Epidemiology of Adenovirus Infections and Outcomes of Cidofovir Treatment in Severely Ill Children

Abstract

Background: An increase in human adenovirus (HAdV) infections among hospitalized children in Singapore was observed since 2013. Young age (<2 years) and significant comorbidities have been associated with severe HAdV infections which can result in significant morbidity and mortality. Cidofovir (CDV) has been used to treat severe HAdV infections despite limited data and efficacy. Methods: This is a retrospective, observational review of infants and children 1 month to 17 years of age with laboratory-confirmed severe HAdV infection, admitted to a pediatric tertiary care hospital in Singapore between January 2013 and September 2017. Severe infection was defined as requiring intensive care unit or high dependency care at any point during hospital admission. Clinical characteristics, potential risk factors for mortality, as well as the outcome of cases treated with CDV were examined. Results: A total of 1167 children were admitted for HAdV infection, of which 85 (7.3%) were severe. For severe infections, the median age was 1.5 years (interquartile range: 0.72–3.2 years). The majority had comorbidities (69.4%) and presented with pneumonia (32.9%). Genotypes HAdV-7 (29.4%) and HAdV-3 (27.0%) were the most common HAdV genotypes identified. Thirteen (15.3%) patients died. Patients who died had a higher proportion of existing neurologic comorbidity (46.2% vs. 13.9%; P = 0.014) and presentation with pneumonia (69.2% vs. 26.4%; P = 0.008) compared with survivors. Patients who presented with pneumonia had a higher risk of 30-day mortality (odds ratio 4.3, 95% confidence interval: 1.0–28.6; P < 0.05). CDV was administered to 17 (20%) children for mainly viremia (47.1%) and/or pneumonia (41.2%). Mortality rate was 41.2% for severe HAdV cases treated with CDV. A significant proportion of patients who died when compared with recovered patients presented with pneumonia (6 of 7, 85.7% vs 1 of 10, 10%; P = 0.004). All 8 patients who had viremia received CDV and survived. Conclusions: Mortality can be high in pediatric patients with severe HAdV infections. HAdV-7 and HAdV-3 were the most common genotypes identified in our cohort with severe HAdV infection. Pneumonia is a potential risk factor for mortality in severe HAdV infections in our cohort. Early CDV administration may be considered in patients with severe HAdV infection and existing comorbidities but more studies are required.

Epidemiology of Adenovirus Pneumonia and Risk Factors for Bronchiolitis Obliterans in Children During an Outbreak in Jilin, China

“…Among those with severe cases, half were <2 years old. This is similar to findings from Singapore, where most children with severe HAdV were <2 years old ( 23 , 24 ). It has been reported that “young children are at increased risk of severe HAdV infection” ( 25 ).…”

Human adenoviruses in paediatric patients with respiratory tract infections in Beijing, China

“…The most common species of HAdV worldwide, affecting the respiratory tracts of both adults and children, are HAdV-B, HAdV-C and HAdV-E, among which HAdV-B3 and HAdV-B7 are the main epidemic strains [44][45][46].…”

Human Adenoviruses in Paediatric Patients With Respiratory Tract Infections in Beijing, China

“…The most common types of HAdV worldwide, affecting the respiratory tracts of both adults and children, are HAdV-B, HAdV-C and HAdV-E, among which HAdV-B3 and HAdV-B7 are the main epidemic strains [40][41][42]. HAdV-55, which often causes outbreaks, is also detected at high rates in cases of adult respiratory tract infection [4,6].…”