Infectious Proctitis due to Human Mpox.

We describe 2 cases of infectious proctitis secondary to human monkeypox in patients presenting with rectal pain. These cases highlight the importance of multidisciplinary management of monkeypox and in expanding case definitions and enabling clinical recognition in patients presenting without skin rash.

Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis.

BACKGROUND: Historically, human monkeypox virus cases in the UK have been limited to imported infections from west Africa. Currently, the UK and several other countries are reporting a rapid increase in monkeypox cases among individuals attending sexual health clinics, with no apparent epidemiological links to endemic areas. We describe demographic and clinical characteristics of patients diagnosed with human monkeypox virus attending a sexual health centre. METHODS: In this observational analysis, we considered patients with confirmed monkeypox virus infection via PCR detection attending open-access sexual health clinics in London, UK, between May 14 and May 25, 2022. We report hospital admissions and concurrent sexually transmitted infection (STI) proportions, and describe our local response within the first 2 weeks of the outbreak. FINDINGS: Monkeypox virus infection was confirmed in 54 individuals, all identifying as men who have sex with men (MSM), with a median age of 41 years (IQR 34-45). 38 (70%) of 54 individuals were White, 26 (48%) were born in the UK, and 13 (24%) were living with HIV. 36 (67%) of 54 individuals reported fatigue or lethargy, 31 (57%) reported fever, and ten (18%) had no prodromal symptoms. All patients presented with skin lesions, of which 51 (94%) were anogenital. 37 (89%) of 54 individuals had skin lesions affecting more than one anatomical site and four (7%) had oropharyngeal lesions. 30 (55%) of 54 individuals had lymphadenopathy. One in four patients had a concurrent STI. Five (9%) of 54 individuals required admission to hospital, mainly due to pain or localised bacterial cellulitis requiring antibiotic intervention or analgesia. We recorded no fatal outcomes. INTERPRETATION: Autochthonous community monkeypox virus transmission is currently observed among MSM in the UK. We found a high proportion of concomitant STIs and frequent anogenital symptoms, suggesting transmissibility through local inoculation during close skin-to-skin or mucosal contact, during sexual activity. Additional resources are required to support sexual health and other specialist services in managing this condition. A review of the case definition and better understanding of viral transmission routes are needed to shape infection control policies, education and prevention strategies, and contact tracing. FUNDING: None.

Complex PrEP: the factors requiring consultant-led review of PrEP users.

INTRODUCTION: HIV-1 pre-exposure prophylaxis (PrEP) has been available in England since March 2020 on the National Health Service using generic emtricitabine and tenofovir disoproxil. 56 Dean Street (56DS) provided PrEP through (1) additional private care from September 2015, estimated to be providing 11% of England's PrEP in 2019; and (2) the IMPACT trial, as well as monitoring those self-sourcing PrEP. Providing PrEP at scale through a nurse-led service required a safety net for complex individuals. 56DS introduced a consultant-led PrEP outpatient service, the PrEP review clinic, in January 2018 and we report the outcomes of this service. METHODS: We present a retrospective case note review of the PrEP review clinic with descriptive outcomes from 26 January 2018 to 20 December 2019. Reason for referral, demographics, PrEP management and PrEP discontinuations were recorded. RESULTS: 13 980 unique users accessed PrEP from 56DS during the two year evaluation period. 220 individuals were seen in the PrEP review clinic. Majority of patients were referred for renal issues (114 of 220, 51.8%), followed by side effects (59 of 220, 26.8%) and comorbidities (38 of 220, 17.2%). Of those with renal issues, 89 (out of 114, 78.1%) users were referred for an abnormal estimated glomerular filtration rate (eGFR). 35 (out of 114, 30.7%) PrEP users had an eGFR between 45 and 59 mL/min/1.73 m2, of whom 2 (5.7%) discontinued PrEP. Majority of users were advised to stop supplements±switch to event-based dosing (24 of 35, 68.6%). Ten PrEP users were referred with an eGFR between 30 and 44 mL/min/1.73 m2; 4 (40%) stopped or did not start PrEP and 6 (60%) were asked to stop supplements±switch to event-based dosing. DISCUSSION: A small proportion of PrEP users have complex PrEP issues. Methods to manage renal dysfunction with PrEP included stopping supplements and switching to event-based dosing. Those with side effects were managed with an array of options, with only modest effectiveness. Other PrEP options are needed to support those with toxicities or intolerances.

Rising rates of recent preexposure prophylaxis exposure among men having sex with men newly diagnosed with HIV: antiviral resistance patterns and treatment outcomes.

INTRODUCTION: Preexposure prophylaxis (PrEP) is contributing to achieve a reduction in HIV diagnoses in men having sex with men (MSM). Albeit infrequent, HIV infections in the context of recent PrEP exposure represent a clinical challenge. METHODS: Data on recent PrEP use and possible reasons leading to HIV infection were analysed in individuals newly diagnosed with HIV at 56 Dean Street clinic in 2016-2020. Demographics, immune-virological parameters, genotypic resistance test results and treatment management in this group were compared with those not reporting recent PrEP exposure using Mann-Whitney U test and Fisher's exact test. RESULTS: Fifty-two of 1030 (5%) individuals reported recent PrEP exposure at HIV diagnosis; 98% were MSM, median age 34 years (interquartile range [IQR] 28-42), 65% of white ethnicity, 65% non-UK-born. 35% reported PrEP intake the day before testing HIV positive, 46% reported sub-optimal PrEP adherence since their last negative HIV test result. Thirty-three of 52 (63%) were self-sourcing PrEP and 9/52 (17%) reported issues with its supply. Recent PrEP use was associated to lower HIV viral load and higher CD4+ cell count at baseline than in counterparts non-recently exposed to PrEP (P < 0.01). M184V mutation was harboured more commonly in the recent PrEP use group (30% vs. 1%, P < 0.01). The proportion of individuals recently exposed to PrEP among those diagnosed with HIV rose sharply, reaching 21% in the first semester of 2020. Viral suppression was achieved by all patients intensified from PrEP to antiretroviral treatment (ART) who remained in care at week 24. DISCUSSION: Rapid PrEP intensification to ART allowed to achieve high rates of HIV viral suppression despite significant rates of M184V mutation harboured in those newly diagnosed with HIV and reporting recent PrEP exposure.

Treponema pallidum PCR testing for diagnosis of mucocutaneous ulcers suspicious for syphilis.

BACKGROUND: Primary syphilis is characterised by the appearance of an ulcerated lesion (chancre) on the anogenital or oral mucosa from which Treponema pallidum DNA may be detectable by PCR. Serological tests for syphilis may be non-reactive in early infection, even after the appearance of a chancre. We reviewed the use of a multiplex-PCR (M-PCR) test to determine the added value of T. pallidum DNA detection in the management of individuals presenting with mucocutaneous ulceration at a sexual health service in central London. METHODS: We performed a cross-sectional analysis of all individuals with detectable T. pallidum DNA from September 2019 to April 2020. Electronic patient records were reviewed and concomitant results for treponemal serology and/or rapid plasma reagin (RPR) extracted, along with demographic data, history of syphilis and indices of sexual behaviour including number of sexual partners contacted. Any subsequent treponemal serology and RPR results were also reviewed. RESULTS: M-PCR swab specimens were performed in 450 individuals, of whom 63 (14%) had detectable T. pallidum DNA; 60 of 63 (95%) were gay or bisexual men and 11 of 63 (17%) were living with HIV. A history of treated syphilis was present in 17 of 63 (27%). Same-day treponemal serology/RPR testing was performed in 58 of 63 (92%) patients. Of the 58 who had same-day syphilis serology/RPR, 9 (16%) had their syphilis infection confirmed by treponemal DNA PCR alone. A total of 165 partners were traced as contacts of infection, of whom 25 (15%) were contacts of individuals diagnosed by M-PCR testing alone. CONCLUSION: In individuals with T. pallidum PCR-positive lesions, around one in six in our cohort were negative on standard diagnostic serological tests for syphilis. Treponemal DNA testing is an important addition to serological assays in individuals with mucocutaneous ulceration who are at risk of recent syphilis infection and facilitates early diagnosis and contact tracing.

The success of HIV combination prevention: The Dean Street model.

The 56 Dean Street combination prevention model, a strong engagement with the LGBTQI community and flexible services adapted to users' changing needs led to an 80% drop in HIV diagnoses in gay, bisexual and other men who have sex with men (GBMSM) from 2015 to 2017. We describe the service changes at 56 Dean Street since 2012 which resulted in an increase in the frequency of HIV testing, the introduction of pre-exposure prophylaxis, earlier HIV diagnosis and a shorter time to viral suppression in those living with HIV. This model could be adapted to deliver similar results in those settings of high HIV prevalence among GBMSM and where access to technological innovation in healthcare and engagement with the community can be achieved.

Safeguarding outcomes of 16 and 17-year-old service users of Sexual Health London (SHL.uk), a pan-London online sexual health service.

Guidance around how to safeguard young people using online sexual health services (e-SHSs) is limited. Sexual Health London (SHL.uk) is an e-SHS, integrated with London's sexual health clinics (SHCs), offering users aged 16 years and above sexually transmitted infection (STI) testing. For a safeguarding risk assessment, under 18s must complete a safeguarding e-triage, and any concern raised results in a 'call back' (CB) by the SHL.uk team. The safeguarding outcomes of CBs between 8 January 2018 and 18 September 2018 were reviewed; 261/454 (57.5%) users never triggered a CB on their e-triage (non-CB group) and 193/454 (42.5%) users triggered one or more CB(s) (CB group). Safeguarding concerns disclosed predominantly related to drug/alcohol use and partner's age imbalance. Successful telephonic risk assessment took place in 84.5% CB cases. Safeguarding outcomes comprised referrals to: SHC in 35.5%; child protection team in 8.5%; social services in 7%. STI positivity was 16.4% and 15.2% in the CB and non-CB groups, respectively. Although a high number of safeguarding triggers were disclosed, only a small proportion warranted referral for further support/intervention. Using e-triage with telephony support to screen and safeguard adolescents accessing an e-SHS was acceptable to users and enabled their clinical and safeguarding needs to be safely met. e-SHS integration within a network of SHCs further supported this model.

Antenatal care among Palestine refugees in Jordan: factors associated with UNRWA attendance.

BACKGROUND: Maternal and neonatal mortality is a global issue acknowledged by the Sustainable Development Goals (SDGs). Adequate ante-natal care (ANC) is pivotal to reducing these mortality rates, while understanding why women don't attend ANC is crucial to addressing the SDGs. AIMS: Using routine primary health care data to determine the factors associated with inadequate attendance by Palestine refugees (PR) to ANC seeking facilities provided by the United Nations Relief and Works agency for Palestine Refugees in the Near East (UNRWA), Jordan. METHODS: A backwards logistic regression model incorporating non-health system factors and health system factors, was performed using UNRWA data. RESULTS: A younger age of women was associated with inadequate ANC visits (P = 0.0009) in the non-health systems model. For health system factors, pregnancy risk status, having a gynaecologist review and the health centre attended were factors found to be significantly associated with ANC attendance (P < 0.0001). CONCLUSIONS: Understanding the health system factors associated with ANC attendance can lead to changes and improvements in UNRWA's operational policies.

The validity of an area-based method to estimate the size of hard-to-reach populations using satellite images: the example of fishing populations of Lake Victoria.

BACKGROUND: Information on the size of populations is crucial for planning of service and resource allocation to communities in need of health interventions. In resource limited settings, reliable census data are often not available. Using publicly available Google Earth Pro and available local household survey data from fishing communities (FC) on Lake Victoria in Uganda, we compared two simple methods (using average population density) and one simple linear regression model to estimate populations of small rural FC in Uganda. We split the dataset into two sections; one to obtain parameters and one to test the validity of the models. RESULTS: Out of 66 FC, we were able to estimate populations for 47. There were 16 FC in the test set. The estimates for total population from all three methods were similar, with errors less than 2.2%. Estimates of individual FC populations were more widely discrepant. CONCLUSIONS: In our rural Ugandan setting, it was possible to use a simple area based model to get reasonable estimates of total population. However, there were often large errors in estimates for individual villages.

Medication adherence by Palestine refugees living in Jordan who have diabetes: a cross-sectional study.

BACKGROUND: The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) estimated that in 2016, 11% of Palestine refugees older than 40 years living in Jordan were diagnosed with diabetes and that the disease is controlled in only 45% of Palestine refugees with diabetes. As medication adherence is one of the most important modifiable self-care behaviours to achieve adequate metabolic control, the aims of this study were to measure medication adherence and to review the factors associated with different levels of medication adherence in patients with diabetes. METHODS: This cross-sectional study was a survey of patients with type 1 and type 2 diabetes who attended medical care at the UNRWA Amman New Camp health centre in Jordan. Medication adherence was measured using the Morisky Medication Adherence Scale (MMAS-8), and results were used as outcome variable. Data on factors associated with adherence were collected using a pre-tested patient questionnaire and patients' electronic records, and these factors were used as explanatory variables. Logistic regression analysis of each explanatory variable against the outcome variable was done to estimate crude odds ratios. Data were analysed using STATA version 13.0. FINDINGS: 763 patients were included in the study. 557 (73%) patients did not adhere to their diabetes drug therapy. Univariate analysis showed that the factors associated with non-adherence were: the use of multiple providers for diabetes care (crude odds ratio 0·51, 95% CI 0·28-0·91) and diabetes drugs (0·22, 0·09-0·56); satisfaction with the quality of UNRWA's diabetes care (4·51, 1·05-19·45) and with the explanation of the disease and treatment presented by UNRWA's health professionals (2·72, 1·24-5·29); and trust in UNRWA's health staff (3·61, 1·4-9·32). INTERPRETATION: Decreased odds of adherence was associated with the use of multiple providers of care and diabetes medication, whereas increased odds of adherence correlated with full satisfaction with the quality of care, explanation of the disease, and treatment and trust in UNRWA health-care staff. These findings show the importance of health-system-related factors in affecting adherence to drug therapy in a population of Palestinian refugees with diabetes who accessed UNRWA health care in Jordan. FUNDING: UNRWA.

HIV and the menopause: A review.

Effective antiretroviral therapy has resulted in a close to normal life expectancy for people living with HIV. This has led to a shift in the age distribution of women living with HIV in the UK, with one in three attending for HIV care estimated to be aged 45-56 years in 2014. The lack of experience of many HIV physicians in managing menopause, and the perceived complexity of managing menopause in women living with HIV by general practitioners means that many women are unable to access appropriate care and support. This is aggravated by the relative paucity of data on menopause in women living with HIV and conflicting results in this field, for example with regard to age of onset of menopause and symptomatology experienced. Furthermore, women living with HIV have unique considerations such as potential interactions between antiretroviral therapy and menopause hormone therapy (previously called hormone replacement therapy) and other physiological concerns such as a multifactorial propensity towards decreased bone mineral density and potentially increased cardiovascular risk. On the whole, menopause hormone therapy is probably underutilised in this group of women due to perceived concerns around drug-drug interactions, as well as fears shared with women in the general population about menopause hormone therapy. Menopausal women should be given adequate information on symptomatology, lifestyle modification and treatment options including menopause hormone therapy. Furthermore, a holistic approach which considers the increased burden of poor mental health in this population is essential.

Serum-free light chains in HIV-associated lymphoma: no correlation with histology or prognosis.

OBJECTIVES: Serum-free light chains (sFLCs) are a biomarker of B-cell proliferation. Two case-control studies found elevated levels of polyclonal sFLCs predict the development of HIV-associated lymphomas (HALs) in people living with HIV. This effect appears greater for non-Hodgkin's lymphomas than Hodgkin's lymphoma. In this study, we measured sFLCs at diagnosis of HALs, and correlated levels with histology and survival. METHODS: The clinic database of the National Centre for HIV Malignancy was used to identify HAL patients, in the antiretroviral treatment era. Levels of sFLCs were measured using stored sera (cases from 1996 to 2008) and prospectively from 2008 to 2014. Serum immunoglobulins were available for 201 patients. We assessed correlations between sFLCs, serum immunoglobulins, and histological subtypes and overall survival. RESULTS: Two hundred and sixty-four patients were identified and 70% had polyclonal sFLC, 8% monoclonal sFLC (90% kappa sFLC), and 22% normal sFLC levels. No significant difference in sFLCs was observed between the three major histological subtypes of HAL (Hodgkin's lymphoma, diffuse large B-cell lymphoma, and Burkitt lymphoma). Elevated sFLCs did not influence overall survival in HAL or for the three subtypes individually. DISCUSSION: Whilst these data confirm the finding of elevated sFLC in HAL, there was no significant difference in sFLC measurements between histological subtypes despite differences in pathogenesis. sFLC did not predict survival in HAL overall or by histological subtype. Elevated sFLCs may predict HAL, but measurement of sFLCs has limited utility in the classification and prognostication of these cases.

Pharmacokinetic and pharmacodynamic drug interactions between antiretrovirals and oral contraceptives.

More than 50 % of women living with HIV in low- and middle-income countries are of reproductive age, but there are limitations to the administration of oral contraception for HIV-infected women receiving antiretroviral therapy due to drug-drug interactions caused by metabolism via the cytochrome P450 isoenzymes and glucuronidation. However, with the development of newer antiretrovirals that use alternative metabolic pathways, options for contraception in HIV-positive women are increasing. This paper aims to review the literature on the pharmacokinetics and pharmacodynamics of oral hormonal contraceptives when given with antiretroviral agents, including those currently used in developed countries, older ones that might still be used in salvage regimens, or those used in resource-limited settings, as well as newer drugs. Nucleos(t)ide reverse transcriptase inhibitors (NRTIs), the usual backbone to most combined antiretroviral treatments (cARTs) are characterised by a low potential for drug-drug interactions with oral contraceptives. On the other hand non-NRTIs (NNRTIs) and protease inhibitors (PIs) may interact with oral contraceptives. Of the NNRTIs, efavirenz and nevirapine have been demonstrated to cause drug-drug interactions; however, etravirine and rilpivirine appear safe to use without dose adjustment. PIs boosted with ritonavir are not recommended to be used with oral contraceptives, with the exception of boosted atazanavir which should be used with doses of at least 35 µg of estrogen. Maraviroc, an entry inhibitor, is safe for co-administration with oral contraceptives, as are the integrase inhibitors (INIs) raltegravir and dolutegravir. However, the INI elvitegravir, which is given in combination with cobicistat, requires a dose of estrogen of at least 30 µg. Despite the growing evidence in this field, data are still lacking in terms of large cohort studies, randomised trials and correlations to real clinical outcomes, such as pregnancy rates, in women on antiretrovirals and hormonal contraception.

A comparison of inpatient admissions in 2012 from two European countries.

INTRODUCTION: This study compares the trends of HIV inpatient admissions between a London tertiary HIV centre (United Kingdom) and four infectious disease wards in Italy (IT) to recognize common patterns across Europe. METHODS: Data regarding HIV inpatient admissions was collected by using discharge diagnostic codes from 1 January to 31 December 2012, including patient demographics, combined antiretroviral therapy (cART) history, CD4, viral load (VL) and mortality rates. Discharge diagnoses were categorized according to the International Classification of Disease (ICD) 9 and 10 system. All ICD categories that reach a 3% threshold of total admissions were analyzed. RESULTS: A total of 731 admissions (257 in Italy and 474 in the United Kingdom) for 521 patients (1.5 mean admission per patient). Female admissions were higher in Italy at 22.6% (n=58) compared to 14.9% (n=47) in the United Kingdom. Median age of patients was 47 years old. There was an undetectable VL in 65.8% (n=169) of admissions in Italy and 67.1% (n=319) in the United Kingdom (p=0.385); 86.4% (n=222) and 82.4% (n=389) of admissions were on cART, respectively. Mean CD4 was 302 in Italy compared to 368 in the United Kingdom (p=0.003). Average length of admission was 16 days with a 10.2% (n=21) mortality rate in Italy compared to 8 days with 2.8% (n=9) mortality in the United Kingdom (p<0.001). HCV co-infection was present in 64.6% (n=166) in Italy and 13.5% (n=64) in the United Kingdom and commonest mode of transmission was needle use in Italy (67.3%, n=173) and men who have sex with men in the UK cohort (59.9%, n=284). The cause of inpatient admissions according to ICD codes can be seen in following Figure 1. CONCLUSIONS: Significant differences in the duration of inpatient admission and mortality rates can be observed between these two cohorts which is secondary to the impact of Hepatitis C co-infection in Italy. However increases in the number of Hepatitis C co-infection patients amongst MSM in London has been reported [1] and route of transmission in Italy is shifting towards MSM [2], therefore it is important to learn how HIV is developing and managed in a global context to help plan future for services. The UK cohort demonstrates a wider range of conditions necessitating admission, and with an ageing HIV population, this is expected to increase in the future, requiring general and specialist HIV physicians to work closely together. The HIV-RNA threshold is 400 copies/mL to account for blips according to British HIV Association (BHIVA) Guidelines 2012 [3].

Prospective stage-stratified approach to AIDS-related Kaposi's sarcoma.

PURPOSE: Combination antiretroviral therapy (cART) is standard of care for patients with HIV diagnosed with Kaposi's sarcoma (KS), but the current role of systemic chemotherapy is undefined. PATIENTS AND METHODS: Since 1998, a prospective stage-stratified approach has been adopted for 469 patients with HIV with KS. Patients with early-stage (T0) KS are treated with cART alone; patients with advanced-stage (T1) KS receive cART plus liposomal anthracycline chemotherapy. Clinical characteristics, overall survival, and KS progression-free survival were analyzed according to stage at presentation and treatment received. RESULTS: A total of 303 patients presented with T0 stage KS, including 237 who were not receiving cART, and 166 patients had T1 stage KS. Patients with T0 KS had higher CD4 cell counts (P < .001); 90% of patients with T0 KS who were not receiving cART and 84% of those with T1 KS were treated in accordance with the stage-stratified approach. Median follow-up was 4.6 years, and 5-year overall survival was 89%; 54 patients have died, 15 as a result of KS. Overall 5-year survival was 92% for T0 KS and 83% to T1 KS (P = .0024). On-treatment analysis of 213 cART-naive patients with T0 KS treated with cART alone revealed 5-year overall survival of 95% and progression-free survival of 77%. For 140 patients with T1 disease treated with cART and liposomal anthracycline chemotherapy, 5-year overall survival was 85%. CONCLUSION: This stage-stratified approach to the management of KS achieves high survival in patients with advanced KS and reduces exposure to chemotherapy in patients with early-stage KS.

Trichomonas vaginalis: an audit of clinical practice and the demography of infected patients at three London genitourinary medicine clinics.

This audit aimed to review clinical standards for Trichomonas vaginalis against British Association of Sexual Health and HIV (BASHH) guidelines. Case notes for patients who had a positive microscopy or culture result were reviewed retrospectively. There was a 0.23% positivity rate for T. vaginalis (n = 84 cases); 96% were female with an average age of 33 years, with proportionally more patients seen in the African/Caribbean population, despite the number of cases being comparable between white (n = 36) and African/Caribbean (n = 34) groups. Seventy percent of patients had both microscopy- and culture-positive results for T. vaginalis. Contact tracing occurred in 87% of patients; 56% of these patients confirmed at least one contact had been treated in the last month. Overall, our data demonstrated a lower positivity rate than expected. Wet microscopy and liquid medium cultures were both important in identifying the infection, but more needs to be done to ensure partner notification has been documented and contacts have been treated.