Risk Factors for Community-Associated Clostridium difficile Infection in Children.

OBJECTIVE: To characterize the medication and other exposures associated with pediatric community-associated Clostridium difficile infections (CA-CDIs). STUDY DESIGN: We performed a case-control study using billing records from the US military health system database. CA-CDI cases included children 1-18 years of age with an outpatient International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic code for Clostridium difficile infection (CDI) from 2001 to 2013. Each case was matched to 3 controls without CDI by age and sex. Children hospitalized at any time before their CDI were excluded. Outpatient pharmacy records were used to identify medication exposures in the preceding 12 weeks. In addition, we evaluated recent outpatient healthcare exposure, exposure to a sibling younger than 1 year of age, or to a family member with CDI. RESULTS: A total of 1331 children with CA-CDI were identified and 3993 controls were matched successfully. Recent exposure to fluoroquinolones, clindamycin (OR 73.00; 95% CI 13.85-384.68), third-generation cephalosporins (OR 16.32; 95% CI 9.11-29.26), proton pump inhibitors (OR 8.17; 95% CI 2.35-28.38), and to multiple classes of antibiotics, each was associated strongly the subsequent diagnosis of CA-CDI. Recent exposure to outpatient healthcare clinics (OR 1.35; 95% CI 1.31-1.39) or to a family member with CDI also was associated with CA-CDI. CONCLUSIONS: CA-CDI is associated with medications regularly prescribed in pediatric practice, along with exposure to outpatient healthcare clinics and family members with CDI. Our findings provide additional support for the judicious use of these medications and for efforts to limit spread of CDI in ambulatory healthcare settings and households.

Development of the Flu-PRO: a patient-reported outcome (PRO) instrument to evaluate symptoms of influenza.

BACKGROUND: To develop content validity of a comprehensive patient-reported outcome (PRO) measure following current best scientific methodology to standardize assessment of influenza (flu) symptoms in clinical research. METHODS: Stage I (Concept Elicitation): 1:1 telephone interviews with influenza-positive adults (≥18 years) in the US and Mexico within 7 days of diagnosis. Participants described symptom type, character, severity, and duration. Content analysis identified themes and developed the draft Flu-PRO instrument. Stage II (Cognitive Interviewing): The Flu-PRO was administered to a unique set of influenza-positive adults within 14 days of diagnosis; telephone interviews addressed completeness, respondent interpretation of items and ease of use. RESULTS: Samples: Stage I: N = 46 adults (16 US, 30 Mexico); mean (SD) age: 38 (19), 39 (14) years; % female: 56%, 73%; race: 69% White, 97% Mestizo. Stage II: N = 34 adults (12 US, 22 Mexico); age: 37 (14), 39 (11) years; % female: 50%, 50%; race: 58% White, 100% Mestizo. SYMPTOMS: Symptoms identified by >50%: coughing, weak or tired, throat symptoms, congestion, headache, weakness, sweating, chills, general discomfort, runny nose, chest (trouble breathing), difficulty sleeping, and body aches or pains. No new content was uncovered during Stage II; participants easily understood the instrument. CONCLUSIONS: Results show the 37-item Flu-PRO is a content valid measure of influenza symptoms in adults with a confirmed diagnosis of influenza. Research is underway to evaluate the suitability of the instrument for children and adolescents. This work can form the basis for future quantitative tests of reliability, validity, and responsiveness to evaluate the measurement properties of Flu-PRO for use in clinical trials and epidemiology studies.

Trends in Well-Child Visits and Routine Vaccination among Children of U.S. Military Members: An Evaluation of the COVID-19 Pandemic Effects.

The COVID-19 pandemic has drastically impacted administration of healthcare including well-child visits and routine vaccinations. The purpose of this study was to determine the impact of COVID-19 pandemic disruption on childhood health maintenance: well-child visits and scheduled vaccinations. We queried the TRICARE Management Activity's Military Health System (MHS) database for outpatient well-child visits and vaccinations for all children 0 to 23 months of age eligible for TRICARE healthcare. The median rate of well-child visits, during the COVID-19 period (March 2020-July 2021), was significantly declined for all demographic groups: all ages, parental military ranks, sex, and regions as compared to the pre-COVID-19 period (February 2019-February 2020). Similar to rates of well-child visits, the rate of vaccinations declined during the COVID-19 period as compared to the pre-COVID-19 period for all demographic groups, except children 12-23 months. Rates of well-child visits for military dependent children under 2 years of age were decreased during the 16 month COVID-19 period, with large increases seen in the first 2 months of the pandemic; the consequences of missed well-child visits and vaccination are unknown.

Tele-TB: Using TeleMedicine to Increase Access to Directly Observed Therapy for Latent Tuberculosis Infection.

INTRODUCTION: Treatment of latent tuberculosis infection (LTBI) decreases risk of progression to active tuberculosis. Traditional treatment regimens required either daily isoniazid for 9 months, with historically poor compliance, or 12-week directly observed therapy (DOT) with isoniazid and rifapentine, with improved compliance but additional challenges of coordinating weekly clinic visits, further complicated if patients must travel a great distance for care. MATERIALS AND METHODS: Our referral area is complicated by congested traffic often resulting in one-way commutes, which can exceed 2 hours. These travel times would be prohibitive for conducting weekly in-clinic DOT. In an effort to improve access to DOT, we implemented TeleMedicine LTBI DOT (vDOT) within a military pediatric infectious diseases clinic. Patients aged 24 months or older diagnosed with LTBI were referred for possible enrollment into our vDOT clinic. All patients without contraindications for receiving isoniazid and/or rifapentine were offered LTBI treatment via weekly vDOT or daily treatment with isoniazid or rifampin. The first visit for vDOT patients was performed in person to discuss treatment options, demonstrate use of TeleMedicine software, and ensure the patient was able to take the medications. Baseline information about patients and travel time to our facility was determined. RESULTS: To date, 16 patients have completed LTBI therapy using vDOT. Average one-way travel time to our facility for patients was 51 minutes. Actual time spent in most vDOT encounters was less than 10 minutes. Appointments were arranged to take place outside usual school and work hours so patients could complete vDOT with minimal interruptions to daily life, resulting in 100% treatment compliance and completion. DISCUSSION: Conducting LTBI DOT using TeleMedicine is a viable and time-saving measure that still allows for high levels of patient compliance and treatment completion while minimizing interruptions to academic and work schedules.

Pediatric Infectious Diseases Encountered During Wartime-Part 1: Experiences and Lessons Learned From Armed Conflict in the Modern Era.

PURPOSE OF REVIEW: Armed conflicts occur globally, with some regions experiencing heightened instability for many years. A better understanding of the infectious disease impact on children in armed conflict will allow aid organizations to anticipate and mitigate the most serious problems. RECENT FINDINGS: Armed conflicts are estimated to have caused approximately 30 million civilian deaths during the past 27 years, with two-thirds occurring in women and children. Children are extremely vulnerable to the mass population displacements, experiencing a combined loss of safety, nutrition, shelter, hygiene, and health care. Under these circumstances, the emergence and prevalence of multiple infectious diseases can result in heightened morbidity and mortality long after active conflict ceases. SUMMARY: Factors leading to increased infectious diseases in populations in crisis due to armed conflict and lessons learned from recent outbreaks are discussed in detail. Acute respiratory infections, diphtheria, measles, varicella, and cholera are a few of the more common infectious diseases that take advantage of populations displaced or disrupted by conflict. Key issues include the ability of countries or non-governmental organizations (NGOs) to keep up with basic childhood immunizations, and how rapidly disease outbreaks are recognized and addressed with disease-specific interventions.

Multisystem Inflammatory Syndrome in Children during the COVID-19 Pandemic: A Case Report on Managing the Hyperinflammation.

The novel human coronavirus of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly swept throughout the entire world. As the ongoing pandemic has spread, recent studies have described children presenting with a multisystem inflammatory disorder sharing the features of Kawasaki disease (KD) and toxic shock syndrome, now named Multisystem Inflammatory Syndrome in Children (MIS-C). These cases report a similar phenotype of prolonged fever, multisystem involvement, and biomarkers demonstrating marked hyperinflammation that occurs temporally in association with local community spread of SARS-CoV-2. Herein, we describe the presentation, clinical characteristics, and management of an 11-year-old boy with prolonged fever, strikingly elevated inflammatory markers, and profound, early coronary artery aneurysm consistent with a hyperinflammatory, multisystem disease temporally associated with coronavirus disease 2019. We highlight our multidisciplinary team's management with intravenous immunoglobulin, methylprednisolone, and an interleukin-1 receptor antagonist, anakinra, as a strategy to manage this multisystem, hyperinflammatory disease process.

Comparable Disease Severity by Influenza Virus Subtype in the Acute Respiratory Infection Consortium Natural History Study.

INTRODUCTION: Since the influenza A/H1N1 pandemic of 2009 to 2010, numerous studies have described the clinical course and outcome of the different subtypes of influenza (A/H1N1, A/H3N2, and B). A recent systematic literature review concluded that there were no appreciable differences in either clinical presentation or disease severity among these subtypes, but study parameters limit the applicability of these results to military populations. We sought to evaluate differences in disease severity among influenza subtypes in a cohort of healthy, primarily outpatient adult U.S. Department of Defense beneficiaries. MATERIALS AND METHODS: From 2009 to 2014, we enrolled otherwise healthy adults age 18 to 65 years with influenza-like illness in an observational cohort study based in 5 U.S. military medical centers. Serial nasopharyngeal swabs were collected for determination of etiology and viral shedding by polymerase chain reaction. The presence and severity of symptoms was assessed by interview and patient diary. RESULTS: Over a 5-year period, a total of 157 adults with laboratory-confirmed influenza and influenza subtype were enrolled. Of these, 69 (44%) were positive for influenza A(H1N1), 69 (44%) for influenza A(H3N2), and 19 (12%) for influenza B. About 61% were male, 64% were active duty military personnel, and 72% had received influenza vaccine in the past 8 months. Almost 10% were hospitalized with influenza. Seasonal influenza virus distribution among enrollees mirrored that of nationwide trends each year of study. Individuals with A/H1N1 had upper respiratory composite scores that were lower than those with A/H3N2. Multivariate models indicated that individuals with A(H1N1) and B had increased lower respiratory symptom scores when compared to influenza A(H3N2) (A[H1N1]: 1.51 [95% CI 0.47, 2.55]; B: 1.46 [95% CI 0.09, 2.83]), whereas no other differences in symptom severity scores among influenza A(H1N1), influenza A(H3N2), and influenza B infection were observed. Overall, influenza season (maximum in 2012-2013 season) and female sex of the participant were found to be associated with increased influenza symptom severity. CONCLUSIONS: Our study of influenza in a cohort of otherwise healthy, outpatient adult Department of Defense beneficiaries over 5 influenza seasons revealed few differences between influenza A(H1N1), influenza A(H3N2), and influenza B infection with respect to self-reported disease severity or clinical outcomes. This study highlights the importance of routine, active, and laboratory-based surveillance to monitor ongoing trends and severity of influenza in various populations to inform prevention measures.

The effect of universal maternal screening on the incidence of neonatal early-onset group B streptococcal disease.

OBJECTIVE: To determine the effect of the revised guidelines on incidence of neonatal early-onset group B streptococcal disease (EoGBS) via retrospective analysis of births in a military population. METHODS: Information from records of all live births within military hospitals from 1993 to 2007 was obtained. The data were divided into three time frames, representing the evolution of identifying and managing at-risk deliveries for GBS transmission. Incidence of EoGBS decreased from 1.95 to 0.72 per 1000 live births following institution of the 1996 Centers for Disease Control and Prevention recommendations and continued to fall to 0.47 per 1000 since the adoption of universal screening in 2002. CONCLUSIONS: Universal culture-based screening is more effective than risk-based screening in preventing EoGBS in term infants. Cases of EoGBS continue to occur, however, at a baseline rate of nearly 0.5 per 1000 births, thus emphasizing the need for rapid diagnostics and ultimately a vaccine.

Spread of methicillin-resistant Staphylococcus aureus USA300 in a neonatal intensive care unit.

BACKGROUND: Reports of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in neonatal intensive care units (NICU) and in otherwise healthy patients without obvious risk factors have been increasing in frequency. Described herein is a cluster of cases of CA-MRSA USA300 strains in an NICU affecting infants, health-care workers and the health-care workers' families. METHODS: Infants and health-care workers with infection and colonization due to MRSA between 1 January 2004 and 30 June 2005 in a tertiary care center NICU in San Antonio, TX were studied. Antimicrobial susceptibility testing and polymerase chain reaction detection of the mecA gene characterized the MRSA isolates. All MRSA cases were reviewed for clinical severity of infection and outcome. RESULTS: During the 18 months studied, a total of four (0.6%) of 676 infants had CA-MRSA bacteremia or colonization. One infant with necrotizing pneumonia died and three health-care workers who directly cared for the infected infants developed soft-tissue infections caused by CA-MRSA. Four family members of two health-care workers subsequently developed soft-tissue infections. All of the analyzed isolates (eight of nine) belonged to pulsed-field type USA300 and possessed Panton-Valentine leukocidin genes, which have been associated with severe skin and soft-tissue infections, and necrotizing pneumonia. CONCLUSIONS: It is likely that the CA-MRSA USA300 strain can be transmitted between NICU patients to health-care workers and their family members. The CA-MRSA cases reported here reinforce the virulence of CA-MRSA USA300 strains and emphasize the need to embrace infection control practices designed to protect hospitalized patients, health-care workers and their family members.

Successful treatment of vancomycin-resistant enterococcal ventriculitis in a pediatric patient with linezolid.

Although vancomycin-resistant Enterococcus infection of the central nervous system is not common, this organism is becoming an increasing problem in nosocomial infections. We report a 17-month-old male infant with an externalized ventricular peritoneal shunt secondary to infection who subsequently developed a vancomycin-resistant Enterococcus faecium ventriculitis. This infection was successfully treated with a 28-day course of linezolid while monitoring linezolid drug levels in both the cerebral spinal fluid and serum. This case supports the use of linezolid in treating such resistant infections. However, our drug level results suggest that further investigation is needed to determine the optimal dosing of linezolid in treatment of central nervous system infection in pediatric patients.

Immunization against Haemophilus influenzae type B fails to prevent orbital and facial cellulitis: results of a 25-year study among military children.

Vaccines against Haemophilus influenzae type B (HI) and Streptococcus pneumoniae (SP) have dramatically reduced the incidence of bacterial meningitis (due to both HI and SP) and epiglottitis (due to HI) in childhood. The effects of these vaccines on other conditions, however, are less clear. We report an analysis of the effect of serial deployment of various HI and SP vaccines over a 25-year period, involving an examination of over half a million pediatric hospitalizations occurring in Army hospitals worldwide. We show that, in marked contrast to the reduction in the number of meningitis and epiglottitis cases, the disease burden of orbital and facial cellulitis--conditions oft attributed to HI and SP-did not diminish.

Health Maintenance Deficits in a Fully Insured Population of Adolescents With Chronic Medical Conditions.

The current national monitoring of routine wellness care and vaccine uptake does not provide data on health maintenance among pediatric populations with chronic medical conditions. In this case-control study that analyzes wellness visits and vaccine uptake among adolescents, ages 16 to 18 years, we identified 938 without (controls) and 74 with (cases) 1 of 12 specific chronic medical conditions. The PPSV23 (23-valent pneumococcal polysaccharide vaccine) is recommended by the Advisory Committee on Immunization Practices for these 12 conditions and served as a measure of uptake for medically indicated vaccines. Our controls were twice as likely as cases to have a documented well visit in the past year, and there was a significantly higher proportion of controls than cases vaccinated with Tdap (tetanus toxoid, reduced diphtheria toxoid, acellular pertussis), MCV-4 (quadrivalent meningococcal conjugate), and HPV (human papillomavirus), all P < .05. More than 60% of cases failed to receive PPSV23. Adolescents with chronic medical conditions are at high risk of neglecting routine health maintenance.

International adoptions by military families: a reexamination.

The adoption of foreign-born children by U.S. families is an increasingly common occurrence, having tripled in the past 15 years. The demographic features of international adoption have changed dramatically over the same time period. Today's foreign-born adoptees originate from a myriad of nations and cultures and present challenging medical and social problems to the practitioners faced with caring for these children and advising their adoptive families. Military families, cosmopolitan and often stationed overseas, adopt a large proportion of these children from foreign lands. Consequently, military health care providers require a familiarity with the special needs of international adoptees and the unique aspects of international adoption, as practiced by military families. We previously reported on this topic more than a decade ago. Much has changed since then, prompting this update.

Zika virus: A primer for clinicians.

The ongoing outbreak of Zika virus infection that began in South America and Central America in 2014 is worrisome because of associations with fetal microcephaly and with Guillain-Barré syndrome. Here we summarize what has happened and what is known so far. As the outbreak continues to evolve, we urge clinicians to watch for updates at cdc.gov.

Otitis Media and Related Complications Among Children with Autism Spectrum Disorders.

Acute otitis media (AOM) symptoms can be masked by communication deficits, common to children with autism spectrum disorders (ASD). We sought to evaluate the association between ASD and otitis media. Using ICD-9-CM diagnostic codes, we performed a retrospective case-cohort study comparing AOM, and otitis-related diagnoses among children with and without ASD. Children with ASD had a significantly increased rate of AOM, otitis media with effusion, otorrhea, and PE tube placement. Children with ASD were more than twice as likely to develop mastoiditis, and to undergo mastoidectomy and tympanoplasty. Children with ASD are more likely to have middle ear infections and otitis-related complications, highlighting the importance of routine middle ear examinations and close attention to hearing impairment in this population.

Type-specific clinical characteristics of adenovirus-associated influenza-like illness at five US military medical centers, 2009-2014.

BACKGROUND: Adenovirus is a recognized cause of influenza-like illness (ILI). The proportion of ILI attributable to adenovirus is not known. Moreover, knowledge gaps remain with respect to the epidemiologic, virologic, and clinical characteristics of adenovirus-associated ILI among otherwise healthy individuals. METHODS: An observational, longitudinal study of <65-year-old patients with febrile ILI at five medical centers was conducted from 2009 to 2014. Nasopharyngeal specimens obtained at enrollment were first tested by single-reaction PCR for adenovirus, then further evaluated by a multiplex PCR assay for other respiratory viral pathogens. Symptoms over a 28-day period were collected. RESULTS: We enrolled 1536 individuals, among whom 43 (2·8%) were positive for adenovirus. The median age of cases was 3·4 years (range: 4 months to 41 years). Three were hospitalized. Species and serotype information was available for 33 (76·7%) cases. Species C (n = 21) was the most common, followed by B3 (n = 9) and one each of E4a, D46, and A. Species C infections were more frequent in children (P < 0·01). Half of the cases were positive for at least one other respiratory viral pathogen. Symptoms were generally mild and most commonly included cough (90%), fatigue (79%), rhinorrhea (74%), loss of appetite (71%), and sore throat (64%). Children with non-C adenovirus infection were more likely to report sore throat (P = 0·05) and hoarseness (P = 0·06) than those with species C infection. CONCLUSIONS: Adenovirus is frequently detected with other respiratory viruses. Persons with non-C adenovirus infections reported more severe symptoms, suggesting there may be species-specific differences in virulence and/or host response to infection.

Fetal breech presentation predisposes to subsequent development of septic arthritis of the hip.

We postulated a link between breech presentation and septic arthritis of the hip. To examine the potential association between these 2 relatively uncommon entities, we used the Patient Administration Systems and Biostatistics Activity (PASBA) database, which contains coded information derived from hospitalizations and ambulatory encounters at U.S. military hospitals worldwide. Among a cohort of nearly 1 million infants born in a 14-year period, 3.37% were found to be in the breech presentation. The rate of septic arthritis of the hip or pelvis during the first year of life among these breech infants was approximately 1/8000, providing a relative risk of 4.1 (95% confidence interval, <1.4-11.7) compared with the rate among nonbreech infants. Fetal breech presentation predisposes to the development of septic hip during the first year of life.

Necrotizing staphylococcal pneumonia in a neonate.

Hospitalized neonates are commonly colonized soon after birth with Staphylococcus aureus. The majority of neonates do not develop infectious sequelae; however, premature neonates appear to be more susceptible to serious infections, such as pneumonia. We report a case of an extremely low birth weight infant who developed necrotizing pneumonia due to methicillin-resistant Staphylococcal aureus (MRSA). The MRSA isolate from this neonate is identical to the strains that have been causing primarily community-associated skin and soft tissue infections. The severe course of this patient may be attributed to the presence of the Panton-Valentine leukocidin gene, a well-known virulence factor leading to soft tissue and pulmonary infections.

Neonatal suppurative submandibular sialadenitis: case report and literature review.

Acute submandibular sialadenitis is rare in the neonatal period and appears to be associated with prematurity. We describe a case of a premature neonate who developed suppurative submandibular sialadenitis from a hypervirulent strain of methicillin-resistant Staphylococcus aureus. The etiology, diagnosis, and treatment of this condition are discussed.

Induction of early inflammatory gene expression in a murine model of nonresuscitated, fixed-volume hemorrhage.

The etiology of many end-organ problems associated with hemorrhage has been attributed to the inflammatory response to hemorrhage. In a murine model of nonresuscitated, fixed-volume hemorrhage, we sought to elucidate the role that hemorrhagic insult alone plays in the generation of the early inflammatory cascade. Differences could be appreciated as early as 1 h post-hemorrhage, with consistent differences detected by 3 h in all of the major cytokine genes studied. Significant upregulation of IL-1beta , IL-6, TNF-alpha, and IL-10 mRNA expression was observed in both the liver and lung samples of mice subjected to fixed-volume hemorrhage when compared with sham-hemorrhaged mice. The cyclooxygenase-2 (COX-2) and inducible nitric oxide synthetase (iNOS) genes also were upregulated in the livers and lungs of hemorrhaged mice. Finally, expression of the genes that encode the Toll-like receptors (TLR)-2 and -4 was increased by hemorrhage. Taken collectively, these data demonstrate that the initial inflammatory cascade associated with hemorrhage occurs within hours after the initial hemorrhagic event, and can be associated with significant modulation of expression of key pro- and anti-inflammatory cytokine, enzyme, and TLR genes, suggesting that these may be possible new therapeutic targets.