Role of respiratory viruses in childhood mortality.

Respiratory viruses have been identified at necropsy in the lungs of 13 out of 24 children who died with observed acute respiratory illness. The histological appearances of the lungs supported the association between virus and death in each of these 13 children and suggested an unidentified virus aetiology in a further five cases. Histological appearances compatible with bacterial infection were found in the lungs of only two of the 24 children. Similar virus and histological findings have been reported in about one-third of victims of the sudden infant death syndrome (cot deaths), indicating a rapid unobserved respiratory virus infection as the most likely mode of death in this group. Evidence that respiratory viruses may be involved in a larger proportion of sudden unexpected deaths, perhaps as antigens in a hypersensitivity reaction, is discussed. Respiratory viruses seem the major identifiable agents contributing to the maintenance of the postneonatal mortality rate since acute respiratory illness and the sudden infant death syndrome together account for about two-thirds of deaths at this age.     

Influenza and Other Respiratory Viruses Detected by Influenza-Like Illness Surveillance in Leyte Island,the Philippines, 2010–2013

This study aimed to determine the role of influenza-like illness (ILI) surveillance conducted on Leyte Island, the Philippines, including involvement of other respiratory viruses, from 2010 to 2013. ILI surveillance was conducted from January 2010 to March 2013 with 3 sentinel sites located in Tacloban city, Palo and Tanauan of Leyte Island. ILI was defined as fever ≥38°C or feverish feeling and either cough or running nose in a patient of any age. Influenza virus and other 5 respiratory viruses were searched. A total of 5,550 ILI cases visited the 3 sites and specimens were collected from 2,031 (36.6%) cases. Among the cases sampled, 1,637 (75.6%) were children aged <5 years. 874 (43.0%) cases were positive for at least one of the respiratory viruses tested. Influenza virus and respiratory syncytial virus (RSV) were predominantly detected (both were 25.7%) followed by human rhinovirus (HRV) (17.5%). The age distributions were significantly different between those who were positive for influenza, HRV, and RSV. ILI cases were reported throughout the year and influenza virus was co-detected with those viruses on approximately half of the weeks of study period (RSV in 60.5% and HRV 47.4%). In terms of clinical manifestations, only the rates of headache and sore throat were significantly higher in influenza positive cases than cases positive to other viruses. In conclusion, syndromic ILI surveillance in this area is difficult to detect the start of influenza epidemic without laboratory confirmation which requires huge resources. Age was an important factor that affected positive rates of influenza and other respiratory viruses. Involvement of older age children may be useful to detect influenza more effectively.     

Family and community factors associated with infant deaths that might be preventable.

A detailed psychosocial study was made of all deaths in babies aged between 8 days and 2 years in Sheffield over two years. An identical assessment was made of a group of control children matched for age. Sixty five children who died and 102 controls were studied. Each index and control child was assessed for 13 potentially adverse social and family factors. The deaths were classified into causal groups. The families of children who died during the course of potentially treatable diseases (those with infections and those who presented as cot deaths but had treatable infection) had a significantly greater number of adverse social factors than the families of children who died from conditions with a poor prognosis, children who presented as completely unexplained cot deaths, and controls. The adverse factors studied, although often related to economic state, appeared to be independent of social class.     

Pertussis immunisation and serious acute neurological illnesses in children.

OBJECTIVE--To determine long term outcome in children who had a severe acute neurological illness in early childhood associated with pertussis immunisation. DESIGN--Follow up study of cases and matched controls. SETTING--Assessment of children at home and at school throughout Britain. SUBJECTS--Children recruited into the national childhood encephalopathy study in 1976-9 were followed up, with one of their two original matched controls, in 1986-9. MAIN OUTCOME MEASURES--Performance in educational attainment tests; behaviour problems reported by teachers and parents; continuing convulsions; evidence of other neurological or physical dysfunction. RESULTS--Over 80% of cases and controls were traced. Case children were significantly more likely than controls to have died or to have some form of educational, behavioural, neurological, or physical dysfunction a decade after their illness. The prevalence of one or more of these adverse outcomes in case children who had been immunised with diphtheria, tetanus, and pertussis vaccine within seven days before onset of their original illness was similar to that in case children who had not been immunised recently. The relative risk for recent diphtheria, tetanus, and pertussis immunisation in children who had died or had any dysfunction in comparison with controls was 5.5 (95% confidence interval 1.6 to 23.7). However, the number of cases associated with vaccine (12) was extremely small and statistically vulnerable, and other possible agents or predisposing factors could not be excluded. CONCLUSIONS--Diphtheria, tetanus, and pertussis vaccine may on rare occasions be associated with the development of severe acute neurological illnesses that can have serious sequelae. Some cases may occur by chance or have other causes. The role of pertussis vaccine as a prime or concomitant factor in the aetiology of these illnesses cannot be determined in any individual case. The balance of possible risk against known benefits from pertussis immunisation supports continued use of the vaccine.     

Sudden and Unexpected Deaths in Infants: Histology and Virology

The histological appearance of lungs of children whose death had been sudden and unexpected has been studied in relation with the viruses found at necropsy. Fifty-one children were investigated and in 33 the lungs had the histological appearance widely accepted as characteristic of the condition previously termed “cot death.” Sixteen had the histological appearance of lymphocytic bronchiolitis, and it was from this group only that viruses were isolated. The viruses isolated were those associated with respiratory infections. Two patients showed the histological appearance of bacterial bronchopneumonia. Viruses are probably responsible for a substantial proportion of unexpected sudden deaths in infancy.     

Severity of respiratory signs and symptoms and virus profiles in Japanese children with acute respiratory illness

Associations between the severity of respiratory signs and symptoms and the respiratory viruses identified in 214 Japanese children with acute respiratory illness (ARI) enrolled between January and December 2012 were studied. Respiratory rate, wheezing, cyanosis, and the use of accessory muscles were used as indices of respiratory severity and phylogenetic analysis of the viruses identified in these children was performed. Respiratory viruses such as respiratory syncytial virus (RSV), human rhinovirus (HRV), human parainfluenza virus (HPIV), and human metapneumovirus (HMPV) were prevalent, being detected in approximately 70% of the patients (151/214 patients). Co‐detection of viruses occurred in about 9% of patients. RSV was identified more frequently in cases scored as moderate/severe than in those scored as mild (P < 0.05). Severity scores of patients with RSV were significantly higher than those of cases with HPIV. Moreover, severity scores in patients with mild disease and co‐detections were higher than in those in whom only HPIV or adenovirus was detected. Phylogenetic analysis showed that many genotypes of HRV‐A and ‐C with wide genetic divergence were associated with acute respiratory illness (ARI). On the other hand, only a limited number of genotypes of RSV were associated with ARI. HPIV and HMPV were associated with ARI at similar frequencies. These results suggest that different respiratory viruses with unique genetic characteristics can be found in patients with mild to severe ARI.     

Association of Respiratory Viruses with Outcomes of Severe Childhood Pneumonia in Botswana

BackgroundThe highest incidence of childhood acute lower respiratory tract infection (ALRI) is in low- and middle-income countries. Few studies examined whether detection of respiratory viruses predicts ALRI outcomes in these settings.MethodsWe conducted prospective cohort and case-control studies of children 1-23 months of age in Botswana. Cases met clinical criteria for pneumonia and were recruited within six hours of presentation to a referral hospital. Controls were children without pneumonia matched to cases by primary care clinic and date of enrollment. Nasopharyngeal specimens were tested for respiratory viruses using polymerase chain reaction. We compared detection rates of specific viruses in matched case-control pairs. We examined the effect of respiratory syncytial virus (RSV) and other respiratory viruses on pneumonia outcomes.ResultsBetween April 2012 and August 2014, we enrolled 310 cases, of which 133 had matched controls. Median ages of cases and controls were 6.1 and 6.4 months, respectively. One or more viruses were detected from 75% of cases and 34% of controls. RSV and human metapneumovirus were more frequent among cases than controls, but only enterovirus/rhinovirus was detected from asymptomatic controls. Compared with non-RSV viruses, RSV was associated with an increased risk of treatment failure at 48 hours [risk ratio (RR): 1.85; 95% confidence interval (CI): 1.20, 2.84], more days of respiratory support [mean difference (MD): 1.26 days; 95% CI: 0.30, 2.22 days], and longer duration of hospitalization [MD: 1.35 days; 95% CI: 0.20, 2.50 days], but lower in-hospital mortality [RR: 0.09; 95% CI: 0.01, 0.80] in children with pneumonia.ConclusionsRespiratory viruses were detected from most children hospitalized with ALRI in Botswana, but only RSV and human metapneumovirus were more frequent than among children without ALRI. Detection of RSV from children with ALRI predicted a protracted illness course but lower mortality compared with non-RSV viruses.     

Terminal symptoms in children dying suddenly and unexpectedly at home. Preliminary report of the DHSS multicentre study of postneonatal mortality.

Terminal symptoms in 145 children who died suddenly and unexpectedly at home were investigated and compared with symptoms in 154 control children. Eighty-five (59%) of the children who died had had terminal symptoms, which in 69 cases (48%) appeared to have been major. Non-specific symptoms were especially common among the children who died. Symptoms were often present for several days before death. Only 12 of the 69 children who died with major symptoms had been seen by a doctor within 24 hours before death. We conclude that many deaths in young children might be prevented if doctors and parents were more aware of the importance of non-specific symptoms as markers of life-threatening illness.     

Giant-cell pneumonia caused by measles and methotrexate in childhood leukaemia in remission.

Four children who had acurate lymphoblastic leukaemia in remission and developed pneumonia were studied. Investigations including electron microscopy and immunofluorescence of lung biopsy material disclosed measles, although there was no clinical evidence of the disease. Despite an identical presentation, two types of illness developed: two children died of giant-cell pneumonia, while the other two developed pneumonia indistinguishable from that associated with methotrexate treatment, recovering when treated with steroids and gammaglobulin. Measles infection is easily overlooked in the absence of rash. The diagnosis may be suggested by clinical and radiological features and confirmed by specific immunofluorescence staining of lung biopsy tissue.     

Investigation of a potential zoonotic transmission of orthoreovirus associated with acute influenza-like illness in an adult patient

Bats are increasingly being recognized as important reservoir hosts for a large number of viruses, some of them can be highly virulent when they infect human and livestock animals. Among the new bat zoonotic viruses discovered in recent years, several reoviruses (respiratory enteric orphan viruses) were found to be able to cause acute respiratory infections in humans, which included Melaka and Kampar viruses discovered in Malaysia, all of them belong to the genus Orthoreovirus, family Reoviridae. In this report, we describe the isolation of a highly related virus from an adult patient who suffered acute respiratory illness in Malaysia. Although there was no direct evidence of bat origin, epidemiological study indicated the potential exposure of the patient to bats before the onset of disease. The current study further demonstrates that spillover events of different strains of related orthoreoviruses from bats to humans are occurring on a regular basis, which calls for more intensive and systematic surveillances to fully assess the true public health impact of these newly discovered bat-borne zoonotic reoviruses.     

Surveillance for Hospitalized Acute Respiratory Infection in Guatemala

Acute respiratory infections (ARI) are an important cause of illness and death worldwide, yet data on the etiology of ARI and the population-level burden in developing countries are limited. Surveillance for ARI was conducted at two hospitals in Guatemala. Patients admitted with at least one sign of acute infection and one sign or symptom of respiratory illness met the criteria for a case of hospitalized ARI. Nasopharyngeal/oropharyngeal swabs were collected and tested by polymerase chain reaction for adenovirus, parainfluenza virus types 1,2 and 3, respiratory syncytial virus, influenza A and B viruses, human metapneumovirus, Chlamydia pneumioniae, and Mycoplasma pneumoniae. Urine specimens were tested for Streptococcus pneumoniae antigen. Blood culture and chest radiograph were done at the discretion of the treating physician. Between November 2007 and December 2011, 3,964 case-patients were enrolled. While cases occurred among all age groups, 2,396 (60.4%) cases occurred in children <5 years old and 463 (11.7%) among adults ≥65 years old. Viruses were found in 52.6% of all case-patients and 71.8% of those aged <1 year old; the most frequently detected was respiratory syncytial virus, affecting 26.4% of case-patients. Urine antigen testing for Streptococcus pneumoniae performed for case-patients ≥15 years old was positive in 15.1% of those tested. Among 2,364 (59.6%) of case-patients with a radiograph, 907 (40.0%) had findings suggestive of bacterial pneumonia. Overall, 230 (5.9%) case-patients died during the hospitalization. Using population denominators, the observed hospitalized ARI incidence was 128 cases per 100,000, with the highest rates seen among children <1 year old (1,703 per 100,000), followed by adults ≥65 years old (292 per 100,000). These data, which demonstrate a substantial burden of hospitalized ARI in Guatemala due to a variety of pathogens, can help guide public health policies aimed at reducing the burden of illness and death due to respiratory infections.     

Effects of Obstruction to Respiration in Infants,with Particular Reference to Mattresses,Pillows, and their Coverings

A comparison was made of pillows of various designs and their effects on the flow of air through the respiratory tract of six children who had been found dead in their cots. The effects of alterations in posture and of soaking the pillow with milk were also studied.There was a wide variation in the obstruction to air flow in pillows of different design. A firm pillow which allows air and fluid to pass through it is best, and is probably superior to a mattress covered with a mackintosh and a sheet.External obstruction to respiration could be a contributory factor in some cases of cot death.     

Studies of respiratory disease in random-source laboratory dogs: viral infections in unconditioned dogs.

A prospective study was conducted to identify the viruses causing respiratory diseases in unconditioned, random-source dogs. During the quarantine period, respiratory disease occurred in 86 of 167 (52%) dogs, and 34 (21%) died. Most affected dogs had a distemper-like illness which required extensive and prolonged care. Histopathologic studies confirmed the diagnosis of canine distemper in 10 of 12 (83%) fatal infections examined. Sixty-seven of 91 (74%) dogs which arrived without canine distemper antibody became ill, and 30 (32%) died. In contrast, only 16 of 67 (24%) dogs with canine distemper antibody had respiratory disease, and only 3 (4%) died. Parainfluenza SV5 and canine adenovirus--type II were recovered from 27 of 54 and 22 of 54 sick dogs, respectively. Canine herpesviruses, canine coronaviruses, and canine parvoviruses were less frequently isolated. Increased antibody titers to SV5 were found consistently, and rises in titer to the other viruses were demonstrated. Many of the sick dogs were infected with two or more viruses. Although several viral agents were detected during these epizootics, prevention of canine distemper appeared to be the key to controlling severe, prolonged, and often fatal respiratory disease.     

Obesity and Respiratory Infection in Infants and Young Children

A controlled trial has been carried out to test the widely held “clinical impression” that overweight infants have a greater liability to respiratory infections than those of normal weight. Two matched groups of children aged between 3 months and 2 years were studied, containing children whose weight was above the 90th percentile, or was between the 25th and 75th percentiles, at the start of the trial.Data from 120 children of the overweight group were available for analysis, of whom 47 experienced at least one respiratory infection during the trial and 73 did not. Of children remaining over the 90th percentile at the end of the trial 19 had suffered respiratory infections and 28 had not. One baby in the overweight group suffered a “cot death” from acute bronchiolitis. In the control group, 103 cases were analysed—23 had suffered a respiratory infection and 80 had remained free of respiratory infection throughout the trial. These figures are statistically significant and suggest that obesity in infants and young children is associated with an increased incidence of acute respiratory infections.     

Prevalence of Herpes and Respiratory Viruses in Induced Sputum among Hospitalized Children with Non Typical Bacterial Community-Acquired Pneumonia

Objective

Few comprehensive studies have searched for viruses in infants and young children with community-acquired pneumonia (CAP) in China. The aim of this study was to investigate the roles of human herpes viruses (HHVs) and other respiratory viruses in CAP not caused by typical bacterial infection and to determine their prevalence and clinical significance.

Methods

Induced sputum (IS) samples were collected from 354 hospitalised patients (infants, n = 205; children, n = 149) with respiratory illness (CAP or non-CAP) admitted to Wenling Hospital of China. We tested for HHVs and respiratory viruses using PCR-based assays. The epidemiological profiles were also analysed.

Results

High rate of virus detection (more than 98%) and co-infection (more than 80%) were found among IS samples from 354 hospitalised infants and children with respiratory illness in this study. Of 273 CAP samples tested, CMV (91.6%), HHV-6 (50.9%), RSV (37.4%), EBV (35.5%), HBoV (28.2%), HHV-7 (18.3%) and rhinovirus (17.2%) were the most commonly detected viruses. Of 81 non- CAP samples tested, CMV (63%), RSV (49.4%), HHV-6 (42%), EBV (24.7%), HHV-7 (13.6%) and HBoV (8.6%) were the dominant viruses detected. The prevalence of several viral agents (rhinovirus, bocavirus, adenovirus and CMV) among IS samples of CAP were significantly higher than that of non-CAP control group. We also found the prevalence of RSV coinfection with HHVs was also higher among CAP group than that of non-CAP control.

Conclusions

With sensitive molecular detection techniques and IS samples, high rates of viral identification were achieved in infants and young children with respiratory illness in a rural area of China. The clinical significance of rhinovirus, bocavirus, adenovirus and HHV (especially CMV) infections should receive greater attention in future treatment and prevention studies of CAP in infants and children.     

Respiratory Viruses Associated Hospitalization among Children Aged <5 Years in Bangladesh: 2010-2014

Background

We combined hospital-based surveillance and health utilization survey data to estimate the incidence of respiratory viral infections associated hospitalization among children aged < 5 years in Bangladesh.

Methods

Surveillance physicians collected respiratory specimens from children aged <5 years hospitalized with respiratory illness and residing in the primary hospital catchment areas. We tested respiratory specimens for respiratory syncytial virus, parainfluenza viruses, human metapneumovirus, influenza, adenovirus and rhinoviruses using rRT-PCR. During 2013, we conducted a health utilization survey in the primary catchment areas of the hospitals to determine the proportion of all hospitalizations for respiratory illness among children aged <5 years at the surveillance hospitals during the preceding 12 months. We estimated the respiratory virus-specific incidence of hospitalization by dividing the estimated number of hospitalized children with a laboratory confirmed infection with a respiratory virus by the population aged <5 years of the catchment areas and adjusted for the proportion of children who were hospitalized at the surveillance hospitals.

Results

We estimated that the annual incidence per 1000 children (95% CI) of all cause associated respiratory hospitalization was 11.5 (10–12). The incidences per 1000 children (95% CI) per year for respiratory syncytial virus, parainfluenza, adenovirus, human metapneumovirus and influenza infections were 3(2–3), 0.5(0.4–0.8), 0.4 (0.3–0.6), 0.4 (0.3–0.6), and 0.4 (0.3–0.6) respectively. The incidences per 1000 children (95%CI) of rhinovirus-associated infections among hospitalized children were 5 (3–7), 2 (1–3), 1 (0.6–2), and 3 (2–4) in 2010, 2011, 2012 and 2013, respectively.

Conclusion

Our data suggest that respiratory viruses are associated with a substantial burden of hospitalization in children aged <5 years in Bangladesh.     

The Clinical and Etiological Characteristics of Influenza-Like Illness (ILI) in Outpatients in Shanghai,China, 2011 to 2013

Introduction

Clinical and etiological characteristics of influenza-like illness (ILI) in outpatients is poorly understood in the southern temperate region of China. We conducted laboratory-based surveillance of viral etiology for ILI outpatients in Shanghai from January 2011 to December 2013.

Materials and Methods

Clinical and epidemiological data from ILI outpatients, both children and adults, were collected. A total of 1970 nasopharyngeal swabs were collected and tested for 12 respiratory viruses using multiplex RT-PCR, and the data were analyzed anonymously.

Results

All 12 respiratory viruses were detected in the specimens. At least one virus was detected in 32.4% of 1970 specimens analyzed, with 1.1% showing co-infections. The most frequently detected agents were influenza A (11.7%), influenza B (9.6%), and rhinoviruses (3.1%).Other viruses were present at a frequency less than 3.0%. We observed a winter peak in the detection rate in ILI patients during 3 years of surveillance and a summer peak in 2012. HCoV, HADV, and HMPV were detected more frequently in children than in adults. Patients infected with influenza virus experienced higher temperatures, more coughs, running noses, headaches and fatigue than patients infected with other viruses and virus-free patients (p<0.001).

Conclusions

The spectrum, seasonality, age distribution and clinical associations of respiratory virus infections in children and adults with influenza-like illness were analyzed in this study for the first time. To a certain extent, the findings can provide baseline data for evaluating the burden of respiratory virus infection in children and adults in Shanghai. It will also provide clinicians with helpful information about the etiological patterns of outpatients presenting with complaints of acute respiratory syndrome, but further studies should be conducted, and longer-term laboratory-based surveillance would give a better picture of the etiology of ILI.     

Multiplex PCR analysis of clusters of unexplained viral respiratory tract infection in Cambodia

Background

Fevers of unknown origin constitute a substantial disease burden in Southeast Asia. In majority of the cases, the cause of acute febrile illness is not identified.

Methods

We used MassTag PCR, a multiplex assay platform, to test for the presence of 15 viral respiratory agents from 85 patients with unexplained respiratory illness representing six disease clusters that occurred in Cambodia between 2009 and 2012.

Results

We detected a virus in 37 (44%) of the cases. Human rhinovirus, the virus detected most frequently, was found in both children and adults. The viruses most frequently detected in children and adults, respectively, were respiratory syncytial virus and enterovirus 68. Sequence analysis indicated that two distinct clades of enterovirus 68 were circulating during this time period.

Conclusions

This is the first report of enterovirus 68 in Cambodia and contributes to the appreciation of this virus as an important respiratory pathogen.

     

Etiological structure of acute respiratory viral infections in children hospitalized in 1981-1999

The role of influenza and parainfluenza viruses, respiratory syncytial viruses and adenoviruses in the etiological structure of morbidity in acute respiratory virus infections (ARVI) in children hospitalized during the 19 year period is analyzed. As the result of examination of 56,287 patients by direct immunofluorescent test, respiratory viruses were detected in 21% of cases. The seasonal character, periodicity and level of ARVI morbidity were established. According to medical records, in the 1990s ARVI took a more severe course in children than that observed in the 1980s. In addition, the data on morbidity among children regarding rotavirus infection and ARVI were found to be similar.