1 WHO Communicable Diseases, Surveillance & Response SARS Diagnostics and Laboratory Needs: the WHO Perspective C.E. Roth Dangerous and New Pathogens Global Alert and Response CSR/WHO

WHO Communicable Diseases, Surveillance & Response (CSR) WHO Alert & Response WHO Alert & Response Detecting and responding to SARS (1) 1)Virtual laboratory network for SARS aetiology and diagnostics  Convened mid-March 2003  13 laboratories in 9 countries, daily telephone conference  identification of SARS coronavirus  face-to-face/video meeting, 16 April 2003

WHO Communicable Diseases, Surveillance & Response (CSR) 2) Virtual network of SARS clinicians 3) Virtual network of SARS epidemiologists 4) Global Outbreak Alert & Response Network  field teams sent to countries, incl lab scientists 5) Modelling group  10 institutions, secure web site WHO Alert & Response WHO Alert & Response Detecting and responding to SARS (2)

WHO Communicable Diseases, Surveillance & Response (CSR) Lab Network Achievements (1) l Established an international group of experts to determine aetiology of SARS and to develop diagnostic tests l Creation of laboratory network - communication through regular teleconferencing and restricted access website l WHO Consultation on the aetiology of SARS and development of diagnostic tests, 16 April 2003 l Coordinated an international scientific research program to understand Ab kinetics, routes and pattern of virus excretion, environmental stability of virus, and animal reservoir l Sequencing of virus strains

WHO Communicable Diseases, Surveillance & Response (CSR) Achievements (2) l Evaluations of SARS diagnostic tests l Prepared guidelines on the use of laboratory tests for SARS diagnosis l Developed procedures for sampling for SARS diagnosis l Published results of research on the environmental stability of the SARS coronavirus l Publication of several scientific papers by the members of the WHO collaborative network on SARS aetiology and diagnosis

WHO Communicable Diseases, Surveillance & Response (CSR) Achievements (3) l WHO training course on SARS diagnosis in Beijing China 26 May to 4 June planned for other sites in near future l Support to national reference laboratories l Production and distribution of standard reagents l Quality assurance l Access to kits l Creation of specimen bank - Hong Kong

WHO Communicable Diseases, Surveillance & Response (CSR) Global Meeting: Laboratory issues 1 Animal models –Pathogenesis of SARS-CoV –Evolution of the disease –Vaccine and antiviral testing Vaccine strain development –Evaluation of different vaccine constructs –Epitope mapping (SARS-CoV & other coronaviruses)

WHO Communicable Diseases, Surveillance & Response (CSR) Global Meeting: Laboratory issues 2 Strain diversity / genomics Antiviral drug screening / human monoclonal antibodies Diagnostic test development – timely reliable tests Need for STANDARDIZATION Need for a well pedigreed panel of specimens to validate future diagnostic assays –Blood/serum, sputum, stool/urine, pathology –Linked to clinical details –Panel of SARS-CoV strains

WHO Communicable Diseases, Surveillance & Response (CSR) Global Meeting: Laboratory issues 3 Reagents –mAbs, polyclonal antisera, expressed antigen Repository of reagents and isolates –WHO leadership in establishing repository –International collaboration –Need for both live and inactivated virus Additional sequencing of SARS- and non-SARS coronaviruses Guidelines for the distribution of SARS-CoV Priority – reliable tests for clinical triage (positive within 2-7 days after symptom onset)

WHO Communicable Diseases, Surveillance & Response (CSR) Current WHO perspective: Public health priorities for diagnostics development (1) l Reliable, early (day 1-2), virus/ag detection assay (lab-based) – - safe case management, conserve resources l Reliable, early, near-patient screening assay - – commence isolation, contact id and follow-up l Network of reference labs (+ logs) for countries w/o adequate lab infrastructure l Sensitive and specific ab assays l Link and analyze epi and clinical data to lab data to answer key questions relevant to diagnostics development and disease transmission

WHO Communicable Diseases, Surveillance & Response (CSR) Process to achieve objectives l Review and expand lab network l Sample banks and repositories (sample and reagent) – Number and location – Agree and finalize operational and legal aspects l Standard reagent supply - long-term l Inventory of current diagnostic assays - within network and commercial candidates l Perform international, multi-centre, evaluation – establish test procedure, incl standard reagents, sample panels – Analyze and publish results rapidly l Access/distribution of appropriate assays l Devise process/criteria for evaluation of new assays

WHO Communicable Diseases, Surveillance & Response (CSR) Process to achieve objectives (2) l Quality assurance and availability of standards - reagents, logistics, training support l Biocontainment issues l SARS Research Advisory Committee – to guide WHO on diagnostic/laboratory/clinical/epi/animal research – focus on issues of relevance to public health

WHO Communicable Diseases, Surveillance & Response (CSR) Constraints and Caveats l Funding - value of network approach l 21 July

WHO Communicable Diseases, Surveillance & Response (CSR) Virus origin Virus stability under different environmental conditions Viral excretion, viral load, routes of transmission, clinical presentation Role of asymptomatic infected individuals Role of products of human origin Virus pathogenicity Identification and use of antiviral drugs Vaccine development SARS epidemic modelling Multidisciplinary PH Multidisciplinary PH SARS research - relevant to archiving and diagnostic development