Is India Polio Free?

In a post-polio world, India cannot sit still
No central Indian agency is tracking non-polio causes of paralysis in India, even though other pathogens can be as deadly. With polio gone, experts say it is high time to begin such surveillance

The global initiative to eradicate polio had big dreams for 2019. It was the latest deadline for the eradication of the polio virus in both Afghanistan and Pakistan. Reports in July, however, indicate that 2019 can be added to a growing heap of missed deadlines. Not only is polio still rife in both countries, but its prevalence seems to be increasing. 
Pakistan has seen four times as many cases of polio thus far in 2019 as it did in the same period last year. Set against this backdrop, the situation in India seems comparativelysanguine. The World Health Organisation (WHO) declared Indian polio-free in 2014, and it has stayed that way since.
But while polio may be in India’s rearview mirror,  other viruses may be rushing to fill the niche left by its eradication. Back in 2015, reports emerged of 208 children in Uttar Pradesh, India’s most populous state, developing polio-like symptoms. Given that the World Health Organization had declared India polio-free scarcely a year ago, the news triggered panic. Had the dreaded virus made a comeback? 
Eventually, a 20 June press release from the Ministry of Health and Family Welfare calmed these apprehensions. It said that even though the cases looked like polio, samples from the children were negative for the virus. What the children had was Acute Flaccid Paralysis (AFP), a broad basket of symptoms with causes other than polio. “India is polio-free,” the press release assured.
Four years later, it isn’t clear what happened to these children. Did they recover—many cases of AFP are transient, and patients make a full recovery. Did some remain paralysed for life? What caused their illnesses, if not the polio virus? No central or state agency knows the answer. This is because India has no systematic program to investigate non-polio AFP cases, even though 36,338 cases were recorded in 2018. 
The lack of research in this critical area is “very tragic,” says C Durga Rao, a microbiologist at Bengaluru’s Indian Institute of Science. Rao has studied viruses associated with AFP in the past.
Even though no central agency investigates every case of AFP, sporadic studies conducted by Rao and other scientists point to the role of some troubling viruses. Many children with paralysis are infected by members of the genus enterovirus, to which polio belongs. This genus has microbes like EV71 and EVD-68, which have been dubbed “the next polio” because of the crippling disease they can cause. 
For example, EV71, which circulates widely in East and Southeast Asia, kills or paralyses a large number of the children it infects. A study by Rao between 2007 and 2009 and another by Mumbai’s Enterovirus Research Centre between 2008 and 2012 found EV71 among AFP cases in India.
Meanwhile, EVD-68—which attracted global attention for being linked to major AFP outbreaks in the USA and Europe recently—was identified in a 2-year-old Maharashtrian child with respiratory illness in 2017.
But these viruses are merely the headline-makers; there are around 70 other enteroviruses capable of harming humans. Out of these, researchers have also identified echovirusesand coxsackieviruses in the stools of India’s AFP-afflicted children. These studies are not definitive proof that the viruses are causing the AFP (the viruses may be present in the children’s bodies without causing harm), but they provide a reason to look deeper. 
Such deeper investigations may reveal that many AFP culprits are not enteroviruses at all. For example, the West Nile Virus and Epstein Barr virus are also known to trigger paralysis. The botulinum toxin, which contaminates foods like milk, can cause a similar syndrome. Finally, some vaccines, such as the influenza jab, trigger an autoimmune illness called Guillain-Barre Syndrome, which looks a lot like AFP.  Nobody has tried so far to pick apart this grab-bag of AFP causes in India systematically. But experts say it is high time to do so.  
The double-edged victory over polio
AFP was first used as a surveillance tool in 1985 when the Pan American Health Organization decided to end polio in the Western Hemisphere. Polio is a difficult disease to diagnose; many other afflictions look a lot like it. So, instead of leaving it to doctors and ill-trained medical workers to spot its symptoms, a decision was made to collect stool from every case that looked like polio. Basically, every AFP case. WHO soon recommended the same strategy, and India followed suit in 1997.
But things didn’t go as expected. Since polio was the biggest cause of AFP in the nineties, the assumption was that the AFP burden would shrink as polio declined. The WHO even estimated the number it would drop to: non-polio AFP cases for every 100,000 children under 15 years (NPAFP rate) ought to shrink to around 1-2 each year, it said.

This happened in countries such as the US and Sri Lanka. But in India, AFP numbers rose. Between 2001 and 2011, for example, India’s NPAFP rate grew 
from 1.88 to 16.14. Total AFP cases, which include NPAFP as well as confirmed and suspected wild poliovirus infections, jumped from over 7,000 to 60,000 per year. And the numbers still haven’t fallen to WHO’s estimate. Even in 2018, polio-free India had an NPAFP rate of 9.73.
Polio experts have proposed several explanations for this spike. The most common one is that India has an exceptionally intensive AFP surveillance network—one of the best in the world. And around 2003, already struggling with a huge number of cases, India dialled its surveillance up a notch, counting even borderline cases as AFP. Further, it began increasing the number of centres that reported AFP cases—from over 20,000 in 2004 to over 35,000 in 2012. And some of the reporting sites weren’t hospitals at all, but even temples and quacks, where families often took stricken children.
The consequence of this was that a number of mild cases, and cases which weren’t even paralysis, were caught in the AFP net, some experts say. “Even a slight injury, which leads to 2-3 days of limping, gets reported by hospitals because surveillance is intense,” says Jagadish M Deshpande, who previously headed the Enterovirus Research Centre and worked on poliosurveillance systems in India. This would mean that a number of AFP cases may not be paralysis at all.
Yet, there are other children who do become permanently disabled. And neither the NationalPolio Surveillance Project (NPSP), nor any other Indian agency has any idea of how many cases fall in this category. This is because of a blindspot in India’s AFP monitoring. “Once the sample is negative for polio, the story ends,” says Govindakarnavar Arunkumar, a virologist at the Manipal Centre for Virus Research in Karnataka. The negative samples are typically not investigated further by NPSP, although external researchers like Durga Rao have conducted occasional studies. 
The patchy data that exists, however, suggests that a significant number of AFP cases end in permanent paralysis.
A critical blindspot
Over a decade ago, C Sathyamala, a researcher from Delhi’s Council for Social Development, sought information on the number of children with long-term symptoms under India’s Right to Information Act. She found that in 2006, NPSP had tracked some 2,043—around 18%—AFP cases in Uttar Pradesh. Out of these, 989 had residual paralysis and 244 died. 
Based on this, Sathyamala argued in a letter to the Indian Journal of Medical Research that intensive surveillance systems couldn’t fully explain the high number of AFP cases in India.
Of course, the information received by Sathyamala pertains to UP alone; nothing is known about NPAFP elsewhere. This paucity of information even when NPSP collects samples from all paralysis cases is disturbing, says T Jacob John, a Vellore-based virologist known for his work on polio. “Doing AFP surveillance from late 1990s, and not knowing the exact clinical diagnosis of every case even in 2019 is diagnostic of a paralysed health management system,” he says.
When asked why no systematic attempt was made by India to uncover top causes of NPAFP, Deshpande said the NPSP had been geared towards polio, because it was the most common illness.  Identifying the reason behind every other case of AFP would be expensive and difficult, given the hundreds of viruses, bacteria and other factors involved, according to him. “If there are ‘n’ number of causes, every cause may not get investigated in the program because the program has to focus on something.”
“Doing AFP surveillance from late1990s, and not knowing the exactclinical diagnosis of every caseeven in 2019 is diagnostic of aparalysed health managementsystem,”
Varun Sagar, a resident of Karnataka’s Tumkur district, is one of the children permanently crippled by AFP. Two years ago, Sagar, a six-year-old with a shy, milk-toothed smile, lost the use of his right arm after a bout of fever. “He woke up one morning and his arm was hanging loose,” says N Gangaiah, his father. Sagar has now begun attending upper kindergarten and is learning to write with his left arm.
In August 2017, after consulting many doctors, Gangaiah took his son to paediatric neurologist Vykuntaraju KN of Bengaluru’s Indira Gandhi Institute of Child Health. The doctor diagnosed the child with Acute Flaccid Myelitis (AFM), a type of AFP in which the myelin—the protective sheath around nerves—is damaged.
Sagar was not the only child with AFM who came to see Vykuntaraju that month. During July and August 2017, nine others with strikingly similar symptoms visited the hospital– an unusual occurrence, says the neurologist. Such a cluster of cases typically points to an outbreak, and so Vykuntaraju conducted further investigations to identify the cause. But despite testing for dozens of pathogens, including West Nile Fever and Zika, the group wasn’t able to identify the culprit, as they reported in a 2018 paper.   
The spectre of the next polio
While Sagar’s family may never know what was behind his illness, one emerging AFM cause that has attracted global attention recently is EVD-68. Around five years ago, the US and Europe saw a sudden rise in children with severe respiratory illness, with a fraction developing AFM. Investigations revealed that the cases were likely due to EVD-68, an enterovirus first isolated over 50 years ago. 
The sudden spike in severe EVD-68 disease was a surprise because this microbe had historically caused only a mild cough and cold. But the AFM outbreaks kept coming. After dying down in 2014, they recurred in 2016 and in 2018, too.
To some researchers, the unexpected emergence of EVD-68 after decades echoes polio’s rise as a global scourge. Before the twentieth century, paralytic polio occurred sporadically, causing small outbreaks. Then, driven by a combination of factors, the disease exploded onto the world scene, afflicting tens of thousands of children at its peak in the mid-twentieth century.
Nobody knows what trajectory EVD-68 will take, but it does look a bit like polio. “It is clear that EV-D68 has increased in pathogenicity since 2014,” says Nicholas M Grassly, an epidemiologist at the Imperial College of London. According to one estimate, EVD-68 attacks neurons and causes AFP in roughly 1 in 100 symptomatic cases. But what made the virus shift its behaviour so dramatically? Some studies suggest that specific mutations that occurred since 2006 may have helped EVD-68 target neurons instead of just the respiratory system.
It is impossible to say if EVD-68 will ever become as widespread as polio. “The simple answer to this is that we don’t know,” says Grassly. But, he adds, it is important to track emerging enteroviruses so that vaccines can be developed to keep them in check.
India’s Pandora’s box
In India, however, such tracking doesn’t happen, so it isn’t even clear if EVD-68 is circulating here. It is present, however, as the Pune-based National Institute of Virology’sfinding of the virus from a child in Maharashtra shows. Vykuntaraju, who has treated children with AFM, says his team couldn’t test for EVD-68 because they didn’t have the lab facilities to do so. 
Mumbai’s Enterovirus Research Centre also looked for EVD-68 in an as-of-yet-unpublished study of over 4,500 stool samples from NPSP in 2014 and 2015, says VK Saxena, the scientist who led the study. They didn’t find the virus, but this doesn’t mean much because EVD68 is difficult to isolate from stool, and requires respiratory samples. 
Meanwhile, India has several other concerning viruses. Take EV71, whose historical trajectory has also reminded scientists of polio. The virus has caused large outbreaks of hand, foot and mouth disease in China and other east Asian countries, with a fraction developing AFP or dying. 
Studies by IISc’s Durga Rao and Mumbai’s Enterovirus Research Centre have found this virus in the stools of AFP patients across India. The mere presence of EV71 in stools doesn’t mean it has caused paralysis—enteroviruses are widely found in the stools of healthy children too, and scientists typically compare the prevalence in healthy children with sick children to find out if the virus is really causing the disease. However, it’s reason enough to stay alert. 
Scientists are not very sure why India hasn’t yet seen massive outbreaks of hand, foot and mouth disease like neighbouring China has, given that EV71 is here too. But according to Saxena, this could be due to the milder varieties of the microbe circulating in India. This situation may change quickly, though. 
In their 2014-15 study, Saxena’s team found a virulent variety of EV71—the genogroup B, linked to hand-foot and mouth disease in Southeast Asia—among AFP-afflicted children in Mizoram. “This is very bad news,” Saxena said. “If the virus spreads to the rest of India, we will be in deep trouble because we are not prepared for anything like that,” he said.   
State of surveillance
The only way to be ready is surveillance. It may not be possible to diagnose all, “but it will be nice to know the top five reasons for AFP in India,” says Gagandeep Kang, a microbiologist and the executive director of Delhi’s Translational Health Science and Technology Institute. 
Such surveillance will neither be straightforward nor cheap. AFP is a huge basket of diseases, under which distinct syndromes like Guillain-Barre and AFM are lumped. So, the first step will be for doctors to identify these syndromes based on a child’s symptoms, says Arunkumar. Merely identifying the virus in stool without correlating it with symptoms is misleading because healthy children excrete viruses too.
Once symptoms are mapped, hospitals can send their samples to a network of well-equipped labs, which will use this data to decide which viruses to test for. For example, a cluster of Guillain-Barre cases could point to zika, while a cluster of AFM incidents could indicate EVD-68 or West Nile. 
This two-step process is important, says Arunkumar, who runs a surveillance project to identify causes of fever across several Indian states. “We need to sub classify cases and investigate appropriately because otherwise it is a very huge investment and you won’t get anything for it,” he says. The fever surveillance project run by Arunkumar was started with a 4-year grant of $9 million from the US’ Centres for Disease Control and Prevention.

Expensive or not, such a system could help identify AFP’s biggest causes and prevent further cases like Varun Sagar’s. At the very least, it will allow the families of affected children to understand why the paralysis occurred. Today, in the absence of a known cause, Sagar’s mother wonders if the cellphone tower next door was the culprit. They will keep guessing at the reasons for years to come.