CVN annual scientific conference programme 2022

Tuesday 10th May (afternoon start)

12.30 CVN provided lunch and opportunity to view sponsor stands

13.25 Welcome to CVN conference

13.30 – 14:00 Avian influenza
Professor Ian H Brown, Head of Virology, Animal and Plant Health Agency

14:00 – 14:30 HHV8 update
Dr Effrossyni Gkrania – Klotsas, Consultant in Infectious Diseases with an interest in primary and secondary immunodeficiencies and transplantation at Cambridge University Hospitals

14:30 – 15:15 Offered papers session 1

14:30 Bosworth A et al (Birmingham). Establishment of “hot labs” for molecular detection of SARS-CoV-2 in a near patient testing environment.

14:45 Godi A et al (UKHSA). Development of serological tools for diagnosis of Human Herpesvirus 8 infection and their application to estimate antibody prevalence in blood and organ donor populations.

15:00 McClure P et al (Nottingham). Whole genome sequencing of the seasonal Coronaviruses 229E, NL63, OC43 and HKU1

15:15 – 15:45 Break (refreshments provided)

15:45 – 16:15 Naked Covid – uncovering the pandemic
Dr Chris Smith, Consultant Medical Virologist, University of Cambridge and Addenbrooke’s Hospital

16:15 – 16:45 Viral Ocular Infections
Dr Gerry Clare, Moorfields Eye Hospital NHS Foundation Trust

16:45 – 17:10 CVN business
Poster Viewing available from 17.10 to 18.00

Evening CVN evening meal

Wednesday 11th May

10:00 – 11:00 Offered papers session 2

10:00 Haywood B et al (UKHSA, LSHTM). Exploring the Variability of the Hepatitis E Virus ORF2 Capsid Protein between Genotypes 1 and 3 in Silico

10:15 Feeney S et al. Surge in cases of Enterovirus D-68 cases post COVID-19 – an epidemiological perspective.

10:30 Kele B et al (Royal London and St Bart’s). HIV-1 sequencing failure in clinical samples is not linked to reported viral load or subtype?

10:45 – 11.15 Break (refreshments provided)

11:15 – 11.45 Offered papers session 3

11:15 Goldstein E et al (Glasgow). A case of HBV viral load discrepancies: Abbott m2000 RealTime vs Alinity m HBV assay

11:30 Shenouda A et al (Birmingham). Primary Cytomegalovirus (CMV) infection inducing acute chest syndrome in a pregnant patient with sickle cell disease HbSS

11.45 – 12.15 CVN Commercial Sponsor slot (several short presentations)

12:15 – 13:15 CVN provided lunch and opportunity to view sponsor stands

13.15 William Tong Prize award

13:30 – 14.00 Novel approaches to the management of hepatitis B and hepatitis delta virus infections
Dr Upkar (Uppy) Gill, Clinical Lecturer and Honorary Consultant Hepatologist, QMUL & Barts Health NHS Trust

14:00 – 14.30 CAR-T cells and viral infections
Dr Sridhar Chaganti, Consultant Haematologist, University Hospital Birmingham

14:30 – 15.00 Immunological impacts of CMV infection
Professor Paul Klenerman, Sidney Truelove Professor of Gastroenterology, Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford

15:00 – 15:30 Late breaker- enhanced incident acute non A-E hepatitis in children Dr Jane Hartley, Paediatric Hepatologist, Birmingham Children’s Hospital

15.30 Closing remarks

Poster Presentations:

  • Goddard M et al. (Coventry). A retrospective audit of screening and management of hepatitis B in patients undergoing immunosuppression at University Hospital Coventry
  • Barclay-Elliott K (Coventry). Impact of Implementing New Rapid COVID-19 Testing Platform in the Emergency Department on Patient Flow and Staff Perceptions of Rapid Testing

How I treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients

Blood. 2016 Oct 19. pii: blood-2016-06-688432.

El Chaer F, Shah DP, Chemaly RF.

Abstract

Cytomegalovirus (CMV) infection is a significant complication in hematopoietic cell transplantation (HCT) recipients. Four antiviral drugs are used for preventing or treating CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. With prolonged and repeated use of these drugs, CMV can become resistant to standard therapy, resulting in increased morbidity and mortality, especially in HCT recipients. Antiviral drug resistance should be suspected when CMV viremia (DNAemia or antigenemia) fails to improve or continue to increase after 2 weeks of appropriately dosed and delivered antiviral therapy. CMV resistance is diagnosed by detecting specific genetic mutations. UL97 mutations confer resistance to ganciclovir and valganciclovir, and a UL54 mutation confers multidrug resistance. Risk factors for resistance include prolonged or previous anti-CMV drug exposure or inadequate dosing, absorption, or bioavailability. Host risk factors include type of HCT and degree of immunosuppression. Depending on the genotyping results, multiple strategies can be adopted to treat resistant CMV infections, albeit no randomized clinical trials exist so far, after reducing immunosuppression (if possible): ganciclovir dose escalation, ganciclovir and foscarnet combination, and adjunct therapy such as CMV-specific cytotoxic T-lymphocyte infusions. Novel therapies such as maribavir, brincidofovir, and letermovir should be further studied for treatment of resistant CMV.\

Click here to read more.

Copyright © 2016 American Society of Hematology.

CVN Research Grants

The CVN Executive invites bids for the 2017-2019 awards round.

Up to £40,000 is available for the 2 year research award and £5,000 each for two pump priming small research awards.

The over-riding consideration for the research grants awards panel will be that the research project should be demonstrably of value to clinical virology laboratories, and applicants will be asked to explain how their research will benefit the CVN.

Applicants must be members of the CVN, or belong to laboratories/organisations that are CVN members.

Applications should be sent to the CVN secretariat ([email protected]) to arrive no later than midday Friday December 16 2016.

All applications will be reviewed by the research grants awards panel and the award decision will be made by midday Friday January 20 2017.

CLINICAL VIROLOGY NETWORK RESEARCH GRANT APPLICATION (Download the following as a Word document from the CVN message board)

Your application should provide the following information:

  • Applicant Surname and Forename.
  • Position held.
  • Institution and Department.
  • Contact details: telephone, email, address of where the work will be carried out.
  • Title of project.
  • Abstract (Max 250 words).
  • Background (Max 1000 words).
  • Please detail the nature and importance of the research question(s) to be addressed.
  • Aims and objectives of proposed research project (max 400 words).
  • Plan of investigation (max 2000 words).
  • How will this research benefit the UK Clinical Virology Network? (Max 250 words)
  • Please describe the anticipated outcomes and outputs of the proposed research and the potential impact these will have on the practice of clinical virology within the UK.
  • Costs
  • Justification of costs (Max 500 words)
  • Ethical issues
  • What, if any, ethical issues would be involved in this study and what are the plans for handling those?

HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis

During the early stages of infection, the HIV-1 capsid protects viral components from cytosolic sensors and nucleases such as cGAS and TREX, respectively, while allowing access to nucleotides for efficient reverse transcription1. Here we show that each capsid hexamer has a size-selective pore bound by a ring of six arginine residues and a ‘molecular iris’ formed by the amino-terminal β-hairpin. The arginine ring creates a strongly positively charged channel that recruits the four nucleotides with on-rates that approach diffusion limits. Progressive removal of pore arginines results in a dose-dependent and concomitant decrease in nucleotide affinity, reverse transcription and infectivity. This positively charged channel is universally conserved in lentiviral capsids despite the fact that it is strongly destabilizing without nucleotides to counteract charge repulsion. We also describe a channel inhibitor, hexacarboxybenzene, which competes for nucleotide binding and efficiently blocks encapsidated reverse transcription, demonstrating the tractability of the pore as a novel drug target.

Hepatitis A virus in the EU/EEA, 1975–2014: A systematic review of seroprevalence and incidence comprising European surveillance data and national vaccination recommendations

Hepatitis A virus in the EU/EEA, 1975–2014: A systematic review of seroprevalence and incidence comprising European surveillance data and national vaccination recommendations

This ECDC report provides a comprehensive picture of Hepatitis A virus (HAV) infection epidemiology in the EU/EEA between 1975 and 2014. The report outlines important knowledge gaps about e.g. laboratory-based surveillance, data available on coverage of HAV vaccination, and data from HAV molecular surveillance, which should be addressed when designing specific prevention and control measures to further decrease HAV circulation in the EU/EEA. – See more at: http://ecdc.europa.eu/en/publications/_layouts/forms/Publication_DispForm.aspx?List=4f55ad51-4aed-4d32-b960-af70113dbb90&ID=1542#sthash.Sdm0k4li.dpuf

Draft revised version of the SABTO guideline out for consultation

MSHOTC guidelines v1 5.1docx

The draft revised version of the SABTO guidelines is out for consultation. This is still a work in progress.

Feedback is welcome and comments should be sent to Gary Mallinson at [email protected], and cc. to [email protected] no later than 25th August 2016.

With kind regards,

Ines
Dr Inês Ushiro-Lumb
Clinical Microbiology Lead for Organ Donation and Transplantation
Consultant Virologist
NHS Blood and Transplant

Advisory Committee on Dangerous Pathogens (ACDP) position for a Clinical Virologist

ACDP are looking for a high calibre candidate at a senior level ideally with a record of achievement at national and/or international level in Clinical Virology.

The ACDP is responsible for providing independent scientific advice to the Health and Safety Executive (HSE), the Department of Health, the Department for Environment, Food and Rural Affairs, and their counterparts under devolution in Scotland, Wales and Northern Ireland, on all aspects of hazards and risks from exposure to pathogens.

There are further details about the role and how to apply in the ACDP information pack. Submit your covering letter and CV and monitoring forms to [email protected].

The closing date for applications is 12:00pm Wednesday 31st August 2016.

Advisory Committee on Safety of Blood Tissues and Organs (SaBTO) position for a Virologist

SaBTO are looking for a high calibre candidate at a senior level ideally with a record of achievement at national and/or international level in Virology.

The SaBTO advises UK Health Departments and Ministers on the safety of blood for transfusion and organs, cells (including stem cells and gametes, in liaison with the regulatory bodies) and tissues for transplantation, and on risk management options.

There are further details about the role and how to apply in the SaBTO information pack. Submit your covering letter and CV and monitoring forms to [email protected].

The closing date for applications is 12:00pm Wednesday 31st August 2016.

Increase in parechovirus infections in Scotland

Parechovirus is a viral infection predominantly affecting those under one year of age. Infection usually manifests as mild respiratory or mild gastrointestinal symptoms. However, infection can lead to severe illness including meningitis, myocarditis and encephalitis, particularly in infants. Parechoviruses are commonly spread and more than 95% of cases are infected early in life, within two to five years of age.

Laboratory detections of parechovirus infections reported to ECOSS by month have been investigated in Scotland for the period January 2012 to May 2016 (Figure 1). Peaks in parechovirus activity (as indicated by a rise in ECOSS reports) have been described in Scotland previously and occur every two years, with the number of laboratory detections in 2016 (up to end May) showing a similar rise to that seen in the previous peak years, 2012 and 2014. Levels of parechovirus in 2013 and 2015 are much lower.

The age profile of parechovirus detections are shown in Figure 2. The majority of laboratory detections were in the under five age group, with around two-thirds (68%) of detections being in those under one. Only a small number of laboratory detections (5.3%) were in individuals over five years.

Parechovirus was detected in alimentary samples (~ 40% samples in Scotland), respiratory samples (~25% samples) and sterile site, principally CSF, samples (~30% samples). Looking at samples from sterile sites as a proxy for severe invasive disease, the main age group developing severe illness was those under one.

In light of the increase in parechovirus detections described, NHS boards and clinicians should be aware of parechovirus as a possible cause of meningitis and encephalitis, especially in infants, and request appropriate testing. Similarly, microbiologists should be aware of the current increase in incidence of parechovirus and recommend testing where appropriate, and refer samples to their regional laboratory if testing is not available locally.

PHE Guidance: Zoonotic diseases: investigation guidelines

uuidelines for the Investigation of Zoonotic Disease (non-foodborne) in England and Wales v2, July 2016

Zoonotic infections can pose a threat to human and animal health. Robust investigation and management of potential zoonotic infections is paramount and requires close collaboration between various governmental and non-governmental agencies and other professionals. These guidelines have been thoroughly revised and updated, with the aims to facilitate multi-agency collaborative working arrangements and to provide overall background on the management of zoonotic incidents and outbreaks.

British HIV Association Guidelines on the Use of Vaccines in HIV-positive Adults (2015)

Dear colleagues

Re: British HIV Association Guidelines on the Use of Vaccines in HIV-positive Adults (2015)

We would like to bring to your attention the recently updated BHIVA recommendations on the use of vaccines in HIV-positive adults. The guidance addresses the use of vaccines against virus infections such as human papilloma virus, influenza, chicken pox, shingles, measles, and yellow fever, and we hope it will be of interest to the CVN membership.

We would like to ask the CVN to help BHIVA disseminate the information and promote education of healthcare professionals about several important concepts. The success of antiretroviral therapy has changed the natural history of HIV infection and protection against vaccine-preventable infections is important to ensure patients enjoy long and healthy lives. HIV-positive people are increasingly likely to engage in activities, travel or occupations that carry a risk of exposure to infectious agents, and these otherwise healthy individuals should not be denied protection or engagement with such activities if evidence indicates vaccination is safe and immunogenic. Yet many misconceptions remain about risk of infection, burden of disease, and safety and efficacy of vaccination in this group, which create barriers to successful implementation.

We hope you will find the guidance useful. Feedback will be gratefully received.

With kind regard

Yours sincerely

Prof Anna Maria Geretti
Chair
BHIVA Writing Group BHIVA Guidelines on the Use of Vaccines in HIV-positive Adults (2015)

Geretti@liverpool.ac.uk

Dr Duncan Churchill
Chair
BHIVA Guidelines Subcommittee

Parechovirus Encephalitis and Neurodevelopmental Outcomes

Pediatrics. 2016 Feb;137(2):1-11. doi: 10.1542/peds.2015-2848. Epub 2016 Jan 20.

Parechovirus Encephalitis and Neurodevelopmental Outcomes

OBJECTIVE: We aimed to describe the clinical features and outcome of human parechovirus (HPeV) encephalitis cases identified by the Australian Childhood Encephalitis (ACE) study.

METHODS: Infants with suspected encephalitis were prospectively identified in 5 hospitals through the (ACE) study. Cases of confirmed HPeV infection had comprehensive demographic, clinical, laboratory, imaging, and outcome at discharge data reviewed by an expert panel and were categorized by using predetermined case definitions. Twelve months after discharge, neurodevelopment was assessed by using the Ages and Stages Questionnaire (ASQ).

RESULTS: We identified thirteen cases of suspected encephalitis with HPeV infection between May 2013 and December 2014. Nine infants had confirmed encephalitis; median age was 13 days, including a twin pair. All had HPeV detected in cerebrospinal fluid with absent pleocytosis. Most were girls (7), admitted to ICU (8), and had seizures (8). Many were born preterm (5). Seven patients had white matter diffusion restriction on MRI; 3 with normal cranial ultrasounds. At discharge, 3 of 9 were assessed to have sequelae; however, at 12 months’ follow-up, by using the ASQ, 5 of 8 infants showed neurodevelopmental sequelae: 3 severe (2 cerebral palsy, 1 central visual impairment). A further 2 showed concern in gross motor development.

CONCLUSIONS: Children with HPeV encephalitis were predominantly young, female infants with seizures and diffusion restriction on MRI. Cranial ultrasound is inadequately sensitive. HPeV encephalitis is associated with neurodevelopmental sequelae despite reassuring short-term outcomes. Given the absent cerebrospinal fluid pleocytosis and need for specific testing, HPeV could be missed as a cause of neonatal encephalopathy and subsequent cerebral palsy.

Elimination of measles and rubella in Europe

According to the conclusions of the European Regional Verification Commission for Measles and Rubella Elimination (RVC), released on 5 April, 32 countries in the European Region have interrupted transmission of endemic measles and/or rubella.

The independent RVC assesses member states’ progress towards elimination of measles and rubella by reviewing epidemiological and laboratory surveillance data submitted by each country’s national verification committee, now established in 50 of the 53 member states.

At its fourth meeting, in October 2015, the RVC was able to assess, for the first time, the performance of each country over 36 consecutive months. According to the Framework for the verification process in the WHO European Region and conclusions of the European Technical Advisory Group of Experts on Immunization, once a country has demonstrated the absence of endemic measles or rubella virus transmission for at least 36 consecutive months, the RVC can verify that the disease has been eliminated.

The RVC was pleased to confirm that 32 countries interrupted transmission of endemic measles and/or rubella in 2014, and to verify that 21 member states had eliminated measles and 20 had eliminated rubella within their borders during the period 2012-2014. High-quality surveillance to detect cases and monitor chains of virus transmission and very high immunization coverage (≥ 95%) with two doses of vaccine against measles and rubella were essential to attain this goal.

In addition to commending countries for achieving these objectives, the RVC made recommendations to help under-performing countries catch up. They identified gaps in surveillance, coverage and annual reporting, which they argue demonstrate that greater commitment and support are urgently needed to achieve elimination throughout the European Region.

Eliminating measles and rubella is a core goal of the European Vaccine Action Plan 2015–2020 and an important part of global efforts to improve health and reduce inequalities (Sustainable Development Goals 3 and 10, respectively). The RVC and WHO are committed to the verification process and will continue to provide support until measles and rubella elimination has been achieved.

Interim guidance: handling and processing of specimens associated with Middle East respiratory syndrome coronavirus (MERS-CoV) in clinical diagnostic laboratories

Guidance: MERS-CoV: clinical diagnostic laboratory specimen handling and processing

From: Public Health England
First published: 18 April 2016
Part of: Middle East respiratory syndrome coronavirus (MERS-CoV): clinical management and guidance

Interim guidance for staff in England, who handle samples from patients with suspected or laboratory-confirmed MERS-CoV infection.

WHO Strategic Advisory Group of Experts (SAGE) advice on dengue immunization

New recommendations for dengue vaccine

Dengue is a mosquito-borne flavivirus disease that has spread to most tropical and many subtropical areas. The disease is caused by four closely related viruses, the Dengue viruses 1-4. There are no specific dengue therapeutics and prevention is currently limited to vector control measures. A dengue vaccine would therefore represent a major advance in the control of the disease.

The first dengue vaccine, Dengvaxia (CYD-TDV) by Sanofi Pasteur, was first registered in Mexico in December, 2015. CYD-TDV is a live recombinant tetravalent dengue vaccine that has been evaluated as a three-dose series on a 0/6/12 month schedule in Phase III clinical studies. It has been registered for use in individuals 9-45 years of age living in endemic areas.

The WHO Strategic Advisory Group of Experts (SAGE) on Immunization reviewed CYD-TDV in April 2016 and recommended countries consider introduction of the vaccine only in geographic settings (national or subnational) with high endemicity. A WHO vaccine position paper will be published outlining WHO recommendations in July 2016.

There are approximately five additional vaccine candidates under evaluation in clinical trials, including other live-attenuated vaccines, as well as subunit, DNA and purified inactivated vaccine candidates. Additional technological approaches, such as virus-vectored and VLP-based vaccines, are under evaluation in preclinical studies.

The growing global epidemic of dengue is of mounting concern, and a safe and effective vaccine is urgently needed. WHO expects vaccines to be an integrated part of the Global dengue prevention and control strategy (2012-2020).

Polio endgame plan – vaccine switch

The World Health Assembly (WHA) Report on Poliomyelitis has been published. The report summarises the status against the Polio Endgame Plan and Resolution WHA68.3, adopted by the WHA in May 2015.

The report notes that strong progress continues to be made towards each of the four objectives of the Polio Eradication and Endgame Strategic Plan 2013-2018 (the Endgame Plan). With only Afghanistan and Pakistan remaining endemic for poliomyelitis, wild poliovirus transmission is at the lowest levels in history, with the fewest-ever reported cases from the fewest-ever affected countries.

The declaration of international spread of wild poliovirus as a Public Health Emergency of International Concern and the temporary recommendations promulgated under the International Health Regulations (2005) remain in effect. In September 2015, the Polio Oversight Board of the Global Polio Eradication Initiative reviewed progress and concluded that wild poliovirus transmission was more likely to be interrupted in 2016 than in 2015. This delay shifted the predicted date for certification of global polio eradication to 2019 and increased the cost of completing polio eradication by US$ 1500 million. In October 2015, WHO’s Strategic Advisory Group of Experts on immunization confirmed its recommendation that the withdrawal of oral polio vaccines containing the type 2 component should occur during the period 17 April – 1 May 2016 in all countries that are using trivalent oral polio vaccine through a globally-synchronized replacement of this vaccine by the bivalent oral polio vaccine. The Group also reaffirmed that, in preparation for this global event, it was crucial that countries met established deadlines to identify facilities holding wild or vaccine-derived poliovirus type 2, destroy all type 2 poliovirus materials and, only where necessary, appropriately contain type 2 poliovirus in essential poliovirus
facilities. The Executive Board at its 138th session noted an earlier version of this report. The text of the report has been updated and revised in light of the Board’s deliberations.

As at 17 February 2016, 74 cases of paralytic poliomyelitis due to wild poliovirus had been reported globally with onset of paralysis in 2015, compared to 359 for 2014. All the cases were reported from Afghanistan and Pakistan and were caused by wild poliovirus type 1. On 20 September 2015, the Global Commission for the Certification of Poliomyelitis Eradication declared global eradication of wild poliovirus type 2. Wild poliovirus type 3 has not been detected globally since November 2012. [Source: WHA Provisional Agenda item, 8 April 2016. http://apps.who.int/gb/ebwha/pdf_files/WHA69/A69_25-en.pdf]

For further details, see the Polio Eradication website http://www.polioeradication.org/.

NIBSC communication

Dear CVN member,

As a follow on from some of the monoplex reagents you may use in your laboratory, that have been developed through a collaboration between the CVN and NIBSC, we have the first multiplex reagent which contains 11 viral targets associated with infections of the immunosuppressed / meningitis. They are:

  • Herpes Simplex -1 and -2
  • Varicella Zoster Virus
  • Cytomegalovirus
  • Human Herpes Virus 6A  and 6B
  • BK virus
  • JC virus
  • Epstein Barr Virus
  • Parvovirus B19
  • Adenovirus

Unlike the monoplex reagents, this control is freeze dried for cheaper and easier shipping and storage. Where  possible we have also calibrated the reagent in International Units against the relevant current WHO International Standards. The product is available from our catalogue Product Code: 15/130-XXX, “Clinical Virology Multiplex I: Immunodeficiency panel working reagent for Nucleic Acid Amplification Tests (NAT)”. The reagent is supplied to be reconstituted into 1ml. and once reconstituted will be stable at 4°C for a week.

Secondly the Result Reporting System (RRS), for the data monitoring of NIBSC serology and NAT quality control reagents (including the Quality Control Reagent Unit (QCRU) and Clinical Virology Network (CVN) reagents) is also freely available via the NIBSC website. RRS has been successfully running for serology assays for several years collecting thousands of data points year on year and now accepts data for Nucleic Acid-based Technologies (NAT) reagents and associated assays; allowing you to compare your results to those of other laboratories and assists with conforming to ISO 15189 guidelines.

Dr Sarah Kempster
Scientist
Division of Virology

NIBSC – A Centre of the MHRA
Blanche Lane
South Mimms
Potters Bar
Herts EN6 3QG
United Kingdom.

Tel: +44 (0)1707 641125

[email protected]

http://www.nibsc.org/

Recommended composition of influenza virus vaccines for use in the 2016–2017 northern hemisphere influenza season

Health Protection Scotland: eWeekly Report:

On 25 February 2016, the World Health Organization (WHO) published recommendations on the composition of the trivalent and quadrivalent vaccines for the 2016/17 northern hemisphere influenza season. The recommendations for the influenza A(H1N1)pdm09 strain remained the same as in the previous year while the recommended strains for influenza A(H3N2) and B viruses have changed from those recommended in 2015/16. WHO recommends that trivalent influenza vaccines should contain the following:

an A/California/7/2009 (H1N1)pdm09-like virus;
an A/Hong Kong/4801/2014 (H3N2)-like virus;
a B/Brisbane/60/2008-like virus.

For the quadrivalent influenza vaccines which contain two influenza B viruses, the WHO recommends that the above three viruses plus a B/Phuket/3073/2013-like virus be used.

As in previous years, national or regional authorities approve the composition and formulation of vaccines used in each country and will be responsible for making recommendations regarding the use of the vaccine.

Zika virus: updated guidance

pdated Zika virus guidance for primary care clinicians in England: produced by PHE in conjunction with the RCGP and the BMA.


Zika virus: Updated interim algorithm for assessing pregnant women with a history of travel


Pregnant women advised to postpone non-essential travel to areas with active Zika virus transmission.

Public Health England (PHE) and the National Travel Health Network and Centre (NaTHNaC) have been carefully monitoring the evolving Zika virus outbreak in South and Central America and the Caribbean and are now issuing updated travel advice for pregnant women and advice on preventing sexual transmission.
Travel and pregnancy

It is recommended that pregnant women should postpone non-essential travel to areas with active Zika transmission until after pregnancy. This is a change to the previous advice which encouraged pregnant women to consider avoiding travel and seek travel health advice.

In addition it is recommended that women should avoid becoming pregnant while travelling in an area with active Zika virus transmission, and for 28 days following return home. If a woman develops symptoms compatible with Zika virus infection on her return to the UK, it is recommended she avoids becoming pregnant for a further 28 days following recovery.

If a woman develops symptoms compatible with Zika virus infection on her return to the UK, it is recommended she avoids becoming pregnant for a further 28 days following recovery.

Advice has also been updated for healthcare professionals. In the event that travel to an area with current active Zika virus transmission cannot be postponed, the pregnant traveller or those planning pregnancy should discuss with their healthcare provider the risks which Zika may present. In addition, the use of scrupulous mosquito bite avoidance measures both during daytime and night time hours (but especially during mid-morning and late afternoon to dusk, when the mosquito is most active) should be emphasised, and an information leaflet provided.

Preventing sexual transmission

A number of cases of sexual transmission of Zika virus have been reported, and in a limited number of cases, the virus has been shown to be present in semen. The risk of sexual transmission of Zika virus is thought to be very low.

Our advice:

  •     condom use is advised for male travellers if their partner is pregnant, during travel and for the duration of the pregnancy
  •     if there is a risk of pregnancy, or pregnancy is planned, condom use is advised during travel and for 28 days on return from an active Zika transmission area if the male traveller does not have any symptoms compatible with Zika virus infection. If a clinical illness compatible with Zika virus infection has been suspected or confirmed, this advice should be followed for 6 months following the start of symptoms.
  •     even if not pregnant or planning to be, couples who wish to reduce the very low risk of virus transmission may consider using condoms if the man has had clinical illness compatible with Zika infection

Dr Dipti Patel, director at NaTHNaC said:

“All travellers, especially pregnant women going to an area where there is current active Zika virus transmission should ensure they seek travel health advice from their GP or a travel clinic well in advance of their trip and consult the NaTHNaC website for up to date information on where current active transmission is occurring and country information.

We strongly advise all travellers to avoid mosquito bites and recommend that pregnant women should postpone non-essential travel to areas where Zika virus outbreaks are ongoing until after their pregnancy. If travel is unavoidable, or they live in areas where active Zika virus transmission is reported, they should take scrupulous insect bite avoidance measures both during daytime and night time hours and also seek advice from their GP, midwife or obstetrician. Women who are planning to become pregnant should discuss their travel plans with their healthcare provider to assess the risk of infection with Zika virus and receive advice on mosquito bite avoidance measures. Tailored advice for pregnancy and travel is available at NaTHNaC’s website.

Professor Paul Cosford, Director for Health Protection & Medical Director at Public Health England, said:

“As our knowledge of the Zika virus, and the evidence linking microcephaly to Zika infection, becomes clearer a more precautionary approach is warranted. This advice will be kept under review and updated as more information becomes available.

“We expect to see small numbers of Zika virus infections in travellers returning to the UK, but the risk to the wider population is negligible as the mosquito vector is not found in the UK. The symptoms of can be similar to other mosquito-borne infections such as dengue, chikungunya and malaria so laboratory testing is essential for the correct diagnosis. If you have recently returned from an area where Zika virus transmissions are currently reported and have a fever or flu-like illness, seek medical attention without delay to exclude malaria and mention your travel history.

“Zika virus is related to dengue virus. The virus is spread by the Aedes mosquito, which predominantly bites during the day. The illness is similar to dengue and chikungunya and is generally mild and self-limiting, lasting 2 to 7 days.

“Symptoms of Zika virus infection may include fever, joint pain, rash, conjunctivitis/red eyes, headache, muscle pain and eye pain. No specific anti-viral treatment is available for Zika virus infection.”

For more information about Zika virus refer to the PHE or NaTHNaC websites.

Public Consultation: Expert Opinion on neuraminidase inhibitors for prevention and treatment of influenza

Preliminary Scientific Advice: Expert Opinion on neuraminidase inhibitors for prevention and treatment of influenza

The report is open for public consultation and all comments are welcome. They will be considered and addressed by the authors prior to publication of the final report.

The deadline for comments is 16 March 2016.

Current recommendations on the use of the neuraminidase inhibitors oseltamivir and zanamivir for the treatment and prophylaxis of influenza disease are appropriate, finds a new expert opinion from ECDC, which today opens for public consultation.

The review of recent systematic reviews and meta-analyses on the use of neuraminidase inhibitors for prevention and treatment of influenza finds that the studies presented strengthen the evidence base for the use of these antiviral treatments.

Continued debate surrounding the effectiveness and safety of these antivirals has led to some uncertainty within the public health community regarding the antivirals’ potential benefits as a treatment option or as prophylaxis for influenza disease. As a result, the public health benefits may be being missed.

The ECDC expert opinion demonstrates that there is evidence for use of neuraminidase inhibitors for treatment and prophylaxis of influenza. It also highlights the importance of further studies and the urgent need for the development of new antivirals with greater efficacy.

Zika Clinical Research Fellowship – University of Liverpool – Closes 04/03/16

In response to the World Health Organisation declaring the Zika outbreak to be a global health emergency the National Institute for Health Research (NIHR) Health Protection Research Unit (HPRU) in Emerging & Zoonotic Infections is looking for a clinical research fellow to develop research in this area.

  • Location: Liverpool
  • Salary: £31,838 to £35,952
  • Hours: Full Time
  • Contract Type: Contract / Temporary
  • Placed on: 11th February 2016
  • Closes: 4th March 2016

Job Ref: R-589369

The University of Liverpool’s Institute of Infection and Global Health was awarded nearly £4 million funding from the National Institute for Health Research (NIHR) to establish a Health Protection Research Unit (HPRU) in Emerging & Zoonotic Infections. The HPRU is a partnership, led by Professor Tom Solomon, with Public Health England and the Liverpool School of Tropical Medicine.

You will demonstrate the potential for outstanding development as a clinical academic and should have an MBChB, MB BS or equivalent medical degree, or have completed foundation training. You will help develop a case control study of neurological disease associated with Zika, support other projects, and develop pilot data which might be used towards a subsequent research fellowship application from NIHR, Wellcome Trust, MRC or other. Your main base will be at the University with some periods in Brazil and possibly other South American countries. The post is available for 1 year. Visit: http://www.hpruezi.nihr.ac.uk/

For full details, or to request an application pack, visit www.liv.ac.uk/working/job_vacancies/ or e-mail [email protected], please quote Job Ref in all enquiries.

22-23/03/16: CVN Conference programme & bursary details

Conference  programme & bursary details:

CVN Conference programme

Tuesday, March 22nd

14.00-14.30 – Update on avian influenza and MERS-CoV – Maria Zambon

14.30-15.00 – The application of rapid molecular respiratory point of care tests in relation to clinical and infection control paediatric practice – Richard Cooke

15.00- 15.30 – Commercial company presentations

15.30-15.45 – Coffee break/posters

15.45-16.15 – Monitoring and treating hepatitis B carriers now and in the future – Patrick Kennedy

16.15-17.00 – CVN meeting:

  • Chairs report
  • Treasurer’s report
  • Research report
  • Training
  • Website update

17.00-17.30 – Join Room 1A: The hostile cell: Intrinsic antiviral immunity – part 1: RNAi – Ronald Van Rij

18.00 Join Debate about RCT and Ebola trials Jake Dunning and panel

20.00 – CVN dinner

Wednesday March 23

10.00 – 13.00 – Offered papers (12 minutes each)

13.00 – Lunch/commercial exhibits/Posters

14.30 – 15.00 – Human animal infections and risk surveillance (HAIRS) and emerging infection risks to human health – Dilys Morgan

15.00-15.30 – The management of patients with herpes simplex encephalitis – the case for steroids – Tom Solomon

15.30 Coffee/Posters

16.00 – 16.30 – Cats, rats and bats: Rabies clinical service case histories and management issues – Kevin Brown

2016 Gilead UK and Ireland Fellowship Programme

Following the success of the Gilead UK and Ireland Fellowship Programme (GUKIFP) from 2009 to 2015, Gilead are pleased to provide details for the Fellowship Programme for 2016.

The aim of the Gilead UK and Ireland Fellowship Programme is to award financial grants (or support and contribution to joint working initiatives between the NHS and Gilead or the NHS, Gilead and the third sector) to generate and promote best practice in the delivery of patient-centred care through innovative and reproducible models in the disease areas – HIV, viral hepatitis (HCV), invasive fungal disease (IFD), cystic fibrosis (CF) and oncology.

For 2016 the Gilead UK & Ireland Fellowship Programme is running two application windows throughout the year to provide additional opportunities to apply for a grant.

Evidence generated from Fellowship projects provides the opportunity to shape public health policy and practice (either at a local or national level) in the UK and Ireland, or to generate new studies or joint ventures to shape clinical care pathways. As an example, HIV data generated over the last 6 years have been successfully published in peer-reviewed journals and used to support the Halve It campaign, a coalition of national experts to tackle the public health challenges posed by HIV (www.halveit.org.uk).

Financial grants will be awarded on a competitive basis to individual organisations or groups of local healthcare providers such as, but not limited to, hospital clinics and patient organisations.

Therapy area criteria grant giving for GUKIFP 2016:

HIV

Topic 1 – Targeted testing

Background: in the HIV aspirational 90% diagnosed, 90% on treatment and 90% undetectable the shortfall remains in those diagnosed. Testing in GUM services and acute hospital settings has increased.

The Fellowship is looking for innovative projects with expectation of reaching and HIV testing at least 250 individuals from higher risk populations in non-GUM/ non-hospital settings. For example, these could include outreach, remote, or other novel testing strategies.

Each application should outline clear plans for linkage to care.

Topic 2 – Service deployment to improve the long-term health of people living with HIV (PLWH)

The Fellowship programme is looking for projects which focus on the development of innovative service models that assess the longer term needs of PLWH.

Viral hepatitis

1.  Local Operational Delivery Networks (ODN) integrated initiatives to evaluate acceptability, feasibility and effectiveness of community based HCV specialist treatment service models according to NHS service specification no F04 S f.

2.  Local innovative initiatives to evaluate acceptability, feasibility and effectiveness of integration of HCV testing into routine healthcare delivery demonstrating successful referral to care.

Grant applications outside of the topics above will still be considered, however they must meet the ethos of the Gilead UK & Ireland Fellowship e.g. be innovative and enable sharing of best practice.

How to apply

All grant or support requests will be assessed against clear criteria and, as in 2015, we expect this will be a highly competitive process. Please visit the Fellowship Programme website for therapy area specific application opening and closing dates. Each project’s funding will be awarded in instalments which are contingent on demonstration of satisfactory progress and successful completion by spring 2017 at the latest.

For 2016, the Gilead UK & Ireland Fellowship Programme is running two application windows throughout the year to provide additional opportunities to apply for a grant. Information relating to the second application window will be provided following the closure of the first application window.

For more information on the Gilead UK and Ireland Fellowship Programme, details of how to apply and the assessment criteria, please visit the Gilead UK and Ireland Fellowship Programme website www.ukifellowshipprogramme.com or contact us at [email protected]

Herpes simplex virus type specific serology assay availability

ervice change by the Virus Reference Department, PHE – Colindale

HSV serology, including the HSV serology typing assay for distinguishing between HSV-specific IgG, will no longer be offered from the Virus Reference Department from the 1st April 2016. HSV-type specific serology testing is available at the Manchester and Southampton Public Health Laboratories, and samples can be sent to either of these laboratories if HSV-typing serology is required. Please note that testing for intrathecal HSV IgG (on paired CSF and serum samples) as part of the investigation of encephalitis or other CNS infections will still be provided at VRD, Colindale.

Call for nominations for a UK SMI Chair for the Virology Working Group – closing date 12 February 2016

The Steering Committee for UK Standards for Microbiology Investigations is seeking nominations for the above post.  Nominations should be submitted to [email protected] by 12 February 2016, and should include a covering letter and a curriculum vitae.  Interviews for the post will be held on 23 February 2016 at Colindale.

Job description for Virology Serology Working Group Chair

2016 Virology Working Group Chair

ToR Working Groups

Zika virus (updated 08/02/2016)

Zika virus is spread via mosquito bites, the common symptoms are pyrexia, rash, arthralgia and conjunctivitis. The illness is usually asymptomatic or causes mild symptoms for up to a week. Hospitalisation is uncommon.

In May 2015 the first confirmed Zika virus infection in Brazil was reported. The outbreak in Brazil has resulted in reports of Guillain-Barre syndrome and pregnant women giving birth to babies with congenital infection, abnormalities (including microcephaly) and poor pregnancy outcomes.

Advice from the Rare and Imported Pathogens Laboratory, Public Health England, Porton:

GPs (and HPTs) should be directed to PHE’s guidance for GPs and, if appropriate, the RCOG interim guidance for pregnant women. If they need further help then they should be contacting their local Trust Microbiologist/Virologist/ID physician.

We would expect that you, the local Infection specialists, would be able to address most GP and local obstetric queries and for those you can’t, as ever, you could call us on the general RIPL number 01980 612348 or, for immediate management/diagnostic advice on an acutely sick patient, on the IFS number.

Essence of the guidance:

Current Zika-like symptoms (that began whilst in affected country or within 2/52 of leaving) and pregnant: test blood and urine

Current Zika-like symptoms (that began whilst in affected country or within 2/52 of leaving) and not pregnant: test blood only

(Note that in acutely sick returning traveller, the broader differential incl malaria needs to be considered, AS USUAL)

Previous Zika-like symptoms (that began whilst in affected country or within 2/52 of leaving) and pregnant: don’t test (U/S follow up)

Previous Zika-like symptoms (that began whilst in affected country or within 2/52 of leaving) and not pregnant: don’t test

Patients should be tested only if they have current symptoms, irrespective of duration.

RIPL are receiving considerable numbers of samples. Note that if the form is very poorly completed and, in particular, if there is no indication that the patient has current Zika-like symptoms, the sample may be stored without testing.


Information on Zika virus can be found via links on our Guideline page or below:

Zika virus resources

Countries and territories with active Zika virus transmission (23/01/2016, source CDC):

  • Barbados
  • Bolivia
  • Brazil
  • Cape Verde
  • Colombia
  • Ecuador
  • El Salvador
  • French Guiana
  • Guadeloupe
  • Guatemala
  • Guyana
  • Haiti
  • Honduras
  • Martinique
  • Mexico
  • Panama
  • Paraguay
  • Puerto Rico
  • Saint Martin
  • Samoa
  • Suriname
  • Venezuela

UK Clinical Virology Network Election results

After the recent election the CVN Executive is now as follows:

Chair: Mark Zuckerman
Email: [email protected]

Vice-Chair / Chair-elect: Matthew Donati
Email: [email protected]

Honorary Secretary: Husam Osman
Email: [email protected]

Honorary Treasurer: Kevin Brown
Email: [email protected]

Meetings Secretary: Stephen Winchester
Email: [email protected]

Audit & Guidelines Secretary: Alison Watt
Email: [email protected]

Biomedical Scientists Representative: Jayne Harwood
Email: [email protected]

Website & Communications Secretary: Eleri Wilson-Davies
Email: [email protected]

Academic Representative: Will Irving
Email: [email protected]

Clinical Scientists Representative: Jonathan Hubb
Email: [email protected]

CVN administrative assistant: Maggie Hopper
Email: [email protected]

Consultant Virologist: Royal Free

Applications are invited for the post of a consultant virologist with a specialist interest in HIV based at the Royal Free Hospital. This is a full-time (10 programmed activities) substantive post. The successful candidate will join 3 existing colleagues (2.2 whole time equivalent) to provide consultant virology support to the Royal Free London NHS Foundation Trust.

For full details, please go to http://jobs.royalfree.nhs.uk quoting the reference 391-1288-T-MK or contact Dr Tanzina Haque, Clinical Lead, Department of Virology, Royal Free Hospital; [email protected].

2015 CVN Elections – Deadline Extended

Nominations Deadline extended for some posts!

The deadline has been extended for the following positions to 5pm on Wednesday 25 November 2015:

  • HONORARY SECRETARY
  • VICE PRESIDENT / PRESIDENT ELECT
  • MEETINGS SECRETARY
  • SCIENTIFIC AFFAIRS & RESEARCH SECRETARY
  • BIOMEDICAL SCIENTIST REPRESENTATIVE

 Please read the attached Roles and Responsibilities document for more information.

If you are interested in standing for one of the positions please find attached a nomination form. This should be returned to Electoral Reform Services by email to [email protected] 

All completed nomination forms must be received by Electoral Reform Services no later than 5pm on Wednesday 25 November 2015.

If you require any further information on completing the nomination form please contact
Ciara Norris on 020 8365 8909.


Regards,

Electoral Reform Services

DexEnceph Study

Launch of DexEnceph Trial: Do steroids improve outcomes in HSV encephalitis?

The Brain Infections Group and the Clinical Virology Network are launching a trial of the use of dexamethasone in patients with Herpes Simplex Virus Encephalitis with the aims of determining if dexamethasone given in the acute stages of HSV encephalitis will improve patient outcomes.

HSV encephalitis is a rare but devastating condition. 10% of patients will die and the remaining survivors are often left with debilitating disability, particularly affecting memory. Despite it being classed as a rare condition, HSV encephalitis has disproportionate effects on patients, relatives and healthcare systems.

The diagnosis of HSV encephalitis will be the cornerstone of patient identifications and enrolment into the trial and thus we have worked in close collaboration to enable trial processes to be acceptable and effective at virology laboratories across the UK.

Involvement of virology and microbiology laboratories will be essential for the success of this trial and therefore we encourage any centre interested in research and brain infections to contact the DexEnceph trial team on [email protected] or telephone 0151 795 9688.

Michael Griffiths, Ian Hart, Cristina Fernandez, Tom Solomon and Mark Zuckerman

On behalf of the Brain Infections Group and Clinical Virology Network.

Genomic analysis of South Korean MERS-CoV isolates

An analysis has been carried out on the recently sequenced MERS-CoV isolates from South Korea and China (ex South Korea). A consensus of the sequences demonstrates clustering with viruses from a recent outbreak in Riyadh in February-March 2015. However, the Chinese and Korean viruses are divergent enough to potentially be derived from a separate zoonotic event in the Arabian Peninsula. However, the originating country cannot be determined with certainty. The new MERS-CoVs are unlikely to be phenotypically different from the MERS-CoV currently circulating in the Arabian Peninsula and therefore there does not appear to be evidence for different virulence or transmission properties.

MERS-CoV outbreak in South Korea

The largest outbreak of MERS-CoV outside of the Arabian peninsula has occurred this week in South Korea. So far there have been at least 25 people infected, with one patient ignoring quarantine and travelling to China. The outbreak started when a 68-year-old man developed symptoms following a business trip to four Middle Eastern countries on 4th May fell ill a week later. He was treated at a number of clinics before being diagnosed with MERS-CoV on 20th May. This single patient appears to have infected at least 22 family members, healthcare workers and fellow patients at a hospital where he was treated from 15th May to 17th May. This superspreading event, seen during the SARS-CoV pandemic, is usually as a result of a breakdown in infection control measures at the hospital. Korea has quarantined approximately 700 people to stop the spread of the virus. However, a 44-year-old man who fell ill after visiting his hospitalised relatives in Seoul ignored the quarantine restrictions and flew to Hong Kong on 26th May and then on to Huizhou in China’s Guangdong province. Chinese authorities have quarantined 67 people believed to have had close contact with the patient and are currently searching for ten more.

START trial ended early due to promising results

The Strategic Timing of Antiretroviral Treatment (START) trial began in March 2009. At that time the WHO recommendation was to start ART only when patients’ CD4 counts had dropped below 200 cells/mcL. This study involving 4685 HIV-infected people has now ended early because results showed that immediate treatment can cut the risk of disease and death in half. START included treatment-naive patients with CD4 counts >500 cells/mcL and  randomly assigned half the patients to start treatment immediately, while the other half were offered ART when their CD4 count fell to 350 or they developed an AIDS-defining illness. The trial was planned to end in December 2016. However, the data safety and monitoring board found that after an average of 3 years, the early treatment group had a 53% reduction in risk of suffering an event. No evidence of undue adverse events was seen. All of the patients are now being offered treatment, with the trial continuing to follow them through 2016. The data is now likely to affect WHO and UK HIV treatment guidelines.

Locum Consultant in Virology – Royal Free Hospital

Applications are invited for the post of a locum consultant virologist based at the Royal Free Hospital. This is a full time (10 programmed activities) locum post, initially for 6 months.  The successful candidate will join 3 existing colleagues (2.2 whole time equivalent) to provide consultant virology support to the Royal Free Hampstead NHS Foundation Trust. For full details, please go to http://jobs.royalfree.nhs.uk/job/v374889 or contact Dr Tanzina Haque, Clinical Lead, Department of Virology, Royal Free Hospital; [email protected].

ESCV 2015

Dear CVN members, there is an ESCV meeting in Edinburgh this year.

Dates for the meeting is 9-12 September.

Keynotes

  • Mario Poljak (Ljubljana, Slovenia) Vaccination against HPV
  • Daniela Huzly (Freiburg, Germany) Congenital infections
  • Marion Koopmans (Rotterdam, Netherlands) Hospital acquired viral infections
  • Mariet Feltkamp (Leiden, Netherlands) Polyomaviruses immunocompromised hosts
  • Rob Schuurman (Utrecht, Netherlands) Antivirals-2015 update
  • Fred Hayden (Charlottesville, USA) Ebola therapeutics and vaccine update
  • Maria Paz Sanchez-Seco (Madrid, Spain) Ebola-virology and public health aspects
  • Olli Ruuskanen (Turku, Finland) Viral respiratory infections
  • Maria Söderlund-Venermo (Helsinki, Finland) Newly identified small DNA viruses
  • Thea Fisher (Copenhagen, Denmark) Enteroviruses
  • Carl Wittwer (Utah, USA) Virology testing past, present, future
  • Paul Heath (London, UK) Controversies in neonatal viral management
  • Mark Zuckerman (London, UK) Interactive clinical case
  • Matt Donati ( Bristol, UK ) Interactive clinical case
  • Husam Osman (Birmingham, UK) Interactive clinical case
  • Will Irving (Nottingham, UK) Interactive clinical case
  • Wendy Barclay (London, UK) Influenza pathogenesis

Registration and Abstract submission are open

  • 31st May 2015: Abstract Submission Closes
  • 1st July 2015: Notification of Abstracts Accepted
  • 31st July 2015: Reduced Rate Registration Closes

VENUE:

The Assembly Rooms
54 George Street Edinburgh
EH2 2LR
United Kingdom

Gilead Drug Shows Promise in Reversing HIV Latency

Aso-called TLR7 agonist has shown promise in early research into its ability to wake infected cells from a dormant, or latent, state and cause them to produce HIV, Project Inform reports. The ultimate hope is that the immune system can then kill those cells and reduce the size of the viral reservoir, possibly contributing to a cure.

Researchers conducted two studies of Gilead Sciences’ TLR7 agonist, GS-9620, which is already in Phase II research as a treatment for hepatitis B virus (HBV): one study among the blood cells of four HIV-positive individuals treated with antiretrovirals, and another study among rhesus macaque monkeys. They presented their findings at the 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle.

Investigators in the human-cell study took the blood cells and incubated them for four days either with GS-9620 or a substance that served as a control. The levels of viral RNA rose in the samples treated with GS-9620, indicating that certain cells had been taken out of a latent state and begun producing virus again.

The other study included 10 monkeys who were infected with SIV, HIV’s simian cousin, and which were treated for the virus so that they had an undetectable viral load. Four monkeys received GS-9620 and six a placebo. GS-9620 was given every two weeks, at escalating doses through the third dose, followed by four more administrations at the same level as the third dose. When compared with the placebo group, the treated monkeys experienced transient and consistent increases in viral load—in the 500 to 1,000 range—coinciding with the fourth through seventh doses. Researchers also found evidence that the drug had reduced the size of the viral reservoir.

A Phase I safety study of GS-9620 has begun among humans.

To read the CROI conference abstract on the primate study, click here.

Anti-HIV Molecule May Lead to Vaccine and Long-Acting Treatment

Anew molecule effectively blocked a simian version of HIV from attaching to immune cells, and may work as both a long-acting treatment and a vaccine for HIV in humans, The New York Times reports. Publishing their findings in the journal Nature, researchers injected a new genetic therapy into four monkeys infected with SIV (HIV’s simian cousin). Then they exposed the animals to SIV six times in increasing doses over a 34-week period, doing the same with four untreated, SIV-positive control monkeys.

HIV—or SIV, in the case of primates—makes initial contact with a CD4 immune cell by latching onto the CD4 receptor on the cell’s surface. This in turn exposes the CCR5 receptor, which the virus latches onto before ultimately infecting the cell. (HIV may latch onto the CXCR4 receptor rather than the CCR5, but that tends to occur later in the course of someone’s infection.)

To develop the therapy, the researchers took a molecule with antibody-like properties that latches onto the CD4 receptor and connected it with a short protein fragment that attaches to the adjacent CCR5 receptor. Next, they fashioned genetic instructions for the manufacture of this fused molecule, which they named eCD4-lg, and put that code into a benign virus that was designed to integrate the instructions into human cells. The idea is to get the human body to produce the SIV-fighting molecule indefinitely. The molecule is meant to work by attaching to the CD4 and CCR5 receptors in a claw-like shape, thus blocking the virus from connecting to the immune cell, thwarting its attempts at infection from the first step.

None of the monkeys treated with eCD4-lg contracted SIV during the study, while all of those who went untreated became SIV positive. Additionally, the eCD4-lg persisted in the monkey’s bodies through the 40 weeks of the study at levels the scientists deemed protective against the virus.

“Our molecule appears to be the most potent and broadest inhibitor of HIV entry so far described in a preclinical study,” study lead Michael Farzan, PhD, a professor in the department of infectious diseases at the Scripps Research Institute in Jupiter, Florida, said in a press release. “If one could inject either eCD4-lg or our gene therapy tool into people with HIV infection, it might control HIV for extended periods in the absence of antiretroviral drugs. Further research will help illuminate the promise of these approaches.”

Indeed, eCD4-lg protected against a wider array of viral strains in laboratory study than any of the anti-HIV broadly neutralizing antibodies researchers have been studying—most can only combat one or two—and with a much simpler method. Additionally, the molecule proved more effective against fighting the virus than any of those antibodies.

The researchers who developed eCD4-lg are now studying the molecule as a potential treatment for monkeys infected with HIV-like viruses.

“This innovative research holds promise for moving us toward two important goals: achieving long-term protection from HIV infection, and putting HIV into sustained remission in chronically infected people,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, which is part of the National Institutes of Health, said in the same press release. The NIAID was the primary funder of the research.

A crisis and its solution: setting up the UK Clinical Virology Network

Clinical virology is a young discipline. Its origins can be found in the series of technical innovations that came to fruition during the second half of the twentieth century: cell culture as a substrate for virus isolation; electron microscopy; availability of antigens for a widening range of serological tests;  onoclonal antibodies; solid phase assays; and, most recently, the greatly enabling polymerase chain reaction. It is no exaggeration to state that virology now sets the pace in the development of medical microbiology, and that its techniques of rapid diagnosis, serology and molecular typing have become the standard by which the rest of microbiology should be judged. Yet a staffing crisis looms in medical virology in UK. The advent of Calman training, the discontinuation of SHO posts, a reduction in national training numbers in microbiology and failure to renew consultant virology posts have all contributed to a paucity of interest for training posts. This may also be linked to the erosion of pathology teaching in the undergraduate curriculum and the reduction in academic posts in microbiology and virology. Few medical schools and universities support chairs in these specialities, a problem highlighted in a recent report from the Academy of Medical Sciences.

Currently, clinical virology services in the United Kingdom are provided by 44 consultant medical virologists, (38 full time) and a dozen grade C Scientists who do clinical work as part of their duties. In most district general hospitals, consequently, the provision of virology advice falls largely to consultant medical microbiologists, few of whom have received specialist training in virology. As clinical virology becomes more complex, many of them are now requesting updates in clinical and laboratory aspects of diagnostic virology. They recognise the rapid developments in molecular diagnostics and antiviral chemotherapy, the new viral vaccines, the identification of new human viruses, and the problems of managing virus infection control in the hospital and local community. They know that the demand for specialist virological advice and support to genitourinary medicine, renal dialysis centres, foetal medicine units and tertiary referral services such as cancer centres, bone marrow transplant and solid organ transplant units also has increased substantially over the last 10 years. Because the 1990s saw no overall growth in the numbers of consultant clinical virologists, each provides, on average,  a consultative service for more than a million people. However, the distribution of consultant clinical virologists today is distorted, reflecting past patterns of investment and current ability to fill posts, rather than current need. Workforce planning has been further disrupted by several early retirements and by the loss of at least 10 accredited clinical virologists to industry. As a result many virologists are carrying very large clinical workloads. They are maldistributed geographically, and too many are practising in isolation. A recent Royal College of Pathologists report recommended that single handed consultant microbiological and virological practice should no longer be regarded as acceptable because of professional isolation and  unreasonable on – call commitments. The specialty of clinical virology in the UK is in danger of losing its critical mass unless some remedial steps are swiftly taken. Last year two well attended meetings identified clearly the problems facing medical virologists in the UK, and sought solutions. A national strategy was formulated, based on the provision of a stable,
high-quality clinical virology service, working to common standards, responsive to local needs, and with equity of access across the country.

Further points made were:

  • the continuing need for high quality surveillance of respiratory, sexually transmitted, bloodborne and vaccine-preventable virus infections COMMUNICABLE DISEASE AND PUBLIC HEALTH VOL 4 NO 4 DECEMBER 2001 239 editorials
  • the attractiveness of a model that delivered services from about 25 specialist virology centres, each staffed by two to three consultant clinical virologists and at least one grade C scientist
  • the potential for the specialist virology centres to provide clinical support, regular training and updates for medical microbiologists working in district general hospitals in their vicinity
  • the need in the short term to support single – handed consultant virologists and in the longer term to redistribute consultant clinical virology posts so that singlehanded practice is phased out
  • the need to increase the rate of deployment of molecular diagnostics (current overall usage is too low, and is highly variable from centre to centre)
  • the need to create sufficient training centres and training posts to safeguard succession planning, and to recognise the value of close interaction between the PHE, NHS and universities
  • the need to draw to the attention of Workforce Development Confederations the case for increasing the numbers of consultant medical virologists and clinical scientists
  • the need to attract sufficient, good quality trainees into virology
  • the need to keep the health department and chief medical officers informed of the development and implementation of this national strategy for clinical virology services
  • finally, the potential value of a national clinical network of virologists with regular meetings and defined outputs

The concept of a national clinical virology network was supported by the great majority of those attending the second national meeting. It was agreed that it could facilitate:

  • development of standardised clinical, laboratory and training protocols; and national quality standards
  • timely and more complete dissemination of professional and management information
  • regular updating of workforce planning information, ensuring accuracy and timeliness
  • clinical and laboratory audits
  • improved interaction between staff, including trainees, in different centres
  • better liaison with main stakeholders including health departments, universities and the PHLS.

After Consultation from medical, clinical scientist and biomedical scientist colleagues in both virology and medical microbiology across the UK, and the PHE, the Royal College of Pathologists and the Academy of Medical Sciences, a Clinical Virology National Strategy document was prepared. The formation of this network was received with enthusiasm by virologists and colleagues in medical microbiology.

The model has sought to deal with the present problems of training and advancement in virology and the network is a means to achieve resolution of present difficulties, but it has neither power nor resources, and its proposals can easily be allowed to drift and the present crisis allowed to deepen. If that happens, the quality of virology services in UK is almost certain to deteriorate, to the progressive detriment of patients and of public health.

Nairovirus isolated from bats

The authors used a combination of whole-genome sequencing and classical viral isolation methods to identify novel nairoviruses from bats captured from a cave in Zambia.

They found that this nairovirus infection is highly prevalent among the giant leaf-nosed bats, Hipposideros gigas with the virus being detected in samples from 16 bats out of 38. Whole-genome analysis of three of the viral isolates (11SB17, 11SB19 and 11SB23) demonstrated a typical bunyavirus trisegmented genome. These strains were found to have formed a single phylogenetic clade that is divergent from other known nairoviruses and has now been given the designation Leopards Hill virus (LPHV). When this virus was injected intraperitoneally into mice, the 11SB17 strain was found to cause only slight body weight loss, while the 11SB23 strain leads to an acute lethal disease that resembles Crimean–Congo haemorrhagic fever in humans. Therefore the authors propose that their LPHV mouse model can be used for research on the pathogenesis of nairoviral haemorrhagic disease.

Click here to read more.

Hospitalisation rates of HIV elite controllers

So-called HIV elite controllers are able to spontaneously suppress HIV viraemias but they also suffer from HIV-induced chronic inflammation that may increase the risk of comorbidities. The authors were interested in the hospitalisation rates and causes of hospitalisation among elite controllers compared to immunologically intact people with medically-controlled HIV. They were able to identify 149 (0.4%) elite controllers among 34,354 people. The unadjusted hospitalisation rates among the medically-controlled, elite controllers, low viraemia and high viraemia groups were: 10.5, 23.3, 12.6 and 16.9 per 100 person-years, respectively. Following adjustment for demographic and clinical factors, elite control was still associated with significantly higher rates of all-cause (adjusted incidence rate ratio [aIRR] 1.77, 95%CI 1.21–2.60), cardiovascular (aIRR 3.19, 95%CI 1.50–6.79) and psychiatric (aIRR 3.98, 95%CI 1.54–10.28) hospitalisation than the medically-controlled group. Non-AIDS-defining infections were the most common reason for hospital admission overall (24.1% of hospitalisations) but were rare among elite controllers (2.7%), who were more likely to be hospitalised due to cardiovascular causes (31.1%). Therefore elite controllers are hospitalised more frequently than people with medically-controlled HIV, and this is usually caused by cardiovascular diseases.

Click here to read more.

Active HCV infection in West Africa

While, sub-Saharan Africa (SSA) has the highest global HCV prevalences, high rates of serologic false positives and low levels of viraemia have made estimating the burden in this area very difficult. The authors prospectively recalled 363 past blood donors (180 who were rapid screen assay (RSA) positive and 183 that were RSA-negative at the time of donation) in order to identify the level of active infection and risk factors for infection. The frequency of active HCV infection ranged from 74.4% to 88% depending upon the criteria used to define activity. Patients with active disease had biochemical evidence of liver inflammation and median viral loads of 5.7 log10 copies/ml. Patients from the northern and upper regions of Ghana appeared to be at greater risk of infection compared to patients from other areas. These risk factors included: traditional circumcision, home birth, tribal scarring and HBV coinfection. Therefore viraemic infections are common among serologically confirmed cases. Several transmission modes are contributing to the current HCV epidemic in Ghana and the distribution of at-risk practices may result in substantial regional variation in prevalence.

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Sofosbuvir compassionate use in liver transplant recipients

Recurrent hepatitis C virus (HCV) infection following liver transplantation (LT) is associated with an accelerated progression of liver disease, which can lead to graft loss and death. The authors provided sofosbuvir and ribavirin on a compassionate-use basis to patients with severe recurrent HCV, including those with fibrosing cholestatic hepatitis (FCH) and decompensated cirrhosis who had a life expectancy of one year or less. All of the patients received 24–48 weeks of sofosbuvir plus ribavirin. Of the first 104 patients analysed, 52 had an early severe recurrence (diagnosed <12 months after LT) and 52 had cirrhosis (diagnosed >12 months after LT). Of 92 patients assessed, 59% achieved sustained virologic response at 12 weeks after the end of treatment (SVR12), with a higher rate (73%) in patients with early severe recurrence. 57% of patients reported a clinical improvement at the last study visit, 22% were unchanged, 3% had a worsened clinical status and 13% had died. Overall, 123 serious adverse events (SAEs) occurred in 47% of the patients. SAEs associated with hepatic decompensation were the most common, with 26 such events occurring in 18% of patients. Therefore sofosbuvir and ribavirin lead to high rates of sustained virologic response in patients with severe recurrent HCV, including patients with early severe recurrence, FCH and cirrhosis.

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Minimum target prices for HCV directly acting antivirals

At present combinations of directly-acting antivirals can be used to treat chronic HCV in the majority of treatment-naïve patients. However, mass treatment programmes in developing countries are only feasible if the costs of treatment and laboratory diagnostics are very low. The authors tried to estimate the minimum costs of directly-acting antiviral treatment and associated diagnostic monitoring. They found that the minimum costs for a 12-week course of combination directly-acting antivirals with the most consistent efficacy results were: US$122 per person for sofosbuvir+daclatasvir, US$152 for sofosbuvir+ribavirin, US$192 for sofosbuvir+ledipasvir and US$115 for MK-8742+MK-5172. Diagnostic testing costs worked out at US$90 for genotyping, US$34 for two HCV antigen tests and US$22 for two full blood count/clinical chemistry assays. Therefore the minimum costs of treatment and diagnostics to treat HCV infection were estimated at US$171–360 per-person without genotyping or US$261–450 per-person with genotyping.

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Burden of HCV and access to services in India

90% of patients infected with the hepatitis C virus (HCV) worldwide live in resource-limited settings. The authors were interested in the prevalence of HCV monoinfection and HIV/HCV coinfection, and HCV care received by people who inject drugs in India. 14,481 people who inject drugs were examined from 15 cities throughout India using respondent-driven sampling. The median age of the participants was 30 years and 92·4% were men. The weighted HCV monoinfection prevalence in this population was 37·2% while the HIV/HCV coinfection prevalence was 13·2%. Risk factors for HCV infection were: high lifetime injection frequency, HIV positivity and a high prevalence of people with HIV RNA (>1000 copies/mL) in the community. Of the HCV-positive patients, 5·5% were aware of their status, 3·0% had seen a doctor for their HCV, 1·4% had taken HCV treatment and 0·4% had undetectable HCV RNA levels. Of the 12,128 participants who had never been previously tested for HCV, 50·5% did not get tested because they had not heard of HCV. Of the HCV-positive patients, 34·4% reported harmful or hazardous alcohol use, of whom 50·4% were dependent, and 65·3% reported needle sharing. Therefore there is an urgent need to include resource-limited settings in the global HCV agenda.

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Foodborne outbreak of hepatitis A virus in Germany

In October 2012, a hepatitis A virus (HAV) outbreak causing 83 laboratory-confirmed cases of disease occurred in Lower Saxony, Germany. The authors identified 77 primary and six secondary cases of infection. 50 primary cases were enrolled together with 52 controls matched for age and sex. They found that 82% of the cases and 60% of the controls had consumed products from a particular bakery (odds ratio [OR] 3.09, 95%CI 1.15–8.68). The cases were also more likely to have eaten sweet pastries (OR 5.74, 95%CI 1.46–22.42). Viral isolates from five selected cases and three positively tested surfaces in the bakery were found to have identical nucleotide sequences. One additional identical isolate was found in a salesperson at the bakery that was suffering from a chronic disease necessitating immunosuppressive treatment. It is likely that this salesperson contaminated products while packing and selling. Therefore it is important to assess whether immunosuppressed food handlers are at risk of contaminating food and therefore may benefit from HAV immunisation.

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Management of pregnant women infected with Ebolavirus

The authors report two cases of confirmed Ebolavirus disease in pregnant women who presented at the Médecins Sans Frontières Ebola treatment centre in Guéckédou, Guinea. Both of the women survived. In both cases a decision was made to induce vaginal delivery. The authors present a number of considerations regarding the management of Ebolavirus-infected pregnant women, including the use of amniocentesis and induced delivery, and whether other invasive medical interventions are justified.

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Ebolavirus disease in Freetown, Sierra Leone

Recently a report of 106 patients with Ebolavirus disease who were treated in Kenema, Sierra Leone was published. The authors report on similar data from 631 patients admitted to the Ebola treatment centre in Freetown, Sierra Leone. This centre had a case fatality rate of 31%, less than the 74% rate reported in the previous article. The authors observed a decreasing case fatality rate from 47.7% among the first 151 patients (20th September to 13th October), to 31.7% among the next 126 patients (14th October to 4th November), to 23.4% among the next 304 patients (5th November to 7th December). The most common symptoms reported at the time of admission were: fatigue, anorexia, fever, vomiting and nausea, diarrhoea, muscle pain, joint pain and headache. Patients were typically admitted 3 or 4 days after the onset of symptoms. The patients that died usually did so within 3 or 4 days of admission. Survivors were hospitalised for about 2 weeks. The treatment protocol used was 1 g of ceftriaxone iv BD and 500 mg of metronidazole iv TDS for 72 hours, together with 500 ml of Ringer’s lactate every 8 or 12 hours and 500 ml of dextrose saline (5% and 0.9%, respectively) intravenously every 8 or 12 hours. All patients also received 10 mg of vitamin K and 160 mg of artemether intramuscularly immediately on admission, as well as a 20 mg zinc sulphate OD, 400 mg ibuprofen BD and 10 mg of metoclopramide iv as needed for nausea or vomiting. After the first 3 days, continuing therapy included 400 mg metronidazole TDS for 7 days, 500 mg cefuroxime BD for 5 days, artesunate–lumefantrine combination-therapy OD for 3 days, 400 mg ibuprofen BD and one capsule of nutrition supplement daily.

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One year into the West African Ebolavirus epidemic

Initially from early June to mid-September 2014, the outbreak of Ebolavirus disease (EVD) in Guinea, Liberia and Sierra Leone grew exponentially, with national doubling times of between 16 and 30 days. The authors originally predicted a cumulative total of 21,000 cases in these three countries by November 2nd. However, the outbreak changed course in September with the increase in case incidence halting in Guinea and Sierra Leone and reversing in Liberia. The authors examined the epidemiology up to 14th December and found that in the preceding 4 weeks the number of confirmed or probable cases of EVD ranged from 77 to 154 per week in Guinea, 73 to 138 in Liberia, and 327 to 537 in Sierra Leone. By 14th December there had been a total of 18,625 confirmed, probable or suspected cases in eight affected countries (the three mentioned above, plus Mali, Nigeria, Senegal, Spain and the United States), with 6971 deaths. With the scale-up of case isolation and safe burial measures the case reproduction numbers for all three countries have now fallen to 1. Therefore while the worst fears of persistent exponential growth beyond September were not realised, EVD still presents a huge challenge in the coming year in West Africa.

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Ebolavirus disease in Congo

The seventh reported outbreak of Ebolavirus disease (EVD) in the Democratic Republic of Congo (DRC) began on 26th July 2014. The authors were interested in whether this outbreak was linked to the ongoing outbreak in West Africa. They found that the outbreak began in Inkanamongo village near Boende town in Équateur province and was confined to that province. In total 69 suspected, probable or confirmed cases were reported between 26th July and 7th October 2014, with eight of these cases being in healthcare workers. 49 people died. The reported weekly case incidence peaked in the weeks of 17th and 24th August and has since fallen sharply. Genome sequencing demonstrated that the Zaire species of the Ebolavirus (EBOV) was responsible for the outbreak. This virus shared 99.2% homology with the most closely related variant from the 1995 outbreak in Kikwit in the DRC and 96.8% homology to the EBOV variants that are currently circulating in West Africa. Therefore the current EVD outbreak in the DRC shares clinical and epidemiologic characteristics with previous EVD outbreaks in equatorial Africa. However, the causal agent is a local EBOV variant that is different from the 2014 epidemic in West Africa.

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Cancer and the breakthroughs

A drug made from tree bark is being combined with radiation therapy to cure cancer, experts revealed yesterday.

The ‘double whammy’ has proved 85 per cent effective in laboratory trials.

Last night the treatment was being hailed as a breakthrough in the battle against the disease which kills 133,000 Britons every year.

British experts who made the discovery are already talking of a ‘long-term cure’ for many common types of cancer after seeing astonishing results in a laboratory experiment involving human tumours grown in mice.

The dual treatment could be available to patients within five years.

Dr Barbara Pedley of the Cancer Research Campaign said last night: ‘We are excited by these results. Our trial shows that the combination can give a complete cure.’

The tests covered all the major forms of cancer which produce solid tumours, including bowel, breast, liver and lung.

The drug, called combretastatin, works by destroying the developing blood vessels which tumours generate to supply themselves. Used on its own, however, it leaves a ‘rim’ of cancerous cells at the edge, allowing the disease to return.

Radiation therapy completes the attack on the tumour by ensuring all the leftover cells are killed off. Antibodies with radioactive ‘warheads’ home in on the disease cells and destroy them.

The advance is part of a new generation of ‘targeted’ cancer therapies. Combretastatin, which is derived from the bark of an African bush willow, leaves normal blood vessels untouched.

The dramatic success story came in a study by the Royal Free Hospital and University College Medical School in London, and the Gray Laboratory Cancer Research Trust. The results were published in the journal Cancer Research.

The scientists found that human tumours grown in mice disappeared completely in 85 per cent of cases. The animals were still free of the disease almost a year afterwards.

Dr Pedley, head of tumour biology at the CRC’s targeting and imaging group at the Royal Free Hospital, said: ‘This combination can produce long-term cures.

‘Although we have been mainly looking at colorectal cancer, it works on a very wide range of cancers – all the solid tumours – which includes breast cancer.’

She said scientists believed the outer tumour cells may rely on the body’s normal blood vessels, which is why combretastatin could not kill them.

Experts now hope to start human trials of the combination therapy as the next stage.

Worldwide tests are expected to begin next year. About 200 patients with a variety of cancers would be recruited to centres in the UK and around the world.

If the trials achieve a similar success rate as those with the mice, they would pave the way for the treatment to become widely available, possibly within five years.

Dr Lesley Walker, director of cancer information at the Cancer Research Campaign, said: ‘This good news confirms what we have been saying all along –treatments that directly target cancers and spare normal tissue will be the therapies of the future.

‘As well as improving the effectiveness of treatment, this combination should greatly reduce side-effects.’

More than 220,000 people are diagnosed with cancer each year in Britain.

The latest findings back up early clinical trials involving 34 patients from London who experienced massive tumour shrinkage after taking combretastatin.

They were carried out by Professor Gordon Rustin, director of medical oncology at Mount Vernon Hospital in Middlesex.

He said yesterday: ‘The results from the trial in mice are very exciting because we are actually seeing a cure.’

Molecular diagnostic tests for 15 enteropathogens causing childhood diarrhoea

Microsporidia are a large group of extreme parasites that invade humans and animals and cost great damage for health care systems and in agriculture; over 1,200 species are known. They live inside their host’s cells and have highly specialized features: They are only able to reproduce inside the host’s cells, they have the smallest known genome of all organisms with a cell nucleus (eukaryotes) and they posses no mitochondria of their own (the cell’s power plant). In addition, they developed a specialized infection apparatus, the polar tube, which they use to insert themselves into the cells of their host. Due to their phenomenal high molecular evolution rate, genome analysis has so far been rather unsuccessful: Their great genomic divergence from all other known organisms further complicates the study of their evolutionary lineage.

The UK CVN consists of Specialist Virology Centres (SVC), each of which is located in an academic centre and act as the driving force for virological service provision in that area. Specialist Virology Units (SVU) are smaller laboratories with virological services which are not as wide ranging as those provided by the SVCs. The UK CVN believes it is critical to work closely with district general hospital microbiology laboratories to provide a cost-effective and evidence based virological service. In addition, the UK CVN includes commercial partners with close working relationship with the network.

Super old Current Opinion in HIV and AIDS Copy

Microsporidia are a large group of extreme parasites that invade humans and animals and cost great damage for health care systems and in agriculture; over 1,200 species are known. They live inside their host’s cells and have highly specialized features: They are only able to reproduce inside the host’s cells, they have the smallest known genome of all organisms with a cell nucleus (eukaryotes) and they posses no mitochondria of their own (the cell’s power plant). In addition, they developed a specialized infection apparatus, the polar tube, which they use to insert themselves into the cells of their host. Due to their phenomenal high molecular evolution rate, genome analysis has so far been rather unsuccessful: Their great genomic divergence from all other known organisms further complicates the study of their evolutionary lineage.

The UK CVN consists of Specialist Virology Centres (SVC), each of which is located in an academic centre and act as the driving force for virological service provision in that area. Specialist Virology Units (SVU) are smaller laboratories with virological services which are not as wide ranging as those provided by the SVCs. The UK CVN believes it is critical to work closely with district general hospital microbiology laboratories to provide a cost-effective and evidence based virological service. In addition, the UK CVN includes commercial partners with close working relationship with the network.