Thursday, February 22, 2018

WHO Update & Risk Assessment On Avian H7N4

Jiangsu Province - Credit Wikipedia


Just a little over a week after the initial announcement from China of the first known human infection with an avian H7N4 virus, we are starting to get details about both the patient and the virus, with a genetic characterization released earlier today (see WHO: Genetic Characteristics Of Avian H7N4).
The World Health Organization has also just released their first update, and a preliminary risk assessment on this emerging virus.  
While additional human cases are possible, the lack of infection among 28 close contacts to the first case is encouraging. We will, of course, be anxious to get further information about this virus, including the results of ferret transmission studies, and its prevalence in poultry.

Human infection with avian influenza A(H7N4) virus – China

Disease outbreak news
22 February 2018

On 14 February 2018, the National Health and Family Planning Commission (NHFPC) of China notified the World Health Organization (WHO) of one case of human infection with avian influenza A(H7N4) virus. This is the first human case of avian influenza A(H7N4) infection to be reported worldwide.

The case-patient was a 68-year-old woman from Jiangsu Province with pre-existing coronary heart disease and hypertension and she developed symptoms on 25 December 2017. Seven days later, she was admitted to a local hospital for treatment of severe pneumonia and was discharged after 21 days. On 12 February, the Chinese Center for Disease Control and Prevention (China CDC) confirmed that the case-patient’s samples were positive for avian influenza A(H7N4). The NHFPC confirmed the diagnosis on 13 February 2018. The case-patient had reported a history of exposure to live poultry before onset of symptoms.

Genetic sequencing of this A(H7N4) virus shows that all the virus segments originated from avian influenza viruses. This virus is sensitive to adamantanes and neuraminidase inhibitors based on genetic sequencing.

Twenty-eight close contacts of the case-patient have been under medical observation. Among close contacts, no abnormal findings have been found and all throat swabs from her contacts have tested negative.
Public health response

The Chinese government conducted a risk assessment, and has enhanced prevention and control measures, surveillance and epidemiological investigations including contact tracing and laboratory testing. Public risk communication and information sharing is ongoing.

WHO is in contact with national authorities and is following the event closely. WHO is facilitating information-sharing with Member States and is closely monitoring the situation, in line with the International Health Regulations (2005).
WHO risk assessment

This is the first report of a human case of avian influenza A(H7N4) infection globally and the case reported exposure to live backyard poultry before illness onset. Genetic analysis of this influenza A(H7N4) virus indicates that it is of avian origin.

Close contacts of the case-patient tested negative for avian influenza A(H7N4) and remained asymptomatic. Current evidence suggests that this virus does not have the ability of sustained transmission to humans, thus the likelihood of sustained human to human transmission is low. Any animal influenza virus that develops the ability of human to human transmission can theoretically cause a pandemic.

It is possible that additional human cases of avian influenza A(H7N4) will be detected, however only one human case has been detected so far, and information on the circulation of avian influenza A(H7N4) in birds is not currently available. Further information needs to be gathered to increase the confidence in this assessment.
WHO advice

The public should avoid contact with high-risk environments such as live animal markets/farms and live poultry, or surfaces that might be contaminated by poultry feces. Hand hygiene with frequent washing or use of alcohol hand sanitizer is recommended. WHO does not recommend any specific different measures for travellers.

WHO does not advise special screening at points of entry with regard to this event, nor does it recommend that any travel or trade restrictions be applied.

Hong Kong Flu Express Wk 7: Flu Remains At A High Level


Although there are some hopeful signs that flu may have finally peaked in Hong Kong, influenza activity remains at a high level, and local schools will resume classes next week after an extended closing for flu and the New Year's Holiday. 

Today's hospital Occupancy report (below) shows a 5% drop over Tuesday's post-holiday 119% peak, although admissions yesterday were still running about 150 over the average for this time of year.

Even with all schools having been closed for two weeks, institutional outbreaks continue to outpace any flu season in recent memory, no doubt inspiring an announcement today from the CHP Public urged to continue their vigilance against influenza as school will soon resume.

Influenza B continues to produce the vast majority of infections, with influenza A (H1N1 & H3N2) making up a minority of cases. Some excerpts from today's Hong Kong Flu Express (week 7) follow:

Flu Express is a weekly report produced by the Respiratory Disease Office of the Centre for Health Protection. It monitors and summarizes the latest local and global influenza activities.

Local Situation of Influenza Activity (as of Feb 21, 2018)

Reporting period: Feb 11 – 17, 2018 (Week 7)

  • The latest surveillance data showed that the local influenza activity remained at a high level in the past few weeks. Currently the predominating virus is influenza B.
  • Influenza can cause serious illnesses in high-risk individuals and even healthy persons. Given that seasonal influenza vaccines are safe and effective, all persons aged 6 months or above except those with known contraindications are recommended to receive influenza vaccine to protect themselves against seasonal influenza and its complications, as well as related hospitalisations and deaths.
  • Apart from adopting personal, hand and environmental hygiene practices against respiratory illnesses, those members of the public who have not received influenza vaccine are urged to get vaccinated as soon as possible for personal protection.


Influenza-like-illness surveillance among sentinel general outpatient clinics and sentinel private doctors, 2014-18

In week 7, the average consultation rate for influenza-like illness (ILI) among sentinel general outpatient clinics (GOPCs) was 7.3 ILI cases per 1,000 consultations, which was lower than 8.9 recorded in the previous week (Figure 1, left). The average consultation rate for ILI among sentinel private doctors was 36.4 ILI cases per 1,000 consultations, which was lower than 71.3 recorded in the previous week (Figure 1, right).

Since the start of the 2017/18 winter influenza season in week 2, 373 adult cases of ICU admission/death with laboratory confirmation of influenza were recorded, in which 228 of them were fatal (as of February 21). Among them, 317 patients had infection with influenza B, 29patients with influenza A(H1N1)pdm09, 17 patients with influenza A(H3N2), three patients with influenza C and seven patients with influenza A pending subtype.

  • In comparison, 283, 207 and 88 adult cases were recorded in the same duration of surveillance(six complete weeks) in the 2014/15 winter, 2015/16 winter and 2017 summer seasons respectively, as compared with 327 cases in the current season (Figure 10, left). The corresponding figures for deaths were 208, 89 and 67 in the above seasons, as compared with 195 deaths in the current season (Figure 10, right).


Severe influenza cases of all ages

• Since the start of the current winter influenza season in week 2, 388 severe influenza cases among all ages have been reported, including 230 deaths (as of February 21).

 • Among the adult fatal cases, about 83% had chronic diseases. Both of the two paediatric fatal cases did not have chronic diseases.
• Among patients with laboratory confirmation of influenza admitted to public hospitals in this season (from January 7 to February 21), 2.0% of admitted cases died during the same episode of admission. So far, it was within the historical range between 1.9% (2015/16 winter season) and 3.3% (2015 summer season).


Global Situation of Influenza Activity
  • In Mainland China (week ending Feb 11, 2018), both southern and northern provinces were still in winter influenza season but the activity continued to decrease. The proportion of influenza A detection was higher than that of influenza B. Influenza A(H1N1) and influenza B Yamagata viruses are predominating while levels of influenza A(H3N2) and influenza B Victoria viruses remained low. In southern provinces, the proportion of ILI cases in emergency and outpatient departments reported by sentinel hospitals was 4.7%, lower than that reported in the previous week (5.1%) but higher than that in the corresponding period in 2015-2017 (2.8%, 4.6%, 2.6%). In northern provinces, that proportion was 3.7%, lower than those reported in the previous week (4.2%) and the corresponding period in 2016 (5.1%), but higher than those in the corresponding period in 2015 and 2017 (both were 2.9%). The proportion of influenza detections in the week ending Feb 11, 2018 was 36.4% (65.2% influenza A and 34.8% influenza B).
  • In Macau (as of Feb 21, 2018), the influenza activity has been slowed down but remained at high level. The proportions of ILI cases in emergency departments among adults and children decreased.
  •  In Taiwan (week ending Feb 17, 2018), influenza activity was similar to the previous week and remained at the peak of the season. In the week ending Feb 17, the proportion of ILI cases in emergency department was 17.61% which was above the threshold of 11.4%. The predominating virus was influenza B.
  •  In Japan (week ending Feb 11, 2018), the influenza season has started in late November 2017. The average number of reported ILI cases per sentinel site has decreased to 45.38 in the week ending Feb 11, 2018 from 54.33 in the previous week. It was higher than the baseline level of 1.00. The predominating virus in the past five weeks was influenza B, followed by influenza A(H3N2) and A(H1N1)pdm09.

WHO: Genetic Characteristics Of Avian H7N4

Credit CDC



Eight days ago, in Jiangsu China Reports 1st Novel H7N4 Human Infection, China announced the first known human infection with avian H7N4 which resulted in a 3-week hospitalization for a 68 year old woman in Jiangsu Province for severe pneumonia.

While human infection with avian H7 viruses hasn't been unheard of, until H7N9 emerged in China in 2013, they were fairly rare and almost always mild.  A few examples include:
After the wake up call from H7N9, when a severe human infection with a novel H7N4 virus is reported from China, we naturally take notice.

Today, in addition to releasing their Recommended Composition Of 2018-2019 Northern Hemisphere Flu Vaccine, the World Health Organization has released a new Antigenic and genetic characteristics of zoonotic influenza viruses report for February 2018.

Included is the following excerpt on the recently reported H7N4 virus, which shows that this virus is a purely avian LPAI H7 strain - distinct from A(H7N9) - although it carries the PB2  637K marker associated with mammalian adaptation.
Researchers have determined the (E627K) substitution in the (PB2) protein - the swapping out of the amino acid Glutamic acid (E) at position 627 for Lysine (K) - makes the an influenza virus better able to replicate at the lower temperatures (roughly 33C) normally found in the upper human respiratory tract (see Eurosurveillance: Genetic Analysis Of Novel H7N9 Virus).
Although the virus was not isolated (only detected by RT-PCR) in the patient, it was isolated from contact poultry.  A brief excerpt (bolding mine) from today's report:

Antigenic and genetic characteristics of zoonotic influenza viruses and candidate vaccine viruses developed for potential use in human vaccines


Influenza A(H7N4)

Influenza A(H7N4) activity from 26 September 2017 to 19 February 2018
The first human case of influenza A(H7N4) virus infection was reported by China. The case was from Jiangsu province, and the individual developed severe pneumonia and survived. The throat swab collected from the patient tested positive for A(H7N4) by real-time RT-PCR and sequencing. The individual had slaughtered chickens prior to illness onset and LPAI A(H7N4) viruses were detected in ducks and chickens on the premises. None of the close contacts of the infected individual reported symptoms and all tested negative for influenza.

Genetic characteristics of the influenza A(H7N4) virus

Viral gene sequence analysis generated from clinical material showed that all segments of the human virus shared high identity with wild bird avian influenza viruses. The HA gene was distinct from the A(H7N9) viruses circulating in China and was characterised as low pathogenicity by HA cleavage site sequence. No mutations associated with reduced susceptibility to neuraminidase inhibitors, amantadine or rimantadine, were found. The PB2 carried the 627K marker associated with mammalian adaptation. Virus has not been isolated from the infected individual.

Influenza A(H7) candidate vaccine viruses

Based on the current antigenic, genetic and epidemiologic data, no new CVVs are proposed. The available A(H7) CVVs, excluding A(H7N9) CVVs listed above, are listed in Table 6.

Whether this is a one-off event, or the first hint of a new emerging threat, is impossible to say.  But the fact that this isn't a reassortment of the already endemic, and highly dangerous H7N9 virus is probably a good sign.

WHO: Recommended Composition Of 2018-2019 Northern Hemisphere Flu Vaccine

The Wide World Of Flu Activity


Twice each year influenza experts gather to discuss recent developments in human and animal influenza viruses around the world, and to decide on the composition of the next influenza season’s flu vaccine. 
While never an easy task, this has become more difficult over the years - particularly with seasonal H3N2 - as the number of genetically distinct groups in circulation has continued to rise (see The Enigmatic, Problematic H3N2 Influenza Virus).
This year marks the 50th consecutive year that H3N2 has been in circulation, having first emerged as a pandemic strain in 1968.  That's a longer reign than any other seasonal flu virus that we are aware of - and in order to survive that long and avoid running out of hosts due to acquired community immunity - it has been forced to continually reinvent itself.
NIAID has a terrific 3-minute video that shows how influenza viruses drift over time, and why the flu shot must be frequently updated, which you can view at this link.
Between the growing diversity among H3N2 viruses, and problems with egg-based vaccine manufacturing introducing small antigenic changes in the vaccine (see PLoS Path.: A Structural Explanation For The Low VE Of Recent H3N2 Vaccines), the track record for the H3N2 component of the seasonal flu vaccine has grown increasingly dismal.

Last years VE (Vaccine Effectiveness) against H3N2, as reported by the CDC's MMWR, was estimated at 34%.  This year's mid-season estimate from the CDC - issued a week ago - only found 25% VE against H3N2, and for certain age groups (adolescents (9-17), and adults 50 and older) - showed no statistically significant protection from the vaccine.
The one bright spot was a 51% VE for children aged 6mos to 8 years. 
Luckily, the other influenza A component - H1N1 - while it continues to evolve, has remained comparatively stable, requiring only 1 strain change since it emerged as a pandemic strain in 2009.  Similarly, Influenza B strains are slow to change, although we've seen some diversity among the Victoria lineage of late.
Due to the time it takes to manufacture and distribute a vaccine, decisions on which strains to include must be made at least six months in advance, which means the composition of next fall's Northern Hemisphere’s vaccine must be decided upon now.
This week the World Health Organization brought together representatives from  GISRS (Global Influenza Surveillance and Response System), along with members of OFFLU (the OIE/FAO Network on Animal Influenza), and other experts to recommend what flu strains to include in next fall's vaccine.
Not unexpectedly, the WHO is recommending a change to the H3N2 component which has performed poorly the past couple of years.  They have also swapped out the old Victoria lineage Influenza B virus for a new strain. 
The following excerpt comes from a much longer and more detailed (8-page) WHO release called: 

Recommended composition of influenza virus vaccines for use in the 2018-2019 northern hemisphere influenza season
There was considerable variation in the predominant virus type circulating in different regions during the period September 2017 to January 2018. Influenza B viruses predominated in many countries, while A(H3N2) viruses predominated in some and A(H1N1)pdm09 viruses circulated widely in Africa, Asia, parts of Europe and in the Middle East.
The vast majority of influenza A(H1N1)pdm09 viruses belonged to genetic subclade 6B.1 and were antigenically indistinguishable from the vaccine virus A/Michigan/45/2015.
Influenza A(H3N2) viruses were associated with outbreaks in several countries. The majority of recent viruses were antigenically related to cell culture-propagated A/Hong Kong/4801/2014-like and A/Singapore/INFMH-16-0019/2016-like viruses; they reacted poorly with ferret antisera raised to many egg-propagated clade 3C.2a viruses but somewhat better to egg-propagated A/Singapore/INFMH-16-0019/2016-like viruses.
Influenza B viruses of the B/Yamagata/16/88 lineage predominated in most regions of the world. Recent B/Yamagata/16/88 lineage viruses were antigenically and genetically closely related to the vaccine virus B/Phuket/3073/2013. Influenza B viruses of the B/Victoria/2/87 lineage were detected in low numbers but a substantial and increasing proportion of these viruses, containing a two amino acid deletion in their HAs, were antigenically distinguishable from the vaccine virus B/Brisbane/60/2008 but closely related to B/Colorado/06/2017.
It is recommended that quadrivalent vaccines for use in the 2018-2019 northern hemisphere influenza season contain the following:
- an A/Michigan/45/2015 (H1N1)pdm09-like virus;
- an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus;
- a B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage); and
- a B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage).
It is recommended that the influenza B virus component of trivalent vaccines for use in the 2018-2019 northern hemisphere influenza season be a B/Colorado/06/2017-like virus of the B/Victoria/2/87-lineage.

The new H3N2 component is the same one that will be used this year in the Southern Hemisphere flu vaccine, which should give us some idea of how well it works. Hopefully it will improve the VE against H3N2 next fall, but concerns remain over the impact of egg-propagated flu vaccines.
Most recent A(H3N2) viruses were well inhibited by ferret antisera raised against cell culture-propagated reference viruses in clade 3C.2a, including A/Hong Kong/4801/2014, A/Michigan/15/2014 and A/Singapore/INFIMH-16-0019/2016.
In contrast, a significantly lower proportion of A(H3N2) viruses was inhibited well by ferret antisera raised against egg-propagated 3C.2a reference virus A/Hong Kong/4801/2014. Recent A(H3N2) viruses were better inhibited by a ferret antiserum raised against the egg-propagated reference virus A/Singapore/INFIMH-16-0019/2016 compared to ferret antisera raised against other recent egg-propagated A(H3N2) viruses.
While the flu vaccine is far from perfect, it – along with practicing good flu hygiene (washing hands, covering coughs, & staying home if sick) – still remains your best strategy for avoiding the flu and staying healthy this winter.
None of this guarantees you won't get the flu.  
But some protection against a potentially deadly virus beats no protection - any day of the week.

Wednesday, February 21, 2018

Nigeria's Lassa Fever Outbreak - Epi Week 7

Credit CDC


Lassa fever is a Viral Hemorrhagic Fever (VHF) endemic to a handful of West African nations - commonly carried by multimammate rats - a local rodent that often likes to enter human dwellings. 
Exposure is typically through the urine or dried feces of infected rodents, and roughly 80% who are infected only experience mild symptoms.
The incubation period runs from 10 days to 3 weeks, and the overall mortality rate is believed to be in the 1%-2% range, although it runs much higher (15%-20%) among those sick enough to be hospitalized.

Although endemic in West Africa, between 2013 and early 2016 Nigeria had seen a steady decline in the number of Lassa Fever cases  - and deaths - with the last significant outbreak reported in 2012.
But in early 2016 that trend began to change with outbreaks starting in Nigeria (see Nigeria: Lassa Fever Outbreak With 40 Fatalities), and then flaring up in both Benin and Togo (see ECDC: Rapid Risk Assessment On Lassa Fever In Nigeria, Benin, Togo, Germany & USA).
Exported cases turned up in Germany and Sweden (see Germany's RKI Statement On Lassa Fever Cluster In Cologne & WHO Lassa Fever Update - Sweden (Imported)). Although Lassa reports in Nigeria eventually slowed, by December of 2016 they were on the rise again, and were fairly consistent through 2017 (see chart below).

Beginning in early January of 2018 those numbers began to increase markedly again (see chart below).

 Some excerpts from the latest (week 7) Epidemiological report from the Nigerian CDC:
  •  In the reporting Week 07 (February 12-18,2018) sixty eight new confirmediI cases were recorded from seven States Edo (35), Ondo (19), Bauchi (1), Ebonyi (7), Anambra (4), Imo(1) and FCT (1) with four new deaths in confirmed cases from two states Ondo (2), and Bauchi (2)
  • From 1st January to 18th February 2018, a total of 913 suspected cases, and 73 deaths have been reported from 17 activeiv States- (Edo, Ondo, Bauchi, Nasarawa, Ebonyi, Anambra, Benue, Kogi, Imo, Plateau, Lagos, Taraba, Delta, Osun, Rivers, FCT, and Gombe) - Figure 1
  • Since the onset of the 2018, 277 cases have been classified as: 272 confirmed cases, 5 probable cases with 59 deaths (54 in Lab confirmed and 5 in probable) -Table 1
  • Case Fatality Rate in confirmed and probable cases is 21%
  •  Fourteen Health Care workers have been affected in six states –Ebonyi (7), Nasarawa (1), Kogi (1), Benue (1), Ondo (1) and Edo (3) with four deaths in Ebonyi (3) and Kogi (1)
  • Predominant age group affected is age group 30-50 (Median Age = 32) - Figure 4
  • The male to female ratio for confirmed cases is 2:1
  •  74% of all confirmed cases are from Edo (45%) and Ondo (29%) states
  •  National RRT team (NCDC staff and NFELTP residents) batch A replaced with batch B to continue response support in Ebonyi, Ondo and Edo States
  • Irrua Specialist Hospital has 39 cases on admission this weekend. FMC Owo has 29 isolation beds, all occupied.
  • A total of 2351 contacts have been identified from 17 active states and 1747 are currently being followed up
  •  Joint NCDC and WHO team on high level visit to Edo, Ondo and Ebonyi states
  • NCDC is collaborating with ALIMA and MSF in Edo, Ondo and Anambra States to support case management
  •  NCDC deployed teams to four Benin Republic border states (Kebbi, Kwara, Niger and Oyo) for enhanced surveillance activities
  • National Lassa fever multi-partner multi-agency Emergency Operations Centre(EOC) continues to coordinate the response activities at all levels
(Continue . . . )

Like many other hemorrhagic fevers, person-to-person transmission may occur with exposure to the blood, tissue, secretions, or excretions of an individual, although the CDC reassures:
Casual contact (including skin-to-skin contact without exchange of body fluids) does not spread Lassa virus. Person-to-person transmission is common in health care settings (called nosocomial transmission) where proper personal protective equipment (PPE) is not available or not used. Lassa virus may be spread in contaminated medical equipment, such as reused needles.
While likely to remain primarily a localized public health threat, we've seen exported cases before, and in 2016 the ECDC offered the following advice to travelers to the region.
Advice to travellers
Travellers to West Africa should be informed of the risk of exposure to Lassa fever virus, particularly in areas currently experiencing outbreaks. The risk is higher in rural areas where living conditions are basic.

Travellers should avoid consumption of foods and drink contaminated by rodent droppings, exposure to rodents or to patients presenting with haemorrhagic fever.

People travelling to these regions to provide care should be aware of the risk of exposure and should apply appropriate personal protective measures.

Saudi MOH Reports 2 MERS Cases


The Saudi MOH has updated their MERS surveillance page today announcing 2 new cases, but for some reason the standard graphics (map & chart) are not available in the English language report, and so I've lifted the graphic (above) from the Arabic version.
No report was filed at all for the 18th, while a `zero cases' report was posted for the 19th
So far, we've seen just 8 days reported during the month of February, with at least two cases announced on the Arabic page that were never posted on the English site, and several recoveries that were never announced as having been infected.
Exactly what is behind this recent erratic reporting, and discrepancies, remains a mystery. 

Details on today's two cases  (one from Riyadh & 1 from Taif) follow: