Pigs as mixing vessels for novel pandemic influenza viruses

In an article to be published in the journal Microbial Pathogenesis, Chinese researchers report on a 4 year serological surveillance project of Influenza A on pigs farms in  Guangdong, Zhejiang, Fujian, and Yunnan Provinces in Southern China.[1] As the authors note, pigs are believe to be intermediate hosts or mixing vessels of pandemic influenza viruses. Influenza viruses can undergo reassortment in pigs, allowing the virus to adapted to humans and possibly cause a pandemic.

The serological study used haemagglutination inhibition (HI) tests to examine antibodies of H5 and H9 viruses among the samples from pigs. The good news is that the researchers failed to find H5 infections (Clade 2.3.2) within the pig samples. A ressortant H5N1 virus from pigs could easily start the next pandemic. H5 viruses have already infected more than 600 people from numerous countries in the last decade, so an H5N1 pandemic is a serious concern.

The bad news is that the authors found an infection rate of at least 3.7% among the samples from pigs for H9 viruses. H9 viruses also pose a pandemic threat for humans. Another serological study from 2009 in China found that a small percentage of farmers  from Xinjiang Uygur autonomous region and Liaoning province tested positive for H9 viruses.[2] A reassortant pandemic virus  does not have to originate in a pig, it could originate in a human infected with  H9 or H5 viruses.

  

[1] Serological surveillance of H5 and H9 avian influenza A viral infections among pigs in southern China

[2] Serological reports of human infections of H7 and H9 avian influenza viruses in northern China

Confusion abounds over the number and geographic distribution of MERS-CoV cases

Slightly more than 100 cases of Middle East Respiratory Coronavirus  (MERS-CoV) infections have been reported from around the world. Despite these few numbers, the actual count of cases is uncertain as is the geographic distribution of the cases.  The case count varies from 94 to 104 as noted in the table below compiled from several sources. [1,2,3,4] 

A review of these reports indicates that the variability in the counts results from several factors. First, some reports such as those from the World Health Organization (WHO) are not current and up-to-date. The fact that WHO is not stating the count by individual member states indicates uncertainty about how to report the geolocations of individual cases (see discussion below). Second, some agencies such as WHO only count officially confirmed cases, while other case lists seem to include probable and suspected cases as well. Third, compounding the enumeration problem is that sometimes asymptomatic cases that test positive for the disease are not counted as a confirmed case.

As noted in the table, there is a differential assignment of cases by geographic location.  There is general agreement on eight countries where MERS-CoV infections have taken place, France Italy, Jordan, Qatar, Tunisia, Kingdom of Saudi Arabia, United Arab Emirates, and the United Kingdom(see map below). However, The European Centre for Disease Prevention and Control (ECDC) appears to consider the location of treatment rather than where the infection was acquired as the primary geographic location. That is why the two cases that were infected in the Middle East but were treated in Germany are counted as cases from Germany by the ECDC. 

A similar reporting discrepancy of the geolocation of cases occurred for the public information on A(H7N9) cases in the People’s Republic of China earlier this year. In some cases the geographic location of an individual’s residence was reported in one town or province,  even though the individual was infected in a different province. In another case, an infected individual was transported to a health care facility in another province for treatment and the individual was counted as a case in that province rather when the individual was infected.

Public health officials should collaborate to develop formal definitions for assigning a geolocation to an individual case. Should it be based on where the individual was infected, the individual’s place of residence, or where the individual was treated?

Fnally, more than 75% of all of MERS-CoV cases have been reported from the Kingdom of Saudi Arabia. Much of the confusion about the number of cases and number of deaths from this deadly disease could be cleared up if the Ministry of Health in Saudi Arabia was more forthcoming and provided more detailed information about the MERS-CoV cases that are occurring in this country.

[1] ECDC - Communicable disease threats report, 18-24 August 2013, week 34

[2] CDC - Middle East Respiratory Syndrome (MERS)

[3] WHO - Middle East respiratory syndrome coronavirus (MERS-CoV) summary and literature update – as of 13 August 2013

[4] FluTrackers - 2012/2013 Case List of Known Novel Coronavirus Patients By Country

 

A(H7N9) Amantadine and Rimantadine Resistance

As noted by the Center for Disease Control, USA (CDC), although A(H7N9) is not currently spreading human-to-human, the disease is often severe and has a high mortality rate and  there is no current vaccine for A(H7N9) influenza.[1] The only viable option for infected individuals is early treatment with antivirals. The CDC recommends early antiviral treatment with neuraminidase inhibitors, noting that laboratory research indicates that adamantane derivatives will not inhibit replication of A(H7N9) virus.

An article published behind a paywall in Antiviral Therapy by Chinese researchers entitled Inhibition of novel reassortant avian influenza H7N9 virus infection in vitro with three antiviral drugs, oseltamivir, peramivir and favipiravir confirms the CDC recommendations. [2] The authors note that A(H7N9) was resistant to amantadine and remantadine, but was sensitive to two neuraminidase inhibitors, oseltamivir, peramivir, and  the investigational drug, favipiravir (T-705). Notably, favipiravir (T-705)  has previously been suggested as a possible therapeutic agent for another novel avian influenza  -- A(H5N1). [3]

[1] Interim Guidance on the Use of Antiviral Agents for Treatment of Human Infections with Avian Influenza A (H7N9)

[2] Inhibition of novel reassortant avian influenza H7N9 virus infection in vitro with three antiviral drugs, oseltamivir, peramivir and favipiravir

[3] T-705 (favipiravir) activity against lethal H5N1 influenza A viruses

h/t tetano

A(H7N9) and the Secretive Chinese

Emerging Infectious Diseases has published (ahead of print) an article entitled Geographic Co-distribution of Influenza Virus Subtypes H7N9 and H5N1 in Humans, China by Chinese researchers comparing the geospatial epidemiologic characteristics of A(H5N1) and A(H7N9) in China.[1] The authors compare the geographic distribution of cases for A(H5N1) and A(H7N9) throughout China at the township level and determine

 . . . that the high-risk areas for human infection with subtype H7N9 and H5N1 viruses are co-distributed in an area bordering the provinces of Anhui and Zhejiang . . .

The township is a level 4 administrative division in China. Within China, level 1 administrative divisions are provinces, province-level municipalities, autonomous region, and special administrative regions. Level 2 are prefecture-level divisions, and county-level divisions are level 3.  Although the analysis was conducted on township-level divisions the authors present the conclusion by provinces.

Generally, with peer reviewed articles the underlying raw data is available for review by other researchers. A review of the citations in this article does not identify any sources for the geographic locations of the cases for either the A(H5N1) cases or the A(H7N9)cases.  While an intensive online search will produce the county level location of almost all of the A(H5N1) cases in China, from 2005 to 2013 (see map below), this is not true for the  A(H7N9) cases.

The Chinese government has greatly restricted the publicly available information on A(H7N9) cases in China. Beside the minimal reporting of cases to the World Health Organization, little information about individuals cases is available. The only geographic information on A (H7N9) cases is aggregate data by provinces (administrative level 1). Almost no county level locational information is publically available for most of the  A(H7N9) cases. In fact, the information on A (H7N9) is so sparse that an accurate number of A(H7N9) deaths by province is not even available [2].

This article demonstrates the Chinese researchers have an abundance of epidemiological data on A(H7N9) cases.  So why is the Chinese government so secretive and why won’t they release the data? 

[1] Geographic Co-distribution of Influenza Virus Subtypes H7N9 and H5N1 in Humans, China

[2] Why is China not reporting the details of individuals who died from an A(H7N9) infection, not even to WHO?

h/t Giuseppe Michieli