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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Microbiology and treatment of cerebrospinal fluid shunt infections in children.

Infections of cerebrospinal fluid (CSF) shunts remain a common surgical complication causing significant morbidity in children with hydrocephalus. As most of the literature regarding these infections includes only small cohorts from a single institution's experience, there remain large knowledge gaps and little support for the prevailing management strategies. Regarding the microbiology of shunt infections, little has changed in the past 10 years, other than the emergence of methicillin-resistant strains of coagulase-negative staphylococcus (CoNS) and Staphylococcus aureus, which remain the two predominant etiologic agents. Molecular diagnostics such as multiplex PCR have been used to identify the complex microflora of shunt infections and in the future could prove a useful adjunct for early diagnosis and targeting of antimicrobial therapy. Antibiotic-impregnated catheters for use in external ventricular drains and CSF shunts have been adopted into clinical practice and appear to reduce the risk of shunt infection by susceptible organisms.

Chronic helminth infection does not exacerbate Mycobacterium tuberculosis infection.

BACKGROUND: Chronic helminth infections induce a Th2 immune shift and establish an immunoregulatory milieu. As both of these responses can suppress Th1 immunity, which is necessary for control of Mycobacterium tuberculosis (MTB) infection, we hypothesized that chronic helminth infections may exacerbate the course of MTB. METHODOLOGY/PRINCIPAL FINDINGS: Co-infection studies were conducted in cotton rats as they are the natural host for the filarial nematode Litomosoides sigmodontis and are an excellent model for human MTB. Immunogical responses, histological studies, and quantitative mycobacterial cultures were assessed two months after MTB challenge in cotton rats with and without chronic L. sigmodontis infection. Spleen cell proliferation and interferon gamma production in response to purified protein derivative were similar between co-infected and MTB-only infected animals. In contrast to our hypothesis, MTB loads and occurrence and size of lung granulomas were not increased in co-infected animals. CONCLUSIONS/SIGNIFICANCE: These findings suggest that chronic filaria infections do not exacerbate MTB infection in the cotton rat model. While these results suggest that filaria eradication programs may not facilitate MTB control, they indicate that it may be possible to develop worm-derived therapies for autoimmune diseases that do not substantially increase the risk for infections.

The effect of rotavirus immunization on rotavirus gastroenteritis hospitalization rates in military dependents.

We conducted a retrospective review of all U.S. military dependents less than 5 years old hospitalized with rotavirus-associated gastroenteritis from July 2003 to June 2009. The two post-vaccine seasons showed a significant reduction of 62.4% (95% CI, 58.6-65.8, P<0.001) in rotavirus gastroenteritis hospitalization rate compared to the three pre-vaccine seasons. Infants less than 12 months old showed the greatest reduction in incidence at 75.3%. A substantial decrease was also seen in unvaccinated children as well. Vaccine efficacy against hospitalization was 86.0% (95% CI, 77.7-91.3) after just a single dose. The overwhelming majority of children hospitalized for rotavirus since the introduction of the vaccine (ranging from 91.8 to 100% per season) had not received any of the rotavirus vaccine series.

Varicella-specific immunoglobulin G titers in commercial intravenous immunoglobulin preparations.

BACKGROUND AND OBJECTIVES: Since the introduction of an effective vaccine in 1995, the incidence of primary varicella zoster virus (VZV) has greatly decreased. However, newborns and immunocompromised patients remain at risk for serious disease. Currently, varicella-specific immunoglobulin is recommended for treatment of nonimmune, exposed, high-risk patients with varicella-specific immunoglobulin. However, product inavailability has led to substitution of intravenous immunoglobulin (IVIg) for such prophylaxis on the basis of studies from the preimmunization era. No studies in the post-vaccine era have shown that IVIg contains adequate varicella-specific antibodies to protect patients at high risk. The overall effect of vaccination on varicella-specific immunoglobulin G (IgG) levels in donor-pooled IVIg products is unknown. We compared the varicella-specific IgG levels in prevaccine and current IVIg products. METHODS: We used stored historic IVIg samples and current samples from our inpatient pharmacy. All samples were tested for varicella-specific IgG levels by enzyme-linked immunosorbent assay. RESULTS: Ten historic lots and 24 current lots were tested. The overall mean value of varicella-specific IgG in the historic lots was 3.07 (SD: 0.70); the current lots had a mean of 3.83 (SD: 0.58). The postvaccine IVIg contained higher levels of antibody than the prevaccine lots. CONCLUSIONS: We found that current IVIg preparations continue to have high levels of varicella-specific IgG despite the changing epidemiology of how immunity has been obtained. Given the results of this study, it is reasonable for physicians to comfortably substitute IVIg for varicella-specific immunoglobulin preparations when treating high-risk patients exposed to VZV.