Madariaga virus, risky to horses and humans, is an emerging pathogen in Latin America – study

A colourised TEM micrograph of a mosquito salivary gland: The virus particles (virions) of eastern equine encephalitis virus are coloured red.
A colourised TEM micrograph of a mosquito salivary gland: The virus particles (virions) of eastern equine encephalitis virus are coloured red. (83,900x magnification) Image: Fred Murphy and Sylvia Whitfield, Public domain, via Wikimedia Commons

Madariaga virus, a mosquito-borne pathogen that can cause severe illness in horses and humans, is actively circulating in northeast Brazil despite vaccination programs in animals, according to researchers.

Madariaga virus, a member of the eastern equine encephalitis virus (EEEV) complex, likely represents an emerging pathogen in Latin America, scientists report in the journal Pathogens.

Laura Gil and her fellow researchers said disturbances in the natural transmission cycle of the virus result in outbreaks in equines and humans. Many infections in horses prove fatal, and the virus can cause high fever and neurological problems in people.

In Brazil, an outbreak of Madariaga virus, confirmed by molecular-based testing, occurred in 2009 in the states of Paraíba and Ceará, in northeast Brazil. Because of that, health authorities recommended vaccination of animals in these regions.

However, in 2019, an outbreak of equine encephalitis was reported in a municipality in Ceará.

The scientists in this latest study successfully isolated Madariaga virus from two horses that died in this outbreak. They also sequenced the genome of the virus, and described the findings of post mortem examinations.

The authors noted that outbreaks of encephalitis and death in equines caused by South American EEEV strains have been reported in Central and South American countries in past decades, but pathogenicity to humans appears to be considerably lower than North American strains.

Nevertheless, a human encephalitis outbreak of South American EEEV in 2010 in Panama raised questions of whether some local strains were becoming more pathogenic to humans.

In 2010, it was proposed that strains from lineages II–IV should be considered a distinct species within the EEEV complex. The new proposed species received the name Madariaga virus.

In Brazil, impactful equine outbreaks caused by EEEV have been reported in all five Brazilian regions, with the first EEEV isolations having occurred in the 1940s, followed by several reports in the next decades.

The researchers, discussing their study, noted that EEEV outbreaks have also been reported in other regions of north-eastern Brazil, indicating that the virus may be endemic in the region, as it may be in other parts of the country.

“Importantly, even though EEEV vaccination in horses was carried out in Ceará after the 2009 outbreak and no equine encephalitis cases were reported in the following years, the outbreak in 2019 indicates that broad vaccination programs in animals are not being achieved in the region.”

The noted that, although South American EEEV/Madariaga strains have been considered less pathogenic for humans than North American strains, Madariaga infection was confirmed in persons with severe neurological disease during an encephalitis outbreak in Panama in 2010.

Changes in the transmission patterns and virulence are common among mosquito-borne viruses, which have the ability to adapt to new hosts, vectors, and ecological niches, they noted.

The clinical signs observed in the two horses that ultimately died — unsteadiness partial paralysis, circling, knuckling, and recumbency — appear to be common in cases of eastern equine encephalitis. “Other acute signs of EEEV infection that were not observed here include fever, abnormal gait, blindness, head-pressing, paralysis, severe depression, and convulsions.”

They said that although some bird species are susceptible to Madariaga virus infection, it has been suggested that the main amplifying reservoirs may be ground-dwelling mammals.

The outbreak in Panama shed some light on the types of reservoirs involved in the local transmission cycle, as the animal with the highest seropositivity rate was the short-tailed cane mouse.

“Madariaga virus is a potential emerging pathogen in Latin America and the several knowledge gaps regarding its transmission cycle, pathogenicity in different hosts, and attack rates, among others, warrant further research at many levels,” the study team concluded.

Surveillance programs should start considering Madariaga virus as an endemic zoonotic agent in Brazil. It should also be considered a potential cause of acute fevers in humans in Venezuela, Haiti, and Brazil — and not only in cases involving neurological disease.

The study team, from a range of institutions, comprised Gil, Tereza Magalhaes, Beatriz Santos, Livia Oliveira, Edmilson Oliveira-Filho, João Cunha, Ana Fraiha, Brenda Rocha, Barbara Longo, Roselene Ecco, Guilherme Faria, Ronaldo Furtini, Safira Drumond, Renata Maranhão, Zélia Lobato, Maria Isabel Guedes, Raffaella Teixeira and Erica Costa.

Gil, L.H.V.G.; Magalhaes, T.; Santos, B.S.A.S.; Oliveira, L.V.; Oliveira-Filho, E.F.; Cunha, J.L.R.; Fraiha, A.L.S.; Rocha, B.M.M.; Longo, B.C.; Ecco, R.; Faria, G.C.; Furtini, R.; Drumond, S.R.M.; Maranhão, R.P.A.; Lobato, Z.I.P.; Guedes, M.I.M.C.; Teixeira, R.B.C.; Costa, E.A. Active Circulation of Madariaga Virus, a Member of the Eastern Equine Encephalitis Virus Complex, in Northeast Brazil. Pathogens 2021, 10, 983.

The study, published under a Creative Commons License, can be read here

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