Had an opportunity to give a presentation on influenza vaccination at the local School of Public Health‘s Health and Safety Day yesterday, and so had to read up a bit.

Influenza is a highly contagious illness caused by the influenza virus, of which there are four main types that we know of, although we primarily focus on influenza A and B viruses because C causes very mild human disease, if at all, whereas D affects cattle. The onset of influenza is abrupt, with typical symptoms such as fever, body ache and dry cough. These symptoms are non-specific, hence the term “influenza-like illness”  (ILI) has been used for the purpose of tracking (and diagnosing) influenza in the absence of a cheap and widely available point-of-care test. Except during an influenza epidemic or pandemic, however, the majority of cases of ILIs are generally not caused by the influenza viruses, but by other viruses, drugs, etc.

Because influenza viruses are RNA viruses, they are highly mutable, and the rapid accumulation of mutations (antigenic drift) explains the need for annual vaccination. A different phenomenon – antigenic shift – is caused by the re-assortment of influenza viruses co-infecting an intermediate host (i.e. bird, pig and human influenza viruses mixing in a pig host). This creates a novel virus which has the potential to cause pandemics. The 2009 influenza A(H1N1) pandemic was caused by one such virus, combining a previous triple reassortment of bird, human and pig virus with a Eurasian pig virus.

Combination screenshot of images obtained from Google Images, depicting antigenic drift and shift.

Many people have the misperception that flu is not dangerous (since most people recover from colds and ILIs). But while the mortality rate is very low, influenza is associated with many deaths because of the large numbers that are infected every year. A paper published by the Ministry of Health more than 10 years ago estimated that an average of 588 deaths (approximately 3.8% of all deaths in Singapore) could be attributed to influenza each year, and in a global update published in the Lancet last year (behind a paywall), Singapore ranked high among countries in terms of mortality from influenza in the elderly (possibly because data were better collated, although that is my biased impression).

Both Europe and USA experienced fairly bad influenza seasons (2017-2018), partly because there was a vaccine mismatch. As can be seen from the chart below, although the US influenza season has run its course, the European season is still ongoing. The predominant US influenza strain was A(H3N2), where a vaccine mismatch was predicted to decrease vaccine efficacy to about 25%, whereas the predominant European influenza strain was B(Yamagata), which the Northern hemisphere trivalent influenza vaccine in 2017 did not cover.

The process of deciding how to formulate Northern and Southern hemisphere influenza vaccines is fairly complex, and is perhaps best summarised in this Scientific American article. Essentially, based on prevailing trends of influenza viruses monitored by laboratories in more than a hundred countries around the world, experts gather in February and September to determine the composition of the influenza vaccines for the  upcoming influenza seasons in the  Northern and Southern hemispheres respectively.

Influenza vaccines are not particularly effective even if the experts predicted accurately. Take for example the following chart from the US Centers for Disease Control and Prevention (CDC) website, which tracked vaccine efficacy since 2004: over 14 influenza seasons, vaccine efficacy ranged from a low of 10% to a high of only 60%.

Screenshot from the US CDC website on influenza vaccine efficacy.

If the vaccine is on average only able to prevent influenza less than half of the time, why do we bother? There are two oft-quoted reasons:

• Even a less effective vaccine may result in milder illness if one does contract influenza post-vaccination.
• Every vaccinated person contributes to overall community herd immunity.

The Cochrane review published a systematic analysis this year stating that on average, vaccinating 5 and 12 children would prevent 1 case of influenza or ILI respectively, which makes a great case for public health cost-efficacy. The numbers are larger for adults – 77 and 29 adults vaccinated would prevent 1 case of influenza or ILI respectively – but nonetheless still cost-effective at a community level given the low cost and high safety of the vaccine.

Singapore, being in the tropics, does not have a defined “influenza season”. As can be seen from the Ministry of Health published data (epidemiological week 10), influenza occurs all year round (although Singapore uses “acute respiratory illness” rather than ILI).

Screenshot from the MOH Weekly Infectious Disease Epidemiological Bulletin, Week 10, 2018.

Another common question that arises is – which vaccine should be used in the tropics or should a person be vaccinated with both Northern and Southern hemisphere vaccines? It turns out that WHO has looked at this issue and issued recommendations. In 2016, for example, WHO placed Singapore in the “Northern hemisphere vaccination zone”, with a recommended vaccination timing of October. In practice, however, both northern and southern hemisphere vaccines are available in Singapore and are prescribed depending on time of year.