Monday, 30 June 2014

A not so curious coincidence: another tick, another phlebovirus.
In recent years there seems to have been a resurgence in Bunyaviruses. There are always incidences of certain members, for example there are thousands of cases of hantavirus each year, as well as the sporadic cases of Crimean-Congo hemorrhagic fever virus. On the other hand there are the new emergents. In Europe, the most dramatic and devastating (at least in animals) has been Schmallenberg virus, which will no doubt now be familiar to more or less all cattle and sheep farmers. 

As far as 'human' viruses are concerned, there have been a couple of highly related viruses: one in the Far East, and one the US. Severe fever with thrombocytopoenia syndrome virus (SFTSV) emerged in China in 2009, and was isolated from one of a series of patients with hemorrhagic fever. The virus from the US is Heartland virus (HV), and was isolated in 2009 from two cases in Missouri. The last few weeks have seen the second death in the US from Heatland virus, this time in Oaklahoma

SFTSV and HV are both members of the phlebovirus genus of the Bunyaviridae. Rift valley fever virus (RVFV), currently one of the great fears for Europe, is also a member of this genus and is spread by mosquitoes. However, unlike RVFV, both SFTSV and HV are associated with ixoid and lone star ticks respectively.

Distribution of the Lone Star tick in the US.

Now a paper has been published describing another tick-borne phlebovirus, named Hunter Island Group virus (HIGV, after the location from which the ticks were sampled), this time from ticks associated with shy albatrosses on an island near Tasmania. Initially an aetiological agent couldn't be found; likely viruses such as Newcastle's disease virus and avian influenza were eliminated as likely causes. Although electron micrographs indicated a virus with morphology suggestive of a bunyavirus, antibody and PCR assays still failed to find a virus. 

Electron microscopic examination results of a newly isolated virus, tentatively named Hunter Island Group virus, isolated from ticks collected from shy albatrosses, Tasmania, Australia. A) Negative-contrast staining of virions. B) Thin section of infected Vero cells showing the presence of viral particles. Original magnification ×100,000; scale bars represent 100 nm,
Electron micrograph images of negatively stained virions (A) and thin sections of vero cell cultures (B). source

Several years later they performed deep sequencing on infected cultures. Although the nucleotide sequences failed to match with anything close, blast searches using the protein sequence revealed similarity with SFTSV. With the foundations of the sequence now known the remaining sequence was filled in, allowing an analysis using the whole genome, as well as the design of molecular assays for the specific detection of HIGV. Perhaps unsurprisingly considering the results from the deep sequencing, the viruses fit into the bunyavirus clade next to SFTSV and Heartland virus. 

Phylogenetic trees of recently isolated bunyaviruses based on amino acid sequences of the polymerase protein (A) encoded by the large segment, the membrane glycoprotein polyprotein (B) encoded by the medium segment, and the nucleocapsid protein (C) and the nonstructural protein (D) encoded by the small segment of selected bunyaviruses. Maximum-likelihood trees were constructed by using MEGA5 ( with bootstrapping at 1,000 replicates. GenBank accession numbers are with
HIGV: phylogenetic trees (amino acid sequence) of the viral polymerase (A), glycoprotein (B), nucleocapsid (C) and NSs (D). source

As the ticks were associated with healthy as well as diseased birds, it was suspected that HIGV wasn't the cause of the outbreak among the shy albatrosses, something which was confirmed when the birds were tested for antibodies against, or the genome of, HIGV. 

Richard Elliott, a well known figure in the bunyavirus  world, says the discovery of this virus wasn't a surprise, and in a way was predicted. The simple truth is that if the ticks are there, then the viruses are there.  

Discussing tick viruses with anyone always seems to leave one unanswered question; what is it that's so repulsive about ticks? 

Wang J, Selleck P, Yu M, Ha W, Rootes C, Gales R, Wise T, Crameri S, Chen H, Broz I, Hyatt A, Woods R, Meehan B, McCullough S, & Wang LF (2014). Novel phlebovirus with zoonotic potential isolated from ticks, australia. Emerging infectious diseases, 20 (6), 1040-3 PMID: 24856477

Sunday, 1 June 2014

Through the looking glass: Guinea, Ebola and life before germ theory

Last week I was at a conference dedicated to viral zoonoses where the opening talk of the meeting was given by Pierre Rollin. Rollin has for a long time been based in the Viral Special Pathogens branch at the CDC in Atlanta, USA. He’s an old hand in outbreaks of savage viruses; a veteran of many Ebola outbreaks, as well as Nipah etc. All in all, he’s someone who can speak from experience. The talk itself ranged across a variety of aspects regarding Ebola virus but concentrated, unsurprisingly, upon the control of outbreaks. Part of the talk was also dedicated to describing the situation in Guinea, from where he’d just returned. 

Health specialists work in an isolation ward for patients in southern Guinea. Photo: 1 April 2014
Ebola in Guinea: hot work, but preventing contact means preventing infection
It’s always more interesting to hear the voice of experience. Books such as The Hot Zone and films such as Outbreak are there to make money and must therefore offer drama; in the case of Ebola endless people with liquefied livers bleeding from every cut and orifice. Rollin pointed out that this is rubbish. Sure, a few do bleed, but only a “minority”; more usually it’s shock and multi organ failure. Gruesome, but not quite as graphic.
One particular point that resonated in the talk was how, in principle, outbreaks of Ebola were easy to control. Find the village, find and isolate those infected and suspected of being infected, plus educate the local population. As remarkably infectious as Ebola is, you need contact with the patient for transmission to occur – sleeping in the same room as an Ebola may be fine (if not recommended), but contact, such as sharing a bed, is a very bad idea. However, if reality were that simple Guinea wouldn't be staring at the prospect of 200 deaths. Speaking to Rollin the next day he confirmed that it was the small details and logistics that caused the most problems. Arriving at a hospital, for example, and finding that the water system is broken. No cleaning. No disinfection. Suddenly something as simple as making up bleach is a challenge. This, though, is a practicality that can be sorted. More difficult is the human aspect: educating the local population. 

 Protective Role for Antibodies in Ebola Vaccine Study Discovered
Education: a poster describing what to (and not to) do regarding Ebola for local population. Image:Medindia.
A recurring theme in Ebola outbreaks is that a lot of cases arise from two population types: healthcare workers, as a result of contact with patients, and, secondly, those involved in traditional practices, such as local ritual burial.
Ritual beliefs still hold fast in many parts of rural Africa. Some locals apparently believe that white man is bringing the disease and is deliberately infecting them. Apparently there are pockets of people in the forests of Guinea who have been hiding bodies from the doctors. In other cases there is a belief that it is spirits and spells that cause the pestilence. In general there’s little understanding of the concept of infectious disease: how many people with even limited knowledge that Ebola is caused by a virus would hug and kiss corpses who had died as a result of the infection? As strong as familial love may be, I think the rational decision may prevail. As a result of all this, there are visits to the likes of witchdoctors and herbal healers that, in turn, become infected and represent a hub of infection for many others.

File:Cholera art.jpg
Miasmas responsible for a cholera epidemic.
To many in a more developed world, this may all sound shockingly primitive. In reality however, this is simply knowledge and education. It was only around the middle of the 19th century that the likes of Louis Pasteur and subsequently Robert Koch really established the germ theory of disease. Prior to this theories of miasmas and mysterious airs still abounded around the world; the ‘mala-aria’ (bad air) derivation of malaria perhaps being one of the most well known. In one sense then, what we are seeing in Guinea is simply life before germ theory. That’s not to say they’re in any way intellectually inferior, more that it is a demonstration that knowledge gathered in more developed nations simply hasn't found its way to other nations. Remoteness inevitably is a factor. But if ever there were an argument for open access journals freely available worldwide....