Vietnam, Malawi: 2 New cycloviruses isolated from patients with severe brain infections

[Gert van der Hoek]

Strange disease emerges in southern province

11/12/2007 ()

VietNamNet Bridge ? Residents of Hamlet 2 in Phuoc **** commune in the southern province of An Giang are now faced with a strange disease; symptoms include contorted mouth, glassy eyes and mild paralysis.

The first case was reported on December 5. The disease has quickly spread in Phuoc **** and neighbouring communes.

By December 10, 34 patients aged between six months and 46 years old were hospitalised at An Phu District General Hospital.

Doctor Phan Van Dien Phuong, Deputy Director of An Phu District General Hospital said clinical symptoms are similar to Japanese encephalitis but tests have come up negative.

More than 100 primary students in An Phu district have stayed home from school for several days.

Doctors from central hospitals and scientists will visit An Phu to do research on the mysterious ailment.

http://english.vietnamnet.vn/social/2007/12/759092/

[Shiloh]

Vietnam: New virus isolated from patients with severe brain infections

Source: http://www.eurekalert.org/pub_releas...-nvi061713.php

Public release date: 18-Jun-2013
Contact: Jen Middleton
j.middleton@wellcome.ac.uk
44-207-611-7262
Wellcome Trust
New virus isolated from patients with severe brain infections

Researchers have identified a new virus in patients with severe brain infections in Vietnam. Further research is needed to determine whether the virus is responsible for the symptoms of disease.

The virus was found in a total of 28 out of 644 patients with severe brain infections in the study, corresponding to around 4%, but not in any of the 122 patients with non-infectious brain disorders that were tested.

Infections of the brain and central nervous system are often fatal and patients who do survive, often young children and young adults, are left severely disabled. Brain infections can be caused by a range of bacterial, parasitic, fungal and viral agents, however, doctors fail to find the cause of the infection in more than half of cases despite extensive diagnostic efforts. Not knowing the causes of these brain infections makes public health and treatment interventions impossible.

Researchers at the Oxford University Clinical Research Unit, Wellcome Trust South East Asia Major Overseas Programme and the Academic Medical Center, University of Amsterdam identified the virus, tentatively named CyCV-VN, in the fluid around the brain of two patients with brain infections of unknown cause. The virus was subsequently detected in an additional 26 out of 642 patients with brain infections of known and unknown causes...

[Giuseppe]

Re: Vietnam: New virus isolated from patients with severe brain infections

[Source: mBio, full page: (LINK). Abstract, edited.]

Identification of a New Cyclovirus in Cerebrospinal Fluid of Patients with Acute Central Nervous System Infections

Le Van Tan a, H. Rogier van Doorn a,b, Ho Dang Trung Nghia a,c,d, Tran Thi Hong Chau d, Le Thi Phuong Tu a, Michel de Vries e*, Marta Canuti e, Martin Deijs e, Maarten F. Jebbink e, Stephen Baker a,b, Juliet E. Bryant a,b, Nguyen Thi Tham a, Nguyen Thi Thuy Chinh BKrong a, Maciej F. Boni a,b, Tran Quoc Loi f, Le Thi Phuong f, Joost T. P. Verhoeven e, Martin Crusat e, Rienk E. Jeeninga e, Constance Schultsz a,g, Nguyen Van Vinh Chau d, Tran Tinh Hien a, Lia van der Hoek e, Jeremy Farrar a,b, Menno D. de Jong a,e

Author Affiliations: Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, South East Asia Infectious Diseases Clinical Research Network, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam (a); Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Centre for Clinical Vaccinology and Tropical Medicine, Oxford, United Kingdom (b); Pham Ngoc Thach University of Medicine, Ho Chi Minh City, Vietnam (c); Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam (d); Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands (e); Dong Thap Provincial Hospital, Dong Thap, Vietnam (f); Department of Global Health-Amsterdam Institute of Global Health and Development, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (h)

Author Notes: * Present address: CBS-KNAW Fungal Biodiversity Center, Utrecht, The Netherlands

Address correspondence to Le Van Tan, tanlv@oucru.org

Invited Editor Amit Kapoor, Columbia University Editor W. Ian Lipkin, Columbia University


ABSTRACT

Acute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology remains unknown in a large proportion of cases. We identified and characterized the full genome of a novel cyclovirus (tentatively named cyclovirus-Vietnam [CyCV-VN]) in cerebrospinal fluid (CSF) specimens of two Vietnamese patients with CNS infections of unknown etiology. CyCV-VN was subsequently detected in 4% of 642 CSF specimens from Vietnamese patients with suspected CNS infections and none of 122 CSFs from patients with noninfectious neurological disorders. Detection rates were similar in patients with CNS infections of unknown etiology and those in whom other pathogens were detected. A similar detection rate in feces from healthy children suggested food-borne or orofecal transmission routes, while high detection rates in feces from pigs and poultry (average, 58%) suggested the existence of animal reservoirs for such transmission. Further research is needed to address the epidemiology and pathogenicity of this novel, potentially zoonotic virus.

IMPORTANCE

Acute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology frequently remains unknown, which hampers development of therapeutic or preventive strategies. Hence, identification of novel pathogens is essential and is facilitated by current next-generation sequencing-based methods. Using such technology, we identified and characterized the full genome of a novel cyclovirus in cerebrospinal fluid (CSF) specimens from two Vietnamese patients with CNS infections of unknown etiology, which was subsequently detected in none of 122 CSF specimens from patients with noninfectious neurological disorders but 4% of 642 CSF specimens from Vietnamese patients with suspected or confirmed CNS infections. Similar detection rates in feces from healthy children suggested food-borne or orofecal transmission routes, while frequent detection in feces from Vietnamese pigs and poultry (average, 58%) suggested the existence of animal reservoirs for such transmission. Further studies are needed to address the epidemiology and pathogenicity of this novel, potentially zoonotic virus.


FOOTNOTES

Citation Tan LV, van Doorn HR, Nghia HDT, Chau TTH, Tu LTP, de Vries M, Canuti M, Deijs M, Jebbink MF, Baker S, Bryant JE, Tham NT, BKrong NTTC, Boni MF, Loi TQ, Phuong LT, Verhoeven JTP, Crusat M, Jeeninga RE, Schultsz C, Chau NVV, Hien TT, van der Hoek L, Farrar J, de Jong MD. 2013. Identification of a new cyclovirus in cerebrospinal fluid of patients with acute central nervous system infections. mBio 4(3):e00231-13. doi:10.1128/mBio.00231-13.

Received 30 March 2013 - Accepted 9 May 2013 - Published 18 June 2013

Copyright ? 2013 Tan et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

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[alert]

Re: Vietnam: New virus isolated from patients with severe brain infections

There have been reports the past several years of an unknown or novel encephalitis virus in parts of Vietnam known locally as "Acmong" virus, from the Vietnamese word for "nightmare", for the nightmarish symptoms it could cause. It was unclear from those reports whether a precise virus has been isolated. It would be informative to know whether these two viruses are in fact the same virus.

Unfortunately, I am unable to find that thread now.

[Emily]

Re: Vietnam: New virus isolated from patients with severe brain infections

Is this the thread, Alert?

Vietnam: Strange disease emerges in southern province

I was wondering about a circo/cyclo virus being a co-factor in the severe H7N9 cases in China:
http://www.flutrackers.com/forum/sho...5&postcount=22

[Giuseppe]

Re: Vietnam: New virus isolated from patients with severe brain infections

There have been reports the past several years of an unknown or novel encephalitis virus in parts of Vietnam known locally as "Acmong" virus, from the Vietnamese word for "nightmare", for the nightmarish symptoms it could cause. It was unclear from those reports whether a precise virus has been isolated. It would be informative to know whether these two viruses are in fact the same virus.

Unfortunately, I am unable to find that thread now.

Is this the thread? http://www.flutrackers.com/forum/showthread.php?t=44584

[alert]

Re: Vietnam: New virus isolated from patients with severe brain infections

I hadn't even seen that thread, but that does appear to be the illness in question. I remember one from 2010 or 2011 that implied "acmong virus" was somewhat seasonal, occurring almost every summer.

I could swear I remember translating and posting articles here on the "acmong virus", and I was not an FT member at the time of that thread.

[Giuseppe]

Re: Vietnam: New virus isolated from patients with severe brain infections

I hadn't even seen that thread, but that does appear to be the illness in question. I remember one from 2010 or 2011 that implied "acmong virus" was somewhat seasonal, occurring almost every summer.

I could swear I remember translating and posting articles here on the "acmong virus", and I was not an FT member at the time of that thread.

The post #5 makes a clear mention to this syndrome: http://www.flutrackers.com/forum/sho...01&postcount=5

[Giuseppe]

Re: Vietnam: New virus isolated from patients with severe brain infections

Ac Mong syndrome is also cited in this Emerging Infectious Diseases Journal article:

http://www.pasteur.fr/ip/resource/filecenter/document/01s-00004j-0dc/litchi-associated-buckwalter.pdf

Litchi?associated Acute Encephalitis in Children, Northern Vietnam, 2004?2009

Juliette Paireau, Nguyen Hai Tuan, R?mi Lefran?ois, Matthew R. Buckwalter, Ngu Duy Nghia, Nguyen Tran Hien, Olivier Lortholary, Sylvain Poir?e, Jean-Claude Manuguerra, Antoine Gessain, Matthew L. Albert, Paul T. Brey, Phan Thi Nga, and Arnaud Fontanet


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[alert]

Re: Vietnam: New virus isolated from patients with severe brain infections

Published Date: 2013-06-18 16:58:55
Subject: PRO/AH/EDR> Circovirus - Viet Nam: acute CNS infection
Archive Number: 20130618.1780170

CIRCOVIRUS - VIET NAM: ACUTE CNS INFECTION
******************************************
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Date: Tue 18 Jun 2013
Source: Bloomberg News [edited]

http://www.bloomberg.com/news/2013-06-18/novel-virus-found-in-vietnam-brain-infection-patients.html

Researchers have discovered a new virus in patients in Viet Nam suffering from severe brain infections, a team of scientists reported today [18 Jun 2013] in mBio, the journal of the American Society for Microbiology. The virus was detected in 28 of 644 patients who had severe brain infections and none of 122 patients who had non-infectious brain disorders, according to researchers at the Oxford University Clinical Research Unit, Wellcome Trust South East Asia Major Overseas Programme and the Academic Medical Center, University of Amsterdam. It's tentatively called CyCV-VN and is part of a group of viruses known as Circoviridae known to circulate in animals such as birds and pigs, they said.

"We don't yet know whether this virus is responsible for causing the serious brain infections we see in these patients, but finding an infectious agent like this in a normally sterile environment like the fluid around the brain is extremely important," Rogier van Doorn, head of emerging infections at the Wellcome Trust Viet Nam Research Programme and Oxford University Clinical Research Unit Hospital for Tropical Diseases in Viet Nam, said in a statement.

Brain infections can be fatal and may leave people who survive them with severe disabilities, the researchers said. Bacteria, parasites, fungi and viruses can cause the infections, though doctors can't pinpoint the cause of more than half of them. The study was funded by the Wellcome Trust, the European Union and the Li Ka-Shing Foundation-University of Oxford Global Health Programme.

[Byline: Andrea Gerlin]

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[Circoviruses are unenveloped single-stranded DNA viruses with ambisense encoding of their genome content. They are widespread and predominantly infect avian species. The authors of the mBio paper, referred to above, detected a novel circovirus in spinal fluid from 4 percent of 642 patients with central nervous system infections of unknown cause and in an average of 58 percent of fecal samples from pigs and poultry, suggesting animals may serve as reservoirs for transmission to humans. The virus, named CyCV-VN, belongs to the _Cyclovirus_ genus, a group that has never before been implicated in human disease.

"The detection of CyCV-VN in a usually sterile material like cerebrospinal fluid is unexpected and may indicate a pathogenic role of this virus as a single or a co-infecting pathogen," according to the authors at the Oxford University Clinical Research Unit in Ho Chi Minh City, Viet Nam. The results in this study, the authors caution, do not provide absolute proof of disease causation, and further work is needed to determine whether this virus poses a threat to human health.

According to the authors, acute central nervous system infections are responsible for illnesses and deaths around the world, but they are a particular problem in tropical regions. These infections can be caused by any of a number of bacterial, parasitic, fungal or viral pathogens, but the majority of cases go undiagnosed despite extensive efforts to identify a cause. "One of our particular interests is to improve patient diagnosis," said Van. "Proper diagnosis is essential to improve clinical management and prevention of these devastating diseases."

Inspired by the high incidence of acute central nervous system infections in Viet Nam, the authors set out to identify previously uncharacterized viruses in undiagnosed patients. Using fluid samples from more than 1700 patients with suspected central nervous system infections or suspected viral encephalitis, the researchers generated 161 000 DNA sequence reads for further analysis. Among these thousands of sequences, the researchers identified a sequence from a virus belonging to the _Cyclovirus_ genus that was present in 2 patients, one adult and one child, both with acute central nervous system infections of unknown cause. Subsequent determination of the entire genome sequence of the virus present in one of the samples established that the virus (named CyCV-VN) is a unique new species of the genus _Cyclovirus_, a group that includes no known pathogens.

Having determined the complete genome sequence, the researchers went back to 642 samples from patients with suspected acute central nervous system infections and were able to detect the virus in samples from 26 patients (4 percent). The virus was not detected at all in samples from patients with non-infectious conditions of the central nervous system, such as multiple sclerosis, a fact that argues that the virus could well be a human pathogen.

This virus was also detected in samples from farm animals in the province where the index patient lived: between 42 percent and 100 percent of fecal samples from pigs, ducks, and chickens in that region harbored viruses that are extremely closely related to CyCV-VN. This suggests that livestock could represent a source for human infection with the virus.

Van also cautions that it is too soon to point an accusing finger at CyCV-VN. "Detection of a virus in human samples alone is insufficient to provide a direct link with an ongoing infection, and the question of causation requires extensive effort."

The authors are currently trying to isolate the virus in cell culture and develop a serological assay. If they are able to identify an antibody response to the virus in patient samples, they would be one step closer to linking the virus to disease. They are also working with research groups outside Viet Nam to explore the geographic spread of the virus.

The full text of this paper by L Van Tan et al, entitled "Identification of a New Cyclovirus in Cerebrospinal Fluid of Patients with Acute Central Nervous System Infections," can be accessed at: http://bit.ly/mbiotip0613d. - Mod.CP

[Ronan Kelly]

Re: Vietnam: New virus isolated from patients with severe brain infections

alert, - you mentioned it here - Litchi?associated Acute Encephalitis in Children, Northern Vietnam, 2004?2009

and here Meningitis: Malaysia

[alert]

Re: Vietnam: New virus isolated from patients with severe brain infections

Wow.

Published Date: 2013-06-24 13:52:47
Subject: PRO/AH/EDR> Circovirus - Viet Nam, Malawi: human, cerebrospinal fluid
Archive Number: 20130624.1789227

CIRCOVIRUS - VIET NAM MALAWI: HUMAN, CEREBROSPINAL FLUID
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In this posting:
[1] Viet Nam, Malawi: Science journal
[2] Malawi: Emerging Infectious Diseases journal

******
[1] Viet Nam, Malawi: Science journal
Date: Thu 20 Jun 2013
Source: Science Now, American Association for the Advancement of Science (AAAS) [edited]

http://news.sciencemag.org/sciencenow/2013/06/new-viruses-found-in-asia-and-af.html

New viruses found in Asia and Africa tentatively linked to neurological disease
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[Authors: Mara Hvistendahl, Martin Enserink]

A mysterious group of viruses known for their circular genome [the family _Circoviridae_] has been detected in patients with severe disease on 2 continents. In papers published independently this week [week of 20 Jun 2013], researchers report the discovery of agents called cycloviruses in Viet Nam and in Malawi. The studies suggest that the viruses -- one of which also widely circulates in animals in Viet Nam -- could be involved in brain inflammation and paraplegia, but further studies are needed to confirm a causative link.

The discovery in Viet Nam grew out of a frustrating lack of information about the causes of some central nervous system (CNS) infections such as encephalitis and meningitis, which can be fatal or leave lasting damage. "There are a lot of severe cases in the hospitals here, and very often we can't come to a diagnosis," says H Rogier van Doorn, a clinical virologist with the Oxford University Clinical Research Unit in the Hospital for Tropical Diseases, Ho Chi Minh City. Extensive diagnostic tests turn up pathogens in only about half of patients with such infections, he says. Van Doorn and colleagues in Viet Nam and at the University of Amsterdam's Academic Medical Center hoped that they might uncover new pathogens using a powerful new technique called next-generation sequencing. The group sequenced all the genetic material in cerebrospinal fluid (CSF) samples taken from more than 100 patients with undiagnosed CNS infections. One sample batch returned a promising lead: a viral sequence belonging to the family _Circoviridae_.

Probing the original patient samples, the scientists ferreted out the sequence in 2 of the samples-one from an adult and one from a child. Next, they expanded their search, testing samples from an additional 642 patients with CNS infections using a sensitive polymerase chain reaction (PCR) test developed to specifically target the detected sequence. Roughly 4 percent of the samples tested positive, the team reported in mBio on Tuesday [18 Jun 2013; see ProMED-post Circovirus - Viet Nam: acute CNS infection 20130618.1780170]. Whole-genome sequencing confirmed that the virus, which the scientists have dubbed CyCV-VN, for cyclovirus-Viet Nam, is novel; it belongs to a genus within the family _Circoviridae_, the guns _Cyclovirus_.

Meanwhile, a team at Erasmus MC in Rotterdam, the Netherlands, had been trying to determine what causes paraplegia in some patients in Malawi, in southeast Africa. It's well known that trauma and some infections can cause people to lose control over their legs, but in many cases, doctors can't find a cause. The Dutch team hunted for viruses in blood serum and CSF samples from 12 patients who had suddenly become paraplegic in 2010 and 2011. They found a new cyclovirus as well; when they tested for the virus in a broader group of 58 paraplegia patients, they found it in 15 percent of 54 serum samples and 10 percent of 40 CSF samples, the team reports in a paper published online this week in Emerging Infectious Diseases [see part [2] below].

Cycloviruses were 1st discovered in 2009-along with a host of other viruses-in fecal samples from South-Asian children suffering from acute flaccid paralysis, by a team led by Eric Delwart of the Blood Systems Research Institute in San Francisco. Since then, they have also been found in human fecal samples from Nigeria and Tunisia, as well as in farm animals, chimpanzees, bats, cockroaches, and dragonflies. While the new viruses are related, says Le Van Tan, a researcher at the Oxford University Clinical Research Unit and the 1st author on the Viet Nam paper, initial comparisons of the genomes suggest that they form 2 new [virus] species. Neither of the studies proves that the viruses cause disease, however, says Delwart, who was not involved in the new papers. In the Malawi study, researchers did not include a control group, so they don't know if healthy people carry the virus as well; in the Viet Nam study, samples taken from a control group of 122 patients with noninfectious CNS conditions tested negative for the new virus. Still, other factors might explain that, Delwart says. It's possible, Delwart says, that these viruses aggravate existing disease; 16 of the 26 people who carried the cyclovirus in the Viet Nam study also had a lab-confirmed infection with another pathogen, such as Japanese encephalitis or dengue. "It may be: one virus, bad; 2 viruses, worse," he says.

Van Doorn says that the team is wary of speculating until more is known about CyCV-VN; the team is sharing its results "with the public and the scientific world so that more research can be initiated," he says. To find out if the new viruses actually cause disease, researchers can try to grow them in cell culture and infect animals with them. Another critical task is to cast a wider net using a PCR test that can pick up related cycloviruses as well as CyCV-VN, Van Doorn says-which could help determine how entrenched cycloviruses are in the population. The Rotterdam group is also planning to look for the virus more broadly, says Saskia Smits, the 1st author on the paper.

The Viet Nam study shed some light on how people may pick up the virus. Because other [members of the family] _Circoviridae _ are known animal pathogens, testing chickens, ducks, and pigs for CyCV-VN was the "obvious next step," Van Doorn says. The scientists checked fecal swabs taken from dozens of animals in Dong Thap province and found what the virologist calls "remarkably high" incidence of the virus: Nearly 60 percent of the animal samples tested positive. Moreover, the animal strains of CyCV-VN showed a 98 percent similarity to those isolated from humans. Because chickens, ducks, and pigs are "commonly held in Viet Nam in backyards and on small farms," Van Doorn says, "there is a lot of possible contact between these viruses and humans."

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******
[2] Malawi: Emerging Infectious Diseases journal
Date: Mon 24 Jun 2013
Source: Emerging Infectious Diseases journal [summ., edited]

http://wwwnc.cdc.gov/eid/article/19/9/13-0404_article.htm

[Ref: Smits SL, Zijlstra EE, van Hellemond JJ, et al: Novel cyclovirus in human cerebrospinal fluid, Malawi, 2010-2011. Emerg Infect Dis 2013, 19(9) DOI: 10.3201/eid1909.130404]
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Abstract
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To identify unknown human viruses, we analyzed serum and cerebrospinal fluid samples from patients with unexplained paraplegia from Malawi by using viral metagenomics. A novel cyclovirus species was identified and subsequently found in 15 percent and 10 percent of serum and cerebrospinal fluid samples, respectively. These data expand our knowledge of cyclovirus diversity and tropism.

The list of diseases caused by viral pathogens is ever changing and growing. Breakthroughs in the field of metagenomics had far-reaching effects on the identification of emerging viral pathogens and on the recognition that an increasing number of diseases that were once attributed to unknown causes are actually caused by infectious agents. Paraplegia is an impairment of motor or sensory functions of the lower extremities. Although it can be caused by spinal cord injury, nontraumatic paraplegia also should be considered, particularly in a tropical environment; tuberculosis and schistosomiasis may play a role, but in many cases, no firm diagnosis can be made. In this study, cerebrospinal fluid (CSF) and serum samples were obtained from 58 patients from Malawi who had paraplegia of unknown etiology and were studied for the presence of known or unknown viruses by using a metagenomics approach.

The Study
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During 2010-2011, we enrolled 58 adults who sought care at Queen Elizabeth Central Hospital in Blantyre, Malawi, for unexplained paraplegia in this study. All procedures were performed in compliance with relevant laws and institutional guidelines. The study was approved by the College of Medicine Research and Ethics Committee.

[Interested readers should access the original text at the URL above to obtain a comprehensive account of the methods, the data generated and the references sited. - Mod.CP]

A cyclovirus genome was obtained by Roche 454-sequencing from serum of patient VS5700009. Cycloviruses (family _Circoviridae_, genus _Cyclovirus_) have been detected in human and chimpanzee feces and tissues of farm animals, bats, and dragonflies. They are non-enveloped viruses with a single-stranded circular DNA genome of approximately 2 kb. The genome contains 2 major inversely arranged open reading frames (ORFs) encoding the putative replication-associated protein (Rep) and capsid protein (Cap). A potential stem-loop structure with a conserved nonanucleotide motif located between the 5'-ends of these 2 ORFs is required to initiate the replication of the viral genome. The genome organization of human cyclovirus VS5700009 (GenBank accession no. KC771281) resembles that of human cycloviruses TN18 and TN25. The Rep ORF of human cyclovirus VS5700009 was interrupted by a 96-bp intron with a splice donor site (GT) and splice acceptor site (AG). The 3' intergenic region between the Rep and Cap ORFs was only 7 bp long. The cyclovirus stem-loop structure with the conserved nonamer sequence (5'-TAATACTAT-3') in the 5' intergenic region was observed, as were 3 other potential ORFs. These latter ORFs are not conserved among cycloviruses and show low partial homology to bacterial enzymes, Phylogenetic analyses were conducted with MEGA5 [molecular evolutionary genetics analysis version 5]. The human cyclovirus VS5700009 Rep protein was most closely related to the Rep proteins of human cycloviruses TN18 and TN25 (approximately 75 percent aa identity). Similar relations, but with much lower amino acid identities, were observed in Cap proteins (approximately 37 percent identity; data not shown). Cycloviruses belong to the same species when sharing more than 85 percent aa identity in the Rep region.

It was concluded that human cyclovirus VS5700009 represents a new cyclovirus species. Most of the closest relatives of human cyclovirus VS5700009 (which include TN18 and TN25) detected in feces from children with non polio acute flaccid paralysis, a condition related to paraplegia, which may indicate that TN25/VS5700009-like viruses may be more pathogenic than other cycloviruses

To determine the prevalence of human cyclovirus VS5700009 in the serum and CSF samples of the 58 patients, a VS5700009-specific PCR was performed. 8 (15 percent) of 54 serum samples and 4 (10 percent) of 40 CSF samples from paraplegia patients were human cyclovirus positive. For several amplicons, the cyclovirus nature was confirmed by Sanger sequencing, and the amplicons showed 75 percent-99 percent identity to human cyclovirus VS5700009. Only in patient VS5700009 were both CSF and serum samples positive for human cyclovirus.

Conclusions
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Our results indicate that cycloviruses are commonly found in serum and CSF of paraplegia patients from Malawi. Diverse cycloviruses have been discovered in human and chimpanzee fecal samples and in muscle tissue of farm animals, such as cows, sheep, goats, and chickens. Cycloviruses have been suggested to cause human enteric infections and were not derived from consumed food because the human and animal cycloviruses showed limited genetic overlap.

Our data indicate that cycloviruses may cause systemic infections and are present in multiple organ compartments in humans. Whether cycloviruses play a role in development of paraplegia remains to be determined; this study lacks a control group of healthy persons, and the relatively high virus prevalence in persons with paraplegia may also reflect high overall prevalence in healthy persons. In addition, the apparent interleaved evolution of human and animal cycloviruses suggests the potential for frequent cross-species exposure and zoonotic transmission.

Our observations expand the knowledge of cycloviruses in humans and show how epidemiologic baseline information on virus host range and tropism in animals may indicate the presence of similar viruses in different organ systems of humans. To clarify the epidemiology and pathogenicity of cycloviruses in humans, additional surveillance should be conducted, especially because the prevalence and diversity of human cycloviruses is relatively high. Cross-species transmission of cycloviruses seems plausible , and closely related cyclovirus species may be pathogenic.

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[The cycloviruses are a genus of viruses of un-enveloped single-stranded DNA viruses with ambisense encoding of their genome content, classified as members the family _Circoviridae_. They are widespread and predominantly infect avian species. Recently virologists in Viet Nam discovered a novel cyclovirus in spinal fluid from 4 percent of 642 patients with central nervous system infections of unknown cause and in an average of 58 percent of fecal samples from pigs and poultry, suggesting animals may serve as reservoirs for transmission to humans.

Now scientists in Rotterdam and Malawi describe another novel cyclovirus which they have detected in 15 percent and 10 percent of serum and cerebrospinal fluid samples, respectively. These findings expand our knowledge of cyclovirus diversity and tropism and possible involvement in human disease.

Together these findings suggest roles for cycloviruses in causation of human disease, specifically neurological rises in accordance with the categories of patients studied.

The Science Now commentary, no [1] above, reveals that in fact cycloviruses were first discovered in 2009 -- along with a host of other viruses -- in fecal samples from South-Asian children suffering from acute flaccid paralysis, by a team led by Eric Delwart of the Blood Systems Research Institute in San Francisco. Since then, they have also been found in human fecal samples from Nigeria and Tunisia, as well as in farm animals, chimpanzees, bats, cockroaches, and dragonflies. Consequently the relationship of specific cycloviruses to human disease remains uncertain, as both the Viet Nam and Rotterdam/Malawi groups recognise. - Mod.CP]

[Giuseppe]

Re: Vietnam, Malawi: 2 New cycloviruses isolated from patients with severe brain infections

[Source: European Centre for Disease Prevention and Control (ECDC), full PDF document: (LINK). Extract.]


COMMUNICABLE DISEASE THREATS REPORT

Week 25, 16-22 June 2013

(?)


New! Novel cyclovirus - Multistate - central nervous system infections

Opening date: 19 June 2013


Epidemiological summary

A mBio article published on 18 June 2013 described the identification of a novel cyclovirus, named CyCV-VN, in cerebrospinal fluid (CSF) specimens from two Vietnamese patients with central nervous system (CNS) infections of unknown etiology. Subsequently CyCV-VN was detected in 26 of 642 (4%) acute-infection CSF specimens (collected from 1999 to 2009), including 10 of 273 (3.7%) CSF specimens from patients with CNS infections of unknown etiology and 16 of 369 (4.3%) samples from patients in whom laboratory-confirmed CNS infection with other pathogens was established. CyCV-DNA could not be detected in 122 CSF specimens collected from Vietnamese patients with noninfectious neurological disorders. CyCV-VN DNA was also detected in 8/188 (4.2%) fecal specimens from healthy children. When specimens from poultry and pigs were tested, the virus was detected in 38/65 (58%).

Another article published online on 10 June 2013 in Emerging Infectious Diseases described the detection of cyclovirus in eight (15%) of 54 serum samples and 4 (10%) of 40 CSF samples from paraplegia patients in Malawi.

(?)


ECDC assessment

This is the first time that cyclovirus is associated with human infection. However further studies are needed in order to definitively establish a causal relationship.


Actions

ECDC is preparing a Rapid Risk Assessment of these findings.

(?)


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