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Global Access Global Access to STD Diagnostic is published by the Division of Sexual » Return of SDI Secretariat to WHO Return of SDI Secretariat to WHO
The major reorganization of WHO takes place with the arrival of its new Director General, Dr. Gro Harlem Brundtland, former Prime Minister of Norway. The new structure of WHO has consolidated multiple separate programs into nine clusters, each led by its own executive director. The structure of the Communicable Diseases Cluster, shown below, is organized horizontally by functional area rather than vertically by disease, and is intended to offer more flexibility and enhance collaboration. In addition to the consolidation of existing programs, a number of new activities have been initiated. The Communicable Diseases Cluster merges activities from several programs, including those dealing with leprosy, tuberculosis, and the control of tropical diseases; emerging and other communicable diseases surveillance and control; and research and training in tropical diseases. The SDI will be managed by Dr. Mark Perkins as part of a diagnostics operation within the Product Research and Development team (circled). The Tuberculosis Diagnostic Initiative and new diagnostics projects for other priority diseases are also managed within that operation. Diagnostics joins Tropical Disease Drug and Vaccine Discovery operations led by Dr. Win Gutteridge in the Product Research and Development team. The SDI expects to benefit from the product discovery and development expertise of that team and from its collaborative relations with industry. The Research and Development Department, in which product research and development is housed, is directed by Dr. Carlos Morel and includes the 25-year-old Special Programme for Research and Training in Tropical Diseases.
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SDI Update
In the immediate past, the SDI had two major committees responsible for guiding its activities. The Steering Committee provided leadership and direction, and was responsible for reviewing grant applications and recommending funding. A Committee of Interested Parties (CIP) was open to those involved in the SDI's goals of developing inexpensive, rapid diagnostic tests for use in resource-poor settings. As the move was made from UNAIDS to WHO, the organization of the SDI also changed. The existing committees were dissolved, and the members were thanked for giving their time and expertise in this endeavour. The previous chairmen, Max Chernesky of the Steering Committee and Paul Delay of the CIP, resigned from those activities. Both are still active within the SDI: Dr. Delay is still a member of the SDI, and Dr. Chernesky chairs the Scientific Advisory Committee. The SDI is now the remaining structure and is chaired by Dr. Julius Schachter. There has been a change in the activities of the SDI. Rather than trying to be a mini funding agency, open to grant applications on test development, the SDI is now endeavouring to evaluate existing rapid STD diagnostic tests in resource-poor settings in preparation for what we presume will be the next generation of rapid diagnostic tests. Thus, we are attempting to develop experience in evaluating tests in the conditions under which they will be used. This is obviously more difficult than test evaluation in sophisticated research laboratories and their collaborating clinics. The SDI will continue funding research activities, within budgetary limitations, and these applications will be reviewed on an ad hoc basis by a Scientific Advisory Committee. Rather than having a standing committee, specific relevant expertise will be sought for each review; Dr. Chernesky will be directing this endeavour. Existing grants will be continued for their committed duration, and if adequate progress is made and appropriate funds are available these projects may receive continued funding. The Global Access Newsletter which was published for the past six years as part of the Program for Appropriate Technology in Health (PATH) in Seattle is now being published at Health Canada and coordinated by Dr. Ann Jolly in the Bureau of HIV/AIDS, STD and TB. We are indebted to individuals such as Jaqueline Sherris, Diane Lachman and coworkers at PATH, who provided unyielding leadership in this project as well as the Rockefeller Foundation for financial support. For the past four years, six projects have been funded by the SDI. This edition of the Newsletter provides summaries of the progress achieved from several of the projects. Diagnostic Monoclonal Antibodies to Hemoglobin-Binding Protein of H. ducreyi
Native (nHgbA, from H. ducreyi) and recombinant HgbA (rHgbA, over-expressed in E. coli) were purified, mice were immunized, and several thousand hybridoma supernatants were screened for reactivity. Several hybridoma cell lines were cloned by limiting dilution, and clones proving to be stable were used to produce 0.5 L amounts of cell supernatant for further characterization. We have purified analytical amounts of IgG from each. We have developed a simple capture ELISA assay using each purified Mab as the capture antibody and rabbit anti-peptide sera as the detection antibody. Mabs have been tested for cross-reactivity against a panel of geographically diverse strains that contain a variety of ribotypes (P.A. Totten, manuscript in preparation). Several Mabs were isolated, characterized and purified. We have grown the geographically diverse strains (above) and prepared the cellular extracts for testing. In our format, H. ducreyi are detergent solubilized, and all Mabs recognize this form of HgbA. Among the several tested, we have identified three unique Mabs that are non-competitive and recognize the HgbA protein from all strains of H. ducreyi tested. We estimate that in a simple, non-optimized capture ELISA, we can readily detect 50 ng of purified HgbA mixed with a cell extract from a mutant H. ducreyi unable to make HgbA. This corresponds roughly to 100,000 bacteria (depending on strain, amount of heme starvation and other variables). We have not tried to optimize this ELISA system, but have used it only for strain surveys. Thus, we have three Mabs in hand, suitable for capture and detection. Christopher Elkins, Ph.D. Rapid Detection for the Diagnosis of Chancroid
During this study, high-titre polyclonal and monoclonal antibodies were produced and purified. Mab BB11 reacted with all strains of H. ducreyi, whereas Mab CC11 and the polyclonal antibody reacted additionally with some other species of Haemophilus. The detection of the epitope for BB11 but not CC11 was enhanced by prior incubation with 0.1% SDS, but not with Triton X-100, Tween 20 or Tween 80. Mab BB11 has proved to be the most useful of the antibodies, and in combination with the polyclonal antibody has been used to develop a capture assay. In addition, Mab BB11 has been successfully conjugated to colloidal gold, and these conjugates recognize H. ducreyi in the lateral flow format. In order to establish the sensitivity and specificity of these antibodies for the detection of H. ducreyi antigen in clinical samples, it is proposed to test them in the capture assay before developing the lateral format further. Antibodies with high sensitivities and specificities often transfer well from ELISA to the lateral flow format. As a source of clinical material, swabs from genital ulcers of more than 200 male patients with genital ulcer disease (GUD) presenting to clinics in South Africa have been collected and transferred, frozen, to St. Mary's, in London. The cause of GUD in these patients has been determined at SAIMR, Johannesburg, by means of tests for Treponema pallidum, H. ducreyi, herpes simplex virus and Chlamydia trachomatis. Optimization of the release of antigen from the swabs and subsequent testing of these samples is currently being undertaken. Catherine Ison, Ph.D. SDI Specimen Collection Panel Progress Report
Laboratory-grown agents are also available for both sensitivity and specificity panels for tests attempting to diagnose sexually transmitted diseases. These include rabbit testicular material for Treponema pallidum as well as normal flora of the genital tract for the specificity panel. J. Schachter, Ph.D. Table 1. SDI Specimen Collection
Development of a one-step immunochromatographic (ICS) strip test for syphilis
In the last half of 1998, Omega and PATH successfully completed transfer of the test to Quorum Diagnostics (Vancouver, Canada); a subsidiary of Omega. Standard operating procedures and other manufacturing documents were drafted and commercial production has recently commenced. An initial prospective field evaluation for the syphilis ICS test on 187 specimens from an STD clinic in Mumbia, India, indicated a sensitivity of 96.6% and a specificity of 96.1% when compared with results of RPR and TPHA tests. This study indicated that the test was positive in several patients with early syphilis that were not yet reactive to RPR test antigen. A retrospective study in Birmingham, Alabama, using 260 STD clinic specimens also demonstrated a high sensitivity and specificity. Similar data have been obtained from panels of sera or plasmas from South Africa and Eastern Europe. Currently, prospective clinical studies are in progress in Mexico, Peru, and the Philippines. Additional studies are being planned. PATH and Omega are presently working on additional improvements to the tests, including the modification of the strip to use whole blood as a specimen. This would allow the test to be run directly from a sample of venous blood, or preferably a finger stick. Milton Tam, Ph.D. STD Diagnostics Initiative Founding Members . Seth Berkley, M.D., The Rockefeller Foundation . Claude Betts, M.D., Pan American Health Organization . Richard Frank, Population Services International . Lieve Fransen, M.D., Ph.D., Commission of the European Communities . Jeffrey Harris, M.D., United States Agency for International Development . Subhash Hira, M.D., Ministry of Health/Zambia . Penelope J. Hitchcock, D.V.M., M.S., National Institutes of Health . King K. Holmes, M.D., Ph.D., University of Washington . Franklyn Judson, M.D., Denver Department of Health and Hospitals . Michael Norgard, Ph.D., University of Texas . Sheila Mitchell, Family Health International . Stephen Morse, Ph.D., Centers for Disease Control and Prevention . Peter Piot, M.D., Ph.D., Institute of Tropical Medicine . Lair Guerra de Macedo Rodrigues, Dr. P.H., Ministry of Health/Brazil . Wendy Roseberry, World Bank . Julius Schachter, Ph.D., University of California, San Francisco . Jimmy E. H. Sng, M.D., Ministry of Health/Singapore . Milton Tam, Ph.D., PATH/Seattle . Hiko Tamashiro, Ph.D., World Health Organization . Kathleen Toomey, M.D., M.P.H., Centers for Disease Control and Prevention . Judith N. Wasserheit, M.D., M.P.H., Centers for Disease Control and Prevention
Global Access to STD Diagnostics is published by the Division of STD Prevention and Control, Bureau of HIV/AIDS, STD & TB, Laboratory Centre for Disease Control, Health Canada. It reports on the activities of the STD Diagnostics Initiative. The Initiative includes leading experts in the field of STD research and control. Content and opinions expressed in Global Access reflect those of the STD Diagnostics Initiative. Questions and comments should be directed to:
© Minister of Health, 1999.
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Last Updated: 1999-12-08 | ![]() |