LIU, HONGJIE PhD, MS*; JAMISON, DEAN PhD†; LI, XIAOJING MD‡; MA, ERJIAN MD‡; YIN, YUEPING PhD§; DETELS, ROGER MD, MS*
*School of Public Health, University of California, Los Angeles; †Fogarty International Center, National Institutes of Health, Bethesda, Maryland, and University of California, Los Angeles; ‡Hefei Anti-Epidemic Station, Anhui, China; and §National Center for STD and Leprosy Control, Nanjing, China
Supported by a grant (1TW00013) from the National Institutes of Health/Fogarty International Center.
The authors thank Drs. Barbara Visscher and Susan Cochran for their assistance and advice in conducting the study, Dr. Lilani Kumaranayake for reviewing the manuscript, and Ms. Jean Savage for preparation of the manuscript.
Dr. Liu is currently at the Department of Community and Family Medicine, School of Medicine, the Chinese University of Hong Kong, China.
Reprint requests: Roger Detels, MD, MS, University of California, Los Angeles, Department of Epidemiology, Box 951772, Los Angeles, CA 90095-1772. E-mail: email@example.com
Received June 27, 2002,
revised August 26, 2002, and accepted September 23, 2002.
RECENTLY, THE INCIDENCE OF sexually transmitted diseases (STDs), including AIDS, has soared in China. 1 Effective programs that provide accurate diagnosis and effective treatment are essential but are rare in China. Studies have indicated that there are obstacles to effective STD management, including lack of laboratory facilities, qualified staff, and financial resources. 2,3 Thus, affordable, effective approaches to manage STDs need to be developed. The World Health Organization (WHO) developed and advocates syndromic management to manage STDs. 4,5 This approach facilitates rapid diagnosis and treatment without requiring sophisticated, time-consuming laboratory tests or advanced medical skills. Although studies in several countries have demonstrated that syndromic management is effective, 6,7 the approach has yet to be evaluated in STD clinics in local settings in China. We first evaluated the validity of syndromic management to treat patients with urethral discharge, dysuria, or genital ulcers and then assessed its cost-effectiveness in comparison with the approach currently used in STD clinics.
The study site and population have been described previously. 8 STD physicians made a presumptive diagnosis based on the physical examination findings and requested that the men provide a specimen for testing for causative agents. The physician's final diagnosis was based on experience as well as the results of the local clinic laboratory tests. Drugs were prescribed according to the physician's judgment.
With use of the WHO syndromic algorithms, men were classified as having either urethral discharge or genital ulcers. For the final analysis, the WHO algorithm was modified to include all men who reported urethral discharge or dysuria.
Laboratories in different STD clinics used different methods. The procedures in each laboratory were performed as usual. 3
The Gold Standard
An aliquot of each specimen was transported to the Chinese National Center for STD Control and Prevention, in Nanjing, for testing. These tests were done without knowledge of the results of the tests performed in the local STD clinic or of the physician's diagnosis. The procedures have been described previously. 8
Cost and Effectiveness Analysis
Only the direct costs incurred by private consumers were included (UNAIDS costing guidelines for HIV prevention strategies). The costs of the current approach included the amount paid for laboratory tests, physical examination (check-up) by physicians, and drugs. Costs were obtained directly from patients’ payment records. The costs of syndromic management included expenses for physical examination, drugs, materials for health education, and condoms.
Correctly treated men were defined as those whose conditions were correctly diagnosed and who were given appropriate drugs. Men who were free of Neisseria gonorrhoeae, Chlamydia trachomatis, or Treponema pallidum infection but had these mistakenly diagnosed and were treated for the infection were classified as overdiagnosed and overtreated. If men with N gonorrhoeae, C trachomatis, or T pallidum infection were mistakenly treated for another infection with drugs not active against the actual infection, they were classified as incorrectly diagnosed and treated. The cost, however, was considered in the cost analysis.
All data were analyzed with SAS software (version 8.01; SAS Institute, Cary, NC). Results from the STD clinics and the national center were compared, with use of the testing results from the national center as the gold standard. The sensitivity, specificity, and positive predictive values (PPVs) of syndromic management were calculated.
Four-hundred seventeen eligible men were invited to participate, but 11 (3%) refused. Thus, 406 men (97%) reporting genitourinary symptoms were interviewed. Three-hundred fifty men (86%) had urethral discharge or dysuria symptoms, and 55 men (14%) had genital ulcers. One man (0.3%) had both urethral discharge and a genital ulcer.
Validity Analysis of Syndromic Management
Validity analysis was performed among 347 men with urethral discharge or dysuria. Of the 290 men with urethral discharge, 227 were positive for N gonorrhoeae and/or C trachomatis. Of 57 men with only dysuria, 13 were positive for one of the two causative agents (Fig. 1). According to the WHO syndromic algorithm, 227 men would have been correctly treated, yielding 95% sensitivity (227/240) and 78% PPV (227/290). Thirteen men with dysuria would not have been treated. Including these 13 men would have increased the sensitivity to 100%, with 69% PPV (Table 1). One-hundred seven men would be overtreated. Thus, we modified the WHO algorithm to include men with dysuria as well in the analyses.
Among 55 men with genital sores or ulcers, 53 had confirmed genital ulcers. Among men with confirmed genital ulcers, 13 were positive for syphilis and 15 were positive for HSV; none of the men without ulcers were positive. None had chancroid. If syndromic management were used, all syphilis patients would have been correctly treated, yielding 100% sensitivity and 25% PPV, but 40 patients would have been overtreated (Fig. 2, Table 1).
Among 347 men with urethral discharge or dysuria, 121 (35%) were correctly treated for gonorrhea and/or chlamydia, 119 (34%) with gonorrhea and/or chlamydia were incorrectly treated, and 107 (31%) without N gonorrhoeae or C trachomatis infection were overtreated. If syndromic management had been used, all 240 men with N gonorrhoeae and/or C trachomatis infection would have been correctly treated, and 107 (31%) patients would have been overtreated. The number of patients (107) overtreated by syndromic management would have been the same as with the current approach.
Among 53 men with ulcers, the current approach correctly treated 12 (23%) with syphilis, overtreated 10 (19%) without syphilis, and incorrectly treated 1 (2%). If syndromic management had been used, all 13 syphilis patients would have been correctly treated, but 40 (75%) patients without syphilis would have been overtreated.
With the current approach, 49% of men with N gonorrhoeae infection (77/158), 25% (7/28) with C trachomatis infection, and 65% (35/54) with both infections were incorrectly treated. With syndromic management, all men would have been correctly treated.
Men underwent a variety of drug treatment regimens and laboratory tests; thus, the costs for treatment differed. The median cost per correctly treated man was $84.27 for gonorrhea, $158.30 for chlamydia, and $177.42 for mixed infections (Table 2). The average cost per correct treatment for urethritis was $323.48 (Table 3). According to the WHO protocol, two drugs are to be used that are effective for both gonorrhea and chlamydia. 9 Ciprofloxacin (500 mg in a single oral dose) is prescribed to treat gonococcal urethritis, and doxycycline (100 mg orally twice daily for 7 days) is used to treat chlamydial urethritis. The cost of the two drugs per patient is $0.79. The fee for a physical examination is $0.60. Syndromic management also requires health education and condom provision. Therefore, $0.79 per patient should be added to cover health education materials ($0.17) and 10 condoms ($0.62), a total of $2.18 per correctly treated patient. The average cost per correctly treated patients with urethritis would be $3.15.
With the current approach, the median cost per correctly treated patient with a genital ulcer was $27.20; the cost was $112 per incorrectly treated patient and $59 per overtreated patient. The average cost per correctly treated syphilis patient was $85.65. For the treatment of syphilis by syndromic management, the WHO recommends benzathine penicillin G (2.4 million units intramuscularly). The cost is $1.93, plus $0.60 for a physical examination and $0.79 for educational material and condoms. The total cost is $3.32, whether the patient receives correct treatment or overtreatment. The average cost per correct treatment for all patients with genital ulcers by syndromic management would be $13.54.
This study indicated that modified syndromic management would have high validity and cost-effectiveness in the treatment of men with STDs and could be easily implemented in China. The urethral discharge algorithm proposed by the WHO, however, would need to be expanded to include dysuria. The inclusion of dysuria was also suggested by another study. 10 A significant advantage of using modified syndromic management is its ability to effectively treat all patients with the mixed N gonorrhoeae and C trachomatis infections; only 35% of the patients were correctly treated by the current approach. The inaccuracy in diagnosis of mixed infections may have been due to the physicians’ inability to make a correct diagnosis or an inaccurate laboratory test. The WHO algorithm for treating patients with genital ulcers would result in effective treatment of all syphilis patients. A proportion of nonsyphilis patients, however, would be overtreated. Because chancroid is rare in China, 11 the treatment for genital ulcer diseases at present may not cover chancroid. An antiviral therapy for herpes is not available in most primary healthcare settings; thus, it is important to treat for syphilis, even if some of the genital ulcers treated are actually caused by herpes. 12 All patients should receive health education.
Overdiagnosis and overtreatment are the major disadvantages of syndromic management, influencing health authorities against the approach. Our study indicated that problems of overtreatment and incorrect treatment with use of modified syndromic management were even less than with the current approach because of the low level of accuracy with the latter. However, the number of overtreated or incorrectly treated patients with genital ulcers was greater with syndromic management than with the current approach. Because the current approach also used RPR and TPHA to diagnosis syphilis, the syndromic and current approaches have almost the same ability to diagnose syphilis. However, laboratory test results usually cannot be obtained immediately, and as a result, patients have to return for treatment 1 or 2 days later. Some patients may not return.
Another major concern of syndromic management of STDs is the cost of drugs from overtreatment and the use of multiple antibiotic drugs. The high cost may cause underutilization of services by patients. 13 The cost per correct treatment by the current approach, with both incorrect treatment and overtreatment considered, was much higher than for syndromic management. The expense with the current approach is associated with the use of multiple intramuscular and intravenous drugs and overdosage of drugs.
The results have important public health implications. First, the results should allay fears that syndromic management results in more overtreatment and higher costs. Second, many STD patients may go to pharmacies and buy drugs directly. Syndromic management does not require a physician's diagnosis and may be used by pharmacists, thereby further reducing costs. Last, use of the modified syndromic management approach can be implemented easily by primary healthcare resources without highly trained staff or laboratories.
In conclusion, use of modified syndromic management for men with urethral discharge and ulcers is a simple, cost-effective approach in resource-poor countries. Overtreatment is no greater problem than with the current approach. Health authorities should consider implementing the approach in China, especially at the primary healthcare level.
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