Sunday, August 20, 2017

Conflicting Reports Of A `Bird Flu' Case In Bekasi Indonesia


The Indonesian press lit up this morning with multiple reports of suspected `Flu Burung', reportedly in a Bekasi bird shop owner who was placed into isolation at a hospital in Jakarta (see Jakarta Post  Bekasi bird shop owner suspected of avian flu infection).

Almost immediately, however, there were reports that the patient had already tested negative for avian flu (presumably H5N1). This from Media Indonesia:
Alleged cases of Avian Influenza occurred in Bekasi

Sunday, 20 August 2017 16:56 pm 


Based on the data obtained, Sudiarti diagnosed by a private hospital on August 13, 2017 suffering from suspected bird flu. Based on the doctor's examination, Sudiarti experiencing shortness of August 7, two days later went to the hospital in Cibitung entrance to the ICU. Allegedly did not have enough charge, Sudiarti then return. Sudiarti suspected of having bird flu, because the sufferer direct contact with poultry, as selling poultry.

Head of Disease Prevention and Control at the Public Health Service Bekasi, Dezi Sukrawati, deliver, based on results of laboratory tests which he received on behalf of Sudiarti negative patients infected with bird flu. Current patients diagnosed with severe pneumonia, a disease that attacks the respiratory organs.

"It's out of his lab test results yesterday, Saturday (19/8), and negative patients infected with bird flu," said Dezi.
(Continue . . . )

After being the world's hot spot for H5N1 infections in the last half of the last decade, cases in Indonesia are now only rarely reported.  Exactly what accounts for this drought in human infections isn't clear.

Given the lack of follow up to most of these media reports, we may never find out what the full story is, but we'll keep an eye on Indonesia in case more cases pop up.

Top Global Infectious Disease Threats (2013-2016) From The CDC's GDD


Four years ago scientists from the CDC's Global Disease Detection (GDD) Operations Center published a review in the Emerging Health Threats Journal called What we are watching—five top global infectious disease threats, 2012: a perspective from CDC’s Global Disease Detection Operations Center.

Described as `global disease threats of particular concern to the CDC'  - although not necessarily the disease threats the CDC found most important or those that required the most resources - the top threats of 2012 were listed as:
  • Avian influenza A (H5N1)
  • Cholera
  • Poliomyelitis (polio) 
  • Enterovirus-71
  • Extensively drug-resistant tuberculosis

Submitted in February of 2013, the article wasn't published until the summer, when an addendum was added mentioning two late-breaking threats; MERS-CoV on the Arabian Peninsula, and H7N9 in China.
Fast forward to today, and researchers from the CDC's GDD have published a new review covering those infectious disease threats that came to the fore between 2013 and 2016.  While several of the older threats remain, today's list has expanded considerably.
Some excerpts, and some comments, but you'll want to follow the link to read the report in its entirety.

What We Are Watching—Top Global Infectious Disease Threats, 2013-2016: An Update from CDC's Global Disease Detection Operations Center To cite this article: Christian Kira A., Iuliano A. Danielle, Uyeki Timothy M., Mintz Eric D., Nichol Stuart T., Rollin Pierre, Staples J. Erin, and Arthur Ray R.. Health Security. August 2017, ahead of print.

Online Ahead of Print: August 14, 2017
To better track public health events in areas where the public health system is unable or unwilling to report the event to appropriate public health authorities, agencies can conduct event-based surveillance, which is defined as the organized collection, monitoring, assessment, and interpretation of unstructured information regarding public health events that may represent an acute risk to public health. The US Centers for Disease Control and Prevention's (CDC's) Global Disease Detection Operations Center (GDDOC) was created in 2007 to serve as CDC's platform dedicated to conducting worldwide event-based surveillance, which is now highlighted as part of the “detect” element of the Global Health Security Agenda (GHSA). The GHSA works toward making the world more safe and secure from disease threats through building capacity to better “Prevent, Detect, and Respond” to those threats. The GDDOC monitors approximately 30 to 40 public health events each day.

In this article, we describe the top threats to public health monitored during 2012 to 2016: avian influenza, cholera, Ebola virus disease, and the vector-borne diseases yellow fever, chikungunya virus, and Zika virus, with updates to the previously described threats from Middle East respiratory syndrome-coronavirus (MERS-CoV) and poliomyelitis.

Detecting, reporting, and responding to significant public health events occurring in areas where the public health system is unable or unwilling to report the event to appropriate public health authorities is a constant challenge for those monitoring global disease activity. To better track public health events in these situations, agencies can conduct event-based surveillance, which is defined as the organized collection, monitoring, assessment, and interpretation of unstructured information regarding public health events that may represent an acute risk to human health.1 

When conducting event-based surveillance, information can be collected through formal channels, such as already-established public health surveillance systems; in such instances, event-based surveillance can be complementary to indicator- or case-based surveillance systems that collect information on individual cases rather than events. Event-based surveillance can also be conducted through informal channels, such as through monitoring media reports, blogs, or even social media. Because events reported through informal channels commonly involve unconfirmed media reports, they must be verified before any action is taken.
         (Continue . . . )

What follows are detailed sections on the top potential infectious disease threats of the past 3 years; Influenza (human, avian & swine), Cholera, Ebola, Vector Borne diseases (Zika, Yellow Fever, Chikungunya), and updates on MERS-CoV and Poliomyelitis.
Progress against Polio, and fewer high profile outbreaks of EV-71 in Asia (see 2012's The Emerging Threat Of EV71) have - at least for now - helped to reduce their threat ranking among top infectious disease threats since the 2012 report.
Influenza (human, avian & swine) deservedly gets a good deal more attention in this latest release, and this past winter's record setting H7N9 epidemic in China obviously has the GDD's full attention. The authors write:
We closely monitor novel influenza A viruses, because influenza A viruses continue to evolve and because zoonotic transmission could herald an increasing pandemic influenza health threat. If a novel influenza A virus acquires the ability for sustained human-to-human transmission, a pandemic can result. Accordingly, early detection of pandemic-potential viruses may aid in the control and possible prevention of the next pandemic.
Although a swine-origin influenza A virus caused the 2009 H1N1 pandemic,10,11 and sporadic transmission of swine-origin influenza A viruses to humans (termed “variant viruses”) continue to be detected in the United States and in other countries with appropriate laboratory capacity, the public health threat posed by avian influenza A viruses appears to be higher because of their diversity and wide circulation among birds worldwide; the birds' migratory flyways may also be conducive to spread of influenza A viruses. Furthermore, some previous pandemic influenza A viruses have been partly of avian origin.11
  The report concludes with:  


This report describes top potential global infectious disease threats that the GDDOC was monitoring during 2013-2016, and does not necessarily describe those public health events that CDC finds most important or events that require the most resources. With the unique platform from which event-based surveillance is conducted, the GDDOC is in a unique position to rapidly identify new threats to public health, including those that could lead to a pandemic.

A sign of the times, perhaps, this latest report is more than 60% longer (6057 words vs. 3732) than the 2012 report.  Another metric, as if we needed it, suggesting that the global threats posed by emerging and re-emerging infectious diseases continues to increase.

For more on this threat, you may wish to revisit:
World Bank: World Ill-Prepared For A Pandemic
The Third Epidemiological Transition (Revisited)
Viral Creep In Second Decade Of The 21st Century

Saturday, August 19, 2017

Nigerian CDC Statement On Kogi Outbreak Investigation


As detailed yesterday in Nigeria Investigating Unknown Disease Outbreak In Kogi State, there are confusing and conflicting reports - along with government denials - of an unknown outbreak of a `hemorrhagic' disease in both Kwara and Koji state. 

 This morning, the Nigerian Tribune is reporting:
Strange disease: Kogi govt denies in death toll 

THE Kogi State government has said it was not true that the death toll on the strange disease that broke out in some villages of Yagba west local government area had risen to 62.

The state commissioner for health, Dr Saka Audu, who said this also added that 39 patients were evacuated from the communities to the state specialist hospital, Lokoja.

According to him, out of the 39 patients, only six were admitted as a result of vomiting and stooling, adding that the patients were responding to treatment.

The commissioner disclosed that the epidermic started six weeks ago at Okunran, Okoloke and Isanlu-Esa all in Yagba West local government area in the western senatorial district of the state.

(Continue . . . )
While it isn't yet clear whether there is a serious outbreak - or what it might be - late yesterday the Nigerian CDC issued the following statement. 

18 August 2017 | Abuja – 

Friday, August 18, 2017

On the 17th of August 2017, the Nigeria Centre for Disease Control (NCDC) Event Based Surveillance (EBS) system detected the news of a strange illness in Kogi State. In addition to this, we had received a report of a strange illness in Kwara State a week before.

Our Surveillance Team immediately contacted the State Epidemiology Teams of both States. Preliminary findings from the States showed that some cases presented with symptoms that fits the case definition of Lassa fever. However, laboratory test came out negative for Lassa fever and tests are now being carried out for other viral diseases in one of our collaborating laboratories.

In Kogi State, the State Epidemiology Team led by the State Commissioner of Health visited towns said to be affected by the strange illness and found five cases with mild illness. The patients were treated and discharged immediately. No other cases/ deaths of unknown illness have been identified. However, samples for routine laboratory investigation have been taken from the sick and results are being awaited.

The Nigeria Centre for Disease Control is supporting Kogi and Kwara States in ongoing investigations and our Rapid Response Team is ready to be deployed as required. We are constantly working with all the State Epidemiologists to ensure the health security of all Nigerians, by developing our laboratory capacity and ability to respond rapidly.

We ask members of the public to continue to ensure proper hygiene and sanitation measures are in place at all times and avoid self-medication. They are also encouraged to report to a health facility immediately if they experience symptoms such as sudden high fever, especially if it does not respond to conventional remedies.

Health workers should ensure universal care precautions while handling patients at all times. If common causes of febrile illnesses are ruled out, health workers should inform the Local Government or State Disease Surveillance and Notification Officer (DSNO) and ensure immediate laboratory investigation.

We will continue to work with the States to monitor the current situation and will share new information received, proactively. Our communication channels remain open.


NCDC toll-free number: 0800-970000-10

SMS 08099555577

Whatsapp 07087110839.

Twitter/Facebook: @NCDCgov

A hat tip to Ronan Kelly on FluTrackers for posting this statement on their Nigerian Outbreak thread.  I'll follow up when more is known, you'll get your most complete day-to-day coverage from the newshounds at FluTrackers

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



At the end of 2015 Chinese and Japanese researchers made headlines when they isolated and characterized a number avian H1N1 virus variants circulating in Chinese pigs that they believed had considerable pandemic potential (see PNAS: The Pandemic Potential Of Eurasian Avian-like H1N1 (EAH1N1) Swine Influenza)

 In the `Significance' section of their report the authors boiled it down to this:
Here, we found that, after long-term evolution in pigs, the EAH1N1 SIVs have obtained the traits to cause a human influenza pandemic.
Xinhua News ran an English Language report on all of this, with interviews with the lead author, which you can read at the following link:

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 . . . )

Admittedly, this somber assessment came at a time when China's H7N9 virus appeared on the decline, and after HPAI H5 had gone mysteriously silent across Europe and North America following the summer of 2015.
There is also a school of thought that suggests while avian flu viruses might have a greater public health impact, swine-origin viruses - because they share the same HA subtype (H1, H2, or H3) as all of the pandemics of the past 130 years - are more likely to jump to humans (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?)

In June of 2016, in Sci Rpts: Transmission & Pathogenicity Of Novel Swine Flu Reassortant Viruses we looked at another study - again out of China - where researchers experimentally infected pigs with one of these Eurasian-Avian H1N1 swine influenza viruses and the 2009 H1N1pdm virus.

In doing so, they generated yielded 55 novel reassortant viruses spread across 17 genotypes, demonstrating not only how readily EAH1N1 SIV can reassort with human H1N1pdm in a swine host, but also finding:
`Most of reassortant viruses were more pathogenic and contagious than the parental EA viruses in mice and guinea pigs'. 
The authors went on to say in their closing remarks:
In summary, our data highlight the potential public health danger of novel viruses arising from reassortment in pigs between circulating EA swine H1N1 and pdm/09 H1N1 viruses. Such reassortants for which there is little apparent cross protection from current vaccines could be much more pathogenic and transmissible than parental viruses.
While human infection with EAH1N1 in China is only rarely reported, last September, in EID Journal: Reassortant EAH1N1 Virus Infection In A Child - Hunan China, 2016, we looked at a report of a boy with severe pneumonia who was infected with a reassortment of  - you guessed it - EAH1N1 and the 2009 H1N1pdm virus.

The authors wrote:
The virus contained 2 surface genes from an EA-H1N1 virus and 4 internal genes from A(H1N1)pdm09 virus.
Compared with JS/1/11 EA-H1N1 virus, the reassortant virus exhibited higher infectivity, virulence, and replication in C57BL/6J mice, demonstrating the need for further evaluation of HuN EA-H1N1 virus to assess the threat it poses to public health. Our results indicate the need for heightened surveillance.
All of which brings us to a new open access study, appearing this week in the Journal of Virology, that finds - among other things - that a single amino acid (AA) change in the HA of the EAH1N1 virus significantly alters its tranmissibility in the guinea pig model.

A number of researchers in today's study - including the lead author Hualan Chen - were part of the 2015 PNAS EAH1N1 study research team. 

A Single-Amino-Acid Substitution at Position 225 in HA Alters the Transmissibility of Eurasian Avian-like H1N1 Swine Influenza Virus in Guinea Pigs 
Zeng Wanga,Huanliang Yanga,Yan Chena,Shiyu Taoa,Liling Liua,Huihui Konga,Shujie Maa,Fei Menga,Yasuo Suzukib,Chuanling Qiaoa and Hualan Chena

Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model.
We used reverse genetics to generate a series of reassortants and mutants in the GX/18 background and tested their transmissibility in guinea pigs.
We found that a single amino acid substitution of glycine (G) for glutamic acid (E) at position 225 (E225G) in the HA1 protein completely abolished the respiratory droplet transmission of GX/18, whereas the substitution of E for G at the same position (G225E) in HA1 enabled HLJ/27 to transmit in guinea pigs.
We investigated the underlying mechanism and found that viruses bearing 225E in HA1 replicated more rapidly than viruses bearing 225G due to differences in assembly and budding efficiency. Our study indicates that the amino acid 225E in HA1 plays a key role in EAH1N1 swine influenza virus transmission and provides important information for evaluating the pandemic potential of field influenza strains. 

IMPORTANCE Efficient transmission among humans is a prerequisite for a novel influenza virus to cause a human pandemic. Transmissibility of influenza viruses is a polygenic trait, and understanding the genetic determinants for transmissibility will provide useful insights for evaluating the pandemic potential of influenza viruses in the field. Several amino acids in the hemagglutinin (HA) protein of influenza viruses have been shown to be important for transmissibility, usually by increasing virus affinity for human-type receptors. 

In this study, we explored the genetic basis of the transmissibility difference between two Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses in guinea pigs, and found that the amino acid glutamic acid at position 225 in the HA1 protein plays a critical role in the transmission of EAH1N1 virus by increasing the efficiency of viral assembly and budding.

 As we've discussed previously (see Differences In Virulence Between Closely Related H5N1 Strains), it sometimes only requires a small change to an influenza virus to change its behavior in a major way.   
Other changes - often in combinations of AA sites - can affect receptor cell binding, replication rates, and adapatation to lower temperatures found in the human airway.  All important traits for any flu virus with pandemic aspirations. 
While much has been learned about these changes in the past decade, the impact of many of these amino acid substitutions remains a mystery. 
Learning about these combinations can hopefully tell us when viruses in the wild are getting closer to becoming a pandemic strain.  After outlining all of the results of their testing, the authors of today's study reiterated their previous assessment.


In the present study, we explored the genetic basis for the difference in transmissibility in guinea pigs of two EAH1N1 swine influenza viruses, GX/18 and HLJ/27, and found that the single amino acid mutation E225G in HA1 abolishes the transmissibility of GX/18, and that the mutation G225E in HA makes HLJ/27 highly transmissible in guinea pigs. We further investigated the underlying mechanism and demonstrated that viruses bearing 225E in their HA1 replicate more rapidly than viruses bearing 225G in HA1 due to differences in their assembly and budding efficiency.
Two lineages of H1N1 SIVs, classical H1N1 SIVs and EAH1N1 SIVs, have been circulating in pigs since 1918 and 1979, respectively. The classical H1N1 SIVs emerged in humans as a reassortant and caused the 2009 H1N1 influenza pandemic, and the HA gene of 2009/H1N1 also belongs to the classical H1N1 SIV lineage. Our present study and a study by Tumpey et al. (10) indicate that 225E and 225D in HA1 play important roles in the transmissibility of EAH1N1 SIVs and classical H1N1 SIVs, respectively.
We checked the HA sequence of the H1N1 SIVs and found that 225G was present in the HA1 gene of the majority of strains detected before the year 2000; however, the number of classical H1N1 SIVs that contain 225D in HA1 gradually increased after 2000 and became predominated after 2009  (Fig. 10A), and the EAH1N1 SIVs that contain 225E in HA1 showed a similar tendency (Fig.256 10B).
These findings suggest that the pandemic potential of the EAH1N1 SIVs is increasing.

While EAH1N1 is the prime swine-origin virus of concern in China, it isn't alone (see Front. Microbiol.: A Novel H1N2 Reassorted Influenza Virus In Chinese Pigs), and similar swine flu evolution continues in North America, Europe, Brazil, and undoubtedly many other places where there is (unfortunately) little or no surviellance.

Some recent blogs include:
I&ORV: Triple-Reassortant Novel H3 Virus of Human/Swine Origin Established In Danish Pigs
Emerg. Microbes & Inf.: Pathogenicity & Transmission Of A Swine Influenza A(H6N6) Virus - China
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

Friday, August 18, 2017

CDC FluView Week 32: 3 Swine Variant Infections (OH, PA, ND)


As telegraphed by yesterday's MMWR, for the 4th week running the CDC today is reporting additional novel flu cases, all three swine variant viral infections linked to attendance of state or county fairs.  Over the past 3 weeks we've seen:
CDC FluView Week 31: 3 More H3N2v Cases Reported in Ohio
FluView Week 30: 1 Additional Swine Variant Report From Ohio - H1N2v
CDC FluView: 11 H3N2v Swine Flu Cases Reported In Ohio
Today's reports deals with 3 patients, from 3 states (Ohio, Pennsylvania, and North Dakota), although it appears the Pennsylvania case was exposed while visiting North Dakota (see yesterday's statement from the North Dakota Health Department).
Two of the cases have been identified as H3N2v, while final subtyping is awaited on the third case. Preliminary testing indicates it is an H3 variant, making H3N2v the most likely culprit.
While rare, it is worth noting we've seen other H3 viruses circulating in North America swine before (see J. Virol: Novel Reassortant Human-like H3N2 & H3N1 Influenza A Viruses In Pigs), so it will be of interest to see what the full lab report finds.

Novel Influenza A Virus:

Three human infections with novel influenza A viruses were reported by three states (North Dakota [1], Ohio [1], and Pennsylvania [1]) during week 32. All three infections were with variant viruses (influenza A viruses that normally circulate in pigs and not people are called variant viruses when detected in people.) 

Viruses from two of the infections have been fully characterized and are influenza A (H3N2) variant (H3N2v) viruses; the third infection has been characterized as an influenza A (H3) variant (H3v) virus at this time (further analysis is being performed at CDC to characterize the neuraminidase protein of this virus). 

All three patients reported exposure to swine in a fair setting during the week preceding illness onset. Two patients reported attendance at the same agricultural fair. The exposure to swine at the agricultural fair reported by the Pennsylvania resident occurred out of state. 

Two of the three patients were children younger than 18 years of age and one patient was an adult aged > 64 years. Two of the three patients were hospitalized but all have fully recovered from their illness. No human-to-human transmission of these viruses has been identified. 

To date, a total of 19 variant virus infections have been reported in the United States during 2017. Eighteen of these have been H3 variant viruses (Texas [1], North Dakota [1], Pennsylvania [1], and Ohio [15]) and one has been with an H1N2 variant virus (Ohio [1]).

Early identification and investigation of human infections with novel influenza A viruses are critical to ensure timely risk assessment and so that appropriate public health measures can be taken. Additional information on influenza in swine, variant influenza infection in humans, and strategies to interact safely with swine can be found at

While rarely as severe as avian flu in humans, swine influenza viruses nevertheless have some pandemic potential. The CDC's IRAT (Influenza Risk Assessment Tool) Rankings monitors and characterizes 14 different novel flu viruses, and has this assessment on H3N2v
H3N2 Variant:[A/Indiana/08/11]

Swine-origin flu viruses do not normally infect humans. However, sporadic human infections with swine-origin influenza viruses have occurred. When this happens, these viruses are called “variant viruses.” Influenza A H3N2 variant viruses (also known as “H3N2v” viruses) with the matrix (M) gene from the 2009 H1N1 pandemic virus were first detected in people in July 2011. The viruses were first identified in U.S. pigs in 2010. In 2011, 12 cases of H3N2v infection were detected in the United States. In 2012, 309 cases of H3N2v infection across 12 states were detected. The latest risk assessment for this virus was conducted in December 2012 and incorporated data regarding population immunity that was lacking a year earlier.
Summary: The summary average risk score for the virus to achieve sustained human-to-human transmission was in the moderate risk category (less than 6). The summary average risk score for the virus to significantly impact public health if it were to achieve sustained human-to-human transmission was in the low-moderate risk category (less than 5).

For some recent blogs on Swine variant influenza, and why the CDC closely monitors these infrequent human infections, you may wish to revisit:

EID Journal: Transmission Of Swine H3N2 To Humans At Agricultural Exhibits - Michigan & Ohio 2016

Ohio: Henry County Fair Closes Pig Barn Over H1N2 Swine Flu

Second Ohio County Fair Closes Hog Barn Over Swine Flu

A Reminder About The `Other' Novel Flu Threat


Saudi MOH Announces Another MERS Case In Jeddah


After skipping a day, the Saudi MOH has another report of a MERS case (exposure under investigation) in Jeddah.  This is the 4th case announced in Jeddah - a major Hajj terminal - since the first week of August, and comes less than 10 days before the start of this year's Hajj.

Today's case is the 24th case reported during the first 18 days of August.

Yesterday the World Health Organization published a Saudi MERS update, with details on 26  case that occurred between July 4th and August 12th, 13 of which were associated with a cluster in a hospital in Al Jawf Region.