I read with great interest a recently published article by Harfouche et al, in the STI.1 The authors have used mathematical modelling to estimate the global and regional burden of Herpes simplex virus -1 (HSV-1) and Herpes simplex virus-2 (HSV-2). I find a serious concern that authors have not provided any information about or proposed model to estimate the incidence and prevalence of HSV-1 and HSV-2 in people living with HIV. This information, and model if any, would be very crucial; as the prevalence and incidence of these viruses especially that of HSV-2, varies significantly in people living with HIV as compared to in those who are living without HIV.2 Not only incidence and prevalence of HSV-2 is different in these two populations but the coinfection of these viruses has important role in HIV pathogenesis and AIDS disease progression. In a recent study we reported that overall prevalence of HSV-1 in Indian adult males was 75.2%. Of these, 68.18% were males living with HIV. The prevalence of HSV-1 in people living with HIV was 77.2% and 71.2% in males without HIV. The difference was not statistically significant. The prevalence increased with age, from 60% in males aged <25 years to 86% in older subjects (P = 0.0188). The overall prevalence of HSV-2 was 28.20% in Indian males. However, the prevalence of HSV-2 in people living with HIV was 39.9% while in males without HIV, it was only 5.1%. The prevalence of HSV-2 in patients living with HIV increased with age, f...
I read with great interest a recently published article by Harfouche et al, in the STI.1 The authors have used mathematical modelling to estimate the global and regional burden of Herpes simplex virus -1 (HSV-1) and Herpes simplex virus-2 (HSV-2). I find a serious concern that authors have not provided any information about or proposed model to estimate the incidence and prevalence of HSV-1 and HSV-2 in people living with HIV. This information, and model if any, would be very crucial; as the prevalence and incidence of these viruses especially that of HSV-2, varies significantly in people living with HIV as compared to in those who are living without HIV.2 Not only incidence and prevalence of HSV-2 is different in these two populations but the coinfection of these viruses has important role in HIV pathogenesis and AIDS disease progression. In a recent study we reported that overall prevalence of HSV-1 in Indian adult males was 75.2%. Of these, 68.18% were males living with HIV. The prevalence of HSV-1 in people living with HIV was 77.2% and 71.2% in males without HIV. The difference was not statistically significant. The prevalence increased with age, from 60% in males aged <25 years to 86% in older subjects (P = 0.0188). The overall prevalence of HSV-2 was 28.20% in Indian males. However, the prevalence of HSV-2 in people living with HIV was 39.9% while in males without HIV, it was only 5.1%. The prevalence of HSV-2 in patients living with HIV increased with age, from 23.3% in males aged <25 years to 47.1% in males aged between 35–39 years (P = 0.0796). Overall, 25.9% males were co-infected with HSV-1 and HSV-2. Of these most (95.6%) were also living with HIV (triply infection). HSV coinfection was higher among married males as compared to unmarried men.2
Prof. Sarman Singh, MD, FRCP
Aarupadai Veedu Medical College & Hospital,
Vinayaka Mission’s Research Foundation (Deemed University)
Pondicherry, India
Email: sarman_singh@yahoo.com
References.
1. Harfouche M, AlMukdad S, Alareeki A, Osman AMM, Gottlieb S, Rowley J, Abu-Raddad LJ, Looker KJ. Estimated global and regional incidence and prevalence of herpes simplex virus infections and genital ulcer disease in 2020: mathematical modelling analyses. Sex Transm Infect. 2024 Dec 10:sextrans-2024-056307. doi: 10.1136/sextrans-2024-056307. Epub ahead of print. PMID: 39658199.
2. Munawwar A, Gupta S, Sharma SK, Singh S. Seroprevalence of HSV-1 and 2 in HIV-infected males with and without GUD: Study from a tertiary care setting of India. J Lab Physicians. 2018 Jul-Sep;10(3):326-331. doi: 10.4103/JLP.JLP_7_18. PMID: 30078971; PMCID: PMC6052809.
We sincerely thank the reader for their interest in our article and for drawing attention to the important issue of HSV infections among people living with HIV (PLHIV). We fully agree that the epidemiology of HSV-1 and HSV-2 infections can differ markedly between PLHIV and the general population, and that coinfection—particularly the interplay between HSV-2 and HIV—has important clinical and public health implications, including for HIV acquisition, transmission, and disease progression. These interactions have been a major focus of our prior work and have been addressed extensively in numerous previous publications.
The present study was designed with a specific scope: to generate global and regional estimates of HSV-1 and HSV-2 infections in the total population, using the best available epidemiological data. Unfortunately, the global data landscape remains too limited to support robust modeling of HSV infections specifically among PLHIV or other key subpopulations. In particular, population-level data disaggregated by HIV status are lacking across most regions of the world.
In summary, the absence of HIV-specific estimates in this analysis does not reflect a lack of recognition of their importance. On the contrary, we have addressed HSV–HIV interactions in earlier studies and remain committed to investigating these important dynamics in future research.
Professor Laith Abu-Raddad, Ph.D.
Weill Cornell Medicine – Qatar
Cornell University...
We sincerely thank the reader for their interest in our article and for drawing attention to the important issue of HSV infections among people living with HIV (PLHIV). We fully agree that the epidemiology of HSV-1 and HSV-2 infections can differ markedly between PLHIV and the general population, and that coinfection—particularly the interplay between HSV-2 and HIV—has important clinical and public health implications, including for HIV acquisition, transmission, and disease progression. These interactions have been a major focus of our prior work and have been addressed extensively in numerous previous publications.
The present study was designed with a specific scope: to generate global and regional estimates of HSV-1 and HSV-2 infections in the total population, using the best available epidemiological data. Unfortunately, the global data landscape remains too limited to support robust modeling of HSV infections specifically among PLHIV or other key subpopulations. In particular, population-level data disaggregated by HIV status are lacking across most regions of the world.
In summary, the absence of HIV-specific estimates in this analysis does not reflect a lack of recognition of their importance. On the contrary, we have addressed HSV–HIV interactions in earlier studies and remain committed to investigating these important dynamics in future research.
Professor Laith Abu-Raddad, Ph.D.
Weill Cornell Medicine – Qatar
Cornell University
Doha, Qatar
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).
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...
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.
Id like to congratulate the authors for highlighting this case of extensively antimicrobial resistant Shigella sonnei in an MSM in Italy which is most likely part of the current S.sonnei outbreak accross europe which has shown to contain plasmids with CTX-M-27. Sexual health , primary care and gastroenterology clinicians continue to prescribe (sometimes inappropriate) antimicrobials to MSM including for asymptomatic extragenital STIs and empirically for diarrhoeal illnesses despite the emergence of antimicrobial resistant N. gonorrhoea, M. genitalium and enteric pathogens including Shigella spp.. Enteric pathogens are particularly efficient in transmitting AMR genes such as bla-CTX-M27 via horizontal transmission of plasmids, hence the rapid evolution of resistant shigella in MSM. The learning points from your paper for clinicians need to be emphasising the need for far better governance around antimicrobial prescribing in this group including empirical management of diarrhoea. We have recently published UK BASHH guidance on antimicrobial prescribing for diarrhoea and enteric pathogens, however more work is needed to control the evolution and transmission of resistant shigella and other STIs in MSM
We read with interest an article by Ikeuchi et al.1 We agree with their conclusion that the relatively low dose of amoxicillin could lead to the cure of syphilis. However, we would like to raise concern that the findings might not be generalized to different populations. The majority of the patients had concurrent HIV infection, and the study setting is well known prestigious center for HIV care in Japan, with decades of HIV care in Tokyo, suggesting that the patients who participated in the study are likely to be adherent to the medications prescribed, because they are instructed thoroughly in taking antiretroviral therapy. In addition, those who did not have HIV infection in the study did not have a previous history of syphilis, and they might also be likely to be adherent to the regimen compared with those who had repeated STDs. As pointed out in the study, the recommended duration of amoxicillin therapy by Japanese STD guideline is very long (4-8 weeks), and we are not sure whether patients with syphilis in general can be adherent to this regimen. Therefore, we consider that the findings by Ikeuchi et al. may not be generalizable, particularly for those who are not very aware of the importance of adherence to the medication, or those who take the risk of STDs lightly (and have repeated STDs). Future studies with different settings and populations might clarify our concerns.
We read with interest an article by Ikeuchi et al.1 We agree with their conclusion that the relatively low dose of amoxicillin could lead to the cure of syphilis. However, we would like to raise concern that the findings might not be generalized to different populations. The majority of the patients had concurrent HIV infection, and the study setting is well known prestigious center for HIV care in Japan, with decades of HIV care in Tokyo, suggesting that the patients who participated in the study are likely to be adherent to the medications prescribed, because they are instructed thoroughly in taking antiretroviral therapy. In addition, those who did not have HIV infection in the study did not have a previous history of syphilis, and they might also be likely to be adherent to the regimen compared with those who had repeated STDs. As pointed out in the study, the recommended duration of amoxicillin therapy by Japanese STD guideline is very long (4-8 weeks), and we are not sure whether patients with syphilis in general can be adherent to this regimen. Therefore, we consider that the findings by Ikeuchi et al. may not be generalizable, particularly for those who are not very aware of the importance of adherence to the medication, or those who take the risk of STDs lightly (and have repeated STDs). Future studies with different settings and populations might clarify our concerns.
Reference
1. Ikeuchi K, Fukushima K, Tanaka M, Yajima K, Imamura A. Clinical efficacy and tolerability of 1.5 g/day oral amoxicillin therapy without probenecid for the treatment of syphilis. Sex Transm Infect 2022; 98:173–177.
It would be good to have known the role of Mycoplasma genitalium in this population where asymptomatic infections by other pathogens were common and at least have mentioned it in the Discussion
Despite significant differences in testing opportunities, screening and access to care, this paper clearly sets out some important epidemiology of STIs accross Europe, particularly among MSM using PrEP. Despite this, there is no mention of sexually transmitted enteric infections, despite a recent outbreak of extensively drug resistant Shigella sonnei which has affected sexual networks of MSM accross Europe. There have been outbreaks of Shigella described in networks of MSM since the 1960s and can cause sugnificant morbidity. There are poor surveillance systems to monitor shigella outbreaks including transmssion of drug resistant organisms. More work is needed on both surveillance and shigella control strategies including awareness amongst both the communities affected and stakeholders including commissioners and public health.
The study by Dean et al. (1) on the treatment of PID was complicated and thought-provoking. Could it be that "mild" PID comprised many cases that were not PID at all? This issue bedevilled studies in the past, so why not here? Am I right in thinking that randomisation was used to try to maintain an evenness of disease severity between the two treatment arms, that is standard (SoC) with ofloxacin plus metronidazole, and an intervention arm (IA) with intramuscular ceftriaxone plus azithromycin and metronidazole? This is an important point when the outcome of each arm is to be compared. Presumably, after diagnosis treatment began without delay, not waiting for the results of microbiological tests which, in fact, showed M.genitalium in about 10% of cases in each arm, a proporttion seen by others (3) in acute PID. Standard treatment was judged to be slightly superior to the alternative treatment. Tests of microbiological cure 6 to 8 weeks after the study started showed a few azithromycin- resistant cases of M.genitalium, roughly comparable in the two arms. Not being aware of this at the start of treatment seems excusable. The reader must also realize that it was a situation experienced up to 9 years ago before an abrupt termination of the study. Today the scene is different, resistance of M.genitalium to azithromycin and other antibiotics being common (4). It has become clear that M.genitalium should be sought early followed rapidly by treatment guided by nothing othe...
The study by Dean et al. (1) on the treatment of PID was complicated and thought-provoking. Could it be that "mild" PID comprised many cases that were not PID at all? This issue bedevilled studies in the past, so why not here? Am I right in thinking that randomisation was used to try to maintain an evenness of disease severity between the two treatment arms, that is standard (SoC) with ofloxacin plus metronidazole, and an intervention arm (IA) with intramuscular ceftriaxone plus azithromycin and metronidazole? This is an important point when the outcome of each arm is to be compared. Presumably, after diagnosis treatment began without delay, not waiting for the results of microbiological tests which, in fact, showed M.genitalium in about 10% of cases in each arm, a proporttion seen by others (3) in acute PID. Standard treatment was judged to be slightly superior to the alternative treatment. Tests of microbiological cure 6 to 8 weeks after the study started showed a few azithromycin- resistant cases of M.genitalium, roughly comparable in the two arms. Not being aware of this at the start of treatment seems excusable. The reader must also realize that it was a situation experienced up to 9 years ago before an abrupt termination of the study. Today the scene is different, resistance of M.genitalium to azithromycin and other antibiotics being common (4). It has become clear that M.genitalium should be sought early followed rapidly by treatment guided by nothing other than the result of antibiotic sensitivity testing. This cannot be questioned and is an action with which the authors, according to their final comments, support. However, it is interesting that the authors of a recent publication (5) recommend using ceftriaxone, doxycycline and metronidazole as standard treatment for acute PID. Curiously, they found infection by M.genitalium was reduced considerably by metronidazole to which it is not sensitive in vitro. It seems the last word has not been said.
References
1. Dean G, Soni S, Pitt R, et al. Treatment of mild-to-moderate pelvic inflammatory disease with a short-course azithromycin-based regimen versus ofloxacin plus metronidazole : results of a multicentre, randomized control trial. Sex Transm Infect 2020
2..Taylor-Robinson D. Investigating the microbial aetiology of pelvic inflammatory disease. Sex Transm Infect. 2003; 79: 424-5.
3. Lewis J, Horner PJ, White PJ. Incidence of pelvic inflammatory disease associated with Mycoplasma genitalium infection : evidence synthesis of cohort study data. Clin Infect Dis. 2020
4. Durukan D, Doyle M, Murray G, et al. Doxycycline and sitafloxacin combination therapy for treating highly resistant Mycoplasma genitalium. Emerg Infect Dis.2020 ; 26: 1870-4.
5. Wiesenfeld HC, Meyn LA, Darville T, et al. A randomized controlled trial of ceftriaxone and doxycycline, with or without metronidazole, for the treatment of acute pelvic inflammatory disease. Clin Infect Dis. 2020: xx (xx) :1-9.
I read with great interest a recently published article by Harfouche et al, in the STI.1 The authors have used mathematical modelling to estimate the global and regional burden of Herpes simplex virus -1 (HSV-1) and Herpes simplex virus-2 (HSV-2). I find a serious concern that authors have not provided any information about or proposed model to estimate the incidence and prevalence of HSV-1 and HSV-2 in people living with HIV. This information, and model if any, would be very crucial; as the prevalence and incidence of these viruses especially that of HSV-2, varies significantly in people living with HIV as compared to in those who are living without HIV.2 Not only incidence and prevalence of HSV-2 is different in these two populations but the coinfection of these viruses has important role in HIV pathogenesis and AIDS disease progression. In a recent study we reported that overall prevalence of HSV-1 in Indian adult males was 75.2%. Of these, 68.18% were males living with HIV. The prevalence of HSV-1 in people living with HIV was 77.2% and 71.2% in males without HIV. The difference was not statistically significant. The prevalence increased with age, from 60% in males aged <25 years to 86% in older subjects (P = 0.0188). The overall prevalence of HSV-2 was 28.20% in Indian males. However, the prevalence of HSV-2 in people living with HIV was 39.9% while in males without HIV, it was only 5.1%. The prevalence of HSV-2 in patients living with HIV increased with age, f...
Show MoreWe sincerely thank the reader for their interest in our article and for drawing attention to the important issue of HSV infections among people living with HIV (PLHIV). We fully agree that the epidemiology of HSV-1 and HSV-2 infections can differ markedly between PLHIV and the general population, and that coinfection—particularly the interplay between HSV-2 and HIV—has important clinical and public health implications, including for HIV acquisition, transmission, and disease progression. These interactions have been a major focus of our prior work and have been addressed extensively in numerous previous publications.
The present study was designed with a specific scope: to generate global and regional estimates of HSV-1 and HSV-2 infections in the total population, using the best available epidemiological data. Unfortunately, the global data landscape remains too limited to support robust modeling of HSV infections specifically among PLHIV or other key subpopulations. In particular, population-level data disaggregated by HIV status are lacking across most regions of the world.
In summary, the absence of HIV-specific estimates in this analysis does not reflect a lack of recognition of their importance. On the contrary, we have addressed HSV–HIV interactions in earlier studies and remain committed to investigating these important dynamics in future research.
Professor Laith Abu-Raddad, Ph.D.
Show MoreWeill Cornell Medicine – Qatar
Cornell University...
Prevalence 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 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 MoreWe 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 MoreId like to congratulate the authors for highlighting this case of extensively antimicrobial resistant Shigella sonnei in an MSM in Italy which is most likely part of the current S.sonnei outbreak accross europe which has shown to contain plasmids with CTX-M-27. Sexual health , primary care and gastroenterology clinicians continue to prescribe (sometimes inappropriate) antimicrobials to MSM including for asymptomatic extragenital STIs and empirically for diarrhoeal illnesses despite the emergence of antimicrobial resistant N. gonorrhoea, M. genitalium and enteric pathogens including Shigella spp.. Enteric pathogens are particularly efficient in transmitting AMR genes such as bla-CTX-M27 via horizontal transmission of plasmids, hence the rapid evolution of resistant shigella in MSM. The learning points from your paper for clinicians need to be emphasising the need for far better governance around antimicrobial prescribing in this group including empirical management of diarrhoea. We have recently published UK BASHH guidance on antimicrobial prescribing for diarrhoea and enteric pathogens, however more work is needed to control the evolution and transmission of resistant shigella and other STIs in MSM
To the editor.
We read with interest an article by Ikeuchi et al.1 We agree with their conclusion that the relatively low dose of amoxicillin could lead to the cure of syphilis. However, we would like to raise concern that the findings might not be generalized to different populations. The majority of the patients had concurrent HIV infection, and the study setting is well known prestigious center for HIV care in Japan, with decades of HIV care in Tokyo, suggesting that the patients who participated in the study are likely to be adherent to the medications prescribed, because they are instructed thoroughly in taking antiretroviral therapy. In addition, those who did not have HIV infection in the study did not have a previous history of syphilis, and they might also be likely to be adherent to the regimen compared with those who had repeated STDs. As pointed out in the study, the recommended duration of amoxicillin therapy by Japanese STD guideline is very long (4-8 weeks), and we are not sure whether patients with syphilis in general can be adherent to this regimen. Therefore, we consider that the findings by Ikeuchi et al. may not be generalizable, particularly for those who are not very aware of the importance of adherence to the medication, or those who take the risk of STDs lightly (and have repeated STDs). Future studies with different settings and populations might clarify our concerns.
Reference
Show More1. Ikeuchi K, Fukushima K, Tanaka M, Yajima K, Im...
It would be good to have known the role of Mycoplasma genitalium in this population where asymptomatic infections by other pathogens were common and at least have mentioned it in the Discussion
Despite significant differences in testing opportunities, screening and access to care, this paper clearly sets out some important epidemiology of STIs accross Europe, particularly among MSM using PrEP. Despite this, there is no mention of sexually transmitted enteric infections, despite a recent outbreak of extensively drug resistant Shigella sonnei which has affected sexual networks of MSM accross Europe. There have been outbreaks of Shigella described in networks of MSM since the 1960s and can cause sugnificant morbidity. There are poor surveillance systems to monitor shigella outbreaks including transmssion of drug resistant organisms. More work is needed on both surveillance and shigella control strategies including awareness amongst both the communities affected and stakeholders including commissioners and public health.
The study by Dean et al. (1) on the treatment of PID was complicated and thought-provoking. Could it be that "mild" PID comprised many cases that were not PID at all? This issue bedevilled studies in the past, so why not here? Am I right in thinking that randomisation was used to try to maintain an evenness of disease severity between the two treatment arms, that is standard (SoC) with ofloxacin plus metronidazole, and an intervention arm (IA) with intramuscular ceftriaxone plus azithromycin and metronidazole? This is an important point when the outcome of each arm is to be compared. Presumably, after diagnosis treatment began without delay, not waiting for the results of microbiological tests which, in fact, showed M.genitalium in about 10% of cases in each arm, a proporttion seen by others (3) in acute PID. Standard treatment was judged to be slightly superior to the alternative treatment. Tests of microbiological cure 6 to 8 weeks after the study started showed a few azithromycin- resistant cases of M.genitalium, roughly comparable in the two arms. Not being aware of this at the start of treatment seems excusable. The reader must also realize that it was a situation experienced up to 9 years ago before an abrupt termination of the study. Today the scene is different, resistance of M.genitalium to azithromycin and other antibiotics being common (4). It has become clear that M.genitalium should be sought early followed rapidly by treatment guided by nothing othe...
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