Update on the Epidemiology, Screening, and Management of Chlamydia trachomatis Infection.

Chlamydia trachomatis infection ("chlamydia") is the most commonly diagnosed bacterial sexually transmitted infection globally, occurring in the genitals (urethra or vagina/cervix), rectum, or pharynx. If left untreated in women, genital chlamydia can ascend into the upper genital tract causing pelvic inflammatory disease, increasing their risk for ectopic pregnancy, infertility, and chronic pelvic pain. In men, chlamydia can cause epididymitis and proctitis. However, chlamydia is asymptomatic in over 80% of cases. This article provides an update on the epidemiology, natural history, and clinical manifestations of chlamydia in adults and discusses the current approaches to its management and control policy.

Biological feasibility and importance of a gonorrhea vaccine for global public health.

There is a growing public health interest in controlling sexually transmitted infections (STIs) through vaccination due to increasing recognition of the global disease burden of STIs and the role of STIs in women's reproductive health, adverse pregnancy outcomes, and the health and well-being of neonates. Neisseria gonorrhoeae has historically challenged vaccine development through the expression of phase and antigenically variable surface molecules and its capacity to cause repeated infections without inducing protective immunity. An estimated 78 million new N. gonorrhoeae infections occur annually and the greatest disease burden is carried by low- and middle-income countries (LMIC). Current control measures are clearly inadequate and threatened by the rapid emergence of antibiotic resistance. The gonococcus now holds the status of "super-bug" as there is currently no single reliable monotherapy for empirical treatment of gonorrhea. The problem of antibiotic resistance has elevated treatment costs and necessitated the establishment of large surveillance programs to track the spread of resistant strains. Here we review the need for a gonorrhea vaccine with respect to global disease burden and related socioeconomic and treatment costs, with an emphasis on the impact of gonorrhea on women and newborns. We also highlight the challenge of estimating the impact of a gonorrhea vaccine due to the need for more data on the burden of gonococcal pelvic inflammatory disease and related sequelae and of gonorrhea-associated adverse pregnancy outcomes and the problem of empirical diagnosis and treatment of STIs in LMIC. There is also a lack of clinical and basic science research in the area of gonococcal/chlamydia coinfection, which occurs in a high percentage of individuals with gonorrhea and should be considered when testing the efficacy of gonorrhea vaccines. Finally, we review recent research that suggests a gonorrhea vaccine is feasible and discuss challenges and research gaps in gonorrhea vaccine development.

Assessment of 35 children with abdominal tuberculosis.

BACKGROUND/AIMS: To contribute to the diagnosis and treatment of pediatric abdominal tuberculosis cases by assessing the clinical, laboratory, and radiological features of patients who presented at our clinic and were diagnosed with abdominal tuberculosis. MATERIALS AND METHODS: Clinical, laboratory, and radiological features were reviewed retrospectively for 35 patients diagnosed with abdominal tuberculosis and followed up at the Pediatric Infectious Diseases Clinic between January 1987 and August 2012. RESULTS: The study group included 16 female (45.7%) and 19 male (54.3%) patients with an age range of 6 months to 16 years (mean: 9.77±4.36 years). Twenty-nine patients were diagnosed with tuberculosis peritonitis, five patients with intestinal tuberculosis, and one patient with pelvic tuberculosis. The most common signs and symptoms were ascites, abdominal pain, abdominal distention, weight loss, and fever. Mean duration of the complaints was 109 days (range: 10 days to 3 years). CONCLUSION: Abdominal tuberculosis is a disease with an insidious course without disease-specific clinical and laboratory signs. When the disease is suspected, laparoscopy or laparotomy could be helpful in diagnosis. Employing ultrasound and computed tomography signs, abdominal tuberculosis should be included in differential diagnoses in regions with a high incidence of tuberculosis when there is abdominal pain, weight loss, ascites, history of contact with individuals with tuberculosis, and positive tuberculin skin test when patients have not been Bacillus Calmette Guerin BCG vaccinated.

Impact and cost-effectiveness of chlamydia testing in Scotland: a mathematical modelling study.

BACKGROUND: Chlamydia is the most common sexually transmitted bacterial infection in Scotland, and is associated with potentially serious reproductive outcomes, including pelvic inflammatory disease (PID) and tubal factor infertility (TFI) in women. Chlamydia testing in Scotland is currently targeted towards symptomatic individuals, individuals at high risk of existing undetected infection, and young people. The cost-effectiveness of testing and treatment to prevent PID and TFI in Scotland is uncertain. METHODS: A compartmental deterministic dynamic model of chlamydia infection in 15-24 year olds in Scotland was developed. The model was used to estimate the impact of a change in testing strategy from baseline (16.8% overall testing coverage; 0.4 partners notified and tested/treated per treated positive index) on PID and TFI cases. Cost-effectiveness calculations informed by best-available estimates of the quality-adjusted life years (QALYs) lost due to PID and TFI were also performed. RESULTS: Increasing overall testing coverage by 50% from baseline to 25.2% is estimated to result in 21% fewer cases in young women each year (PID: 703 fewer; TFI: 88 fewer). A 50% decrease to 8.4% would result in 20% more PID (669 additional) and TFI (84 additional) cases occurring annually. The cost per QALY gained of current testing activities compared to no testing is £40,034, which is above the £20,000-£30,000 cost-effectiveness threshold. However, calculations are hampered by lack of reliable data. Any increase in partner notification from baseline would be cost-effective (incremental cost per QALY gained for a partner notification efficacy of 1 compared to baseline: £5,119), and would increase the cost-effectiveness of current testing strategy compared to no testing, with threshold cost-effectiveness reached at a partner notification efficacy of 1.5. However, there is uncertainty in the extent to which partner notification is currently done, and hence the amount by which it could potentially be increased. CONCLUSIONS: Current chlamydia testing strategy in Scotland is not cost-effective under the conservative model assumptions applied. However, with better data enabling some of these assumptions to be relaxed, current coverage could be cost-effective. Meanwhile, increasing partner notification efficacy on its own would be a cost-effective way of preventing PID and TFI from current strategy.

Pelvic inflammatory disease: identifying research gaps--proceedings of a workshop sponsored by Department of Health and Human Services/National Institutes of Health/National Institute of Allergy and Infectious Diseases, November 3-4, 2011.

In November 2011, the National Institutes of Health convened a workshop of basic researchers, epidemiologists, and clinical experts in pelvic inflammatory disease to identify research gaps hindering advances in diagnosis, treatment, and prevention. This article summarizes the presentations, discussions, and conclusions of this group and highlights significant controversies that reveal aspects of pelvic inflammatory disease research that would most greatly benefit from the application of newer molecular, immunologic, and radiologic techniques. Multiple limitations to performing new clinical trials exist; however, emerging data from ongoing clinical trials will add to the current body of knowledge regarding prevention and treatment strategies. In addition, use of established health care databases could serve as a valuable tool for performance of unbiased epidemiologic outcome studies.

Single daily dose of moxifloxacin versus ofloxacin plus metronidazole as a new treatment approach to uncomplicated pelvic inflammatory disease: a multicentre prospective randomized trial.

OBJECTIVES: To evaluate the efficacy and safety of moxifloxacin versus ofloxacin plus metronidazole in patients with uncomplicated pelvic inflammatory disease (uPID; defined as PID symptoms and signs, but no complications such as septicemia, perihepatitis, and tubo-ovarian abscess) in Turkey. STUDY DESIGN: This was a multicenter, prospective, randomized, parallel-group study conducted between June 2010 and March 2013 in four hospitals in Turkey. Women received a 14-day course of either oral moxifloxacin at 400mg once daily (n = 560) or oral ofloxacin at 400mg twice daily plus oral metronidazole at 500 mg twice daily (n = 543). RESULTS: A total of 1156 women were randomized to the study. Total compliance was achieved in 1103 patients. For the primary measure of efficacy (clinical cure), moxifloxacin showed no difference compared with ofloxacin plus metronidazole (445/560 [79.5%] vs. 449/543 [82.7%]; p = 0.172). Bacteriological cure rates were high and comparable between treatment arms (99/119 [83.2%] vs. 93/110 [84.5%]; p = 0.781). Drug-related adverse events occurred less frequently with moxifloxacin than with ofloxacin plus metronidazole (210/560 [37.5%] vs. 252/543 [46.4%]; p = 0.003). Furthermore, moxifloxacin treatment was lower in cost and achieved higher patient compliance compared with ofloxacin plus metronidazole (31.4 Euros vs. 23.4 Euros and 7/578 (1.2%) vs. 22/578 (3.8%), respectively; p = 0.005). CONCLUSIONS: In patients with uPID, once-daily moxifloxacin monotherapy was clinically and microbiologically as efficacious as twice-daily ofloxacin plus metronidazole therapy and was associated with fewer drug-related adverse events, lower patient non-compliance, and a lower treatment cost.

Screening and treating Chlamydia trachomatis genital infection to prevent pelvic inflammatory disease: interpretation of findings from randomized controlled trials.

We critically reviewed randomized controlled trials evaluating chlamydia screening to prevent pelvic inflammatory disease (PID) and explored factors affecting interpretation and translation of trial data into public health prevention. Taken together, data from these trials offer evidence that chlamydia screening and treatment is an important and useful intervention to reduce the risk of PID among young women. However, the magnitude of benefit to be expected from screening may have been overestimated based on the earliest trials. It is likely that chlamydia screening programs have contributed to declines in PID incidence through shortening prevalent infections, although the magnitude of their contribution remains unclear. Program factors such as screening coverage as well as natural history factors such as risk of PID after repeat chlamydia infection can be important in determining the impact of chlamydia screening on PID incidence in a population. Uptake of chlamydia screening is currently suboptimal, and expansion of screening among young, sexually active women remains a priority. To reduce transmission and repeat infections, implementation of efficient strategies to treat partners of infected women is also essential. Results of ongoing randomized evaluations of the effect of screening on community-wide chlamydia prevalence and PID will also be valuable.

Long-term trends in Chlamydia trachomatis infections and related outcomes in a U.S. managed care population.

BACKGROUND: Given recent increasing case rates of Chlamydia trachomatis infection, we evaluated trends in chlamydia rates and related health outcomes in women and men aged 15 to 44 years who were enrolled in a Pacific Northwest health plan. METHODS: We identified chlamydia, pelvic inflammatory disease (PID), ectopic pregnancy, and male urethritis cases occurring annually during 1997-2007 using computerized health plan databases, calculating rates per 100,000 person-years (py) by gender and 5-year age groups. We also calculated annual chlamydia testing rates. RESULTS: In women, chlamydia testing rates increased by approximately 23% (220 tests per 1000 py in 1997 to 270 tests per 1000 in 2007). Chlamydia diagnosis rates rose from 449 cases/100,000 py in 1997 to 806/100,000 in 2007, a 79% increase (P = 0.01). Increases were greatest during 2005-2007, also the period of major conversion to nucleic acid amplification test. PID rates in this interval declined steadily from 823 cases/100,000 py to 473/100,000 (P < 0.01). Ectopic pregnancy rates remained unchanged. In men, chlamydia testing rates increased nearly 3.5-fold, from 12 to 42 tests per 1000 py. Chlamydia rates for men also rose significantly throughout the study interval (from 91 cases/100,000 py to 218/100,000; P < 0.01) as did urethritis diagnosis rates (P < 0.01). CONCLUSION: Between 1997 and 2007, annual health plan chlamydia rates increased significantly for both women and men. These trends may be due in part to increased testing rates and increased use of more sensitive tests, but they likely do not explain the increased urethritis rates. During this same interval, we observed steady declines in PID rates, consistent with other national data sources.

Measuring the uptake and impact of Chlamydia screening programs--easier said than done.

The passage of the landmark United States (U.S.) Patient Protection and Affordable Care Act (ACA) of 2010 has placed a new emphasis on prevention services, including increased access, coverage, and improved quality of care. In this legislation, chlamydia screening qualifies along with other preventive services (The Patient Protection and Affordable Care Act, P.H. 111-148, March 2010, §2,713) as an essential health service benefit by virtue of having an "A" rating ("strongly recommended") from the U.S. Preventive Services Task Force. However, along with this important commitment of public health resources comes accountability by demonstrating outcomes and results. It should not come as a surprise that in the current era of unprecedented government budget reductions, there is a compelling need for evidence-based prioritization and impact assessment. Funding agencies increasingly need health program data to show the impact of investment in preventive services, and chlamydia screening is no exception. However, measuring the population-level impact of chlamydia screening expansion in the U.S. since the 1980s has been problematic; conflicting data on screening uptake, chlamydia burden, and adverse reproductive outcomes, including pelvic inflammatory disease (PID) and tubal factor infertility, have all been challenging to interpret, despite compelling epidemiologic evidence supporting intervention.

Chlamydia trachomatis trends in the United States among persons 14 to 39 years of age, 1999-2008.

BACKGROUND: We report the first population-based assessment of national trends in chlamydia prevalence in the United States. METHODS: We investigated trends in chlamydia prevalence in representative samples of the U.S. population aged 14 to 39 years using data from five 2-year survey cycles of the National Health and Nutrition Examination Survey from 1999 to 2008. Prevalence estimates and 95% confidence intervals (CI) are reported stratified by age, gender, and race/ethnicity. Percent change in prevalence over this time period was estimated from regression models. RESULTS: In the 2007-2008 cycle, chlamydia prevalence among participants aged 14 to 39 years was 1.6% (95% CI: 1.1%-2.4%). Prevalence was higher among females (2.2%, 95% CI: 1.4%-3.4%) than males (1.1%, 95% CI: 0.7%-1.7%). Prevalence among non-Hispanic black persons was 6.7% (95% CI: 4.6%-9.9%) and was 2.5% (95% CI: 1.6%-3.8%) among adolescents aged 14 to 19 years. Over the five 2-year cycles, there was an estimated 40% reduction (95% CI: 8%-61%) in prevalence among participants aged 14 to 39 years. Decreases in prevalence were notable in men (53% reduction, 95% CI: 19%-72%), adolescents aged 14 to 19 years (48% reduction, 95% CI: 11%-70%), and adolescent non-Hispanic black persons (45%, reduction, 95% CI: 4%-70%). There was no change in prevalence among females aged 14 to 25 years, the population targeted for routine annual screening. CONCLUSIONS: On the basis of population estimates of chlamydia prevalence, the overall chlamydia burden in the United States decreased from 1999 to 2008. However, there remains a need to reduce prevalence in populations most at risk and to reduce racial disparities.

A review of the epidemiology, diagnosis and evidence-based management of Mycoplasma genitalium.

Mycoplasma genitalium is attracting increasing recognition as an important sexually transmitted pathogen. Presented is a review of the epidemiology, detection, presentation and management of M. genitalium infection. Accumulating evidence suggests that M. genitalium is an important cause of non-gonococcal, non-chlamydial urethritis and cervicitis, and is linked with pelvic inflammatory disease and, possibly, obstetric complications. Although there is no standard detection assay, several nucleic acid amplification tests have >95% sensitivity and specificity for M. genitalium. To date, there is a general lack of established protocols for screening in public health clinics. Patients with urethritis or cervicitis should be screened for M. genitalium and some asymptomatic sub-groups should be screened depending on individual factors and local prevalence. Investigations estimating M. genitalium geographic prevalence document generally low incidence, but some communities exhibit infection frequencies comparable to that of Chlamydia trachomatis. Accumulating evidence supports an extended regimen of azithromycin for treatment of M. genitalium infection, as data suggest that stat 1 g azithromycin may be less effective. Although data are limited, azithromycin-resistant cases documented to date respond to an appropriate fluoroquinolone (e.g. moxifloxacin). Inconsistent clinical recognition of M. genitalium may result in treatment failure and subsequent persistence due to ineffective antibiotics. The contrasting nature of existing literature regarding risks of M. genitalium infection emphasises the need for further carefully controlled studies of this emerging pathogen.

What is the cost of pelvic inflammatory disease and how much could be prevented by screening for chlamydia trachomatis? Cost analysis of the Prevention of Pelvic Infection (POPI) trial.

OBJECTIVES: To describe healthcare settings attended by women with clinical pelvic inflammatory disease (PID), to calculate the cost of a PID episode and to estimate how many cases could be prevented in London annually at current chlamydia screening levels. METHODS: An ethnically diverse sample of 2259 16-24 year old, sexually active, female London students were recruited to a chlamydia screening trial in 2004-2006 of whom 94% (2115) were followed up after 12 months for incidence of PID. A cost analysis examined healthcare settings attended by women with PID, the cost of an episode of PID and the number of cases of PID in London due to untreated chlamydia at baseline that could be prevented per year at 2009 annual screening levels. RESULTS: Of 35 PID cases, 17 (47%) first presented in general practice, 15 (42%) at a genitourinary medicine clinic, two elsewhere and one was admitted to hospital. The average number of consultations for a PID episode was 2.0 (range 1-4) and the average cost was £163 (range £29-960). Assuming 414,345 sexually active women aged 16-24 in London, 6% chlamydia prevalence at baseline and a 7.3% difference in PID rates between screened and unscreened chlamydia positives, 391 (95% CI--44 to 882) cases of chlamydia-associated PID costing £63,733 could be prevented each year in London at 21.5% 2009 annual screening levels. CONCLUSIONS: Most women with PID were managed in the community. The number and cost of PID cases prevented by a single annual chlamydia screen is low suggesting that cost effectiveness may depend mainly on the prevention of long-term sequelae.

The program cost and cost-effectiveness of screening men for Chlamydia to prevent pelvic inflammatory disease in women.

BACKGROUND: Because men transmit Chlamydia trachomatis to women, screening men to prevent pelvic inflammatory disease in women may be a viable strategy. However, the cost-effectiveness of this approach requires careful assessment. METHODS: Data from a demonstration project and longitudinal study that examined screening men for chlamydia were applied to a compartment-based transmission model to estimate the cost-effectiveness of screening men for chlamydia compared with alternative interventions, including expanded screening of women and combining disease investigation specialist-provided partner notification with screening. Cases of pelvic inflammatory disease and quality-adjusted life years lost were the primary outcome measures. A male screening program that screened 1% of men in the population annually was modeled. RESULTS: A program targeting high-risk men for screening (those with a larger number of partners in the previous year than the general population and a higher chlamydia prevalence) was cost saving compared with using equivalent program dollars to expand screening of lower-risk women. Combining partner notification with male screening was more effective than screening men alone. In sensitivity analyses, the male program was not always cost saving but averaged $10,520 per quality-adjusted life year saved over expanded screening of women. CONCLUSIONS: Screening men can be a cost-effective alternative to screening women, but the men screened must have a relatively high prevalence compared with the women to whom screening would be expanded (under baseline assumptions, the prevalence in screened men was 86% higher than that of screened women). These modeling results suggest that programs targeting venues that have access to high-risk men can be effective tools in chlamydia prevention.

Cost-effectiveness of screening strategies for Chlamydia trachomatis using cervical swabs, urine, and self-obtained vaginal swabs in a sexually transmitted disease clinic setting.

BACKGROUND: We evaluated the cost-effectiveness of Chlamydia screening strategies that use different methods of specimen collection: cervical swabs, urines, and self-obtained vaginal swabs. METHODS: A decision analysis was modeled for a hypothetical cohort of 10,000 per year of women attending sexually transmitted disease (STD) clinics. Incremental cost-effectiveness of 4 screening strategies were compared: 1) Endocervical DNA probe test (PACE2, Gen-Probe), 2) Endocervical AC2 (Aptima Combo 2, Gen-Probe), 3) Self-Obtained Vaginal AC2, and 4) Urine AC2. Sensitivities of the vaginal, urine, and cervical AC2 tests were derived from 324 women attending STD clinics. The primary outcome was cases of pelvic inflammatory disease prevented. The model incorporated programmatic screening and treatment costs and medical cost savings from sequelae prevented. RESULTS: Chlamydia prevalence in the sampled population was 11.1%. Sensitivities of vaginal, urine, and cervical AC2 were 97.2%, 91.7%, and 91.7%, respectively. The sensitivity of the DNA probe was derived from the literature and estimated at 68.8%. The self-obtained vaginal AC2 strategy was the least expensive and the most cost-effective, preventing 17 more cases of pelvic inflammatory disease than the next least expensive strategy. CONCLUSIONS: Use of a vaginal swab to detect Chlamydia in this STD clinic population was cost-saving and cost-effective.

Cost effectiveness of home based population screening for Chlamydia trachomatis in the UK: economic evaluation of chlamydia screening studies (ClaSS) project.

OBJECTIVE: To investigate the cost effectiveness of screening for Chlamydia trachomatis compared with a policy of no organised screening in the United Kingdom. DESIGN: Economic evaluation using a transmission dynamic mathematical model. SETTING: Central and southwest England. PARTICIPANTS: Hypothetical population of 50,000 men and women, in which all those aged 16-24 years were invited to be screened each year. MAIN OUTCOME MEASURES: Cost effectiveness based on major outcomes averted, defined as pelvic inflammatory disease, ectopic pregnancy, infertility, or neonatal complications. RESULTS: The incremental cost per major outcome averted for a programme of screening women only (assuming eight years of screening) was 22,300 pounds (33,000 euros; $45,000) compared with no organised screening. For a programme screening both men and women, the incremental cost effectiveness ratio was approximately 28,900 pounds. Pelvic inflammatory disease leading to hospital admission was the most frequently averted major outcome. The model was highly sensitive to the incidence of major outcomes and to uptake of screening. When both were increased the cost effectiveness ratio fell to 6200 pound per major outcome averted for screening women only. CONCLUSIONS: Proactive register based screening for chlamydia is not cost effective if the uptake of screening and incidence of complications are based on contemporary empirical studies, which show lower rates than commonly assumed. These data are relevant to discussions about the cost effectiveness of the opportunistic model of chlamydia screening being introduced in England.

Overestimation of complication rates in evaluations of Chlamydia trachomatis screening programmes--implications for cost-effectiveness analyses.

BACKGROUND: Cost-effectiveness analyses of screening programmes for asymptomatic Chlamydia trachomatis infection suggest that screening at low prevalences in the population is cost-effective. However, the decision models in these studies are based on assumptions about the risk of complications, which are derived from the literature. Incorrect assumptions may lead to under- or overestimation of the effectiveness of screening. The first objective of this paper is to evaluate the assumptions about the probability of complications after an asymptomatic C. trachomatis infection. The second objective is to calculate alternative rates by using available data on the incidence of complications. METHODS: We identified cost-effectiveness studies via Medline, and evaluated these for the evidence for the quoted probabilities. In addition, the probability of complications was calculated for Amsterdam from available registration data. RESULTS: In the three studies that were identified, the assumptions for the rates of pelvic inflammatory disease (PID) (clinical and subclinical) after C. trachomatis infection varied from 15% to 80%, and for ectopic pregnancy, tubal factor infertility, and chronic pelvic pain after PID from 5-25%, 10-20%, and 18-30%, respectively. The assumptions were based on data from high-risk populations, case-control data, and data not accounting for misdiagnoses. Using data obtained from local registrations, we estimated the probability of a clinical PID (0.43%), ectopic pregnancy (0.07%), and tubal factor infertility (0.02%) for women with a current infection. These estimates were consistently lower than the estimates based on the literature. CONCLUSIONS: We argue that an overestimation of the current complication rates is likely. The effect of overestimation is potentially the greatest in populations with a low prevalence, since the currently assumed cost savings associated with screening may disappear when using more realistic estimates for complications.

Cost-effectiveness of screening swab or urine specimens for Chlamydia trachomatis from young Canadian women in Ontario.

BACKGROUND: Undetected and untreated Chlamydia trachomatis infections can result in a significant health burden. Diagnostic testing refers to tests performed on patients with symptoms, whereas screening refers to testing specimens in asymptomatic patients. The goal of diagnostic testing and screening programs are early identification of infections to prevent upper tract infection and transmission to other partners. GOAL: To compare the costs and outcomes of alternative diagnostic testing and screening programs for women ages 15 to 24 years in the province of Ontario, Canada. STUDY DESIGN: Using outcome probabilities from the literature and a consensus group, together with the costs from insurance billing, a decision analytic model was constructed to determine the baseline risk of C trachomatis and related sequelae. Seven diagnostic testing and screening programs were compared over a 10-year period. The programs compared included the use of nucleic acid amplification assays collected from urine or endocervical swab specimens. RESULTS: Largely because of lower sensitivity the urine-based testing or screening programs were dominated by the swab-based programs. The move from swab-based testing to a swab-based screening program for high-risk women costs $1873 per case of C trachomatis averted. Expanding the program further to include all women in Ontario between 15 and 24 years of age is considerably more costly at $5990 per case averted. CONCLUSIONS: It is more costly and more effective to screen and treat high-risk women ages 15 to 24 years for C trachomatis than to perform only swab-based diagnostic testing on symptomatic women. Expanding the screening program to include all women ages 15 to 24 years is considerably more expensive and only moderately more effective than screening only high-risk women.