Epidemiology of Chlamydia trachomatis Marjan Javanbakht, MPH, PhD Los Angeles County Department of Health Services Sexually Transmitted Disease Program

Taxonomy History Epidemiology Implication Conclusion Taxonomy Chlamydia trachomatis is an important pathogen of humans and 1 of 4 species within the genus C. trachomatis (natural host: humans) C. pneumoniae (natural host: humans) C. psittaci (natural host: birds, lower mammals) C. pecorum (natural host: sheep, cattle, and swine) 4 biovars of C. trachomatis Murine biovar Swine biovar Lymphogranuloma venereum (LGV) biovar Trachoma biovar CT is an important pathogen of humans and is 1 of 4 species within the genus though only two of these species have humans as their natural host. C. trachomatis has 4 biovars and you don’t really need to know the details of this, but I just wanted to note that there is an LGV biovar that causes the disease it’s name after and a trachoma biovar which causes the more common genital tract diseases and trachoma.

Taxonomy History Epidemiology Implication Conclusion History Human disease caused by C. trachomatis have been recognized since antiquity Trachoma was described in Egyptian papyri LGV was described in the 8th century However, the genital tract infections were not recognized until identification of the organism in the 20th century First isolated from patients with LGV in 1930s First isolate from genital tract (other than LGV) was made in 1959 Major breakthrough in 1960s was the development of tissue culture isolation procedures

Taxonomy History Epidemiology Implication Conclusion History: 1975 -1985 1975 – 1985 thought of as cell culture era which made it possible to: link C. trachomatis to specific clinical syndromes Majority of NGU in men was attributed to chlamydia Cervicitis and pelvic inflammatory disease also associated with chlamdyia In terms of prevention, culture era focused on teaching clinicians to recognize chlamydia associated symptoms Provide empiric treatment for patients based on chlamydia associated syndromes without actual diagnostic testing Likewise provide treatment of partners of these empirically treated patients

History: 1975 -1985 Limitations of cell culture Taxonomy History Epidemiology Implication Conclusion History: 1975 -1985 Limitations of cell culture Due to expense and technical difficulty, chlamydia testing by cell culture never became widely available Consequently, screening programs were not feasible Focus of prevention efforts was largely directed at patients attending STD clinics and family planning clinics

Taxonomy History Epidemiology Implication Conclusion History: 1985 – 1995 1985 -1995 nonculture tests (i.e., antibody tests) became available for chlamydia which allowed for: Widespread access to clinic based testing Increased opportunities to screen for adolescent women and other high risk groups Screening of pregnant women and selective screening in low prevalence populations became feasible for the first time Although more people screened, most treatment remained syndromic and empiric

Taxonomy History Epidemiology Implication Conclusion History: 1990’s - present Mid 1990’s – present, nucleic acid amplification tests (NAATS) became available for routine clinical use These tests have had a major impact on our understanding of the epidemiology and approaches to prevention because of 3 unique characteristics: Improved sensitivity (by as much as 20%) Urine based testing (no pelvic exams, urethral swabs, presence of physician not required  access to new patient populations  increase in number screened) Ability to test for multiple pathogens (CT/GC)

Taxonomy History Epidemiology Implication Conclusion History: 1990’s - present Revisions of Chlamydia epidemiology in the NAATS era (last 10 years): Because of increased sensitivity, NAATS tests have demonstrated an increased prevalence in all populations Increased recognition of and emphasis on asymptomatic infections Prevalence of ~10% in female recruits joining the army (even higher among adolescents) Prevalence of 2-7% in a random sample of households participating in NHANES III Door-to-door household survey of women 18-29 showed a 3.2% overall prevalence (even higher among adolescents)

History: 1990’s - present Impact of NAATS on prevention Taxonomy History Epidemiology Implication Conclusion History: 1990’s - present Impact of NAATS on prevention Expanded efforts to screen asymptomatic young women New venues to identify asymptomatic adolescents – a group least likely to be encountered in routine clinical care Street-based testing (eg., mobile van outreach) High-school based testing Testing of military recruits

History: 1990’s - present Impact of NAATS on prevention (cont’d) Taxonomy History Epidemiology Implication Conclusion History: 1990’s - present Impact of NAATS on prevention (cont’d) Increased appreciation of the high incidence of recurrent/persistent urogenital infections especially among adolescents 15% recurrence in 3-years among women in Washington State Chlamydia registry; 17% recurrence within 2 years among women under 20 17% recurrence in 4-years among young women (10-24 years) in Los Angeles County; with highest incidence rate among those aged 10-14 years CDC multicenter cohort study to evaluate recurrences of chlamydial infection found 13% recurrence 4 months after identification and initial therapy

History: 1990’s - present Impact of NAATS on prevention (cont’d) Taxonomy History Epidemiology Implication Conclusion History: 1990’s - present Impact of NAATS on prevention (cont’d) Until NAATS era recommendation for all chlamydia screening was focused on women, but because of new test rationale emerged to screen young men Most importantly, noninvasive test makes it more acceptable to men Substantial prevalence of asymptomatic infection in men Identification and treatment in men would constitute primary prevention for women Identification and treatment of asymptomatic male reservoir might help to prevent reinfection in women

Epidemiology Most frequently reported bacterial STI in the U.S. Taxonomy History Epidemiology Implication Conclusion Epidemiology Most frequently reported bacterial STI in the U.S. Estimated annual incidence of 3 million cases Estimated annual costs exceeding 2 billion Under-reporting is substantial since most cases are asymptomatic “Silent” disease because 75% of women and 50% of men are not aware of their infection If symptoms do occur, usually 1 – 3 weeks after exposure Symptoms include discharge (vaginal, penile, rectal), burning sensation when urinating, bleeding between menstrual cycle, pain and swelling in testicles CT infections are not only the most commonly reported notifiable disease but also the most prevalent of all reported STIs. Read bullets.

Taxonomy History Epidemiology Implication Conclusion Epidemiology Like the disease, the damage that chlamydia causes is “silent” ~40% of women with untreated chlamydia develop PID  chronic pelvic pain, infertility, and ectopic pregnancy Chlamydia infections can facilitate transmission of HIV Infected women are 2-5 times more likely to become infected with HIV if exposed Complications among men rare, but can cause pain, fever, and rarely sterility

Reported Sexually Transmitted Diseases, United States, 2004 Taxonomy History Epidemiology Implication Conclusion Reported Sexually Transmitted Diseases, United States, 2004 In 2002, over 834 thousand cases of chlamydia were reported to CDC from 50 states and DC and really represents the largest proportion of all STDs reported to the CDC. As you can see, the reported number of chlamydia infections was more than twice the number of reported cases of gonorrhea. Source: CDC Sexually Transmitted Disease Report, 2004

Taxonomy History Epidemiology Implication Conclusion Chlamydia — Number of states that require reporting of Chlamydia trachomatis infections: United States, 1987–2003 Although regulations for reporting started in 1986-1987, the year 2000 was the first time all 50 states and the district of columbia had regulations requiring the reporting of chlamydia cases to CDC. All States and DC CA reporting LA reporting

Chlamydia — Rates: United States, 1984–2004 Taxonomy History Epidemiology Implication Conclusion Chlamydia — Rates: United States, 1984–2004 Potential reasons for continuing increase: Use of more sensitive diagnostic tests Expansion of screening services More complete national reporting Improvement in information systems for reporting 320 51 Note: As of January 2000, all 50 states and the District of Columbia had regulations requiring the reporting of chlamydia cases. Source: CDC Sexually Transmitted Disease Report, 2004

Chlamydia — Rates by sex: United States, 1984–2004 Taxonomy History Epidemiology Implication Conclusion Chlamydia — Rates by sex: United States, 1984–2004 Potential reasons for gender differential: 1. Greater number of women screened 2. Sex partners of women not diagnosed or reported 485 134 In 2002, the overall rate of reported chlamydial infection among women in the US was over 3 times higher than the rate among men. Again, why would that be??? Well, it likely reflects a greater number of women screened for the infection. The lower rates among the men suggest that many of the sex partners of women with chlamydia are not diagnosed or reported. However with the advent of highly sensitive nucleic amplification tests that can be performed on men (as compared to urethral swabs which are far more invasive), symptomatic and asymptomatic men are increasingly being diagnosed with chlamydial infections. For example, from 1998 – 2002 there was a 55% increase in the infection rate in men, while the increase in women was about 20% for the same period. Nonetheless, it’s absolutely critical that sexual partners of the infected women are treated as well – because just treating the women isn’t really going to work because her sexual partner is likely to reinfect her. And this is where partner delivered therapy will play a key role in breaking the cycle of transmission – where the infected women will not only get treatment for herself but for her partner as well. Urine screening* *From 2000 – 2004: 47% increase (males): 100 - 147 cases per 100,000; 22% increase (females): 397 to 485 cases per 100,000 Source: CDC Sexually Transmitted Disease Report, 2004

Chlamydia — Age- and sex-specific rates: United States, 2004 Taxonomy History Epidemiology Implication Conclusion Chlamydia — Age- and sex-specific rates: United States, 2004 For women, the highest age specific rates of reported chlamydia in 2002 were among 15 – 19 year olds and 20 – 24 year olds. Although the age specific rates were substantially lower in men, they are highest in the same age groups. Chlamydia really is a disease of youth – physiologically young women are more susceptible to the bacteria. Source: CDC Sexually Transmitted Disease Report, 2004

Chlamydia Reported Rates by Race and Gender: United States, 2004 Taxonomy History Epidemiology Implication Conclusion Chlamydia Reported Rates by Race and Gender: United States, 2004 In addition to gender disparities, there are also racial and ethnic disparities. In 2004, the rate of chlamydia among African-American females in the United States was more than seven and a half times higher than the rate among white females (1,722.3 and 226.6 per 100,000, respectively) (Table 11B). The chlamydia rate among African-American males was 11 times higher than that among white males (645.2 and 57.3 per 100,000 respectively). Source: CDC Sexually Transmitted Disease Report, 2004

Chlamydia — Rates by state: United States and outlying areas, 2004 Taxonomy History Epidemiology Implication Conclusion Chlamydia — Rates by state: United States and outlying areas, 2004 In terms of the geographic distribution, in 2002 reported rates of chlamydia in the southern states were higher than the rates in most other regions of the US. And we see that california is also one of the states with more than 300 per 100,000 Note: The total rate of chlamydia for the United States and outlying areas (Guam, Puerto Rico and Virgin Islands) was 316.7 per 100,000 population. Source: CDC Sexually Transmitted Disease Report, 2004

Chlamydia — Rates by county: United States, 2004 Taxonomy History Epidemiology Implication Conclusion Chlamydia — Rates by county: United States, 2004 Specifically, in terms of a breakdown of rates by county, we can see that LA is one of the county’s with rates greater than 300 per 100,000 in 2002 Source: CDC Sexually Transmitted Disease Report, 2004

Reported Sexually Transmitted Diseases, Los Angeles County, 2004 Taxonomy History Epidemiology Implication Conclusion Reported Sexually Transmitted Diseases, Los Angeles County, 2004 So now we will look more specifically at Los Angeles County data. In 2002, over35 thousand cases of chlamydia were reported to the county STD program and similar to national trends it represents the largest proportion of all STDs reported to the county and in fact LA county contributed to 4% of the cases nationally. As you can see, the reported number of chlamydia infections was about 4 times the number of reported cases of gonorrhea. (4% of national cases) Source: LAC DHS STD Program 2004

Los Angeles County Chlamydia Rates, 1991-2004 Taxonomy History Epidemiology Implication Conclusion Los Angeles County Chlamydia Rates, 1991-2004 Potential reasons for continuing increase: Use of more sensitive diagnostic tests Expansion of screening services More complete reporting Improvement in information systems for reporting There has been a net increase in the rate of chlamydia infections since reporting began in LA county in 1991. Again, the reasons from this increase are similar to those we discussed in terms of the national data. You can see that the urine test were introduced in 1996 which is not only a more sensitive test, but it’s also less invasive. Source: LAC DHS STD Programs 2004

Los Angeles County Chlamydia Rates by Gender, 1991- 2004 Taxonomy History Epidemiology Implication Conclusion Los Angeles County Chlamydia Rates by Gender, 1991- 2004 Potential reasons for gender differential: 1. Greater number of women screened 2. Sex partners of women not diagnosed or reported In 2002, the overall rate of reported chlamydial infection among women in the county was over 2 times higher than the rate among men. Again, why would that be??? Well, it likely reflects a greater number of women screened for the infection. The lower rates among the men suggest that many of the sex partners of women with chlamydia are not diagnosed or reported. However with the advent of highly sensitive nucleic amplification tests that can be performed on men (as compared to urethral swabs which are far more invasive), symptomatic and asymptomatic men are increasingly being diagnosed with chlamydial infections. For example, from 1998 – 2002 there was a 88% increase in the infection rate in men, while the increase in women was about 32% for the same period. Nonetheless, it’s absolutely critical that sexual partners of the infected women are treated as well – because just treating the women isn’t really going to work because her sexual partner is likely to reinfect her. And this is where partner delivered therapy will play a key role in breaking the cycle of transmission – where the infected women will not only get treatment for herself but for her partner as well. *From 2000 – 2004: 80% increase (males): 132 to 238 cases per 100,000; 21% increase (females): 469 to 569 cases per 100,000 Source: LAC DHS STD Programs 2004

Los Angeles County Chlamydia Rates by Age and Gender, 2004 Taxonomy History Epidemiology Implication Conclusion Los Angeles County Chlamydia Rates by Age and Gender, 2004 For women, the highest age specific rates of reported chlamydia in 2002 were among 15 – 19 year olds and 20 – 24 year olds. Although the age specific rates were substantially lower in men, they are highest in the same age groups. Source: LAC DHS STD Programs 2004

Los Angeles County Chlamydia Rates by Gender and Ethnicity, 2004 Taxonomy History Epidemiology Implication Conclusion Los Angeles County Chlamydia Rates by Gender and Ethnicity, 2004 In addition to gender disparities, there are also racial and ethnic disparities. In 2002, the reported rate of chlamydia among AA females in the LA county was 10 times higher than the rate among white females and the rate among AA males was also 10 times higher as compared to white males. Source: LAC DHS STD Programs 2004

Chlamydia Rates by Service Planning Area, Los Angeles County, 2003 In terms of geographic distribution, we see the age adjusted rate of reported chlamydia by service planning area. The highest reported rates are in the south SPA which is essentially includes cities such as ………….

Taxonomy History Epidemiology Implication Conclusion Implications Age is the most important risk marker for chlamydia infection U.S. Preventive Task Force recommends that clinicians routinely screen all sexually active women aged 25 and younger Evidence supports repeat screening every 3 to 4 months for those who initially test positive as well as continued 6 month screenings in this group However, practice falls short of recommendations Only 2 – 42% of physicians offered screening to their sexually active patients under the age of 25 Only 18% of female CT positive STD clinic clients in Los Angeles County retested within 4 months Thus, educational efforts are needed to foster chlamydia practices among physicians and resources to enhance case management and follow-up Points to take away from this presentation…..

Partner Treatment/Management Taxonomy History Epidemiology Implication Conclusion Partner Treatment/Management The importance of the role of patient-delivered partner therapy (PDPT) In 2001 CA authorized PDPT for sex partners of patients with chlamydial infection – aka expedited partner therapy Clinic guidelines for PDPT Once patient is diagnosed, clinician discusses the importance of partner treatment Clinician assesses the patients ability to notify relevant sex partners (within past 60 days) Likelihood that partners will return for evaluation and patients comfort level in delivering the medication is evaluated Patients receive a therapy packet as well as an information sheet to deliver to their partners Partners are strongly advised to visit a doctor for evaluation and follow-up Points to take away from this presentation…..

Partner Treatment/Management Taxonomy History Epidemiology Implication Conclusion Partner Treatment/Management Given the burden of disease, traditional strategies of self-referral or health-department assisted follow-up and management maybe ineffective or not feasible Review of 3 randomized trials on PDPT showed reduction in re-infection rates In Los Angeles County PDPT used to improve treatment rates in incarcerated women and their partners Evaluation of acceptability from patient and partner perspective demonstrated that: It is widely favored regardless of demographic and behavioral characteristics Most useful for steady partners (vs. Casual or Once-Only partners) Points to take away from this presentation…..

Conclusion Most common bacterial STD Taxonomy History Epidemiology Implication Conclusion Conclusion Most common bacterial STD Chlamydia rates have been increasing since the late 80s Increase rates are due (in part) to: increased screening and use of more sensitive screening tests Gender disparities probably reflect increased screening among women However, the availability of urine based tests have resulted in more men being tested for chlamydia Can be easily treated and cured with antibiotics All sexual partners should be evaluated, tested, and treated to avoid reinfection Points to take away from this presentation…..

References Gaydos CA, Howell MR, Pare B, et al. Chlamydia Trachomatis Infection in female military recruits. N Engl J Med 1998; 339:739-744 Mertz KJ, McQuillian GM, Levine WC, et al. A pilot study of the prevalence of chlamydial infection in a national household survey. Sex Transm Dis 1998; 25:225-228 Klausner JD, McFarland W, Bolan G, et al. Knock-knock: a population based survey of risk behavior, health care access, and Chlamydia trachomatis infection among low-income women in the San Francisco bay area. J Infect Dis 2001; 183:1087-1092 Xu F, Schillinger JA, Markowitz LE, et al. Repeat Chlamydia trachomatis infection in women: analysis through a surveillance registry in Washington State, 1993 – 1998. Am J Epidemiol 2000; 152:1164 – 1170 Whittington WLH, Kent C, Kissinger P, et al. Determinants of persistent and recurrent Chlamydia trachomatis infection in young women: results of a multicententer cohort study. Sex Transm Dis 2001; 28:117 – 123 Burstein GR, Gaydos CA, Diener-West M, Howell MR, Zenilman JM, Quinn TC. Incident Chlamydia trachomatis infections among inner-city adolescent females. JAMA 1998; 280:521-596 Mangione-Smith R, McGlynn EA, Hiatt L. Screening for chlamydia in adolescents and young women. Arch Pediatr Adolesc Med. 2000; 154:1108 -1113 Points to take away from this presentation…..