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.
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
Correspondence to: Nicola Low, Professor of Epidemiology and Public Health, Institute of Social and Preventive Medicine, University of Bern, Mittelstrasse 43, 3012 Bern, Switzerland. nicola.low@ispm.unibe.ch; Tel: +41 31 631 30 92
Title: Research on Mycoplasma genitalium is more important than expanding testing
We are glad that Taylor-Robinson and Ong offer some support for the conclusion of our systematic review,1 that asymptomatic populations, in the community or in clinics, should not be tested routinely for M. genitalium. The first British Association of Sexual Health and HIV (BASHH) guideline about the management of Mycoplasma genitalium, published on 8th July 2018, supports this conclusion.2 We would like to clarify, however, that the absence of evidence for clinical and public health benefit of screening3 and the harm of inducing de novo mutations and spreading resistance to macrolide antimicrobials4 are more important than economic considerations.
Taylor-Robinson and Ong’s statement that “testing worldwide should continue to support or modify this conclusion”5 could lead to pro...
Correspondence to: Nicola Low, Professor of Epidemiology and Public Health, Institute of Social and Preventive Medicine, University of Bern, Mittelstrasse 43, 3012 Bern, Switzerland. nicola.low@ispm.unibe.ch; Tel: +41 31 631 30 92
Title: Research on Mycoplasma genitalium is more important than expanding testing
We are glad that Taylor-Robinson and Ong offer some support for the conclusion of our systematic review,1 that asymptomatic populations, in the community or in clinics, should not be tested routinely for M. genitalium. The first British Association of Sexual Health and HIV (BASHH) guideline about the management of Mycoplasma genitalium, published on 8th July 2018, supports this conclusion.2 We would like to clarify, however, that the absence of evidence for clinical and public health benefit of screening3 and the harm of inducing de novo mutations and spreading resistance to macrolide antimicrobials4 are more important than economic considerations.
Taylor-Robinson and Ong’s statement that “testing worldwide should continue to support or modify this conclusion”5 could lead to problems. Uncontrolled testing and treatment of different groups of people will also advance “the seemingly unstoppable march of MG to complete antibiotic resistance” because M. genitalium has an unusually high probability of developing de novo resistance during treatment with a single 1g dose of azithromycin. We found, in a mathematical modelling study, that an estimated probability of resistance of 12% (95% confidence interval 8 to 17%) can explain why 50% or more of detected M. genitalium infections are already resistant to macrolides in some countries.4
The rational use of new commercial molecular tests, for detection of both M. genitalium and its antimicrobial resistance determinants, should be promoted in the context of international programmes of research and surveillance. Experts have prioritised research to determine whether screening of asymptomatic populations will reduce important clinical disease outcomes.3 Systematic reviews can help, by synthesising the existing research literature and highlight gaps in the research base. A forthcoming systematic review, linked to the review of prevalence studies, will address the dynamics and natural history of M. genitalium (PROSPERO protocols CRD42015020420, CRD42015020405, https://www.crd.york.ac.uk/prospero/) and improve the knowledge base for future mathematical modelling studies. Taylor-Robinson and Ong highlight additional basic research questions about the immunology of M. genitalium and the respiratory pathogen M. pneumoniae.
In our view, diagnostic testing accompanied by testing for macrolide resistance should be limited to defined groups of symptomatic patients and treatment algorithms, such as those recommended in the BASHH guideline,2 must be evaluated in randomised controlled trials. The research community should do all it can to ensure that responsible use of testing for M. genitalium advances the objectives of research and public health, whilst mitigating the spread of antimicrobial resistance.
References
1. Baumann L, Cina M, Egli-Gany D, et al. Prevalence of Mycoplasma genitalium in different population groups: systematic review and meta-analysis. Sex Transm Infect 2018 doi: 10.1136/sextrans-2017-053384
2. Soni S, Horner P, Rayment M, et al. 2018 BASHH UK national guideline for the management of infection with Mycoplasma genitalium. 2018.
3. Martin DH, Manhart LE, Workowski KA. Mycoplasma genitalium From Basic Science to Public Health: Summary of the Results From a National Institute of Allergy and Infectious Disesases Technical Consultation and Consensus Recommendations for Future Research Priorities. J Infect Dis 2017;216(suppl_2):S427-S30. doi: 10.1093/infdis/jix147
4. Cadosch R, Garcia V, Althaus CL, et al. De novo mutations drive the spread of macrolide resistant Mycoplasma genitalium: a mathematical modelling study. bioRxiv 2018:321216.
5. Taylor Robinson D, Ong J. Prevalence of Mycoplasma genitalium. Sexually Transmitted Infections 2018 15.06.2018. https://sti.bmj.com/content/94/4/255.responses (accessed 19.07.2018).
The work by Baumann et al.(1) is valuable because it indicates populations for which screening for Mycoplasma genitalium (MG)) is not worthwhile economically. However, as molecular detection tests are now available commercially, testing worldwide should continue to support or modify this conclusion and so help in the development of management guidelines and also provide data for MG modelling.
Another aspect of infection which requires more attention is the precise role of MG in balanoposthitis, epididymitis,, chronic prostatitis, reactive arthritis, and, of course, pelvic inflammatory disease, all of which, apart from chronic prostatitis, have some association with MG (2).
In addition, it is noteworthy that Mycoplasma pneumoniae (MP), which infects the respiratory tract, and is also responsible for some autoimmune side effects, does so in early childhood without causing disease. The latter usually occurs as an immunological response to reinfection later in life. MG is different genomically from MP but has much in common antigenically and might behave in a similar way to MP. Could asymptomatic MG infection, which is seen occasionally, be an example of this? Potentiation or even inhibition of MG infection in the genital tract by MP infection in the respiratory tract earlier in life is also possible. This idea is not supported by studies in mice, but the human situation might be quite different. In this regard, use of an existing specific serological test for MG m...
The work by Baumann et al.(1) is valuable because it indicates populations for which screening for Mycoplasma genitalium (MG)) is not worthwhile economically. However, as molecular detection tests are now available commercially, testing worldwide should continue to support or modify this conclusion and so help in the development of management guidelines and also provide data for MG modelling.
Another aspect of infection which requires more attention is the precise role of MG in balanoposthitis, epididymitis,, chronic prostatitis, reactive arthritis, and, of course, pelvic inflammatory disease, all of which, apart from chronic prostatitis, have some association with MG (2).
In addition, it is noteworthy that Mycoplasma pneumoniae (MP), which infects the respiratory tract, and is also responsible for some autoimmune side effects, does so in early childhood without causing disease. The latter usually occurs as an immunological response to reinfection later in life. MG is different genomically from MP but has much in common antigenically and might behave in a similar way to MP. Could asymptomatic MG infection, which is seen occasionally, be an example of this? Potentiation or even inhibition of MG infection in the genital tract by MP infection in the respiratory tract earlier in life is also possible. This idea is not supported by studies in mice, but the human situation might be quite different. In this regard, use of an existing specific serological test for MG might provide helpful data. In dealing with an infection where there is still much to seek and understand, the seemingly unstoppable march of MG to complete antibiotic resistance is the most worrying aspect. Although vaccination against MP infection has been only partially successful, it must be said again that this approach to prevention should receive urgent attention in the battle agaist MG infection (3).
David Taylor-Robinson (1), Jason J Ong (2)
(1) Section of Infectious Diseases, St Mary's Campus, imperial College London, UK
(2) Department of Clinical Research, London School of Hygiene and Tropical Medicine, UK
REFERENCES
1.Baumann L, Cina M, Egli-Gany D, et al. Prevalence of Mycoplasma genitalium in different population groups: systematic review and meta-analysis. Sex Transm Infect 2018; 94: 255-262.
2.Taylor-Robinson D, Jensen JS. Mycoplasma genitalium; from chrysalis to multicolored butterfly. Clin Microbiol Rev 2011; 24: 498-514.
3.Taylor-Robinson D. Diagnosis and antimicrobial treatment of Mycoplasma genitalium infection: sobering thoughts. Expert Rev Anti Infect Ther 2014; 12: 715-722.
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
The authors estimated vertical transmission of Chlamydia trachomatis by a retrospective analysis using national registry data and clinical records and concluded that transmission was much lower (<2%) than the rate commonly quoted (50-70%). Their suggested explanation is that the modern use of highly sensitive NAATs detects nonviable chlamydiae so that mothers testing positive could actually be noninfectious whereas older studies based on use of culture only identified infectious pregnant women. That is not a likely explanation for such a big difference. When NAAT performance with cervical swabs was evaluated about 2/3 of NAAT positive specimens were culture positive.
A more likely explanation comes from examining their case definition. It is not chlamydial infection, but rather laboratory confirmed cases of chlamydial conjunctivitis or pneumonia. And that is very different. When prospective studies were being done in San Francisco 175 infants born to chlamydia infected mothers were followed: 31 (18%) developed pneumonia; 29 (17%) conjunctivitis; 64 (37%) were culture positive and 105 (60%) had serologic evidence of infection. Thus there were many more infections than cases of conjunctivitis and pneumonia. But the difference between cases of disease and infection in the Finnish material is probably greater. In the prospective study there were cases of very mild disease that would likely not have been diagnosed in ordinary circumstances (seeing the whole clinical s...
The authors estimated vertical transmission of Chlamydia trachomatis by a retrospective analysis using national registry data and clinical records and concluded that transmission was much lower (<2%) than the rate commonly quoted (50-70%). Their suggested explanation is that the modern use of highly sensitive NAATs detects nonviable chlamydiae so that mothers testing positive could actually be noninfectious whereas older studies based on use of culture only identified infectious pregnant women. That is not a likely explanation for such a big difference. When NAAT performance with cervical swabs was evaluated about 2/3 of NAAT positive specimens were culture positive.
A more likely explanation comes from examining their case definition. It is not chlamydial infection, but rather laboratory confirmed cases of chlamydial conjunctivitis or pneumonia. And that is very different. When prospective studies were being done in San Francisco 175 infants born to chlamydia infected mothers were followed: 31 (18%) developed pneumonia; 29 (17%) conjunctivitis; 64 (37%) were culture positive and 105 (60%) had serologic evidence of infection. Thus there were many more infections than cases of conjunctivitis and pneumonia. But the difference between cases of disease and infection in the Finnish material is probably greater. In the prospective study there were cases of very mild disease that would likely not have been diagnosed in ordinary circumstances (seeing the whole clinical spectrum is an advantage of prospective studies). I do not know what the triggers would be for laboratory testing in Finland, but there must have been a bias towards more severe cases of conjunctivitis and pneumonia. Thus there would be an underestimation of chlamydia pneumonia and conjunctivitis cases in the population, and no real measure of chlamydia infection. This study did not measure vertical transmission of Chlamydia trachomatis.
The authors impute a biological mechanism to the high incidence of syphilis in men who have sex with men using anti-retroviral drugs (in particular, HAART). We suggest, empiric data do not support the biological hypothesis, and behavioral explanations (i.e. increased condomless sex and selection of higher risk partners) are supported by stronger evidence.
Randomized double-blind trials of pre-exposure prophylaxis (PrEP) for HIV prevention [1] provide a rigorous test of the author’s hypothesis. The methodological strength includes an unconfounded and clearly unexposed control group and an exposed group which received an agent that would putatively increase susceptibility — tenofovir disoproxil fumarate (TDF) co-formulated with emtricitabine (FTC). A unique feature is that these trials were blinded and PrEP was unproven that the time trials were undertaken; hence, we would not expect that the TDF/FTC-exposed group would adopt higher risk practices.
An analysis of the iPrEx trial [2], a randomized PrEP trial in men who have sex with men/trans women, found [1] a relative rate of syphilis acquisition for TDF/FTC of 1.14 with a 0.95 confidence interval (0.90 to 1.45) compared to placebo. Incident syphilis, can be difficult to differentiate from a previous infection. Among those with a negative rapid plasma reagin titer at screening the relative rate of an on-study infection was 1.03, 0.95 CI (0.76 to 1.38). Adherence, was low in the iPrEx study and when pharmaco...
The authors impute a biological mechanism to the high incidence of syphilis in men who have sex with men using anti-retroviral drugs (in particular, HAART). We suggest, empiric data do not support the biological hypothesis, and behavioral explanations (i.e. increased condomless sex and selection of higher risk partners) are supported by stronger evidence.
Randomized double-blind trials of pre-exposure prophylaxis (PrEP) for HIV prevention [1] provide a rigorous test of the author’s hypothesis. The methodological strength includes an unconfounded and clearly unexposed control group and an exposed group which received an agent that would putatively increase susceptibility — tenofovir disoproxil fumarate (TDF) co-formulated with emtricitabine (FTC). A unique feature is that these trials were blinded and PrEP was unproven that the time trials were undertaken; hence, we would not expect that the TDF/FTC-exposed group would adopt higher risk practices.
An analysis of the iPrEx trial [2], a randomized PrEP trial in men who have sex with men/trans women, found [1] a relative rate of syphilis acquisition for TDF/FTC of 1.14 with a 0.95 confidence interval (0.90 to 1.45) compared to placebo. Incident syphilis, can be difficult to differentiate from a previous infection. Among those with a negative rapid plasma reagin titer at screening the relative rate of an on-study infection was 1.03, 0.95 CI (0.76 to 1.38). Adherence, was low in the iPrEx study and when pharmacology is taken into account, the hazard ratio for TDF/FTC among those with drug detected in plasma was 1.00, 0.95 CI (0.62 to 1.61), compared to placebo. Finally, we found that the incidence of syphilis decreased during the period of the trial in the TDF/FTC group (from 6.3 per 100 person years in the first year to 3.7 per 100 person years in subsequent years).
It is unlikely a biological TDF/FTC effect on syphilis acquisition would be missed when effects on HIV replication, bone mineral density, lipids, symptoms (e.g., nausea), and kidney function were readily detected in the iPrEx study even in the presence of suboptimal adherence. Randomized controlled trials are the gold standard in clinical research and this PrEP trial provides formidable evidence against the authors hypothesis.
References
1. Solomon MM, Mayer KH, Glidden DV. Syphilis predicts HIV incidence among men and transgender women who have sex with men in a preexposure prophylaxis trial. Clin Infect Dis. 2014; 59:1020-6. doi: 10.1093/cid/ciu450.
2. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363 :2587-99. doi: 10.1056 NEJMoa1011205.
I'm writing to ask if the authors considered an alternate hypothesis:
perhaps the symptoms of primary infection with syphilis are easier to
ignore than chlamydia and gonorrhea--the latter two often cause painful
urination and discharge, while with syphilis (in men) a chancre often
appears in the genital area, usually (but not always) on the penis. These
sores are often painless.
I'm writing to ask if the authors considered an alternate hypothesis:
perhaps the symptoms of primary infection with syphilis are easier to
ignore than chlamydia and gonorrhea--the latter two often cause painful
urination and discharge, while with syphilis (in men) a chancre often
appears in the genital area, usually (but not always) on the penis. These
sores are often painless.
To me it seems quite reasonable that the painless chancre symptoms of
primary syphilis infection would be a lot easier to ignore than those of
chlamydia and gonorrhea, which manifests in pain and quite obvious
discharge. Those with the latter two would likely seek out treatment and
cease sexual activity (and thereby reduce the spread), while individuals
with syphilis may just ignore the comparatively benign symptom, and
continue to spread it to others. So, infection with different diseases
likely results in different behavioral responses, which in turn affect the
rates.
I'm just a layperson so I apologize if this is ridiculous or already
accounted for, but I hope this perspective might help!
As few studies have examined the relation between pubic hair grooming
and sexually transmitted infections (STIs), we took advantage of
nationally representative survey data to begin to explore this possible
association and to develop hypotheses for future prospective studies. In
our analysis, we observed a positive association between self-reported
pubic hair grooming and STI history, which we interpreted in several
poss...
As few studies have examined the relation between pubic hair grooming
and sexually transmitted infections (STIs), we took advantage of
nationally representative survey data to begin to explore this possible
association and to develop hypotheses for future prospective studies. In
our analysis, we observed a positive association between self-reported
pubic hair grooming and STI history, which we interpreted in several
possible ways given the limitations of our study (e.g., its cross-
sectional study design, self-reported assessment of grooming and STIs, and
lack of information on additional possible confounders, such as condom
use) Interpretations of our findings included: a) grooming-associated
epithelial microtears leading to increased risk of cutaneous STIs; b)
grooming-related protection against lice by pubic hair removal; c)
residual confounding by characteristics common to both grooming and STIs,
such as risky sexual behaviors; and d) what we believe is the most likely
interpretation, a combination of all of these explanations given our
differing magnitudes of association by type of STI. Based on these
interesting hypothesis-generating findings, we recommended that additional
epidemiologic studies be conducted with prospective data collection,
laboratory confirmation of STIs, and collection detailed STI risk
information to elucidate the mechanisms underlying our findings.
In response to Ojha and colleagues' concerns about confounding by
gender, race, income, and sexual frequency, we adjusted our analyses for
these variables: gender (male, female), race (White/Caucasian,
Black/African American, Hispanic/Latino, Mixed Races, or Other), income
(<$50,000, $50,000-74,999, $75,000-99,000, and >$100,000 USD), and
sexual frequency (daily, weekly, monthly, every three months or less). We
also repeated the analyses with and without survey weights. The
association between grooming and a history of STI remained (aOR= 1.71, 95%
CI 1.37-2.15). The other analyses yielded generally similar magnitudes of
association and the same inferences as the results presented in our
manuscript.
Notwithstanding these largely unchanged estimates, we believe that
residual confounding is still a possible interpretation of our findings
and encourage more research on this topic. However, even in the presence
of residual confounding, we would like to reinforce that use of grooming
as a marker of high-risk sexual behaviors may still have value for STI
prevention efforts to help identify individuals who would benefit most
from STI prevention counseling.
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 MoreError 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 MorePrevalence of Mycoplasma genitalium
Response to: Taylor-Robinson D and Ong J
Authors: Nicola Low, Lukas Baumann, Manuel Cina, Myrofora Goutaki, Hammad Ali, Dianne Egli-Gany
Correspondence to: Nicola Low, Professor of Epidemiology and Public Health, Institute of Social and Preventive Medicine, University of Bern, Mittelstrasse 43, 3012 Bern, Switzerland. nicola.low@ispm.unibe.ch; Tel: +41 31 631 30 92
Title: Research on Mycoplasma genitalium is more important than expanding testing
We are glad that Taylor-Robinson and Ong offer some support for the conclusion of our systematic review,1 that asymptomatic populations, in the community or in clinics, should not be tested routinely for M. genitalium. The first British Association of Sexual Health and HIV (BASHH) guideline about the management of Mycoplasma genitalium, published on 8th July 2018, supports this conclusion.2 We would like to clarify, however, that the absence of evidence for clinical and public health benefit of screening3 and the harm of inducing de novo mutations and spreading resistance to macrolide antimicrobials4 are more important than economic considerations.
Taylor-Robinson and Ong’s statement that “testing worldwide should continue to support or modify this conclusion”5 could lead to pro...
Show MoreThe work by Baumann et al.(1) is valuable because it indicates populations for which screening for Mycoplasma genitalium (MG)) is not worthwhile economically. However, as molecular detection tests are now available commercially, testing worldwide should continue to support or modify this conclusion and so help in the development of management guidelines and also provide data for MG modelling.
Show MoreAnother aspect of infection which requires more attention is the precise role of MG in balanoposthitis, epididymitis,, chronic prostatitis, reactive arthritis, and, of course, pelvic inflammatory disease, all of which, apart from chronic prostatitis, have some association with MG (2).
In addition, it is noteworthy that Mycoplasma pneumoniae (MP), which infects the respiratory tract, and is also responsible for some autoimmune side effects, does so in early childhood without causing disease. The latter usually occurs as an immunological response to reinfection later in life. MG is different genomically from MP but has much in common antigenically and might behave in a similar way to MP. Could asymptomatic MG infection, which is seen occasionally, be an example of this? Potentiation or even inhibition of MG infection in the genital tract by MP infection in the respiratory tract earlier in life is also possible. This idea is not supported by studies in mice, but the human situation might be quite different. In this regard, use of an existing specific serological test for MG m...
Dear 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...
The authors estimated vertical transmission of Chlamydia trachomatis by a retrospective analysis using national registry data and clinical records and concluded that transmission was much lower (<2%) than the rate commonly quoted (50-70%). Their suggested explanation is that the modern use of highly sensitive NAATs detects nonviable chlamydiae so that mothers testing positive could actually be noninfectious whereas older studies based on use of culture only identified infectious pregnant women. That is not a likely explanation for such a big difference. When NAAT performance with cervical swabs was evaluated about 2/3 of NAAT positive specimens were culture positive.
Show MoreA more likely explanation comes from examining their case definition. It is not chlamydial infection, but rather laboratory confirmed cases of chlamydial conjunctivitis or pneumonia. And that is very different. When prospective studies were being done in San Francisco 175 infants born to chlamydia infected mothers were followed: 31 (18%) developed pneumonia; 29 (17%) conjunctivitis; 64 (37%) were culture positive and 105 (60%) had serologic evidence of infection. Thus there were many more infections than cases of conjunctivitis and pneumonia. But the difference between cases of disease and infection in the Finnish material is probably greater. In the prospective study there were cases of very mild disease that would likely not have been diagnosed in ordinary circumstances (seeing the whole clinical s...
The authors impute a biological mechanism to the high incidence of syphilis in men who have sex with men using anti-retroviral drugs (in particular, HAART). We suggest, empiric data do not support the biological hypothesis, and behavioral explanations (i.e. increased condomless sex and selection of higher risk partners) are supported by stronger evidence.
Randomized double-blind trials of pre-exposure prophylaxis (PrEP) for HIV prevention [1] provide a rigorous test of the author’s hypothesis. The methodological strength includes an unconfounded and clearly unexposed control group and an exposed group which received an agent that would putatively increase susceptibility — tenofovir disoproxil fumarate (TDF) co-formulated with emtricitabine (FTC). A unique feature is that these trials were blinded and PrEP was unproven that the time trials were undertaken; hence, we would not expect that the TDF/FTC-exposed group would adopt higher risk practices.
An analysis of the iPrEx trial [2], a randomized PrEP trial in men who have sex with men/trans women, found [1] a relative rate of syphilis acquisition for TDF/FTC of 1.14 with a 0.95 confidence interval (0.90 to 1.45) compared to placebo. Incident syphilis, can be difficult to differentiate from a previous infection. Among those with a negative rapid plasma reagin titer at screening the relative rate of an on-study infection was 1.03, 0.95 CI (0.76 to 1.38). Adherence, was low in the iPrEx study and when pharmaco...
Show MoreI'm writing to ask if the authors considered an alternate hypothesis: perhaps the symptoms of primary infection with syphilis are easier to ignore than chlamydia and gonorrhea--the latter two often cause painful urination and discharge, while with syphilis (in men) a chancre often appears in the genital area, usually (but not always) on the penis. These sores are often painless.
To me it seems quite reasonable...
As few studies have examined the relation between pubic hair grooming and sexually transmitted infections (STIs), we took advantage of nationally representative survey data to begin to explore this possible association and to develop hypotheses for future prospective studies. In our analysis, we observed a positive association between self-reported pubic hair grooming and STI history, which we interpreted in several poss...
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