Syndromic Surveillance as a Tool for Case-Based Varicella Reporting in Georgia, 2016-2019.

OBJECTIVES: Syndromic surveillance can be used to enhance notifiable disease case-based surveillance. We analyzed features of varicella reported in Georgia to evaluate case detection through syndromic surveillance and to compare varicella reported through syndromic surveillance with varicella reported from all other sources. METHODS: Syndromic surveillance was incorporated into case-based varicella surveillance by the Georgia Department of Public Health (GDPH) in May 2016. A cross-sectional study design evaluated syndromic and nonsyndromic varicella reported to GDPH from May 1, 2016, through December 31, 2019. Varicella was reported by nonsyndromic sources including health care providers, schools, and laboratories. We identified syndromic varicella cases from urgent care and emergency department visit data with discharge diagnoses containing the terms "varicella" or "chickenpox." RESULTS: Syndromic notifications accounted for 589 of 2665 (22.1%) suspected varicella reports investigated by GDPH. The positive predictive value was 33.1% for syndromic notifications and 31.3% for nonsyndromic notifications. Mean days from rash onset to GDPH notification was 3.2 days fewer (P < .001) among patients identified through syndromic notification than among patients identified through nonsyndromic notification. The odds of varicella identified by syndromic notification being outbreak-associated were 0.18 (95% CI, 0.09-0.36) times those of varicella identified through nonsyndromic notification. PRACTICE IMPLICATIONS: Syndromic notifications were an effective, timely means for varicella case detection. Syndromic patients were significantly less likely than nonsyndromic patients to be outbreak-associated, possibly because of early detection. Syndromic surveillance enhanced case-based reporting for varicella in Georgia and was a useful tool to improve notifiable disease surveillance.

Genetic Stability of Parainfluenza Virus 5-Vectored Human Respiratory Syncytial Virus Vaccine Candidates after In Vitro and In Vivo Passage.

Human respiratory syncytial virus (RSV) is the leading etiologic agent of lower respiratory tract infections in children, but no licensed vaccine exists. Previously, we developed two parainfluenza virus 5 (PIV5)-based RSV vaccine candidates that protect mice against RSV challenge. PIV5 was engineered to express either the RSV fusion protein (F) or the RSV major attachment glycoprotein (G) between the hemagglutinin-neuraminidase (HN) and RNA-dependent RNA polymerase (L) genes of the PIV5 genome [PIV5-RSV-F (HN-L) and PIV5-RSV-G (HN-L), respectively]. To investigate the stability of the vaccine candidates in vitro, they were passaged in Vero cells at high and low multiplicities of infection (MOIs) for 11 generations and the genome sequences, growth kinetics, and protein expression of the resulting viruses were compared with those of the parent viruses. Sporadic mutations were detected in the consensus sequences of the viruses after high-MOI passages, and mutation rates increased under low-MOI-passage conditions. None of the mutations abolished antigen expression. Increased numbers of mutations correlated with increased growth rates in vitro, indicating that the viruses evolved through the course of serial passages. We also examined the in vivo stability of the vaccine candidates after a single passage in African green monkeys. No mutations were detected in the consensus sequences of viruses collected from the bronchoalveolar lavage (BAL) fluid of the animals. In vivo, mutations in RSV G and PIV5 L were found in individual isolates of PIV5-RSV-G (HN-L), but plaque isolates of PIV5-RSV-F (HN-L) had no mutations. To improve upon the PIV5-RSV-F (HN-L) candidate, additional vaccine candidates were generated in which the gene for RSV F was inserted into earlier positions in the PIV5 genome. These insertions did not negatively impact the sequence stability of the vaccine candidates. The results suggest that the RSV F and G gene insertions are stable in the PIV5 genome. However, the function of the foreign gene insertion may need to be considered when designing PIV5-based vaccines.IMPORTANCE The genetic stability of live viral vaccines is important for safety and efficacy. PIV5 is a promising live viral vector and has been used to develop vaccines. In this work, we examined the genetic stability of a PIV5-based RSV vaccine in vitro and in vivo We found that insertions of foreign genes, such as the RSV F and G genes, were stably maintained in the PIV5 genome and there was no mutation that abolished the expression of RSV F or G. Interestingly, the function of the inserted gene may have an impact on PIV5 genome stability.