Identification and Characterization of a Novel Echarate Virus Variant Causing Acute Febrile Illness in Central Peru

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The genus Phlebovirus, belonging to the order Bunyavirales and family Phenuiviridae, comprises 66 species, globally distributed and transmitted by various vectors such as sandflies, mosquitoes, or ticks. Among them, sandfly phlebovirus can cause a spectrum of symptoms, ranging from unspecific to severe manifestations, often leading to misdiagnosis.

In Peru, Echarate virus (ECHV), Maldonado virus, and Candiru virus are known phleboviruses causing febrile illnesses.

Patient Presentation and Background

In June 2019, a 20-year-old man working in civil construction was admitted to Hospital Regional Docente de Medicina Tropical Julio César Demarini Caro in Chanchamayo, Peru. The patient presented with a 2-day history of fever, malaise, chills, muscle pain, headache, and other symptoms commonly associated with febrile illnesses. The clinical presentation resembled diseases like dengue, malaria, and influenza. The patient’s blood samples were subjected to laboratory analysis and further investigations.

Laboratory Analysis and Sequencing

Under passive clinic-based surveillance for acute febrile illness (AFI) approved by Peru’s Ministry of Health and the US Naval Medical Research Unit South Institutional Review Board, the patient’s acute serum sample was inoculated into Vero and C6/36 cells. The Vero cells showed cytopathic effects, indicating a viral infection. Indirect immunofluorescence assays (IFA) using pooled polyclonal antisera identified the presence of a bunyavirus.

Subsequent molecular characterization involved RNA extraction, whole-genome sequencing using unbiased approaches (SISPA and WTA), and bioinformatics analysis using EDGE Bioinformatics tools, VirusSeeker, and MetaDetector.

Genomic Characterization and Phylogenetic Analysis

The sequencing results revealed a novel variant of Echarate virus, designated as the ECHV variant (Chanchamayo–Junín). The genomic analysis indicated high amino acid identity with ECHV, specifically >95% for the large and small segments. However, the medium (M) segment showed 76.5% nucleotide identity and 86.36% amino acid identity with ECHV.

The predicted NSm sequence of the isolated virus exhibited 78.6% identity with ECHV. Phylogenetic analyses demonstrated the new variant’s placement within the Candiru virus complex, closely related to ECHV but forming a distinct clade in the NSm and glycoprotein trees.


TABLE 1 – Echarate Virus: A Detailed Report

The Echarate virus (ECHV) belongs to the genus Phlebovirus within the family Phenuiviridae. Phleboviruses are arthropod-borne viruses (arboviruses) transmitted by phlebotomine sandflies, mosquitoes, or ticks. ECHV was first identified in 1959 in Peru and has since been detected in several other countries in South America, including Bolivia, Ecuador, and Brazil.

Genome and structure:

ECHV is a negative-sense, single-stranded RNA virus with three segments: L (large), M (medium), and S (small). The L segment encodes the RNA-dependent RNA polymerase, the M segment encodes the glycoproteins, and the S segment encodes the nucleocapsid protein.

Transmission:

ECHV is primarily transmitted by the bite of infected phlebotomine sandflies. Sandflies are small, nocturnal insects that feed on the blood of humans and animals. When a sandfly bites an infected animal, it takes up the virus in its blood meal. The virus then replicates in the sandfly’s gut and salivary glands. When the sandfly bites another animal, it can transmit the virus through its saliva.

Clinical symptoms:

ECHV infection can cause a range of clinical symptoms, including:

  • Fever
  • Headache
  • Muscle aches
  • Fatigue
  • Nausea and vomiting
  • Diarrhea
  • Skin rash
  • Aseptic meningitis (inflammation of the membranes surrounding the brain and spinal cord)
  • Encephalitis (inflammation of the brain)

In some cases, ECHV infection can be fatal.

Diagnosis:

ECHV infection can be diagnosed by a variety of methods, including:

  • Virus isolation: This involves isolating the virus from a patient’s blood or other tissue samples.
  • Reverse transcription polymerase chain reaction (RT-PCR): This is a sensitive and specific test that can detect the presence of ECHV RNA in a patient’s blood or other tissue samples.
  • Serological tests: These tests detect antibodies to ECHV in a patient’s blood.

Treatment:

There is no specific treatment for ECHV infection. Treatment is supportive and may include:

  • Rest
  • Fluids
  • Pain relievers
  • Anti-inflammatory medications

In severe cases, patients may require hospitalization and intensive supportive care.

Prevention:

There is no vaccine available to prevent ECHV infection. However, there are a number of things that people can do to reduce their risk of infection, including:

  • Using insect repellent containing DEET when outdoors
  • Wearing long sleeves and pants when outdoors
  • Using mosquito nets
  • Avoiding areas where sandflies are common
  • Controlling sandfly populations

Recent findings:

A recent study published in the journal Emerging Infectious Diseases reported the identification of a novel ECHV variant isolated from a patient with acute febrile illness in Peru. The virus was found to be a natural reassortant of the Echarate virus (large and small segments) with a yet-unidentified phlebovirus (M segment). This finding highlights the importance of continued surveillance and research on ECHV and other phleboviruses.

Future directions:

Further research is needed to develop a better understanding of the epidemiology, pathogenesis, and treatment of ECHV infection. Additionally, research is needed to develop a vaccine to prevent ECHV infection.

Conclusion:

ECHV is an emerging arbovirus that can cause a range of clinical symptoms, including fever, headache, muscle aches, fatigue, and in severe cases, aseptic meningitis or encephalitis. There is no specific treatment for ECHV infection, and prevention is based on avoiding sandfly bites. Continued surveillance and research are needed to develop a better understanding of ECHV and to control its spread.

References:


Conclusions and Public Health Implications

This study unveils the existence of a novel Echarate virus variant in the jungle of central Peru, emphasizing the importance of ongoing AFI biosurveillance to detect emerging pathogens. The clinical symptoms of the new variant overlap with other prevalent tropical diseases, necessitating continuous monitoring for timely identification and appropriate public health responses. Ecologic studies are urged to understand the variant’s prevalence, potential vectors, and reservoirs, crucial for ensuring the health and safety of the population and US service members deployed in affected areas in Peru.

Acknowledgment

Ms. Troncos, a research technician at the Virology and Emerging Infections Department of the US Naval Medical Research Unit SOUTH, Lima, Peru, contributed to the identification and characterization of viruses causing illnesses in humans.


reference link: https://wwwnc.cdc.gov/eid/article/29/9/23-0374_article

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