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Antimicrobials are the most frequently prescribed drug in pediatrics, with an estimated 37% of infants and 61% of hospitalized children having received them. Approximately 20–50% of prescriptions have been shown to be potentially unnecessary or inappropriate. The World Health Organization (WHO) estimates that the continued increase in antimicrobial resistance by the year 2050 will lead to the death of 10 million people per year. This paper describes a protocol to be used in a future study to evaluate the implementation of a quarterly syndromic antibiogram, aimed to improve the use of antibiotics for the treatment of pediatric bacterial infections at the Maputo Central Hospital, Mozambique. This study uses implementation science methods framed by the Dynamic Adaption Process (DAP) and RE-AIM conceptual frameworks to develop a multi-phase, mixed-methods evaluation utilizing qualitative and quantitative approaches. The pediatric inpatient services at HCM consist of approximately 18 physicians and 60 nurses. Additionally, the microbiology laboratory consists of eight laboratory technicians. We anticipate analyzing approximately 9,000 medical records. Qualitative methods include in-depth interviews with clinicians, laboratory technicians, and administrators to explore current knowledge and practices around antibiotic decision making, facilitators and barriers to intervention implementation, as well as acceptability and satisfaction with the intervention roll-out. Qualitative analysis will be performed with NVivo 12 software. Quantitative methods include extracting data from existing records from the pediatric ward of Hospital Central de Maputo (HCM) guided by the RE-AIM framework to explore intervention utilization and other factors influencing its implementation. Quantitative descriptive and inferential statistical analysis will be performed using R Studio statistical software. The findings from this evaluation will be shared with hospital administrators and relevant national policymakers and may be used by the Ministry of Health in deciding to expand this approach to other hospitals. The expected results of this research include the development of standard operating guidelines for the creation, distribution, and use of a quarterly syndromic antibiogram for antibiotic decision making that is informed by local epidemiology. Findings from this study will be used to develop a larger multi-site trial in Mozambique. [ABSTRACT FROM AUTHOR]

Background: Acute diarrhea is a common health problem in children, especially those under five years of age (U5). The mortality rate due to acute diarrhea among U5 children accounted for 11% in Lao PDR in 2016. No study has been done to investigate the etiologic pathogens of acute diarrhea and the risk factors associated with dehydration status among U5 children hospitalized with acute diarrhea in this region. Objectives: The study aimed to evaluate the clinical characteristics, etiological agents and associated factors of dehydration status of acute diarrhea among hospitalized U5 children in Savannakhet Province, Lao PDR. Methods: This retrospective study reviewed paper-based medical records with available stool examination results of 33 U5 children hospitalized with acute diarrhea in Savannakhet Provincial Hospital, Lao PDR between Jan. 2018 and Dec. 2019. Descriptive statistics were used to describe clinical characteristics and etiologic agents of acute diarrhea of the children. Nonparametric test, Pearson's Chi-square test and Fisher exact test were used to determine the risk factors associated with level of dehydration of the participants. Results: Vomiting was the most common symptom (66.6%), followed by fever (60.6%). Dehydration was found in 48.4% of subjects. Rotavirus was the most common identified pathogen with a prevalence of 55.5%. Bacterial enteric infection was identified in 15.1% of patients. There is a significantly higher prevalence of dehydration among children with acute diarrhea caused by rotavirus compared to those with negative rotavirus testing (70.0% vs. 12.5%, p = 0.02). Conclusions: Rotavirus was the most prevalent pathogen of acute diarrhea among U5 children. Pediatric patients with acute diarrhea caused by rotavirus had a higher prevalence of dehydration compared to those with negative rotavirus testing. [ABSTRACT FROM AUTHOR]

Background: There are limited data on the experiences of children being treated for drug-resistant tuberculosis (DR-TB), and most work in the area has been done with older children and adolescents. Comprehensive explorations of the caregiver experiences in this area are also lacking. Objective: To describe the experiences of being treated for drug-resistant tuberculosis of children and their caregivers. Methods: This was a qualitative study done using focus group discussions (FGDs) among three different groups of participants: 1) health care providers involved in the care of children being treated for DR-TB (including physicians, nurses, and pharmacists)—herein referred to as providers; 2) household caregivers of children being treated for DR-TB—herein referred to as caregivers; and 3) children who were being treated for DR-TB—herein referred to as children. The population was a convenience sample and included children hospitalized between January 1, 2018, and June 30, 2020, ages 0–14 years old, as well as their caregivers and providers. Focus group transcripts and notes were analysed using a thematic network analysis based in grounded theory The analysis was iterative and the coding system developed focused on "stressful experiences" as well as ways to address them along the diagnostic and treatment journey. This paper follows the COREQ guidelines. Results: 16 children between the ages 7 and 14 years participated in 5 FGDs, 30 caregivers participated in 7 FGDs, and 12 providers participated in 3 FDGs. Data from the children and the caregivers were the focus of this analysis, although some themes were informed by the discussions with the providers as well. In general, it was reported that for a child diagnosed with DR-TB, there is a lived experience of stress that impacts their physical, mental, and social well-being. These pediatric patients and their families therefore develop strategies for coping with these disruptions to their lives. In general, there were major disruptive experiences that resulted from the process around receiving a diagnosis of DR-TB and second distinct set of stressful experiences that occurred during the treatment of DR-TB once the diagnosis had been made. These stresses occur in the physical, mental, and social realms, and families develop multiple strategies to cope with them, demonstrating resilience in the face of this disease. Conclusion: Addressing the stresses experienced by children and their caregivers through child-friendly DR-TB testing, treatment, and counseling is not only essential for ending TB but also for enacting a human-rights based approach to child health in general. Children with DR-TB are a vulnerable population, and they have often been the last to benefit from advances in general pediatric care and in DR-TB care more specifically. [ABSTRACT FROM AUTHOR]

Background: Pain is the most misunderstood, underdiagnosed, and undertreated/untreated medical problem, particularly in children. The main aim of this study was to assess practice and factors associated with pediatrics pain management among nurses working in Bahir Dar city public hospitals, Amhara region, North West Ethiopia, 2022. Method: An institutional-based cross-sectional concurrent mixed study design was conducted on randomly selected 421 nurses from November 1 to 30/2022. Purposively selected 8 nurses in different positions and qualifications were included in a qualitative study. A structured self-administered questionnaire and a semi-structured in-depth interview questionnaire were used for data collection. Epi info version 7.1 was used for data entry and SPSS version 25 was used for analysis. ATLAS ti version 7.0 and thematic analysis were used for qualitative study. Binary logistic regression was done to identify predictor variables associated with outcome variables at p <0.05 with a 95% confidence interval. Hosmer and Lemeshow's tests were checked for model goodness of fit, which was 0.71. Result: The good practice of pediatric pain management among nurses for hospitalized children was 216 (53.6%) (95% CI- 48.4% to 58.3%). Knowledge [AOR = 3.95; 95%CI: (2.30, 6.79)], attitude [AOR = 2.57; 95% CI: (1.53–4.30)], qualified in BSC pediatrics and child health nurses [AOR = 6.53; 95%CI: (1.56–27.25)], year of experience in pediatrics unit [(AOR = 1.92; 95% CI: (1.03–3.56)] and gating pain management training [AOR = 3.31; 95% CI: (1.73–6.33)] were significant factors. Four themes inadequate knowledge of pain assessment and management practice, inadequate professional commitment, organization-related factors, and impacts of family knowledge, culture, and economic status were explored. Conclusion: Only half of the participants had good practice. Knowledge, attitude, nurses qualified in BSC pediatrics and child health, years of experience in the pediatrics department, and pain management training were associated factors. From the qualitative findings, the unavailability of anti-pain drugs, lack of training, assessment tools, continuous monitoring and evaluation, updated protocols, shortage of resources, and others were the barriers to proper pain management. This study concludes that applying effective pain management practices to hospitalized children remains a challenge. Therefore, it is better to put further effort towards improving pediatric pain management practice. [ABSTRACT FROM AUTHOR]

Objective: There is conflicting evidence whether subtypes of Respiratory syncytial virus have different seasonality or are differentially associated with clinical severity. We aimed to explore the associations between disease severity and RSV subtypes RSV-A and RSV-B and to describe the circulation of RSV subtypes pattern by season and age. Methods: Active prospective hospital surveillance for RSV-A and RSV-B in children <59 months of age was conducted during 2015–2018. All febrile children 12–59 months of age were enrolled, whereas children <12 months were eligible if presenting with fever or respiratory symptoms. Risk factors and upper and lower respiratory tract infection was identified by linkage to national registry data and analyzed using penalized maximum likelihood logistic regression. Results: Both RSV-A and B were found to co-circulate throughout all three study seasons, and no clear seasonal pattern was identified. Likewise, we found no association between sex or measures of severity with RSV-A or RSV-B. There was significantly more RSV-A than RSV-B among children with comorbidities. Conclusions: No association was found between disease severity or sex and RSV subtypes RSV-A and RSV-B in hospitalized young children in Norway. [ABSTRACT FROM AUTHOR]

Introduction: In 2012, the World Health Organization revised treatment guidelines for childhood pneumonia with lower chest wall indrawing (LCWI) but no 'danger signs', to recommend home-based treatment. We analysed data from children hospitalized with LCWI pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) study to identify sub-groups with high odds of mortality, who might continue to benefit from hospital management but may not be admitted by staff implementing the 2012 guidelines. We compare the proportion of deaths identified using the criteria in the 2012 guidelines, and the proportion of deaths identified using an alternative set of criteria from our model. Methods: PERCH enrolled a cohort of 2189 HIV-negative children aged 2–59 months who were admitted to hospital with LCWI pneumonia (without obvious cyanosis, inability to feed, vomiting, convulsions, lethargy or head nodding) between 2011–2014 in Kenya, Zambia, South Africa, Mali, The Gambia, Bangladesh, and Thailand. We analysed risk factors for mortality among these cases using predictive logistic regression. Malnutrition was defined as mid-upper-arm circumference <125mm or weight-for-age z-score <-2. Results: Among 2189 cases, 76 (3·6%) died. Mortality was associated with oxygen saturation <92% (aOR 3·33, 1·99–5·99), HIV negative but exposed status (4·59, 1·81–11·7), moderate or severe malnutrition (6·85, 3·22–14·6) and younger age (infants compared to children 12–59 months old, OR 2·03, 95%CI 1·05–3·93). At least one of three risk factors: hypoxaemia, HIV exposure, or malnutrition identified 807 children in this population, 40% of LCWI pneumonia cases and identified 86% of the children who died in hospital (65/76). Risk factors identified using the 2012 WHO treatment guidelines identified 66% of the children who died in hospital (n = 50/76). Conclusions: Although it focuses on treatment failure in hospital, this study supports the proposal for better risk stratification of children with LCWI pneumonia. Those who have hypoxaemia, any malnutrition or those who were born to HIV positive mothers, experience poorer outcomes than other children with LCWI pneumonia. Consistent identification of these risk factors should be prioritised and children with at least one of these risk factors should not be managed in the community. [ABSTRACT FROM AUTHOR]

Globally, viral pathogens are the leading cause of acute respiratory infection in children under-five years. We aim to describe the epidemiology of viral respiratory pathogens in hospitalized children under-two years of age in Eastern Province of Sierra Leone, during the second year of the SARS-CoV-2 pandemic. We conducted a prospective study of children hospitalized with respiratory symptoms between October 2020 and October 2021. We collected demographic and clinical characteristics and calculated each participant´s respiratory symptom severity. Nose and throat swabs were collected at enrollment. Total nucleic acid was purified and tested for multiple respiratory viruses. Statistical analysis was performed using R version 4.2.0 software. 502 children less than two-years of age were enrolled. 376 (74.9%) had at least one respiratory virus detected. The most common viruses isolated were HRV/EV (28.2%), RSV (19.5%) and PIV (13.1%). Influenza and SARS-CoV-2 were identified in only 9.2% and 3.9% of children, respectively. Viral co-detection was common. Human metapneumovirus and RSV had more than two-fold higher odds of requiring O2 therapy while hospitalized. Viral pathogen prevalence was high (74.9%) in our study population. Despite this, 100% of children received antibiotics, underscoring a need to expand laboratory diagnostic capacity and to revisit clinical guidelines implementation in these children. Continuous surveillance and serologic studies among more diverse age groups, with greater geographic breadth, are needed in Sierra Leone to better characterize the long-term impact of COVID-19 on respiratory virus prevalence and to better characterize the seasonality of respiratory viruses in Sierra Leone. [ABSTRACT FROM AUTHOR]

Introduction: Community acquired pneumonia (CAP) is a leading cause of under-five mortality in India and Streptococcus pneumoniae is the main bacterial pathogen for it. Pneumococcal Conjugate Vaccine 13 (PCV13) has been introduced in a phased manner, in the national immunization program of India since 2017/2018. The primary objective of this study was to evaluate the effectiveness of PCV13 on chest radiograph (CXR)-confirmed pneumonia, in children hospitalized with WHO-defined severe CAP. Methods: This prospective, multi-site test-negative study was conducted in a hospital-network situated in three districts of Northern India where PCV13 had been introduced. Children aged 2–23 months, hospitalized with severe CAP and with interpretable CXR were included after parental consent. Clinical data was extracted from hospital records. CXRs were interpreted by a panel of three independent blinded trained radiologists. Exposure to PCV13 was defined as ≥2 doses of PCV13 in children aged ≤ 12 months and ≥ 1 dose(s) in children > 12 months of age. Our outcome measures were CXR finding of primary endpoint pneumonia with or without other infiltrates (PEP±OI); vaccine effectiveness (VE) and hospital mortality. Results: From 1st June 2017-30th April 2021, among 2711 children included, 678 (25.0%) were exposed to PCV1. CXR positive for PEP±OI on CXR was found in 579 (21.4%), of which 103 (17.8%) were exposed to PCV. Adjusted odds ratio (AOR) for PEP±OI among the exposed group was 0.69 (95% CI, 0.54–0.89, p = 0.004). Adjusted VE was 31.0% (95% CI: 11.0–44.0) for PEP±OI. AOR for hospital mortality with PEP±OI was 2.65 (95% CI: 1.27–5.53, p = 0.01). Conclusion: In severe CAP, children exposed to PCV13 had significantly reduced odds of having PEP±OI. Since PEP±OI had increased odds of hospital mortality due to CAP, countrywide coverage with PCV13 is an essential priority. [ABSTRACT FROM AUTHOR]

Background: Malaria remains a major public health challenge in Africa where annually, ~250,000 children with malaria experience a neurologic injury with subsequent neuro-disability. Evidence indicates that a higher temperature during the acute illness is a risk factor for post-infectious neurologic sequelae. As such, aggressive antipyretic therapy may be warranted among children with complicated malaria at substantial risk of brain injury. Previous clinical trials conducted primarily in children with uncomplicated malaria and using only a single antipyretic medication have shown limited benefits in terms of fever reduction; however, no studies to date have examined malaria fever management using dual therapies. In this clinical trial of aggressive antipyretic therapy, children hospitalized with central nervous system (CNS) malaria will be randomized to usual care (acetaminophen every 6 hours for a temperature ≥ 38.5°C) vs. prophylactic acetaminophen and ibuprofen every 6 hours for 72 hours. Methods: In this double-blinded, placebo controlled, two-armed clinical trial, we will enroll 284 participants from three settings at Queen Elizabeth Central Hospital in Blantyre, Malawi; at the University Teaching Hospitals Children's Hospital in Lusaka, Zambia and at Chipata Central Hospital, Chipata, Zambia. Parents or guardians must provide written informed consent. Eligible participants are 2–11 years with evidence of P. falciparum malaria infection by peripheral blood smear or rapid diagnostic test with CNS symptoms associated with malaria. Eligible children will receive treatment allocation randomization either to standard of care for fever management or to prophylactic, scheduled treatment every 6 hours for 72 hours with dual antipyretic therapies using acetaminophen and ibuprofen. Assignment to treatment groups will be with 1:1 allocation using blocked randomization. The primary outcome will be maximum temperature in the 72 hours after enrolment. Secondary outcomes include parasite clearance as determined by quantitative Histidine Rich Protein II and seizures through 72 hours after enrolment. Discussion: This clinical trial seeks to challenge the practice paradigm of limited fever treatment based upon hyperpyrexia by evaluating the fever-reduction efficacy of more aggressive antipyretic using two antipyretics and prophylactic administration and will elucidate the impact of antipyretics on parasite clearance and acute symptomatic seizures. If aggressive antipyretic therapy is shown to safely reduce the maximum temperature, a clinical trial evaluating the neuroprotective effects of temperature reduction in CNS malaria is warranted. [ABSTRACT FROM AUTHOR]

Introduction: Several global initiatives put parent involvement at the forefront of enabling children's well-being and development and to promote quality of care for newborns and hospitalized young children aged 0–24 months. Scanty evidence on mistreatment such as delays or neglect and poor pain management among newborns exists, with even less exploring the experience of their parents and their hospitalized young children. To address this gap, authors reviewed research on experience of care for hospitalized young children and their parents, and potential interventions that may promote positive experience of care. Methods: A scoping review of English language articles, guidelines, and reports that addressed the experiences of care for newborns and sick young children 0–24 months in health facilities was conducted. Multiple databases: PubMed, PROSPERO, COCHRANE Library and Google Scholar were included and yielded 7,784 articles. Documents published between 2009 and November 2020, in English and with evidence on interventions that addressed family involvement and partnership in care for their sick children were included. Results: The scoping review includes 68 documents across 31 countries after exclusion. Mistreatment of newborns comprises physical abuse, verbal abuse, stigma and discrimination, failure to meet professional standards, poor rapport between providers and patients, poor legal accountability, and poor bereavement and posthumous care. No literature was identified describing mistreatment of hospitalized children aged 60 days– 24 months. Key drivers of mistreatment include under-resourced health systems and poor provider attitudes. Positive experience of care was reported in contexts of good parent-provider communication. Three possible interventions on positive experience of care for hospitalized young children (0–24 months) emerged: 1) nurturing care; 2) family centered care and 3) provider and parental engagement. Communication and counseling, effective provider-parental engagement, and supportive work environments were associated with reduced anxiety and stress for parents and hospitalized young children. Few interventions focused on addressing providers' underlying attitudes and biases that influence provider behaviors, and how they affect engaging with parents. Conclusion: Limited evidence on manifestations of mistreatment, lack of respectful care, drivers of poor experience and interventions that may mitigate poor experience of care for hospitalized young children 0–24 months especially in low resource settings exists. Design and testing appropriate models that enhance socio-behavioral dimensions of care experience and promote provider-family engagement in hospitals are required. [ABSTRACT FROM AUTHOR]

Background: We aimed to provide regional data on clinical symptoms, medical resource utilization (MRU), and risk factors for increased MRU in hospitalized respiratory syncytial virus (RSV)-infected Belgian pediatric population. Methods: This prospective, multicenter study enrolled RSV (+) hospitalized children (aged ≤5y) during the 2013–2015 RSV seasons. RSV was diagnosed within 24h of hospitalization. Disease severity of RSV (+) patients was assessed until discharge or up to maximum six days using a Physical Examination Score (PES) and a derived score based on ability to feed, dyspnea and respiratory effort (PES3). MRU (concomitant medications, length of hospitalization [LOH], and oxygen supplementation) was evaluated. Kaplan-Meier survival analysis was performed to compare MRU by age and presence of risk factors for severe disease. Association between baseline covariates and MRU was analyzed using Cox regression models. Results: In total, 75 children were included, Median (range) age was 4 (0–41) months, risk factors were present in 18.7%, and early hospitalization (≤3 days of symptom onset) was observed in 57.3% of patients. Cough (100%), feeding problems (82.2%), nasal discharge (87.8%), and rales and rhonchi (82.2%) were frequently observed. Median (range) LOH and oxygen supplementation was 5 (2–7) and 3 (1–7) days. Oxygen supplementation, bronchodilators, and antibiotics were administered to 58.7%, 64.0%, and 41.3% of the patients, respectively. Age <3 months and baseline total PES3 score were associated with probability and the duration of receiving oxygen supplementation. LOH was not associated with any covariate. Conclusion: RSV is associated with high disease burden and MRU in hospitalized children. Oxygen supplementation but not length of hospitalization was associated with very young age and the PES3 score. These results warrant further assessment of the PES3 score as a predictor for the probability of receiving and length of oxygen supplementation in RSV hospitalized children. Registration: NCT02133092 [ABSTRACT FROM AUTHOR]

Research registries are a powerful tool for boosting recruitment into clinical trials. However, little is known about how parents approach the decision to enroll their child in a pediatric participant research registry (PPRR). We conducted in-person, written, or telephone surveys with parents/guardians of children hospitalized at Children's Hospital of Omaha, Nebraska to identify attitudes towards and barriers to enrollment in PPRRs. Overall, our population (N = 36) had positive attitudes toward PPRRs, with 77.8% (CI: 61.6, 88.4) of participants stating they were "somewhat" or "very" likely to enroll their child. Likelihood to enroll differed between various recruitment and enrollment methods, with participants stating they would be more likely to enroll their child in a PPRR if they were recruited by their child's primary care provider or a nurse in clinic (p = 0.02) and less likely to enroll if they were recruited through social media (p<0.001). Additionally, over 90% of participants who were likely to enroll their child in a PPRR (N = 28) were also willing to provide demographic, medical, and lifestyle information. However, these participants remained concerned about inappropriate sharing of their information with insurance or for-profit companies (53.6%, CI: 35.8, 70.4) and about receiving unwanted telephone calls from the registry (78.6%, CI: 60.0, 90.0). Parents are generally willing to enroll their child in a PPRR. However, to optimize enrollment, investigators must understand parental preferences for and concerns surrounding enrollment in a PPRR. [ABSTRACT FROM AUTHOR]

The present study was done to identify the viral diversity, seasonality and burden associated with childhood acute respiratory tract infection (ARTI) in Sri Lanka. Nasopharyngeal aspirates (NPA) of hospitalized children (1 month—5 years) with ARTI were collected in 2 centers (wet and dry zones) from March 2013 to August 2014. Respiratory viral antigen detection by immunofluorescence assay (IFA) was used to identify the infecting viruses. IFA negative 100 NPA samples were tested for human metapeumovirus (hMPV), human bocavirus and corona viruses by polymerase chain reaction. Of the 443 and 418 NPAs, 37.2% and 39.4% were positive for any of the 8 different respiratory viruses tested from two centers studied. Viral co-infection was detected with respiratory syncytial virus (RSV) in both centers. Peak viral detection was noted in the wet zone from May-July 2013 and 2014 and in the dry zone from December-January 2014 suggesting a local seasonality for viral ARTI. RSV showed a clear seasonality with a direct correlation of monthly RSV infections with rainy days in the wet zone and an inverse correlation with temperature in both centers. The case fatality rate was 2.7% for RSV associated ARTI. The overall disability adjusted life years was 335.9 and for RSV associated ARTI it was 241.8. RSV was the commonly detected respiratory virus with an annual seasonality and distribution in rainy seasons in the dry and wet zones of Sri Lanka. Identifying the virus and seasonality will contribute to employ preventive measures and reduce the empirical use of antibiotics in resource limited settings. [ABSTRACT FROM AUTHOR]

Background: Severe acute malnutrition is defined by <70% weight for length/height, by visible severe wasting, by the presence of pitting edema, and in children 6 to 59 months of age, mid upper arm circumference <110 mm. Severe acute malnutrition remains to be a worldwide problem, claiming lives of millions of children, especially in sub-Saharan Africa and south Asia. Though the Ethiopian national guideline states the total length of stay in therapeutic feeding units should not be more than four weeks, there is huge difference, varying from 8 to 47 days of stay. Therefore, the objective of this study was to assess length of stay to recover from severe acute malnutrition and associated factors among under five children hospitalized to the public hospitals in Aksum Town. Methods: Sample size was calculated using STATA version 12.0. A retrospective cohort study was conducted using pretested questionnaire in the public hospitals in Aksum on children aged 0–59 months. Cleaned data was entered to Epi info version 7.1.4 and then exported into SPSS version 21 for analysis. Bivariable and multivariable analyses were performed using Kaplan Meier and Cox regression models. During bivariable analysis, variables with p-value < 0.05 were selected for multivariable analysis to identify independent factors associated with length of stay. Results: A total of 564 participants enrolled to the study. The rate of recovery was 56% with median length of stay of 15 days (95% CI: 14.1, 15.9). The independent predictors of length of stay to recovery were presence of diarrhea at admission (AHR = 0.573, 95% CI: 0.415–0.793), being HIV positive (AHR = 0.391, 95% CI: 0.194–0.788), palmar pallor (AHR = 0.575, 95% CI: 0.416–0.794), presence of other co-morbidities at admission (AHR = 0.415, 95% CI: 0.302–0.570) and not being treated with plumpy nut (AHR = 0.368, 95% CI: 0.262–0.518). Conclusions: Length of stay is in the acceptable range of the international and national set of standards. Nevertheless, the recovery rate was lower compared to the Sphere standard. Presence of diarrhea, palmar pallor, HIV other co-morbidities and not treated with plumpy nut were found independent protective factors for recovery from sever acute malnutrition. [ABSTRACT FROM AUTHOR]

Background: Respiratory diseases, including pneumonia, are the second largest cause of under-five mortality in Mongolia and the most common cause of childhood hospitalization. However information regarding the contribution of Streptococcus pneumoniae to pneumonia causation in Mongolia is limited. We aimed to describe the epidemiology of hospitalized children aged 2–59 months with pneumonia, enrolled into a surveillance program in the period prior to pneumococcal conjugate vaccine (PCV) introduction, in Mongolia. Methods: An expanded pneumonia surveillance program enrolled children, who met the surveillance case definition, at participating hospitals, between April 2015 and May 2016. Cumulative incidence rates were calculated by district for all pneumonia endpoints using district specific denominators from the Mongolian Health Department census for 2016. Socio-economic and disease-associated factors were compared between districts using chi-squared tests. Results: A total of 4318 eligible children with pneumonia were enrolled over the 14 month period. Overall the incidence for all-cause pneumonia in children aged 12–59 months was 31.8 per 1000 population; children aged 2–11 months had an almost four-fold higher incidence than children aged 12–59 months. Differences were found between districts with regards to housing type, fuel used for cooking, hospital admission practices and the proportions of severe and primary endpoint pneumonia. Discussion: This study shows a high burden of pneumonia in children aged 2–59 months in Mongolia prior to PCV introduction. Rates differed somewhat by district and age group and were influenced by a number of socio-economic factors. It will be important to consider these differences and risk factors when assessing the impact of PCV introduction. [ABSTRACT FROM AUTHOR]

Background: Incidence of community acquired pneumonia is high globally. In Bangladesh, more male children than female children are brought to hospitals for pneumonia. We examined if there was disparities in the severity of illness and outcome by sex among children who were admitted with pneumonia to hospitals in Bangladesh. Methods: Hospitalized children, aged 2 to 59 months, meeting a case definition of pneumonia were recruited in seven hospitals following parental consent. At baseline, study doctors obtained socio-demographic characteristics and care seeking behaviors for pneumonia, and then clinical data were collected throughout the hospital stay. Multivariate analysis was performed to determine if the sex of the child had a relationship with either illness severity on admission or outcome in the hospital. Results: Between May 2004 and December 2008, 6,856 children, including 35% females, were recruited. A total of 1,371 (19.9%) children had non-severe pneumonia, 4,118 (60.0%) had severe pneumonia, and 1,367 (19.9%) had very severe pneumonia. A higher proportion of hospitalized females had very severe pneumonia as compared to males (21.5% versus 19.1%; P = 0.01), but there was no difference by sex in the proportion of children with severe or non-severe pneumonia. There was no difference by sex observed in the clinical management provided in the hospital, but a greater proportion of females (4.7%) as compared to males (3.6%) died in hospitals (P = 0.04). In multivariate analyses, female sex was associated with very severe pneumonia on admission (OR: 1.26, 95% CI: 1.09–1.47) and fatal outcome in the hospitals (OR: 1.31, 95% CI: 1.01–1.71). Death in female children admitted with very severe pneumonia was 4 times higher than that reported in males (OR: 4.37, 95% CI: 3.24–5.89). Conclusion: Our data demonstrates a sex-based disparity in the severity of pneumonia and deaths among children admitted to hospitals in Bangladesh, despite no existing disparity by sex in hospital treatment. These findings call for further investigations to explore the determinants of health seeking behavior by parents with children with pneumonia in a community that favors males to females, and to understand the role of differences by sex in childhood pneumonia outcomes in Bangladesh. [ABSTRACT FROM AUTHOR]

Uncertainty remains regarding the magnitude of effectiveness of influenza vaccines for preventing serious outcomes, especially among young children. We estimated vaccine effectiveness (VE) against laboratory-confirmed influenza hospitalizations among children aged 6–59 months. We used the test-negative design in hospitalized children in Ontario, Canada during the 2010–11 to 2013–14 influenza seasons. We used logistic regression models adjusted for age, season, and time within season to calculate VE estimates by vaccination status (full vs. partial), age group, and influenza season. We also assessed VE incorporating prior history of influenza vaccination. We included specimens from 9,982 patient hospitalization episodes over four seasons, with 12.8% testing positive for influenza. We observed variation in VE by vaccination status, age group, and influenza season. For the four seasons combined, VE was 60% (95%CI, 44%-72%) for full vaccination and 39% (95%CI, 17%-56%) for partial vaccination. VE for full vaccination was 67% (95%CI, 48%-79%) for children aged 24–59 months, 48% (95%CI, 12%-69%) for children aged 6–23 months, 77% (95%CI, 47%-90%) for 2010–11, 59% (95%CI, 13%-81%) for 2011–12, 33% (95%CI, –18% to 62%) for 2012–13, and 72% (95%CI, 42%-86%) for 2013–14. VE in children aged 24–59 months appeared similar between those vaccinated in both the current and previous seasons and those vaccinated in the current season only, with the exception of 2012–13, when VE was lower for those vaccinated in the current season only. Influenza vaccination is effective in preventing pediatric laboratory-confirmed influenza hospitalizations during most seasons. [ABSTRACT FROM AUTHOR]

Background: Despite a high burden of respiratory syncytial virus (RSV) infections among children, data on demographic and clinical characteristics of RSV are scarce in low and middle income countries. This study aims to describe the viral etiologies, the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a lower respiratory tract infections (LRTI), focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity. Methods: A prospective study among children under two years of age, hospitalized with LRTI was conducted in two referral pediatric hospitals in Ho Chi Minh City, Vietnam, from May 2009 to December 2010. Socio-demographic, clinical data and nasopharyngeal swabs were collected on enrolment and discharge. Multiplex real-time RT-PCR (13 viruses) and quantitative RSV RT-PCR were used to identify viral pathogens, RSV load and subgroups. Results: Among 632 cases, 48% were RSV positive. RSV infections occurred at younger age than three other leading viral infections i.e rhinovirus (RV), metapneumovirus (MPV), parainfluenza virus (PIV-3) and were significantly more frequent in the first 6 months of life. Clinical severity score of RSV infection was significantly higher than PIV-3 but not for RV or MPV. In multivariate analysis, RV infection was significantly associated with severity while RSV infection was not. Among RSV infections, neither viral load nor viral co-infections were significantly associated with severity. Young age and having fever at admission were significantly associated with both RSV and LRTI severity. A shift in RSV subgroup predominance was observed during two consecutive rainy seasons but was not associated with severity. Conclusion: We report etiologies, the epidemiological and clinical characteristics of LRTI among hospitalized children under two years of age and risk factors of RSV and LRTI severity. [ABSTRACT FROM AUTHOR]

This retrospective study was aimed to identify risk factors of intravenous (IV) infiltration for hospitalized children. The participants were 1,174 children admitted to a general hospital, who received peripheral intravenous injection therapy at least once, and had complete records. Data were analyzed with frequency and percentage or mean and standard deviation were calculated, and odds ratio (OR) from univariate and multiple logistic regressions. The number and % of infiltrations were 92 and 7.8%, respectively. IV infiltration risk factors were lower limb (OR = 1.72), phenytoin (OR = 11.03), 10% dextrose (OR = 6.55), steroids (OR = 6.21), vancomycin (OR = 4.10), high-concentration electrolytes (OR = 3.49), and ampicillin/sulbactam combination (OR = 3.37). Nurses working at children’s hospitals should consider the risk of IV infiltration for children receiving IV infusion therapy and make a preventive effort to identify IV infiltration in high-risk children at an early stage. [ABSTRACT FROM AUTHOR]

Human coronaviruses (HCoVs) are associated with a variety of clinical presentations in children, but their role in disease remains uncertain. The objective of our prospective study was to investigate HCoVs associations with various clinical presentations in hospitalized children up to 6 years of age. Children hospitalized with acute bronchiolitis (AB), acute gastroenteritis (AGE), or febrile seizures (FS), and children admitted for elective surgical procedures (healthy controls) were included in the study. In patients with AB, AGE, and FS, a nasopharyngeal (NP) swab and blood sample were obtained upon admission and the follow-up visit 14 days later, whereas in children with AGE a stool sample was also acquired upon admission; in healthy controls a NP swab and stool sample were taken upon admission. Amplification of polymerase 1b gene was used to detect HCoVs in the specimens. HCoVs-positive specimens were also examined for the presence of several other viruses. HCoVs were most often detected in children with FS (19/192, 9.9%, 95% CI: 6–15%), followed by children with AGE (19/218, 8.7%, 95% CI: 5.3–13.3%) and AB (20/308, 6.5%, 95% CI: 4.0–9.8%). The presence of other viruses was a common finding, most frequent in the group of children with AB (19/20, 95%, 95% CI: 75.1–99.8%), followed by FS (10/19, 52.6%, 95% CI: 28.9–75.6%) and AGE (7/19, 36.8%, 95% CI: 16.3–61.6%). In healthy control children HCoVs were detected in 3/156 (1.9%, 95% CI: 0.4–5.5%) NP swabs and 1/150 (0.7%, 95% CI: 0.02–3.3%) stool samples. It seems that an etiological role of HCoVs is most likely in children with FS, considering that they had a higher proportion of positive HCoVs results than patients with AB and those with AGE, and had the highest viral load; however, the co-detection of other viruses was 52.6%. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: Acute respiratory infections (ARI) are the major worldwide health problem associated with high morbidity and mortality rates. Human adenovirus (HAdV) is one of the most common pathogens associated with viral ARI, and thus calls for specific diagnosis and better understanding of the epidemiology and clinical characteristics. Methods: Total 4,130 children with ARI requiring hospitalization from 2012 to 2013 were retrospectively studied. Throat swab specimens were collected from each patient. Fluorescence Quantitative PCR was performed to detect adenovirus as well as other common ARI-related pathogens. The seven HAdV hypervariable regions (HVRs) of the hexon gene from fifty-seven HAdVs-positive samples collected in the seasonal peaks were sequenced. Phylogenetic analysis of HVRs was also conducted to confirm the molecular types and genetic variation. In addition, epidemiological features and co-infection with other human respiratory pathogens were investigated and analyzed. Results: Of 4,130 hospitalized pediatric patients tested, the positive rates of respiratory syncytial virus (RSV), Mycoplasma pneumoniae (MP), and HAdV were 13.7%, 13.2%, and 12.0%, respectively. The HAdV positive patients accounted for 7.9%, 17.2%, 17.5% and 10.7% in age groups <1, 1–3, 3–6 and 6–14 years, respectively. Eighty-four HAdV positive children were co-infected with other respiratory pathogens (84/495, 17.0%). The most common co-infection pathogens with HAdV were MP (57.1%) and Human Bocavirus (HBoV) (16.7%). The majority of HAdV infected patients were totally recovered (96.9%, 480/495); However, four (0.8%) patients, who were previously healthy and at the age of 2 years or younger died of pneumonia. Seasonal peaks of HAdV infection occurred in the summer season of 2012 and 2013; the predominant HAdV type was HAdV-3 (70%), followed by HAdV-7 (28%). These epidemiological features were different from those in Northern China. The HAdV-55 was identified and reported for the first time in Guangzhou metropolitan area. Phylogenetic analysis indicated that all the HVR sequences of the hexon gene of HAdV-3 and -7 strains have high similarity within their individual types, and these strains were also similar to those circulating in China currently, indicating the conservation of hexon genes of both HAdV-3 and HAdV-7. Conclusions: Knowledge of the epidemiological features and molecular types of HAdV, a major pathogen of pediatric ARI, as well as other co-infected respiratory pathogens circulating in Guangzhou, southern China, is vital to predict and prevent future disease outbreaks in children. This study will certainly facilitate HAdV vaccine development and treatment of HAdV infections in children. [ABSTRACT FROM AUTHOR]

Background: Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. Objectives: To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). Methods: We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. Results: 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. Conclusion: The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role. [ABSTRACT FROM AUTHOR]

Background: The risk of bacteremia is considered low in children with acute bronchiolitis. However the rate of occult bacteremia in infants with RSV infection is not well established. The aim was to determine the actual rate and predictive factors of bacteremia in children admitted to hospital due to confirmed RSV acute respiratory illness (ARI), using both conventional culture and molecular techniques. Methods: A prospective multicenter study (GENDRES-network) was conducted between 2011–2013 in children under the age of two admitted to hospital because of an ARI. Among those RSV-positive, bacterial presence in blood was assessed using PCR for Meningococcus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, in addition to conventional cultures. Results: 66 children with positive RSV respiratory illness were included. In 10.6% patients, bacterial presence was detected: H. influenzae (n = 4) and S. pneumoniae (n = 2). In those patients with bacteremia, there was a previous suspicion of bacterial superinfection and had received empirical antibiotic treatment 6 out of 7 (85.7%) patients. There were significant differences in terms of severity between children with positive bacterial PCR and those with negative results: PICU admission (100% vs. 50%, P-value = 0.015); respiratory support necessity (100% vs. 18.6%, P-value < 0.001); Wood-Downes score (mean = 8.7 vs. 4.8 points, P-value < 0.001); GENVIP scale (mean = 17 vs. 10.1, P-value < 0.001); and length of hospitalization (mean = 12.1 vs. 7.5 days, P-value = 0.007). Conclusion: Bacteremia is not frequent in infants hospitalized with RSV respiratory infection, however, it should be considered in the most severe cases. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the contribution of breastfeeding to Rotavirus (RV)-induced antigenemia and/or RNAemia and disease severity in Indian children (<2 yrs age). Methods: Paired stool and serum samples were collected from (a) hospitalized infants with diarrhea (n = 145) and (b) healthy control infants without diarrhea (n = 28). Stool RV-antigen was screened in both groups by commercial rapid-test and enzyme immunoassay. The disease severity was scored and real-time-PCR was used for viral-load estimation. Serum was evaluated for RV-antigenemia by EIA and RV-RNAemia by RT-PCR. Data was stratified by age-group and breastfeeding status and compared. Results: Presence of RV-antigenemia and RV-RNAemia was positively related with presence of RV in stool. Disease severity and stool viral-load was significantly associated with RV-antigenemia[(r = 0.74; CI:0.66 to 0.84; P<0.0001,R2 = 0.59) and (r = -0.55; CI:-0.68 to -0.39; P<0.0001,R2 = 0.31) respectively], but not with RV-RNAemia. There was significant reduction in RV-antigenemiarate in the breast-fed group compared to non-breastfed infants, especially in 0–6 month age group (P<0.001). Non-breastfed infants were at risk for RV-antigenemia with severe disease manifestations in form of high Vesikari scores correlating with high fever, more vomiting episodes and dehydration. Conclusion: RV-antigenemia was common in nonbreastfed children with severe RV-diarrhea and correlated with stool RV-load and disease severity. [ABSTRACT FROM AUTHOR]

Background: There are very limited data on children with pneumonia in Mali. The objective was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children <5 years of age in Mali. Methods: A prospective hospital-based case-control study was implemented in the Pediatric department of Gabriel Touré University Hospital at Bamako, Mali, between July 2011-December 2012. Cases were children with radiologically-confirmed pneumonia; Controls were hospitalized children without respiratory features, matched for age and period. Respiratory specimens, were collected to identify 19 viruses and 5 bacteria. Whole blood was collected from cases only. Factors associated with pneumonia were assessed by multivariate logistic regression. Results: Overall, 118 cases and 98 controls were analyzed; 44.1% were female, median age was 11 months. Among pneumonia cases, 30.5% were hypoxemic at admission, mortality was 4.2%. Pneumonia cases differed from the controls regarding clinical signs and symptoms but not in terms of past medical history. Multivariate analysis of nasal swab findings disclosed that S. pneumoniae (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.6–7.0), human metapneumovirus (aOR = 17.2, 95% CI: 2.0–151.4), respiratory syncytial virus [RSV] (aOR = 7.4, 95% CI: 2.3–23.3), and influenza A virus (aOR = 10.7, 95% CI: 1.0–112.2) were associated with pneumonia, independently of patient age, gender, period, and other pathogens. Distribution of S. pneumoniae and RSV differed by season with higher rates of S. pneumoniae in January-June and of RSV in July-September. Pneumococcal serotypes 1 and 5 were more frequent in pneumonia cases than in the controls (P = 0.009, and P = 0.04, respectively). Conclusions: In this non-PCV population from Mali, pneumonia in children was mainly attributed to S. pneumoniae, RSV, human metapneumovirus, and influenza A virus. Increased pneumococcal conjugate vaccine coverage in children could significantly reduce the burden of pneumonia in sub-Saharan African countries. [ABSTRACT FROM AUTHOR]

Background: The reduction in the deaths of millions of children who die from infectious diseases requires early initiation of treatment and improved access to care available in health facilities. A major challenge is the lack of objective evidence to guide front line health workers in the community to recognize critical illness in children earlier in their course. Methods: We undertook a prospective observational study of children less than 5 years of age presenting at the outpatient or emergency department of a rural tertiary care hospital between October 2012 and April 2013. Study physicians collected clinical signs and symptoms from the facility records, and with a mobile application performed recordings of oxygen saturation, heart rate and respiratory rate. Facility physicians decided the need for hospital admission without knowledge of the oxygen saturation. Multiple logistic predictive models were tested. Findings: Twenty-five percent of the 3374 assessed children, with a median (interquartile range) age of 1.02 (0.42–2.24), were admitted to hospital. We were unable to contact 20% of subjects after their visit. A logistic regression model using continuous oxygen saturation, respiratory rate, temperature and age combined with dichotomous signs of chest indrawing, lethargy, irritability and symptoms of cough, diarrhea and fast or difficult breathing predicted admission to hospital with an area under the receiver operating characteristic curve of 0.89 (95% confidence interval -CI: 0.87 to 0.90). At a risk threshold of 25% for admission, the sensitivity was 77% (95% CI: 74% to 80%), specificity was 87% (95% CI: 86% to 88%), positive predictive value was 70% (95% CI: 67% to 73%) and negative predictive value was 91% (95% CI: 90% to 92%). Conclusion: A model using oxygen saturation, respiratory rate and temperature in combination with readily obtained clinical signs and symptoms predicted the need for hospitalization of critically ill children. External validation of this model in a community setting will be required before adoption into clinical practice. [ABSTRACT FROM AUTHOR]

The emergence and rapid spread of unusual DS-1-like G1P[8] rotaviruses in Japan have been recently reported. During rotavirus surveillance in Thailand, three DS-1-like G1P[8] strains (RVA/Human-wt/THA/PCB-180/2013/G1P[8], RVA/Human-wt/THA/SKT-109/2013/G1P[8], and RVA/Human-wt/THA/SSKT-41/2013/G1P[8]) were identified in stool specimens from hospitalized children with severe diarrhea. In this study, we sequenced and characterized the complete genomes of strains PCB-180, SKT-109, and SSKT-41. On whole genomic analysis, all three strains exhibited a unique genotype constellation including both genogroup 1 and 2 genes: G1-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. This novel genotype constellation is shared with Japanese DS-1-like G1P[8] strains. Phylogenetic analysis revealed that the G/P genes of strains PCB-180, SKT-109, and SSKT-41 appeared to have originated from human Wa-like G1P[8] strains. On the other hand, the non-G/P genes of the three strains were assumed to have originated from human DS-1-like strains. Thus, strains PCB-180, SKT-109, and SSKT-41 appeared to be derived through reassortment event(s) between Wa-like G1P[8] and DS-1-like human rotaviruses. Furthermore, strains PCB-180, SKT-109, and SSKT-41 were found to have the 11-segment genome almost indistinguishable from one another in their nucleotide sequences and phylogenetic lineages, indicating the derivation of the three strains from a common origin. Moreover, all the 11 genes of the three strains were closely related to those of Japanese DS-1-like G1P[8] strains. Therefore, DS-1-like G1P[8] strains that have emerged in Thailand and Japan were assumed to have originated from a recent common ancestor. To our knowledge, this is the first report on whole genome-based characterization of DS-1-like G1P[8] strains that have emerged in an area other than Japan. Our observations will provide important insights into the evolutionary dynamics of emerging DS-1-like G1P[8] rotaviruses. [ABSTRACT FROM AUTHOR]

Background: Contact tracing, to identify source cases with untreated tuberculosis (TB), is rarely performed in high disease burden settings when the index case is a young child with TB. As TB is strongly associated with HIV infection in these settings, we used source case investigation to determine the prevalence of undiagnosed TB and HIV in the caregivers and household contacts of hospitalised young children diagnosed with TB in South Africa. Methods: Caregivers and household contacts of 576 young children (age ≤7 years) with TB diagnosed between May 2010 and August 2012 were screened for TB and HIV. The primary outcome was the detection of laboratory-confirmed, newly-diagnosed TB disease and/or HIV-infection in close contacts. Results: Of 576 caregivers, 301 (52·3%) self-reported HIV-positivity. Newly-diagnosed HIV infection was detected in 63 (22·9%) of the remaining 275 caregivers who self-reported an unknown or negative HIV status. Screening identified 133 (23·1%) caregivers eligible for immediate anti-retroviral therapy (ART). Newly-diagnosed TB disease was detected in 23 (4·0%) caregivers. In non-caregiver household contacts (n = 1341), the prevalence of newly-diagnosed HIV infection and TB disease was 10·0% and 3·2% respectively. On average, screening contacts of every nine children with TB resulted in the identification of one case of newly-diagnosed TB disease, three cases of newly diagnosed HIV-infection, and three HIV-infected persons eligible for ART. Conclusion: In high burden countries, source case investigation yields high rates of previously undiagnosed HIV and TB infection in the close contacts of hospitalised young children diagnosed with TB. Furthermore, integrated screening identifies many individuals who are eligible for immediate ART. Similar studies, with costing analyses, should be undertaken in other high burden settings–integrated source case investigation for TB and HIV should be routinely undertaken if our findings are confirmed. [ABSTRACT FROM AUTHOR]

Background: Influenza A(H1N1)pdm09, A(H3N2) and B viruses have co-circulated in the human population since the swine-origin human H1N1 pandemic in 2009. While infections of these subtypes generally cause mild illnesses, lower respiratory tract infection (LRTI) occurs in a portion of children and required hospitalization. The aim of our study was to estimate the prevalence of these three subtypes and compare the clinical manifestations in hospitalized children with LRTI in Guangzhou, China during the post-pandemic period. Methods: Children hospitalized with LRTI from January 2010 to December 2012 were tested for influenza A/B virus infection from their throat swab specimens using real-time PCR and the clinical features of the positive cases were analyzed. Results: Of 3637 hospitalized children, 216 (5.9%) were identified as influenza A or B positive. Infection of influenza virus peaked around March in Guangzhou each year from 2010 to 2012, and there were distinct epidemics of each subtype. Influenza A(H3N2) infection was more frequently detected than A(H1N1)pdm09 and B, overall. The mean age of children with influenza A virus (H1N1/H3N2) infection was younger than those with influenza B (34.4 months/32.5 months versus 45 months old; p<0.005). Co-infections of influenza A/ B with mycoplasma pneumoniae were found in 44/216 (20.3%) children. Conclusions: This study contributes the understanding to the prevalence of seasonal influenza viruses in hospitalized children with LRTI in Guangzhou, China during the post pandemic period. High rate of mycoplasma pneumoniae co-infection with influenza viruses might contribute to severe disease in the hospitalized children. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is the leading cause of hospitalization especially in young children with respiratory tract infections (RTI). Patterns of circulating RSV genotypes can provide a better understanding of the molecular epidemiology of RSV infection. We retrospectively analyzed the genetic diversity of RSV infection in hospitalized children with acute RTI admitted to University Hospital Heidelberg/Germany between October 2012 and April 2013. Nasopharyngeal aspirates (NPA) were routinely obtained in 240 children younger than 2 years of age who presented with clinical symptoms of upper or lower RTI. We analyzed NPAs via PCR and sequence analysis of the second variable region of the RSV G gene coding for the attachment glycoprotein. We obtained medical records reviewing routine clinical data. RSV was detected in 134/240 children. In RSV-positive patients the most common diagnosis was bronchitis/bronchiolitis (75.4%). The mean duration of hospitalization was longer in RSV-positive compared to RSV-negative patients (3.5 vs. 5.1 days; p<0.01). RSV-A was detected in 82.1%, RSV-B in 17.9% of all samples. Phylogenetic analysis of 112 isolates revealed that the majority of RSV-A strains (65%) belonged to the novel ON1 genotype containing a 72-nucleotide duplication. However, genotype ON1 was not associated with a more severe course of illness when taking basic clinical/laboratory parameters into account. Molecular characterization of RSV confirms the co-circulation of multiple genotypes of subtype RSV-A and RSV-B. The duplication in the G gene of genotype ON1 might have an effect on the rapid spread of this emerging RSV strain. [ABSTRACT FROM AUTHOR]

Adenoviruses have been recognized as important causal pathogens of community-acquired diarrhea (CAD) among children, but their role in hospital-acquired diarrhea (HAD) is not well-understood. Hospitalized children with acute diarrhea and children who visited the outpatient department due to diarrhea were investigated from 2011 to 2012. Adenovirus was detected in stool specimens by PCR and further characterized by sequencing and phylogenetic analysis. SPSS software (version 19.0) was used for statistical analyses. A total of 2233 diarrheal children were enrolled in this study; this sample was comprised of 1371 hospitalized children, including 885 with CAD (IP-CAD) and 486 with HAD, and 862 outpatients with CAD (OP-CAD). Among these 2,233 patients, adenovirus was detected in 219 cases (9.8%). The positive rates for adenovirus were significantly different between the IP-CAD (9.3%), HAD (13.8%) and OP-CAD (8.1%) cases (X2 = 11.76, p = 0.003). The positive rate of adenovirus was lower in infants under six months of age compared to the positive rates in the other age groups. Of the 219 of adenovirus positive patients, 91 (41.6%) were identified as having serotype 41. Although enteric adenovirus (group F) was the most frequently detected adenovirus among children with either CAD or HAD, the role of non-enteric adenoviruses, especially the adenovirus 31 type (19.7%), cannot be ignored in diarrheal children. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of data on malaria among hospitalized children in malaria endemic areas. We determined the prevalence, presentation and treatment outcomes of malaria and anemia among children in two hospitals in Rakai, Uganda. Methods: Children under five years hospitalized in Kalisizo hospital or Bikira health center in Rakai district, Uganda between May 2011 and May 2012 were enrolled and followed-up until discharge, death or referral. Data were collected on social-demographic characteristics, current and past illnesses and clinical signs and symptoms. Blood smears, hemoglobin (Hgb) levels and HIV testing were performed from finger/heel prick blood. The associations between malaria infection and other factors were estimated using log-binomial regression to estimate adjusted prevalence risk ratios (aPRR) and 95% confidence intervals (CIs), controlling for clustering at health facilities. Results: 2471 children were enrolled. The most common medical presentations were fever (96.2%), cough (61.7%), vomiting (44.2%), diarrhea (20.8%), and seizures (16.0%). The prevalence of malaria parasitemia was 54.6%. Children with malaria were more likely to present with a history of fever (aPRR 2.23; CI 1.18–4.24) and seizures (aPRR 1.12; CI 1.09–1.16). Confirmed malaria was significantly lower among girls than boys (aPRR 0.92; CI 0.91–0.93), HIV infected children (aPRR 0.60 CI 0.52–0.71), and children with diarrhea (aPRR 0.76; CI 0.65–0.90). The overall prevalence of anemia (Hgb<10 g/dl) was 56.3% and severe anemia (Hgb<6 g/dL) was 17.8%. Among children with severe anemia 76.8% had malaria parasitemia, of whom 93.1% received blood transfusion. Malaria associated mortality was 0.6%. Conclusion: There was a high prevalence of malaria parasitemia and anemia among inpatient children under five years. Malaria prevention is a priority in this population. [ABSTRACT FROM AUTHOR]

Pneumonia is one of the major public health problems in children under five years of age. The aim of this study was to analyze the time, place, and characteristics of the distribution of pneumonia in hospitalized children under five years of age at the Dhaulagiri Zonal Hospital (DZH) in Nepal. A descriptive cross-sectional study was carried out at DZH from July 16, 2008 to August 17, 2011 for hospitalized children under five years of age and diagnosed with pneumonia. The main bacterial cause of pneumonia was Streptococcus pneumoniae and the main viral cause was Respiratory Syntical Virus (RSV). The majority of children admitted for treatment of pneumonia were males (60%), from upper class ethnic groups, and common among those aged 29 days to one year (49.1% of overall pneumonia cases). Data from this study show that pneumonia episodes in DZH occurred throughout the year with a sharp increase in the occurrence at the end of August to September. More cases were recorded during the rainy seasons and winter months in all three study years. The cases were from households most concentrated in Baglung municipality where the hospital is located. Pneumonia was found in higher proportions among hospitalized male children, those aged 29 days to one year, and in upper ethnic groups, during the rainy seasons and in winter months, and among local populations near the hospital in the rural western region of Nepal. Strengthening community-based case management, prevention strategies, and health care delivery system would help reduce pneumonia cases and the overall burden associated with it. [ABSTRACT FROM AUTHOR]

Astroviruses are globally known enteropathogens causing gastroenteritis and diarrhea, with eight well defined serotypes. Epidemiological studies have recognized serotype-1 as the most common subtype but no such data is available in Pakistan. During 2009–2010, we found astroviruses in 41 out of 535 (7%) samples collected from hospitalized children. Thirty one strains belonged to serotype-1 and clustered into two distinct lineages. Serotype-3, -4 and -6 were detected with 97–98% genetic homology to Indian and Chinese strains. [ABSTRACT FROM AUTHOR]

Background: The swine-origin influenza A(H1N1)pdm09 pandemic of 2009 had a slower spread in Europe than expected. The human rhinovirus (HRV) has been suggested to have delayed the pandemic through viral interference. The importance of co-infections over time during the pandemic and in terms of severity of the disease needs to be assessed. Objective: The aim of this study was to investigate respiratory viruses and specifically the presence of co-infections with influenza A(H1N1)pdm09 (H1N1) in hospitalized children during the H1N1 pandemic. A secondary aim was to investigate if co-infections were associated with severity of disease. Methods: A retrospective study was performed on 502 children with influenza-like illness admitted to inpatient care at a pediatric hospital in Stockholm, Sweden during the 6 months spanning the H1N1 pandemic in 2009. Respiratory samples were analyzed for a panel of 16 viruses by real-time polymerase chain reaction. Results: One or more viruses were detected in 61.6% of the samples. Of these, 85.4% were single infections and 14.6% coinfections (2-4 viruses). The number of co-infections increased throughout the study period. H1N1 was found in 83 (16.5%) children and of these 12 (14.5%) were co-infections. HRV and H1N1 circulated to a large extent at the same time and 6.0% of the H1N1-positive children were also positive for HRV. There was no correlation between co-infections and severity of disease in children with H1N1. Conclusions: Viral co-infections were relatively common in H1N1 infected hospitalized children and need to be considered when estimating morbidity attributed to H1N1. Population-based longitudinal studies with repeated sampling are needed to improve the understanding of the importance of co-infections and viral interference. [ABSTRACT FROM AUTHOR]

Background: Upper respiratory tract infection (URTI) is a major reason for hospitalization in childhood. More than 80% of URTIs are viral. Etiological diagnosis of URTIs is important to make correct clinical decisions on treatment methods. However, data for viral spectrum of URTIs are very limited in Shanghai children. Methods: Nasopharyngeal swabs were collected from a group of 164 children aged below 3 years who were hospitalized due to acute respiratory infection from May 2009 to July 2010 in Shanghai. A VRDAL multiplex PCR for 10 common respiratory viruses was performed on collected specimens compared with the Seeplex® RV15 ACE Detection kit for 15 respiratory viruses. Results: Viruses were detected in 84 (51.2%) patients by VRDAL multiplex PCR, and 8 (4.9%) of cases were mixed infections. Using the Seeplex® RV15 ACE Detection kit, viruses were detected in 129 (78.7%) patients, 49 (29.9%) were co-infected cases. Identified viruses included 37 of human rhinovirus (22.6% of cases), 32 of influenza A virus (19.5%), 30 of parainfluenzavirus-2 (18.3%), 23 of parainfluenzavirus-3 (14.0%), 15 of human enterovirus (9.1%), 14 each of parainfluenzavirus-1, respiratory syncytial virus B and adenovirus (8.5%), 8 of coronavirus 229E/NL63 (4.9%), 6 of human bocavirus (3.7%), 5 each of influenza B virus and respiratory syncytial virus A (3.0%), 3 of parainfluenzavirus-4 (1.8%), 2 of coronavirus OC43/HKU1 (1.2%), and 1 human metapneumovirus (0.6%). Conclusions: A high frequency of respiratory infections (78.7%) and co-infections (29.9%) was detected in children with acute respiratory infection symptoms in Shanghai. The Seeplex® RV15 ACE detection method was found to be a more reliable high throughput tool than VRDAL method to simultaneously detect multiple respiratory viruses. [ABSTRACT FROM AUTHOR]

Background: There have been few studies on children hospitalized with influenza published from mainland China. We performed a retrospective review of medical charts to describe the epidemiology, clinical features and direct medical cost of laboratory-proven influenza hospitalized children in Suzhou, China. Methods: Retrospective study on children with documented influenza infection hospitalized at Suzhou Children Hospital during 2005-2009 was conducted using a structured chart review instrument. Results: A total of 480 children were positive by immuno-fluorescent assay for influenza during 2005-2009. The hospitalizations for influenza occurred in 8-12 months of the year, most commonly in the winter with a second late summer peak (August-September). Influenza A accounted for 86.3%, and of these 286 (59.6%) were male, and 87.2% were <5 years of age. The median length of hospital stay was 7 days. Fever was the most common symptom, occurring in 398 (82.9%) children. There were 394 (82.1%) children with pneumonia and 70.2% of these hospitalized children had radiographic evidence of a pulmonary infiltrate. One hundred and twelve children (23.3%) required oxygen treatments and 13 (2.7%) were transferred to the ICU. Multivariable logistic regression showed that compared with the ≤6 months children, those aged >60 months old had shorter hospital stay (OR = 0.45); children with oxygen treatment tended to have longer hospital stays than those without oxygen treatment (OR = 2.14). The mean cost of each influenza-related hospitalization was US$ 624 (US$ 1323 for children referred to ICU and US$ 617 for those cared for on the wards). High risk children had higher total cost than low-risk patients. Conclusion: Compared to other countries, in Suzhou, children hospitalized with influenza have longer hospital stay and higher percentage of pneumonia. The direct medical cost is high relative to family income. Effective strategies of influenza immunization of young children in China may be beneficial in addressing this disease burden. [ABSTRACT FROM AUTHOR]

Background: In recent years, efforts have been made to improve paediatric drug therapy. The aim of this research was to investigate any changes regarding the frequency and nature of adverse drug reactions (ADRs) in hospitalized children in one paediatric general medical ward over a 9-year period. Methodology: Two prospective observational cohort studies were conducted at a large University hospital in Germany in 1999 and 2008, respectively. Children aged 0-18 years admitted to the study ward during the study periods were included. ADRs were identified using intensive chart review. Uni- and multivariable regression has been used for data analysis. Results: A total of 520 patients (574 admissions) were included [1999: n = 144 (167); 2008: n = 376 (407)]. Patients received a total of 2053 drugs [median 3, interquartile range (IQR) 2-5]. 19% of patients did not receive any medication. Median length of stay was 4 days (IQR 3-7; range 1-190 days) with a significantly longer length of stay in 1999. The overall ADR incidence was 13.1% (95% CI, 9.8-16.3) varying significantly between the two study cohorts [1999: 21.9%, 95% CI, 14.7-29.0; 2008: 9.2%, 95% CI, 5.9-12.5 (p<0.001)]. Antibacterials and corticosteroids for systemic use caused most of the ADRs in both cohorts (1999; 2008). Exposure to systemic antibacterials decreased from 62.9% to 43.5% whereas exposure to analgesics and anti-inflammatory drugs increased from 17.4% to 45.2%, respectively. The use of high risk drugs decreased from 75% to 62.2%. In 1999, 45.7% and in 2008 96.2% of ADRs were identified by treating clinicians (p<0.001). Conclusions: Between 1999 and 2008, the incidence of ADRs decreased significantly. Improved treatment strategies and an increased awareness of ADRs by physicians are most likely to be the cause for this positive development. Nevertheless further research on ADRs particularly in primary care and the establishment of prospective pharmacovigilance systems are still needed. [ABSTRACT FROM AUTHOR]

The objective of the study was to describe systemic bacterial infections occurring in acutely ill and hospitalized children in a rural region in Ghana, regarding frequency, incidence, antimicrobial susceptibility patterns and associations with anthropometrical data. Blood cultures were performed in all children below the age of five years, who were admitted to Agogo Presbyterian Hospital (APH), Asante Region, Ghana, between September 2007 and July 2009. Medical history and anthropometrical data were assessed using a standardized questionnaire at admission. Incidences were calculated after considering the coverage population adjusted for village-dependent health-seeking behavior. Among 1,196 hospitalized children, 19.9% (n = 238) were blood culture positive. The four most frequent isolated pathogens were nontyphoidal salmonellae (NTS) (53.3%; n = 129), Staphylococcus aureus (13.2%; n = 32), Streptococcus pneumoniae (9.1%; n = 22) and Salmonella ser. Typhi (7.0%; n = 17). Yearly cumulative incidence of bacteremia was 46.6 cases/1,000 (CI 40.9-52.2). Yearly cumulative incidences per 1,000 of the four most frequent isolates were 25.2 (CI 21.1-29.4) for NTS, 6.3 (CI 4.1-8.4) for S. aureus, 4.3 (CI 2.5-6.1) for S. pneumoniae and 3.3 (CI 1.8-4.9) for Salmonella ser. Typhi. Wasting was positively associated with bacteremia and systemic NTS bloodstream infection. Children older than three months had more often NTS bacteremia than younger children. Ninety-eight percent of NTS and 100% of Salmonella ser. Typhi isolates were susceptible to ciprofloxacin, whereas both tested 100% susceptible to ceftriaxone. Seventy-seven percent of NTS and 65% of Salmonella ser. Typhi isolates were multi-drug resistant (MDR). Systemic bacterial infections in nearly 20% of hospitalized children underline the need for microbiological diagnostics, to guide targeted antimicrobial treatment and prevention of bacteremia. If microbiological diagnostics are lacking, calculated antimicrobial treatment of severely ill children in malariaendemic areas should be considered. [ABSTRACT FROM AUTHOR]

Background: Limited data are available describing the clinical presentation and risk factors for admission to the intensive care unit for children with 2009 H1N1 infection. Methods: We conducted a retrospective chart review of all hospitalized children with 2009 influenza A (H1N1) and 2008-09 seasonal influenza at The Children's Hospital, Denver, Colorado. Results: Of the 307 children identified with 2009 H1N1 infections, the median age was 6 years, 61% were male, and 66% had underlying medical conditions. Eighty children (26%) were admitted to the ICU. Thirty-two (40%) of the ICU patients required intubation and 17 (53%) of the intubated patients developed acute respiratory distress syndrome (ARDS). Four patients required extracorporeal membrane oxygenation. Eight (3%) of the hospitalized children died. Admission to the ICU was significantly associated with older age and underlying neurological condition. Compared to the 90 children admitted during the 2008-09 season, children admitted with 2009 H1N1 influenza were significantly older, had a shorter length of hospitalization, more use of antivirals, and a higher incidence of ARDS. Conclusions: Compared to the 2008-09 season, hospitalized children with 2009 H1N1 influenza were much older and had more severe respiratory disease. Among children hospitalized with 2009 H1N1 influenza, risk factors for admission to the ICU included older age and having an underlying neurological condition. Children under the age of 2 hospitalized with 2009 H1N1 influenza were significantly less likely to require ICU care compared to older hospitalized children. [ABSTRACT FROM AUTHOR]

Background: Serious bacterial infections are a major source of morbidity and mortality in HIV-infected children. The spectrum of disease is wide, and responsible organisms vary according to setting. The use of antibiotic prophylaxis and the emergence of multi-drug resistant bacteria necessitate examination of responsible organisms and their antibiotic susceptibility. Methodology/Principal Findings: A retrospective cohort study of all HIV-positive pediatric admissions at an urban public sector hospital in Cape Town between January 2002 and June 2006 was conducted. Children between the ages of one month and nine years with laboratory confirmed HIV status, serious bacterial infection, and a hospital length of stay of 5 days or more, were eligible for inclusion. Organisms isolated from blood, urine, and cerebral spinal fluid cultures and their antimicrobial susceptibility were examined, and compared according to timing of isolation to distinguish nosocomial versus community-acquired. One hundred and forty-one children were identified (median age 1.2 years), 39% of whom were on antiretrovirals started before or during this hospitalization. Bacterial infections involved all organ systems, however pneumonia was most common (67%). S. pneumoniae and S. aureus were the most common gram positive and K. pneumoniae was the most common gram negative organism. K pneumoniae isolates were resistant to many first and second line antibiotics, and were all considered nosocomial. All S. aureus isolates were methicillin resistant, some of which were community-acquired. Conclusions/Significance: Bacterial infections are an important source of co-morbidity in HIV-infected children in resourcelimited settings. Clinicians should have a low threshold to initiate antibiotics in children requiring hospitalization. Broad-spectrum antibiotics should be used judiciously. Clinicians caring for HIV-infected children should be cognizant of the most common organisms affecting such children, and of their local antimicrobial susceptibilities, when treating empirically for serious bacterial infections. [ABSTRACT FROM AUTHOR]