Rise and fall of the new variant ofChlamydia trachomatisin Sweden: mathematical modelling study

Abstract

ObjectivesA new variant of Chlamydia trachomatis (nvCT) was discovered in Sweden in 2006. The nvCT has a plasmid deletion, which escaped detection by two nucleic acid amplification tests (Abbott-Roche, AR), which were used in 14 of 21 Swedish counties. The objectives of this study were to assess when and where nvCT emerged in Sweden, the proportion of nvCT in each county and the role of a potential fitness difference between nvCT and co-circulating wild-type strains (wtCT).MethodsWe used a compartmental mathematical model describing the spatial and temporal spread of nvCT and wtCT. We parameterised the model using sexual behaviour data and Swedish spatial and demographic data. We used Bayesian inference to fit the model to surveillance data about reported diagnoses of chlamydia infection in each county and data from four counties that assessed the proportion of nvCT in multiple years.ResultsModel results indicated that nvCT emerged in central Sweden (Dalarna, Gävleborg, Västernorrland), reaching a proportion of 1% of prevalent CT infections in late 2002 or early 2003. The diagnostic selective advantage enabled rapid spread of nvCT in the presence of high treatment rates. After detection, the proportion of nvCT decreased from 30%–70% in AR counties and 5%–20% in counties that Becton Dickinson tests, to around 5% in 2015 in all counties. The decrease in nvCT was consistent with an estimated fitness cost of around 5% in transmissibility or 17% reduction in infectious duration.ConclusionsWe reconstructed the course of a natural experiment in which a mutant strain of C. trachomatis spread across Sweden. Our modelling study provides support, for the first time, of a reduced transmissibility or infectious duration of nvCT. This mathematical model improved our understanding of the first nvCT epidemic in Sweden and can be adapted to investigate the impact of future diagnostic escape mutants.

Changes in the Trend of Sexually Acquired Chlamydia Infections in Sweden and the Role of Testing: A Time Series Analysis

“…This difference in the rate of increase could not be explained by nvCT because it emerged in 1 to 3 counties in 2002 to 2003 and gradually spread to all unable-to-detect counties toward 2006, as was estimated in a modeling study. 13 The biggest long-term role nvCT had was national reinforcement of control measures (testing and following partner notification) in the second period, including adoption of the National action plan for chlamydia prevention. 27 During the period 2009–2018, chlamydia notification rates continued to decline in both groups of counties with the proportion of nvCT among all chlamydia cases dropping to low levels (5%) in the respective group of counties toward 2015.…”

“… 9 , 10 This unforeseen incident led to false-negative test results, 11 leading to many thousands of undetected cases of chlamydia and missed partner notification, even before 2006. 12 , 13 After the introduction of assays able to detect nvCT in all counties, the national notification rates of chlamydia increased in 2007 to 2008 owing to the detection of accumulated undiagnosed cases of nvCT. 14 Meanwhile, only sporadic or no cases of nvCT were reported in a number of European countries and the United States.…”

Diagnosis of Chlamydia trachomatis genital infections in the era of genomic medicine

“…Earlier versions of some commercial NAAT systems had failed to detect this variant as the targets for these NAATs were located in the acquired deletion site of the plasmid. While designing in-house PCRs or using commercial NAAT systems for CT detection, ability to detect this variant should be considered to avoid false-negative results [66][67][68].…”

Targeted surveillance strategies for efficient detection of novel antibiotic resistance variants

“…Use of traditional nucleic acid amplification tests (NAATs) for pathogen identification and genotype-based diagnostics for antibiotic resistance can select for genetic variants that escape detection ( Smid et al, 2019 ). Mutations and/or deletions at the NAAT target locus that cause an amplification failure have arisen in Neisseria gonorrhoeae, Chlamydia trachomatis, Staphylococcus aureus, and Plasmodium falciparum , resulting in false negative diagnostic errors only detected when using another diagnostic platform ( Berhane et al, 2018 ; Herrmann et al, 2008 ; Guglielmino et al, 2019 ; Lee et al, 2018a ).…”