Background

The SDI was founded in 1990 in response to a widely-perceived need to improve care for patients with sexually transmitted infections (STIs) in resource-limited settings through improved diagnostics.  It is estimated that 80-90% of the global burden of STIs occurs in the developing world where there is limited or no access to diagnostics.  In particular, there is an urgent need for improved diagnostics for STIs in HIV endemic areas as studies in sub-Saharan Africa have shown that STIs are important cofactors in the transmission of HIV infection.

The SDI secretariat had been housed in various agencies since its inception and has most recently moved from UNAIDS to the World Health Organization, where it is managed out of the Special Programme for Research and Training in Tropical Diseases (TDR).  The placement of SDI in the Product Research and Development group of TDR allows the initiative to benefit from the considerable expertise in product development, evaluation and implementation in the group and to exploit synergies in the development of diagnostics for other communicable diseases.

Mission

The mission of SDI is to promote the development, evaluation and application of affordable, rapid, simple point-of-care STI diagnostics for primary health care settings in developing countries.

Past achievements

In the past, SDI funded research and product development projects for the development of rapid antigen-based immunochromogenic strip (ICS) tests for the detection of syphilis and H. ducreyi infection, a dipstick-format test for the detection of C. trachomatis nucleic acid in urine, and the formation of a specimen bank to aid assay development and evaluation.  

Though many useful reagents and techniques were developed during the course of the above contracts, none of those investments have yet resulted in a distribution-ready test thought likely to have a significant impact.  In the meantime, industry involvement in diagnostic development has increased in this area.

A strategic decision was made in 2000 to shift away from direct investment in product research and development and work instead to facilitate industry efforts towards the production of diagnostics appropriate for resource limited settings, to develop quality standards for diagnostics evaluations and to evaluate the performance and utility of commercially available rapid diagnostics for STIs.

SDI activities 2001- June 2002

Diagnostics Evaluation  

Preparations for the formation of a network of SDI laboratory and field sites to perform evaluations of rapid STI diagnostics were initiated with the following activities:

1) Update of the inventory of rapid point of care STI diagnostics marketed and in commercial development

In Jan-Feb, 2001, a rapid survey was conducted which showed that more than 40 rapid tests of interest to SDI are being marketed by over 30 companies and several more are in development.

2) Priority for rapid STI diagnostics and preparation for field trials

Representative of the move to internationalize SDI activities and attract new donors, a consultation on point-of-care STI diagnostics was held on 29-30 January 2001, co-hosted by TDR and the Wellcome Trust for 34 participants from 16 countries, to re-evaluate the priority diagnostic needs for STIs, to prepare for field trials by the establishment of field trial site criteria and trial design, and to identify obstacles to test development and deployment. 

At the meeting, representatives of the Wellcome Trust, CDC, NIH and USAID presented their activities in this area and expressed interest in identifying areas of common interest with SDI acting as the co-ordinating body and a clearing house for activities in this area.  SDI will develop a framework for collaboration and synergism in this area in the next biennium.  There was a high level of enthusiasm for diagnostics evaluation from the participants, a few of whom have already evaluated some rapid tests available in their own country.  SDI can play an important role in setting up guidelines for the evaluation of rapid diagnostics for STI.  Participants reviewed disease priorities and concluded that the need for simple rapid diagnostics was greatest for three curable STIs, syphilis, gonorrhoea and chlamydia.  

Since field trials are costly and there are many tests to evaluate, it was agreed that a two-step process for evaluation be developed where tests will first undergo screening in a laboratory-based evaluation and a few of the most promising tests will then be selected for field trials.  Participants also identified criteria for field site selection, required elements of field trial design and site preparation and a research agenda for further diagnostics development.

3) A technical meeting with past SDI advisory committee members

In February 2001, a meeting was held with key members of past SDI leadership with the following outcomes: 1) the specimen bank inventory was updated;  2) commercial activity in STI diagnostics was reviewed; and 3)  the mechanism for evaluating the analytical sensitivity, specificity and reproducibility of existing point-of-care STI tests was discussed.

4) Laboratory-based evaluation of rapid STI diagnostics

In May 2001, the first meeting of the SDI ad hoc expert working group on laboratory-based evaluation of  STI diagnostics was convened to:  i) initiate preparations for the formation of a network of laboratory sites for the evaluation of rapid syphilis diagnostics, ii) to develop terms of reference for the STI laboratories at the CDC, USA, the Public Health Laboratory Service (PHLS), UK, and the Institute of Tropical Medicine, Belgium, to act as reference laboratories for SDI.  

It was agreed that a network of laboratory sites in diverse geographical areas would be needed for the laboratory-based evaluation of rapid syphilis diagnostics to identify possible variations in test performance under different endemic conditions.  Diagnostics for chlamydia and gonorrhea will be evaluated and ranked by the SDI reference laboratories.

5) Request for applications (RFA) for laboratory and field evaluation sites

RFAs were advertised widely in June and July, 2001 at the Meeting of the International Society for STD Research in Berlin, through the WHO/TDR web site, and the SDI mailing list.  Thirty-five field site applications were received in September from 31 countries in response to the RFA for field sites and 26 applications were received from 23 countries for the RFA for laboratory sites.  These were reviewed independently by the SDI ad hoc expert working groups for laboratory and field evaluations in October, 2001.  

Seven laboratory sites received funding for evaluation of syphilis diagnostics.  An eighth laboratory site from the USA was included on a no-cost basis in accordance with the need for geographic diversity for syphilis diagnostics evaluations.  Eight field sites were short-listed for funding pending the outcome of site visits to review site facilities, data management, laboratory facility and proficiency records, and to confirm government and community support for site activities.  The WHO/TDR Diagnostics Steering Committee has now approved all short-listed sites as recommended by the SDI ad hoc expert working group for field diagnostic evaluations. Click here to see the list of sites

6) Preparations for field trials

Selection of tests for field evaluations:  a meeting of the ad hoc expert working groups for laboratory-based evaluations and for field trials has been scheduled for July 29-31, 2002 to review the laboratory-based evaluation data and select promising tests for field evaluations.

Protocol Development:  in November, 2001, a panel of field trial experts,  principal applicants of short-listed field sites, a test developer and a representative from the diagnostics industry were invited to Geneva to discuss the essential elements of field trial protocols for all three priority STIs.  Once the sites are selected, the protocols will be adapted to site conditions and be translated into the local language for ethics review and approval.

Workshops on Good Clinical Practice (GCP) and Good Laboratory Practice (GLP):  to ensure that field trials are conducted in accordance with the principles and practice of GCP and GLP, WHO/TDR trained GCP and GLP trainers will be giving workshops at each site prior to the start of field trials.

Site proficiency:  Proficiency panels will be sent to each site to ensure each site's proficiency at performing reference standard tests to be used as "gold standards" for rapid diagnostic evaluations.

It is expected that field trials of promising STI diagnostics may be started in the last quarter of 2002.

Diagnostics research and development:

1) Test development

A final year of funding is under consideration for the development of an isothermal nucleic acid amplification assay for gonorrhoea and chlamydia, pending interest of a partner from industry to commercialise the technology and make the test available to the public sector on preferential terms for developing countries.

2) Mathematical modelling

Modellers from the London School of Hygiene and Tropical Medicine were contracted to develop a model to determine the performance characteristics required for a rapid test to be cost-effective at various settings and for different populations.  This work, which gives useful information to guide rapid test development, will be submitted for publication in a peer-reviewed journal. A longer term contract has now been awarded to this group to extend the model to assess the impact of rapid diagnostics on patient management and disease control in various settings.

Establishment of quality standards in diagnostics evaluations

Discussions on guideline development was initiated at the first meeting of the ad hoc working group for laboratory based evaluations in May 2001.  The scope of the guidelines and the essential elements to be included were developed by SDI  in consultation with the heads of SDI reference laboratories and of the field trials expert working group at a meeting in April 2002.  The draft guidelines will be presented for discussion at a meeting of SDI ad hoc working groups for laboratory and field evaluations in July 2002.  On completion, the guidelines for laboratory-based and field evaluation of STI diagnostics will be made available on the SDI web site.

Communications

Two electronic SDI Newsletters were sent out in 2001 to interested individuals on the SDI mailing list to inform them of SDI activities.  SDI has since obtained approval for the creation of a SDI web site to ensure the timely dissemination of information on STI rapid tests and SDI activities. A final SDI newsletter will be sent at the end of June 2002 to announce the web site.   The SDI web site, which will be active by the end of July, 2002, will feature the SDI mission and work plan, current SDI activities, results of test evaluations (as they become available), and a STI diagnostics publication review.  The purpose of this publication review is to provide health care providers in all economic settings with timely and concise information on new developments in the laboratory diagnosis of STIs.  Quarterly reviews on new peer-reviewed publications of STI diagnostics will be provided by STI experts with annotated commentaries.  Dr. King Holmes, University of Washington, has agreed to be the editor-in-chief of the SDI publication review.

In Feb, 2002, WHO, in collaboration with 5 leading publishing companies, launched an "Access to Research" internet initiative, the HealthInterNetwork site (HINARI). Now doctors, researchers, health policy-makers and others in about 70 developing countries will gain free access to one of the world's largest collections of biomedical literature through the Internet.  More details on this initiative can be found in a separate file with this edition of the SDI news.   Please note that research institutes in developing countries, interested in using these information resources, need to register with the network (see under "Register" on the HealthInterNetwork website).