Acute Lower Respiratory Tract Illness Research Articles

Adjuvanted Vaccine to Prevent Respiratory Syncytial Virus in Adults Ages 60 Years and Older

Respiratory syncytial virus (RSV) is a prevalent cause of acute lower respiratory tract illness that disproportionately affects older adults, young children, and infants, which can lead to hospitalizations and death. The health impact on the elderly and infants accentuates the need for effective preventive strategies. Arexvy is the first approved vaccine to prevent lower respiratory tract illness caused by RSV in older adults ages 60 and older. It contains recombinant respiratory syncytial virus glycoprotein F stabilized in the prefusion conformation. Arexvy offers approximately 83% protection in adults and appears to maintain effectiveness for up to two RSV seasons. The vaccine was generally well tolerated in clinical trials, with the most frequently observed and reported adverse events being mild to moderate injection site pain, fatigue, myalgia, headache, and arthralgia. This article includes a description of Arexvy, the target population, contraindications, side effects, and clinical implications when considering the use of this vaccine.

Frequency and Risk of Emergency Medical Service Interhospital Transportation of Patients With Acute Lower Respiratory Tract Illness During the COVID-19 Pandemic in the US

This study compares the frequency of hospital-to-hospital transportation events and associated life-threatening deterioration during transport among patients with acute lower respiratory tract illness during vs before the COVID-19 pandemic.

Novel HLA-B7-restricted human metapneumovirus epitopes enhance viral clearance in mice and are recognized by human CD8+ T cells

Human metapneumovirus (HMPV) is a leading cause of acute lower respiratory tract illness in children and adults. Repeated infections are common and can be severe in young, elderly, and immunocompromised persons due to short-lived protective humoral immunity. In turn, few protective T cell epitopes have been identified in humans. Thus, we infected transgenic mice expressing the common human HLA MHC-I allele B*07:02 (HLA-B7) with HMPV and screened a robust library of overlapping and computationally predicted HLA-B7 binding peptides. Six HLA-B7-restricted CD8+ T cell epitopes were identified using ELISPOT screening in the F, M, and N proteins, with M195–203 (M195) eliciting the strongest responses. MHC-tetramer flow cytometric staining confirmed HLA-B7 epitope-specific CD8+ T cells migrated to lungs and spleen of HMPV-immune mice. Immunization with pooled HLA-B7-restricted peptides reduced viral titer and protected mice from virulent infection. Finally, we confirmed that CD8+ T cells from HLA-B7 positive humans also recognize the identified epitopes. These results enable identification of HMPV-specific CD8+ T cells in humans and help to inform future HMPV vaccine design.

Community Mortality Due to Respiratory Syncytial Virus in Argentina: Population-based Surveillance Study.

BackgroundMany deaths in infants from low-middle income countries (LMICs) occur at home or upon arrival to health facilities. Although acute lower respiratory tract illness plays an important role in community mortality, the accuracy of mortality rates due to respiratory syncytial virus (RSV) remains unknown.MethodsAn active surveillance study among children aged under 5 years old (U5) was performed in Buenos Aires, Argentina, between January and December 2019, to define the burden and role of RSV in childhood community mortality.ResultsA total of 63 families of children U5 participated in the study. Based on a combined approach of tissue sampling, verbal autopsies, and expert’s analysis, RSV infection was found in the causal chain of 11 from 12 cases with positive molecular biology results in respiratory samples. The estimated mortality rate due to RSV among infants was 0.27 deaths/1000 live births. The mean age of RSV-related household deaths was 2.8 months of age (standard deviation [SD] 1.7), and 8/12 were male infants (66.7%). Dying at home from RSV was associated with Streptococcus pneumoniae and/or Moraxella catarrhalis lung coinfection (75%), living in slums and settlement (odds ratio [OR], 17.09; 95% confidence interval [CI], 1.3–219.2), and other underlying comorbidities (OR, 14.87; 95% CI, 1.3–164.6).ConclusionsInfant community mortality rates due to RSV are higher than those reported in industrialized countries and similar to those reported in hospital-based studies in the same catchment population.

Integrating epidemiological and genetic data with different sampling intensities into a dynamic model of respiratory syncytial virus transmission

Respiratory syncytial virus (RSV) is responsible for a significant burden of severe acute lower respiratory tract illness in children under 5 years old; particularly infants. Prior to rolling out any vaccination program, identification of the source of infant infections could further guide vaccination strategies. We extended a dynamic model calibrated at the individual host level initially fit to social-temporal data on shedding patterns to include whole genome sequencing data available at a lower sampling intensity. The study population was 493 individuals (55 aged < 1 year) distributed across 47 households, observed through one RSV season in coastal Kenya. We found that 58/97 (60%) of RSV-A and 65/125 (52%) of RSV-B cases arose from infection probably occurring within the household. Nineteen (45%) infant infections appeared to be the result of infection by other household members, of which 13 (68%) were a result of transmission from a household co-occupant aged between 2 and 13 years. The applicability of genomic data in studies of transmission dynamics is highly context specific; influenced by the question, data collection protocols and pathogen under investigation. The results further highlight the importance of pre-school and school-aged children in RSV transmission, particularly the role they play in directly infecting the household infant. These age groups are a potential RSV vaccination target group.

Human parainfluenza virus surveillance in pediatric patients with lower respiratory tract infections: a special view of parainfluenza type 4

ObjectiveCharacterize the role of human parainfluenza virus and its clinical features in Brazilian children under 2 years of age presenting with acute lower respiratory tract infections. MethodsReal‐time assays were used to identify strains of human parainfluenza virus and other common respiratory viruses in nasopharyngeal aspirates. One thousand and two children presenting with acute lower respiratory tract illnesses were enrolled from February 2008 to August 2010. ResultsOne hundred and four (10.4%) patients were human parainfluenza virus positive, of whom 60 (57.7%) were positive for human parainfluenza virus‐3, 30 (28.8%) for human parainfluenza virus‐4, 12 (11.5%) for human parainfluenza virus‐1, and two (1.9%) for human parainfluenza virus‐2. Seven (6.7%) patients had more than one strain of human parainfluenza virus detected. The most frequent symptoms were tachypnea and cough, similar to other viral respiratory infections. Clinical manifestations did not differ significantly between human parainfluenza virus‐1, ‐2, ‐3, and ‐4 infections. Human parainfluenza virus‐1, ‐3, and ‐4 were present in the population studied throughout the three years of surveillance, with human parainfluenza virus‐3 being the predominant type identified in the first two years. ConclusionHuman parainfluenza viruses contribute substantially to pediatric acute respiratory illness (ARI) in Brazil, with nearly 30% of this contribution attributable to human parainfluenza virus‐4.

A Cross-sectional Surveillance Study of the Frequency and Etiology of Acute Respiratory Illness Among Pregnant Women.

Other than influenza, little is known about the consequences of viral acute respiratory illness (ARI) on pregnant women and fetuses. Our objectives were to determine the frequency of ARI due to respiratory viruses and the associated clinical outcomes during pregnancy. Pregnant women in their second or third trimester were enrolled if they reported having symptoms of ARI or were healthy within the preceding 2 weeks. Nasopharyngeal secretions were evaluated for respiratory viruses by molecular diagnostic assays. Clinical outcomes were evaluated at enrollment and via a follow-up telephone-based questionnaire 2 weeks later. There were 155 pregnant participants, with 81 ARI cases and 91 healthy controls. Acute lower respiratory tract illness (ALRTI) was identified in 29 cases (36%). Human rhinovirus (HRV), respiratory syncytial virus (RSV), and influenza virus accounted for 75% of virus-positive cases of ALRTI. Cases with ALRTI often reported a longer duration of illness, history of allergies, symptoms of wheezing, shortness of breath, or chest pain, and use of prescription medication. Two cases with ALRTI reported decreased fetal movement; a third case with ALRTI was hospitalized. In over one third of ARI cases, participants had symptoms consistent with ALRTI. Infection with HRV, RSV, or influenza virus was commonly detected in patients with ALRTI. Viral ALRTI during pregnancy appears to be common and is associated with significant morbidity.

Genetic variability human respiratory syncytial virus subgroups A and B in Turkey during six successive epidemic seasons, 2009-2015.

Human respiratory syncytial virus (HRSV) is most important viral respiratory pathogen of acute lower respiratory tract infections in infants and young children worldwide. The circulating pattern and genetic characteristics in the HRSV attachment glycoprotein gene were investigated in Turkey during six consecutive seasons from 2009 to 2015. HRSVA was dominant in the all epidemic seasons except 2011‐2012 season. Partial sequences of the HVR2 region of the G gene of 479 HRSVA and 135 HRSVB were obtained. Most Turkish strains belonged to NA1, ON1, and BA9, which were the predominant genotypes circulating worldwide. Although three novel genotypes, TR‐A, TR‐BA1, and TR‐BA2, were identified, they were not predominant. Clinical data were available for 69 HRSV‐positive patients who were monitored due to acute lower respiratory tract illness. There were no significant differences in the clinical diagnosis, hospitalization rates, laboratory findings and treatment observed between the HRSVA and HRSVB groups, and co‐infections in this study. The major population afflicted by HRSV infections included infants and children between 13 and 24 months of age. We detected that the CB1, GB5, and THB strains clustered in the same branch with a bootstrap value of 100%. CB‐B and BA12 strains clustered in the same branch with a bootstrap value of 65%. The BA11 genotype was clustered in the BA9 genotype in our study. The present study may contribute on the molecular epidemiology of HRSV in Turkey and provide data for HRSV strains circulating in local communities and other regions worldwide.

Why gone too soon? Examining social determinants of neonatal deaths in northwest Ethiopia using the three delay model approach

BackgroundWithout improving the survival of newborns, meaningful reduction in under-five mortality is difficult. Most neonatal deaths are preventable when appropriate and timely care is sought. In Ethiopia, there is lack of evidence on the type and contribution of delays in treatment seeking to neonatal deaths.MethodsA community based social autopsy (SA) of 39 neonatal deaths was conducted from March 16 to 24, 2016 in Dabat Health and Demographic Surveillance System (HDSS) in northwest Ethiopia. The result was linked with verbal autopsy (VA) information completed for each of the deaths as part of the ongoing HDSS. The SA tool was adapted from INDEPTH Network. Three delay model approach was used to classify the delay types that contributed for the deaths investigated. Descriptive statistics was used to analyze the data.ResultsSA was completed for 37 (94.9%) of the 39 neonatal deaths. Of all the deaths, 51.3% (19/37) of them occurred within the first 24 h, 75.6% (28/37) within the first 6 days and the remaining in 7–28 days. Birth asphyxia was the leading cause of death (34%) followed by bacterial sepsis (31%) and prematurity (16%). The median time from recognition of illness to initiation of modern treatment was 1 day (IQR 1–2.5 days). Delay in treatment seeking outside home (delay one) was associated with 81% of the deaths. Delay in receiving care at a health facility (delay three) and delay in transport (delay two) were associated with 16 and 3% of the deaths, respectively. The major contributors of death for delay one were bacterial sepsis (33.3%), birth asphyxia (30%), unspecified illness (20%) and acute lower respiratory tract illnesses (6.7%). For delay three, the major causes of death included birth asphyxia (50%), prematurity (33.3%) and bacterial sepsis (16.7%).ConclusionsDelays created at home and at health facility were the major delays contributing to the death of newborns. More focus has to be given in improving delays at home and at health facility.

Human parainfluenza virus surveillance in pediatric patients with lower respiratory tract infections: a special view of parainfluenza type 4

ObjectiveCharacterize the role of human parainfluenza virus and its clinical features in Brazilian children under 2 years of age presenting with acute lower respiratory tract infections. MethodsReal-time assays were used to identify strains of human parainfluenza virus and other common respiratory viruses in nasopharyngeal aspirates. One thousand and two children presenting with acute lower respiratory tract illnesses were enrolled from February 2008 to August 2010. ResultsOne hundred and four (10.4%) patients were human parainfluenza virus positive, of whom 60 (57.7%) were positive for human parainfluenza virus-3, 30 (28.8%) for human parainfluenza virus-4, 12 (11.5%) for human parainfluenza virus-1, and two (1.9%) for human parainfluenza virus-2. Seven (6.7%) patients had more than one strain of human parainfluenza virus detected. The most frequent symptoms were tachypnea and cough, similar to other viral respiratory infections. Clinical manifestations did not differ significantly between human parainfluenza virus-1, -2, -3, and -4 infections. Human parainfluenza virus-1, -3, and -4 were present in the population studied throughout the three years of surveillance, with human parainfluenza virus-3 being the predominant type identified in the first two years. ConclusionHuman parainfluenza viruses contribute substantially to pediatric acute respiratory illness (ARI) in Brazil, with nearly 30% of this contribution attributable to human parainfluenza virus-4.

Actin-Related Protein 2 (ARP2) and Virus-Induced Filopodia Facilitate Human Respiratory Syncytial Virus Spread.

Human respiratory syncytial virus (RSV) is an enveloped RNA virus that is the most important viral cause of acute pediatric lower respiratory tract illness worldwide, and lacks a vaccine or effective antiviral drug. The involvement of host factors in the RSV replicative cycle remains poorly characterized. A genome-wide siRNA screen in human lung epithelial A549 cells identified actin-related protein 2 (ARP2) as a host factor involved in RSV infection. ARP2 knockdown did not reduce RSV entry, and did not markedly reduce gene expression during the first 24 hr of infection, but decreased viral gene expression thereafter, an effect that appeared to be due to inhibition of viral spread to neighboring cells. Consistent with reduced spread, there was a 10-fold reduction in the release of infectious progeny virions in ARP2-depleted cells at 72 hr post-infection. In addition, we found that RSV infection induced filopodia formation and increased cell motility in A549 cells and that this phenotype was ARP2 dependent. Filopodia appeared to shuttle RSV to nearby uninfected cells, facilitating virus spread. Expression of the RSV F protein alone from a plasmid or heterologous viral vector in A549 cells induced filopodia, indicating a new role for the RSV F protein, driving filopodia induction and virus spread. Thus, this study identified roles for ARP2 and filopodia in RSV-induced cell motility, RSV production, and RSV cell-to-cell spread.

Use of antibiotics in children younger than two years in eight countries: a prospective cohort study.

ObjectiveTo describe the frequency and factors associated with antibiotic use in early childhood, and estimate the proportion of diarrhoea and respiratory illnesses episodes treated with antibiotics.MethodsBetween 2009 and 2014, we followed 2134 children from eight sites in Bangladesh, Brazil, India, Nepal, Pakistan, Peru, South Africa and the United Republic of Tanzania, enrolled in the MAL-ED birth cohort study. We documented all antibiotic use from mothers’ reports at twice-weekly visits over the children’s first two years of life. We estimated the incidence of antibiotic use and the associations of antibiotic use with child and household characteristics. We described treatment patterns for diarrhoea and respiratory illnesses, and identified factors associated with treatment and antibiotic class.FindingsOver 1 346 388 total days of observation, 16 913 courses of antibiotics were recorded (an incidence of 4.9 courses per child per year), with the highest use in South Asia. Antibiotic treatment was given for 375/499 (75.2%) episodes of bloody diarrhoea and for 4274/9661 (44.2%) episodes of diarrhoea without bloody stools. Antibiotics were used in 2384/3943 (60.5%) episodes of fieldworker-confirmed acute lower respiratory tract illness as well as in 6608/16742 (39.5%) episodes of upper respiratory illness. Penicillins were used most frequently for respiratory illness, while antibiotic classes for diarrhoea treatment varied within and between sites.ConclusionRepeated antibiotic exposure was common early in life, and treatment of non-bloody diarrhoea and non-specific respiratory illnesses was not consistent with international recommendations. Rational antibiotic use programmes may have the most impact in South Asia, where antibiotic use was highest.

Novel HLA-A2-restricted human metapneumovirus epitopes reduce viral titers in mice and are recognized by human T cells

Human metapneumovirus (HMPV) is a major cause of morbidity and mortality from acute lower respiratory tract illness, with most individuals seropositive by age five. Despite the presence of neutralizing antibodies, secondary infections are common and can be severe in young, elderly, and immunocompromised persons. Preclinical vaccine studies for HMPV have suggested a need for a balanced antibody and T cell immune response to enhance protection and avoid lung immunopathology. We infected transgenic mice expressing human HLA-A*0201 with HMPV and used ELISPOT to screen overlapping and predicted epitope peptides. We identified six novel HLA-A2 restricted CD8+ T cell (TCD8) epitopes, with M39–47 (M39) immunodominant. Tetramer staining detected M39-specific TCD8 in lungs and spleen of HMPV-immune mice. Immunization with adjuvant-formulated M39 peptide reduced lung virus titers upon challenge. Finally, we show that TCD8 from HLA-A*0201 positive humans recognize M39 by IFNγ ELISPOT and tetramer staining. These results will facilitate HMPV vaccine development and human studies.

Bayesian latent class estimation of the incidence of chest radiograph-confirmed pneumonia in rural Thailand.

Pneumonia is a leading cause of mortality and morbidity worldwide with radiographically confirmed pneumonia a key disease burden indicator. This is usually determined by a radiology panel which is assumed to be the best available standard; however, this assumption may introduce bias into pneumonia incidence estimates. To improve estimates of radiographic pneumonia incidence, we applied Bayesian latent class modelling (BLCM) to a large database of hospitalized patients with acute lower respiratory tract illness in Sa Kaeo and Nakhon Phanom provinces, Thailand from 2005 to 2010 with chest radiographs read by both a radiology panel and a clinician. We compared these estimates to those from conventional analysis. For children aged <5 years, estimated radiographically confirmed pneumonia incidence by BLCM was 2394/100 000 person-years (95% credible interval 2185-2574) vs. 1736/100 000 person-years (95% confidence interval 1706-1766) from conventional analysis. For persons aged ⩾5 years, estimated radiographically confirmed pneumonia incidence was similar between BLCM and conventional analysis (235 vs. 215/100 000 person-years). BLCM suggests the incidence of radiographically confirmed pneumonia in young children is substantially larger than estimated from the conventional approach using radiology panels as the reference standard.

MIP-1α level in nasopharyngeal aspirates at the first wheezing episode predicts recurrent wheezing

Respiratory virus-induced wheezing, such as that induced by respiratory syncytial virus (RSV) and human rhinovirus, is an important risk factor for recurrent wheezing and childhood asthma. However, no biomarkers for predicting recurrent wheezing have been identified. We searched for predictors of recurrent wheezing using nasopharyngeal aspirates obtained from patients during the first wheezing episode who were hospitalized with an acute lower respiratory tract illness. We enrolled 82 infants during the first wheezing episode (median age, 5.0 months) who were hospitalized for acute lower respiratory tract illness between August 2009 and June 2012 and followed these patients for 2.5 years. Nasopharyngeal aspirates and blood samples were obtained on the first day of hospitalization. Viral genomes were identified by using RT-PCR and sequencing. Levels of 33 cytokines, tryptase, IgE, anti-RSV IgE, and anti-RSV IgG were measured by using ELISAs or the Bio-Plex multiplex assay. Predictors of recurrent wheezing were examined by using a stepwise logistic regression model with backward elimination. Sixty percent of the patients experienced recurrent wheezing episodes. One or more viruses were detected in the nasopharynxes of 93% of the patients during the first wheezing episode. IFN-γ, IL-2, IL-9, MIP-1α, and MIP-1β levels were significantly higher among patients with recurrent wheezing than among those without recurrent wheezing (P < .05 or .01). The stepwise model demonstrated that the MIP-1α level (odds ratio, 7.72; 95% CI, 1.50-39.77; P = .015) was the strongest independent predictor of the occurrence of recurrent wheezing. An increased MIP-1α level in nasopharyngeal aspirates from patients with acute respiratory symptoms during the first wheezing episode caused by viral infections might predict recurrent wheezing.

Burden of Invasive Nontyphoidal Salmonella Disease in a Rural and Urban Site in Kenya, 2009-2014.

Invasive infections with nontyphoidal Salmonella (NTS) lead to bacteremia in children and adults and are an important cause of illness in Africa; however, few data on the burden of NTS bacteremia are available. We sought to determine the burden of invasive NTS disease in a rural and urban setting in Kenya. We conducted the study in a population-based surveillance platform in a rural setting in western Kenya (Lwak), and an informal urban settlement in Nairobi (Kibera) from 2009 to 2014. We obtained blood culture specimens from participants presenting with acute lower respiratory tract illness or acute febrile illness to a designated outpatient facility in each site, or any hospital admission for a potentially infectious cause (rural site only). Incidence was calculated using a defined catchment population and adjusting for specimen collection and healthcare-seeking practices. A total of 12 683 and 9524 blood cultures were analyzed from Lwak and Kibera, respectively. Of these, 428 (3.4%) and 533 (5.6%) grew a pathogen; among those, 208 (48.6%) and 70 (13.1%) were positive for NTS in Lwak and Kibera, respectively. Overall, the adjusted incidence of invasive NTS disease was higher in Lwak (839.4 per 100,000 person-years of observation [PYO]) than in Kibera (202.5 per 100,000 PYO). The highest adjusted incidences were observed in children <5 years of age (Lwak 3914.3 per 100,000 PYO and Kibera 997.9 per 100,000 PYO). The highest adjusted annual incidence was 1927.3 per 100,000 PYO (in 2010) in Lwak and 220.5 per 100,000 PYO (in 2011) in Kibera; the lowest incidences were 303.3 and 62.5 per 100,000 PYO, respectively (in 2012). In both sites, invasive NTS disease incidence generally declined over the study period. We observed an extremely high burden of invasive NTS disease in a rural area of Kenya and a lesser, but still substantial, burden in an urban slum. Although the incidences in both sites declined during the study period, invasive NTS infections remain an important cause of morbidity in these settings, particularly among children <5 years old.

The Unrecognized Burden of Influenza in Young Kenyan Children, 2008-2012.

Influenza-associated disease burden among children in tropical sub-Saharan Africa is not well established, particularly outside of the 2009 pandemic period. We estimated the burden of influenza in children aged 0–4 years through population-based surveillance for influenza-like illness (ILI) and acute lower respiratory tract illness (ALRI). Household members meeting ILI or ALRI case definitions were referred to health facilities for evaluation and collection of nasopharyngeal and oropharyngeal swabs for influenza testing by real-time reverse transcription polymerase chain reaction. Estimates were adjusted for health-seeking behavior and those with ILI and ALRI who were not tested. During 2008–2012, there were 9,652 person-years of surveillance among children aged 0–4 years. The average adjusted rate of influenza-associated hospitalization was 4.3 (95% CI 3.0–6.0) per 1,000 person-years in children aged 0–4 years. Hospitalization rates were highest in the 0–5 month and 6–23 month age groups, at 7.6 (95% CI 3.2–18.2) and 8.4 (95% CI 5.4–13.0) per 1,000 person-years, respectively. The average adjusted rate of influenza-associated medically attended (inpatient or outpatient) ALRI in children aged 0–4 years was 17.4 (95% CI 14.2–19.7) per 1,000 person-years. Few children who had severe laboratory-confirmed influenza were clinically diagnosed with influenza by the treating clinician in the inpatient (0/33, 0%) or outpatient (1/109, 0.9%) settings. Influenza-associated hospitalization rates from 2008–2012 were 5–10 times higher than contemporaneous U.S. estimates. Many children with danger signs were not hospitalized; thus, influenza-associated severe disease rates in Kenyan children are likely higher than hospital-based estimates suggest.

Viral aetiology of acute lower respiratory tract illness in hospitalised paediatric patients of a tertiary hospital: One year prospective study

Context: Acute lower respiratory tract infections (ALRI), ranked as the second leading cause of death are the primary cause of hospitalisation in children. Viruses are the most important causative agents of ALRI. Aim: To study the viral aetiology of ALRI in children at a tertiary care hospital. Setting and Design: One year prospective observational study in a tertiary care hospital of King George’s Medical University, Lucknow. Material and Methods: Nasopharyngeal aspirate (NPA) was collected from children admitted with signs and symptoms of ALRI who were aged 0-14 years. Samples were transported to the laboratory at 4°C in viral transport media and processed for detection of respiratory syncytial virus (RSV) A and B, influenza virus A and B, adenovirus (ADV), human Boca virus (HBoV), human metapneumo virus (hMPV) and parainfluenzavirus 1, 2, 3 and 4 using mono/multiplex real-time polymerase chain reaction (RT-PCR). STATA was used for statistical analysis. Results: In one year, 188 NPAs were screened for respiratory viruses, of which 45.7% tested positive. RSV was most commonly detected with 21.3% positivity followed by measles virus (8.5%), influenza A virus (7.4%), ADV (5.3%), influenza B virus (1.6%), hMPV (1.1%) and HBoV (0.5%). Month wise maximum positivity was seen in December and January. Positivity rate of RSV was highest in children aged < 1 year, which decreased with increase in age, while positive rate of influenza virus increased with increasing age. Conclusion: The occurrence of viral predominance in ALRI is highlighted.

Do oral corticosteroids reduce the severity of acute lower respiratory tract illnesses in preschool children with recurrent wheezing?

Oral corticosteroids (OCSs) are recommended for severe wheezing episodes in children. However, limited evidence supports this intervention in preschool children with outpatient wheezing illnesses. We sought to investigate whether OCSs reduce symptom scores during acute lower respiratory tract illnesses (LRTIs) in preschool children with recurrent wheeze. We performed post hoc and replication analyses in 2 outpatient cohorts of children aged 1 to 5 years with episodic wheezing participating in clinical trials. We compared symptom scores during LRTIs that were or were not treated with OCSs, adjusting for differences in disease and episode severity covariates. We stratified episodes by severity by using a propensity model. The primary outcome was the area under the curve (AUC) of total symptom scores among the more severe episodes. Two hundred fifteen participants from the Acute Intervention Management Strategies trial experienced 798 acute LRTIs, 112 of which were defined as severe based on propensity scores. The AUCs of total symptom scores did not differ between the episodes that were (n = 70) and were not (n = 42) treated with OCSs (P = .46) nor was there an OCS treatment effect on individual symptom scores. Similar analyses of the Maintenance Versus Intermittent Inhaled Corticosteroids in Wheezing Toddlers trial, involving 278 participants with 133 severe LRTIs, confirmed the above findings (P = .46 for AUC of total symptoms score comparison). In 2 separate cohorts of preschool children with episodic wheezing, OCS treatment during clinically significant LRTIs did not reduce symptom severity during acute LRTIs, despite asthma controller medication use during most episodes. These findings need to be confirmed in a prospective randomized controlled trial.

Epidemiology, Seasonality, and Burden of Influenza and Influenza-Like Illness in Urban and Rural Kenya, 2007-2010

The epidemiology and burden of influenza remain poorly defined in sub-Saharan Africa. Since 2005, the Kenya Medical Research Institute and Centers for Disease Control and Prevention-Kenya have conducted population-based infectious disease surveillance in Kibera, an urban informal settlement in Nairobi, and in Lwak, a rural community in western Kenya. Nasopharyngeal and oropharyngeal swab specimens were obtained from patients who attended the study clinic and had acute lower respiratory tract (LRT) illness. Specimens were tested for influenza virus by real-time reverse-transcription polymerase chain reaction. We adjusted the incidence of influenza-associated acute LRT illness to account for patients with acute LRT illness who attended the clinic but were not sampled. From March 2007 through February 2010, 4140 cases of acute LRT illness were evaluated in Kibera, and specimens were collected from 1197 (27%); 319 (27%) were positive for influenza virus. In Lwak, there were 6733 cases of acute LRT illness, and specimens were collected from 1641 (24%); 359 (22%) were positive for influenza virus. The crude and adjusted rates of medically attended influenza-associated acute LRT illness were 6.9 and 13.6 cases per 1000 person-years, respectively, in Kibera, and 5.6 and 23.0 cases per 1000 person-years, respectively, in Lwak. In both sites, rates of influenza-associated acute LRT illness were highest among children <2 years old and lowest among adults ≥50 years old. In Kenya, the incidence of influenza-associated acute LRT illness was high in both rural and urban settings, particularly among the most vulnerable age groups.