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Advances in control of sexually transmitted diseases in developing countries

1998; Elsevier BV; Volume: 351; Linguagem: Inglês

10.1016/s0140-6736(98)90009-5

1474-547X

Philippe Mayaud, Sarah Hawkes, David Mabey,

Adolescent Sexual and Reproductive Health

Sexually transmitted diseases (STDs) impose an enormous burden of morbidity and mortality in many developing countries, both directly through their impact on reproductive and child health,1Wasserheit J The significance and scope of reproductive tract infections among third world women.Suppl Int J Gynaecol Obstet. 1989; 3: 145-163Summary Full Text PDF PubMed Scopus (117) Google Scholar and indirectly through their role in facilitating the sexual transmission of HIV infection.2Laga M Diallo MO Buvé A Interrelationship of STD and HIV: where are we now?.AIDS. 1994; 8 (suppl): S119-S124Google Scholar It has been estimated that in urban populations in sub-Saharan Africa, for example, STDs are responsible for some 17% of the total burden of disease in women of reproductive age.3Over M Piot P HIV infection and sexually transmitted diseases.in: Jamison DT Mosley WH Measham AR Bobadilla JL Disease control priorities in developing countries. Oxford University Press, New York1993: 455-527Google Scholar Yet it is only in recent years that these diseases have been accorded any priority by national ministries of health or by the international community. The increased interest in STD control in developing countries is largely a result of the HIV epidemic. Reports of an association between the "classic" STDs and HIV infection4Cameron DW Simonsen NJ D'Costa LJ et al.Female to male transmission of human immunodeficiency virus type 1: risk factors for seroconversion in men.Lancet. 1989; ii: 403-407Summary Scopus (632) Google Scholar, 5Laga M Manoka A Kivuvu M et al.Non-ulcerative sexually transmitted diseases as risk factor for HIV-1 transmission in women: results from a cohort study.AIDS. 1993; 7: 95-102Crossref PubMed Scopus (1053) Google Scholar have now been supplemented by virological studies showing that intercurrent STDs increase concentrations of HIV in genital secretions6Ghys PD Fransen K Diallo MO et al.The association between cervico-vaginal HIV shedding sexually transmitted diseases and immunosuppression in female sex workers in Abidjan, Cote d'Ivoire.AIDS. 1997; 11: 85-93Crossref Scopus (293) Google Scholar, 7Mostad SB Overbaugh DM DeVange MJ et al.Hormonal contraception, vitamin A deficiency, and other risk factors for shedding of HIV-1 infected cells from the cervix and vagina.Lancet. 1997; 350: 922-927Summary Full Text Full Text PDF PubMed Scopus (267) Google Scholar, 8Cohen MS Hoffman IF Royce RA et al.Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1.Lancet. 1997; 349: 1868-1873Summary Full Text Full Text PDF PubMed Scopus (734) Google Scholar (see also p sIII5); but more importantly, it has been shown that improved clinical services for STDs can significantly reduce the incidence of HIV infection in developing countries, and that this can be achieved by low-technology, sustainable, and highly cost-effective programmes.9Grosskurth H Mosha F Todd J et al.Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial.Lancet. 1995; 346: 530-536PubMed Scopus (1190) Google Scholar, 10Mayaud P Mosha F Todd J et al.Improved treatment services significantly reduce the prevalence of sexually transmitted diseases in rural Tanzania: results of a randomised controlled trial.AIDS. 1997; 11: 1873-1880Crossref PubMed Scopus (102) Google Scholar, 11Gilson L Mkanje R Grosskurth H et al.Cost-effectiveness of improved STD treatment services as a preventive intervention against HIV in Mwanza Region, Tanzania.Lancet. 1997; 350: 1805-1809Summary Full Text Full Text PDF PubMed Scopus (144) Google Scholar In the first decade of the AIDS epidemic, considerable resources were devoted to primary prevention through health education, but there was little evidence that it affected sexual behaviour in developing countries. However, condom promotion through social marketing had some spectacular successes–eg, in Ethiopia, where condom sales increased in 5 years from less than 500 000 per year to nearly 20 million.12Lamptey PR Goodridge G Condoms.in: Dallabetta G Laga M Lamptey P Control of sexually transmitted diseases. A handbook for the design and management of programs. AIDSCAP/FHI, Arlington, VA1996: 73-103Google Scholar Similarly, an intensive condom-promotion campaign in Thailand targeted brothel owners, prostitutes, and their clients and led to a rapid and striking fall in the incidence of reported STDs and HIV.13Hanenberg RS Rojanapithayakorn W Kunasol P Sokal DC Impact of Thailand's HIV-control programme as indicated by the decline of sexually transmitted diseases.Lancet. 1994; 344: 243-246Summary PubMed Scopus (378) Google Scholar, 14Nelson KE Celentano DD Eiumtrakol S et al.Changes in sexual behavior and decline in HIV infection among young men in Thailand.N Engl J Med. 1996; 335: 297-303Crossref PubMed Scopus (321) Google Scholar A community-randomised trial in the Mwanza Region of Tanzania showed that improved clinical services for STDs, with the syndromic approach recommended by WHO in rural health centres and dispensaries, reduced the incidence of HIV infection by about 40% over 2 years.9Grosskurth H Mosha F Todd J et al.Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial.Lancet. 1995; 346: 530-536PubMed Scopus (1190) Google Scholar The intervention had five components: a reference STD clinic was set up as a training centre and to monitor the aetiology of STD syndromes and the antimicrobial susceptibility of local strains of Neisseria gonorrhoeae; healthcare providers were trained in STD management, using the syndromic approach and offering health education and condoms in a non-judgmental manner; a continuous supply of antimicrobial drugs of proven local efficacy was provided; a regular system of supervisory visits to health facilities was instituted, at which in-service training was given and drug supplies and patient records were checked; and health education was given at village level to inform the population about the improved services and to encourage them to attend early for STD-related symptoms. This Mwanza intervention had no detectable impact on sexual behaviour, and condom acceptance was very low; it appeared that the reduction in HIV incidence was due to a decrease in the duration of symptomatic STDs. The prevalence of serological syphilis was also reduced, and the prevalence of symptomatic urethritis in men decreased by almost 50%.10Mayaud P Mosha F Todd J et al.Improved treatment services significantly reduce the prevalence of sexually transmitted diseases in rural Tanzania: results of a randomised controlled trial.AIDS. 1997; 11: 1873-1880Crossref PubMed Scopus (102) Google Scholar The intervention was highly cost-effective, at US$218 per HIV infection averted, and US$10 per disability-adjusted life year saved.11Gilson L Mkanje R Grosskurth H et al.Cost-effectiveness of improved STD treatment services as a preventive intervention against HIV in Mwanza Region, Tanzania.Lancet. 1997; 350: 1805-1809Summary Full Text Full Text PDF PubMed Scopus (144) Google Scholar The Mwanza trial was the first to show conclusively that improved clinical services for STDs can reduce the incidence of HIV infection and the prevalence of bacterial STDs. However, the trial highlighted the fact that other measures in addition to effective syndromic management are needed to control STDs effectively. A high prevalence of symptomless infections was documented in both men and women,15Grosskurth H Mayaud P Mosha F et al.Asymptomatic gonorrhoea and chlamydial infection in rural Tanzanian men.BMJ. 1996; 312: 277-280Crossref PubMed Scopus (68) Google Scholar, 16Mayaud P Grosskurth H Changalucha J et al.Risk-assessment and other screening options for gonorrhea and chlamydial infections in women attending rural Tanzanian antenatal clinics.Bull World Health Organ. 1995; 73: 621-630PubMed Google Scholar suggesting that improved case finding and screening strategies need to be developed, and emphasising the urgent need for simple and cheap laboratory diagnostic tests for this purpose. The intervention had no impact on the prevalence of STDs in women attending antenatal clinics, in whom symptoms and clinical signs are poor predictors of the presence of an STD.10Mayaud P Mosha F Todd J et al.Improved treatment services significantly reduce the prevalence of sexually transmitted diseases in rural Tanzania: results of a randomised controlled trial.AIDS. 1997; 11: 1873-1880Crossref PubMed Scopus (102) Google Scholar Furthermore, the syndromic management of vaginal discharge in women led to considerable overtreatment if ail women with this complaint were treated for gonorrhoea and chlamydial infection.15Grosskurth H Mayaud P Mosha F et al.Asymptomatic gonorrhoea and chlamydial infection in rural Tanzanian men.BMJ. 1996; 312: 277-280Crossref PubMed Scopus (68) Google Scholar In an attempt to reduce overtreatment for these infections in women, the WHO have proposed that the specificity of the syndromic-management algorithm for vaginal discharge can be improved by including a "risk assessment" step (figure 1, panel). This algorithm is based on the results of a study in Kinshasa which identified sociodemographic and sexual behavioural risk factors for gonorrhoea and chlamydial infections in women.17Vuylsteke B Laga M Alary M et al.Clinical algorithms for the screening of women for gonococcal and chlamydial infection: evaluation of pregnant women and prostitutes in Zaire.Clin Infect Dis. 1993; 17: 82-88Crossref PubMed Scopus (141) Google Scholar Although the algorithm undoubtedly reduces the need for unnecessary treatment, evaluations in other countries in Africa have suggested that it is at best only about 70% sensitive and 70% specific.18Thomas T Choudhri S Kariuki C Moses S Identifying cervical infection among pregnant women in Nairobi, Kenya; limitations of risk-assessment and symptom-based approaches.Genitourin Med. 1996; 72: 334-338PubMed Google Scholar, 19Mayaud P, ka-Gina G, Cornelissen J, et al. Validation of a WHO algorithm with risk-assessment for the clinical management of vaginal discharge in Mwanza, Tanzania. Sex Transm Dis (in press).Google Scholar. Furthermore, specificity of the syndromic flowcharts is unlikely to be improved in many countries through the use of sexual behaviour risk-assessment, because it relies on asking women about socially sanctioned behaviours.PanelSexually transmitted disease syndromes and aetiologles covered by syndromic managementGenital ulcer syndrome (presence of an ulcer, excludes typical herpes blisters)Treated for chancroid and syphilis (treatment for donovanosis could be added/substituted in countries with high prevalence of this disease–eg, Papua New Guinea, south India, Sri Lanka, parts of South Africa)Urethral discharge syndrome (presence of a discharge if necessary after "milking" the urethra)Treated for gonorrhoea and chlamydia initially and for Trichomonas vaginalis in case of treatment failure or add second-line therapy for gonorrhoea if suspected resistanceOrchiepididymitis (hot, tender, painful scrotum, after exclusion of surgical or medical causes such as torsion, trauma, mumps) Treated for gonorrhoea and chlamydia (+suspension, rest, and analgesics, if appropriate)Vaginal discharge (accompanied or not with itching) Treated for gonorrhoea, chlamydia, T vaginalis, and bacterial vaginosis, unless discharge appears like thrush, in which case only treatment for Candida albicans is givenPelvic inflammatory disease (low abdominal pain accompanied by painful cervical motion, after exclusion Of other surgical emergencies)Treated for gonorrhoea, chlamydia and anaerobic bacteria, T vaginalis, and bacterial vaginosisInguinal bubo (painful swollen inguinal lymph nodes without presence of an ulcer, after exclusion of local/regional obvious infectious causes)Treated for chancroid and lymphogranuloma venereumAlgorithms and treatment regimens must be adapted to the local level of the facility, and local STD aetiologies.The choice of drugs depends on local antimicrobial susceptibility, drugs availability, and procurement costs.Usually treatment is given at first visit, if possible treat with single dose of antibiotics taken immediately; patients are required to present after 7 days in case of treatment failures. Genital ulcer syndrome (presence of an ulcer, excludes typical herpes blisters) Treated for chancroid and syphilis (treatment for donovanosis could be added/substituted in countries with high prevalence of this disease–eg, Papua New Guinea, south India, Sri Lanka, parts of South Africa) Urethral discharge syndrome (presence of a discharge if necessary after "milking" the urethra) Treated for gonorrhoea and chlamydia initially and for Trichomonas vaginalis in case of treatment failure or add second-line therapy for gonorrhoea if suspected resistance Orchiepididymitis (hot, tender, painful scrotum, after exclusion of surgical or medical causes such as torsion, trauma, mumps) Treated for gonorrhoea and chlamydia (+suspension, rest, and analgesics, if appropriate) Vaginal discharge (accompanied or not with itching) Treated for gonorrhoea, chlamydia, T vaginalis, and bacterial vaginosis, unless discharge appears like thrush, in which case only treatment for Candida albicans is given Pelvic inflammatory disease (low abdominal pain accompanied by painful cervical motion, after exclusion Of other surgical emergencies) Treated for gonorrhoea, chlamydia and anaerobic bacteria, T vaginalis, and bacterial vaginosis Inguinal bubo (painful swollen inguinal lymph nodes without presence of an ulcer, after exclusion of local/regional obvious infectious causes) Treated for chancroid and lymphogranuloma venereum Algorithms and treatment regimens must be adapted to the local level of the facility, and local STD aetiologies. The choice of drugs depends on local antimicrobial susceptibility, drugs availability, and procurement costs. Usually treatment is given at first visit, if possible treat with single dose of antibiotics taken immediately; patients are required to present after 7 days in case of treatment failures. The International Conference on Population and Development, held in Cairo in 1994, recommended that all countries should make reproductive health care, including "treatment of reproductive-tract infections, STDs, and other reproductive health conditions" accessible to all individuals.20United Nations Programme of action of the UN International Conference on Population and Development. United Nations, New York1994Google Scholar After this recommendation, and the encouraging results of the Mwanza study, the provision of syndromic STD management for women attending antenatal or family planning clinics has assumed high priority on the international health agenda. This approach makes sense in some urban or rural populations in sub-Saharan Africa, where up to 40% of antenatal clinic attenders may have an STD,10Mayaud P Mosha F Todd J et al.Improved treatment services significantly reduce the prevalence of sexually transmitted diseases in rural Tanzania: results of a randomised controlled trial.AIDS. 1997; 11: 1873-1880Crossref PubMed Scopus (102) Google Scholar, 16Mayaud P Grosskurth H Changalucha J et al.Risk-assessment and other screening options for gonorrhea and chlamydial infections in women attending rural Tanzanian antenatal clinics.Bull World Health Organ. 1995; 73: 621-630PubMed Google Scholar, 17Vuylsteke B Laga M Alary M et al.Clinical algorithms for the screening of women for gonococcal and chlamydial infection: evaluation of pregnant women and prostitutes in Zaire.Clin Infect Dis. 1993; 17: 82-88Crossref PubMed Scopus (141) Google Scholar, 19Mayaud P, ka-Gina G, Cornelissen J, et al. Validation of a WHO algorithm with risk-assessment for the clinical management of vaginal discharge in Mwanza, Tanzania. Sex Transm Dis (in press).Google Scholar but it should not be considered a universal panacea. In populations with a lower STD prevalence the unquestioning application of syndromic STD management may be counterproductive, since it will lead to overtreatment on a large scale, wasting scarce resources and potentially subjecting women who are mistakenly informed that they have an STD to serious social consequences. It is important that resources for STD control should be concentrated on individuals at higher risk, and that both sexes should be included; indeed it makes more sense to target men, who are perhaps at greater risk than their rural spouses, and in whom the symptoms and signs of STDs are easier to recognise.21Hawkes S. Why include men? Establishing sexual health clinics for men in rural Bangladesh. Health Policy Planning (in press).Google Scholar Targeted programmes aimed at modifying the sexual behaviour of men and women through peer education, increasing condom use, and providing STD services near the work place have demonstrated their acceptability and effectiveness in reducing STD/HIV incidence among long-distance truck drivers, factory workers, and prostitutes in eastern and southern Africa.22Jackson DJ Rakwar JP Richardson BA et al.Decreased incidence of sexually transmitted diseases among trucking company workers in Kenya: results of a behavioural risk-reduction programme.AIDS. 1997; 11: 903-909Crossref PubMed Scopus (73) Google Scholar, 23Ngugi EN Wilson D Sebstad J Plummer FA Moses S Focused peer-mediated educational programme among female sex workers to reduce sexually transmitted disease and human immunodeficiency virus transmission in Kenya and Zimbabwe.J Infect Dis. 1996; 174: S240-S247Crossref PubMed Google Scholar Piot's operational model, originally developed to identify deficiencies in tuberculosis control programmes, has been adapted by Fransen and others to conceptualise the barriers to effective STD control (figure 2). Improved services such as those implemented in Mwanza can increase the proportion of STDs cured, but need to be supplemented by: primary prevention activities, behavioural interventions to improve treatment seeking behaviour, and efforts to identify and treat people with symptomless infections.24Hayes R Wawer M Gray R et al.Randomized trials of STD treatment for HIV prevention: report of an international workshop.Genitourin Med. 1997; 73: 432-443PubMed Google Scholar Primary prevention is particularly important in adolescents, a group that may have a high incidence of STDs,9Grosskurth H Mosha F Todd J et al.Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial.Lancet. 1995; 346: 530-536PubMed Scopus (1190) Google Scholar, 25Brabin L Kemp J Obunge OK et al.Reproductive tract infections and abortion among adolescent girls in rural Nigeria.Lancet. 1994; 344: 300-304Google Scholar and may also be more susceptible than their elders to behaviour-change messages. Peer-led programmes for sexual education that emphasise the development of life skills still need to be developed and implemented. In addition, clinical services for reproductive health, including STD treatment and family planning, need to be made more "adolescent friendly". Some people with symptomless STDs may be detected and treated through partner notification, but this process is more likely to identify secondary "dead end" sexual contacts than source contacts, the group of greatest public-health importance.26Njeru EK Eldridge GD Ngugi EN Plummer FA Moses S STD partner notification and referral in primary level health centers in Nairobi, Kenya.Sex Transm Dis. 1995; 22: 231-235Crossref PubMed Scopus (24) Google Scholar Screening programmes that rely on laboratory tests are not usually available to those at risk in developing countries; even antenatal screening for syphilis, which is a simple, cheap, and highly cost-effective strategy for STD control is seldom practised.27Temmerman M Mohamedali F Fransen L Syphilis prevention in pregnancy: an opportunity to improve reproductive and child health in Kenya.Health Policy Planning. 1993; 8: 122-127Crossref Scopus (39) Google Scholar In certain populations with a high prevalence of symptomless STDs, the potential impact of targeted presumptive antibiotic treatment has been demonstrated. For example, in Nairobi, Kenya, pregnant women were treated with a single-dose oral antibiotic. This treatment resulted in decreases in rates of preterm birth, low-birthweight infants, and STDS.28Gichangi PB Ndinya-Achola JO Ombete J Nagelkerke NJ Temmerman M Antimicrobial prophylaxis in pregnancy: a randomised, placebo-controlled trial with cefetamet-pivoxil in pregnant women with a poor obstetric history.Am J Obstet Gynecol. 1997; 177: 680-684Summary Full Text Full Text PDF PubMed Scopus (29) Google Scholar A large randomised trial of repeated population-based rounds of mass STD treatment is being conducted in the Rakai district of Uganda to assess the likely impact of this intervention on HIV and STD incidence. Preliminary results have shown a substantial reduction of some STDs, although some of the pathogens or conditions quickly return to their pre-treatment levels (eg, bacterial vaginosis).29Wawer MJ Sewankambo NK Gray RH et al.Community-based trial of STD control for AIDS prevention; Rakai district, Uganda.in: Abstract S40. International Congress of Sexually Transmitted Diseases, Seville 1997 Oct 19–22Google Scholar It is questionable, however, whether such an approach could be sustained in the long term. The importance of properly conducted randomised controlled trials to measure the impact and cost-effectiveness of such innovative health interventions that could lead to strategic health policy decisions cannot be over-emphasised.24Hayes R Wawer M Gray R et al.Randomized trials of STD treatment for HIV prevention: report of an international workshop.Genitourin Med. 1997; 73: 432-443PubMed Google Scholar In this review we have highlighted the areas where advances have been made in recent years; there are many areas where more research and work are required. For example, STD control in both low-prevalence and high-prevalence areas would be greatly simplified with the development and distribution of low-cost, effective, and simple-to-use diagnostic tests for common STDs (such as gonorrhoea and chlamydial infection). These tests would not only be able to identify those symptomatic people with an STD, but could also be used in screening programmes for those with symptomless infection. Research should continue on the development of affordable and effective vaccines against STDs, although issues of delivery and coverage will remain a problem.30Barbosa-Cesnik CT Gerbase A Heymann D STD vaccines—an overview.Genitourin Med. 1997; 73: 336-342PubMed Google Scholar Somewhat surprisingly, towards the end of the second decade of the AIDS pandemic, we still have no good evidence that primary prevention works; there is a need for randomised controlled trials of primary prevention packages.31Oakley A Fullerton D Holland J et al.Sexual health education interventions for young people: a methodological review.BMJ. 1995; 310: 158-162Crossref PubMed Scopus (198) Google Scholar Perhaps the greatest advance in STD control in developing countries in recent years is the fact that these once neglected diseases are now high on the international health agenda. It is disappointing that in spite of the proven benefit and cost-effectiveness of simple STD-control measures, so few developing countries have implemented them widely. One of the most important but intractable questions on the research agenda must be: what are the barriers that prevent research findings being translated into policy at the country level, and how can they be overcome? One barrier is the relative absence of appropriate models of service provision upon which STD programmes can be grafted (for example, how to integrate comprehensive STD care into primary-healthcare systems which are often biased towards family planning and maternal/child health). A related constraint concerns the dearth of operational research which addresses questions of how to apply recent STD research findings in considerably more complex and disparate contexts around the world. In addressing such policy issues, STD researchers should be cognisant of the multitude of actors and agendas that contribute to the process of policy development and implementation; researchers are but one set of players in a well-populated field.32Walt G Health policy: an introduction to process and power.in: Zed Books, London1996: 178-201Google Scholar Recognition of how the policy process works locally and at national levels may help researchers to more easily and widely disseminate their findings and see them translated into appropriate action.