INFLUENZA A, B & PANDEMIC H1N1 in 2019

Overview

H1N1 (2009 pandemic swine flu) is a subtype of influenza A virus, which causes upper and lower respiratory tract infections. There are four types of influenza viruses: influenza A, B, C, and D, but only influenza A and B viruses cause clinically important human disease and seasonal epidemics. Influenza A viruses cause the most severe clinical disease and are the commonest cause of seasonal epidemics and pandemics in human populations.(1,2)

In humans, the symptoms of swine flu are similar to those of seasonal influenza A infections, viz. chills, fever, sore throat, muscle pains, severe headache, coughing, weakness, and general discomfort.(1)

Disease symptoms caused by an influenza B virus infection are remarkably similar to those caused by influenza A virus infections.(3)

Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus: the hemagglutinin (H) and the neuraminidase (N). There are 18 different hemagglutinin subtypes and 11 different neuraminidase subtypes (H1 through H18 and N1 through N11). Theoretically, any combination of the 18 hemagglutinins and 11 neuraminidase proteins are possible, but not all have been found in animals and even fewer have been found to infect humans.(2)

Influenza B viruses diverged from influenza A viruses at some time point in the distant past. Currently, two influenza B lineages are distinguished on the basis of their HA glycoprotein: the B/Victoria lineage (named after the B/Victoria/2/1987 strain) and the B/Yamagata lineage (named after the B/Yamagata/16/1988 strain).(3)

Influenza viruses can change into “new” Influenza viruses in two different ways:

  • Antigenic Drift(4)
    • These are small changes (or mutations) in the genes of influenza viruses that can lead to changes in the surface proteins of the virus:
      • These changes happen continually over time as the virus replicates.
      • When antigenic drift occurs, the body’s immune system may not recognize and prevent sickness caused by the newer influenza viruses. As a result, a person becomes susceptible to flu infection again, as antigenic drift has changed the virus enough that a person’s existing antibodies won’t recognize and neutralize the newer influenza viruses.
  • Antigenic Shift(4)
    • This is an abrupt, major change in an influenza A virus. This can result from
      • Direct infection of humans with a non-human influenza A virus, (such as one circulating among birds or pigs).
      • Antigenic shift also can happen when a non-human influenza A virus (for example an avian influenza virus) exchanges genetic information with other influenza A viruses in a process called genetic reassortment, and the resultant new virus is able to infect people.

If the new virus causes illness in infected people and can spread easily from person to person, an influenza pandemic can occur.(4)

For influenza B viruses, there is no conclusive evidence for continuous circulation in animal species. This limits the potential for zoonotic transmission of antigenically distinct influenza B viruses and the risk of pandemic outbreaks caused by Influenza B.(3)

Influenza and Pandemics

While Influenza B has never caused a pandemic in recorded history, variant strains of the influenza A virus were responsible for 3 global pandemics in just the 20th century: The Spanish flu in 1918, the Asian flu in 1957, and the Hong Kong flu in 1968.(5)

The swine-origin, novel H1N1 strain of Influenza A was responsible for the first pandemic of the 21st century, affecting more than 214 countries and causing more than 18,449 deaths.(5)

In India, this pandemic resulted in 27,236 cases and 981 deaths in 2009 and 20,604 cases and 1,763 deaths during 2010.(6)

Post the pandemic, another wave hit India in 2015 with 42,592 reported cases and 2,990 deaths.(6)

Burden of H1N1 in India

Between Jan 2014 and Nov 2019, there have been 127,673 laboratory confirmed cases of H1N1 in India with a total of 8,075 deaths. The highest number of cases detected in this time period was in 2015 (42,592 cases with 2991 deaths) followed by 2017 (38,811 cases with 2,266 deaths) (Figure 1).(7)

Figure 1 – Number of H1N1 cases and deaths in India (2014-2019)

Figure 1 – Number of H1N1 cases and deaths in India (2014-2019)

The highest number of cases reported over the past 6 years were from the states of Gujarat (22,463 cases), Maharashtra (19,792 cases), Rajasthan (18,204 cases), Delhi (11,195 cases) and Karnataka (10,933 cases) (Figure 2).(7)

Figure 2 – Infographic depicting state-wise categorisation of number of reported H1N1 cases (Jan 2014 to Nov 2019)

The deaths in 2015 & 2017, were more than two times higher than seen during the pandemic year of 2009. 4 states in India contributed the lion’s share of confirmed cases and deaths. These states were – Gujarat (517 deaths in 2015 & 431 deaths in 2017), Maharashtra (905 deaths in 2015 and 788 deaths in 2017), Rajasthan (472 deaths in 2015 & 279 deaths in 2017) and Madhya Pradesh (367 deaths in 2015 &146 deaths in 2015).(7)

As can be noted, Maharashtra alone accounted for 30.3% of all H1N1 deaths in India in 2015 and 34.7% in 2017 – the highest share of deaths in India.(7)

In fact, when one looks at the consolidated figures for the past 6 years, Maharashtra leads the pack with the highest share of deaths (2014-2019 Nov) with 30.38%. This is followed by Gujarat with 16.17% and Rajasthan with 15.57% (Figure 3). In summation, almost one-third of all H1N1 deaths in India over the last 6 years have been from Maharashtra alone.(7)

There is scant epidemiological data for Influenza B in India with only a few states reporting it to the IDSP – the focus being on H1N1.

Changing trends

As per experts, it has been noted that since 2017, there have been at least two, yearly peaks for the virus. One in February to April (peaking in March) and the second one, August to October (peaking in September).(6)

However, when we performed an in-house study on cases tested as part of our H1N1 test profile, we discovered that the percentage of positive cases peaked in July and August 2019 and then declined sharply in September, irrespective of prolonged monsoons this year.

The highest number of H1N1 positive cases were seen in July, followed by February, again bucking the conventional trend of peaks in August to October (Figure 4).

Figure 4 – Comparison of number of H1N1 influenza A & non-H1N1 influenza A and negative cases, from tests done between January and November

The peak for influenza A cases (when including both H1N1 and non-H1N1 influenza) was seen to be in July and August (Figure 4 and Figure 5)

Figure 5 – Comparison of percentages of H1N1 influenza A, non-H1N1 influenza A and negative cases from tests done between January and November

A rising trend in the number of non H1N1 influenza A cases can be seen towards the monsoon months – something that can be more clearly illustrated when comparing the percentage positivity. There are a higher proportion of non-H1N1 influenza A cases from July onwards (and a corresponding dip in H1N1 cases), all the way till November (Figure 6).

Figure 6 – Trend of percentage positivity of H1N1 influenza A and non-H1N1 influenza A amongst the total cases tested between January and November

It could be that this trend is part of H1N1 declining as part of the natural cycling of Influenza virus epidemics, with another strain taking over. This bears further observation and study.

On analysis of data of cases tested for Influenza A and Influenza B, we see that Influenza B cases are not as numerous as Influenza A cases for most of the year; with no cases of Influenza B being detected in the first 4 months of the year (Figure 7). The number and percentage positivity of Influenza A is much higher than Influenza B until the month of August (Figure 7,8 & 9). However, this trend flips in September and October where the percentage positivity of Influenza B overtakes that of Influenza A (Figure 9).

Figure 7 – Comparison of number of influenza A & influenza B and negative cases, from tests done between January and November

Figure 8 – Comparison of percentages of influenza A, influenza B and negative cases from tests done between January and November

Figure 9 – Trend of percentage positivity of influenza A and influenza B amongst the total cases tested between January and November

As can be seen from figures 8 & 9, the number & percentage of Influenza B positive cases have overtaken those of Influenza A during the peak of winter.

Influenza B, as mentioned before, does not cause pandemics. Nonetheless, this Influenza B trend should be monitored and a higher index of suspicion should be applied amongst patients with flu-like symptoms.

Take Home Message:

  • Western India, especially Maharashtra has a disproportionately high burden of H1N1 cases and deaths, when one takes the data of the past 6 years into account.
  • The epidemiological trends of H1N1 are changing from the classical model – a higher index of suspicion is warranted even in the so-called “off-season” months.
  • This year, non-H1N1 Influenza A viruses showed a sharp peak in the monsoon months with positive cases still being detected in October & November.
  • Influenza B cases also showed an increase during the monsoon months and with the onset of winter – therefore, screening for Influenza B is of importance when evaluating patients with flu-like symptoms.

References:

  1. Dandagi GL, Byahatti SM. An insight into the swine-influenza A (H1N1) virus infection in humans. Lung India Off Organ Indian Chest Soc. 2011;28(1):34–8.
  2. Questions and Answers | Pandemic Influenza (Flu) | CDC [Internet]. 2019 [cited 2019 Nov 20]. Available from: https://www.cdc.gov/flu/pandemic-resources/basics/faq.html
  3. van de Sandt CE, Bodewes R, Rimmelzwaan GF, de Vries RD. Influenza B viruses: not to be discounted. Future Microbiol. 2015 Sep;10(9):1447–65.
  4. CDC. How Flu Viruses Can Change [Internet]. Centers for Disease Control and Prevention. 2019 [cited 2019 Nov 20]. Available from: https://www.cdc.gov/flu/about/viruses/change.htm
  5. Rewar S, Mirdha D, Rewar P. Treatment and Prevention of Pandemic H1N1 Influenza. Ann Glob Health. 2016 Mar 29;81(5):645.
  6. Kulkarni S, Narain J, Gupta S, Dhariwal A, Singh S, Macintyre Cr. Influenza A (H1N1) in India: Changing epidemiology and its implications. Natl Med J India. 2019;0(0):0.
  7. Central Surveillance Unit, Integrated Disease Surveillance Programme. Seasonal Influenza (H1N1)– State/UT- wise, Year- wise number of cases and deaths from 2012 to 2019 (till 03rd November , 2019) [Internet]. National Centre for Disease Control; 2019 Nov [cited 2019 Nov 19]. Available from: https://ncdc.gov.in/showfile.php?lid=280



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