How Can Whole-Genome Sequencing Help Eradicate Tuberculosis?
Total Page:16
File Type:pdf, Size:1020Kb
How can whole-genome sequencing help eradicate tuberculosis? ECCMID, Amsterdam 2016 Timothy Walker University of Oxford ESCMID eLibrary by author I have nothing to declare ESCMID eLibrary by author Scientific / technical obstacles to progress Reservoir of 2 billion people with latent infection Vaccine is insufficiently effective Unable to predict which latently infected patients will manifest disease Available diagnostics are often basic (e.g. limited to smear microscopy) Phenotypic DST, where available, is slow, expensive, and imperfect Treatment courses are long, can be toxic and expensive for drug resistant disease PreventionESCMID of transmission remains relatively eLibrary neglected by author ESCMID eLibrary by author ESCMID eLibrary by author ESCMID eLibrary by author ESCMID eLibrary by author REACHING THE TARGETS To reach the targets set out in the End TB Strategy, the annual decline in global TB incidence rates must first accelerate from an average of 2% per year in 2015 to 10% per year by 2025. Secondly, the proportion of people with TB who die from the disease (the case-fatality ratio) needs to decline from a projected 15% in 2015 to 6.5% by 2025. These declines in deaths and incidence by 2025 while ambitious are feasible with existing tools complemented by universal health coverage and social protection. Global strategy and targets for To sustain progress beyond 2025 and achieve the SDG* tuberculosis prevention, care 2030 and End TB 2035 targets, additional tools must be ENDING THE TB EPIDEMIC and control after 2015 available by 2025. In particular, a new vaccine that is Ending the global TB epidemic is feasible with dramatic effective pre- and post-exposure and a safer and more decline i n TB deaths and cases, and elimination of effective treatment for latent TB infection are needed to economic and social burden of TB. Failure to do so Gwill obal strategy and targets for tuberculosis reduce the number of new TB cases arising from the carry serious individual and global public health Global strategy and targets for prevenatpiporonxim,a ctealy r2 ebil liaonn pedop cle owonrldtwridoe lw ahof atree inrf e2cte0d 15 consequences. tuberculosis prevention, care with M. tuberculosis, as well as better diagnosticasn adn cdo snatfreorl after 2015 and easier treat ment including shorter drug regimens for TB Achievement of this goal by 2035 requires: A world free of tuberculosis VISION disease. For new tools to be available by 2025, greatly – zero deaths, disease and suffering due to tuberculosis 1. Expanding the scope and reach of interventions for Gl obal esntharnacedt eangd yim maendiadte tinaverstgmeentts sin froesera rcthu abnde rculosis TB care and prevention, with a focus on high-impGaOctA, L End the global tuberculosis epidemic development ar e required. integrated and patient-centered approaches; MILESTONES TARGETS pINDrICeATvOReS n tion, care and control after 2015 2. Eliciti ng full benefits of health and development 2020 2025 SDG 2030* END TB 2035 Redu ction in numbeTr hofe T Bf digeauthrse below shows the projected acceleration of the 35% 75% 90% 95% policies and systems, through engaging a mcuocmhp ared with 2015d (e%c) l ine in global TB incidence rates with optimization of wider set of collaborators across governmeRendtu,c tion in TB incidceunrcer erantet tools coAm wboi2nr0le%dd f rewei tohf tpurboegr5c0ru%el soss isto wards 80u%n iversal 90% VcIoSmIOpaNre d with 2015 (%) (<85/100 000) (<55/100 000) (<20/100 000) (<10/100 000) communities and the private sector; health coverage –a znedr os odecaiatlh sp, rdoisteacsteio ann dfr soumffe 2ri0n1g 5d,u aen tod ttuhbee rculosis TB-affected families facing Zero Zero Zero Zero catastrophic costs due to TB (%) 3. Pursuing new scientific knowledge and innovatGi oOnAsL additional impacEt nodf tnheew g ltooboalls t ubbye 2rc0u2l5o.s is epidemic that can dramatically change TB prevention PanRdIN CIPLES MILESTONES TARGETS IN DICATORS care. 1. Government stewardship and accountabilit2y0, 2w0it h monitoring a2n0d2 e5va luation SDG 2030* END TB 2035 Re2d. ucSttiroonn ign cnouamlitbioern owf iTthB cdievailt shosc iety organizations and communities 3. Protection and promotion of human rights, 3e5th%ic s and equity 75% 90% 95% To ensure full impact, these actions must buildco mopna red with 2015 (%) Re4d. ucAtdioanp itna tTiBon in ocfi dthene cset rraatteeg y and targets at co2u0n%t ry level, with glob50a%l c ollaboration 80% 90% principles of government stewardship, engagemencot mopfa r ed with 2015 (%) (<85/100 000) (<55/100 000) (<20/100 000) (<10/100 000) PILLARS AND COMPONENTS civil society, human rights and equity, and adaptatioTnB- atfofe cted families facing 1. INTEGRATED, PATIENT-CENTRED CARE ANDZ ePrRoE VENTION Zero Zero Zero catastrophic costs due to TB (%) the unique context of diverse epidemics and settings . A. Early diagnosis of tuberculosis including universal drug-susceptibility testing, and systematic screening of PRINCcIoPnLtaEcSts and high-risk groups B. Treatment of all people with tuberculosis including drug-resistant tuberculosis, and patient support 1. Government stewardship and accountability, with monitoring and evaluation C. Collaborative tuberculosis/HIV activities, and management of co-morbidities 2. Strong coalition with civil society organizations and communities D. Preventive treatment of persons at high risk, and vaccination against tuberculosis 3.2 . P BrOoLteDc PtiOoLnI CaInEdS ApNroDm SoUtPioPnO oRfT hIVuEm SaYnST rEigMhSts , ethics and equity 4. AAd. aPpotlaittiicoanl coofm thmeit smtreantte wgyit ha nade tqauragteet sre asto cuorcuenst froyr l etuvbeel,r wcuiltohs igsl ocabrael acnodll apbreovreantitoionn ESCMIDB. Engagement of communities, ci vil society orga nizaeLibrarytions, and public and private care providers PILLARS AND COMPONENTS C. Universal health coverage policy, and regulatory frameworks for case notification, vital registration, quality 1. INTEGRATED, PATIENT-CENTRED CARE AND PREVENTION and rational use of medicines, and infection control A. Early diagnosis of tuberculosis including universal drug-susceptibility testing, and systematic screening of KEY TB FACTS D. Social protection, poverty alleviation and actions on other determinants of tuberculosis contacts and high-risk groups In 2013, 9 million people fell ill with TB and 1.5 milli3o. nIN dTEieNdSI FfIrEoDm RE iStE, AinRCcHlu AdNinDg IN 3N6O0V A0T0I0O Na mong people who were HIV-positive. BA. TDreisactomveerny,t doefv aelllo ppemoepnlet awnidt hra tpuibde urpctualkoes iosf i neclwu dtoinogls d, irnutge-rrveesnitsitoannst a tnudb setrrcautelogsieiss, and patient support In 2013 , there were an estimated 480 000 new cases CoB.f . CmRoeulslaletbaiordcrrhau tgiov -eor pettusimbiseitzreac unimlto psTliesB/m.H eInVt atcitoinv iatineds ,i manpda cmt, aanadg permomenote o ifn cnoo-vmatoiorbnsid ities D. Preventive treatment of persons at high risk, and vaccination against tuberculosis 2.T H BEO GLDLO PBOALLI CSITERSA ATNEGDY S AUNPDPO TRATRIGVEET SSY FSOTRE MTUSB ERCULOSIS PREVENTION, CARE AND CONTROL AFTER 2015, ACHIEVEMENTS CHALLENGES A. PoliticaWl EcoRmE EmNitDmOeRnStE wD iBthY aAdLeLq MuaEtMe BreEsRo SuTrAceTsE Sfo Ar Tt uTbHeEr c2u0l1o4s iWs cOaRreLD a nHdE ApLreTHve AnStiSoEnM BLY. B. Engagement of communities, civil society organizations, and public and private care providers * The U nited Nations is in th e proc ess of dbyefining a post-2015 develo pmentauthor agenda. A set of “Sustainable Development Goals” (SDGs) are being developed for 20C3.0 ; UTBn isi vpreorpsoaseld h toe bael tphar tc oof vthee raagegned ap aondli gcoya,ls a. nd regulatory frameworks for case notification, vital registration, quality and rational use of medicines, and infection control D. Social protection, poverty alleviation and actions on other determinants of tuberculosis 3. INTENSIFIED RESEARCH AND INNOVATION 45% decreasA. eD is covery, dev3el ompmilenlit aondn ra ppide upotapkel oef n ew tools, iMnteDRrventi-oTns Band c straistegiiess 37 million B. Research to optimize implementation and impact, and promote innovations lives saved in TB mortality rate who fall ill with TB still detection, waiting lists for treatment and since 2000 since 1990 unreached every year THE GLOBAL STRATEGY AND TARGETS FOR TUBERCULOSIS PREVquaENTlIiOtyN of, C AcRaEr eA ND CONTROL AFTER 2015, WERE ENDORSED BY ALL MEMBER STATES AT THE 2014 WORLD HEALTH ASSEMBLY. WHO Global Tuberculosis Report 2014 * The United Nations is in the process of defining a post-2015 development agenda. A set of “Sustainable Development Goals” (SDGs) are being developed for 2030; TB is proposed to be part of the agenda and goals. © World Health Organization December 2014 Desirable characteristics of a new diagnostic assay: 1. Identify the species 2. Determine all drug susceptibilities 3. Identify predictors of virulence 4. Link the organism to others to indicate source of acquisition 5. Rapid / point-of-care 6. Affordable ESCMID7. One single assay eLibrary by author ESCMIDIdentifying mycobacterial eLibrary species by author Mycobacterium abscessus Mycobacterium diernhoferi Mycobacterium hafniae (aka haemophilum) Mycobacterium riyadhense Mycobacterium acapulcensis Mycobacterium doricum Mycobacterium hassiacum Mycobacterium rufum Mycobacterium aemonae Mycobacterium duvalii Mycobacterium heckeshornense Mycobacterium runyonii (aka chelonae) Mycobacterium africanum Mycobacterium elephantis Mycobacterium heidelbergense Mycobacterium rutilum Mycobacterium agreste Mycobacterium europaeum Mycobacterium hiberniae Mycobacterium salmoniphilum Mycobacterium