Zika: Improved diagnostics for Zika virus infection in South America through an established laboratory partnership between Brazil, Colombia and the UK.

Lead Research Organisation: University of Liverpool
Department Name: UNLISTED

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Technical Summary

Accurate diagnostics for Zika virus (ZIKV) underpins all public health responses and
epidemiology studies of the outbreak. Currently available diagnostics: nucleic acid
amplification tests (NAAT) and antibody ELISA, have critical problems [1]. NAAT are
potentially highly sensitive. However, ZIKV is cleared rapidly during recovery (often within 1
week), limiting the time post-infection NAAT can usefully be used. ELISAs, IgM and IgG,
detect antibody reponses to ZIKV over a longer time-frame. However, they exhibit reduced
specificity through cross-reactivity against other flaviviruses, e.g. dengue, circulating in
South America. Guidance from WHO, CDC and ECDC caution interpretation of these tests [2].
We aim to refine and validate more specific serological tests (Plaque Reduction Neutralisation
Test [PRNT] and Non-structural protein 1 [NS1] ELISA) and assess the time-frame postinfection
that portable NAAT provide accurate diagnosis. This will be achieved through an
established partnership between the Health Protection Research Unit in Emerging and
Zoonotic Infections (HPRU-EZI), Public Health England, Fiocruz (Rio,Brazil) and Laboratorio
de Virología (Colombia).
OBJECTIVES
1. Establish and confirm diagnostic accuracy of new serological tests;
a) ZIKV PRNT (most specific serological test for ZIKV).
b) ZIKV NS1 ELISA (reduced cross-reactivity with other flaviviral antibodies).
2. Field validation of new rapid ZIKV point-of-care NAAT.
OUTPUTS
Tests, protocols and training will be available to local laboratory networks for patient use and
to support further diagnostic studies.
OUTCOMES
Fiocruz and Laboratorio de Virología provide central diagnostic services for their national
public health teams. Tests and training will strengthen diagnostic services, and improve
management of suspected ZIKV patients.

People

ORCID iD

Publications

10 25 50
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Brasil P (2016) Zika Virus Infection in Pregnant Women in Rio de Janeiro. in The New England journal of medicine

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Soares CN (2016) Fatal encephalitis associated with Zika virus infection in an adult. in Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology

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Balmaseda A (2017) Antibody-based assay discriminates Zika virus infection from other flaviviruses. in Proceedings of the National Academy of Sciences of the United States of America

 
Title Books and Leaflets for families with children with congenital zika Virus - 3 books/leaflets produced (online and paper copies produced) 
Description Three booklets were produced and distributed among families with Children with congenital Zika Syndrome. The books were a pictorial guide displaying the problems children with congenital infection syndromes, such as Congenital Zika Syndromes can suffer. The booklets also included practical advice on how to promote child stimulation and how to construct toys to stimulate , engage and develop the abilities of children with congenital difficulties. 
Type Of Art Artwork 
Year Produced 2017 
Impact Very positive feedback received. Material was shared and distributed through social media. High level of engagement of families from all backgrounds. 
URL https://movimentozika.org.br/
 
Title Music play therapy for children with Congenital Zika Syndrome 
Description Production of audio clips and films exhibiting the positive value of music for Children with Congenital Zika Syndrome. The videos display how children can actively participate, enjoy and be stimulated by both the production of music and exposure to music. Videos capture relaxation and enjoyment of children involved in creating/listening to the music. Videos capture relaxation carers involved in the events. 
Type Of Art Film/Video/Animation 
Year Produced 2017 
Impact Families reported relaxation of children involved in creating/listening to the music. Families also reported how these activities reduced 'stress' felt by the carers. 
 
Title Use of Art and theatre to improve understanding around Congenital Zika Syndrome and Zika Virus 
Description Production of Artwork by families with children affected by Congenital Zika Syndrome as an exercise to discover and learn more about zika virus. Artwork was later exhibited in NGO facilities. 
Type Of Art Artwork 
Year Produced 2017 
Impact Improvement of the levels of knowledge and understanding of these families. Very positive feedback. Outstanding results. More interest around the science of Zika Virus gained. 
 
Title Video tutorials of supportive activities for Children with congenital Zika Syndrome 
Description Production of short video tutorials (5mins) casting carers showing how to perform activities (such as physiotherapy / stretches/ music stimulation / play stimulation) to support development and relaxation of children with congenital Zika Syndrome. Tutorials were performed at two sites in Brazil: Pernambuco and Rio de Janeiro. Development of a series of of short video tutorials that can be disseminated via the families WhatsApp and facebook networks. 
Type Of Art Film/Video/Animation 
Year Produced 2017 
Impact Carers report gaining new skills and confidence in managing their children. Carers report decreased sense of 'stigmatisation, isolation and helplessness in meeting carers with similar problems, being able to share these problems and disseminate useful skills. 
 
Description The study demonstrated cross-reactivity in ELISA testing between Zika and Dengue virus. The study and subsequent publications have been referred to clinical teaching (such as the annual Neuro-ID course) to clinicians and microbiologists to be aware of the pitfalls in diagnostic testing of viruses (particularly flaviviruses) using ELISA, and to consider use of plaque reduction neutralisation testing to confirm elisa results.
First Year Of Impact 2021
Sector Healthcare
 
Description Influence on use/interpretaion of serological diagnostic assays for Zika
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Influenced Training of Medical Students and Postgraduate Students on Practice - Recife, Brazil
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
Impact Extensive Training was provided to groups of Medical Students as well as postgraduate students of Occupational Therapy and Physiotherapy on Zika Virus, Congenital Zika Virus and understanding the challenges of the diagnosis of Zika virus.
 
Description COVID-19 Neurological Disease: a Global Meta-Analysis and Prospective Case Control Study in Brazil, India and Malawi.
Amount £869,860 (GBP)
Funding ID MR/V033441/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 10/2020 
End 04/2022
 
Description EUROPEAN COMMISSION DIRECTORATE-GENERAL FOR RESEARCH & INNOVATIO
Amount € 11,000,000 (EUR)
Funding ID 734584 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 10/2017 
End 09/2020
 
Description European Society of Clinical Microbiology and Infectious diseases - Young Scientists Attendance Award
Amount $500 (USD)
Organisation Infectious Diseases Society of America 
Sector Academic/University
Country United States
Start 02/2017 
End 04/2017
 
Description NIHR Health Protection Research Unit in Emerging and Zoonotic Infections - Public Engagement Award
Amount £600 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 03/2017 
End 03/2018
 
Description Porterfield Prize in International Virology
Amount $1,000 (USD)
Organisation University of Oxford 
Department Sir William Dunn School of Pathology
Sector Academic/University
Country United Kingdom
Start 02/2017 
End 02/2018
 
Title Hand Held PCR Portable Machine for Arboviral Diagnosis 
Description Tested, improved and optimize a new assay using a portable PCR machine for Zika virus Diagnosis using body fluid samples. equipment tested in local environment in South America. Work carried out in collaboration with PHE and Fiocruz, Brazil. Research equipment provided to FIOCruz. 
Type Of Material Technology assay or reagent 
Year Produced 2016 
Provided To Others? Yes  
Impact Development and assessment of rapid diagnostic assays for Zika virus diagnosis that could be used in the field instead of a laboratory. 
 
Title Pathogen Specific PCR development in Fiocruz, Recife, Brazil 
Description Building on our Brazilian research links developed during our Zika Grant and the activities undertaken in our Indonesia award, we are working with the Virology unit, within Fiocruz, Recife, Brazil top broaden their Pathogen Specific PCR diagnostics, to detect a range of viruses and bacteria associated with central nervous system infections (meningitis/encephalitis). The methods being introduced in Fiocruz are based on the protocols developed as part of our Indonesia award. 
Type Of Material Technology assay or reagent 
Year Produced 2019 
Provided To Others? No  
Impact Once established the tool will be available to clinicians based in Brazilian hospitals to help guide management of suspected meningo-encephalitis 
 
Title Large Dataset with Arboviral diagnostic results from Brazilian population 
Description Unique collection of data of over 300 patient samples with flavivirus exposure (Zika, Dengue, Yellow fever etc). Arboviral diagnostic assays were performed by our team and results were appended into database. Relevant demographics were also included. This database is currently accessible to the research team. We aim to acquire further funding to develop this into a more accessible online database for local laboratories another research groups. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact Publication under review. (MG et al., 2017 ) Various oral presentations at National and International Conferences. Poster presentation at National Conference. Database shared with Brazilian Collaborators. 
 
Description Collaboration in Recife (Brazil) Uniao de Maes dos anges 
Organisation Union of Mothers of Angels
Country Brazil 
Sector Charity/Non Profit 
PI Contribution We organized workshops for families affected by Congenital Zika Syndrome which are members of this NGO on public health and Zika virus and diagnosis to support their understanding around zika virus. Families affected by Congenital Zika Virus and related complications benefited from it.
Collaborator Contribution Uniao de Maes de anjos joined very positively the workshops, talks, lectures and activities organized. Their main office was used for the organization of these activities. Their feedback and suggestions were used in the development of more targeted public health messages.
Impact Social Impact on the organization of this charity. More than 450 families have benefited from this public health support. Training of soft skills of local professionals from different areas.
Start Year 2016
 
Description Liverpool - Hospital Federal Dos Servidores de Estado (Rio de Janeiro, Brazil) 
Organisation Hospital Federal dos Servidores do Estado
Country Brazil 
Sector Hospitals 
PI Contribution Training to the team of physicians on the adequate diagnostic algorithm for each type of case. Training on body fluids material handling for keeping good samples for arboviral diagnosis and immunological work. Strengthen the arboviral diagnosis for their cases. Provided extra diagnostic assay results for their cases with suspected Zika virus infection Planned future work
Collaborator Contribution Provided relevant human body fluid samples for diagnostic development and optimization Provided relevant human body fluid samples for arboviral diagnosis. Contribute on expanding our network of collaborators in Rio de Janeiro (develop a network of 12 hospitals that collaborate)
Impact - Meeting organized in Pernambuco involving members from Liverpool and Hospital Federal do Servidores do Estado - Publication: Cristiane N. Soares, Patrícia Brasil, PhD, Raquel Medialdea Carrera, et al. (2016) Fatal encephalitis associated with Zika virus infection in an adult - Further work planned -Better arboviral laboratory diagnostic support provided to the patients attending this public hospital.
Start Year 2016
 
Description Liverpool - PHE 
Organisation Public Health England
Country United Kingdom 
Sector Public 
PI Contribution development of research methodology in refining PRNT for ZIka shared personnel shared expertise shared resources - CL3 facilities / clinical samples
Collaborator Contribution development of research methodology in refining PRNT for ZIka shared personnel shared expertise shared resources - CL3 facilities / clinical samples shared expertise
Impact See section on medical products
Start Year 2016
 
Description Liverpool -Fiocruz Recife (Pernambuco) 
Organisation Oswaldo Cruz Foundation (Fiocruz)
Department Fiocruz Pernambuco
Country Brazil 
Sector Hospitals 
PI Contribution Provide training and advice for diagnosis of arboviral disease using body fluids. Exchange of laboratory protocols and harmonize the diagnostic algorithms for Zika and Chikungunya diagnosis Strengthen the online storage of diagnostic results Various visits to the institution and laboratory by various team members Planned further work together
Collaborator Contribution Exchange of laboratory protocols Training and expertise on immunology of Zika virus for its use in developing better diagnosis Planned further work together
Impact Various large meetings and seminars involving members of different institutions in Pernambuco working with Zika. Multi-disciplinry collaboration involving physicians, epidemiologists, virologists and immunologist.
Start Year 2016
 
Description Liverpool- Cali (Colombia) 
Organisation Fundacion Clinica Valle del Lili, Cali
Country Colombia 
Sector Hospitals 
PI Contribution sharing of clinical/laboratory expertise
Collaborator Contribution sharing of clinical / diagnostic expertise
Impact Sharing of clinical resources. Enables us to begin to develop an inter-country resource of clinical samples for future research and diagnostic test validation/assessment in South America
Start Year 2017
 
Description Liverpool- Oswaldo Cruz Institute (Rio de Janeiro, Brazil) 
Organisation Oswaldo Cruz Foundation (Fiocruz)
Department Flavivirus Laboratory
Country Brazil 
Sector Charity/Non Profit 
PI Contribution Development of methods for robust / accurate assessment of arboviral diagnostic assays Sharing of laboratory techniques Sharing of personnel - Liverpool PhD student attached to Oswaldo Cruz Institute in laboratory in Rio Provision of laboratory equipment (mobile PCR units) Provision of laboratory consumables (beyond project aims)
Collaborator Contribution Diagnostic and laboratory support Sharing of laboratory personnel in (Fiocuz Rio and Recife) Engagement / involvement of clinical personnel from Fiocruz and other hospitals in Rio and Recife (Brazil) and Calle (Colombia) Sharing of laboratory resources in Fiocriz Rio and Recife Sharing of clinical / sample resources
Impact Grant award - Zika Preparedness Latin American Network / ZikaPLAN European Commission - 7million EUR One publication - co-author Raquel Medialdea-Carrera (PhD student). Brasil P et al. Zika Virus Infection in Pregnant Women in Rio de Janeiro. N Engl J Med. 2016 Dec 15;375(24):2321-2334. DOI: 10.1056/NEJMoa1602412 Two manuscripts under review:- "The challenge of Zika virus diagnosis after acute infection  -  anti-Zika virus NS1 antibody ELISAs exhibit poor accuracy in Brazilian patients". Emerging Infectious Diseases "The spectrum of neurological disease associated with Zika and chikungunya viruses in adults in Rio de Janeiro, Brazil: a case series." Lancet Global Health
Start Year 2016
 
Description Saúde Crianca - Brazilian NGO 
Organisation Saúde Criança Association
Country Brazil 
Sector Charity/Non Profit 
PI Contribution Collaboration to conduct a series of workshops to support families affected by Zika Virus and to provide advice regarding diagnostic testing. We supported this NGO and advised this NGO on how best to manage this group of patients.
Collaborator Contribution Workshops were organized in the facilities of this organization. The organization contacted with some of the families affected by Zika Virus to benefit from this public health expert support.
Impact Over 12 different professionals came to work together. Great capacitation and cascade of training. Over 80 different families from the Estate of Rio de Janeiro have benefited.
Start Year 2017
 
Title Refinement of Zika PRNT diagnostic assay 
Description Refinement of plaque reduction neutralisation test (PRNT) for Zika virus Refined methodology to speed up read-out from PRNT Refined methodology to reduce inter and intra user variation in test Translating refined methodology back to local (South American) laboratories to establish as Zika diagnostic reference test 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2017
Development Status Actively seeking support
Impact None as yet. Potential to lead to establishment of more sustainable / reliable PRNT in local laboratories. In current absence of alternative accurate serological could improve accuracy of diagnosis of Zika patients - particularly among patients presenting after 10 days from acute illness (when PCR for Zika virus unreliable). This would be particularly useful for patients with neurological complications of Zika or mothers of suspected newborn microcephaly cases (both patient groups often present after 10 days from acute illness). 
 
Description Activities in Rio with Movimento Zika - NGO 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Three workshops were organized for families and public affected by Congenital Zika Syndrome in Rio de Janeiro in collaboration with the NGO Movimento zika. Workshops were led by health professionals, scientists and creative artists. Topics of discussion included public health advice, making a diagnosis and the science behind Zika and Congenital Zika syndrome.
Year(s) Of Engagement Activity 2017
 
Description Article in Spanish Newspaper 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Article written by one of the researchers working in this project about the Zika work and results.
Year(s) Of Engagement Activity 2017
URL https://elpais.com/elpais/2017/12/18/planeta_futuro/1513624563_747984.html
 
Description Article in journal for the general public 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Article published in the magazine the conversation about Zika and zika Virus Diagnosis focused on the General Public
Year(s) Of Engagement Activity 2017
URL https://theconversation.com/four-reasons-why-we-shouldnt-forget-about-zika-75257
 
Description Articles on Zika published in Newspaper 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact RMC, PhD student whose work was supported by this grant published in national Spanish newspapers various articles for the general public. This work contributed changing the views regarding managing of Zika virus cases in Spain as well as educating the general population. This work was also distributed in other Spanish speaking coutries
Year(s) Of Engagement Activity 2016
URL http://www.lne.es/sociedad/2016/07/27/zika-enemigo-embarazadas/1961759.html
 
Description Articles regarding Zika virus published in online magazin 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact RMC, PhD student whose work was supported by this grant published in a well-known online Magazine articles regarding Zika virus.
Good feedback received and further new collaborations stablished. Strong interest among members of the general public concerned about the risks of Zika virus infection.
Year(s) Of Engagement Activity 2016
URL http://colefcafecv.com/wp-content/uploads/2016/09/art6.24.pdf
 
Description Biotechnology Meeting Point (Spain) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Talk given by RMC, PhD whose work was supported by the MRC grant, at the International Biotechnolgy Congress of Spain as part of the Biotechnology Meeting Point. Talk given on research experience and pathways to get exposure to science for the benefit of the general public.
Year(s) Of Engagement Activity 2016
 
Description British National Science and Engineering Week Workshops 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact We organized workshops and interactive activities for children from disadvantaged schools. Great discussion and engagement. Reported very positive feedback and increased interest in biology.
Year(s) Of Engagement Activity 2007,2015,2016,2017
 
Description Engagement and impact in Article in The Guardian 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Article published in The Guardian describing one of the NGO groups we partner with in Brazil (UMA) and the collaborative work we do. Readers of the article have since contacted to ask how they can support / get involved helping families with congenital Zika syndrome.
Year(s) Of Engagement Activity 2018
URL https://www.theguardian.com/global-development/2018/feb/05/zika-virus-heavy-toll-families-brazil-rec...
 
Description Infectious Science (talks) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact We organized 3 Infectious Science events that consist in scientific talks in a well-known pub in Liverpool. Six expert researchers give talks at each event to a general audience. Aproximately 70 individuals have come to each of our events.
Rerported very strong interest, public wants this events to be organized more frequently. Reported high engagement with science and increased interest in learning and being involved. Great success of having large amounts of non-scientists among the public.
Year(s) Of Engagement Activity 2016,2017
URL https://www.facebook.com/events/386141618422637
 
Description Meet the Scientist at the Museum Event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact We organized an exhibition and brief interactive experiments in the World Museum in Liverpool on April 2016 and January 2017. Hundreds of children and their families came to learn about our research, our outputs and the impact of our work. Children had the opportunity to engage and learn in an enjoyable way. We received a really good feedback.
Year(s) Of Engagement Activity 2016,2017
URL https://www.liverpool.ac.uk/health-and-life-sciences/meet-the-scientists
 
Description Online publication for World Defects Day 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Video of workshops undertaken by our Zika Engagement and Support Team (ZEST) in Brazil for Congenital Zika syndrome children and their families was presented on global birth defects website (https://globalbirthdefects.tghn.org/) as part of Birth Defects day.
Year(s) Of Engagement Activity 2019
URL https://globalbirthdefects.tghn.org
 
Description Workshops organized with Families with children with Congenital Zika Syndrome ini Recife, Brazil 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact A series of workshops were organized in collaboration with the NGO Uniao de Maes dos Anjos (UMA). UMA is a group of families of children with Congenital Zika Syndrome, based in Recife (Pernambuco region of Brazil). Workshop topics included Zika Virus, Diagnosis of Zika and Congenital Zika Syndrome. Workshops were led by a variety of professionals, including health professionals, psychologists, musicians and artists and postgraduate medical students. Over 300 families have been directly reached by the workshops. Again, we have received very positive feedback verbally and in response to questionnaire. Families reported change in opinion and behaviour following attendance of workshops. Carers report gaining new skills and confidence in managing their children. Carers report decreased sense of stigmatisation, isolation and helplessness in meeting carers with similar problems, being able to share these problems and discuss/develop positive strategies/approaches. Postgraduate Medical students reported value of close engagement with families to better understand the challenges (medical, social and economic) these families faced. Families sent us videos of their children performing new range of activities following workshop attendance. Families requested participation in further workshops and recommended attendance to other families within their networks. Videos of the workshops were recorded. These will act as training videos for other families affected by Congenital Zika, disseminated by their 'WhatsApp' and 'facebook' networks. In collaboration with UMA we continue providing the workshops after the research funding ended.
Year(s) Of Engagement Activity 2017,2018,2019
URL https://pt-br.facebook.com/uniaodemaesdeanjos
 
Description Workshops with families affected by Zika in Rio de Janeiro 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact A series of activities and workshops for families (children/carers) impacted by congenital Zika. Topics included Zika Virus, Diagnosis of Zika and Congenital Zika Syndrome were organized in Rio de Janeiro in collaboration with the NGO Saude Crianca. The activities were led by a variety of professionals, including health professionals, musicians and artists. We received very positive feedback verbally and in response to questionnaire. Families reported change in opinion and behaviour following attendance of workshops. Families requested participation in further workshops and recommended attendance to other families within their networks. Videos of the workshops were recorded. These will act as training videos for other families affected by Congenital Zika, disseminated by their 'WhatsApp' network. In collaboration with Saude Crianca we continue providing the workshops after the research funding ended.
Year(s) Of Engagement Activity 2017,2018,2019
URL https://www.liverpool.ac.uk/infection-and-global-health/public-engagement/zika-engagement/