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.
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.
Dear Editor, I am a contraception doctor working in the UK who reads STI. I have an interest in education. I read Dewsnap et al's publication in this months journal and am shocked as it is almost identical to one from a few years ago. Surely this is blatant Plagiarism although one of the authors is the same. Does the BMJ group know this? is this allowed in the BASHH column. Does BASHH know? does the previous author who wrote the original know (? David Richardson?)
Please note that this article is almost identical to one written by Daniel Richardson and colleagues in 2017? Did you not use anti plagiarism software? I am an editor of another journal but have keen interest in sexual health and the journal. I am shocked that this has been allowed to go to publication an print. I do not know Daniel Richardson, but they should be informed and action should be taken by you or the BMJ group.
It was a study that we evaluated the incidence of these pathogens on population that had done the molecular test to IST in a big laboratory in Brazil, this is only an epidemiological study. The microorganism have been chosen according availability of tests offered, so it was not evaluated the pathogenicity of each microorganism. Besides that our objective is only describe the profile of brazilian population, and did not correltated any data with clinical treatment. The molecular technology in Brazil is used as confirmatory of clinical diagnostic. The microorganism incidence in Brazil could be different from others countries due to characteristics of our population.
We read with interesting the recent report by Mwasakifwa and colleagues demonstrating that presence of mucopurulent ano-rectal discharge on clinical examination was associated with identification of a sexually transmitted organism by NAAT testing in men who have sex with men (MSM) with symptomatic proctitis.1 We also showed that sexually transmitted proctitis in MSM is often associated with more than one organism and that even with sensitive NAAT testing, there are a significant proportion of cases of MSM with proctitis with negative microbiology tests.2 We were however surprised that Mwasakifwa and colleagues did not identify any cases of syphilis in their analysis. This may have been because syphilis PCR testing was only conducted in a small proportion of cases? Ano-rectal syphilis was first described between 1945-1966 although most of these cases had anal ulceration with pain on defecation. Syphilis ‘proctitis’ was first described in 1975 from the USA in a man with rectal pain and discharge.3 In our series of MSM with proctitis, we reported 6/78(8%) cases of syphilis based upon PCR testing from the rectal mucosa during proctoscopy.2 The recent increase in infectious syphilis particularly in MSM is likely to increase the number of cases of ano-rectal syphilis. The clinical features of syphilis as the epidemic evolves may be changing and more MSM are presenting with painful lesions than was previously believed. We do agree that clinical examination of the ano-rectal area...
We read with interesting the recent report by Mwasakifwa and colleagues demonstrating that presence of mucopurulent ano-rectal discharge on clinical examination was associated with identification of a sexually transmitted organism by NAAT testing in men who have sex with men (MSM) with symptomatic proctitis.1 We also showed that sexually transmitted proctitis in MSM is often associated with more than one organism and that even with sensitive NAAT testing, there are a significant proportion of cases of MSM with proctitis with negative microbiology tests.2 We were however surprised that Mwasakifwa and colleagues did not identify any cases of syphilis in their analysis. This may have been because syphilis PCR testing was only conducted in a small proportion of cases? Ano-rectal syphilis was first described between 1945-1966 although most of these cases had anal ulceration with pain on defecation. Syphilis ‘proctitis’ was first described in 1975 from the USA in a man with rectal pain and discharge.3 In our series of MSM with proctitis, we reported 6/78(8%) cases of syphilis based upon PCR testing from the rectal mucosa during proctoscopy.2 The recent increase in infectious syphilis particularly in MSM is likely to increase the number of cases of ano-rectal syphilis. The clinical features of syphilis as the epidemic evolves may be changing and more MSM are presenting with painful lesions than was previously believed. We do agree that clinical examination of the ano-rectal area, including proctoscopy is a vital skill for sexual health clinicians and in the age of self-taken samples: we need to continue to teach and maintain this skill. Whether syphilis causes a true proctitis or ulceration of the anal canal remains debatable and is difficult to distinguish clinically, however we recommend that all MSM presenting with proctitis are tested for Syphilis using both PCR testing and serology.
1. Mwasakifwa GE, Nugent C, Varma R.Proctitis in gay and bisexual men. Are Microscopy and proctoscopy worthwhile? Sexually Transmitted Infections 2020 (online first)
2. Pinto Sander N, Fitzpatrick C, Parkes L, Richardson D. Sexually transmitted proctitis in men who have sex with men. Sexually Transmitted Infections 2019;95:471.
3. Nazemi MM, Musher DM, Schell RF, Milo S. Syphilitic proctitis in a homosexual JAMA 1975;231(4)389
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.
The Research Letter by Marinho FL and Zauli D (1) is interesting, but it raises several contentious issues. Understanding the prevalence of genital-tract micro-organisms that constitute the genital microbiome (2) is important (3) and the authors were concerned with this in respect of six micro-organisms that were detected by a molecular method (PCR). Whether they give them equal weight so far as pathogenicity is concerned is unclear because they did not relate them to any specific clinical disease. We appreciate that any micro-organism mentioned, including U. urealyticum, might have pathogenic potential under certain circumstances (4), but finding U. urealyticum as the most prevalent (62.47%) followed by M. hominis (9.31%) does not elevate their status as pathogens and raises clinically important questions of whether these micro-organisms, including U. parvum, should be tested for at all in a diagnostic procedure, unless part of a research programme, and, if tested, whether such positive results justify treatment. Admittedl the authors do not expressly state that, on the basis of a positive test result, patients would be treated automatically with antibiotics. Nevertheless, we must emphasize that the use of antibiotics in many such cases would seem inappropriate, not least because it might promote antibiotic resistance, sometimes in microbes of undoubted importance, such as N. gonorrhoeae and M. genitalium (6). Modern molecular technology is a boon, but it must not be al...
The Research Letter by Marinho FL and Zauli D (1) is interesting, but it raises several contentious issues. Understanding the prevalence of genital-tract micro-organisms that constitute the genital microbiome (2) is important (3) and the authors were concerned with this in respect of six micro-organisms that were detected by a molecular method (PCR). Whether they give them equal weight so far as pathogenicity is concerned is unclear because they did not relate them to any specific clinical disease. We appreciate that any micro-organism mentioned, including U. urealyticum, might have pathogenic potential under certain circumstances (4), but finding U. urealyticum as the most prevalent (62.47%) followed by M. hominis (9.31%) does not elevate their status as pathogens and raises clinically important questions of whether these micro-organisms, including U. parvum, should be tested for at all in a diagnostic procedure, unless part of a research programme, and, if tested, whether such positive results justify treatment. Admittedl the authors do not expressly state that, on the basis of a positive test result, patients would be treated automatically with antibiotics. Nevertheless, we must emphasize that the use of antibiotics in many such cases would seem inappropriate, not least because it might promote antibiotic resistance, sometimes in microbes of undoubted importance, such as N. gonorrhoeae and M. genitalium (6). Modern molecular technology is a boon, but it must not be allowed to foster unwanted outcomes.
References
1). Marinho FL, Zauli D. Cross-sectional study of patients tested for STIs using molecular methods in Brazil. Sex Transm Infect. Published
Online First: 26 Dec.2019. doi: 10.1136/sextrans-2019-054362
2). Taylor-Robinson D, Horner P, Pallecaros A. Understanding the terms we use: support for using 'Sexually Shared Microbiota' (SSM). Int J STD
& AIDS. 2020 Jan 16. doi. org/10.1177/09564624. 19885780
3). Taylor-Robinson D, Horner P, Pallecaros A. Diagnosis of some genital-tract infections: part 2. Molecular tests and the new challenges. Int J
STD & AIDS. In press
4). Beeton ML, Payne MS, Jones L. The role of Ureaplasma spp. in the development of nongonococcal urethritis and infertility among men. Clin
Microbiol Revs 2019; 32: 1-16
5). Horner P, Donders G, Cusini M, et al. Should we be testing for urogenital Mycoplasma hominis, Ureaplasma parvum and Ureaplasma urealyticum
in men and women? -- a position statement from the European STI Guidelines Editorial Board. J Eur Acad Dermatol
Venereol 2018; 32: 1845-1851. doi 10.1111/jdv.15146
6). Soni S, Horner P, Rayment M, et al. BASHH UK National Guideline for the Management of Infection with Mycoplasma genitalium. 2018.
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
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 MoreAlthough 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...
Dear Editor, I am a contraception doctor working in the UK who reads STI. I have an interest in education. I read Dewsnap et al's publication in this months journal and am shocked as it is almost identical to one from a few years ago. Surely this is blatant Plagiarism although one of the authors is the same. Does the BMJ group know this? is this allowed in the BASHH column. Does BASHH know? does the previous author who wrote the original know (? David Richardson?)
This should be addressed with COPE?
Yours Marie
Please note that this article is almost identical to one written by Daniel Richardson and colleagues in 2017? Did you not use anti plagiarism software? I am an editor of another journal but have keen interest in sexual health and the journal. I am shocked that this has been allowed to go to publication an print. I do not know Daniel Richardson, but they should be informed and action should be taken by you or the BMJ group.
Dear David Taylor-Robinson,
We are very grateful with your contribution.
It was a study that we evaluated the incidence of these pathogens on population that had done the molecular test to IST in a big laboratory in Brazil, this is only an epidemiological study. The microorganism have been chosen according availability of tests offered, so it was not evaluated the pathogenicity of each microorganism. Besides that our objective is only describe the profile of brazilian population, and did not correltated any data with clinical treatment. The molecular technology in Brazil is used as confirmatory of clinical diagnostic. The microorganism incidence in Brazil could be different from others countries due to characteristics of our population.
Best regards.
Danielle Alves Gomes Zauli
We read with interesting the recent report by Mwasakifwa and colleagues demonstrating that presence of mucopurulent ano-rectal discharge on clinical examination was associated with identification of a sexually transmitted organism by NAAT testing in men who have sex with men (MSM) with symptomatic proctitis.1 We also showed that sexually transmitted proctitis in MSM is often associated with more than one organism and that even with sensitive NAAT testing, there are a significant proportion of cases of MSM with proctitis with negative microbiology tests.2 We were however surprised that Mwasakifwa and colleagues did not identify any cases of syphilis in their analysis. This may have been because syphilis PCR testing was only conducted in a small proportion of cases? Ano-rectal syphilis was first described between 1945-1966 although most of these cases had anal ulceration with pain on defecation. Syphilis ‘proctitis’ was first described in 1975 from the USA in a man with rectal pain and discharge.3 In our series of MSM with proctitis, we reported 6/78(8%) cases of syphilis based upon PCR testing from the rectal mucosa during proctoscopy.2 The recent increase in infectious syphilis particularly in MSM is likely to increase the number of cases of ano-rectal syphilis. The clinical features of syphilis as the epidemic evolves may be changing and more MSM are presenting with painful lesions than was previously believed. We do agree that clinical examination of the ano-rectal area...
Show MoreDear 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...
The Research Letter by Marinho FL and Zauli D (1) is interesting, but it raises several contentious issues. Understanding the prevalence of genital-tract micro-organisms that constitute the genital microbiome (2) is important (3) and the authors were concerned with this in respect of six micro-organisms that were detected by a molecular method (PCR). Whether they give them equal weight so far as pathogenicity is concerned is unclear because they did not relate them to any specific clinical disease. We appreciate that any micro-organism mentioned, including U. urealyticum, might have pathogenic potential under certain circumstances (4), but finding U. urealyticum as the most prevalent (62.47%) followed by M. hominis (9.31%) does not elevate their status as pathogens and raises clinically important questions of whether these micro-organisms, including U. parvum, should be tested for at all in a diagnostic procedure, unless part of a research programme, and, if tested, whether such positive results justify treatment. Admittedl the authors do not expressly state that, on the basis of a positive test result, patients would be treated automatically with antibiotics. Nevertheless, we must emphasize that the use of antibiotics in many such cases would seem inappropriate, not least because it might promote antibiotic resistance, sometimes in microbes of undoubted importance, such as N. gonorrhoeae and M. genitalium (6). Modern molecular technology is a boon, but it must not be al...
Show MoreSir,
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....
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