Abstract

Traditional modes of investigating influenza nosocomial transmission have entailed a combination of confirmatory molecular diagnostic testing and epidemiological investigation. Common hospital-acquired infections like influenza require a discerning ability to distinguish between viral isolates to accurately identify patient transmission chains. We assessed whether influenza hemagglutinin sequence phylogenies can be used to enrich epidemiological data when investigating the extent of nosocomial transmission over a four-month period within a paediatric Hospital in Cape Town South Africa. Possible transmission chains/channels were initially determined through basic patient admission data combined with Maximum likelihood and time-scaled Bayesian phylogenetic analyses. These analyses suggested that most instances of potential hospital-acquired infections resulted from multiple introductions of Influenza A into the hospital, which included instances where virus hemagglutinin sequences were identical between different patients. Furthermore, a general inability to establish epidemiological transmission linkage of patients/viral isolates implied that identified isolates could have originated from asymptomatic hospital patients, visitors or hospital staff. In contrast, a traditional epidemiological investigation that used no viral phylogenetic analyses, based on patient co-admission into specific wards during a particular time-frame, suggested that multiple hospital acquired infection instances may have stemmed from a limited number of identifiable index viral isolates/patients. This traditional epidemiological analysis by itself could incorrectly suggest linkage between unrelated cases, underestimate the number of unique infections and may overlook the possible diffuse nature of hospital transmission, which was suggested by sequencing data to be caused by multiple unique introductions of influenza A isolates into individual hospital wards. We have demonstrated a functional role for viral sequence data in nosocomial transmission investigation through its ability to enrich traditional, non-molecular observational epidemiological investigation by teasing out possible transmission pathways and working toward more accurately enumerating the number of possible transmission events.

Highlights

  • Despite the existence of infection control policies and protocols, nosocomial transmission of respiratory viruses is a common problem that can occur in virtually any health-care setting [1,2,3,4,5,6,7]

  • For the purpose of this investigation the transmission case definitions were as follows: (1) a suspected hospitalacquired influenza infection (HAI) case was defined as an influenza PCR positive individual who did not present to the hospital with respiratory symptoms or was confirmed to be influenza negative by laboratory testing within three days of admission (Fig 1); and (2) a suspected community-acquired infection (CAI) case was defined as a patient with laboratory-confirmed Influenza A (H1N1pdm) at or within three days of admission

  • The Red Cross War Memorial Hospital (RXH) building complex consists of several buildings, most with multiple levels, each physically separated to limit nosocomial transmission between wards

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Summary

Introduction

Despite the existence of infection control policies and protocols, nosocomial transmission of respiratory viruses is a common problem that can occur in virtually any health-care setting [1,2,3,4,5,6,7]. Investigation of influenza nosocomial transmission has required a combination of confirmatory influenza diagnostic testing (usually PCR) and epidemiological investigation. PCR-based molecular diagnostic assays are generally limited in their capacity to classify etiologic agents beyond the type/subtype level. While this is acceptable for the diagnosis of uncommon hospital acquired infections (HAIs), for more common causes of HAIs such as influenza it is desirable to apply assays that yield enough data to more accurately distinguish unique patient transmission chains. In conjunction with epidemiological data such assays could be effectively used to test whether patient infections have a nosocomial origin [6, 14,15,16,17]

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