Monday, January 22, 2018

WHO: Yellow Fever Update & Risk Assessment - Brazil

Yellow Fever  In Brazil - Credit WHO


Last year's Yellow Fever epidemic in Brazil was the worst in years (see epi chart above), with the virus is turning up in urban areas that have not experienced outbreaks in decades (see Brazil: Yellow Fever Updates From The MOH, The CDC, and University of Wisconsin).  
While the outbreak peaked in January, it lingered on until the end of April, with only sporadic cases reported until last December.  Since then, we've seen a tripling of new human cases, along with reports of outbreaks in non-human primates.
Last week, the WHO announced that Vaccination Recommended For Visitors to São Paulo State. Complicating matters, there remains a serious shortage of the Yellow Fever Vaccine (see CDC Announcement: Yellow Fever Vaccine Access).

Today the WHO has released the following DON (Disease Outbreak News) report on the rise in Yellow Fever cases in Brazil.  I'll return with a postscript:

Yellow fever – Brazil

Disease outbreak news
22 January 2018

From 1 July 2017 through 14 January 2018, 35 confirmed human cases of yellow fever were reported in Brazil (Figure 1), including 20 deaths and 145 suspected cases who are under investigation. In recent weeks, the number of confirmed human cases of yellow fever has tripled in Brazil, mainly in the states of São Paulo and Minas Gerais. Confirmed cases were notified in the states of São Paulo (20 cases, including 11 deaths), Rio de Janeiro (three cases, including one death), and Minas Gerais (11 cases, including seven deaths), and in the Federal District (one fatal case).

All confirmed cases are likely to have acquired their infections in geographic locations where there are documented epizootics in non-human primates. In Minas Gerais cases are reported in municipalities where no human cases were detected during the outbreak in 2016/2017. In São Paulo, the highest proportion of cases is reported in Maripora, an area located 15 kilometers from the northern area of the municipality of São Paulo. The new cases in Rio de Janeiro are reported in the municipalities of Valença and Teresópolis; the latter is located 96 kilometers from the city of Rio de Janeiro.

On 11 January 2018, a case of yellow fever was confirmed in The Netherlands (PCR positive) in a returning traveller with history of stay in the municipality of Mairipora and Atibaia, state of Sao Paulo, Brazil, from 19 December 2017 through 8 January 2018, an area where the circulation of yellow fever virus is currently occurring. The case has no history of yellow fever vaccination. The onset of illness was 7 January 2018, when the patient reported symptoms of high fever, headache, myalgia, nausea, vomiting and diarrhoea.

Although epizootics have been reported throughout 2017, there was a significant increase from September 2017. The high number of epizootics and animals concerned indicates a high level of circulation of the virus in ecosystems favorable for transmission. From 1 July 2017 through 14 January 2018, there were 2442 epizootics in non-human primates reported in 21 federal entities, including areas that were previously not considered to be at risk for yellow fever. Of these, 411 were laboratory-confirmed, 747 are under investigation, 817 were classified as indeterminate and 467 were ruled-out. The confirmed epizootics for yellow fever were reported by four states (Mato Grosso, Minas Gerais, Rio de Janeiro, and São Paulo); however, the majority (88%) of the confirmed epizootics were registered in the state of São Paulo.

Public health response

Since September 2017, when yellow fever was confirmed in human cases and epizootics in São Paulo, national authorities have been intensifying vaccination activities through routine and preemptive immunization campaigns. In addition, state and municipality health authorities have been strengthening healthcare services for management of cases and have been carrying out risk communication.

In early January 2018, to reduce the risk of a large yellow fever outbreak, the Brazilian Ministry of Health announced plans to conduct a mass yellow fever vaccination campaigns which will include both standard (0.5 mL) and fractional (0.1 mL) doses. The campaigns will take place in São Paulo and Rio de Janeiro, from 25 January through 17 February and in Bahia, from 19 February through 3 March. The aim is to vaccinate 21.8 million people (16.5 million with the fractionated dose and 5.3 million with the standard dose) who live in 77 municipalities in these three states.
WHO risk assessment

The number of epizootics reported since July 2017 continues to be a concern, especially near urban areas of large cities, such as São Paulo, and in municipalities that were previously not considered at risk for yellow fever.

While measures implemented by the Brazilian authorities during the 2016/2017 outbreak have contributed to the occurrence of a smaller number of cases when comparing the periods from 28 November 2016 through 15 January 2017 with 27 November 2017 through 14 January 2018. The large number of unvaccinated people who continue to live in areas with ecosystems favorable for transmission of the yellow fever virus represent a elevated risk for the change in the current transmission pattern.

It is expected that the decision of the Brazilian authorities to carry out a mass vaccination campaign against yellow fever, including standard (0.5 ml) and fractional (0.1 ml) doses, can effectively limit the transmission of yellow fever. It is important to note that, due to its scale and scope, this mass vaccination campaign will likely be characterized by significant logistical challenges.

The recent occurrence of a confirmed yellow fever case in an unvaccinated traveller reveals the need for States Parties to reinforce the dissemination of recommendations for international travellers.

The current WHO recommendations for international travellers going to Brazil were updated on 16 January 2018 and are available at the link below:
WHO recommendations for travellers, Brazil

Travellers returning with viraemia may pose a risk to the establishment of local yellow fever transmission cycles predominantly in areas where the vector is present.

To date, there has been no evidence of yellow fever transmission by Aedes aegypti. In entomological studies conducted during the 2016/2017 outbreak in some of the affected states, it was found that the isolated Haemagogus mosquitoes were positive for yellow fever.

WHO continues to monitor the epidemiological situation and review the risk assessment based on the latest available information.
         (Continue . . .)

While they don't mutate as quickly as influenza viruses, mosquito-borne viruses like Yellow Fever, Chikungunya, and Zika all evolve over time.

Until 2005, Chikungunya was a little known virus which was only found in East and Central Africa, and had never caused an urban epidemic. 
But after a new mutation emerged that allowed it to be carried by the Aedes Albopictus `Asian tiger’ mosquito (see A Single Mutation in Chikungunya Virus Affects Vector Specificity and Epidemic Potential), the virus quickly cut a swath across the Indian ocean, into the Pacific, and eventually to Central and South America. 
Similarly, we've seen studies showing that A single mutation in the prM protein of Zika virus contributes to fetal microcephaly, and in Emerging Microbes & Infect: Growing Genetic Diversity Of Zika Viruses In Latin America, researchers found a high level of genetic diversity among Zika viruses sequenced from Brazil, with no clear sign of a dominant strain.
Not surprisingly, Yellow Fever has not been exempt from this evolutionary process.
Last May, in Fiocruz Institute: Sequencing Of Yellow Fever Virus Shows 8 Genetic Changes - Brazil, researchers sequenced the genome of two recent Yellow Fever viruses isolated from Howler Monkeys - and found a number of novel mutations (amino acid changes) that have never been seen in the Yellow Fever virus previously.

From the study, the authors wrote:
. . . .  we detected eight unique amino acid changes in the viral proteins, which are located in the structural capsid protein (1 change), and the components of viral replicase complex, the NS3 (2 changes) and NS5 (5 changes) proteins, suggesting a potential role in the capacity of viral infection to vertebrate and/or invertebrate hosts and spreading in the ongoing outbreak. 
Whether these specific changes are behind the sudden increase in Yellow Fever in Brazil remains to be determined, but scientists now have a plausible mechanism to investigate.

But beyond Yellow Fever, Zika, and Chikungunya this is a reminder than old scourges have a habit of reinventing themselves, and we can't necessarily assume they will always behave in the future the same way they have behaved in the past.

H9N2 Adaptation In Minks


Mink are a member of the Mustelidae family of carnivorous mammals, which also includes  badgers, otters, weasels, martens, ferrets, and wolverines. Many of these species are susceptible to flu viruses – most notably ferrets – which are often used in influenza research.
While small peridomestic animals like mink, skunks, and rabbits are known to be susceptible to certain types of influenza infection, we are still learning about their ability spread these viruses to other species, or how host adaptation might influence the evolution of flu viruses.
A little over 8 years ago, in 2009's That Touch Of Mink Flu, we looked at a story out of Denmark, where at least 11 mink farms in the Holstebro were reported to be infected with a variant of the human H3N2 virus.
Mink farming has become big business in China in recent years, with more than 60 million raised in 2012. Increasingly fox and raccoon dogs are raised on the same farms, increasing the odds of interspecies transmission of novel viruses.
In China, farmed animals are often fed a diet that includes raw poultry or poultry products (cite), which increases their risk of exposure to avian viruses. This practice inadvertently led to the deaths of hundreds of exotic tigers in Thailand in 2004 (see HPAI H5: Catch As Cats Can) from HPAI H5N1. 
In 2015, we revisited mink flu in That Touch Of Mink Flu (H9N2 Edition), after a study was published in the Virology Journal on a serological survey of antibodies to H9N2 (along with H5 & H7 viruses) in Chinese farmed minks, along with the results of experimental infection of minks with the H9N2 virus.

That 2015 study found that mink inoculated with the H9N2 subtype replicated the virus in their lungs (and to a lesser extent) heart, brain, and kidney. While H9N2 infection was non-fatal for mink, they developed lung lesions, edema, and shed the virus through their respiratory tract.

Last August, in That Touch Of Mink Flu (H9N2) - Revisited, we looked at yet another study - published in Nature's Scientific Reports - on the seroprevalence and transmissibility of H9N2 from minks to other peridomestic animals.

The authors wrote:
Transmission experiments showed that close contact between H9N2 infected mink and naïve contact mink, foxes and raccoon dogs resulted in spread of the virus to the sentinel animals as determined by virus isolation and/or seroconversion. H9N2-challenged foxes and raccoon dogs also showed H9N2 IAV could infect these animals without clinical signs and virus shedding, but with seroconversion.
A serosurvey in foxes and raccoon dogs demonstrated that H9N2 IAV circulated in these hosts. In some areas in China, mink, foxes and raccoon dogs are raised on the same farms, which could increase the chance for H9N2 IAV to cross the species barrier.
Our findings suggest that the potential exists for H9N2 IAV transmission to humans exposed to fur animals. Virological and epidemiological surveillance of IAVs in mink, foxes and raccoon dogs should be strengthened for public health.
Although farmed poultry and live bird markets are generally viewed as posing the greatest threat for producing a new pandemic strain, other animals - such as swine, which sparked the 2009 H1N1 pandemic - are also candidates (see Arch. Virology: Isolation & Characterization Of H5N1 In Swine - China 2015).
Somewhat further down the list are a number of lesser threats, including farmed mink, dogs, and foxes.
While H9N2 is regarded as having only moderate pandemic potential on its own (see CDC IRAT score), it more than makes up for that by its promiscuity - lending its internal genes to a long list of successful and dangerous HPAI & LPAI viruses, including H5N8, H5N6, and H7N9 (see graphic below).

H7N9 Genetic Structure - Credit Eurosurveillance

All of which serves as prelude to a short communications published last week in Transboundary and Emerging Diseases that characterizes two H9N2 viruses isolated from mink in 2014 in China.

One isolate caused no signs of illness in mice, while the other carried a mammalian adaptation (701N in PB2 protein) that  substantially increased its virulence in mice.  First the abstract (the full report is behind a paywall), then I'll return with more.

H9N2 influenza virus isolated from minks has enhanced virulence in mice
Xue R1, Tian Y1,2,3, Hou T2, Bao D2, Chen H2, Teng Q2, Yang J2, Li X2, Wang G4, Li Z2, Liu Q2.

First published: 14 January 2018Full publication history
DOI: 10.1111/tbed.12805 View/save citation


H9N2 is one of the major subtypes of influenza virus circulating in poultry in China, which has a wide host range from bird to mammals. Two H9N2 viruses were isolated from one mink farm in 2014. Phylogenetic analysis showed that internal genes of the H9N2 viruses have close relationship with those of H7N9 viruses.
Interestingly, two H9N2 were separated in phylogenetic trees, indicating that they are introduced to this mink farm in two independent events.
And further mice studies showed that one H9N2 caused obvious weight loss and 20% mortality in infected mice, while another virus did not cause any clinical sign in mice infected at the same dose.
Genetic analysis indicated that the virulent H9N2 contain a natural mutation at 701N in PB2 protein, which was reported to contribute to mammalian adaptation. However, such substitution is absent in the H9N2 avirulent to mice.
Circulation of H9N2 in mink may drive the virus to adapt mammals; continual surveillance of influenza virus in mink was warranted.

This 701N amino acid host adaptation is one of several we've been watching closely for several years in the evolution of H7N9 in China. Last October, in Cell Research: Another Cautionary H7N9 Study Out Of China, we looked at a study which warned of `alarming mutations' they saw occurring across an array of H7N9 viruses in China.

Mutations that can not only change LPAI H7N9 viruses into highly pathogenic ones, but that can also potentially make them a greater human pandemic threat.

An excerpt from the study by Hualan Chen et al.H7N9 virulent mutants detected in chickens in China pose an increased threat to humans - follows:
Importantly, some H7N9 viruses obtained an insertion of four amino acids in their hemagglutinin (HA) cleavage site and were lethal in chickens. The index strain was not lethal in mice or ferrets, but readily obtained the 627K or 701N mutation in its PB2 segment upon replication in ferrets, causing it to become highly lethal in mice and ferrets and to be transmitted efficiently in ferrets by respiratory droplet.
H7N9 viruses bearing the HA insertion and PB2 627K mutation have been detected in humans in China. Our study indicates that the new H7N9 mutants are lethal to chickens and pose an increased threat to human health, and thus highlights the need to control and eradicate the H7N9 viruses to prevent a possible pandemic.
Going back to 2014, in PLoS Path: Genetics, Receptor Binding, and Transmissibility Of Avian H9N2, we saw similar changes in the PB2 segment of the H9N2 virus when passaged through ferrets.
Perhaps most concerning, of 35 H9N2 viruses tested, all bound preferentially to alpha 2,6 receptor cells -  the type commonly found in the human upper respiratory tract - rather than to alpha 2,3 receptor cells which are found in the gastrointestinal tract of birds.
While this 701N mutation isn't new, finding it naturally occurring in a mink farm in China is another indication that H9N2 viruses are slowly accruing mammalian adaptations over time. 
The H9N2 virus is currently viewed as posing far less of a public health threat than H7N9 or H5N6, but its ability to readily lend its internal genes to other subtypes makes any move towards enhanced virulence or transmissibility something we need to watch. 
For more on the impact of this 701D mutation, you may wish to revisit:
Science: H7N9 Transmissibility Study In Ferrets

Sunday, January 21, 2018

Russia As An Outlier in This Year's Flu Epidemic

Epi Week 2 - 2018


While the United States, Western Europe, and Asia are all dealing with a moderately severe-to-severe flu season, one usually hard-hit region of the world has so far gotten a pass this winter; Russia.

Russia - which often reports severe winter flu seasons even when the rest of the world has only mild or moderate flu - has yet to reach their epidemic threshold this winter - coming closest (under by 1.4%) in early December (week 51).

As we saw two weeks ago in Eurosurveillance: Changes In Timing Of Influenza Epidemics - WHO European Region 1996-2016, over the past 2 decades Russia's flu seasons have tended to peak earlier with each passing year.  
There is still time, however, for another late season flu surge in Russia.
While flu activity is up slightly this week over last, the latest surveillance report from the Russian Research Institute of Influenza, shows a remarkably mild flu season for January.  

Week 08.01.2018-14.01.2018

Influenza and ARI morbidity data

Epidemiological data show increase of influenza and other ARI activity in Russia in comparison with previous week. The nationwide ILI & ARI morbidity level (51.4 per 10 000 of population) was lower than the new national baseline (calculated in country) for 2017-2018 season (72.6) by 29.2%.

ILI and ARI epidemic thresholds were exceeded in 12 of 61 cities collaborating with two WHO NICs in Russia.
Cumulative number of diagnosed influenza cases
Cumulative results of influenza laboratory diagnosis by different tests were submitted by 51 RBLs and two WHO NICs. According to these data as a result of 1668 patients investigation the overall proportion of respiratory samples positive for influenza was estimated as 2.8%, including 0.5% for influenza A(H1N1)pdm09 virus, 1.3% for influenza A(H3N2) virus, 0.06% for influenza type A virus and 0.9% for influenza type B virus. 



Influenza and ARI morbidity data.  Increased influenza and other ARI activity was registered during the week 02.2018 in traditional surveillance system in Russia. The nationwide ILI & ARI morbidity level (51.4 per 10 000 of population) was lower than the national baseline by 29.2%.

Etiology of ILI & ARI morbidity. The overall proportion of respiratory samples tested positive for influenza  was estimated as 2.8%, including 0.5% for influenza A(H1N1)pdm09 virus, 1.3% for influenza A(H3N2) virus, 0.06% for influenza A virus and 0.9% for influenza type B virus. Percent of positive ARI cases of non-influenza etiology (PIV, adeno- and RSV) was estimated as 22.9% of investigated patients by IFA and 19.2% by PCR. 

Antigenic characterization. 7 influenza viruses were characterized antigenically including 5 influenza A(H3N2) strains and 2 influenza type B strains. All influenza A(H3N2) strains were related to influenza A/Hong Kong/4801/2014 virus. All influenza type B strains were belonged to Yamagata line and were like B/Phuket/3073/2013 reference virus.

Genetic characterizationOne influenza A(H3N2) virus was characterized in Saint-Petersburg NIC. Virus belonged to genetic subgroup 3C.2a1 and was like A/Bolzano/07/2016 reference virus. 4 influenza A(H3N2) strains from clinical samples were characterized in Saint-Petersburg NIC. Viruses belonged to genetic subgroup 3C.2a and were like A/Hong Kong/4801/2014 reference virus.

In sentinel surveillance system clinical samples from 87 SARI and ILI/ARI patients were investigated by rRT-PCR. 5 influenza cases were detected among SARI patients, including 1 influenza A(H1N1)pdm09 case, 3 influenza A(H3N2) cases and 1 influenza B case. Among ILI/ARI patients 5 influenza cases were detected, including 1 influenza A(H1N1)pdm09 case, 1 influenza A(H3N2) case and 3 influenza B cases.

This week's weekly (translated) summary from  Rospotrebnadzor reflects the low incidence of flu, along with high (46.6%) vaccination rate - a product of a massive campaign that began two years ago - for the current flu season.

On the situation on the incidence of influenza and acute respiratory viral infection and the course of immunization of the population in the Russian Federation


According to the WHO EURO in the European region recorded growth of influenza caused by influenza virus subtypes A (H3N2) and type B. +
At week 02 (08.01.2018-14.01.2018) in the Russian Federation there is a low incidence of influenza and SARS.
By the total population exceeding the weekly epidemic threshold incidence of SARS and influenza reported in 3 of the Russian Federation. Excess epidporoga the central city without exceeding epidporoga on the subject of the Russian Federation, recorded in 2 cities of Russian Federation.
Among children in age group of 0-2 years week thresholds of disease epidemic of SARS and influenza are exceeded in 5 Russian regions, among children in the age group 3-6 years - in 8 regions of Russia, among children in the age group 7-14 - in 6 regions of Russia, among people older than 15 years - in 3 of the Russian Federation.
Laboratory examined the reporting week, more than 3.3 thousand people in the 57 -. E cases of influenza A viruses are found in 32 - x - influenza B viruses
In the structure of positive findings parainfluenza viruses accounted for 16%, adenoviruses - 17%, RS viruses - 30%, other viruses are not influenza etiology - 35%. The proportion of influenza viruses in the structure of the positive findings was 10%.
Rospotrebnadzor continues to monitor the progress of immunization against influenza.
On 12/01/2018 at the expense of the federal budget vaccinated more than 17 million. Children (99.9% of the planned number) and more than 40.6 million. Adults (99.9%), in Vol. H. The more than 174 thousand. Pregnant women
From other sources vaccinated 8.1 million people, including through employer -. 6.6 million people..

Summary vaccinated more than 67.3 million. People (46.6% of the population).
The situation is under the control of Rospotrebnadzor.

All of which proves, once again, how fickle and unpredictable seasonal flu can be.

Saudi MOH: 3 New MERS Cases


Daily MERS-CoV reporting from the Saudi MOH continues to be a bit erratic, with updates sometimes posted belatedly, and the English language page occasionally missing reports that are posted on the Arabic page. 
Six days ago, in Saudi MOH Reports 1 New MERS Case & 3 Deaths, I reported on an update for January 13th that appeared on the Arabic list, but not on the English list. That data remains absent on the English language report.

Today the Arabic list shows 3 more MERS cases over three days (18th, 19th, 20th) while the English language list only shows 2 cases (18th & 20th).  It is possible this third case will be added to the English side in the next couple of days.
In any event, between the two lists we have 3 more cases, bringing January's reported total to 16 cases and 11 deaths.
The first case, reported yesterday, is of a 60 y.o. female in critical condition from Al Quryat, is dated the 18th,  and is listed as a primary case (no listed risk exposure).
The second case, dated the 20th on the English list - is dated the 19th on the Arabic list.  This one is a 58 y.o. male from Najran - also a primary case with no risk exposure - listed in stable condition.

The Arabic report for the 20th also appears to be a primary case from near Buraidah.  Since it is in graphic form, translation software won't decipher the details.

Although reports were slow during the month of December, we've seen an uptick in cases since the first of the year.  Of the 16 cases we are aware of in 2018, 3 have been linked to recent camel exposure, 12 are primary (community acquired), and 1 was a secondary HCW exposure.

Exactly how these community acquired cases arise remains a bit of a mystery, although sporadic community transmission from mildly ill or asymptomatic carriers is considered a possibility.
We saw a 2016 study (see EID Journal: Estimation of Severe MERS Cases in the Middle East, 2012–2016) suggesting that as much as 60% severe of Saudi MERS cases go undiagnosed. A 2013 study published in The Lancet Infectious Diseases, that estimated for every case identified, there are likely 5 to 10 that go undetected.
The last WHO EMRO MERS report was for the month of  November, while the last WHO GAR update on MERS was published on December 19th, but only current to December 8th.

Despite this recent uptick, and gaps in the data, the good news is we've seen no signs of any sustained or efficient transmission of the MERS virus outside of health care facilities.
That said, there have been some signs suggesting the MERS virus has gotten a little better at transmitting in the community (see Study: A Pandemic Risk Assessment Of MERS-CoV In Saudi Arabia).
So we keep watch on these reports for any signs that the status quo has changed.

Friday, January 19, 2018

CDC FluView Week #2 - Flu Still Rising


Although there were hopes expressed last week that influenza was beginning to plateau across the nation, today's FluView report shows another hefty increase in outpatient visits for ILI (Influenza-like Illness), and cumulative hospitalizations (all ages) have jumped by nearly 50% (22.7 to 31.5) since last week.

Last week the P&I mortality rate (which lags other data) was at the epidemic threshold of 7.0% for week 51, while this weeks report has it at 8.2% (see below) - well above the epidemic threshold of 7.1% for week 52.

P&I Mortality is a notoriously trailing indicator, and these numbers are subject to revision,  as severely ill patients may survive for days or weeks before succumbing and there are often delays in reporting adult flu deaths.

Sadly, another 10 pediatric flu deaths are reported for week 2. While nationally reportable, these numbers likely only capture 1/2 to 1/3rd of the pediatric flu deaths each year, and we often see belated reporting in this category as well.

 This week's summary from a much longer, and far more detailed report:
2017-2018 Influenza Season Week 2 ending January 13, 2018

All data are preliminary and may change as more reports are received.

During week 2 (January 7-13, 2018), influenza activity increased in the United States.
  • Viral Surveillance: The most frequently identified influenza virus subtype reported by public health laboratories during week 2 was influenza A(H3). The percentage of respiratory specimens testing positive for influenza in clinical laboratories increased.
  • Pneumonia and Influenza Mortality: The proportion of deaths attributed to pneumonia and influenza (P&I) was above the system-specific epidemic threshold in the National Center for Health Statistics (NCHS) Mortality Surveillance System.
  • Influenza-associated Pediatric Deaths: Ten influenza-associated pediatric deaths were reported
  • Influenza-associated Hospitalizations: A cumulative rate of 31.5 laboratory-confirmed influenza-associated hospitalizations per 100,000 population was reported.
  • Outpatient Illness Surveillance:The proportion of outpatient visits for influenza-like illness (ILI) was 6.3%, which is above the national baseline of 2.2%. All 10 regions reported ILI at or above region-specific baseline levels. New York City, Puerto Rico, and 32 states experienced high ILI activity; 9 states experienced moderate ILI activity; the District of Columbia and six states experienced low ILI activity; and three states experienced minimal ILI activity.
  • Geographic Spread of Influenza:The geographic spread of influenza in Puerto Rico and 49 states was reported as widespread; Guam reported regional activity; the District of Columbia and one state reported local activity; and the U.S. Virgin Islands reported sporadic activity.

There are reports from some parts of the country that the intensity of flu may be starting to wane.  Even so, there is like another 6 to 10 weeks of flu activity ahead, and the potential for seeing a `second wave' of influenza B or H1N1 later in the spring.

PNAS: Infectious Virus Exhaled In Breath Of Symptomatic Seasonal Flu Cases

Youtube Video (no sound)


Last weekend, in his Virology Down Under blog, Dr. Ian Mackay took a long look at the ways humans shed and spread influenza viruses (see Influenza virus transmission: with or without symptoms, you’re dropping Flu virus). It is an excellent review, well worth reading in its entirety,
Ian looked at both large droplet and fine aerosol transmission from coughing, sneezing and simply just breathing - along with fomite contamination - even from asymptomatic carriers
 While viral RNA had been detected simply from the exhalation of flu victims, Ian cautioned:
Viruses were not able to be grown in culture, or culture was not used in these studies and this is a limitation because we can’t say with certainty that viruses were breathed out during such studies could infect a susceptible person; we don’t know if the positive results mean infectious virus was present.
This is a topic I wrote about a couple of weeks ago myself, while reviewing a Journal of Infectious Disease study (see  J.I.D.: Asymptomatic Summertime Shedding Of Respiratory Viruses).
Well science marches on, and a new study published yesterday in the Journal PNAS (Proceedings of the National Academy of Science) provides additional evidence for, and gives considerable more weight to, the idea that flu carriers exhale substantial quantities of infectious influenza virus
Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community

Jing Yana,b, Michael Granthama,1, Jovan Pantelica,2, P. Jacob Bueno de Mesquitaa, Barbara Alberta, Fengjie Liua,3, Sheryl Ehrmanb,4, Donald K. Miltona,5, EMIT Consortium6


Lack of human data on influenza virus aerosol shedding fuels debate over the importance of airborne transmission. We provide overwhelming evidence that humans generate infectious aerosols and quantitative data to improve mathematical models of transmission and public health interventions.
We show that sneezing is rare and not important for—and that coughing is not required for—influenza virus aerosolization. Our findings, that upper and lower airway infection are independent and that fine-particle exhaled aerosols reflect infection in the lung, opened a pathway for a deeper understanding of the human biology of influenza infection and transmission. Our observation of an association between repeated vaccination and increased viral aerosol generation demonstrated the power of our method, but needs confirmation.


Little is known about the amount and infectiousness of influenza virus shed into exhaled breath. This contributes to uncertainty about the importance of airborne influenza transmission. 

We screened 355 symptomatic volunteers with acute respiratory illness and report 142 cases with confirmed influenza infection who provided 218 paired nasopharyngeal (NP) and 30-minute breath samples (coarse >5-µm and fine ≤5-µm fractions) on days 1–3 after symptom onset. We assessed viral RNA copy number for all samples and cultured NP swabs and fine aerosols. 

We recovered infectious virus from 52 (39%) of the fine aerosols and 150 (89%) of the NP swabs with valid cultures. The geometric mean RNA copy numbers were 3.8 × 104/30-minutes fine-, 1.2 × 104/30-minutes coarse-aerosol sample, and 8.2 × 108 per NP swab. Fine- and coarse-aerosol viral RNA were positively associated with body mass index and number of coughs and negatively associated with increasing days since symptom onset in adjusted models.
Fine-aerosol viral RNA was also positively associated with having influenza vaccination for both the current and prior season. NP swab viral RNA was positively associated with upper respiratory symptoms and negatively associated with age but was not significantly associated with fine- or coarse-aerosol viral RNA or their predictors. Sneezing was rare, and sneezing and coughing were not necessary for infectious aerosol generation. Our observations suggest that influenza infection in the upper and lower airways are compartmentalized and independent.
         (Continue . . . )

 The full, open access study can be read here, and it contains  a number of gems. 
  • Men shed influenza viruses in greater quantity than women through fine aerosols.
  • But women cough more frequently
  • Most surprisingly, they observed `6.3 (95% CI 1.9–21.5) times more aerosol shedding among cases with vaccination in the current and previous season compared with having no vaccination in those two seasons.'
This is the first detection of a possible vaccination connection and must be verified by additional studies, and then perhaps a reason can be attached.

In addition to releasing a short video, the University of Maryland School of Public Health published the following press release (see excerpt below) on this new study.  You'll also find a pretty good picture of the Gesundheit II machine they used in their study on their site.

Flu may be spread just by breathing, new study shows; coughing and sneezing not required

January 18, 2018
It is easier to spread the influenza virus (flu) than previously thought, according to a new University of Maryland-led study released today. People commonly believe that they can catch the flu by exposure to droplets from an infected person’s coughs or sneezes or by touching contaminated surfaces. But, new information about flu transmission reveals that we may pass the flu to others just by breathing.


“We found that flu cases contaminated the air around them with infectious virus just by breathing, without coughing or sneezing,” explained Dr. Donald Milton, M.D., MPH, professor of environmental health in the University of Maryland School of Public Health and lead researcher of this study. “People with flu generate infectious aerosols (tiny droplets that stay suspended in the air for a long time) even when they are not coughing, and especially during the first days of illness. So when someone is coming down with influenza, they should go home and not remain in the workplace and infect others.”

Researchers from the University of Maryland, San Jose State University, Missouri Western State University and University of California, Berkeley contributed to this study funded by the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health.

(Continue . . . )

All of these tests were conducted on symptomatic, flu positive cases and illustrate why it is important to stay home when you are sick, even if you aren't coughing or sneezing up a storm.
What may be a `mild flu' for you could easily be deadly for someone else.
As we've discussed previously, people can spread influenza during the 24 hours before symptoms appear - or may have such minor symptoms as to not realize they are ill - (see PLoS One: Influenza Viral Shedding & Asymptomatic Infections).

While asymptomatic spread still provides a loophole for the virus to spread, this study lends  additional support to the idea of having and wearing simple surgical masks when you are home with the flu and are around other family members - even if you aren't coughing or sneezing. 

But most of all, this study shows us just how easily influenza can spread in the community, even from someone who doesn't appear all that sick.