Influenza virus infection during pregnancy and in specific populations

Abstract

Influenza virus infection causes approximately 1 billion infections worldwide each year. These infections are usually self-limiting, but serious complications may occur, in particular in adults aged 65 years or older, patients with cardiovascular disease, asthma or autoimmune disorders and pregnant women. In this thesis we studied several aspects of influenza virus infection. Pregnant women appear to be at an increased risk of complications of influenza virus infection, especially during the third trimester, and in particular to be admitted to an intensive care unit. In pregnant women with infection that does not require hospitalization, pregnancy outcome is normal. By contrast, severe maternal disease requiring hospitalization is associated with poor pregnancy outcome like preterm birth and stillbirth. Chronic villitis is present in 47% of placentas of fetuses whose mother had been affected by influenza infection during pregnancy. Influenza A(H1N1)pdm2009 virus was not present in these placentas. Considering treatment of pregnant women with antiviral drugs, observational studies suggest a window of opportunity to prevent escalation of disease severity, since severe disease and intensive care admission is associated with delayed (>48 hours after symptom onset) compared to prompt (≤48 hours) initiation of treatment with antiviral drugs. Safety data on antiviral drugs in pregnant women are reassuring. There appears to be no increased risk of congenital anomalies or other adverse pregnancy outcome. Still, these data have to be interpreted with caution given the relatively small number of exposed fetuses / neonates that have been studied. Furthermore, in contrast to results from placental models that suggested low penetrance of the drug, we found that the concentration of oseltamivir (carboxylate) in cord blood is at therapeutic levels. Vaccination is considered safe and reduces both maternal and neonatal morbidity from influenza virus infection. It is unclear if vaccination reduces the incidence of preterm birth, number of small-for-gestational age neonates and stillbirth. Approximately half of gynecologists in the Netherlands discuss influenza vaccination with their patients, especially with those with comorbidity. Their main motivation to discuss the topic is the ability of influenza vaccination to prevent maternal infection. It is well known that influenza vaccination is safe. Its effects on the prevention of maternal and neonatal infection are less well known. In critically ill, immunocompromised patients, testing for resistance to antiviral drugs and treatment with a combination of different antiviral drugs may be useful since viral shedding in these patients is prolonged and mutations that induce resistance to antiviral drugs occur more often in these patients. Incidentally, neurological symptoms may develop as a complication of influenza virus infection. Attribution of these symptoms to influenza infection is difficult. We suggest a diagnostic pathway to aid clinicians in early and correct diagnosis. Supportive therapy combined with oseltamivir and corticosteroids are customary treatments. It is recommended for health care workers to receive an influenza vaccine. We showed that there are significant differences in the nature and severity of side effects upon intramuscular and intradermal vaccination. This difference did not result in a preference among vaccinated subjects for one type of vaccine.