How many more deaths will it take before we go beyond half measures?
How many more deaths will it take before we go beyond half measures?
In January 2010, Prime Minister Manmohan Singh received a letter written in blood. He didn’t have to read it to know what it said—the medium and the signature were sufficient to tell the story. It was signed by Dr RN Singh, a paediatrician from Gorakhpur.
I do not know if the blood was Dr Singh’s own, it might well have been. It was a statement of extreme despair. It could have belonged to any doctor in Gorakhpur, for encephalitis was, once again, on its annual killing spree.
The PMO was quick to respond. In addition to the vaccination drive planned in all districts of Uttar Pradesh, it offered a research facility devoted to encephalitis, a rehabilitation centre, and a sanitation awareness campaign.
That was last year.
This year, encephalitis arrived in April, like it has since 1978. 400 children have died. If you had watched them die, you’d know Dr Singh’s letter could not have been typed, nor written in ink. Blood was the only possible medium.
When treating a child with encephalitis, anguish and helplessness are a doctor’s principal emotions. What begins as a simple fever in an infant or toddler quickly imprisons him in silence. He may have seizures, or he slips into a coma which may kill or maim. There’s nothing the doctor can do to stop this accelerating malignance.
The paraphernalia of hospital care mocks the doctor with its futility. Drips, tubes, drugs—are all fresh assaults on the frail body. Trapped within his impenetrable shell of silence, the little patient gives up his bodily functions, one by one. The signposts of diagnoses have failed. What is one to do but await the inevitable?
Anger very quickly replaces helplessness as the doctor is blamed for his ignorance and inefficiency. The blame game now begins in earnest. After running the gauntlet of hospital administration, it passes to the family doctor, is transmitted by him to the municipality, and rapidly arrives at the Prime Minister’s Office.
Meanwhile, more children die. Weak, hungry, malnourished, the most of them, and their parents too poor to provide even the 600 daily calories needed to keep body and soul together.
No, there’s no famine, but the children are all hungry just the same. They don’t have enough food to fuel them through the day—where will they source the reserves of energy needed to fight this frightening disease?
This has happened almost every year since 1978. How did it all go so wrong?
Encephalitis literally means ‘inflammation of the brain.’ As a catch-all term, it is a warning. No matter what its cause, a diagnosis of encephalitis is the worst kind of bad news.
Sometimes encephalitis is a complication of a common childhood illness, like measles or chickenpox. Such cases are sporadic.
Epidemics of encephalitis are usually primary, caused by a specific infecting organism, commonly a virus. The Gorakhpur outbreaks since 1978 have been caused by the Japanese Encephalitis Virus. This year, opinion is muddled: is it JEV or is it a water-borne enterovirus? The second guess is more convenient: it condones a failed vaccination drive, and ignores an inconvenient necessity that must be addressed if encephalitis is to be eradicated from Gorakhpur. This essay considers Gorakhpur’s history of JEV, and discusses how the cyclical massacre of innocents calls for a shift of perspective.
A flavivirus, and not much to look at, JEV is a single strand of RNA wrapped in a tough coat. When it enters the bloodstream, it means big trouble. The viral particle hooks up with white blood cells and multiplies madly. This phase, which can last anything from five days to a fortnight, is marked by fever and chills. IgM, an immunoglobulin, appears in the serum—it will also register on an ELISA test. The real mischief starts when viral particles enter astrocytes. These are brain cells that form the blood-brain barrier, a filter that protects the body’s most important organ from toxins in the circulating blood.
Once this barrier is breached, viral particles commandeer neurons and kill them. Simultaneously, an intense inflammatory response from the microglia, the defence cells of the brain, releases toxic chemicals that destroy even more neurons. Also targeted are neuronal progenitor cells, which possess the potential to regenerate neurons. This severe damage translates into a wide range of neurological abnormalities, from seizures to coma. Eventually, the brain becomes so sick that the vital centres that regulate life are affected, and the child dies.
Japanese Encephalitis, naturally, was first identified in Japan, in 1871. Fifty years later, it swept Japan again. More than 6,000 people were affected. There were outbreaks in 1927, 1934 and 1935.
In 1934, the virus was identified in a ‘transfected’ monkey brain. But that was just the formal introduction. It would take another few years before we got to learn its peculiar home life.
The Japanese Encephalitis Virus (JEV) leads a Panchatantra existence: its closest companions are a pig, a stork and a mosquito. In this happy company, JEV lived a modest and retiring life in a small patch of forest for thousands, perhaps even millions of years.
Then things changed. Man entered the picture, and yanked JEV out of grey anonymity. Today, JEV is a dreaded killer virus that strikes across continents.
How did it acquire this criminal profile?
This is a story any child will understand, but adults will quickly discredit.
So far, adults have made all the decisions that keep killing the children of Gorakhpur, year after year after year. Isn’t it time to listen to a story a child could understand?
As I said earlier, it is a Panchatantra story. It is, in fact, the first text of those five volumes: Mitrabhedam, the Betrayal of Friends.
Thousands of years ago, in the forests of Indonesia, JEV lived with its friends, the ancestors of the pig and the egret. JEV visited the pig and the egret by hitching a ride with the mosquito. You could say that JEV’s life was spent travelling from one friend to another, it did not possess a home of its own.
Then things changed.
JEV didn’t change—not at first.
The egret was the first to change its lifestyle, sometime in the early 19th century.
The mosquito followed suit.
The pig, meanwhile, had made a deal with the Outsider.
JEV’s life was messed up.
Travel was fine, but these were new schedules. To make things worse, the mosquito changed its flight plan, and offloaded JEV right into the Outsider. JEV found itself stranded in bleak unfriendly territory, with no future there for its kind. This new place was a dead end. All JEV could do was to lash out. And, it did.
Which takes us to the year 1870, in Japan, when JEV emerged as a killer epidemic.
Tell this story to any child and ask her to explain it to you. She’ll tell you that the villain isn’t JEV at all. It isn’t the mosquito either, because like JEV, the mosquito was confused by what the pig and the egret did. She’ll tell you that all four friends betrayed each other because of the Outsider.
So why can’t you see who the real villain is? Look in the mirror and you’ll find the Outsider smiling back at you.
Transpose this story from Indonesia to India.
Today in Gorakhpur the Outsider is Man.
The first JEV epidemic recorded in India was in 1955, in North Arcot District of Tamil Nadu and in the neighbouring districts in Andhra Pradesh.
JEV was isolated from mosquitoes in this area in 1958. Since the 1970s there have been outbreaks of JEV in almost every state in India. In Uttar Pradesh, in Gorakhpur and its eastern districts, there have been outbreaks every year since 1978.
Children are the most commonly affected. This suggests that adults have obtained immunity, the virus is now at home in such an area, and the disease has become endemic. It will now stay dormant till the conditions are right and ripe for an outbreak.
These conditions are more than the schedule of outbreaks visible to the casual observer.
Everybody in Gorakhpur knows that encephalitis breaks out in August and maintains its killing spree till the monsoon is past. The facile conclusion is that it corresponds to the mosquito season. But is that all there is to it?
What has made Gorakhpur a special target for JEV since 1978? What sort of changes has Gorakhpur seen in these past 30 years?
Canals and irrigation projects have converted large tracts of previously fallow land into paddy fields. This has increased the area of submerged land, which also stays wet for longer periods in the year. The region around Gorakhpur is famous for the migratory waterfowl. The Dudhwa National Park is just one officially designated area, but all of Lakhimpur Khairi is ornithologist heaven. And, while we’re on topic, what about the khair trees that gave the place its name? What has supplanting them done to the ecology?
Birds of the species Ardeidae—storks, egrets, herons—form the natural reservoir of JEV. When a mosquito bites a bird, it quaffs the virus in its sip of blood. The mosquito does not get sick. It just goes ahead and bites a pig—which brings us to the next chapter in the Gorakhpur story.
Out of India’s 135 million domesticated pigs, an estimated 32 per cent live in Uttar Pradesh. That’s nearly 50 million pigs in the environs of Gorakhpur. The pig is JEV’s ‘amplifying host.’ The moment a mosquito bites a pig, JEV is on velvet—all it has to do is lie back, unbutton, loosen and multiply.
Pigs in Gorakhpur don’t sicken with JEV, they simply go about their lives full of the virus, but they do get bitten by mosquitoes, which then go on to bite human babies.
The pig industry in Gorakhpur is very lucrative. Small piggeries coexist within the walls of hutments. There are slaughterhouses in every lane. The pig, in life and in death, has become an inseparable part of Gorakhpur’s human existence.
According to the Panchatantra story, it’s time now for JEV to strike out against the Outsider.
If you want to dismiss this as a fairytale, how about a dose of hard science instead?
The most relevant science lies in this angry protest: Baap dada ke zamaane mein aisa kabhi nahin hua.
The relevant question is: Kyoon nahin?
The most threatening aspect of an outbreak is the element of surprise. It springs out of nowhere, goes where it will, and very often disappears just as abruptly. Lawless, capricious, indiscriminate, it mocks the physician’s discipline by imposing a new one of its own. Whether it is an epidemiologist from today’s technologically sophisticated laboratory, or the beleaguered paediatrician in a crowded hospital ward, or indeed the terrified caregivers of the sick, the questions they ask about an epidemic are always the same:
Where did it come from? Where will it go?
The science of epidemiology consists of cracking the logic of this seemingly lawless behaviour. To some extent, it’s like the forensics of criminal profiling. The first and most important step is to identify the pattern.
This isn’t always easy.
When there is an outbreak of a known disease, even bizarre variations can be judged against the backdrop of previous knowledge. What do we do when faced with something we’ve never seen before?
‘Emerging diseases’ is the label given to diseases that appear unexpectedly in a population that has never experienced the illness before, or has had a long disease-free period. The pathogen may have come from a different geographical environment, or may have existed in the same environment in a different form, very often in another species. Once it invades the new host population, it must establish itself to cause disease, and propagate to spread the disease through the population. The disease is then recognised as having emerged.
Many emerging diseases have a dangerous potential. They spread quickly. And they hit hard. Most of them have their origin geographically distant from the area where they emerge.
It isn’t just the element of surprise that decides spread and affect. There are two terms scientists use in relation with germs that are worth knowing.
The first is pathogenic. The second, just a nuance away, is virulence.
Germs can be read like a Cave Canem, a ‘Beware of Dog’ sign. Pathogenic says ‘this dog will bite.’ Virulence tells you how hard.
Emerging diseases are caused by pathogens that often show increased virulence. This may be due to factors in the pathogen itself, or factors in the host, or circumstantial factors influencing the interaction between host and pathogen. Understanding these factors eventually decides our response to the disease.
Overall, 1,415 different species are recognised as capable of causing disease in humans. (This is at the time of writing, and the count is forever rising.) Of these, 177 have been marked as ‘emerging.’ Among these are bacteria, fungi, viruses, parasites, protozoa and prions.
A large proportion of the emerging diseases these cause are zoönoses.
The WHO defines zoönoses as ‘diseases or infections that are naturally transmitted between vertebrate animals and humans.’ Out of 177 emerging diseases, 130 are zoönoses. These may affect just one other species in addition to ours, or many species (wide host range).
Most zoönotic pathogens are poorly transmitted between human beings—rabies is an example. Others, like tuberculosis, are transmitted so rapidly between humans (once they have made the leap from animal to man), that the original source of the infection is almost forgotten. Yet others—like bubonic plague, SARS and Avian flu—thrive in humans in tandem with their animal carrier. There are some others that will persist in infecting humans only if the infection is reintroduced: this means outbreaks of disease in humans will be small and will soon burn out.
These patterns are interesting not only to the epidemiologist, but to those who examine the rise and fall of civilisations. The relationship between history and disease becomes apparent once we focus upon the factors that force a disease to emerge. Epidemiologists call these factors drivers. These are ecological changes that give the pathogen the opportunity it needs to emerge.
In the SARS pandemic of 2003, the infecting organism was traced to palm civets (Paguma larvata), sold alongside domestic livestock in Chinese markets. Initially, it was presumed the palm civet was the natural reservoir for this virus. It later became evident that these were sick civets. Where did they acquire the virus? From some, as yet, unidentified form of wild life. In the markets they were packed close with domestic livestock—
and their human owners. Overcrowding, the proximity between wild and domesticated species, precipitated the species jump of the SARS Corona Virus. From infected humans it spread rapidly by aerosol.
As we encroach on wild reserves, we provide even greater opportunity for zoönoses to emerge.
In Malaysia, the pig farming industry all but folded up after the Nipah virus outbreak of 1998. The virus was backtracked to the rainforest where a species of ‘flying fox’ (fruit bats) abound. The flying fox is a natural reservoir for the virus, and has genetic immunity against its effects. Not so the pig. So when a pig farm in Nipah encroached on the rainforest, its stock intruded on the fruit bat’s habitat. The trees overhead rained half-
eaten fruit that the pigs gobbled up greedily. The fruit was soaked in bat saliva rich with paramyxovirus (later named Nipah virus).
The pigs developed a respiratory illness, ‘one mile cough,’ along with neurological signs. Their human handlers quickly developed encephalitis.
The pigs were susceptible hosts; the pneumonia they developed caused the virus to be dispersed as a highly infective aerosol.
The virus entered humans through the respiratory route. Person-to-person transmission was not observed throughout the epidemic of febrile encephalitis that killed more than half its victims. Eventually, the epidemic was contained by slaughtering over a million pigs.
When the disease emerged in Bang- ladesh two years later, it was sporadic, and the virus was isolated in a local species of fruit bat. But there were no pigs in this story.
Between February and April 2004, 36 people in Faridpur district developed signs of Nipah fever and 27 died of acute respiratory distress syndrome. This meant the virus had stepped up its virulence. For the first time, the infection had spread by person-to-person contact via the respiratory route. The disease had emerged in a new, more dangerous form. The cause was eventually traced to a common tad (palmyra) tree. All the victims drank toddy tapped in the traditional manner—in an open pot left dangling beneath a bark-cut high up on the trunk. Apparently, the villagers of Faridpur were not the only connoisseurs of palm toddy. Fruit bats flitted in for quick sips, and left the backwash of their virus-rich saliva in the toddy.
Pandemic influenza has been related to the pig-duck farming tradition in China. The duck is a natural reservoir of the virus, and the pig, when in close proximity, acquires the virus and then acts as a mixing bowl for rapid recombinations that produce a virulent strain.
These are but a few of the steps in the complicated pas de deux between host and pathogen that makes for uneasy co-existence.
None of this understanding is reflected in the strategy adopted at Gorakhpur in the past decade.
There has been a great deal of research done by Indian scientists: microbiologists, virologists, entomologists, veterinarians, ecologists. None of this work has been translated into action. Instead, quarrels over the production, purchase, supply, quality and efficacy of vaccine dominate every debate. As the new election cycle nears there is a frenzy of fogging with DEET and pyrethrin for mosquito control. This leaves a toxic cladding on every surface except the new generation of mosquito larvae hatching immune to such minor discomforts.
That is thirty long years of hitting the head against the wall. Time to rethink strategy.
Yes, vaccination has worked in other countries, but these countries have also addressed the root cause. So instead of pouring more money into a vaccination programme where the outreach is limited, and where the efficacy is doubtful, I suggest we shift perspective and address an entirely new set of questions.
Let us begin with seasonality. Every year, around 2,000 patients with Acute Encephalitis Syndrome (a blanket diagnosis that may include other causes besides JEV) are hospitalised in Gorakhpur. Every year the disease peaks between the months of July and November. This is also the time when migratory birds winter in the Terai, the marshlands surrounding Gorakhpur. The increase in rice cultivation has meant more submerged land and more visiting birds.
JEV has five known genotypes. Till 2007, the Gorakhpur virus was GIII JEV. In 2009, samples tested positive for GI JEV as well. GI JEV is common in Japan and Korea.
How did it get here? Did it hitch a ride on a migratory bird?
Birds travel fast and very far, and understanding their migratory patterns would help us predict and contain the diseases they may transmit. More important, man-made changes in ecology also affect migratory patterns. What implication does this have on the disease? Egrets and herons around Gorakhpur carry antibodies to JEV. Monitoring migratory birds would tell us more about the virus we’re dealing with.
The vaccine used so far is specific to GIII JEV. Encephalitis in a vaccinated child does not necessarily mean the vaccine is of poor quality: the infection itself may be caused by a different genotype of JEV. So also, an increase in the number of adult cases would suggest a new infecting agent to which the population has no immunity.
Culex mosquitoes have been identified as vectors in JEV: mainly genus C. vishnui, especially Culex tritaeniorhynchus. These insects could be the most sensitive indicators to an approaching epidemic. Testing these for viraemia could be one part of the surveillance system.
The most relevant member of JEV’s Facebook page is, without question, the pig. Remember, it is the amplifying host.
There are reasons why the pig has been ignored so far, the chief being money. There’s money in pigs for Uttar Pradesh, and any stratagem to get between the pig and the bank is likely to be met with resistance at many levels.
The arguments advanced against tampering with the pig industry are likely to be quasi-scientific: though it is an amplifying host, the pig doesn’t fall sick, and doesn’t transmit its viral load except through the mosquito.
That’s what we suppose. The truth may be quite different.
When species exist in such close proximity, transmission may take place in ways we haven’t yet imagined. The pig’s secretions may coat fomites, and worst of all, the virus may be transmitted as an aerosol by the pig’s exhalations. Considering the high levels of virus in the blood of apparently healthy pigs, almost any egress from the animal spells potential contagion.
Traditionally, in all cultures, slaughterhouses were always far removed from habitation. That rule no longer applies. With the almost cancerous spread of urbanisation, I will not be surprised to soon find one in a mall. From the complaints of Gorakhpur citizens, it is clear that pigs are slaughtered in the midst of heavily populated localities. This means spillage of large viral loads. Do you need reminding that the pig is an amplifying host for JEV?
The first step in the strategy against JEV should be the separation of pigs from human habitation. The slaughter of 50 million pigs, or 100 million birds, is not the answer. All zoönotic epidemics have come about through human greed that usurps and alters ecology.
Lore is a wonderful way of learning new and effective ways to deal with a crisis.
During the Third Pandemic of Plague in 1896, the British in India refused to accept the link between ratfall and bubonic plague even though the previous outbreak in Canton had started in that manner. The Cantonese had anticipated the outbreak. Though India retained only a remote recall of bubonic plague, sporadic ‘rat fever’ outbreaks were always linked by villagers to instances of ratfall. British bureaucracy preferred to ignore local wisdom. It would be another two years before French researcher Paul-Louis Simond demonstrated the rat’s role in the plague, and forced the British to finally accept what was a self-evident truth.
The present strategy against JEV seems argued on similar lines.
Spraying insecticide against mosquitoes—which are either out of range, or resistant to the chemicals—is of no use. Why not examine instead nature’s own way of controlling mosquito populations? Rice fields, and other marshlands, have their own predators that thrive on mosquito larvae—damselfly nymphs, gerrids, notonectids, tadpole shrimp—
and entomologists know them all. In addition there are reliable fish—gambusia, guppies—that function as local agents that clean up bodies of water. All of these gorge on mosquito larvae and offer low maintenance containment strategies.
To contain an epidemic it is necessary to anticipate it. That can only be done by pooling scientific skills. The paediatrician doesn’t know what the entomologist does. The ecologist doesn’t know what the virologist does. And the policymaker knows nothing at all, except what looks good on paper. At the end of this long line of experts is the desperate taxpayer watching over his dying child.
It is the child who will give us the solution to the Panchatantra virus.
The Panchatantra is almost as vagile as JEV—there’s not a country it hasn’t visited. It is worth recalling its first journey.
The King of Persia sent his envoy to India instructing him to return with the land’s greatest treasure. The man brought home the Panchatantra. Nobody questioned his judgment. It was read in Persia, as it was read here—a dialogue between man and his environment. It provided no answers, but was full of questions.
So here’s one more question.
What if it’s some other kind of bug that’s causing the encephalitis in Gorakhpur? There are hundreds more, aren’t there?
True. But even so, the questions raised by the Panchatantra virus would still apply.
So listen, I implore you to the tale of a bug, a mosquito, a pig and an egret, to decide how we can stop betraying them. Let’s restore their co-existence, and make it possible for the children of Gorakhpur to play in the streets again.
Bombay surgeons Ishrat Syed and Kalpana Swaminathan write together as Kalpish Ratna. Their next book Once Upon A Hill (HarperCollins-India; April 2012) examines the ecology of Gilbert Hill in Andheri. Nyagrodha—The Ficus Chronicles (Penguin-India; 2006) is their version of the Panchatantra