Discrimination based on gender identity and decision-making regarding HIV/STI-protected sex, a cross-sectional study among trans and non-binary people in Germany.

BACKGROUND: Trans and non-binary people are often discriminated against. Discrimination has a negative impact on health and may affect sexual health and behavior. We explored the relationship between discrimination based on gender identity and the perceived ability to make decisions about their sex life to feel as protected as desired from HIV and sexually transmitted infections (STI) among trans and non-binary people in Germany. Secondarily, we assessed whether feeling unable of making HIV/STI-protected sex decisions was associated with behaviors related to increased HIV/STI risk. METHODS: We conducted a cross-sectional study using data from the Sexual Health and HIV/STI in Trans and Non-Binary Communities (TASG) survey conducted online between March-July 2022 among trans and/or non-binary people aged 18 years and older living in Germany. We described the prevalence of frequent discrimination based on gender identity. We calculated prevalence ratios (PR) with 95% confidence intervals (95% CI) for the associations between frequent experienced discrimination based on gender identity and feeling unable of making HIV/STI-protected sex decisions, and between feeling unable of making HIV/STI-protected sex decisions and behaviors related to increased HIV/STI risk. RESULTS: Among 3077 participants, 22% reported frequent discrimination based on gender identity. Participants experiencing such discrimination reported 1.4 times more often to feel unable to make HIV/STI-protected sex decisions (PR 1.4, 95% CI 1.1-1.8). This perceived inability was associated with increased prevalence of sex under drug influence (PR 2.9, 95% CI 2.3-3.7) and condomless penetrative sex with multiple partners without PrEP (PR 2.0, 95% CI 1.4-2.9). CONCLUSION: Feeling unable to make decisions to feel protected from HIV/STI among trans and non-binary people was associated with both frequent discrimination and behaviors that increase the HIV/STI risk. Strategies for empowering trans and non-binary people to assert their sexual decision-making needs should be explored.

Durability for 12 months of antibody response to a booster dose of monovalent BNT162b2 in adults who had initially received 2 doses of inactivated vaccine.

This study examined the strength and durability of antibody responses in 277 adults who received a heterologous third dose of the BNT162b2 vaccine, following two doses of an inactivated vaccine. Neutralizing antibody levels against both the ancestral virus and Omicron BA.2 subvariant decreased from one month to 6 months after the third dose, and were then maintained at 12 months. Participants who received both a fourth dose and reported a SARS-CoV-2 infection had the highest antibody titers at 365 days after the third dose. Individuals with chronic medical conditions had lower antibody levels against the Omicron BA.2 subvariant at 12 months after the third dose. The results suggest that the heterologous third dose provides durable neutralizing antibody responses, which may be influenced by subsequent infection or vaccination and pre-existing medical conditions. These findings may help explain the differences in immune protection between vaccination and natural infection.

An observational study on imported COVID-19 cases in Hong Kong during mandatory on-arrival hotel quarantine.

Background: Hong Kong enforced stringent travel restrictions during the COVID-19 pandemic. Understanding the characteristics of imported COVID-19 cases is important for establishing evidence-based control measures. Methods: Retrospective cohort study summarising the characteristics of imported cases detected in Hong Kong between 13 November 2020 and 31 January 2022, when compulsory quarantine was implemented. Findings: A total of 2269 imported COVID-19 cases aged 0-85 years were identified, of which 48.6 % detected on arrival. A shorter median delay from arrival to isolation was observed in Delta and Omicron cases (3 days) than in ancestral strain and other variants cases (12 days; p < 0.001). Lower Ct values at isolation were observed in Omicron cases than in ancestral strain or other variants cases. No Omicron cases were detected beyond 14 days after arrival. Cases detected after 14 days of quarantine (n=58, 2.6 %) were more likely asymptomatic at isolation and had higher Ct value during isolation, some of them indicating re-positivity or post-arrival infections. Conclusions: Testing inbound travellers at arrival and during quarantine can detect imported cases early, but may not prevent all COVID-19 introductions into the community. Public health measures should be adapted in response to the emergence of SARS-CoV-2 variants based on evidence from ongoing surveillance.

Comparison of control and transmission of COVID-19 across epidemic waves in Hong Kong: an observational study.

Background: Hong Kong contained COVID-19 for two years but experienced a large epidemic of Omicron BA.2 in early 2022 and endemic transmission of Omicron subvariants thereafter. We reflected on pandemic preparedness and responses by assessing COVID-19 transmission and associated disease burden in the context of implementation of various public health and social measures (PHSMs). Methods: We examined the use and impact of pandemic controls in Hong Kong by analysing data on more than 1.7 million confirmed COVID-19 cases and characterizing the temporal changes non-pharmaceutical and pharmaceutical interventions implemented from January 2020 through to 30 December 2022. We estimated the daily effective reproductive number (Rt) to track changes in transmissibility and effectiveness of community-based measures against infection over time. We examined the temporal changes of pharmaceutical interventions, mortality rate and case-fatality risks (CFRs), particularly among older adults. Findings: Hong Kong experienced four local epidemic waves predominated by the ancestral strain in 2020 and early 2021 and prevented multiple SARS-CoV-2 variants from spreading in the community before 2022. Strict travel-related, case-based, and community-based measures were increasingly tightened in Hong Kong over the first two years of the pandemic. However, even very stringent measures were unable to contain the spread of Omicron BA.2 in Hong Kong. Despite high overall vaccination uptake (>70% with at least two doses), high mortality was observed during the Omicron BA.2 wave due to lower vaccine coverage (42%) among adults ≥65 years of age. Increases in antiviral usage and vaccination uptake over time through 2022 was associated with decreased case fatality risks. Interpretation: Integrated strict measures were able to reduce importation risks and interrupt local transmission to contain COVID-19 transmission and disease burden while awaiting vaccine development and rollout. Increasing coverage of pharmaceutical interventions among high-risk groups reduced infection-related mortality and mitigated the adverse health impact of the pandemic. Funding: Health and Medical Research Fund.

Comparative antibody and cell-mediated immune responses, reactogenicity, and efficacy of homologous and heterologous boosting with CoronaVac and BNT162b2 (Cobovax): an open-label, randomised trial.

BACKGROUND: Few trials have compared homologous and heterologous third doses of COVID-19 vaccination with inactivated vaccines and mRNA vaccines. The aim of this study was to assess immune responses, safety, and efficacy against SARS-CoV-2 infection following homologous or heterologous third-dose COVID-19 vaccination with either one dose of CoronaVac (Sinovac Biotech; inactivated vaccine) or BNT162b2 (Fosun Pharma-BioNTech; mRNA vaccine). METHODS: This is an ongoing, randomised, allocation-concealed, open-label, comparator-controlled trial in adults aged 18 years or older enrolled from the community in Hong Kong, who had received two doses of CoronaVac or BNT162b2 at least 6 months earlier. Participants were randomly assigned, using a computer-generated sequence, in a 1:1 ratio with allocation concealment to receive a (third) dose of CoronaVac or BNT162b2 (ancestral virus strain), stratified by types of previous COVID-19 vaccination (homologous two doses of CoronaVac or BNT162b2). Participants were unmasked to group allocation after vaccination. The primary endpoint was serum neutralising antibodies against the ancestral virus at day 28 after vaccination in each group, measured as plaque reduction neutralisation test (PRNT50) geometric mean titre (GMT). Surrogate virus neutralisation test (sVNT) mean inhibition percentage and PRNT50 titres against omicron BA.1 and BA.2 subvariants were also measured. Secondary endpoints included geometric mean fold rise (GMFR) in antibody titres; incidence of solicited local and systemic adverse events; IFNγ+ CD4+ and IFNγ+ CD8+ T-cell responses at days 7 and 28; and incidence of COVID-19. Within-group comparisons of boost in immunogenicity from baseline and between-group comparisons were done according to intervention received (ie, per protocol) by paired and unpaired t test, respectively, and cumulative incidence of infection was compared using Kaplan-Meier curves and a proportional hazards model to estimate hazard ratio. The trial is registered with ClinicalTrials.gov, NCT05057169. FINDINGS: We enrolled participants from Nov 12, 2021, to Jan 27, 2022. We vaccinated 219 participants who previously received two doses of CoronaVac, including 101 randomly assigned to receive CoronaVac (CC-C) and 118 randomly assigned to receive BNT162b2 (CC-B) as their third dose; and 232 participants who previously received two doses of BNT162b2, including 118 randomly assigned to receive CoronaVac (BB-C) and 114 randomly assigned to receive BNT162b2 (BB-B) as their third dose. The PRNT50 GMTs on day 28 against ancestral virus were 109, 905, 92, and 816; against omicron BA.1 were 9, 75, 8, and 86; and against omicron BA.2 were 6, 80, 6, and 67 in the CC-C, CC-B, BB-C, and BB-B groups, respectively. Mean sVNT inhibition percentages on day 28 against ancestral virus were 83%, 96%, 87%, and 96%; against omicron BA.1 were 15%, 58%, 19%, and 69%; and against omicron BA.2 were 43%, 85%, 50%, and 90%, in the CC-C, CC-B, BB-C, and BB-B groups, respectively. Participants who had previously received two doses of CoronaVac and a BNT162b2 third dose had a GMFR of 12 (p<0·0001) compared with those who received a CoronaVac third dose; similarly, those who had received two doses of BNT162b2 and a BNT162b2 third dose had a GMFR of 8 (p<0·0001). No differences in CD4+ and CD8+ T-cell responses were observed between groups. We did not identify any vaccination-related hospitalisation within 1 month after vaccination. We identified 58 infections when omicron BA.2 was predominantly circulating, with cumulative incidence of 15·3% and 15·4% in the CC-C and CC-B groups, respectively (p=0·93), and 16·7% and 14·0% in the BB-C and BB-B groups, respectively (p=0·56). INTERPRETATION: Similar levels of incidence of, presumably, omicron BA.2 infections were observed in each group despite very weak antibody responses to BA.2 in the recipients of a CoronaVac third dose. Further research is warranted to identify appropriate correlates of protection for inactivated COVID-19 vaccines. FUNDING: Health and Medical Research Fund, Hong Kong. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Risk of within-hotel transmission of SARS-CoV-2 during on-arrival quarantine in Hong Kong: an epidemiological and phylogenomic investigation.

Background: On-arrival quarantine has been one of the primary measures to prevent the introduction of SARS-CoV-2 into Hong Kong since the start of the pandemic. Most on-arrival quarantines have been done in hotels, with the duration of quarantine and testing frequency during quarantine modified over time along with other pandemic control measures. However, hotels are not designed with infection control in mind. We aimed to systematically study the potential risk of acquisition of SARS-CoV-2 infection among individuals undergoing hotel quarantine. Methods: We examined data on each laboratory-confirmed COVID-19 case identified in on-arrival quarantine in a hotel in Hong Kong between 1 May 2020 and 31 January 2022. We sequenced the whole genomes of viruses from cases that overlapped with other confirmed cases in terms of the hotel of stay, date of arrival and date of testing positive. By combining multiple sources of evidence, we identify probable and plausible transmission events and calculate the overall risk of transmission. Findings: Among 221 imported cases that overlapped with other cases detected during hotel quarantine with available sequence data, phylogenomic analyses identified five probable and two plausible clusters of within-hotel transmission. Only two of these clusters were recognised at the time. Including other clusters reported in Hong Kong, we estimate that 8-11 per 1000 cases identified in hotel quarantine may be infected by another unlinked case during quarantine, or 2-3 per 100,000 overseas arrivals. Interpretation: We have identified additional undetected occurrences of COVID-19 transmission within hotel quarantine in Hong Kong. Although hotels provide suboptimal infection control as improvised quarantine facilities, the risk of contracting infection whilst in quarantine is low. However, these unlikely events could have high consequences by allowing the virus to spread into immunologically naïve communities. Additional vigilance should be taken in the absence of improved controls to identify such events. If on-arrival quarantine is expected to be used for a long time, quarantine facilities could be purpose-built to minimise the risk of transmission. Funding: Health and Medical Research Fund, Hong Kong.

Slow Waning of Antibodies Following BNT162b2 as a Third Dose in Adults Who Had Previously Received 2 Doses of Inactivated Vaccine.

We administered BNT162b2 as a third dose to 314 adults aged ≥30 years who had previously received 2 doses of inactivated vaccine. We collected blood samples before the third dose and again after 1 month and 6 months, and found robust antibody responses to the ancestral strain at 6 months after receipt of BNT162b2. Antibody responses to Omicron BA.2 by live virus neutralization were weaker after the third dose and had declined to a low level by 6 months.

Immunogenicity of a Third Dose of BNT162b2 to Ancestral Severe Acute Respiratory Syndrome Coronavirus 2 and the Omicron Variant in Adults Who Received 2 Doses of Inactivated Vaccine.

BACKGROUND: Limited data exist on antibody responses to mixed vaccination strategies that involve inactivated coronavirus disease 2019 (COVID-19) vaccines, particularly in the context of emerging variants. METHODS: We conducted an open-label trial of a third vaccine dose of a messenger RNA (mRNA) vaccine (BNT162b2, Fosun Pharma/BioNTech) in adults aged ≥30 years who had previously received 2 doses of inactivated COVID-19 vaccine. We collected blood samples before administering the third dose and 28 days later and tested for antibodies to the ancestral virus using a binding assay (enzyme-linked immunosorbent assay [ELISA]), a surrogate virus neutralization test (sVNT), and a live virus plaque reduction neutralization test (PRNT). We also tested for antibodies against the Omicron variant using live-virus PRNT. RESULTS: In 315 participants, a third dose of BNT162b2 substantially increased antibody titers on each assay. Mean ELISA levels increased from an optical density of 0.3 to 2.2 (P < .001), and mean sVNT levels increased from an inhibition of 17% to 96% (P < .001). In a random subset of 20 participants, the geometric mean PRNT50 titers rose substantially, by 45-fold from day 0 to day 28 against the ancestral virus (P < .001) and by 11-fold against the Omicron variant (P < .001). In daily monitoring, post-vaccination reactions subsided within 7 days for more than 99% of participants. CONCLUSIONS: A third dose of COVID-19 vaccine with an mRNA vaccine substantially improved antibody levels against the ancestral virus and the Omicron variant with a well-tolerated safety profile in adults who had received 2 doses of inactivated vaccine 6 months earlier. CLINICAL TRIALS REGISTRATION: NCT05057182.

Strength and durability of antibody responses to BNT162b2 and CoronaVac.

We studied 2780 adults in Hong Kong who received CoronaVac inactivated virus vaccine (Sinovac) and BNT162b2 mRNA vaccine ("Comirnaty", BioNTech/Fosun Pharma). We compared rates of antibody waning over time using an enzyme-linked immunosorbent assay for spike receptor binding domain and a surrogate virus neutralization test. We found stronger and more durable antibody responses to two doses of the mRNA vaccine, and slightly stronger initial antibody responses to each vaccine in younger adults and women. The weaker and less durable responses following CoronaVac support earlier provision of third doses to persons who previously received two doses of this vaccine.

Epidemiological characteristics and outcomes of COVID-19 cases: mortality inequalities by socio-economic status, Barcelona, Spain, 24 February to 4 May 2020.

BackgroundPopulation-based studies characterising outcomes of COVID-19 in European settings are limited, and effects of socio-economic status (SES) on outcomes have not been widely investigated. AimWe describe the epidemiological characteristics of COVID-19 cases, highlighting incidence and mortality rate differences across SES during the first wave in Barcelona, Catalonia, Spain.MethodsThis population-based study reports individual-level data of laboratory-confirmed COVID-19 cases diagnosed from 24 February to 4 May 2020, notified to the Public Health Agency of Barcelona and followed until 15 June 2020. We analysed end-of-study vital status and the effects of chronic conditions on mortality using logistic regression. Geocoded addresses were linked to basic health area SES data, estimated using the composed socio-economic index. We estimated age-standardised incidence, hospitalisation, and mortality rates by SES.ResultsOf 15,554 COVID-19-confirmed cases, the majority were women (n = 9,028; 58%), median age was 63 years (interquartile range: 46-83), 8,046 (54%) required hospitalisation, and 2,287 (15%) cases died. Prevalence of chronic conditions varied across SES, and multiple chronic conditions increased risk of death (≥ 3, adjusted odds ratio: 2.3). Age-standardised rates (incidence, hospitalisation, mortality) were highest in the most deprived SES quartile (incidence: 1,011 (95% confidence interval (CI): 975-1,047); hospitalisation: 619 (95% CI: 591-648); mortality: 150 (95% CI: 136-165)) and lowest in the most affluent (incidence: 784 (95% CI: 759-809); hospitalisation: 400 (95% CI: 382-418); mortality: 121 (95% CI: 112-131)).ConclusionsCOVID-19 outcomes varied markedly across SES, underscoring the need to implement effective preventive strategies for vulnerable populations.

COVID-19 transmission in Hong Kong despite universal masking.

OBJECTIVES: mask-wearing outside the home has been almost universal in Hong Kong since late January 2020 with very high compliance. Nevertheless, community spread of COVID-19 has still occurred. We aimed to assess the settings where COVID-19 transmission occurred and determine the fraction of transmission events that occurred in settings where masks are not usually worn. METHODS: we reviewed detailed information provided by the Hong Kong Department of Health on local COVID-19 cases diagnosed up to 30 September 2020 to determine the most likely settings in which transmission occurred. We classified them in probably mask-on or mask-of and compared the prevalence of asymptomatic infections in these settings. RESULTS: among the 2425 cases (65.3%, 2425/3711) with information on transmission setting, 77.6% of the transmission occurred in household and social settings where face masks are not usually worn. Infections that occurred in mask-on settings were more likely to be asymptomatic (adjusted odds ratio 1.33; 95% confidence interval: 1.04, 1.68). CONCLUSIONS: we conclude that universal mask-wearing can reduce transmission, but transmission can continue to occur in settings where face masks are not usually worn. The higher proportion of asymptomatic cases in mask-on settings could be related to a milder disease presentation or earlier case detection.

Trends and differences in sexual practices and sexually transmitted infections in men who have sex with men only (MSMO) and men who have sex with men and women (MSMW): a repeated cross-sectional study in Melbourne, Australia.

OBJECTIVES: In the 2010s, there has been an increase in sexually transmitted infections (STI) in men who have sex with men (MSM) in Australia, and since 2015 also in urban heterosexuals. Men who have sex with both men and women (MSMW) have characteristics that may differ from both men who have sex with men only (MSMO) and heterosexual men. We aimed to compare the sexual practices and the trends in HIV/STI positivity between MSMO and MSMW. DESIGN: Repeated cross-sectional study. SETTING: A sexual health centre in Melbourne, Australia. PARTICIPANTS: MSM aged 18 years and above who attended the Melbourne Sexual Health Centre for the first time between 2011 and 2018. This includes 12 795 MSMO and 1979 MSMW. PRIMARY OUTCOME MEASURES: Demographic characterics, sexual practices and HIV/STI positivity. RESULTS: Compared with MSMW, MSMO were more likely to practice anal sex and to have condomless receptive anal sex with casual male partners, and less likely to have a current regular relationship. Over the 8-year period, there was an increase in condomless receptive anal sex with casual male partners for both groups (MSMO: from 46.2% to 63.3%, ptrend <0.001; MSMW: from 41.3% to 57.9%, ptrend=0.011). Syphilis positivity increased in MSMO (from 5.5% to 7.9%, ptrend=0.012) and MSMW (from 0.9% to 6.4%, ptrend=0.004) and HIV remained stable. Gonorrhoea increased among MSMO from 2011 to 2014 (from 6.7% to 9.6%, ptrend=0.002), and remained stable from 2015 to 2018. MSMO had higher odds of testing positive for gonorrhoea (adjusted OR (aOR) 1.36, 95% CI 1.13 to 1.64), chlamydia (aOR 1.39, 95% CI 1.16 to 1.67), syphilis (aOR 1.74, 95% CI 1.37 to 2.22) and HIV (aOR 4.60, 95% CI 2.43 to 8.70) than MSMW. CONCLUSIONS: MSMW have overall lower condomless sex and lower HIV/STI positivity. In the last years, changes in sexual practices in MSM have affected both MSMW and MSMO leading to an increased STI risk.

Clinical presentation of asymptomatic and symptomatic women who tested positive for genital gonorrhoea at a sexual health service in Melbourne, Australia.

Gonorrhoea cases in women have been rising in Australia in the 2010s but the cause of the increase is not well understood. This cross-sectional study aimed to describe the characteristics of genital gonorrhoea infection in women attending the Melbourne Sexual Health Centre, Australia. Gonorrhoea cases were diagnosed by nucleic acid amplification test (NAAT) and/or culture. Genitourinary specimens were obtained in 12 869 clinic visits in women aged 16 years or above between August 2017 and August 2018. Genital gonorrhoea was detected in 142 (1.1%) of the visits. Almost half of the cases were asymptomatic, 47.9% [95% confidence interval (CI) 39.8-56.1%]; yellow, green or pus-like vaginal discharge was present in 11.3% (95% CI 7.0-17.6%) and other genital symptoms in 40.8% (95% CI 33.1-49.1%) of the cases. The mean time between last sexual contact and onset of symptoms was 7.3 days and between the onset of symptoms to presentation to the clinic was 12.1 days. Half of the cases of genital gonorrhoea among women are asymptomatic and these cases would have been missed by testing of only symptomatic women. Further epidemiological and behavioural research is required to understand the temporal changes in sexual practices among women in Australia.

Clinical presentation of asymptomatic and symptomatic heterosexual men who tested positive for urethral gonorrhoea at a sexual health clinic in Melbourne, Australia.

BACKGROUND: Asymptomatic screening for gonorrhoea in heterosexual men is currently not recommended in many countries including Australia, given the prevalence is relatively low in the heterosexual population. We aimed to determine the proportion of urethral gonorrhoea cases among heterosexual men attending a sexual health clinic that was asymptomatic and symptomatic, the time since last sexual contact to the onset of symptoms and the time to clinic presentation following the onset of symptoms. METHODS: This was a cross-sectional study that included heterosexual men aged 16 years or above attending the Melbourne Sexual Health Centre (MSHC) in Australia between August 2017 and August 2018. Gonorrhoea cases were diagnosed by nucleic acid amplification testing (NAAT) and/or culture. Descriptive analyses were conducted for all gonorrhoea cases including demographic characteristics, recent sexual practices, reported urethral symptoms and duration, sexual contact with a person diagnosed with gonorrhoea, investigations performed and laboratory results. RESULTS: There were 116 confirmed cases of urethral gonorrhoea in heterosexual men over the study period of which 6.0% (95% CI: 2.7-12.1%) were asymptomatic. Typical urethral discharge was present in 80.2% (95% CI: 71.9-86.5%) of men. The mean time between last sexual contact and the onset of symptoms was 7.0 days, and between the onset of symptoms to presentation to the clinic was 5.6 days. CONCLUSIONS: A small proportion of heterosexual men with urethral gonorrhoea do not have any symptoms. Heterosexual men with urethral symptoms usually seek for healthcare within a week, prompting rapid healthcare-seeking behaviour.

Catalonia Suicide Risk Code Epidemiology (CSRC-Epi) study: protocol for a population-representative nested case-control study of suicide attempts in Catalonia, Spain.

INTRODUCTION: Suicide attempts represent an important public health burden. Centralised electronic health record (EHR) systems have high potential to provide suicide attempt surveillance, to inform public health action aimed at reducing risk for suicide attempt in the population, and to provide data-driven clinical decision support for suicide risk assessment across healthcare settings. To exploit this potential, we designed the Catalonia Suicide Risk Code Epidemiology (CSRC-Epi) study. Using centralised EHR data from the entire public healthcare system of Catalonia, Spain, the CSRC-Epi study aims to estimate reliable suicide attempt incidence rates, identify suicide attempt risk factors and develop validated suicide attempt risk prediction tools. METHODS AND ANALYSIS: The CSRC-Epi study is registry-based study, specifically, a two-stage exposure-enriched nested case-control study of suicide attempts during the period 2014-2019 in Catalonia, Spain. The primary study outcome consists of first and repeat attempts during the observation period. Cases will come from a case register linked to a suicide attempt surveillance programme, which offers in-depth psychiatric evaluations to all Catalan residents who present to clinical care with any suspected risk for suicide. Predictor variables will come from centralised EHR systems representing all relevant healthcare settings. The study's sampling frame will be constructed using population-representative administrative lists of Catalan residents. Inverse probability weights will restore representativeness of the original population. Analysis will include the calculation of age-standardised and sex-standardised suicide attempt incidence rates. Logistic regression will identify suicide attempt risk factors on the individual level (ie, relative risk) and the population level (ie, population attributable risk proportions). Machine learning techniques will be used to develop suicide attempt risk prediction tools. ETHICS AND DISSEMINATION: This protocol is approved by the Parc de Salut Mar Clinical Research Ethics Committee (2017/7431/I). Dissemination will include peer-reviewed scientific publications, scientific reports for hospital and government authorities, and updated clinical guidelines. TRIAL REGISTRATION NUMBER: NCT04235127.

The safety of isoniazid tuberculosis preventive treatment in pregnant and postpartum women: systematic review and meta-analysis.

BACKGROUND: The World Health Organization (WHO) recommends tuberculosis (TB) preventive treatment for high-risk groups. Isoniazid preventive therapy (IPT) has been used globally for this purpose for many years, including in pregnancy. This review assessed current knowledge about the safety of IPT in pregnancy. METHODS: We searched PubMed, Embase, CENTRAL, Global Health Library and HIV and TB-related conference abstracts, until May 15, 2019, for randomised controlled trials (RCTs) and non-randomised studies (NRS) where IPT was administered to pregnant women. Outcomes of interest were: 1) maternal outcomes, including permanent drug discontinuation due to adverse drug reactions, any grade 3 or 4 drug-related toxic effects, death from any cause and hepatotoxicity; and 2) pregnancy outcomes, including in utero fetal death, neonatal death or stillbirth, preterm delivery/prematurity, intrauterine growth restriction, low birth weight and congenital anomalies. Meta-analyses were conducted using a random-effects model. RESULTS: After screening 1342 citations, nine studies (of 34 to 51 942 participants) met inclusion criteria. We found an increased likelihood of hepatotoxicity among pregnant women given IPT (risk ratio 1.64, 95% CI 0.78-3.44) compared with no IPT exposure in one RCT. Four studies reported on pregnancy outcomes comparing IPT exposure to no exposure among pregnant women with HIV. In one RCT, adverse pregnancy outcomes were associated with IPT exposure during pregnancy (odds ratio (OR) 1.51, 95% CI 1.09-2.10), but three NRS showed a protective effect. CONCLUSIONS: We found inconsistent associations between IPT and adverse pregnancy outcomes. Considering the grave consequences of active TB in pregnancy, current evidence does not support systematic deferral of IPT until postpartum. Research on safety is needed.

Tuberculosis recurrences and predictive factors in a vulnerable population in Catalonia.

BACKGROUND: Patients with a history of tuberculosis (TB) have a high probability of recurrence because long-term cure is not always maintained in successfully treated patients. The aim of this study was to identify the probability of TB recurrence and its predictive factors in a cohort of socially vulnerable patients who completed treatment in the TB referral center in Catalonia, which acts as the center for patients with social and health problems. METHODS: This retrospective open cohort study included all patients diagnosed with TB who were admitted and successfully treated in Serveis Clínics between 2000 and 2016 and who remained disease-free for a minimum of 1 year after treatment completion. We calculated the incidence density of TB recurrences per person-years of follow-up. We also estimated the cumulative incidence of TB recurrence at 1, 2, 5, and 10 years of follow-up. Bivariate analysis was conducted using Kaplan-Meier curves. Multivariate analysis was conducted using Cox regression. Hazard ratios (HR) were calculated with their 95% confidence intervals (95%CI). RESULTS: There were 839 patients and 24 recurrences (2.9%), representing 0.49 per 100 person-years. The probability of a recurrence was 0.63% at 1 year of follow-up, 1.35% at 2 years, and 3.69% at 5 years. The multivariate analysis showed that the predictive factors of recurrence were age older than 34 years (aHR = 3.90; CI = 1.06-14.34 at age 35-45 years and aHR = 3.88; CI = 1.02-14.80 at age >45 years) and resistance to at least one anti-TB drug (aHR = 2.91; CI = 1.11-7.65). CONCLUSIONS: Attention should be paid to socially vulnerable persons older than 34 years with a previous episode of resistant TB. Surveillance resources should be directed toward adequately treated patients who nevertheless have a high risk of recurrence.

Meningococcal vaccine uptake among men who have sex with men in response to an invasive meningococcal C disease outbreak in Melbourne, Australia.

OBJECTIVE: In 2017, there was an outbreak of invasive meningococcal disease (IMD) serogroup C among men who have sex with men (MSM) in Victoria, Australia. A government-funded free meningococcal (MenACWY) vaccination programme targeting all MSM living in Victoria was launched between December 2017 and December 2018. The aim of this study was to examine the vaccine uptake among MSM attending a sexual health clinic in Melbourne. METHODS: This was a retrospective clinical audit of MSM attending the Melbourne Sexual Health Centre (MSHC) during the vaccination programme. We calculated the proportion of MSM who received the meningococcal vaccine on their first visit and at any time during the programme. We performed univariable and multivariable logistic regression to identify the factors associated with the vaccine uptake on the first visit. RESULTS: Of the 10 370 MSM who attended MSHC, 55.5% received the vaccine on their first visit and 67.4% at any time during the programme. MSM had higher odds of receiving the vaccine on the first visit if they were aged 16-25 years (adjusted OR (aOR) 1.21; 95% CI 1.08 to 1.35) or 26-35 years (aOR 1.17; 95% CI 1.07 to 1.29) in comparison with MSM older than 35 years; were HIV-negative and not on pre-exposure prophylaxis (aOR 1.80; 95% CI 1.56 to 2.09); had more than four male partners in the last 12 months (aOR 1.16; 95% CI 1.06 to 1.27); had male partners only (aOR 2.24; 95% CI 1.96 to 2.55); or were born overseas (aOR 1.11; 95% CI 1.03 to 1.21). CONCLUSIONS: Two-thirds of the MSM attending a sexual health clinic received at least one dose of meningococcal vaccine. The vaccination programme coincided temporally with a dramatic reduction in the incidence of IMD. Vaccination should be further promoted among MSM and men who have sex with both men and women.

Cost-Effectiveness of the Screening for the Primary Prevention of Fragility Hip Fracture in Spain Using FRAX®.

To assess the cost-effectiveness of the primary prevention of fragility hip fractures through opportunistic risk-based screening using FRAX® among women aged 70 to 89 years, and the subsequent treatment with alendronate in women at high-risk, from the Spanish national health system perspective. We performed a discrete-event simulation model. Women were categorized in low, intermediate and high-risk of fragility hip fracture through screening based on the FRAX® risk assessment tool score (Spanish version). Low-risk women received lifestyle recommendations whereas the high-risk group was assigned to alendronate treatment. For women at intermediate-risk, treatment decision was based on a recalculated score considering bone mineral density (BMD). The cost-effectiveness analysis tested six scenarios defined by different FRAX® cut-off values assessing the incremental costs per averted fracture in 20 years. Deterministic sensitivity analysis was performed. We included a random sample of 5146 women obtained from a Spanish cohort of women referred for BMD. The most cost-effective intervention had an Incremental Cost-effectiveness Ratio (ICER) of 57,390 € per averted hip fracture and consisted of using the FRAX® score without BMD and treating women with a score higher than 5%. The ICER exceeded the acceptability threshold of 25,000 € in all the scenarios. Sensitivity analysis based on time to fracture, treatment efficacy, adherence to treatment and cost of dependence resulted in ICERs ranging from 39,216 € to 254,400 €. An ICER of 24,970 € was obtained when alendronate cost was reduced to 1.13 € per month. The use of FRAX® as screening tool followed by alendronate treatment is not cost-effective in senior women in Spain. Other primary preventions strategies are advisable.