Tag Archives: pandemic

CDC Update: Candida Auris – April 2018

https://www.cdc.gov/fungal/candida-auris/tracking-c-auris.html

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Not quite two years ago (June 2016) the CDC issued a Clinical Alert to U.S. Health care facilities about the Global Emergence of Invasive Infections Caused by the Multidrug-Resistant Yeast Candida auris.

C. auris is an emerging fungal pathogen that was first isolated in Japan in 2009. It was initially found in the discharge from a patient’s external ear (hence the name `auris’).  Retrospective analysis has traced this fungal infection back over 20 years.

Since then the CDC and public health entities have been monitoring an increasing number of cases (and hospital clusters) in the United States and abroad, generally involving bloodstream infections, wound infections or otitis.

Adding to the concern:

  1. C. auris infections have a high fatality rate
  2. The strain appears to be resistant to multiple classes of anti-fungals  
  3. This strain is unusually persistent on fomites in healthcare environments.
  4. And it can be difficult for labs to differentiate it from other Candida strains

The CDC has updated their C. Auris surveillance page, where they show – as of April 30th  – 279 confirmed cases and 29 probable cases, across 11 states.  An increase of more than 10% over the previous month.
 

https://www.cdc.gov/fungal/candida-auris/tracking-c-auris.html

 

Additionally, based on targeted screening in four states reporting clinical cases, the CDC reports an additional 517 patients have been discovered to be asymptomatically colonized with C. auris.

As previously mentioned, this isn’t just a United States’ problem, but a global health threat.  This fungal infection, which was first detected in Japan in 2009, has now turned up on multiple continents.

For more on this emerging fungal pathogen, you may wish peruse the CDC’s dedicated web page:

General Information about Candida auris
Tracking Candida auris
Patients and Family Members
Healthcare Professionals
Fact Sheet
Publications

And for some older blogs on the topic, you may wish to revisit:

MMWR: Ongoing Transmission of Candida auris in Health Care Facilities

MMWR: Investigation of the First Seven Reported Cases of Candida auris In the United States

mSphere: Comparative Pathogenicity of UK Isolates of the Emerging Candida auris

Indian Government Responds To Reported Nipah Outbreak In Kerala

http://www.who.int/csr/disease/nipah/Global_NiphaandHendraRisk_20090510.png?ua=1

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The Nipah virus – normally carried by fruit bats common to S.E. Asia – was only first identified 20 years ago after an outbreak in Malaysia, which spread from bat to pigs – and then from pigs to humans – eventually infecting at least 265 people, killing 105 (see Lessons from the Nipah virus outbreak in Malaysia).

Similar to Australia’s Hendra virus – Nipah – because of its high mortality and (limited) human-to-human transmissibility – has garnered a reputation among researchers as having at least some pandemic or bio-terrorism potential.

  • In Steven Soderbergh’s 2011 pandemic thriller `Contagion’, technical advisor Ian Lipkin – director of Columbia University’s Center for Infection and Immunity in New York – painstakingly created a fictional MEV-1 pandemic virus based on a mutated Nipah virus. 
  •  In 2015’s Blue Ribbon Study Panel Report on Biodefense a bi-partisan panel described a fictional biological attack on Washington D.C.  using a genetically engineered Nipah virus as part of their presentation. 
  • Just last week, in the Johns Hopkins Clade X exercise, a genetically altered Nipah virus (spliced onto a parainfluenza backbone) was the cause of their fictional pandemic.  
  • And earlier this year, in WHO List Of Blueprint Priority Diseases, we saw Nipah and Henipaviral diseases listed among the 8 viral threats in need of urgent accelerated research and development.    

Overnight, India media (and now Western media) have been reporting on an outbreak of Nipah in Kozhikode, in India’s southern Kerala state (see Crof’s blog Kozhikode: 11 die of suspected Nipah virus infection; medical officials say no need to panic).

While the Indian media is known for its hyperbole, and the exact number of cases and/or deaths vary between accounts – other reports – such as the BBC’s  Deadly Nipah virus claims victims in India at least confirm the main points of the story.

The only official statement I’ve found (the MOH website remains typically silent) has been the following brief press release from the Press Information bureau.

Ministry of Health and Family Welfare           21-May, 2018 13:51 IST

Shri J P Nadda assures all support to Kerala Government to manage Nipah Virus; Sends a multi-disciplinary Central team to investigate the outbreak

In view of the rising number of cases and reported deaths due to Nipah Virus in Kozhikode, Kerala, Shri J P Nadda, Union Minister of Health and Family Welfare has assured all support to the Kerala Government and has directed a multi-disciplinary Central team from National Centre for Disease Control to immediately visit the district, and assist the State and closely monitor the situation. The team will reach Kerala today.

“We are closely monitoring the situation. I have spoken to Shri Alphons and Smt K Shailaja, Health Minister, Kerala and assured them all support of the Central government. I have also dispatched a Central team to assist the State government and initiate required steps,” the Union Health Minister said in a statement from Geneva.

On the directions of the Health Minister, Smt. Preeti Sudan, Secretary (HFW) has also spoken to the Principal Health Secretary of Kerala and reviewed the situation.

The Central team includes Dr Sujeet K Singh, Director, National Centre for Disease Control, Dr S K Jain, Head Epidemiology, NCDC, Dr P Ravindran, Director, Emergency Medical Relief (EMR), Dr Naveen Gupta, Head Zoonosis, NCDC along with two clinicians and one expert from Ministry of Animal Husbandry.

Over the past decade nearly all of the reported Nipah outbreaks have come out of Bangladesh, often linked to date palm sap collection (see Bangladesh: Nipah Update).

Fruit bats of the Pteropodidae family have a preference for roosting in the tops of trees rather than caves, which allows them to contaminate date juice collection jars with their virus laden urine and feces

Once infected via a zoonotic exposure, humans can transmit the virus on to others, albeit not terribly efficiently (see EID Journal Person-to-Person Transmission of Nipah Virus in a Bangladeshi Community).

While outbreaks of Nipah have tended to be limited in size, we’ll be following the events in Kozhikode (pop. 550,000) closely, as our knowledge of the virus is limited as well.

Stay tuned. 

New Ebola virus disease case confirmed in a third DRC health zone

Alert, alert…

The Democtraic Republic of the Congo (DRC) Ministry of Health (MOH) today announced that 1 of 2 suspected EVD cases in the Mbandaka Health Zone has tested positive for Ebola virus.[1]

This weekend, two suspected cases of haemorrhagic fever were reported in the health zone of Wangata, one of the health zones of the city of Mbandaka. After analysis, one of the two samples was positive for Ebola virus disease.
-TRANSLATED from [1]

Zoomed in section of the adjacent DRC map highlighting the Wangata Health Zone (purple area) housing ta new EVD confirmed case, just below Mbandaka (Pin4), capital of Équateur Province.

What does it mean?

This is of particular concern as the cases lie adjacent to Mbandaka, the capital of Équateur province and a city of approximately 1 million people.[2]

Now is certainly a good time to have the experimental Ebola virus vaccine (V920) onsite and ready to be distributed to healthcare workers and contacts of cases in a ring vaccination format. This approach encircles cases with vaccinated people to prevent further spread from known foci of infection.[2]

New numbers

Case numbers have now changed again. As at the 15th May:

 

Table from DRC MOH.[1]

  • 44 total EVD cases (includes suspect, probable and confimred)
  • 2 new suspect cases, 1 each in Bikoro and Wangata health zones
    • 21 suspect cases
    • 20 probable cases
    • 3 confirmed cases
    • 23 deaths (proportion of fatal cases = 52%)

Case numbers are always changing so please use these as a guide only.

This latest turn of events is something to keep a close eye on. When EVD reaches more populated areas and transport hubs, we’ve seen how things can quickly spiral out of control. Hopefully the fast and collaborative response to date will stay on top of things.

It’s still too early to tell whether this outbreak is under control or not yet.

References…

  1. Special Communication from His Excellency the Minister of Health on May 16, 2018 on the evolution of the Ebola epidemic in the Democratic Republic of Congo
    https://us13.campaign-archive.com/?u=89e5755d2cca4840b1af93176&id=a902d8be0b
  2. Experimental Vaccine Will be Used against Ebola Outbreak in the DRC
    https://www.scientificamerican.com/article/experimental-vaccine-will-be-used-against-ebola-outbreak-in-the-drc/
  3. Effective Post-Exposure Treatment of Ebola Infection
    https://www.ncbi.nlm.nih.gov/pubmed/17238284
  4. Recombinant vesicular stomatitis virus vector mediates postexposure protection against Sudan Ebola hemorrhagic fever in nonhuman primates
    https://www.ncbi.nlm.nih.gov/pubmed/18385248
  5. Efficacy of Vesicular Stomatitis Virus-Ebola Virus Postexposure Treatment in Rhesus Macaques Infected With Ebola Virus Makona
    https://www.ncbi.nlm.nih.gov/pubmed/27496978
  6. Postexposure Treatment of Marburg Virus Infection
    https://wwwnc.cdc.gov/eid/article/16/7/10-0159_article
  7. Recombinant vesicular stomatitis virus vector mediates postexposure protection against Sudan Ebola hemorrhagic fever in nonhuman primates
    https://www.ncbi.nlm.nih.gov/pubmed/18385248

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Emerg. Infect. & Microbes: Novel Triple-Reassortant influenza Viruses In Pigs, Guangxi, China

Yikes!

Triple%2BReassortment%2BIn%2BSwine%2BHos

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As pork production rises around the world – particularly in countries where there is poor biosecurity and little surveillance – the risks of seeing another novel swine flu virus emerge as a pandemic threat continues to grow. 

While we watch avian H5 & H7 flu viruses with particular concern – mainly due to their high mortality rates in humans – swine, or swine-avian-human triple reassortant viruses – are perhaps even more likely to emerge as a pandemic threat.

Two and a half years ago, Chen Hualan – director of China’s National Avian Influenza Reference Laboratory – gave an interview to Xinhua where she pegged the EA (Eurasian Avian-like) H1N1 swine virus (EAH1N1) as having perhaps the greatest pandemic potential of any of the novel viruses in circulation.

Avian-like H1N1 swine flu may “pose highest pandemic threat”: study

WASHINGTON, Dec. 28 (Xinhua) — The Eurasian avian-like H1N1 (EAH1N1) swine flu viruses, which have circulated in pigs since 1979, have obtained the ability to infect humans and may “pose the highest pandemic threat” among the flu viruses currently circulating in animals, Chinese researchers said Monday.

“Pigs are considered important intermediate hosts for flu viruses,” Chen Hualan, director of China’s National Avian Influenza Reference Laboratory, who led the study, said in an written interview with Xinhua.

“Based on scientific analysis and comprehensive comparison of the main animal flu viruses: H1N1, H3N2, H5N1, H7N9, H9N2 and EAH1N1, we found the EAH1N1 is the one most likely to cause next human flu pandemic. We should attach great importance to the EAH1N1.”

(Continue . . . )

And indeed, we’ve been following the evolution of EAH1N1, along with other novel swine-origin viruses in China, with considerable interest.  A few recent blogs include:

Emerg. Microbes & Infect.: Effect Of D701N Substitution In PB2 Of EAH1N1 Swine Flu Viruses

J. Virology: A Single Amino Acid Change Alters Transmissability Of EAH1N1 In Guinea Pigs

Emerg. Microbes & Inf.: Pathogenicity & Transmission Of A Swine Influenza A(H6N6) Virus – China

Lest anyone think this is strictly a Chinese problem, we’ve also spent considerable time looking at the evolution and emergence of North American, European, and South American swine flu viruses as well.  Regions not mentioned are likely to have little or no surveillance and reporting.

I&ORV: Triple-Reassortant Novel H3 Virus of Human/Swine Origin Established In Danish Pigs

EID Journal: Characterization of a Novel Human Influenza A(H1N2) Virus Variant, Brazil

MMWR: Investigation Into H3N2v Outbreak In Ohio & Michigan – Summer 2016

J. Virol: Novel Reassortant Human-like H3N2 & H3N1 Influenza A Viruses In Pigs

And as we discussed yesterday (see PNAS: Broad Receptor Engagement of PDCoV May Potentiate Its Cross-Species Transmissibility), influenza isn’t the only zoonotic disease concern when it comes to pigs.

Nature’s Scientific Reports carries two related studies (albeit by different authors) on influenza in China’s commercial swine production industry.  The first, which is linked below with a short quote, is an article on surveillance.

Prospective surveillance for influenza. virus in Chinese swine farms

Benjamin D. Anderson, Mai-Juan Ma, Guo-Lin Wang, Zhen-Qiang Bi, Bing Lu, Xian-Jun Wang, Chuang-Xin Wang, Shan-Hui Chen, Yan-Hua Qian, Shao-Xia Song, Min Li, Teng Zhao, Meng-Na Wu, Laura K. Borkenhagen, Wu-Chun Cao & Gregory C. Gray

Excerpt

Overall, these first year data suggest that IAV is quite ubiquitous in the swine production environment and demonstrate an association between the different types of environmental sampling used. Given the mounting evidence that some of these viruses freely move between pigs and swine workers, and that mixing of these viruses can yield progeny viruses with pandemic potential, it seems imperative that routine surveillance for novel IAVs be conducted in commercial swine farms.

The second study (below) tells us a lot more about the growing number of novel triple reassortant swine-origin flu viruses circulating in Guangxi, China over the past few years.

Out of 15 isolates selected, researchers found 10 novel reassortant viruses (see chart below), all hybrids of EAH1N1, H1N1/09, CS H1N1, and HL H3N2, and all reportedly replicated in mice without adaptation, with several proving to be lethal. 

https://www.nature.com/articles/s41426-018-0088-z

Being a snapshot in time, and taken from a single Chinese province (ranked 11th in population), this likely only reveals a fraction of the viral diversity on Chinese pig farms.

I’ve only posted the link, abstract, and as short excerpt from the discussion. Follow the link below to read it in its entirety.

Novel triple-reassortant influenza viruses in pigs, Guangxi, China 

Ping He, Guojun Wang, Yanning Mo, Qingxiong Yu, Xiong Xiao, Wenjuan Yang,
Weifeng Zhao, Xuan Guo, Qiong Chen, Jianqiao He, Mingli Liang, Jian Zhu, Yangbao Ding, Zuzhang Wei, Kang Ouyang, Fang Liu, Hui Jian, Weijian Huang,
Adolfo García-Sastre & Ying Chen

Emerging Microbes & Infections volume 7, Article number: 85 (2018)
doi:10.1038/s41426-018-0088-z


Published:16 May 2018

Abstract

Considered a “mixing vessel” for influenza viruses, pigs can give rise to new influenza virus reassortants that can threaten humans. During our surveillance of pigs in Guangxi, China from 2013 to 2015, we isolated 11 H1N1 and three H3N2 influenza A viruses of swine origin (IAVs-S). 

Out of the 14, we detected ten novel triple-reassortant viruses, which contained surface genes (hemagglutinin and neuraminidase) from Eurasian avian-like (EA) H1N1 or seasonal human-like H3N2, matrix (M) genes from H1N1/2009 pandemic or EA H1N1, nonstructural (NS) genes from classical swine, and the remaining genes from H1N1/2009 pandemic. 

Mouse studies indicate that these IAVs-S replicate efficiently without prior adaptation, with some isolates demonstrating lethality. Notably, the reassortant EA H1N1 viruses with EA-like M gene have been reported in human infections. Further investigations will help to assess the potential risk of these novel triple-reassortant viruses to humans.

       (SNIP)

Currently, influenza A H1N1 and H3N2 viruses are the circulating seasonal influenza A viruses subtypes in human. The H1N1/2009 pandemic became the current seasonal H1N1 virus.

Our EA H1N1 HAs share < 73.7 and 78.1% similarity with the H1N1/2009 pandemic vaccine strain (A/Michigan/45/2015 H1N1), at nucleotide level and amino acid level, respectively. Our H3N2 IAVs-S share < 94.1 and 91.5% similarity with the H3N2 vaccine strain (A/Hong Kong/4801/2014 H3N2), at nucleotide level and amino acid level, respectively.

Studies have reported that seasonal trivalent inactivated influenza vaccine induce poor cross-reactive antibodies to EA H1N1 virus23 and does not protect against swine H3N257. Importantly, according to the risk assessment tool, which is developed by the Centers for Disease Control and Prevention in the United States to evaluate the pandemic potential of different influenza strains58, we found that the EA H1N1 and swine H3N2 viruses are among the animal viruses with the highest risk score in Yang’s analysis26. Besides, at least one human infection with a similar reassortant IAV-S has been reported22.

We suggest that intensive surveillance of IAV-S and of swine-to-human infections with the IAV-S described in our study should be a priority for future research.

(Continue . . . .)

Human T-Lymphotropic Virus type 1 (HTLV-1): a primer

What is HTLV-1?

HTLV-1 is a human delta retrovirus assigned to the genus Deltaretrovirus, species Primate T-lymphotropic virus 1 [5]. It was first described in 1980.[10]

ViralZone:www.expasy.org/viralzone,
SIB Swiss Institute of Bioinformatics [6]

Soon thereafter Japanese researchers identified endemic virus, especially in southwestern Japan.[8,9]

These viruses infect a cell and make new DNA from their RNA genetic blueprint using an enzyme called reverse transcriptase.[7] This DNA then acts as a blueprint to manufacture more RNA and then viral proteins. The DNA form inserts into a random site in the host cell genome.[19] This form of HTLV-1 is called the provirus. The order of making RNA first then DNA is the reverse (retro) of the usual ‘direction’ of protein manufacture in human cells which is from DNA to RNA to protein.

HTLV-1 infects T and B lymphocytes, monocytes, endothelial cells, and fibroblasts, using a common molecular, ubiquitous cell surface molecule, the glucose transporter 1, as its receptor.[12]

HTLV-1 is established mostly in resource-limited regions of the world, infecting an estimated 10-20 million people.[9] Australia hosts the distinct HTLV-1c strain although little is known about its distribution.[1,17] It is predicted that HTLV-1c arrived and then divided into at least 2 further distinct groups (clades) around 3,000-9,000 years ago.[17,18]

In Australia, HTLV-1 infection occurs in the middle of the country (‘central Australia’ mostly reported in the Northern Territory but also Western Australia and South Australia) and antibodies in sera collected in 1956 from Aboriginal Australians in Cape York, Queensland.[20] In some communities, greater than 40% of Aboriginal Australian adults are HTLV-1 infected.[13]

An HTLV-1 timeline. Some discoveries of interest are shown. Click to enlarge.

What does HTLV-1 do?

Infection is generally without symptoms. In 3-5% of those infected develop a highly malignant T-cell neoplasm known as adult T-cell leukaemia/lymphoma (ATLL).[11] This can take decades to develop. There is an estimated 23.6 ATLL cases /100,000 population among Australian adult HTLV-1 carriers.[16]

Infection can also result in HTLV-1-associated-myeIopathy/tropical-spastic-paraparesis (HAM/TSP) and other inflammatory diseases involving the lungs, central nervous system and eyes.[1,10]

Crusted scabies has also been described as a marker for HTLV-1 infection.[2,3]

Bronchiectasis is the most common evidence of HTLV-1 infection among Aboriginal Australians.[1] 

How is HTLV-1 transmitted?

Epidemiological aspects and world distribution of HTLV-1 infection. Gessain & Cassar 2012. Front. Microbiol., 15 November 2012  [8]

The virus can be passed to a susceptible new host via prolonged breastfeeding, sexual transmission ( 4X more frequently male to female[9]),  via HTLV-1-contaminated blood or blood-product transfusion or intravenous drug use.[8]

Japan successfully deployed a program to reduce transmission methods to reduce mother-to-child-transmission.[14]

How do we test for HTLV-1?

Detecting the presence of antibody to viral proteins as a result of infection is a widely used and relatively inexpensive method that fits into the workflow of the modern serology laboratory. Specificity issues were an early and ongoing issue.[8]

The detection of proviral DNA using PCR methods is a sensitive way to identify infected blood cells. Enhanced methods can quantify how much provirus is present which is related to disease progression. A typical healthy infected person may have proviral DNA in 0.1-1% of peripheral blood cells.[10] Virus levels are generally stable but a rise has been associated with the development of HAM/TSP and proviral load is higher in bronchiectasis.[10,15] 

References…

  1. Human T-Lymphotropic Virus type 1c subtype proviral loads, chronic lung disease and survival in a prospective cohort of Indigenous Australians.
    http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006281
  2. Crusted scabies: a clinical marker of human T-lymphotropic virus type 1 infection in central Australia.
    https://www.mja.com.au/journal/2014/200/11/crusted-scabies-clinical-marker-human-t-lymphotropic-virus-type-1-infection
  3. HTLV-I and scabies in Australian Aborigines
    https://www.thelancet.com/journals/lancet/article/PII0140-6736(93)91186-P/abstract
  4. Human T-lymphotropic virus 1: recent knowledge about an ancient infection
  5. https://talk.ictvonline.org/ictv-reports/ictv_9th_report/reverse-transcribing-dna-and-rna-viruses-2011/w/rt_viruses/161/retroviridae
  6. https://viralzone.expasy.org/59
  7. Retrovirus
    https://www.britannica.com/science/retrovirus
  8. Epidemiological aspects and world distribution of HTLV-1 infection
    https://www.frontiersin.org/articles/10.3389/fmicb.2012.00388/full
  9. HTLV-1 infections
    http://jcp.bmj.com/content/53/8/581
  10. Detection and isolation of type c retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC350514/
  11. HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma—A Tale of Two Proteins: Tax and HBZ
    http://www.mdpi.com/1999-4915/8/6/161
  12. The Ubiquitous Glucose Transporter GLUT-1 Is a Receptor for HTLV
    https://doi.org/10.1016/S0092-8674(03)00881-X
  13. The prevalence and clinical associations of HTLV-1 infection in a remote Indigenous community
    https://www.mja.com.au/journal/2016/205/7/prevalence-and-clinical-associations-htlv-1-infection-remote-indigenous
  14. Establishment of the milk-borne transmission as a key factor for the peculiar endemicity of human T-lymphotropic virus type 1 (HTLV-1): the ATL Prevention Program Nagasaki
    https://www.jstage.jst.go.jp/article/pjab/87/4/87_4_152/_article
  15. Higher Human T-Lymphotropic Virus Type 1 Subtype C Proviral Loads Are Associated With
    Bronchiectasis in Indigenous Australians: Results of a Case-Control Study
    https://academic.oup.com/ofid/article-lookup/doi/10.1093/ofid/ofu023
  16. Variant Human T-cell Lymphotropic Virus Type 1c and Adult T-cell Leukemia, Australia
    https://wwwnc.cdc.gov/eid/article/19/10/13-0105_article
  17. Human T-Cell Lymphotropic Virus Type 1 Subtype C Molecular Variants among Indigenous Australians: New Insights into the Molecular Epidemiology of HTLV-1 in Australo-Melanesia
    http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0002418
  18. Detailed phylogenetic analysis of primate T-lymphotropic virus type 1 (PTLV-1) sequences from orangutans (Pongo pygmaeus) reveals new insights into the evolutionary history of PTLV-1 in Asia
    https://www.sciencedirect.com/science/article/pii/S1567134816302180
  19. Nonspecific integration of the HTLV provirus genome into adult T-cell leukaemia cells.
    https://www.ncbi.nlm.nih.gov/pubmed/6328324
  20. Antibodies to HTLV‐I in populations of the southwestern Pacific
    https://ift.tt/2GqBKQG

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