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Polio-like disease in the news: much ado about nothing?
In Context
Polio-like disease in the news: much ado about nothing? Reports of polio-like acute flaccid paralysis have received much attention in both the USA and India. Uncertainty about causes and the fear of polio lie behind the media coverage. But why does uncertainty persist? Dara Mohammadi investigates. For more on polio surveillance and expected rates of AFP see http://www.emro.who.int/polio/ strategy-surveillance/
US National Archives and Records Administration/Science Photo Library
For AFP data in all countries, by year since 1996 see http://apps. who.int/immunization_ monitoring/en/diseases/ poliomyelitis/case_count.cfm
For most westerners, the threat of polio has been long-forgotten: filtered out from sepia-tinted memories of childhood. Little wonder, then, that news of a mysterious polio-like disease in California, USA, earlier this year caused such a stir. In February, Keith Van Haren (Lucile Packard Children’s Hospital, Stanford University) and Emmanuelle Waubant (University of California San Francisco Medical Center) and colleagues reported five cases of a polio-like illness affecting children over the past year: each of the children had paralysis in one or more limbs. The investigators were quick to rule out polio. Other known possible causes of paralysis were also discounted: Guillain–Barré syndrome, West Nile virus, hypokalaemia, and diphtheria. The investigators did, though, detect enterovirus 68 in respiratory samples from two of the five children. Enterovirus 68 commonly causes lower respiratory tract illness in
A US public campaign poster on polio from 1943
650
children, and as with all enteroviruses can infrequently invade the CNS and possibly cause a polio-like paralysis. But, Mark Pallansch, Director of the Division of Viral Diseases at the US Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA), explains that a causative relation between the presence of this common virus and paralysis cannot be assumed. “Detection of common agents in nonsterile sites is never diagnostic”, he tells The Lancet Neurology. Children often carry such viruses asymptomatically or with respiratory symptoms, but to be diagnostic for causation it would have to be found in the CSF of one or both of the two infected children—which it was not. The other three children had no diagnosis. “Our interpretation is that there is no specific aetiology linked to those five cases.” The CDC expects to see about one case of non-polio acute flaccid paralysis (AFP) per 100 000 children—a known and globally constant background rate of flaccid paralysis in countries not endemic for polio. Using this rate, Pallansch explains, Californian health officials would expect to see about 75 cases of flaccid paralysis a year. Of these, 25–50 can be expected to be Guillain–Barré syndrome. Except for a few other possible causes, the remaining cases of paralysis are categorised as unexplained. “So, the remaining 25 or so expected cases in California would be something that would be in the category that these kids fall into [unexplained AFP]”, he says. “We have to ask ourselves: is five an unusually high number? It’s probably more than any two neurologists would be expected to see. But is it statistically unusual? Probably not. It’s probably not outside of what would be due to chance alone.”
Formal assessment would require a case–control series. But the small number of patients in the Californian series means that any such study would be underpowered to draw meaningful conclusions. The CDC is working with the State of California to try to put these cases into the context of state-wide non-polio AFP prevalence. The State had independently searched for other cases: they found about 20 in the past 3 years; ages ranged from infants to 80 years, and most also had no specific diagnosis. The CDC is working with state health officials to establish criteria for the definition of AFP to help to get a clearer picture of numbers, and is also doing a literature review of all reported causes of flaccid paralysis. A literature review? It’s not exactly the high-tech forensic methods that the American public might hope the CDC would be doing. But, according to Pallansch, the USA’s surveillance system for such neurological infections is “very loose”—not through neglect, but, perversely, as a consequence of advanced neurological care. The more confident a neurologist is in his or her clinical diagnosis, the less likely they are to report ‘polio-like disease’ to a central system. More pressing for Pallansch and colleagues at the state level is figuring out whether the CDC has the resources to pursue a dogged, full-scale investigation to elucidate the reasons behind these and other unexplained cases of AFP. “There’s no argument that it’s absolutely a serious clinical condition, and yes, maybe we should know more about it”, he says. “But these are extremely rare cases which might not be linked, and there are other competing priorities and limited resources.” www.thelancet.com/neurology Vol 13 July 2014
In Context
AFP is a highly heterogeneous group of disorders. A case can be classified as AFP—whether or not the cause is known—if a patient shows weakness or paralysis and reduced muscle tone. Much room for ambiguity, then. And a possible reason for such a cloudy epidemiological picture across the globe. A case in point is India, which was declared polio-free in February, 2012. Here, media reports abound of an “alarming rise” in the number of nonpolio AFP cases, which has dovetailed the decreasing number of polio cases in the past 10 years. In 2003, the country reported 8000 cases of non-polio AFP. In 2011, the year in which the country’s last recorded case of polio occurred, that number had reached 60 000. More than 50 000 cases were reported last year, and so far this year India has recorded nearly 15 000 cases—more than any other country. India is a large country, so a large number of AFP cases is not surprising, but it’s the case per 100 000 children ratio that has piqued people’s interests. WHO has set a minimum expected reporting rate of about two cases per 100 000 children in polio-endemic countries; in India this number is around 12. In Uttar Pradesh and Bihar alone, where most of the AFP cases have been recorded, it is higher still, nudging 30. Media reports have linked this spike in AFP cases to the extensive use of oral polio vaccine (OPV) used by the country over the past few years as it stepped up efforts to eliminate the wild poliovirus. The argument goes that in the regions where most of these AFP cases have occurred, children have received more doses of OPV. In Uttar Pradesh and Bihar, for example, children have received on average 23 doses owing to the high prevalence of diarrhoeal disease in the area, which reduces the effectiveness of each drop of vaccine. “There are a few active anti-vaccine groups in India”, says Hamid Jafari, Director of the Global Polio Eradication Initiative (WHO, Geneva, Switzerland), “and they’ve come up with this www.thelancet.com/neurology Vol 13 July 2014
hypothesis without substantiating it with any biological plausibility or rationale. It just doesn’t fit with any of the experience or understanding about vaccine-associated paralytic polio.” He explains that the incidence of vaccineassociated paralytic polio is generally constant worldwide at about 2–4 cases per million birth cohort—much less than what has been seen in India. “The numbers just don’t add up.”
‘“In India, the polio surveillance system is intentionally dialled to a very high level of sensitivity... so it’s going to pick up a higher proportion of mild AFP.”’ Instead, he says these large numbers of non-polio AFP are a product of the intensified surveillance for polio in the country. WHO broadened the AFP case definition to include very mild cases of even transient weakness or facial paralysis. They do this to increase the number of stool samples taken and thereby increase the chance of detecting circulating virus. “In India, the polio surveillance system is intentionally dialled to a very high level of sensitivity”, Jafari says, “so it’s going to pick up a higher proportion of mild AFP.” Increased numbers of AFP are reported in all countries with active polio surveillance, but numbers vary by country because of differences in factors such as the effectiveness of polio surveillance networks and country-specific disease burdens. India’s numbers are high, Jafari says, because the country is still operating with the impressive polio surveillance machinery that managed to eliminate the disease. T Jacob John, a virologist and paediatrician formerly at the Christian Medical College (Vellore, India) puts another angle on the high number of AFP cases. “Putting them together makes no epidemiological sense other than as part of polio surveillance”, he says. “Every case of AFP needs to be diagnosed clinically before we can assess them as such and assess causality.”
But this, he says, is not happening. “India’s health-care system is a mess. The polio eradicators are interested in finding every child who is reported to have AFP. They collect the stool, look for poliovirus, and if there’s no poliovirus it’s not their concern. This is the unfortunate situation in India. Whose responsibility is it to look at each case and make sure each case is diagnosed properly? It’s the healthcare system’s. And they’re silent— they’re not participating in this debate at all.” John states that India’s health-care system is at “near anarchy”: a mix of public and private health care, with little regulation and with levels of practitioners’ medical qualification (if any) varying greatly. “There is more AFP where nutrition, access to care, and sanitation are worse: where everything is loaded against children. So some doctor—or quack—says that it’s AFP and it’s reported as AFP. Nobody has to go and confirm diagnosis. There is no follow-up. These numbers mean nothing.” Among the other causes of possible paralysis—including bacterial meningitis, Japanese encephalitis, mumps, even diarrhoea and dehydration with hypokalaemia— that are not being diagnosed, John suspects that a major cause of paralysis is post-traumatic neuropathy after injections. Despite a nationwide ban on intramuscular injections in children’s buttocks, many unregulated and poorly trained doctors still do them. If they hit the sciatic nerve, the child has a transient paralysis; in some cases paralysis is permanent. “If the country has traumatic neuritis in the hundreds, you can imagine how ill-equipped our system is—we can’t even standardise injections of little children”, says John. “For me, these high numbers of AFP cases do nothing more than raise a red flag for the state of our [India’s] health management system.”
Dara Mohammadi 651
Polio-like disease in the news: much ado about nothing? Reports of polio-like acute flaccid paralysis have received much attention in both the USA and India. Uncertainty about causes and the fear of polio lie behind the media coverage. But why does uncertainty persist? Dara Mohammadi investigates. For more on polio surveillance and expected rates of AFP see http://www.emro.who.int/polio/ strategy-surveillance/
US National Archives and Records Administration/Science Photo Library
For AFP data in all countries, by year since 1996 see http://apps. who.int/immunization_ monitoring/en/diseases/ poliomyelitis/case_count.cfm
For most westerners, the threat of polio has been long-forgotten: filtered out from sepia-tinted memories of childhood. Little wonder, then, that news of a mysterious polio-like disease in California, USA, earlier this year caused such a stir. In February, Keith Van Haren (Lucile Packard Children’s Hospital, Stanford University) and Emmanuelle Waubant (University of California San Francisco Medical Center) and colleagues reported five cases of a polio-like illness affecting children over the past year: each of the children had paralysis in one or more limbs. The investigators were quick to rule out polio. Other known possible causes of paralysis were also discounted: Guillain–Barré syndrome, West Nile virus, hypokalaemia, and diphtheria. The investigators did, though, detect enterovirus 68 in respiratory samples from two of the five children. Enterovirus 68 commonly causes lower respiratory tract illness in
A US public campaign poster on polio from 1943
650
children, and as with all enteroviruses can infrequently invade the CNS and possibly cause a polio-like paralysis. But, Mark Pallansch, Director of the Division of Viral Diseases at the US Centers for Disease Control and Prevention (CDC; Atlanta, GA, USA), explains that a causative relation between the presence of this common virus and paralysis cannot be assumed. “Detection of common agents in nonsterile sites is never diagnostic”, he tells The Lancet Neurology. Children often carry such viruses asymptomatically or with respiratory symptoms, but to be diagnostic for causation it would have to be found in the CSF of one or both of the two infected children—which it was not. The other three children had no diagnosis. “Our interpretation is that there is no specific aetiology linked to those five cases.” The CDC expects to see about one case of non-polio acute flaccid paralysis (AFP) per 100 000 children—a known and globally constant background rate of flaccid paralysis in countries not endemic for polio. Using this rate, Pallansch explains, Californian health officials would expect to see about 75 cases of flaccid paralysis a year. Of these, 25–50 can be expected to be Guillain–Barré syndrome. Except for a few other possible causes, the remaining cases of paralysis are categorised as unexplained. “So, the remaining 25 or so expected cases in California would be something that would be in the category that these kids fall into [unexplained AFP]”, he says. “We have to ask ourselves: is five an unusually high number? It’s probably more than any two neurologists would be expected to see. But is it statistically unusual? Probably not. It’s probably not outside of what would be due to chance alone.”
Formal assessment would require a case–control series. But the small number of patients in the Californian series means that any such study would be underpowered to draw meaningful conclusions. The CDC is working with the State of California to try to put these cases into the context of state-wide non-polio AFP prevalence. The State had independently searched for other cases: they found about 20 in the past 3 years; ages ranged from infants to 80 years, and most also had no specific diagnosis. The CDC is working with state health officials to establish criteria for the definition of AFP to help to get a clearer picture of numbers, and is also doing a literature review of all reported causes of flaccid paralysis. A literature review? It’s not exactly the high-tech forensic methods that the American public might hope the CDC would be doing. But, according to Pallansch, the USA’s surveillance system for such neurological infections is “very loose”—not through neglect, but, perversely, as a consequence of advanced neurological care. The more confident a neurologist is in his or her clinical diagnosis, the less likely they are to report ‘polio-like disease’ to a central system. More pressing for Pallansch and colleagues at the state level is figuring out whether the CDC has the resources to pursue a dogged, full-scale investigation to elucidate the reasons behind these and other unexplained cases of AFP. “There’s no argument that it’s absolutely a serious clinical condition, and yes, maybe we should know more about it”, he says. “But these are extremely rare cases which might not be linked, and there are other competing priorities and limited resources.” www.thelancet.com/neurology Vol 13 July 2014
In Context
AFP is a highly heterogeneous group of disorders. A case can be classified as AFP—whether or not the cause is known—if a patient shows weakness or paralysis and reduced muscle tone. Much room for ambiguity, then. And a possible reason for such a cloudy epidemiological picture across the globe. A case in point is India, which was declared polio-free in February, 2012. Here, media reports abound of an “alarming rise” in the number of nonpolio AFP cases, which has dovetailed the decreasing number of polio cases in the past 10 years. In 2003, the country reported 8000 cases of non-polio AFP. In 2011, the year in which the country’s last recorded case of polio occurred, that number had reached 60 000. More than 50 000 cases were reported last year, and so far this year India has recorded nearly 15 000 cases—more than any other country. India is a large country, so a large number of AFP cases is not surprising, but it’s the case per 100 000 children ratio that has piqued people’s interests. WHO has set a minimum expected reporting rate of about two cases per 100 000 children in polio-endemic countries; in India this number is around 12. In Uttar Pradesh and Bihar alone, where most of the AFP cases have been recorded, it is higher still, nudging 30. Media reports have linked this spike in AFP cases to the extensive use of oral polio vaccine (OPV) used by the country over the past few years as it stepped up efforts to eliminate the wild poliovirus. The argument goes that in the regions where most of these AFP cases have occurred, children have received more doses of OPV. In Uttar Pradesh and Bihar, for example, children have received on average 23 doses owing to the high prevalence of diarrhoeal disease in the area, which reduces the effectiveness of each drop of vaccine. “There are a few active anti-vaccine groups in India”, says Hamid Jafari, Director of the Global Polio Eradication Initiative (WHO, Geneva, Switzerland), “and they’ve come up with this www.thelancet.com/neurology Vol 13 July 2014
hypothesis without substantiating it with any biological plausibility or rationale. It just doesn’t fit with any of the experience or understanding about vaccine-associated paralytic polio.” He explains that the incidence of vaccineassociated paralytic polio is generally constant worldwide at about 2–4 cases per million birth cohort—much less than what has been seen in India. “The numbers just don’t add up.”
‘“In India, the polio surveillance system is intentionally dialled to a very high level of sensitivity... so it’s going to pick up a higher proportion of mild AFP.”’ Instead, he says these large numbers of non-polio AFP are a product of the intensified surveillance for polio in the country. WHO broadened the AFP case definition to include very mild cases of even transient weakness or facial paralysis. They do this to increase the number of stool samples taken and thereby increase the chance of detecting circulating virus. “In India, the polio surveillance system is intentionally dialled to a very high level of sensitivity”, Jafari says, “so it’s going to pick up a higher proportion of mild AFP.” Increased numbers of AFP are reported in all countries with active polio surveillance, but numbers vary by country because of differences in factors such as the effectiveness of polio surveillance networks and country-specific disease burdens. India’s numbers are high, Jafari says, because the country is still operating with the impressive polio surveillance machinery that managed to eliminate the disease. T Jacob John, a virologist and paediatrician formerly at the Christian Medical College (Vellore, India) puts another angle on the high number of AFP cases. “Putting them together makes no epidemiological sense other than as part of polio surveillance”, he says. “Every case of AFP needs to be diagnosed clinically before we can assess them as such and assess causality.”
But this, he says, is not happening. “India’s health-care system is a mess. The polio eradicators are interested in finding every child who is reported to have AFP. They collect the stool, look for poliovirus, and if there’s no poliovirus it’s not their concern. This is the unfortunate situation in India. Whose responsibility is it to look at each case and make sure each case is diagnosed properly? It’s the healthcare system’s. And they’re silent— they’re not participating in this debate at all.” John states that India’s health-care system is at “near anarchy”: a mix of public and private health care, with little regulation and with levels of practitioners’ medical qualification (if any) varying greatly. “There is more AFP where nutrition, access to care, and sanitation are worse: where everything is loaded against children. So some doctor—or quack—says that it’s AFP and it’s reported as AFP. Nobody has to go and confirm diagnosis. There is no follow-up. These numbers mean nothing.” Among the other causes of possible paralysis—including bacterial meningitis, Japanese encephalitis, mumps, even diarrhoea and dehydration with hypokalaemia— that are not being diagnosed, John suspects that a major cause of paralysis is post-traumatic neuropathy after injections. Despite a nationwide ban on intramuscular injections in children’s buttocks, many unregulated and poorly trained doctors still do them. If they hit the sciatic nerve, the child has a transient paralysis; in some cases paralysis is permanent. “If the country has traumatic neuritis in the hundreds, you can imagine how ill-equipped our system is—we can’t even standardise injections of little children”, says John. “For me, these high numbers of AFP cases do nothing more than raise a red flag for the state of our [India’s] health management system.”
Dara Mohammadi 651