Tag Archives: pandemic

Guillain-Barré syndrome – France – French Polynesia

On 24 November 2015, health authorities in French Polynesia reported unknown and unspecified causes of morbidity and mortality in the context of concomitant outbreaks of Zika and dengue (serotypes 1 and 3) viruses. This update provides additional information on the clinical findings as well as the epidemiological and laboratory investigations of these cases.

Between October 2013 and April 2014, French Polynesia experienced the largest Zika virus outbreak ever recorded in the country. During this period of time, 32,000 patients (11.5% of the population) were assessed for the infection and 8,750 suspected cases were reported by the national surveillance system. Of the suspected cases, 383 were later laboratory-confirmed by reverse transcription polymerase chain reaction (RT-PCR).

State laws heighten influenza vaccination rates among health care workers

A new study from the University of Pittsburgh School of Medicine shows that state laws requiring health care works to receive their influenza vaccines can raise vaccination rates.

Between 2000 and 2005, New Hampshire and Maine were the only two states with flu vaccine requirement laws specifically for people working in the health care industry. In those five years, health care workers had a 22.5 percent average for their influenza vaccination rates.

Between 2006 and 2011, 19 other states added state laws for influenza vaccination requirements. When this happened, health care workers had a 50.9

percent average for influenza vaccination.

“Flu vaccination for all health care workers has long been recommended as one of the most effective ways to avoid infecting vulnerable patients with influenza, which kills thousands of people every year,” Dr. Chyongchiou Jeng Lin, lead author and associate professor in Pitt’s Department of Family Medicine, said. “State laws mandating that health care workers get flu vaccinations are an effective method to potentially save lives.”

The study, available in the Journal of the National Medical Association, analyzed influenza vaccination rates between 2000 and 2011. The researchers made scores for each of the states determined according to the law’s rigor.

“We’re finding that the higher the score — meaning the state has a law and includes components like a mandate or education — the greater the probability that the vaccination rate among health care workers will be higher,” Lin said.

Cell Stem Cell: Zika Virus Infects Human Cortical Neural Progenitors

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Although we’ve a compelling spatial-temporal link between Zika virus outbreaks and increases in microcephaly in Brazil (and to a lesser extent in French Polynesia), we still lack proof of causation. 

One of the many barriers to proving causation is finding a plausible mechanism by which the Zika virus could produce the kind of profound fetal brain anomalies that have been reported.

Today, in a brief report published in the journal Cell Stem Cell, researchers working with lab-grown human stem cells have shown the Zika virus selectively infects the type of cells that form the brain’s cortex, and importantly, infection `increases cell death and dysregulates cell-cycle progression, resulting in attenuated hNPC growth.’

The full report can be accessed at the link below.  Below that you’ll find a link and some excerpts from a press release.

Highlights

  • Zika virus (ZIKV) infects human embryonic cortical neural progenitor cells (hNPCs)
  • ZIKV-infected hNPCs produce infectious ZIKV particles
  • ZIKV infection leads to increased cell death of hNPCs
  • ZIKV infection dysregulates cell cycle and transcription in hNPCs

Summary

The suspected link between infection by Zika virus (ZIKV), a re-emerging flavivirus, and microcephaly is an urgent global health concern. The direct target cells of ZIKV in the developing human fetus are not clear. Here we show that a strain of the ZIKV, MR766, serially passaged in monkey and mosquito cells efficiently infects human neural progenitor cells (hNPCs) derived from induced pluripotent stem cells.

 Infected hNPCs further release infectious ZIKV particles. Importantly, ZIKV infection increases cell death and dysregulates cell-cycle progression, resulting in attenuated hNPC growth. Global gene expression analysis of infected hNPCs reveals transcriptional dysregulation, notably of cell-cycle-related pathways. Our results identify hNPCs as a direct ZIKV target. 

In addition, we establish a tractable experimental model system to investigate the impact and mechanism of ZIKV on human brain development and provide a platform to screen therapeutic compounds.

Zika virus infects human neural stem cells

Cell Press 

The Zika virus infects a type of neural stem cell that gives rise to the brain’s cerebral cortex, Johns Hopkins and Florida State researchers report March 4 in Cell Stem Cell. On laboratory dishes, these stem cells were found to be havens for viral reproduction, resulting in cell death and/or disruption of cell growth.
While this study does not prove the direct link between Zika and microcephaly, it does pinpoint where the virus may be doing the most damage.

 The researchers, led by Guo-li Ming and Hongjun Song of the Johns Hopkins University School of Medicine and Hengli Tang of Florida State University, with collaborators at the Emory University School of Medicine, worked around the clock for a month to conduct the study, which provides a new platform to learn about the Zika virus using neuronal cells derived from human induced pluripotent stem cells. In the near future, the researchers hope to grow mini-brains from the stem cells to observe the long-term effects of Zika infection on neural tissue and to screen for potential therapeutics. 

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### This study was supported by The Florida State University, the National Institutes of Health, and the Maryland Stem Cell Research Fund.

Fiocruz: Zika Virus Experimentally Introduced Into Culex Mosquitoes

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It is widely assumed that the Aedes Aegypti mosquito (and very possibly the Aedes Albopictus) are the primary mosquito vectors for Zika, Dengue and Chikungunya. Both are well distributed in Central and South America, and both make serious inroads into North America as well.

But there are other mosquito species known to carry diseases that can  infect humans, and few have been examined to see if they can transmit Zika. 

During yesterday’s PAHO press conference the speaker from the FIOCRUZ (Fundação Oswaldo Cruz) scientific research institute announced their researchers had experimentally infected Culex mosquitoes with the Zika virus, and that the virus was was subsequently detected in their salivary glands. 

Culex is a large genus of mosquitoes that contains hundreds of species, which are well distributed around the globe, and range much farther than do Aedes mosquitoes.

Several breeds of Culex are known to vector diseases including West Nile virus, Japanese encephalitis, and St. Louis encephalitis.  Whether they can vector the Zika virus is still not known, and may not be for several more months.

Last January, in FIOCRUZ Researchers Investigate Other Possible Zika Mosquito Vectors, we looked at ongoing research into non-Aedes Zika vectors by researcher Constância Ayres, followed again in February by a Lancet commentary (see Identification Of Zika Virus Vectors).

While some headlines overnight are prematurely declaring Culex a vector of Zika, for now it is only a possibility, as explained in the following (translated) report from Pernambuco nordeste.

02/03/2016 17h36 – Updated 03/02/2016 17h36

Still can not confirm that the common mosquito transmits the disease. The  end result of the research will be known within eight months.


The ease of spread of zika virus in Culex mosquitoes infected in the laboratory was confirmed on Wednesday (2) by the researcher Constance Ayres, of vector design of the Oswaldo Cruz Foundation institution ( Fiocruz ) in Pernambuco . “This means that, in the laboratory, the virus managed to escape some barriers in the mosquito and reached the salivary gland,” the researcher explained. The Culex is the common mosquito, popularly known as muriçoca or stilt.

During the second day of the workshop A, B, C, D, E Zika virus, held in Recife , the biologist presented the preliminary results of research showing the spread of the virus to the mosquito ‘s salivary gland, where happen to transmission disease to humans. After performing three infections in 200 Culex mosquitoes (the first two in December last year and the third in February), research shows the vector competence of mosquito in the laboratory.

The survey results are still partial, it is still not possible to say whether the mosquito is capable of transmitting the virus to zika people. “To complete this, lack identify in the field the species of mosquito infected with the virus zika,” says the biologist. 

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Culex mosquitoes, while more plentiful and better distributed than the Aedes mosquito, are more likely to get a blood meal from birds than from humans.  Which is not to say they don’t bite humans, only that humans are not their primary target.

Some Culex mosquitoes feed exclusively on birds, while others feed on birds and mammals, providing a `bridge‘ for vectoring diseases like West Nile Virus from birds to humans. From the EID Journal, we get:


To evaluate the role of Culex mosquitoes as enzootic and epidemic vectors for WNV, we identified the source of vertebrate blood by polymerase chain reaction amplification and sequencing portions of the cytochrome b gene of mitochondrial DNA.

All Cx. restuans and 93% of Cx. pipiens acquired blood from avian hosts; Cx. salinarius fed frequently on both mammals (53%) and birds (36%). Mixed-blood meals were detected in 11% and 4% of Cx. salinarius and Cx. pipiens, respectively. American robin was the most common source of vertebrate blood for Cx. pipiens (38%) and Cx. restuans (37%). American crow represented less than 1% of the blood meals in Cx. pipiens and none in Cx. restuans.

Human-derived blood meals were identified from 2 Cx. salinarius and 1 Cx. pipiens. Results suggest that Cx. salinarius is an important bridge vector to humans, while Cx. pipiens and Cx. restuans are more efficient enzootic vectors in the northeastern United States.  

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While it has been estimated that humans provide less than 5% of blood meals to Culex mosquitoes, given their number – particularly in densely populated urban areas – their ability to spread diseases remains substantial.

But whether they will prove to be a significant factor in the spread of Zika is something we’ll simply have to wait to see.

WHO: Statement Of 8th IHR Committee On Polio As A PHEIC

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Credit WHO

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While Zika is getting all of the media’s attention these days, not quite two years ago (May 2014) – after convening a meeting of their Emergency Committee – we saw the WHO Declare  Polio Spread A Public Health Emergency Of International Concern (PHEIC).

Since then the IHR committee has met regularly to discuss progress in eradicating Polio and consider its status. Yesterday the WHO posted the results of their 8th consultation, where they decided to extend the PHEIC designation another 3 months. 

While noting that progress has been made over the past two years in controlling wild type polio, they cited two  recent reports of exportations last fall from Pakistan into Afghanistan. 

And while relatively rare, we continue to see scattered reports of vaccine derived Poliovirus (cVDPV) around the world.  The IHR committee reports: 

In 2015, six outbreaks of circulating vaccine derived poliovirus have occurred – three cVDPV type 1 outbreaks (Ukraine, Madagascar and Lao People’s Democratic Republic) and three cVDPV type 2 outbreaks (Myanmar, Nigeria and Guinea). Six additional cases of cVDPV type 2 have been reported in Guinea since the last meeting.

 
These vaccine derived infections come from the use of the oral (Sabin) polio vaccine (OPV) which contains three attenuated (weakened) polio virus strains, that activates an immune response in the body, and for a few weeks causes the weakened virus to be shed in the feces. 

This is considered a `good’ side effect, for in areas with poor sanitation, this vaccine-virus can spread in the community for a limited time conveying extra immunity.

But as the WHO explains: 

On rare occasions, if a population is seriously under-immunized, an excreted vaccine-virus can continue to circulate for an extended period of time. The longer it is allowed to survive, the more genetic changes it undergoes. In very rare instances, the vaccine-virus can genetically change into a form that can paralyse – this is what is known as a circulating vaccine-derived poliovirus (cVDPV).

For Polio to be completely eradicated, the use of the OPV must eventually be  phased out, and the final push completed using the older inactivated Salk vaccine (see   Polio Eradication and Endgame Strategic Plan 2013–2018 ). 

Unlike the oral vaccine which has been the workhorse of the global polio eradication initiative, the inactivated polio vaccine (IPV) must be delivered via an injection, and by a trained health care professional.

IPV is also much more expensive than OPV, but is the only path to eradication. Follow the link below to read the entire IHR statement, I’ve only included some highlights from the text.

WHO statement
1 March 2016 

The eighth meeting of the Emergency Committee under the International Health Regulations (2005) (IHR) regarding the international spread of poliovirus was convened via teleconference by the Director-General on 12 February 2016. As with the seventh meeting, the Emergency Committee reviewed the data on circulating wild poliovirus as well as circulating vaccine-derived polioviruses (cVDPV). The latter is particularly important as cVDPVs reflect serious gaps in immunity to poliovirus due to weaknesses in routine immunization coverage in otherwise polio-free countries. In addition, it is essential to stop type 2 cVDPVs in advance of the globally synchronized withdrawal of type 2 OPV in April 2016. 

The following IHR States Parties submitted an update on the implementation of the Temporary Recommendations since the Committee last met on 10 November 2015: Afghanistan, Pakistan and Guinea.


(BIG SNIP)

Conclusion

The Committee unanimously agreed that the international spread of polio remains a Public Health Emergency of International Concern (PHEIC) and recommended the extension of the Temporary Recommendations for a further three months. The Committee considered the factors expressed in reaching this conclusion at the seventh meeting still applied:

  • The continued international spread of wild poliovirus during 2015 involving Pakistan and Afghanistan.
  • The risk and consequent costs of failure to eradicate globally one of the world’s most serious vaccine preventable diseases.
  • The continued necessity of a coordinated international response to improve immunization and surveillance for wild poliovirus, stop its international spread and reduce the risk of new spread.
  • The serious consequences of further international spread for the increasing number of countries in which immunization systems have been weakened or disrupted by conflict and complex emergencies. Populations in these fragile states are vulnerable to outbreaks of polio. Outbreaks in fragile states are exceedingly difficult to control and threaten the completion of global polio eradication during its end stage.
  • The importance of a regional approach and strong cross-border cooperation, as much international spread of polio occurs over land borders, while recognizing that the risk of distant international spread remains from zones with active poliovirus transmission.
  • Additionally with respect to cVDPV:
    • cVDPVs also pose a risk for international spread, and if there is no urgent response with appropriate measures, particularly threaten vulnerable populations as noted above;
    • The emergence and circulation of VDPVs in four WHO regions demonstrates significant gaps in population immunity at a critical time in the polio endgame;
    • There is a particular urgency of stopping type 2 cVDPVs in advance of the globally synchronized withdrawal of type 2 component of the oral poliovirus vaccine in April 2016.

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FDA: Recommendations To Reduce Risk Of Zika Infection From Human Cell & Tissue Transplants

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Credit CDC

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We’ve previously discussed efforts to protect the blood supply from the Zika Virus (see WHO: Interim Guidance To Maintain Safety Of Blood Supply From Zika Virus), but donated human cells, tissues, and cellular and tissue-based products (HCT/Ps) represent another area of risk.

Yesterday the FDA released new recommendations designed to reduce the risks of Zika contamination of these types of donated biologicals.

The FDA recommends  a 6-month moratorium on accepting from donors (living or deceased) HCT/Ps (human cells, tissues, and cellular and tissue-based products) who had been diagnosed with Zika virus infection, were in an area with active Zika virus transmission, or had sex with a male with either of those risk factors.

As we are still learning about the persistence of the Zika virus in humans, these recommendations may be changed down the road.

FDA issues recommendations to reduce the risk of Zika virus transmission by human cell and tissue products

For Immediate Release

March 1, 2016

Release

As an additional safety measure against the emerging Zika virus outbreak, the U.S. Food and Drug Administration today issued new guidance for immediate implementation providing recommendations to reduce the potential transmission risk of Zika virus from human cells, tissues, and cellular and tissue-based products (HCT/Ps). The guidance addresses donation of HCT/Ps from both living and deceased donors, including donors of umbilical cord blood, placenta, or other gestational tissues.

The new guidance is a part of the FDA’s ongoing efforts to protect HCT/Ps and blood products from Zika virus transmission. On Feb. 16, the FDA issued recommendations for reducing the risk of Zika virus via blood transfusion in the U.S.

“Though there is more to be learned about the transmission of Zika virus, given what we know about the virus at this point, which also is informed by our understanding of similar viruses, we must address the potential risk of Zika virus transmission by human cells and tissues,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “Providing HCT/P establishments with donor eligibility recommendations will help reduce that potential risk.”

There is a potential risk that the Zika virus can be transmitted by HCT/Ps used as part of a medical, surgical, or reproductive procedure. HCT/Ps include products such as corneas, bone, skin, heart valves, hematopoietic stem/progenitor cells (HPCs), gestational tissues such as amniotic membrane, and reproductive tissues such as semen and oocytes.

According to the Centers for Disease Control and Prevention, Zika virus can be spread by a man to his sexual partners. And to date, there have been several cases of sexual transmission in the U.S. Current information about Zika virus detection in semen suggests that a period of ineligibility longer than the waiting period that has been recommended for donors of Whole Blood and blood components is necessary for HCT/P donors.

Recommendations for living donors of HCT/Ps: Donors should be considered ineligible if they were diagnosed with Zika virus infection, were in an area with active Zika virus transmission, or had sex with a male with either of those risk factors, within the past six months. Donors of umbilical cord blood, placenta, or other gestational tissues should be considered ineligible if they have had any of the above risk factors at any point during their pregnancy.

Recommendations for deceased (non-heart-beating) donors: Donors should be considered ineligible if they were diagnosed with Zika virus infection in the past six months.

A deferral period of six months was chosen because of the limited data available on the length of time the virus can persist in all tissues. Zika virus has been detected in tissues and body fluids after the virus is no longer detectable in the blood stream, and has been detected in semen possibly up to 10 weeks after the onset of symptoms. Given the uncertainty, six months was determined to provide the appropriate level of caution.

Less evidence exists regarding the potential for transmission of Zika virus by HCT/Ps typically recovered from deceased donors. As more information becomes available, the understanding of the risks to recipients of HCT/Ps, including HCT/Ps recovered from deceased donors, may evolve. The FDA will continue to monitor the situation, and will carefully evaluate new information regarding the associated risks as it becomes available.

In addition to the guidance documents addressing the nation’s blood supply and HCT/Ps, the FDA continues to prioritize the development of blood donor screening and diagnostic tests that may be useful for identifying the presence of or recent infection with the virus, prepare to evaluate the safety and efficacy of investigational vaccines and therapeutics that might be developed, and review technology that may help suppress populations of the mosquitoes that can spread the virus.

The FDA, an agency within the U.S. Department of Health and Human Services, promotes and protects the public health by, among other things, assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

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