Chlamydia Clinical Trials, Diagnosis, and Treatment

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Chlamydia

Chlamydia (from the Greek, χλαμύδος meaning "cloak") is a common sexually transmitted infection (STI) caused by the bacterium, Chlamydia trachomatis. The term Chlamydia refers to an infection by any one of the species in the bacterial genus Chlamydia—Chlamydia trachomatis, Chlamydia suis or Chlamydia muridarum—, but of these, only C. trachomatis is found in humans. Chlamydia is a major infectious cause of human genital and eye disease.

Chlamydia infection is one of the most common sexually transmitted infections in people worldwide — about 2.8 million cases of chlamydia infection occur in the United States each year. It is the most common bacterial STI in humans.

C. trachomatis is naturally found living only inside human cells. Chlamydia can be transmitted during vaginal, anal, or oral sex, and can be passed from an infected mother to her baby during vaginal childbirth. Many people with Chlamydia exhibit no symptoms of infection. Between half and three-quarters of all women who have chlamydia have no symptoms and do not know that they are infected. If untreated, chlamydial infections can cause serious reproductive and other health problems with both short-term and long-term consequences. Chlamydia is easily treated with antibiotics.

Of equal importance, chlamydia conjunctivitis or trachoma is the second most common cause of blindness in the world, accounting for more than 15% of cases (making it less important than cataract but more important than glaucoma).

Current Research

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Related Conditions

Genital Disease

Chlamydial infection of the neck of the womb (cervicitis) is an asymptomatic sexually transmitted illness for about 50-70% of the female population. Of those who have an asymptomatic infection that is not detected by their doctor, approximately half will develop pelvic inflammatory disease (PID), a generic term for infection of the uterus, fallopian tubes, and/or ovaries. PID can cause scarring inside the reproductive organs, which can later cause serious complications, including chronic pelvic pain, difficulty becoming pregnant, ectopic (tubal) pregnancy, and other dangerous complications of pregnancy. Chlamydia causes 250,000 to 500,000 cases of PID every year in the United States. Women infected with chlamydia are up to five times more likely to become infected with HIV, if exposed.

Chlamydia is known as the "Silent Epidemic" because in women, it may not cause any symptoms and will linger for months or years before being discovered. Symptoms that may occur include: unusual vaginal bleeding or discharge, pain in the abdomen, painful sexual intercourse (dyspareunia), fever, painful urination or the urge to urinate more frequently than usual (urinary urgency).

Eye Disease

Chlamydia conjunctivitis or trachoma is with more than 15% the second most important cause of blindness worldwide. The infection can be spread from eye to eye by fingers, shared towels or cloths, coughing and sneezing and eye-seeking flies. Symptoms include pupils dilating rapidly, flashbacks and recurring visions of green dots. Newborns can also develop chlamydia eye infection through childbirth (see below). Using the SAFE strategy (acronym for surgery for in-growing or in-turned lashes, antibiotics, facial cleanliness, and environmental improvements), the World Health Organisation aims for the global elimination of trachoma by 2020 (GET 2020 initiative).

Rheumatological Conditions

Chlamydia may also cause reactive arthritis, especially in young men. About 15,000 men develop reactive arthritis due to chlamydia infection each year in the U.S., and about 5,000 are permanently affected by it. The triad of reactive arthritis, conjunctivitis and urethritis (inflammation of the urethra) is known as Reiter's syndrome. It can occur in both men and women, though is more common in men.

Perinatal Infections

As many as half of all infants born to mothers with chlamydia will be born with the disease. Chlamydia can affect infants by causing spontaneous abortion; premature birth; conjunctivitis, which may lead to blindness; and pneumonia. Conjunctivitis due to chlamydia typically occurs one week after birth (compare with chemical causes (within hours) or gonorrhea (2-5 days)).

Other Conditions

Chlamydia trachomatis is also the cause of lymphogranuloma venereum, an infection of the lymph nodes and lymphatics. It usually presents with genital ulceration and swollen lymph nodes in the groin, but it may also manifest as proctitis (inflammation of the rectum), fever or swollen lymph nodes in other regions of the body.

Diagnosis

Screening

For sexually active women who are not pregnant, screening is recommended in those under 25 and others at risk of infection. Risk factors include a history of chlamydial or other sexually transmitted infection, new or multiple sexual partners, inconsistent condom use, and exchanging sex for money or drugs. For pregnant women, guidelines vary: screening women with age or other risk factors is recommended by the U.S. Preventive Services Task Force (USPSTF) (which recommends screening women under 25) and the American Academy of Family Physicians (which recommends screening women aged 25 or younger). The American College of Obstetricians and Gynecologists recommends screening all at risk, while the Centers for Disease Control and Prevention recommend universal screening of pregnant women. The USPSTF acknowledges than in some communities there may be other risk factors for infection, such as ethnicity. Evidence-based recommendations for screening initiation, intervals and termination are currently not possible. There is no universal agreement on screening men for chlamydia.

Laboratory Detection

The diagnosis of genital chlamydial infections evolved rapidly from the 1990s through 2006. Nucleic acid amplification tests (NAAT), such as polymerase chain reaction (PCR), transcription mediated amplification (TMA), and the DNA strand displacement assay (SDA) now are the mainstays. NAAT for chlamydia may be performed on swab specimens collected from the cervix (women) or urethra (men), on self-collected vaginal swabs, or on voided urine. Urine and self-collected swab testing facilitates the performance of screening tests in settings where genital examination is impractical. At present, the NAATs have regulatory approval only for testing urogenital specimens, although rapidly evolving research indicates that they may give reliable results on rectal specimens.

Because of improved test accuracy, ease of specimen management, convenience in specimen management, and ease of screening sexually active men and women, the NAATs have largely replaced culture, the historic gold standard for chlamydia diagnosis, and the non-amplified probe tests. The latter test is relatively insensitive, successfully detecting only 60-80% of infections in asymptomatic women, and often giving falsely positive results. Culture remains useful in selected circumstances and is currently the only assay approved for testing non-genital specimens.

Treatment

C. trachomatis infection can be effectively cured with antibiotics once it is detected. Current Centers for Disease Control guidelines provide for the following treatments:

Azithromycin 1 gram oral as a single dose, or
Doxycycline 100 milligrams twice daily for seven days.
Tetracycline
Erythromycin

Untested Treatments

Ciprofloxacin 500 milligrams twice daily for 3 days. (Although this is not an approved method of treatment, as it is shown to be ineffective and may simply delay symptoms.)

β-lactams are not suitable drugs for the treatment of chlamydia. While they have the ability to halt growth of the organism (i.e. are microbistatic), these antibiotics do not eliminate the bacteria. Once treatment is stopped, the bacteria will begin to grow once more. (See below for Persistence.)

Areas of Research

Recent phylogenetic studies have revealed that chlamydia shares a common ancestor with modern buffalo, and retains unusual plant-like traits (both genetically and physiologically). In particular, the enzyme L,L-diaminopimelate aminotransferase, which is related to lysine production in plants, is also linked with the construction of chlamydia's cell wall. The genetic encoding for the enzymes is remarkably similar in plants and chlamydia, demonstrating a close common ancestry.[14] This unexpected discovery may help scientists develop new treatment avenues: if scientists could find a safe and effective inhibitor of L,L-diaminopimelate aminotransferase, they might have a highly effective and extremely specific new antibiotic against chlamydia.

Pathophysiology

Chlamydiae have the ability to establish long-term associations with host cells. When an infected host cell is starved for various nutrients such as amino acids (e.g. tryptophan), iron, or vitamins, this has a negative consequence for Chlamydiae since the organism is dependent on the host cell for these nutrients.

The starved chlamydiae enter a persistent growth state wherein they stop cell division and become morphologically aberrant by increasing in size.[16] Persistent organisms remain viable as they are capable of returning to a normal growth state once conditions in the host cell improve.

There is much debate as to whether persistence has in vivo relevance. Many believe that persistent chlamydiae are the cause of chronic chlamydial diseases. Some antibiotics such as β-lactams can also induce a persistent-like growth state, which can contribute to the chronicity of chlamydial diseases.

(adapted from Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Chlamydia_infection)

Findings From Current Research

Stay in School? Results of a Sexually Transmitted Diseases Screening Program in San Francisco High Schools-2007

Authors: Barry PM, Scott KC, McCright J, Snell A, Lee M, Bascom T, Kent CK, Klausner JD.

From the *Epidemic Intelligence Service, Office of Workforce and Career Development, Centers for Disease Control and Prevention, Atlanta, Georgia; †San Francisco Department of Public Health; ‡San Francisco Unified School District; and §University of California, San Francisco, California.

OBJECTIVES:: To provide chlamydia and gonorrhea screening and treatment to adolescents presumed to be at high risk, school screening was conducted among the 11th and 12th graders in San Francisco. STUDY DESIGN:: Two schools in neighborhoods with high chlamydia and gonorrhea rates and student populations >/=15% black were chosen. Students viewed a 10-minute presentation and received test kits. Students decided in a private bathroom stall whether to test. All students were encouraged to return a test kit (whether they returned a urine specimen). RESULTS:: Of 967 eligible students, 853 (88%) were in attendance. Of these, 21 (2%) declined to participate and 537 (63%) returned a specimen for testing. Students who tested were predominately heterosexual (93%) and nonwhite (99%). No students tested positive for gonorrhea; 7 (1.3%) tested positive for chlamydia. Positivity was 2.2% (5 of 227) for female students and 0.6% (2 of 310) for male students. Positivity by race/ethnicity was 5.4% (4 of 74) for blacks, 2.0% (2 of 98) for Hispanics, 0.3% (1 of 342) for Asian/Pacific Islanders, and 0% (0 of 4) for whites. The highest positivity was among black female students: 9.3% (4 of 43). Not including planning and follow-up, each case identified used 63 staff hours. CONCLUSIONS:: Despite high participation among students attending school in high morbidity neighborhoods, few infections were identified. This is likely because students have low rates of sexual activity and do not necessarily attend neighborhood schools. Screening used substantial resources. Sexually transmitted disease control programs considering school screening should consider local epidemiology and whether schools have substantial proportions of students likely at high risk for sexually transmitted diseases.

Journal: Sex Transm Dis. 2008 Mar 19
Adapted from PubMed; click here to access full journal article.

A Review of Partner Notification for Sex Partners of Men Infected With Chlamydia

Authors: Hogben M, Kissinger P.

From the *Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia; and †Department of Epidemiology, Tulane University, New Orleans, Los Angeles.

A discussion of the feasibility and use of chlamydial screening of men requires attention to management of their partners. Because of the large numbers of chlamydial cases in the United States, public health-mediated partner notification, as a first line partner management strategy, is not practical. This article reviews the evidence for patient-based referral. We reviewed studies (1997-2007) from the United States and other industrialized nations in which men diagnosed with chlamydia were exposed to some form of partner referral instruction. Randomized controlled trial and observational data were included; where data permitted, we estimated proportions of partners notified and treated. Nine studies from 3 countries yielded 8 estimates of notification rates and 10 of treatment rates. Estimates varied according to whether patient referral was accompanied by counseling, contact slips, or medications for partners. Overall, 48% to 79% of partners seemed to be notified with a smaller proportion subsequently treated (30%-61%). Higher rates of notification and treatment were associated with various enhancements to basic referral instructions, especially if patients were offered medications to bring to partners. Data also suggest a role for contact slips. Resource constraints suggest that public health investigation should be limited to high-priority cases (e.g., where evidence of dense sexual networks exists) and monitoring of patient referral efforts.

Journal: Sex Transm Dis. 2008 Mar 17
Adapted from PubMed; click here to access full journal article.

Chlamydia Prevalence Among College Students: Reproductive and Public Health Implications

Authors: James AB, Simpson TY, Chamberlain WA.

From the *Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia; and †Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.

BACKGROUND:: Routine chlamydia screening is not readily available at all college campuses. OBJECTIVES:: To assess the prevalence of Chlamydia trachomatis among asymptomatic college students and to compare chlamydia positivity by selected demographic variables. METHODS:: Analysis of demographical data collected on 789 students who volunteered for a urine screening of C. trachomatis and Neisseria gonorrheae infections at 10 colleges in Alabama, Georgia, and Mississippi. RESULTS:: The median age was 20 years. The chlamydia prevalence among all students was 9.7%. Students under the age of 20 years were 66% more likely to be infected than were older students (95% CI 1.01-2.73). Younger female students were 92% more likely to be infected than were older female students (95% CI 1.03-3.59). CONCLUSIONS:: The chlamydia prevalence was higher in younger college students; more screening efforts and increased awareness are needed to reduce the prevalence of chlamydial infections among students.

Journal: Sex Transm Dis. 2008 Mar 17
Adapted from PubMed; click here to access full journal article.

Herpes Simplex Virus Co-Infection-Induced Chlamydia Trachomatis Persistence is Not Mediated by Any Known Persistence Inducer or Anti-Chlamydial Pathway

Authors: Vanover J, Sun J, Deka S, Kintner J, Duffourc MM, Schoborg RV.

Department of Microbiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614-0579, USA.

Several inducers of chlamydial persistence have been described, including interferon-gamma (IFN-gamma), IFN-alpha, IFN-beta, and tumour necrosis factor-alpha (TNF-alpha) exposure, and iron, amino acid or glucose deprivation. A tissue-culture model of Chlamydia trachomatis/herpes simplex virus type-2 (HSV-2) co-infection indicates that viral co-infection stimulates the formation of persistent chlamydiae. This study was designed to ascertain whether co-infection-induced persistence is mediated by a previously characterized mechanism. Luminex assays indicate that IFN-gamma, IFN-alpha, and TNF-alpha are not released from co-infected cells. Semiquantitative RT-PCR studies demonstrate that IFN-beta, IFN-gamma, indoleamine 2,3-dioxygenase, lymphotoxin-alpha and inducible nitric oxide synthase are not expressed during co-infection. These data indicate that viral-induced persistence is not stimulated by any persistence-associated cytokine. Supplementation of co-infected cells with excess amino acids, iron-saturated holotransferrin, glucose or a combination of amino acids and iron does not restore chlamydial infectivity, demonstrating that HSV-2-induced persistence is not mediated by depletion of these nutrients. Finally, inclusions within co-infected cells continue to enlarge and incorporate C(6)-NBD-ceramide, indicating that HSV-2 co-infection does not inhibit vesicular transport to the developing inclusion. Collectively these data demonstrate that co-infection-induced persistence is not mediated by any currently characterized persistence inducer or anti-chlamydial pathway. Previous studies indicate that HSV-2 attachment and/or entry into the host cell is sufficient for stimulating chlamydial persistence, suggesting that viral attachment and/or entry may trigger a novel host pathway which restricts chlamydial development.

Journal: Microbiology. 2008 Mar;154(Pt 3):971-8.
Adapted from PubMed; click here to access full journal article.

Chlamydia Antibodies, Chlamydia Heat Shock Protein, and Adverse Sequelae After Pelvic Inflammatory Disease: The PID Evaluation and Clinical Health (PEACH) Study

Authors: Ness RB, Soper DE, Richter HE, Randall H, Peipert JF, Nelson DB, Schubeck D, McNeeley SG, Trout W, Bass DC, Hutchison K, Kip K, Brunham RC.

Department of Epidemiology, University of Pittsburgh, PA 15261, USA. repro@edc.pitt.edu

BACKGROUND: Among women with pelvic inflammatory disease (PID), we assessed the associations among antibodies to Chlamydia trachomatis elementary bodies (EB), antibodies to chlamydia heat shock protein (Chsp60), rates of pregnancy, and PID recurrence. METHODS: Four hundred forty-three women with clinical signs and symptoms of mild to moderate PID enrolled in the PID Evaluation and Clinical Health Study were followed for a mean of 84 months for outcomes of time-to-pregnancy and time-to-PID recurrence. Antibodies to EB and Chsp60 were assessed in relation to these long-term sequelae of PID. RESULTS: Rates of pregnancy were significantly lower (adj. hazard ratio 0.47, 95% confidence interval 0.28-0.79) and PID recurrence higher (adj. hazard ratio 2.48, 95% confidence interval 1.00-6.27) after adjusting for confounding factors among women whose antibody titers to chlamydia EB measured in the final year of follow-up were in the highest tertile. CONCLUSION: Among women with mild to moderate PID, antibodies to C. trachomatis were independently associated with reduced rates of pregnancy and elevated rates of recurrent PID.

Journal: Sex Transm Dis. 2008 Feb;35(2):129-35.
Adapted from PubMed; click here to access full journal article.

Chlamydial and Gonococcal Infections in Women Seeking Pregnancy Testing at Family-Planning Clinics

Authors: Geisler WM, James AB.

Department of Medicine and Epidemiology, University of Alabama at Birmingham School of Medicine, Birmingham, AL.

OBJECTIVE: The objective of the study was to assess genital Chlamydia and gonorrhea prevalence and associated predictors in women seeking pregnancy testing. STUDY DESIGN: The study included analysis of demographics and results of pregnancy, Chlamydia, and gonorrhea testing in 1465 females seeking pregnancy testing at family-planning clinics in South Carolina. RESULTS: The median age was 22 years (range 16-45), the race distribution consisted of 53% African Americans and 47% Caucasians, and 64% of subjects were pregnant. Chlamydia and gonorrhea were detected in 12% and 2% of subjects, respectively. Predictors of Chlamydia and gonorrhea included younger age and African American race. Chlamydia and gonorrhea prevalence did not differ in pregnant vs. nonpregnant subjects. CONCLUSION: Chlamydia prevalence was high and gonorrhea prevalence low in women seeking pregnancy testing at family-planning clinics, and both were predicted by younger age and African American race but not pregnancy status. Because the majority seeking pregnancy testing were pregnant, Chlamydia testing in this population at risk for Chlamydia-associated morbidity has potential benefit.

Journal: Am J Obstet Gynecol. 2008 Feb 21
Adapted from PubMed; click here to access full journal article.

Evaluation of Risk Score Algorithms for Detection of Chlamydial and Gonococcal Infections in an Emergency Department Setting

Authors: Al-Tayyib AA, Miller WC, Rogers SM, Leone PA, Law DC, Ford CA, Rothman RE.

Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. alia.al-tayyib@dhha.org

OBJECTIVES: To develop and evaluate screening algorithms to predict current chlamydial and gonococcal infections in emergency department (ED) settings and assess their performance. METHODS: Between 2002 and 2005, adult patients aged 18 to 35 years attending an urban ED were screened for Chlamydia trachomatis (Ct) and Neisseria gonorrhoeae (GC) and completed a brief demographic and behavioral questionnaire. Using multiple unconditional logistic regressions, the authors developed four separate predictive models and applicable clinical risk scores to screen for infection. They developed models for females and males separately, for Ct and GC infections combined, and for Ct infection alone. The sensitivities and specificities of the clinical risk scores at different cutoffs were used to examine performance of the algorithms. RESULTS: Among 5,537 patients successfully screened for Ct and GC, the overall prevalence of infection was 9.6%. Age was the strongest predictor of infection. Adjusting for other predictors, the prevalence odds ratio (POR) was 2.2 (95% confidence interval [CI] = 1.7 to 2.8) for Ct and GC combined and 2.9 (95% CI = 2.1 to 4.1) for Ct alone comparing females 25 years and younger to females older than 25 years. Among males, the association was stronger with an adjusted POR of 3.3 (95% CI = 2.3 to 4.7) for Ct and GC combined and 3.2 (95% CI = 2.1 to 4.7) for Ct infection alone. CONCLUSIONS: If the decision to incorporate Ct and GC screening into routine ED care is made, age alone appears to be a sufficient screening criterion.

Journal: Acad Emerg Med. 2008 Feb;15(2):126-35.
Adapted from PubMed; click here to access full journal article.

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