Prenatal Maternal Immunization for Infant Protection: A Review of the Vaccines Recommended, Infant Immunity and Future Research Directions.

Prenatal maternal immunization is an effective tool to protect mothers and infants from poor health outcomes due to infectious diseases. We provide an overview of the rationale for the use of prenatal vaccines, discuss the immunologic environment of the maternal-fetal interface including the impact of maternal vaccines prenatally and subsequently on the infant's immune response, and review vaccines currently recommended in pregnancy and landscape for the future of maternal vaccination. This review aims to provide an understanding of the recent history and progress made in the field and highlight the importance of continued research and development into new vaccines for pregnant populations.

Reactive Case Detection and Treatment and Reactive Drug Administration for Reducing Malaria Transmission: A Systematic Review and Meta-Analysis.

Many countries pursuing malaria elimination implement "reactive" strategies targeting household members and neighbors of index cases to reduce transmission. These strategies include reactive case detection and treatment (RACDT; testing and treating those positive) and reactive drug administration (RDA; providing antimalarials without testing). We conducted systematic reviews of RACDT and RDA to assess their effect on reducing malaria transmission and gathered evidence about key contextual factors important to their implementation. Two reviewers screened titles/abstracts and full-text records using defined criteria (Patient = those in malaria-endemic/receptive areas; Intervention = RACDT or RDA; Comparison = standard of care; Outcome = malaria incidence/prevalence) and abstracted data for meta-analyses. The Grading of Recommendations, Assessment, Development, and Evaluations approach was used to rate certainty of evidence (CoE) for each outcome. Of 1,460 records screened, reviewers identified five RACDT studies (three cluster-randomized controlled trials [cRCTs] and two nonrandomized studies [NRS]) and seven RDA studies (six cRCTs and one NRS); three cRCTs comparing RDA to RACDT were included in both reviews. Compared with RDA, RACDT was associated with nonsignificantly higher parasite prevalence (odds ratio [OR] = 1.85; 95% CI: 0.96-3.57; one study) and malaria incidence (rate ratio [RR] = 1.30; 95% CI: 0.94-1.79; three studies), both very low CoE. Compared with control or RACDT, RDA was associated with non-significantly lower parasite incidence (RR = 0.73; 95% CI: 0.36-1.47; 2 studies, moderate CoE), prevalence (OR = 0.78; 95% CI: 0.52-1.17; 4 studies, low CoE), and malaria incidence (RR = 0.93; 95% CI: 0.82-1.05; six studies, moderate CoE). Evidence for reactive strategies' impact on malaria transmission is limited, especially for RACDT, but suggests RDA might be more effective.

Cat Scratch Disease: 9 Years of Experience at a Pediatric Center.

Background: A more complete understanding of the epidemiology, risk factors, and clinical features of cat scratch disease (CSD) in children could help guide patient care. Methods: We conducted a retrospective analysis of children presenting to a tertiary pediatric hospital system in Atlanta, Georgia between January 1, 2010 and December 31, 2018 who had serology, polymerase chain reaction, and/or cytopathological results consistent with a Bartonella henselae infection. We also retrospectively reviewed veterinary diagnostic results performed at the University of Georgia from 2018 to 2020 to ascertain the burden of bartonellosis in companion animals within the state. Results: We identified 304 children with CSD over 9 years with the largest proportion of diagnoses made during August (41 of 304, 13.5%) and September (47 of 304, 15.5%). The median age of child cases was 8.1 years (interquartile range [IQR], 5.4-12.1); 156 (51.3%) were female; 242 of 262 (92.4%) reported feline exposure; and 55 of 250 (22%) reported canine exposure of those with exposure histories documented in the medical record. Although lymphadenopathy was present on physical examination in the majority of cases (78.8%), atypical presentations lacking lymphadenopathy were also common (63 of 304, 20.7%). Among children with radiographic imaging, 20 of 55 (36.4%) had splenomegaly and 21 of 55 (38.1%) had splenic and/or hepatic microabscesses. Among veterinary data, Bartonella seroprevalence was 12 of 146 (8.2%), all among canines, with a geographic distribution that spanned the state of Georgia. Conclusions: Distinguishing clinical features of CSD included subacute regional lymphadenopathy in school-aged children in the late summer, almost all of whom had cat exposure. Atypical clinical manifestations of CSD were also commonly identified.

Insights on the differentiation of stillbirths and early neonatal deaths: A study from the Child Health and Mortality Prevention Surveillance (CHAMPS) network.

INTRODUCTION: The high burden of stillbirths and neonatal deaths is driving global initiatives to improve birth outcomes. Discerning stillbirths from neonatal deaths can be difficult in some settings, yet this distinction is critical for understanding causes of perinatal deaths and improving resuscitation practices for live born babies. METHODS: We evaluated data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network to compare the accuracy of determining stillbirths versus neonatal deaths from different data sources and to evaluate evidence of resuscitation at delivery in accordance with World Health Organization (WHO) guidelines. CHAMPS works to identify causes of stillbirth and death in children <5 years of age in Bangladesh and 6 countries in sub-Saharan Africa. Using CHAMPS data, we compared the final classification of a case as a stillbirth or neonatal death as certified by the CHAMPS Determining Cause of Death (DeCoDe) panel to both the initial report of the case by the family member or healthcare worker at CHAMPS enrollment and the birth outcome as stillbirth or livebirth documented in the maternal health record. RESULTS: Of 1967 deaths ultimately classified as stillbirth, only 28 (1.4%) were initially reported as livebirths. Of 845 cases classified as very early neonatal death, 33 (4%) were initially reported as stillbirth. Of 367 cases with post-mortem examination showing delivery weight >1000g and no maceration, the maternal clinical record documented that resuscitation was not performed in 161 cases (44%), performed in 14 (3%), and unknown or data missing for 192 (52%). CONCLUSION: This analysis found that CHAMPS cases assigned as stillbirth or neonatal death after DeCoDe expert panel review were generally consistent with the initial report of the case as a stillbirth or neonatal death. Our findings suggest that more frequent use of resuscitation at delivery and improvements in documentation around events at birth could help improve perinatal outcomes.

Automated Identification of Immunocompromised Status in Critically Ill Children.

BACKGROUND: Easy identification of immunocompromised hosts (ICHs) would allow for stratification of culture results based on host type. METHODS: We utilized antimicrobial stewardship program (ASP) team notes written during handshake stewardship rounds in the pediatric intensive care unit (PICU) as the gold standard for host status; clinical notes from the primary team, medication orders during the encounter, problem list, and billing diagnoses documented prior to the ASP documentation were extracted to develop models that predict host status. We calculated performance for three models based on diagnoses/medications, with and without natural language processing from clinical notes. The susceptibility of pathogens causing bacteremia to commonly used empiric antibiotic regimens was then stratified by host status. RESULTS: We identified 844 antimicrobial episodes from 666 unique patients; 160 (18.9%) were identified as ICHs. We randomly selected 675 initiations (80%) for model training and 169 initiations (20%) for testing. A rule-based model using diagnoses and medications alone yielded a sensitivity of 0.87 (08.6-0.88), specificity of 0.93 (0.92-0.93), and positive predictive value (PPV) of 0.74 (0.73-0.75). Adding clinical notes into XGBoost model led to improved specificity of 0.98 (0.98-0.98) and PPV of 0.9 (0.88-0.91), but with decreased sensitivity 0.77 (0.76-0.79). There were 77 bacteremia episodes during the study period identified and a host-specific visualization was created. CONCLUSIONS: An electronic health record-based phenotype based on notes, diagnoses, and medications identifies ICH in the PICU with high specificity.

A Retrospective Test-Negative Case-Control Study to Evaluate Influenza Vaccine Effectiveness in Preventing Hospitalizations in Children.

BACKGROUND: Vaccination is the primary strategy to reduce influenza burden. Influenza vaccine effectiveness (VE) can vary annually depending on circulating strains. METHODS: We used a test-negative case-control study design to estimate influenza VE against laboratory-confirmed influenza-related hospitalizations among children (aged 6 months-17 years) across 5 influenza seasons in Atlanta, Georgia, from 2012-2013 to 2016-2017. Influenza-positive cases were randomly matched to test-negative controls based on age and influenza season in a 1:1 ratio. We used logistic regression models to compare odds ratios (ORs) of vaccination in cases to controls. We calculated VE as [100% × (1 - adjusted OR)] and computed 95% confidence intervals (CIs) around the estimates. RESULTS: We identified 14 596 hospitalizations of children who were tested for influenza using the multiplex respiratory molecular panel; influenza infection was detected in 1017 (7.0%). After exclusions, we included 512 influenza-positive cases and 512 influenza-negative controls. The median age was 5.9 years (interquartile range, 2.7-10.3), 497 (48.5%) were female, 567 (55.4%) were non-Hispanic Black, and 654 (63.9%) children were unvaccinated. Influenza A accounted for 370 (72.3%) of 512 cases and predominated during all 5 seasons. The adjusted VE against influenza-related hospitalizations during 2012-2013 to 2016-2017 was 51.3% (95% CI, 34.8% to 63.6%) and varied by season. Influenza VE was 54.7% (95% CI, 37.4% to 67.3%) for influenza A and 37.1% (95% CI, 2.3% to 59.5%) for influenza B. CONCLUSIONS: Influenza vaccination decreased the risk of influenza-related pediatric hospitalizations by >50% across 5 influenza seasons.

Influenza vaccine effectiveness and disease burden in children and adolescents with sickle cell disease: 2012-2017.

BACKGROUND: Data are limited on the burden of influenza and seasonal influenza vaccine effectiveness (VE) in children with sickle cell disease (SCD). METHODS: We used a prospectively collected clinical registry of SCD patients 6 months to 21 years of age to determine the influenza cases per 100 patient-years, vaccination rates, and a test-negative case-control study design to estimate influenza VE against medically attended laboratory-confirmed influenza infection. Influenza-positive cases were randomly matched to test-negative controls on age and influenza season in 1:1 ratio. We used adjusted logistic regression models to compare odds ratio (OR) of vaccination in cases to controls. We calculated VE as [100% × (1 - adjusted OR)] and computed 95% confidence intervals (CIs) around the estimate. RESULTS: There were 1037 children with SCD who were tested for influenza, 307 children (29.6%) had at least one influenza infection (338 infections, incidence rate 3.7 per 100 person-years; 95% CI, 3.4-4.1) and 56.2% of those tested received annual influenza vaccine. Overall VE pooled over five seasons was 22.3% (95% CI, -7.3% to 43.7%). Adjusted VE estimates ranged from 39.7% (95% CI, -70.1% to 78.6%) in 2015/2016 to -5.9% (95% CI, -88.4% to 40.4%) in the 2016/17 seasons. Influenza VE varied by age and was highest in children 1-5 years of age (66.6%; 95% CI, 30.3-84.0). Adjusted VE against acute chest syndrome during influenza infection was 39.4% (95% CI, -113.0 to 82.8%). CONCLUSIONS: Influenza VE in patients with SCD varies by season and age. Multicenter prospective studies are needed to better establish and monitor influenza VE among children with SCD.