Emma Aarons

Presence and Persistence of Zika Virus RNA in Semen, United Kingdom, 2016.

Zika virus RNA has been detected in semen collected several months after onset of symptoms of infection. Given the potential for sexual transmission of Zika virus and for serious fetal abnormalities resulting from infection during pregnancy, information regarding the persistence of Zika virus in semen is critical for advancing our understanding of potential risks. We tested serial semen samples from symptomatic male patients in the United Kingdom who had a diagnosis of imported Zika virus infection. Among the initial semen samples from 23 patients, Zika virus RNA was detected at high levels in 13 (56.5%) and was not detected in 9 (39.1%); detection was indeterminate in 1 sample (4.4%). After symptomatic infection, a substantial proportion of men have detectable Zika virus RNA at high copy numbers in semen during early convalescence, suggesting high risk for sexual transmission. Viral RNA clearance times are not consistent and can be prolonged.

Post-exposure prophylaxis against Ebola virus disease with experimental antiviral agents: A case-series of health-care workers

BACKGROUND Although a few international health-care workers who have assisted in the current Ebola outbreak in west Africa have been medically evacuated for treatment of Ebola virus disease, more commonly they were evacuated after potential accidental exposure to Ebola virus. An urgent need exists for a consensus about the risk assessment of Ebola virus transmission after accidental exposure, and to investigate the use of post-exposure prophylaxis (PEP). Experimental vaccines have occasionally been used for Ebola PEP, but newly developed experimental antiviral agents have potential advantages. Here, we describe a new method for risk assessment and management of health-care workers potentially exposed to Ebola virus and report the use of experimental antiviral therapies for Ebola PEP in people. METHODS We devised a risk assessment and management algorithm for health-care workers potentially exposed to Ebola virus and applied this to eight consecutive individuals who were medically evacuated to the UK from west Africa between January, and March, 2015. PEP with antiviral agents was given to health-care workers assessed to have had substantial risk exposures to Ebola virus. Participants were followed up for 42 days after potential exposure. FINDINGS Four of eight health-care workers were classified as having had low risk exposures and managed by watchful waiting in the community. None of these health-care workers developed Ebola virus disease. The other four health-care workers had intermediate or maximum risk exposures and were given PEP with antiviral agents. PEP was well tolerated with no serious adverse effects. None of these four health-care workers, including two with maximum risk exposures from penetrating injuries with freshly used hollow-bore needles, developed Ebola virus disease. INTERPRETATION Standardised risk assessment should be adopted and consensus guidelines developed to systematically study the efficacy and safety of PEP with experimental agents. New experimental antiviral treatments are a viable option for PEP against Ebola. FUNDING Royal Free London NHS Foundation Trust.

Evaluation of the Biofire FilmArray BioThreat-E Test (v2.5) for Rapid Identification of Ebola Virus Disease in Heat-Treated Blood Samples Obtained in Sierra Leone and the United Kingdom

ABSTRACT Rapid Ebola virus (EBOV) detection is crucial for appropriate patient management and care. The performance of the FilmArray BioThreat-E test (v2.5) using whole-blood samples was evaluated in Sierra Leone and the United Kingdom and was compared with results generated by a real-time Ebola Zaire PCR reference method. Samples were tested in diagnostic laboratories upon availability, included successive samples from individual patients, and were heat treated to facilitate EBOV inactivation prior to PCR. The BioThreat-E test had a sensitivity of 84% (confidence interval [CI], 64% to 95%) and a specificity of 89% (CI, 73% to 97%) in Sierra Leone (n = 60; 44 patients) and a sensitivity of 75% (CI, 19% to 99%) and a specificity of 100% (CI, 97% to 100%) in the United Kingdom (n = 108; 70 patients) compared to the reference real-time PCR. Statistical analysis (Fishers exact test) indicated there was no significant difference between the methods at the 99% confidence level in either country. In 9 discrepant results (5 real-time PCR positives and BioThreat-E test negatives and 4 real-time PCR negatives and BioThreat-E test positives), the majority (n = 8) were obtained from samples with an observed or probable low viral load. The FilmArray BioThreat-E test (v2.5) therefore provides an attractive option for laboratories (either in austere field settings or in countries with an advanced technological infrastructure) which do not routinely offer an EBOV diagnostic capability.

Non-fatal case of Crimean-Congo haemorrhagic fever imported into the United Kingdom (ex Bulgaria), June 2014

Crimean-Congo haemorrhagic fever (CCHF) was diagnosed in a United Kingdom traveller who returned from Bulgaria in June 2014. The patient developed a moderately severe disease including fever, headaches and petechial rash. CCHF was diagnosed following identification of CCHF virus (CCHFV) RNA in a serum sample taken five days after symptom onset. Sequence analysis of the CCHFV genome showed that the virus clusters within the Europe 1 clade, which includes viruses from eastern Europe.

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.

Development and Operation of Ebola Diagnostic Laboratories Led By Public Health England in Sierra Leone during the West African Ebola Outbreak 2013-2015

The Ebola outbreak 2013-2015 created an urgent need for humanitarian response. Public Health England (PHE), in partnership with the Ministry of Defence (MoD) and Defence Science and Technology Laboratory (DSTL), were tasked by the UK Government (through the Department for International Development (DfID)) to provide Ebola Virus Disease (EVD) diagnostic laboratories. These diagnostic laboratories supported the Ebola Treatment Units (ETU) being established in Sierra Leone. PHE operated arguably the largest diagnostic facilities in Sierra Leone by one unilateral donor: operating 3 laboratories (co-located with ETUs), each processing up to 200 samples a day. During the time of operation (October 2014 to December 2015) over 400 civilian UK staff on rotation were deployed in these laboratories, and between them processed greater than 40,000 samples (~6% positivity rate). Here we summarise the laboratory set-up, design rationale, scope and processes deployed. This information can inform planning in response to future outbreaks. Correspondence to: Daniel Bailey, Public Health England, Porton Down, Salisbury SP4 0JG, UK, Tel: +44 (0)1980 619913; E-mail: Daniel.Bailey@phe.gov.uk

A non-fatal case of hantavirus cardiopulmonary syndrome imported into the UK (ex Panama), July 2014

Highlights • Detection of hantavirus cardiopulmonary syndrome imported into Europe.• Additional evidence that Choclo hantavirus is currently circulating and causing human disease in Panama.• Novel diagnostic and sequencing assays for identifying cases of Choclo hantavirus infection.

Assessment of Metagenomic MinION and Illumina sequencing as an approach for the recovery of whole genome sequences of chikungunya and dengue viruses directly from clinical samples.

The recent global emergence and re-emergence of arboviruses has caused significant human disease. Common vectors, symptoms and geographical distribution make differential diagnosis both important and challenging. We performed metagenomic sequencing using both the Illumina MiSeq and the portable Oxford Nanopore MinION to study the feasibility of whole genome sequencing from clinical samples containing chikungunya or dengue virus, two of the most important arboviruses. Direct metagenomic sequencing of nucleic acid extracts from serum and plasma without viral enrichment allowed for virus and coinfection identification, subtype determination and in the majority of cases elucidated complete or near-complete genomes adequate for phylogenetic analysis. This work demonstrates that metagenomic whole genome sequencing is feasible for over 90% and 80% of chikungunya and dengue virus PCR-positive patient samples respectively. It confirms the feasibility of field metagenomic sequencing for these and likely other RNA viruses, highlighting the applicability of this approach to front-line public health.