Egger, Matthias

Low, Nicola

RERO DOC Digital Library

International Journal of Epidemiology 2002;31:891–893Chlamydia trachomatis is the world’s most common bacterialsexually transmitted infection, with an estimated 89 millionnew cases each year.1 Genital chlamydia poses a major globalpublic health problem because it is a transmissible cause ofsevere reproductive morbidity, including pelvic inflammatorydisease, impaired fertility and ectopic pregnancy in women.2Chlamydia can be cured with antibiotics and transmissionprevented by treating sexual partners, but most infections areasymptomatic so they remain undiagnosed. Early diagnosis ispossible, with DNA amplification techniques now providinghighly sensitive and specific tests3 that are more acceptable topatients than previous methods because they can be performedon non-invasively collected genital specimens. Probably morethan any other single factor, these technological advances inchlamydial diagnosis are driving the current health policydebate about the introduction of national chlamydia screeningprogrammes.4,5 But do we have enough evidence about theeffectiveness of screening and about the natural history ofchlamydial disease to be sure that proposed screening pro-grammes will be the most effective and cost-effective way ofpreventing the long term consequences of infection?The appropriateness of screening for disease prevention isusually assessed according to principles set out by Wilson andJungner in 1966.6 These criteria have been expanded by policy-making bodies such as the UK National Screening Committee toemphasize the rigorous standards of research evidence requiredto demonstrate effectiveness and the programme aspects ofscreening.7 Genital chlamydia has been judged to fulfil thesecriteria either in whole,8,9 or in part.4,10 So how strong is theevidence? The first randomized trial evaluated the effect ofchlamydia screening on the incidence of pelvic inflammatorydisease in women in a health maintenance organization ful-filling criteria for being at high risk of infection.11 This approachwould be classified as a selective population screening strategy.The incidence of pelvic inflammatory disease at one year was56% (95% CI: 10–80%) lower in the intervention than thecontrol group. The potential for bias introduced by the studydesign, however, makes the results difficult to interpret.10,12,13In particular, randomization was performed before women wereinvited for screening, and those allocated to the screening armwere more vigorously recruited.11 Thus, of more than 36 000women randomized to intervention and control groups in aratio of 1:2, only 2607 (7.1%) were included in the analysis,with the ratio of intervention to control groups falling to 1:1.6.More recently, randomized trials in Denmark have also evalu-ated population screening, inviting school students14 and youngpeople in the general population15 to submit self-taken urine orvaginal specimens for chlamydia testing. Amongst women in theschool-based study the incidence of pelvic inflammatory diseaseat one year was reduced by 50%.14 Over 45% of study partici-pants were, however, lost to follow-up in this study. Whilstevidence from randomized trials is essential, problems with trialquality that could bias the estimated benefits of chlamydiascreening could lead to future challenges and debate about thejustification for screening programmes, as has recently happenedwith breast cancer screening.16–18 Furthermore, the randomizedtrials evaluated population-based approaches to screening butthey have also been cited as evidence in support of opportun-istic screening of people using existing health services.8,19 It isunclear to what extent the results of population-based screeningcan be extrapolated to opportunistic strategies.Observational data from chlamydia screening programmesestablished before randomized trials were performed alsoprovide evidence that screening is associated with reductions inthe prevalence of genital chlamydia, pelvic inflammatorydisease and ectopic pregnancy.20–22 Programmes were set up inSweden21 and parts of the US20 during the mid-1980s toconduct opportunistic screening on unselected, mostly female,populations attending a variety of health care settings. Five to 9years after implementation, proportions of positive samplestested by laboratories in these programmes had decreased byone- to two-thirds.20,21 However, surveillance data from countrieswith23 and without24 screening programmes have shown similarrecent increases in the prevalence of chlamydia (Figure). Changesin population prevalence are clearly influenced by the numberof people being tested and, although this has increased in Sweden,the proportion of positive tests has also increased from a nadirof 4.1% in 1994 to 6.1% in 2000.23 These findings suggest thatthe opportunistic screening approach to chlamydia control mayhave reached its limit.A potential explanation for the resurgence of chlamydia inSweden could be the failure to include men comprehensively inthe screening programme. Opportunistic programmes onlyreach health service users, and amongst young sexually activepeople, these are mostly women. In Sweden only 20–25% ofchlamydia specimens come from men.21 Control of chlamydiatransmission should occur through partner notification, which© International Epidemiological Association 2002 Printed in Great BritainEDITORIALWhat should we do about screening forgenital chlamydia?Nicola Lowa and Matthias Eggerba Department of Social Medicine, University of Bristol, UK.b Institute for Social and Preventive Medicine, University of Berne,Switzerland.Correspondence: Dr Low, Department of Social Medicine, University ofBristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK. E-mail:nicola.low@bristol.ac.uk891is compulsory in Sweden. It has also been widely assumed thatprevalence of chlamydia is lower in men than women becauseof lower female to male transmission efficiency and because themajority of infections in men were presumed to be symptomaticand to present early for testing and treatment.25 Anotherapplication of DNA amplification diagnostic techniques has shownthis assumption to be false. Several studies have now estimatedthe prevalence of chlamydia in population-based samples usingnon-invasive home-collected specimens.26–29 In the Europeanstudies, chlamydia prevalence was 2.2–2.3% in men and 1.5–2.9%in women.13,26,28 A smaller study from Baltimore found, in ourcalculation, crude prevalence rates of 3.2% (95% CI: 0.1–7.9%)and 5.2% (95% CI: 2.5–9.3%) in Black men and women, and3.3% (95% CI: 0.1–8.5%) and 0% (upper CI: 2.6%) in men andwomen of other ethnic groups.29 Together, these studies suggestthat the circulating pool of asymptomatic untreated chlamydiamay be similar in men and women. A strategy combining oppor-tunistic screening in health care settings, which tends to miss alarge proportion of men at risk, and partner notification maynot be sufficient to produce sustained reductions in chlamydiaprevalence.The case in favour of chlamydia screening for a range ofpopulations and screening strategies has also been made on thegrounds of cost-effectiveness.30–33 Most of the cost savingsachieved through screening come from the predicted costs oftreatment of complications avoided.32,34 Economic models arehighly sensitive to assumptions about the incidence of compli-cations34 but these are notoriously difficult to measure. Studiesestimating the rate of progression from lower genital tractchlamydia to pelvic inflammatory disease are hindered by smallsample size and a lack of objective diagnostic criteria for pelvicinflammatory disease. The most widely cited study found pelvicinflammatory disease in 6 of 20 women with chlamydia (30%,95% CI: 12–54%).35 Uncertainty about, and especially over-estimation of the incidence of complications, could give misleadingresults about the cost-effectiveness of screening interventions.Piecing together the natural history of chlamydial disease isfraught with problems,2,10,34 not least because of the ethics ofstudying the prognosis of untreated infection. The long termoutcomes of laparoscopically confirmed pelvic inflammatorydisease have been studied in cohort studies36,37 with up to 25 yearsof follow-up.37 These studies are of limited use, however, becausethey report only the proportions of women developing infertilityor ectopic pregnancy, without taking into account thelongitudinal nature of the data, losses to follow up over time orconfounding by contraceptive choice or sexual behaviour. Further-more, in the largest study, chlamydia status at baseline was notknown.37Ideally, individual or cluster randomized controlled trials inwhich the potential for bias has been minimized should com-pare the effect of different screening strategies with no screeningon the incidence of pelvic inflammatory disease and chlamydia.A cluster trial is now being piloted in Scotland (Phil Wilson,University of Glasgow, personal communication). Screening forchlamydia in men also needs to be evaluated and methods ofincluding men in chlamydia screening programmes considered.The ongoing Chlamydia Screening Studies (ClaSS) in the Avonand West Midlands regions of England were set up to determinethe prevalence in the sexually active male and female popu-lation and to examine the feasibility, acceptability and costs of amass screening programme. A similar project is ongoing in fourregional municipal health services in the Netherlands.38 Initialresults from the Chlamydia Pilot Studies in the Wirral andPortsmouth, England, indicate that opportunistic screening isfeasible in a range of settings in the National Health Service, andsignificant population coverage can be achieved.39 In order tomodel more accurately the cost effectiveness of chlamydia screen-ing programmes we also need to improve our understanding ofthe natural history of chlamydial disease. A linkage study inUppsala, Sweden, where widespread opportunistic screeningwas introduced in 1985, will provide information on the incidenceof sequelae in women who screened positive for chlamydia,women who screened negative, and women who declined toparticipate in the programme (Björn Herrmann, University ofUppsala, personal communication). The results from a numberof ongoing studies will thus fill some of the important gaps inthe evidence base. Surely, in the UK and elsewhere, we shouldavoid pressure to implement a screening programme prematurelywithout being sure that this is the most sustainable approach tocontrolling chlamydia and its reproductive consequences.References1 World Health Organization. Global Prevalence and Incidence of SelectedCurable Sexually Transmitted Infections. Overview and Estimates. Geneva:WHO, 2001.2 Cates W Jr, Rolfs RT Jr, Aral SO. Sexually transmitted diseases, pelvicinflammatory disease, and infertility: an epidemiologic update.Epidemiol Rev 1990;12:199–220.3 Black CM. Current methods of laboratory diagnosis of Chlamydiatrachomatis infections. Clin Microbiol Rev 1997;10:160–84.4 Johnson AM, Grun L, Haines A. Controlling genital chlamydialinfection: advances in diagnosis and treatment may make screeningworthwhile. BMJ 1996;313:1160.5 Mardh PA. Is Europe ready for STD screening? Genitourin Med1997;73:96–98.892 INTERNATIONAL JOURNAL OF EPIDEMIOLOGYFigure Trends in diagnoses of genital chlamydia in Sweden andEngland and Wales 1988–2000Source: Sweden (Dr Torsten Berglund, personal communication), Englandand Wales (Public Health Laboratory Service and Office for NationalStatistics). The higher recorded prevalence of chlamydia in Sweden probablyreflects higher testing rates and differences in national surveillance systems.Genital chlamydia is compulsorily notifiable in Sweden and surveillance datainclude reports of infections diagnosed in all clinical settings. Chlamydia is notnotifiable in England and Wales and surveillance data come from diagnosesmade in genito-urinary clinics only.6 Wilson JMG, Jungner G. Principles and Practice of Screening for Disease.Geneva: World Health Organization, 1968.7 Department of Health. Second Report of the UK National ScreeningCommittee. London: The Stationery Office, 2000.8 CMO’s Expert Advisory Group on Chlamydia trachomatis. London:Department of Health, 1998.9 Boag F, Kelly F. Screening for Chlamydia trachomatis. The case forscreening is made, but much detail remains to be worked out. BMJ1998;316:1474.10 Stephenson JM. Screening for genital chlamydial infection. Br MedBull 1998;54:891–902.11 Scholes D, Stergachis A, Heidrich FE, Andrilla H, Holmes KK, StammWE. Prevention of pelvic inflammatory disease by screening forcervical chlamydial infection. N Engl J Med 1996;334:1362–66.12 Sellors J, Paavonen J. Screening for chlamydia to prevent pelvicinflammatory disease. N Engl J Med 1996;335:1531–32.13 The ClaSS Study Group. Evidence is not (yet) enough for evidencebased policy of chlamydia screening. BMJ 2001;322:364–65.14 Østergaard L, Andersen B, Moller JK, Olesen F. Home sampling versusconventional swab sampling for screening of Chlamydia trachomatis inwomen: A cluster-randomized 1-year follow-up study. Clin Infect Dis2000;31:951–57.15 Andersen B, Olesen F, Moller JK, Østergaard L. Population-basedstrategies for outreach screening of urogenital Chlamydia trachomatisinfections: A randomized, controlled trial. J Infect Dis 2002;185:252–58.16 Gøtzche PC, Olsen O. Is screening for breast cancer withmammography justifiable? Lancet 2000;355:129–34.17 McLellan F. Independent US panel fans debate on mammography.Lancet 2002;359:409.18 The CBCG Editors. Screening mammography: setting the recordstraight. Lancet 2002;359:439–40.19 Pimenta J, Catchpole M, Gray M, Hopwood J, Randall S. Evidencebased health policy report. Screening for genital chlamydial infection.BMJ 2000;321:629–31.20 Hillis SD, Nakashima A, Amsterdam L et al. The impact of acomprehensive chlamydia prevention program in Wisconsin. FamPlann Perspect 1995;27:108–11.21 Herrmann B, Egger M. Genital Chlamydia trachomatis infections inUppsala County, Sweden, 1985–1993: declining rates for how muchlonger? Sex Transm Dis 1995;22:253–60.22 Egger M, Low N, Davey Smith G, Lindblom B, Herrmann B. Screeningfor chlamydial infections and the risk of ectopic pregnancy in a countyin Sweden: ecological analysis. BMJ 1998;316:1776–80.23 Swedish Institute for Infectious Disease Control. Communicable Diseasesin Sweden 2000. The Annual Report of the Department of Epidemiology.Stockholm: Smittskyddsinstitutet, 2001.24 PHLS, DHSS&PS, and Scottish ISD(D)5 Collaborative Group. SexuallyTransmitted Infections in the UK: New Episodes Seen at GenitourinaryMedicine Clinics, 1995–2000. Trends in Sexually Transmitted Infections withSpecial Reference to Young People. London: PHLS, 2001.25 Quinn TC, Gaydos C, Shepherd M et al. Epidemiologic andmicrobiologic correlates of Chlamydia trachomatis infection in sexualpartnerships. JAMA 1996;276:1737–42.26 Fenton KA, Korovessis C, Johnson AM et al. Sexual behaviour inBritain: reported sexually transmitted infections and prevalent genitalChlamydia trachomatis infection. Lancet 2001;358:1851–54.27 The ClaSS Study Group. Population-based estimates of chlamydiaprevalence in England. Int J STD AIDS 2001;12:72.28 van Valkengoed GM, Boeke AJP, van den Brule AJC et al. Systematicscreening for asymptomatic Chlamydia trachomatis infections by homeobtained mailed urine samples in men and women in generalpractice. Nederlands Tijdschrift voor Geneeskunde 1999;143:672–76.29 Turner CF, Rogers SM, Miller HG et al. Untreated gonococcal andchlamydial infection in a probability sample of adults. JAMA2002;287:726–33.30 Genc M, Mårdh A. A cost-effectiveness analysis of screening andtreatment for Chlamydia trachomatis infection in asymptomaticwomen. Ann Intern Med 1996;124:1–7.31 Genc M, Ruusuvaara L, Mårdh PA. An economic evaluation ofscreening for Chlamydia trachomatis in adolescent males. JAMA1993;270:2057–64.32 Paavonen J. Is screening for Chlamydia trachomatis infection costeffective? Genitourin Med 1997;73:103–04.33 Marrazzo JM, Celum CL, Hillis SD, Fine D, DeLisle S, Handsfield HH.Performance and cost-effectiveness of selective screening criteria forChlamydia trachomatis infection in women. Implications for a nationalChlamydia control strategy. Sex Transm Dis 1997;24:131–41.34 van Valkengoed IG, Postma MJ, Morre SA et al. Cost effectivenessanalysis of a population based screening programme for asymp-tomatic Chlamydia trachomatis infections in women by means ofhome obtained urine specimens. Sex Transm Infect 2001;77:276–82.35 Stamm WE, Guinan ME, Johnson C, Starcher T, Holmes KK,McCormack WM. Effect of treatment regimens for Neisseriagonorrhoeae on simultaneous infection with Chlamydia trachomatis. N Engl J Med 1984;310:545–49.36 Svensson L, Mårdh PA, Westrom L. Infertility after acute salpingitis withspecial reference to Chlamydia trachomatis. Fertil Steril 1983;40:322–29.37 Westrom L, Joesoef R, Reynolds G, Hagdu A, Thompson SE. Pelvicinflammatory disease and fertility. A cohort study of 1844 womenwith laparoscopically verified disease and 657 control women withnormal laparoscopic results. Sex Transm Dis 1992;19:185–92.38 van Bergen JE. Onderzoek naar prevalentie en interventie Chlamydiatrachomatis [A study of the prevalence of and interventions forChlamydia]. SOA Bulletin 2001;3.39 Pimenta JM, Rogers PA, Catchpole M and Chlamydia Pilot Group.Screening for Genital Chlamydial Infection: Results from a UK Pilot Study.Presented at the 26th PHLS Annual Scientific Conference. Universityof Warwick, 17–19 September 2001.CANCER FOLLOWING CARDIAC CATHETERIZATION IN CHILDHOOD 893

What should we do about screening for genital chlamydia?

Abstract

Similar works

Full text

Available Versions

RERO DOC Digital Library