Relative role of community transmission and campus contagion in driving the spread of SARS-CoV-2: Lessons from Princeton University.

Mathematical models have played a crucial role in exploring and guiding pandemic responses. University campuses present a particularly well-documented case for institutional outbreaks, thereby providing a unique opportunity to understand detailed patterns of pathogen spread. Here, we present descriptive and modeling analyses of SARS-CoV-2 transmission on the Princeton University (PU) campus-this model was used throughout the pandemic to inform policy decisions and operational guidelines for the university campus. Epidemic patterns between the university campus and surrounding communities exhibit strong spatiotemporal correlations. Mathematical modeling analysis further suggests that the amount of on-campus transmission was likely limited during much of the wider pandemic until the end of 2021. Finally, we find that a superspreading event likely played a major role in driving the Omicron variant outbreak on the PU campus during the spring semester of the 2021-2022 academic year. Despite large numbers of cases on campus in this period, case levels in surrounding communities remained low, suggesting that there was little spillover transmission from campus to the local community.

Multistate Outbreak of Burkholderia cepacia Complex Bloodstream Infections After Exposure to Contaminated Saline Flush Syringes: United States, 2016-2017.

BACKGROUND: Burkholderia cepacia complex (Bcc) has caused healthcare-associated outbreaks, often in association with contaminated products. The identification of 4 Bcc bloodstream infections in patients residing at a single skilled nursing facility (SNF) within 1 week led to an epidemiological investigation to identify additional cases and the outbreak source. METHODS: A case was initially defined via a blood culture yielding Bcc in a SNF resident receiving intravenous therapy after 1 August 2016. Multistate notifications were issued to identify additional cases. Public health authorities performed site visits at facilities with cases to conduct chart reviews and identify possible sources. Pulsed-field gel electrophoresis (PFGE) was performed on isolates from cases and suspect products. Facilities involved in manufacturing suspect products were inspected to assess possible root causes. RESULTS: An outbreak of 162 Bcc bloodstream infections across 59 nursing facilities in 5 states occurred during September 2016-January 2017. Isolates from patients and pre-filled saline flush syringes were closely related by PFGE, identifying contaminated flushes as the outbreak source and prompting a nationwide recall. Inspections of facilities at the saline flush manufacturer identified deficiencies that might have led to the failure to sterilize a specific case containing a partial lot of the product. CONCLUSIONS: Communication and coordination among key stakeholders, including healthcare facilities, public health authorities, and state and federal agencies, led to the rapid identification of an outbreak source and likely prevented many additional infections. Effective processes to ensure the sterilization of injectable products are essential to prevent similar outbreaks in the future.

Varicella Vaccine Effectiveness in Preventing Community Transmission in the 2-Dose Era.

OBJECTIVES: We examined overall and incremental effectiveness of 2-dose varicella vaccination in preventing community transmission of varicella among children aged 4 to 18 years in 2 active surveillance sites. One-dose varicella vaccine effectiveness (VE) was examined in those aged 1 to 18 years. METHODS: From May 2009 through June 2011, varicella cases identified during active surveillance in Antelope Valley, CA and Philadelphia, PA were enrolled into a matched case-control study. Matched controls within 2 years of the patient's age were selected from immunization registries. A standardized questionnaire was administered to participants' parents, and varicella vaccination history was obtained from health care provider, immunization registry, or parent records. We used conditional logistic regression to estimate varicella VE against clinically diagnosed and laboratory-confirmed varicella. RESULTS: A total of 125 clinically diagnosed varicella cases and 408 matched controls were enrolled. Twenty-nine cases were laboratory confirmed. One-dose VE (1-dose versus unvaccinated) was 75.6% (95% confidence interval [CI], 38.7%-90.3%) in preventing any clinically diagnosed varicella and 78.1% (95% CI, 12.7%-94.5%) against moderate or severe, clinically diagnosed disease (≥50 lesions). Among subjects aged ≥4 years, 2-dose VE (2-dose versus unvaccinated) was 93.6% (95% CI, 75.6%-98.3%) against any varicella and 97.9% (95% CI, 83.0%-99.7%) against moderate or severe varicella. Incremental effectiveness (2-dose versus 1-dose) was 87.5% against clinically diagnosed varicella and 97.3% against laboratory-confirmed varicella. CONCLUSIONS: Two-dose varicella vaccination offered better protection against varicella from community transmission among school-aged children compared with 1-dose vaccination.

Varicella outbreak in a daycare: challenges and opportunities for preventing varicella outbreaks in this setting.

As a result of single-dose varicella vaccination, daycare outbreaks have become rare. We investigated a daycare outbreak resulting from a misdiagnosed varicella case in an unvaccinated attendee. Of 25 attendees aged 12-32 months without evidence of immunity, 7 (28%) were unvaccinated due to religious/philosophical opposition or recent 1st birthday. Single-dose vaccination reduced disease by 92% compared with no vaccination.

Knowledge, attitudes, and practices for diagnosing breakthrough varicella in the outpatient setting.

OBJECTIVES: We assessed provider knowledge, attitudes, and practices for the management of breakthrough varicella and identified barriers to implementation of laboratory testing and reporting. METHODS: We surveyed 145 health-care providers (HCPs) from 30 pediatric practices in Philadelphia who did not have a history of laboratory testing for breakthrough varicella. The self-administered survey instrument collected information on clinicians' practices for management of children presenting with rash, infection-control strategies, reporting to public health agencies, and laboratory testing. RESULTS: Among the 144 HCPs who completed the survey, 73 (51%) had practiced for more than 10 years. While 115 HCPs (80%) would elect to evaluate a child with rash in the office, only 19 (13%) would submit diagnostics. When patients had a known recent exposure to varicella, 84 HCPs (58%) would use laboratory tests: 40% would use direct fluorescent antibody staining on a specimen from a cutaneous lesion, 24% would use polymerase chain reaction on a lesion specimen, 21% would use acute and convalescent serology, and 10% would use other tests. While waiting for test results, 82 HCPs (57%) would advise that the child be kept at home, 39 (27%) would notify the local health department, and 33 (23%) would inform the school nurse. CONCLUSION: As varicella becomes increasingly uncommon, laboratory confirmation becomes more critical for appropriate diagnosis, similar to poliomyelitis and measles. Our findings suggest that HCPs need further education regarding laboratory confirmation, containment, and reporting of breakthrough varicella.

Herpes simplex virus infection in young infants during 2 decades of empiric acyclovir therapy.

OBJECTIVE: To describe the clinical presentation of HSV-infected young infants and to seek distinctive features that could permit a targeted approach to empiric use of acyclovir. METHODS: Case study of neonatal HSV during a 22-year period of an institutional strategy of consistent use of acyclovir empirically in all infants with onset of an illness at ≤ 21 days of age for which antibiotics were given empirically. Multiple sources were used to optimize HSV case data, and to estimate the rate of HSV infection in empirically treated infants. RESULTS: A total of 32 infants with perinatally acquired HSV infection were identified. All received acyclovir empirically at admission. At presentation, 50% of infants had only nonspecific complaints, which was fever in 75%. After testing, 75% of infants with HSV had central nervous system (CNS) infection, including 40% who presented with mucocutaneous lesions, 83% with seizures, and 94% with nonspecific complaints. Cerebrospinal fluid (CSF) polymerase chain reaction confirmed CNS infection in 16 of 22 (73%) patients tested. Cultures of mucocutaneous lesion yielded HSV in 8 of 10 cases, but culture of CSF was negative in all 26 cases tested, and screening cultures of unaffected mucosal sites were the only HSV-confirmatory test in a single patient. Laboratory and CSF findings were not distinctive in patients with HSV. Age of ≤ 21 days at onset of symptoms captured 90% of all infants with HSV and 94% of those with nonspecific complaints. An estimated 1.3% of empirically treated patients had HSV infection. CONCLUSIONS: Early manifestations of perinatally acquired HSV are frequently nonspecific, yet CNS infection is common. Empiric acyclovir strategy narrowly restricted to infants with onset of illness at ≤ 21 days of age, who would receive antibiotics empirically, captured 90% of HSV cases and anticipated a rate of HSV CNS infection similar to that of bacterial meningitis.

Implementation of rotavirus immunization in Philadelphia, Pennsylvania: high levels of vaccine ineligibility and off-label use.

OBJECTIVE: Our goal was to predict, using delayed diphtheria-tetanus-acellular pertussis vaccination as an indicator, whether the current narrowly defined age limits for pentavalent rotavirus vaccine exclude a substantial proportion of children from complete immunization against rotavirus and to assess adherence of providers to recommended age limits by examining the first 6 months of use of pentavalent rotavirus vaccine in Philadelphia, Pennsylvania. PATIENTS AND METHODS: Data from a computerized children's immunization registry in Philadelphia were analyzed. Demographics and age at immunization with first 3 diphtheria-tetanus-acellular pertussis doses were examined from 2001 to 2005. Similar characteristics were evaluated for children who received pentavalent rotavirus vaccine doses during the first 6 months of its availability (August 2006 through January 2007). RESULTS: During the 5-year period, 24 403 of 103 967 recipients of first diphtheria-tetanus-acellular pertussis vaccine were >12 weeks of age; only 56 411 of 79 564 first diphtheria-tetanus-acellular pertussis recipients 12 weeks of age. Hospital-based providers were less likely to administer pentavalent rotavirus vaccine off-label. CONCLUSIONS: With the current level of vaccine implementation and current pentavalent rotavirus vaccine recommendations for series initiation, a substantial proportion of children are expected to be excluded from receiving any pentavalent rotavirus vaccine or completing the series. In the first 6 months of availability, pentavalent rotavirus vaccine frequently was used off-label for age, underscoring the importance of education of immunization providers. Current outreach programs for finding 10-month-old toddlers delinquent for immunizations will not improve the possibility of protection against rotavirus.

Routine laboratory testing data for surveillance of rotavirus hospitalizations to evaluate the impact of vaccination.

OBJECTIVE: The recent implementation of a rotavirus vaccination program in the United States makes it imperative to assess the impact of immunization on the incidence of severe rotavirus disease leading to hospitalization. Active surveillance for laboratory-confirmed rotavirus hospitalizations is the ideal approach for surveillance, but requires substantial resources to implement. We examined laboratory and hospital discharge data for 2 tertiary care pediatric hospitals to assess the utility of routine laboratory testing data for surveillance of rotavirus gastroenteritis and to estimate rotavirus disease burden. DESIGN: We obtained all discharge records of hospitalizations for acute gastroenteritis among children <5 years of age at Children's Mercy Hospital (CMH), Kansas City, from July 2000 to June 2005 and at Children's Hospital of Philadelphia (CHOP) from July 2004 to June 2006. We linked these discharge records to laboratory results of rotavirus testing to evaluate epidemiologic differences in children who were tested and not tested for rotavirus and to estimate overall rotavirus burden by extrapolating clinical testing results to the untested group. RESULTS: At CMH, of the 3702 children with acute gastroenteritis, 69% (n = 2552) were discharged during the winter (January through May) months, when rotavirus is most common. Similarly, at CHOP, 62% (n = 779) of the 1261 gastroenteritis discharges occurred during the winter months. During these months, 47% (n = 1197 of 2552) of the discharges at CMH and 56% (n = 438 of 779) of the discharges at CHOP were tested for rotavirus and of those tested, 71% (n = 853 of 1197) and 55% (n = 242 of 438) were positive, respectively. At both hospitals, children with and without rotavirus testing had similar gender and race/ethnicity, but the rate of testing differed by age at CHOP and by month of admission at CMH. After adjusting for these differences, we estimate that 56%-70% of winter and 34%-48% of year-round gastroenteritis in children <5 years can be attributable to rotavirus. Overall, 3%-5% of all hospitalizations in children <5 years of age were caused by rotavirus. CONCLUSIONS: Sentinel hospitals where a large proportion of children hospitalized for gastroenteritis are routinely tested for rotavirus could provide a useful and cost-efficient platform to complement ongoing active surveillance efforts to evaluate the impact of rotavirus vaccination. The data reaffirm the substantial burden of rotavirus hospitalizations in US children and the potential health benefits of vaccination.

Resource consumption in the infection control management of pertussis exposure among healthcare workers in pediatrics.

OBJECTIVE: To assess consumption of resources in the infection control management of healthcare workers (HCWs) exposed to pertussis and to assess avoidability of exposure. SETTING: Tertiary care children's medical center. METHODS: Analysis of the extent of and reasons for HCW exposure to pertussis during contact with children with the disease, whether exposures were avoidable (because of the failure to recognize a case or to order or adhere to isolation precautions) or unavoidable (because the case was not recognizable or because another diagnosis was confirmed), and the cost of implementing exposure management. INTERVENTIONS: Interventions consisted of an investigation of every HCW encounter with any patient who was confirmed later to have pertussis from the time of hospital admission of the patient, use of azithromycin as postexposure prophylaxis (PEP) for exposed HCWs, performance of 21-day surveillance for cough illness, testing of symptomatic exposed HCWs for Bordetella pertussis, and enhanced preexposure education of HCWs. RESULTS: From September 2003 through April 2005, pertussis was confirmed in 28 patients (median age, 62 days); 24 patients were admitted. For 11 patients, pertussis was suspected, appropriate precautions were taken, and no HCW was exposed. Inadequate precautions for 17 patients led to 355 HCW exposures. The median number of HCWs exposed per exposing patient was 9 (range, 1-86 HCWs; first quartile mean, 2; fourth quartile mean, 61). Exposure was definitely avoidable for only 61 (17%) of 355 HCWs and was probably unavoidable for 294 HCWs (83%). The cost of 20-month infection control management of HCWs exposed to pertussis was $69,770. The entire cohort of HCWs involved in direct patient care at the facility could be immunized for approximately $60,000. CONCLUSIONS: Exposure of HCWs to pertussis during contact with children who have the disease is largely unavoidable, and management of this exposure is resource intensive. Universal preexposure vaccination of HCWs is a better utilization of resources than is case-based postexposure management.