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Tracking the next pandemic: Avian Flu Talk

Ebola victims without symptoms can still be contag

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Albert View Drop Down
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    Posted: October 31 2014 at 2:51pm
This is not necessarily Latest News as it came out a few weeks ago, but is still interesting regarding asymptomatic carriers being infectious, and with no symptoms.  They can carry the virus for two weeks with no symptoms, and while being infectious.  Maybe people like Hickox should be kept away from others for a minimum of 14 days.



Ebola victims without symptoms can still be contagious

German doctors show CDC wrong about spread of disease

October 6, 2014

Is the “Conventional Wisdom” All Wrong?

The New York Times reported in 2000:

The Ebola virus, which has caused deaths from high fever and bleeding in African outbreaks, can also infect without producing illness, according to a new finding by African and European scientists.

The possibility of asymptomatic infection was only suggested in earlier studies, they said in last week’s issue of The Lancet, a medical journal published in London. Now they said they had documented such infections for the first time. They found that the Ebola virus could persist in the blood of asymptomatic infected individuals for two weeks after they were first exposed to an infected individual. How much longer the virus can persist is unknown.

***

If people can be carriers without showing symptoms, it means control might be more difficult.

“This degree of containment would be virtually impossible if symptom-free carriers posed a significant threat of infection,” Dr. Alan G. Baxter of Newtown, Australia, wrote in an editorial in the same issue of The Lancet.

***

An immediate effect is to raise the need to reassess health policy about one of the most virulent viruses known and to determine how often healthy carriers transmit it, said the scientific team headed by Dr. E. M. Leroy of Franceville, Gabon.

***

Dr. Leroy’s team studied 25 individuals who never developed symptoms although they lived with family members and cared for them without using gloves and other precautions in two outbreaks in Gabon in 1996.

Using standard virologic techniques, the scientists from Gabon, Germany and France said they could not detect the virus in the blood of the healthy contacts. But Dr. Leroy’s succeeded by using a technique known as polymerase chain reaction to grow the tiny amount of virus present.

Here is the study published in Lancet.  And here is the editor’s comment.

The Lancet study does not warn of an apocalyptic scenario where any casual contact could cause infection. It is more focused on contagion through sex or blood transfusions.

But Western governments and scientists have repeatedly said that Ebola carriers can only infect others if they are showing symptoms.  So they need to adjust their strategies to account for potential contagion from people who aren’t showing any symptoms.




The Lancet Study:

Human asymptomatic Ebola infection and strong inflammatory response


Summary

Background

Ebola virus is one of the most virulent pathogens, killing a very high proportion of patients within 5—7 days. Two outbreaks of fulminating haemorrhagic fever occurred in northern Gabon in 1996, with a 70% case-fatality rate. During both outbreaks we identified some individuals in direct contact with sick patients who never developed symptoms. We aimed to determine whether these individuals were indeed infected with Ebola virus, and how they maintained asymptomatic status.

Methods

Blood was collected from 24 close contacts of symptomatic patients. These asymptomatic individuals were sampled 2, 3, or 4 times during a 1-month period after the first exposure to symptomatic patients. Serum samples were analysed for the presence of Ebola antigens, virus-specific IgM and IgG (by ELISA and western blot), and different cytokines and chemokines. RNA was extracted from peripheral blood mononuclear cells, and reverse-transcriptase-PCR assays were done to amplify RNA of Ebola virus. PCR products were then sequenced.

Findings

11 of 24 asymptomatic individuals developed both IgM and IgG responses to Ebola antigens, indicating viral infection. Western-blot analysis showed that IgG responses were directed to nucleoprotein and viral protein of 40 kDa. The glycoprotein and viral protein of 24 kDa genes showed no nucleotide differences between symptomatic and asymptomatic individuals. Asymptomatic individuals had a strong inflammatory response characterised by high circulating concentrations of cytokines and chemokines.

Interpretation

This study showed that asymptomatic, replicative Ebola infection can and does occur in human beings. The lack of genetic differences between symptomatic and asymptomatic individuals suggest that asymptomatic Ebola infection did not result from viral mutations. Elucidation of the factors related to the genesis of the strong inflammatory response occurring early during the infectious process in these asymptomatic individuals could increase our understanding of the disease.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2800%2902405-3/fulltext



And the old story that I was originally going to post on this thread from Oct 8th.  Thought I would tell the whole story behind the news.

Ebola victims without symptoms can still be contagious

tom_frieden

CDC Director Tom Frieden speaking to a House Foreign Affairs subcommittee on the Ebola virus

NEW YORK – A group of German medical doctors in a peer-reviewed medical journal article published by Oxford University Press have challenged a key assumption regarding the Ebola virus repeatedly asserted by Dr. Thomas Frieden, director of the Centers for Disease Control and Prevention in Atlanta.


The researchers found that a patient showing no symptoms of the disease can still transmit a virus like Ebola by air if droplets containing the virus are transmitted to another person by a sneeze or cough.

As WND reported Tuesday, the World Health Organization has admitted that “wet and bigger droplets from a heavily infected individual, who has respiratory symptoms caused by other conditions or who vomits violently could transmit the Ebola virus over a short distance to another nearby person.”

WHO said it could happen when “virus-laden heavy droplets are directly propelled, by coughing or sneezing onto the mucus membranes or skin with cuts or abrasions of another person.”

Still, WHO added a qualification, insisting the transmission of Ebola by sneezing or coughing is not within its definition of airborne transmission.

News broke Wednesday morning that the first person diagnosed with Ebola in the U.S., Thomas Eric Duncan, had died in Dallas. The victim’s home neighborhood in the Liberian capital, meanwhile, remained under quarantine.

Later Wednesday, a Texas sheriff’s deputy was rushed to the hospital in Frisco, Texas, with Ebola symptoms after delivering a quarantine notice to the apartment where Duncan was staying.

WND reported Wednesday Liberia is preventing journalists from reporting Ebola-related stories from health care centers in the country unless they obtain written permission from the government. The news came as the World Health Organization issued a statement warning that the officially reported decline in new cases in Liberia over the past three weeks “is unlikely to be genuine,” because problems with data gathering continue.

What do YOU think? What is your reaction to death of Dallas Ebola victim? Sound off in today’s WND poll

‘Not easily detected’

The German physicians, led by Dr. Timm H. Westhoff of the Department of Nephrology at the Carité Campus Benjamin Franklin in Berlin, noted in a virology blog published Feb. 12, 2009, that acute viral infections such as Ebola hemorrhagic fever may cause little or no clinical symptoms in a so-called “inapparent infection” yet may be contagious.

“A well-known example is poliovirus: over 90% are without infections,” Westhoff and his colleagues continued. “During an inapparent infection, sufficient virus replication occurs in the host to induce antiviral antibodies, but not enough to cause disease. Such infections are important for the spread of infection, because they are not easily detected.”

Westhoff and his colleagues then made the key point that individuals with an inapparent infection, showing no symptoms, can yet spread diseases such as polio.

“During the height of the polio epidemic in the United States, the quarantine of paralyzed patients had no effect on the spread of the disease, because 99 percent of the infected individuals had no symptoms and were leading normal lives spreading infection.”

Westhoff and his colleagues also discussed the risk of spreading Ebola by sneezing or coughing.

“An example of a classic acute infection is uncomplicated influenza,” the medical doctors noted. “Virus particles are inhaled in droplets produced by sneezing or coughing, and begin replicating in ciliated columnar epithelial cells of the respiratory tract. As new infectious virions are produced, they spread to neighboring cells.”

The point was clear: “Inapparent infections probably are important features of pathogens that are well-adapted to their hosts. They replicate sufficiently to endure the spread to new hosts, but not enough to damage the host and prevent transmission.”

Westhoff and his associates conclude: “Acute viral infections are responsible for epidemics of disease involving millions of individuals each year, such as influenza and measles. When vaccines are not available, acute infections are difficult to control – most are complete by the time the patient feels ill, and the virus has already spread to another host.”

The German physicians published in 2008 the fundamental medical research that formed the basis for their blog comments, demonstrating kidney-transplant patients could carry the norovirus infection that is common in cases of acute gastroenteritis, even if the patient was asymptomatic.

Westhoff’s 2008 study provided “the first evidence” that norovirus, typically a self-limiting disease of short duration, can cause chronic infection in renal transplant recipients,” even when there are no symptoms of acute gastroenteritis evident in the patient.

Dr. Norman M. Balog, D.O., a board-certified family doctor practicing in Silver Spring, Maryland, brought the research of the German medical team to the attention of WND as evidence that the CDC’s Frieden could not prove his assertion air travel was safe as long as a person infected with Ebola were not showing symptoms. An infected person can go as long as 21 days in an incubation period before being infected.

“Dr. Freiden is either completely uninformed of this research,” Balog explained to WND in an exclusive telephone interview, “or he is deliberately lying because he does not want to panic the general public.”

Balog pointed out that asymptomatic carriers of diseases infecting others is a phenomenon that has been widely documented in virology studies for decades.

“There’s a good potential that on any given day a person you may shake hands with will have Strep Group A Streptococcus that causes sore throats,” he pointed out. “Shaking hands you take the risk you are going to get the Streptococcus virus, even if the person you shook hands with looked perfectly well.”

Balog explained to WND much of the fundamental research on Ebola, including the conditions under which asymptomatic carriers of the disease can infect others, has yet to be conducted and reported in peer-reviewed medical journals.

“Dr. Freiden and the CDC have been reassuring the American public from the beginning of the current outbreak that we can contain and control Ebola, no problem; but the first assurances were three continents ago,” he pointed out. “Now we have Ebola in the United States and in Spain. Where is Ebola going to show up next?”

Balog was critical of the steps taken so far by the CDC to contain the Ebola outbreak.

“Ebola is spreading a lot faster than anybody expected,” he said.

“But even today we are not stopping people from West Africa from boarding international air flights; health officials in Dallas did not put up a fence around Duncan’s apartment complex; and it took several days before Dallas health authorities found anyone qualified to clean up the vomit outside Duncan’s apartment. And then the workers just washed the vomit down into the town storm drains.”

Balog pointed out the medical literature on virology commonly says asymptomatic but infected individuals can spread a disease to others before showing any signs of being sick.

“We have medical models that say a person is capable of secreting a virus like Ebola in bodily fluids before the person displays symptoms of the disease,” he stressed, “and that medical evidence is simply being ignored by Dr. Frieden and the CDC when the public is told repeatedly it’s OK to let Ebola-infected people fly as long as they don’t have a fever.”


Read more at http://www.wnd.com/2014/10/ebola-victims-without-symptoms-could-still-be-contagious/#Jt08BxzbTd7eIkvc.99




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Post Options Post Options   Thanks (1) Thanks(1)   Quote Albert Quote  Post ReplyReply Direct Link To This Post Posted: October 31 2014 at 3:00pm
Here's more on the Lancet study. Interesting stuff.  Hickox would be force quarantined if they cited the Lancet study in court.


Despite our inability to isolate Ebola virus on vero E6 cells from stored serum from the seven asymptomatic individuals, these data do show that asymptomatic, replicative Ebola-virus infection occurs in human beings.

First, these individuals mounted Ebola-specific humoral responses, mainly directed against the proteins NP and VP40, indicating either true infection or antigenic stimulation. Concentrations of IgM and IgG started to rise between 10 and 18 days and between 17 and 25 days, respectively, after the infectious contact, indicating no prior immunity. The appearance of IgM and IgG when viral RNA disappeared may suggest that humoral responses can have a protective role in asymptomatic infection. These findings also confirmed the immunogenicity of NP and VP40 and were consistent with results obtained in symptomatic human beings who survived the disease7 and with other results obtained in animal studies.11 The appearance of antibodies came somewhat later in asymptomatic patients than in symptomatic patients who recovered7 (day 3 following disease onset, about 8—11 days after presumed exposure assuming a 5—8 day incubation period).

Despite seroconversion, circulating Ebola antigen was never detected in asymptomatic individuals. Then, to lower the detection threshold and to distinguish passive immunisation from true infection in the asymptomatic individuals, we developed a reverse-transcriptase PCR assay to detect viral RNA fragment in the L gene in peripheral-blood mononuclear cells with primers described previously.10 We tested circulating white blood cells rather than serum because filoviruses replicate in cells of the monocyte and macrophage lineage both in vitro12 and in vivo.13—14 Ebola RNA was detected in samples from asymptomatic individuals after two rounds of amplification. The need to apply nested PCR to detect viral RNA in these asymptomatic individuals compared with a direct PCR in symptomatic cases15 is suggestive of a very low viral load, consistent with the absence of detectable circulating antigens. Moreover, detection of viral genomic RNA in peripheral-blood mononuclear cells for 2 weeks after exposure together with detection of positive-stranded viral RNA indicate viral replication. In fact, it has been shown that the Ebola genome is transcribed into monocistronic RNA (mRNA), which is complementary to viral genomic RNA. Replication works via a full-length positive-strand antigenome that serves as the template for synthesis of the negative-strand genome.1

These findings show that some individuals were infected with the virus without developing symptoms. Results from previous outbreaks had only indicated that such an asymptomatic infection was possible. During the first three outbreaks of Ebola virus in Sudan and Zaire in 1976 and 1979, WHO teams noticed that individuals had symptoms that ranged in severity, from mild (and probably asymptomatic) to rapidly fatal.16 Moreover, the immunofluorescence showed higher antibody prevalence among asymptomatic family members who had had physical contact with clinical cases than among the general population who had no contact with symptomatic patients.17, 18 More recently, a cohort of 152 household contacts of convalescents was studied for up to 21 months during the Kikwit outbreak in Republic Democratic of the Congo.19 Blood samples of only five such individuals were IgM and IgG positive. Although the authors could not exclude the possibility of false positive (5 [3%] of 152), they suggested that mild cases may occur.

Interestingly, guinea pigs and mice develop a very mild or subclinical infection when inoculated with wild-type Ebola virus, but serial passage leads to increasing pathogenicity and high lethality.14, 20 Genomic sequence analysis of the entïre genome of guinea-pig-adapted Ebola virus showed several nucleotide substitutions, mainly in the VP24 gene; only changes in VP24 led to switches in the predicted aminoacid sequence, suggesting a direct link between VP24 mutations and appearance of pathogenicity of the virus (Volchkov, unpublished data). Furthermore, the GP protein is known to be involved in the virus binding to cellular receptors and entry into cells,4 and is suspected to inhibit innate immunity to the virus, facilitating virus replication and symptoms.21 Thus, the complete open reading frame of these two genes was sequenced by nested-PCR amplification.

The nucleotide divergence between GP and VP24 occurring in Yambuku (Mayinga strain) and Ebola in Gabon was found to be 1·5% and 0·5%, respectively, despite the fact that they were isolated more than 20 years and almost 2000 km apart. This confirms the genetic stability of the virus. Moreover, isolates from all nine patients tested had identical GP and VP24 nucleotide sequences. These findings suggest genetic variability between symptomatic (survivors and deceased patients) and asymptomatic individuals, and are consistent with the lack of changes seen in the most variable region of GP during repeated human-to-human passages and during prolonged virus persistence within the same patients in the Kikwit outbreak in 1995.22 These data suggest that asymptomatic Ebola infection in human beings does not result from viral mutations, and that no different virus variants cocirculated during the Gabon outbreak.

The seven asymptomatic individuals in our study had an early and strong inflammatory response with high circulating levels of IL-1β, TNF, IL-6, MCP-1, MIP-1α, MIP-1β (figure 3). IL-1β, IL-6, and TNF have been shown to be major triggers and regulators of inflammatory responses to microbial pathogens, inducing further cytokine release, endothelial cell activation, acute-phase proteins synthesis, and fever.23, 24 MCP-1, MIP-1α, and MIP-1β have a role in the recruitment of immune cells to the site of infection (being potent chemoattractants for monocytes and lymphocyte effector cells), and also enhance the capacity of these cells to adhere to the vascular endothelium.25, 26 The pro-inflammatory cytokine response in the asymptomatic individuals might have directly or indirectly inhibited viral repliation in its target cells, probably at the site of infection. Indeed, the cytokines involved have been shown to inhibit virus replication either directly27, 28 or indirectly by stimulating immunological functions such as antigen presentation, cytokine production, inflammation, phagocytosis, and cytotoxic activity.29, 30

We estimate that our earliest samples from symptomatic patients are between 8 and 12 days after infection, that is 2—3 days after the onset of symptoms. At this time-point, in the infectious process in patients who died, proinflammatory cytokines (IL-1β, TNF, IL-6, MIP-1α, and MIP-1β) were not detected in any samples, whereas patients who recovered from symptomatic disease had intermediate to low plasma concentrations of these same cytokines (data not shown). Comparison between patients has the limitation that symptomatic patients were sampled a few days later than the asymptomatic ones (8—11 versus 7 days after infection in asymptomatic individuals). However, given the fact that symptomatic patients have a continuous infection, inflammatory cytokines should still be detectable between 8 and 11 days after infection if they were present at high concentrations a few days earlier. These observations are consistent with studies showing a close correlation between the severity of Ebola disease in guinea pigs and mice during serial passage as well as the loss of inflammatory cell infiltration around infected loci.14, 20 In the same way, light microscopic examination of liver and skin tissues from 13 fatal and one non-fatal human case during the Kikwit outbreak showed that perivascular infiltrates of inflammatory cells were absent or mild.31 These observations suggest a link between clinical status and inflammatory responses. Although it is possible that some individuals mount a local cellular mechanism that inhibits replication, or that the infectious dose in these individuals was so small that even a modest inflammatory response could clear virus, this response may be involved in some way in the rapid control of virus and absence of symptoms. The public-health impact of Ebola infection needs also to be reassessed in light of these new findings. The risk of transmission via blood products donated by such individuals or via semen should be taken into consideration in public-health policy since infectious filovirus have already been found in semen from symptomatic patients 2—3 months after symptoms.32, 33

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Albert Quote  Post ReplyReply Direct Link To This Post Posted: October 31 2014 at 3:09pm
There are rumors that Hickox roommate in Sierra Leone got Ebola. If she was an asymptomatic carrier  she's probably only infectious for a few days.  Maybe the last day or two and for the next couple. Let's hope she's not one of the carriers, or her BF is in trouble.  
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Post Options Post Options   Thanks (0) Thanks(0)   Quote CRS, DrPH Quote  Post ReplyReply Direct Link To This Post Posted: October 31 2014 at 7:03pm
Thanks, Albert!  You know that I've been screaming (literally) about inapparent infection with Ebola since the outset of this outbreak.  It's nice to see some highly qualified virologists endorse this possibility.  

The concept of "you are only contagious if you are symptomatic" is just PC garbage in my opinion.  

The German physicians, led by Dr. Timm H. Westhoff of the Department of Nephrology 

at the Carité Campus Benjamin Franklin in Berlin, noted in a virology blog published Feb. 12, 2009, 

that acute viral infections such as Ebola hemorrhagic fever may cause little or no clinical symptoms in 

a so-called “inapparent infection” yet may be contagious.

“A well-known example is poliovirus: over 90% are without infections,” Westhoff and his 

colleagues continued. “During an inapparent infection, sufficient virus replication occurs in the host 

to induce antiviral antibodies, but not enough to cause disease. Such infections are important for the 

spread of infection, because they are not easily detected.”

Westhoff and his colleagues then made the key point that individuals with an inapparent infection,

 showing no symptoms, can yet spread diseases such as polio.

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Albert Quote  Post ReplyReply Direct Link To This Post Posted: November 01 2014 at 6:20am
It does explain why they lost control of it and why cases are exploding. Of course it also means that anyone coming in from the region should be isolated for at least 14 days. If any country gets an asymptotic case or super spreader it's all she wrote. Very dangerous cases/scenario. Hickox bf shouldn't disregard any flu like symptoms over the next couple weeks.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote cobber Quote  Post ReplyReply Direct Link To This Post Posted: November 01 2014 at 6:49am
Me thinks the same doc. 


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Post Options Post Options   Thanks (1) Thanks(1)   Quote Albert Quote  Post ReplyReply Direct Link To This Post Posted: November 01 2014 at 7:02am
Health officials are suppressing this information now, especially after the quarantine fiasco with Hickox and MSF.  She in fact should have been quarantined based on this information.

If Maine again would have cited this info Hickox would have been forced to quarantine for the suspicion of contracting a communicable disease, as symptoms are not necessary in spreading the disease.   This info is being pushed to the side big time.  


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