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A New Phlebovirus Associated with Severe Febrile Illness in Missouri (N Engl J Med., abstract, edited)

Giuseppe

Emeritus
[Source: The New England Journal of Medicine, full page: (LINK). Abstract, edited.]

Original Article

A New Phlebovirus Associated with Severe Febrile Illness in Missouri


Laura K. McMullan, Ph.D., Scott M. Folk, M.D., Aubree J. Kelly, M.S., Adam MacNeil, Ph.D., Cynthia S. Goldsmith, M.G.S., Maureen G. Metcalfe, B.S., Brigid C. Batten, M.P.H., C?sar G. Albari?o, Ph.D., Sherif R. Zaki, M.D., Ph.D., Pierre E. Rollin, M.D., William L. Nicholson, Ph.D., and Stuart T. Nichol, Ph.D.

N Engl J Med 2012; 367:834-841, August 30, 2012



Two men from northwestern Missouri independently presented to a medical facility with fever, fatigue, diarrhea, thrombocytopenia, and leukopenia, and both had been bitten by ticks 5 to 7 days before the onset of illness. Ehrlichia chaffeensis was suspected as the causal agent but was not found on serologic analysis, polymerase-chain-reaction (PCR) assay, or cell culture. Electron microscopy revealed viruses consistent with members of the Bunyaviridae family. Next-generation sequencing and phylogenetic analysis identified the viruses as novel members of the phlebovirus genus. Although Koch's postulates have not been completely fulfilled, we believe that this phlebovirus, which is novel in the Americas, is the cause of this clinical syndrome.



The findings and conclusions of this report are those of the authors and do not necessarily represent the views of the CDC.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

Drs. McMullan and Folk contributed equally to this article.

We thank Christopher Paddock and Jana Ritter for their consultation on histopathological and immunohistochemical analyses, Amy Denison for extraction and quality assessment of nucleic acids from bone marrow?biopsy samples, Mike Flint and Anita McElroy for discussions and editorial assistance in the preparation of the manuscript, and Ute Str?her and the Viral Special Pathogens Branch diagnostics group for providing ELISA data on viral IgG.



Source Information

From the Viral Special Pathogens Branch (L.K.M., A.M., C.G.A., P.E.R., S.T.N.) and the Infectious Disease Pathology Branch (C.S.G., M.G.M., B.C.B., S.R.Z.), Division of High-Consequence Pathogens and Pathology, and the Rickettsial Zoonoses Branch, Division of Vector-Borne Diseases (A.J.K., W.L.N.), Centers for Disease Control and Prevention, Atlanta; and Heartland Regional Medical Center, St. Joseph, MO (S.M.F).


Address reprint requests to Dr. Nichol at the Viral Special Pathogens Branch MS G14 or to Dr. Nicholson at the Rickettsial Zoonoses Branch MS G13, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, MS G-14, Atlanta, GA 30333, or at snichol@cdc.gov or wnicholson@cdc.gov.
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Re: A New Phlebovirus Associated with Severe Febrile Illness in Missouri (N Engl J Med., abstract, edited)

Interesting. The above post refers to the tick-borne phlebovirus as "novel in the Americas". I wonder if it is related to the SFTS virus:

http://www.flutrackers.com/forum/showthread.php?t=152202

which is also a tick-borne phlebovirus native to China which was discovered only very recently.
 
Re: A New Phlebovirus Associated with Severe Febrile Illness in Missouri (N Engl J Med., abstract, edited)

The article below says SFTS is the closest relative, yet the CDC expert said the two viruses are still distinct from each other. The article link below has some additional facts:

  1. Both infections occured in 2009, 3 years ago.
  2. Both of the infected patients were farmers.
  3. One farmer was 57 and one 67 when they were infected.
  4. The 57-yr-old remembered only one tick bite; the 67-yr-old said he was bitten 20x per day while working on an outdoor project.
  5. The CDC expert and local health officials have been 'scouring' the region for signs of the new virus without success.

New tick-borne virus puts the bite on Missouri farmers By JoNel Aleccia, NBC News

What puzzles me is that the men seemed to respond to antibiotic treatment used to treat Ehrlichia chaffeensis, yet a virus is proposed to be the cause of their illnesses. I don't think it is even certain yet that they were infected by a tick.
 
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Re: A New Phlebovirus Associated with Severe Febrile Illness in Missouri (N Engl J Med., abstract, edited)

CIDRAP says the novel virus is indeed similiar to STFS. That's potentially troubling, because there has been some report of possible H2H spread of STFS virus in China.

http://www.cidrap.umn.edu/cidrap/content/influenza/swineflu/news/auge3012scan.html

Two severe illnesses in Missouri caused by novel virus
Researchers from the US Centers for Disease Control and Prevention say they have identified a novel phlebovirus as the cause of severe illnesses in two Missouri farmers. One patient, a previously healthy 57-year-old man, was hospitalized for 10 days after a tick bite; the other, a 67-year-old man with type 2 diabetes, was hospitalized for 12 days after receiving numerous tick bites, according to the authors' report in today's New England Journal of Medicine. The patients suffered from fever, fatigue, anorexia, nonbloody diarrhea, and, in one case, headache. Both men recovered, but one of them said he has had fatigue and recurrent headaches in the 2 years since the illness. The initially suspected cause of the illnesses was Ehrlichia chaffeensis, but it was not found. Electron miscrocopy suggested the possibility of a bunyavirus (the family that includes phleboviruses), and sequencing and phylogenetic analysis led to the conclusion that the pathogen was a novel phlebovirus, which the authors call the Heartland virus. "Although Koch's postulates [for identifying a new pathogen] have not been completely fulfilled, our findings are consistent with the identification of a new pathogenic virus in the United States," the article states. "This novel virus . . . is a distinct member of the phlebovirus genus and is most closely related to tickborne phleboviruses, notably the recently isolated SFTSV." The authors did not determine which tick species carried the virus, but one possibility is the lone star tick, which is abundant in Missouri, they write.
 
Re: A New Phlebovirus Associated with Severe Febrile Illness in Missouri (N Engl J Med., abstract, edited)

This article suggests that ther was a geographical cluster of 14 illnesses, 12 of which were due to ehrlichiosis, and the other two to this novel virus.

http://www.npr.org/blogs/health/201...us-new-heartland-virus-discovered-in-missouri

Mysterious New 'Heartland Virus' Discovered In Missouri by Richard Knox

06:18 pm

August 29, 2012

Two men from northwestern Missouri became ill after tick bites infected them with a previously unknown virus.

Two men from northwestern Missouri became ill after tick bites infected them with a previously unknown virus.
Two Missouri farmers have been infected with a brand-new tick-borne virus that the Centers for Disease Control and Prevention is calling the Heartland virus.

The men recovered but suffered serious illness that required hospital care and weeks of convalescence. Symptoms included fever, severe fatigue, headache and nausea. Their platelet counts plummeted, but even though platelets are necessary for blood clotting, the men didn't suffer abnormal bleeding.

snip

Folk is well-known to the CDC. "Whenever he sends us a sample, we pay attention because we're likely to find something," Nicholson says. In this case, Folk sent samples from 14 patients back in 2009.

Two of them puzzled the CDC experts — and then surprised them when electron microscope studies revealed a novel virus now called Heartland. The other dozen cases involved a more common tick-borne bacterial infection called ehrlichiosis.

[snip]
 
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Re: A New Phlebovirus Associated with Severe Febrile Illness in Missouri (N Engl J Med., abstract, edited)

Published Date: 2012-08-30 22:09:33
Subject: PRO/AH/EDR> Heartland virus - USA (MO)
Archive Number: 20120830.1274007

HEARTLAND VIRUS - USA (MISSOURI)
********************************
A ProMED-mail post
http://www.promedmail.org
ProMED-mail is a program of the
International Society for Infectious Diseases
http://www.isid.org

Date: Wed 29 Aug 2012
Source: Vitals, NBC News [edited]
http://vitals.nbcnews.com/_news/201...borne-virus-puts-the-bite-on-missouri-farmers


When 2 Missouri farmers wound up hospitalized with fever, fatigue, low blood cell counts and elevated liver enzymes in 2009, doctors suspected ticks were to blame. Both men recently had reported tick bites, including a 57-year-old whose wife plucked a single critter off his abdomen with tweezers and a 67-year-old man who figured he was bitten 20 times a day for 2 weeks while rebuilding fences on his 40-acre [16 ha] farm.

"I was getting worse and worse," recalled the man, now 60, of Sheridan, Missouri, the victim with the single bite. The men had all the symptoms of ehrlichiosis, a potentially dangerous bacterial infection spread by ticks. But when scientists cultured samples of the farmers' blood, the bacteria were nowhere to be found.

"We placed it into the culture, and then we didn't get anything," recalled Dr. William L. Nicholson, a research microbiologist who specializes in emerging and zoonotic infectious with the Centers for Disease Control and Prevention. "And that, to us, indicated that we had something else in there that we weren't testing for."

[snip]

The 2 Missouri men were hospitalized for nearly 2 weeks and took a couple months to recover. One of the men, who also works at the local Energizer Eveready Battery Co. in nearby Maryville, says he still has problems with short-term memory, fatigue and headaches 3 years after the infection.

The 2nd victim, now 70, said he's fine now. Neither man seemed much impressed with being infected by a never-before-seen virus, though both are glad it didn't turn out to be worse. "I guess I never give it much thought," said one of the men. "But I was glad they saved my life."

[Byline: JoNel Aleccia]

--
Communicated by:
George A. Robertson, PhD
Senior Technical Advisor
Vaccine Development Global Program
PATH
455 Massachusetts Ave NW, Suite 1000 Washington, DC 20001 USA

[It will be interesting to see how many cases emerge now that the virus is shown to be present in the central USA. This finding will undoubtedly elicit a study to determine which tick species, or other arthropods, are involved in transmission, what the reservoir hosts are, and the frequency with which humans are infected. The tick-borne SFTSV was shown to be geographically relatively widespread in China after its initial discovery. One cannot help but wonder how many similar cases in the USA have occurred previously, perhaps due to heartland virus infection, but were undiagnosed. - Mod.TY

[snip]
 
Re: A New Phlebovirus Associated with Severe Febrile Illness in Missouri (N Engl J Med., abstract, edited)

I got the wrong impression from what I read in other articles, (I thought the patients did start to improve with standard treatment for suspected Ehrlichia chaffeensis.)

So the recovery must have been a response from their own immune systems, aided by supportive care.

http://www.foxnews.com/health/2012/08/30/new-heartland-virus-discovered-in-sick-missouri-farmers/
New 'Heartland' virus discovered in sick Missouri farmers
By Rachael Rettner
Published August 30, 2012
MyHealthNewsDaily

Two men in Missouri who became severely ill after sustaining tick bites were found to be infected with a new type of virus, according to a study from the Centers of Disease Control and Prevention (CDC).

Both men were admitted to hospitals after experiencing high fevers, fatigue, diarrhea and loss of appetite. They were originally thought to be suffering from a bacterial infection, but doubts arose when they didn't improve after being treated with antibiotics...

Read more: http://www.foxnews.com/health/2012/...vered-in-sick-missouri-farmers/#ixzz25Axt1j9I
 
Re: A New Phlebovirus Associated with Severe Febrile Illness in Missouri (N Engl J Med., abstract, edited)

There might be a new detail in the article below. The younger man had chest pain as a symptom.

http://www.nytimes.com/2012/09/04/health/research/new-tick-borne-heartland-virus-has-scientists-puzzled.html
New Virus Tied to Ticks Poses Puzzle for Doctors
By DENISE GRADY
Published: September 3, 2012

For a year and a half, scientists have been swarming over a 100-acre farm in northwestern Missouri, catching ticks and drawing blood from raccoons, possums, turkeys and deer.

?They even bled my horses, and my dogs and cats,? the owner of the farm said. ?They got to looking at me, and I said, ?I already gave.? ? ...
 
Re: A New Phlebovirus Associated with Severe Febrile Illness in Missouri (N Engl J Med., abstract, edited)

http://www.capradio.org/news/npr/story?storyid=204527407
Unusual Tick-Borne Virus Lurks In Missouri's Woods

By Michaeleen Doucleff


Last year, virologists traced the mysterious illness of two Missouri farmers to a virus never seen before. Now, scientists have found the so-called Heartland virus in ticks. The discovery means the U.S. has another tick-borne illness on its hands — and "another reason to avoid getting bit."
Tuesday, July 23, 2013
[snip]
No other cases of the Heartland virus have been reported since its discovery last year. And Savage thinks the risk of infection is still low.

"That's just speculative," he says. "With viruses, there are often a lot of people who are asymptomatic."...
 
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