UK and Brazilian researchers uncover hidden spread of Zika virus in Brazil and Americas using virus genome sequences

Professor Nick Loman from the University of Birmingham testing zika samples in Brazil.

An international research collaboration has studied the genetics of Zika virus in Brazil and beyond, providing a new understanding of the disease and its rapid spread through space and time.

The research has significant public health implications and has the potential to improve responses to future outbreaks.
The research published today in Nature, was led by the Universities of Birmingham and Oxford in partnership with FioCruz Bahia, the University of São Paulo, and supported by the Brazilian Ministry of Health.

By carrying out genome sequencing to understand the virus’ genetic make-up, the team were able to track the spread of the virus across Brazil. The study showed that Zika’s establishment within Brazil - and its spread from there to other regions - occurred before Zika transmission in the Americas was first discovered. By revealing this ‘hidden’ epidemic, the results will help scientists to better understand the link between the Zika epidemic and reports of birth defects and other diseases.

With little known at the time about the epidemiology and evolution of Zika virus, the researchers travelled 2,000 km across the northeast Brazil in June last year. The team travelled in a minibus, equipped with cutting-edge mobile DNA sequencing capabilities and tested samples from more than 1,300 patients infected with the virus.

In February 2016 Zika was declared a ‘Public Health Emergency of International Concern’ by the World Health Organisation (WHO) in response to evidence that the infection can cause birth defects in the foetuses of infected pregnant women. The virus can be transmitted from an infected pregnant woman to her developing baby, causing problems including severe microcephaly – a condition that results in babies being born with a smaller head size.

Dr. Nuno Faria, of the University of Oxford’s Department of Zoology, said: “Despite there being probably millions of cases of the Zika virus in Brazil, there was only a handful of known virus genomes prior to our work. A better understanding of Zika virus’ genetic diversity is critical to vaccine design, and also to identify areas where surveillance is most needed”.

Professor Oliver Pybus also of the University of Oxford’s Department of Zoology said “We generated Zika virus genomes to establish the virus’ epidemic history in the Americas. We showed that the virus was present in Brazil for a full year prior to the first confirmed cases in May 2015.

“We also found that northeast Brazil, which was the region with the most recorded cases of Zika and microcephaly, was the nexus of the epidemic in Brazil and played a key role in its spread within Brazil to major urban centres, such as Rio de Janeiro and São Paulo, before spreading across the Americas. We now have a better understanding of the epidemiology of the virus.”

During the genome sequencing journey that travelled across Brazil, the researchers used the portable MinION DNA sequencer from the company Oxford Nanopore Technologies, which started as an Oxford University spinout company. The portable device weighs less than 100g and is powered by the USB port of a laptop, so is ideal for cross-country fieldwork.

Professor Nick Loman, of the University of Birmingham’s School of Biosciences, said: “Genome sequencing has become a powerful tool for studying emerging infectious diseases, however, genome sequencing directly from clinical samples without isolation remains challenging for viruses such as Zika.

“We developed a new protocol that allows for real-time genomic sequencing – something of vital importance when managing viral outbreaks as it can provide real insight into how a virus is spreading, transmitting and evolving.

“What’s more, using equipment like portable nanopore sequencing we were able to carry out emergency epidemiological research more quickly, to get immediate results when working in the field, as on the road in Brazil.

“This new protocol will doubtless prove hugely beneficial to researchers working in remote areas around the world during times of viral outbreaks.”

The research project was funded by the Medical Research Council’s Zika Rapid Response Initiative, USAID, and supported by the Wellcome Trust and the Newton Fund. It highlights the importance of creating trusted cross-institutional partnerships and sharing data openly during disease focused research field work.

Prof Luiz Alcantara from FioCruz Bahia, Brazil, said: “The project is now expanding to other geographic areas in Brazil, where we are tackling not only Zika virus but also dengue and chikungunya viruses, as well as the very recent ongoing yellow fever epidemics. The threat posed from viruses transmitted by mosquitos in Brazil is severe and there is a pressing need to better understand their epidemiology in order to prevent their spread.”

As part of a co-operative international effort to share valuable data and results, the report was published together with two companion papers on the genetics and evolution of the Zika virus epidemic.

Zika remains a significant public health threat and the research highlights a need for continued research and surveillance of Zika and other mosquito-tranmitted viruses in Brazil. Together, the papers paint a collective picture of the scale of impact of Zika, offering potential recommendations for future rapid detection and control of virus epidemics.

Ends

For further information or interviews contact:

1. Emma McKinney, Press Office, University of Birmingham, at 0121 414 6681 or e.j.mckinney@bham.ac.uk
2. Lanisha Butterfield, Media Relations Manager, University of Oxford, at 01865 280531 or lanisha.butterfield@admin.ox.ac.uk


Notes to Editors

• Faria et al. (2017). ‘Establishment and cryptic transmission of Zika virus in Brazil and the Americas’ DOI: 10.1038/nature22401
• To access the research paper log onto: http://nature.com/articles/doi:10.1038/nature22401
• The Zika virus was first isolated in 1947, in a rhesus monkey in a forest near Entebbe, Uganda. Although serologic evidence indicated additional human exposure during subsequent decades in parts of Africa and Asia, before the 2007 Yap Islands Zika virus outbreak, only 14 cases of human Zika virus disease had been documented.
• In approximately one in five cases, Zika virus infections result in Zika fever, a minor illness that causes symptoms such as fever and a rash.
• The virus is spread mainly by the Aedes aegypti mosquito, which is commonly found throughout the tropical and subtropical Americas. It can also be spread by the Aedes albopictus "Asian tiger" mosquito, which is distributed as far north as the Great Lakes region in North America. Men infected with Zika can transmit the virus to their sexual partners.
• The University of Birmingham is ranked amongst the world’s top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, teachers and more than 5,000 international students from over 150 countries.
• The Mathematical, Physical and Life Sciences Division (MPLS) is one of four academic divisions at the University of Oxford, representing the non-medical sciences. Oxford is one of the world’s leading universities for science, and MPLS is at the forefront of scientific research across a wide range of disciplines. Research in the mathematical, physical and life sciences at Oxford was rated the best in the UK in the 2014 Research Excellence Framework (REF) assessment. MPLS received £133m in research income in 2014/15.