Young Zambian infants with symptomatic RSV and pertussis infections are frequently prescribed inappropriate antibiotics

Pediatric community-acquired pneumonia (CAP) remains a pressing global health concern, particularly in low-resource settings where diagnosis and treatment rely on empiric, symptoms-based guidelines such as the WHO's Integrated Management of Childhood Illness (IMCI). This study details the delivery of IMCI-based health care in a cohort of 1,320 young infants and their mothers in a low-resource urban community in Lusaka, Zambia. We prospectively monitored mother/infant pairs across infants' first four months of life, recording symptoms of respiratory infection and antibiotics prescriptions (predominantly penicillins), and tested nasopharyngeal (NP) samples for Respiratory syncytial virus (RSV) and Bordetella pertussis. Symptoms and antibiotics use were more common in infants (43% and 15.7%) than in mothers (16.6% and 8%), while RSV and B. pertussis were observed at similar rates in infants (2.7% and 32.5%) and mothers (2% and 35.5%), albeit frequently at very low levels. In infants, we observed strong associations between symptoms, pathogen detection, and antibiotics use. Critically, we demonstrate that non-macrolide antibiotics were commonly prescribed for pertussis infections, some of which persisted across many weeks. We speculate that improved diagnostic specificity and/or clinician education paired with timely, appropriate treatment of pertussis could substantially reduce the burden of this disease while reducing the off-target use of penicillins.

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Clinical Features of Human Metapneumovirus-Associated Community-acquired Pneumonia Hospitalizations

Clinical Infectious Diseases ◽

10.1093/cid/ciaa088 ◽

2020 ◽

Cited By ~ 1

Author(s):

Leigh M Howard ◽

Kathryn M Edwards ◽

Yuwei Zhu ◽

Carlos G Grijalva ◽

Wesley H Self ◽

...

Keyword(s):

Clinical Features ◽

Bacterial Pneumonia ◽

Pathogen Detection ◽

Population Based ◽

Community Acquired Pneumonia ◽

Human Metapneumovirus ◽

Presenting Symptoms ◽

Active Population ◽

Syncytial Virus ◽

Tract Infections

Abstract Background Human metapneumovirus (HMPV) is a leading cause of respiratory tract infections. Few studies have compared the clinical characteristics and severity of HMPV-associated pneumonia with other pathogens. Methods Active, population-based surveillance was previously conducted for radiographically confirmed, community-acquired pneumonia hospitalizations among children and adults in 8 United States hospitals. Clinical data and specimens for pathogen detection were systematically collected. We described clinical features of all HMPV-associated pneumonia and, after excluding codetections with other pathogen types, we compared features of HMPV-associated pneumonia with other viral, atypical, and bacterial pneumonia and modeled the severity (mild, moderate, and severe) and length of stay using multivariable proportional odds regression. Results HMPV was detected in 298/2358 (12.6%) children and 88/2320 (3.8%) adults hospitalized with pneumonia and was commonly codetected with other pathogens (125/298 [42%] children and 21/88 [24%] adults). Fever and cough were the most common presenting symptoms of HMPV-associated pneumonia and were also common symptoms of other pathogens. After excluding codetections in children (n = 1778), compared to HMPV (reference), bacterial pneumonia exhibited increased severity (odds ratio [OR], 3.66; 95% confidence interval [CI], 1.43–9.40), respiratory syncytial virus (RSV; OR, 0.76; 95% CI, .59–.99) and atypical (OR, 0.39; 95% CI, .19–.81) infections exhibited decreased severity, and other viral pneumonia exhibited similar severity (OR, 0.88; 95% CI, .55–1.39). In adults (n = 2145), bacterial (OR, 3.74; 95% CI, 1.87–7.47) and RSV pneumonia (OR, 1.82; 95% CI, 1.32–2.50) were more severe than HMPV (reference), but all other pathogens had similar severity. Conclusions Clinical features did not reliably distinguish HMPV-associated pneumonia from other pathogens. HMPV-associated pneumonia was less severe than bacterial and adult RSV pneumonia, but was otherwise as or more severe than other common pathogens.

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Respiratory syncytial virus in severe lower respiratory infections in previously healthy young Ethiopian infants

BMC Pediatrics ◽

10.1186/s12887-021-02675-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Abate Yeshidinber Weldetsadik ◽

Frank Riedel

Keyword(s):

Respiratory Syncytial Virus ◽

Rainy Season ◽

Clinical Laboratory ◽

Respiratory Infections ◽

Clinical Parameter ◽

Imaging Data ◽

Chi Square ◽

Young Infants ◽

Rsv Infection ◽

Syncytial Virus

Abstract Background Respiratory Syncytial Virus (RSV) is the commonest cause of acute lower respiratory infections (ALRI) in infants. However, the burden of RSV is unknown in Ethiopia. We aimed to determine the prevalence, seasonality and predictors of RSV infection in young infants with ALRI for the first time in Ethiopia. Methods We performed RSV immuno-chromatographic assay from nasopharyngeal swabs of infants, 29 days to 6 months of age. We included the first 10 eligible infants in each month from June 2018 to May 2019 admitted in a tertiary pediatric center. Clinical, laboratory and imaging data were also collected, and chi-square test and regression were used to assess associated factors with RSV infection. Results Among a total of 117 study children, 65% were male and mean age was 3 months. Bronchiolitis was the commonest diagnosis (49%). RSV was isolated from 26 subjects (22.2%) of all ALRI, 37% of bronchiolitis and 11% of pneumonia patients. Although RSV infection occurred year round, highest rate extended from June to November. No clinical or laboratory parameter predicted RSV infection and only rainy season (Adjusted Odds Ratio (AOR) 10.46 [95%. C.I. 1.95, 56.18]) was independent predictor of RSV infection. Conclusions RSV was isolated in a fifth of young infants with severe ALRI, mostly in the rainy season. Diagnosis of RSV infection in our setting require specific tests as no clinical parameter predicted RSV infection. Since RSV caused less than a quarter of ALRI in our setting, the other causes should be looked for in future studies.

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Clinical metagenomics assessments improve diagnosis and outcomes in community-acquired pneumonia

BMC Infectious Diseases ◽

10.1186/s12879-021-06039-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Fei Xie ◽

Zhimei Duan ◽

Weiqi Zeng ◽

Shumei Xie ◽

Mingzhou Xie ◽

...

Keyword(s):

Patient Outcomes ◽

Clinical Management ◽

Pathogen Detection ◽

Community Acquired Pneumonia ◽

Diagnostic Methods ◽

Trial Registration ◽

Clinical Trial Registry ◽

Registration Number ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

Abstract Background Identifying the causes of community-acquired pneumonia (CAP) is challenging due to the disease’s complex etiology and the limitations of traditional microbiological diagnostic methods. Recent advances in next generation sequencing (NGS)-based metagenomics allow pan-pathogen detection in a single assay, and may have significant advantages over culture-based techniques. Results We conducted a cohort study of 159 CAP patients to assess the diagnostic performance of a clinical metagenomics assay and its impact on clinical management and patient outcomes. When compared to other techniques, clinical metagenomics detected more pathogens in more CAP cases, and identified a substantial number of polymicrobial infections. Moreover, metagenomics results led to changes in or confirmation of clinical management in 35 of 59 cases; these 35 cases also had significantly improved patient outcomes. Conclusions Clinical metagenomics could be a valuable tool for the diagnosis and treatment of CAP. Trial registration Trial registration number with the Chinese Clinical Trial Registry: ChiCTR2100043628.

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Progress in Defining the Role of RSV in Allergy and Asthma: From Clinical Observations to Animal Models

Clinical and Developmental Immunology ◽

10.1080/10446670410001722131 ◽

2004 ◽

Vol 11 (2) ◽

pp. 113-119 ◽

Cited By ~ 22

Author(s):

W. V. Kalina ◽

L. J. Gershwin

Keyword(s):

Animal Models ◽

Rna Virus ◽

Allergic Sensitization ◽

Upper Respiratory Tract ◽

Young Infants ◽

Wide Range ◽

Similar Disease ◽

Rsv Infection ◽

Syncytial Virus ◽

The Impact

Respiratory syncytial virus (RSV), an RNA virus in the family Paramyxoviridae, causes respiratory disease in humans. A closely related bovine RSV is responsible for a remarkably similar disease syndrome in young cattle. Severe RSV disease is characterized by bronchiolitis. The impact of RSV on human health is demonstrated annually when infants are admitted to the hospital in large numbers. Nearly every child will have been infected with RSV by the age of 3 years. While the disease is most severe in young infants and elderly people, it can re-infect adults causing mild upper respiratory tract disease throughout life. In addition, there is growing evidence that RSV infection may also predispose some children to the development of asthma. This is based on the observation that children who wheeze with RSV-induced bronchiolitis are more likely to develop into allergic asthmatics. Recent studies describe attempts to create an RSV induced asthma model in mice and other species; these have shown some degree of success. Such reports of case studies and animal models have suggested a wide range of factors possibly contributing to RSV induced asthma, these include timing of RSV infection with respect to allergen exposure, prior allergic sensitization, environmental conditions, exposure to endotoxin, and the genetic background of the person or animal. Herein, we primarily focus on the influence of RSV infection and inhalation of extraneous substances (such as allergens or endotoxin) on development of allergic asthma.

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Respiratory syncytial virus (RSV) community-acquired pneumonia (CAP) in a hospitalized adult with human immunodeficiency virus (HIV) mimicking influenza A and Pneumocystis (carinii) jiroveci pneumonia (PCP)

Heart & Lung ◽

10.1016/j.hrtlng.2011.05.004 ◽

2012 ◽

Vol 41 (1) ◽

pp. 76-82 ◽

Cited By ~ 4

Author(s):

Burke A. Cunha ◽

Uzma Syed ◽

Jean E. Hage

Keyword(s):

Human Immunodeficiency Virus ◽

Respiratory Syncytial Virus ◽

Influenza A ◽

Pneumocystis Carinii ◽

Community Acquired Pneumonia ◽

Immunodeficiency Virus ◽

Syncytial Virus

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Oseltamivir Use Among Children and Adults Hospitalized With Community-Acquired Pneumonia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofw254 ◽

2016 ◽

Vol 4 (1) ◽

Cited By ~ 2

Author(s):

Ikwo K. Oboho ◽

Anna Bramley ◽

Lyn Finelli ◽

Alicia Fry ◽

Krow Ampofo ◽

...

Keyword(s):

Intensive Care Unit ◽

Differential Diagnosis ◽

Odds Ratio ◽

Adjusted Odds Ratio ◽

Influenza Season ◽

Community Acquired Pneumonia ◽

Severe Illness ◽

Factors Associated ◽

Icu Admission ◽

Clinician Education

Abstract Background Data on oseltamivir treatment among hospitalized community-acquired pneumonia (CAP) patients are limited. Methods Patients hospitalized with CAP at 6 hospitals during the 2010−2012 influenza seasons were included. We assessed factors associated with oseltamivir treatment using logistic regression. Results Oseltamivir treatment was provided to 89 of 1627 (5%) children (<18 years) and 143 of 1051 (14%) adults. Among those with positive clinician-ordered influenza tests, 39 of 61 (64%) children and 37 of 48 (77%) adults received oseltamivir. Among children, oseltamivir treatment was associated with hospital A (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 1.36−4.88), clinician-ordered testing performed (aOR, 2.44; 95% CI, 1.47−5.19), intensive care unit (ICU) admission (aOR, 2.09; 95% CI, 1.27−3.45), and age ≥2 years (aOR, 1.43; 95% CI, 1.16−1.76). Among adults, oseltamivir treatment was associated with clinician-ordered testing performed (aOR, 8.38; 95% CI, 4.64−15.12), hospitals D and E (aOR, 3.46−5.11; 95% CI, 1.75−11.01), Hispanic ethnicity (aOR, 2.06; 95% CI, 1.18−3.59), and ICU admission (aOR, 2.05; 95% CI, 1.34−3.13). Conclusions Among patients hospitalized with CAP during influenza season, oseltamivir treatment was moderate overall and associated with clinician-ordered testing, severe illness, and specific hospitals. Increased clinician education is needed to include influenza in the differential diagnosis for hospitalized CAP patients and to test and treat patients empirically if influenza is suspected.

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Navigating Clinical Utilization of Direct-from-Specimen Metagenomic Pathogen Detection: Clinical Applications, Limitations, and Testing Recommendations

Clinical Chemistry ◽

10.1093/clinchem/hvaa183 ◽

2020 ◽

Vol 66 (11) ◽

pp. 1381-1395

Author(s):

Laura M Filkins ◽

Alexandra L Bryson ◽

Steve A Miller ◽

Stephanie L Mitchell

Keyword(s):

Clinical Studies ◽

Pathogen Detection ◽

Clinical Laboratory ◽

Fungal Infections ◽

Case Reports ◽

Study Data ◽

Community Acquired Pneumonia ◽

Clinical Impact ◽

Clinical Utilization ◽

Clinical Indications

Abstract Background Metagenomic next generation sequencing (mNGS) is becoming increasingly available for pathogen detection directly from clinical specimens. These tests use target-independent, shotgun sequencing to detect potentially unlimited organisms. The promise of this methodology to aid infection diagnosis is demonstrated through early case reports and clinical studies. However, the optimal role of mNGS in clinical microbiology remains uncertain. Content We reviewed studies reporting clinical use of mNGS for pathogen detection from various specimen types, including cerebrospinal fluid, plasma, lower respiratory specimens, and others. Published clinical study data were critically evaluated and summarized to identify promising clinical indications for mNGS-based testing, to assess the clinical impact of mNGS for each indication, and to recognize test limitations. Based on these clinical studies, early testing recommendations are made to guide clinical utilization of mNGS for pathogen detection. Finally, current barriers to routine clinical laboratory implementation of mNGS tests are highlighted. Summary The promise of direct-from-specimen mNGS to enable challenging infection diagnoses has been demonstrated through early clinical studies of patients with meningitis or encephalitis, invasive fungal infections, community acquired pneumonia, and other clinical indications. However, the proportion of patient cases with positive clinical impact due to mNGS testing is low in published studies and the cost of testing is high, emphasizing the importance of improving our understanding of ‘when to test’ and for which patients mNGS testing is appropriate.

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In utero tobacco smoke exposure alters lung inflammation, viral clearance, and CD8+T-cell responses in neonatal mice infected with respiratory syncytial virus

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00338.2018 ◽

2019 ◽

Vol 317 (2) ◽

pp. L212-L221 ◽

Cited By ~ 2

Author(s):

Nagarjuna R. Cheemarla ◽

Ifeanyi K. Uche ◽

Kaitlin McBride ◽

Shan Naidu ◽

Antonieta Guerrero-Plata

Keyword(s):

Respiratory Syncytial Virus ◽

T Cell ◽

Cigarette Smoke ◽

Lung Inflammation ◽

In Utero ◽

Smoke Exposure ◽

Viral Clearance ◽

Cigarette Smoke Exposure ◽

Young Infants ◽

Syncytial Virus

Maternal smoking during pregnancy and exposure of infants to cigarette smoke are strongly associated with adverse health effects in childhood including higher susceptibility to respiratory viral infections. Human respiratory syncytial virus (HRSV) is the most important cause of lower respiratory tract infection among young infants. Exacerbation of respiratory disease, including HRSV bronchiolitis and higher susceptibility to HRSV infection, is well correlated with previous smoke exposure. The mechanisms of recurrence and susceptibility to viral pathogens after passive smoke exposure are multifactorial and include alteration of the structural and immunologic host defenses. In this work, we used a well-established mouse model of in utero smoke exposure to investigate the effect of in utero smoke exposure in HRSV-induced pathogenesis. Sample analysis indicated that in utero exposure led to increased lung inflammation characterized by an increased influx of neutrophils to the airways of the infected mice and a delayed viral clearance. On the other hand, decreased HRSV-specific CD8+T-cell response was observed. These findings indicate that cigarette smoke exposure during pregnancy alters HRSV-induced disease as well as several aspects of the neonatal immune responses.

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