Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

Volume 17, Number 8—August 2011

Letter

Seroepidemiology of Saffold Cardiovirus Type 2

On This Page

Tables

Suggested citation for this article

To the Editor: Saffold virus (SAFV) is a new human virus belonging to the genus Cardiovirus of the family Picornaviridae (16). The virus has also been named human Theiler’s-like cardiovirus (4). To date, 8 SAFV genotypes are known, based on molecular variation in the P1 region, which codes for the viral capsid (5). SAFVs are detected in respiratory and fecal samples from infants and children <6 years of age. The virus is generally detected at low frequency (0.5%–3%) in the general population, but in Afghanistan and Pakistan higher incidences have been reported (10%–12%) (5). Detection is mainly based on molecular techniques because virus isolation is cumbersome. Other than gastroenteritis, no clear disease manifestations are known (18), although recently, researchers in Japan have suggested that for a select group of children, SAFV infection may cause pharyngitis and tonsillitis (7). In rodents, however, cardioviruses are serious pathogens that can cause myocarditis, meningoencephalitis, and pancreatitis.

Previously, we have shown that SAFV-3 infections are ubiquitous and are transmitted early in life (6). This conclusion was based on antibody testing by virus neutralization, a highly specific test that can discriminate serotypes within a single species, but formal proof for existence of serotypes was lacking. Extrapolated to other genotypes, the finding would indicate a high infection rate for SAFVs, which is at odds with the low detection frequency reported in most studies. Most SAFV-2 isolates, from our laboratory and others, grow poorly in cell culture, which hampers reading of neutralization. Recently, however, a SAFV-2 strain was isolated in Finland that grows well in HeLa cells and shows clear cytopathic effects (SAFV-2-FIN2008, GenBank accession no. FR682076; S. Blomgvist et al., unpub. data). This strain enabled us to set up a virus neutralization test similar to that described for SAFV-3 (6). For comparison, we used strain SAFV-3(NL2007) (GenBank accession no. FM207487), which was isolated in Nijmegen (6). The virus neutralization test was performed on HeLa cells with 100 TCID50 of virus per serum dilution. Virus–serum mixtures were incubated for 1 hour at 37°C and overnight at 7°C to stabilize virus–antibody complexes (6). Human serum samples submitted previously were tested by using 3-fold dilution steps and duplicate testing (6). The results are presented in the Table. A low seroprevalence was found for SAFV-2 and SAFV-3 at 9 months of age, which is at the nadir of immunoglobulin G levels in infants. At the age of 24 months, a high seroprevalence of antibodies was found in the Netherlands for SAFV-2 and -3, pointing to early acquisition of infection with both strains. In Finland, the seroprevalence for SAFV-2 and -3 was lower in young children, which suggests somewhat lower infection rate similar to what has been reported for enteroviruses (9). A high seroprevalence of 97%–100% was found in persons >4 years of age in Cameroon, Indonesia, and the Netherlands (Table). A high prevalence of SAFV-2 antibodies was recently also reported in blood donors from the United States (8). Thus, the seroepidemiology of SAFV-2 is similar to that of SAFV-3. As depicted in the last 3 columns of the Table, on several occasions serum samples independently neutralized either SAFV-2 or SAFV-3, which suggests that the viruses behave as different serotypes.

In conclusion, SAFV-2 and SAFV-3 show an almost identical epidemiologic pattern with infection acquired early in life and with a high seroprevalence in different continents. The outcome is concordant with universal occurrence of infection by both genotypes. Because several times there was a clear discrepancy between antibody titers against one or the other of the 2 genotypes, we conclude that they behave as separate serotypes, although weak cross-reactivity (below the detection limit of 1:15) cannot be excluded. Accepting that SAFV genotypes correspond with existence of different serotypes, the infection rate in the first years of life must be quite high, similar to that for human parechoviruses and enteroviruses, which are found in 15%–18% of stool samples from children <5 years of age (10). The low SAFV detection rate remains thereby difficult to explain.

The outcome can be explained by a short duration of virus excretion in stool, which, however, is unlikely for an infection spreading by the fecal–oral route. Alternatively, it may be that the virus is unstable in stool and rapidly degrades, such that fecal samples are inadequate for diagnosis of the infection. Other specimens, however, such as respiratory samples, yielded also low numbers of positive findings (4). Remarkably, the study with a high prevalence of positive stool samples made use of primers selected in a conserved region of 2C helicase (5), whereas other studies used primers in the 5′ noncoding region (3,4). Hence, a difference in sensitivity between the different PCRs may be responsible for the discrepancy between seroepidemiology and the low diagnostic yield by PCR. This discrepancy, however, awaits further investigation.

Jochem GalamaComments to Author , Kjerstin Lanke, Jan Zoll, Merja Roivainen, and Frank van Kuppeveld
Author affiliations: Author affiliations: Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands (J. Galama, K. Lanke, J. Zoll, F. van Kuppeveld); Nijmegen Center for Molecular Life Sciences, Nijmegen (J. Galama, K. Lanke, J. Zoll, F. van Kuppeveld); Nijmegen Institute for Infection, Inflammation and Immunity, Nijmegen (J. Galama, K. Lanke, J. Zoll, F. van Kuppeveld); National Institute for Health and Welfare, Helsinki, Finland (M. Roivainen)

References

  1. Jones MS, Lukashov VV, Ganac RD, Schnurr DP. Discovery of a novel human picornavirus in a stool sample from a pedriatric patient presenting with fever of unknown origin. J Clin Microbiol. 2007;45:214450. DOIPubMed
  2. Abed Y, Boivin G. New Saffold cardioviruses in 3 children, Canada. Emerg Infect Dis. 2008;14:8346.PubMed
  3. Drexler JF, de Souza Luna LK, Stöcker A, Silva Almeida P, Medrado Ribeiro TC, Petersen N, Circulation of three lineages of a novel Saffold cardiovirus in humans. Emerg Infect Dis. 2008;14:1398405. DOIPubMed
  4. Chiu CY, Greninger AL, Kanada K, Kwok T, Fischer KF, Runckel C, Identification of cardioviruses related to Theiler’s murine encephalomyelitis virus in human infections. Proc Natl Acad Sci U S A. 2008;105:141249. DOIPubMed
  5. Blinkova O, Kapoor A, Victoria J, Naeem A, Shaukat S, Sharif S, Cardioviruses are genetically diverse and common enteric infections in South Asian children. J Virol. 2009;83:463141. DOIPubMed
  6. Zoll J, Erkens Hulshof S, Lanke K, Verduyn Lunel F, Melchers WJ, Schoondermark-van de Ven E, Saffold virus, a human Theiler’s-like cardiovirus, is ubiquitous and causes infection early in life. PLoS Pathog. 2009;5:e1000416. DOIPubMed
  7. Itagaki T, Abiko C, Aoki Y, Ikeda T, Mizuta K, Noda M, Saffold cardiovirus infection in children associated with respiratory disease and its similarity to Coxsackievirus infection. Ped Infect Dis J. 2011 Mar 7; [Epub ahead of print].
  8. Chiu CY, Greninger AL, Chen EC, Haggerty TD, Personnet J, Delwart E, Cultivation and serological characterization of the human Theiler’s-like cardiovirus associated with diarrheal disease. J Virol. 2010;84:440714. DOIPubMed
  9. Viskari H, Ludvigsson J, Uibo R, Salur L, Marciulionyte D, Hermann R, Relationship between the incidence of type 1 diabetes and maternal enterovirus antibodies: time trends and geographical variation. Diabetologia. 2005;48:12807. DOIPubMed
  10. Benschop K, Thomas X, Serpenti C, Molenkamp R, Wolthers K. High prevalence of human parechovirus (HPeV) genotypes in the Amsterdam region and identification of specific HPeV variants by direct genotyping of stool samples. J Clin Microbiol. 2008;46:396570. DOIPubMed

Table

Suggested citation for this article: Galama J, Lanke K, Zoll J, Roivainen M, van Kuppeveld F. Seroepidemiology of Saffold cardiovirus type 2 [letter]. Emerg Infect Dis [serial on the Internet]. 2011 Aug [date cited]. http://dx.doi.org/10.3201/eid1708.101953

DOI: 10.3201/eid1708.101953

Related Links

Table of Contents – Volume 17, Number 8—August 2011

Comments to the Authors

Please use the form below to submit correspondence to the authors or contact them at the following address:

Jochem Galama, Department of Medical Microbiology, Radboud University Nijmegen Medical Center, PO Box 9101, 6500HB, Nijmegen, the Netherlands

character(s) remaining.

Comment submitted successfully, thank you for your feedback.

Comments to the EID Editors

Please contact the EID Editors via our Contact Form.

TOP