Important Cause Of Childhood Morbidity Research Articles

Detection and diversity of gastrointestinal viruses in wastewater from Caracas, Venezuela, 2021-2022

Gastrointestinal viruses (GIV) are an important cause of childhood morbidity and mortality, particularly in developing countries. Their epidemiological impact in Venezuela during the COVID-19 pandemic remains unclear. GIV can also be detected in domestic sewage. Ninety-one wastewater samples from urban areas of Caracas collected over 12 months and concentrated by polyethylene-glycol-precipitation, were analyzed by multiplex reverse-transcription-PCR for rotavirus/calicivirus/astrovirus and enterovirus/klassevirus/cosavirus, and monoplex-PCR for adenovirus and Aichi virus. The overall frequency of virus detection was 46.2%, fluctuating over months, and peaking in the rainy season. Adenoviruses circulated throughout the year, especially type F41, and predominated (52.7%) over caliciviruses (29.1%) that peaked in the rainy months, rotaviruses (9.1%), cosaviruses (5.5%), astroviruses and enteroviruses (1.8%). Aichi-virus and klassevirus were absent. Rotavirus G9/G12, and P[4]/P[8]/P[14] predominated. The occurrence of GIV in wastewater reflects transmission within the population of Caracas and the persistence of a potential public health risk that needs to be adequately monitored.

Interaction of the Hemagglutinin Stalk Region with Cell Adhesion Molecule (CADM) 1 and CADM2 Mediates the Spread between Neurons and Neuropathogenicity of Measles Virus with a Hyperfusogenic Fusion Protein.

Measles virus (MeV), the causative agent of measles, is an enveloped RNA virus of the family Paramyxoviridae, which remains an important cause of childhood morbidity and mortality. MeV has two envelope glycoproteins, the hemagglutinin (H) and fusion (F) proteins. During viral entry or virus-mediated fusion between infected cells and neighboring susceptible cells, the head domain of the H protein initially binds to its receptors, signaling lymphocytic activation molecule family member 1 (SLAM) and nectin-4, and then the stalk region of the H protein transmits the fusion-triggering signal to the F protein. MeV may persist in the human brain and cause a fatal neurodegenerative disease, subacute sclerosing panencephalitis (SSPE). Recently, we showed, using in vitro cell culture, that cell adhesion molecule (CADM) 1 and CADM2 are host factors that trigger hyperfusogenic mutant F proteins, causing cell-to-cell fusion and the transfer of the MeV genome between neurons. Unlike conventional receptors, CADM1 and CADM2 interact in cis (on the same membrane) with the H protein and then trigger membrane fusion. Here, we show that alanine substitutions in part of the stalk region (positions 171-175) abolish the ability of the H protein to mediate membrane fusion triggered by CADM1 and CADM2, but not by SLAM. The recombinant hyperfusogenic MeV carrying this mutant H protein loses its ability to spread in primary mouse neurons as well as its neurovirulence in experimentally infected suckling hamsters. These results indicate that CADM1 and CADM2 are key molecules for MeV propagation in the brain and its neurovirulence in vivo. IMPORTANCE Measles is an acute febrile illness with skin rash. Despite the availability of highly effective vaccines, measles is still an important cause of childhood morbidity and mortality in many countries. The World Health Organization estimates that more than 120,000 people died from measles worldwide in 2021. Measles virus (MeV), the causative agent of measles, can also cause a fatal progressive neurological disorder, subacute sclerosing panencephalitis (SSPE), several years after acute infection. There is currently no effective treatment for this disease. In this study, using recombinant MeVs with altered receptor usage patterns, we show that cell adhesion molecule (CADM) 1 and CADM2 are host factors critical for MeV spread in neurons and its neurovirulence. These findings further our understanding of the molecular mechanism of MeV neuropathogenicity.

Twenty-Year Experience and Outcomes in a National Pediatric Pulmonary Hypertension Service.

Rationale: Pediatric pulmonary hypertension is an important cause of childhood morbidity and mortality, but there are limited data on the range of associated diseases, contributions of different pulmonary hypertension subtypes, therapeutic strategies, and clinical outcomes in children. Objectives: To report the 20-year experience of a large UK National Pediatric Pulmonary Hypertension Service focusing on epidemiology and clinical outcomes. Methods: Consecutive patients presenting between 2001 and 2021 were included, and survival analysis was performed for incident patients. Measurements and Main Results: Of 1,353 patients assessed, a pulmonary hypertension diagnosis was made in 1,101 (81.4%) patients (51% female, median age, 2.6 [interquartile range, 0.8-8.2] years). The most common form was pulmonary arterial hypertension in 48%, followed by 32.3% with pulmonary hypertension due to lung disease. Multiple contributory causes of pulmonary hypertension were common, with 16.9% displaying features of more than one diagnostic group. The annual incidence of childhood pulmonary hypertension was 3.5 (95% confidence interval [CI], 3.3-3.8) per 1 million children, and the prevalence was 18.1 (95% CI, 15.8-20.4) per 1 million. The incidence was highest for pulmonary hypertension due to lung disease in infancy (15.0 [95% CI, 12.7-17.2] per 1 million per year). Overall, 82.4% patients received pulmonary arterial hypertension therapy, and escalation to triple therapy during follow-up was required in 13.1%. In 970 (88.1%) incident patients, transplant-free survival was 86.7% (95% CI, 84.5-89%) at 1 and 68.6% (95% CI, 64.7-72.6%) at 10 years. Pulmonary hypertension due to left heart disease had the lowest survival (hazard ratio, 2.0; 95% CI, 1.36-2.94; P < 0.001). Conclusions: Clinical phenotypes of pediatric pulmonary hypertension are heterogeneous and overlapping, with clinical phenotypes that evolve throughout childhood. Despite widespread use of pulmonary arterial hypertension therapy, the prognosis remains poor.

Outcome of treatment of children with epilepsy in a Nigerian tertiary hospital

Background: Epilepsy, the most predominant noncontagious neurologic disorder affecting children and carrying profound levels of social stigma, is an important cause of childhood morbidity globally. Objectives: This study aims at describing the prevalence, etiological risk factors, seizure pattern/associated comorbidities, and outcome of treatment with antiepiletic drugs (AEDs) among patients with epilepsy attending the neurology clinic of Federal Medical Center, Asaba, Delta State, Nigeria. Materials and Methods: A 10-year review of all patients seen at the neurology clinic of the tertiary institution. Information including history/physical examination, socio-demographic variables, and electroencephalogram (EEG) findings was collected from the clinic records of the patients between January 2009 and December 2019. A total of 105 patients presented with clinical features of epilepsy classified based on the 2017 International League Against Epilepsy classification. All data obtained from the clinic records were analyzed using the SPSS, Version 23.0, software. Results: Of the 302 patients seen with different neurologic morbidities, 105 had epilepsy, giving a prevalence rate of 34.7%, occurring more in children aged 6 months to 3 years with a male predisposition (55.2%). Generalized tonic-clonic (GTC) seizure was identified as the most predominant type 9/105(8.6%), severe birth asphyxia and cerebral palsy were the most common cause, and comorbidity of epilepsy, respectively. Sodium valproate was the commonly used AED with 55.8% good outcome. Conclusion: Epilepsy is still an underreported childhood neurologic morbidity in our environment. Good outcome recorded can be attributed to high levels of adherence to medication and absence of associated metabolic disorders or intracranial structural lesions.

Short-Stalk Isoforms of CADM1 and CADM2 Trigger Neuropathogenic Measles Virus-Mediated Membrane Fusion by Interacting with the Viral Hemagglutinin.

Measles virus (MeV), an enveloped RNA virus in the family Paramyxoviridae, usually causes acute febrile illness with skin rash but in rare cases persists in the brain, causing a progressive neurological disorder, subacute sclerosing panencephalitis (SSPE). MeV bears two envelope glycoproteins, the hemagglutinin (H) and fusion (F) proteins. The H protein possesses a head domain that initially mediates receptor binding and a stalk domain that subsequently transmits the fusion-triggering signal to the F protein. We recently showed that cell adhesion molecule 1 (CADM1; also known as IGSF4A, Necl-2, and SynCAM1) and CADM2 (also known as IGSF4D, Necl-3, and SynCAM2) are host factors enabling cell-cell membrane fusion mediated by hyperfusogenic F proteins of neuropathogenic MeVs as well as MeV spread between neurons lacking the known receptors. CADM1 and CADM2 interact in cis with the H protein on the same cell membrane, triggering hyperfusogenic F protein-mediated membrane fusion. Multiple isoforms of CADM1 and CADM2 containing various lengths of their stalk regions are generated by alternative splicing. Here, we show that only short-stalk isoforms of CADM1 and CADM2 predominantly expressed in the brain induce hyperfusogenic F protein-mediated membrane fusion. While the known receptors interact in trans with the H protein through its head domain, these isoforms can interact in cis even with the H protein lacking the head domain and trigger membrane fusion, presumably through its stalk domain. Thus, our results unveil a new mechanism of viral fusion triggering by host factors. IMPORTANCE Measles, an acute febrile illness with skin rash, is still an important cause of childhood morbidity and mortality worldwide. Measles virus (MeV), the causative agent of measles, may also cause a progressive neurological disorder, subacute sclerosing panencephalitis (SSPE), several years after acute infection. The disease is fatal, and no effective therapy is available. Recently, we reported that cell adhesion molecule 1 (CADM1) and CADM2 are host factors enabling MeV cell-to-cell spread in neurons. These molecules interact in cis with the MeV attachment protein on the same cell membrane, triggering the fusion protein and causing membrane fusion. CADM1 and CADM2 are known to exist in multiple splice isoforms. In this study, we report that their short-stalk isoforms can induce membrane fusion by interacting in cis with the viral attachment protein independently of its receptor-binding head domain. This finding may have important implications for cis-acting fusion triggering by host factors.

Birth prevalence of congenital heart disease among newborns in a tertiary hospital in Benin City, Nigeria.

Congenital heart disease (CHD) is an important cause of childhood morbidity. The birth prevalence and distribution of CHD among neonates in a tertiary hospital in Nigeria was determined. This descriptive, cross-sectional study involved consecutive neonates in the neonatal and postnatal wards of the hospital. Bedside echocardiography was conducted on all neonates. Data entry and analysis was done with IBM-SPSS version 20.0. A total of 2 849 neonates were recruited, consisting of 1 482 (52.0%) males. Forty-one neonates had CHD, giving a birth prevalence of 14.4/1 000 live births. Of the 41 with CHD, 21 (51.2%) were male. Thirty-six (87.8%) neonates had acyanotic CHD, of which the commonest was isolated ventricular septal defect [11 (26.8%)]. Transposition of the great arteries [3 (7.3%)] was the commonest cyanotic CHD. The birth prevalence of 14.4/1 000 live births in this study is high and buttresses the need for strengthening existing cardiac services in Nigeria.

Twenty-year experience and outcomes in a national paediatric pulmonary hypertension service

Abstract Background/Introduction Paediatric pulmonary hypertension (PH) is an important cause of childhood morbidity and mortality, but there are limited data on the range of associated diseases (including several paediatric-specific aetiologies), contributions of different PH subtypes, therapeutic strategies and clinical outcomes in paediatric patients. Purpose In this study, we report the 20-year experience of a UK National Paediatric Pulmonary Hypertension Service focusing on the aetiology, management and outcomes of children with PH. Methods Consecutive patients presenting to the service between January 2001 and January 2021 were included in this retrospective study. Other inclusion criteria were: age ≤18 years at diagnosis and diagnosis of PH following specialist assessment. Only incident patients (without pre-existing PH) were entered in the survival analysis. Results A total of 1104 (81.5%) PH patients were included during the study period: 51% female, median age 2.6 [0.8–8.2] years. The most common PH diagnosis was group 1 (pulmonary arterial hypertension, PAH) in 532 (48.2%) patients, followed by group 3 PH (due to lung disease) in 358 (32.4%), group 2 (101, 9.1%), group 5 (93, 8.4%), and group 4 disease (20, 1.8%). The most common PAH subgroup was PAH associated with congenital heart disease (CHD, 63.3%), followed by idiopathic PAH (22.4%). One quarter of patients (23.6%) had multiple contributory factors for PH, fitting more than one diagnostic group. Resolution of PH, defined as normalisation of pulmonary artery pressures following cessation of PAH therapy, occurred in 172 (15.6%) patients at a median age of 3.7 [2.1–5.7] years and was more common in group 3 than other PH groups (33.5% vs. 9.1% at 5 years post-diagnosis, p&amp;lt;0.0001). Overall, 909 (82.3%) patients received PAH therapy. Patients with group 3 PH were as likely to receive PAH therapy as an initial treatment strategy as group 1 patients (86.6% vs. 82.3%, p=0.11), but were more likely to receive sildenafil monotherapy (p=0.002) and less likely to be offered triple therapy (p&amp;lt;0.0001). During follow-up, maintenance or escalation to triple therapy was required in 103 (9.3%) patients and was far more common in idiopathic compared to other PAH subgroups (37.7% vs. 7.8%, p&amp;lt;0.0001). Transplant-free survival was 86.7% (95% CI: 84.5–88.9%) at 1 year, 74.2% (95% CI: 71.1–77.5%) at 5 years, and 68.9% (95% CI: 65.1–73%) at 10 years (Figure 1). PAH related to CHD had the highest transplant-free survival (HR 0.62, 95% CI: 0.46–0.84, p=0.002). Group 2 had the lowest transplant-free survival (HR 2.09, 95% CI: 1.42–3.09, p=0.0002) whereas groups 3,4 and 5 did not differ significantly from PAH (Figure 2). Conclusions In this large, national cohort of paediatric PH patients, the most common type of PH was PAH, followed by group 3 PH. Multiple contributory causes for PH are common and PH resolution was not uncommon, especially in group 3 patients. Despite widespread use of PAH therapy, the prognosis remains guarded. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Dr Constantine has received a PhD grant from Janssen-Cilag Ltd. as the CHAMPION PhD Fellow. Figure 1Figure 2

EFFECTIVENESS OF STRUCTURED NURSING INTERVENTION ON NUTRITIONAL STATUS OF UNDERFIVE CHILDREN, KNOWLEDGE AND PRACTICE OF MOTHERS REGARDING THE PREVENTION AND MANAGEMENT OF PROTEIN ENERGY MALNUTRITION IN SELECTED COASTAL VILLAGES OF KERALA.

Malnutrition is not only an important cause of childhood morbidity and mortality, but leads also to permanent impairment of physical and possibly, of mental growth of those who survive. The study was carried out to nd out the effectiveness of structured nursing intervention on nutritional status of underve children, knowledge and practice of mothers regarding prevention and management of malnutrition in selected coastal villages of Kerala. Samples consisted of 122 underve children who were identied with different degrees of malnutrition and their mothers. Pre experimental study design was used. Anthropometric parameters (Weight, Height, MUAC) were checked. Structured knowledge questionnaire and practice check list were used to measure the knowledge and practice of mothers related to the prevention and management of malnutrition. All the measurements were carried out once before the Structured Nursing Intervention and three times after the intervention. Structured Nursing Intervention was found to be effective in improving the knowledge and practice of mothers related to prevention and management of malnutrition among underve children (p &lt; 0.001). Percentage of grade I malnutrition reduced from 83.6% in pre test to 63.69% in post test III. Z test was carried out and it was concluded that Structured Nursing Intervention had signicant inuence on the nutritional status of underve children (Z = 3.33**, p value &lt;0.01).

CADM1 and CADM2 Trigger Neuropathogenic Measles Virus-Mediated Membrane Fusion by Acting in cis.

Measles virus (MeV), an enveloped RNA virus in the family Paramyxoviridae, is still an important cause of childhood morbidity and mortality worldwide. MeV usually causes acute febrile illness with skin rash, but in rare cases persists in the brain, causing a progressive neurological disorder, subacute sclerosing panencephalitis (SSPE). The disease is fatal, and no effective therapy is currently available. Although transsynaptic cell-to-cell transmission is thought to account for MeV propagation in the brain, neurons do not express the known receptors for MeV. Recent studies have shown that hyperfusogenic changes in the MeV fusion (F) protein play a key role in MeV propagation in the brain. However, how such mutant viruses spread in neurons remains unexplained. Here, we show that cell adhesion molecule 1 (CADM1; also known as IGSF4A, Necl-2, and SynCAM1) and CADM2 (also known as IGSF4D, Necl-3, SynCAM2) are host factors that enable MeV to cause membrane fusion in cells lacking the known receptors and to spread between neurons. During enveloped virus entry, a cellular receptor generally interacts in trans with the attachment protein on the envelope. However, CADM1 and CADM2 interact in cis with the MeV attachment protein on the same cell membrane, causing the fusion protein triggering and membrane fusion. Knockdown of CADM1 and CADM2 inhibits syncytium formation and virus transmission between neurons that are both mediated by hyperfusogenic F proteins. Thus, our results unravel the molecular mechanism (receptor-mimicking cis-acting fusion triggering) by which MeV spreads transsynaptically between neurons, thereby causing SSPE. IMPORTANCE Measles virus (MeV), an enveloped RNA virus, is the causative agent of measles, which is still an important cause of childhood morbidity and mortality worldwide. Persistent MeV infection in the brain causes a fatal progressive neurological disorder, subacute sclerosing panencephalitis (SSPE), several years after acute infection. However, how MeV spreads in neurons, which are mainly affected in SSPE, remains largely unknown. In this study, we demonstrate that cell adhesion molecule 1 (CADM1) and CADM2 are host factors enabling MeV spread between neurons. During enveloped virus entry, a cellular receptor generally interacts in trans with the attachment protein on the viral membrane (envelope). Remarkably, CADM1 and CADM2 interact in cis with the MeV attachment protein on the same membrane, triggering the fusion protein and causing membrane fusion, as viral receptors usually do in trans. Careful screening may lead to more examples of such "receptor-mimicking cis-acting fusion triggering" in other viruses.

Surveillance for Invasive Salmonella Disease in Bamako, Mali, From 2002 to 2018.

Background Salmonella enterica bloodstream infections are an important cause of childhood morbidity and mortality, including in Mali. We report 17 years of surveillance for nontyphoidal and typhoidal S. enterica infections among inpatients and outpatients at l’Hôpital Gabriel Touré, the main source of pediatric tertiary care in Bamako, Mali.MethodsBetween June 2002 and December 2018, a blood culture was collected from 54 748 children aged ≤15 years with fever and/or suspected invasive bacterial infection who provided consent (38 152 inpatients, 16 596 outpatients). Bacterial pathogens were identified using standard microbiological techniques and serovars of S. enterica were determined by PCR and/or agglutination with antisera.ResultsNontyphoidal Salmonella (NTS) was identified in 671 enrolled inpatients (1.8% of all enrolled inpatients, 13.8% of enrolled inpatients with a positive culture). S. Enteritidis, the most common NTS serovar, accounted for 38.5% of all NTS isolates (n = 258), followed by S. Typhimurium (31.7%, n = 213). The median (SD) age of children with a culture positive for NTS was 1.8 (3) years. Overall case fatality was 20.9%. An additional 138 inpatients (0.4%) had a positive culture for typhoidal Salmonella. NTS was identified in 11 outpatients (0.07%), while typhoidal Salmonella was found in 49 outpatients (0.3%). The annual incidence of invasive NTS disease decreased over the study period, but case fatality remained high.ConclusionsAlthough incidence decreased, NTS remained a major cause of invasive bacterial infection and mortality among hospitalized children in Bamako, while typhoidal Salmonella was uncommon. Because 87% of NTS belonged to only 4 serovars, a multivalent vaccine may be an effective strategy to reduce the burden and mortality of invasive NTS.

Assessing the burden of viral co-infections in acute gastroenteritis in children: An eleven-year-long investigation.

Acute gastroenteritis is an important cause of childhood morbidity and mortality worldwide. A number of pathogens are responsible for human acute gastroenteritis. The recent introduction of syndromic assays for the diagnosis of enteric infections, including a wide panel of enteric pathogens, has unveiled the frequency of mixed infections. This study was carried out to assess the burden of viral co-infections and the genetic diversity of the viruses detected in children hospitalized with acute gastroenteritis in Italy. A total of 4161 stool samples collected from diarrheic children over 11 years, from January 2008 to December 2018, were investigated for the presence of four enteric viruses, i.e. group A rotavirus, norovirus, astrovirus and adenovirus. The samples were initially screened by either molecular or immunochromatographic assays and subsequently confirmed by Real-time PCR and sequence analyses. At least one viral agent was detected in 48.6 %of specimens. Rotavirus was the most prevalent virus (24.7 %) followed by norovirus (19.6 %), adenovirus (5.3 %) and astrovirus (3%). Co-infections were detected in 8.3 % of virus-positive patients, with common viral combination being rotavirus with norovirus (70.6 % of co-infections) or with astrovirus (9.6 %). A variety of viral genotypes was detected in co-infections and in single infections. Using Real-time PCR cycle thresholds as a proxy measure of fecal viral load, rotavirus was generally detected at higher levels in co-infected patients. Combining and deciphering measurable indicators of viral load and epidemiological information could be useful for an accurate interpretation of viral co-infections.

Rapid Reduction of Campylobacter Species in the Gut Microbiome of Preschool Children after Oral Azithromycin: A Randomized Controlled Trial.

Campylobacter has emerged as a potential important cause of childhood morbidity in sub-Saharan Africa. Biannual mass azithromycin distribution has previously been shown to reduce all-cause child mortality in sub-Saharan Africa. We conducted a randomized controlled trial in Burkina Faso in which children were randomized in a 1:1 fashion to a 5-day course of azithromycin or placebo to investigate the effect of oral antibiotics on the gut microbiome. We evaluated the changes in the gut microbiome of preschool children treated with azithromycin using metagenomic DNA sequencing. We found that three Campylobacter species were reduced with azithromycin treatment compared with placebo. These results were consistent with other studies that have shown decreases in Campylobacter species after azithromycin treatment, generating the hypothesis that a decrease in Campylobacter may contribute to observations of reduction in mortality following azithromycin distribution.

Prevalence of Electrocardiogram Abnormalities in Human Immunodeficiency Virus-Infected Children

HIV is an important cause of childhood morbidity and mortality affecting more than 1.3 million children worldwide, one of the morbidity is cardiac abnormalities. Cardiovascular abnormalities are still subclinical during childhood then become symtomatic in adulthood. Electrocardiography is effective to detect cardiac diseases. This study aimed to assess ECG changes in HIV infected children and describe ECG abnormalities in HIV-infected children with or without HAART. From 70 subjects, we found the most common abnormality was sinus tachycardia in 17 patients (24.3%), sinus bradycardia 1 patient (1.4%) and 2 patients with sinus arrhythmia (2.9%). The mean QTc interval was 0.42 seconds (±0.07) and 14 patients (20%) had prolongation. The mean PR interval was 0.12 seconds (±0.02), 11 patients (15.7%) experienced prolongation of PR interval. The mean QRS duration was 0.06 seconds (±0.09). Left ventricular enlargement was present in 6 patients (8.6%), conduction disturbance which is characterized by Bundle branch block was found in 2 patients (2.9%) and ST changes was seen in 2 patients (2.9%). Other ECG abnormalities are characterized by right ventricle hyperthropy in 4 patients and a patient had T tall. The prevalence of cardiac abnormalities based on ECG examination from this study was 51.3%, consist of heart rhythm abnormality, prolonged PR interval, prolonged QTc interval, bundle branch block, ventricle hypertrophy and ST changes.

Abdominal blunt trauma in children: experience from a single center

Background: Abdominal blunt trauma (ABT) remains an important cause of childhood morbidity and sometimes, mortality. Recently the approach for management of ABT has tilted towards conservative one with excellent results. In this study, we present our experience of ABT from a teaching hospital.Methods: All patients below 17 years with ABT between December 2012 and May 2016 were studied retrospectively and methods and results analyzed.Results: A total of 33 patients presented with ABT, mainly due to fall from height or road-traffic accidents. Age ranged from 3 to17 years. Of the 33 patients, 30 patients had solid organ injuries and only 3 patients had isolated hollow viscus injuries. Operative intervention was needed in 6 (18.2%) patients, of whom three needed upfront surgery. They had had hollow viscus injury. Others who developed signs and symptoms of other injuries included duodenal injury, ureteric transection and delayed adhesive intestinal obstruction following bile leak, one each. Average hospital stay of patients with solid organ injury was 5.4±1.6 days while for those with hollow viscus injury requiring operative intervention, this was 12.3±2.4 days. There was no mortality.Conclusions: ABT is a frequent emergency in children in the developing world. Prompt initial management significantly affects the eventual outcome. Imaging studies are the cornerstone of diagnosing the type and extent of injury. Most patients can be managed conservatively. However, constant masterly vigilance is needed to pick up the evolving signs, thereby avoiding possible complications and morbidity.

Application of a nucleic acid-based multiplex kit to identify viral and atypical bacterial aetiology of lower respiratory tract infection in hospitalized children.

Lower respiratory tract infections (LRTIs), particularly those acquired in hospitals, are an important cause of childhood morbidity and mortality. Understanding the aetiology and epidemiology of LRTIs is necessary for clinical management, reduction of antibiotic usage, vaccine development and prevention of nosocomial infection. In this study, we aimed to detect 13 viruses and atypical bacteria in nasopharyngeal secretion specimens from hospitalized children with LRTIs. From January 2014 to December 2016, nasopharyngeal secretion specimens were prospectively collected from 3232 children aged between 1 and 72 months. Nucleic acid was extracted and analysed using the SureX13 respiratory pathogen multiplex kit as per the manufacturer's instructions. A total of 2874 (88.9 %) children tested positive for viral and/or atypical bacterial infections, and 965 (29.9 %) were co-infected with multiple pathogens. The most frequently detected respiratory tract pathogens (RTPs) were rhinovirus, respiratory syncytial virus, parainfluenza virus and adenoviruses. The rates of RTP and co-infection positivity in the toddler group were significantly higher than those in the infant and preschool groups. The SureX13 respiratory pathogen multiplex kit has the ability to effectively detect a range of RTPs in hospitalized paediatric patients with LRTIs.

Determining the pneumococcal conjugate vaccine coverage required for indirect protection within Asia and the Pacific: a prospective observational study

Abstract Background Pneumococcal disease is an important cause of childhood morbidity and mortality worldwide. Evidence is required to support the introduction of pneumococcal conjugate vaccines (PCVs) in low-income and middle-income countries (LMICs). PCVs prevent disease through both direct protection of vaccinated individuals, and indirect protection of unvaccinated people via reduction of nasopharyngeal carriage and transmission of vaccine-type (VT) pneumococci. We aimed to determine the degree of this indirect effect after introduction of 13-valent PCV (PCV13) at three sites in Asia-Pacific, and describe the relationship between PCV coverage and indirect protection. Methods We are recruiting and swabbing children aged 2–59 months, admitted to participating hospitals with acute respiratory tract infections in Laos, Mongolia, and Papua New Guinea. Pneumococci are detected using lytA qPCR and serotyped by microarray. We are comparing risk of VT carriage in undervaccinated cases by village/subdistrict-level PCV13 coverage in children younger than 5 years. Individual PCV status is determined using written records and village PCV coverage is determined by administrative data or survey. Recruitment is due to finish in March, 2019. Findings As of June, 2018, we have recruited 1208, 1056, and 897 cases, and tested 1099, 624, and 405 samples, from Laos, Mongolia, and Papua New Guinea, respectively. Overall, pneumococcal carriage varied from 37% in Laos to 88% in Papua New Guinea. In Laos, VT carriage decreased from 18% to 6% from the first to the third year post-PCV. In Papua New Guinea, VT carriage decreased from 54% to 37% from the first to the third year after PCV introduction. In Mongolia, VT carriage decreased from 31% pre-PCV to 24% in the first year after PCV. Undervaccinated children from villages with less than 50% coverage are 1·08 (95% CI 0·69–1·79) and 1·44 (95% CI 0·99–2·10) times more likely to be carrying VT than those from villages with 50% or more coverage, among the 336 in Laos and 83 children in Papua New Guinea, respectively, for whom we have both PCV and carriage data. This difference does not reach statistical significance. Interpretation In the absence of feasible methods for pneumococcal disease surveillance in LMICs, studies of nasopharyngeal carriage of VT pneumococci, which is a prerequisite for disease, provide useful information to guide vaccine policy. The inclusion of three sites, which have contrasting vaccine schedules and pneumococcal epidemiology, enable us to explore factors that could maximise indirect protection from PCVs. Funding Bill & Melinda Gates Foundation, Gavi the Vaccine Alliance.

Childhood tuberculosis in a South-East Nigerian tertiary hospital: Treatment outcomes and determinants

Abstract Background and Objectives: Tuberculosis (TB) is an important cause of childhood morbidity and mortality. Understanding the barriers to successful childhood TB treatment is vital to curbing the scourge of childhood TB. This study examined the outcomes and factors that influence the outcomes of childhood TB treatment in a South-East Nigerian tertiary hospital. Methods: A 10-year review of the medical records of under-15 year olds, who received anti-TB treatment at Nnamdi Azikiwe University Teaching Hospital, Nnewi, was carried out. Data were analyzed using SPSS version 20. Results: Majority of the 501 childhood TB cases were new (89.6%) and pulmonary (73.3%) TB cases. TB-HIV coinfection occurred in 42.5% of cases. The rate of successful treatment was 62.9%. About 57.5% completed treatment, 5.4% were cured, 7.0% were transferred out, 21.4% were lost to follow-up, 0.4% had treatment failure while 8.4% died. Majority (61.6%) of deaths or loss to follow-up occurred during the first 2 months of treatment. Factors significantly associated with treatment outcomes were ascertainment of HIV status (P = 0.049), disease site (P = 0.013), nutritional status (P = 0.039), Mantoux test result (P = 0.002), and period of treatment (P = 0.005). Conclusion: Findings indicate high rate of unsuccessful childhood TB treatment outcomes. Efforts should be intensified to ensure improved outcomes through proactive search for childhood TB cases, early diagnosis and treatment, as well as adherence to and completion of treatment. Special attention should be given to high-risk groups including those with unknown HIV status, extrapulmonary TB, and severe malnutrition. It is imperative to determine the HIV status of all childhood TB cases.

Prevalence and risk factors of under nutrition among under three children in an urban community in Ludhiana city

Background: Under nutrition is important cause of childhood morbidity and mortality. In India burden of underweight children in under 5 years of age is still 35.7% (NFHS-4) and is 22% in Punjab which is still considered to be a major public health problem. Thus this study was planned to find prevalence and risk factors of under nutrition in under 3 children in urban Ludhiana.Methods: It is community based cross-sectional study conducted in under 3 year children in field practice area of Urban Health Centre under Department of Community Medicine, Dayanand Medical College, Ludhiana. Minimum sample size of 368 was calculated. Data was collected from routine surveillance by ANMs in their visits to area. Under nutrition was taken as weight for age as per standard growth chart used in India (WHO based). Statistical analysis: Microsoft Excel, Chi square test, SPSS.Results: Out of 387 children, 82 (21.2%) were underweight [17 (4.4%) severely and 65 (16.8%) moderately underweight]. Increasing age, partial immunization, low birth weight and high birth order were significantly associated, while gender, type of family, SES, mother’s BMI &amp; literacy and exclusive breast feeding were not significantly associated with prevalence of underweight.Conclusions: Increasing age, partial immunization, low birth weight and high birth order were all significantly associated with underweight. Maternal and child health services need to be strengthened.

Clinical Features and Outcome of Children with Severe Lower Respiratory Tract Infection Admitted to a Pediatric Intensive Care Unit in South Africa.

Severe acute lower respiratory tract infection (ALRTI) remains an important cause of childhood morbidity and mortality. This is a 12-month retrospective cohort study of children (0-12 years) admitted to a pediatric intensive care unit (PICU) with ALRTI to investigate risk factors, clinical course and in-hospital survival. In total, 265 patients (median age = 4 months [2-12 months]) were identified. In all,102 (38.5%) had co-morbid disease. Twenty-seven (10.2%) were HIV-infected and 87 (32.8%) were HIV-exposed. In-hospital mortality was 34 (12.8%)-24 (9.1%) in PICU and 10 in the wards. Median duration of intensive care unit was 4.0 days (2.0-8.0) and hospital stay was 12.5 days (7.9-28.0). In total, 192 (72.5%) children required invasive ventilation and 42 (15.8%) required inotropic support. Risk factors for mortality included severe malnutrition (odds ratio [OR] = 8.25; 95% confidence interval [CI] = 1.47-46.21), informal housing (OR = 11.87; CI = 1.89-20.81) or inotropic support (OR = 44.35; CI = 8.20-239.92). HIV exposure or infection was associated with a longer duration of hospital stay (OR = 4.41; CI = 2.44-6.39). Severe ALRTI is associated with a high mortality with several factors impacting on in-hospital survival.

The aetiologies of central nervous system infections in hospitalised Cambodian children

BackgroundCentral nervous system (CNS) infections are an important cause of childhood morbidity and mortality. The aetiologies of these potentially vaccine-preventable infections have not been well established in Cambodia.MethodsWe did a one year prospective study of children hospitalised with suspected CNS infection at Angkor Hospital for Children, Siem Reap. Cerebrospinal fluid specimens (CSF) samples underwent culture, multiplex PCR and serological analysis to identify a range of bacterial and viral pathogens. Viral metagenomics was performed on a subset of pathogen negative specimens.ResultsBetween 1st October 2014 and 30th September 2015, 284 analysable patients were enrolled. The median patient age was 2.6 years; 62.0% were aged <5 years. CSF white blood cell count was ≥10 cells/μL in 116/272 (42.6%) cases. CNS infection was microbiologically confirmed in 55 children (19.3%). Enteroviruses (21/55), Japanese encephalitis virus (17/55), and Streptococcus pneumoniae (7/55) accounted for 45 (81.8%) of all pathogens identified. Of the pathogens detected, 74.5% (41/55) were viruses and 23.6% (13/55) were bacteria. The majority of patients were treated with ceftriaxone empirically. The case fatality rate was 2.5%.ConclusionsEnteroviruses, JEV and S. pneumoniae are the most frequently detected causes of CNS infection in hospitalised Cambodian children.