Saffold cardiovirus (SAFV) was first described in 2007,[from a 1981 human sample; 10] and since then has been found to consist of 11 genotypes (SAFV-1 to SAFV-11; [13] ) of viruses associated with gut, airway and perhaps neurological illnesses in humans.[9,11] I briefly wrote about them here in 2018. They all belong to the species, Cardiovirus B.

Don’t test, don’t find, can’t know

SAFVs are not usually a part of any routine laboratory screen. Realistically, the same can be said for other viruses found in humans because unfortunately, we don’t look for every viral threat every time. In the case of SAFV, the association between the presence of a SAFV and it causing any particular illness remains pretty tenuous because studies are mostly quite small and there aren’t many of them (fewer than 80 papers mention “saffold virus)”.

We know that SAFVs can cause infections early in life and that they can transmit widely. Many children and adults worldwide have antibodies to a SAFV, indicating past infection.[3-7] These infections seem to happen mostly at a young age.

A new respiratory illness SAFV study from Japan

A new study from Japan looked over some of their old results,[14-16] and added them to some new testing results. They found SAFV-2 in some children with respiratory illness. The virus-positive children usually had fever (86-92% of SAFV positive samples) and, less often (22%-46%), had mouth ulcers (herpangina), pharyngitis and tonsillitis.[1] The findings were similar among those children who tested positive for SAFV-3, although they more often had herpangina. They’d also found some SAFV-6 in their earlier data, associated with “acute upper respiratory tract inflammation”.[16]

In Japan, SAFV detection among the ill occurred mostly during autumn.[1] Autumn and winter seem to be the peak season elsewhere in the world as well.[8,9]

Different SAFVs, different parts of the body?

This new study found that a 2009 SAFV2 variant was closely related to a strain we characterized in Brisbane in 2011 suggesting that the SAFVs are circulating worldwide. That’s not a surprise for viruses that spread easily via the faecal-oral and, quite probably, via a respiratory droplet route.[12,17,19]

SAFV-1, 2, and 6 probably best fit with being transmitted between humans through a respiratory transmission route based on what we know. The others, SAFV-4-11, may be more likely to be transmitted via a faecal-oral path.

Because more work is needed before we make too many assumptions in this realm, I wrote that last sentence in pencil, not pen. I wouldn’t be surprised if both modes come into play.

Shy pathogen or wily passenger?

Interestingly, as reported in other studies,[12] including our own from 2012,[8] the Japanese study found quite a high proportion of co-infections, in other words, more than one virus identified per sample tested. We had previously reported that 5/8 (63%) instances of SAFV were accompanied by the co-detection of another virus. This latest study found 53% (32/60) had a buddy virus, although the numbers in this paper are a bit hard to tally).

In a 2017 report, a case-control study from patients in southern China identified a high proportion of SAFV in the samples from well control children.[20] The authors concluded they found no support for a causal role for SAFV (or Aichi virus) in acute gastroenteritis in children. Big call.

More work is needed to define what SAFV is capable of in the absence of other viruses just in case the other viruses are the real pathogens and SAFV is just a passenger.

Saffold viruses need more work

SAFVs don’t exist as 11 genotypes because they feel like it. The less commonly detected genotypes may well be out there causing something that we haven’t identified yet. Maybe they are in a body compartment we don’t test much. Or don’t test comprehensively. Maybe they mostly cause minor illness that we don’t go to see a doctor about.

My presumption is that the rare SAFV genotypes haven’t just disappeared in the meantime but may not have been further sought in the areas from which they were first identified. SAFV4-SAFV11 viruses were first identified in samples collected 2007 to 2009 using nucleotide sequencing on positives identified from studies in Pakistan, Afghanistan and Nigeria.[13,18,unpub] Stool samples came from the acute flaccid paralysis (AFP) network in Afghanistan and Pakistan. I suspect follow-up epidemiology studies just aren’t a top priority.

Research to answer such basic and perhaps unsexy questions needs funding and funding needs a good application underpinned by good justification. It’s tough to pitch a good reason if there isn’t enough research supporting that reason in the first place. See the circularity of that problem?

A lab with funding to just look for viral stuff anywhere in the world’s human places with access to good clinical support to help it all make sense. My dream.

References

1. Detection of Saffold viruses from children with acute respiratory infections in Yamagata, Japan, between 2008 and 2015
   https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmv.24928
2. A newly designed real-time RT-PCR for SAFV detects SAFV-2 and SAFV-3 in the respiratory tracts of ill children during 2011
   https://www.ncbi.nlm.nih.gov/pubmed/22832058
3. Cultivation and Serological Characterization of a Human Theiler’s-Like Cardiovirus Associated with Diarrheal Disease
   https://jvi.asm.org/content/84/9/4407
4. Saffold Virus, a Human Theiler’s-Like Cardiovirus, Is Ubiquitous and Causes Infection Early in Life
   https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000416
5. Saffold virus infection in children. Malaysia, 2009.
   https://dx.doi.org/10.3201/eid1708.101380
6. Seroepidemiology of Saffold cardiovirus (SAFV) genotype 3 in Japan
   https://www.ncbi.nlm.nih.gov/pubmed/23107837
7. Seroepidemiology of saffold cardiovirus type 2
   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381534/
8. A newly designed real-time RT-PCR for SAFV detects SAFV-2 and SAFV-3 in the respiratory tracts of ill children during 2011
   https://www.ncbi.nlm.nih.gov/pubmed/22832058
9. Gastroenteritis and the novel picornaviruses aichi virus, cosavirus, saffold virus, and salivirus in young children
   https://www.ncbi.nlm.nih.gov/pubmed/23602437
10. Discovery of a novel human picornavirus in a stool sample from a pediatric patient presenting with fever of unknown origin
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1933019/
11. The preparation of an infectious full-length cDNA clone of Saffold virus
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062622/
12. Saffold virus, an emerging human cardiovirus
    https://www.ncbi.nlm.nih.gov/pubmed/27723176
13. SAFV sequences on picornaviridae.com
    http://www.picornaviridae.com/cardiovirus/cardiovirus_b/safv_seqs.htm
14. Sequence and phylogenetic analyses of Saffold cardiovirus from children with exudative tonsillitis in Yamagata, Japan
    https://www.ncbi.nlm.nih.gov/pubmed/20608765
15. Saffold Cardiovirus Infection in Children Associated With Respiratory Disease and Its Similarity to Coxsackievirus Infection
    https://www.ncbi.nlm.nih.gov/pubmed/21386746
16. The impact of Saffold cardiovirus in patients with acute respiratory infections in Yamagata, Japan
    https://www.ncbi.nlm.nih.gov/pubmed/21428851
17. New Saffold Cardioviruses in 3 Children, Canada
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600268/
18. Genetic diversity of circulating Saffold viruses in Pakistan and Afghanistan
    https://www.ncbi.nlm.nih.gov/pubmed/24899154
19. Saffold Cardioviruses of 3 Lineages in Children with Respiratory Tract Infections, Beijing, China
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321900/
20. Analysis of Aichi virus and Saffold virus association with pediatric acute gastroenteritis
    https://www.ncbi.nlm.nih.gov/pubmed/2799278