Australia: Acute Flaccid Paralysis & EV71

WHO Guidance On HFMD

 

 

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ProMed Mail carried a report over the weekend from Professor Bruce Thorley of the National Enterovirus Reference Laboratory in Australia that described 5 recent cases of acute flaccid paralysis (AFP) in children who tested positive for the EV71 virus.

EV71 – which is most often reported in Asia and the Western Pacific region - is one of more than 60 non-polio enteroviruses that can cause human illness. While it is frequently linked to severe outbreaks of HFMD (Hand, Foot, & Mouth Disease), EV71 is capable of producing other serious neurological illnesses – including poliomyelitis-like paralysis - as well.

A snippet from the ProMed  report, then I’ll return with more.

 

Detection of enterovirus 71 sub-genogroup C4a in specimens from cases of acute flaccid paralysis, Australia

 

Australia conducts surveillance for cases of acute flaccid paralysis (AFP) in children less than 15 years of age as part of the national polio surveillance program funded by the Australian government.

 

From January to early May 2013, human enterovirus 71 (EV71) was detected in stool specimens from 5 of 14 (36 percent) AFP cases in children. EV71 was also detected in specimens from cases of hand-foot-mouth disease (HFMD) and non-paralytic neurological illness by members of the Enterovirus Reference Laboratory Network of Australia.

 

A phylogenetic analysis of the VP1 genomic region identified homology with the EV71 C4a sub-genogroup circulating in China and South East Asia, which has been associated with more severe neurological complications than other sub-genogroups in recent years.

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HFMD is normally a mild childhood illness, most often caused by the Coxsackie A16 virus and more rarely by Coxsackie A10 here in the United States. In recent years, we’ve seen the emergence of the Coxsackie A6 virus which has been linked to somewhat more severe HFMD cases (see MMWR: Coxsackievirus A6 Notes From The Field).

 

But Enterovirus 71 has been linked to the most severe cases of HFMD – particularly across Asia - with serious outbreaks recorded over the past 15 years in places like China, Taiwan, Malaysia, Hong Kong, and last year in both Vietnam and Cambodia (see Updating The Cambodian EV71 Story).

 

An article that appeared in early 2001 in Clinical Infectious Diseases (cite Neurological Manifestations of Enterovirus 71 Infection in Children during an Outbreak of Hand, Foot, and Mouth Disease in Western Australia Peter McMinn, Ivan Stratov, Lakshmi Nagarajan, and Stephen Davis) describes its impact this way:

 

Children <4 years of age are particularly susceptible to the most severe forms of EV71-associated neurological disease, including meningitis, brain-stem and/or cerebellar encephalitis, and poliomyelitis-like paralysis.

 

The neurological complications of EV71 infection may occasionally cause permanent paralysis or death. Several large epidemics of severe EV71 infection in young children, including numerous cases of fatal brain-stem encephalitis, have recently been reported in Southeast Asia [10–12].

 

Like other RNA viruses we monitor, EV71 is constantly evolving, creating new strains or lineages, and as a result we’ve seen repeated outbreaks over the years.

 

During the late 1990s and early 2000s, genotypes C1, C2, B3, and B4 were most commonly reported as sparking outbreaks in Malaysia, Singapore, and Taiwan.

 

By 2005 emerging genotype C4 had replaced B4 in Taiwan, while in China C4 (which had split into 2 distinct lineages, C4a and C4b) caused major HFMD outbreaks in 2007–2009 (see Phylogenetic analysis of Enterovirus 71 circulating in Beijing, China from 2007 to 2009.)

 

The spread and diversity of EV71 – Credit WHO

 

As shown in the chart above, the more aggressive C4 genotype – which first appeared in China in 1998 - has made significant inroads across much of Asia and the Western Pacific over the past 15 years. 

 

Among the challenges of controlling EV71 outbreaks are:

• No currently available vaccine
• A moving viral target, with new strains evolving and emerging over time
• Many children can carry (and shed) the virus asymptomatically (see Incidence Rates of Enterovirus 71 Infections in Young Children during a Nationwide Epidemic in Taiwan, 2008–09)
• Patients may shed virus for month or longer (see Long persistence of EV71 specific nucleotides in respiratory and feces samples of the patients with Hand-Foot-Mouth Disease after recovery)

 

For now, control and prevention are limited to promoting good hygiene, and removing children with signs of the disease from child care or school environments. 

 

This from the Queensland Health Department.

 

Transmission

EV71 infection is transmitted from person to person by direct contact with nose and throat secretions, saliva, fluid from blisters or the faeces of infected people.
The virus may continue to be excreted in the faeces for several weeks. A person is infectious for as long as the virus is present in the faeces.

Treatment

Treatment of EV71 neurological disease usually focuses on the person's symptoms. Currently there is no specific treatment.

Prevention

Good hygiene is the single most effective way of preventing the spread of EV71 infection. Hands should be washed thoroughly in soap and water for at least 20  seconds and then dried thoroughly. It is important to wash hands after going to the toilet, touching soiled linen or articles, changing nappies and before preparing or eating food. Teach children to wash their hands effectively before eating or drinking and after going to the toilet.

Control

Children with hand foot and mouth disease should be excluded from child care and schools until all blisters have healed.

Children with enterovirus 71 neurological disease should be excluded from childcare/school until they have a written medical clearance from a doctor or public health unit confirming that the virus is no longer being excreted in their faeces.

 

A growing problem, in 2009 China reported 1,155,525 HFMD cases, including 13,810 severe cases and 353 deaths. Among laboratory confirmed cases, EV71 was responsible for 41% of cases, 82% of severe cases, and 93% of the deaths (cite WHO HFMD Guide Pg.6). 

 

Numbers that illustrate just how big an impact this normally `mild’ childhood disease can have.

 

For more on HFMD, including the more severe Enterovirus-71 (EV-71), you may wish to revisit the following blogs:

 

The Emerging Threat Of EV71

China: A Recombinant EV-71

HFMD Rising In China

China Sounds Alert Over EV-71 Virus

The Emerging Threat Of EV71

 

Photo Credit University of Iowa

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Although only recently making headlines in the mainstream media, Enterovirus 71 has been known for decades, and has been responsible for a number of severe disease outbreaks in small children, particularly across southeast Asia.

 

For some earlier blogs on this virus and some of the outbreaks it has caused, you may wish to revisit:

China: A Recombinant EV-71

China Sounds Alert Over EV-71 Virus

China: EV71 Claims 28th Victim, Authorities Warn of Possible `Mass Outbreak'

HFMD Outbreak In China Spreads To 25,000 Children

 

But it has been the recent outbreak in Cambodia (see Updating The Cambodian EV71 Story) that has helped to propel this virus into the public’s consciousness, and we are now seeing reports in the media on practically a daily basis.

Today, several reports, including one from the Philippines where Assistant Health Secretary Eric Tayag ominously warns that even as the world seeks to eradicate polio from the last four countries, that the EV71 virus may soon become `the new polio’.

 

EV-71 is the 'new polio,' health experts warn

by Rappler.com

Updated 07/17/2012 7:33 PM

MANILA, Philippines - Two children in the Philippines have been tested positive for "human enterovirus," but the strain is not similar to the EV-71 that has killed kids in Cambodia, the Department of Health said Tuesday, July 17.

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A bit premature perhaps, given that the numbers of severe EV71 infections currently pale in comparison to the horrific spread of Polio during the first half of the 20th century.

 

But there are some valid comparisons between the two viruses.  Both are highly contagious, and both strike predominantly in young children and can cause serious – even fatal – neurological damage. 

 

From The Lancet, we’ve this 2008 report that makes a similar comparison.

 

Enterovirus 71 infection: a new threat to global public health?

The Asia-Pacific region has seen more frequent and widespread outbreaks of enterovirus 71 infections in the past decade. Clinicians and researchers are calling for a better understanding of the evolution of such epidemics and for more proactive international public health polices. Jane Qiu reports.

Enterovirus 71 (EV71), a single-stranded RNA virus that belongs to the same category as poliovirus, has made another comeback in many parts of Asia. The reported frequency of EV71 infections are rising on a weekly basis: in Hong Kong, the number of cases reached 79 by late August, the highest in a decade. In some cases, EV71 infections cause hand—foot—mouth disease (HFMD), a common, contagious disease that usually affects children and that is characterised by flu-like symptoms; rash on hands, feet, and buttocks; mouth ulcers; poor appetite; and vomiting and diarrhoea.

 

However, HFMD can be life threatening, particularly if the virus causes inflammation of the brain stem, which can progress to heart failure and pulmonary oedema.

 

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With no vaccine, and no specific antiviral treatments available, the focus is on stopping the spread of the virus through good hygiene, and when needed, school closures.

 

Today, from Thailand’s The Nation, we get this report indicating that a number of schools are being closed due to HFMD.

 

 

29 Bangkok schools suspend classes following HFMD outbreak

July 17, 2012 6:46 pm

 

At least 29 schools in Bangkok have suspended some of their classes or shut down their whole facilities in the wake of the hand, foot, and mouth disease or HFMD outbreak.

 

"In Bangkok, most patients are young children aged not over four years old," Dr Wongwat Liewlak said Tuesday as the head of Bangkok Metropolitan Administration (BMA) Communicable Diseases Control Division.

According to the Public Health Ministry, 12,581 people have come down with the HMFD in Thailand between January 1 and July 9 this year. There is no report of casualties.

 

Another report out of Thailand, carried by Xinhua News, indicates:

 

Top Bangkok primary school closes due to hand, foot and mouth disease

Updated: 2012-07-17 15:46:00

(Xinhua)

BANGKOK, July 17 (Xinhua) -- Bangkok's top-rated Chulalongkorn University Demonstration Elementary School suspended classes from Tuesday through Friday after a number of students were infected with hand, foot and mouth disease, Thai News Agency reported.

 

Chalermpol Daoruang, the school's deputy director, said that the temporary closure came after an unspecified number of Grade 1 and 2 students were diagnosed with hand, foot and mouth disease ( HFMD).

(Continue . . .)

 

And yet another report, out of Taiwan today, CDC reports six new enterovirus cases. The good news: all but one of these cases have already been released from the hospital.

 

Whether EV71 turns out to be 2012’s disease-du-jour, or ends up becoming a pervasive public health problem remains to be seen.

 

It has the potential, but it may not have the `legs’.

 

Encouragingly, there does appear to be work going on to create a vaccine against EV71.  In the meantime, like everyone else, we’ll continue to watch the virus for signs of spread, or changes in its behavior.

WHO/Cambodian MOH Announcement On HFMD Outbreak

 

 

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My thanks go to Ronan Kelly on FluTrackers for finding and  posting the joint announcement between the World Health Organization, and the Cambodian Ministry of Health regarding the recent outbreak of severe HFMD in that country.

 

The announcement is in a PDF FILE, which makes cutting and pasting here problematic.  You can click this link, or the image below, to read the 2 page report.

 

 

Essentially, this report finds that the EV71 virus was the prime cause of the outbreak; with only a small percentage of cases testing positive for other pathogens (Strep suis, Haemophilus Influenzae type B, etc.). 

 

The report suggests the use of steroids may have worsened the outcome in some cases.

 

The Cambodian government, in conjunction with the World Health Organization, will conduct enhanced surveillance for neuro-respiratory syndrome which may accompany severe HFMD due to EV71.

 

This report appears to assign a minor role, if any, to the other infectious agents which have been widely mentioned in the media.

Updating The Cambodian EV71 Story

 

 

 

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Over the past several days we’ve seen some confusing (and conflicting) reports on the `mystery illness’ in Cambodia which has claimed the lives of more than 50 children over the past few months (see EV71: Cambodia’s Prime Suspect).

 

Complicating the investigation, these children were treated by a variety of doctors in different clinics across 14 provinces, and many died and were buried before proper testing could be done.

 

Overnight  ProMed Mail posted (see Undiagnosed illness, fatal, child - Cambodia (06): pathogen mix) a CNN  report that a combination of pathogens – including enterovirus 71, Streptococcus suis and dengue fever – will be named responsible for these child deaths, and that the inappropriate use of steroids in their treatment exacerbated their illnesses.

 

An official announcement from the World Health Organization is expected shortly, but as of this writing has not yet been published.

 

But we do have some tweets this morning from the WHO twitter account that continue to highlight the EV71 virus as the major cause of the outbreak.

 

 

 

And this morning Xinhua News is reporting that:

 

HFMD causes child deaths in Cambodia: WHO

English.news.cn   2012-07-12 19:55:37

The severe form of hand, foot and mouth disease (HFMD) was the cause of illnesses and deaths of 54 Cambodian children since April, concluded the findings of a joint investigation on Thursday.

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Whatever other contributing factors might be involved, the EV71 virus is perfectly capable of producing serious – even fatal – illness on its own. 

 

The classic symptoms of a blistering rash on the hands, feet, and mouth associated with HFMD are not always present. Sometimes the patient only presents with severe neurological symptoms.

 

 

Outbreaks of EV71 are neither new, nor rare, although the mortality rate in this Cambodian outbreak does appear unusually high (admittedly difficult to know, since we don’t know how many mild cases went uncounted).

 

The past decade has seen numerous outbreaks of EV71, resulting in the deaths of hundreds of children across Asia (see China: EV71 Claims 28th Victim, Authorities Warn of Possible `Mass Outbreak', FMD Outbreak In China Spreads To 25,000 Children).

 

 

We have also seen signs that the virus continues to evolve (see China: A Recombinant EV-71).

 

While no new cases have been reported in the past several days, with no vaccine and no effective antiviral treatment available, fears continue to run high in Cambodia. The following report from Bangkok Post indicates that some Cambodians with small children are attempting to enter Thailand to escape the outbreak.

 

   Cambodians flee to Sa Kaeo

Published: 12/07/2012 at 08:07 AM

The hand, foot and mouth disease (HFMD) scare has resulted in a mass exodus of Cambodian parents with young children into Sa Kaeo province.

 

The Aranyaprathet immigration checkpoint was yesterday crowded with Cambodian travellers, most of them with young children, eager to enter Thailand.

 

The Cambodian parents were mainly workers and vendors at the Rong Kleau border market in Thailand.

 

(Continue . . . )

 

 

When we get an official announcement from the WHO, or the CDC, as to the cause of these deaths, I’ll post it.  For now, however, the EV71 virus still appears to be the prime suspect in this outbreak.

EV71: Cambodia’s Prime Suspect

 

Photo Credit University of Iowa

 

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Although normally a mild childhood disease, HFMD (Hand, Foot, & Mouth Disease) has taken center stage in the media these past few days as one of the viruses (EV71) associated with that illness has been tentatively linked to dozens of deaths of Cambodian children over the past three months.

 

The epidemiological investigation is ongoing, with researchers looking for any possible complicating factors (or changes to the virus) that might explain the unusually high mortality rate being reported with this outbreak. 

 

We should know more in a few days, but as you’ll see, the EV71 virus doesn’t need any help to be deadly. 

 

HFMD can be caused by a variety of viruses, and most of the time, it is mild and only rarely requires medical attention.

 

The most common cause of the illness is the Coxsackie A16 virus, and more rarely the Coxsackie A10 virus. In recent years, we’ve also seen the emergence of the Coxsackie A6 virus which has been linked to somewhat more severe HFMD cases (see MMWR: Coxsackievirus A6 Notes From The Field).

 

But it is Enterovirus 71 that has been linked to the most severe cases of HFMD – particularly across Asia - with serious outbreaks recorded over the past dozen years in places like China, Taiwan, Malaysia, Hong Kong and most recently, Vietnam.

 

In addition to the classic HFMD symptoms, this virus has been known to produce serious neurological illness, including life threatening encephalitis. 

 

You can find more details on HFMD, and EV71, in the World Health Organization’s Hand, Foot and Mouth Disease Information Sheet, from which I’ve excerpted the following:

 

• HFMD is usually a mild disease, and nearly all patients recover in 7 to 10 days without medical treatment and complications are uncommon.
  • Dehydration is the most common complication of HFMD infection caused by coxsackieviruses; it can occur if intake of liquids is limited due to painful sores in the mouth.
  • Rarely, patients develop "aseptic" or viral meningitis, in which the person has fever, headache, stiff neck, or back pain, and may need to be hospitalized for a few days.
• HFMD caused by EV71 has been associated with meningitis and encephalitis, and on occasion can cause severe complications, including neurological, cardiovascular and respiratory problems. Cases of fatal EV71 encephalitis have occurred during outbreaks.

 

While the recent outbreak in Cambodia has raised alarms around the world, deadly outbreaks of EV71 are nothing new.  Last May, in CDC Issues HFMD Travel Notice For Vietnam, we looked at an outbreak that had claimed more than 20 lives.

 

In the News
Hand, Foot, and Mouth Disease in Vietnam

Released: May 25, 2012

What Is the Current Situation?

As of April 29, 2012, the Vietnam Ministry of Health has confirmed nearly 40,000 cases of hand, foot, and mouth disease (HFMD) since the beginning of 2012. Cases have occurred in 63 provinces, and 20 deaths (all in children under 5) have occurred in 10 provinces.

(Continue . . .)

 

The CDC also provides several  multimedia products related to hand, foot, and mouth disease.

 

• CDC Feature: Hand, Foot, & Mouth Disease
  An article that provides the basics about hand, foot, and mouth disease, who is commonly affected, symptoms, how it spreads, and ways to prevent it.
• Podcast: Hand, Foot, and Mouth Disease
  A CDC pediatrician and dad talks about hand, foot, and mouth disease, its symptoms, and tips to prevent your family from getting this disease.

 

Similarly, we’ve seen reports this week indicating that Hand, foot, mouth disease kills 240 in China.

 

We are seeing reaction to the Cambodian outbreak from several health departments across Asia, including Hong Kong, Thailand, and the Philippines.

 

First, Hong Kong’s CHP (Centre for Health Protection) which sent out this Update on An Unknown Disease in Cambodia letter to doctors in the region on July 9th, which asks that doctors notify the CHP of any suspected cases with recent travel history to Cambodia.

 

Possibly related, the CHP is reporting on Two cases of severe paediatric enterovirus infection, although the causative virus is not indentified.

 

In Thailand, The Nation newspaper is reporting that the MOH has instructed schools to close if an unusual number of HFMD cases are reported.

 

Disease warning for schools

The Nation July 10, 2012 5:47 pm

The Public Health Ministry on Tuesday instructed schools and nurseries nationwide to close if they find that students in five classes or more have contracted hand, foot and mouth disease.

(Continue . . . )

 

And perhaps the most proactive of all is the Philippines, where the Department of Health has ordered increased surveillance at airports, and has declared  EV-71 to be a notifiable disease. 

 

Here is the official press release:

 

DOH MAKES ENTEROVIRUS-71 INFECTION AS A NOTIFIABLE DISEASE

July 10, 2012

(Press Release – 10 July 2012)

Health Secretary Enrique T. Ona instructed today the Department of Health (DOH) National Epidemiology Center to include Enterovirus-71 (EV-71) infection as a notifiable disease in the country. This will compel all health providers especially physicians to report individual cases or even outbreaks.

 

“Mandatory notification will improve monitoring of EV-71 infections and ensure that necessary measures are in place to guarantee that the Philippines is free from the highly fatal severe form of EV-71 infections that have claimed the lives of at least 60 children in Cambodia since April this year,” Ona said.

 

Also, the DOH and the World Health Organization (WHO) clarified today that the Cambodian EV-71 was of the encephalitis type and not hand foot and mouth disease (HFMD) as earlier reported. Affected Cambodian children generally presented with fever followed by rapid respiratory deterioration and impaired consciousness. Death occurred 24 hours from hospital confinement.

 

EV-71 causes different diseases of varying intensity. These include the often mild hand, foot and mouth disease (HFMD), acute respiratory disease, acute flaccid paralysis (polio-like) and the deadly brainstem encephalitis. HFMD is characterized as a self-limiting illness presenting with fever and accompanied by skin lesions or rashes.

 

EV-71 infections do occur in the country but are reported with irregularity. Fatal EV-71 infection is still very rare in the Philippines.

 

Proper disposal of baby diapers or human waste, strict personal hygiene and regular hand washing prevent viral spread. The virus is known to be excreted in the feces since it is found in human intestines.

 

 

The DOH urges parents and day-care personnel to clean and disinfect toys and teaching tools that are easily shared with other children. This can prevent EV-71 infections, as there are no known effective drugs or vaccines.

 

 

‘There is still no travel restriction to and from Cambodia and incoming passengers will be subjected to thermal screening upon arrival in all international airports as a routine quarantine procedure,” the health chief concluded.

 

The statement above, that the `(WHO) clarified today that the Cambodian EV-71 was of the encephalitis type and not hand foot and mouth disease (HFMD)’ is something I’ve not been able to locate on the WHO site yet.  

 

And last, but certainly not least, Lisa Schnirring of CIDRAP NEWS wrote a detailed report last night on the Cambodian outbreak, which you can read at:

 

Enterovirus 71 cited in puzzling Cambodian infections

Lisa Schnirring Staff Writer

Jul 9, 2012 (CIDRAP New) – Lab analysis in the mysterious recent illnesses and deaths of dozens of Cambodian children pointed to enterovirus 71 (EV-71), a virus that causes hand, foot, and mouth disease (HFMD) and can lead to severe complications in some patients, the World Health Organization (WHO) announced today.

(Continue . . .)

 

 

The peak season for HFMD is summer and fall, which suggests that we will be hearing about outbreaks of EV71, and other HFMD viruses, for months to come.