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OBJECTIVE To describe the epidemiologic and clinical syndromes associated with pediatric neuroinvasive arboviral infections among children in the United States from 2003 through 2012. METHODS We reviewed data reported by state health departments to ArboNET, the national arboviral surveillance system, for 2003 through 2012. Children (<18 years) with neuroinvasive arboviral infections (eg, meningitis, encephalitis, or acute flaccid paralysis) were included. Demographic, clinical syndrome, outcome, geographic, and temporal data were analyzed for all cases. RESULTS During the study period, 1217 cases and 22 deaths due to pediatric neuroinvasive arboviral infection were reported from the 48 contiguous states. La Crosse virus (665 cases; 55%) and West Nile virus (505 cases; 41%) were the most common etiologies identified. Although less common, Eastern equine encephalitis virus (30 cases; 2%) resulted in 10 pediatric deaths. La Crosse virus primarily affected younger children, whereas West Nile virus was more common in older children and adolescents. West Nile virus disease cases occurred throughout the country, whereas La Crosse and the other arboviruses were more focally distributed. CONCLUSIONS Neuroinvasive arboviral infections were an important cause of pediatric disease from 2003 through 2012. Differences in the epidemiology and clinical disease result from complex interactions among virus, vector, host, and the environment. Decreasing the morbidity and mortality from these agents depends on vector control, personal protection to reduce mosquito and tick bites, and blood donor screening. Effective surveillance is critical to inform clinicians and public health officials about the epidemiologic features of these diseases and to direct prevention efforts.

Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen‐specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined. Infection status for 10 common enteropathogens—adenovirus, astrovirus, norovirus, rotavirus, sapovirus, Campylobacter , ETEC, Shigella , Cryptosporidium and Giardia —was matched by date with hydrometeorological variables from a global Earth observation dataset—precipitation and runoff volume, humidity, soil moisture, solar radiation, air pressure, temperature, and wind speed. Models were fitted for each pathogen, accounting for lags, nonlinearity, confounders, and threshold effects. Different variables showed complex, non‐linear associations with infection risk varying in magnitude and direction depending on pathogen species. Rotavirus infection decreased markedly following increasing 7‐day average temperatures—a relative risk of 0.76 (95% confidence interval: 0.69–0.85) above 28°C—while ETEC risk increased by almost half, 1.43 (1.36–1.50), in the 20–35°C range. Risk for all pathogens was highest following soil moistures in the upper range. Humidity was associated with increases in bacterial infections and decreases in most viral infections. Several virus species' risk increased following lower‐than‐average rainfall, while rotavirus and ETEC increased with heavier runoff. Temperature, soil moisture, and humidity are particularly influential parameters across all enteropathogens, likely impacting pathogen survival outside the host. Precipitation and runoff have divergent associations with different enteric viruses. These effects may engender shifts in the relative burden of diarrhea‐causing agents as the global climate changes.

Helicobacter pylori strains may be either cagA 1 or cagA 2 , and in logitudinal studies, infection with a cagA 1 strain has been associated with increased risk for the development of atrophic gastritis and cancer of the distal stomach. We sought to determine the relative proportion of strains producing CagA in different geographic locales, and the extent to which CagA seroprevalence varied in countries with different gastric and esophageal cancer rates. Using an enzyme-linked immunosorbent assay (ELISA) to detect serum IgG to CagA, we examined sera from 468 asymptomatic H. pylori-infected adults from Canada, Peru, China, Thailand, The Netherlands and 3 different ethnic groups in New Zealand. The CagA seroprevalence in Peru and Thailand (82.2% and 78.8%, respectively) were each substantially higher than for the Chinese (37.9%), Canadian (41.9%), Dutch (39.0%) and New Zealand (28.2%) subjects, but within each population, rates were relatively constant across gender and age groups. Reported gastric but not esophageal cancer rates for the 8 studied populations were significantly associated with H. pylori seroprevalence. Variation in CagA positivity rates was not significantly associated with variation in either gastric or esophageal cancer rates. Our data suggest that CagA seroprevalence is not the major factor influencing gastric cancer rates. Int.

OBJECTIVES:The tuberculin skin test (TST) has been preferred for screening young children for latent tuberculosis infection (LTBI) because of concerns that interferon-g release assays (IGRAs) may be less sensitive in this high-risk population. In this study, we compared the predictive value of IGRAs to the TST for progression to tuberculosis disease in children, including those ,5 years old.METHODS: Children ,15 years old at risk for LTBI or progression to disease were tested with TST, QuantiFERON-TB Gold In-Tube test (QFT-GIT), and T-SPOT.TB test (T-SPOT) and followed actively for 2 years, then with registry matches, to identify incident disease.RESULTS: Of 3593 children enrolled September 2012 to April 2016, 92% were born outside the United States; 25% were ,5 years old. Four children developed tuberculosis over a median 4.3 years of follow-up. Sensitivities for progression to disease for TST and IGRAs were low (50%-75%), with wide confidence intervals (CIs).

BACKGROUND: Diagnostic strategies based on empirical testing and treatment to identify herpes simplex virus (HSV) infection in neonates may not be appropriate for older children in whom the most common presentation of severe infection is encephalitis, a rare and clinically recognizable condition. METHODS: Use of acyclovir in infants and children in 6 common non-HSV infection–related diagnosis-related groups was characterized between 1999 and 2012 at 15 US pediatric hospitals by using the Pediatric Health Information System database. Characteristics of non-neonatal patients at 1 institution tested for HSV encephalitis over a 6.5-year period were then analyzed to identify factors associated with potentially unnecessary testing and treatment. RESULTS: Acyclovir use increased from 7.6% to 15.6% (P &lt; .001) from 1999 to 2012. Much of this increase came in infants 30 to 60 days of age (82.7% increase, P &lt; .001) and in patients with milder disease severity (44.8% increase, P &lt; .001). Length of stay was increased by 2 days for children treated with acyclovir (P &lt; .001). At our institution, 1394 HSV cerebrospinal fluid polymerase chain reactions were performed in children &gt;30 days old, with only 3 positive results (0.22%). Comparison of the 3 subjects with positive testing and 55 with negative testing revealed that all cases, but only 4% (95% confidence interval 1.2%–14.0%) of noncases had clinical characteristics typical of HSV encephalitis. CONCLUSIONS: Strategies for diagnosis and empirical treatment of suspected HSV encephalitis beyond the neonatal period have trended toward the approach common for neonates without evidence of an increase in disease incidence. This may result in increased medical costs and risk to patients.

Colonization with Helicobacter pylori eventuates in varied clinical outcomes, which relate to both bacterial and host factors. Here we examine the relationships between cagA status, serum and gastric juice antibody responses, and gastric inflammation in dyspeptic patients. Serum, gastric juice, and gastric biopsy specimens were obtained from 89 patients undergoing endoscopy. H. pylori colonization and cagA status were determined by histology, culture, and PCR methods, and acute inflammation and chronic inflammation in the gastric mucosa were scored by a single pathologist. Serum and gastric juice antibodies to H. pylori whole-cell and CagA antigens were determined by enzyme-linked immunosorbent assay. Relationships between variables were sequentially analyzed using univariate and multivariate statistical methods. Of the 89 subjects, 62 were colonized by H. pylori. By univariate analyses, levels of serum immunoglobulin G (IgG) and IgA and gastric juice IgA antibodies against whole-cell and CagA antigens each were significantly higher in the H. pyloripositive group than in the H. pylori-negative group (P < 0.001). H. pylori and CagA seropositivities were both significantly associated with enhanced inflammation in gastric antrum and body (P < 0.02). The presence of gastric juice antibodies to H. pylori antigens was associated with more severe gastric inflammation. However, in multivariate analyses, only the presence of serum antibodies against CagA and, to a lesser extent, whole-cell antigens remained significantly associated with acute and chronic inflammation in antrum and body (P < 0.05). Thus, serum antibody response to CagA correlates with severity of gastric inflammation. Furthermore, given the relationships demonstrated by multivariate analysis, determination of gastric juice antibodies may provide a better representation of serum, rather than secretory, immune response.

Background Acute bacterial meningitis (ABM) remains a significant cause of pediatric illness and death in low and middle income countries (LMICs). Identifying severity risk factors and predictive scores may guide interventions to reduce poor outcomes. Methods Data from a prospective surveillance study for ABM in children aged 0-59 months admitted to 3 referral hospitals in Guatemala City from 2000-2007 was analyzed. ABM was defined as positive cerebrospinal fluid (CSF) culture; positive latex agglutination; or CSF WBC > 100 cells/mL. Univariate and multivariate analyses of risk factors at hospital admission that predicted major morbidity or death during hospitalization were performed, along with validation of the predictive Herson-Todd (HTS). Results Of 809 children with ABM episodes, 221 (27.3%) survived with major morbidity, and 192 (23.7%) died. Among 383 children with non-missing data, the most significant multivariate predictors for death or major morbidity were seizure (OR 101.5, p<0.001), CSF glucose < 20 mg/dL (OR 5.3, p = 0.0004), symptom duration > 3 days (OR 3.7, p=0.003), and coma (OR 6.3, p=0.004). Of 221 children with a HTS score > 5, 204 (92%) died or suffered major morbidity (OR 10.3, p<0.0001). Conclusion ABM is a cause of considerable morbidity and mortality in Guatemala. Several clinical risk factors and the composite Herson-Todd Score predicted death or major morbidity. These predictors could help clinicians in LMIC guide medical care for ABM, and could contribute to the public health impact assessment in preventing meningitis with vaccines.