September 15, 2010

Jaundice in Japan

I am just back from Yokohama, Japan, where I went to attend the United States-Japan Cooperative Medical Sciences Program (USJCMSP) Workshop on “Enteric Viral Hepatitis A and E in Asia”. As the name suggests, most of the participants were from USA and Japan, but there were a few from elsewhere as well.

Yokohama is Japan's second largest city about one hour south-west of Tokyo by fast train. The Narita Express (N’EX) takes 90 minutes to get there from the airport. It is clean, efficient and a very comfortable reserved train. The fare is JPY 3,500 one-way or JPY 5,500 return (~ Rs. 3000 or $65). A new feature for tourists is the NEX-Suica combination ticket for the same price. The Suica is a top-up card that enables cash-free local travel and shopping.

The Tokyo metro is one of the world’s best. The stations are busy but functional in every way; some of the larger ones are underground cities. The only problem is that ticket machines at many smaller stations are almost always in Japanese, leaving the traveler a bit lost. But help in the form of an official or eager youngsters ready to practice their English, is never far away.

There was no time to explore Yokohama, partly because of the busy conference schedule and partly due to the weather, which remained rainy and windy due to a passing typhoon. The planned walk in a Japanese garden followed by dinner in a traditional Japanese house was limited to the latter. From the bus and hotel windows, Yokohama appeared to be a modern city with skyscrapers and skywalks. This was my forth visit to Japan, the first being in 1993. One visible change I noticed was an increase in the number of cafes. Coffee drinking is becoming popular in Japan as well. A Cappuccino is never far away.


The Yokohama Sakuragicho Washington Hotel (where I stayed) was large and functional to meet the needs of a business traveler. For JPY 11,500 (~ Rs. 6400 or $140) one gets a room that fills up very quickly with just the bed and a counter that accommodates a TV screen, a hot plate and has room for a laptop. Internet was fast and free. The toilet was small enough for me to touch both walls while standing in the middle. But, it had everything that one needs – a shower-cum-bath, a basin, a toilet, soap, shampoo, conditioner, clean towels. And water from the tap is drinkable.

The Japanese toilet has also undergone a transformation. All toilets now have bidets. This is a device, which at the push of a button extends from under the flap to wash you after the job is done. And it is hands-free!! Here is the link to a video that is a funny, real-life experience of using a Japanese toilet.

At the conference a researcher even showed data that correlated a drop in hepatitis A virus transmission in Japan to the introduction of bidets. Technology to the aid of public health.

The conference was quite good. There were about 50 people, many of them the world’s experts on hepatitis viruses. The talks were excellent and the discussions meaningful. The focus was to discuss new developments in the biology, epidemiology, pathogenesis and control of enteric hepatitis A and E. Hepatitis A and E viruses (HAV and HEV) are enteric, i.e. infect through the gut but finally affect the liver causing jaundice, a lot of morbidity and about 1% mortality in affected patients. Both viruses are transmitted primarily through contaminated water and food, and sanitation is central to their control. As expected, countries that are poor and have large populations deprived of development are also endemic for these viruses. It is estimated that the cumulative burden of HAV and HEV is 5 billion and 2 billion, respectively (world population ~6.8 billion). This is enough reason to study these viruses and the diseases they cause.

What were the highlights of this conference? Many interesting new studies were reported that described the changing epidemiology of HAV and HEV, and recent outbreaks in Asia. While most Asian countries do not see hepatitis A as a clinical disease because it is so endemic that by 10 years of age pretty much everyone is exposed, has asymptomatic infection and is then protected for life. But with widely disparate standards of hygiene in many countries, the generation growing up on bottled water in our countries is increasingly at risk. A vaccine is available, but is expensive and is impractical for use in the vaccination programme of a country like India.

Hepatitis E epidemiology is however very interesting. At any time in India no more than about 30-40% people show exposure (based on antibodies to HEV). This leads to a lot of disease in young adults. HEV also causes high mortality in pregnant women, but the reasons are not fully understood. Proposals made at this conference suggested that pregnancy is a state of immunosuppression (to preserve the fetus) and viral infection compounds the problem. But why don’t all viral infections lead to high mortality like HEV. The use of proteomic and metabolomic technologies are beginning to unravel the host status during these infections, and allowing us to understand these details.

The recently published clinical trial for a new HEV vaccine was presented at this conference. This trial tested a Chinese recombinant HEV vaccine in almost 100,000 people – half of whom got the vaccine and the other half got a placebo (the hepatitis B vaccine). These people were then followed up for one year to see how many get naturally infected with HEV. There were no infections in the vaccine group and 15 infections in the placebo group, giving a one-year efficacy of 100%. But it is these same numbers that illustrate the economics of using HEV vaccines. If there were 15 infections among 48,000 persons over 1 year, this gives a rate of 0.0003. In other words, over 3000 persons will have to be vaccinated to prevent 1 infection over one year. That is clearly not affordable, unless the vaccine is dirt cheap.

An interesting example of the hygiene hypothesis was also presented. This hypothesis suggests that lack of early childhood exposure to infectious agents, gut parasites and allergens increases susceptibility to allergy and asthma. In a retrospective study of atopy and respiratory allergies, Italian men with these allergic conditions showed significantly less exposure to HAV and the gut parasite Toxoplasma gondii. laeding the authors to conclude - "Respiratory allergy is less frequent in people heavily exposed to orofecal and foodborne microbes." Click here to read the paper.

The cellular receptor for HAV is a protein called TIM-1 (also called HAVcr1). It has been shown to regulate the development of asthma in humans. There are two forms of this gene - the long form and the short form. The long form of TIM-1 protects from allergy/asthma but 1 or 2 copies of this gene result in more severe HAV disease. During human evolution, HAV infection has driven natural selection of the short form of this gene, which protect from HAV but predisposes the carrier to allergy/asthma. This is a great example of environment and gene interaction.

The bottom line is - A little dirt never hurts. How much is enough? That is the question to ponder over in an over-sanitized world.

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