Flu clue

Ability to change their genetic footprint quickly makes influenza viruses dangerous

35-The-flu-viruses-belong The flu viruses belong to the family of RNA viruses (as opposed to DNA viruses) that typically lack a proofreading mechanism and have the highest mutation rates of any organisms on earth | Vishnu V. Nair

The family of flu viruses is a dangerous foe. This year alone, a strain of the virus—Influenza A(H1N1)pdm09, also known as swine flu—has claimed 448 lives among the 14,803 cases that have been reported across the country. The big swine flu outbreak was in 2009-2010 when 2,744 people died, and then in 2015, resulting in 2,990 deaths.

“The main influenza season in India coincides with the monsoon months (June to September). But, in between, we also see summer peaks in February to March, as we did in 2015 [and again this year]. The exception is Jammu and Kashmir with its temperate climate. In India, influenza occurs throughout the year with a major seasonal peak during monsoon,” says Dr G. Arunkumar, head, Manipal Centre for Virus Research (MCVR).

Influenza viruses, say experts, fall in two categories—Influenza A (with several subtypes) and Influenza B (with only two subtypes). What turns the influenza viruses into formidable foes is that they change their genetic footprint rather quickly. The flu viruses belong to the family of RNA viruses (as opposed to DNA viruses) that typically lack a proofreading mechanism (error-correcting process) and have the highest mutation rates of any organisms on earth. Several high-profile viral diseases, such as Ebola, SARS and MERS, which have emerged recently, can be traced to the RNA family.

“When the Influenza A viruses replicate their genome, due to the absence of a proofreading mechanism, a lot of errors or mutations take place,” says Dr Nivedita Gupta, senior scientist, Indian Council of Medical Research (ICMR). “These mutations cause changes in the virus strain, and give it the power to trick the host’s immune system.” The high rate of errors, the characteristic of having fewer genes and smaller genomes means that the virus-host relationship is less complex, and allows the virus to jump hosts quickly as well. “The Influenza A viruses reside in the wildlife populations, particularly wild aquatic birds. Sometimes, during replication activity, one part of the genome will be chopped off and taken from the host’s genes. This mixing of genes is called reassortment, leading to a newer strain of the influenza virus,” says Gupta.

The only way to counter the virus, says Gupta, is through a vaccine (a cocktail of different strains of Influenza A and B viruses). Each year, in February, based on a pool—fed by surveillance data gathered by several countries—the World Health Organization identifies the key strains of the flu virus and recommends the strains to be included in the vaccine. The recommendations are made for countries in the northern and southern hemisphere. For instance, this year (2019-2020), the WHO recommendation for a vaccine for northern hemisphere—that India may follow—should have four strains of the flu virus. These four (two each from the Influenza A and B) family are: A/Brisbane/02/2018 (H1N1)pdm09-like virus, A (H3N2) [since this strain may vary, the exact will be announced on March 21], B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage), and B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage).

Based on the WHO recommendations, the respective countries match the strains with their own surveillance data, and ask vaccine manufacturers to build the annual vaccine accordingly. However, “after the WHO recommendation in February, by the time the vaccine comes out, it is already September,” says Gupta. “By then, the changes in the virus would have happened already.”

Besides, the manufacturing process also allows some room for variations. Flu shots are devised by growing the viruses in the hen’s fertilised eggs and incubated for several days to allow the viruses to replicate. The virus-containing fluid is then harvested from the eggs, and the influenza viruses for the vaccine are inactivated (killed), before the virus antigen is purified. “Even when inside the egg, the virus strain can change, creating a mismatch between the vaccine and the strain that is causing the disease,” she says.

Still, Gupta says the shot is worth the trouble. “Even if it gives 50 per cent protection, it is recommended. This is because it will help in reducing the transmission of the virus among humans,” she says.

In India though, our vaccine uptake is suboptimal. “It is difficult for the government to provide the vaccine free of cost. We have been stressing that the high-risk groups should get the vaccine at least. In Maharashtra, the state government is doing so for all high-risk groups. Elsewhere, aside of the high-risk groups, whoever can get the shot, should get it,” says Gupta.

Arunkumar, however, stresses on a different strategy to counter the foe— shifting the skewed focus from the H1N1 strain, and creating stronger disease surveillance systems. “In India, it is unfortunate that we are giving attention to only one strain of the influenza virus [Influenza A (H1N1)pdm09 virus]. Other influenza viruses, which have been here for many years, are also active and cause hospitalisation. But attention is given only to Influenza A (H1N1)pdm09, because it arrived in India as part of the 2009 pandemic,” says Arunkumar. When H1N1 activity is low, everyone is under the impression that influenza has been controlled, without realising the fact that Influenza A/H3N2 or Influenza B is still active, he says.

Data from the National Centre of Disease Control maps only cases and deaths due to the H1N1 strain, and that is where the fallacy lies. “Together, all influenza strains [A/H1N1, A/H3N2 and Influenza B (Victoria/Yamagata)] account for around 15-20 per cent of hospital admissions due to fever,” says Arunkumar. “This may reach up to 30-40 per cent during influenza season. The burden is huge, but not recognised. Instead the focus is on the number of deaths. What about the sickness and the work days lost?”

Testing and surveillance for other strains should be given equal importance. “Flu viruses alternate in activity and peak,” says Arunkumar. “As of now, testing for the other strains is limited to centres such as National Centre for Disease Control, MCVR, ICMR-Viral Research & Diagnostic Laboratories and the National Institute of Virology. Let us not glorify one strain at the cost of ignoring the other three strains and the losses they cause.”