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.
Dear editor,
We thank Dr. Latini et al. for providing the data for the potential effects of SARS-CoV-2 pandemic on sexual lifestyle and epidemiology of sexually transmitted infections (STIs).1 In the study the author highlighted the importance to check the lasting effects of SARS-CoV-2 on STIs. As China is the first country to generally alleviate lockdown of most cities since beginning of April and the returns to usual lifestyle for nearly 6 months, we’re able to tract the epidemiology of STIs during the post-outbreak period in China.
According to the monthly report disclosed by Chinese Center for Disease Control and Prevention (Accessed from http://www.nhc.gov.cn/jkj/pqt/new_list.shtml), during the lockdown period of the first quarter, the number of newly diagnosed cases of HIV, syphilis and gonorrhea were 9695, 102273 and 16439, which reduced substantially by 27.3%, 19.3% and 38.2% compared to the previous year. After lockdown alleviation, the number of new cases returned, but not exceeding the previous years. The total new cases of HIV, syphilis and gonorrhea changed by -4.4%, -5.6% and -18.9% in the second quarter and -7.8%, -9.5% and +0.7% in the third quarter compared with 2019, respectively. As the number of new STIs in China is constantly growing in the past years, the reduction of new cases of STIs in 2020 after lockdown alleviation indicates a lasting effect of SARS-CoV-2. This may result from...
Dear editor,
We thank Dr. Latini et al. for providing the data for the potential effects of SARS-CoV-2 pandemic on sexual lifestyle and epidemiology of sexually transmitted infections (STIs).1 In the study the author highlighted the importance to check the lasting effects of SARS-CoV-2 on STIs. As China is the first country to generally alleviate lockdown of most cities since beginning of April and the returns to usual lifestyle for nearly 6 months, we’re able to tract the epidemiology of STIs during the post-outbreak period in China.
According to the monthly report disclosed by Chinese Center for Disease Control and Prevention (Accessed from http://www.nhc.gov.cn/jkj/pqt/new_list.shtml), during the lockdown period of the first quarter, the number of newly diagnosed cases of HIV, syphilis and gonorrhea were 9695, 102273 and 16439, which reduced substantially by 27.3%, 19.3% and 38.2% compared to the previous year. After lockdown alleviation, the number of new cases returned, but not exceeding the previous years. The total new cases of HIV, syphilis and gonorrhea changed by -4.4%, -5.6% and -18.9% in the second quarter and -7.8%, -9.5% and +0.7% in the third quarter compared with 2019, respectively. As the number of new STIs in China is constantly growing in the past years, the reduction of new cases of STIs in 2020 after lockdown alleviation indicates a lasting effect of SARS-CoV-2. This may result from changes of sexual lifestyle or reduced hospital visits. More studies focusing on sex behaviors after lockdown alleviation are needed.
Reference:
1. Latini A, Magri F, Donà MG, et alIs COVID-19 affecting the epidemiology of STIs? The experience of syphilis in RomeSexually Transmitted Infections Published Online First: 27 July 2020. doi: 10.1136/sextrans-2020-054543
We apologise for the delay in responding to your letter. We were only recently notified of this by email. Thank you for taking the time to construct your letter in response to our published short report, to which you raise several points which require addressing.
Firstly we feel it is important to highlight that although this service evaluation focussed specifically on HIV, we acknowledged that the HIV sampling kit was part of a more comprehensive STI kit (syphilis, chlamydia, and gonorrhoea tests). We were upfront with this fact in our report, and therefore refute the claim by the responder that our paper failed to consider the wider test portfolio required by sexual health screening services.
Of greater concern to us, we note a major error in the calculations from the data provided by the responders for their “RRR” and “HIV result obtained/ STI kit requested” values. This is important, as the foundation of their concluding statement is based on this error. The responder's have incorrectly used the number of returned kits (256,717) instead of the number of requested kits (319,485) in calculating the RRR (request-to-return ratio) and the “HIV result obtained/STI kit requested” proportion. Applying the correct calculation, the RRR value using the responder's data is not 1.36 (256,717/188,187) but 1.70 (319,485/188,187). The “HIV result obtained/STI kit requested” proportion using the correct calculation is 58.9% (188,187/319,485) and not 73.3%...
We apologise for the delay in responding to your letter. We were only recently notified of this by email. Thank you for taking the time to construct your letter in response to our published short report, to which you raise several points which require addressing.
Firstly we feel it is important to highlight that although this service evaluation focussed specifically on HIV, we acknowledged that the HIV sampling kit was part of a more comprehensive STI kit (syphilis, chlamydia, and gonorrhoea tests). We were upfront with this fact in our report, and therefore refute the claim by the responder that our paper failed to consider the wider test portfolio required by sexual health screening services.
Of greater concern to us, we note a major error in the calculations from the data provided by the responders for their “RRR” and “HIV result obtained/ STI kit requested” values. This is important, as the foundation of their concluding statement is based on this error. The responder's have incorrectly used the number of returned kits (256,717) instead of the number of requested kits (319,485) in calculating the RRR (request-to-return ratio) and the “HIV result obtained/STI kit requested” proportion. Applying the correct calculation, the RRR value using the responder's data is not 1.36 (256,717/188,187) but 1.70 (319,485/188,187). The “HIV result obtained/STI kit requested” proportion using the correct calculation is 58.9% (188,187/319,485) and not 73.3% as they have presented. We note that using the data provided by the responder's, the successful processing proportions of their MT samples were lower than that from our DBS samples (84.6% vs 98.8% for the DBS). The data presented by the responder’s highlights there are MT processing issues once a sample has been successfully returned by the user, and we would be interested to know the reasons for these processing failures, which account for 15.4% of their returned samples (compared with 0.2% of returned DBS samples from our paper). For these reasons it becomes clear that the responder’s claims do not undermine the findings of our study.
We would like to address the responder's comments about the “low return rates for postal testing” to which the responder's regard as a shortfall within this research. As detailed in the report, data collection spanned a short 4-month period, where return rates were found to be 68.7% for MT and 66.5% for DBS. We do not accept that these rates are considered as “low”. The return rates are average when compared with other peer-reviewed published data with a STI kit return rate focus, with rates ranging from 32.8% - 84% (Osmond 2000, Elliot 2015, Cordwell 2015, Manavi 2017, Turner 2019). The impressive return rates described by the responder's are provided without much context (e.g. is this looking at a historic complete data-set of all their kit requests across the nation, or is this a snapshot over a short time period from a region, which included kits that may have been requested, but returns fell outside of the time-period?). Without this context to frame the responder's return rates to, it is impossible to make inferences on their return rates. Had they provided the same data, but stated it was from the same region as our study, these comments would have been more credible.
Some of the critiques made by the responder's were already addressed in the short report, and we fail to understand why these points have been raised again, and presented as new information. We clearly acknowledged our small sample size (550) in our limitations, and encouraged further comparative evaluations, of greater numbers, across different regions to test the robustness of our report. We additionally addressed the low processing rates of MT from our report by stating that a large proportion of samples were of insufficient volumes supplied by the kit user (accounting for 22.5% of all MT samples). Our report also addressed the disadvantages of DBS, citing a more complex extraction process, higher cost and fewer laboratories accredited to analyse these samples. The nature of the comparative review meant that assessing the “real-world true HIV negative results” was difficult in the context of service provision. Our clinical experience makes us certain that outside of the remit of prospective research, service providers would not ask its users to do two differing HIV tests (besides point-of care testing) for HIV negative results. Pragmatically, it is usually easier to verify reactive results, as most sexual health clinics will mandate repeat HIV testing with the gold standard venous blood sampling. Once again, we acknowledge this fact in our report.
Several criticisms raised by the responder's towards our laboratory methodology appear to be misplaced, and perhaps should have been directed towards the potential for operator-based (client-dependent) difficulties. We agree that MT samples used in a clinical setting and stored in controlled laboratory conditions may have remained stable in excess of 4 days (the responder's quoted 8 days for their laboratory). We know that in reality, these laboratory conditions cannot be replicated by the general public (e.g. users may leave samples on surfaces exposed to direct sunlight, or leave them in their bag for extended periods of time before posting). Furthermore, as part of the UKAS accredited laboratory validation process, the laboratory used for this report identified samples older than 4 days (stored in realistic conditions) were associated with a higher false positive HIV rate (compared to those which were under 4 days).
We would like to provide some clarity of some of the questions asked by the responder's. Regarding their comment on the lack of quantification of what was considered a haemolysed sample. We can confirm that this process was two-stage. Obviously haemolysed blood was rejected manually. Borderline samples however, were still put through the analyser, and those which were rejected by the instrument software were deemed to have been done so due to haemolysis.
Regarding the responder's commentary about the quoted sensitivities and specificities of the assays; these standardised references are explicitly with reference to venous blood samples and not capillary blood samples. The quoted sensitivities and specificities are not necessarily transferrable between the two, and laboratory-based validation processes are required to ensure test accuracy. The laboratory used in our report had previously conducted sensitivity and specificity studies to which they have validated the DBS assay, which was directly compared with known HIV-positive whole blood samples. From this, they found that an 8-fold reduction in concentration was acceptable in order to make a diagnosis. Furthermore, the process was accredited for routine use following a successful UKAS inspection. We would like to add that we do comment in our supplementary data that both DBS filter paper and MT containers were CE marked, as the responder's seemed to infer otherwise.
While the responder's rightly state a small sample (200-400microlitres of serum once centrifuge) is required for processing, they have omitted some key points. Firstly, the sample that the user provides is not serum, but whole blood; and therefore more than 400microlitres of blood will be required from the user. Insufficient samples in our study were in reference to whole blood volumes. In order to obtain 200-400microlitres of serum, you need to start off with 1ml of blood, which was not what was being achieved by many of the MT users in our report. We also dispute being able to carry out all the 5 tests mentioned (HIV, Syphilis Ab, Hepatitis B, Hepatitis C, and quantitative syphilis RPR and TPHA) with 200-400microlitres of serum, which the responder's have made an ambiguous reference to.
We strongly refute the claim of author bias considering that at the time the report was conducted, the service was offering both MT and DBS. We also refute the responder’s suggestion of inadequate procedural quality control, and have justified this in our report, supplementary details and in this response letter.
In summary, the data compiled by the responder's was inaccurate and misleading regarding their overall HIV result-to-STI kits requested, and RRR values. The data they have provided do not compare favourably to the performance the DBS from our report. Their data suggests that much of their success was driven by higher kit return rates compared to our paper (80.4% vs our papers 68.7% for MT and 66.5% for DBS). The responder's data suggests that they too experienced a drop in the successful processing rate for MT (84.6% compared with 98.8% for our papers DBS). This drop was also observed in our paper when comparing MT and DBS. This in essence, is the key message that our short paper concludes with, and the responder’s results seem to fit this narrative. With our report being a comparative evaluation (as opposed to a single arm evaluation), we were able to state that from our findings that return rates were not the deciding factor in the RRR values of the MT or DBS modalities, as they were the same. If we apply this logic to the responder’s data, it may be reasonable to suggest that should they use DBS, their RRR value would be nearing 1.00, when we factor in the high kit return rates that they have presented in their response letter.
We would encourage the responder's to fully publish their data in a peer-reviewed journal, in order for its readers to draw conclusions from their results. This is a rapidly expanding area and it has not been thoroughly explored through research.
Peter J White, MRC Centre for Outbreak Analysis & Modelling and NIHR Health Protection Research Unit in Modelling and Health Economics, Imperial College London.
Other Contributors:
Joanna Lewis, MRC Centre for Outbreak Analysis & Modelling, Imperial College London.
Paddy J Horner, Population Health Sciences, and NIHR Health Protection Research Unit in Behavioural Science and Evaluation, University of Bristol.
Pitt et al. commented “asymptomatic patients are not recommended for M. genitalium testing except sexual contacts... The current approach might need rethinking if asymptomatic infections are found to be an important reservoir for AMR and/or a source of infection and disease”.[1]
Recent analysis of the POPI cohort found 4.9% (95%CrI 0.4%–14.1%) of M. genitalium infections in women progressed to pelvic inflammatory disease, compared with 14.4% (5.9%–24.6%) of Chlamydia trachomatis infections.[2] Combined with its lower prevalence this means that M. genitalium is a much less important cause of disease in women than C. trachomatis.[2]
There is considerable uncertainty in the natural history and epidemiology of M. genitalium,[3] and we don’t know the importance of asymptomatic infection in transmission. Low bacterial load might limit infectivity but a long duration of infection[2,3] means there may be many potentially-infectious sex-acts. In fact, the BASHH guidelines are motivated by concern about transmission from asymptomatic...
Peter J White, MRC Centre for Outbreak Analysis & Modelling and NIHR Health Protection Research Unit in Modelling and Health Economics, Imperial College London.
Other Contributors:
Joanna Lewis, MRC Centre for Outbreak Analysis & Modelling, Imperial College London.
Paddy J Horner, Population Health Sciences, and NIHR Health Protection Research Unit in Behavioural Science and Evaluation, University of Bristol.
Pitt et al. commented “asymptomatic patients are not recommended for M. genitalium testing except sexual contacts... The current approach might need rethinking if asymptomatic infections are found to be an important reservoir for AMR and/or a source of infection and disease”.[1]
Recent analysis of the POPI cohort found 4.9% (95%CrI 0.4%–14.1%) of M. genitalium infections in women progressed to pelvic inflammatory disease, compared with 14.4% (5.9%–24.6%) of Chlamydia trachomatis infections.[2] Combined with its lower prevalence this means that M. genitalium is a much less important cause of disease in women than C. trachomatis.[2]
There is considerable uncertainty in the natural history and epidemiology of M. genitalium,[3] and we don’t know the importance of asymptomatic infection in transmission. Low bacterial load might limit infectivity but a long duration of infection[2,3] means there may be many potentially-infectious sex-acts. In fact, the BASHH guidelines are motivated by concern about transmission from asymptomatic infections. If asymptomatic infections are not treated then one expects a greater average number of transmission events per infection than if they were treated, but those transmitted infections that cause symptoms will tend to be treatable. Alternatively, if asymptomatic infections were treated routinely with current regimens then the short-term effect would be reduced transmission, but at the cost of increased drug resistance – which frequently arises de novo on azithromycin treatment, even after doxycycline pre-treatment – leading to more hard-to-treat (or even untreatable) infections in the future. In 2010–12 16.1% of infections had AMR-conferring mutations,[1] and with widespread use of azithromycin this is likely to have increased since, considering the large and rapid increases in resistance seen elsewhere.
Ultimately, we need effective regimens and testing for resistance. We agree more modelling is required,[1] and hope a future Natsal survey will provide valuable up-to-date information on M. genitalium prevalence and drug-resistance.
References
1. Pitt R, Unemo M, Sonnenberg P, et al. Antimicrobial resistance in Mycoplasma genitalium sampled from the British general population. Sex Transm Infect 2020; 96(6):464-468.
2. 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; [online 23 July 2020] doi.org/10.1093/cid/ciaa419
3. Birger R, Saunders J, Estcourt C, et al. Should we screen for the sexually-transmitted infection Mycoplasma genitalium? Evidence synthesis using a transmission-dynamic model. Sci Rep 2017; 7: 16162.
Competing interests None declared.
Disclaimer The views expressed are those of the authors and not necessarily those of the Department of Health and Social Care, MRC, NHS, NIHR, or Public Health England.
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 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
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
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...
Show MoreDear editor,
Show MoreWe thank Dr. Latini et al. for providing the data for the potential effects of SARS-CoV-2 pandemic on sexual lifestyle and epidemiology of sexually transmitted infections (STIs).1 In the study the author highlighted the importance to check the lasting effects of SARS-CoV-2 on STIs. As China is the first country to generally alleviate lockdown of most cities since beginning of April and the returns to usual lifestyle for nearly 6 months, we’re able to tract the epidemiology of STIs during the post-outbreak period in China.
According to the monthly report disclosed by Chinese Center for Disease Control and Prevention (Accessed from http://www.nhc.gov.cn/jkj/pqt/new_list.shtml), during the lockdown period of the first quarter, the number of newly diagnosed cases of HIV, syphilis and gonorrhea were 9695, 102273 and 16439, which reduced substantially by 27.3%, 19.3% and 38.2% compared to the previous year. After lockdown alleviation, the number of new cases returned, but not exceeding the previous years. The total new cases of HIV, syphilis and gonorrhea changed by -4.4%, -5.6% and -18.9% in the second quarter and -7.8%, -9.5% and +0.7% in the third quarter compared with 2019, respectively. As the number of new STIs in China is constantly growing in the past years, the reduction of new cases of STIs in 2020 after lockdown alleviation indicates a lasting effect of SARS-CoV-2. This may result from...
We apologise for the delay in responding to your letter. We were only recently notified of this by email. Thank you for taking the time to construct your letter in response to our published short report, to which you raise several points which require addressing.
Firstly we feel it is important to highlight that although this service evaluation focussed specifically on HIV, we acknowledged that the HIV sampling kit was part of a more comprehensive STI kit (syphilis, chlamydia, and gonorrhoea tests). We were upfront with this fact in our report, and therefore refute the claim by the responder that our paper failed to consider the wider test portfolio required by sexual health screening services.
Of greater concern to us, we note a major error in the calculations from the data provided by the responders for their “RRR” and “HIV result obtained/ STI kit requested” values. This is important, as the foundation of their concluding statement is based on this error. The responder's have incorrectly used the number of returned kits (256,717) instead of the number of requested kits (319,485) in calculating the RRR (request-to-return ratio) and the “HIV result obtained/STI kit requested” proportion. Applying the correct calculation, the RRR value using the responder's data is not 1.36 (256,717/188,187) but 1.70 (319,485/188,187). The “HIV result obtained/STI kit requested” proportion using the correct calculation is 58.9% (188,187/319,485) and not 73.3%...
Show MorePeter J White, MRC Centre for Outbreak Analysis & Modelling and NIHR Health Protection Research Unit in Modelling and Health Economics, Imperial College London.
Other Contributors:
Joanna Lewis, MRC Centre for Outbreak Analysis & Modelling, Imperial College London.
Paddy J Horner, Population Health Sciences, and NIHR Health Protection Research Unit in Behavioural Science and Evaluation, University of Bristol.
Pitt et al. commented “asymptomatic patients are not recommended for M. genitalium testing except sexual contacts... The current approach might need rethinking if asymptomatic infections are found to be an important reservoir for AMR and/or a source of infection and disease”.[1]
Show MoreRecent analysis of the POPI cohort found 4.9% (95%CrI 0.4%–14.1%) of M. genitalium infections in women progressed to pelvic inflammatory disease, compared with 14.4% (5.9%–24.6%) of Chlamydia trachomatis infections.[2] Combined with its lower prevalence this means that M. genitalium is a much less important cause of disease in women than C. trachomatis.[2]
There is considerable uncertainty in the natural history and epidemiology of M. genitalium,[3] and we don’t know the importance of asymptomatic infection in transmission. Low bacterial load might limit infectivity but a long duration of infection[2,3] means there may be many potentially-infectious sex-acts. In fact, the BASHH guidelines are motivated by concern about transmission from asymptomatic...
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 MoreWe 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...
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