The lifetime risk of tuberculosis (TB) for infected contacts is often mentioned to be 5-10%, but these estimates are based on studies conducted decades ago, and thus may not reflect current ...epidemiologic conditions.
To estimate the risk of TB among contacts with evidence of infection and to compare this with estimates often stated in the literature.
A retrospective cohort study was performed using records on contacts of pulmonary TB patients at the Public Health Service Amsterdam, 2002-2011. The Public Health Service Amsterdam TB electronic registration system identified TB cases during follow-up until October 2012; these were defined as coprevalent if diagnosed less than or equal to 180 days and incident if diagnosed greater than 180 days after TB diagnosis of index patient. Cumulative TB risk was estimated with Kaplan-Meier curves.
Of 9,332 contacts of pulmonary TB patients, 4,774 were screened for latent TB infection (LTBI) of whom 739 (16%) had evidence of infection. Among these the 5-year Kaplan-Meier TB cumulative risk was 9.5% (95% confidence interval, 7.5-11.9). This varied by age: 33.3% of 36 contacts aged less than 5 years, 19.1% of 84 contacts aged 5-14 years, and 6.7% of 619 contacts aged greater than or equal to 15 years (log rank, P < 0.001). Of 739 contacts with evidence of infection, 57 had coprevalent TB and 14 developed incident TB. Of patients without coprevalent TB but with LTBI diagnosis, 45% received preventive therapy. Five-year risk of incident TB was 2.4% (95% confidence interval, 1.2-4.7) among contacts with LTBI who did not start preventive therapy.
Five-year risk of TB among contacts with evidence of infection was higher compared with older estimates, and differed considerably by age. Incidence of TB among contacts with LTBI was low, suggesting limited impact may be expected of expanding preventive therapy.
To evaluate whether ethnicity is independently associated with vaginal microbiota (VMB) composition in women living in Amsterdam, the Netherlands, as has been shown for American women.
Women (18-34 ...years, non-pregnant, N = 610) representing the six largest ethnic groups (Dutch, African Surinamese, South-Asian Surinamese, Turkish, Moroccan, and Ghanaian) were sampled from the population-based HELIUS study. Sampling was performed irrespective of health status or healthcare seeking behavior. DNA was extracted from self-sampled vaginal swabs and sequenced by Illumina MiSeq (16S rRNA gene V3-V4 region).
The overall prevalence of VMBs not dominated by lactobacilli was 38.5%: 32.2% had a VMB resembling bacterial vaginosis and another 6.2% had a VMB dominated by Bifidobacteriaceae (not including Gardnerella vaginalis), Corynebacterium, or pathobionts (streptococci, staphylococci, Proteus or Enterobacteriaceae). The most prevalent VMB in ethnically Dutch women was a Lactobacillus crispatus-dominated VMB, in African Surinamese and Ghanaian women a polybacterial G. vaginalis-containing VMB, and in the other ethnic groups a L. iners-dominated VMB. After adjustment for sociodemographic, behavioral and clinical factors, African Surinamese ethnicity (adjusted odds ratio (aOR) 5.1, 95% confidence interval (CI) 2.1-12.0) and Ghanaian ethnicity (aOR 4.8, 95% CI 1.8-12.6) were associated with having a polybacterial G. vaginalis-containing VMB, and African Surinamese ethnicity with a L. iners-dominated VMB (aOR 2.8, 95% CI 1.2-6.2). Shorter steady relationship duration, inconsistent condom use with casual partners, and not using hormonal contraception were also associated with having a polybacterial G. vaginalis-containing VMB, but human papillomavirus infection was not. Other sexually transmitted infections were uncommon.
The overall prevalence of having a VMB not dominated by lactobacilli in this population-based cohort of women aged 18-34 years in Amsterdam was high (38.5%), and women of sub-Saharan African descent were significantly more likely to have a polybacterial G. vaginalis-containing VMB than Dutch women independent of modifiable behaviors.
OBJECTIVES AND DESIGN: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.
METHODS: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.
RESULTS: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.
CONCLUSION: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.
Abstract
Background
Frailty is associated with mortality and morbidity in the general geriatric population, but less is known about its impact among the aging but generally younger population with ...human immunodeficiency virus (HIV).
Methods
The impact of frailty on all-cause mortality during 6 years of follow-up and incident comorbidity during 4 years of follow-up was assessed among 598 HIV-positive and 550 comparable HIV-negative participants aged ≥ 45 years of the AGEhIV Cohort Study. Frailty encompasses 5 domains; weight loss, low physical activity, exhaustion, decreased grip strength, and slow gait speed. Presence of ≥ 3 denotes frailty, 1–2 prefrailty, and 0 robust. Multivariable Cox and logistic regression models were used to assess the independent relationships of frailty with both outcomes, adjusting for HIV infection and traditional risk factors.
Results
At baseline, 7.5% (n = 86) of participants were frail. During follow-up, 38 participants died. Mortality rate was significantly higher among frail participants: 25.7/1000 person-years of follow-up (PYFU) (95% confidence interval CI, 14.2–46.4) compared with prefrail (7.2/1000 PYFU 95% CI, 4.7–11.2) and robust (2.3/1000 PYFU 95% CI, 1.1–4.9). In fully adjusted analyses, frailty remained strongly associated with death (hazard ratio, 4.6 95% CI, 1.7–12.5) and incident comorbidity (odds ratio, 1.9 95% CI, 1.1–3.1). No interactions were observed between frailty and HIV status in all analyses.
Conclusions
Frailty is a strong predictor of both mortality and incident comorbidity independent from other risk factors.
Clinical Trials Registration
NCT01466582.
Frailty was a strong predictor of mortality and incident comorbidity in our HIV-positive and HIV-negative participants who, although aging, were not yet considered of geriatric age. Moreover, frailty impacted the risk of these outcomes independently from other recognized risk factors.
OBJECTIVE:To investigate the impact of Dutch COVID-19 restrictions on sexual behavior and HIV/STI acquisition among men who have sex with men (MSM) participating in the Amsterdam Cohort Studies (ACS) ...on HIV in Amsterdam.
METHODS:ACS participants complete a questionnaire on sexual behaviour and are tested for HIV/STI biannually. They may also be tested at the sexually transmitted infections (STI) clinic in-between study visits. On May 29, 2020, ACS participants were invited to complete an online questionnaire on health, COVID-19 risk perceptions and sexual behavior. Determinants of reporting casual sex partners (CSP) during COVID-19 restrictions were examined using logistic regression.
RESULTS:353/683 MSM (52%; median age 47; IQR 38-53) completed the questionnaire. Since COVID-19, 73% reported a reduction in number of CSP. CSP during COVID-19 restrictions were reported by 133 (38%) MSM and, in multivariable analysis, was associated with not having a college/university degree, being single, lower perceived importance of avoiding COVID-19, number of CSP before COVID-19 and current PrEP use (p<0.05 for all). During COVID-19 restrictions, no HIV infections were diagnosed and the STI positivity rate was 8%.
CONCLUSION:Since COVID-19, the number of CSP decreased among MSM and there may have been a temporary reduction in HIV/STI transmission. Some MSM were not fully compliant to social distancing regulations and reported CSP, which was related to prior sexual behavior and low perceived importance of avoiding COVID-19. For these men, it is important to maintain accessible HIV/STI-related testing and care during times of lockdown.
Neisseria gonorrhoeae causes gonorrhoea, a common sexually transmitted infection. Emerging strains resistant to first-line ceftriaxone threaten N gonorrhoeae management. Hence, alternative treatments ...are needed. We aimed to evaluate the efficacy of ertapenem, gentamicin, and fosfomycin as alternative treatments for anogenital N gonorrhoeae.
In a randomised, controlled, double-blind, non-inferiority trial (three experimental groups and one control group) at the Centre for Sexual Health in Amsterdam, Netherlands, we included adults aged 18 years or older, with anorectal or urogenital gonorrhoea. With random permuted blocks, participants were randomly assigned (1:1:1:1) to receive intramuscular 500 mg ceftriaxone (control group), intramuscular 1000 mg ertapenem, intramuscular 5 mg/kg gentamicin (maximum 400 mg), or oral 6 g fosfomycin. The primary outcome was the proportion of participants with a negative nucleic acid amplification test of the predefined primary infected site, 7−14 days after treatment. The primary analysis was per protocol (ie, excluding those lost to follow-up). The modified intention-to-treat analysis included all randomly assigned patients with anogenital gonorrhoea considering those lost-to-follow-up as treatment failure. Non-inferiority was established if the lower Hochberg-corrected 95% CI for difference between the experimental and control groups was greater than −10%. For the analysis of adverse events, we included all participants who received medication. The trial was registered at ClinicalTrials.gov (NCT03294395) and is complete.
Between Sept 18, 2017, and June 5, 2020, from 2160 patients invited to participate, we assigned 346 (16%) participants to receive either ceftriaxone (n=103), ertapenem (n=103), gentamicin (n=102), or fosfomycin (n=38). The fosfomycin group was terminated early after interim analysis revealed less than 60% efficacy. In the primary per-protocol analysis, 93 (100%) of 93 patients in the ceftriaxone group, 86 (99%) of 87 patients in the ertapenem group, 79 (93%) of 85 patients in the gentamicin group, and four (12%) of 33 patients in the fosfomycin group cleared N gonorrhoeae (risk difference vs ceftriaxone −0·01 95% CI −0·08 to 0·05 for ertapenem and −0·07 −0·16 to −0·01 for gentamicin). Thus, ertapenem proved non-inferior to ceftriaxone. In mITT analysis, risk differences versus ceftriaxone were −0·08 (−0·17 to 0·003) for ertapenem and −0·11 (−0·21 to −0·04) for gentamicin. We observed a higher proportion of patients with at least one adverse event in the ertapenem group (58 56% of 103) and fosfomycin group (36 95% of 38) versus the ceftriaxone group (24 23% of 103).
Single-dose 1000 mg ertapenem is non-inferior to single-dose 500 mg ceftriaxone in gonorrhoea treatment. Yet, 5 mg/kg gentamicin (maximum 400 mg) is not non-inferior to ceftriaxone. Ertapenem is a potential effective alternative for anogenital N gonorrhoeae infections and merits evaluation for ceftriaxone-resistant infections.
ZonMw and GGD-Amsterdam.
For the Dutch translation of the abstract see Supplementary Materials section.
Men who have sex with men (MSM) are at high risk for anal cancer, primarily related to human papillomavirus genotype 16 (HPV16) infections. At 8.5 per 100,000 per year, the incidence rate of anal ...cancer among MSM is similar to that of cervical cancer among adult women in the Netherlands. However, MSM are not included in most HPV vaccination programs. We explored the potential effectiveness of prophylactic immunization in reducing anogenital HPV16 transmission among MSM in the Netherlands.
We developed a range of mathematical models for penile-anal HPV16 transmission, varying in sexual contact structure and natural history of infection, to provide robust and plausible predictions about the effectiveness of targeted vaccination. Models were informed by an observational cohort study among MSM in Amsterdam, 2010-2013. Parameters on sexual behavior and HPV16 infections were obtained by fitting the models to data from 461 HIV-negative study participants, considered representative of the local MSM population. We assumed 85% efficacy of vaccination against future HPV16 infections as reported for HIV-negative MSM, and age-specific uptake rates similar to those for hepatitis B vaccination among MSM in the Netherlands. Targeted vaccination was contrasted with vaccination of 12-year-old boys at 40% uptake in base-case scenarios, and we also considered the effectiveness of a combined strategy. Offering vaccine to MSM without age restrictions resulted in a model-averaged 27.3% reduction (90% prediction interval PI 11.9%-37.5%) in prevalence of anal HPV16 infections, assuming similar uptake among MSM as achieved for hepatitis B vaccination. The predicted reduction improved to 46.1% (90% PI 21.8%-62.4%) if uptake rates among MSM were doubled. The reductions in HPV16 infection prevalence were mostly achieved within 30 years of a targeted immunization campaign, during which they exceeded those induced by vaccinating 40% of preadolescent boys, if started simultaneously. The reduction in anal HPV16 prevalence amounted to 74.8% (90% PI 59.8%-93.0%) under a combined vaccination strategy. HPV16 prevalence reductions mostly exceeded vaccine coverage projections among MSM, illustrating the efficiency of prophylactic immunization even when the HPV vaccine is given after sexual debut. Mode of protection was identified as the key limitation to potential effectiveness of targeted vaccination, as the projected reductions were strongly reduced if we assumed no protection against future infections in recipients with prevalent infection or infection-derived immunity at the time of immunization. Unverified limitations of our study include the sparsity of data to inform the models, the omission of oral sex in transmission to the penile or anal site, and the restriction that our modeling results apply primarily to HIV-negative MSM.
Our findings suggest that targeted vaccination may generate considerable reductions in anogenital HPV16 infections among MSM, and has the potential to accelerate anal cancer prevention, especially when combined with sex-neutral vaccination in preadolescence.
Summary Following large-scale roll-out of antiretroviral therapy in sub-Saharan Africa, the non-clinical efficacy of antiretroviral therapy has received little attention. We aimed to systematically ...review virological efficacy and drug-resistance outcomes of programmes of antiretroviral therapy in sub-Saharan Africa. 89 studies with heterogeneous design, definitions, and methods were identified. Overall, in on-treatment analysis, 10 351 (78%) of 13 288 patients showed virological suppression after 6 months of antiretroviral therapy, 7413 (76%) of 9794 after 12 months, and 3840 (67%) of 5690 after 24 months. Long-term virological data are scarce. Genotyping results were available for patients with virological failure (HIV-1 RNA greater than 1000 copies per mL). Most patients (839 of 849; 99%) were infected with a non-B HIV-1 subtype. However, drug-resistance patterns were largely similar to those in subtype B. Resistance profiles were associated with the antiretroviral drugs commonly used: the lamivudine-associated M184V mutation was most common, followed by K103N which is associated with non-nucleoside reverse transcriptase inhibitors. Thymidine-analogue mutations and the K65R mutation were less common. First-line antiretroviral therapy regimens used in sub-Saharan Africa are effective. Profiles of drug resistance suggest that a second-line treatment regimen based on protease inhibitors, with a backbone of nucleoside reverse transcriptase inhibitors, is a reasonable option for patients with HIV in sub-Saharan Africa who experience first-line treatment failure.
Abstract
Background
Knowledge on genital type-specific human papillomavirus (HPV) prevalence among men is important for prevention of HPV-related cancers and other diseases. Men who have sex with men ...(MSM) have higher anal prevalence than men who have sex with women only (MSW) but for genital HPV this is unclear. We performed a systematic review and meta-analysis of type-specific genital HPV prevalence among men, by sexual orientation.
Methods
MEDLINE and Embase were used for searching publications reporting on male genital HPV prevalence with data from November 2011 onwards. A random-effects meta-analysis was conducted estimating pooled type-specific and grouped external genital and urethral HPV prevalence. Subgroup analyses were conducted for sexual orientation.
Results
Twenty-nine studies were eligible. Of those, 13 studies reported prevalence among MSM, 5 among MSW, and 13 studies did not stratify by sexual orientation. The most common genotypes were HPV-6 and HPV-16 for both anatomical locations, although heterogeneity was high. HPV prevalence was similar among studies reporting on MSW, MSM, and men with unknown sexual orientation.
Conclusions
Genital HPV is common among men, with HPV-6 and HPV-16 being the most common genotypes. Type-specific HPV genital prevalence appears to be similar among MSM and MSW, which contrasts with earlier findings on anal HPV.
Genital HPV is common among men, with HPV-6 and HPV-16 being most common for the external genitals and urethra. No difference is observed for men who have sex with men and men who have sex with women.
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