Etiologies of outpatient medically attended acute respiratory infections among young Ecuadorian children prior to the start of the 2020 SARS-CoV-2 pandemic.

BACKGROUND: Implementation of respiratory virus prevention measures requires detailed understanding of regional epidemiology; however, data from many tropical countries are sparse. We describe etiologies of ambulatory pediatric acute respiratory tract infections (ARTI) in Ecuador immediately preceding the onset of the SARS-CoV-2 pandemic. METHODS: Children < 5 years presenting to a designated study site with an ARTI were eligible. Informed consent was obtained. Demographic and clinical data were recorded. A nasopharyngeal swab was collected, processed, and analyzed using multiplex polymerase chain reaction (PCR) for common respiratory pathogens. Rhinovirus/enterovirus positive samples were further characterized by genomic sequencing. RESULTS: A total of 820 subjects were enrolled in the study between July 2018 and March 2020. A total of 655 (80%) samples identified at least one pathogen. Rhinoviruses (44%) were most common, followed by enteroviruses (17%), parainfluenza viruses (17%), respiratory syncytial virus (RSV) (15%), and influenza viruses (13%). Enterovirus D68 was the most common enterovirus detected and was among the leading causes of bronchiolitis. Seasonal RSV and influenza virus activity were different along the coast compared with the highlands. CONCLUSIONS: Ongoing regional surveillance studies are necessary to optimize available and emerging pathogen-specific preventative measures.

Multi-component cancer prevention awareness program to improve adolescent HPV vaccine uptake.

OBJECTIVE: We introduced a multi-component cancer prevention awareness program to primary care practices across New York State to evaluate its impact on adolescent human papillomavirus (HPV) vaccination rates. METHODS: Eight pediatric and three family medicine practices were recruited to participate in this program. On-site training sessions were provided for all practice providers and staff to discuss the importance of HPV vaccine and cancer prevention and teach strategies for delivering a strong vaccine recommendation. Each practice received a study-specific booklet that included HPV vaccine information and other commonly provided cancer prevention guidance. These booklets were distributed to all adolescents and their parents during well visits over a one-year period. Practice specific and county-wide HPV vaccination rates were assessed before and 12 months after the program training session. RESULTS: One year after program initiation, aggregate data show statistically higher vaccine series initiation rates among 11-12 and 13-18-year-olds and higher vaccine series completion rates among 13-18-year-olds. The greatest and most consistent improvements were seen in vaccine initiation rates for the 11-12-year-old cohort. Disparities in vaccine uptake were observed by gender and medical specialty. CONCLUSION: Cancer prevention education targeting providers, office staff, patients, and parents, improved adolescent HPV vaccine series initiation rates.

Medically Attended Outpatient Coronavirus Infections in Ecuadorean Children During the 20 Months Preceding Countrywide Lockdown Related to the SARS-CoV-2 Pandemic of 2020.

BACKGROUND: Human coronaviruses (HCoVs) cause respiratory tract infections during childhood manifesting as common colds, bronchiolitis, croup and pneumonia. In temperate geographies, HCoV activity peaks between December and March. The epidemiology and manifestations of HCoV infections have not been previously reported from Ecuador. METHODS: Children <5 years who presented with ≥2 symptoms consistent with an acute respiratory tract infection were eligible for enrollment. After obtaining informed consent, demographic data and details regarding the acute illness were recorded. Secretions collected with a nasopharyngeal swab underwent diagnostic testing using multiplex polymerase chain reaction. RESULTS: A total of 850 subjects were enrolled. A total of 677 (80%) tested positive for at least 1 pathogen, including 49 (7.2%) who tested positive for ≥1 HCoV type. HCoV-NL63 was the most frequent type detected (39%), followed by HCoV-OC43 (27%), 229E (22%) and HKU1 (12%). Nearly all subjects who tested positive for HCoV had nasal congestion or secretions (47/49; 96%). The most frequent syndromic diagnosis was common cold (41%), followed by bronchiolitis (27%). We found no association between the infecting HCoV type and subject's syndromic diagnosis (P > 0.05) or anatomic location of infection (upper vs. lower respiratory tract; P > 0.05). The 2018-2019 peak HCoV activity occurred from October to November; the 2019-2020 peak occurred from January to February. CONCLUSIONS: HCoVs were detected in ~7% of outpatient Ecuadorean children <5 years of age with symptoms of acute respiratory tract infection. The most frequently detected HCoV types, and the period of peak HCoV activity differed for the 2018-2019 and 2019-2020 seasons.

A quality improvement education initiative to increase adolescent human papillomavirus (HPV) vaccine completion rates.

HPV vaccine uptake is low, nationwide. Quality improvement (QI) principles have the potential to change practice; however, not all providers are confident with QI skills. We developed an educational program designed to enhance QI skills and improve HPV vaccination rates. Five pediatric practices participated in the pilot initiative. Training consisted of presentations regarding QI methods, data tracking and analysis, and system changes to reduce missed opportunities. Monthly for 6 months, participants performed chart audits, captured data, printed run charts, and developed, implemented, and tracked interventions. Outcome measures included rates of HPV vaccine completion and missed opportunities. A second phase included eight different pediatric practices who received similar training. Outcome measures included rates of HPV vaccine initiation and completion. Over the 6 months, mean HPV vaccine completion rates increased (45% to 65%) and missed opportunities for HPV vaccination decreased (45% to 19%) in the pilot program. When the program was replicated in phase 2, an increase was seen in both HPV vaccine initiation (46% to 61%) and completion (62% to 94%) rates. Combining QI education with workflow-focused strategies was associated with a reduction in missed opportunities and a substantial increase in HPV vaccine completion rates.

Associations between population based voting trends during the 2016 US presidential election and adolescent vaccination rates.

BACKGROUND: Politics play a role in the dissemination of public health information, including immunization-related issues. We aim to describe relationships between HPV vaccination rates and state voting patterns during the 2016 US presidential election. METHODS: We classified each of the 50 states as either "Red" or "Blue," based on whether a higher proportion of the state's casted votes were for the Republican or Democratic nominee during the 2016 US presidential election. State-specific HPV, Tdap, and meningococcal vaccination rates were obtained from the 2016-National Immunization Survey-Teen. State socio-demographic factors and HPV vaccine legislation were obtained from the US Census Bureau and National Conference of State Legislatures. Vaccination rates and socio-demographic variables were compared using independent t-tests. Multiple linear regression compared vaccination rates between "Red" and "Blue" states, adjusting for percentage of both uninsured children and educational attainment. RESULTS: Compared to "Blue" states, "Red" states had significantly lower unadjusted HPV vaccine series initiation (56% vs 66%, p < 0.05) and completion (39% vs 50%, p < 0.05) rates; yet had similar rates of Tdap (88% vs 89%, p > 0.05) and meningococcal (79% vs 83%, p > 0.05) vaccinations. After adjusting for potential confounders, the regression-adjusted mean rate for HPV vaccine initiation and completion remained significantly lower for "Red" states compared to "Blue" states (57% vs 65%, p < 0.05, and 41% vs 48%, p < 0.05, respectively). CONCLUSION: HPV vaccination rates are associated with statewide-level voting patterns. Future interventions aimed at improving HPV vaccination rates should consider engaging local and national elected leaders to be proactive in disseminating accurate and authoritative immunization information.

Cancer Prevention Education for Providers, Staff, Parents, and Teens Improves Adolescent Human Papillomavirus Immunization Rates.

OBJECTIVE: To develop a program to educate providers, office staff, patients, and parents on life-long cancer prevention strategies, including the use of human papillomavirus (HPV) vaccine to improve adolescent HPV vaccination rates. STUDY DESIGN: A 2-phase program was implemented at 6 pediatric practices across upstate New York. Phase 1 included provider and staff education regarding practice-specific vaccination challenges and discussion of the contents of a study-specific cancer-prevention booklet, which included HPV vaccine information. Throughout phase 2, the booklets were distributed to all adolescents and their parents during office visits over a 12-month period. Practice-specific, countywide, and statewide HPV vaccination rates were assessed before phase 1, and 6 and 12 months after the launch of phase 2. RESULTS: One year after implementing phase 2 in 6 practices, adolescent HPV vaccine series initiation increased by at least 10% in 3 practices, and at least 5% in 5 practices. Similarly, adolescent vaccine series completion rates increased by more than 10% in 3 practices. The percent change in vaccine series completion rates across all study sites postintervention ranged from 12% to 20% for 11- to 12-year-olds, and from 7% to 23% for 13- to 18-year-olds. CONCLUSIONS: Cancer prevention education targeting providers, office staff, patients, and parents was modestly effective for improving adolescent HPV vaccination rates.

Preventing Pediatric Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) infection in infants is a major cause of morbidity and mortality worldwide. Despite intense research efforts, safe and effective vaccines have remained elusive. Risk factors for the development of severe disease are well known, and those infants at highest risk are identified to receive RSV prophylaxis in the form of anti-RSV monoclonal antibody. Still, many other infant groups remain at risk and could benefit from an effective RSV prevention program. An explosion of clinic research activity is bringing unprecedented progress. Several of the most promising approaches currently being evaluated in clinical trials are reviewed. [Pediatr Ann. 2018;47(9):e371-e376.].

Immunization attitudes and practices among family medicine providers.

OBJECTIVE: To describe immunization attitudes and practices among family medicine providers across New York State. METHODS: In this cross-sectional survey study, family medicine providers across New York State completed a questionnaire to assess vaccine beliefs and barriers and immunization practices. STATISTICAL ANALYSIS: Descriptive statistical methods were used to define provider characteristics, knowledge and vaccine practices. RESULTS: Completed questionnaires from 226 family medicine providers were included for analysis. As a group, 207/218 (95%) of providers who answered the question state they always recommend standard pediatric vaccines. Of the 209 providers who answered both questions, 47 (22%) state they always recommend standard pediatric vaccines but do not always recommend HPV vaccine to eligible 11-12 year-old patients. Only 75% of providers strongly disagreed with the statement 'vaccinating adolescents against HPV increases the likelihood of unprotected sex'. Even though 178/190 (94%) and 164/188 (87%) of surveyed family medicine providers reported recommending that their pregnant patients receive influenza vaccine and Tdap vaccine, respectively, only 134/185 (72%) routinely do so in their office. CONCLUSION: Most family medicine providers self-report always recommending standard pediatric vaccines, however only a minority are following ACIP recommendations. Educational sessions to update family medicine providers on ACIP recommendations and address individual provider concerns may improve provider vaccine confidence and uptake of vaccines by their patients.

Nasopharyngeal pneumococcal carriage rates among HIV-infected adults following widespread pediatric use of conjugate pneumococcal vaccine-13.

BACKGROUND: Nasopharyngeal pneumococcal carriage rates among HIV-infected adults has not been described since conjugate pneumococcal vaccine-13 (PCV13) was added to the universal infant and childhood vaccination schedule in 2010. METHODS: HIV-infected adults presenting for routine health care visits to the Designated AIDS Center in Syracuse, NY between December 2013 and June 2015 were eligible for enrollment. Demographic, medical, and social history were recorded after obtaining informed consent. Nasopharyngeal samples were collected and cultured for the presence of Streptococcus pneumoniae using standard microbiologic techniques. Antibiotic susceptibility testing was performed using E-test→. RESULTS: 707 nasopharyngeal samples were collected from 414 HIV-infected adults. 18 samples were culture positive for S. pneumoniae; 1 (6%) isolate was of vaccine-type, 9 (50%) were non-vaccine types, and 8 (44%) were non-typeable. The 18 isolates were recovered from 15 different patients (4% of those enrolled). Three patients were culture positive for pneumococcus isolated from 2 consecutive samples, with non-typeable pneumococci identified consecutively from 2 patients and serotype 35B identified consecutively from 1 patient. The most commonly identified non-vaccine serotypes were 35B and 15B/C. Identified pneumococci were penicillin and cefotaxime susceptible. CONCLUSION: Four percent of HIV-infected adults in our study population were colonized with S. pneumoniae. The non-vaccine serotypes 35B and 15B/C predominated.

Pediatric provider vaccine hesitancy: An under-recognized obstacle to immunizing children.

OBJECTIVE: To describe vaccine attitudes among pediatric healthcare providers attending immunization conferences. STUDY DESIGN: Attendees of 5 American Academy of Pediatrics (AAP)-sponsored vaccine conferences held between June and November 2013 anonymously completed a questionnaire assessing vaccine attitudes and practices prior to the opening of educational sessions. Pearson's chi-square tests and Fisher's exact tests were used to analyze associations between vaccine attitudes, vaccine practices and provider characteristics. RESULTS: 680 providers attending AAP-sponsored vaccine conferences were included. 661/666 (99%) enrolled providers state they routinely recommend standard pediatric vaccines, yet, 30 (5%) state that they do not routinely recommend influenza and/or human papillomavirus (HPV) vaccines. These providers expressed vaccine safety (87/680 (13%)) and efficacy (21/680 (31%)) concerns and stated belief in vaccine misperceptions: vaccine causes autism (34/668, 5%), multiple vaccines at a single visit reduces vaccine efficacy (43/680, 6%) or overwhelms the immune system (63/680, 9%), and administering HPV vaccine will increase the likelihood of unprotected adolescent sexual activity (29/680, 4%). Six percent of providers who do not routinely recommend all pediatric vaccines correctly identified themselves as vaccine hesitant. CONCLUSION: Vaccine hesitancy is under-recognized among pediatric providers attending AAP-sponsored immunization conferences. Educational interventions tailored to address provider vaccine concerns are needed to improve provider vaccine confidence.

Chronic meningococcemia presenting as a recurrent painful rash without fever in a teenage girl.

Chronic meningococcemia is a rare diagnosis seen in patients with recurrent fever and rash. We describe a case of chronic meningococcemia in a teenage girl who presented with a recurrent painful rash, without fever, over a period of 8 weeks.

Vaccine attitudes and practices among obstetric providers in New York State following the recommendation for pertussis vaccination during pregnancy.

UNLABELLED: To determine factors associated with obstetric provider recommendation of pertussis vaccine (Tdap) to their pregnant patients following the Advisory Committee on Immunization Practices (ACIP) recommendation that Tdap be given in the third trimester of each pregnancy. Obstetric providers across New York State anonymously completed a standard set of questions to assess vaccine recommendation knowledge and practice. STATISTICAL ANALYSIS: Descriptive statistical methods were used to define provider characteristics, knowledge and vaccine practices. Factors associated with recommendation were analyzed using odds ratios. 133 obstetric providers were included in the study. 11% and 13% expressed concern with pertussis vaccine safety and efficacy, respectively, in pregnant women. 92% of obstetric providers stated that they knew ACIP recommendations for Tdap during pregnancy, 80% recommended Tdap to all eligible patients, but only 67% provided Tdap vaccine in their office. Provider knowledge of recommendation (OR 23.33), routine provider recommendation of influenza vaccine (OR 12.5), and administration of pertussis vaccine in the office (OR 7.01) were all factors strongly associated with routine provider recommendation of Tdap vaccine to eligible pregnant women (P < 0.05). Providers expressed concerns with cost of Tdap, the need to administer Tdap with each pregnancy, vaccine safety, low incidence of pertussis in the area, and administration of pertussis vaccine at the hospital after delivery. Educational programs are needed to improve provider vaccine confidence and recommendation.

Pertussis vaccine for adults: Knowledge, attitudes, and vaccine receipt among adults with children in the household.

BACKGROUND: Pertussis is a highly contagious vaccine preventable disease resulting in significant infant morbidity and mortality. Despite the recommendations for pertussis vaccine (Tdap) in adults, coverage rates in this age group remain suboptimal. We sought to determine factors associated with Tdap receipt among adults with children in the household who live in central New York. METHODS: The study team surveyed Tdap immunization status of adults who accessed medical services for their children provided by Golisano Children's Hospital, Syracuse, New York. Adults who did not know their Tdap vaccine status were excluded. Each participant was asked a standard set of questions to determine factors associated with Tdap receipt. Logistic regression was used to calculate simple and adjusted odds ratios for Tdap receipt in relation to adults' demographic characteristics, knowledge of Tdap and physician recommendations. RESULTS: Eight hundred twenty four participants were included in this study; 34% had received Tdap in the past 5 years; 58% reported that their provider or child's pediatrician recommended adult Tdap vaccination. Tdap receipt was associated with knowing the symptoms of pertussis infection, female gender, younger age, and provider recommendation (p<0.05). Participants whose provider recommended Tdap vaccine were 24.6 times more likely to receive vaccine when compared to those whose providers did not recommend vaccine (95% CI: 16.3, 37.2, p<0.05). CONCLUSION: Tdap coverage rates are low among this study population, with provider recommendation most strongly associated with Tdap receipt. Future steps to improve vaccine coverage should include both increasing community awareness and determining barriers to provider recommendation.

Influenza vaccine hesitancy in a low-income community in central New York State.

OBJECTIVE: Influenza vaccine (IV) coverage rates remain suboptimal among US adults. Socioeconomic disparities exist in IV coverage. We describe influenza vaccine attitudes among a low-income community in central New York. METHODS: Adults attending a Salvation Army function during December 2012 were surveyed regarding IV including their intention to be immunized. On-site IV was offered to eligible participants. RESULTS: The 1041 participants included Whites (non-Hispanics), African Americans, Hispanics, Native Americans, and multi-racial ethnicities. At time of enrollment, 386 (37%) participants had already received 2012-13 IV. Of the 655 unimmunized participants, 299 (46%) stated intent to receive IV, evenly distributed by age, gender, and ethnicity. Of the 312 participants who declined IV, 46% did so because of IV misperceptions. Of the 299 participants who intended to receive vaccine but had not yet done so, 284 (95%) stated the reason for delay was difficult access to vaccine. Intent to receive vaccine was strongly associated with the belief that IV is safe and/or effective (P < 0.05). CONCLUSION: IV misperceptions regarding IV efficacy and safety result in suboptimal vaccine uptake in this low-income community, regardless of age, gender, or ethnicity.

Local production of CCL3, CCL11, and IFN-γ correlates with disease severity in murine parainfluenza virus infection.

BACKGROUND: Using a murine model of parainfluenza virus infection (mPIV1 or Sendai virus; SeV), we compared the inflammatory responses to lethal and sub-lethal infections in inbred DBA/2 mice. METHODS: Mice were intranasally inoculated with either 1.6×10(3) or 1.6×10(5) infectious units (IU) of SeV or diluent control. Clinical data including daily weights, oxygen saturation, and lung function via whole body plethysmography were collected on days 0, 3-7, and 9-14. Clarified whole lung homogenates were evaluated for inflammatory markers by enzyme-linked immunoassay (ELISA). Data were analyzed using ANOVA or Student t-tests, as appropriate. RESULTS: Mice inoculated with 1.6×10(5) IU of SeV developed a lethal infection with 100% mortality by day 7, while mice inoculated with 1.6×10(3) IU developed a clinically significant infection, with universal weight loss but only 32% mortality. Interestingly, peak virus recovery from the lungs of mice inoculated with 1.6×10(5) IU of SeV did not differ substantially from that detected in mice that received the 100-fold lower inoculum. In contrast, concentrations of CCL5 (RANTES), CCL11 (eotaxin), interferon-γ, CXCL10 (IP-10), and CCL3 (MIP-1α) were significantly higher in lung tissue homogenates from mice inoculated with 1.6×105 IU (p < 0.05). In the lethal infection, levels of CCL11, interferon- γ and CCL3 all correlated strongly with disease severity. CONCLUSION: We observed that severity of SeV-infection in DBA/2 mice was not associated with virus recovery but rather with the levels of proinflammatory cytokines, specifically CCL11, interferon- γ and CCL3, detected in lung tissue in response to SeV infection.

Community-centered education improves vaccination rates in children from low-income households.

OBJECTIVE: We partnered with the Salvation Army to educate resource-poor families regarding childhood immunizations in an effort to improve vaccine coverage rates. METHODS: Eligibility for enrollment included children of families presenting at registration for our Salvation Army holiday gift program, available to families with an annual income <150% of federal poverty guidelines. Parents completed a questionnaire, were provided each child's vaccination status as documented in the New York State Immunization Information System, and interacted with the study team to address immunization-related concerns. Missed vaccines were identified and parents were directed to their child's medical home for necessary immunizations. Vaccine coverage was ascertained via the New York State Immunization Information System every 6 to 8 weeks with telephone follow-up for children who remained delayed. The McNemar test and standard 2-proportion comparison were used to determine confidence intervals when analyzing matched or independent data, respectively. RESULTS: A total of 1531 children were enrolled; 416 (28%) of the 1477 children with accurate immunization records were vaccine complete. When we excluded influenza vaccine, 1034 (70%) of children had received all other recommended vaccines. Nine months later, vaccine completion rates increased from 28% to 45%, largely because of improvements in influenza vaccination rates, which increased by 17% (confidence interval [CI] 15.5-19.5), a significant improvement over county (8%, 95% CI 7.4-8.1) and statewide (5%, 95% CI 4.7-4.8) rates during the same period. CONCLUSIONS: Immunization rates in poor children are suboptimal. Partnering with community-based organizations to address parental concerns, provide education, and perform follow-up was effective in improving immunization rates, particularly for influenza vaccine.

Novel inflammatory markers, clinical risk factors and virus type associated with severe respiratory syncytial virus infection.

BACKGROUND: Virus-induced inflammation contributes to respiratory syncytial virus (RSV) pathogenesis. We sought to determine the specific mediators that are associated with more severe illness in young children. METHODS: Children ≤ 5 years of age seen in our emergency department for respiratory symptoms from September 1998 to May 2008 were eligible for enrollment. Nasopharyngeal wash samples were collected from all eligible patients, and clinical data were recorded. Individuals were included in this study if nasopharyngeal wash samples were positive for RSV only. Patients enrolled in the study were stratified by disease severity, defined as mild (not hospitalized), moderate (hospitalized) or severe (requiring intensive care unit stay). Concentrations of individual inflammatory biomarkers in nasopharyngeal wash fluids were determined using the Luminex human 30-plex assay. RESULTS: Eight hundred fifty-one patients met study criteria: 268 (31.5%) with mild, 503 (59.1%) with moderate and 80 (9.4%) with severe illness. As expected, illness severity was directly associated with young age, prematurity, heart or lung disease, infection with RSV group A and elevated concentrations of interleukin (IL)-2R, IL-6, CXCL8, tumor necrosis factor-α, interferon-α, CCL3, CCL4 and CCL2. In addition, we report several novel and mechanistically important inflammatory biomarkers of severe RSV disease, including IL-1ß, IL1-RA, IL-7, epidermal growth factor and hepatocyte growth factor. CONCLUSIONS: In a large, longitudinal study (10 years, 851 enrolled patients) limited to RSV infection only, in which well-known risk factors are confirmed, we identified 5 novel biomarkers specifically of severe disease. These markers may ultimately serve to elucidate disease mechanisms.

IL-21 promotes the pathologic immune response to pneumovirus infection.

IL-21 is a cytokine with pleiotropic actions, promoting terminal differentiation of B cells, increased Ig production, and the development of Th17 and T follicular helper cells. IL-21 is also implicated in the development of autoimmune disease and has antitumor activity. In this study, we investigated the role of IL-21 in host defense to pneumonia virus of mice (PVM), which initiates an infection in mice resembling that of respiratory syncytial virus disease in humans. We found that PVM-infected mice expressed IL-21 in lung CD4(+) T cells. Following infection, Il21r(-/-) mice exhibited less lung infiltration by neutrophils than did wild-type (WT) mice and correspondingly had lower levels of the chemokine CXCL1 in bronchoalveolar lavage fluid and lung parenchyma. CD8(+), CD4(+), and γδ T cell numbers were also lower in the lungs of PVM-infected Il21r(-/-) mice than in infected WT mice, with normal Th17 cytokines but diminished IL-6 production in PVM-infected Il21r(-/-) mice. Strikingly, Il21r(-/-) mice had enhanced survival following PVM infection, and moreover, treatment of WT mice with soluble IL-21R-Fc fusion protein enhanced their survival. These data reveal that IL-21 promotes the pathogenic inflammatory effect of PVM and indicate that manipulating IL-21 signaling may represent an immunomodulatory strategy for controlling PVM and potentially other respiratory virus infections.

Viral etiology of acute febrile respiratory illnesses in hospitalized children younger than 24 months.

BACKGROUND: Respiratory infections are a leading cause of pediatric hospitalizations. This study investigated whether virus-virus or virus-Bordetella co-infections are more frequent or more severe than previously recognized. METHODS: This is a 3-year prospective study of children younger than 24 months hospitalized with a febrile respiratory illness. Viral pathogens were detected using multiplex polymerase chain reaction (PCR), enzyme-linked immunoassays, and/or viral cultures from nasopharyngeal samples. Bordetella infections were detected by PCR. RESULTS: A total of 201 patients were enrolled. Respiratory viruses were detected in 187 (93%) patients, with 52 (28%) multipathogen infections. The most common viruses detected were respiratory syncytial virus and rhinovirus/enterovirus. There were no differences in illness severity when comparing patients infected with one pathogen and those with multipathogen infection. CONCLUSION: Virus co-infection in young children hospitalized with an acute febrile respiratory infection is common but does not appear to be associated with illness severity.

Inflammatory responses to acute pneumovirus infection in neonatal mice.

BACKGROUND: The innate immune responses of neonates differ dramatically from those of adults. Here we examine the acute inflammatory responses of neonatal and weanling mice infected with pneumonia virus of mice (PVM), a rodent pathogen (family Paramyxoviridae, genus Pneumovirus) that replicates the sequelae of severe respiratory syncytial virus infection. RESULTS: We demonstrate that virus replication proceeds indistinguishably in all age groups (inoculated at 1, 2, 3 and 4 weeks of age), although inflammatory responses vary in extent and character. Some of the biochemical mediators detected varied minimally with age at inoculation. Most of the mediators evaluated demonstrated elevated expression over baseline correlating directly with age at the time of virus inoculation. Among the latter group are CCL2, CCL3, and IFN-γ, all cytokines previously associated with PVM-induced inflammatory pathology in mature mice. Likewise, we detect neutrophil recruitment to lung tissue in all age groups, but recruitment is most pronounced among the older (3 - 4 week old) mice. Interestingly, all mice exhibit failure to thrive, lagging in expected weight gain for given age, including the youngest mice that present little overt evidence of inflammation. CONCLUSIONS: Our findings among the youngest mice may explain in part the phenomenon of atypical or minimally symptomatic respiratory infections in human neonates, which may be explored further with this infection model.