Leishmaniasis is increasingly reported among travellers. Leishmania species vary in sensitivity to available therapies. Fast and reliable molecular techniques have made species-directed treatment ...feasible. Many treatment trials have been designed poorly, thus developing evidence-based guidelines for species-directed treatment is difficult. Published guidelines on leishmaniasis in travellers do not aim to be comprehensive or do not quantify overall treatment success for available therapies. We aimed at providing comprehensive species-directed treatment guidelines.
English literature was searched using PubMed. Trials and observational studies were included if all cases were parasitologically confirmed, the Leishmania species was known, clear clinical end-points and time points for evaluation of treatment success were defined, duration of follow-up was adequate and loss to follow-up was acceptable. The proportion of successful treatment responses was pooled using mixed effects methods to estimate the efficacy of specific therapies. Final ranking of treatment options was done by an expert panel based on pooled efficacy estimates and practical considerations. 168 studies were included, with 287 treatment arms. Based on Leishmania species, symptoms and geography, 25 clinical categories were defined and therapy options ranked. In 12/25 categories, proposed treatment agreed with highest efficacy data from literature. For 5/25 categories no literature was found, and in 8/25 categories treatment advise differed from literature evidence. For uncomplicated cutaneous leishmaniasis, combination of intralesional antimony with cryotherapy is advised, except for L. guyanensis and L. braziliensis infections, for which systemic treatment is preferred. Treatment of complicated (muco)cutaneous leishmaniasis differs per species. For visceral leishmaniasis, liposomal amphotericin B is treatment of choice.
Our study highlights current knowledge about species-directed therapy of leishmaniasis in returning travellers and also demonstrates lack of evidence for treatment of several clinical categories. New data can easily be incorporated in the presented overview. Updates will be of use for clinical decision making and for defining further research.
OBJECTIVESChemsex (i.e., drug use during sex) is practiced by some men who have sex with men (MSM) and is associated with high-risk behavior. In a cross-sectional study at the sexually transmitted ...infection (STI) clinic of Amsterdam, we explored chemsex practices, risk behavior, and STI prevalence.
METHODA survey on chemsex (γ-hydroxybutyrate, crystal methamphetamine, and/or mephedrone) was offered to clinic clients during routine STI screening and to Amsterdam users of a gay online dating app. Associations were assed using χ test and multivariable regression.
RESULTSChemsex in the past 6 months was practiced by 866 (17.6%) of 4925 MSM clients and by 159 (1.5%) of 10857 non-MSM clients. Among gay dating app users, the proportion that reported chemsex engagement was higher than among MSM visiting the STI clinic (29.3% 537/1832 vs. 17.6%; P < 0.001). Chemsex was a significant risk factor for bacterial STI in HIV-negative MSM visiting the STI clinic (adjusted odd ratio, 1.5; 95% confidence interval, 1.2–1.8), but not in HIV-positive MSM. A majority practiced chemsex once a month or less, and 87.0% reported sex without drug use in the past month.
CONCLUSIONSIn Amsterdam, chemsex is frequently practiced and significantly associated with bacterial STI in HIV-negative MSM but not in HIV-positive MSM. Future prevention strategies to reduce STI incidence should especially target HIV-negative MSM engaging in chemsex.
WHO estimated that nearly 1 million people become infected every day with any of four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea, syphilis, and trichomoniasis. Despite ...their high global incidence, STIs remain a neglected area of research. In this Commission, we have prioritised five areas that represent particular challenges in STI treatment and control. Chlamydia remains the most commonly diagnosed bacterial STI in high-income countries despite widespread testing recommendations, sensitive and specific non-invasive testing techniques, and cheap effective therapy. We discuss the challenges for chlamydia control and evidence to support a shift from the current focus on infection-based screening to improved management of diagnosed cases and of chlamydial morbidity, such as pelvic inflammatory disease. The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is globally recognised. We review current and potential future control and treatment strategies, with a focus on novel antimicrobials. Bacterial vaginosis is the most common vaginal disorder in women, but current treatments are associated with frequent recurrence. Recurrence after treatment might relate to evidence that suggests sexual transmission is integral to the pathogenesis of bacterial vaginosis, which has substantial implications for the development of effective management approaches. STIs disproportionately affect low-income and middle-income countries. We review strategies for case management, focusing on point-of-care tests that hold considerable potential for improving STI control. Lastly, STIs in men who have sex with men have increased since the late 1990s. We discuss the contribution of new biomedical HIV prevention strategies and risk compensation. Overall, this Commission aims to enhance the understanding of some of the key challenges facing the field of STIs, and outlines new approaches to improve the clinical management of STIs and public health.
Summary Background Anal cancer is an increasing issue in HIV-positive men who have sex with men (MSM). Screening for its precursor, anal intraepithelial neoplasia (AIN), is subject of discussion. ...Current treatment options are suboptimum and have not been compared in a prospective trial. We compared efficacy and side-effects of imiquimod, topical fluorouracil, and electrocautery for the treatment of AIN. Methods In this open-label randomised trial, we included HIV-positive MSM older than 18 years visiting the HIV outpatient clinic of the Academic Medical Center, Amsterdam, Netherlands. Patients with histologically confirmed AIN were randomly assigned to receive either 16 weeks of imiquimod (three times a week), 16 weeks of topical fluorouracil (twice a week), or monthly electrocautery for 4 months. Randomisation was done with random block sizes of three and six, stratified for AIN grade (AIN grades 1, 2, or 3) and AIN location (peri-anal or intra-anal). Participants were assessed by high-resolution anoscopy 4 weeks after treatment. Responding patients returned for follow-up 24 weeks, 48 weeks, and 72 weeks after treatment. The primary endpoint was histological resolution of AIN measured 4 weeks after treatment and AIN recurrence at week 24, week 48, and week 72 after treatment. The primary analysis was done in a modified intention-to-treat population, including all patients who had received their assigned treatment at least once. The trial is registered at the Netherlands Trial Register , number NTR1236. Findings Between Aug 12, 2008, and Dec 1, 2010, we screened 388 HIV-positive MSM for AIN by high resolution anoscopy. Of the 246 (63%) patients who had AIN, 156 (63%) were randomly assigned to either receive imiquimod (54 patients), topical fluorouracil (48 patients), or electrocautery (46 patients) following withdrawing of consent by eight patients. Modified intention-to-treat analysis showed a complete response in 13 (24%, 95% CI 15–37) patients in the imiquimod group, eight (17%, 8–30) of patients in the fluorouracil group, and 18 (39%, 26–54) of patients in the electrocautery group (p=0·027). At week 24, 11 (22%) of 50 responders had recurrence; at week 48, 22 (46%) of 48 had recurred; and at week 72, 30 (67%) of 45 had recurred. Recurrence was observed at 72 weeks in 10 (71%) of 14 patients treated with imiquimod, seven (58%) of 12 patients treated with fluorouracil, and 13 (68%) of 19 patients treated with electrocautery. Grade 3–4 side-effects were noted in 23 (43%) of 53 patients in the imiquimod group, 13 (27%) of 48 patients in the fluorouracil group, and eight (18%) patients in the electrocautery group (p=0·019). The most common side-effects were pain, bleeding, and itching. Seven serious adverse events occurred, all not related to the study. Interpretation Electrocautery is better than imiquimod and fluorouracil in the treatment of AIN, but recurrence rates are substantial. Funding Anna Maurits de Cock foundation provided funding for the video colposcope.
Hepatitis C virus (HCV) has been recognized as an emerging sexually transmitted infection (STI) among HIV-positive MSM. However, HIV-negative MSM at high risk for HIV might also be at increased risk ...for HCV. We studied the HCV prevalence in HIV-negative MSM who start preexposure prophylaxis (PrEP) in Amsterdam. Phylogenetic analysis was used to compare HCV strains obtained from HIV-negative and HIV-positive MSM.
At enrolment in the Amsterdam PrEP demonstration project, HIV-negative MSM were tested for the presence of HCV antibodies and HCV RNA. If positive for HCV RNA, an HCV NS5B gene fragment (709 bp) was sequenced and compared with HCV isolates from HIV-positive MSM (n = 223) and risk groups other than MSM (n = 153), using phylogenetic analysis.
Of 375 HIV-negative MSM enrolled in Amsterdam PrEP, 18 (4.8%, 95% confidence interval 2.9-7.5%) of participants were anti-HCV and/or HCV RNA positive at enrolment; 15 of 18 (83%) had detectable HCV RNA. HCV genotyping showed genotype 1a (73%), 4d (20%), and 2b (7%). All HCV-positive MSM starting PrEP were part of MSM-specific HCV clusters containing MSM with and without HIV.
HCV prevalence among HIV-negative MSM who started PrEP was higher than previously reported. All HIV-negative HCV-positive MSM were infected with HCV strains already circulating among HIV-positive MSM. The increasing overlap between sexual networks of HIV-positive and HIV-negative MSM might result in an expanding HCV-epidemic irrespective of HIV-status. Hence, routine HCV testing should be offered to MSM at high risk for HIV, especially for those enrolling in PrEP programs.
Background and Aims
Men who have sex with men (MSM) are at high risk for both drug use and sexually transmitted infections (STI). We aimed to (1) identify subgroups of drug use during sex among MSM ...in Amsterdam and after classifying participants and (2) compare sexual behaviour and STI across groups.
Design
Cross‐sectional study. Latent class analysis was used to identify subgroups with similar drug use patterns, between which sexual behaviour and STI prevalence were compared.
Setting
Four different studies conducted at the STI out‐patient clinic in Amsterdam, the Netherlands, between January 2014 and June 2016.
Participants
A total of 1130 self‐declared MSM, aged ≥ 18 years.
Measurements
Self‐reported drug use, laboratory‐confirmed STI, socio‐demographics, sexual behaviour (including number of partners), condom use.
Findings
Median age was 40 years interquartile range (IQR) = 32–47. We identified five latent classes of users, which we labelled: ‘no substance’ (n = 162), ‘alcohol’ (n = 159), ‘nitrites and erectile dysfunction drugs (EDD)’ (n = 286), ‘polydrug’ (n = 257) and ‘chems’ (n = 266). Median number of sex partners significantly differed across classes (P < 0.001), ranging from two (IQR = 1–6) in the ‘no substance’ class to 20 (IQR = 10–45) in the ‘chems’ class. The proportion of MSM reporting condomless anal sex also differed across classes (P < 0.001), ranging from 45.6% in the ‘no substance’ class to 86.5% in the ‘chems’ class. Compared with the ‘no substance’ class, the odds of STI were 3.9‐fold 95% confidence interval (CI) = 1.1–14.4 higher in the ‘alcohol’ class, 8.9‐fold (95% CI = 2.7–29.2) higher in the ‘nitrites and EDD’ class, 12.8‐fold (95% CI = 3.9–41.9) higher in the ‘polydrug’ class and 15.0‐fold (95% CI = 4.6–48.8) higher in the ‘chems’ class.
Conclusion
There are five distinct classes of drug use in a sexual context among men who have sex with men in Amsterdam, the Netherlands. Classes with higher levels of drug use appear to coincide with higher levels of sexual risk behaviour and sexually transmitted infections.
To date, women are most often diagnosed with bacterial vaginosis (BV) using microscopy based Nugent scoring or Amsel criteria. However, the accuracy is less than optimal. The aim of the present study ...was to confirm the identity of known BV-associated composition profiles and evaluate indicators for BV using three molecular methods.
Evaluation of indicators for BV was carried out by 16S rRNA amplicon sequencing of the V5-V7 region, a tailor-made 16S rRNA oligonucleotide-based microarray, and a PCR-based profiling technique termed IS-profiling, which is based on fragment variability of the 16S-23S rRNA intergenic spacer region. An inventory of vaginal bacterial species was obtained from 40 females attending a Dutch sexually transmitted infection outpatient clinic, of which 20 diagnosed with BV (Nugent score 7-10), and 20 BV negative (Nugent score 0-3).
Analysis of the bacterial communities by 16S rRNA amplicon sequencing revealed two clusters in the BV negative women, dominated by either Lactobacillus iners or Lactobacillus crispatus and three distinct clusters in the BV positive women. In the former, there was a virtually complete, negative correlation between L. crispatus and L. iners. BV positive subjects showed cluster profiles that were relatively high in bacterial species diversity and dominated by anaerobic species, including Gardnerella vaginalis, and those belonging to the Families of Lachnospiraceae and Leptotrichiaceae. Accordingly, the Gini-Simpson index of species diversity, and the relative abundance Lactobacillus species appeared consistent indicators for BV. Under the conditions used, only the 16S rRNA amplicon sequencing method was suitable to assess species diversity, while all three molecular composition profiling methods were able to indicate Lactobacillus abundance in the vaginal microbiota.
An affordable and simple molecular test showing a depletion of the genus Lactobacillus in combination with an increased species diversity of vaginal microbiota could serve as an alternative and practical diagnostic method for the assessment of BV.
This review focuses on recent developments in the diagnosis, treatment, management, and strategies for the prevention and control of cutaneous leishmaniasis (CL) caused by both Old and New World
...Leishmania
species. CL is caused by the vector-borne protozoan parasite
Leishmania
and is transmitted via infected female sandflies. The disease is endemic in more than 98 countries and an estimated 350 million people are at risk. The overall prevalence is 12 million cases and the annual incidence is 2–2.5 million. The World Health Organization considers CL a severely neglected disease and a category 1 emerging and uncontrolled disease. The management of CL differs from region to region and is primarily based on local experience-based evidence. Most CL patients can be treated with topical treatments, but some
Leishmania
species can cause mucocutaneous involvement requiring a systemic therapeutic approach. Moreover,
Leishmania
species can vary in their sensitivity to available therapeutic options. This makes species determination critical for the choice of treatment and the clinical outcome of CL. Identification of the infecting parasite used to be laborious, but now the
Leishmania
species can be identified relatively easy with new DNA techniques that enable a more rational therapy choice. Current treatment guidelines for CL are based on poorly designed and reported trials. There is a lack of evidence for potentially beneficial treatments, a desperate need for large well-conducted studies, and standardization of future trials. Moreover, intensified research programs to improve vector control, diagnostics, and the therapeutic arsenal to contain further incidence and morbidity are needed.
A curated Web-based user-friendly sequence typing tool based on antimicrobial resistance determinants in
was developed and is publicly accessible (https://ngstar.canada.ca). The
Sequence Typing for ...Antimicrobial Resistance (NG-STAR) molecular typing scheme uses the DNA sequences of 7 genes (
,
,
,
,
,
, and 23S rRNA) associated with resistance to β-lactam antimicrobials, macrolides, or fluoroquinolones. NG-STAR uses the entire
sequence, combining the historical nomenclature for
types I to XXXVIII with novel nucleotide sequence designations; the full
sequence and a portion of its promoter region; portions of
,
,
, and
; and 23S rRNA sequences. NG-STAR grouped 768 isolates into 139 sequence types (STs) (
= 660) consisting of 29 clonal complexes (CCs) having a maximum of a single-locus variation, and 76 NG-STAR STs (
= 109) were identified as unrelated singletons. NG-STAR had a high Simpson's diversity index value of 96.5% (95% confidence interval CI = 0.959 to 0.969). The most common STs were NG-STAR ST-90 (
= 100; 13.0%), ST-42 and ST-91 (
= 45; 5.9%), ST-64 (
= 44; 5.72%), and ST-139 (
= 42; 5.5%). Decreased susceptibility to azithromycin was associated with NG-STAR ST-58, ST-61, ST-64, ST-79, ST-91, and ST-139 (
= 156; 92.3%); decreased susceptibility to cephalosporins was associated with NG-STAR ST-90, ST-91, and ST-97 (
= 162; 94.2%); and ciprofloxacin resistance was associated with NG-STAR ST-26, ST-90, ST-91, ST-97, ST-150, and ST-158 (
= 196; 98.0%). All isolates of NG-STAR ST-42, ST-43, ST-63, ST-81, and ST-160 (
= 106) were susceptible to all four antimicrobials. The standardization of nomenclature associated with antimicrobial resistance determinants through an internationally available database will facilitate the monitoring of the global dissemination of antimicrobial-resistant
strains.
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