H5N1

WHO: Influenza A(H1N2)v-United States of America

A WHO DON: Influenza A(H1N2)v-United States of America. Excerpt:

Situation at a glance:  

On 4 August 2023, the United States International Health Regulations (IHR) National Focal Point informed PAHO/WHO of a human infection with a novel influenza A(H1N2) variant virus identified in the State of Michigan. This was confirmed by Reverse Transcription Polymerase Chain Reaction at the United States (US) Centers for Disease Control and Prevention (CDC) on August 2.  

The case was not hospitalized and is recovering from the illness. Investigations by local public health officials identified swine exposure by the patient at an agricultural fair.  

Additional public health response efforts including enhanced surveillance for cases is undergoing. Given the potential impact on public health, human infections with these viruses need to be monitored closely. In this event, there was no reported evidence of sustained human-to-human transmission, the illness was mild and no further influenza variant virus transmission in the community has been identified.  

Description of the case:  

On 4 August 2023, the United States IHR National Focal Point informed PAHO/WHO of a human infection with a novel influenza A(H1N2) variant virus identified in the State of Michigan and confirmed by the US CDC.   

According to the report, the case is under 18 years old, with no comorbidities, resident in the State of Michigan, who developed respiratory illness on 29 July 2023. The case presented with fever, cough, sore throat, muscle aches, headache, shortness of breath, diarrhea, nausea, dizziness, and lethargy. On 29 July, the case sought medical care at an emergency department, and an upper respiratory tract specimen was collected on 30 July. The specimen tested positive for influenza A virus on the same day. On 1 August, the patient received influenza antiviral treatment (Oseltamivir).  

On 31 July, the specimen was tested at the Michigan Department of Health and Human Services (MDHHS), and RT-PCR results were positive for influenza A virus but lacked reactivity with diagnostic tests for contemporary human influenza viruses representing either (H1) pdm09 or (H3) subtypes. The specimen was then sent to the US CDC for further testing and received on 2 August. On the same day, RT-PCR analysis of the specimen indicated an influenza A(H1N2) variant (v) virus. The virus was isolated and subsequent analysis including genetic sequencing is underway.  

The case was not hospitalized. Investigation by local public health officials identified swine exposure by the patient at an agricultural fair, that took place between 23 and 29 July, within 10 days prior to illness onset. Additional investigation did not identify respiratory illness in any of the patient’s close contacts or household contacts. No additional cases were identified related to this agriculture fair. No person-to-person transmission of influenza A(H1N2)v virus associated with this case has been identified. No additional cases of human infection with A(H1N2)v virus have been identified as of 10 August 2023.  

This is the first influenza A(H1N2)v virus infection identified in the United States this year. Since 2005, there have been 512 influenza A variant virus infections (all subtypes), including 37 (human infections with influenza A (H1N2)v viruses reported in the United States.

ECDC: Influenza virus characterisation, September 2019

ECDC has published Influenza virus characterisation, September 2019. The executive summary:

Since the July 2019 characterisation report1, a further three shipments of influenza-positive specimens from EU/EEA countries were received at the London WHO CC, the Francis Crick Worldwide Influenza Centre (WIC). A total of 1 511 virus specimens, with collection dates after 31 August 2018, have been received.  

The 85 A(H1N1)pdm09 test viruses characterised antigenically since the last report showed equivalent good reactivity with antisera raised against both the A/Michigan/45/2015 2018–19 vaccine virus and the A/Brisbane/02/2018 2019–20 vaccine virus. The 613 test viruses with collection dates from week 40/2018 genetically characterised at the WIC, including two H1N2 reassortants, have all fallen in subclade 6B.1A, defined by S74R, S164T and I295V HA1 substitutions; 564 of these viruses also have HA1 S183P substitution, often with additional substitutions in HA1 and/or HA2.  

Since the last report, 37 A(H3N2) viruses successfully recovered had sufficient HA titre to allow antigenic characterisation by HI assay in the presence of oseltamivir; all were poorly recognised by antisera raised against the vaccine virus, egg propagated A/Singapore/INFIMH-16-0019/2016. Of the 505 viruses with collection dates from week 40/2018 genetically characterised at the WIC, 399 were clade 3C.2a (with 43 3C.2a2, 17 3C.2a3, eight 3C.2a4 and 331 3C.2a1b); 106 were clade 3C.3a.  

Ten B/Victoria-lineage viruses have been characterised in this reporting period. All recent viruses have HA1 amino acid substitutions of I117V, N129D, and V146I compared to B/Brisbane/60/2008 (clade 1A), a previous vaccine virus. Groups of viruses defined by deletions of two (Δ162-163, 1A(Δ2)) or three (Δ162-164, 1A(Δ3)) amino acids in HA1 have emerged, with the Δ162-164 group having subgroups of Asian and African origin. These virus groups are antigenically distinguishable by HI assay. Of 20 viruses from EU/EEA countries this season that have been characterised genetically, one has been clade 1A, two 1A(Δ2) and 17 1A(Δ3) (16 African and one Asian subgroup).   

Nine B/Yamagata-lineage viruses have been characterised antigenically in this reporting period, giving a total to 23 for the 2018–19 season. All have HA genes that encode HA1 amino acid substitutions of L172Q and M251V compared to, but remain antigenically similar to, the vaccine virus B/Phuket/3073/2013 (clade 3) recommended for use in quadrivalent vaccines for the next northern hemisphere influenza season. 

Flu News Europe, week 3

Flu News Europe has published its week 3 update. Excerpt:

Week 3/2019 (14-20 January 2019) 

• Influenza activity continued to increase in the European Region. Samples collected from individuals presenting with ILI or ARI to sentinel primary health care sites yielded an influenza positivity rate of 48.8%. 

• Influenza type A virus detections dominated with A(H1N1)pdm09 viruses being more prevalent than A(H3N2). Very few influenza B viruses were detected. 

• Data from the 23 Member States and areas reporting to the EuroMOMO project indicated that generally all-cause mortality was at expected levels for this time of year, but a few countries observed some excess mortality in elderly populations. 

• In Sweden, a seasonal reassortant A(H1N2) influenza virus was detected in a specimen collected at the end of December from an adult. Preliminary whole genome sequence analysis suggests that the virus is a seasonal reassortant containing HA and NS, NP, PA, PB1 and PB2 genes of human seasonal A(H1N1)pdm09 influenza virus and NA genes of human seasonal A(H3N2) influenza virus. No increase in virulence is expected compared to seasonal influenza strains. Further analysis is being conducted by the WHO Collaborating Center on influenza.  More information can be found here. 

2018/19 season overview  

• Influenza activity in Europe is increasing, with both subtypes of influenza A viruses circulating widely. Countries should continue to encourage vaccination. In addition, countries are encouraged to use antivirals in accordance with national guidelines. 

• In general, current influenza vaccines tend to work better against influenza A(H1N1)pdm09 and influenza B viruses than against influenza A(H3N2) viruses. Preliminary results from Canada where the predominate circulating viruses are influenza A(H1N1)pdm09 viruses, indicate good vaccine effectiveness. 

Case of seasonal reassortant A(H1N2) influenza virus infection, the Netherlands, March 2018

Via Eurosurveillance: Case of seasonal reassortant A(H1N2) influenza virus infection, the Netherlands, March 2018. The discussion section:

Human seasonal reassortant A(H1N2) influenza viruses harbouring the H1 from human seasonal A(H1N1) and seven segments from human seasonal influenza A(H3N2) virus have been detected before during an outbreak in China in 1988/89 and from 2000 to 2003 starting in Asia and spreading worldwide. However, the latter failed to co-circulate in the long term or to replace the A(H1N1) or A(H3N2) influenza viruses that were in circulation at the time. 

A sporadic case of seasonal reassortant A(H1N2) influenza virus harbouring the H1 from human influenza A(H1N1)pdm09 virus and the other seven segments from human seasonal influenza A(H3N2) virus was detected in India during the influenza pandemic in 2009. In a mixture of reassortants generated by in vitro coinfection with seasonal A(H1N1)pdm09 and A(H3N2) influenza viruses, sporadic virus with the current 2:6 constellation of genome segments was detected. Furthermore, in a transmission experiment with guinea pigs infected with this mixture of reassortant viruses, the influenza A(H1N2) virus with the NS segment from influenza A(H1N1)pdm09 virus was not detected in contact animals. 

In conclusion, this is the first time a seasonal reassortant A(H1N2) influenza virus with HA and NS from influenza A(H1N1)pdm09 virus and the other six segments of influenza A(H3N2) virus is reported in a human natural infection. The patient recovered fully and there is no evidence of extended spreading of the reassortant virus in humans. Published evidence indicates limited capacity for transmission of seasonal reassortant A(H1N2) influenza viruses. However, laboratories, especially national influenza centres, should stay vigilant for reassortant human seasonal influenza viruses with mixed genome segments from A(H1N1)pdm09 and A(H3N2) influenza viruses.

WHO: Human infection with a seasonal reassortant A(H1N2) influenza virus – Netherlands

WHO has published Human infection with a seasonal reassortant A(H1N2) influenza virus – Netherlands. Excerpt:

On 20 March 2018, the National International Health Regulations focal point for the Netherlands notified WHO about a human infected with a new reassortant A(H1N2) of seasonal influenza viruses that was detected in the routine sentinel influenza surveillance for influenza-like illness and other acute respiratory infections in the Netherlands. The patient is a child aged less than two years old, who had onset of symptoms in early March 2018. He was seen by a general practitioner, but did not require hospitalization and has fully recovered. 

The general practitioner who attended to this case participates in the sentinel influenza surveillance network. With permission from the parent accompanying the child, nose and throat swabs were collected for virus detection. 

On 18 March, the Dutch National Influenza Centre (NIC), which is a collaboration of the Erasmus University Medical Center in Rotterdam and the National Institute for Public Health and the Environment (RIVM) in Bilthoven, reported that the patient was confirmed to be infected by an A(H1N2) influenza virus by real-time polymerase chain reaction (RT-PCR). Sanger sequencing of the haemagglutinin (HA) and neuraminidase (NA) genes, and full genome sequencing revealed that the virus is a reassortant A(H1N2) of seasonal influenza viruses, and is made up of genes from currently circulating seasonal influenza virus subtypes A(H1N1)pdm09 (the haemagglutinin [HA] and the nonstructural [NS] protein genes) and A(H3N2) (the rest of the genes).  

The patient had not travelled abroad, was not vaccinated against influenza, did not use influenza antivirals and had no underlying disease. 

Further investigations revealed that the parents had symptoms of (predominantly) gastrointestinal infection in the two weeks preceding onset of disease in the index. No laboratory testing was performed. Contact investigation was extended to the day care center attended by the child before onset of the illness. After the onset of illness, the index case did not attend daycare anymore. According to a post on ProMED, extended contact investigation at the child’s daycare did not reveal any actual disease.  

Other reassortant A(H1N2) viruses of seasonal A(H1N1) and A(H3N2) influenza viruses have been detected in the past e.g. between 2000–2003 (2). However the genetic constellations differed from that of the current virus [i.e. the HA was derived from a seasonal A(H1N1) virus and the other seven genes from seasonal A(H3N2) viruses].

Flu News Europe, week 11

An excerpt from today's Flu News Europe:

Week 11/2018 (12-18 March 2018)

• Influenza viruses continue to circulate widely in the Region with some eastern European countries that have only recently reported increased activity, experiencing a late start to the season with increased circulation of influenza type A viruses. 

• Similar to the previous week, 44% of the individuals sampled from primary healthcare settings tested positive for influenza viruses, despite the peak rate for the Region occurring in week 05/2018. 

• Both influenza virus types A and B were co-circulating with the majority being type B viruses and B/Yamagata continuing to be the dominant lineage. 

• Similar proportions of influenza type A and B viruses were reported in patients admitted to ICU, with the majority of severe cases reported this season being due to influenza type B and occurring in persons above the age of 15 years. 

• A seasonal reassortant A(H1N2) influenza virus consisting of HA and NS genes of human seasonal A(H1N1)pdm09 influenza virus and M, NA, NP, PA, PB1 and PB2 genes of human seasonal A(H3N2) influenza virus was detected in the Netherlands. As the reassortant virus genome contains a mixture of genes from currently circulating seasonal influenza viruses, no increase in virulence is expected. Having similar HA with circulating strains, the current vaccine is expected to offer protection against this reassortant. The neuraminidase showed no evidence for reduced sensitivity to neuraminidase inhibitors. There is no evidence for extensive spread of this A(H1N2) influenza virus.

Novel human-like influenza A viruses circulate in swine in Mexico and Chile

Via PLOS Currents Outbreaks: Novel Human-like Influenza A Viruses Circulate in Swine in Mexico and Chile. The abstract:

Introduction: Further understanding of the genetic diversity and evolution of influenza A viruses circulating in swine (IAV-S) is important for the development of effective vaccines and our knowledge of pandemic threats. Until recently, very little was known of IAV-S diversity in Latin America, owing to a lack of surveillance. 

Methods: To address this gap, we sequenced and conducted a phylogenetic analysis of 69 hemagglutinin (HA) sequences from IAV-S isolates collected in swine in Mexico and Chile during 2010-2014, including the H1N1, H1N2, and H3N2 subtypes. 

Results: Our analysis identified multiple IAV-S lineages that appear to have been circulating undetected in swine for decades, including four novel IAV-S lineages of human seasonal virus origin that have not been previously identified in any swine populations globally. We also found evidence of repeated introductions of pandemic H1N1 viruses from humans into swine in Mexico and Chile since 2009, and incursions of H1 and H3 viruses from North American swine into Mexico. 

Discussion: Overall, our findings indicate that at least 12 genetically distinct HA lineages circulate in Latin American swine herds, only two of which have been found in North American swine herds. Human-to-swine transmission, spatial migration via swine movements, and genomic reassortment are the key evolutionary mechanisms that generate this viral diversity. Additional antigenic characterization and whole-genome sequencing is greatly needed to understand the diversity and independent evolution of IAV-S in Latin America. 

H7N9 and "digital epidemiology"

Via NEJM, a report on Influenza A (H7N9) and the Importance of Digital Epidemiology. It's good to see "digital disease surveillance" recognized as part of the global response to outbreaks. But I am amazed and slightly embarrassed to be described as a "journalist" in the same breath as Helen Branswell, who's one of the very best health journalists in the world. Excerpt:

In this and other outbreaks, digital disease surveillance has supplemented the critical laboratory studies and work in the trenches by public health officials and epidemiologists, by leveraging widespread use of the Internet, mobile phones, and social media. 

Many of these added insights come from the general population, whose access to technology enables rapid information flow. In 2013, there are 6.8 billion cell-phone subscribers; 2.7 billion people are online; and by the end of the year, there will be more than 2 billion mobile broadband subscriptions worldwide. A large percentage of the online population publicly shares information on social media services: in both the United States and China, for example, more than half the population with access to the Internet uses social media services. 

Digital data can be used in at least four ways for studying infectious-disease dynamics. First, they can be used for early detection of disease outbreaks. This capacity was illustrated most recently in China, when a hospital employee uploaded an image of the medical record of a patient with H7N9 infection to Sina Weibo, a popular Chinese social network similar to Twitter. The post was promptly deleted, but it appears to have accelerated the government's acknowledgment of four new cases (see figure, Panel B). More generally, because digital surveillance is not limited by the hierarchies of traditional public health infrastructure, geographic communication barriers, and geopolitical obstacles, it has improved the timeliness of outbreak detection substantially in recent years. 

Second, these data can be used to continuously monitor disease levels. With proper filtering by automated systems (see the Journal's H7N9 HealthMap tracking system [http://healthmap.org/h7n9]), analyst-driven systems (e.g., the Global Public Health Intelligence Network of Canada), vigilant journalists on Twitter (e.g., Crawford Kilian [@Crof] and Helen Branswell [@HelenBranswell]), and crowd-sourced systems (e.g., FluTrackers and ProMED-mail), informal data sources such as news media, e-mail lists, blogs, and social media can complement formal public health surveillance by offering real-time clues to disease dynamics. Internet-based surveillance systems provided important early epidemic intelligence during the 2003 outbreak of severe acute respiratory syndrome (SARS) and the 2009 H1N1 influenza pandemic, enhancing transparency by rapidly publicizing outbreak information.3 

Third, Internet-based data from social media can be used to assess disease-relevant health-related behaviors and sentiments relevant to disease control. During the H1N1 pandemic, sentiments about vaccination extracted from Twitter were shown to correlate well geographically with subsequent vaccination coverage throughout the United States. Such analyses could provide important information to aid in planning and in the distribution of limited resources, as well as improving public health communications efforts. 

Fourth, these data provide researchers with an additional method for examining the period before an outbreak came to light. Despite international agreement that transparency is critical during an outbreak, accusations of delayed reporting are common and can be difficult to dispel. Time-series analysis of the volume of influenza-related searches on the Chinese Web search engine Baidu shows a low level of activity in the months leading up to the first announced H7N9 cases, which suggests that widespread unreported outbreaks were not festering before the announcement.

Venezuela: Government hiding 400,000 H1N1 cases?

Evidently Venezuela's current flu outbreak has triggered the political equivalent of a cytokine storm. Via El Universal, a report datelined Maracaibo:  Diputado Barrientos: "400 mil casos de AH1N1 oculta el Gobierno". [Deputy Barrientos: "Government hiding 400,000 H1N1 cases"] Excerpt, with my translation:

"De las 23 entidades federales del país, la gripe AH1N1 llegó a 20. A pesar de la falta de registros oficiales, sobre todo en casos de muerte, se habla de 40 decesos por la influenza. Por cada fallecido hay nueve mil 900 infectados, lo que ubicado los casos en más de 400 mil en todo el país", afirmó, William Barrientos, diputado a la Asamblea Nacional por el Zulia. 

"Of the country's 23 federal states, H1N1 flu has reached 20. Despite the lack of official records, especially deaths, some 40 persons are said to have died from influenza. For every death there are 9,900 cases, which would put the national total of cases at over 400,000," says William Barrientos, National Assembly deputy for Zulia state.

El legislador rechazó que las autoridades sanitarias no hayan aceptado que se trata de una epidemia, y no de un brote como aseguran. 

The legislator claimed that health authorities have not accepted that they're dealing with an epidemic, and not just the outbreak they claim it to be.

 "No se ha decretado la alerta porque en ese caso, el Gobierno tendría que reconocer que no se establecieron los cercos epidemiológicos de forma adecuada", dijo. 

"They haven't decreed an alert because in that case the government would have to admit that they didn't establish adequate epidemiological barriers," he said.

El parlamentario desmintió a Isabel Iturria, ministra de Salud, quien recientemente aseguró que se habían vacunado a tres millones de personas en todo el país. 

He denied Health Minister Isabel Iturria's recent claim that 3 million persons have been vaccinated nationwide.

"Las campañas de inmunización desde 2010 a 2012 no se cumplieron en su totalidad. Solo 18 % de la población infantil se vacunó en 2011, y 16 % en 2012", denunció. 

"Immunization campaigns from 2010 to 2012 weren't totally completed. Only 18% of the child population was immunized in 2011 and 16% in 2012," he charged.

En el Táchira, Nelsa Contreras, adjunta de epidemiología de la Corporación Regional de Salud, aclaró que no está circulando en el Táchira el virus AH1N5 y, que los únicos virus que están registrados son el AH1N1 y AH3N2.

In Táchira, Nelsa Contreras, adjunct in epidemiologist with the Regional Health Corporation, clarified that the H5N1 virus is not circulating in Táchira, and said the only viruses recorded are H1N1 and H3N2.

We still don't really know the numbers infected in the H1N1 pandemic of 2009, so a case fatality is hard to estimate. But the estimate given by Deputy Barrientos suggests the Venezuelan outbreak is killing only 0.04% of those infected. When the country is also suffering from one of the highest murder rates in the world, H1N1 deaths should be the least of their concerns.

As for having to deny a death from H5N1, that seems like a straight misunderstanding between a doctor and the family of a flu fatality. A confirmed case of human H5N1 anywhere in the western hemisphere would set off alarms worldwide.

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.