tuberculosis in children (2006 publication "Guidance for national tuberculosis programmes on the management of tuberculosis in children" http://whqlibdoc.who.int/hq/2006/WHO_HTM_TB_2006.371_eng.pdf ), many National Tuberculosis Programmes (NTPs) do not systematically include the management of children with TB as part of their routine operations. For the last two years, the childhood TB subgroup has been promoting the implementation of the guidelines in high TB burden countries through technical assistance to NTPs and working in close collaboration with other relevant groups of the Stop TB Partnership, including the DOTS Expansion Working Group, the MDR-TB Working Group and the TB/HIV Working Group. This fifth annual meeting of the childhood TB subgroup was held on 14 October 2008 in Paris, France. The meeting was divided into two parts. The morning session discussed country-level experience in policy implementation. The afternoon session focused on new developments in the field of childhood TB. The meeting was widely attended by the members of the subgroup, NTP managers and other representatives from 22 high TB burden countries, technical partners and WHO staff. This report outlines the main issues discussed during the meeting. The agenda appears in Annex 1 and the list of participants in Annex 2. All the presentation from the meeting are available and will be circulated to the meeting participants on a CD. 1. Progress report by Robert Gie, chairperson of the childhood TB subgroup. In the past year the childhood TB subgroup was involved in several initiatives: Consultation meeting of the group of paediatric experts, organized by WHO in July 2008, during which the literature review of the pharmacokinetics of isoniazid, rifampicin and pyrazinamide was discussed. As a result of this consultation, the group recommended changes to the current drug doses of the above first line drugs and identified future research areas. A soon as the new dosing is included in the WHO's Essential Drug List, the "Guidance for national tuberculosis programmes on the management of tuberculosis in children" will need to be revised. A workshop coordinated by Penny Enarson and chaired by Robert Gie was convened at the International Union Against Tuberculosis and Lung Disease (The Union) office in Paris to discuss and review a draft document on the prevention, diagnosis and treatment of tuberculosis in HIV-infected children. Several TB programme reviews included childhood TB issues and technical assistance was provided to Myanmar, Indonesia, Philippines and Cambodia in developing national guidelines for management of TB in children. Participation in the revision of the International Standards for TB Care (ISTC), workshop organized by the Retooling Task Force and revision of the BCG vaccination guidelines. Dr Gie also listed main challenges in the field of childhood TB and needs for training in high burden countries. 2. Three country reports on childhood TB activities Philippines - presented their experience in developing national guidelines on management of TB in children - collaborative work between the national TB programme (NTP), Philippine Paediatric Society and the multiple partners working in TB control. Integrating childhood TB with HIV - the Malawi experience. The presentation emphasized the importance of prompt initiation of TB treatment in HIV-infected children with confirmed or presumptive TB disease and the challenges in initiating the ART after starting TB treatment. The following issues need to be taken into account: child’s age, pill burden, potential drug interactions, overlapping toxicities and possible IRIS. Challenges of managing a child with MDR-TB - presented by Romania listed the difficulties with the diagnosis (TB in children is rarely culture positive), treatment with 2nd line drugs (drug formulations are inadequate for paediatric dosing), psychological and educational problems of children undergoing a very long therapy, sometimes in in-patient conditions. 3. BCG: new considerations for an old vaccine in HIV-endemic settings Anneke Hesseling presented the new considerations that need to be taken into account before a BCG vaccine is administered to neonates in high HIV prevalence setting. In view of the recent findings, mostly from research in South Africa, WHO has revised the BCG vaccination guidelines for infants at risk for HIV infection. The revised guidelines can be uploaded from the WHO website. http://www.who.int/wer/2007/wer8221.pdf Update from the "Expert group meeting on the dosing of childhood TB medicines" and proposed next steps on practical implementation of new recommendations Peter Donald presented the results of the literature review looking at evidence from studies on pharmacokinetics of three anti-TB drugs (isoniazid, rifampicin and pyrazinamide) in adults and children. The findings of the review suggest that there is a need for higher dosages in children to achieve serum concentrations comparable to those in adults. These findings were presented and discussed at the paediatric expert group meeting organized by WHO in July 2008. The group recommended an increase of dosing as follows: The dose of Pyrazinamide in children above 3 months of age should be 35 mg/kg (range 30-40) per day. The maximum daily dose should not exceed the recommended adult daily dose. The dose of Isoniazid in children above 3 months of age for treatment or prophylaxis (treatment of latent TB infection) should be 10 mg/kg (range 10-15) per day. The maximum daily dose should not exceed the recommended adult daily dose. The dose of Rifampicin in children above 3 months of age should be 15 mg/kg (range 10-20) per day. Dosages at higher ranges may be preferable for children under 10 kg and children with HIV infection or malnutrition. The maximum daily dose should not exceed the recommended adult daily dose. The recommendations from this technical meeting were presented to the STB department at WHO which decided that there is a need to update of the treatment guidelines for children (2006 document "Guidance for national tuberculosis programmes on the management of tuberculosis in children"). Another consequence is the need to develop new formulations of the fixed-dose combinations (FDC) that would be appropriate for the treatment of children. A full report from that meeting is available at WHO website. http://www.who.int/selection_medicines/committees/subcommittee/2/TB.pdf Update on the activities of the Retooling Task Force was presented by Davide Manissero. The Retooling Task Force was established by the Stop TB Partnership's Coordinating Board in 2006 to plan for adoption and introduction of new tools (vaccine, diagnostics and drugs) in high TB burden countries. The presenter summarized the activities and plans of the task force. More information is available at the Stop TB website http://www.stoptb.org/retooling/ Update on the revision of ISTC - reported by Davide Manissero The International Standards for TB care (ISTC) are undergoing revision to harmonize the document with WHO guidelines and include all new developments in diagnosis and treatment. In order to promote Childhood TB within the ISTC, it was decided that Standard 6 becomes the ‘single’ childhood diagnostic standard, incorporating references to pediatric diagnosis found in other standards. With regard to treatment, new drug dosing will be addressed. The discussion on treatment of LTBI will be broadened to include HIV - infected patients and other immunecompromising conditions. Update from the childhood TB - TB/HIV meeting - by Penny Enarson and Lulu Muhe A 3-day workshop was organized where different stakeholders discussed the draft guideline on the diagnosis and treatment of HIV+ children suspected of having TB. Participants represented leading agencies and included HIV experts, childhood TB experts, expert pediatricians, clinical researchers, appropriate staff from NTPs and NAPs in high HIV prevalent settings. After the workshop a writing team was established to re-draft the guidelines after which they will be disseminated for review, including to all members of the Stop TB Partnership's childhood TB subgroup. The draft will also be reviewed against existing WHO guidelines and any new recommendation will require grade profiling to take into account the quality of evidence, trade off between benefits and harms, costs, values and preferences and feasibility of implementation. The final guideline will become available in the 2nd quarter of 2009. Proposal to establish a Core-team, participation in other constituencies and next year planning The Secretariat and the Chair are receiving an increasing number of requests for technical assistance from high burden countries as well as a growing number of requests for plans, reports, slides, etc. from the DEWG and the Stop TB Partnership. In addition, the sub-group needs to be represented at different constituencies (other working groups and task-forces) At the same time the size of the sub-group has increased to incorporate more members from the national TB programmes. All of the above have mad the work of the Chair and the Secretariat difficult and time consuming. The Chair and the Secretariat proposed that a core-tem be established with the below suggested terms of reference: Assist with the preparatory work for the annual meeting of the Childhood TB sub-group. Assist with the preparatory work for the bi-annual plan of activities and reports to the DEWG and the Stop TB Partnership. Hold regular conferences, usually by telephone, to assist faster decision making related to the sub-group activities. Assist in preparing joint missions in support of countries in need of technical assistance on behalf of the sub-group. Ensure a clear approach to country assistance whereby a technical agency is identified to coordinate external assistance. Identify gaps in country technical assistance and develop plans to fill the gaps. The proposed composition of the core-team was presented and discussed. It was agreed that the core-team will consist of: Eight members, of which two are permanent o Chair of the sub-group o Secretary of the sub-group Other non-permanent core-team members will be serving for 2 years (with a possible renewal for 2 more terms of 2 years) or alternatively 3 years (with a possible renewal for 1 more term of 3 years) and they will represent: o Technical agency - 2 members o Donor agency - 1 member o Country representatives - 2 members o Civil society representative - 1 member If and when necessary, ad-hoc members will be invited to join to work on specific topics as identified by the core-team. In order to start all necessary arrangements, it was proposed that an interim core-team be shortly established (with a timeline of 6 months) in order to oversee a formal process of selecting the permanent core-team. CDC volunteered to be part of that interim core team. The Secretariat will circulate an email to all sub-group members on the above process. The representation of the sub-group in other constituencies was discussed. Anneke Hesseling will attend the meeting of FIND to better understand the requirements for childhood TB subgroup. Tony Harries will be representing the sub-group in the TB/HIV working group (as he already is a member of the TB/HIV core team). Davide Manissero will continue representing the sub-group in the Retooling Task Force and the ISTC revision committee. Ana Bierrenbach and Ikushi Onozaki will represent the sub-group in the Impact Measurement Task Force. The sub-group also started planning for next year's annual meeting. Two options were considered: Cancun , Mexico, December 2009 (before the Union's Annual Conference) or Prior to DEWG meeting (September- October 2009). This second option would facilitate the attendance of NTP managers from 22 high burden countries) The secretariat will circulate an email to the subgroup later in the year when the dates and venue for the DEWG meeting will be available. Finally, the bi-annual planning should start early 2009 and will be pursued by the interim coreteam. Annex 1: Agenda 8:30 - 9:00 Registration All Childhood TB sub-group members and NTP managers from 22 HBC 9:00 - 9:15 Opening, welcoming words to the subgroup members and NTP managers Chair, Robert Gie 9:15 - 9:30 Report from Chair on sub-group activities since the last meeting Robert Gie 9:30 - 10:45 Country reports on childhood TB activities Development of childhood TB guidelines Cleotilde Hidalgo How, Philippines Integrating childhood TB with HIV Charles Mwansambo, Malawi Challenges of managing a child with MDR-TB Adriana Sorete-Arbore, Romania 10:45 - 11:00 Coffee break 11:00 - 11:30 Discussion 11:30 - 12:00 BCG: new considerations for an old vaccine in HIV-endemic settings 12:00 - 12:15 Discussion 12:15 - 12:30 Next steps on childhood TB activities at country level 12:30 - 14:00 Lunch break Anneke Hesseling, South Africa Chair and All Childhood TB subgroup members 14: 00 - 14:30 Update from the "Expert group meeting on the dosing of childhood TB medicines" and proposed next steps on practical implementation of new recommendations Peter Donald 14:30 - 14:45 Questions and discussion 14:45 - 15:00 Update on the activities of the Retooling Task Force Davide Manissero 15:00 - 15:30 Update on the revision of ISTC Davide Manissero 15:30 - 15:45 Discussion 15:45 - 16:00 Coffee break 16:00 - 16:30 Update from the childhood TB - TB/HIV meeting Penny Enarson Lulu Muhe 16:30 - 16:45 Discussion 16:45 - 17:00 Proposal to establish a Core-team Malgosia Grzemska/ Robert Gie 17:00 - 17:30 Summary, plans for next meeting, etc Chair, Robert Gie Annex 2: List of participants Childhood TB subgroup members 1. Professor Robert GIE - Chair of the Subgroup Department Head Department of Paediatrics & Child Health University of Stellenbosch, Faculty of Medicine P.O. Box 19063, 7505 Tygerberg, South Africa Tel: +27 21 938 9444; Fax: +27 21 938 9138 Email: [email protected] 2. Professor Valentina AKSENOVA Head, Laboratory on Prevention Diagnosis and Treatment of Tuberculosis in Children and Adolescents Research Institute of Phthisiopulmonology I.M. Sechenov Moscow Medical Academy 4 Dostoievsky Str., 101478 Moscow, Russian Federation Tel: +7 495 681 8422 (institute) and +7 495 681 9236 (pediatric department ) +7 495 631.1112 Email: [email protected] and [email protected] 3. Dr Lucia ALVAREZ HERNANDEZ Paediatric Infectious Diseases Coordinator Standards for Tuberculosis Care Union and Centro Nacional de Vigilancia Epidemiologica y control de enfermedades (CENAVECE) Calle Chihuahua No 228 Colonia Roma Codigo, Postal 06700, Delegación Cuauhtémoc Mexico Distrito Federal, Mexico Tel: 52 64 0026 or 25 14 64 36 or 56 52 6262 or 6263 Mobile: +44 55 29 55 34 95 Email: [email protected] 4. Professor Peter DONALD University of Stellenbosch Western Cape Tygerberg 7505, South Africa Email: [email protected] 5. Ms Penny ENARSON Head, Child Lung Health Division International Union Against Tuberculosis & Lung Disease (The Union) 68 Blvd St Michel, 75006 Paris, France Tel: +33 1 56 80 28 25; Fax: +33 1 44 29 90 87 Email: [email protected] 6. Ms Deliana GARCIA Migrant Clinicians Network P.O. Box 164285, Austin, Texas, 78716-4285, USA Email: [email protected] 7. Dr Steven GRAHAM Centre for International Child Health University of Melbourne Department of Paediatrics Royal Children's Hospital Melbourne Flemington Rd, Parkville, VIC 3052, Australia Tel: +61 3 9345 4788 and +61 3 9345 5522 (Switchboard) Fax: +61 3 9345 6667 Email: [email protected] 8. Dr Anthony D. HARRIES Senior Advisor International Union Against Tuberculosis & Lung Disease (The Union) 68 Blvd St Michel 75006 Paris, France Email: [email protected] 9. Dr Anneke C. HESSELING Senior Researcher Desmond Tutu TB Centre Department of Paediatrics and Child Health, Faculty of Health Sciences Stellenbosch University, Room 0084 Clinical Building PO Box 19063, Francie van Zijl Drive, Tygerberg, 7505, South Africa Tel: +27 21 9389173; Fax: +27 21 9389179 Email: [email protected] Address for correspondence Old Inn Cottage, Vears Lane, Colden Common, Winchester SO21 1TQ, UK Phone: + 44 1962 714 297 10. Professor Cleotilde HIDALGO HOW Professor, Department of Pharmacology & Toxicology University of the Philippines (UP) College of Medicine 547 Pedro Gil Street, Ermita 1000 Manila, Philippines Tel: +63 2 526 4248; Fax: +63 2 521 8251 Email: [email protected] 11. Dr Mamodikoe MAKHENE Medical Officer TB Section Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases, National Institutes of Health 6610 Rockledge Dr Room 5043, MSC 6604 Bethesda, MD 20892, USA Tel: +301-496-5305 Fax: +301-496-8030 Email: [email protected] 12. Dr Davide MANISSERO Unit of Scientific Advice European Centre for Disease Prevention and Control Tomtebodavagen 11A S-171 83 Stockholm, Sweden Tel +46 8-58-60-1218; Mobile: +46 761251637 Fax +46 8-58-60-1001 Email: [email protected] 13. Dr Heather MENZIES Centers for Disease Control and Prevention International Research and Programs Branch Division of Tuberculosis Elimination National Center for HIV, STD, and TB Prevention 1600 Clifton Rd, MS E-10 Atlanta, GA 30333 Tel: 404-639-8488 Fax: 404-639-1566 Email: [email protected] and [email protected] 14. Dr Charles MWANSAMBO Head, Department of Paediatrics Lilongwe Central Hospital P.O. Box 149, Lilongwe, Malawi Tel: +265 (0) 1 753 555; Fax: +265 (0) 1 756 380 Email: [email protected] 15. Dr Clydette POWELL Medical Officer Bureau for Global Health Office of Health, Infectious Disease, and Nutrition Division of Infectious Disease US Agency for International Development (USAID) RRB - GH/HIDN/ID 3.7.82 1300 Pennsylvania Ave, NW Washington, D.C. 20523-3700, USA Tel: +1 202 712 0027; Fax: +1 202 216 3702 Email: [email protected] 16. Dr Mary REICHLER Division of Tuberculosis Elimination Centers for Disease Control and Prevention (CDC) Tel: 001 404 639-5350 Fax: 001 404 639-8961 Email: [email protected] and [email protected] 17. Dr Adriana SORETE ARBORE County Manager Clinic of Pulmonary Diseases 30-nth, Dr. I. Cihac Street Iasi, 700115, Romania Tel direct : +40 0744 647980 and Tel.hospital: +40 0232 239408 Fax hospital : +40 0232 270918 Email: [email protected] 18. Dr Fraser Douglas WARES Medical Officer WHO India New Delhi, India Tel cell: +919810146323, other tel numbers +91 11 23061922, 23061923, 23061926, Email: [email protected] 19. Dr Carol J. WORRELL Medical Officer Pediatric, Adolescent, and Maternal AIDS Branch Center for Research for Mothers and Children National Institute of Child Health and Human Development National Institutes of Health 6100 Executive Boulevard, Room 4B11F Bethesda, MD 20892-7510, USA Tel: +301-435-6842; Fax. +301-496-8678 Email: [email protected] WHO Secretariat 20. Dr Malgosia GRZEMSKA - Secretary to the subgroup Medical Officer, Stop TB Department World Health Organization, 1211 Geneva 27, Switzerland Tel: +41 22 7913989; Fax: +41 22 7914706 Email: [email protected] 21. Dr Ana BIERRENBACH Epidemiologist, Stop TB Department World Health Organization, 1211 Geneva 27, Switzerland Tel: +41 22 791 1248 Email: [email protected] 22. Dr Léopold BLANC Coordinator, TBS/Stop TB Department World Health Organization, 1211 Geneva 27, Switzerland Tel: +41 22 791 4266 [email protected] 23. Dr Christian GUNNEBERG Medical Officer, Stop TB Department World Health Organization, 1211 Geneva 27, Switzerland Tel: +41 22 791 2732; Email: [email protected] 24. Dr Lulu Mussa MUHE Medical Officer, Child and Adolescent Health and Development (CAH) World Health Organization, 1211 Geneva 27, Switzerland Tel: 41 22 791 3988 Email: [email protected] 25. Dr Ikushi ONOZAKI Medical Officer, Stop TB Department World Health Organization, 1211 Geneva 27, Switzerland Tel: +41 22 791 2583 Email: [email protected] 26. Dr Salah OTTMANI Medical Officer, Stop TB Department World Health Organization, 1211 Geneva 27, Switzerland Tel: +41 22 791 3923 Email: [email protected] NTP Managers and country representatives who attended the meeting 27. Bangladesh Dr Abdul Awal MIAH [email protected] 28. Bangladesh Professor Pravat Chandra BARUA Line Director, NTP [email protected] 29. Brazil Dr Draurio BARREIRA [email protected] 30. Cambodia Dr MAO TANG EANG [email protected] 31. China Dr WANG Lixia [email protected] 32. Democratic Republic of the Congo Dr André Okumu NDONGOSIEME [email protected] 33. Ethiopia Mr Bekele CHAKA [email protected] 34. Mozambique Dr Paula SAMO GUDO [email protected] and [email protected] 35. Mozambique Dr Z. Cuna MOH Mozambique [email protected] 36. Mozambique Dr Matilde Basiliog Association national for Nurses Mozambique [email protected] 37. Mozambique Prof Dr Elizabete Nunes Association Medical de Mozambique [email protected] 38. Myanmar Dr WIN MAUNG [email protected] 39. Nigeria Dr Betrand ODUME [email protected] 40. Philippines Dr Rosalind VIANZON [email protected] 41. Russian Federation Dr Elena SKACHKOVA [email protected] 42. Russian Federation Professor Yulia MIKHAILOVA [email protected] 43. United Republic of Tanzania Dr Saidi EGWAGA NTLP Manager [email protected] 44. United Republic of Tanzania Dr Fred Lwilla NTLP [email protected] 45. Thailand Dr Sriprapa NATENIYOM [email protected] and [email protected] 46. Viet Nam Dr DINH NGOC SY [email protected] and [email protected] and [email protected] 47. Zimbabwe Dr Charles SANDY [email protected] Other attendants: Technical Partners 48. Dr René L'Herminez Consultant, KNCV Tuberculosis Foundation P.O. Box 146, 2501 CC The Hague, The Netherlands Tel. +31 70 416.7250 [email protected] 49. Dr Bonita Mangura Professor of Medicine New Jersey Medical School, Global Tuberculosis Institute 225 Warren Street, 2nd Floor, East Wing P.O. Box 1709, Newark, NJ 07101-1709, USA Phone: 973-972-3270 Fax: 973-972-3268 [email protected] 50. Dr David McNeele Tibotec, USA Phone: +1 609 730.7556 Email: [email protected] 51. Dr Nauman Safdar Association for Social Development Pakistan [email protected] WHO regional and country staff AFR 52. Dr Bah Keita Regional Adviser TB World Health Organization Regional Office for Africa Congo - Brazzaville Cell: +242 765.4550 Email: [email protected] 53. Dr Wilfred Nkhoma WHO regional Office for Africa Harare, Zimbabwe [email protected] 54. Dr Abebe Eshetu NPO/TB WHO Ethiopia Cell: +251 912 014931 [email protected] 55. Dr Daniel Argaw WHO Ethiopia PO BOX 3069 Addis Abeba, Ethiopia [email protected] 56. Dr Diriba Agegnehu TB/HIV NPO, WHO Ethiopia PO BOX 3069 Addis Abeba, Ethiopia [email protected] 57. Dr Ayodele Awe NPO/TB WHO Nigeria World Health Organisation, Nigeria Country Office, FCT, Abuja, Nigeria Mobile: +234-8023144120, +234-8035250215 e mail: [email protected] , [email protected] 58. Dr Amos Omoniyi WHO NPO TB/HIV, Nigeria Country Office, FCT, Abuja [email protected] 59. Dr Mwendaweli Maboshe NPO TB Zambia Cell: +260 97872868 [email protected] AMR 60. Dr Mirtha Del Granado Regional Adviser TB Pan American Health Organization/World Health Organization 525, 23rd Street, NW. Washington, DC 20037 [email protected] 61. Dr Rafael Lopez-Olarte Medical Officer Pan American Health Organization/World Health Organization 525, 23rd Street, NW. Washington, DC 20037 [email protected] 62. Dr Yamil Silva Pan American Health Organization/World Health Organization 525, 23rd Street, NW. Washington, DC 20037 [email protected] EUR 63. Dr Richard Zaleskis Regional Adviser TB World Health Organization Regional Office for Europe Scherfigsvej 8 DK-2100 Copenhagen Ø Denmark Tel: +45 39 171335 [email protected] SEAR 64. Dr Firdosi Mehta Medical Officer WHO Indonesia [email protected] WPR 65. Dr Pieter van Maaren Regional Adviser TB World Health Organization Regional Office for Western Pacific Manila, Philippines [email protected] 66. Mr Bernard Tomas Technical Officer TB World Health Organization Regional Office for Western Pacific Manila, Philippines [email protected] 67. Dr Giampaolo Mezzabotta Medical Officer WHO Viet Nam [email protected] 68. Dr Michael Voniatis Medical Officer WHO Philippines [email protected]