Why do we need quality-assured diagnostic tests for sexually transmitted infections?

Nature Reviews Microbiology

Volumn 4, Issue 12, 2006, Pages 909-921

  Peeling, Rosanna W ^a   Mabey, David ^b   Herring, Alan ^c   Hook III, Edward W ^d  

^a WORLD HEALTH ORGANIZATION   (Switzerland)

^b LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE   (United Kingdom)

^c UNIVERSITY OF BRISTOL   (United Kingdom)

^d University of Alabama at Birmingham   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC AGENT; AZITHROMYCIN; BENZATHINE PENICILLIN; CEFTRIAXONE; MACROLIDE; PENICILLIN DERIVATIVE; PENICILLIN G; QUINOLINE DERIVED ANTIINFECTIVE AGENT; TETRACYCLINE DERIVATIVE; CEPHALOSPORIN DERIVATIVE;

ANTIBIOTIC RESISTANCE; ANTIBIOTIC SENSITIVITY; BACTERIAL INFECTION; CHLAMYDIA TRACHOMATIS; CHLAMYDIASIS; CLINICAL PROTOCOL; DEVELOPING COUNTRY; DIAGNOSTIC TEST; GENE SEQUENCE; GENOME; GONORRHEA; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; NEISSERIA GONORRHOEAE; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; QUALITY CONTROL; REVIEW; SENSITIVITY AND SPECIFICITY; SEXUALLY TRANSMITTED DISEASE; SYMPTOM; SYPHILIS; TREPONEMA PALLIDUM; ARTICLE; BACTERIAL IMMUNITY; BACTERIUM CULTURE; COST EFFECTIVENESS ANALYSIS; DRUG EFFICACY; DRUG RESPONSE; DRUG TREATMENT FAILURE; HEALTH CARE ACCESS; HEALTH CARE COST; PREGNANCY; REAGIN TEST; SERODIAGNOSIS; SINGLE DRUG DOSE;

ANTI-BACTERIAL AGENTS; BACTERIAL INFECTIONS; BACTERIOLOGICAL TECHNIQUES; FEMALE; HIV INFECTIONS; HUMANS; INFANT; INFANT, NEWBORN; MALE; PREGNANCY; PREGNANCY COMPLICATIONS, INFECTIOUS; QUALITY CONTROL; SEXUALLY TRANSMITTED DISEASES, BACTERIAL; CHLAMYDIA INFECTIONS; DEVELOPING COUNTRIES; DIAGNOSTIC TESTS, ROUTINE; GONORRHEA; POINT-OF-CARE SYSTEMS; SYPHILIS;

BACTERIA (MICROORGANISMS); CHLAMYDIA;

EID: 33751095619     PISSN: 17401526     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrmicro1555     Document Type: Review

References (124)

1. WHO. Global Prevalence and Incidence of Selected Curable Sexually Transmitted Infections: Overview and Estimates [online], (WHO, Geneva, 2001).
2. Schmid, G. Economic and programmatic aspect of congenital syphilis prevention. Bull. World Health Organ. 82, 402-409 (2004).
3. Schulz, K. F., Cates, W. & O'Mara, P. R. Pregnancy loss, infant death, and suffering: The legacy of syphilis and gonorrhoea in Africa. Genitourin. Med. 63, 320-325 (1987).
4. Gerbase, A. C., Rowley, J. T. & Mertens, T. E. Global epidemiology of sexually transmitted diseases. Lancet 351, (Suppl. 3), 2-4 (1998).
5. Fleming, D. T. & Wasserheit, J. N. From epidemiological synergy to public health policy and practice: The contribution of other sexually transmitted diseases to the sexual transmission of HIV infection. Sex. Transm. Infect. 75, 3-17 (1999).
6. Cohen, M. S. et al. Reduction of concentration of HIV-1 in semen after treatment of urethritis: Implications for prevention of sexual transmission of HIV-1. Lancet 349, 1868-1873 (1997).
7. Freeman, E. E. Herpes simplex virus 2 infection increases HIV acquisition in men and women: Systematic review and meta analysis of longitudinal studies. AIDS 20, 73-83 (2006).
8. Buchacz, K. et al. Syphilis increases HIV viral load and decreases CD4 cell counts in HIV-infected patients with new syphilis infections. AIDS 18, 2075-2079 (2004).
9. Hayes, R. J. & White, R. G. Amplified HIV transmission during early stage infection. J. Infect. Dis. 193, 604-605 (2006).
10. Musher, D. M. in Sexually Transmitted Diseases, 3rd edn, (eds Holmes, K. K. et al.) 479-485 (McGraw-Hill, Newyork, 1999).
11. Singh, A. E. & Romanowski, B. Syphilis: Review with emphasis on clinical, epidemiologic, and some biologic features. Clin. Microbiol. Rev. 12, 187-209 (1999).
12. Swartz, M. N., Musher, D. M. & Healy, B. P. in Sexually Transmitted Diseases, 3rd edn, (eds Holmes, K. K. et al.) 487-509 (McGraw-Hill, New York, 1999).
13. Romanowski, B., Sutherland, R., Fick, G. H., Mooney, D., Love, E. J. Serologic response to treatment of infectious syphilis. Ann. Intern. Med. 114, 1005-1009 (1991).
14. Radolf, J. D., Sanchez, P. J., Schulz, K. F. & Murphy, F. K. in Sexually Transmitted Diseases, 3rd edn, (eds Holmes, K. K. et al.) 1165-1189 (McGraw-Hill, New York, 1999).
15. Berman, S. M. Maternal syphilis: Pathophysiology and treatment. Bull. World Health Organ. 82, 433-438 (2004).
16. Genç, M. & Ledger, W. J. Syphilis in pregnancy. Sex. Transm. Infect. 76, 73-79 (2000).
17. Michelow, I. C. et al. Central nervous system infection in congenital syphilis. N. Engl. J. Med. 346, 1792-1798 (2002).
18. Sheffield, J. S. et al. Placental histopathology of congenital syphilis. Obstet. Gynecol. 100, 126-133 (2002).
19. Watson-Jones, D. et al. Syphilis in pregnancy in Tanzania. I. Impact of maternal syphilis on outcome of pregnancy. J. Infect. Dis. 186, 940-947 (2002).
20. Fiumara, N. J., Fleming, W. L., Downing, J. G. & Good, F. The incidence of prenatal syphilis at the Boston City Hospital. N. Engl. J. Med. 245, 634-640 (1951).
21. Hollier, L. M., Harstad, T. W., Sanchez, P. J., Twickler, D. M. & Wendel, G. D. Fetal syphilis: Clinical and laboratory characteristics. Obstet. Gynecol. 97, 947-953 (2001).
22. Sanchez, P. J. et al. Evaluation of molecular methodologies and rabbit infectivity testing for the diagnosis of congenital syphilis and neonatal central nervous system invasion by Treponema pallidum. J. Infect. Dis. 167, 148-157 (1993).
23. Riedner, G. et al. Single dose azithromycin versus penicillin G benzathine for the treatment of early syphilis. N. Engl. J. Med. 353, 1236-1244 (2005).
24. Watson-Jones, D. et al. Syphilis in pregnancy in Tanzania. II. The effectiveness of antenatal syphilis screening and single-dose benzathine penicillin treatment for the prevention of adverse pregnancy outcomes. J. Infect. Dis. 186, 948-957 (2002).
25. Sheffield, J. S. et al. Congenital syphilis after maternal treatment for syphilis during pregnancy. Am. J. Obstet. Gynecol. 186, 569-573 (2002).
26. Golden, M. R., Marra, C. M. & Holmes, K. K. Update on syphilis: resurgence of an old problem. JAMA 290, 1510-1514 (2003).
27. Rolfs, R. T et al. A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. The Syphilis and HIV Study Group. N. Engl. J. Med. 337, 307-314 (1997).
28. Tanaka, M. et al. Analysis of mutations within multiple genes associated with resistance in a clinical isolate of Neisseria gonorrhoeae with reduced ceftriaxone susceptibility that shows a multidrug-resistant phenotype. Int. J. Antimicrob. Agents 27, 20-26 (2006).
29. Alary, M. et al. Evaluation of clinical algorithms for the diagnosis of gonococcal and chlamydial infections among men with urethral discharge or dysuria and women with vaginal discharge in Benin. Sex. Transm. Infect. 74 (Suppl. 1), 44-49 (1998).
30. Djajakusumah, T., Sudigdoadi, S., Keersmaekers, K. & Meheus, A. Evaluation of syndromic patient management algorithm for urethral discharge. Sex. Transm. Infect. 74 (Suppl. 1), 29-33 (1998).
31. Mayaud, P. et al. Validation of a WHO algorithm with risk assessment for the clinical management of vaginal discharge in Mwanza, Tanzania. Sex. Transm. Infect. 74 (Suppl. 1), 77-84 (1998).
32. Mukenge, L. et al. Syndromic versus laboratory-based diagnosis of cervical infections among female sex workers in Benin: Implications of non-attendance for return visits. Sex. Transm. Dis. 29, 324-330 (2002).
33. Hawkes, S. et al. Reproductive-tract infections in women in low-income, low-prevalence situations: Assessment of syndromic management in Matlab, Bangladesh. Lancet 354, 1776-1781 (1999).
34. Vickerman, P., Watts, C. H., Alary, M., Mabey, D. & Peeling, R. Sensitivity requirements for the point of care diagnosis of Chlamydia trachomatis and Neiserria gonorrhoeae in women. Sex. Transm. Infect. 79, 363-368 (2003).
35. Tapsall, J. Antibiotic resistance in Neisseria gonorrhoeae. Clin. Infect. Dis. 41 (Suppl. 4), 263-268 (2005).
36. Garcia-Moreno, C. & Watts, C. H. Violence against women: Its importance for HIV/AIDS. AIDS 14 (Suppl. 3), 253-265 (2000).
37. Peeling, R. W. & Ye, H. Diagnostic tools for preventing and managing maternal and congenital syphilis: An overview. Bull. World Health Organ. 82, 439-446 (2004).
38. von Wassermann, A. P., Neisser, A. & Bruck, C. Eine serodiagnostische Reaktion bei Syphilis. Deutsche medicinische Wochenschrift, Berlin 32, 745-746 (1906).
39. Young, H., Aktas, G. & Moves, A. Enzywell recombinant enzyme immunoassay for the serological diagnosis of syphilis. Int. J. STD AIDS 11, 288-291 (2000).
40. WHO/TDR. Laboratory-Based Evaluation of Rapid Syphilis Diagnostics. Sexually Transmitted Diseases Diagnostics Initiative (SDI) Report: Diagnostics Evaluations Series No. 1 [online], (WHO/TDR, Geneva, 2003).
41. Young, H., Moves, A., de Ste Croix, I. & McMillan, A. A new recombinant antigen latex agglutination test (Syphilis Fast) for the rapid serological diagnosis of syphilis. Int. J. STD AIDS 9, 196-200 (1998).
42. Fears, M. B. & Pope, V. Syphilis fast latex agglutination test, a rapid confirmatory test. Clin. Diagn. Lab. Immunol. 8, 841-842 (2001).
43. Zarakolu, P. et al. Preliminary evaluation of an immunochromatographic strip test for specific Treponema pallidum antibodies. J. Clin. Microbiol. 40, 3064-3065 (2002).
44. West, B., Walraven, G., Morison, L., Brouwers, J. & Bailey, R. Performance of the rapid plasma reagin and the rapid syphilis screening tests in the diagnosis of syphilis in field conditions in rural Africa. Sex. Transm. Infect. 78, 282-285 (2002).
45. Sato, N. S. et al. Assessment of the rapid test based on an immunochromatography technique for detecting anti-Treponema pallidum antibodies Rev. Inst. Med. Trop. Sao Paulo 45, 319-322 (2003).
46. Diaz, T. et al. Evaluation of the Determine Rapid Syphilis TP assay using sera. Clin. Diagn. Lab. Immunol. 11, 98-101 (2004).
47. Siedner, M., Zapitz, V, Ishicla, M., De La, R. R. & Klausner, J. D. Performance of rapid syphilis tests in venous and fingerstick whole blood specimens. Sex. Transm. Dis. 31, 557-560 (2004).
48. Montoya, P. J. et al. Comparison of the diagnostic accuracy of a rapid immunochromatographic test and the rapid plasma reagin test for antenatal syphilis screening in Mozambique. Bull. World Health Organ. 84, 97-104 (2006).
49. Mabey, D. et al. Prospective, multi-centre clinic-based evaluation of four rapid diagnostic tests for syphilis. Sex. Transm. Infect. (in the press).
50. Vickerman, P. et al. Modelling the cost-effectiveness of introducing rapid syphilis tests into an antenatal syphilis screening programme in Mwanza, Tanzania. Sex. Transm. Infect. (in the press).
51. Koumans, E. H., Johnson, R. E., Knapp, J. S. & St Louis, M. E. Laboratory testing for Neisseria gonorrhoeae in men and women introduced non-culture tests: A performance review with clinical and public health considerations. Clin. Infect. Dis. 27, 1171-1180 (1998).
52. Manavi, K., Young, H. & Clutterbuck, D. Sensitivity of microscopy for the rapid diagnosis of gonorrhoea in men and women and the role of gonorrhoeae serovars. Int. J. STO AIDS 14, 390-394 (2003).
53. Van Dyck, E., Leven, M., Pattyn, S., Van Damme, L. & Laga, M. Detection of Chlamydia trachomatis and Neisseria gonorrhoeae by enzyme immunoassay, culture and three nucleic acid amplified tests. J. Clin. Microbiol. 39, 1751-1756 (2001).
54. Boyadzhyan, B., Yashida, B., Yatabe, H., Patnaik, M. & Hill, C. S. Comparison of the APTIMA CT and GC assays with the APTIMA COMBO 2 assay, the Abbott LCx assay, and Direct Fluorescent-Antibody and culture assays for detection of Chlamydia trachomatis and Neisseria gonorrhoeae. J. Clin. Microbiol. 42, 3089-3093 (2004).
55. Darwin, L. H. et al. Comparison of Digene hybrid capture 2 and conventional culture for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in cervical specimens. J. Clin. Microbiol. 40, 641-644 (2002).
56. Van Dyck, E., Smet, H., Van Damme, L. & Laga, M. Evaluation of the Roche Neisseria gonorrhoeae 16 S rRNA PCR for confirmation of AMPLICOR PCR-positive samples and comparison of its diagnostic performance according to storage conditions and preparation of endocervical specimens. J. Clin. Microbiol. 39, 2280-2282 (2001).
57. Martin, D., Cammarata, C. & Van Der pol, B. Multicenter evaluation of AMPLICOR and automated COBAS AMPLICOR CT/NG tests for Neisseria gonorrhoeae. J. Clin. Microbiol. 38, 3544-3549 (2000).
58. Moncada, J. et al. The effect of urine testing in evaluations of the sensitivity of the Gen-Probe APTIMA® Combo 2 assay on endocervical swabs for Chlamydia trachomatis and Neisseria gonorrhoeae. The infected patient standard reduces sensitivity of single site evaluation. Sex. Transm. Dis. 31, 273-277 (2004).
59. Martin, D. H. et al. Use of multiple nucleic acid amplification tests to define the infected-patient "gold standard" in clinical trials of new diagnostic tests for Chlamydia trachomatis infections. J. Clin. Microbiol. 42, 4749-4758 (2004).
60. Gaydos, C. A. et al. Performance of the APTIMA Combo 2 assay for the multiplex detection of Chlamydia trachomatis and Neisseria gonorrheae in female urine and endocervical swab specimens. J. Clin. Microbiol. 41, 304-309 (2003).
61. Black, C. M. Current methods of laboratory diagnosis of Chlamydia trachomatis infections. Clin. Microbiol. Rev. 10, 160-184 (1997).
62. Palmer, H. M., Mallinson, H., Wood, R. & Herring, A. J. Evaluation of the specificities of five DNA amplification methods for the detection of Neisseria gonorrhoeae. J. Clin. Microbiol. 41, 835-837 (2003).
63. Diermert, D. J., Libman, M. D. & Lebel, P. Confirmation by 16S r RNA PCR of the COBAS AMPLICOR CT/NG test for diagnosis of Neisseria gonorrhoeae infection in a low-prevalence population. J. Clin. Microbiol. 40, 4056-4059 (2002).
64. Benzaken, A. S. The diagnosis of gonococcal infection in high risk women using a rapid test. Sex. Transm. Infect. (in the press).
65. Yin, Y. P. et al. Clinic-based evaluation of Clearview Chlamydia MF for detection of Chlamydia trachomatis in vaginal and cervical specimens from women at high-risk in China. Sex. Transm. Infect. (in the press).
66. Petti, C. A., Polage, C. R., Quinn, T. C., Ronald, A. R. & Sande, M. A. Laboratory medicine in Africa: A barrier to effective health care. Clin. Infect. Dis. 42, 377-82 (2006).
67. Cliff, M., Mayaud, P., Brugha, R. & Semakafu, A. M. Integrating reproductive health services in a reforming health sector: The case of Tanzania. Repro. Health Matters 11, 37-48 (2003).
68. World Bank. World Development Report 2004: Making Services work for Poor People [online], (The World Bank, New York)
69. Vickerman, P., Watts, C., Peeling, R. W., Mabey, D. & Alary, M. Modeling the cost-effectiveness of rapid point-of-care diagnostic tests for the control of HIV and other sexually transmitted infections amongst female sex workers in Cotonou, Benin. Sex. Transm. Infect. (in the press).
70. Gift, T. L., Pate, M. S., Hook, E. W. 3rd, Kassler, W. J. The rapid test paradox: When fewer cases detected lead to more Aases treated: a decision analysis of tests for Chlamydia trachomatis. Sex. Transm. Dis. 26, 232-240 (1999).
71. Mukenge, L. et al. Syndromic versus laboratory-based diagnosis of cervical infections among female sex workers in Benin: Implications of non-attendance for return visits. Sex. Transm. Dis. 29, 324-330 (2002).
72. Connor, N., Roberts, J. & Nicoll, A. Strategic option for antenatal screening for syphilis in the United Kingdom: A cost effectiveness analysis. J. Med. Screen. 7, 7-13 (2000).
73. Terris Prestholt, F. et al. Is antenatal syphilis screening still cost effective in sub-Saharan Africa. Sex. Transm. Infect. 79, 375-381 (2003).
74. Rotchford, K., Lombard, C., Zuma, K. & Wilkinson, D. Impact on perinatal mortality of missed opportunities to treat maternal syphilis in rural South Africa: Baseline results from a clinic randomized controlled trial. Trop. Med. Int. Health 5, 800-804 (2000).
75. Dorigo-Zetsma, J. W. Performance of routine syphilis serology in the Ethiopian cohort on HIV/AIDS. Sex. Transm. Infect. 80, 96-99 (2004).
76. Temmerman, M., Mohamedali, F. & Fransen, L. Syphilis prevention in pregnancy: An opportunity to improve reproductive and child health in Kenya. Health Policy Plan. 8, 122-127 (1993).
77. Gloyd, S., Chai, S. & Mercer, M. A. Antenatal syphilis in sub-Saharan Africa: Missed opportunities for mortality reduction. Health Policy Plan. 16, 29-34 (2001).
78. Vickerman, P., Peeling, R. W., Watts, C. & Mabey, D. Detection of gonococcal infection: Pros and cons of a rapid test. Mol. Diagn. 9, 175-179 (2005).
79. Michel, C. E. C. et al. A rapid point-of-care assay to target antibiotic treatment for trachoma elimination. Lancet 367, 1585 (2006).
80. Radolf, J. D., Norgard, M. V. & Schulz, W. W. Outer membrane ultrastructure explains the limited antigenicity of virulent Treponema pallidum. Proc. Natl Acad. Sci. USA 86, 2051-2055 (1989).
81. Cox, D. L., Chang, P., McDowell, A. & Radolf, J. D. The outer membrane, not a coat of host proteins, limits the antigenicity of virulent. Treponema pallidum. Infect. Immun. 60, 1076-1083 (1992).
82. Salazar, J. C., Hazlett, K. R. & Radolf, J. D. The immune response to infection with Treponema pallidum, the stealth pathogen. Microbes Infect. 4, 1133-1140 (2002)
83. Stamm, L. V. in Sexually Transmitted Diseases, 3rd edn, (eds Holmes, K. K. et al.) 467-472 (McGraw-Hill, New York, 1999).
84. Fraser, C. M. et al. Complete genome sequence of Treponema pallidum, the syphilis spirochete. Science 281, 375-381 (1998).
85. Blanco, D. R., Miller, J. N. & Lovett, M. A. Surface antigens of the syphilis spirochete and their potential as virulence determinants. Emery. Infect. Dis. 3, 11-20 (1997).
86. Centurion-Lara, A. et al. Treponema pallidum major sheath protein homologue Tpr K is a target of opsonic antibody and the protective immune response. J. Exp. Med. 189, 647-656 (1999).
87. Morgan, C. A., Lukehart, S. A. & Van Voorhis, W. C. Protection against syphilis correlates with specificity of antibodies to the variable regions of Treponema pallidum repeat protein K. Infect. Immun. 71, 5605-5612 (2003).
88. Leader, B. T. Antibody responses elicited against the Treponema pallidum repeat proteins differ during infection with different isolates of Treponema pallidum subsp. pallidum. Infect. Immun. 71, 6054-6057 (2003).
89. Centurion-Lara, A. et al. Gene conversion: A mechanism for generation of heterogeneity in the tprK gene of Treponema pallidum during infection. Mol. Microbiol. 52, 1579-1596 (2004).
90. Podwinska, J., Lusiak, M., Zaba, R. & Bowszyc, J. The pattern and level of cytokines secreted by Th1 and Th2 lymphocytes of syphilitic patients correlate to the progression of the disease. FEMS Immunol. Med. Microbiol. 28, 1-14 (2000).
91. Van Voorhis, W. C. et al. Primary and secondary syphilis lesions contain mRNA for Th1 cytokines. J. Infect. Dis. 173, 491-495 (1996).
92. Fan, Y. M., Zeng, W. J., Wu, Z. H. & Li, S. F. Immunophenotypes, apoptosis, and expression of Fas and Bcl-2 from peripheral blood lymphocytes in patients with secondary early syphilis. Sex. Transm. Dis. 31, 221-224 (2004).
93. Wicher, V. & Wicher, K. Pathogensis of maternal-fetal syphilis revisited. Clin. Infect. Dis. 33, 354-363 (2001).
94. Stephens, R. S. et al. Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 282, 754-759 (1998).
95. Zhong, G., Fan, P., Ji, H., Dong, F. & Huang, Y. Identification of a chlamydial protease-like activity factor responsible for the degradation of host transcription factors. J. Exp. Med. 193, 935-942 (2001).
96. Wehrl, W., Brinkmann, V., Jungblut, P. R., Meyer, T. F. & Szczepek, A. J. From the inside out - processing of the chlamydial autotransporter PmpD and its role in bacterial adhesion and activation of human host cells. Mol. Microbiol. 51, 319-334 (2004).
97. Crane, D. D. et al. Chlamydia trachomatis polymorphic membrane protein D is a species-common pan-neutralizing antigen. Proc. Natl Acad. Sci. USA 103, 1894-1899 (2006).
98. Carlson, J. H., Porcella, S. F., McClarty, G. & Caldwell, H. D. Comparative genomic analysis of Chlamydia trachomatis oculotropic and genitotropic strains. Infect. Immun. 73, 6407-6418 (2005).
99. Caldwell, H. D. et al. Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiates between genital and ocular Isolates. Implications in pathogenesis and infection tropism. J. Clin. Invest. 111, 1757-1769 (2003).
100. Belland, R. J. et al. Chlamydia trachomatis cytotoxicity associated with complete and partial cytotoxin genes. Proc. Natl Acad. Sci. USA 24, 13984-13989 (2001).
101. Bailey, R., Duong, T., Carpenter, B., Whittle, H. & Mabey, D. The duration of human ocular chlamydial infection is age dependent. Epidemiol. Infect. 123, 479-486 (1999).
102. Wang, S. P., Grayston, J. T. & Alexander, E. R. Trachoma vaccine studies in monkeys. Am. J. Ophthalmol. 63, 1615-1620 (1967).
103. Peeling, R. W. & Mabey, D. C. W. Heat shock protein expression and immunity in chlamydial infections. Infect. Dis. Obstet. Gynecol. 7, 72-79 (1999).
104. Peeling, R. W. et al. Antibody response to the 60-kDa chlamydial heat-shock protein is associated with scarring trachoma. J. Infect. Dis, 177, 256-259 (1998).
105. Beatty, W., Morrison, R. P. & Byrne, G. I. Persistent chlamydiae: From cell culture to a paradigm for chlamydial pathogenesis. Microbiol. Rev. 58, 686-699 (1994).
106. Bailey, R. L., Holland, M. J., Whittle, H. C. & Mabey, D. C. W. Subjects recovering from human ocular chlamydial infection have enhanced lymphoproliferative responses to chlamydial antigens compared to persistently diseased controls. Infect. Immun. 63, 389-392 (1995).
107. Faal, H. et al. Conjunctival FOXP3 expression in trachoma: Evidence for T regulatory activity in human Chlamydia trachomatis infection? PloS Medicine 3, e266 (2006).
108. Burton, M. J., Bailey, R. L., Jeffries, D., Mabey, D. C. W. & Holland, M. J. Cytokine and fibrogenic gene expression in the conjunctiva of subjects from a trachoma endemic Gambian community. Infect. Immun. 72, 7352-7356 (2004).
109. Conway, D. J. et al. Scarring trachoma is associated with polymorphism in the tumour necrosis factor alpha (TNF-α) gene promoter and with elevated TNF-α in tear fluid. Infect. Immun. 1003-1006 (1997).
110. Natividad-Sancho, A., Bailey, R., Holland, M., Kwiatkowski, D. & Mabey, D. Susceptibility to trachomatous scarring and trichiasis in Gambians varies with SNP haplotypes at the interferon-gamma and interleukin-10 loci. Genes Immun. 6, 332-340 (2005).
111. Simons, M. P., Nauseef, W. M. & Apicella, M. A. Interactions of Neisseria gonorrhoeare with adherent polymorphonuclear leukocytes. Infect. Immun. 73, 1971-1977 (2005).
112. Edwards, J. L. & Apicella, M. A. The role of lipooligosaccharide in Neisseria gonorrhoeae pathogenesis of cervical epithelia: Lipid A serves as a C3 acceptor molecule. Cell. Microbiol. 4, 585-598 (2002).
113. Edwards, J. L. & Apicella, M. A. The molecular mechanisms used by Neisseria gonorrhoeae to initiate infection differ between men and women. Clin. Micro. Rev. 17, 965-981 (2004).
114. Cohen, M. S. et al. Human experimentation with Neisseria gonorrhoeae: rationale, methods and implications for the biology of infection and vaccine development. J. Infect. Dis. 169, 532-537 (1994).
115. McGee, Z. A. et al. Pathogenic mechanisms for Neisseria gonorrhoeae: observations on damage to human fallopian tubes in organ culture by gonococci of colony type 1 or type 4. J. Infect. Dis. 143, 413-422 (1981).
116. Virji, M. et al. The role of common and type-specific antigenic domains in adhesion and virulence of gonococci for human epithelial cells. J. Gen. Microbiol. 130, 1089-1095 (1984).
117. Bessen, D. et al. Interactions of gonococci with HeLa cells: Attachment, detachment, replication, penetration and the role of protein II. Infect. Immun. 54, 154-160 (1986).
118. Virji, M. et al. Role of anti-pilus antibody in host defense against gonococcal infection studied with monoclonal anti-pilus antibodies. Infect. Immun. 49, 621-628 (1985).
119. Boslego, J. et al. Efficacy trial of a parenteral gonococcal pilus vaccine in men. Vaccine 3, 154-162 (1991).
120. Koomey, M. et al. Effects of recA mutations on pilus antigenic variation and phase transition in Neisseria gonorrhoeae. Genetics 17, 391-398 (1987).
121. Connell, T. D. et al. Recombination among protein II genes of Neisseria gonorrhoeae generates new coding sequences and increases structural variability in the protein II family. Mol. Microbiol. 2, 227-236 (1988).
122. Pohlner, J. et al. Genome structure and extracellular secretion of Neisseria gonorrhoecre IgA protease. Nature 325, 458-462 (1987).
123. Alary, M. et al. Evaluation of a rapid point-of-care test for the detection of gonococcal infection among female sex workers in Benin. Sex. Transm. Infect. (in the press).
124. Black, C. M. et al. Head-to-head multicenter comparison of DNA probe and nucleic acid amplification tests for Chlamydia trachomatis infection in women performed with an improved reference standard. J. Clin. Microbiol. 40, 3757-3763 (2002).