EVALUATING DIAGNOSTICS
Evaluation of rapid diagnostic tests: syphilis
WHO/TDR Sexually Transmitted Diseases Diagnostics Initiative
Syphilis is a curable sexually transmit- countries2,3. Approximately 30% of preg- I. DIAGNOSTIC TESTS FOR SYPHILIS ted infection caused by the bacterium nant women with syphilis will give birth to T. pallidum cannot be cultured in the labora- Treponema pallidum. The infection can a stillborn baby, and another 30% to a live tory, but can be identified in lesions using also be passed from a mother to her fetus baby with congenital syphilis, a condition dark-field or fluorescent microscopy or by during pregnancy. As a cause of genital ulcer which has a range of severe effects, includ- molecular techniques. As most infected indi- disease, syphilis has been associated with ing growth retardation, and which can have viduals are asymptomatic or have transient an increased risk of HIV transmission and a mortality rate of up to 50%. These condi- lesions, serological tests are the diagnostic acquisition. tions are preventable if infected mothers test of choice for detection of syphilis9. The Most infected individuals have no are identified before the third trimester of characteristics of the commonly used sero- symptoms and therefore a serological test pregnancy, and treated appropriately. logical tests for syphilis are shown in TABLE 1. must be used to screen for infection. The Early detection and treatment is crucial Simple flocculation assays, such as the WHO estimates that 12 million new cases for preventing severe long-term complica- rapid plasma reagin (RPR) test, are widely of syphilis occur every year, most of which tions in the patient and the adverse preg- used for serodiagnosis of, or screening for, are in settings where there is limited or no nancy outcomes detailed above. syphilis. These tests detect antibodies to access to laboratory screening services1. Treatment also prevents further trans- phospholipid antigens such as cardiolipin. Left untreated, syphilis can eventually mission of the infection. The World Anti-cardiolipin antibodies can occur in a cause severe granulomatous lesions and Development Report cites antenatal screen- range of tissue-damaging diseases in mam- cardiovascular or neurological damage. ing and treatment for syphilis as one of the mals; these tests are therefore not specific Syphilis in pregnancy is a major cause of most cost-effective health interventions for T. pallidum infection and are commonly adverse pregnancy outcome in developing available4–8. referred to as ‘non-treponemal’ tests.
Table 1 | Characteristics of serological tests for syphilis Non-treponemal tests Treponemal tests Test characteristic RPR VDRL Rapid test EIA TPPA/TPHA FTA-ABS Specimen Serum or plasma Serum or plasma Serum or whole Serum or plasma Serum or plasma Serum or plasma blood Sensitivity 86–100% 78–100% 84–98% 82–100% 85–100% 70–100% Specificity 93–98% 98–100% 94–98% 97–100% 98–100% 94–100% Ease of use Easy Easy Easy Moderate Complex Complex Level of use Exam room, Exam room, Exam room, Intermediate lab, Reference lab Reference lab on-site lab on-site lab on-site lab reference lab Equipment required Rotator, Light microscope, None Incubator, microwell Incubator Fluorescence refrigerator refrigerator plate washer and microscope reader Training Minimal Minimal Minimal Moderate Extensive Extensive Average cost US$ 0.5 US$ 0.5 US$ 0.19–3 US$ 3 US$ 3 US$ 3 Comments Reagents require Reagents require Most tests can be Allows high- Used as Used as refrigeration refrigeration stored at room throughput confirmatory confirmatory test; temperature for screening; test; does not does not distinguish 9–18 months does not distinguish distinguish between prior between prior between prior treated and active treated and active treated and active infection infection infection EIA, enzyme immunoassay; FTA-ABS, fluorescent treponemal antibody-absorption test; RPR, rapid plasma reagin test; TPHA/TPPA, Treponema pallidum haemagglutination assay/ Treponema pallidum particle agglutination assay; VDRL, venereal diseases research laboratory test.
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(TPHA) or the closely related T. pallidum high prevalence settings where large num- particle-agglutination assay (TPPA). These bers of the target population have already confirmatory tests are more technically been screened and treated. Some suggested demanding and are not widely available in algorithms for use of rapid tests are shown in most developing countries outside reference FIGURE 120,21 and are discussed below. laboratories. In settings where RPR is not available, an RDT can be used to increase access to II. THE NEED FOR EVALUATION OF testing or for prenatal screening to prevent SYPHILIS RDTs congenital syphilis. Until recently, serological testing for syphilis In settings where non-treponemal tests, required a laboratory with trained person- such as the RPR test, are available, it might nel, refrigeration for the storage of reagents be possible to use RDTs as a screening test, and electricity to run equipment such as a and then perform quantitative non-trepone- refrigerator, centrifuge and shaker. As such mal tests to determine whether the patient facilities are generally not available in remote has an active infection. This approach is areas, blood or serum samples must be trans- useful in areas of low disease prevalence. By ported to regional or central facilities for test- selecting combinations of RDTs, it might ing. The results are therefore only available also be possible to use a sensitive RDT as a days or weeks after testing10 and specimens screening test and a more specific RDT as a or results can sometimes be lost in transit. It confirmatory test. is common for individuals who are tested not Targeting syphilis screening to at-risk to return for their test results or treatment, individuals is cost-effective. Given the resulting in adverse clinical outcomes, con- potentially serious sequelae of syphilis and tinued transmission of infection and wasted the increased risk of HIV transmission, the resources. following groups should be targeted for Simple, point-of-care Treponema-specific screening: rapid diagnostic tests (RDTs) are now com- • Pregnant women (to prevent congenital mercially available11–20. These tests can use syphilis) whole blood from a finger prick as well as • Individuals with, or at risk of, contracting, serum or plasma. They might be suitable for sexually transmitted infections (STIs) use in primary healthcare settings for the • Sex workers diagnosis of syphilis but until recently, there • Clients of sex workers were only limited data on their performance • Men who have sex with men characteristics. Evaluating the performance • Intravenous drug users of both current and future tests, their utility Consecutive patients of the desired in a disease control programme and their target population presenting to clinics at acceptability to patients and healthcare pro- the evaluation sites should be informed viders will improve the diagnosis of syphilis about the study and asked to participate. in primary healthcare settings in developing Patients who give consent should undergo countries and reduce unnecessary treatment. an interview and a physical examination Figure 1 | Suggested rapid diagnostic test according to the routine clinic protocol at algorithms and treatment decision points for III. GENERAL ISSUES IN STUDY DESIGN the site. Participants can be asked ques- syphilis. Treatment includes treating patients 1. Reference standards tions concerning their age, gender, history and contacts, counselling, recommending con- dom use and offering HIV testing. RPR, rapid The reference standard test for Treponema- of STIs, recent STI treatment history and plasma reagin test. specific tests should be TPHA, TPPA, pregnancy status, as suggested in the sample enzyme immunoassay (EIA) or the fluores- data-collection form shown in APPENDIX 1. cent treponemal antibody absorption test A sample informed consent form is shown False-positive results are often encountered, (FTA-ABS). Each test should be performed in APPENDIX 2. especially in pregnant women, leading to on sera by laboratory staff, according to the unnecessary treatment. Some common manufacturer’s directions. IV. FACTORS AFFECTING TEST conditions associated with false-positive PERFORMANCE test results are malaria, tuberculosis, viral 2. Local epidemiology, choice of study 1. Specimen sampling and preparation fevers, trypanosomiasis, leprosy and other population and sampling RDTs can be used with whole blood, serum treponemal infections in addition to syphilis. The local epidemiology of syphilis is impor- or plasma. However, TPHA, TPPA and other Non-infectious causes of cross-reactivity tant in selecting the appropriate test. Once reference tests must be performed on serum include drug addiction, connective tissue positive, Treponema-specific tests, including and will require specimen transport to a disease, pregnancy and advanced age. the new point-of-care RDTs, usually remain laboratory. The stage at which the serum is Positive RPR results therefore need to positive throughout the patient’s life and so removed from the clotted blood will depend be confirmed with treponemal tests that cannot distinguish between past syphilis, on the circumstances. If the reference labo- use Treponema-specific antigens such as treated syphilis and syphilis that requires ratory is distant, it might be necessary, for the T. pallidum haemagglutination assay treatment. RDTs are therefore less useful in the purposes of the evaluation, to provide
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to receive the materials. The shipment Box 1 | General biosafety guidelines should then be moved immediately to • Treat all specimens as potentially infectious moderate temperature storage (<30°C if • Wear protective gloves and laboratory gown while handling specimens possible). Leaving materials on airport • Do not eat, drink or smoke in the laboratory tarmacs, in customs sheds or in vehicles • Do not wear open-toe footwear in the laboratory should be avoided. • Dispose of sharp objects such as lancets and needles in appropriate sharps containers 2.2. Ground transportation. Ground trans- • Clean up spills with appropriate disinfectants e.g. 1% bleach portation during any stage of delivery to • Decontaminate all waste materials with an appropriate disinfectant the test sites should be carried out without • Dispose of all waste, including test kits, in a biohazard container and autoclave, if available delay and with attention to the ambient temperature while the vehicle is moving and if parked. Avoid leaving RDT kits in vehicles centrifugation facilities at the field sites. If exposure to humidity after removal from the parked in the sun. undue delays in reaching the laboratory can packaging or if the packaging is damaged. be avoided, the serum can be removed after Most manufacturers recommend RDT 2.3 Storage. Storage at the central and final transport. In this situation, the residue of the storage at temperatures between 2°C and field facilities should be within the manufac- whole-blood specimen should also be sent 30°C. The expiry dates are generally set turer’s specifications (usually below 30°C). to the laboratory where trained personnel according to these conditions. If RDT kits Maximize the time that RDTs are stored should repeat the RDT as soon as possible are stored at temperatures exceeding the in centralized, controlled conditions and after the specimen has been received. recommended limits, it is likely that their minimize uncontrolled storage in remote For whole-blood samples, 2–3 ml of shelf life will be reduced and sensitivity lost areas. Smaller box sizes can help achieve this. blood should be collected from each patient before the expiry date. The maintenance of Select a cool peripheral storage location; in tubes that have generally been pre-treated temperatures below 30°C for shipment of thatch roofing can be cooler than iron. with an anticoagulant such as tri-potas- RDTs is essential. The transport of RDTs Available shade should be maximised and sium ethylenediaminetetraacetic acid from manufacturers and within countries the use of evaporative cooling cabinets (EDTA). Some RDTs specify what type of should be monitored as follows: should be considered. anticoagulant is compatible for use with the Transport and storage at temperatures test and others can be used with or without 2.1. Shipping from the manufacturers. above 30°C is sometimes unavoidable in anticoagulants. An aliquot of whole blood Before shipping, the manufacturer should many remote locations where RDTs are should be used immediately to perform the contact the consignees with details of most useful. In such circumstances, it is RDT at the clinic and the remainder should the airway bill numbers, airline carrier, essential that the sensitivity of the tests is be transported to the laboratory to repeat flight number, numbers of containers and monitored at appropriate intervals. WHO the RDT on whole blood, if required. If only expected arrival time. These details should is currently developing recommendations finger-prick blood is used, consider storing be sent by e-mail and also by facsimile trans- for quality-assurance procedures to address extra blood as blood spots on filter paper for mission (fax). these issues. additional testing if necessary. These blood The air carrier should be notified in writ- spots should be air-dried and stored in a ing of the temperature storage requirements 3. Training of staff sealed bag with dessicant. by the manufacturer and by clear markings Adequate training and supervision of the For serum samples used for reference on all cartons and related documents (stow- end-users of RDTs should be integrated as testing, 2–3 ml of blood should be collected age of the shipment close to the skin of some far as possible into existing health worker from each patient in plain tubes and either aircraft might result in freezing). training and quality-assurance schemes. Staff processed on site or sent to the laboratory. The manufacturer should initiate the ship- should be proficient at performing the refer- It is important that all specimen collection ment only when the consignee confirms that ence test and the RDTs under evaluation. The tubes are labelled with a study number. the shipping notification has been received. laboratory should subscribe to an external Blood samples can be transported at The consignees then arrange to have quality-assurance scheme and participate in ambient temperature or on wet ice if avail- customs agents or other personnel on site Proficiency Panel testing at least twice a year. able. The serum samples should be divided into two aliquots and labelled. One aliquot o should be stored at 4 C until use and the Box 2 | General guidelines for the use of test kits other aliquot should be frozen at −20°C or −70°C for further testing if necessary. • Note lot number and expiry date: a kit should not be used beyond the expiry date • Ensure correct storage conditions: if a desiccant is included in the package, do not use the kit if 2. Transport and storage of RDTs the desiccant has changed colour Exposure of RDTs to high temperatures, par- • If test kits are stored in the refrigerator, they should be brought to room temperature (about ticularly during transport and storage, can 30 minutes) before use. The use of cold test kits can lead to false negative results. be a major contributor to poor test perform- • Damaged kits should be discarded ance. Transfer from the manufacturer, and • Use test kits immediately after opening road transport within a country, are particu- • Reagents from one kit should not be used with those of another kit larly vulnerable times. High humidity can • Test should be performed exactly as described in the product insert rapidly degrade RDTs, especially prolonged
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Box 3 | Minimum standards for field component of sensitivity/specificity trials of syphilis RDTs All trials should follow the general criteria for diagnostics trials outlined in Evaluation of diagnostic tests for infectious diseases: general principles in this supplement. The points listed below should be considered in the design and conduct of all evaluations of all comparative field trials of treponemal RDTs, and should be documented. This information should also be recorded in published trials.
Checklist for study design and analysis of results Rationale for the evaluation and for what indication, for example: Describe the evaluation procedure: ❏ Need rapid tests to increase the specificity of syndromic management ❏ Time of strip or device package opening to time of use or for screening high-risk population ❏ Blood collection (venous or finger prick using lancet and capillary) ❏ Need to evaluate performance and ease of use in field setting ❏ Specimen processing (whole blood or serum, blood transfer to test device or strip, device provided by manufacturer or pipette etc) ❏ Time from blood collection to placing sample on RDT, and how whole Record details of RDTs used: blood or serum stored in this interval ❏ Manufacturer (company name, site of manufacture) ❏ Time taken to obtain reading (as per manufacturer’s instructions, or if ❏ Batch number delayed, for how long and reason for delay) ❏ Packaging type (sealed individually, multiple strips in same canister, ❏ Record each line on the strip separately, starting with the control line. and so on) A record of intensity is not necessary as the test is not quantitative ❏ Inclusion of desiccant with strips ❏ Inclusion of lancets/capillary tubes needed to perform the test (or otherwise note the items used) Record organization and training of test readers/technicians: ❏ Is product under evaluation for regulatory approval or is it ❏ One or multiple readers commercially available? ❏ Same technician/reader per test type, or alternating ❏ Blinding to reference standard test results, results of other RDT readers, and to clinical presentation (the latter might not be possible Describe storage /transport conditions since receipt at evaluation site in some circumstances) ❏ Date of manufacture, if available ❏ Identity of technicians/readers for later analysis (can be coded) ❏ Date of expiry ❏ Training/experience in use of test (including date of training and ❏ Duration of storage on site validation of quality of training), and comparison with intended end- ❏ State and type of packaging, and whether canisters of test strips or users reagent bottles have been opened before the start of the study (tests in damaged packaging should not be used) ❏ General temperature and humidity at storage (monitoring of Record significant difficulties encountered with testing: temperature and humidity if possible). Tests should be stored away ❏ Significant or recurrent problems encountered in kit preparation or from direct sunlight. specimen collection (including opening of packaging, etc.) ❏ Time to complete use from opening of canister or bottled reagents ❏ Any deviations from manufacturer’s instructions (when dipsticks with this type of packaging are used) ❏ Record what is done with indeterminate results, how many tests had to be repeated ❏ Consider a formal independent qualitative appraisal of ‘ease of use’ of Describe the trial site: product by each technician ❏ Climatic conditions (mean local temperature and humidity) ❏ Workplace conditions (type of facility, lighting used for reading RDTs) ❏ Local STI epidemiology, if known Ensure reference standard test is performed correctly: ❏ Kit or reagents used ❏ Proficiency and training of technicians (subscription to external Describe the study population: quality-assurance programmes) ❏ Inclusion criteria (symptoms and signs, if any) ❏ Mechanism for blinding from RDT results ❏ Exclusion criteria ❏ Demographics (age, sex) ❏ Recent treatment or antibiotic use Describe methods of data analysis: ❏ Consider collecting blood dried on filter paper or in EDTA to allow for additional testing as necessary. The criteria for settling discordant Describe the recruitment process: results should be formulated beforehand and clearly stated. ❏ Who will be responsible for recruitment? ❏ Describe the process of obtaining informed consent* ❏ Describe what test results will be used to guide treatment of patients
*Issues concerning ethics and patient consent are detailed in Evaluation of diagnostic tests for selected infectious diseases: general principles in this supplement. See APPENDICES 1 and 2 for sample data-collection and informed consent forms.
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Concise, clear standard operating pro- 4. Testing Data from the patient (APPENDIX 1), cedures (SOPs) should be prepared in local All tests should be performed according to results from the tests at the clinic, the results languages for the health workers who are the manufacturer’s directions. Any devia- of the RDTs from the reference laboratory trained to perform the test. The instruc- tions from the recommended procedure and the results of the reference standard tions for sample processing and should be recorded. test should be entered into a standardized the interpretation of results should be clear. Blinding is necessary to ensure spreadsheet for analysis. Double entry independence of test results in the reduces the chance of error. Some form of 4. Recent treatment evaluation. Laboratory staff should be data backup such as transfer to a disc should Recent treatment of cases will have little blinded to the RDT results at the clinic and be performed at the end of each day. impact on the result of the test as treponemal vice versa. The collected information, as well as tests, once positive, will usually remain so As the interpretation of RDT results is the frozen serum samples, should be for life. subjective, it is recommended that at least kept until the study has ended, the data two individuals read the test results inde- have been analysed and final publication 5. Laboratory facilities and testing sites pendently. The results of RDTs performed in achieved. The reference laboratory should have clear the clinic can also be evaluated against RDTs SOPs for both the confirmatory treponemal performed by trained laboratory technicians VIII. ANALYSIS OF RESULTS test and the RDT. The study should be con- to assess the feasibility of using these tests in The sensitivity, specificity, positive and nega- ducted in accordance with Good Clinical field settings. tive predictive values and 95% confidence Practice (GCP) and Good Laboratory As staff at busy clinics might not be able intervals for each RDT compared to the Practice (GLP) or Good Clinical Laboratory to read the RDT results at exactly the time results obtained with the reference test Practice (GCLP) guidelines. GLP guidelines recommended, it would be of interest to should be calculated. have been largely developed for drug assess whether the test results are stable BOX 3 contains a checklist of all the points studies to provide data on drug toxicology 1 hour after the recommended time for that should be considered in the design and and efficacy for the purposes of regulatory reading. conduct of all evaluations of comparative approval. Some of these materials are inap- field trials of syphilis RDTs. propriate and often too complex for trials of VI. QUALITY ASSURANCE diagnostics or vaccines. As a result of As the temperatures that RDTs are sub- For details contact: the EU Clinical Trials Directive, GCLP jected to during transport can affect their Alan Herring at the Veterinary School, University of Bristol, Langford House, guidelines have been developed specifi- sensitivity, the sensitivity of RDTs should Langford, North Somerset, cally to provide guidance for laboratories be checked at a central laboratory with a BS40 5DN, UK. involved in clinical trials. GCLP guide- well-characterized quality-control panel on Ron Ballard at the Division of AIDS, STD and TB lines have been published by the British receipt from the manufacturer, and periodi- Laboratory Research, CDC, Association of Research Quality Assurance cally throughout the recommended shelf life. 1,600 Clifton Road, (BARQA)22. Peripheral health centres should be alerted Atlanta, Georgia 30333, USA. to any depreciation of test quality during David Mabey at the Clinical Research Unit, 6. Co-morbidities transport. London School of Hygiene & Tropical Medicine, The presence of syphilis has been All positive reference standard tests and Keppel Street, London, WC1E 7HT, UK. associated with an increased risk of HIV 10% of the specimens that test negative co-infection. Syphilis increases the risk (these should be selected sequentially, for Rosanna W. Peeling* at the UNICEF/UNDP/World Bank/WHO Special Programme for Research & of transmission of HIV infection. The example, select every tenth negative sample) Training in Tropical Diseases (TDR), presence of a positive RDT for syphilis should be sent to an external laboratory for 20 Avenue Appia, therefore presents an excellent opportunity validation. CH-1211, Geneva 27, for counselling and to offer testing for HIV To assess whether RDTs can truly be Switzerland. and other STIs. performed adequately by untrained person- *e-mail: [email protected] Copyright © WHO, on behalf of TDR (WHO/TDR) 2006 nel, all RDTs should also be performed at doi:10.1038/nrmicro1563 V. CONDUCTING THE EVALUATION the laboratory by laboratory technicians 1. WHO. Global Prevalence and Incidence of Selected 1. Obtaining informed consent using whole blood (if feasible) and serum. Curable Sexually Transmitted Infections: Overview and Estimates. [online],
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7. Terris Prestholt, F. et al. Is antenatal syphilis screening 13. Fears, M. B. & Pope, V. Syphilis fast latex agglutination 19. Montoya, P. J. et al. Comparison of the diagnostic still cost effective in sub-Saharan Africa? Sex Transm. test, a rapid confirmatory test. Clin. Diagn. Lab. accuracy of a rapid immunochromatographic test and Infect. 79, 375–381 (2003) Immunol. 8, 841–842 (2001). the rapid plasma reagin test for antenatal syphilis 8. World Bank. World Development Report 1993: 14. Zarakolu, P. et al. Preliminary evaluation of an screening in Mozambique. Bull. World Health Organ. Investing in Health (Oxford University Press for the immunochromatographic strip test for specific 84, 97–104 (2006). World Bank, 1993) Treponema pallidum antibodies. J. Clin. Microbiol. 40, 20. WHO/TDR. Laboratory-Based Evaluation of Rapid 9. Peeling, R. W. & Ye, H. Diagnostic tools for preventing 3064–3065 (2002). Syphilis Diagnostics. [online],
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APPENDIX 1 | SAMPLE CLINIC DATA-COLLECTION FORM FOR THE EVALUATION OF SYPHILIS RDTs
Name of clinic: ______Date of clinic visit: ______(day/month/year)
Study number: ______(Abbreviation for site location followed by consecutive no. 001–2000) M F Age or date of birth (day/month/year): ______Sex: ❏ ❏
Reason for presentation to clinic: Yes No Prenatal care: ❏ ❏ Family planning: ❏ ❏ Termination of pregnancy: ❏ ❏ At risk of STI: ❏ ❏ Other: specify______
Yes No Have you ever had an STD? ❏ ❏ If yes, please specify______
Yes No Have you ever had syphilis? ❏ ❏ If yes, when?______
Yes No Were you given treatment? ❏ ❏ Was your partner infected? ❏ ❏ Was your partner treated? ❏ ❏ Are you pregnant? ❏ ❏
Clinical diagnosis______
Yes No If a rapid test is available at this clinic, are you willing to wait for the results? ❏ ❏ If Y, will you wait 30 min. ___, 1 hour ____, 2 hours ____?
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APPENDIX 2 | SAMPLE INFORMED CONSENT FORM FOR THE EVALUATION OF SYPHILIS RDTs (A separate patient information sheet containing this information should also be provided)
A | PURPOSE OF THE STUDY are acceptable in terms of accuracy, everyone Only members of the study team (doctors, Syphilis is a common disease caused by a who comes to the clinic might benefit from nurses and social workers) will have access sexually transmitted bacterium. Although the receiving their results and treatment the to information linking your name with your infection can cause serious health problems same day. study number. such as ulcers, nerve damage and sometimes death, in some people it might not show any F | COMPENSATION H | QUESTIONS AND FREEDOM TO symptoms. You can therefore be infected dur- There will be no monetary compensation WITHDRAW FROM THE STUDY ing sexual intercourse by a partner who looks for this study, but routine medical consulta- You can withdraw from the study at any healthy. Furthermore, during unprotected tion and appropriate referral services are time without affecting your present or future sexual intercourse with a partner infected available. medical care at the clinic. You can contact with the AIDS virus (HIV), a man or woman any of the study personnel if you have ques- infected with syphilis will have a higher risk G | CONFIDENTIALITY STATEMENT tions about the research. of acquiring HIV than a person not infected The records concerning your participation You can speak with a specific field worker or with the syphilis bacterium. are to be used only for the purpose of this nursing assistant We can detect syphilis with a simple research project. Your name will not be used (Name______). blood test here at the clinic but it can take a on any study forms or labels on laboratory You can also call the clinic during working few days to get the results back to you. There specimens or in any report resulting from hours (Tel: ______). are new tests available which can give us this study. At the beginning of the study, we results in an hour but we do not know if they will give you a study identification number I | RESULTS PUBLICATION are as accurate as the test we now use. We and this number will be used on the forms When the researchers have analysed the would like to ask for your help in comparing and on the laboratory specimens. Any data, the results and the explanation of its the new test to the test we normally use at information obtained in connection with implications will be posted at the clinic for the clinic. If the new test works well, perhaps this study will be kept strictly confidential. everyone’s information. we will be able to give a more rapid diagno- sis of syphilis in the future. J | PARTICIPANT STATEMENT B | PROCEDURES TO BE FOLLOWED I have been informed verbally and in writing about this study and understand what is If you agree to participate in the study, the involved. I also know whom to contact if I need more information. I understand that con- doctor or nurse will give you a physical fidentiality will be preserved. I understand that I am free to withdraw from the study at any examination and ask you some questions time without affecting the care I normally receive at the clinic. I agree to participate in this according to standard clinic procedure. study as a volunteer subject and will be given a copy of this information sheet to keep. He/she will take 2–5 ml of blood from you, as is the normal procedure at the clinic. We will ______use a portion of this blood to do a rapid test Date Name of study participant in addition to the normal laboratory test. You will not receive treatment based on the rapid ______test result as we are not sure how accurate it is. Signature (or thumb print or cross) of study participant
C | VOLUNTARY PARTICIPATION ______During the interview, you can choose not Date Name of witness to answer any particular question. A deci- sion not to participate, or to withdraw from ______participation, will not affect the care you will Signature of witness receive at the clinic in any way. If you do agree to become a study participant, you can with- draw from the study at any time (verbally). K | INVESTIGATOR’S STATEMENT I, the undersigned, have defined and explained to the volunteer in a language he/she D | DISCOMFORT AND RISKS understands, the procedures of this study, its aims and the risks and benefits associated with You might feel a small amount of discomfort his/her participation. I have informed the volunteer that confidentiality will be preserved, while your blood is taken and you might that he/she is free to withdraw from the trial at any time without affecting the care he/she have some bruising at the place where the will receive at the clinic. Following my definitions and explanations the volunteer agrees to blood is taken. The bruise should disappear participate in this study. in a short time. ______E | BENEFITS Date Name of investigator who gave the information about There will be no immediate benefits from the study your participation in the study. When the study results are known and the rapid tests Signature: ______
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