Human Respiratory Syncytial Virus Caused Lower Respiratory Tract Infection: Clinical and Molecular Characterization in Hospitalized Children in Latvia. Summary of the Doctoral Thesis

Abstract

Human respiratory syncytial virus (HRSV) represents a particular challenge in pediatric infectious diseases. First, it is the most common etiologic agent of lower respiratory tract infections in infants and young children, which is the leading cause of hospitalization and mortality in this age group. Second, there is no effective specific treatment available. Third, although effective and safe vaccine is a global priority, its research is still in phase I clinical trials. One of the challenges in vaccine development, the high variability of the virus, was addressed in this study. A total of 207 hospitalized children with lower respiratory tract infections were prospectively enrolled in the study over three consecutive seasons. For HRSV diagnosis and group, HRSV-A and B, differentiation a polymerase chain reaction based method was developed that tested positive 88 (42.5%) of the patients. The seasonal activity lasted from weeks 51 to 19. During the annual outbreaks, HRSV caused more than 90% of bronchiolitis and 50% of pneumonia. Children with HRSV lower respiratory tract infection were significantly younger than those with non-HRSV and were mostly less than 6-month-old. Molecular analysis revealed that the strains of both groups co-circulated, however HRSV-A viruses predominated for the first two consecutive seasons followed by an HRSV-B dominant season. Within the groups, viruses belonged to the worldwide dominant genotypes NA1 (HRSV-A) and BA-IV (HRSV-B). Clinical characteristics of infections caused by the different groups or genotypes were not statistically significant. In 2012, recently described HRSV-A genotype ON1 emerged in Latvia. Its characteristic 72-nucleotide duplication in the G gene was exploited to reconstruct the global spread and population dynamics of this genotype. This is the first molecular epidemiologic study of HRSV in Latvia and it has several important findings. It emphasizes the need for precise HRSV seasonality data. In this study several new HRSV strains were detected and deposited in GenBank database. This is also the first study suggesting a hypothesis of the global dissemination and population dynamics of the novel genotype ON1. The data presented here can be used to optimize timing of immunoprophylaxis in the high-risk infants in Latvia and to develop global public health interventions.