What is the overlap between HIV and shigellosis epidemics in England: further evidence of MSM transmission?

BACKGROUND: Evidence suggests that sexual transmission between men has replaced foreign travel as the predominant mode of Shigella transmission in England. However, sexuality and HIV status are not routinely recorded for laboratory-reported Shigella, and the role of HIV in the Shigella epidemic is not well understood. METHODS: The Modular Open Laboratory Information System containing all Shigella cases reported to Public Health England (PHE) and the PHE HIV and AIDS Reporting System holding all adults living with diagnosed HIV in England were matched using a combination of Soundex code, date of birth and gender. RESULTS: From 2004 to 2015, 88 664 patients were living with HIV, and 10 269 Shigella cases were reported in England; 9% (873/10 269) of Shigella cases were diagnosed with HIV, of which 93% (815/873) were in men. Shigella cases without reported travel history were more likely to be living with HIV than those who had travelled (14% (751/5427) vs 3% (134/4854); p<0.01). From 2004 to 2015, the incidence of Shigella in men with HIV rose from 47/100 000 to 226/100 000 (p<0.01) peaking in 2014 at 265/100 000, but remained low in women throughout the study period (0-24/100 000). Among Shigella cases without travel and with HIV, 91% (657/720) were men who have sex with men (MSM). HIV preceded Shigella diagnosis in 86% (610/720), and 65% (237/362) had an undetectable viral load (<50 copies/mL). DISCUSSION: We observed a sustained increase in the national rate of shigellosis in MSM with HIV, who may experience more serious clinical disease. Sexual history, HIV status and STI risk might require sensitive investigation in men presenting with gastroenteritis

Prevalence and characteristics of gastrointestinal infections in men who have sex with men diagnosed with rectal chlamydia infection in the UK: an 'unlinked anonymous' cross-sectional study.

INTRODUCTION: Gastrointestinal infections (GII) can cause serious ill health and morbidity. Although primarily transmitted through faecal contamination of food or water, transmission through sexual activity is well described, especially among men who have sex with men (MSM). METHODS: We investigated the prevalence of GIIs among a convenience sample of MSM who were consecutively diagnosed with rectal Chlamydia trachomatis (CT) at 12 UK genitourinary medicine clinics during 10 weeks in 2012. Residual rectal swabs were coded, anonymised and tested for Shigella, Campylobacter, Salmonella, shiga toxin-producing Escherichia coli and enteroaggregative E. coli (EAEC) using a real-time PCR. Results were linked to respective coded and anonymised clinical and demographic data. Associations were investigated using Fisher's exact tests. RESULTS: Of 444 specimens tested, overall GII prevalence was 8.6% (95% CI 6.3% to 11.6%): 1.8% (0.9% to 3.6%) tested positive for Shigella, 1.8% (0.9% to 3.6%) for Campylobacter and 5.2% (3.5% to 7.7%) for EAEC. No specimens tested positive for Salmonella or other diarrhoeagenic E. coli pathotypes. Among those with any GII, 14/30 were asymptomatic (2/7 with Shigella, 3/6 with Campylobacter and 9/17 with EAEC). Shigella prevalence was higher in MSM who were HIV-positive (4.7% (2.1% to 10.2%) vs 0.5%(0.1% to 3.2%) in HIV-negative MSM; p=0.01). CONCLUSIONS: In this small feasibility study, MSM with rectal CT appeared to be at appreciable risk of GII. Asymptomatic carriage may play a role in sexual transmission of GII

Horizontal antimicrobial resistance transfer drives epidemics of multiple Shigella species

International audienceHorizontal gene transfer has played a role in developing the global public health crisis of antimicrobial resistance (AMR). However, the dynamics of AMR transfer through bacterial populations and its direct impact on human disease is poorly elucidated. Here, we study parallel epidemic emergences of multiple Shigella species, a priority AMR organism, in men who have sex with men to gain insight into AMR emergence and spread. Using genomic epidemiology, we show that repeated horizontal transfer of a single AMR plasmid among Shigella enhanced existing and facilitated new epidemics. These epidemic patterns contrasted with slighter, slower increases in disease caused by organisms with vertically inherited (chromosomally encoded) AMR. This demonstrates that horizontal transfer of AMR directly affects epidemiological outcomes of globally important AMR pathogens and highlights the need for integration of genomic analyses into all areas of AMR research, surveillance and management

Genomic epidemiology of Shigella in the United Kingdom shows transmission of pathogen sublineages and determinants of antimicrobial resistance

Shigella are globally important diarrhoeal pathogens that are endemic in low-to-middle income nations and also occur in high income nations, typically in travellers or community-based risk-groups. Shigella phylogenetics reveals population structures that are more reliable than those built with traditional typing methods, and has identified sublineages associated with specific geographical regions or patient groups. Genomic analyses reveal temporal increases in Shigella antimicrobial resistance (AMR) gene content, which is frequently encoded on mobile genetic elements. Here, we whole genome sequenced representative subsamples of S. flexneri 2a and S. sonnei (n = 366) from the United Kingdom from 2008 to 2014, and analysed these alongside publicly available data to make qualitative insights on the genomic epidemiology of shigellosis and its AMR within the broader global context. Combined phylogenetic, epidemiological and genomic anlayses revealed the presence of domestically-circulating sublineages in patient risk-groups and the importation of travel-related sublineages from both Africa and Asia, including ciprofloxacin-resistant sublineages of both species from Asia. Genomic analyses revealed common AMR determinants among travel-related and domestically-acquired isolates, and the evolution of mutations associated with reduced quinolone susceptibility in domestically-circulating sublineages. Collectively, this study provides unprecedented insights on the contribution and mobility of endemic and travel-imported sublineages and AMR determinants responsible for disease in a high-income nation

Bedside detection of awareness in the vegetative state: a cohort study

Summary Background Patients diagnosed as vegetative have periods of wakefulness, but seem to be unaware of themselves or their environment. Although functional MRI (fMRI) studies have shown that some of these patients are consciously aware, issues of expense and accessibility preclude the use of fMRI assessment in most of these individuals. We aimed to assess bedside detection of awareness with an electroencephalography (EEG) technique in patients in the vegetative state. Methods This study was undertaken at two European centres. We recruited patients with traumatic brain injury and non-traumatic brain injury who met the Coma Recovery Scale-Revised definition of vegetative state. We developed a novel EEG task involving motor imagery to detect command-following—a universally accepted clinical indicator of awareness—in the absence of overt behaviour. Patients completed the task in which they were required to imagine movements of their right-hand and toes to command. We analysed the command-specific EEG responses of each patient for robust evidence of appropriate, consistent, and statistically reliable markers of motor imagery, similar to those noted in healthy, conscious controls. Findings We assessed 16 patients diagnosed in the vegetative state, and 12 healthy controls. Three (19%) of 16 patients could repeatedly and reliably generate appropriate EEG responses to two distinct commands, despite being behaviourally entirely unresponsive (classification accuracy 61–78%). We noted no significant relation between patients' clinical histories (age, time since injury, cause, and behavioural score) and their ability to follow commands. When separated according to cause, two (20%) of the five traumatic and one (9%) of the 11 non-traumatic patients were able to successfully complete this task. Interpretation Despite rigorous clinical assessment, many patients in the vegetative state are misdiagnosed. The EEG method that we developed is cheap, portable, widely available, and objective. It could allow the widespread use of this bedside technique for the rediagnosis of patients who behaviourally seem to be entirely vegetative, but who might have residual cognitive function and conscious awareness

Safety of darunavir and atazanavir in HIV-infected children in Europe and Thailand

none22sinoneBailey, Heather; Collins, Intira Jeannie; Childs, Tristan; Tostevin, Anna; Goetghebuer, Tessa; Valerius, Niels; Königs, Christoph; Galli, Luisa; Marczynska, Magda; Marques, Laura; Ene, Luminita; Voronin, Evgeny; Okhonskaia, Liubov; Noguera-Julian, Antoni; Rojo, Pablo; Amador, Jose Tomas Ramos; Naver, Lars; Rudin, Christoph; Jourdain, Gonzague; Tookey, Pat; Giaquinto, Carlo; Judd, AliBailey, Heather; Collins, Intira Jeannie; Childs, Tristan; Tostevin, Anna; Goetghebuer, Tessa; Valerius, Niels; Königs, Christoph; Galli, Luisa; Marczynska, Magda; Marques, Laura; Ene, Luminita; Voronin, Evgeny; Okhonskaia, Liubov; Noguera Julian, Antoni; Rojo, Pablo; Amador, Jose Tomas Ramos; Naver, Lars; Rudin, Christoph; Jourdain, Gonzague; Tookey, Pat; Giaquinto, Carlo; Judd, Al

Pain perception in disorders of consciousness: Neuroscience, clinical care, and ethics in dialogue

peer reviewedPain, suffering and positive emotions in patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious states (MCS) pose clinical and ethical challenges. Clinically, we evaluate behavioural responses after painful stimulation and also emotionally-contingent behaviours (e.g., smiling). Using stimuli with emotional valence, neuroimaging and electrophysiology technologies can detect subclinical remnants of preserved capacities for pain which might influence decisions about treatment limitation. To date, no data exist as to how healthcare providers think about end-of-life options (e.g., withdrawal of artificial nutrition and hydration) in the presence or absence of pain in non-communicative patients. Here, we aimed to better clarify this issue by re-analyzing previously published data on pain perception (Prog Brain Res 2009 177, 329–38) and end-of-life decisions (J Neurol 2010 258, 1058–65) in patients with disorders of consciousness. In a sample of 2259 European healthcare professionals we found that, for VS/UWS more respondents agreed with treatment withdrawal when they considered that VS/UWS patients did not feel pain (77%) as compared to those who thought VS/UWS did feel pain (59%). This interaction was influenced by religiosity and professional background. For MCS, end-of-life attitudes were not influenced by opinions on pain perception. Within a contemporary ethical context we discuss (1) the evolving scientific understandings of pain perception and their relationship to existing clinical and ethical guidelines; (2) the discrepancies of attitudes within (and between) healthcare providers and their consequences for treatment approaches, and (3) the implicit but complex relationship between pain perception and attitudes toward life-sustaining treatments

Neurocognition and quality of life after reinitiating antiretroviral therapy in children randomized to planned treatment interruption

Item does not contain fulltextOBJECTIVE: Understanding the effects of antiretroviral treatment (ART) interruption on neurocognition and quality of life (QoL) are important for managing unplanned interruptions and planned interruptions in HIV cure research. DESIGN: Children previously randomized to continuous (continuous ART, n = 41) vs. planned treatment interruption (PTI, n = 47) in the Pediatric European Network for Treatment of AIDS (PENTA) 11 study were enrolled. At study end, PTI children resumed ART. At 1 and 2 years following study end, children were assessed by the coding, symbol search and digit span subtests of Wechsler Intelligence Scale for Children (6-16 years old) or Wechsler Adult Intelligence Scale (>/=17 years old) and by Pediatrics QoL questionnaires for physical and psychological QoL. Transformed scaled scores for neurocognition and mean standardized scores for QoL were compared between arms by t-test and Mann-Whitney U test, respectively. Scores indicating clinical concern were compared (<7 for neurocognition and <70 for QoL tests). RESULTS: Characteristics were similar between arms with a median age of 12.6 years, CD4(+) of 830 cells/mul and HIV RNA of 1.7 log10copies/ml. The median cumulative ART exposure was 9.6 in continuous ART vs. 7.7 years in PTI (P = 0.02). PTI children had a median of 12 months off ART and had resumed ART for 25.2 months at time of first assessment. Neurocognitive scores were similar between arms for all tests. Physical and psychological QoL scores were no different. About 40% had low neurocognitive and QoL scores indicating clinical concern. CONCLUSION: No differences in information processing speed, sustained attention, short-term memory and QoL functioning were observed between children previously randomized to continuous ART vs. PTI in the PENTA 11 trial