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Swine ‘flu’ in pregnancy 

Swine ‘flu’ in pregnancy
Swine ‘flu’ in pregnancy

Mark H Almond

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date: 14 December 2018

Expert commentary by Mark J Griffiths

Case history

A 26-year-old pregnant female referred herself to the labour ward, reporting reduced fetal movements and a 3-day history of an influenza-like illness comprising coryzal symptoms, hot and cold sweats, headaches, fevers, and myalgia. Examination revealed that she was febrile (>38̊C), resulting in her admission for observation and cardiotocography (CTG), which was reportedly normal.

Her medical history included recurrent urinary tract infections, childhood asthma, hypertension, whilst taking the oral contraceptive pill, and an episode of numbness of the right hand that had previously been investigated for demyelination by MRI. She was a non-smoker, took no regular medications, and had no known drug allergies.

Swine ‘flu’ in pregnancy Learning point Pulmonary physiology and pathology during pregnancy

As serum progesterone concentrations increase throughout pregnancy, hyperventilation (with an associated respiratory alkalosis) may occur due to increased stimulation of the respiratory centres within the brain. The gravid uterus results in decreases in both the RV and FRC, whilst the TLC decreases slightly in the third trimester. The FEV1, FVC, and peak expiratory flow rate (PEFR) do not change significantly [1].

Pregnancy results in a state of relative immunosuppression, and the following pulmonary complications should be borne in mind (Table 20.1, derived from [1]).

Table 20.1 Pulmonary complications of pregnancy

Deterioration of pre-existing

Respiratory disease

Asthma (worsens in one-third)

Lymphangioleiomyomatosis (LAM)

Cardiac disease

Peripartum cardiomyopathy

Structural heart disease, e.g. mitral stenosis

Autoimmune disease


Wegener’s granulomatosis

Pulmonary infection


S. pneumoniae, commonest pathogen M. pneumoniae, commonest atypical


Influenza A








Secondary to








Amniotic fluid


Data from Pereira A, Krieger BP. Pulmonary complications of pregnancy. Clinics in chest medicine. 2004;25:299–310.

Following her admission, she remained febrile, despite paracetamol, and, by day 3, had developed a cough productive of clear sputum. Her chest was noted to be clear on auscultation; however, as her pyrexia remained at >38̊C, she was commenced on IV co-amoxiclav and clarithromycin for CAP.

Swine ‘flu’ in pregnancy Expert comment

During an influenza pandemic, the patient who was at risk, in the case of A/H1N1 2009 influenza, owing to the history of asthma and current pregnancy, ideally should have been treated with antiviral agents on presentation. In the review of maternal deaths in the UK related to A/H1N1 2009 influenza from April 2009 to January 2010, seven out of eight deaths reported were associated with an avoidable delay in the administration of antiviral agents, and none of the women had been vaccinated.

The following day, fetal tachycardia was noted, resulting in a subsequent emergency lower segment Caesarean section (LSCS) under spinal anaesthesia. Intraoperatively, the patient’s oxygen saturations were 92% on 10 L of oxygen, subsequently dropping post-operatively to 90% on 15 L via a non-rebreathe mask. A boy was delivered and subsequently transferred to the special care baby unit (SCBU).

She was reviewed by the medical registrar on the labour ward who noted diminished breath sounds and crepitations at the left base, with a subsequent chest radiograph revealing extensive left-sided consolidation. An ABG showed a PaO2 of 8.5 kPa on 15 L/minute of oxygen, and she was transferred to the HDU for CPAP and arterial line insertion. Concurrently, an H1N1 throat swab was sent for reverse transcriptase polymerase chain reaction (rt-PCR), in addition to Legionella and pneumococcal urinary antigens.

Swine ‘flu’ in pregnancy Clinical tip Clinical diagnostic criteria for pandemic influenza (pH1N1)

  • Fever (>38̊C) or a history of fever; AND

  • Influenza-like illness (two or more of the following symptoms: cough, sore throat, rhinorrhoea, limb or joint pain, headache, vomiting, or diarrhoea); OR

  • Severe and/or life-threatening illness suggestive of an infectious process.

Notably, gastrointestinal symptoms (diarrhoea, vomiting, and abdominal pain) are more prominent in pH1N1, relative to seasonal influenza (<10%), and up to one-third of patients may be afebrile at presentation [2]. Most adults with pH1N1 experience mild symptoms, with 50% recovering within 7 days of symptom onset and a further 25% within 10 days.

Swine ‘flu’ in pregnancy Clinical tip Diagnostic criteria for ARDS

Following the initial description of ARDS in 1967, it took a further 27 years before it was formally defined in 1994 by the AECC; however, issues regarding reliability and validity of the definition emerged. The 2012 Berlin definition eliminates the term ‘acute lung injury’ (Table 20.2) [3].

Table 20.2 2012 Berlin definition of ARDS


Within 1 week of a known clinical insult or new or worsening respiratory symptoms

Chest imaging

Bilateral opacities—not fully explained by effusions, lobar/lung collapse, or nodules

Origin of oedema

Respiratory failure not fully explained by cardiac failure or fluid overload

Need objective assessment (e.g. echocardiography) to exclude hydrostatic oedema if no risk factor present


Mild: 200 mmHg < PaO2/FiO2 < 300 mmHg, with PEEP/CPAP >5 cmH2O

Moderate: 100 mmHg < PaO2/FiO2 < 200 mmHg, with PEEP >5 cmH2O

Severe: PaO2/FiO2 < 100 mmHg, with PEEP >5 cmH2O

Swine ‘flu’ in pregnancy Learning point Complications of pandemic H1N1 influenza A

Influenza viruses are a significant cause of morbidity and mortality globally, resulting in severe illness in 3–5 million people and death in up to 500,000 during epidemic years. These viruses are members of the Orthomyxoviridae family and subclassified into influenza A, B, and C, of which only influenza A has pandemic potential. Influenza pandemics occur when a virus expressing a novel haemagglutinin (HA) or neuraminidase (NA) surface glycoprotein infects a population with no prior immunity. The devastating effects of this were demonstrated by the 1918 H1N1 pandemic in which approximately 20–50 million people died worldwide.

Over the past century, four pandemics have taken place:

  • 1918: Spanish influenza (H1N1);

  • 1957: Asian influenza (H2N2);

  • 1968: Hong Kong influenza (H3N2);

  • 2009: Mexican influenza (H1N1).

Although it is now generally considered that the 2009 H1N1 pandemic resulted in mild disease in most individuals, serious complications still occurred, as listed in Table 20.3, both pulmonary and extrapulmonary [4].

Table 20.3 Pulmonary and extrapulmonary complications of 2009 H1N1 pandemic


Primary influenza pneumonia

Secondary bacterial pneumonia

Pulmonary superinfection with atypical pathogens

Exacerbations of chronic lung disease (asthma and COPD)

Respiratory failure and ARDS


Cardiac: pericarditis and myocarditis

Muscular: myositis and rhabdomyolysis

Neurologic: encephalopathy, encephalomyelitis, transverse myelitis, aseptic meningitis, Guillain–Barré syndrome

Gastrointestinal: acute pancreatitis

Rothberg MB, Haessler SD. Complications of seasonal and pandemic influenza. Crit. Care Med. 2010 Apr;38(4 Suppl):e91–7.

Swine ‘flu’ in pregnancy Expert comment

Following cellular endocytosis of the influenza virus, pathogen-associated molecular patterns (PAMPs), such as single- or double-stranded RNA, are detected by endosomal (toll-like receptors (TLRs)) or cytoplasmic (retinoic inducible gene 1 (RIG-1)) pathogen recognition receptors (PRRs) that, in turn, induce the expression of type I and III interferons. Interferons act in an autocrine and paracrine fashion to induce an antiviral state through the upregulation of interferon-stimulated genes (ISGs) such as the myxovirus resistance gene A (MxA) and interferon-induced transmembrane protein 3 (IFITM3) [5]. Peripheral blood mononuclear cells (PBMCs) isolated from healthy pregnant women have been shown to produce significantly less type I and III interferon when stimulated with pH1N1/09, compared with PBMCs from non-pregnant women, potentially contributing to their increased susceptibility to adverse outcomes [6].

Despite a PEEP of 10 cmH2O and an FiO2 of 1.0, she remained in type 1 respiratory failure, with a PaO2 of 6.8 kPa, resulting in her transfer to the adult intensive care unit (AICU) for intubation. By this point, her chest radiograph had deteriorated, demonstrating bilateral patchy changes, consistent with ARDS, and dense left lower lobe collapse and consolidation (Figure 20.1).

Figure 20.1 Frontal portable chest radiograph shortly after placement of a right internal jugular catheter for extracorporeal membrane oxygenation (ECMO: arrow heads). In the midline, an endoscope has been placed to carry out a transoesophageal echocardiogram. This was used to determine the cardiac structure and function, to exclude intracardiac shunts, and to optimize the placement of the ECMO cannula.

Figure 20.1
Frontal portable chest radiograph shortly after placement of a right internal jugular catheter for extracorporeal membrane oxygenation (ECMO: arrow heads). In the midline, an endoscope has been placed to carry out a transoesophageal echocardiogram. This was used to determine the cardiac structure and function, to exclude intracardiac shunts, and to optimize the placement of the ECMO cannula.

Her throat swab tested positive on rt-PCR for pH1N1, and she was commenced on oseltamivir, a NA inhibitor. After she was placed in the prone, rather than supine, position, her PaO2 improved to 9.23 kPa; however, with no significant progress made, the decision was made to transfer her to a tertiary centre for ECMO.

Swine ‘flu’ in pregnancy Expert comment

Management of an antenatal patient on the ICU necessitates special consideration. Failed intubation is significantly commoner in the obstetric population, relative to other anaesthetic intubations, with diminished FRC and increased oxygen consumption, resulting in rapid desaturation upon hypoventilation [7]. These factors should predispose to intubations being carried out electively and by the most experienced operators available. Haemodynamic instability may result from compression of the vena cava by the gravid uterus in the supine position. This can be mitigated by positioning patients on their left side or with the right hip elevated, in preference to repeated fluid challenges which will increase the formation of pulmonary oedema. Mechanical hyperventilation should be avoided, as this may adversely affect uterine blood flow. Neither prone positioning nor ECMO are absolutely contraindicated by pregnancy, although both present particular challenges to the intensive care team.

Swine ‘flu’ in pregnancy Clinical tip Referral criteria to secondary care and critical care


  • signs of respiratory distress;

  • hypoxia (oxygen saturations <94% on air);

  • dehydration or shock;

  • any signs of sepsis;

  • altered conscious level.

Critical care:

  • severe dyspnoea;

  • hypoxaemia with PaO2 <8 kPa despite maximal oxygen therapy;

  • refractory hypotension;

  • septic shock;

  • GCS <10 or deteriorating conscious level;

  • severe acidosis (pH <7.26);

  • influenza-related pneumonia and CURB-65* ≥4 or bilateral primary viral pneumonia.

* CURB-65 score: confusion, urea >7 mmol/L, respiratory rate ≥30/minute, low systolic (<90 mmHg) or diastolic (≤60 mmHg), blood pressure, age ≥65 years.

Source: from reference [2].

On arrival at the tertiary ECMO centre, her oxygen saturations ranged from 70% to 82% on 100% oxygen. Veno-venous ECMO was instituted, following which her systolic blood pressure dropped to 40 mmHg, recovering with vasopressor support. On arrival in the ICU, she had a sinus tachycardia, maintaining a mean arterial pressure (MAP) of 86 mmHg supported by high levels of noradrenaline. Transthoracic echocardiography revealed a markedly impaired global systolic function and a pericardial effusion, presumed to be secondary to influenza-induced myocarditis and pericarditis that was not causing a tamponade. Her antibiotics were changed at this point to include piperacillin with tazobactam, in addition to clarithromycin and oseltamivir.

Swine ‘flu’ in pregnancy Evidence base Referral to an ECMO centre and mortality amongst patients with severe 2009 influenza A (H1N1)


  • ECMO was used to treat H1N1/09-related ARDS during the 2009 pandemic [8].


  • Patients with H1N1-related ARDS.


  • Retrospective cohort study.

  • ECMO-referred versus matched non-ECMO-referred patients.

  • (ECMO-referred patients defined as all patients with H1N1-related ARDS who were referred, accepted, and transferred to one of four adult ECMO centres in the UK during winter 2009–2010).

Primary outcome

  • Survival to hospital discharge analysed according to intention-to-treat.


  • Mortality in ECMO-referred patients versus non-ECMO-referred patients:

    • 23.7% versus 52.5% (when individual matching used);

    • 24.0% versus 46.7% (when propensity matching used);

    • 24.0% versus 50.7% (when GenMatch matching used).


  • For patients with H1N1-related ARDS, referral and transfer to an ECMO centre was associated with lower hospital mortality, compared with matched non-ECMO-referred patients.

Swine ‘flu’ in pregnancy Clinical tip Distinguishing between primary viral pneumonia and secondary bacterial pneumonia

During the 2009 H1N1 pandemic, influenza-related pneumonia was found in 40% of hospitalized patients in the US, and, in Australasia, 49% of the critically ill patients were diagnosed with viral pneumonia and 20% had secondary bacterial pneumonia [2].

Signs suggestive of the development of influenza-related pneumonia include dyspnoea, recrudescent fever, tachypnoea, cyanosis, and bilateral crepitations. Distinguishing between a primary viral pneumonia and a secondary bacterial pneumonia can be difficult in the clinical setting. The clinical parameters listed in Table 20.4 may aid differentiation [9, 10].

Table 20.4 Clinical parameters that help distinguish between a primary viral pneumonia and a secondary bacterial pneumonia

Primary viral pneumonia

Secondary bacterial pneumonia

Onset of respiratory compromise

1–2 days after initial symptoms

4–7 days after initial symptoms

Antibiotic response

Slow or non-responsive



Normal to low



CRP <20 mg/L

Procalcitonin <0.5 micrograms/L

CRP >20 mg/L

Procalcitonin >0.5 micrograms/L

Lower respiratory tract diagnostic specimen

Normal flora

Gram stain/culture shows predominant organism


Primary fever

Secondary fever after period of defervescence

Over the following 3 days, the patient’s inflammatory markers deteriorated, with her WCC reaching 20.2 × 109/L and her CRP increasing from 149 to 443 mg/L. A CT thorax revealed dense consolidation, bilateral pleural effusions, and anteriorly a predominantly ground glass appearance with few patchy areas of normal lung parenchyma. To aid recruitment and ventilation, a right-sided intercostal chest drain was inserted under ultrasound guidance, subsequently draining 1.7 L. Despite the positive H1N1 throat swab rt-PCR, BAL fluid was negative for influenza A and B, herpes simplex virus, and Pneumocystis jirovecii; additionally, Legionella and pneumococcal urinary antigens were negative. In light of the deteriorating inflammatory markers, IV zanamivir was commenced after successful application for its use on a compassionate basis.

By day 20, intravascular haemolysis had developed, complicating her ECMO, and a large right-sided pleural collection had developed (Figure 20.2), necessitating a right anterolateral thoracotomy for evacuation of the haematoma, whilst on ECMO. Two litres of blood were drained, and two surgical chest drains subsequently placed. When the patient returned to the AICU, the drains became blocked by a blood clot, necessitating an immediate drain replacement.

Figure 20.2 CT thorax revealing a large right-sided haemothorax with compression of the consolidated right lung.

Figure 20.2
CT thorax revealing a large right-sided haemothorax with compression of the consolidated right lung.

The following day, N-acetylcysteine (NAC) was commenced, as her LFTs unexpectedly deteriorated, with the alkaline phosphatase (ALP) rising to 947 from 115 IU/L, gamma-glutamyl transpeptidase (GGT) to 1543 from 102, and aspartate transaminase (AST) to 143 from 21 IU/L. Her bilirubin remained normal, and a liver ultrasound failed to demonstrate any architectural abnormalities, thrombosis, or biliary tract obstruction. Furthermore, a widespread erythematous, blanching, papular rash developed predominantly on her limbs, associated with an elevated eosinophil count of 12.3 × 109/L, which may have been a manifestation of DRESS (drug reaction, eosinophilia, systemic symptoms), possibly secondary to piperacillin/tazobactam. Due to the reduced cardiac output, her renal function also deteriorated, with a rise in her creatinine from a baseline of 62–253 micromoles/L; continuous veno-venous haemodiafiltration (CVVHDF) was subsequently commenced.

A significant left-sided pneumothorax developed on day 23, requiring insertion of a third chest drain. A subsequent CT thorax revealed the progression of ARDS, with diffuse ground glass shadowing, superimposed on reticular changes and traction dilatation of the bronchioles, consistent with fibrotic change, in addition to a further right-sided pneumothorax, for which a fourth chest drain was inserted (Figure 20.3).

Figure 20.3 Late in the clinical course, the lung parenchyma is distorted, contracted, and riddled with cystic airspaces. There are large bilateral pneumothoraces, four intercostal chest drains visible, and a small right-sided haemothorax.

Figure 20.3
Late in the clinical course, the lung parenchyma is distorted, contracted, and riddled with cystic airspaces. There are large bilateral pneumothoraces, four intercostal chest drains visible, and a small right-sided haemothorax.

By day 31, despite the presence of four chest drains on suction, her ventilatory requirements had improved to such a degree that she could be weaned from ECMO to an arteriovenous extracorporeal carbon dioxide removal (ECCOR) device, which is associated with a lower risk of haemorrhagic complications. Unfortunately, she developed gross icterus, as her liver function continued to deteriorate, the bilirubin rising to 390 micromoles/L. Consequently, her case was discussed with the local tertiary liver unit who felt that it was likely to be sepsis-related liver dysfunction, with a prognosis of survival of only 5–10%.

By day 33, the patient’s list of diagnoses was extensive, and ultimately overwhelming, including ARDS with increasing ventilatory requirements whilst on ECCOR, renal failure necessitating haemofiltration, liver failure (on NAC), ongoing sepsis, and increasing vasopressor and inotrope requirements in the context of myocarditis-induced biventricular cardiac failure. The possibility of restarting ECMO was discussed with the family; however, it was decided that it would not change the ultimate outcome. The patient died on day 36, after spending >800 hours on ECMO.


Following the emergence of the first cases of pH1N1 in Mexico in March 2009, the virus spread rapidly, achieving pandemic status within 3 months. The pH1N1 virus resulted from the combination of two genes from a Eurasian swine virus with six genes from a ‘triple-reassortant’ North American swine virus lineage (see Learning point, p. 249). In the US alone, the pandemic accounted for an estimated 59 million illnesses, 265,000 hospitalizations, and 12,000 deaths by mid-February 2010 [11].

The pandemic virus differed from seasonal influenza in its propensity to affect young and middle-aged adults (aged 20–65), rather than the elderly. In the UK, 474 deaths were reported in the pandemic phase, of whom one-third had minimal or no underlying health problems. Risk factors for severe disease included asthma, cardiac disease, immunosuppression, pregnancy and post-partum states, diabetes mellitus, and obesity. Fewer than 1% of patients in the UK were admitted to hospital; however, of these, 12–15% required critical care, placing a huge burden on services [2].

Swine ‘flu’ in pregnancy Learning point Origins of the 2009 H1N1 influenza A pandemic

Epidemic influenza viruses are derived from pandemic viruses by antigenic drift, i.e. gradual minor antigenic changes caused by point mutations in HA and NA molecules, whereas reassortment and interspecies transmission result in the introduction of viruses with new HA and NA subtypes into human populations, thus resulting in pandemics. Epidemics are caused by influenza A and B viruses, whereas only influenza A viruses have pandemic potential [12].

The 1918 ‘Spanish’ influenza pandemic was most probably caused by the transmission of an avian H1N1 virus to humans. Following 1918, H1N1 from that outbreak continued to circulate in humans, causing annual epidemics. Due to the segmented nature of the genome in influenza viruses, they are especially prone to reassortment events if one host is co-infected by two different viruses. This allows genetic material from viruses that usually circulate in birds to be introduced to human adapted viruses. The 1957 Asian pandemic was caused by a novel H2N2 virus that retained five genome segments from the 1918 H1N1 virus but obtained three new segments from an avian H2N2 virus. Similarly, in 1968, the circulating human H2N2 recombined with the HA from an avian H3 virus, resulting in the H3N2 ‘Hong Kong’ pandemic. The H3N2 and H1N1 subtypes have continued to co-circulate and to cause human seasonal influenza outbreaks into the twentieth-first century [13].

The 2009 H1N1 pandemic was unexpected (an H5N1 pandemic was predicted) and challenged the concept that the introduction of a new HA subtype is necessary to result in a pandemic [12]. In fact, the eight gene segments for the 2009 pandemic virus originate from at least four different sources and three different hosts. In the late 1990s, a ‘triple reassortant’ virus emerged in pigs, comprising the PA and PB2 genes from an avian reservoir, the PB1 and NA of a human H3N2, and the four other genes, including the HA, from the ‘classical’ swine virus that had been circulating since 1918. This ‘triple reassortant’ virus subsequently recombined with a Eurasian avian-like H1N1 virus that had been circulating in pigs since the 1970s (receiving the NA and M genes), resulting in the 2009 H1N1 pandemic virus.

The 2009 H1N1 virus is not the same as the H1N1 virus that has been circulating in humans, causing seasonal epidemics, since the 1918 pandemic. Although both viruses have HA proteins derived from the 1918 pandemic, the 2009 virus contained the HA from the ‘classical’ swine influenza virus, which, unlike the seasonal human H1, had been under relatively little antigenic pressure, thus introducing a novel antigen into the human population [13].

The diagnosis in this case was based upon both the clinical presentation and the positive rt-PCR throat swab. Laboratory diagnosis of pH1N1/09 is best achieved through real-time rt-PCR analysis of both combined nasopharyngeal and throat swabs and nasopharyngeal aspirates plus tracheobronchial aspirates in ventilated patients [14]. There is a high incidence of false-negative results, so repeated testing of both upper respiratory swabs and tracheobronchial aspirates is required to exclude a viral infection with confidence. If there is a high index of suspicion, antiviral therapy should be continued until repeated samples are negative [15]. Although rt-PCR is the most sensitive and specific method of diagnosis, it has limited availability, and nasopharyngeal aspiration can be both unpleasant and negative in the presence of influenza-related pneumonia. Rapid influenza antigen and immunofluorescent antibody tests are available that can distinguish influenza A and B; however, they are not able to distinguish seasonal and pandemic influenza A, nor are they as sensitive and specific as rt-PCR [16]. Confirmation of pH1N1/09 infection can only be made by rt-PCR or viral culture.

With regard to management, the Department of Health issued recommendations in October 2009, outlining the treatment of pH1N1 in both the primary and secondary care settings, updating previous BTS guidelines [2]. The recommendation for clinically diagnosed uncomplicated influenza infection is prompt commencement of antiviral therapy plus symptomatic management (antipyretics, good fluid intake, smoking avoidance, rest, and topical decongestants). Hospitalized patients should be administered antibiotics within 4 hours of admission. For severe influenza-related pneumonia, 10 days of parenteral co-amoxiclav plus a macrolide (e.g. clarithromycin) should be given (for penicillin-allergic patients, second-generation cephalosporins may be used as an alternative), extending to 14–21 days where Staphylococcus aureus or Gram-negative enteric bacilli pneumonia is suspected or confirmed. The routine use of corticosteroids in influenza-associated pneumonia is not recommended, and their use may increase mortality.

The NA inhibitor oseltamivir (75 mg orally bd for 5 days) is the drug of choice for most patients because it achieves higher systemic levels than inhaled zanamivir. Early administration of antiviral agents is associated with a better prognosis and limits progression to pulmonary infiltrates, but they still confer benefit if started >48 hours and up to 7 days after symptom onset. H1N1 is resistant to the adamantanes (e.g. amantadine), but oseltamivir-resistant strains have remained relatively rare, with only 45 cases recognized in the UK from 6,379 influenza-positive samples tested [17]. Zanamivir (10 mg inhaled bd for 5 days) is the antiviral of choice in renal failure and for pregnant women—unless they have asthma, COPD, or difficulty using inhaled preparations, in which case oseltamivir should be used. IV zanamivir is not licensed in the UK but has been used, as in this instance, as part of a compassionate-use programme for critically ill patients.

In contrast to seasonal H1N1 influenza, oseltamivir resistance remained relatively low throughout the 2009 pandemic. In the 2 years prior to April 2011, 27,000 pH1N1/09 viruses were tested for NA resistance by the WHO, and only 447 oseltamivir-resistant viruses were identified [18]. The majority of resistant organisms were detected in patients undergoing oseltamivir treatment; however, 14% were isolated from patients with no previous history of oseltamivir treatment, suggesting either spontaneous mutation conferring resistance or transmission of resistant strains from patients who received treatment.

Unsurprisingly, immunocompromised patients, especially those with haematological malignancies or haematopoietic stem cell transplantation (HSCT), were at greatest risk of developing oseltamivir-resistant influenza. Almost half (49%) of the oseltamivir-resistant cases were isolated from immunosuppressed patients, and, of these, half had no prior exposure to antiviral drugs [18]. The majority of resistant cases were associated with a histidine-to-tyrosine mutation (H275Y) in the NA of the virus (alternatively called the H274Y mutation, depending on the NA numbering system used), although other mutations have been identified.

Infection control is of paramount importance during an influenza pandemic, and nosocomial outbreaks were identified during the 2009 H1N1 pandemic, emphasizing the need for adherence to infection control standards in hospitals. Naturally, hand hygiene is a critical element of infection control precautions and, in order to inactivate influenza A, should be carried out for 20–30 s with alcohol hand gel and 40–60 s with handwashing (including thorough drying). Good respiratory hygiene measures (‘catch it, bin it, kill it’) should also be adhered to, not only in the ward environment, but also in communal waiting areas and during patient transport. Respiratory droplets typically travel only 1 m, but ideally patients should be isolated, rather than cohorted, and fluid-repellent surgical masks worn when working in close contact with symptomatic patients. Aerosol-generating procedures, including the use of NIV, should be carried out in well-ventilated single rooms, with the doors closed, wearing a gown, gloves, eye protection, and a filtering face piece 3 (FFP3) face mask. Notably, the administration of nebulized medications and pressured humidified oxygen is not considered to represent a significant infection risk [19].

Vaccination is safe and effective and offers the best means of decreasing the number of individuals infected with influenza. In a study involving over 95,000 children and young adults in Beijing, a monovalent vaccine was 87.3% effective in preventing pH1N1, and there was no association with Guillain–Barré syndrome [20]. During the winter of 2010, a trivalent vaccine that included protection against pH1N1 was available, but uptake was poor in at-risk groups and amongst health-care workers (25% in the National Health Service (NHS)). Health-care workers in the UK accept that vaccination against hepatitis B is required to perform their role, but this is not yet the case for influenza.

Swine ‘flu’ in pregnancy Learning point Influenza vaccination

The WHO monitors the epidemiology of influenza viruses throughout the world. Each year, it makes recommendations about the three strains to be included in vaccines for the forthcoming winter. The majority of current inactivated influenza vaccines are trivalent, containing two subtypes of influenza A and one type B virus. Trivalent vaccines give around 60–70% protection against infection when influenza virus strains in the vaccine are well matched with those in circulation. Quadrivalent vaccines, with an additional strain of influenza B virus, were first authorized for use in the UK in 2013. Following immunization, antibody levels may take up to 10–14 days to reach protective levels. In 2012, the Joint Committee on Vaccination and Immunization (JCVI) recommended that the influenza vaccination programme be extended to all children aged 2 to <17 years old.

Goals of immunization:

  • protection of those who are most at risk of serious illness/death;

  • reducing transmission of infection.

Trivalent influenza vaccine should be offered, ideally before the virus starts to circulate, to:

  • all those aged 65 years or older;

  • all those aged 6 months or older in clinical risk groups:

    • chronic respiratory disease: asthma, COPD, cystic fibrosis, bronchiectasis, ILD;

    • chronic heart disease: chronic heart failure, congenital heart disease;

    • chronic kidney disease: chronic kidney disease 3, 4, and 5, nephrotic syndrome, transplant;

    • chronic liver disease: cirrhosis, chronic hepatitis, biliary atresia;

    • chronic neurological disease: stroke, transient ischaemic attack, compromised respiratory function;

    • diabetes mellitus;

    • immunosuppression;

    • pregnant women: at any stage of pregnancy;

    • morbid obesity (class III): adults with a BMI of ≥40 kg/m2 [21].

A final word from the expert

The clinical issues presented by this case illustrate the need for intensivists to liaise closely with other specialties. The organisms which cause pneumonia, their treatment, and identification change quite markedly from year to year, requiring input from clinical microbiologists and public health physicians. Similarly, obstetricians and midwives, where appropriate, should be constantly available to support the intensive care team to optimize care for the mother and baby. After the A/H1N1 2009 influenza pandemics of 2009–2010, a national ECMO service was commissioned to provide retrieval to one of five specialist centres and advanced organ support for the patients most severely affected by ARDS.


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