Thursday, July 20, 2017

Week 28: Hong Kong's Flu Activity Increases To `A Very High Level'.

Credit HK Flu Express - Week 28


It is rare that we should find ourselves talking this much about seasonal influenza in mid-July, but this summer's surge of flu in South East China (see yesterday's Macao, Hong Kong & Guangdong Province All Reporting Heavy Flu Activity) is more than just a little unusual.
Hardest hit (at least, based on reporting), has been Hong Kong, which after declaring their winter flu season over in mid-April (see chart above), was forced to reinstate their enhanced surveillance for severe seasonal influenza system in early May.
Hong Kong's `regular' flu season - which ran from February through April this year - ended with 74 severe cases and 42 deaths. Since it unexpectedly re-awoke in May, Hong Kong has reported an additional 312 severe cases and 208 deaths.
In the 7 days since the last (week 27) update, Hong Kong reported another 76 severe flu cases, and 53 deaths. Included are 5 severe pediatric cases, including 1 death.
Some excerpts from this morning's HK Flu Express, then I'll return with a bit more.
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 Jul 19, 2017)

Reporting period: Jul 9 – 15, 2017 (Week 28)

  • The latest surveillance data showed that the local influenza activity further increased to a very high level in the past week. It is foreseen that the influenza activity will remain at a very high level in the coming weeks.
  • The Centre for Health Protection (CHP) has collaborated with the Hospital Authority (HA) and private hospitals to reactivate the enhanced surveillance for severe seasonal influenza cases (i.e. influenza-associated admissions to intensive care unit or deaths) among patients aged 18 or above since May 5, 2017. As of Jul 19, 297 severe cases (including 205 deaths) were recorded. Separately, 15 cases of severe paediatric influenza-associated complication/death (including three deaths) (aged below 18 years) were recorded in the same period.
  • Apart from adopting personal, hand and environmental hygiene practices against respiratory illnesses, those members of the public who have not received influenza vaccine may get the vaccination as soon as possible for personal protection.
  • 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 for personal protection.

Laboratory surveillance, 2013-17

Among the respiratory specimens received in week 28, 2746 (40.66%) were tested positive for seasonal influenza viruses, including 107 (1.58%) influenza A(H1), 2549 (37.75%) influenza A(H3), 73 (1.08%) influenza B and 17 (0.25%) influenza C.
The percentage of respiratory specimens tested positive for seasonal influenza viruses last week was 40.66%, which was higher than 35.87% recorded in the previous week (Figure 2). Among the influenza viruses detected in the last week, the proportions of A(H3), A(H1), B and C were 92.8%, 3.9%, 2.7% and 0.6% respectively.


Surveillance of severe influenza cases
(Note: The data reported are provisional figures and subject to further revision)

Since the activation of the enhanced surveillance for severe influenza infection on May 5, 2017, a total of 312 severe cases (including 208 deaths) were recorded cumulatively (as of Jul 19) (Figure 9). These included:

  • 297 cases (including 205 deaths) among adult patients aged 18 years or above. Among them, 257 patients had infection with influenza A(H3N2), 21 patients with influenza A(H1N1)pdm09, 11 patients with influenza B and eight patients with influenza A pending subtype. 101 (34.0%) were known to have received the influenza vaccine for the 2016/17 season. Among the 205 fatal cases, 85 (41.5%) were known to have received the influenza vaccine. In the winter season in early 2017, 66 adult severe cases (including 41 deaths) were filed.
  • 15 cases (including three deaths) of severe paediatric influenza-associated complication/ death. Thirteen (86.7%) cases did not receive the influenza vaccine for the 2016/17 season. To date in 2017, 23 paediatric cases (including four deaths) were filed.
Enhanced surveillance for severe seasonal influenza (Aged 18 years or above)
  • In week 28, 72 cases of influenza associated ICU admission/death were recorded (including 50 deaths), which was higher than 39 cases (including 16 deaths) recorded in week 27. In the first 4 days of week 29 (Jul 16 to 19), 38 cases of influenza associated ICU admission/death were recorded, in which 25 of them were fatal.
Surveillance of severe paediatric influenza-associated complication/death (Aged below 18 years)
  •  In week 28, three cases of severe paediatric influenza-associated complication/ death (including one fatal case) were reported. In the first 4 days of week 29 (Jul 16 to 19), two cases of severe paediatric influenza-associated complication were reported. The case details are as follow:

 (Continue . . . .)
Although the percentage of fatal cases known to have received a flu vaccine is fairly high at 41.5%, Hong Kong ramps up their annual flu vaccination program in the fall, focusing primarily on high risk groups like the elderly and pregnant women. 
With such a late season surge, presumably some of protective effects of last year's vaccine have begun to wane, particularly among the elderly. 
Add in that the highest risk groups are the ones most apt to get vaccinated, and the growing diversity among the H3N2 subtype (see Eurosurveillance: Emergence Of A Novel Subclade Of Seasonal A/H3N2 - London), and this number - while disappointing - isn't all that surprising. 

While flu vaccines are still available, next fall's flu vaccination program is set to begin in October (see Seasonal influenza vaccination programmes in 2017/18 to be launched), and will be targeted towards the following priority groups.

Lastly, although hardest hit have been those over 65, this morning the CHP is reporting on yet another severe pediatric case.

The Centre for Health Protection (CHP) of the Department of Health is today (July 20) investigating a case of severe paediatric influenza A infection.
"The local seasonal influenza activity remains at a very high level and it is expected to remain very active in the coming weeks. We strongly urge the public, particularly children, the elderly and chronic disease patients, to adopt strict personal, hand and environmental hygiene both locally and during travel in the summer," a spokesman for the CHP said.
The 1-year-old baby boy, with good past health, has developed fever, cough and runny nose since July 12. He was taken to the Accident and Emergency Department of Kwong Wah Hospital on July 17 and was admitted for management on the same day. He was subsequently taken to a private hospital yesterday (July 19) for further treatment and was later transferred to the Paediatric Intensive Care Unit of Prince of Wales Hospital on the same day as his condition deteriorated.
The clinical diagnosis was influenza A infection complicated with severe pneumonia and he is now in stable condition.

WHO Update: H7N9 In China - July 19th

H7N9 Epi Curve (July 12th)  - Credit FAO


While we appear to have reached the long awaited summer lull in H7N9 activity on the Chinese Mainland, China continues to provide the World Health Organization with details on cases that were announced last month.

Yesterday the WHO published the following Disease Outbreak News update with details on 21 cases reported in the second half of June.
Included are details on two small clusters (of 2 cases each). In both clusters, investigators determined that human-to-human transmission was unlikely to have occurred.

Disease outbreak news 
19 July 2017 

On 19 June 2017, the National Health and Family Planning Commission of China (NHFPC) notified WHO of five additional laboratory-confirmed cases of human infection with avian influenza A(H7N9) virus in China. On 24 June 2017, the NHFPC notified WHO of 10 additional laboratory-confirmed cases of human infection with avian influenza A(H7N9) virus in China. On 30 June 2017, the NHFPC notified WHO of six additional laboratory-confirmed cases of human infection with avian influenza A(H7N9) virus in China.

Details of the case patients

On 19 June 2017, the NHFPC reported five laboratory-confirmed human cases of infection with avian influenza A(H7N9) virus in China. Onset dates ranged from 25 April to 6 June 2017. Of these five cases, one was female. The median age was 55 years (range 41 to 68 years). The case patients were reported from Beijing (1), Guangxi (1), Guizhou (1), Hunan (1), and Zhejiang (1). At the time of notification, there was one death. Four cases were diagnosed as having severe pneumonia. Three cases were reported to have had exposure to poultry or live poultry market, and two had no known poultry exposure. No case clustering was reported. 

On 24 June 2017, the NHFPC reported 10 laboratory-confirmed human cases of infection with avian influenza A(H7N9) virus in China. Onset dates ranged from 5 to 19 June 2017. All cases were male. The median age was 53.5 years (range 31 to 79 years). The cases were reported from Anhui (1), Beijing (2), Guizhou (1), Hebei (1), Inner Mongolia (1), Jiangsu (1), Sichuan (2), and Tianjin (1). This is the first case reported in Inner Mongolia since the virus emerged in 2013 although two cases were recently reported from Shaanxi province but who had likely exposure in Inner Mongolia. At the time of notification, there were two deaths. Eight cases were diagnosed as having either pneumonia (4) or severe pneumonia (4). Nine cases were reported to have had exposure to poultry or live poultry market, and one had no known poultry exposure.

One cluster with two cases was reported and both cases are from Panzhihua City, Sichuan Province, and had exposure to the same live poultry market. The cluster includes:
  • A 79-year-old male, who had symptom onset on 12 June 2017 and was admitted to hospital with severe pneumonia on 15 June 2017, then died on the 21 June 2017. He was living on an upper floor of the live poultry market and passed regularly through the market.
  • A 48-year-old male, who had symptom onset on 7 June 2017 and was admitted to hospital with severe pneumonia on 11 June 2017. He is a seller of poultry at the same live poultry market.
On 30 June 2017, the NHFPC reported six laboratory-confirmed human cases of infection with avian influenza A(H7N9) virus in China. Onset dates ranged from 11 to 23 June 2017. Three cases were male. The median age was 37.5 years (range 4 to 72 years). The cases were reported from Guizhou (1), Shanxi (1), and Yunnan (4) provinces. At the time of notification no associated deaths were reported. Four cases were diagnosed as having either pneumonia (1) or severe pneumonia (3). Two mild cases, identified through ILI surveillance, were reported: one in a child with exposure to market poultry and one in an adult. Five cases were reported to have had exposure to poultry or live poultry market, and one had no known poultry exposure. These are the first cases reported with exposure to the virus in Yunnan province. Previous cases reported from Yunnan province had likely exposure in a neighbouring province.

One cluster with two cases was reported, which include:
  • A 33-year-old female from Wenshan, Yunnan Province had symptom onset on 17 June 2017 and was admitted to hospital with severe pneumonia on the same day. She had no apparent exposure to live poultry.
  • Her sister-in-law, a 42-year-old female also from Wenshan, Yunnan Province, visited her in the hospital, developed mild symptoms on 21 June and was hospitalized on 24 June 2017. Investigation of the case revealed that she ran a shop near a live poultry market and bought live poultry from the market on a daily basis before her symptom onset. The investigation concluded that the likely source of her infection was exposure to the virus from visiting live poultry markets.
To date, a total of 1554 laboratory-confirmed human infections with avian influenza A(H7N9) virus have been reported through IHR notification since early 2013.

Public health response

The Chinese government at national and local level is taking preventive measures which include:
  • Continuing to guide the provinces to strengthen assessment, and prevention and control measures.
  • Continuing to strengthen control measures focusing on hygienic management of live poultry markets and cross-regional transportation.
  • Conducting detailed source investigations to inform effective prevention and control measures.
  • Continuing to detect and treat human infections with avian influenza A(H7N9) early to reduce mortality.
  • Continuing to carry out risk communication and issue information notices to provide the public with guidance on self-protection.
  • Strengthening virology surveillance to better understand levels of virus contamination in the environment as well as mutations, in order to provide further guidance for prevention and control.

WHO risk assessment

The number of human infections with avian influenza A(H7N9) virus and the geographical distribution in the fifth epidemic wave (i.e. onset since 1 October 2016) is greater than earlier waves. This suggests that the virus is spreading, and emphasizes that further intensive surveillance and control measures in both human and animal health sector are crucial.

According to the epidemiological curve, the number of reported cases on a weekly basis seems to have peaked in early February and is slowly decreasing. The peak in cases this year corresponds to the timing of the peak in cases in previous years. 

Most human cases are exposed to avian influenza A(H7N9) virus through contact with infected poultry or contaminated environments, including live poultry markets. Since the virus continues to be detected in animals and environments, and live poultry vending continues, further human cases can be expected. Additional sporadic human cases of avian influenza A(H7N9) in other provinces in China that have not yet reported human cases are also expected. Similarly, sporadic human cases of avian influenza A(H7N9) detected in countries bordering China would not be unexpected. Although small clusters of cases of human infection with avian influenza A(H7N9) virus have been reported including those involving patients in the same ward, current epidemiological and virological evidence suggests that this virus has not acquired the ability of sustained transmission among humans. Therefore the likelihood of further community level spread is considered low.
Close analysis of the epidemiological situation and further characterization of the most recent viruses are critical to assess associated risk and to adjust risk management measures in a timely manner.

(Continue . . . .)

Wednesday, July 19, 2017

Texas DSHS: Cyclospora Cases Rising



While fairly common in developing tropical, or sub-tropical countries, Cyclosporiasis – an infection usually acquired through consuming food or water contaminated with Cyclospora cayetanensis - is relatively rare in the United States.
Unlike the more common cryptosporidium, which can be easily be passed from human-to-human, Cyclospora is rarely transmitted directly from an infected host.
This is because hosts infected with Cyclospora shed unsporulated (non-infective) cysts in their stool which require days or even weeks to mature into infectious agents. Infection is characterized by prolonged bouts of watery diarrhea, which may persist or reoccur over a period of weeks.
We tend to see non-travel acquired Cyclospora cases in the United States during the summer months, usually peaking in June or July.
In 2013 we saw a particularly widespread event, with 631 cases reported from 25 states and New York City (link). Texas was the hardest hit (270 cases), followed by Iowa (140 cases) and Nebraska (87 cases).
This outbreak slowed, and finally ended, by the end of  August.
The CDC’s MMWR carried a brief post-mortem on the outbreak (link) which identified not one – but at least two separate outbreaks – and that `the food item associated with illness in Texas was different from that implicated in restaurant-associated cases in Iowa and Nebraska’.

On Monday, the Texas DSHS issued the following statement on a recent surge in Cyclospora infections in their state.  Health officials there are particularly anxious to track down the source, in hopes that a repeat of 2013's outbreak can be avoided.

Cyclospora on the Rise in Texas; Testing, Reporting Key to Finding Source
News Release
July 17, 2017

A spike in illnesses caused by the parasite Cyclospora in June and July is prompting the Texas Department of State Health Services to ask health care providers to be on guard for the illness, pursue testing, and report cases to their local health department. Within the past month, 68 cases have been reported in the state, and DSHS is working with local health departments to gather information about the illnesses and identify a source.

Cyclosporiasis is an intestinal illness caused by consuming food or water contaminated with the microscopic Cyclospora parasite. The main symptom is watery diarrhea lasting a few days to a few months. Additional symptoms may include loss of appetite, fatigue, weight loss, abdominal cramps, bloating, increased gas, nausea, vomiting and a low fever. Symptoms may come and go multiple times over a period of weeks or months.

People with symptoms that could be related to Cyclospora should contact their health care provider for treatment. A health advisory issued today asks providers to test patients who have diarrhea lasting more than a few days or diarrhea accompanied by severe loss of appetite or fatigue. Health care providers should promptly report cases so that public health can investigate them and attempt to determine the source in order to head off future cases.

Past outbreaks in the U.S. have been associated with consumption of imported fresh produce, including fresh pre-packaged salad mix, raspberries, basil, snow peas, and mesclun greens. Texas has had multiple outbreaks linked to cilantro.

DSHS recommends thoroughly washing all fresh produce, but that may not entirely eliminate the risk because Cyclospora can be very difficult to wash off. Cooking will kill the parasite. Infection is generally not transmitted directly from person-to-person. There were 148 cases of cyclosporiasis in Texas reported last year.
The CDC maintains an extensive Cyclosporiasis (Cyclospora Infection) web page, where you can find additional information.  There you will find additional information on outbreaks, epidemiology, and Treatment, which according to the CDC:

Trimethoprim/sulfamethoxazole (TMP/SMX), sold under the trade names Bactrim*, Septra*, and Cotrim*, is the usual therapy for Cyclospora infection. No highly effective alternative antibiotic regimen has been identified yet for patients who do not respond to the standard treatment or have a sulfa allergy.

Most people who have healthy immune systems will recover without treatment. If not treated, the illness may last for a few days to a month or longer. Symptoms may seem to go away and then return one or more times (relapse). Anti-diarrheal medicine may help reduce diarrhea, but a health care provider should be consulted before such medicine is taken. People who are in poor health or who have weakened immune systems may be at higher risk for severe or prolonged illness.
Under Prevention and Control, they write:
On the basis of the currently available information, avoiding food or water that may have been contaminated with feces is the best way to prevent cyclosporiasis. Treatment with chlorine or iodine is unlikely to kill Cyclospora oocysts. No vaccine for cyclosporiasis is available.

The U.S. Food and Drug Administration's (FDA) Center for Food Safety and Applied Nutrition (CFSAN) publishes detailed food safety recommendations for growers and suppliers. In its Guide to Minimize Microbial Food Safety Hazards for Fresh Fruits and Vegetables, CFSAN describes good agricultural practices (GAPs) and good manufacturing practices (GMPs) for fresh fruits and vegetables. The guidelines address the growing, harvesting, sorting, packaging, and storage processes; following the guidelines can help reduce the overall risk for microbial contamination during these processes. The precise ways that food and water become contaminated with Cyclospora oocysts are not fully understood.

CDC monitors the occurrence of cyclosporiasis in the United States and helps state health departments identify and investigate cyclosporiasis outbreaks to prevent additional cases of illness.

Macao, Hong Kong & Guangdong Province All Reporting Heavy Flu Activity

Hong Kong, Macau & S.E. Guangdong Province


The unusually severe summer flu surge which was first reported in Hong Kong in early May (see Hong Kong CHP Reports A Late Season Flu Surge), and shortly thereafter in Taiwan (see here & here), continues to spread, with reports of increased flu activity in Macao and across much of Guangdong Province on the mainland.
Today, for the second time in three days, Hong Kong's CHP has again appealed for vigilance against flu, after reporting two more severe pediatric cases yesterday.
In today's statement they also reference the high levels of flu being reporting now in Guangdong Province and in neighboring Macao. Given their close proximity, and the amount of travel between these locations, this spread is not unexpected even if the severity and timing of this flu outbreak are unusual.

A round up of reports this morning, first from Hong Kong, then Macao, and finally Guangdong Province.

     The Centre for Health Protection (CHP) of the Department of Health today (July 19) reported that local seasonal influenza activity further increased to a very high level in the past week, coupled with ongoing severe influenza cases, high consultation rates in sentinel clinics/doctors and a large number of institutional outbreaks.

     "The latest surveillance data of the summer influenza season showed that the rate of influenza-like illness in Accident and Emergency Departments and the influenza-associated admission rate in public hospitals remain high. Influenza activities in Guangdong and Macau are also high. As local influenza is expected to remain very active in the coming weeks, we strongly urge the public, particularly children, the elderly and chronic disease patients, to adopt strict personal, hand and environmental hygiene both locally and during travel in the summer," a spokesman for the CHP said.

     The positive percentage of seasonal influenza viruses among respiratory specimens received by the CHP further increased from 35.87 to 40.66 per cent from the week of July 2 to that of July 9. The vast majority (92 per cent) was influenza A(H3).

     "Epidemiological experience shows that the predominance of H3 virus has affected elderly persons most, many of whom have underlying illnesses, as observed from more outbreaks reported by elderly homes. They should promptly report to the CHP in case of an increase in respiratory illnesses for immediate epidemiological investigations and outbreak control," the spokesman added.

     In the above period, the number of institutional outbreaks of influenza-like illness increased from 42 (affecting 234 persons) to 44 (229 persons). As of yesterday (July 18), 16 (83 persons) had been recorded this week. In the last four weeks, about half of the outbreaks (53 per cent) were reported by residential care homes for the elderly, followed by about one-fifth (21 per cent) from kindergartens and child care centres.

     Regarding severe influenza cases, in adults, 289 cases of influenza-associated admission to the Intensive Care Unit or death (including 199 deaths) were recorded with the Hospital Authority and private hospitals during the enhanced surveillance from May 5 to yesterday. Most (249 cases) were H3.

     In children, 23 cases of severe influenza-associated complication or death (four deaths) have been detected so far in 2017, with 16 H3, six H1, and one influenza B cases.

     "Hong Kong has entered the summer influenza season since mid-May. The public should wash or clean hands frequently, especially before touching the mouth, nose or eyes, or after touching public installations such as handrails or door knobs. Wear a mask when respiratory symptoms develop, especially when going to crowded places or attending gatherings. High-risk persons may wear masks against infections," the spokesman said.

     "Young children aged six months or above yet to receive seasonal influenza vaccination of the current season may get vaccinated as soon as possible for better personal protection," the spokesman added.

     In addition, influenza activities in neighbouring areas remained high with H3 virus predominating so far. Macau has entered the summer influenza season. Influenza activities in southern provinces of the Mainland have been on the rise recently. In the southern hemisphere, influenza activity in Australia and New Zealand is rising.
        (Continue . . . )

To put this summer wave's severity into perspective, during Hong Kong's regular flu season (Jan-April 2017) they reported just 66 adult severe cases and 41 deaths.  Over the past 10 weeks those numbers have more than quadrupled. 
Yesterday in neighboring Macao, which has only about 1/12th the population of Hong Kong, their Health Bureau issued a lengthy statement on their recent flu surge as well.  
Health Bureau is closely monitoring the influenza situation in Macao has taken a series of measures to prevent the peak of influenza

The Health Bureau said it was closely monitoring the situation of the flu in Macao. According to the monitoring data, Macao has entered the summer flu peak, influenza virus activity is active, Macao has recorded severe cases of influenza and death cases. In response to the peak of the flu, the Secretary for Health, Mr Lee Chin-lun, today (July 18) convened a meeting to review the current response to the relevant departments and will take a series of measures to enhance the peak of influenza. The Health Bureau urges members of the public, medical staff, medical institutions and residential homes to take precautions to prevent the changes in the disease.

The monitoring revealed that influenza-like illness increased significantly compared with the same period last year

In order to monitor the influenza situation in Macao, the Health Bureau has set up a tight monitoring mechanism. The monitoring revealed that influenza-like illness in Macao increased significantly compared with the same period of last year. Among them, the hospital influenza surveillance data show that the latest week in Australia (28 weeks) the number of influenza-like cases increased, including adult emergency due to influenza-like cases, the proportion of total attendance per person, 117 times per person, about Usually 4 times; and the proportion of pediatric emergency for every thousand people 214 times, about 2 times the normal day.

The Department of Health's Public Health Laboratory will also isolate the respiratory samples of influenza-like illnesses. The results showed that 57 of the respiratory samples of 127 influenza-like illnesses collected by the Public Health Laboratory in the past week were positive for 57 influenza viruses (41.9%), 11 (19.3%) of influenza A virus and 4 (7.0%) of influenza A (H1N1) virus samples. The positive rate was 44.9%.
         (Continue . . . )

While not hit as hard as Hong Kong, the following chart from Macao's latest Influenza Surveillance report shows influenza's upward trend in June at a time of the year when flu  is normally declining.

Relation between the number of users with flu-like symptoms and the total number of users of the Urgent Care for Adults of CHCSJ (weekly) (from the 1st week of 2014 to the 27th week of 2017)

Meanwhile, in Guangdong Province (pop 108 million), where official statistics are harder to come by, Guangdong's CDC website did publish the following media report yesterday.  Their short-term forecast - of flu levels falling to their baseline levels by the end of July - is considerably more optimistic than Hong Kong's.

Guangdong is still in the peak season of seasonal influenza

Release Date: 2017-07-18 Views: Contributed by: Information Department of Publicity: 

It is expected that the outbreak of influenza will gradually fall to the baseline level at the end of July

Xinhua News reporter Li Qiuling correspondent Liang Ning interns Cao Zhenzhen reported that the new Express reporter learned from the Guangdong Provincial Center for Disease Control and Prevention, Guangdong is still at the peak of seasonal influenza, the recent monitoring data show that the overall incidence of influenza in Guangdong Province Began to show a downward trend, is expected in late July will gradually fall to the baseline incidence level.

Guangdong Provincial Center for Disease Control and Prevention, deputy director of Song Tie told reporters, according to the center of the outbreak of influenza outbreak monitoring data show that since January this year, the province's influenza-like cases outpatient clinic (ILI%) 4.19% , Down by 10% from 4.65% in the same period last year. The highest level of influenza-like illness was in late June and ILI% was 6.63%. But from the monitoring point of view, since mid-July began to decline. Song Tie said that according to previous years of monitoring analysis, the flu epidemic is expected at the end of July will gradually fall to the baseline incidence level.

Disease control experts also introduced this year, the advantages of influenza in Guangdong strains of influenza A H3N2 influenza virus, accounting for 75% of influenza outbreaks. "In general, every year from May to July is the seasonal season of influenza in Guangdong Province at this stage of the province's seasonal influenza virus is still active, but with the gradual decline in the proportion of influenza-like cases and the arrival of summer vacation is expected to province schools The outbreak of the epidemic will be significantly reduced, but it should be noted that the summer camp and centralized training institutions still exist the risk of aggregation of influenza. "Song Tie also said:" September after school children re-gathered, schools, nursery institutions will have The occurrence of respiratory and intestinal infectious diseases, the risk of aggregation of the epidemic, the relevant departments should be done before the school prevention and control work.

(Reproduced from July 18, 2017 New Express A09 version)

Meanwhile, as reported yesterday in this blog, the regular flu season in the southern hemisphere is picking up steam.

Tuesday, July 18, 2017

New IFITM3 Genetic Marker May Help Identify High Risk Flu Patients


One of the great inequities of life is that some people are at a higher risk of experiencing severe flu infections than others.  Sometimes that has to do with their age, immune system, or comorbidities . . . . and sometimes it boils down to their genetics. 
Being able to identify those patients who's genetic traits put them a greater risk of severe illness or death from influenza would be huge advantage in prioritizing treatment - particularly during a pandemic. 
Over the past decade we've followed a number research projects into several genetic markers, including the Interferon-induced transmembrane protein 3  (IFITM3) protein, whose levels are controlled by the IFITM3 gene.

  • In late 2009, in The Best Defense, we looked at research from Harvard Medical School and the Howard Hughes Medical Institute, that identified the IFITM3 protein as capable of inhibiting the replication of influenza, and other viruses, such as West Nile and Dengue.
  • We revisited the IFITM3 story again in early 2012, in Luck Of The Draw, when we looked at research from the Wellcome Trust Sanger Institute, that found that people who carried a particular variant of the IFITM3 gene - (SNP rs12252-C) -  were more likely to be hospitalized with severe influenza. 
  • And again in 2013, in PNAS, we saw reseach that found IFITM3 CC gene variant (aka C/C Genotype) is linked to hypercytokinemia (aka a `Cytokine Storm’), and a severe outcome, in H7N9 infections.    
  • And in 2015, in A Genetic Predisposition To Severe Flu Infection, we looked at a  study published in Science Express that identified yet another (rare) genetic marker -  a mutation of the IRF7 gene -  linked to a lack of interferon production which can lead to a more severe influenza infection.
Today the Journal Nature has published a new study on the role played by a mutation in the IFITM3 gene on influenza severity.  As I write this, the link doesn't appear to be working, but it will hopefully go live soon.
Research | 17 July 2017
SNP-mediated disruption of CTCF binding at the IFITM3 promoter is associated with risk of severe influenza in humans
E Kaitlynn Allen, Adrienne G Randolph, Tushar Bhangale, Pranay Dogra, Maikke Ohlson, Christine M Oshansky, Anthony E Zamora, John P Shannon, David Finkelstein, Amy Dressen, John DeVincenzo, Miguela Caniza, Ben Youngblood, Carrie M Rosenberger & Paul G Thomas
In the meantime, we do have the abstract from PubMed, and a press release from St. Jude Children's Research Hospital  in Memphis.  
Nat Med. 2017 Jul 17. doi: 10.1038/nm.4370. [Epub ahead of print]

SNP-mediated disruption of CTCF binding at the IFITM3 promoter is associated with risk of severe influenza in humans.

Allen EK1, Randolph AG2, Bhangale T3, Dogra P1, Ohlson M4, Oshansky CM1, Zamora AE1, Shannon JP1, Finkelstein D5, Dressen A3, DeVincenzo J6,7, Caniza M8, Youngblood B1, Rosenberger CM4, Thomas PG1.


Previous studies have reported associations of IFITM3 SNP rs12252 with severe influenza, but evidence of association and the mechanism by which risk is conferred remain controversial. We prioritized SNPs in IFITM3 on the basis of putative biological function and identified rs34481144 in the 5' UTR. We found evidence of a new association of rs34481144 with severe influenza in three influenza-infected cohorts characterized by different levels of influenza illness severity.
We determined a role for rs34481144 as an expression quantitative trait locus (eQTL) for IFITM3, with the risk allele associated with lower mRNA expression. The risk allele was found to have decreased IRF3 binding and increased CTCF binding in promoter-binding assays, and risk allele carriage diminished transcriptional correlations among IFITM3-neighboring genes, indicative of CTCF boundary activity.
Furthermore, the risk allele disrupts a CpG site that undergoes differential methylation in CD8+ T cell subsets. Carriers of the risk allele had reduced numbers of CD8+ T cells in their airways during natural influenza infection, consistent with IFITM3 promoting accumulation of CD8+ T cells in airways and indicating that a critical function for IFITM3 may be to promote immune cell persistence at mucosal sites.Our study identifies a new regulator of IFITM3 expression that associates with CD8+ T cell levels in the airways and a spectrum of clinical outcomes.

A considerably less technical summation can be found on the St. Jude Children's Research Hospital website, portions of which I've excerpted below. Follow the link to read it in its entirety.
Newly identified genetic marker may help detect high-risk flu patients

Researchers led by St. Jude Children's Research Hospital have identified a genetic variation associated with influenza severity and the supply of killer T cells that help patients fight the infection

Memphis, Tennessee, July 17, 2017

Researchers have discovered an inherited genetic variation that may help identify patients at elevated risk for severe, potentially fatal influenza infections. The scientists have also linked the gene variant to a mechanism that explains the elevated risk and offers clues about the broader anti-viral immune response.

St. Jude Children's Research Hospital led the research, which appears as an advance, online publication today in the scientific journal Nature Medicine.

Researchers screened 393 flu patients ranging from infants to 70 years old. Patients with a particular inherited variation in the gene IFITM3 were more than twice as likely to develop severe, life-threatening flu symptoms as those who carried the protective version of the gene.

Working at the molecular level, the investigators showed how expression of the IFITM3 protein was reduced in killer T cells of patients with the high-risk variant compared to other patients. Researchers also found more killer T cells—which help patients fight the infection—in the upper airways of flu patients with the protective variant compared to other patients.

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In addition to the previously discussed IFITM3 (rs12252) and mutations of the IRF7 gene, last year Chinese researchers (see Nature: Mulitple Gene Mutations Identified In Patients With A/H7N9) reported finding 21 genes that showed a high rate of mutation among infected patients when compared to the general population, including the IFITM3 gene.

While we are a long way from knowing all of the genetic risk factors for severe influenza (and likely other viral infections), researchers continue to expand their watch list, and more importantly, their understanding of how these mutations work.

NSW: Sydney Hospitals `Slammed' By Flu-Like Cases


Unlike Hong Kong and Taiwan (see yesterday's  Hong Kong Hospitals Scramble To Deal With Mounting Flu Surge) - both of which sit in the northern hemisphere - it isn't unusual or unexpected to see influenza begin to ramp up in Australia in July, although their peak doesn't usually arrive until August or September (see NSW Surveillance chart below).

The above snapshot, current as of 9 days ago, shows influenza in New South Wales making its earliest surge since 2012, something we discussed in late June. The most recent (week 27) NSW Health Influenza Surveillance Report summary noted:

  • Surveillance data indicates a marked rise in activity over the last week and it is expected to continue to rise throughout July.
  • The impact of influenza on the health sector is steadily increasing.
  • Influenza A strains were more common than influenza B strains

Overnight Australian media has been filled with reports of over crowded ERs, ambulances `queued 10 deep' outside of hospitals waiting to unload patients, and paramedic response times plummeting as hospital's are being `slammed' by flu cases.

Typical of these reports are the following, first from The Age.

Huge delays as Sydney hospital emergency departments swamped with patients

Kate Aubusson

Paramedics and emergency departments in Sydney's south-west have been inundated by huge numbers of sick patients, causing major delays in ambulance transfers and hospital admissions.

Emergency staff say their emergency departments have been clogged with patients over the past 36 hours, many presenting with flu-like symptoms, causing significant delays in admissions times.
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And this from ABC News.

Ambulances queued up 10 deep outside Liverpool Hospital in Sydney
By state political reporter Sarah Gerathy

Ambulances have been queued 10 deep for hours outside some overstretched emergency wards across south-western Sydney, with doctors having to "tuck people in every corner" due to a surge in patients in the past 48 hours.

The acting director of emergency medicine at Liverpool Hospital said the hospital had been "slammed" and it was trying to do everything it could to ease the queue of ambulances and make sure paramedics could get back on the road.
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Although they pale in comparison, these reports should provide some inkling of what hospitals and emergency services would have to deal with during a full fledged pandemic (see Australian Doc: ICU’s Were On `Verge of Collapse’ During Pandemic).
The ability of our medical system to deal with a sudden, possibly overwhelming, surge of patients during a pandemic - or other disaster - remains one of their greatest challenges.   
Two years ago, in COCA Call : Disaster/Emergency Preparedness For Clinicians, the CDC provided some guidance on the management of multiple critically ill patients during a disaster or pandemic. That presentation and supporting materials may be accessed at:
Emergency Preparedness for Clinicians - From Guidelines to the Front Line

Like Hong Kong and Taiwan, New South Wales appears to be dealing with a combination of Influenza A H3N2 and H1N1, and Influenza B.  H3N2 appears to be edging out H1N1, but about 87% of the influenza A positive isolates were not subtyped in the latest report.

Non-influenza respiratory viruses, including Rhinovirus, RSV, Parainfluenza, and Adenovirus are also being reported as part of their winter respiratory season mix, and so while Influenza A may seem the obvious culprit, we'll have to await further word as to exactly which virus has sparked this recent run on Sydney's hospitals.
Influenza seasons can vary greatly in terms of severity and timing, with H3N2 dominant seasons usually hitting the elderly hardest. Even in non-pandemic years, there can be as much as a 10-fold difference in flu mortality. 
While the recent severe flu in Hong Kong, and these latest reports from NSW, can't tell us with any certainty what kind of flu season we will see this fall, we have come off two relatively mild flu seasons in a row (see FluView Chart below).

At some point that pendulum will swing, and we'll see another severe flu season. In When Influenza Goes Rogue we looked back at some of these extreme non-pandemic years, and the overriding lesson is that flu has an enormous capacity to surprise us.