Vaccines: An Emerging Multi-Modal Tool in the Fight Against Cancer.

Vaccines play an import role in cancer prevention as well as a growing role in cancer therapeutics. This article explores current knowledge regarding the role of vaccines (HPV and HBV vaccines) in protecting against preventable risk factors for select cancers as well as anti-cancer vaccines currently being used in practice. Current data suggests that routine childhood vaccination against HPV and HBV is an effective strategy for not only protecting against life-altering infectious diseases but also protecting against adult-onset cancers. Furthermore, while current vaccination practices and anti-cancer therapeutics have come a long way in recent decades, examination of CDC data also identifies areas for growth and improvement.

Clinical Practice Guideline by the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA): 2023 Guideline on Diagnosis and Management of Acute Bacterial Arthritis in Pediatrics.

This clinical practice guideline for the diagnosis and treatment of acute bacterial arthritis (ABA) in children was developed by a multidisciplinary panel representing the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA). This guideline is intended for use by healthcare professionals who care for children with ABA, including specialists in pediatric infectious diseases and orthopedics. The panel's recommendations for the diagnosis and treatment of ABA are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the diagnosis and treatment of ABA in children. The panel followed a systematic process used in the development of other IDSA and PIDS clinical practice guidelines, which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) (see Figure 1). A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.

Clinical Practice Guideline by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America: 2021 Guideline on Diagnosis and Management of Acute Hematogenous Osteomyelitis in Pediatrics.

This clinical practice guideline for the diagnosis and treatment of acute hematogenous osteomyelitis (AHO) in children was developed by a multidisciplinary panel representing Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA). This guideline is intended for use by healthcare professionals who care for children with AHO, including specialists in pediatric infectious diseases, orthopedics, emergency care physicians, hospitalists, and any clinicians and healthcare providers caring for these patients. The panel's recommendations for the diagnosis and treatment of AHO are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the diagnosis and treatment of AHO in children. The panel followed a systematic process used in the development of other IDSA and PIDS clinical practice guidelines, which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.

Modeling HPV vaccination scale-up among urban young men who have sex with men in the context of HIV.

INTRODUCTION: Young men who have sex with men (YMSM) are at high risk to contract human papillomavirus (HPV). While an effective vaccination exists, its use among YMSM is markedly lower compared to non-MSM and women. This study compares scaling up HPV vaccination in conjunction with other prevention strategies. METHODS: An agent-based model of urban YMSM (≤26 years of age) reflective of the demography of Philadelphia, PA, simulated for up to ten years of follow-up to examine anal and oral transmission of the HPV genotypes covered in the nonavalent (9v) vaccine: 6, 11, 16, 18, 31, 33, 45, 52, 58. Starting HPV prevalences ranged from a high of 18% (type 6) to a low of 6% (type 31); overall 65% of individuals carried any HPV genotype. Simulated levels of vaccination were ranged from 0% to 13% (present-day level), 25%, 50%, 80% (Healthy People 2020 target), and 100% in conjunction with condom use and HIV seroadaptive practices. The primary outcome was the relative reduction in HPV infection. RESULTS: Compared to present-day vaccination levels (13%), scaling-up vaccination led to expected declines in 10-year post-simulation HPV prevalence. Anal HPV (any 9v types) declined by 9%, 27%, 46%, and 58% at vaccination levels of 25%, 50%, 80%, and 100%, respectively. Similarly, oral HPV (any 9v types) declined by 11%, 33%, 57%, and 71% across the same levels of vaccine uptake. Comparing the prevention strategies, condoms blocked the greatest number of anal transmissions when vaccination was at or below present-day levels. For oral transmission, vaccination was superior to condom use at all levels of coverage. CONCLUSIONS: Public health HPV preventions strategies should continue to emphasize the complementary roles of condoms and vaccination, especially for preventing oral infection. Improving vaccination coverage will ultimately have the greatest impact on reducing HPV infection among YMSM.

Hepatitis C in Pregnant Women and Their Children.

Hepatitis C virus (HCV) infection presents unique challenges in the setting of pregnancy. HCV can contribute to pregnancy-related morbidity and pregnancy can influence the course of HCV infection. There is a significant risk of transmission to the fetus and newborn infant. Identification of HCV infection in women of childbearing potential and those who are currently pregnant offers important opportunities for the woman and for past, present and future children.

Spatial and environmental correlates of organism colonization and infection in the neonatal intensive care unit.

OBJECTIVE: To examine organism colonization and infection in the neonatal intensive care unit as a result of environmental and spatial factors. STUDY DESIGN: A retrospective cohort of infants admitted between 2006 and 2015 (n = 11 428), to assess the relationship between location and four outcomes: methicillin-resistant Staphylococcus aureus (MRSA) colonization; culture-confirmed late-onset sepsis; and, if intubated, endotracheal tube colonization with Pseudomonas aeruginosa or Klebsiella pneumonia. Independent risk factors were identified with mixed-effects logistic regression models and Moran's I for spatial autocorrelation. RESULT: All four outcomes statistically clustered by location; neighboring colonization also influenced risk of MRSA (p < 0.05). For P. aeruginosa, being in a location with space for more medical equipment was associated with 2.61 times the odds of colonization (95% CrI: 1.19, 5.78). CONCLUSION: Extrinsic factors partially explained risk for neonatal colonization and infection. For P. aeruginosa, infection prevention efforts at locations with space for more equipment may lower future colonization.

A Network Model of Hand Hygiene: How Good Is Good Enough to Stop the Spread of MRSA?

BACKGROUND Simulation models have been used to investigate the impact of hand hygiene on methicillin-resistant Staphylococcus aureus (MRSA) transmission within the healthcare setting, but they have been limited by their ability to accurately model complex patient-provider interactions. METHODS Using a network-based modeling approach, we created a simulated neonatal intensive care unit (NICU) representing the potential for per-hour infant-infant MRSA transmission via the healthcare worker resulting in subsequent colonization. The starting prevalence of MRSA colonized infants varied from 2% to 8%. Hand hygiene ranged from 0% (none) to 100% (theoretical maximum), with an expected effectiveness of 88% inferred from literature. RESULTS Based on empiric care provided within a 1-hour period, the mean number of infant-infant MRSA transmissible opportunities per hour was 1.3. Compared to no hand hygiene and averaged across all initial colonization states, colonization was reduced by approximately 29%, 51%, 67%, 80%, and 86% for the respective levels of hygiene: 24%, 48%, 68%, 88%, and 100%. Preterm infants had a 61% increase in MRSA colonization, and mechanically ventilated infants had a 27% increase. CONCLUSIONS Even under optimal hygiene conditions, horizontal transmission of MRSA is possible. Additional prevention paradigms should focus on the most acute patients because they are at greatest risk. Infect Control Hosp Epidemiol 2017;38:945-952.

Assessing Occupancy and Its Relation to Healthcare-Associated Infections.

Occupancy has been associated with risk for healthcare-associated infections, yet its definition varies widely. Occupancy can be modeled as a function of census, acuity of the patient care unit, staffing ratio, or some combination. This article discusses the appropriate parameterization of these measures and how to interpret their impact. Infect Control Hosp Epidemiol 2016:1-3.

Antimicrobial prescription errors in hospitalized children: role of antimicrobial stewardship program in detection and intervention.

BACKGROUND: Antimicrobial stewardship programs (ASP) are an effective strategy to ensure that antibiotics are used in accordance with scientific evidence to improve patient outcome, minimize antimicrobial (AM) resistance, and reduce hospital costs. The article describes the impact of the implementation of an ASP on AM prescription errors. METHODS: Prospective, single-center study performed at a tertiary pediatric teaching hospital that actively monitored 13 targeted AMs (amikacin, amphotericin B, cefepime, ceftriaxone, ciprofloxacin, fluconazole, levofloxacin, linezolid, meropenem, piperacillin-tazobactam, tobramycin, vancomycin, and voriconazole) and microbiology data. The ASP was implemented using CareNet and PharmNet. An infectious disease physician and pharmacist determined the need for intervention. RESULTS: The authors screened 5564 dispensed prescriptions of the 13 targeted AMs. The rate of AM errors associated with these was 0.09/1000 doses administered and 5 errors/1000 patient days. CONCLUSIONS: Active surveillance and optimization of computerized physician order entry system allows early detection and intervention of AMs prescriptions errors in hospitalized children.

Why are young infants tested for herpes simplex virus?

BACKGROUND: The polymerase chain reaction (PCR)-based test to detect herpes simplex virus (HSV) genome in cerebrospinal fluid (CSF) has become the test of choice for diagnosing this infection. The utility of this test in young infants undergoing sepsis evaluations is unknown. OBJECTIVES: We sought to identify the factors that prompted physicians to include HSV PCR in their evaluation of young infants undergoing lumbar puncture. In addition, the impact of ordering this test on patient management was assessed. METHODS: This case-control study included infants 0 to 60 days who were evaluated by lumbar puncture at the Alfred I. duPont Hospital for Children over a 5-year period. Case patients had CSF HSV PCR ordered as part of their evaluation and control patients did not. RESULTS: Eighty-eight case patients and 83 control patients were identified. The median patient age was 12 days and most patients (55%) were male. Both groups were similar in demographics. Herpes simplex virus infection was diagnosed by PCR in 3.4% of cases. The occurrence of a seizure (adjusted odds ratio [OR], 8.3; 95% confidence interval [CI], 1.7-41.0), the performance of CSF enteroviral PCR testing (adjusted OR, 4.7; 95% CI, 1.4-15.8), and the decision to obtain hepatic transaminases (adjusted OR, 5.6; 95% CI, 2.7-11.8) were associated with the decision to perform CSF HSV PCR testing. Use of health care resources associated with PCR testing was considerable. DISCUSSION: The occurrence of a seizure, the performance of CSF enteroviral PCR testing, and the decision to obtain hepatic transaminases were independently associated with the decision to perform CSF HSV PCR testing. Features traditionally associated with neonatal HSV infection, such as elevated numbers of CSF white blood cells or red blood cells, did not appear to influence the decision to perform CSF HSV PCR testing. The yield of testing in this population was low. Clinicians should weigh the benefits of early diagnosis in a few patients against the consequences of excessive testing in this population.

Pediatricians knowledge, views, and perspectives on smallpox and smallpox vaccine.

Increasing concerns regarding smallpox as a biologic weapon have led to massive production of vaccinia vaccine and targeted vaccination campaigns. A regional mail survey was conducted among pediatricians to assess their knowledge and perceptions on smallpox and smallpox vaccine. Fifty-nine percent of the responders were unable to differentiate chickenpox from smallpox, and the majority would not accept vaccination in the absence of an outbreak and would not recommend smallpox vaccine to their patients. Even in previously vaccinated pediatricians, willingness to receive smallpox vaccine is poor and vaccination campaigns in the absence of a smallpox outbreak may not be successful.

Prediction of Lyme meningitis in children from a Lyme disease-endemic region: a logistic-regression model using history, physical, and laboratory findings.

BACKGROUND: Differentiating Lyme meningitis (LM) from other forms of aseptic meningitis (AM) in children is a common diagnostic dilemma in Lyme disease-endemic regions. Prior studies have compared clinical characteristics of patients with LM versus patients with documented enteroviral infections. No large studies have compared patients with LM to all patients presenting with AM and attempted to define a clinical prediction model. OBJECTIVE: To create a statistical model to predict LM versus AM in children based on history, physical, and laboratory findings during the initial presentation of meningitis. METHODS: Children older than 2 years presenting to the Alfred I. duPont Hospital for Children between October 1999 and September 2004 were identified if both Lyme serology and cerebrospinal fluid (CSF) were collected during the same hospital encounter. Patients were considered to have Lyme disease only if they met Centers for Disease Control and Prevention criteria (documented erythema migrans and/or positive Lyme serology). Patients were eligible for study inclusion if they had documented meningitis (CSF white blood cell count: >8 per mm3). Retrospective chart review abstracted duration of headache and cranial neuritis (papilledema or cranial nerve palsy) on physical examination and percent CSF mononuclear cells. Using logistic-regression analysis, the type of meningitis (LM versus AM) was simultaneously regressed on these 3 variables. The Hosmer-Lemeshow test was performed and the area under the receiver operating characteristic curve was calculated. RESULTS: A total of 175 children with meningitis were included in the final statistical model. Logistic-regression analysis included 27 patients with LM and 148 patients classified as having AM. Duration of headache, cranial neuritis, and percent CSF mononuclear cells independently predicted LM. The Hosmer-Lemeshow test revealed a good fit for the model, and the Nagelkerke R2 effect size demonstrated good predictive efficacy. Odds ratios based on the logistic-regression results were calculated for these variables. The final model was transformed into a clinical prediction model that allows practitioners to calculate the probability of a child having LM. CONCLUSIONS: Longer duration of headache, presence of cranial neuritis, and predominance of CSF mononuclear cells are predictive of LM in children presenting with meningitis in a Lyme disease-endemic region. The clinical prediction model can help guide the clinician about the need for parenteral antibiotics while awaiting serology results.

Diagnostic utility of Borrelia burgdorferi cerebrospinal fluid polymerase chain reaction in children with Lyme meningitis.

BACKGROUND: Cerebrospinal fluid (CSF) laboratory tests are frequently collected to help differentiate Lyme meningitis from other causes of aseptic meningitis. Previous studies using Lyme CSF polymerase chain reaction (PCR) have yielded varied results (sensitivity between 10 and 90%). No studies have specifically examined the diagnostic utility of Lyme CSF-PCR in North American children with Lyme meningitis. METHODS: Retrospective chart review of children presenting to a children's hospital in a Lyme-endemic region between October 1999 and September 2004. Patients were included if they had both Lyme serology and Lyme CSF-PCR performed during the same hospital encounter and had documented meningitis. Patients were considered to have Lyme meningitis if they had meningitis and met CDC criteria for Lyme disease. The Lyme CSF-PCR assay amplified a Borrelia burgdorferi DNA flagellin gene sequence. RESULTS: Of 108 patients with meningitis who qualified for the study, 20 patients met criteria for Lyme meningitis and 88 were classified as aseptic meningitis. Positive Lyme CSF-PCR was found in 1 patient (1 of 20, 5%) with Lyme meningitis and one patient classified as aseptic meningitis (1 of 88, 1%). Lyme CSF-PCR had a sensitivity of 5% and a specificity of 99%. The only Lyme meningitis patient with positive Lyme CSF-PCR had the highest CSF white blood cell count and CSF protein values compared with the other Lyme meningitis patients. CONCLUSIONS: This is the first study to evaluate Lyme CSF-PCR exclusively in North American children. This commercially available laboratory test is not generally helpful for identifying Lyme meningitis because of its low sensitivity.

Musculoskeletal infections in children.

Serious musculoskeletal infections in children include osteomyelitis, septic arthritis, pyomyositis, and necrotizing fasciitis. The epidemiology, pathophysiology, and microbiology of each of these infections are reviewed. Specific diagnostic studies and management strategies are discussed. Prompt recognition and treatment is emphasized to prevent potential long-term sequelae.