Abstract
The “silent epidemic” of Chlamydia trachomatis threatens to cause reproductive damage and infertility in many of the 50 million women who acquire it each year. Female reproductive tract infection has more recently been linked to stillbirth and premature delivery. Innate immune cells and mediators appear to be the primary players in pathogenesis, with neutrophils playing a prominent role in disease development. Although adaptive antibody and CD4 T cell responses appear primarily protective, these responses are inefficient. Infections are frequently chronic as a result, and when infection is diagnosed and treated with appropriate antibiotics, repeated infection is the rule. The lack of acute symptoms in many infected individuals contributes to the high prevalence of chlamydial infection. Although chronic sequelae are relatively rare in men, and many women sustain infection without developing pelvic inflammatory disease or chronic sequelae, the extremely high prevalence of chlamydial infection leads to significant morbidity and healthcare costs. A vaccine is urgently needed to prevent infection, but given the difficulties of inducing a CD4 T cell memory response that can home quickly to the genital tract, induction of sterilizing immunity may not be possible. A vaccine that prevents disease by lowering bacterial burden and dampening production of tissue-damaging responses may be possible. Until an efficacious vaccine is developed, screening and treatment programs appear to be the best method of disease prevention.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Miller WC, Ford CA, Morris M, Handcock MS, Schmitz JL, Hobbs MM et al (2004) Prevalence of Chlamydial and gonococcal infections among young adults in the United States. JAMA 291:2229–2236
LaMontagne DS, Fenton KA, Randall S, Anderson S, Carter P (2004) Establishing the national Chlamydia screening programme in England: results from the first full year of screening. Sex Transm Infect 80:335–341
Ford CA, Pence BW, Miller WC, Resnick MD, Bearinger LH, Pettingell S et al (2005) Predicting adolescents’ longitudinal risk for sexually transmitted infection: results from the National Longitudinal Study of Adolescent Health. Arch Pediatr Adolesc Med 159:657–664
Griffiths E, Gupta RS (2002) Protein signatures distinctive of Chlamydial species: horizontal transfers of cell wall biosynthesis genes glmU from archaea to Chlamydiae and murA between Chlamydiae and Streptomyces. Microbiology 148:2541–2549
O’Connell CM, Abdelrahman YM, Green E, Darville HK, Saira K, Smith B et al (2011) TLR2 activation by Chlamydia trachomatis is plasmid-dependent and plasmid-responsive chromosomal loci are coordinately regulated in response to glucose limitation by C. trachomatis but not by C. muridarum. Infect Immun 79(3):1044–1056
Stephens RS (2003) The cellular paradigm of Chlamydial pathogenesis. Trends Microbiol 11:44–51
Karimi O, Ouburg S, de Vries HJ, Pena AS, Pleijster J, Land JA et al (2009) TLR2 haplotypes in the susceptibility to and severity of Chlamydia trachomatis infections in Dutch women. Drugs Today (Barc) 45(Suppl B):67–74
Darville T, O’Neill JM, Andrews CW Jr, Nagarajan UM, Stahl L, Ojcius DM (2003) Toll-like receptor-2, but not toll-like receptor-4, is essential for development of oviduct pathology in Chlamydial genital tract infection. J Immunol 171:6187–6197
Frazer LC, O’Connell CM, Andrews CW Jr, Zurenski MA, Darville T (2011) Enhanced neutrophil longevity and recruitment contribute to the severity of oviduct pathology during C. muridarum infection. Infect Immun 79(10):4029–4041
Shah AA, Schripsema JH, Imtiaz MT, Sigar IM, Kasimos J, Matos PG et al (2005) Histopathologic changes related to fibrotic oviduct occlusion after genital tract infection of mice with Chlamydia muridarum. Sex Transm Dis 32:49–56
Darville T, Andrews CW Jr, Laffoon KK, Shymasani W, Kishen LR, Rank RG (1997) Mouse strain-dependent variation in the course and outcome of Chlamydial genital tract infection is associated with differences in host response. Infect Immun 65:3065–3073
Ramsey KH, Sigar IM, Schripsema JH, Shaba N, Cohoon KP (2005) Expression of matrix metalloproteinases subsequent to urogenital Chlamydia muridarum infection of mice. Infect Immun 73:6962–6973
Imtiaz MT, Distelhorst JT, Schripsema JH, Sigar IM, Kasimos JN, Lacy SR et al (2007) A role for matrix metalloproteinase-9 in pathogenesis of urogenital Chlamydia muridarum infection in mice. Microbes Infect
Molano M, Meijer CJ, Weiderpass E, Arslan A, Posso H, Franceschi S et al (2005) The natural course of Chlamydia trachomatis infection in asymptomatic Colombian women: a 5-year follow-up study. J Infect Dis 191:907–916
Burstein GR, Gaydos CA, Diener-West M, Howell MR, Zenilman JM, Quinn TC (1998) Incident Chlamydia trachomatis infections among inner-city adolescent females (see comments). JAMA 280:521–526
Arno JN, Katz BP, McBride R, Carty GA, Batteiger BE, Caine VA et al (1994) Age and clinical immunity to infections with Chlamydia trachomatis. Sex Transm Dis 21:47–52
Kimani J, Maclean IW, Bwayo JJ, MacDonald K, Oyugi J, Maitha GM et al (1996) Risk factors for Chlamydia trachomatis pelvic inflammatory disease among sex workers in Nairobi, Kenya. J Infect Dis 173:1437–1444
Brunham RC, Kimani J, Bwayo J, Maitha G, Maclean I, Yang C et al (1996) The epidemiology of Chlamydia trachomatis within a sexually transmitted diseases core group. J Infect Dis 173:950–956
Cohen CR, Koochesfahani KM, Meier AS, Shen C, Karunakaran K, Ondondo B et al (2005) Immunoepidemiologic profile of Chlamydia trachomatis infection: importance of heat-shock protein 60 and interferon- gamma. J Infect Dis 192:591–599
Su H, Feilzer K, Caldwell HD, Morrison RP (1997) Chlamydia trachomatis genital tract infection of antibody-deficient gene knockout mice. Infect Immun 65:1993–1999
Morrison SG, Morrison RP (2005) A predominant role for antibody in acquired immunity to Chlamydial genital tract reinfection. J Immunol 175:7536-7542
Brunham RC, Kuo CC, Cles L, Holmes KK (1983) Correlation of host immune response with quantitative recovery of Chlamydia trachomatis from the human endocervix. Infect Immun 39:1491–1494
Brunham RC, Peeling R, Maclean I, McDowell J, Persson K, Osser S (1987) Postabortal Chlamydia trachomatis salpingitis: correlating risk with antigen-specific serological responses and with neutralization. J Infect Dis 155:749–755
World Health Organization (WHO) (2001) Global prevalence and incidence of selected curable sexually transmitted infections: overview and estimates. WHO, Geneva
Sturm-Ramirez K, Brumblay H, Diop K, Gueye-Ndiaye A, Sankale JL, Thior I et al (2000) Molecular epidemiology of genital Chlamydia trachomatis infection in high-risk women in Senegal, West Africa. J Clin Microbiol 38:138–145
Kilmarx PH, Black CM, Limpakarnjanarat K, Shaffer N, Yanpaisarn S, Chaisilwattana P et al (1998) Rapid assessment of sexually transmitted diseases in a sentinel population in Thailand: prevalence of Chlamydial infection, gonorrhoea, and syphilis among pregnant women–1996. Sex Transm Infect 74:189–193
Warszawski J, Meyer L, Weber P (1999) Criteria for selective screening of cervical Chlamydia trachomatis infection in women attending private gynecology practices. Eur J Obstet Gynecol Reprod Biol 86:5–10
Gaydos CA, Howell MR, Quinn TC, McKee KT Jr, Gaydos JC (2003) Sustained high prevalence of Chlamydia trachomatis infections in female army recruits. Sex Transm Dis 30:539–544
Cohen DA, Nsuami M, Etame RB, Tropez-Sims S, Abdalian S, Farley TA et al (1998) A school-based Chlamydia control program using DNA amplification technology. Pediatrics 101:e1
Best D, Ford CA, Miller WC (2001) Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infection in pediatric private practice. Pediatrics 108:E103
Stamm WE, Koutsky LA, Benedetti JK, Jourden JL, Brunham RC, Holmes KK (1984) Chlamydia trachomatis urethral infections in men. Prevalence, risk factors, and clinical manifestations. AnnIntern Med 100:47–51
Schachter J, Grossman M, Holt J, Sweet R, Spector S (1979) Infection with Chlamydia trachomatis: involvement of multiple anatomic sites in neonates. J Infect Dis 139:232–234
Jones RB, Rabinovitch RA, Katz BP, Batteiger BE, Quinn TS, Terho P et al (1985) Chlamydia trachomatis in the pharynx and rectum of heterosexual patients at risk for genital infection. AnnIntern Med 102:757–762
Quinn TC, Goodell SE, Mkrtichian E, Schuffler MD, Wang SP, Stamm WE et al (1981) Chlamydia trachomatis proctitis. N Eng J Med 305:195–200
Rahman MU, Cantwell R, Johnson CC, Hodinka RL, Schumacher HR, Hudson AP (1992) Inapparent genital infection with Chlamydia trachomatis and its potential role in the genesis of Reiters syndrome. DNA Cell Biol 11:215–219
Keat A, Thomas BJ, Taylor Robinson D (1983) Chlamydial infection in the aetiology of arthritis. Br Med Bull 39:168–174
Koskela P, Anttila T, Bjorge T, Brunsvig A, Dillner J, Hakama M et al (2000) Chlamydia trachomatis infection as a risk factor for invasive cervical cancer. Int J Cancer 85:35–39
Plummer FA, Simonsen JN, Cameron DW, Ndinya-Achola JO, Kreiss JK, Gakinya MN et al (1991) Cofactors in male-female sexual transmission of human immunodeficiency virus type 1. J Infect Dis 163:233–239
Paavonen J, Vesterinen E, Mardh PA (1982) Infertility as a sequela of Chlamydial pelvic inflammatory disease. Scand J Infect Dis Suppl 32:73–76
Haggerty CL, Gottlieb SL, Taylor BD, Low N, Xu F, Ness RB (2010) Risk of sequelae after Chlamydia trachomatis genital infection in women. J Infect Dis 201(Suppl 2):S134–55
Rahm VA, Gnarpe H, Odlind V (1988) Chlamydia trachomatis among sexually active teenage girls. Lack of correlation between Chlamydial infection, history of the patient and clinical signs of infection. Br J Obstet Gynaecol 95:916–919
Bachmann LH, Richey CM, Waites K, Schwebke JR, Hook III EW (1999) Patterns of Chlamydia trachomatis testing and follow-up at a University Hospital Medical Center. Sex Transm Dis 26:496–499
Geisler WM, Wang C, Morrison SG, Black CM, Bandea CI, Hook III EW (2008) The natural history of untreated Chlamydia trachomatis infection in the interval between screening and returning for treatment. Sex Transm Dis 35:119–123
Morre SA, van den Brule AJ, Rozendaal L, Boeke AJ, Voorhorst FJ, de Blok S et al (2002) The natural course of asymptomatic Chlamydia trachomatis infections: 45 % clearance and no development of clinical PID after one-year follow-up. Int J STD AIDS 13(Suppl 2):12–18
Oakeshott P, Kerry S, Aghaizu A, Atherton H, Hay S, Taylor-Robinson D et al (2010) Randomised controlled trial of screening for Chlamydia trachomatis to prevent pelvic inflammatory disease: the POPI (prevention of pelvic infection) trial. BMJ 340:c1642
Svensson L, Westrom L, Ripa KT, Mardh PA (1980) Differences in some clinical and laboratory parameters in acute salpingitis related to culture and serologic findings. Am J Obstet Gynecol 138(7 Pt 2):1017–1021
Hillis SD, Owens LM, Marchbanks PA, Amsterdam LE, Mac Kenzie WR (1997) Recurrent Chlamydial infections increase the risks of hospitalization for ectopic pregnancy and pelvic inflammatory disease. Am J Obstet Gynecol 176:103–107
Ness RB, Smith KJ, Chang CC, Schisterman EF, Bass DC (2006) Prediction of pelvic inflammatory disease among young, single, sexually active women. Sex Transm Dis 33:137–142
Schachter J, Grossman M, Sweet RL, Holt J, Jordan C, Bishop E (1986). Prospective study of perinatal transmission of Chlamydia trachomatis. JAMA 255:3374–3377
Datta P, Laga M, Plummer FA, Ndinya-Achola JO, Piot P, Maitha G et al (1988) Infection and disease after perinatal exposure to Chlamydia trachomatis in Nairobi, Kenya. J Infect Dis 158:524–528
Alexander ER, Harrison HR (1983) Role of Chlamydia trachomatis in perinatal infection. Rev Infect Dis 5:713–719
Rours IG, Hammerschlag MR, Ott A, De Faber TJ, Verbrugh HA, de Groot R et al (2008) Chlamydia trachomatis as a cause of neonatal conjunctivitis in Dutch infants. Pediatrics 121:e321–326
Chandler JW, Alexander ER, Pheiffer TA, Wang SP, Holmes KK, English M (1977) Ophthalmia neonatorum associated with maternal Chlamydial infections. Trans Am Acad Ophthalmol Otola 83:302–308
Persson K, Ronnerstam R, Svanberg L, Pohla MA (1983) Neonatal Chlamydial eye infection: an epidemiological and clinical study. Br J Ophthalmol 67:700–704
Beem MO, Saxon EM (1977) Respiratory-tract colonization and a distinctive pneumonia syndrome in infants infected with Chlamydia trachomatis. N Engl J Med 296:306–310
Schachter J, Lum L, Gooding CA, Ostler B (1975) Pneumonitis following inclusion blennorrhea. J Pediatr 87:779–780
Rours GI, Hammerschlag MR, Van Doornum GJ, Hop WC, de Groot R, Willemse HF et al (2009) Chlamydia trachomatis respiratory infection in Dutch infants. Arch Dis Child 94:705–707
Tipple MA, Beem MO, Saxon EM (1979) Clinical characteristics of the afebrile pneumonia associated with Chlamydia trachomatis infection in infants less than 6 months of age. Pediatrics 63:192–197
Johnson RE, Newhall WJ, Papp JR, Knapp JS, Black CM, Gift TL et al (2002) Screening tests to detect Chlamydia trachomatis and Neisseria gonorrhoeae infections–2002. MMWR Recomm Rep 51:1–38
Blake DR, Lemay CA, Gaydos CA, Quinn TC (2005) Performance of urine leukocyte esterase in asymptomatic male youth: another look with nucleic acid amplification testing as the gold standard for Chlamydia detection. J Adolesc Health 36:337–341
Black CM (1997) Current methods of laboratory diagnosis of Chlamydia trachomatis infections. Clin Microbiol Rev 10:160–184
Schachter J, Stamm WE, Quinn TC, Andrews WW, Burczak JD, Lee HH (1994) Ligase chain reaction to detect Chlamydia trachomatis infection of the cervix. J Clin Microbiol 32:2540–2543
Jaschek G, Gaydos CA, Welsh LE, Quinn TC (1993) Direct detection of Chlamydia trachomatis in urine specimens from symptomatic and asymptomatic men by using a rapid polymerase chain reaction assay. J Clin Microbiol 31:1209–1212
Rours GI, Verkooyen RP, Willemse HF, van der Zwaan EA, van Belkum A, de Groot R et al (2005) Use of pooled urine samples and automated DNA isolation to achieve improved sensitivity and cost-effectiveness of large-scale testing for Chlamydia trachomatis in pregnant women. J Clin Microbiol 43:4684–4690
Shafer MA, Moncada J, Boyer CB, Betsinger K, Flinn SD, Schachter J (2003) Comparing first-void urine specimens, self-collected vaginal swabs, and endocervical specimens to detect Chlamydia trachomatis and Neisseria gonorrhoeae by a nucleic acid amplification test. J Clin Microbiol 41:4395–4399
Knox J, Tabrizi SN, Miller P, Petoumenos K, Law M, Chen S et al (2002) Evaluation of self-collected samples in contrast to practitioner-collected samples for detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis by polymerase chain reaction among women living in remote areas. Sex Transm Dis 29:647–654
Hammerschlag MR, Roblin PM, Gelling M, Tsumura N, Jule JE, Kutlin A (1997) Use of polymerase chain reaction for the detection of Chlamydia trachomatis in ocular and nasopharyngeal specimens from infants with conjunctivitis. Pediatr Infect Dis J 16:293–297
Martin DH, Mroczkowski TF, Dalu ZA, McCarty J, Jones RB, Hopkins SJ et al (1992) A controlled trial of a single dose of azithromycin for the treatment of Chlamydial urethritis and cervicitis. N Engl J Med 327:921–925
Gaydos CA, Crotchfelt KA, Howell MR, Kralian S, Hauptman P, Quinn TC (1998) Molecular amplification assays to detect Chlamydial infections in urine specimens from high school female students and to monitor the persistence of Chlamydial DNA after therapy. J Infect Dis 177:417–424
Workowski KA, Berman SM (2006) Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep 55:1–94
Kelsey JJ, Moser LR, Jennings JC, Munger MA (1994) Presence of azithromycin breast milk concentrations: a case report. Am J Obstet Gynecol 170:1375–1376
Cates W Jr, Wasserheit JN (1991) Genital Chlamydial infections: Epidemiology and reproductive sequelae. Am J Obstet Gynecol 164(Suppl):1771–1781
Stamm WE, Holmes KK, Mardh PA, Sparling PF, Wiesner PJ (1999) Chlamydia trachomatis infections of the adult. Sexually transmitted diseases. Mcgraw-hill book company, New York, p 407–422
Westrom L, Joesoef R, Reynolds G, Hagdu A, Thompson SE (1992) Pelvic inflammatory disease and fertility. A cohort study of 1,844 women with laparoscopically verified disease and 657 control women with normal laparoscopic results. Sex Transm Dis 19:185–192
Gencay M, Koskiniemi M, Ammala P, Fellman V, Narvanen A, Wahlstrom T et al (2000) Chlamydia trachomatis seropositivity is associated both with stillbirth and preterm delivery. APMIS 108:584–588
Hollegaard S, Vogel I, Thorsen P, Jensen IP, Mordhorst CH, Jeune B (2007) Chlamydia trachomatis C-complex serovars are a risk factor for preterm birth. In Vivo 21:107–112
Fejgin MD, Cohen I, Horvat-Kohlmann M, Charles AG, Luzon A, Samra Z (1997) Chlamydia trachomatis infection during pregnancy: can it cause an intrauterine infection? Isr J Med Sci 33:98–102
Andrews WW, Goldenberg RL, Mercer B, Iams J, Meis P, Moawad A et al (2000) The Preterm Prediction Study: association of second-trimester genitourinary Chlamydia infection with subsequent spontaneous preterm birth. Am J Obstet Gynecol 183:662–668
Kovacs L, Nagy E, Berbik I, Meszaros G, Deak J, Nyari T (1998) The frequency and the role of Chlamydia trachomatis infection in premature labor. Int J Gynaecol Obstet 62:47–54
Rastogi S, Das B, Salhan S, Mittal A (2003) Effect of treatment for Chlamydia trachomatis during pregnancy. Int J Gynaecol Obstet 80:129–137
Blas MM, Canchihuaman FA, Alva IE, Hawes SE (2007) Pregnancy outcomes in women infected with Chlamydia trachomatis: a population-based cohort study in Washington State. Sex Transm Infect 83:314–378
Moss NJ, Ahrens K, Kent CK, Klausner JD (2006) The decline in clinical sequelae of genital Chlamydia trachomatis infection supports current control strategies. J Infect Dis 193:1336–1338 (author reply 8–9)
Brunham RC, Pourbohloul B, Mak S, White R, Rekart ML (2006) Reply to Hagdu and to Moss et al. J Infect Dis 193:1338–1339
Brunham RC, Pourbohloul B, Mak S, White R, Rekart ML (2005) The Unexpected Impact of a Chlamydia trachomatis Infection Control Program on Susceptibility to Reinfection. J Infect Dis 192:1836–1844
Vickers DM, Osgood ND (2010) Current crisis or artifact of surveillance: insights into rebound Chlamydia rates from dynamic modelling. BMC Infect Dis 10:70
Hammerschlag MR, Cummings C, Roblin PM, Williams TH, Delke I (1989) Efficacy of neonatal ocular prophylaxis for the prevention of Chlamydial and gonococcal conjunctivitis. N Eng J Med 320:769–772
Cong Y, Jupelli M, Guentzel MN, Zhong G, Murthy AK, Arulanandam BP (2007) Intranasal immunization with Chlamydial protease-like activity factor and CpG deoxynucleotides enhances protective immunity against genital Chlamydia muridarum infection. Vaccine 25:3773–3780
Ifere GO, He Q, Igietseme JU, Ananaba GA, Lyn D, Lubitz W et al (2007) Immunogenicity and protection against genital Chlamydia infection and its complications by a multisubunit candidate vaccine. J Microbiol Immunol Infect 40:188–200
Pal S, Peterson EM, Rappuoli R, Ratti G, De La Maza LM (2006) Immunization with the Chlamydia trachomatis major outer membrane protein, using adjuvants developed for human vaccines, can induce partial protection in a mouse model against a genital challenge. Vaccine 24:766–775
Acknowledgements
Toni Darville is supported by United States National Institutes of Health grants (AI054624 and U19 AI084024).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this chapter
Cite this chapter
Darville, T. (2013). Recognition and Treatment of Chlamydial Infections from Birth to Adolescence. In: Curtis, N., Finn, A., Pollard, A. (eds) Hot Topics in Infection and Immunity in Children IX. Advances in Experimental Medicine and Biology, vol 764. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4726-9_8
Download citation
DOI: https://doi.org/10.1007/978-1-4614-4726-9_8
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-4725-2
Online ISBN: 978-1-4614-4726-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)