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Apr 16, 2015

Summary of HEV and Nepal series

This disease may be new to you and may be you may just brush aside saying, "Well, this is none of my business!!" If you are thinking in that line, wait a minute!! Let me share you common suffering from this disease, which is rampant in low income settings. You may be avid hiker or trekker or you may also have a plan to travel to countries like Nepal, India, and Pakistan. When you get infected, whatever a person of strength and stamina, you will be bed ridden so quick that you have to get hospitalized for weeks. During this illness, you feel so miserable that you completely lose your appetite, lethargic, aversion to anything food or even its smell, and you turn yellow including your white of your eye bulb. Oh yes again, this disease is miserable, and it is said, this disease takes hold in your body after you ingest food or drinks that are contaminated with human soils. This happens in places, where when there is poor water supply, sanitation and hygiene practices. Remember, this may take the form of outbreaks affecting hundreds and thousands of people. The worst part is if this disease affects pregnant women. There is high chance of losing your pregnancy and even death of mothers due to liver complications that lead to fulminant hepatic failure and painful death. We know, this disease has not caught much of global attention like recent Ebola Virus Diseases, but remember, this disease is like a silent death that spread invisibly like bush fire with huge toll of illnesses and deaths in developing countries among impoverished population.

Where are we in its understanding?

HEV is a public health problem in low income settings causing havoc in many parts of the country. For example, let me share with you two outbreaks that provide clear perspective into the gravity of HEV problem in our country. One was the confirmed HEV outbreak in the premises of prime ministerial official residence in the year 2007, where then prime minister himself, cabinet ministers and other staffs caught this viral illness and bedridden for weeks. The second HEV outbreak is very recent in the month of May and April, 2014, which occurred in the heart of Biratnagar municipality in eastern part of the country. This outbreak was national headline, where thousands of municipality residence was taken ill and some of them died. In both outbreaks, the root cause for the disease outbreak was found to be the fecal contamination of drinking water. These two recent examples could provide us with a sense of urgency as to the extent of public health problem in Nepal that need to be addressed with available preventive tools. 

There are few facts I need to write for our memory and keeping facts straight before i conclude this series for next one. Here follows some facts on HEV:
  • Incubation period (IP) is approximately 40 days
  •  most important acute viral hepatitis among adults in much of central and southeastern  Asia and the Indian Subcontinent and the second most important hepatitis in the Middle east and North Africa
  • Up to 20 % clinical attack rate and an associated high incidence of fetal wastage
  • In endemic countries, genotypes 1 and 2 predominate and contaminated water is the major source of infection.
  •  Seronegative children and adults are at general risk of disease and pregnant women are at special risk for severe or fulminant hepatitis in endemic regions
  • With regards to vaccination - HEV vaccination is best suited to be included in EPI schedule rather than providing this vaccine in campaign mode. 

Before going into preventive measures available for this illness, let us try to delve into following discussion. To be more objective, I did a quick review of paper in PubMed and was fortunate to find series studies re: to HEV in Nepal since early 1980s. For our convenience, let us try to dissect these studies as below:

     Literature pre - 2000: Almost all studies were conducted and reported from Kathmandu valley from early as 1980s. Majority of the studies are hospital based done among admitted inpatients supplemented with serological test for its diagnosis. Few studies are also conducted among travelers or expatriate in the valley, Nepalese army in UN mission - Haiti and notably among pregnant women. One study was not human but done among local swine in the Kathmandu valley. The findings from these studies suggested that HEV is endemic in Kathmandu valley of significant public health importance and directly relates to poor water, sanitation and hygiene practices. Also, one study reports that local swine population is the host for this disease and suggests HEV as zoonotic illness. Another implication that these studies brings to our notice are that travelers / expatriates visiting Nepal are at risk; thereby this could affect tourism business. Also, there is every likely that the disease could spread to other geographical locations.

2   Literature post - 2000: All studies post-2000 add to HEV knowledge that have been gathered from studies in Kathmandu valley. What stands out in these studies is most of them are molecular in nature. These studies have clearly outlined the genotypic profile of HEV circulating in Kathmandu valley. Also, other studies done among pregnant women diagnosed with HEV infection adds to our knowledge that HEV remains serious threat to the health of mother and unborn child. Additionally, one study add that HEV has been detected to rodents in Kathmandu so adding to knowledge that some of the genotypes are zoonotic in origin, which later has implication in designing measures to control and prevention of this illness. Most important is that there was a conduct of HEV vaccine trial among Nepalese army. The vaccine tested in this controlled trial was “Hecolin” - which is licensed for use in China. 

With this background, I think, you can get a visual picture how common Nepali people must be living their life in rural impoverished community. Well, some month ago, when I wrote a brief note on cholera outbreak in some remote part of Terai, I got a public comment that it is not what I depicted in my writing. But we can hide the fact that there was an outbreak of significant impact in the communities. This we cannot deny and I hope one of my friends could be in a position to acknowledge that there exist challenges in clean water and sanitation delivery to the much needed people. However, we can debate on this public health issue. It can be controversial for those leaving in affluence. One contention I would like to bring out and be vocal outright with this background of long history of HEV studies with yearly outbreaks in Nepal, how long do we have to wait for this HEV vaccine?

Vaccine in Demand

The fruits of science have to be available for the community if the vaccine against HEV is tested in the same population during its clinical development. Before we go into technical jargon or say business case that is required for HEV vaccine to secure its place in WHO prequalified list so we can use this vaccine in public through UN agencies - let me walk you through some of the noise heard for this vaccine in Nepal. Of other countries, I cannot objectively tell or write now. But I can guess, same must be the case and scenario on other South Asian countries, where HEV outbreaks occurs yearly in impoverished population.

I Google - ed "HEV in News in Nepal" - I came across pretty long list of online news or even oped pieces. One stand out among those read and is written by Dr. Buddha Basnyat in Nepali Times. This opinion piece (#Issue 591 - Feb 2012) strongly states on possible public health use of HEV vaccine (in Nepal) comparing with SA 14 - 14 - 2, live attenuated vaccine against Japanese encephalitis (JE) also produced and licensed in China. This vaccine was also not WHO pq ed at the time when Nepalese health authority decided to use it country wide in endemic districts. This JE vaccination started in campaign mode and later introduced into routine immunization. This way, JE vaccination has been a successful program in controlling and preventing debilitating serious brain viral infection. Now, we see such a visible public health impact that anybody when travels to Terai districts can hear such stories of success. The strength that lies hidden in this endeavor is the background surveillance of Acute Encephalitis Syndrome (AES), which provided clear picture as to the epidemiology of this disease, so policy makers were able to provide direction for the country. If so is the case for HEV vaccination in Nepal, my only question is “Do we have such robust background surveillance data to guide our policy makers so they can take policy decision?" Otherwise, i can agree to what Mr. Basnyat point of view, when another HEV vaccine which was tested in Nepalese population - why not make Hecolin (Chinese vaccine) available for public health use here in Nepal? 

One key constraint is lack of comprehensive surveillance data to back up our argument for introducing HEV vaccine in the community especially vulnerable population. So, for me, I would love to see comprehensive epidemiological picture of HEV across the country. Therefore, one way would be to review all the literature so far published and use modeling tools, or conduct surveillance (active vs. passive) based on availability of budget aligning with interested parties to gauze and weigh the gravity of HEV problem in Nepal. Let us see how far this will go or else may be, there must be a way to extrapolate the findings of other country experience and create public demand for this vaccine. In that case, the recent outbreak of HEV in Biratnagar could be one scenario; we can build one for effective advocacy.

Where are we in its vaccine development?

When we remember those days of extreme weakness with bouts of vomiting with incessant nausea that gripped your guts, we can now feel the suffering. However, it is comforting to know so much have been studied on HEV and we do know the basic epidemiology including the genotypic mapping of HEV circulating in Nepal. Notably, some of the human phases of clinical trials were also conducted in Kathmandu among Nepalese population. 
However, there is only one voice that we have heard and now I have started to understand why the candidate vaccine meant for HEV is still not there in public health or even in private market arena? In this aspect, I read a short letter in response to a paper published in a leading science journal. Dr. Buddha Basnyat (a senior scientist seriously studying infectious diseases in Nepal) has raised a serious ethical question as to why vaccine industry or research organizations who have invested so much of their time and money to develop HEV vaccine and now, there is no vaccine when there is high demand in the community. In the letter titled Neglected HEV and Typhoid Vaccine, he raises a serious question, “These vaccines against hepatitis E.......are not available, despite their proven efficacy and safety. If GSK, Walter....were not going to develop these vaccines or make them available after their successful testing in Nepal and Vietnam, why were they tested? And if these organizations will not develop them further, is there a responsibility to make them available to others who might?"

Nitty Gritty of HEV

HEV is an area that needs much advocacy from the community and national level like Nepal / India / Ethiopia, where HEV is still serious public health issue. We should not wait for it instead we need to advocate to the global health community. This is what i have been saying we should work simultaneously from both end - at international fora as well build base at the community level and have find a meeting point where international authorities and community health leaders can sit together and have a meaningful but fruitful outcome from all the penny invested in such study re: HEV or any other vaccines.

I think, I have shared enough about HEV outbreaks in Nepal. Now, at my personal level, a concrete research concept is what the need of the hour along with active collaboration with academician and public health professionals in Nepal. For this, we need to review papers so far published re: HEV in Nepal and find out knowledge gaps where we need to address. Also, the key to what we plan can only be successful if we partner with international organizations, who can advocate on this problem at an international forum. 

Therefore, this planned review (that we need to write) has to bring out the comprehensive HEV epidemiology in Nepal. It should also incorporate opinion from all stakeholders, who has a role to play in bringing this much needed vaccine to the community. Finally, we need to acknowledge that there is a huge demand for HEV vaccine in countries like Nepal, Ethiopia, India, Myanmar. This has been spelled out by leading physicians and researchers in Nepal as well. The only remaining challenge is whether the voice of demand for HEV vaccine has reached those who invest or has resources to focus available fund in this area or not? I think, it has reached and it all lie within us how efficiently advocate on this HEV issue at national or international level. Importantly, I believe we have to raise awareness in the national as well as community level.

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Anuj in Himalayas

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