Sereina A. Herzog

The role of reinfection and partner notification in the efficacy of Chlamydia screening programs.

Repeated Chlamydia trachomatis infections after treatment are common. One reason is reinfection from untreated partners in ongoing sexual partnerships. Mathematical models that are used to predict the impact of screening on reducing chlamydia prevalence often do not incorporate reinfection and might overestimate the expected impact. We describe a pair compartmental model that explicitly incorporates sexual partnership duration and reinfection. The pair model predicts a weaker impact of screening when compared directly with a model that does not accommodate partnerships. Effective management of sex partners to prevent reinfection might need to be strengthened in chlamydia control programs.

Timing of progression from Chlamydia trachomatis infection to pelvic inflammatory disease: a mathematical modelling study

BackgroundPelvic inflammatory disease (PID) results from the ascending spread of microorganisms from the vagina and endocervix to the upper genital tract. PID can lead to infertility, ectopic pregnancy and chronic pelvic pain. The timing of development of PID after the sexually transmitted bacterial infection Chlamydia trachomatis (chlamydia) might affect the impact of screening interventions, but is currently unknown. This study investigates three hypothetical processes for the timing of progression: at the start, at the end, or throughout the duration of chlamydia infection.MethodsWe develop a compartmental model that describes the trial structure of a published randomised controlled trial (RCT) and allows each of the three processes to be examined using the same model structure. The RCT estimated the effect of a single chlamydia screening test on the cumulative incidence of PID up to one year later. The fraction of chlamydia infected women who progress to PID is obtained for each hypothetical process by the maximum likelihood method using the results of the RCT.ResultsThe predicted cumulative incidence of PID cases from all causes after one year depends on the fraction of chlamydia infected women that progresses to PID and on the type of progression. Progression at a constant rate from a chlamydia infection to PID or at the end of the infection was compatible with the findings of the RCT. The corresponding estimated fraction of chlamydia infected women that develops PID is 10% (95% confidence interval 7-13%) in both processes.ConclusionsThe findings of this study suggest that clinical PID can occur throughout the course of a chlamydia infection, which will leave a window of opportunity for screening to prevent PID.

Effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections: observational study, systematic reviews and mathematical modelling

BACKGROUND Partner notification is essential to the comprehensive case management of sexually transmitted infections. Systematic reviews and mathematical modelling can be used to synthesise information about the effects of new interventions to enhance the outcomes of partner notification. OBJECTIVE To study the effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections (STIs). DESIGN Secondary data analysis of clinical audit data; systematic reviews of randomised controlled trials (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) published from 1 January 1966 to 31 August 2012 and of studies of health-related quality of life (HRQL) [MEDLINE, EMBASE, ISI Web of Knowledge, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] published from 1 January 1980 to 31 December 2011; static models of clinical effectiveness and cost-effectiveness; and dynamic modelling studies to improve parameter estimation and examine effectiveness. SETTING General population and genitourinary medicine clinic attenders. PARTICIPANTS Heterosexual women and men. INTERVENTIONS Traditional partner notification by patient or provider referral, and new partner notification by expedited partner therapy (EPT) or its UK equivalent, accelerated partner therapy (APT). MAIN OUTCOME MEASURES Population prevalence; index case reinfection; and partners treated per index case. RESULTS Enhanced partner therapy reduced reinfection in index cases with curable STIs more than simple patient referral [risk ratio (RR) 0.71; 95% confidence interval (CI) 0.56 to 0.89]. There are no randomised trials of APT. The median number of partners treated for chlamydia per index case in UK clinics was 0.60. The number of partners needed to treat to interrupt transmission of chlamydia was lower for casual than for regular partners. In dynamic model simulations, >10% of partners are chlamydia positive with look-back periods of up to 18 months. In the presence of a chlamydia screening programme that reduces population prevalence, treatment of current partners achieves most of the additional reduction in prevalence attributable to partner notification. Dynamic model simulations show that cotesting and treatment for chlamydia and gonorrhoea reduce the prevalence of both STIs. APT has a limited additional effect on prevalence but reduces the rate of index case reinfection. Published quality-adjusted life-year (QALY) weights were of insufficient quality to be used in a cost-effectiveness study of partner notification in this project. Using an intermediate outcome of cost per infection diagnosed, doubling the efficacy of partner notification from 0.4 to 0.8 partners treated per index case was more cost-effective than increasing chlamydia screening coverage. CONCLUSIONS There is evidence to support the improved clinical effectiveness of EPT in reducing index case reinfection. In a general heterosexual population, partner notification identifies new infected cases but the impact on chlamydia prevalence is limited. Partner notification to notify casual partners might have a greater impact than for regular partners in genitourinary clinic populations. Recommendations for future research are (1) to conduct randomised controlled trials using biological outcomes of the effectiveness of APT and of methods to increase testing for human immunodeficiency virus (HIV) and STIs after APT; (2) collection of HRQL data should be a priority to determine QALYs associated with the sequelae of curable STIs; and (3) standardised parameter sets for curable STIs should be developed for mathematical models of STI transmission that are used for policy-making. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Describing the progression from Chlamydia trachomatis and Neisseria gonorrhoeae to pelvic inflammatory disease: systematic review of mathematical modeling studies.

Background: Chlamydia screening is recommended to prevent pelvic inflammatory disease (PID). A systematic review was conducted to determine how the natural history of Chlamydia trachomatis or Neisseria gonorrhoeae infection and progression to PID have been described in mathematical modeling studies. Methods: Four databases, from their earliest dates to October 2009, and reference lists of included studies were searched. Models were defined as dynamic if progression from infection to PID was time dependent and static otherwise. Descriptions of the natural history of infection and parameter values used for progression to PID were extracted from all studies. Details of how disease progression was implemented were extracted from reports of dynamic models. Results: Forty-five publications from 40 unique models were included. Nine models were classed as dynamic, including 4 Markov, 3 compartmental, and 2 individual-based models. There were 28 static decision analysis models. For 3 publications, the model type could not be determined. Among the dynamic models, there were explicit statements that C. trachomatis could progress to PID uniformly throughout the infection, in the first 6 months of infection, in the second half of infection, or that there is a most likely interval from the initial infection for the development of PID, which varies from 1 to 12 months. In static models, the average fraction of cases of chlamydia developing PID was 22%. Conclusion: The reporting of key items in mathematical modeling studies about PID could be improved. The potential timings of progression to PID identified in this review can be investigated further to advance our understanding about how chlamydia screening interventions work to prevent PID.

Individual and Population Level Effects of Partner Notification for Chlamydia trachomatis

Partner notification (PN or contact tracing) is an important aspect of treating bacterial sexually transmitted infections (STIs), such as Chlamydia trachomatis. It facilitates the identification of new infected cases that can be treated through individual case management. PN also acts indirectly by limiting onward transmission in the general population. However, the impact of PN, both at the level of individuals and the population, remains unclear. Since it is difficult to study the effects of PN empirically, mathematical and computational models are useful tools for investigating its potential as a public health intervention. To this end, we developed an individual-based modeling framework called Rstisim. It allows the implementation of different models of STI transmission with various levels of complexity and the reconstruction of the complete dynamic sexual partnership network over any time period. A key feature of this framework is that we can trace an individual’s partnership history in detail and investigate the outcome of different PN strategies for C. trachomatis. For individual case management, the results suggest that notifying three or more partners from the preceding 18 months yields substantial numbers of new cases. In contrast, the successful treatment of current partners is most important for preventing re-infection of index cases and reducing further transmission of C. trachomatis at the population level. The findings of this study demonstrate the difference between individual and population level outcomes of public health interventions for STIs.

Insights into the timing of repeated testing after treatment for Chlamydia trachomatis: data and modelling study

Objectives The objective of this study was to determine the optimal time interval for a repeated Chlamydia trachomatis (chlamydia) test. Methods The authors used claims data for US women aged 15–25 years who were enrolled in commercial health insurance plans in the MarketScan database between 2002 and 2006. The authors determined the numbers of initial positive and negative tests that were followed by a repeated test and the positivity of repeated tests. The authors used a dynamic transmission pair model that reflects the partnership formation and separation processes in 15–25 year olds to determine the time course of repeated infections in women under different levels of notifying the current partner. The authors then explored the additional impact of repeated testing uptake on reducing chlamydia prevalence. Results 40% (4949/12 413) of positive tests were followed by a repeated test compared with 22% (89 119/402 659) of negative tests at any time. Positivity of repeated tests followed by an initial positive test was high: 15% (736) after a positive test versus 3% (2886) after a negative test. The transmission model showed a peak in repeated infections between 2 and 5 months after treatment. For a chlamydia testing uptake of 10% per year, the additional impact of repeated testing on reducing chlamydia population prevalence was modest. Conclusions The mathematical model predictions support the recommended interval for repeat chlamydia testing. This study provides information that can be used to design randomised controlled trials to determine more effective interventions to prevent chlamydial reinfection.

Maternal and neonatal outcomes in pregnant women with PCOS: comparison of different diagnostic definitions

STUDY QUESTION Does the prevalence of adverse maternal and neonatal outcomes vary in women diagnosed with polycystic ovary syndrome (PCOS) according to different definitions? SUMMARY ANSWER A comparison of different criteria revealed that there is a substantial risk for perinatal complications in PCOS women, regardless of the used definition. WHAT IS KNOWN ALREADY Pregnant women with PCOS are susceptible to perinatal complications. At present, there are three main definitions for PCOS. So far, we are aware of only one study, which found that the elevated risk for complications varied widely depending on the different phenotypes and features but only considered a relatively small sample size for some of the phenotypes. STUDY DESIGN, SIZE, DURATION Retrospective matched cohort study. PARTICIPANTS/MATERIALS, SETTING, METHODS Data of primiparous women with PCOS according to ESHRE/ASRM 2003 criteria and healthy controls giving birth to neonates ≥500 g were included. A total of 885 women were analysed: out of 177 women with PCOS, 85 (48.0%) met the National Institutes of Health (NIH) 1990 criteria, another 14 (7.9%) featured the additional phenotypes defined by The Androgen Excess and PCOS Society (AE-PCOS) 2006 criteria, 78 (44.1%) were classified as PCOS exclusively by the ESHRE/ASRM 2003 definition, and 708 represented the control group. MAIN RESULTS AND THE ROLE OF CHANCE The prevalence of adverse maternal (49.4 versus 64.3 versus 60.3%, P = 0.313) and neonatal (27.1 versus 35.7 versus 23.1%, P = 0.615) outcomes did not differ within the three PCOS groups (ESHRE/ASRM, NIH, AE-PCOS, respectively). Compared with healthy controls, the risk for maternal complications was increased in PCOS patients [odds ratio (OR) 2.57; 95% confidence interval (CI) 1.82-3.64; P < 0.001] while there was no difference in neonatal complications (OR 0.83; 95% CI 0.56-1.21; P = 0.343). LIMITATIONS, REASONS FOR CAUTION A limitation of our study is its retrospective design and the relatively small sample size, particularly in the AE-PCOS subgroup. WIDER IMPLICATIONS OF THE FINDINGS Since women with PCOS have, regardless of the used definition, a high risk of maternal and neonatal complications they should be informed and advised to follow regular checks in units where problems can be detected early to allow specialized care. STUDY FUNDING/COMPETING INTERESTS Marietta Blau Grant (Austrian Agency for International Cooperation in Education and Research; OeAD-GmbH) and mobility scholarship (Medical University of Graz).

Reinfection by untreated partners of people treated for Chlamydia trachomatis and Neisseria gonorrhoeae: mathematical modelling study

Objectives Reinfection after treatment for Chlamydia trachomatis or Neisseria gonorrhoeae reduces the effect of control interventions. We explored the impact of delays in treatment of current partners on the expected probability of reinfection of index cases using a mathematical model. Methods We used previously reported parameter distributions to calculate the probability that index cases would be reinfected by their untreated partners. We then assumed different delays between index case and partner treatment to calculate the probabilities of reinfection. Results In the absence of partner treatment, the medians of the expected reinfection probabilities are 19.4% (IQR 9.2–31.6%) for C trachomatis and 12.5% (IQR 5.6–22.2%) for N gonorrhoeae. If all current partners receive treatment 3 days after the index case, the expected reinfection probabilities are 4.2% (IQR 2.1–6.9%) for C trachomatis and 5.5% (IQR 2.6–9.5%) for N gonorrhoeae. Conclusions Quicker partner referral and treatment can substantially reduce reinfection rates for C trachomatis and N gonorrhoeae by untreated partners. The formula we used to calculate reinfection rates can be used to inform the design of randomised controlled trials of novel partner notification technologies like accelerated partner therapy.

Circadian Macular Volume Changes in the Healthy Human Choroid

PURPOSE To investigate a potential circadian fluctuation of the choroidal volume in healthy adults by enhanced depth imaging (EDI) via spectral-domain optical coherence tomography (SD OCT). DESIGN Prospective observational case series. METHODS Thirty healthy eyes of 15 healthy subjects with a median age of 26 years (range 22-55) underwent EDI SD OCT scans for macular choroidal volume measurement every 3 hours within a 24-hour period at a single tertiary center. The mean ocular perfusion pressure was calculated for each eye at each of the 8 time points as 2/3(mean arterial pressure-intraocular pressure [IOP]). The circadian fluctuation of the macular choroidal volume as well as the association with axial length, mean ocular perfusion pressure, or IOP was assessed using a linear mixed model. RESULTS Macular choroidal volume showed a significant circadian fluctuation (P < .05) and was lowest at midday (mean ± SD, 10.14 ± 2.62 mm(3)) and highest at 3 AM (mean ± SD, 10.66 ± 2.70 mm(3)). Of all factors tested, only mean ocular perfusion pressure showed a significant association with macular choroidal volume fluctuation (P = .016). CONCLUSIONS Macular choroidal volume shows a significant circadian pattern with higher values at night and lower values during the day in young adults. Besides time, mean ocular perfusion pressure is significantly associated with this fluctuation.

Direct and indirect effects of screening for Chlamydia trachomatis on the prevention of pelvic inflammatory disease: a mathematical modeling study.

Background: Pelvic inflammatory disease (PID) results from the ascending spread of microorganisms, including Chlamydia trachomatis, to the upper genital tract. Screening could improve outcomes by identifying and treating chlamydial infections before they progress to PID (direct effect) or by reducing chlamydia transmission (indirect effect). Methods: We developed a compartmental model that represents a hypothetical heterosexual population and explicitly incorporates progression from chlamydia to clinical PID. Chlamydia screening was introduced, with coverage increasing each year for 10 years. We estimated the separate contributions of the direct and indirect effects of screening on PID cases prevented per 100,000 women. We explored the influence of varying the time point at which clinical PID could occur and of increasing the risk of PID after repeated chlamydial infections. Results: The probability of PID at baseline was 3.1% by age 25 years. After 5 years, the intervention scenario had prevented 187 PID cases per 100,000 women and after 10 years 956 PID cases per 100,000 women. At the start of screening, most PID cases were prevented by the direct effect. The indirect effect produced a small net increase in PID cases, which was outweighed by the effect of reduced chlamydia transmission after 2.2 years. The later that progression to PID occurs, the greater the contribution of the direct effect. Increasing the risk of PID with repeated chlamydial infection increases the number of PID cases prevented by screening. Conclusions: This study shows the separate roles of direct and indirect PID prevention and potential harms, which cannot be demonstrated in observational studies.