Case spectrum from XMRV irrelevance to Global Pandemic
Hi SiverbladeTE and dannybex,
I just wanted to add to what SilverbladeTE has said. I want to do a risk analysis. The sad thing is that I am happy if XMRV turns out to be a non-issue, and also if it turns out to be a nightmare pandemic, but for different reasons. I am also unhappy about it along a similar line of reasoning. The reason is that it is good for the world, and bad for us, if XMRV is a non issue. It is dire for the world, but offers us hope, if XMRV is a nightmare pandemic. At least then the world will be forced to deal with the issue, and focus on a cure - and we will benefit.
Let me sum up the cases for everyone to consider. I think the real case is somewhere toward the worst case, but we wont know for sure until we have hard evidence. While I am listing these as discrete cases, it is more a spectrum from "what the hell are we even talking about this for?" all the way to "why the hell has the world allowed this to happen?".
1. The first case is either for very low prevalence (e.g. XMRV is all a mistake) or very low pathogenicity. In this case most XMRV is a laboratory contaminant (no I don't believe that, I am just listing the possibilities), or XMRV is a mostly benign passenger virus.
2. If XMRV has low prevalence but minimal pathogenicity, it might still explain ME/CFS by inducing a type of autoimmune response. This is the autoimmune theory of ME/CFS, and may include molecular mimicry as a mechanism. This definitely opens the question as to whether other pathogens may induce the same autoimmune response. At this prevalence XMRV can probably only explain some ME/CFS instances. Under this case it is also possible that XMRV is a bystander virus, and we need to look elsewhere for causation.
3. If XMRV has slightly higher prevalence, but low pathogenicity there is only slightly more of an issue. In this case something like the Japanese prevalence data of 1.7% is more accurate, and the higher percentages are statistical anomalies, clusters, or lab mistakes. It is similar to case 2, although it might explain most ME/CFS instances.
4. If XMRV has moderate prevalence, say just under 4%, then it can explain most ME/CFS instances and still be a major problem for the world. At this prevalence cancer risks could become significant if XMRV can induce cancer (e.g. prostate cancer, CLL or MCL). One of the issues here is that this prevalence figure is probably low because some cases will not be detected. In addition, we finally have to acknowledge a possible several percent more from the non-well population. The final prevalence could thus easily be 7%.
5.a. This is the figure that SilverbladeTE mentioned - 7%. Two studies have shown around that prevalence. The cancer and neuroimmune risks could be even worse at this prevalence. Of course, it also depends on pathogenicity. For this case I am going to look at low pathogenicity first. In this case ME/CFS is probably also again an autoimmune disorder. Cancer and other neuroimmune risk could be more from inflammatory responses and immune disregulation than from direct viral impact.
5.b. For higher pathogenicity, it is more likely that XMRV can directly induce neuroimmune diseases and cancer. It is possibly the direct cause of most ME/CFS, although it still might require other factors such as genetics or co-pathogens. If this case is correct, ME/CFS is probably a global pandemic. It is time for the world to be worried.
6. I am not going to discuss low pathogenicity in the worst case scenario. I am going to jump straight in and give my nightmare scenario, a major pandemic of Biblical proportions sweeping the world. All figures are uncertain at this point, so I am going to simplify the argument a little - the final outcome could be a little better or worse than what I will discuss. Lets presume the healthy population has an XMRV and related virus prevalence of 8%. Add one or two percent more to allow for false negatives (I am not going to bother discussing false positives here, this is the worst case possibility). This could be a percent or two more. Add in the neuroimmune disease and cancer from the virus, and we are talking several percent more. This problem could be 10%-12% of the world population at risk of premature death, most of whom are infectious (albeit I think the evidence is clear that XMRV transmission rates may be very low). This is in accord with the Dubbo studies which showed that the single biggest risk factor for developing ME/CFS was severe infection, and that 10-12% of these infected will develop severe post viral fatigue. At this prevalence, the risk of being infected is probably much higher than half a century ago, and we can expect XMRV to spread much faster. Until we can screen the blood supply, anyone who has a blood transfusion without appropriate viral deactivation of the blood is at extreme risk. This is very much a nightmare scenario - and nobody can prove this is not what we are facing.
The risk is that we have no certainty that it is case one, or case six or anything in between. We need to KNOW. Simply hoping this will go away without investing in the science is extreme stupidity. If the science can prove, and not just suggest, that XMRV is non-issue that is a good result. We can then move on and look for other causes of ME/CFS.
If however, case six can be proven, we will finally know what we are dealing with. The sooner we can determine if this case is correct, the better it will be for the world, in terms of health, suffering, panic and economic impact. It is this scenario which, until disproved, should compel the world to fund research. Failure to do so is verging on complicity in global genocide. If it is correct, we can finally divert the resources to this problem that it deserves - this will be like HIV research on speed. Fortunately we have both a large HIV research community and over half a century of research into murine leukemia viruses to give it a boost. This was a lucky break, I would not expect the universe to give us another one if we ignore the warning.
Seriously worried,
Alex Young