Serum Anti-PGL-1 IgG, IgM, and IgA in a 3-Year Follow-up Study of 4–15-Year-old Leprosy Contacts Background: In 2015, the detection rate of leprosy in Santana do Ipanema municipality, Alagoas state, Brazil, was 39.3 cases per 100,000 inhabitants, and among young people below 15 years of age, it was 32.8 cases per 100,000 inhabitants. Material and methods: A prospective study was carried out from 2015 to 2017, in Santana do Ipanema city, with 69 leprosy contacts in the age group of 4–15 years. Measurement of serum IgM, IgG, and IgA against phenolic glycolipid antigen-1 (PGL-1) was done by an indirect enzyme-linked immunosorbent assay. Results: A high frequency of positive anti-PGL-1 IgM was found in both paucibacillary and multibacillary contacts. Twenty-three participants presented suspected lesions and 45 did not. In both groups a high frequency of positive IgM was found. In regard to anti-PGL-1 IgG, it was found a strong association between its positivity and the presence of lesions (relative risk of 3.25). Eight new cases of leprosy were diagnosed, five of which were seropositive for anti-PGL-1. Again, a striking association was found between positive IgG and leprosy (relative risk of 8.5). No significant association was found between IgM isotype and disease, nor between IgA and disease. Conclusions: The present study reinforces the importance of measuring the three anti-PGL-1 isotypes in follow-up studies of leprosy contacts. Moreover, positive anti-PGL-1 IgG is associated with a high associated risk of disease.

Hypergammaglobulinemia and Impaired Transplacental Transfer of Respiratory Syncytial Virus Antibody in Papua New Guinea Background: Passively-acquired respiratory syncytial virus (RSV) neutralizing antibody (Ab) can protect against RSV-associated lower respiratory tract illness. Maternal RSV immunization is, therefore, an attractive strategy for protection of very young infants. Vaccines for this purpose are currently being evaluated in clinical trials, but conditions such as preterm birth, placental malaria, maternal hypergammaglobulinemia and HIV infection might threaten this strategy. Each has been shown to impair transplacental Ab transfer for a variety of pathogens, but RSV-specific data are limited. Work in The Gambia demonstrated that placental malaria impaired transplacental transfer of RSV Ab, but a subsequent study in malaria-endemic Papua New Guinea (PNG) indicated that such associations may have been confounded by hypergammaglobulinemia (IgG > 1700 mg/dL). Methods: Here we confirm and extend those findings by measuring RSV neutralizing Ab and maternal IgG in sera from a larger cohort of 325 mother/infant pairs in PNG, and demonstrate the applicability of a high-throughput assay for assessment of neutralizing Ab. Results: One-third of mother-infant pairs demonstrated impaired RSV Ab transfer. Infants of hypergammaglobulinemic women were more likely to have both impaired transfer [cord-to-maternal titer ratio <1.0, adjusted odds ratio (OR): 3.36 (95% confidence interval: 1.81–6.30)] and the lowest RSV cord titers [adjusted OR: 5.09 (95% confidence interval: 1.95–13.32, P < 0.001)], but neither outcome was associated with placental malaria. Conclusions: Once maternal RSV vaccines become available, successful implementation will require clear understanding and mitigation of factors that can impair passive protection, necessitating epidemiologic studies of such relationships ahead of vaccine availability. This study underscores the need to focus on hypergammaglobulinemia as a condition of importance.

Recurrent Pneumococcal Meningitis in Children: A Multicenter Case–control Study Background: Pneumococcal meningitis (PM) is a serious disease that can rarely recur at a later time after the initial episode. Methods: A retrospective multicenter case–control study was conducted with data for children 18 years of age or younger obtained from the National Observatory of Bacterial Meningitis in Children between January 2001 and September 2015. Cases were all patients with RPM. Each case was matched with 2 randomized controls with a single PM episode in the year of the first episode of PM in the case and born the same year. Case and control data were compared. Results: Among the 1634 PM episodes in children 18 years of age or younger, 24 (1.5%) children had RPM. RPM cases were significantly less frequent than single PM cases in winter (27% vs. 48%; P=0.03) and showed significantly less concomitant ear, nose and throat infections when considering the first episode (30% vs. 56%, P = 0.04) and all episodes (28% vs. 56%, P < 0.01). Cerebrospinal fluid leakage was frequent in RPM cases versus controls (83% vs. 10%, P < 0.01), including 25% discovered after the third PM episode. Immune deficiency was absent in cases and present in 15% of controls. Cases and controls did not differ in death rate or neurologic outcome. Conclusions: RPM is rare in children. Cerebrospinal fluid leakage must be considered.

Comparison of Nonpolio Enteroviruses in Children With Herpangina and Hand, Foot and Mouth Disease in Taiwan Background: Nonpolio enterovirus (NPEV) infections are often present with herpangina (HA) and hand, foot and mouth disease (HFMD). Most countries sample NPEVs in HFMD cases, targeting enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) that are associated with outbreaks and severe complications. HA is also monitored in Taiwan and several other countries, but its viral characteristics are underreported. Methods: Through Taiwan’s National Virologic Surveillance, information regarding ~100,000 child respiratory samples (2002–2015) was linked to concurrent (0–6 days before the sampling date) outpatient records from the National Health Insurance databases, including ~15,000 HA-related and ~7000 HFMD-related samples. We assessed sample representation and NPEV positive rates, and estimated total numbers of EV-A71 and CV-A16. Results: There were more HA events (4.0 millions) than HFMD events (1.2 millions) in Taiwan. In every 1000 events with HFMD and HA, 6.0 and 4.1, respectively, respiratory samples were collected. The NPEV positive rate in HFMD-related samples was 48%, consistent across most sampling seasons, and predominantly EV-A71 or CV-A16 (74%). By comparison, the HA-related samples had a lower positive rate overall (43%), occasionally EV-A71 or CV-A16 (13%), and the positive rate depended strongly on HA incidence (P < 10–12). Compared with sampling HFMD alone, inclusion of HA-related information predicted an earlier onset of EV-A71 outbreak in 2011, and predicted 30% more EV-A71 cases. Conclusions: This is the first representative report on viral characteristics of HA. Our findings confirm that HFMD monitoring is a reliable strategy, but there is a measurable additional benefit when HA is also monitored.

Global Elimination of Chronic Hepatitis No abstract available

Excluding Clinically Significant Bacteremia by 24 Hours in Otherwise Well Febrile Children Younger Than 16 Years: A Study of More Than 50,000 Blood Cultures Background: In febrile children given empiric parenteral antibiotics, guidelines advise provisional reporting of negative blood cultures and antibiotic review after 36 hours incubation for neonates and 48 hours for older children. Following improvements in culture processing and childhood vaccination, we revisited this important clinical topic, assessing time to exclude clinically significant bacteremia in well-appearing febrile children with no comorbidities or features of sepsis. Methods: We analyzed the results of all 53,276 pediatric blood cultures taken during an 8-year period at a UK hospital. Results: 1308 (2.5%) cultures were positive, of which 333 (25.5%) grew pathogens typically associated with clinically significant bacteremia. The remaining 975 (74.5%) grew organisms associated with contaminated culture, or with opportunistic infection only in children with relevant risk factors. Time to positivity (TTP) from incubation was significantly shorter for the 333 definite pathogens than the 975 contaminating/opportunistic organisms, with 92% of definite pathogens identified by 24 hours incubation. Only 3 of all definite pathogens were identified after 24 hours in children otherwise eligible for discharge at 24 hours. There was no significant difference in TTP for definite pathogens between neonates and older children. Median time from specimen collection to incubation was 3 hours. Conclusions: Clinically significant bacteremia can be excluded by 24 hours incubation in well-appearing febrile children with no comorbidities or features of sepsis. This is the largest dataset of its kind, and the second to compare neonates and older children. Our findings may inform future guidelines, facilitating earlier antibiotic review and discharge.

Validation of the British Thoracic Society Severity Criteria for Pediatric Community-acquired Pneumonia Background: The British Thoracic Society (BTS) guideline for pediatric community-acquired pneumonia (CAP) outlines severity criteria to guide clinical decision-making. Our objective was to examine the predictive performance of the criteria on the need for hospitalization (NFH) and disposition. Methods: This was a retrospective cohort study of children 3 months–18 years of age diagnosed with CAP in an urban, pediatric emergency department (ED) in the United States from September 2014 to August 2015. Children with chronic medical conditions, recent ED visits, and ED transfers were excluded. The main outcomes were interventions or diagnoses that necessitate hospitalization (ie, NFH) and disposition (eg, admit vs. discharge). Test characteristics, stratified by age, were calculated for each outcome. Results: Of 518 eligible children, 56.6% (n = 293) were discharged from the ED with 372 children meeting at least 1 BTS criterion. Overall BTS criteria were specific but not sensitive for NFH nor for disposition. For children <1 year of age sensitive criteria included not feeding and temperature for NFH and tachycardia, cyanosis and not feeding for disposition. For children ≥1 year of age, tachycardia had a sensitivity of >0.60 for both outcomes. The areas under the receiver operator characteristic curves for predicting any BTS criteria was 0.57 for NFH and 0.84 for disposition. Conclusions: The BTS CAP severity criteria had fair to excellent ability to predict NFH and disposition, respectively. Although specific, the low sensitivity and poor discriminatory ability for NFH of these criteria suggest a need for improved prognostic tools for children with CAP.

Invasive Haemophilus influenzae Disease at Texas Children’s Hospital, 2011 to 2018 Background: Universal vaccination with Haemophilus influenzae type b conjugate vaccines has significantly changed the epidemiology of invasive H. influenzae disease in the United States. We reviewed the epidemiology, clinical features, and outcomes in 61 patients with invasive H. influenzae disease evaluated at Texas Children’s Hospital (TCH). Methods: Cases of invasive H. influenzae disease, defined as isolation of the organism from cerebrospinal fluid, blood, synovial fluid or pleural fluid, during 2011 to 2018 among children cared for at TCH in Houston, TX, were included. Results: We identified 61 cases of invasive H. influenzae disease in children ≤18 years of age. The overall hospitalization rate due to invasive H. influenzae disease increased between 2011 and 2018 (0 vs. 0.64/1000 hospitalizations; P = 0.019). The majority (80%) of infections occurred in children <5 years of age. Of the 61 H. influenzae infections, 24 (39.3%) infections were caused by nontypeable H. influenzae strains, 18 (29.5%) infections were caused by H. influenzae type a, 12 (19.7%) infections were caused by H. influenzae type f, 3 (4.9%) infections were caused by H. influenzae type e and 4 (6.6%) isolates were not typed. A total of 78.7% of the isolates were β-lactamase negative. The most common clinical presentations were bacteremia without a source, pneumonia and meningitis. Conclusions: The hospitalization rate for H. influenzae invasive disease increased over an 8-year period at TCH. The overall trend was mainly driven by an increasing number of invasive infections caused by nontypeable H. influenzae and H. influenzae type a. Morbidity was substantial, especially in meningitis cases.

Causes of Pediatric Meningitis in Botswana: Results From a 16-Year National Meningitis Audit Background: Central nervous system infections are an important cause of childhood morbidity and mortality in high HIV-prevalence settings of Africa. We evaluated the epidemiology of pediatric meningitis in Botswana during the rollout of antiretroviral therapy, pneumococcal conjugate vaccine and Haemophilus influenzae type B (HiB) vaccine. Methods: We performed a cross-sectional study of children (<15 years old) evaluated for meningitis by cerebrospinal fluid (CSF) examination from 2000 to 2015, with complete national records for 2013–2014. Clinical and laboratory characteristics of microbiologically confirmed and culture-negative meningitis were described and incidence of Streptococcus pneumoniae, H. influenzae and cryptococcal meningitis was estimated for 2013–2014. Results: A total of 6796 unique cases were identified. Median age was 1 year [interquartile range 0–3]; 10.4% (435/4186) of children with available HIV-related records were known HIV-infected. Overall, 30.4% (2067/6796) had abnormal CSF findings (positive microbiologic testing or CSF pleocytosis). Ten percent (651/6796) had a confirmed microbiologic diagnosis; including 26.9% (175/651) Cryptococcus, 18.9% (123/651) S. pneumoniae, 20.3% (132/651) H. influenzae and 1.1% (7/651) Mycobacterium tuberculosis. During 2013–2014, national cryptococcal meningitis incidence was 1.3 cases per 100,000 person-years (95% confidence interval, 0.8–2.1) and pneumococcal meningitis incidence 0.7 per 100,000 person-years (95% confidence interval, 0.3–1.3), with no HiB meningitis diagnosed. Conclusions: Following HiB vaccination, a marked decline in microbiologically confirmed cases of H. influenzae meningitis occurred. Cryptococcal meningitis remains the most common confirmed etiology, demonstrating gaps in prevention-of-mother-to-child transmission and early HIV diagnosis. The high proportion of abnormal CSF samples with no microbiologic diagnosis highlights limitation in available diagnostics.

Influenza in Children With Special Risk Medical Conditions: A Systematic Review and Meta-analysis Background: Children with special risk medical conditions (SRMC) are over-represented in influenza hospitalizations. A systematic review was undertaken to determine whether children with SRMCs experience greater complications or severity following influenza infection. Methods: Bibliographies of pertinent articles were searched in MEDLINE and EMBASE (1990 to March 2018) and contact made with the investigators of unpublished studies containing relevant data. Studies of children (aged ≤18 years) with a SRMC hospitalized with influenza were included. Outcomes were pneumonia, intensive care unit (ICU) admission, mechanical ventilation, neurologic outcomes (seizures, encephalopathy), death and length of stay in hospital or ICU. Results: Twenty-two studies met inclusion criteria. Compared with healthy peers, children with SRMC had higher odds of ICU admission [pooled odds ratio (OR) 1.66 (95% confidence interval (CI): 1.25–2.21)], for mechanical ventilation [pooled OR 1.53 (95% CI: 0.93–2.52)] and death [pooled OR 1.34 (95% CI: 0.74–2.41)]. Additionally, children with SRMC were more likely to develop bacterial pneumonia (crude OR 1.7; 95% CI: 1.1–2.6) or experience prolonged hospital length of stay [adjusted rate ratio 1.75 (95% CI: 1.44–2.11)]. The level of GRADE evidence was low for all outcomes considered in this review. Conclusions: While there was evidence that ICU management and bacterial pneumonia increases in children with SRMC, evidence showing an increase in the probability of death or need for mechanical ventilation was inconsistent. Further research using large datasets should evaluate the impact of complications and associated morbidity from influenza in SRMC children.