H5N1

A mathematical model for zoonotic disease transmission

Via Vaccine News Daily: Scientists develop mathematical model for zoonotic disease transmission. Excerpt:

Scientists from the United Kingdom and the United States recently developed a new mathematical disease model that can produce transmissibility estimates for emerging zoonotic diseases like the swine flu. 

Simon Cauchemez and colleagues from Imperial College London and the U.S. Centers for Disease Control and Prevention developed the tool to better evaluate the potential pandemic threat posed by swine flu. Previously, transmissibility estimates were derived from detailed outbreak investigations which can be resource intensive and subject to bias, MedicalNewsToday.com reports. 

In a study published in PLOS Medicine, the authors developed a method to use limited data to derive unbiased estimates of transmissibility. The mathematical model uses data from standard case investigations, including the proportion of cases infected by the natural reservoir, to estimate the pandemic potential of a zoonotic virus. The scientists applied the new approach to assess human-to-human transmissibility of H1N1v, H1N2v and H3N2v, Nipah virus and Vibrio cholerae. 

The study demonstrated the applicability of the novel approach during zoonotic and certain non-zoonotic outbreaks in estimating the number of individuals infected by a case.

Influenza alarm sounds across Korea

Via The Jeju Weekly: Influenza alarm sounds across Korea. Excerpt:

The Korea Center for Disease Control and Prevention (KCDC) issued its influenza monitoring results last week. These show the rate of influenza at 4.8 per 1000 people, which is above the standard rate of 4 per 1000. The influenza watch alarm was thus sounded on Jan. 17. 

The rate of occurrence has rapidly increased over the last three years, and its term lasts for six to eight weeks. According to KCDC, during times of peak occurrence, people are five times more likely to contract influenza than at other times. 

The influenza detection rate was 17.6 percent between Jan. 6-12, having increased dramatically from just 2.5% in the period Dec. 16-22, 2012. A total of 109 cases were detected, with strains A/H1N1pdm09, A/H3N2 and B type accounting for 63, 43 and three cases, respectively.   

The regions of Incheon, Gwangju, Gangwon and Seoul show higher rates than elsewhere and the most at-risk age group is 20 to 49 years of age, having an infection rate 26.2 percent higher than any other group. 

Children aged under seven ranked as the second most at-risk group, with an infection rate 24.3 percent higher than others. Over 65s are the least affected group, with only a 5.7 percent infection rate.

Swine flu evolves under the radar

Via New Scientist, more on the paper by Webster et al.: Threatwatch: Swine flu evolves under the radar. Click through for the full report and a lot of links. Excerpt:

Two weeks ago, a woman died after catching flu from a pig at an agricultural fair in Ohio. Now a new study has found that pigs in Korea are harbouring a similar strain of flu that is more lethal and contagious – at least in animals – than the experimental bird flu that caused intense controversy last year. 

Robert Webster and colleagues at St. Jude Children's Research Hospital in Memphis, Tennessee, put an H1N2 flu virus, from the lungs of a pig slaughtered in South Korea in 2009, into the noses and windpipes of three ferrets. All the animals died, which is worrying, as ferrets catch and develop flu in a similar way to humans. 

What's more, the virus was transmitted via airborne droplets to three ferrets in nearby cages, killing two of them. 

In passing between the ferrets, the H1N2 acquired two mutations that made it more contagious and more virulent in the animals. The mutated version also grew faster than the original pig virus in cells cultured from the human nose and lung, and in fresh samples of human alveoli. In an intact lung, this alveolar growth could cause lethal pneumonia. 

This increase in virulence and transmissibility remained when the team created a virus identical to the original H1N2 but with those two mutations added. That makes this virus apparently more dangerous than the controversial H5N1 bird flu created last year by a group in the Netherlands. 

Initially, that virus was only deadly to ferrets when placed in their windpipes, and it did not transmit between them. However, when it was artificially passed from one ferret to another, it mutated and became transmissible. Although it was still lethal in the ferrets' tracheas, it did not kill when they merely inhaled it. 

The work provoked a bitter dispute over whether researchers should create such dangerous viruses or publish the procedures. Similar research on H5N1 remains blocked under a precautionary moratorium but no such restrictions apply to H1N2. 

"This is important research about something that is already going on in nature," says Tony Fauci, head of the US National Institute for Allergy and Infectious Disease in Bethesda, Maryland, which funded the work.

The continuing threat of triple-reassortant swine viruses

Via PNAS, a report contributed by Dr. Robert G. Webster: Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses. The abstract:

Efficient worldwide swine surveillance for influenza A viruses is urgently needed; the emergence of a novel reassortant pandemic H1N1 (pH1N1) virus in 2009 demonstrated that swine can be the direct source of pandemic influenza and that the pandemic potential of viruses prevalent in swine populations must be monitored. 

We used the ferret model to assess the pathogenicity and transmissibility of predominant Korean triple-reassortant swine (TRSw) H1N2 and H3N2 influenza viruses genetically related to North American strains. 

Although most of the TRSw viruses were moderately pathogenic, one [A/Swine/Korea/1204/2009; Sw/1204 (H1N2)] was virulent in ferrets, causing death within 10 d of inoculation, and was efficiently transmitted to naive contact ferrets via respiratory droplets. 

Although molecular analysis did not reveal known virulence markers, the Sw/1204 virus acquired mutations in hemagglutinin (HA) (Asp-225-Gly) and neuraminidase (NA) (Ser-315-Asn) proteins during the single ferret passage. The contact-Sw/1204 virus became more virulent in mice, replicated efficiently in vitro, extensively infected human lung tissues ex vivo, and maintained its ability to replicate and transmit in swine. 

Reverse-genetics studies further indicated that the HA225G and NA315N substitutions contributed substantially in altering virulence and transmissibility. 

These findings support the continuing threat of some field TRSw viruses to human and animal health, reviving concerns on the capacity of pigs to create future pandemic viruses. 

Apart from warranting continued and enhanced global surveillance, this study also provides evidence on the emerging roles of HA225G and NA315N as potential virulence markers in mammals.

Ed Yong has a good item on this report at Nature News & Comment. 

US: CDC confirms two human infections with novel influenza viruses

Thanks to Lisa Schnirring at CIDRAP for sending a heads-up on this CDC report: CDC confirms two human infections with novel influenza viruses. Note the plural. Excerpt:

CDC has confirmed two cases of human infection with two different novel influenza A viruses in different states. Both patients have fully recovered. While the viruses infecting both patients have been found in U.S. swine and some of the prior human infections with these viruses have been associated with direct or close swine contact, there are no reports of direct or close contact with swine prior to illness onset in either of these cases. 

Laboratory testing at CDC has confirmed that both novel viruses are susceptible to the antiviral medications oseltamivir (Tamiflu®) and zanamivir (Relenza®). 

West Virginia 

One case of human infection with a novel influenza virus was reported by West Virginia and involves infection of a child with the novel influenza A (H3N2) virus with genes from swine, human, and avian lineages with the M gene from the 2009 H1N1 virus that was first identified in August 2011. Ten prior human infections with this virus in four other states have been confirmed. These occurred in Indiana (2), Pennsylvania (3), Maine (2), and Iowa (3). 

These novel influenza A (H3N2) viruses are substantially different from currently circulating seasonal (human) influenza A (H3N2) viruses, but are distantly related to human influenza viruses that circulated among people in the 1990s. For that reason, some adults may have some residual immunity against this virus. This might help explain why 10 of the 11 cases that have been detected have occurred in children. 

Most human infections with viruses that circulate in swine (but not humans) have been associated with swine exposure, but limited human-to-human transmission associated with these viruses is thought to have occurred as well, most recently in Iowa. 

While an investigation is ongoing in West Virginia, no direct or indirect contact with swine has been reported, implying that limited human-to-human transmission of this virus may have occurred again. 

No ongoing community transmission of this virus has been detected in the United States. However, CDC is taking this situation very seriously. Surveillance surrounding reported cases is being further enhanced and, as a precaution, a vaccine virus has been developed and provided to manufacturers for them to begin vaccine production should that become necessary. 

Minnesota 

The other case of novel influenza A virus infection was reported by Minnesota, and is associated with a different influenza virus; an influenza A (H1N2) virus that circulates in swine  in the United States, but does not normally infect or cause illness in humans. This case also was in a child. 

This is only the second case of human infection with this novel influenza A (H1N2) virus reported to CDC since novel influenza virus infections became nationally notifiable in 2007. The first such case was identified in Michigan in 2007. 

By some characteristics, this H1N2 virus is close to human influenza A (H1N1) viruses called “A/New Caledonia /20/99-like,” which circulated and caused illness among people as recently as 2007. As a result, people who were exposed to A/New Caledonia/20/99-like viruses may have some existing immune protection against the virus detected in Minnesota. 

Again, no direct or indirect contact with swine has been reported with this case, implying that limited human-to-human transmission may have occurred in this instance as well.