Epidemiological, social, diagnostic and economic evaluation of population screening for genital chlamydial infection

OBJECTIVES: To investigate epidemiological, social, diagnostic and economic aspects of chlamydia screening in non-genitourinary medicine settings. METHODS: Linked studies around a cross-sectional population-based survey of adult men and women invited to collect urine and (for women) vulvovaginal swab specimens at home and mail these to a laboratory for testing for Chlamydia trachomatis. Specimens were used in laboratory evaluations of an amplified enzyme immunoassay (PCE EIA) and two nucleic acid amplification tests [Cobas polymerase chain reaction (PCR), Becton Dickinson strand displacement amplification (SDA)]. Chlamydia-positive cases and two negative controls completed a risk factor questionnaire. Chlamydia-positive cases were invited into a randomised controlled trial of partner notification strategies. Samples of individuals testing negative completed psychological questionnaires before and after screening. In-depth interviews were conducted at all stages of screening. Chlamydia transmission and cost-effectiveness of screening were investigated in a transmission dynamic model. SETTING AND PARTICIPANTS: General population in the Bristol and Birmingham areas of England. In total, 19,773 women and men aged 16-39 years were randomly selected from 27 general practice lists. RESULTS: Screening invitations reached 73% (14,382/19,773). Uptake (4731 participants), weighted for sampling, was 39.5% (95% CI 37.7, 40.8%) in women and 29.5% (95% CI 28.0, 31.0%) in men aged 16-39 years. Chlamydia prevalence (219 positive results) in 16-24 year olds was 6.2% (95% CI 4.9, 7.8%) in women and 5.3% (95% CI 4.4, 6.3%) in men. The case-control study did not identify any additional factors that would help target screening. Screening did not adversely affect anxiety, depression or self-esteem. Participants welcomed the convenience and privacy of home-sampling. The relative sensitivity of PCR on male urine specimens was 100% (95% CI 89.1, 100%). The combined relative sensitivities of PCR and SDA using female urine and vulvovaginal swabs were 91.8% (86.1, 95.7, 134/146) and 97.3% (93.1, 99.2%, 142/146). A total of 140 people (74% of eligible) participated in the randomised trial. Compared with referral to a genitourinary medicine clinic, partner notification by practice nurses resulted in 12.4% (95% CI -3.7, 28.6%) more patients with at least one partner treated and 22.0% (95% CI 6.1, 37.8%) more patients with all partners treated. The health service and patients costs (2005 prices) of home-based postal chlamydia screening were 21.47 pounds (95% CI 19.91 pounds, 25.99) per screening invitation and 28.56 pounds (95% CI 22.10 pounds, 30.43) per accepted offer. Preliminary modelling found an incremental cost-effectiveness ratio (2003 prices) comparing screening men and women annually to no screening in the base case of 27,000 pounds/major outcome averted at 8 years. If estimated screening uptake and pelvic inflammatory disease incidence were increased, the cost-effectiveness ratio fell to 3700 pounds/major outcome averted. CONCLUSIONS: Proactive screening for chlamydia in women and men using home-collected specimens was feasible and acceptable. Chlamydia prevalence rates in men and women in the general population are similar. Nucleic acid amplification tests can be used on first-catch urine specimens and vulvovaginal swabs. The administrative costs of proactive screening were similar to those for opportunistic screening. Using empirical estimates of screening uptake and incidence of complications, screening was not cost-effective.

Uptake of regular chlamydia testing by U.S. women: a longitudinal study

Background Routine chlamydia screening is a recommended preventive intervention for sexually active women aged ≤25 years in the U.S. but rates of regular uptake are not known. Purpose This study aimed to examine rates of annual chlamydia testing and factors associated with repeat testing in a population of U.S. women. Methods Women aged 15–25 years at any time from January 1, 2002, to December 31, 2006 who were enrolled in 130 commercial health plans were included. Data relating to chlamydia tests were analyzed in 2009. Chlamydia testing rates (per 100 woman-years) by age and rates of repeated annual testing were estimated. Poisson regression was used to examine the effects of age and previous testing on further chlamydia testing within the observation period. Results In total, 2,632,365 women were included. The chlamydia testing rate over the whole study period was 13.6 per 100 woman years after adjusting for age-specific sexual activity; 8.5 (95% CI=6.0, 12.3) per 100 woman-years in those aged 15 years; and 17.7 (95% CI=17.1, 18.9) in those aged 25 years. Among women enrolled for the entire 5-year study period, 25.9% had at least one test but only 0.1% had a chlamydia test every year. Women tested more than once and older women were more likely to be tested again in the observation period. Conclusions The low rates of regular annual chlamydia testing do not comply with national recommendations and would not be expected to have a major impact on the control of chlamydia infection at the population level.

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.

Selective immunisation strategy to protect newborns at risk for transmission of hepatitis B: retrospective audit of vaccine uptake

BACKGROUND: 90% of newborns infected perinatally will develop chronic hepatitis B infection with the risk of liver cirrhosis or hepatocellular carcinoma. In Switzerland, screening of all pregnant women for hepatitis B virus (HBV) has been recommended since 1983. Neonates at risk for perinatally acquired HBV are passively and actively immunised immediately after birth as well as at 1 and 6 months of age. The objective of this study was to evaluate the proportion of newborns immunised in accordance with the proposed vaccination schedule. METHODS: Patient records of 3997 mothers who gave birth to a liveborn infant during a two-year period at Zürich University Hospital were screened by computer. 128 women were identified as HBsAg positive or anti-HBc alone positive. Of 133 infants born to these mothers, complete data were available for 94 (71%). RESULTS: Immunisation was started in 88 infants (94%), but only in 78 (83%) within the first 24 hours of life. 85 (90%) received the 2nd immunisation but only 72 (77%) within the given time limit. 80 (85%) of the infants received the 3rd immunisation but only 69 (73%) within the correct time limit. In summary, only 51 (54%) of the infants at risk for HBV infection were immunised correctly (immunoglobulin within 24 hours and active prophylaxis at 0, 1 and 6 months). CONCLUSIONS: The success of the immunisation strategy following maternal screening and selective immunisation of newborns at risk for HBV infection is limited for various reasons (lack of screening results at birth, problems with correct documentation and communication). To overcome these drawbacks, selective vaccination strategy should be improved and general vaccination strategy, including infants, should be reconsidered.

Repeat chlamydia screening among adolescents: cohort study in a school-based programme in New Orleans

OBJECTIVES To describe uptake of chlamydia screening, determine rates of repeated yearly screening and investigate determinants of repeated participation in an organised school-based screening programme. METHODS The authors analysed data from 1995 to 2005 from female and male students in up to 13 schools in New Orleans, Louisiana, USA. The authors calculated proportions of students tested among all enrolled students and among those with parental consent and the percentage of positive chlamydia tests in each school year. The authors used random effects logistic regression to examine the effect of past screening history on subsequent participation. RESULTS 35 041 students were registered for at least one school year. Overall coverage was >30% in all school years. Among all students registered for 4 years, 10.6% (95% CI 9.3% to 12.0%) of women and 12.7% (95% CI 11.2% to 14.2%) of men had a test every year. Among students with parental consent for 4 years, 49.3% (95% CI 44.6% to 54.1%) of women and 59.3% (95% CI 54.5% to 64.0%) of men had a test every year. Among students registered for 2 or more years, those with a previous positive chlamydia test were less likely to have a subsequent test (female adjusted OR 0.77, 95% CI 0.67 to 0.88 and male adjusted OR 0.84, 95% CI 0.69 to 1.02). Chlamydia positivity increased over time. CONCLUSIONS High levels of uptake can be achieved in school-based chlamydia screening programmes, but repeated yearly screening is difficult to sustain over time.

Development and Validation of a Fast and Homogeneous Cell-Based Fluorescence Screening Assay for Divalent Metal Transporter 1 (DMT1/SLC11A2) Using the FLIPR Tetra.

Divalent metal ion transporter 1 (DMT1) is a proton-coupled Fe(2+) transporter that is essential for iron uptake in enterocytes and for transferrin-associated endosomal iron transport in many other cell types. DMT1 dysfunction is associated with several diseases such as iron overload disorders and neurodegenerative diseases. The main objective of the present work is to develop and validate a fluorescence-based screening assay for DMT1 modulators. We found that Fe(2+) or Cd(2+) influx could be reliably monitored in calcium 5-loaded DMT1-expressing HEK293 cells using the FLIPR Tetra fluorescence microplate reader. DMT1-mediated metal transport shows saturation kinetics depending on the extracellular substrate concentration, with a K0.5 value of 1.4 µM and 3.5 µM for Fe(2+) and Cd(2+), respectively. In addition, Cd(2+) was used as a substrate for DMT1, and we find a Ki value of 2.1 µM for a compound (2-(3-carbamimidoylsulfanylmethyl-benzyl)-isothiourea) belonging to the benzylisothioureas family, which has been identified as a DMT1 inhibitor. The optimized screening method using this compound as a reference demonstrated a Z' factor of 0.51. In summary, we developed and validated a sensitive and reproducible cell-based fluorescence assay suitable for the identification of compounds that specifically modulate DMT1 transport activity.

Guineensine is a novel inhibitor of endocannabinoid uptake showing cannabimimetic behavioral effects in BALB/c mice

High-content screening led to the identification of the N-isobutylamide guineensine from Piper nigrum as novel nanomolar inhibitor (EC50 = 290 nM) of cellular uptake of the endocannabinoid anandamide (AEA). Noteworthy, guineensine did not inhibit endocannabinoid degrading enzymes fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL) nor interact with cannabinoid receptors or fatty acid binding protein 5 (FABP5), a major cytoplasmic AEA carrier. Activity-based protein profiling showed no inhibition of serine hydrolases. Guineensine also inhibited the cellular uptake of 2-arachidonoylglycerol (2-AG). Preliminary structure–activity relationships between natural guineensine analogs indicate the importance of the alkyl chain length interconnecting the pharmacophoric isobutylamide and benzodioxol moieties for AEA cellular uptake inhibition. Guineensine dose-dependently induced cannabimimetic effects in BALB/c mice shown by strong catalepsy, hypothermia, reduced locomotion and analgesia. The catalepsy and analgesia were blocked by the CB1 receptor antagonist rimonabant (SR141716A). Guineensine is a novel plant natural product which specifically inhibits endocannabinoid uptake in different cell lines independent of FAAH. Its scaffold may be useful to identify yet unknown targets involved in endocannabinoid transport.