Sunday, January 31, 2016

EID Journal: Zika's Evolution And Spread To The Western Hemisphere

Credit ECDC

Epidemiological update

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Epidemiological update

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The parallels between the evolution and progression of Zika and Chikungunya are nothing less than striking. 

Until the middle of the last decade both were relatively obscure, neglected tropical diseases, which were limited to sparking small low-impact outbreaks in east and central Africa. Both produced (generally mild) dengue-like symptoms, and both launched themselves on their respective world tours around the same time via the Indian Ocean/Pacific island route.

Chikungunya was the first out of the gate, making a surprise leap to the Indian Ocean island of RĂ©union in 2005. There, it infected nearly 1/3rd of the island’s 770,000 residents (see 2006 EID article Chikungunya Disease Outbreak, Reunion Island) in just a matter of months.

From there it quickly cut a swath across the Indian ocean, into southeast Asia, and into the Pacific.

It arrived on the  French Part of St. Martins in the fall of 2013, likely carried in by an infected tourist, and quickly spread across the Caribbean and into South and Central America. In the two years since it arrived in the Americas, it has likely infected more than 2 million people.

Zika appears to have arrived in Brazil in 2014, probably carried in by a viremic visitor from the South Pacific, where the virus had slowly been spreading since 2007 (see 2009 EID Journal Zika Virus Outside Africa by Edward B. Hayes).

As its symptoms are generally milder than both CHKV and Dengue, it wasn't until the summer of 2015 that Brazil recognized it was in the midst of a Zika epidemic.

But by October it was reported in Columbia, and over the next four months, it appeared in more than 2 dozen countries and territories across the Caribbean, South and Central America. It is likely already present in many other regions, but has yet to be picked up by surveillance. 

It has only been since November that suspicions have been raised that Zika infection might not be quite as benign as previously believed (see WHO To Convene IHR Emergency Committee Meeting On Zika).

This rapid spread, and possible shift in virulence, has led to speculation that the Zika virus has changed somehow from its milder African version; transmitting more efficiently via mosquitoes or perhaps replicating more efficiently in human hosts.  

Nearly two months ago, in Paper: Zika Adaptations To Humans Helped Spark Global Spread, we looked at a study - yet to be peer reviewed - by researchers at the University of Sao Paulo and the Pasteur Institute of Dakar (Senegal) who believe they have uncovered genetic changes in the Zika virus that occurred after the virus reached the South Pacific in 2007, that may make it better adapted to human physiology.

While we've yet to see any definitive proof that such a change has occurred, in the past few days the subject has come up repeatedly in the media.

A few days ago the Harvard University School of Public Health ran an article called Zika virus in Brazil may be mutated strain while the New Scientist recently carried a report called Did Zika’s recent mutations let it explode as a global threat?

Today, a report from the Anadolu Agency also touches on this idea, with an interview with a Ugandan researcher who believes the virus has adapted to humans during its trek across the Pacifc.

Uganda virus expert says Zika adapting to humans

A top scientist at the Uganda-based facility that first identified the Zika virus has told Anadolu Agency that the bug is multiplying and becoming more adaptable to humans.

Dr. Julius Lutwama, senior principal research officer at the Uganda Virus Research Institute, said the virus outbreak in the Americas can only be reduced by supportive treatment and through controlling disease-carrying mosquitoes.

“There are two strains of the Zika virus, which include the African Zika virus and the Asian strain, which are slightly different,” he said.

“The strain that is causing problems in the Americas comes from Asia, went to Micronesia, Polynesia and moved to South America.” 

Again, all of this is far from settled science, but it is worth noting that CHKV appears to have benefited from a mutation in the middle of the last decade that allowed it to spread more  efficiently by the Aedes Albopictus mosquito (see A Single Mutation in Chikungunya Virus Affects Vector Specificity and Epidemic Potential).

We have, quite frankly, very little research in the literature on Zika - at least when you compare it to what's available for Dengue, Chikungunya, or West Nile Virus.  That will change over time, now that Zika is viewed as potentially more dangerous than previously believed, but good research takes time. 

Below you'll find an early example, via the CDC's EID Journal. A letter reviewing the expansion of Zika out of Africa (and its similarities to CHKV), along with phylogenic analysis of early samples collected in the Americas.

It doesn't answer the question as to whether the virus has recently `adapted' to humans or mosquitoes, but it does find the Zika virus has evolved into 3 distinct genotypes (East Africa, West Africa, and Asia) and that the Asian genotype is the one that has arrived in the Americas.

Follow the link to read:

Volume 22, Number 5—May 2016


Phylogeny of Zika Virus in Western Hemisphere, 2015

To the Editor: Zika virus (ZIKV) belongs to the genus Flavivirus, family Flaviviridae, and is transmitted by Aedes spp. mosquitoes. Clinical signs and symptoms of human infection with ZIKV include fever, headache, malaise, maculopapular rash, and conjunctivitis.
ZIKV was first isolated in 1947 from the blood of a febrile sentinel rhesus monkey during a study of yellow fever in the Zika Forest of Uganda (1). During the next 20 years, ZIKV isolates were obtained primarily from East and West Africa during arbovirus surveillance studies in the absence of epidemics. During those 20 years, cases of ZIKV infection were detected sporadically; however, given the clinical similarity of ZIKV and dengue virus infections and the extensive cross-reactivity of ZIKV antibodies with dengue viruses, it is possible that ZIKV was associated with epidemics that were incorrectly attributed to dengue viruses. Beginning in 2007, substantial ZIKV outbreaks were reported first in Yap Island (Federated States of Micronesia), then in French Polynesia, and then in other Pacific Islands (24).

Genetic studies have revealed that ZIKV has evolved into 3 distinct genotypes: West African (Nigerian cluster), East African (MR766 prototype cluster), and Asian. It has been postulated that the virus originated in East Africa and then spread into both West Africa and Asia ≈50–100 years ago (5). In early 2015, cases of ZIKV infection were detected in Rio Grande State, northern Brazil, and limited sequence analyses revealed that the virus was most closely related to a 2013 ZIKV from French Polynesia, within the Asian clade (6).


As reported by Musso et al. (8), the phylogeny and movement of ZIKV and chikungunya virus are strikingly similar. Each virus is grouped into 3 genotypes of very similar geographic distribution: East Africa, West Africa, and Asia. For both viruses, it also seems that viruses from East Africa moved into Asia ≈50–100 years ago and evolved into a unique Asian genotype (9,10). In addition, the similarity with respect to the recent movement of these viruses from Asia into the Pacific Islands and then into the New World (9) is noteworthy. It seems that similar ecologic and/or human social factors might be responsible for the movement of chikungunya virus and ZIKV into the New World at approximately the same time. 

Further studies might elucidate the exact mechanism of this transcontinental movement, leading to effective prevention strategies.

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