Back To The Camel `Shed’

 

# 9300

 

 

Sometimes studies are published, and for whatever reason, they don’t get the immediate attention they deserve.  Often, it is because we are otherwise occupied with a bigger story, such as the media was during the last week of September when Ebola was the only infectious disease story people were really interested in.

 

Little noticed at the time, was the publication in the CDC’s EID Journal of an important study on MERS-CoV shedding by camels, which I wrote about on September 25th in EID Journal: Replication & Shedding Of MERS-CoV In Inoculated Camels.

 

This study had the bad luck to be published the same week  we saw the CDC Statement On MMWR Ebola Estimates, which predicted potentially 550,000 to 1.4 million Ebola cases in Liberia and Sierra Leone by the end of January if swift action wasn’t taken, the CDC issued a HAN: Acute Neurologic Illness with Focal Limb Weakness of Unknown Etiology in Children, and just 4 days before we learned that Thomas Duncan was America’s first imported Ebola case (see Dallas,Tx Patient Tests Positive For Ebola).

This week, however, that study is back in the news thanks to a press release from the University of Colorado, and with the recent uptick in MERS cases in Saudi Arabia, the Arabic press is taking notice as well.

You can read the full study, and my original post on it, at this link.   The UC press release, follows:

 

Camels emit dangerous MERS virus, Colorado State University researchers confirm

Danielle Adney, left, and Vienna Brown with two of the camels in the MERS vaccine project at CSU.

FORT COLLINS - In a finding with global health implications, a research team led by a doctoral student at Colorado State University has confirmed for the first time that camels vent volumes of the deadly Middle East Respiratory Syndrome (MERS) virus, making them the likeliest suspect for spreading the pathogen to people.

Now the CSU team is testing a vaccine that could keep camels from shedding the MERS virus, which has caused acute respiratory illness in about 900 people across the Arabian Peninsula since it was identified in 2012.

The CSU researchers, partnering with an arm of the National Institutes of Health, demonstrated that infected camels shed large amounts of MERS virus, primarily through their nostrils. They also established for the first time that the virus develops in the animals’ upper respiratory system, and that camels shed infectious virus for up to a week.

The findings were not surprising to many scientists who study viral infectious disease – camels have been a primary suspect as a source of MERS – yet confirming the source is essential to advancing science, knowledge and solutions.

“This is a necessary step in looking at the interaction between the virus and the host species, the camel,” said Mark Pallansch, director of the Division of Viral Diseases in the Center for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases.

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This study not only shows that infected camels can shed massive amounts of the MERS coronavirus from their nasal discharges, that they can do so without showing overt signs of serious illness. 

 

Over the summer we saw the KSA MOH Reiterate Camel Warnings On MERS, urging breeders and owners to limit their contact with camels, and to use PPEs (masks, gloves, protective clothing) when in close contact with their animals.

 

And as recently as yesterday, we saw the the Saudi MOH remind citizens to:

• Avoid contact with camels, especially if they are sick, and their body fluids secretions.
• If you must be in contact with camels, wear a disposable mask over your mouth and nose, gloves, and a protective medical gown.
• Boil fresh camel milk, if not pasteurized.
• Cook camel meat (including liver) well before consumption.

PLoS One: Influenza Viral Shedding & Asymptomatic Infections

Photo Credit PHIL (Public Health Image Library)

 

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Despite major advances in the study of influenza viruses, there remain significant gaps in our understanding of just how they work once they infect a human (or any other animal) host. 

 

Basic questions, such as `How long are we infectious?’, or `How common are asymptomatic infections?’  remain only partially answered.

 

Complicating matters, variations in individual host’s immune responses, and different strains of flu may produce varying results. Meaning that most studies can only add incrementally to our knowledge, rather than completely answering these questions.

 

Previously, we’ve seen evidence of asymptomatic and `presymptomatic’ shedding of influenza viruses.

 

In 2011, in EID Journal: Pre-Symptomatic Influenza Transmission we looked at three clusters of suspected pre-symptomatic transmission of the 2009 H1N1 virus in Japan.

 

And in Pre-Symptomatic Transmission Of H1N1 Influenza In the Ferret Model, researchers inoculated ferrets with the 2009 H1N1 flu, and then placed them near uninfected ferrets (some in direct contact, others in adjacent cages) at different stages after infection.

 

They then tested the exposed ferrets to see when, and under what circumstances, they became infected. They found that ferrets became infectious just 24 hours after becoming infected, and nearly 24 hours before showing the earliest outward signs of infection (fever).

 

 

The importance of all of this is, if presymptomatic and asymptomatic carriers of a flu virus are able to efficiently transmit the illness on to others, then strategies that seek to identify and isolate flu cases would have only limited success in containing a pandemic.

 

Similarly, understanding how long a person sheds the virus after becoming infected is crucial, so we can know when it is (relatively) safe for flu victims to return to work or school without endangering others.

 

The CDC’s general take on this topic is:

 

The Flu Is Contagious

Most healthy adults may be able to infect others beginning 1 day before symptoms develop and up to 5 to 7 days after becoming sick. Children may pass the virus for longer than 7 days. Symptoms start 1 to 4 days after the virus enters the body. That means that you may be able to pass on the flu to someone else before you know you are sick, as well as while you are sick. Some persons can be infected with the flu virus but have no symptoms. During this time, those persons may still spread the virus to others.

 

 

Yesterday, a new study appeared in PloS One, conducted in Germany over 4 flu seasons (2007-2011) and involving 4 flu strains - seasonal (A(H3N2), A(H1N1), influenza B, and pandemic (A(H1N1)pdm09 - that looks at many of these transmission issues. 

 

Comparison of Shedding Characteristics of Seasonal Influenza Virus (Sub)Types and Influenza A(H1N1)pdm09; Germany, 2007–2011

Thorsten Suess, Cornelius Remschmidt, Susanne B. Schink, Brunhilde Schweiger, Alla Heider, Jeanette Milde, Andreas Nitsche, Kati Schroeder, Joerg Doellinger, Christian Braun, Walter Haas, Gérard Krause, Udo Buchholz

Background

Influenza viral shedding studies provide fundamental information for preventive strategies and modelling exercises. We conducted a prospective household study to investigate viral shedding in seasonal and pandemic influenza between 2007 and 2011 in Berlin and Munich, Germany.

Methods

Study physicians recruited index patients and their household members. Serial nasal specimens were obtained from all household members over at least eight days and tested quantitatively by qRT-PCR for the influenza virus (sub)type of the index patient. A subset of samples was also tested by viral culture. Symptoms were recorded daily.

Results

We recruited 122 index patients and 320 household contacts, of which 67 became secondary household cases. Among all 189 influenza cases, 12 were infected with seasonal/prepandemic influenza A(H1N1), 19 with A(H3N2), 60 with influenza B, and 98 with A(H1N1)pdm09. Nine (14%) of 65 non-vaccinated secondary cases were asymptomatic/subclinical (0 (0%) of 21 children, 9 (21%) of 44 adults; p = 0.03).

 

Viral load among patients with influenza-like illness (ILI) peaked on illness days 1, 2 or 3 for all (sub)types and declined steadily until days 7–9. Clinical symptom scores roughly paralleled viral shedding dynamics.

 

On the first day prior to symptom onset 30% (12/40) of specimens were positive. Viral load in 6 asymptomatic/subclinical patients was similar to that in ILI-patients. Duration of infectiousness as measured by viral culture lasted approximately until illness days 4–6. Viral load did not seem to be influenced by antiviral therapy, age or vaccination status.

Conclusion

Asymptomatic/subclinical infections occur infrequently, but may be associated with substantial amounts of viral shedding. Presymptomatic shedding may arise in one third of cases, and shedding characteristics appear to be independent of (seasonal or pandemic) (sub)type, age, antiviral therapy or vaccination; however the power to find moderate differences was limited.

 

 

While this was a relatively small study, and their findings don’t always align perfectly with others we’ve seen (for instance, children didn’t appear contagious any longer than adults), it does provide us with some interesting data.

 

• First, nearly 1/3rd of cases began shedding virus while pre-symptomatic
• Second, viral loads in (six studied) asymptomatic cases were similar to that to patients exhibiting ILI (influenza-like-illness) symptoms.
• Third, viral load among symptomatic patients peaked on illness days 1, 2 or 3 and declined steadily until days 7–9

 

Some other gems (bolding mine) excerpted from this open access article include:

 

• Overall 63% of non-vaccinated secondary household cases had an ILI-syndrome and the proportion of asymptomatic/subclinical secondary cases was 14%.
• Frequency distribution of clinical symptoms did not differ between A(H1N1)pdm09 cases and non-pandemic influenza cases.
• Interestingly, 21% of adult secondary cases were asymptomatic/subclinical, while all children that contracted influenza were symptomatic.
• Based on the population of ambulatory patients investigated we found no evidence that the amount of shedding is particularly higher in children, nor that duration of viral shedding is significantly longer in children compared to adults.

 

 

The authors conclude by saying:

 

In summary, our study addresses several important questions on clinical manifestation, duration of infectiousness, viral shedding patterns, including shedding before symptom onset and in asymptomatic/subclinical patients, as well as the effect of vaccination and antiviral therapy on viral shedding.

 

Important single results include the finding that children do not seem to be infected asymptomatically, that shedding one day before symptom onset may occur in one third of influenza patients, that asymptomatic/subclinical influenza patients occur rarely, but viral load (and probably infectiousness) may be substantial, and vaccinated influenza patients do not show different shedding patterns compared to non-vaccinated cases with ILI.

 

Overall results do not show marked differences between seasonal influenza (sub)types and influenza A(H1N1)pdm09.

Roundup Of H1N1 Studies From Eurosurveillance

 

 

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Eurosurveillance is a European scientific journal `devoted to the epidemiology, surveillance, prevention and control of communicable diseases.’

 

This week’s issue Volume 14, Issue 49, 10 December 2009 features several rapid communications pieces relating to the 2009 H1N1 pandemic virus, and the public and HCWs (Health Care Worker’s) response to it from various places in Europe.  

 

Since we appear to be blessed with a relatively quiet Sunday Morning news cycle, I’ve posted the links and brief summaries of these dispatches below.

 

From a pure science standpoint, the first articles listed on the prolonged shedding of the H1N1 virus (14 and 28 days) in patients without immunosuppression, even with the administration of oseltamivir, is of perhaps the most interest.

 

Although the `conventional wisdom’ states that individuals with the flu shed the virus only for 5 to 7 days, we’ve seen a number of studies over the past few months that refute that contention. 

 

A couple of blogs on the subject include:

 

Swine Flu: The Gift That Keeps On Giving

They Walk Among Us

 

It should be noted that being able to detect – with highly sensitive PCR testing – the shedding of virus particles doesn’t necessarily mean that these people were still contagious.

 

Still, this is a fascinating finding.  The virus was tested and did not exhibit the H275Y Tamiflu resistant mutation, and yet the virus remained detectable in one patient for 14 days and in another for 28 days.

 

 

Prolonged shedding of influenza A(H1N1)v virus: two case reports from France 2009

by H Fleury, S Burrel, C Balick Weber, R Hadrien, P Blanco, C Cazanave, M Dupon

We observed a prolonged shedding of virus 14 and 28 days after symptom onset in two patients with pandemic H1N1 influenza, who did not have immunodepression and were treated with neuraminidase inhibitor.

 

This prolonged shedding was not associated with the emergence of resistance mutation H275Y in the viral neuraminidase gene.

 

 

Public perceptions in relation to intention to receive pandemic influenza vaccination in a random population sample: evidence from a cross-sectional telephone survey

 

by V Sypsa, T Livanios, M Psichogiou, M Malliori, S Tsiodras, I Nikolakopoulos, A Hatzakis

A cross-sectional telephone survey on a nationally representative sample of 1,000 Greek households was performed to assess the acceptability of the pandemic influenza A(H1N1)v vaccine, factors associated with intention to decline and stated reasons for declining vaccination.

 

The survey was initiated the last week of August 2009 (week 35) and is still ongoing (analysis up to week 44). The percentage of participants answering they would “probably not/definitely not” accept the vaccine increased from 47.1% in week 35 to 63.1% in week 44 (test for trend: p<0.001).

 

More than half of the people which chronic illnesses (53.3%) indicated “probably not/definitely not”. Factors associated with intention to decline vaccination were female sex, age between 30-64 years, perception of low likelihood of getting infected or of low risk associated with influenza, and absence of household members suffering from chronic illnesses.

 

For the majority of the respondents (59.8%), the main reason for intending to decline vaccination was the belief that the vaccine might not be safe. Promotion of vaccination programmes should be designed taking into account the attitudinal barriers to the pandemic vaccine.

 

 

Behaviours regarding preventive measures against pandemic H1N1 influenza among Italian healthcare workers, October 2009

by G La Torre, D Di Thiene, C Cadeddu, W Ricciardi, A Boccia

A survey on attitudes and behaviours towards preventive measures against pandemic H1N1 influenza 2009 was carried out during the month of October 2009 in Italy through an online questionnaire adapted to the Italian situation from a similar survey of the Harvard School of Public Health in the United States (US).

 

Results show that the intention to get vaccinated against pandemic H1N1 influenza 2009 is generally low and that there are differences in attitudes and behaviours towards preventive measures against pandemic H1N1 influenza 2009 between physicians and nurses, especially concerning vaccination. Differences relate also to sex, region of residence and marital status.

 

 

 

Behaviour of the pandemic H1N1 influenza virus in Andalusia, Spain, at the onset of the 2009-10 season

 

by JM Mayoral Cortés, L Puell Gómez, E Pérez Morilla, V Gallardo García, E Duran Pla, JC Fernandez Merino, J Guillén Enriquez, JC Carmona, G Andérica, I Mateos, JM Navarro Marí, M Pérez Ruiz, A Daponte

 

In Andalusia, Spain, the pandemic influenza A(H1N1)v virus has spread throughout the community, being the dominant influenza strain in the season so far. The current objective of the Andalusia Health Service is focussed on the mitigation of the health and social impact by appropriate care of the patients at home or in health centres.

 

The 2009-10 seasonal influenza epidemic started early compared with to previous seasons. This article analyses the influenza A(H1N1)v situation in Andalusia until the week 39/2009.

 

 

IDSA: Kids Shed Virus Longer Than Adults

 

# 3913

 

 

More evidence, presented at the IDSA (the Infectious Diseases Society of America) in Philadelphia this week, indicating that children shed the influenza virus longer than adults.  

 

This isn’t the first time we’ve heard this sort of data (see Swine Flu: The Gift That Keeps On Giving).

 

The guidance from the CDC for staying home, and not going to work or school, has been scaled back from at least 7 days or 24 hours after symptoms disappear – to 24 hours after fever is gone (without using fever reducing drugs).  

 

Which means that some people may be returning to work or school following an illness while still shedding the virus.

 

Whether this really makes much of a difference is debatable. 

 

Shedding enough virus to be detectable by today’s modern RT-PCR testing or culture, and being contagious and able to spread the virus, may be two entirely different propositions.  

 

It it is believed that people can shed the flu virus for to 24 hours before ever showing symptoms – and that some may carry the virus asymptomatically, and spread the virus to others - without ever falling ill themselves (see They Walk Among Us ).

 

All of which makes it virtually impossible to keep the virus out of the schools and workplace.  Since you can’t tell who is shedding the virus and who isn’t, the only real defense is to get vaccinated, and to practice good flu hygiene. 

 

This report from Medpage Today.

 

 

IDSA: Kids Shed H1N1 Flu Longer than Adults

By Michael Smith, North American Correspondent, MedPage Today
Published: October 30, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.

 

PHILADELPHIA -- Children appear to shed particles of the H1N1 pandemic flu virus longer than adults do, which may have implications for how long they stay out of school, a researcher said here.

 

The finding comes from an analysis of an outbreak in a Pennsylvania elementary school in May and June, according to Achuyt Bhattarai, MD, of the CDC.

 

Analysis of a series of specimens from affected children and their household contacts also showed that younger children tended to shed the virus longer than older kids, Bhattarai told attendees at the annual meeting of the Infectious Diseases Society of America.

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