Multiple introductions of monkeypox virus to Ireland during the international mpox outbreak, May 2022 to October 2023.

BackgroundMpox, caused by monkeypox virus (MPXV), was considered a rare zoonotic disease before May 2022, when a global epidemic of cases in non-endemic countries led to the declaration of a Public Health Emergency of International Concern. Cases of mpox in Ireland, a country without previous mpox reports, could reflect extended local transmission or multiple epidemiological introductions.AimTo elucidate the origins and molecular characteristics of MPXV circulating in Ireland between May 2022 and October 2023.MethodsWhole genome sequencing of MPXV from 75% of all Irish mpox cases (182/242) was performed and compared to sequences retrieved from public databases (n = 3,362). Bayesian approaches were used to infer divergence time between sequences from different subclades and evaluate putative importation events from other countries.ResultsOf 242 detected mpox cases, 99% were males (median age: 35 years; range: 15-60). All 182 analysed genomes were assigned to Clade IIb and, presence of 12 distinguishable subclades suggests multiple introductions into Ireland. Estimation of time to divergence of subclades further supports the hypothesis for multiple importation events from numerous countries, indicative of extended and sustained international spread of mpox. Further analysis of sequences revealed that 92% of nucleotide mutations were from cytosine to thymine (or from guanine to adenine), leading to a high number of non-synonymous mutations across subclades; mutations associated with tecovirimat resistance were not observed.ConclusionWe provide insights into the international transmission dynamics supporting multiple introductions of MPXV into Ireland. Such information supported the implementation of evidence-informed public health control measures.

Recreational and sexualised drug use among gay, bisexual, and other men who have sex with men (gbMSM) in Ireland-Findings from the European MSM internet survey (EMIS) 2017.

BACKGROUND: Gay, bisexual, and other men who have sex with men (gbMSM) report a higher prevalence of drug use in comparison to the general male population. However, in Ireland, there is a paucity of literature regarding the prevalence of drug use and its determinants among gbMSM. AIMS/OBJECTIVES: To quantify the prevalence of (i) recreational drug use (RDU) and (ii) sexualised drug use (SDU) among gbMSM in Ireland, and to identify the factors associated with these drug use practices. METHODS: The European MSM Internet Survey (EMIS) 2017 was an online, anonymous, internationally-promoted questionnaire. Two binary outcomes were included in our analyses: (1) RDU and (2) SDU in the previous year. Multivariable-adjusted logistic regression explored factors associated with these outcomes, and all independent covariates were adjusted for one another. RESULTS: Among gbMSM without HIV (n = 1,898), 40.9% and 13.1% engaged in RDU and SDU in the previous year, respectively. Among diagnosed-positive gbMSM (n = 141), the past-year respective prevalence estimates were 51.8% and 26.2%. Increased odds of RDU were observed among gbMSM who were younger (vs. 40+ years) (18-24 years; AOR 2.96, 95% CI 2.05-4.28, 25-39 years; AOR 1.66, 95% CI 1.27-2.16), lived in Dublin (vs. elsewhere) (AOR 1.47, 95% CI 1.17-1.83), and engaged in condomless anal intercourse (CAI) in the previous year (vs. none) (1-2 partners; AOR 1.79, 95% CI 1.34-2.38, 6+ partners; AOR 1.79, 95% CI 1.18-2.71). Greater odds of SDU were identified among those who lived in Dublin (vs. elsewhere) (AOR 1.50, 95% CI 1.07-2.10), and engaged in CAI (vs. none) (1-2 partners; AOR 3.16, 95% CI 2.05-4.88, 3-5 partners; AOR 2.50, 95% CI 1.47-4.26, and 6+ partners; AOR 3.79, 95% CI 2.23-6.43). CONCLUSION: GbMSM report a high prevalence of drug use in Ireland. Targeted interventions, including harm reduction campaigns, may be needed to support healthier drug use choices among this community.

Hepatitis A and B vaccination in gbMSM in Ireland: findings from the European MSM Internet Survey 2017 (EMIS-2017).

OBJECTIVES: Gay, bisexual and other men who have sex with men (gbMSM) have a higher risk of acquiring hepatitis A and B viruses (HAV and HBV) than the general population and are recommended for vaccination against both in Ireland. This study aims to determine the prevalence of self-reported HAV and HBV infection and vaccination among gbMSM in Ireland and explore factors associated with self-reported HAV and HBV vaccination among gbMSM. METHODS: This study analysed Irish data from the European MSM Internet Survey 2017 (EMIS-2017) to measure the prevalence of self-reported HAV and HBV infection and vaccination among gbMSM in Ireland. Multivariable logistic regression was used to explore the associations between sociodemographic, healthcare-related and behavioural factors and self-reported vaccination. RESULTS: There were 2083 EMIS-2017 respondents in Ireland. Among HIV-negative gbMSM, 4.6% and 4.4% reported previous HAV and HBV infection, respectively, and 51% and 57% reported the receipt of one or more vaccine dose for HAV and HBV, respectively. In the multivariable analysis, HIV-negative gbMSM had lower odds of self-reported HAV vaccination if they lived outside the capital, Dublin (aOR 0.61, 95% CI: 0.48 to 0.78), had no third-level education (aOR 0.65, 95% CI: 0.45 to 0.92), were not tested for HIV in the last year (aOR 0.39, 95% CI: 0.31 to 0.50), had never tried to obtain pre-exposure prophylaxis (PrEP, aOR 0.60, 95% CI: 0.38 to 0.96) and had not been diagnosed with a sexually transmitted infection (STI) in the previous year (aOR 0.42, 95% CI: 0.28 to 0.63). Similar associations were observed for self-reported HBV vaccination. CONCLUSIONS: Self-reported vaccination against HAV and HBV among gbMSM in Ireland is high, but the level of vaccination remains insufficient to protect against future HAV and HBV infections and outbreaks. Efforts to increase vaccination coverage among gbMSM should focus on men who live outside the capital, have lower educational attainment and do not engage with sexual health services.

BK polyomavirus associated progressive multifocal leukoencephalopathy in a person living with HIV.

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease of the white matter central nervous system occurring in immunocompromised patients particularly those with T cell deficiency such as in HIV, haematological and solid organ malignancies and those taking immunomodulatory medications. PML is caused by JC virus however in rare cases BK virus has been isolated in the cerebral spinal fluid of patients presenting with PML. In this case we describe a 49 year old man who presented to the emergency department with a 2 week history of progressive right sided weakness and dysarthria. His background history included HIV diagnosed in 2005, he had not engaged with care in the past 2 years and had not been taking anti-retroviral therapy (ART). Other past medical history included untreated hepatitis C. His CD4 count was 90 (11%) cells/mm3 on admission and his HIV viral load VL) was 141,000 copies/ml. Magnetic resonance imaging(MRI) showed a hypointense lesion on T1, hyperintense on T2 and FLAIR without diffusion restriction and without mass effect. A lumbar puncture was performed which confirmed JC virus was positive (PCR <50 copies/ml) and also revealed BK virus was positive (PCR 46,511 copies/ml). The patient was commenced on tenofovir alafenamide fumarate/emtricitabine/darunavir/cobicistat in combination with dolutegravir 50mg twice daily. On day 40 post commencement of ART the patient was readmitted with worsening of his right arm weakness and dysarthria. A repeat MRI was performed which showed the hyperdense lesion on T2 and FLAIR appeared slightly larger with some slight enhancement with gadolinium contrast but no other features suggesting PML immune reconstitution inflammatory syndrome (IRIS). The CD4 count had increased to 141(17%) and HIV VL had decreased to 85 copies/ml. A clinical diagnosis of PML IRIS was made and the patient was commenced on prednisolone 30mg BD which lead to an initial improvement in symptoms. Interestingly in this case, both JC virus and BK virus were detected in the CSF of this patient with the level of JC virus being too low to quantify. BK virus was not detectable on peripheral serum sampling suggesting that BK virus is replicating in the CNS independent of other body sites. There have been 5 case reports in the literature of BK virus as the cause of PML. Testing for BK virus should be considered in patients presenting with signs and symptoms of PML and encephalitis particularly when no other cause is found.

Successful Treatment of Cryptococcal Meningitis and Cryptococcoma with Isavuconazole in a Patient Living with HIV.

We describe the successful use of isavuconazole for treatment of an HIV-positive patient with cryptococcal meningitis following induction therapy with liposomal amphotericin B and flucytosine. Because the Cryptococcus neoformans isolate from cerebrospinal fluid had a borderline minimum inhibitory concentration of 8 mg/L, initial consolidation therapy was given with a daily dose of fluconazole 1200 mg based on area under the curve to minimum inhibitory concentration modelling data. Toxicity, and the radiological emergence of a cryptococcoma in the setting of immune reconstitution inflammatory syndrome, prompted a therapeutic switch to isavuconazole. Subsequent imaging after 19 weeks of isavuconazole shows a significant reduction in cryptococcoma size from 11 mm to complete resolution. The patient remains well after 210 days of therapy with a view to completion of treatment after 1 year.

Virtual HIV pre-exposure prophylaxis outpatient service in the era of COVID-19.

In the midst of the COVID-19 pandemic, health care providers have had to rapidly change how they deliver care to patients. We discuss how we are delivering a virtual HIV pre-exposure prophylaxis (PrEP) service during this time; challenges faced; challenges expected and goals for the coming months.

A proposal for changes to the European Union syphilis surveillance case definition using evidence from evaluations in Ireland.

Syphilis remains a disease of public health importance, with considerable health effects if not treated. Concurrent infection with syphilis and untreated HIV facilitates HIV transmission. The incidence of syphilis in Europe has been increasing, particularly among men who have sex with men (MSM) and in MSM with HIV. However, there is heterogeneity among countries in the case definition used for syphilis and in reported syphilis notification rates. In Ireland, we have undertaken a number of refinements of the national syphilis surveillance system since 2014, including refinement of the laboratory thresholds for notification (rapid plasma reagin 1:16 and/or positive IgM). This article outlines the steps taken and some of the challenges we faced. Our current case definition now accurately reflects the epidemiology of syphilis in Ireland and our current surveillance provides timely information for action, while not reducing the sensitivity of the system too much. For countries where surveillance is driven mainly by laboratory reporting and where obtaining clinical details is challenging, these thresholds for notification may be a pragmatic solution.

Does U=U for breastfeeding mothers and infants? Breastfeeding by mothers on effective treatment for HIV infection in high-income settings.

Can the campaign Undetectable=Untransmittable (U=U), established for the sexual transmission of HIV, be applied to the transmission of HIV through breastfeeding? European AIDS Clinical Society and, to some extent, American guidelines now state that mothers with HIV who wish to breastfeed should be supported, with increased clinical and virological monitoring. This Viewpoint summarises existing evidence on transmission of HIV through breastfeeding, differences in HIV dynamics and viral load between breastmilk and plasma, and the effects of antiretroviral therapy on infants. At present, insufficient evidence exists to make clear recommendations for the required frequency of clinical and virological monitoring for mother and infant in a breastfeeding relationship or for the action to be taken in the event of viral rebound. We propose a roadmap for collaborative research to provide the missing evidence required to enable mothers who wish to breastfeed to make a fully informed choice.

Using data from a behavioural survey of men who have sex with men (MSM) to estimate the number likely to present for HIV pre-exposure prophylaxis (PrEP) in Ireland, 2017.

In Ireland, men who have sex with men (MSM) have increased HIV risk. Pre-exposure prophylaxis (PrEP), combined with safe sex practices, can reduce HIV acquisition. We estimated MSM numbers likely to present for PrEP by applying French PrEP criteria to Irish MSM behavioural survey data. We adjusted for survey bias, calculated proportions accessing testing services and those likely to take PrEP. We estimated 1-3% of MSM in Ireland were likely to present for PrEP.

Point-of-care testing for HIV in an Irish prison setting: results from three major Irish prisons.

HIV is more prevalent in the prison population compared to the general population. Prison inmates are at an increased risk of blood-borne infections. Considerable stigma has been documented amongst inmates with HIV infection. In collaboration with the schools, healthcare facilities, prison authorities and inmate Irish Red Cross groups in Wheatfield, Cloverhill and Mountjoy prisons in Dublin, Ireland, the Department of Genito Urinary Medicine and Infectious Diseases at St James' Hospital in Dublin developed a campaign for raising awareness of HIV, educating inmates about HIV and tackling HIV stigma. Following this campaign, large-scale point-of-care testing for HIV was offered over a short period. In total, 741 inmates were screened for HIV. One inmate tested positive for HIV. We experienced a large number of invalid test results, requiring formal laboratory serum testing, and a small number of false positive results. Large-scale point-of-care testing in the Irish prison setting is acceptable and achievable.

Injection of new psychoactive substance snow blow associated with recently acquired HIV infections among homeless people who inject drugs in Dublin, Ireland, 2015.

In February 2015, an outbreak of recently acquired HIV infections among people who inject drugs (PWID) was identified in Dublin, following similar outbreaks in Greece and Romania in 2011. We compared drug and risk behaviours among 15 HIV cases and 39 controls. Injecting a synthetic cathinone, snow blow, was associated with recent HIV infection (AOR: 49; p=0.003). Prevention and control efforts are underway among PWID in Dublin, but may also be needed elsewhere in Europe.

National Guidelines for the prevention of mother-to-child transmission of HIV across Europe - how do countries differ?

OBJECTIVES: The aim was to summarize national prevention of mother-to-child transmission (PMTCT) guidelines across Europe and to identify differences between these. METHODS: A survey was conducted using a structured questionnaire sent to experts in 25 European countries from January to March 2012, requesting a copy of the national guidelines. Responses were received from 23 countries. RESULTS: Twenty-two (96%) countries supported a policy to recommend antenatal HIV screening for all pregnant women (15: opt-out strategy; 8: opt-in strategy). For HIV-positive women in whom the only indication for antiretroviral therapy (ART) was PMTCT, the recommended gestational age for commencing ART varied from 12 to 28 weeks: initiation before 19 weeks gestation was recommended in guidelines from nine countries; in France, the UK and the Netherlands, there was a wide range, from 14 to 24 weeks, whereas the Swiss and Ukrainian guidelines recommended starting at 24-28 weeks and the German/Austrian and Lithuanian at 28 weeks. Six national guidelines recommended inclusion of Zidovudine in antenatal ART regimens, and seven (37%) allowed continuation of Efavirenz for women conceiving on this drug. According to nine guidelines, zidovudine should always be used intrapartum. Eighteen national guidelines stated that HIV-positive women on successful ART can have a vaginal delivery. Viral load thresholds for vaginal delivery were <1000 copies/ml in 5 countries, <400 copies/ml in 3 and <50 copies/ml in 11 countries. CONCLUSION: There are important differences across Europe in national PMTCT guidelines, with most variation seen where the evidence-base remains limited. Such differences should be considered when interpreting research and surveillance findings.

Colposcopy is not necessary to assess the risk to the cervix in HIV-positive women: an international cohort study of cervical pathology in HIV-1 positive women.

The objectives of this prospective multicentre international cohort study are to describe the characteristics of a cohort of HIV-1 positive women and determine the best management system by comparing cervical pathology according to results of cytology, colposcopy and human papillomavirus (HPV) testing at baseline and throughout follow-up. A. Cohorts of known HIV-positive women were recruited from 6 hospital-based European centres and a community-based South African centre. Following registration, women were reviewed every 6 months to undergo cervical surveillance including cytology, colposcopy, histopathology and HPV testing, using the HPV hybrid capture assay. Independent risk factors for the incidence of cytological abnormality and acquisition/clearance of HPV infection during follow up were identified. A total of 1,534 women were recruited, 400 of which were from South Africa. At baseline, among European women, 66% had normal cytology and half were HPV negative and among South African women, 45% had normal cytology and one third (32%) were HPV negative. The sensitivity of cytology (>/=ASCUS) matched with that of colposcopy to detect CIN2+. Rate of detection of high grade CIN at 2 years was similar in European and South African women (11 and 9.3%, respectively). Cytology and HPV testing alone were each sufficiently sensitive as a screening test at 2 yearly intervals. Our data confirm the high prevalence of low-grade cytological abnormalities and high-risk HPV infection. Cytology appears to be sufficient for cervical surveillance, with HPV testing being less specific with poor positive predictive value. There appears to be no additional benefit from routine colposcopy.

Steady-state lopinavir levels in third trimester of pregnancy.

Stek and colleagues reported low lopinavir levels in the third trimester of pregnancy at standard dosing. Since their initial report in 2003, we have taken steady-state trough lopinavir levels in all pregnant women in the third trimester; the results of 26 women on a lopinavir/ritonavir regimen are reported. The median trough level was 3.66 microg/ml, range 0.25-9.97; the median HIV viral load was 49 copies/ml at delivery. All infants were HIV polymerase chain reaction negative at 3 months.

Cervical screening and management of cervical intraepithelial neoplasia in HIV-positive women.

The high prevalence of abnormal cervical cytology in the context of immunosuppression has been recognized for many years. In response to repeated observations of cervical cancers in HIV-infected women, moderate and severe cervical dysplasia were designated as early symptomatic HIV infection (Category B) by the Centers for Disease Control and Prevention (CDC) in 1993, and invasive cervical cancer as an AIDS-defining condition (Category C). HIV-infected women, therefore, differ from the general population not only with a greater risk for more, but also potentially more severe cervical disease. In the era of highly active antiretroviral therapy, with HIV-infected women living for longer, there is a clear need to address this increased risk with appropriate management guidelines which this review attempts to provide.

Emergence of antiretroviral resistance in HIV-positive women receiving combination antiretroviral therapy in pregnancy.

BACKGROUND: Antenatal antiretroviral therapy is integral to preventing vertical transmission of HIV-1. The impact of temporary triple antiretroviral therapy in pregnancy on the emergence of antiretroviral resistance has not been studied. OBJECTIVE: To determine the impact of temporary triple antiretroviral therapy in pregnancy on emergence of antiretroviral resistance. METHODS: Pregnant HIV-1 infected women with a pre-treatment CD4 cell count >300 x 10(6)/l initiated triple antiretroviral therapy in the third trimester and discontinued postpartum. Genotypic resistance testing was performed after antiretroviral cessation and on pretreatment samples when postpartum samples showed primary mutations. RESULTS: In a cohort of 50 women who initiated antiretroviral therapy in pregnancy, 39 (78%) had postpartum HIV-1 nucleotide sequences available for analysis: 35 of these (90%) were previously antiretroviral naive. Seven primary mutations, V106A (one), Y181C (two), G190A (one), K101E (one), M184V (one), T215S (one) were detected in five (13%) women. All five were on regimens that included nevirapine and all were antiretroviral therapy naive prior to the index pregnancy. Four had no mutations detected pretreatment (one did not have a pretreatment analysis available; viral load 83 copies/ml). The median duration of antiretroviral exposure was 70 days. CONCLUSION: Emergence of genotypic resistance is significant in this cohort of pregnant women. All mutations detected were in those that took nevirapine-containing regimens. The clinical implications of these mutations are unknown.