Pregnant women are at higher risk of developing complications following influenza, particularly in their second and third trimesters, due to their altered immunity and physiological adaptations (Jamieson et al, 2006). Certainly, during the H1N1 virus pandemic, there were 12 reported maternal deaths in the UK (Lim and Mahmood, 2011).
This flu season has the potential to mirror the spike in flu that is happening in Australia in the Southern Hemisphere (Siddique, 2018; Gallagher, 2019; World Health Organization [WHO], 2019b). In Australia during their flu season, influenza A (H3N2) was found to be predominant among the subtype influenza A viruses and was higher than usual flu seasons (WHO, 2019a). Often, as healthcare workers' evidence has shown, we can be ill-informed about the benefit of vaccination and do not educate our patients about it (Broughton et al, 2009).
Flu is caused by a member of the RNA viruses of the family Orthomyxoviridae family of which there are four types of seasonal influenza viruses: types A, B, C and D (National Institute for Health and Care Excellence [NICE], 2019a; WHO, 2019a). They are classified into subtypes according to the proteins on the surface of the virus such as hemagglutinin (HA) and the neuraminidase (NA) (WHO, 2019a). Influenza A viruses are the more significant of the types of flu and can lead to pandemics. The current influenzae A types circulating in the general population are A (H1N1) and A (H3N2) influenza viruses (WHO, 2019a). This can change, however, as surface antigens from influenza A make these viruses antigenically labile and the minor changes which can occur are called antigenic drift which occur progressively from season to season, meaning that the flu vaccination must change year-on-year (Duncan, 2015; Public Health England [PHE], 2018).
Transmission
Influenza is highly infectious with an incubation period of 1–3 days, enabling it to spread quickly in crowded areas including schools and nurseries (PHE, 2018). It is transmitted by droplets, airborne or through direct contact with infected secretions (Lau et al, 2010) and cannot survive long on skins but can survive longer on hard surfaces (Greatorex et al, 2011; Mukherjee et al, 2012). It can survive on hard, non-porus surfaces for up to 24–72 hours (Greatorex et al, 2011).
Increased susceptibility in pregnancy
The changes that occur during pregnancy in a woman's immune system allow tolerance to paternally derived fetal antigens and include suppression of the cell-mediated immunity maternal lymphocytes (Lederman, 1984). This also leads to a reduced proliferative response to soluble antigens and to allogeneic lymphocytes (Kanagasabai et al, 2010).
Certainly, cell-mediated immunity is modified by an increase in T-helper cells, as opposed to T-killer cells, to reduce the risk of rejection of the fetus (Lim and Mahmood, 2011). Therefore, in pregnancy, there is a shift from cell-mediated immunity toward humoral immunity which makes pregnant women more susceptible to viral pathogens such as influenza (Jamieson et al, 2006). Pregnant women are therefore at high risk of severe complications of influenza, particularly during interpandemic periods (Neuzil et al, 1998).
Symptoms
The symptoms of influenza are an unusual sudden onset of a high fever, dry cough, headache, myalgia, severe malaise, sore throat and a runny nose (Duncan, 2015; PHE, 2018). Generally, this can be an unpleasant but self-limiting disease with recovery usually within 2–7 days. In pregnancy, this is complicated by a reduced lung capacity and anaemia (Jamieson et al, 2006).
The most common complications of influenza in adults according to NICE (2019a) are:
Other complications such as bronchitis, secondary bacterial pneumonia or otitis media particularly in children, can occur (PHE, 2018). Other more serious complications are meningitis, encephalitis or meningoencephalitis. The risk of these complications is higher amongst children under six months of age (Agyeman et al, 2004; Newland et al, 2007; Zhang et al, 2012). The other related complication is the reduced formulary for prescribing antibiotics in pregnancy, particularly if a woman develops a super infection.
Effects of influenzae on the fetus
The effects of maternal influenza infection on the fetus are not fully understood but previous pandemics have reported high rates of spontaneous abortion, preterm birth and birth defects were reported in cases of women with pneumonia (Rasmussen et al, 2008; Siston et al, 2010). The risk of birth defects is debatable as they have not been identified in all studies (Acs et al, 2005).
Prevention
Prevention, and particularly immunisation, are key aspects of the Department of Health's (DoH) management of influenzae (NHS England, 2019). The national flu immunisation programme aims to protect those who are at high risk of flu-associated morbidity and mortality, and each vaccine includes protection against influenza A (H1N1) and A (H3N2), and one or two influenza B viruses (PHE, 2019).
Influenza activity is monitored in the UK through sentinel GP practices, virological surveillance and weekly reports form PHE, Health Protection Scotland, Public Health Wales and the Public Health Agency in Northern Ireland. This information feeds to the Joint Committee on Vaccination and Immunisation ([JCVI], 2019) which also relies on surveillance from the WHO to recommend the seasonal flu vaccines.
Since 2012, the flu vaccine is recommended as the main aspect of prevention for pregnant women worldwide (WHO, 2019a). Pregnant women are recommended for seasonal influenza vaccinations and identified as a priority group for vaccination in the event of a pandemic.
Data on influenza vaccine safety in pregnancy is considered inadequate by some researchers but there are a few studies that report no serious side-effects in women or their infants, including no indication of harm from vaccination in the first trimester (Mak et al, 2008).
Certainly, the data reflecting administration of influenza vaccines during the first trimester appear to be limited but studies have not noted an association between the influenza vaccination and adverse pregnancy outcomes (Heikkinen et al, 2012; Chambers et al, 2013; McMillan et al, 2015). Donahue et al (2017) looked at the association of spontaneous abortion with receipt of inactivated influenza vaccine containing H1N1pdm09 in the 2010–2011 and 2011–2012 campaigns, and found that there was no association with an increased risk for spontaneous abortion.
Certainly, when discussing the risk of vaccination versus the risk of complication from flu, the influenza vaccine should be administered anytime during pregnancy, before and during the influenza season (Grohskopf et al, 2019). Vaccination appears to be the best way to decrease a woman's risk of influenza and complications during pregnancy, but it also has the potential of added benefit of protecting infants from infection (Naleway, 2006).
The DoH is aiming at vaccinating at least 75% of those aged under 65 ‘at risk’, including pregnant women (PHE, 2019b). Previous campaigns have only reached 55% of the eligible population, (PHE, 2019b).
The main reasons for not receiving vaccination were found to be the lack of knowledge about the vaccine importance, concerns for effects on fetal and maternal health, and lack of knowledge about where to obtain vaccination (Fisher et al, 2011). Campaigns like the best-practice alert or text messaging has resulted in a significantly higher rate attendance for vaccination (Klatt and Hopp, 2012; Moniz et al, 2013). Ultimately, as healthcare professionals, we can advise women about how they prevent catching influenzae if we ourselves are informed.
2019–2020 influenza campaign
This season, there are two vaccines which the JCVI advises are equally suitable for use. There is the standard egg-grown, quadrivalent influenza vaccine (QIVe) and the newly licenced, cell-based quadrivalent influenza vaccine (QIVc). Both offer protection against four strains of flu recommended by the WHO (2019a).
The 2019–2020 trivalent vaccines are recommended to protect against influenza protect against:
Encouraging vaccination is a key part of the prevention strategy, particularly if our flu season mirrors spike in A (H3N2) in Australia (Siddique, 2018; Gallagher, 2019; WHO, 2019b).
Management
NICE (2019a) suggests that the management of influenzae includes conservative management of the symptoms and the prescribing of antiviral drugs if all the following apply:
| To treat the symptoms, provide advice along the lines of: |
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| They should also: |
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| Advise the person that: |
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| The clinician must adhere to the local and national prescribing guidelines during seasonal flu or a pandemic | |
| 1. Oseltamivir | |
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| Prevention of influenza | For adults: 75 mg once daily for 10 days for post-exposure prophylaxis; for up to 6 weeks during an epidemic |
| Treatment of influenza, in the immunocompromised | For adults: 75 mg twice daily for 10 days |
| 2. Zanamir | |
| Post-exposure prophylaxis of influenza | For adults: 10 mg once daily for 10 days (inhalation) |
| Prevention of influenza during an epidemic | For adults: 10 mg once daily for up to 28 days |
| Treatment of influenza | For adults: 10 mg twice daily for 5 days (for up to 10 days if resistance to Oseltamivir suspected) |
NICE (2019a) and the PHE (2019a) recommend that antiviral medicines may be prescribed at any time in the secondary care setting for patients with suspected seasonal influenza infection. In general practice, patients need to undergo laboratory testing for influenza and GPs have strict guidelines with regards to prescribing antiviral medication. In both cases, particularly if an individual develops symptoms despite antiviral prophylaxis or has a persistent infection, the potential development of antiviral resistance should be considered (PHE, 2019a).
Antiviral medication
All influenza viruses have two surface glycoproteins or antigens: a hemagglutinin and neuraminidase, which define the strain of influenza (Moscona, 2005). The neuraminidase adheres to the cellular-receptor sialic acid residues in a cell and releases the virus which invades new cells. Without neuraminidase, a person would be exposed to the virus but would necessarily develop the infection (Moscona, 2005).
Ultimately, neuraminidase can lead to destruction of the respiratory epithelium and increases bacterial adherence exposure to bacterial superinfections (Peltola and McCullers, 2004). Neuraminidase also exposes the pneumococcal receptors on the host cells by removing terminal sialic acids, thus increasing the likelihood of invasion of Streptococcus pneumoniae (McCullers and Bartmess, 2003).
The virus also causes virus-induced immunosuppression and an increase in inflammatory responses, thus producing an increase in bacteria receptors (Peltola and McCullers, 2004). Pneumonia is one of the significant complications of influenza and has a high rate of mortality in both immunocompromised and healthy individuals (Rello et al, 2009; Rello and PopVicas, 2009). The antivirals that can be prescribed are a class of drugs called neuraminidase inhibitors, preventing this action.
Pregnant women who are in an ‘at risk’ group should be prescribed antiviral drugs if the national surveillance schemes indicate that influenza virus is circulating, and they can start treatment within 48 hours of the onset of symptoms (NICE, 2019a). The antivirals prescribed are Oseltamivir and Zanamivir are a newer class of neuraminidase inhibitors and are most effective for the treatment of influenza if started within a few hours of the onset of symptoms, but they are licensed for use within 48 hours of the first symptoms (Duncan, 2013; NICE, 2019b).
They can reduce the duration of symptoms by about 1–1.5 days (Duncan, 2013; NICE, 2019b). There is evidence that some strains of the influenza A virus have reduced susceptibility to Oseltamivir but Zanamivir may be effective (de Clercq et al, 2006; Sugaya et al, 2007; Kawai et al, 2009). The first-line treatment in immunocompromised patients is Oseltamivir PO, unless the dominant circulating strain has a higher risk for developing, Oseltamivir resistance then Zanamivir (INH) is advised, (Joint Formulary Committee, 2019; PHE, 2019).
If there is a question of Zanamivir resistance, then treatment, urgent resistance testing and advice from local infection specialists can be sought (PHE, 2019). The safety data on Oseltamivir and pregnancy is limited but ultimately it has been identified as a drug of choice, particularly during a pandemic, as the potential benefit outweighs the risk (Joint Formulary Committee, 2019).
Breastfeeding women
Although there is limited safety data about Zanamivir, it can be used in women who are breastfeeding when the potential benefit outweighs the risk such as during a pandemic (Joint Formulary Committee, 2019).
Summary
As we head into the flu 2020's season in the Northern Hemisphere, we are aware there may be higher numbers of flu than usual (Gallagher, 2019). The best approach to management of influenzae is through vaccination and education (Duncan, 2015). It is therefore important to remind pregnant women to have their flu vaccination to prevent them developing flu or experiencing its complications. This is particularly important considering suggestions that this season will have higher-than-normal cases of influenzae (Siddique, 2018; Gallagher, 2019; WHO, 2019b).