ECDC Rapid Risk Assessment On Zika Virus Epidemic

Credit ECDC

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The ECDC has published a 20 page, data-rich, overview and analysis on the Zika virus called  Rapid Risk Assessment: Zika virus disease epidemic: potential association with microcephaly and Guillain-Barré syndrome (first update).

As we've come to expect from the ECDC, it is comprehensive, well documented, and makes an invaluable reference.  

You'll want to download to read and keep this PDF file handy, as it is simply too large to excerpt the full  gist here.


You'll find sections devoted to genetic lineage and possible changes to the Zika virus (see AFD Blog Paper: Zika Adaptations To Humans Helped Spark Global Spread), the risks from blood transfusion, advice to international travelers and their doctors, and of course the two big (and as yet, unanswered) $64 questions:

Risk of microcephaly and other congenital central nervous system malformations

To date, health authorities have reported eight adverse pregnancy outcomes and/or other congenital CNS malformations with laboratory confirmation of Zika virus in amniotic fluid, placenta or foetal tissues. In addition, information on six cases of Zika virus detection in newborns from the Paraíba State with partly severe congenital malformations has been recently published. All fourteen reported cases have history of exposure in Brazil.

After performing a retrospective analysis following the alert from Brazil, the health authorities of French Polynesia reported an increase from an average of one case annually to 17 cases of CNS malformations in foetuses and infants during 2014–2015, following a Zika virus outbreak in 2013–2014.

No cases of microcephaly or other CNS malformations potentially related to Zika virus have been reported from other countries of Americas and Caribbean affected by Zika virus outbreaks. However, autochthonous transmission of Zika virus did presumably not start before the last trimester of 2015 in most of these countries, and the prospective monitoring of congenital malformations will support the evaluation of the association with Zika virus infections.


In summary, the evidence regarding a causal link between Zika virus infections during pregnancy and congenital CNS malformations is growing, although the available information is not yet sufficient to confirm it. The definitions of suspected cases applied in the epidemiological surveillance protocol for Brazil are broad and will capture many healthy children who are within the normal variation as well as children with medical conditions that are unrelated to Zika virus infections. The cases identified with the surveillance protocol will need to be further investigated and assessed, and many will have to be followed over time. It is expected that many of the suspected cases will be reclassified and discarded. So far, no results have been made public from the epidemiological studies that reportedly are ongoing and may substantiate or disprove the association between intra-uterine Zika virus infections and congenital lesions in CNS.

Risk of Guillain–Barré syndrome
 

No new scientific evidence about the association of GBS and Zika virus infection has been published since the ECDC RRA published on 10 December 2015. Two new countries, El Salvador and Venezuela (according to media), have reported an unusual increase above the baseline, concomitant with the development of Zika outbreaks in the country. This observation supports a temporal and spatial association as that seen in French Polynesia.

The bottom line is, despite a growing body of evidence, there is not yet conclusive proof that microcephalic births or the rise in GBS are due to Zika virus infection.  For now, however, it remains the most likely culprit.

With no vaccine, no specific treatment, and far too many unanswered questions - the immediate focus is on prevention. 

Better mosquito control, limiting personal exposure to mosquitoes, and taking steps (using repellents, wearing long sleeved shirts, etc.) to prevent mosquito bites will be the best way to limit the spread of Zika, along with Dengue and Chikungunya.

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Macquarie Scholarship Interview session

 Macquarie Scholarship Interview session 

JM EDUCATION GROUP, Penang will be organising 

the Macquarie University Scholarship Opportunities Info Session in our office at  441-1-4, Pulau Tikus Plaza, Burmah Road, 

10350 Penang

 on 27^thJanuary 2016, Wednesday, 2pm-3.30pm.  

Please bring along your recent academic results for offer letters. For further details, please call 04-2277376

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EID Journal: H5N1 In Egypt

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Despite the overly reassuring (and quite possibly fanciful) statements coming out of Egypt's MOH this year (see Egyptian MOH Statement: No Bird Flu Cases Since Last Summer)  the expectation is many - perhaps even most - human avian flu infections go undetected. 


It's a phenomenon we've seen repeated in China with H7N9, where estimates (see Lancet: Clinical Severity Of Human H7N9 Infection) ran from 12 to 200 times the official number of cases, to the United States where Swine variant flu infections in 2012 (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012)) were estimated 200 times greater than reported.

Similarly, Saudi Arabia has reported 1285 MERS infections to date, yet a seroprevalence study published last April in the Lancet (see Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study  by Drosten & Memish et al.,  projected 44 951 (95% CI 26 971–71 922) individuals older than 15 years might be seropositive for MERS-CoV in Saudi Arabia.

None of these are actual head counts, yet based on the limited serological studies that have been done and some calculations way above my pay grade, the numbers are probably reasonable extrapolations.  


Last year Egypt reported roughly 160 H5N1 cases, four time more than in any twelve month period before.  These represented only those sick enough to be hospitalized, and lucky enough to be tested. Presumably some number were only mildly ill, were misdiagnosed,  or otherwise lost in the shuffle.

Last year we also saw evidence that the H5N1 virus in Egypt - which has been poorly controlled for a decade - had developed some `mammalian' mutations (see Eurosurveillance: Emergence Of A Novel Cluster of H5N1 Clade 2.2.1.2) that might have made it easier for the virus to jump to humans. 

Over the years we've seen several analyses indicating that most of the poultry vaccines in use have been ineffective (see A Paltry Poultry Vaccine) and may only have hidden signs of infection in poultry, allowing viruses to spread and mutate. 


All of which brings us to an EID Journal study, published today, that suggests there may have been tens (perhaps, hundreds) of thousands of human H5N1 infections in Egypt over the past decade.

If true, it would dramatically lower the CFR (Case Fatality Rate) for the virus (a good thing), but it would aslo indicate the virus is more human adapted than previously thought (a not-so good thing).

The authors base this assumption on a limited serological study that found antibodies for H5 in roughly 2% of the people tested.  Even more remarkably, this study found 5.6% to 7.5% seroprevlance of antibodies to H9N2, an even less commonly reported human infection.


I've only excerpted the abstract, along with a few choice selections from this lengthy, data-rich, and fascinating report. It is well worth reading in its entirety.

Avian Influenza A(H5N1) Virus in Egypt

Ghazi Kayali , Ahmed Kandeil, Rabeh El-Shesheny, Ahmed S. Kayed, Asmaa M. Maatouq, Zhipeng Cai, Pamela P. McKenzie, Richard J. Webby, Samir El Refaey, Amr Kandeel, and Mohamed A. Ali 

Abstract

In Egypt, avian influenza A subtype H5N1 and H9N2 viruses are enzootic in poultry. The control plan devised by veterinary authorities in Egypt to prevent infections in poultry focused mainly on vaccination and ultimately failed. Recently, widespread H5N1 infections in poultry and a substantial increase in the number of human cases of H5N1 infection were observed. We summarize surveillance data from 2009 through 2014 and show that avian influenza viruses are established in poultry in Egypt and are continuously evolving genetically and antigenically. We also discuss the epidemiology of human infection with avian influenza in Egypt and describe how the true burden of disease is underestimated. We discuss the failures of relying on vaccinating poultry as the sole intervention tool. We conclude by highlighting the key components that need to be included in a new strategy to control avian influenza infections in poultry and humans in Egypt.

An unprecedented increase in the number of human infections with the highly pathogenic avian influenza A(H5N1) virus was observed in Egypt during the 2014–15 winter season. The World Health Organization reported that 31 cases were confirmed in 2014, of which 27 were in persons infected as of September (1). The Ministry of Health and Population in Egypt confirmed 31 cases in 2014 and 88 in January and February 2015. Thus, the official number of cases during September 2014–February 2015 was 114, including 36 deaths. Furthermore, in February 2015, the first human case of subtype H9N2 virus infection in Egypt was reported. These events compelled national and international authorities to examine the reasons behind the increase in human infections and implement control measures.

(SNIP)

Extent of Avian Influenza Infection in Egypt

In Egypt, the number of reported human cases of avian influenza infection appears to be underestimated. An underestimation might result in an overestimation of the case-fatality rate, but it would certainly underestimate the extent of human infection with avian influenza viruses. Results from a controlled, serologic cohort study of persons in Egypt exposed and not exposed to poultry estimated the seroprevalence of antibodies against H5N1 (titers >80) at 2% (19).

If this seroprevalence were to be extrapolated to the entire poultry-exposed population in Egypt, the true number of infections would amount to several hundred thousand. These figures are even more striking when it comes to human infection with H9N2 viruses. The seroprevalence of H9N2 antibodies detected in the same cohort study (19) ranged from 5.6% to 7.5%, whereas just 1 case of H9N2 infection was reported.

H5N1 viruses elicit a poor humoral immune response, providing low antibody titers that typically fade over a short period (20,21). Thus, relying on serologic testing to detect prevalence or incidence of infection can yield underestimated results. 

(SNIP)

Conclusions

Egypt is one of the few countries where H5N1 virus has become enzootic and is the only country with a high number of H5N1 outbreaks among poultry and cases among human. During the 2014–15 winter season, a sudden and substantial increase in human infection with H5N1 viruses was observed. There is no obvious or confirmed reason for this increase, but data indicate the following:

1) H9N2 virus is co-circulating and co-infecting with H5N1 viruses,

2) H5N1 viruses causing the infections possess some mutations that were rarely seen in the past, and

3) the poultry vaccination program is failing.

However, our perspective was limited to the data available through our surveillance program, which might not be representative of the epizootiology of avian influenza virus in Egypt. Regardless of the causes of the recent increase in human H5N1 cases, this situation evolved because of the ineffective control strategy that was implemented. Controlling the situation requires a One Health approach, but certainly the greater share of responsibility now lies with the veterinary side.

Dr. Kayali is a staff scientist at the St. Jude Children’s Research Hospital, Memphis, TN. His research interests are the epidemiology of influenza and viral zoonotic diseases.

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Exploring The Zika - Guillain-Barré Connection

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The exact cause of Guillain-Barré Syndrome - a rare immune disorder that damages nerve cells, and can cause muscle weakness and sometimes paralysis - is unknown, but it often follows a viral or bacterial illness.

In the United States between 3,000 and 6,000 cases are reported every year.  Most people recover fully, but some may have lingering neurological damage.

Not quite two years ago (Feb 2014), in Zika, Dengue & Unusual Rates Of Guillain Barre Syndrome In French Polynesia, we saw the first hint that a relatively obscure, and previously thought to be mild virus - Zika - might be causing neurological symptoms following an outbreak in the South Pacific.


Unlike Dengue, or even Chikungunya, little had been written about the Zika virus, although in 2009 the CDC’s EID Journal carried a report called Zika Virus Outside Africa by Edward B. Hayes that explored the virus's arrival in Yap Island where 70% of the population was affected.

While most cases had reported relatively mild symptoms, the author cautioned that until the West Nile Virus began causing neuroinvasive symptoms in Romania and North America, it too was considered a fairly innocuous viral infection.

In February of 2014, a report came from Le Centre d’Hygiène et de Salubrité Publique  (CHSP) in French Polynesia Bulletins health surveillance in French Polynesia and related documents which reported of 41 Guillain-Barré syndrome (GBS) and 26 cases of other neurological complications they believed linked to the ongoing Zika/Dengue outbreak which had started in 2013.

The expected incidence of GBS is 1 to 2 cases per 100,000 population per year . With a population of 275,000, one would expect fewer than 10 cases per year in that sized population. 

A month later, in Eurosurveillance: Zika Virus Infection Complicated By Guillain-Barré Syndrome, we looked at a report that calculated a 20 fold increase in GBS after the arrival of Zika in French Polynesia.   The authors wrote:

Since the beginning of this epidemic, and as up to 8,200 cases of ZIKA infection have already been reported of a 268,000 total population, the incidence of GBS has been multiplied by 20 in French Polynesia (data not shown), raising the assumption of a potential implication of ZIKA.

Since these islands were seeing a concurrent Dengue outbreak there was speculation that co-infection by Dengue and Zika  - or sequential arboviral immune stimulation - might predispose one to more severe illness. 

Adding some credence to this notion, with dengue, it is usually a person's second infection that causes severe illness, while the first infection is usually mild.

The prevailing theory is that the host’s immune system - which already has neutralizing antibodies to the first DENV infection - mistakenly identifies the second DENV infection as being the same strain.


Rather than creating new neutralizing antibodies to fight the infection, it deploys its existing cross reactive, but non-neutralizing (read: ineffective) antibodies to the field of battle.

Sometimes called OAS or Original Antigenic Sin, this is the immunological equivalent of taking a knife to a gun fight.

Since many populations now seeing  Zika have long dealt with Dengue, or Chikungunya - or both - teasing out the cause or causes of increased neurological side effects (including microcephaly) isn't going to be easy.

It is worth noting that a there is now a suspected link between GBS and Chikungunya infection as well (see Eurosurveillance Increase in cases of Guillain-Barré syndrome during a Chikungunya outbreak, French Polynesia, 2014 to 2015).

Earlier this week PAHO released an updated epidemiological report on Zika, and mentioned the Polynesian increase in GBS, along with increased reports in Brazil and El Salvador (see PAHO: Epidemiological Update On Zika - Jan 17th) where they wrote:

Currently, similar situations are being investigated in other countries of the Americas. These findings are consistent with a temporal and spatial link between Zika virus circulation and the increase of GBS. Although the etiopathogenesis and associated risk factors have not yet been well established, Member States should implement surveillance systems to detect unusual increases in cases and prepare health services for patients care with neurological conditions.

Today the World Health Organization published the following statement on the increase in GBS in El Salvador.

Guillain-Barré syndrome – El Salvador

Disease Outbreak News
21 January 2016 

The National IHR Focal Point of El Salvador has notified PAHO/WHO of an unusual increase of Guillain-Barré Syndrome (GBS) in the country. In El Salvador, the annual average number of GBS is 169; however, from 1 December 2015 to 6 January 2016, 46 GBS were recorded, including 2 deaths. 

Of the 46 GBS cases, 25 (54%) are male and 35 (76%) are 30 years old or older. All cases were hospitalized and treated with plasma exchange or intravenous immunoglobulin. One of the two deceased patients had a history of multiple underlying chronic diseases. Out of the 22 patients whose information was available, 12 (54%) presented with febrile rash illness in the 15 days prior to the onset of symptoms consistent with GBS.

Investigations are ongoing to determine the cause of infection and acquire further details about the laboratory diagnosis. Possible associations between GBS and Zika virus infection are also being investigated. Since the confirmation of the first case of Zika virus infection in November 2015 until 31 December 2015, Salvadoran health authorities reported 3,836 suspected cases of Zika virus infection.

(Continue . . . )

Unlike microcephalic births, which are a lagging indicator, GBS symptoms usually appear within days or weeks of acute infection, and therefore may give us a more immediate read on the progress and severity Zika's spread.

Despite all of this, it is not at all a certainty that Zika - or even a combination of Zika and other viral infections (concurrent or sequential) - is responsible for this apparent increased incidence of GBS.

The evidence, however - while not conclusive - continues to mount.

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WHO: Updated Q&A On The Zika Virus

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The World Health Organization has released an updated (Jan 20th) Q&A file on the Zika virus, one that offers an assessment of the risk and advice to travelers.

Cautionary advice that falls far short of what some other health agencies have offered in recent days.

Granted, the link between Zika infection and Microcephaly has not yet been conclusively established, and the risks of other complications (Guillain-­Barré Syndrome, meningitis) are only just now coming to light.

We'll know far more about the actual risks six months from now.

But where the WHO only advises pregnant women to `take extra care to protect themselves from mosquito bites', our own CDC (see CDC Level II Travel Advisory) recommends that pregnant women `consider postponing travel to the areas where Zika virus transmission is ongoing'.
 

The United States is not alone.  On Monday Hong Kong's CHP recommended `Pregnant women should consider deferring their trip to areas with past or current evidence of ongoing Zika virus transmission'.

Meanwhile, the governments of Jamaica and Columbia have both recommended women postpone becoming pregnant for the next 6 months to a year, until the risks of Zika can be better understood. By contrast, under Should pregnant women be concerned about Zika?, the WHO states:  
 

Health authorities are currently investigating a potential link between Zika virus in pregnant women and microcephaly in their babies. Until more is known, women who are pregnant or planning to become pregnant should take extra care to protect themselves from mosquito bites.

Under Should I avoid travelling to areas where Zika virus is occurring?, the WHO states:  

Based on available evidence, WHO is not recommending any travel or trade restrictions related to Zika virus disease. 

But grants that:  As a precautionary measure, some national governments may make public health and travel recommendations to their own populations, based on their assessments of the available evidence and local risk factors.

It may well turn out that some of the initial response to Zika turns out to be overdone.  Or not.  We'll know better in a few months.


But given the tragic impact to families and society of these birth defects, this is one crisis you really don't want to be seen playing catch-up with.

Zika virus disease: Questions and answers

Online Q&A
20 January 2016
 

Where does Zika virus occur?

Zika virus occurs in tropical areas with large mosquito populations, and is known to circulate in Africa, the Americas, Southern Asia and Western Pacific.

Zika virus was discovered in 1947, but for many years only sporadic human cases were detected in Africa and Southern Asia. In 2007, the first documented outbreak of Zika virus disease occurred in the Pacific. Since 2013, cases and outbreaks of the disease have been reported from the Western Pacific, the Americas and Africa. Given the expansion of environments where mosquitoes can live and breed, facilitated by urbanisation and globalisation, there is potential for major urban epidemics of Zika virus disease to occur globally.
 
How do people catch Zika virus?
 
People catch Zika virus by being bitten by an infected Aedes mosquito – the same type of mosquito that spreads dengue, chikungunya and yellow fever.
 
What are the symptoms of Zika virus disease?
 
Zika virus usually causes mild illness; with symptoms appearing a few days after a person is bitten by an infected mosquito. Most people with Zika virus disease will get a slight fever and rash. Others may also get conjunctivitis, muscle and joint pain, and feel tired. The symptoms usually finish in 2 to 7 days.
 
What might be the potential complications of Zika virus?
 
Because no large outbreaks of Zika virus were recorded before 2007, little is currently known about the complications of the disease.
 
During the first outbreak of Zika from 2013 - 2014 in French Polynesia, which also coincided with an ongoing outbreak of dengue, national health authorities reported an unusual increase in Guillain-Barré syndrome. Retrospective investigations into this effect are ongoing, including the potential role of Zika virus and other possible factors. A similar observation of increased Guillain-Barré syndrome was also made in 2015 in the context of the first Zika virus outbreak in Brazil.

In 2015, local health authorities in Brazil also observed an increase in babies born with microcephaly at the same time of an outbreak of Zika virus. Health authorities and agencies are now investigating the potential connection between microcephaly and Zika virus, in addition to other possible causes. However more investigation and research is needed before we will be able to better understand any possible link.

Should pregnant women be concerned about Zika?

Health authorities are currently investigating a potential link between Zika virus in pregnant women and microcephaly in their babies. Until more is known, women who are pregnant or planning to become pregnant should take extra care to protect themselves from mosquito bites.

If you are pregnant and suspect that you may have Zika virus disease, consult your doctor for close monitoring during your pregnancy.
 
What is microcephaly?
 
Microcephaly is a rare condition where a baby has an abnormally small head. This is due to abnormal brain development of the baby in the womb or during infancy. Babies and children with microcephaly often have challenges with their brain development as they grow older.
Microcephaly can be caused by a variety of environmental and genetic factors such as Downs syndrome; exposure to drugs, alcohol or other toxins in the womb; and rubella infection during pregnancy.
 
How is Zika virus disease treated?
 
The symptoms of Zika virus disease can be treated with common pain and fever medicines, rest and plenty of water. If symptoms worsen, people should seek medical advice. There is currently no cure or vaccine for the disease itself.
 
How is Zika virus disease diagnosed?
 
For most people diagnosed with Zika virus disease, diagnosis is based on their symptoms and recent history (e.g. mosquito bites, or travel to an area where Zika virus is known to be present). A laboratory can confirm the diagnosis by blood tests.
 
What can I do to protect myself?
 
The best protection from Zika virus is preventing mosquito bites. Preventing mosquito bites will protect people from Zika virus, as well as other diseases that are transmitted by mosquitoes such as dengue, chikungunya and yellow fever.

This can be done by using insect repellent; wearing clothes (preferably light-coloured) that cover as much of the body as possible; using physical barriers such as screens, closed doors and windows; and sleeping under mosquito nets. It is also important to empty, clean or cover containers that can hold water such as buckets, flower pots or tyres, so that places where mosquitoes can breed are removed.

Should I avoid travelling to areas where Zika virus is occurring?
 
Travellers should stay informed about Zika virus and other mosquito-borne diseases and consult their local health or travel authorities if they are concerned.
 
To protect against Zika virus and other mosquito-borne diseases, everyone should avoid being bitten by mosquitoes by taking the measures described above. Women who are pregnant or planning to become pregnant should follow this advice, and may also consult their local health authorities if travelling to an area with an ongoing Zika virus outbreak.
 
Based on available evidence, WHO is not recommending any travel or trade restrictions related to Zika virus disease. As a precautionary measure, some national governments may make public health and travel recommendations to their own populations, based on their assessments of the available evidence and local risk factors.
 
What is WHO doing?
 
To help countries prepare for and respond to Zika, WHO is working with ministries of health to improve laboratory capacity to detect the virus, providing recommendations for clinical care and follow-up of infected patients (in collaboration with national professional associations and experts), and encouraging monitoring and reporting on the virus’s spread and the emergence of complications.
 
WHO is also coordinating with countries that have reported outbreaks of Zika virus and other partners to investigate the potential relationships between Zika and microcephaly and other issues.

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Middlesex University -United Kingdom

2016 Scholarship for Asia Pacific Region

For more information, please contact/visit your nearest JM Office today

                  

                                                                                                                                                                    Article is courtesy of  Middlesex University

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Swansea University - United Kingdom

Swansea University Medical School will be accepting applications from international students for its Graduate Entry Medicine course for September 2016 entry.  The Graduate Entry Medicine Programme is a fully independent  four-year programme based primarily in Swansea and west Wales, although students may undergo placements in other parts of Wales if they wish. We have designed an integrated medical curriculum, where the basic biomedical sciences are learnt in the context of clinical medicine, public health, pathology, therapeutics, ethics and psycho-social issues in patient management. This, together with a high emphasis on clinical and communication skills, will provide you with everything you'll need to practise medicine competently and confidently.  The curriculum, with its learning weeks and clinical placements, is intentionally not structured in a conventional ‘body systems’ approach but is designed to reflect the way in which clinicians approach patients and how patients present to doctors. This innovative approach will help you to develop a way of thinking and of engaging with information that mimics that used in clinical practice. As you work your way through learning weeks, clinical placements and practical sessions, you will acquire knowledge and build up your repertoire of clinical understanding and skills. Themes and strands, which run longitudinally throughout the Programme, will help you make links with other aspects you are learning, and with things you have previously considered as well as how all this relates to clinical practice. For more information, please contact/visit your nearest JM Office today                                                                                                                                                                                                   Article is courtesy of Swansea University

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