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.

Nigeria Investigating Unknown Disease Outbreak In Kogi State


For the past couple of weeks there have been repeated reports of a fatal disease outbreak in Kwara State, Nigeria (see FluTrackers thread Oro-Ago, Nigeria: Questionable report of dozens of deaths due to undiagnosed hemorrhagic illness)

While first thought to be Lassa fever, the outbreak was dismissed as a rumor by the local government (see Kwara Government Denies Disease Outbreak in Oro Ago Community) last week. According to the government press release of August 11th:
The State’s Commissioner for Health, Alhaji Suleiman Alege, on Friday told newsmen in Ilorin, that the report is a mere rumor as the ministry has no confirmed outbreak of disease fatalities in any part of the state.
Fast forward to last night and Pathfinder at FluTrackers has picked up fresh reports (see Nigeria - ​ Mysterious illness kills 62 in Kogi) from the neighboring state of Kogi of a very similar sounding outbreak.

As is often the case, media reports don't always align, and official government reports are slow to emerge. Typical of what is being reported, this comes from Channels Television :
Nigeria: 50 Killed As Disease Hits Kogi, KwaraAn unknown illness has thrown many families in Kogi State into mourning and left health authorities with a puzzle to solve.

The state Commissioner for Health, Dr Saka Audu, told Channels Television that so far, 62 people have been killed by the illness which was initially thought to have been Lassa fever by many people.

This is because it has some symptoms that are similar to Lassa fever such as diarrhea, abdominal pain, and vomiting.

The worst hit community is Okoloke in Yagba West Local Government Area of the state. Other areas are Okunran and Isanlu-Esa – both villages in Yagba West LGA.

With over 60 people dead and Lassa fever ruled out as a cause, the government has taken samples of the disease and is hoping to identify the illness as quickly as possible to prevent more deaths, according to the commissioner.

Unlike Kwara State, the Kogi government appears to have acknowledged they have an outbreak.   This much more detailed report comes from 

Nigeria: 50 Killed As Disease Hits Kogi, Kwara

By Itodo Daniel Sule, Romoke Ahmad and Akor Ojoma

At least 50 people have been killed in the last three weeks by a yet-to-be ascertained ailment in three communities in Kogi State, the state government announced yesterday.

The affected communities are Okunran, Okoloke and Isanlu-Esa all in Yagba West local government area of the state, according to the state health commissioner Dr Saka Audu.

Authorities in neighbouring Kwara State are also investigating reports of an outbreak which allegedly claimed some lives in Oro-Ago community in Ifelodun local government area of the state.

The Oloro of Oro-Ago, Oba Tafa Dada and the President of Oro-Ago Development Union, Mr Olaniyi Olushola raised the alarm of the strange illness that hit some members of the community, especially the herders which they said claimed many lives.
But Dr Audu confirmed yesterday during a visit to the affected communities to assess the health situation, saying a technical team was earlier sent to take samples which were sent to General Hospital Irua, Edo State, for investigation.

"We are here to make sure we determine the cause of these mysterious deaths and then quickly proffer a solution to it," he said.

(Continue . . . )

Although I'll follow up when more is known, you'll get your most complete day-to-day coverage from the newshounds at FluTrackers.

China MOA Confirms H5N6 Outbreak In Quail - Guizhou Province

Credit Wikipedia


Less than three weeks after announcing a large outbreak of HPAI H5N1 in Inner Mongolia, China's Ministry of Agriculture has announced an outbreak of HPAI H5N6 in quail farms in Guizhou Province.

Due to the imprecise nature of translation software, it isn't entirely clear whether more than one farm was affected, but the report refers to `some farmers'

Luodian County, Guizhou province occurred poultry with H5N6 subtype highly pathogenic bird flu
Issued by: Ministry of Agriculture press office Date: 2017-08-18 14:27 Keywords: bird flu; epidemic; Guizhou

  Ministry of Agriculture press office issued August 18, Luodian County, Guizhou province occurred poultry with H5N6 subtype highly pathogenic bird flu.

  August 10, Luodian County, Guizhou province some farmers rearing of quail suspected bird flu symptoms appear, the incidence 13103, died 9752. August 13, animal disease prevention and control center in Guizhou Province diagnosed with suspected bird flu. August 18, by the National Avian Influenza Reference Laboratory confirmed the outbreaks as H5N6 subtype highly pathogenic bird flu.

  After the outbreak, according to the relevant local prevention plans and technical specifications, adhere to the prevention and control law, science and prevention and control, really good job epidemic disposal, have been culling and safe disposal of poultry 8110. Currently, the outbreaks has been effectively controlled.

While H5N6 has been known to infect humans (n=16), it has been 9 months since the last reported case.  In the meantime, we've seen H5N6 move beyond China, Vietnam, and Laos and into South Korea, Japan, and Taiwan. 
As it has spread, it has reassorted numerous times, producing multiple genotypes (see Emerg. Microbes & Inf.: Human Infections With A Novel Reassortant H5N6).
Due to the extensive use of H5 vaccines in Chinese poultry, large outbreaks of HPAI H5 viruses in commercial flocks have become relatively rare, although there is ample evidence that these viruses continue to circulate widely as sub-clinical infections. 
Subclinical Highly Pathogenic Avian Influenza Virus Infection among Vaccinated Chickens, China). 
Study: Recombinant H5N2 Avian Influenza Virus Strains In Vaccinated Chickens 
EID Journal: Subclinical HPAI In Vaccinated Poultry – China

Seeing two `breakout' events so close together - particularly this late in the summer - is a bit unusual.
This fall China will roll out a new combination H5 + H7 poultry vaccine (see China MOA Orders HPAI H7N9 Vaccine Deployed Nationwide This Fall) which they hope will help control HPAI H5 viruses like H5N1, H5N6 and H5N8, plus the rapidly spreading LPAI and HPAI versions of H7N9.
After more than a dozen years of use in China, however, poultry vaccines have not proved to be a panacea for bird flu. For more on some of the challenges of controlling avian flu with poultry vaccines, you may wish to revisit:
Virology: Selection Of Antigenic Variants Of An H5N1 HPAI Virus In Vaccinated Chickens
New Scientist: The Downsides To Using HPAI Poultry Vaccines

PLoS Bio: Imperfect Poultry Vaccines, Unintended Results