Although we agree with Ghanem et al. that CSF TPPA titer is a valuable test for the diagnosis of neurosyphilis[1], we would like to emphasize that a cut-off TPPA titer should be recommended with caution as proposed by others [2]. Such semi-quantitative laboratory tests may vary depending on the operator or reagent. Our IQC from a single patient during a 2 years period showed that TPPA inaccuracy is about 2 titers (Table). Moreover, a 2 log2 variation is accepted by organisms providing samples for external quality assessment for syphilis serology [3]. Similarly to what occurs with neuroborreliosis, quantifying anti-treponema pallidum IgG (antiTp- IgG) in CSF, immunoassays in serum and intrathecal antibodies index could be a reliable approach for the diagnosis of neurosyphilis. We found some positive antiTp-IgG index in CSF with TPPA titers below 320, suggesting an intrathecal synthesis of anti-treponema pallidum IgG. The diagnosis of neurosyphilis still lacks a gold standard test and further research is warranted. 1. Ghanem, K.G., Cerebrospinal fluid treponemal antibody titres: a breakthrough in the diagnosis of neurosyphilis. Sex Transm Infect, 2020.
2. Marra, C.M., et al., Cerebrospinal Fluid Treponema pallidum Particle Agglutination Assay for Neurosyphilis Diagnosis. J Clin Microbiol, 2017. 55(6): p. 1865-1870.
3. Muller, I., et al., Is serological testing a reliable tool in laboratory diagnosis of syphilis? Meta-analysis of eight external quality control sur...
Although we agree with Ghanem et al. that CSF TPPA titer is a valuable test for the diagnosis of neurosyphilis[1], we would like to emphasize that a cut-off TPPA titer should be recommended with caution as proposed by others [2]. Such semi-quantitative laboratory tests may vary depending on the operator or reagent. Our IQC from a single patient during a 2 years period showed that TPPA inaccuracy is about 2 titers (Table). Moreover, a 2 log2 variation is accepted by organisms providing samples for external quality assessment for syphilis serology [3]. Similarly to what occurs with neuroborreliosis, quantifying anti-treponema pallidum IgG (antiTp- IgG) in CSF, immunoassays in serum and intrathecal antibodies index could be a reliable approach for the diagnosis of neurosyphilis. We found some positive antiTp-IgG index in CSF with TPPA titers below 320, suggesting an intrathecal synthesis of anti-treponema pallidum IgG. The diagnosis of neurosyphilis still lacks a gold standard test and further research is warranted. 1. Ghanem, K.G., Cerebrospinal fluid treponemal antibody titres: a breakthrough in the diagnosis of neurosyphilis. Sex Transm Infect, 2020.
2. Marra, C.M., et al., Cerebrospinal Fluid Treponema pallidum Particle Agglutination Assay for Neurosyphilis Diagnosis. J Clin Microbiol, 2017. 55(6): p. 1865-1870.
3. Muller, I., et al., Is serological testing a reliable tool in laboratory diagnosis of syphilis? Meta-analysis of eight external quality control surveys performed by the german infection serology proficiency testing program. J Clin Microbiol, 2006. 44(4): p. 1335-41.
The paper by Jordan SJ et al (1) is thought stimulating. The CDC guideline to regard 2-4 PMN/HPF as depicting NGU is possibly not widely observed, despite having been said 5 years ago (2). This and the inference that 1 or <1 PMN/HPF means no NGU must put a strain on those counting and poses the question of what variation might exist between observers.
When 5 different micro-organisms were sought but not found in urethritis, the invitation was there to consider the role of oral and anal bacteria and those occurring in BV. An association between this and NGU has been noted in the past (3). Unfortunately it was not taken into account here. It is also curious that when looking at the role of Ureaplasma species, the authors did not consider U.parvum. Admittedly, others have considered it to be less important than U.urealyticum (4) but not banished it to the graveyard completely.
Finally, the issue of bacterial load is important in considering pathogenicity. The authors state that they used quantitative PCRs but they did not provide ANY quantitative results. Why is that? These and longitudinal studies are required.
I believe the conclusion of the authors is not fully founded. Remember, Koch's postulates have been fulfilled for U.urealyticum (5).
REFERENCES
1. Jordan SJ, Toh E, Williams AJ, et al. Aetiology and prevalence of mixed-infections and mono-infections in non-gonococcal urethritis in men: a case-control study. Sex Transm Inf 2020;...
The paper by Jordan SJ et al (1) is thought stimulating. The CDC guideline to regard 2-4 PMN/HPF as depicting NGU is possibly not widely observed, despite having been said 5 years ago (2). This and the inference that 1 or <1 PMN/HPF means no NGU must put a strain on those counting and poses the question of what variation might exist between observers.
When 5 different micro-organisms were sought but not found in urethritis, the invitation was there to consider the role of oral and anal bacteria and those occurring in BV. An association between this and NGU has been noted in the past (3). Unfortunately it was not taken into account here. It is also curious that when looking at the role of Ureaplasma species, the authors did not consider U.parvum. Admittedly, others have considered it to be less important than U.urealyticum (4) but not banished it to the graveyard completely.
Finally, the issue of bacterial load is important in considering pathogenicity. The authors state that they used quantitative PCRs but they did not provide ANY quantitative results. Why is that? These and longitudinal studies are required.
I believe the conclusion of the authors is not fully founded. Remember, Koch's postulates have been fulfilled for U.urealyticum (5).
REFERENCES
1. Jordan SJ, Toh E, Williams AJ, et al. Aetiology and prevalence of mixed-infections and mono-infections in non-gonococcal urethritis in men: a case-control study. Sex Transm Inf 2020; 306-11.
2. Workowski KA, Bolan GA, Papp JR. Sexually transmitted disease treatment guidelines, 2015.MMWR Recomm Rep 2015; 64: 1-137.
3. Keane FE, Thomas BJ, Whitaker L, et al. An association between non-gonococcal urethritis and bacterial vaginosis and the implications for
patients and their sexual partners. Genitourin. Med 1997; 73: 373-7.
4. Zhang N, Wang R, Li X, et al. Are Ureaplasma spp. a cause of nongonococcal urethritis ? A systematic review and meta-analysis. PLoS One
2014; 9: e113771.
5. Taylor-Robinson D, Csonka GW, Prentice MJ. Human intra-urethral inoculation of ureaplasmas. Quart J Med 1977; 183: 309-26.
We have read the interesting manuscript “Antimicrobial resistance in Mycoplasma genitalium sampled from the British general population”, from Pitt et al.1 In 56 M. genitalium-positive specimens, macrolide resistance was detected in 9 (16.1%). These results agree with the low rate of resistance (<20%) detected in studies carried out mainly in general population,2 but contrast with the higher rates (>40%) obtained in patients mainly attended in sexually transmitted infections units.3 These two scenarios (general versus core population) could be considered in the management of the M. genitalium infection.
In our context (80-90% general population), the macrolide resistance rate was 16.3% (43/263).2 After detection of macrolide resistance-associated mutations with rapid techniques, guided antibiotic therapy was prescribed (azithromycin 500 mg day 1 and 250 mg days 2-5, or moxifloxacin) , and sexual partners control and test of cure after 3 weeks recommended. Despite patients adhering to the antibiotic regimen initially indicated, treatment failure was 6%.
Recently, a resistance-guided sequential treatment with doxycycline followed with azithromycin or moxifloxacin has been proposed.3 In this study the macrolide resistance rate was 68% and the treatment failure 7%. In our opinion, this strategy could be appropriate in populations with high macrolide resistance rate (main conclusion of this study), and healthcare contexts in that guided ther...
We have read the interesting manuscript “Antimicrobial resistance in Mycoplasma genitalium sampled from the British general population”, from Pitt et al.1 In 56 M. genitalium-positive specimens, macrolide resistance was detected in 9 (16.1%). These results agree with the low rate of resistance (<20%) detected in studies carried out mainly in general population,2 but contrast with the higher rates (>40%) obtained in patients mainly attended in sexually transmitted infections units.3 These two scenarios (general versus core population) could be considered in the management of the M. genitalium infection.
In our context (80-90% general population), the macrolide resistance rate was 16.3% (43/263).2 After detection of macrolide resistance-associated mutations with rapid techniques, guided antibiotic therapy was prescribed (azithromycin 500 mg day 1 and 250 mg days 2-5, or moxifloxacin) , and sexual partners control and test of cure after 3 weeks recommended. Despite patients adhering to the antibiotic regimen initially indicated, treatment failure was 6%.
Recently, a resistance-guided sequential treatment with doxycycline followed with azithromycin or moxifloxacin has been proposed.3 In this study the macrolide resistance rate was 68% and the treatment failure 7%. In our opinion, this strategy could be appropriate in populations with high macrolide resistance rate (main conclusion of this study), and healthcare contexts in that guided therapy could not be rapidly applied. On the other hand, adherence and adverse events associated with antibiotics used should be keeping in mind: 89.9% with doxycycline versus 100% with azithromycin, and 15.2% versus 8.6% , respectively.3 Moreover, other authors have described a lower adherence to doxycycline (100 mg/12h, 7 days) in M. genitalium infections and a clinical response <50%.
We think sequential resistance-guided therapy results should be more studied in the real medical practice, taking in care the different contexts of the population studied (general population versus core groups with more previous antibiotic treatments), as well as non-compliance and secondary effects due to unnecessary overtreatment with doxycycline in macrolide susceptible infections.
References
1. Pitt R, Unemo M, Sonnenberg P, Alexander S, Beddows S, Cole MJ, Clifton S, Mercer CH, Johnson AM, Ison CA, Field N. Antimicrobial resistance in Mycoplasma genitalium sampled from the British general population. Sex Transm Infect. 2020. pii: sextrans-2019-054129. doi: 10.1136/sextrans-2019-054129.
2. Piñeiro L, Idigoras P, de la Caba I, López-Olaizola M, Cilla G. Guided antibiotic therapy for Mycoplasma genitalium infections: Analysis of mutations associated with resistance to macrolides and fluoroquinolones. Enferm Infecc Microbiol Clin. 2019;37(6):394-7.
3. Read TRH, Fairley CK, Murray GL, Jensen JS, Danielewski J, Worthington K, Doyle M, Mokany E, Tan L, Chow EPF, Garland SM, Bradshaw CS. Outcomes of Resistance-guided Sequential Treatment of Mycoplasma genitalium Infections: A Prospective Evaluation. Clin Infect Dis. 2019;68(4):554-60.
We thank Piñeiro et al for their interest in our study using data from Britain’s third National Survey of Sexual Attitudes and Lifestyle (Natsal-3).1 This was a probability sample survey undertaken in 2010-12, with Mycoplasma genitalium testing results from urine available for over 4,500 participants aged 16-44 years.2 In this follow-up paper, we reported genotypic data on mutations associated with macrolide and fluoroquinolone resistance.
We read with interest that Piñeiro et al also found relatively low levels (<20%) of macrolide resistance in a Spanish, mainly general population sample in 2014-17.3 However, the low macrolide resistance (16%) found in our study is probably due not only to the general population sample, but also to the specimens being collected nearly a decade ago. Since 2010-12, there is evidence that macrolide resistance in M. genitalium has rapidly increased globally, and we anticipate finding higher levels of genotypic macrolide resistance in the general population in Britain in 2022 when Natsal-4 is expected to report findings.4 These data will be important to inform national and international understanding of incidence and prevalence as well as updated management and infection control strategies.
We appreciate both the relatively low treatment failure rate in the referenced Spanish study by Piñeiro et al,3 and the treatment strategy...
We thank Piñeiro et al for their interest in our study using data from Britain’s third National Survey of Sexual Attitudes and Lifestyle (Natsal-3).1 This was a probability sample survey undertaken in 2010-12, with Mycoplasma genitalium testing results from urine available for over 4,500 participants aged 16-44 years.2 In this follow-up paper, we reported genotypic data on mutations associated with macrolide and fluoroquinolone resistance.
We read with interest that Piñeiro et al also found relatively low levels (<20%) of macrolide resistance in a Spanish, mainly general population sample in 2014-17.3 However, the low macrolide resistance (16%) found in our study is probably due not only to the general population sample, but also to the specimens being collected nearly a decade ago. Since 2010-12, there is evidence that macrolide resistance in M. genitalium has rapidly increased globally, and we anticipate finding higher levels of genotypic macrolide resistance in the general population in Britain in 2022 when Natsal-4 is expected to report findings.4 These data will be important to inform national and international understanding of incidence and prevalence as well as updated management and infection control strategies.
We appreciate both the relatively low treatment failure rate in the referenced Spanish study by Piñeiro et al,3 and the treatment strategy informed by initial detection of macrolide resistance-associated mutations followed by azithromycin 1.5 g given over 5 days (if no macrolide resistance mutations detected) or moxifloxacin (if macrolide resistance mutations detected). This is in line with the current European guidelines.5 A similar but modified regimen using resistance-guided sequential treatment with doxycycline followed by azithromycin 2.5 g given over four days (if no macrolide resistance mutations) or moxifloxacin (if macrolide resistance mutations) is also described by Piñeiro et al, referencing a paper using sitafloxacin instead of moxifloxacin.6 Sitafloxacin may be more effective against M. genitalium than moxifloxacin because the doxycycline-sitafloxacin arm in the study clinically failed in only 7.8% of patients despite the observation that 20% of patients had ParC fluoroquinolone resistance-associated mutations.6 Furthermore, the cure rate for patients with M. genitalium samples with ParC S83I mutations (a common “fluoroquinolone resistance mutation”), possibly further potentiated by a concomitant GyrA M95I or D99N mutation, has been shown to be significantly higher with sitafloxacin compared to moxifloxacin.7 However, Durukan et al8 subsequently evaluated the same resistance-guided sequential treatment with doxycycline-moxifloxacin instead of doxycycline-sitafloxacin and found similar high cure rates.
Initiating empirical treatment of patients with, for example, symptomatic non-gonococcal urethritis with doxycycline, before laboratory results are available, currently appears to be the best choice because doxycycline will, (1) cure Chlamydia trachomatis infections, (2) cure 30-40% of M. genitalium infections,5 and (3) significantly decrease the M. genitalium load in most cases not achieving cure,6 which improves the cure rate of subsequent treatment. As Piñeiro et al mention,3 the adherence and adverse events of treatments are also important. However, the reported adherence to the doxycycline regimen in the studies discussed above was high, i.e. at 90-94%,6,8 and the adverse events were mainly mild grade 1. In fact, Durukan et al8 reported even fewer adverse events with doxycycline compared to azithromycin. Clearly, the adherence to treatment regimens and frequency of adverse events can significantly differ by setting, study population, and study.
There are still major gaps in our understanding about the distribution, natural history and pathology of M. genitalium, particularly in different anatomical sites, and about the sequelae of asymptomatic infections. For the moment, the primary focus in clinical practice should be on detecting and treating symptomatic patients (particularly with non-gonococcal urethritis and symptoms and/or signs of pelvic inflammatory disease), even though this may not be effective as a means to reduce population prevalence. We whole-heartedly agree with the need for more M. genitalium research, including on the epidemiology; pathogenesis; serious complications and sequelae; treatment approaches (sequential resistance-guided, ideal azithromycin dose regimen (1.5,3,5 2.0 g,9 2.5 g,6,8 or other, and how the total dose should be divided), associations with “fluoroquinolone resistance mutations” and treatment outcomes with different fluoroquinolones, and the pharmacokinetics/pharmacodynamics, compliance and adverse effects of the treatments in different settings), particularly where evaluated using randomised controlled clinical trials; and other mechanisms to manage and control M. genitalium including how to suppress AMR emergence. Ultimately, new antimicrobials and ideally a vaccine are needed for sustainable management and control of M. genitalium infections.
Magnus Unemo1, Pam Sonnenberg2, Nigel Field3
1 WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
2 Centre for Population Research in Sexual Health and HIV, Institute for Global Health, UCL, London, United Kingdom
3 Centre for Molecular Epidemiology and Translational Research, Institute for Global Health, UCL, London, United Kingdom
Correspondence to Dr Nigel Field, Centre for Molecular Epidemiology and Translational Research, Institute for Global Health, UCL, London WC1E 6JB, UK; nigel.field@ucl.ac.uk
Competing interests None.
REFERENCES
Pitt R, Unemo M, Sonnenberg P, et al. Antimicrobial resistance in Mycoplasma genitalium sampled from the British general population. Sex Transm Infect 2020. pii: sextrans-2019-054129. doi: 10.1136/sextrans-2019-054129.
Sonnenberg P, Ison CA, Clifton S, et al. Epidemiology of Mycoplasma genitalium in British men and women aged 16–44 years: evidence from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). Int J Epidemiol 2015;44:1982-94.
Piñeiro L, Idigoras P, de la Caba I, et al. Guided antibiotic therapy for Mycoplasma genitalium infections: Analysis of mutations associated with resistance to macrolides and fluoroquinolones. Enferm Infecc Microbiol Clin 2019;37:394-7.
Mercer CH, Clifton S, Prior G, et al. Collecting and exploiting data to understand a nation's sexual health needs: Implications for the British National Surveys of Sexual Attitudes and Lifestyles (Natsal). Sex Transm Infect 2019;95:159–61.
Jensen JS, Cusini M, Gomberg M, et al. 2016 European guideline on Mycoplasma genitalium infections. J Eur Acad Dermatol Venereol 2016;30:1650–6.
Read TRH, Fairley CK, Murray GL, et al. Outcomes of resistance-guided sequential treatment of Mycoplasma genitalium infections: A prospective evaluation. Clin Infect Dis 2019;68:554-60.
Murray GL, Bodiyabadu K, Danielewski J, et al. Moxifloxacin and sitafloxacin treatment failure in Mycoplasma genitalium infection: Association with parC mutation G248T (S83I) and concurrent gyrA mutations. J Infect Dis. 2019;jiz550. doi:10.1093/infdis/jiz550
Durukan D, Read TRH, Murray G, et al. Resistance-guided antimicrobial therapy using doxycycline-moxifloxacin and doxycycline-2.5g azithromycin for the treatment of Mycoplasma genitalium infection: efficacy and tolerability. Clin Infect Dis 2019;ciz1031. doi:10.1093/cid/ciz1031
Soni S, Horner P, Rayment M, et al. British Association for Sexual Health and HIV national guideline for the management of infection with Mycoplasma genitalium (2018). Int J STD AIDS. 2019;30:938–50.
Ang et al [1] discussed rising syphilis incidence among HIV positive men in Singapore. The diagnostic test used for syphilis in this study (RPR) is a non-specific treponemal antibody test. This limitation should be acknowledged while interpreting results. However, it is of good epidemiological value for public health programs for behavioural intervention. An important opportunity for sexual health promotion that can be missed if overlooked is post-treatment follow up for RPR titre monitoring. BASHH guidelines recommend follow up RPR titre post treatment until sero-fast or sustained 4 fold decrease in titre (at 3, 6 and 12 months).
An audit at our central London clinic showed that 31% of men had a bacterial STI when followed up for RPR monitoring post-treatment for syphilis [2]. Of 32 men (mean age 37 years; range 21- 75 years; 31 MSM), 11 were HIV positive. Six patients attended follow up visits at 3,6, and 12 months post treatment , 9 attended two follow up visits , 6 attended one follow up visit. Ten (31%) had a bacterial STI diagnosis (6 Chlamydia, 6 Gonorrhea, 1 LGV) during follow up. This highlighted the importance of STI screening and sexual health promotion for the MSM cohort during follow up for RPR monitoring in our clinic. Opportunistic screening for STI should be conducted across the globe where resources permit.
Reference:
[1] Ang LW, Wong C, Ng O et al. Incidence of syphilis among HIV-infected
men in Singapore, 2006–2017: temporal tren...
Ang et al [1] discussed rising syphilis incidence among HIV positive men in Singapore. The diagnostic test used for syphilis in this study (RPR) is a non-specific treponemal antibody test. This limitation should be acknowledged while interpreting results. However, it is of good epidemiological value for public health programs for behavioural intervention. An important opportunity for sexual health promotion that can be missed if overlooked is post-treatment follow up for RPR titre monitoring. BASHH guidelines recommend follow up RPR titre post treatment until sero-fast or sustained 4 fold decrease in titre (at 3, 6 and 12 months).
An audit at our central London clinic showed that 31% of men had a bacterial STI when followed up for RPR monitoring post-treatment for syphilis [2]. Of 32 men (mean age 37 years; range 21- 75 years; 31 MSM), 11 were HIV positive. Six patients attended follow up visits at 3,6, and 12 months post treatment , 9 attended two follow up visits , 6 attended one follow up visit. Ten (31%) had a bacterial STI diagnosis (6 Chlamydia, 6 Gonorrhea, 1 LGV) during follow up. This highlighted the importance of STI screening and sexual health promotion for the MSM cohort during follow up for RPR monitoring in our clinic. Opportunistic screening for STI should be conducted across the globe where resources permit.
Reference:
[1] Ang LW, Wong C, Ng O et al. Incidence of syphilis among HIV-infected
men in Singapore, 2006–2017: temporal trends and associated risk factors. Sex Transm Infect 2020;96:293–299
[2] Sivaraj V, Rajapaksha D, Fitzgerald N et al. STI events after syphilis diagnosis:
one year follow up of a subset cohort. BASHH annual conference; P 32; International Journal of STD & AIDS 2019, Vol. 30(7S) 1–114
We read with interest the informative Short Report by Wang et al. about Jarisch–Herxheimer reaction during therapy of congenital syphilis [1] and wish to make a few comments:
1. The authors included in their review all patients hospitalized between 1 January 2010 to 31 November 2015. However, no such date like 31 November 2015 actually exists.
2. Authors state that 'rapid pulse and breathing' were present in all 11/11 patients of Jarisch–Herxheimer reaction. However, they have not stated the age of these patients in the study. 'Pulse and breathing' are age-dependent variables, and in neonates pulse rate may be up to 120 to 160 beats per minute, and breathing up to 40 to 60 breaths per minute. Therefore, it is important to see how many of the Jarisch–Herxheimer reaction cases were neonates as in many of these case, pulse and respiratory may be within normal range.
3. The recommended duration of treatment for congenital syphilis is 10 days and not 14 days as followed in this study [2].
References:
1. Wang C, He S, Yang H, Liu Y, Zhao Y, Pang L. Unique manifestations and risk factors of Jarisch-Herxheimer reaction during treatment of child congenital syphilis. Sex Transm Infect. 2018 Dec;94(8):562-564.
We read with interest the informative Short Report by Wang et al. about Jarisch–Herxheimer reaction during therapy of congenital syphilis [1] and wish to make a few comments:
1. The authors included in their review all patients hospitalized between 1 January 2010 to 31 November 2015. However, no such date like 31 November 2015 actually exists.
2. Authors state that 'rapid pulse and breathing' were present in all 11/11 patients of Jarisch–Herxheimer reaction. However, they have not stated the age of these patients in the study. 'Pulse and breathing' are age-dependent variables, and in neonates pulse rate may be up to 120 to 160 beats per minute, and breathing up to 40 to 60 breaths per minute. Therefore, it is important to see how many of the Jarisch–Herxheimer reaction cases were neonates as in many of these case, pulse and respiratory may be within normal range.
3. The recommended duration of treatment for congenital syphilis is 10 days and not 14 days as followed in this study [2].
References:
1. Wang C, He S, Yang H, Liu Y, Zhao Y, Pang L. Unique manifestations and risk factors of Jarisch-Herxheimer reaction during treatment of child congenital syphilis. Sex Transm Infect. 2018 Dec;94(8):562-564.
We read with interest the short report by van Aar et al. discussing potential implications of chlamydia expedited partner therapy (EPT) which entails patient delivered partner therapy.1 The authors highlight a number of factors which may influence the benefit-risk balance of providing EPT, many of which resonate with our experience of Accelerated Partner Therapy (APT).2 APT is an adaptation of EPT, which includes a telephone consultation between the sex partner and prescriber (to meet UK prescribing guidance), provision of a self-sampling kit for sexually transmitted infections (STIs) and HIV for a sex partner in addition to antibiotics and information on STIs and HIV. APT has been piloted among predominately heterosexual contacts of chlamydia and gonorrhoea.3
The authors report a chlamydia positivity rate of 34.2% among chlamydia-notified partners in the Netherlands and proposed that the use of EPT for all contacts risks exposing the majority of contacts to potentially unnecessary antimicrobial therapy. Furthermore, just over 1% of these contacts also had gonorrhoea, accounting for about 10% of all gonorrhoea infections detected during the study time period, raising additional concerns about inadequate therapy and antimicrobial resistance.
In England in 2016, chlamydia positivity among chlamydia contacts attending specialist sexual health services (SHS) was 40%, representing 19% of all chlamydia diagnoses made in SHS that year.4 This is...
We read with interest the short report by van Aar et al. discussing potential implications of chlamydia expedited partner therapy (EPT) which entails patient delivered partner therapy.1 The authors highlight a number of factors which may influence the benefit-risk balance of providing EPT, many of which resonate with our experience of Accelerated Partner Therapy (APT).2 APT is an adaptation of EPT, which includes a telephone consultation between the sex partner and prescriber (to meet UK prescribing guidance), provision of a self-sampling kit for sexually transmitted infections (STIs) and HIV for a sex partner in addition to antibiotics and information on STIs and HIV. APT has been piloted among predominately heterosexual contacts of chlamydia and gonorrhoea.3
The authors report a chlamydia positivity rate of 34.2% among chlamydia-notified partners in the Netherlands and proposed that the use of EPT for all contacts risks exposing the majority of contacts to potentially unnecessary antimicrobial therapy. Furthermore, just over 1% of these contacts also had gonorrhoea, accounting for about 10% of all gonorrhoea infections detected during the study time period, raising additional concerns about inadequate therapy and antimicrobial resistance.
In England in 2016, chlamydia positivity among chlamydia contacts attending specialist sexual health services (SHS) was 40%, representing 19% of all chlamydia diagnoses made in SHS that year.4 This is similar to the positivity reported by van Aar. A different pattern is seen in the 2016 English National Chlamydia Screening Programme audit, which is restricted to 15 to 24 year olds testing in any setting (health and non-healthcare). Positivity in contacts was 62% suggesting that in this age-group the majority would benefit from empirical treatment.5 Therefore, the appropriateness of EPT/APT within different populations (defined by age or by testing service type) may vary depending on chlamydia prevalence within the population group of interest, willingness to access testing and testing location. The time between exposure and testing is not reported by van Aar but could contribute to lower positivity among contacts if they test within two weeks of exposure.
A key difference between EPT and APT is the inclusion of self-sampling kit for STIs, including HIV, in addition to antibiotics and information. We agree with the authors that testing for partners is an essential component of clinical management and every effort should be made to link testing and treatment practices. This can facilitate further rounds of partner notification (PN) and ensure that those at risk of infections are tested for a range of STIs. The acceptability and uptake of self-sampling in general appears to be high and in the APT pilot, chlamydia and gonorrhoea self-sampling kits were returned by 55% of contacts receiving the APT intervention.3 6
The authors state that EPT should not be recommended ‘for sex partners with a migration background from STI/HIV endemic regions’ even if self-sampling kits were included, because their data showed high rates of coinfections and greater potential to miss STIs in these populations. This may assume that EPT would reach the same populations as patient referral. However, EPT and APT could offer opportunities to treat and test partners who may otherwise not be notified or would not attend healthcare settings – people who might otherwise be missed by traditional PN approaches. Nevertheless, we acknowledge that the acceptability and uptake of EPT/APT among sex partners and the index may potentially be influenced by socio-cultural norms and thereby, future studies should seek to explore the impact of these factors.
A large scale APT chlamydia PN randomised controlled trial will be starting in the UK in summer 2018 and will involve the index partners delivering an ‘APT pack’ to eligible partners.7 These packs will contain chlamydia treatment and self-sampling kits for chlamydia, gonorrhoea, HIV and syphilis in an attempt to increase testing among partners. This trial will provide evidence on the cost-effectiveness of APT in addition to greater understanding of sex partners’ readiness to provide samples for testing using self-sampling kits. Importantly, the APT intervention has been informed by a robust theoretical framework and behavioural change techniques. Further research on the feasibility of using EPT/APT among men who have sex with men is needed and will be conducted as part of this study.
If we are to improve PN outcomes, irrespective of how PN is delivered, a range of options will be required, tailored to meet the needs of patients and their partners. Thus EPT/APT are a valuable addition to PN strategies.
Acknowledgements
This article is written on behalf of the LUSTRUM team (www.lustrum.org.uk/co-investigators). The LUSTRUM Programme of Research is funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Reference Number RP-PG-0614-20009). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The funders had no involvement in the writing of this manuscript or the decision to submit for publication.
References
1. van Aar F, van Benthem BHB, van den Broek IVF, et al. STIs in sex partners notified for chlamydia exposure: implications for expedited partner therapy. Sex Transm Infect 2018.
2. Dombrowski JC, Golden MR. Accelerated partner therapy: a promising new partner treatment option. Sex Transm Infect 2012;88(1):2-3.
3. Estcourt C, Sutcliffe L, Cassell J, et al. Can we improve partner notification rates through expedited partner therapy in the UK? Findings from an exploratory trial of Accelerated Partner Therapy (APT). Sex Transm Infect 2012;88(1):21-6.
4. Public Health England. Table 7: STI diagnoses & partner notification, 2012 - 2016. Available at https://www.gov.uk/government/uploads/system/uploads/attachment_data/fil....
5. Public Health England. Partner notification in chlamydia screening. National Audit Report. May 2016. https://www.gov.uk/government/uploads/system/uploads/attachment_data/fil....
6. Fajardo-Bernal L, Aponte-Gonzalez J, Vigil P, et al. Home-based versus clinic-based specimen collection in the management of Chlamydia trachomatis and Neisseria gonorrhoeae infections. Cochrane Database Syst Rev 2015(9):CD011317.
7. LUSTRUM. Limiting Undetected Sexually Transmitted Infections to Reduce Morbidity Study Website. https://www.lustrum.org.uk/ Last accessed 18th January 2018.
Impact of Expedited Partner Therapy (EPT) Implementation on Chlamydia Incidence in the USA
Letter to the Editor:
Assuming that a sexual partner has only one Sexually Transmitted Infection (STI) is a dangerous practice and should be discouraged. The Expedient Partner Therapy implementation on Chlamydia is one such assumption. In a study conducted by (Zemouri, Wi, Kiarie, Seuc, Moqasale et.al 2016) they highlighted that Sexually Transmitted Infection (STI) case management is one of the top priorities in controlling STIs to break the chain of infection and transmission. They further reiterated that Syndromic case management provides a standardized evidence-based approach using clinical management algorithms, and flowcharts that can be used consistently across providers. Clinicians that treat patients with STIs should be cognizant that Expedited Partner Treatment is inadequate because there is at least a third infected sexual partner other than the partner being treated.
Another factor that should be considered when administering Expedited Partner Therapy is the possibility, of the partner, manifesting other symptoms of a STI to be treated that has not yet been identified in the patient. It is useful to administer the risk score test which is a 6 point research base quiz to each patient being treated for STI. These questions can only be answered by the patient for it to be considered reliable. Each question has a number of points assigned to potential ans...
Impact of Expedited Partner Therapy (EPT) Implementation on Chlamydia Incidence in the USA
Letter to the Editor:
Assuming that a sexual partner has only one Sexually Transmitted Infection (STI) is a dangerous practice and should be discouraged. The Expedient Partner Therapy implementation on Chlamydia is one such assumption. In a study conducted by (Zemouri, Wi, Kiarie, Seuc, Moqasale et.al 2016) they highlighted that Sexually Transmitted Infection (STI) case management is one of the top priorities in controlling STIs to break the chain of infection and transmission. They further reiterated that Syndromic case management provides a standardized evidence-based approach using clinical management algorithms, and flowcharts that can be used consistently across providers. Clinicians that treat patients with STIs should be cognizant that Expedited Partner Treatment is inadequate because there is at least a third infected sexual partner other than the partner being treated.
Another factor that should be considered when administering Expedited Partner Therapy is the possibility, of the partner, manifesting other symptoms of a STI to be treated that has not yet been identified in the patient. It is useful to administer the risk score test which is a 6 point research base quiz to each patient being treated for STI. These questions can only be answered by the patient for it to be considered reliable. Each question has a number of points assigned to potential answers, and higher points mean higher STI risk (Coughlin, 2016). Implementing the expedient partner therapy negate retrieving pertinent information regarding a patient’s sexual behavior and habits.
In managing a patient with STI, health education and promotion should form an integral part of each patient’s management regime. The use of condoms cannot be overemphasized and should form the basis of all discussions when treating patients with STIs. Expedient Partner Therapy decreases the opportunity to give this valuable information to all affected partners.
Zemouri, C., Wi, TE., Kiarie, J., Seuc, A., Mogasale, V., Latif, A., & Broutet. N. (2016). The Performance of the Vaginal Discharge Syndromic Management in Treating Vaginal and Cervical Infection: A Systematic review and Meta-Analysis. https://www.ncbi.nim.nih.gov/pubmed/27706174
Fleiss et al. make several dubious claims in their article [1], but one is of particular interest. Some authors have now begun to rely upon the assertion that the subpreputial wetness contains lysozyme, and suggest that this may help to protect against HIV.[2,3] Although the epidemiological evidence suggests otherwise,2 our understanding of the mechanisms involved is important, and this claim is wo...
Fleiss et al. make several dubious claims in their article [1], but one is of particular interest. Some authors have now begun to rely upon the assertion that the subpreputial wetness contains lysozyme, and suggest that this may help to protect against HIV.[2,3] Although the epidemiological evidence suggests otherwise,2 our understanding of the mechanisms involved is important, and this claim is worthy of careful examination.
Fleiss et al. rely upon two sources.[4,5] One found lysozyme in apocrine glands, among other enzymes.[5] The other is a case report involving an apocrine gland in the prepuce.[4] However, a more recent pathological study,[6] cited by the authors, found that "unlike true skin of the penile shaft and outer surface of the prepuce, the mucosal surface of the prepuce is completely free of lanugo hair follicles, sweat and sebaceous glands."
If the mucosal surface is completely free of such glands, then it must be the outer surface of the prepuce that benefits from the lysozyme. Indeed, if the prepuce functions as a "one way valve" as the authors assert, the subpreputial moisture would be completely unaffected.
With such weak evidence, the assertion that the subpreputial wetness contains lysozyme must be regarded as an untested hypothesis at best.
References
Fleiss P, Hodges F, Van Howe RS. Immunological functions of the human prepuce. Sex Trans Infect. 1998;74(5):364-7
Siegfried N, Muller M, Volmink J, et al. Male circumcision for prevention of heterosexual acquisition of HIV in men (Cochrane Review). The Cochrane Library, issue 3. Oxford: Update Software; 2003.
Hill G, Denniston GC. HIV and circumcision: new factors to consider. Sex Transm Infect. 2003;79:495-496
Ahmed A, Jones AW. Apocrine cystodenoma: a report of two cases occurring on the prepuce. Br J Derm. 1969;81:899-901
Frolich E, Shaumberg-Lever F, Kissen C. Immunelectron microscopic localization of cathepsin B in human apocrine glands. J Cutan Pathol. 1993; 20: 54-60
Taylor JR, Lockwood AP, Taylor AJ. The prepuce: specialized mucosa of the penis and its loss to circumcision. Br J Urol. 1996;77:591-5
Error in the calculation of person-time in the before-PrEP period by Beymer et al.
S.H. Hulstein, E. Hoornenborg, M.F. Schim van der Loeff
Department of Infectious Diseases, GGD Amsterdam
Studies on STI incidence and PrEP use are often hampered by the absence of STI incidence data in the period before PrEP; Beymer et al.1 set out to improve on this. They report on the STI incidence before and after initiation of PrEP in a cohort of men who have sex with men (MSM) at the Los Angeles LGBT Center, California, US. We fear that there are some flaws in the analysis, which may affect the conclusions.
The analysis was based on 275 men who were tested at least once in the period before PrEP was started, and at least once after PrEP was started. The reported persontime in the before- PrEP period was just over half the person-time after PrEP initiation (93.60 versus 168.93), but the numbers of tests before and after PrEP initiation were not very different: 755 and 908, respectively. This discrepancy could not be explained by differences in their frequency of STI testing, which were reported to be similar in the before- and after-PrEP period. An explanation is that the person-time before the first STI visit was not taken into account. This would mean that the person-time in the before-PrEP period was underestimated, in turn leading to an artificially high before-PrEP STI incidence....
Error in the calculation of person-time in the before-PrEP period by Beymer et al.
S.H. Hulstein, E. Hoornenborg, M.F. Schim van der Loeff
Department of Infectious Diseases, GGD Amsterdam
Studies on STI incidence and PrEP use are often hampered by the absence of STI incidence data in the period before PrEP; Beymer et al.1 set out to improve on this. They report on the STI incidence before and after initiation of PrEP in a cohort of men who have sex with men (MSM) at the Los Angeles LGBT Center, California, US. We fear that there are some flaws in the analysis, which may affect the conclusions.
The analysis was based on 275 men who were tested at least once in the period before PrEP was started, and at least once after PrEP was started. The reported persontime in the before- PrEP period was just over half the person-time after PrEP initiation (93.60 versus 168.93), but the numbers of tests before and after PrEP initiation were not very different: 755 and 908, respectively. This discrepancy could not be explained by differences in their frequency of STI testing, which were reported to be similar in the before- and after-PrEP period. An explanation is that the person-time before the first STI visit was not taken into account. This would mean that the person-time in the before-PrEP period was underestimated, in turn leading to an artificially high before-PrEP STI incidence. The observed decrease in incidence rates for all STIs (except syphilis) reported in Table 3 would thus be an artefact of the analysis, rather than a real phenomenon.
If the pre-test person-time would have been taken into account, the analyses might have shown that STI incidences in the after-PrEP period would have been similar or higher than in the before-PrEP period.
More studies are needed that examine whether the incidence rate of STIs increases after initiation of PrEP; appropriate analyses of such data are essential.
References
Beymer MR et al. Does HIV pre-exposure prophylaxis use lead to a higher incidence of sexually transmitted infections? A case-crossover study of men who have sex with men in Los Angeles, California. Sex Trans Infect Epub ahead of print. Doi:10.1136/sextrans.2017-053377
Although we agree with Ghanem et al. that CSF TPPA titer is a valuable test for the diagnosis of neurosyphilis[1], we would like to emphasize that a cut-off TPPA titer should be recommended with caution as proposed by others [2]. Such semi-quantitative laboratory tests may vary depending on the operator or reagent. Our IQC from a single patient during a 2 years period showed that TPPA inaccuracy is about 2 titers (Table). Moreover, a 2 log2 variation is accepted by organisms providing samples for external quality assessment for syphilis serology [3]. Similarly to what occurs with neuroborreliosis, quantifying anti-treponema pallidum IgG (antiTp- IgG) in CSF, immunoassays in serum and intrathecal antibodies index could be a reliable approach for the diagnosis of neurosyphilis. We found some positive antiTp-IgG index in CSF with TPPA titers below 320, suggesting an intrathecal synthesis of anti-treponema pallidum IgG. The diagnosis of neurosyphilis still lacks a gold standard test and further research is warranted. 1. Ghanem, K.G., Cerebrospinal fluid treponemal antibody titres: a breakthrough in the diagnosis of neurosyphilis. Sex Transm Infect, 2020.
Show More2. Marra, C.M., et al., Cerebrospinal Fluid Treponema pallidum Particle Agglutination Assay for Neurosyphilis Diagnosis. J Clin Microbiol, 2017. 55(6): p. 1865-1870.
3. Muller, I., et al., Is serological testing a reliable tool in laboratory diagnosis of syphilis? Meta-analysis of eight external quality control sur...
The paper by Jordan SJ et al (1) is thought stimulating. The CDC guideline to regard 2-4 PMN/HPF as depicting NGU is possibly not widely observed, despite having been said 5 years ago (2). This and the inference that 1 or <1 PMN/HPF means no NGU must put a strain on those counting and poses the question of what variation might exist between observers.
Show MoreWhen 5 different micro-organisms were sought but not found in urethritis, the invitation was there to consider the role of oral and anal bacteria and those occurring in BV. An association between this and NGU has been noted in the past (3). Unfortunately it was not taken into account here. It is also curious that when looking at the role of Ureaplasma species, the authors did not consider U.parvum. Admittedly, others have considered it to be less important than U.urealyticum (4) but not banished it to the graveyard completely.
Finally, the issue of bacterial load is important in considering pathogenicity. The authors state that they used quantitative PCRs but they did not provide ANY quantitative results. Why is that? These and longitudinal studies are required.
I believe the conclusion of the authors is not fully founded. Remember, Koch's postulates have been fulfilled for U.urealyticum (5).
REFERENCES
1. Jordan SJ, Toh E, Williams AJ, et al. Aetiology and prevalence of mixed-infections and mono-infections in non-gonococcal urethritis in men: a case-control study. Sex Transm Inf 2020;...
Dear Editor,
We have read the interesting manuscript “Antimicrobial resistance in Mycoplasma genitalium sampled from the British general population”, from Pitt et al.1 In 56 M. genitalium-positive specimens, macrolide resistance was detected in 9 (16.1%). These results agree with the low rate of resistance (<20%) detected in studies carried out mainly in general population,2 but contrast with the higher rates (>40%) obtained in patients mainly attended in sexually transmitted infections units.3 These two scenarios (general versus core population) could be considered in the management of the M. genitalium infection.
Show MoreIn our context (80-90% general population), the macrolide resistance rate was 16.3% (43/263).2 After detection of macrolide resistance-associated mutations with rapid techniques, guided antibiotic therapy was prescribed (azithromycin 500 mg day 1 and 250 mg days 2-5, or moxifloxacin) , and sexual partners control and test of cure after 3 weeks recommended. Despite patients adhering to the antibiotic regimen initially indicated, treatment failure was 6%.
Recently, a resistance-guided sequential treatment with doxycycline followed with azithromycin or moxifloxacin has been proposed.3 In this study the macrolide resistance rate was 68% and the treatment failure 7%. In our opinion, this strategy could be appropriate in populations with high macrolide resistance rate (main conclusion of this study), and healthcare contexts in that guided ther...
We thank Piñeiro et al for their interest in our study using data from Britain’s third National Survey of Sexual Attitudes and Lifestyle (Natsal-3).1 This was a probability sample survey undertaken in 2010-12, with Mycoplasma genitalium testing results from urine available for over 4,500 participants aged 16-44 years.2 In this follow-up paper, we reported genotypic data on mutations associated with macrolide and fluoroquinolone resistance.
We read with interest that Piñeiro et al also found relatively low levels (<20%) of macrolide resistance in a Spanish, mainly general population sample in 2014-17.3 However, the low macrolide resistance (16%) found in our study is probably due not only to the general population sample, but also to the specimens being collected nearly a decade ago. Since 2010-12, there is evidence that macrolide resistance in M. genitalium has rapidly increased globally, and we anticipate finding higher levels of genotypic macrolide resistance in the general population in Britain in 2022 when Natsal-4 is expected to report findings.4 These data will be important to inform national and international understanding of incidence and prevalence as well as updated management and infection control strategies.
We appreciate both the relatively low treatment failure rate in the referenced Spanish study by Piñeiro et al,3 and the treatment strategy...
Show MoreAng et al [1] discussed rising syphilis incidence among HIV positive men in Singapore. The diagnostic test used for syphilis in this study (RPR) is a non-specific treponemal antibody test. This limitation should be acknowledged while interpreting results. However, it is of good epidemiological value for public health programs for behavioural intervention. An important opportunity for sexual health promotion that can be missed if overlooked is post-treatment follow up for RPR titre monitoring. BASHH guidelines recommend follow up RPR titre post treatment until sero-fast or sustained 4 fold decrease in titre (at 3, 6 and 12 months).
An audit at our central London clinic showed that 31% of men had a bacterial STI when followed up for RPR monitoring post-treatment for syphilis [2]. Of 32 men (mean age 37 years; range 21- 75 years; 31 MSM), 11 were HIV positive. Six patients attended follow up visits at 3,6, and 12 months post treatment , 9 attended two follow up visits , 6 attended one follow up visit. Ten (31%) had a bacterial STI diagnosis (6 Chlamydia, 6 Gonorrhea, 1 LGV) during follow up. This highlighted the importance of STI screening and sexual health promotion for the MSM cohort during follow up for RPR monitoring in our clinic. Opportunistic screening for STI should be conducted across the globe where resources permit.
Reference:
Show More[1] Ang LW, Wong C, Ng O et al. Incidence of syphilis among HIV-infected
men in Singapore, 2006–2017: temporal tren...
Sir,
We read with interest the informative Short Report by Wang et al. about Jarisch–Herxheimer reaction during therapy of congenital syphilis [1] and wish to make a few comments:
1. The authors included in their review all patients hospitalized between 1 January 2010 to 31 November 2015. However, no such date like 31 November 2015 actually exists.
2. Authors state that 'rapid pulse and breathing' were present in all 11/11 patients of Jarisch–Herxheimer reaction. However, they have not stated the age of these patients in the study. 'Pulse and breathing' are age-dependent variables, and in neonates pulse rate may be up to 120 to 160 beats per minute, and breathing up to 40 to 60 breaths per minute. Therefore, it is important to see how many of the Jarisch–Herxheimer reaction cases were neonates as in many of these case, pulse and respiratory may be within normal range.
3. The recommended duration of treatment for congenital syphilis is 10 days and not 14 days as followed in this study [2].
References:
1. Wang C, He S, Yang H, Liu Y, Zhao Y, Pang L. Unique manifestations and risk factors of Jarisch-Herxheimer reaction during treatment of child congenital syphilis. Sex Transm Infect. 2018 Dec;94(8):562-564.
2. CDC 2015 Sexually Transmitted Diseases Treatment Guidelines. Congenital syphilis. Available at https://www.cdc.gov/std/tg2015/congenital.htm...
Show MoreDear Editor,
We read with interest the short report by van Aar et al. discussing potential implications of chlamydia expedited partner therapy (EPT) which entails patient delivered partner therapy.1 The authors highlight a number of factors which may influence the benefit-risk balance of providing EPT, many of which resonate with our experience of Accelerated Partner Therapy (APT).2 APT is an adaptation of EPT, which includes a telephone consultation between the sex partner and prescriber (to meet UK prescribing guidance), provision of a self-sampling kit for sexually transmitted infections (STIs) and HIV for a sex partner in addition to antibiotics and information on STIs and HIV. APT has been piloted among predominately heterosexual contacts of chlamydia and gonorrhoea.3
The authors report a chlamydia positivity rate of 34.2% among chlamydia-notified partners in the Netherlands and proposed that the use of EPT for all contacts risks exposing the majority of contacts to potentially unnecessary antimicrobial therapy. Furthermore, just over 1% of these contacts also had gonorrhoea, accounting for about 10% of all gonorrhoea infections detected during the study time period, raising additional concerns about inadequate therapy and antimicrobial resistance.
In England in 2016, chlamydia positivity among chlamydia contacts attending specialist sexual health services (SHS) was 40%, representing 19% of all chlamydia diagnoses made in SHS that year.4 This is...
Show MoreImpact of Expedited Partner Therapy (EPT) Implementation on Chlamydia Incidence in the USA
Show MoreLetter to the Editor:
Assuming that a sexual partner has only one Sexually Transmitted Infection (STI) is a dangerous practice and should be discouraged. The Expedient Partner Therapy implementation on Chlamydia is one such assumption. In a study conducted by (Zemouri, Wi, Kiarie, Seuc, Moqasale et.al 2016) they highlighted that Sexually Transmitted Infection (STI) case management is one of the top priorities in controlling STIs to break the chain of infection and transmission. They further reiterated that Syndromic case management provides a standardized evidence-based approach using clinical management algorithms, and flowcharts that can be used consistently across providers. Clinicians that treat patients with STIs should be cognizant that Expedited Partner Treatment is inadequate because there is at least a third infected sexual partner other than the partner being treated.
Another factor that should be considered when administering Expedited Partner Therapy is the possibility, of the partner, manifesting other symptoms of a STI to be treated that has not yet been identified in the patient. It is useful to administer the risk score test which is a 6 point research base quiz to each patient being treated for STI. These questions can only be answered by the patient for it to be considered reliable. Each question has a number of points assigned to potential ans...
Dear Editor,
Fleiss et al. make several dubious claims in their article [1], but one is of particular interest. Some authors have now begun to rely upon the assertion that the subpreputial wetness contains lysozyme, and suggest that this may help to protect against HIV.[2,3] Although the epidemiological evidence suggests otherwise,2 our understanding of the mechanisms involved is important, and this claim is wo...
Error in the calculation of person-time in the before-PrEP period by Beymer et al.
S.H. Hulstein, E. Hoornenborg, M.F. Schim van der Loeff
Department of Infectious Diseases, GGD Amsterdam
Studies on STI incidence and PrEP use are often hampered by the absence of STI incidence data in the period before PrEP; Beymer et al.1 set out to improve on this. They report on the STI incidence before and after initiation of PrEP in a cohort of men who have sex with men (MSM) at the Los Angeles LGBT Center, California, US. We fear that there are some flaws in the analysis, which may affect the conclusions.
The analysis was based on 275 men who were tested at least once in the period before PrEP was started, and at least once after PrEP was started. The reported persontime in the before- PrEP period was just over half the person-time after PrEP initiation (93.60 versus 168.93), but the numbers of tests before and after PrEP initiation were not very different: 755 and 908, respectively. This discrepancy could not be explained by differences in their frequency of STI testing, which were reported to be similar in the before- and after-PrEP period. An explanation is that the person-time before the first STI visit was not taken into account. This would mean that the person-time in the before-PrEP period was underestimated, in turn leading to an artificially high before-PrEP STI incidence....
Show MorePages