Sunday, 25 November 2012

When is a zoonosis not a zoonosis?
Zoonosis. One of the current glam terms in virology. At it's simplest, a zoonosis refers to a disease that is transmitted to humans from animals.

But it's possible to pause and think, what actually counts as a zoonosis?

On the WHO website it's classed as "any disease or infection that is naturally transmissible from vertebrate animals to humans and vice-versa".

From Wikipedia "an infectious disease that is transmitted between species (sometimes by a vector) from animals to humans or from humans to animals".

From the medical dictionary....."refers to diseases that can be passed from animals, whether wild or domesticated, to humans".

In all of these definitions the key word is 'disease'. Look it up and disease suggests there's some sort of pathology, with overt symptoms - admittedly this too is wide open for discussion. Taking this forward, if an animal virus infects a human, but doesn't cause disease, can that then be classed as a zoonosis?

Dealing with an outbreak of Hendra virus; passed from bats to horses...and on to the handlers

I was told once that, many years ago, people who mouth pipetted viruses were seropositive for the (livestock) viruses they were working on. If there were symptoms, they weren't sufficiently serious to become part of the story, so in this case we might argue that there was no disease. That fits with the definition - no disease, therefore not a zoonosis - and indeed these viruses are not regarded as being zoonotic.  

Mouth pipetting; no longer a method of choice

An interesting paper which has recently been accepted into the Journal of Virology describing the isolation and characterisation of two novel paramyxoviruses, Achimota virus 1 and Achimota virus 2 (genus Rubulavirus) from bats (Baker et al., 2012). I enjoy a bit of virus discovery and it's nice to see a study done well with a good level of characterisation and epidemiology. The authors collected urine samples from under an Eidolon helvum bat roost and added them to cultured cells in the lab. Using the viruses recovered from the isolations they could then work out the seroprevalence, the results of which showed that there was evidence of the virus infection in E. helvum samples throughout the geographical range of this species. Variations in seropositivity among different age groups, and from year to year also showed that there has been active circulation of the virus. 

Bizarrely, one of the most intriguing things was the title, namely the "potentially-zoonotic" bit. The genus Rubulavirus contains some serious viruses, notably mumps virus, so this is an important point. The authors speculate about the zoonotic possibility based upon serology, where they found 3 people out of 442 to have evidence of prior exposure to the virus. 

But does this constitute a zoonosis? One of the positive samples was from a febrile patient, so perhapsThe authors acknowledge that whether or not these viruses are zoonotic will take some nailing down. As discussed above though, seroconversion against a livestock virus does not lead to the livestock virus becoming classed as zoonotic. So does the finding of 3/422 being seropositive for these viruses mean that they are zoonotic? Is seroconversion really sufficient to class something as zoonotic? 

Baker, K., Todd, S., Marsh, G., Crameri, G., Barr, J., Kamins, A., Peel, A., Yu, M., Hayman, D., Nadjm, B., Mtove, G., Amos, B., Reyburn, H., Nyarko, A., Suu-Ire, R., Murcia, P., Cunningham, A., Wood, J., & Wang, L. (2012). Novel potentially-zoonotic paramyxoviruses from the African straw-colored fruit bat, Eidolon helvum Journal of Virology DOI: 10.1128/JVI.01202-12

Tuesday, 13 November 2012

Crystal meth....a new way to treat influenza?
It wouldn't be unreasonable to suspect that smoking methamphetamine, one of the most widespread and damaging illicit drugs, would lead to enhanced susceptibility to various respiratory pathogens, such as influenza. That's what Chen et al had in mind when they set out to see whether meth had such an effect on influenza replication in cell culture; after all, it's already associated with enhanced susceptibility to other pathogens such as HIV and HCV (due to biological, as well as behavioural, factors). It seems this may not be the case. The study used levels of meth which are likely to be found in meth users blood, so in that sense it's realistic. When they tried infecting cells pre-treated with meth with influenza A virus, whilst the virus was able to replicate, it didn't reach the levels of control cells which hadn't been treated with meth. Similarly, when they looked for the expression of viral proteins in infected cells, they found that, as the concentration of meth increased, the level of viral protein decreased, further showing that meth is detrimental to influenza replication in this system.

Treating cells with increasing amounts of meth resulted in a does dependent reduction in the expression of the viral proteins M1 and NS1.

So how does meth affect the influenza virus lifecycle? Treating the virus with meth and then infecting untreated cells didn't make a difference to the number or size of the plaques which were formed, suggesting that meth doesn't affect the ability of the virus particles to infect and replicate in the cells. Therefore it's presumably downstream of entry; extrapolating to a human, meth therefore might not prevent the chances of becoming infected. Indeed, the study found the inhibitory effects to occur during the actual replication. Interestingly, the inhibitory effect doesn't appear to be significantly linked to enhancing the interferon response.

Treating influenza virus with meth didn't alter the development or size of plaques
This all leads to the tongue in cheek suggestion that if you catch influenza then smoking a bit of crystal meth may help treat the infection. Perhaps it does, and it will be intriguing to see whether the method of action can be determined and therefore less damaging drugs discovered, but that would not justify consuming meth, one of the most ravaging and repulsive drugs around. For a start, one of the stark realities about this paper is that it is using cultured cells, which doesn't really mimic the complexity of the respiratory tract. Then there are the effects of the drug: enhanced susceptibility to other pathogens, addiction, depression, heart disease, anxiety, 'meth mouth', altered heart and breathing rates, diahorrea, constipation, insomnia, hallucinations etc. etc.........

Meth mouth

......anyone fancy a cohort study???

         Chen, Y., Wu, K., & Chen, C. (2012). Methamphetamine Reduces Human Influenza A Virus Replication PLoS ONE, 7 (11) DOI: 10.1371/journal.pone.0048335