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The role of Myeloid-Derived Suppressor Cells (MDSC) in infant immune ontogeny is unknown. Here, we evaluated MDSC frequency and relationship with infant vaccine responses throughout the first year of life in a prospective cohort study. Ninety-one South African infant-mother pairs were enrolled at delivery, and blood samples were collected at 0, 6, 10, and 14 weeks, 6 months, 9 months, and 1 year. MDSC frequencies were quantified, and immune responses to the childhood vaccines Bacillus Calmette-Guérin (BCG), hepatitis B (HepB), and combination diphtheria, tetanus, and pertussis (dTaP) were measured by Ag-specific CD4+ T cell proliferation and interferon gamma (IFN-γ) production. Vaccine-specific Ab responses to HepB, dTaP, and Haemophilus influenzae type b (Hib) were quantified via Enzyme-Linked Immunosorbent assay (ELISA). MDSC frequency in mother-infant pairs was strongly correlated; the frequency of MDSC decreased in both mothers and infants during the months after delivery/birth; and by 1 year, infant MDSC frequencies rebounded to birth levels. Higher MDSC frequency at vaccination was associated with a lack of subsequent IFN-γ release in response to vaccine Ags, with the exception of BCG. With the exception of a weak, positive correlation between MDSC frequency at 6 weeks (time of initial vaccination) and peak Hepatitis B surface antigen Ab titer, Polymorphonuclear Myeloid-Derived Suppressor Cells (PMN-MDSC) was not correlated with T cell proliferation or Ab responses in this study. The potential for MDSC-mediated suppression of vaccine Ag-specific IFN-γ responses should be explored further, and considered when evaluating candidate infant vaccines.

Background Development of a cytomegalovirus (CMV) vaccine is a high priority. However, the ability of antibodies to protect against CMV infection is not well characterized. Studies of maternal antibodies in infants offer the potential to identify humoral correlates of protection against postnatal acquisition. Methods This hypothesis-generating study analyzed 29 Ugandan mother-infant pairs that were followed weekly for CMV acquisition. Seventeen mothers and no infants were infected with human immunodeficiency virus (HIV). We evaluated the association between CMV-specific immunoglobulin G (IgG) responses in mothers at the time of delivery and their infants’ CMV status at 6 months of age. We also assessed levels of CMV-specific IgG in infants at 6 weeks of age. CMV-specific IgG responses in the mother-infant pairs were then analyzed on the basis of perinatal HIV exposure. Results We found similar levels of multiple CMV glycoprotein–specific IgG binding specificities and functions in mothers and infants, irrespective of perinatal HIV exposure or infant CMV status at 6 months of age. However, the glycoprotein B–specific IgG titer, measured by 2 distinct assays, was higher in infants without CMV infection and was moderately associated with delayed CMV acquisition. Conclusions These data suggest that high levels of glycoprotein B–specific IgG may contribute to the partial protection against postnatal CMV infection afforded by maternal antibodies, and they support the continued inclusion of glycoprotein B antigens in CMV vaccine candidates.

Background There is no uniform guideline for postchemotherapy vaccination of children with acute lymphoblastic leukemia (ALL). We evaluated waning immunity to 14 pneumococcal serotypes, pertussis toxin (PT), tetanus toxoid (TT) and varicella, and immunogenicity of postchemotherapy diphtheria, tetanus, pertussis, hepatitis B, polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) and pneumococcal vaccination among previously vaccinated children treated for ALL. Methods This was a multicenter trial of children with ALL enrolled 4–12 months postchemotherapy completion. Exclusion criteria included: infant ALL, relapsed ALL, and stem cell transplant recipients. Immunocompetent children were recruited as controls. Postchemotherapy participants received DTaP-IPV-Hib and 13-valent pneumococcal conjugate vaccine (PCV13) concurrently, followed by 23-valent pneumococcal polysaccharide vaccine (PPV23) 2 months later. Serology was measured at baseline, 2 and 12 months postvaccination. Adverse events were captured via surveys. Results At enrollment, postchemotherapy participants (n = 74) were less likely than controls (n = 78) to be age-appropriately immunized with DTaP (41% vs 89%, P, In this multicenter trial, previously vaccinated children treated for acute lymphoblastic leukemia had lower antibody levels than controls to Streptococcus pneumoniae, tetanus toxoid, pertussis toxin, and varicella. Booster vaccination was immunogenic and well tolerated, suggesting benefit of systematic revaccination postchemotherapy.

Cytomegalovirus (CMV) infection occurs frequently in young children, who, when infected, are then a major source of transmission. Oral CMV shedding by 14 infants with primary infection was comprehensively characterized using quantitative polymerase chain reaction weekly for ≥9 months. Three phases of oral shedding were identified: expansion, transition, and clearance. Viral expansion occurred over a median of 7 weeks, with a median doubling time of 3 days. During the transition phase, expansion slowed over a median of 6 weeks before peak viral load was reached. Clearance was slow (22-day median half-life), and shedding did not resolve during observation for any infant. Mathematical modeling demonstrated that prolonged oral CMV expansion is explained by a low within-host reproduction number (median, 1.63) and a delayed immune response that only decreases the infected cell half-life by 44%. Thus, the prolonged oral CMV shedding observed during primary infection can be explained by slow viral expansion and inefficient immunologic control.

Congenital cytomegalovirus infection (cCMV) is the most common congenital infection, occurring in approximately 0.5% of live births. Most infected newborns are asymptomatic, but up to 20% develop sensorineural hearing loss or other permanent neurologic sequelae. The presentation of newborns with symptomatic cCMV is highly variable, and the infection is usually not diagnosed in the absence of a screening program. Newborn cCMV screening programs are estimated to be beneficial and cost-effective, and are increasingly being implemented. Diagnosis requires direct detection of virus in a sample obtained before 3 weeks of life, and is best performed by polymerase chain reaction (PCR) of saliva or urine, either of which is more sensitive than dried blood spot. Antiviral treatment of selected newborns with cCMV-related disease appears to improve hearing and neurocognitive outcomes. All infected infants should be evaluated promptly to determine appropriate therapy, and receive close audiologic and developmental follow-up.

BACKGROUND: RSV prophylaxis with palivizumab is restricted to evidence-based indications in infants at relatively higher hospital admission risk. The RSV Program’s criteria follow CPS and AAP guidelines, but adjudication is needed in conditions of questionable efficacy or in infants who have a moderate risk of contracting RSV. In 2015–16, a blinded simple-majority Panel-of-Three adjudication (PoTA) process was implemented where adjudicators are from different specialities (e.g. neonatology, Peds ID, etc.) and are neither caregivers nor have funding that can be traced to the manufacturer/vendor for conflict of interest (COI) and bias avoidance. OBJECTIVES: To review adjudications across 3 RSV seasons (2015–2018) and determine the benefits and challenges associated with the PoTA structure. DESIGN/METHODS: All cases of PoTAs were reviewed and categorized based on age of infant, season, and diagnosis. Seasonal admissions with RSV & LRTI were ascertained provincially using 7 RSV-related acute respiratory infection ICD-10 codes, and cross-checked using the Program’s palivizumab database. The reliability of agreement within PoTAs during each season was measured with average pairwise percent agreement (APPA) and Fleiss kappa. RESULTS: In the 2015–16, 2016–17, and 2018-18 seasons, 67/467 applications (14.2%), 64/416 (15.4%), and 64/452 (13.9%) were adjudicated, with overall approval rates of 51%, 42% and 33% respectively. There was a trend towards lower approval rates from 2015–16 (range: 42–60%) to 2017–18 (25–38%), with a median approval turnaround time of 3 days. Infants with “exceptional conditions” (e.g. progressive neuromuscular and central nervous system disorders) comprised the largest category of applicants undergoing PoTA, followed by infants with significant pulmonary disabilities. Infants with immunodeficiencies were consistently approved in >80% of cases. In 2015–16, 2016–17 and 2017–18, the APPA and Fleiss kappa were found to be 78.1% and 0.57, 76.0% and 0.51 (moderate agreements) and 83.3% and 0.63 (moderate-to-substantial agreement). Unanimous decisions were reached in 46%, 47%, and 48% of cases amongst 3 adjudicators, for each season, respectively. Hospitalization rates were 20/82 (5 RSV+) in approved, and 3/113 (2 RSV+) in non-approved cases over 3 seasons. CONCLUSION: We describe an adjudication process that balances transparency and independence of adjudicators from one another. Timely decisions were reached in most cases, and the rates of hospitalized infants in the non-approved category remained small. The PoTA reached agreement in the adjudication decision in most cases and the low hospitalization rates in non-approved infants suggest that the decision process is both safe and efficient.

BACKGROUND: RSV palivizumab prophylaxis remains controversial in infants 29-34w GA without bronchopulmonary dysplasia (BPD). In our RSV Program these infants only qualify if they cumulate risk factors (e.g. # siblings, breastfeeding, smoking at home, daycare attendance, etc.; for risk score>42 pts) and their date of discharge is after Oct01. This risk score was developed from the literature (including FLIP and PICNIC studies) and has been in use since 2013. We track all seasonal RSV=related admissions in infants ≤24 months. OBJECTIVES: To compare RSV-related hospitalizations between infants who exceeded the risk threshold versus those who did not, across 4 RSV seasons. DESIGN/METHODS: The RSV season runs from Nov01 to Apr30, so by definition all first season infants are 42 pts; Group 2: infants 29-34w, age ≤2 months with a risk score ≤42 pts; Group 3: infants 29-34w, age 2–6 months with a risk score ≤42 pts. RSV-related admissions were obtained by linking 3 databases: Discharge Abstract Database using 7 RSV-related ICD-10 diagnostic codes, Perinatal Services regional Perinatal Data Registry (to establish the gestational age of infants), and RSV Program database. RESULTS: Only 355/2652 (13.3%) of infants 29-34w were admitted into the Program. Despite prophylaxis, Group 1 infants had higher RSV-related hospitalization rates than infants in Group 2. In subgroup analysis, infants born 29-32w were at increased risk in Groups 1 and 3, whereas infants 29-32w in Group 2 were not at increased risk, compared to infants 33–34 weeks (by 95% confidence intervals – not shown). Table shows proportions of RSV-related admissions with p-values defined between groups. CONCLUSION: The regional risk score safely and effectively selects the 13% of 29 to 34w infants ≤2mo with a high risk of RSV-related hospitalizations. [Image: see text]

A working group representing the American Society of Transplantation, Pediatric Infectious Diseases Society, and International Pediatric Transplant Association has developed a collaborative effort to identify and develop core knowledge in pediatric transplant infectious diseases. Guidance for patient care environments for training and core competencies is included to help facilitate training directed at improving the experience for pediatric infectious diseases trainees and practitioners in the area of pediatric transplant infectious diseases.

Epidemics of enterovirus serotype 71 (EV71) infection in Asia appear to be increasing in size and severity, and there is increasing concern for pandemic spread. Efforts are underway to develop an effective EV71 vaccine. However, the immunologic correlates of protection against EV71 infection are not fully understood, and studies suggest that severe complications may result from a combination of pathological immune responses and direct viral effects. Severe disease and death typically occur only in young children, which is likely due in part to a lack of EV71-specific adaptive immunity but possibly also due to age-dependent hyperactive innate immune responses. Infants are the primary targets of EV71 vaccination strategies. Therefore, studies are needed to understand the interplay between age, immunopathology, and severity of EV71 infection to distinguish protective from harmful immune responses and to guide the development of effective EV71 vaccines. This review summarizes our current understanding and outlines the next steps forward.

Among 30 human immunodeficiency virus type 1 (HIV-1)–infected women who received single-dose nevirapine (NVP), 17 (57%) had NVP-resistant HIV-1 detected in breast milk. NVP resistance in breast milk persisted for at least 8 months postpartum and was apparently transmitted to at least 1 infant. NVP resistance was detected less often in women who also received zidovudine.

Pediatric transplant infectious disease (PTID) is a growing area of clinical practice in pediatric infectious disease practice that faces challenges in education and training of practitioners: • Variable numbers and types of cases at different clinical centers, resulting in overall lack of experience • Relative paucity of diagnostic and randomized therapeutic trials, resulting in weak evidence base on which to base management guidelines