Despite using the majority of space here discussing the fun, frivolous and delicious episodes of life in Paris, these moments represent only a very small slice of my time. The remaining (by which I mean most) hours/days are spent working. I have no aspirations of turning this space into a discussion of lab life or highly specific scientific questions (I have friends who do that far better than I), but I think for all the other friends and family out there reading, it would be nice to get a primer of what I am really doing in Paris. Besides trying every macaron in a 10-mile radius, of course.
I came to Paris in the autumn of 2008 as a newly minted Ph.D. (in Virology) ready to pursue a post-doctoral project poised to merge questions of innate immunity and virus infection, using hepatitis C virus as a model. Twenty months later, I see this statement as a vastly naïve understatement of the multiple projects I have taken on – some of which have been left by the wayside and others that are just now coming to fruition. I spend 90% of my time and energy working on two of these projects and, in particular, it is my work in Cairo, Egypt, that I would like to discuss here in the coming days.
Hepatitis C virus (HCV) infects more than 180 million people worldwide. Stop for a second and think about that number. That is five times the number of people with HIV. It is three percent of the Earth’s population. This is a huge problem for all of us. There is no vaccine.
(Sorry for the French. That is % of individuals in the region that are/have been infected)
HCV is primarily transmitted through the exchange of blood and/or bodily fluids: transfusions with a contaminated blood supply (extremely rare with today’s screening procedures), vaccinations or medical procedures performed with insufficiently sterilized instruments, IV drug use and, to a small extent, unprotected sexual contact. Once infected, only 20% of individuals will display any symptoms while the majority (80%) will have no idea that they have just acquired the virus. In response to infection, our immune system mounts a multi-pronged attack, both on the virus and on the infected cells, which, in this case, are hepatocytes, the cells that make up the liver. In 20-40% of the cases (depending on the infecting strain) the immune system is victorious and the virus is eliminated from the system (i.e. spontaneous clearance); however, in 60-80% of patients, the virus continues to grow in the liver and the patient is considered chronically infected. 20% of chronically infected individuals will go on to eventually (10-20 years later) develop hepatocellular carcinoma (liver cancer).
All is not without hope for those chronic HCV patients, the combination treatment of interferon and ribavirin given for one year is effective at promoting the clearance of the virus in 50% of patients. Moreover, there are new antiviral drugs due to come onto the market in the next few years that have shown promise at increasing that clearance rate (to 80-90%) in clinical trials. How, why and when these drugs work is still a mystery to the field. However, many of those who need the therapy in the developing world will have no access and/or the drugs will have no effect on the strains of virus infecting their geographical regions.
This is where we come to Egypt. Egypt has a unique situation. Due to a mass schistosomiasis treatment campaign sponsored by the government from the mid-1960’s through the 1970’s using poorly sterilized needles, a large portion of the populace is infected with HCV. Approximately 10% to 20% (in urban and rural areas, respectively) of Egyptians carry the virus. Infections continue to spread through IV injections and an assortment of medical procedures. Additionally, the strain (termed ‘genotype’ because each strain has a considerably different genetic code from other strains) infecting Egypt is genotype 4, whereas genotype 1 infects most of the patients in the USA and Western Europe. While, at first it seems that all HCVs should be created equal, they are not. Many of the drugs in development for the next generation of treatment either have not been tested against genotype 4, or are known to not be active against this strain of virus.
Before you get downright depressed, there are some benefits in this situation when it comes to studying the virus and the immunology of HCV infection. In the USA, the prevalence of infection is approximately 1% of the population. With such a low number of patients walking around and, upon infection, only 20% of that 1% showing any symptoms, it is very difficult to identify newly transmitted (‘acute’) HCV cases. In Cairo, however, where the prevalence of infection is so high, these patients are much easier to identify through a network of ‘fever hospitals’ throughout the city. Finding, observing and treating these newly infected patients is key for a two main reasons: (1) the earlier one receives drug therapy for HCV, the higher chance that it will be effective at promoting clearance of the virus, and (2) 20-40% of these individuals will be able to spontaneously clear HCV on their own within the first six months after infection by a mechanism that remains to be identified.
The hard work (and our projects) come with point number 2. As part of a much larger network of extremely talented epidemiologists, virologists, social scientists and immunologists, we recruit acutely infected HCV patients into our clinical study. We monitor them at multiple times in that first stage of infection, collecting blood samples to look at the ongoing immune responses that are fighting the virus. And, by comparing the data from those patients who are able to spontaneously clear the virus from those who develop persistent infection, we are hoping to identify factors that contribute to the ability of one individual to clear their virus. Furthermore, if we could manipulate these factors or exploit them synthetically in a way to boost their anti-viral effects, perhaps we could develop novel therapies to treat HCV patients who may not be capable of clearing their virus naturally. That is the grand challenge.
For more reading (mostly with academic journal access, sorry):
On the causes of HCV in Egypt:
Frank, C. et al., Lancet. 2000: 887-891.
On the treatment of HCV in Egypt:
On HCV in the US:
Armstrong, G.L. et al., Annals of Internal Medicine. 2006: 705-714
Thanks to friends (and colleagues) C & J, for the geographic HCV distribution graphic and last minute research.