Surveillance of congenital Zika syndrome in England and Wales: methods and results of laboratory, obstetric and paediatric surveillance.

The spread of the Zika virus (ZIKV) in the Americas led to large outbreaks across the region and most of the Southern hemisphere. Of greatest concern were complications following acute infection during pregnancy. At the beginning of the outbreak, the risk to unborn babies and their clinical presentation was unclear. This report describes the methods and results of the UK surveillance response to assess the risk of ZIKV to children born to returning travellers. Established surveillance systems operating within the UK - the paediatric and obstetric surveillance units for rare diseases, and national laboratory monitoring - enabled rapid assessment of this emerging public health threat. A combined total of 11 women experiencing adverse pregnancy outcomes after possible ZIKV exposure were reported by the three surveillance systems; five miscarriages, two intrauterine deaths and four children with clinical presentations potentially associated with ZIKV infection. Sixteen women were diagnosed with ZIKV during pregnancy in the UK. Amongst the offspring of these women, there was unequivocal laboratory evidence of infection in only one child. In the UK, the number and risk of congenital ZIKV infection for travellers returning from ZIKV-affected countries is very small.

Personal protective equipment solution for UK military medical personnel working in an Ebola virus disease treatment unit in Sierra Leone.

The combination of personal protective equipment (PPE) together with donning and doffing protocols was designed to protect British and Canadian military medical personnel in the Kerry Town Ebola Treatment Unit (ETU) in Sierra Leone. The PPE solution was selected to protect medical staff from infectious risks, notably Ebola virus, and chemical (hypochlorite) exposure. PPE maximized dexterity, enabled personnel to work in hot temperatures for periods of up to 2h, protected mucosal membranes when doffing outer layers, and minimized potential contamination of the doffing area with infectious material by reducing the requirement to spray PPE with hypochlorite. The ETU was equipped to allow medical personnel to provide a higher level of care than witnessed in many existing ETUs. This assured personnel working as part of the international response that they would receive as close to Western treatment standards as possible if they were to contract Ebola virus disease (EVD). PPE also enabled clinical interventions that are not seen routinely in West African EVD treatment regimens, whilst providing a robust protective barrier. Competency in using PPE was developed during a nine-day pre-deployment training programme. This allowed over 60 clinical personnel per deployment to practice skills in PPE in a simulated ETU and in classrooms. Overall, the training provided: (i) an evidence base underpinning the PPE solution chosen; (ii) skills in donning and doffing of PPE; (iii) personnel confidence in the selected PPE; and (iv) quantifiable testing of each individual's capability to don PPE, perform tasks and doff PPE safely.

Genome sequence analysis of Ebola virus in clinical samples from three British healthcare workers, August 2014 to March 2015.

We determined complete viral genome sequences from three British healthcare workers infected with Ebola virus (EBOV) in Sierra Leone, directly from clinical samples. These sequences closely resemble those previously observed in the current Ebola virus disease outbreak in West Africa, with glycoprotein and polymerase genes showing the most sequence variation. Our data indicate that current PCR diagnostic assays remain suitable for detection of EBOV in this epidemic and provide confidence for their continued use in diagnosis.

Multiplex molecular testing for management of infectious gastroenteritis in a hospital setting: a comparative diagnostic and clinical utility study.

Laboratory diagnosis and clinical management of inpatients with diarrhoea is complex and time consuming. Tests are often requested sequentially and undertaken in different laboratories. This causes prolonged unnecessary presumptive isolation of patients, because most cases are non-infectious. A molecular multiplex test (Luminex(®) Gastrointestinal Pathogen Panel (GPP)) was compared with conventional testing over 8 months to determine diagnostic accuracy, turnaround times, laboratory costs, use of isolation facilities and user acceptability. A total of 262 (12%) patients had a pathogen detected by conventional methods compared with 483 (22.1%) by GPP. Most additional cases were detected in patients developing symptoms in the first 4 days of admission. Additional cases were detected because of presumed improved diagnostic sensitivity but also because clinicians had not requested the correct pathogen. Turnaround time (41.8 h) was faster than bacterial culture (66.5 h) and parasite investigation (66.5 h) but slower than conventional testing for Clostridium difficile (17.3 h) and viruses (27 h). The test could allow simplified requesting by clinicians and a consolidated laboratory workflow, reducing the overall number of specimens received by the laboratory. A total of 154 isolation days were saved at an estimated cost of £30 800. Consumables and labour were estimated at £150 641 compared with £63 431 for conventional testing. Multiplex molecular testing using a panel of targets allowed enhanced detection and a consolidated laboratory workflow. This is likely to be of greater benefit to cases that present within the first 4 days of hospital admission.

The United Kingdom public health response to an imported laboratory confirmed case of a novel coronavirus in September 2012.

On 22 September 2012, a novel coronavirus, very closely related to that from a fatal case in Saudi Arabia three months previously, was detected in a previously well adult transferred to intensive care in London from Qatar with severe respiratory illness. Strict respiratory isolation was instituted. Ten days after last exposure, none of 64 close contacts had developed severe disease, with 13 of 64 reporting mild respiratory symptoms. The novel coronavirus was not detected in 10 of 10 symptomatic contacts tested.

Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012.

Coronaviruses have the potential to cause severe transmissible human disease, as demonstrated by the severe acute respiratory syndrome (SARS) outbreak of 2003. We describe here the clinical and virological features of a novel coronavirus infection causing severe respiratory illness in a patient transferred to London, United Kingdom, from the Gulf region of the Middle East.

In utero treatment of severe fetal anaemia due to parvovirus B19 in one fetus in a twin pregnancy--a case report and literature review.

BACKGROUND: Parvovirus B19 (PVB19) is a well-established cause of nonimmune hydrops fetalis and fetal anaemia in pregnancy. However, discordant viral infection of only 1 fetus in a twin pregnancy is a rare occurrence. CASE REPORT: A 40-year-old female with dichorionic, diamniotic twin pregnancy presented at 22 weeks with fetal hydrops and severe anaemia in 1 twin. Maternal PVB19 infection was confirmed, and the affected fetus was treated with a single intrauterine transfusion. The only subsequent complication developed was that the affected fetus was growing on the 5th centile. The affected twin continued to grow, and 2 live twins were delivered by caesarean section at 36 weeks. By 18 months of age, the affected twin had normal development. CONCLUSION: PVB19 may selectively affect 1 fetus in a dichorionic, diamniotic twin pregnancy and may be treated efficiently with intrauterine transfusion. Discordant viral infection in this case suggests that the viral load may be limited to 1 placenta and/or that different individual immunological fetal response starts very early in utero.

Adaptation to blockade of human immunodeficiency virus type 1 entry imposed by the anti-CCR5 monoclonal antibody 2D7.

The second extracellular loop (ECL2) domain of CC-chemokine receptor 5 (CCR5) has been proposed as a specific target site for therapeutic agents aimed at blocking CCR5-dependent entry by human immunodeficiency virus type I (HIV-1). We have adapted two CCR5-using HIV-1 isolates, prototypic JR-CSF, and a primary isolate, 11-121, to replicate in vitro in the presence of high concentrations of a monoclonal antibody (MAb 2D7) specific for the CCR5 ECL2 domain. The 75% inhibitory concentrations (IC(75)) for the two 2D7-adapted isolates were approximately 100-fold higher than those for corresponding control isolates passaged without the MAb. Adapted isolates did not acquire the ability to use CXCR4, CCR3, or CCR1. Env clones derived from MAb 2D7-adapted JR-CSF showed several gp120 mutations that were not found in any of the control JR-CSF clones. The in vitro observations suggest that CCR5-using HIV-1 strains might also be able to adapt in vivo to evade an ECL2-blocking therapeutic agent.

CXCR4 as a functional coreceptor for human immunodeficiency virus type 1 infection of primary macrophages.

The coreceptors used by primary syncytium-inducing (SI) human immunodeficiency virus type 1 isolates for infection of primary macrophages were investigated. SI strains using only CXCR4 replicated equally well in macrophages with or without CCR5 and were inhibited by several different ligands for CXCR4 including SDF-1 and bicyclam derivative AMD3100. SI strains that used a broad range of coreceptors including CCR3, CCR5, CCR8, CXCR4, and BONZO infected CCR5-deficient macrophages about 10-fold less efficiently than CCR5(+) macrophages. Moreover, AMD3100 blocked infection of CCR5-negative macrophages by these strains. Our results therefore demonstrate that CXCR4, as well as CCR5, is used for infection of primary macrophages but provide no evidence for the use of alternative coreceptors.

[Comparative analysis of distribution of mutant alleles of the gene coding for the CCR-5 chemokine receptor, among people in Russia, infected and not infected with HIV-1]. / Sravnitel'nyi analiz rasprostraneniia mutantnogo allelia gena, kodiruiushchego khemokinovyi retseptor CCR-5, sredi infitsirovannykh i neinfitsirovannykh VICh-1 lits v Rossii.

Comparative analysis of the distribution of deletion mutations of CC-chemokine receptor 5 (CCR-5) gene among HIV-1 infected and not infected subjects in Russia showed the incidence of the heterozygous genotype to be 17.8% among both HIV-infected and seronegative subjects. The incidence of the homozygous genotype for the deletion among seronegative individuals was 0.6%, but no homozygotes were found among HIV-1 infected patients. Study of the incidence of the mutant CCR-5 allele among patients infected with different HIV-1 subtypes showed that the susceptibility of heterozygotes to HIV-1 infection was not associated with any special genetic subtype.

A broad range of chemokine receptors are used by primary isolates of human immunodeficiency virus type 2 as coreceptors with CD4.

Like human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), HIV-2 requires a coreceptor in addition to CD4 for entry into cells. HIV and SIV coreceptor molecules belong to a family of seven-transmembrane-domain G-protein-coupled receptors. Here we show that primary HIV-2 isolates can use a broad range of coreceptor molecules, including CCR1, CCR2b, CCR3, CCR4, CCR5, and CXCR4. Despite broad coreceptor use, the chemokine ligand SDF-1 substantially blocked HIV-2 infectivity of peripheral blood mononuclear cells, indicating that its receptor, CXCR4, was the predominant coreceptor for infection of these cells. However, expression of CXCR4 together with CD4 on some cell types did not confer susceptibility to infection by all CXCR4-using virus isolates. These data therefore indicate that another factor(s) influences the ability of HIV-2 to replicate in human cell types that express the appropriate receptors for virus entry.

Encephalitozoon cuniculi isolated from the urine of an AIDS patient, which differs from canine and murine isolates.

A species of Encephalitozoon has been isolated from the urine of a patient with the acquired immunodeficiency syndrome and maintained in vitro in Madin Darby Canine Kidney cells. When examined by random amplified polymorphic DNA polymerase chain reaction the new isolate was found to differ from E. hellem and to have amplified products in common with murine and canine E. cuniculi. However, it more closely resembled the canine than the murine isolate. Sodium dodecylsulphate polyacrylamide gel electrophoresis differentiated between all three isolates of E. cuniculi, with a band at 42-45 kDa present in the murine isolate only, bands at 52 kDa present in the canine and human isolates but not the murine, and a single band at 60 kDa (murine) and 65 kDa (canine) replaced by two bands at 55 and 70 kDa in the human isolate. The 55 kDa and 70 kDa antigens were also revealed as characteristic bands of the human isolate by Western blotting. The study has thus revealed that the species Encephalitozoon cuniculi is not a homogeneous entity.

Variations in clinical experience of pre-registration house officers: the effect of London.

A postal questionnaire was used to examine possible differences in clinical experience of pre-registration house officers (PHROs) in eight former English regions, and, within the Thames regions, between teaching hospitals, and non-teaching hospitals in Inner London, Outer London and outside London. The main measurements were the numbers of patients clerked in an average week as emergency, routine or day admissions or as outpatients; the number of patients under the respondents' care at time of reply; the experience of specific clinical conditions gained; the overall adequacy of clinical experience; and the suitability of posts for preparing respondents to work as casualty officers, senior house officers, or general practitioners. The results indicate that less clinical experience was acquired by PRHOs training in the Thames regions. They had fewer admissions per week, fewer patients, and exposure to fewer surgical conditions. Within the Thames regions, there was a gradient of improving educational quality (in all areas of this study) from the teaching hospitals, through the non-teaching hospitals in inner and in outer London, and then to the hospitals outside London. No differences were found between Thames region posts outside London and non-Thames regions.

Reversible renal failure caused by a microsporidian infection.

OBJECTIVE: To report a case of renal failure associated with microsporidian infection in an HIV-seropositive patient. DESIGN: Case report. SETTING: Chelsea and Westminster Hospital, London, England, UK. PATIENT: An HIV-seropositive patient presented febrile with abdominal pain who developed renal failure. Renal biopsy and urinalysis showed infection with a microsporidian of the genus Encephalitozoon. INTERVENTION: Treatment with albendazole (400 mg) twice daily was associated with disappearance of infection from the urine, clinical improvement and return of renal function virtually to normal. CONCLUSION: HIV-seropositive individuals with renal failure should have urine screened for microsporidia. The administration of albendazole in such cases may reverse renal failure.

Preregistration house officers in the Thames regions: changes in quality of training after four years.

OBJECTIVE: To measure changes in the training and workload of preregistration house officers over four years. DESIGN: Postal questionnaire. SETTING: The Thames health regions. PARTICIPANTS: 1049 preregistration house officers. RESULTS: Response rate was 69% (725 replies). The proportion of house officers officially on duty > 83 hours a week fell from at least 42% to 21%, and the proportion officially on duty < or = 72 hours rose from no more than 9% to 40%. Adequate guidance in breaking bad news increased from 25% to 46% (p < 0.0001; 95% confidence interval for difference, 16.2% to 25.8%) and guidance in pain control increased from 36% to 46% (p < 0.01; 5.0% to 15.0%). The number of house officers attending an induction course increased from 61% to 94% (p < 0.001; 28.9% to 37.1%). There was no change in the proportion unable to attend formal educational sessions because of clinical commitments or in levels of satisfaction with consultants' educational supervision. The median number of inpatients under house officers' care fell from 20 to 17, but the numbers of patients clerked in an average week showed little change. House officers were less satisfied with the clinical experience their post provided (proportion dissatisfied rose from 30% to 39%; p < 0.01; 4.2% to 13.8%) and less enthusiastic about recommending their post to a friend (proportion neutral or not recommending rose from 30% to 42%, p < 0.0001; 7.9% to 16.9%). CONCLUSION: Despite progress in reducing hours of duty and providing induction courses, the training that hospitals and consultants provide for house officers is still unsatisfactory and inconsistent with the General Medical Council's recommendations.

Preregistration house officers in eight English regions: survey of quality of training.

OBJECTIVE: To assess the quality of preregistration house officer training in eight English regions. DESIGN: Postal questionnaire. SETTING: Thames, East Anglian, Mersey, Northern, and Wessex regions. PARTICIPANTS: 1670 preregistration house officers. MAIN OUTCOME MEASURES: Education, hours of work, workload, conditions of work, and attitudes to job and medicine as a career. RESULTS: Response rate was 69% (1146 replies). Most house officers had attended induction courses (1036/1129 (92%)); 74% (757/1024) found them satisfactory. The proportions who had never received adequate guidance on how to break bad news and how to control pain were 59% (670/1135) and 56% (634/1136) respectively. There was much variation between regions. Overall, 65% (736/1138) reported confidence in performing cardiopulmonary resuscitation. Most respondents (95% (1089/1142)) worked an on call rota, 3% (36) a partial shift, and 0.6% (seven) a full shift; 19% (202) were on duty for average weekly hours that exceeded the targets for 1 April 1993. House officers had a median of 20 patients under their care and clerked a median of 10 emergency cases, six routine cases, and two day cases a week. Over half (690/1128 (61%)) could not obtain hot food after 8 pm, 20% (223/1095) did not always have clean sheets available in their on call room, and 45% (462/1036) did not consider the protection of staff against violence to be adequate at their hospital. The most important problems with the preregistration year were inappropriate or non-medical tasks (ranked first by 360 respondents), hours of work (359), and pay for out of hours work (167). Overall 57% (646/1125) would encourage a friend to apply for their post, but only 24% (266/1112) would encourage a friend to take up medicine and 44% (494/1112) would discourage the idea. CONCLUSIONS: House officers' training is deficient in important respects, with inappropriate tasks and heavy clinical workloads impeding the provision of proper education.

Aseptic arthritis associated with herpes zoster.

Arthritis associated with herpes zoster is rarely reported. We describe the clinical features of an immunocompromised 54-year-old woman who developed sterile arthritis of a knee in association with acute ipsilateral zoster of the L1/L2 dermatomes.

Survey of "do not resuscitate" orders in a district general hospital.

OBJECTIVE: To evaluate the local use of written "Do not resuscitate" orders to designate inpatients unsuitable for cardiopulmonary resuscitation in the event of cardiac arrest. DESIGN: Point prevalence questionnaire survey of inpatients' medical and nursing records. SETTING: 10 acute medical and six acute surgical wards of a district general hospital. PARTICIPANTS: Questionnaires were filled in anonymously by nurses and doctors working on the wards surveyed. MAIN OUTCOME MEASURES: Responses to questionnaire items concerning details about each patient, written orders not to resuscitate in the medical case notes and nursing records, whether prognosis had been discussed with patients' relatives, whether a "crash call" was perceived as appropriate for each patient, and whether the "crash team" would be called in the event of arrest. RESULTS: Information was obtained on 297 (93.7%) of 317 eligible patients. Prognosis had been discussed with the relatives of 32 of 88 patients perceived by doctors as unsuitable for resuscitation. Of these 88 patients, 24 had orders not to resuscitate in their medical notes, and only eight of these had similar orders in their nursing notes. CONCLUSIONS: In the absence of guidelines on decisions about resuscitation, orders not to resuscitate are rarely included in the notes of patients for whom cardiopulmonary resuscitation is thought to be inappropriate. Elective decisions not to resuscitate are not effectively communicated to nurses. There should be more discussion of patients' suitability for resuscitation between doctors, nurses, patients, and patients' relatives. Suitability for resuscitation should be reviewed on every consultant ward round.