Cases Of Lower Respiratory Tract Infection Research Articles

Economic burden of respiratory syncytial virus in adults in Germany – a health claims analysis between 2015 and 2018

Aims Respiratory syncytial virus (RSV) causes severe lower respiratory tract infections (LRTI) in infants and adults. While the clinical burden was recently estimated in adults in Germany, little is known about the economic burden yet. To fill this gap, we aimed to assess hospital and outpatient healthcare resource utilization (HRU) and costs of RSV infections in adults in Germany. Methods In this retrospective, observational study on nationwide, representative, anonymized claims data (2015–2018), we identified patients ≥18 years with ICD-10-GM-codes specific to RSV (‘RSV-specific’). To increase sensitivity, patients with unspecified LRTIs (including unspecified bronchitis, bronchiolitis, bronchopneumonia, and pneumonia) during RSV seasons were also included as cases potentially caused by RSV (‘RSV-possible’). RSV-related HRU (hospital days, ICU and ventilation treatment, drug dispensation) and direct costs were estimated per episode. Excess costs per episode and for follow-up periods were compared to a matched control cohort. All outcomes were reported per healthcare sector and stratified by age and risk groups as well as disease severity (ICU admission/ventilation). Results Direct inpatient and outpatient mean episode costs were 3,473€and 82€, respectively, with substantially higher costs for severe cases requiring intensive care and/or ventilation (10,801€). Direct costs for RSV-specific cases were higher than for RSV-possible cases (inpatients: 6,247€vs. 3,450€; outpatients: 127€vs. 82€). Moreover, costs were significantly higher for RSV patients than for controls and increased over time (inpatients: 5,140€per episode vs 10,093€per year; outpatients: 46€per quarter vs 114€per year). Limitations While the number of RSV-specific cases was low, inclusion of seasonal LRTI cases likely increased the sensitivity to detect RSV cases and allowed a better estimation total costs of RSV. Conclusions The economic burden of RSV-LRTI in adults in Germany is substantial, persists long-term and is particularly high in the elderly. This highlights the need for cost-effective prevention measures.

The nasopharyngeal microbiome in South African children with lower respiratory tract infection: a nested case-control study of the Drakenstein Child Health Study.

Lower respiratory tract infection (LRTI) is a leading cause of infant morbidity and mortality globally. LRTI may be caused by viral or bacterial infections, individually or in combination. We investigated associations between LRTI and infant nasopharyngeal (NP) viruses and bacteria in a South African birth cohort. In a case-control study of infants enrolled in the Drakenstein Child Health Study (DCHS), LRTI cases were identified prospectively and age-matched with controls from the cohort. NP swabs were tested using quantitative real-time polymerase chain reaction (qPCR) and 16S rRNA gene amplicon sequencing. We calculated adjusted Conditional Odds Ratios (aORs) for qPCR targets and used mixed effects models to identify differentially abundant taxa between LRTI cases and controls and explore viral-bacterial interactions. Respiratory Syncytial Virus (RSV) [aOR: 5.69, 95% CI: 3.03-10.69], human rhinovirus (HRV) [1.47, 1.03-2.09], parainfluenza virus [3.46, 1.64-7.26], adenovirus [1.99, 1.08-3.68], enterovirus [2.32, 1.20-4.46], Haemophilus influenzae [1.72, 1.25-2.37], Klebsiella pneumoniae [2.66, 1.59-4.46], or high-density (> 6.9 log10 copies/mL) Streptococcus pneumoniae [1.53, 1.01-2.32] were associated with LRTI. Using 16S sequencing, LRTI was associated with increased relative abundance of Haemophilus (q = 0.0003) and decreased relative abundance of Dolosigranulum (q = 0.001), Corynebacterium (q = 0.091) and Neisseria (q = 0.004). In samples positive for RSV, Staphylococcus and Alloprevotella were present at lower relative abundance in cases than controls. In samples positive for parainfluenza virus or HRV, Haemophilus was present at higher relative abundance in cases. The associations between bacterial taxa and LRTI are strikingly similar to those identified in high-income countries, suggesting a conserved phenotype. RSV was the major virus associated with LRTI. H. influenzae appears to be the major bacterial driver of LRTI, acting synergistically with viruses. The Gram-positive bacteria Dolosigranulum and Corynebacteria may protect against LRTI, while Staphylococcus was associated with reduced risk of RSV-related LRTI. National Institutes of Health of the USA, Bill and Melinda Gates Foundation, National Research Foundation South Africa, South African Medical Research Council, L'Oréal-UNESCO For Women in Science South Africa, Australian National Health and Medical Research Council.

Syndromic case definitions for lower respiratory tract infection (LRTI) are less sensitive in older age: an analysis of symptoms among hospitalised adults

BackgroundLower Respiratory Tract Infections (LRTI) pose a serious threat to older adults but may be underdiagnosed due to atypical presentations. Here we assess LRTI symptom profiles and syndromic (symptom-based) case ascertainment in older (≥ 65y) as compared to younger adults (< 65y).MethodsWe included adults (≥ 18y) with confirmed LRTI admitted to two acute care Trusts in Bristol, UK from 1st August 2020- 31st July 2022. Logistic regression was used to assess whether age ≥ 65y reduced the probability of meeting syndromic LRTI case definitions, using patients’ symptoms at admission. We also calculated relative symptom frequencies (log-odds ratios) and evaluated how symptoms were clustered across different age groups.ResultsOf 17,620 clinically confirmed LRTI cases, 8,487 (48.1%) had symptoms meeting the case definition. Compared to those not meeting the definition these cases were younger, had less severe illness and were less likely to have received a SARS-CoV-2 vaccination or to have active SARS-CoV-2 infection. Prevalence of dementia/cognitive impairment and levels of comorbidity were lower in this group.After controlling for sex, dementia and comorbidities, age ≥ 65y significantly reduced the probability of meeting the case definition (aOR = 0.67, 95% CI:0.63–0.71). Cases aged ≥ 65y were less likely to present with fever and LRTI-specific symptoms (e.g., pleurisy, sputum) than younger cases, and those aged ≥ 85y were characterised by lack of cough but frequent confusion and falls.ConclusionsLRTI symptom profiles changed considerably with age in this hospitalised cohort. Standard screening protocols may fail to detect older and frailer cases of LRTI based on their symptoms.

Lower respiratory tract infections in children with congenital lung abnormalities.

We aimed to determine if the incidence of lower respiratory tract infections (LRTI) among children with asymptomatic, observationally managed congenital lung abnormalities (CLA) differed from that of symptomatic patients who underwent surgery. Second, we sought to compare the pre- and post-resection incidence of LRTI in patients who underwent surgery. This retrospective cohort study included patients born between 1999 and 2021 with CLA confirmed by CT scan who were enrolled in a prospective longitudinal follow-up program. The LRTI incidence rates at 1, 2, 5, 8, and 12 years were compared between surgically and observationally managed patients using incidence rate ratios (IRR). Differences in pre- and post-resection LRTI incidence rates among patients who underwent CLA-related surgery were assessed through IRR. Among 217 included patients, 81 (37%) had undergone surgery and 136 (63%) had been observationally managed. The LRTI incidence rates did not significantly differ at any follow-up moment between the surgical and observational groups. Among the children who underwent CLA-related surgery, the pre-resection LRTI incidence rates were significantly higher than the post-resection LRTI incidence rates (IRR of 3.57, 95% confidence interval: [2.00; 6.33], p < .001). We could not demonstrate differences in LRTI incidence throughout childhood between patients with surgically and observationally managed CLA. We recommend discussing cases of LRTI in patients with CLA in a multidisciplinary setting, using additional diagnostics such as chest X-ray to screen for CLA involvement, enabling a well-considered decision on surgical resection of the lesion.

Risk factors for the development of severe or very severe respiratory syncytial virus-related lower respiratory tract infection in Indian infants: A cohort study in Melghat, India.

Respiratory syncytial virus (RSV) is undoubtedly the single most important cause of severe lower respiratory tract infection (LRTI) globally. While new prevention measures in young infants have become available, their use in developing countries is likely many years away. While risk factors for severe or very severe RSV LRTI in impoverished rural areas likely differ to urban areas, there are very few studies, especially those conducted in India, the major country contributing to the global burden of disease. Active surveillance for acute LRTI in enrolled infants and children <2 years of age, was conducted through weekly home visits in 93 villages of Melghat, India, from August 2016 to December 2020. Local hospitals and primary health centres were surveyed for admissions of enrolled subjects. Nasopharyngeal swabs were collected from children with severe, or very severe LRTIs and all who died, with RSV testing using nucleic acid tests at ICMR, National Institute of Virology Pune. Risk factors for both RSV associated and non-RSV associated, severe and very severe LRTI were identified through univariate and multivariate logistic regression. There were 483 severe or very severe RSV LRTI cases and 2807 non-RSV severe or very severe LRTI infections in a cohort of 13,318 children. Weight for age z-score ≤-2, the use of kerosene or wood for cooking, obtaining drinking water from a public tap and low gestational age significantly increased the risk of RSV LRTI. A higher wealth score index and water purification were protective. Comparison with non-RSV LRTI showed male sex as an additional risk factor. The analysis highlighted the risk of kerosene use [OR = 17.8 (3.0-104.4) (p ≤ 0.001)] and [OR = 3.4 (0.8-14.4) (p ≤ 0.05)] for RSV and non-RSV LRTIs, respectively. Nutritional status and environmental air quality are predisposing factors for developing an RSV LRI in young children, factors which are amenable to environmental and behavioural interventions.

Epidemiological study of respiratory syncytial virus infection in adults during the pandemic of COVID-19

IntroductionWhile respiratory syncytial virus (RSV) is one of the most common pathogens in adults admitted to the ICU due to respiratory diseases, no reports regarding the occurrence rate of RSV infections in adults in Japan during the COVID-19 pandemic exist. Patients and methodsWe conducted this retrospective study to examine the exact occurrence rate of RSV infections in adults. We reviewed all patients (≥18 years) with any respiratory symptoms who received quantitative polymerase chain reaction (PCR) using nasopharyngeal samples for respiratory viruses by GeneLEAD at the Aichi Medical University Hospital between November 2022 and November 2023. ResultsA total of 541 adult patients who underwent PCR test were enrolled in this study. RSV was identified in 18 cases (3.3 %); 8 (1.5 %) upper and 10 (1.8 %) lower respiratory tract infections. Influenza A and SARS-CoV-2 were found in 10 (1.8 %) and 61 (11.3 %), respectively. Patients with RSV infections and COVID-19 had more comorbidities than those with Influenza virus infections.As for RSV-associated with lower respiratory tract infection cases, 10 developed acute respiratory failure, resulting in 1 fatal case due to pneumonia and 1 died of septic shock due to ileus. The 30-, 90-day mortality rates were 1 (6 %) and 2 (11 %) respectively. ConclusionAbout 3 % of adults had RSV infections during the COVID-19 pandemic. The outcomes of RSV infections in adults were similar to those by COVID-19. Those with comorbidities should have a preventive method against RSV infections, the same as for COVID-19.

Infants hospitalized with lower respiratory tract infections during the first two years of life have increased risk of pediatric obstructive sleep apnea.

Lower respiratory tract infections (LRTI) during the first 2 years of life increase the risk of pediatric obstructive sleep apnea (OSA), but whether this risk varies by LRTI severity is unknown. We analyzed data from 2962 children, aged 0-5 years, with early-life LRTI requiring hospitalization (severe LRTI, n = 235), treated as outpatients (mild LRTI, n = 394) and without LRTI (reference group, n = 2333) enrolled in the Boston Birth Cohort. Kaplan-Meier survival estimates and Cox proportional hazards models adjusted by pertinent covariables were used to evaluate the risk of pediatric OSA. Compared to children without LRTI, those with mild LRTI were at a higher risk of having OSA (hazard ratio [HR] 1.44, 95% confidence interval [CI]: 1.01-2.05), and those with severe LRTI were at the highest risk (HR 2.06, 95% CI: 1.41-3.02), independently of relevant covariables (including maternal age, race, gestational age, and type of delivery). Additional risk factors linked to a higher risk of OSA included prematurity (HR 1.34, 95% CI 1.01-1.77) and maternal obesity (HR 1.82, 95% CI 1.32-2.52). The time elapsed between LRTI and OSA diagnosis was similar in mild and severe LRTI cases, with medians of 23 and 25.5 months, respectively (p = .803). Infants with severe early-life LRTI have a higher risk of developing OSA, and surveillance strategies to identify OSA need to be particularly focused on this group. OSA monitoring should continue throughout the preschool years as it may develop months or years after the initial LRTI hospitalization.

Routine Metagenomics Service for ICU Patients with Respiratory Infection.

Rationale: Respiratory metagenomics (RMg) needs evaluation in a pilot service setting to determine utility and inform implementation into routine clinical practice. Objectives: Feasibility, performance, and clinical impacts on antimicrobial prescribing and infection control were recorded during a pilot RMg service. Methods: RMg was performed on 128 samples from 87 patients with suspected lower respiratory tract infection (LRTI) on two general and one specialist respiratory ICUs at Guy's and St Thomas' NHS Foundation Trust, London. Measurements and Main Results: During the first 15 weeks, RMg provided same-day results for 110 samples (86%), with a median turnaround time of 6.7 hours (interquartile range = 6.1-7.5 h). RMg was 93% sensitive and 81% specific for clinically relevant pathogens compared with routine testing. Forty-eight percent of RMg results informed antimicrobial prescribing changes (22% escalation; 26% deescalation) with escalation based on speciation in 20 out of 24 cases and detection of acquired-resistance genes in 4 out of 24 cases. Fastidious or unexpected organisms were reported in 21 samples, including anaerobes (n = 12), Mycobacterium tuberculosis, Tropheryma whipplei, cytomegalovirus, and Legionella pneumophila ST1326, which was subsequently isolated from the bedside water outlet. Application to consecutive severe community-acquired LRTI cases identified Staphylococcus aureus (two with SCCmec and three with luk F/S virulence determinants), Streptococcus pyogenes (emm1-M1uk clone), S. dysgalactiae subspecies equisimilis (STG62647A), and Aspergillus fumigatus with multiple treatments and public health impacts. Conclusions: This pilot study illustrates the potential of RMg testing to provide benefits for antimicrobial treatment, infection control, and public health when provided in a real-world critical care setting. Multicenter studies are now required to inform future translation into routine service.

Vaccination of pneumococcal infection in patients with systemic lupus erythe matosus and antiphospholipid syndrome: experience of 6 years of use

Infections remain one of the main causes of morbidity and mortality in patients with immuno-inflammatory rheumatic diseases. Objective – to study the efficacy, immunogenicity and safety of the 23-valent polysaccharide pneumococcal vaccine (PPV-23) in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (AРS). Materials and methods. 91 patients were included in the study: 78 with SLE, of which 18 (23 %) – with secondary AРS, 13 – with primary AРS. 85 patients received immunosuppressive therapy, including 30 – genetically engineered biological drugs (bDMARD); 23 – anticoagulants. PPV-23 was administered subcutaneously, patients were observed for a year after vaccination. Results. Local reactions were observed in 49% of patients with SLE and secondary AРS, in 23% of patients with primary AРS. General reactions were noted in isolated cases, were short-term and did not require additional prescriptions. During the follow-up period, no exacerbations of SLE, relapses of thrombosis and thromboembolism associated with vaccination were detected; no development of new autoimmune diseases was registered. 10 (13%) patients with SLE were immunized against the background of high activity of the disease, no adverse reactions were recorded. In some patients, a transient increase in a-DNA and ANF was observed during the year without signs of exacerbation of the disease. 56% of patients with SLE and secondary AРS, 15.4% with primary AРS were “responders” to the vaccine. There was no negative effect on the immune response of the dose of GC &gt;10 mg/day, age, duration and activity of the disease. With the treatment of bDMARD, a full-fledged vaccine response was recorded much less frequently than with standard therapy (38% and 67.4%, respectively; p=0.01). After vaccination, there was a significant decrease in the number of lower respiratory tract infections (LRTI) (p=0.0001), including community-acquired pneumonia (PN) (p=0.03) and acute bronchitis (p=0.04), ENT infections (p=0.001). In the treatment of rituximab (RTM), compared with belimumab (BLM), a greater number of LRTI was observed, mainly due to PN. After vaccination on RTM therapy, the number of INDP in general (p=0.008) and PN in particular (p=0.03) decreased, isolated cases of LRTI and ENT organs were recorded on BLM therapy. Within 4–6 years after vaccination, 30 patients with SLE retained the clinical effect of vaccination, while immunogenicity decreased to 18%. Conclusion. Safety, sufficient immunogenicity, and clinical efficacy of PPV-23 in patients with SLE and AРS have been shown. The use of bDMARD reduces the vaccine response. Immunization performed prior to or during treatment with bDMARD lasting &lt;1 year increases the number of vaccine responders.

Association of anemia with acute lower respiratory tract infection in children aged 2 months to 5 years

Background: In developing countries lower respiratory tract infection (LRTI) is a major cause of death in children. Various risk factors like low birth weight, malnutrition, vitamin A deficiency, lack of breastfeeding, poor socioeconomic status, large family size, young age and air pollution have been proposed for development of lower respiratory infections. Anemia is one of the commonest cofactor of LRTI. Methods: A case-control study was conducted among 150 children in the age group of 2 months-5 years who attended the department of paediatrics during February 2021 to July 2022. Accordingly, 75 cases of LRTI and 75 normal controls (age and gender matched) were enrolled. Their parents were interviewed using a semi-structured questionnaire. Blood investigations were done and documented in a proforma. Results: On studying the age distribution, maximum children were in the age group of 1-3 years. Male preponderance was found with male: female ratio being 1.27:1. Study shows that 74.67% of the cases and 34.67% of the controls were found anemic. Anemia was found to be a significant risk factor for LRTI (p&lt;0.001). Conclusions: Anemia was significantly found in patients with LRTIs and these patients were found to be more susceptible to LRTIs. Prevention of anemia, due to whatever etiology, early diagnosis and treatment is important to reduce the incidence of LRTIs in children.

Burden of Lower Respiratory Tract Infections Preventable by Adult Immunization With 15- and 20-Valent Pneumococcal Conjugate Vaccines in the United States.

Updated recommendations of the US Advisory Committee on Immunization Practices indicate that all adults aged ≥65 years and adults aged <65 years with comorbid conditions should receive 15- and 20-valent pneumococcal conjugate vaccines (PCV15/20). We aimed to assess the potential impact of these recommendations on the burden of lower respiratory tract infections (LRTIs) among adults. We estimated the incidence of LRTI cases and associated hospital admissions among enrollees of Kaiser Permanente Southern California from 2016 through 2019. We used a counterfactual inference framework to estimate excess LRTI-associated risk of death up to 180 days after diagnosis. We used prior estimates of PCV13 effectiveness against LRTI to model potential direct effects of PCV15/20 by age group and risk status. Use of PCV15 and PCV20, respectively, could prevent 89.3 (95% confidence interval, 41.3-131.8) and 108.6 (50.4-159.1) medically attended LRTI cases; 21.9 (10.1-32.0) and 26.6 (12.4-38.7) hospitalized LRTI cases; and 7.1 (3.3-10.5) and 8.7 (4.0-12.7) excess LRTI-associated deaths, each per 10 000 person-years. Among at-risk adults aged <65 years, use of PCV15 and PCV20 could prevent 85.7 (39.6-131.5) and 102.7 (47.8-156.7) medically attended LRTI cases per 10 000 person-years; 5.1 (2.4-8.6) and 6.2 (2.8-10.2) LRTI hospitalizations per 10 000 person-years, and 0.9 (0.4-1.4) and 1.1 (0.5-1.7) excess LRTI-associated deaths per 10 000 person-years. Our findings suggest recent recommendations, including PCV15/20 within adult pneumococcal vaccine series, may substantially reduce LRTI burden.

Evaluation of Antibiotics Used for Lower Respiratory Tract Infections in a Tertiary Care Hospital

Objective: The main objective of the study was to evaluate patterns of antibiotics prescribed for Lower respiratory tract infections (LRTIs) in a tertiary care hospital. Methodology: A prospective observational study was conducted in the pulmonology and general medicine departments of a tertiary care hospital. The data was collected from the in- patient department after considering inclusion and exclusion criteria for a period of 6 months. Antibiotics prescribed were compared with the guidelines mentioned in the European respiratory society guidelines (ERS), Indian respiratory guidelines, IDSA guidelines, and NICE guidelines to determine the appropriateness of therapy. Statistical tools like Chi-square test were applied to the data by using SPSS software. Result: A total of 284 patients diagnosed with various LRTIs, male 55% patients predominated over female patients of 45%. The majority of the patients were under age group of 61-70 years (24%), literates (71.84%), and symptoms of SOB (88.73%), Cough (69.01%), generalized weakness/body pains (54.92%), fever (50.70%), wheeze (11.26%) and chest pain (9.85%). Among all cases of LRTI, most of the patients 56.4% were diagnosed with viral pneumonia (COVID-19). Higher number of patients was treated with beta-lactam antibiotics. Inj.Piperacillin/tazobactum (38%), Tab.Cefpodoxime proxetil/Clavulanic acid (41%), Inj.Cefaperazone/Sulbactum (35%) and Inj.Amoxicillin/Clavulanic acid (23%) were frequently used. Conclusion: Lower respiratory tract infections are mostly seen in males, elder age groups and in literate patients. Present study showed that the antibiotics were used taking into consideration various clinical and diagnostic evidences like radiology, bio-markers, patient condition and severity of the disease. However the establishment of antibiotic stewardship program is necessary to ensure safe and appropriate use of antibiotics and to prevent antibiotic resistance in patients.

Optimizing next-generation RSV prevention in Mali: A cost-effectiveness analysis of pediatric vaccination, maternal vaccination, and extended half-life monoclonal antibody immunoprophylaxis.

Respiratory syncytial virus (RSV) is the most common cause of early childhood lower respiratory tract infection (LRTI) in low- and middle-income countries (LMICs). Maternal vaccines, birth-dose extended half-life monoclonal antibodies (mAbs), and pediatric vaccines are under development for prevention of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in young children. We analyzed the health and economic impact of RSV interventions used alone or in combinations in Mali. We modeled age-specific and season-specific risks of RSV LRTI in children through three years, using WHO Preferred Product Characteristics and data generated in Mali. Health outcomes included RSV LRTI cases, hospitalizations, deaths, and disability-adjusted life-years (DALYs). We identified the optimal combination of products across a range of scenarios. We found that mAb delivered at birth could avert 878 DALYs per birth cohort at an incremental cost-effectiveness ratio (ICER) of $597 per DALY averted compared to no intervention if the product were available at $1 per dose. Combining mAb with pediatric vaccine administered at 10/14 weeks, 1947 DALYs would be prevented. The ICER of this combination strategy is $1514 per DALY averted compared to mAb alone. Incorporating parameter uncertainty, mAb alone is likely to be optimal from the societal perspective at efficacy against RSV LRTI above 66%. The optimal strategy was sensitive to economic considerations, including product prices and willingness-to-pay for DALYs. For example, the combination of mAb and pediatric vaccine would be optimal from the government perspective at a willingness-to-pay above $775 per DALY. Maternal vaccine alone or in combination with other interventions was never the optimal strategy, even for high vaccine efficacy. The same was true for pediatric vaccine administered at 6/7 months. At prices comparable to existing vaccine products, extended half-life RSV mAbs would be impactful and efficient components of prevention strategies in LMICs such as Mali.

Model-estimated impacts of pediatric respiratory syncytial virus prevention programs in Mali on asthma prevalence.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) in young children and is associated with subsequent recurrent wheezing illness and asthma (wheeze/asthma). RSV prevention may therefore reduce wheeze/asthma prevalence. We estimated the contribution of RSV LRTI and the impact of RSV prevention on recurrent wheeze/asthma in Mali. We simulated 12 consecutive monthly birth cohorts in Mali and estimated RSV LRTI cases through 2 years and recurrent wheeze/asthma prevalence at 6 years under different RSV prevention scenarios: status quo, seasonal birth-dose extended half-life mAb, and seasonal birth-dose extended half-life mAb followed by 2 doses of pediatric vaccine (mAb+ vaccine). We used World Health Organization (WHO) Preferred Product Characteristics for RSV prevention, demographic and RSV epidemiologic data from Mali, regional recurrent wheeze/asthma prevalence, and relative risk of recurrent wheeze/asthma given early childhood RSV LRTI. Among the simulated cohort of 778,680 live births, 10.0% had RSV LRTI by 2 years and 89.6% survived to 6 years. We estimated that 13.4% of all recurrent wheeze/asthma at 6 years was attributable to RSV LRTI. Recurrent wheeze/asthma prevalence at 6 years was 145.0 per 10,000 persons (RSV LRTI attributable) and 1084.2 per 10,000 persons (total). In mAb and mAb+ vaccine scenarios, RSV LRTI cases decreased by 11.8% and 44.4%, respectively, and recurrent wheeze/asthma prevalence decreased by 11.8% and 44.4% (RSV LRTI attributable) and 1.6% and 5.9% (total). In Mali, RSV prevention programs may have a meaningful impact on chronic respiratory disease, strengthening the case for investment in RSV prevention.

Exposure-response relationship of residential dampness and mold damage with severe lower respiratory tract infections among under-five children in Nigeria.

In-home visits were conducted among 178 children hospitalized with LRTI matched by age (±3 months), sex, and geographical location with 180 community-based children without LRTI. Trained study staff evaluated the indoor environment using a standardized home walkthrough checklist and measured visible dampness and mold damage. Damp-moldy Index (DMI) was also estimated to quantify the level of exposure. Exposure-response relationships of dampness and mold exposure with severe LRTI were assessed using multivariable restricted cubic spline regression models adjusting for relevant child, housing, and environmental characteristics. Severe LRTI cases were more often male than female (61.8%), and the overall mean (SD) age was 7.3 (1.35) months. Children exposed to dampness <0.3 m2 (odds ratio [OR] = 2.11; 95% confidence interval [CI] = 1.05, 4.36), and between 0.3 and 1.0 m2 (OR = 2.34; 95% CI = 1.01, 7.32), had a higher odds of severe LRTI compared with children not exposed to dampness. The restricted cubic spline showed a linear exposure-response association between severe LRTI and residential dampness (P < 0.001) but a nonlinear relationship with DMI (P = 0.01). Residential dampness and DMI were exposure-dependently associated with higher odds of severe LRTI among under-five children. If observed relationships were causal, public health intervention strategies targeted at reducing residential dampness are critically important to mitigate the burden of severe LRTI among under-five children.

Pathogens associated with hospitalization due to acute lower respiratory tract infections in children in rural Ghana: a case–control study

Respiratory infections are one of the most common causes of death among children under the age of five years. Data on prevalence and relevance of specific organisms in African children are still lacking. This case–control-study investigated prevalence and relevance of specific organisms in Ghanaian children admitted to hospital with symptoms of lower respiratory tract infection (LRTI). Pharyngeal swabs were taken and tested by PCR for 19 respiratory isolates. Adjusted odds ratios (aORs) were calculated to estimate associations between isolates and admission with LRTI. Population attributable fractions (PAFs) were calculated to assess the proportion of LRTI cases due to a particular pathogen. The study included 327 cases and 562 controls. We found associations between detection and admission for LRTI for influenza (aOR 98.6; 95% confidence interval (CI) 20.0–1789.6), respiratory syncytial virus (aOR 40.2; 95% CI 7.2–758.6), H. influenzae (aOR 4.1; 95% CI 2.2–7.9) and S. pneumoniae (aOR 2.4; 95% CI 1.7–3.4). PAFs ≥ 10% were observed for S. pneumoniae (30%; 95% CI 26–42), H. influenzae (10%; 95% CI 2–19) and influenza (10%; 95% CI 2–18). This study highlights the need for heightened surveillance and development of effective vaccines for respiratory pathogens other than SARS-CoV-2 in the future.

Comparison of next-generation sequencing with traditional methods for pathogen detection in cases of lower respiratory tract infection at a community hospital in Eastern China

Lower respiratory tract infection (LRTI) is still a threat to human health. Metagenomics next-generation sequencing (NGS) provides an efficient and unbiased way to identify LRTI pathogens, and has been shown to have several advantages over traditional methods. However, its application is currently limited in low-resource settings. Our aim was to collect and analyze data on LRTI cases at a county-level community hospital in Eastern China over one year, in order to compare the efficiency of NGS and traditional methods including culture, nucleic acid amplification and antibody techniques. We performed NGS of bronchoalveolar lavage fluid (BALF) for pathogen identification in 71 patients with LRTI. We compared the detection rates, identified pathogens, and turnaround time of NGS with traditional methods. Pathogens were detected using traditional methods in 19 cases, and the results were compared with those obtained with the NGS technique in 60 cases. The pathogen detection rate of NGS (84.5%) was much higher than that of the traditional methods (26.8%). Moreover, with the traditional methods considered the gold standard, the consistency rate between NGS and traditional methods was 68.4%. For the 19 cases in which the traditional method was used, the main pathogens included invasive Aspergillus (5 cases), Pseudomonas aeruginosa (3 cases), Candida albicans (3 cases), and Staphylococcus aureus (2 cases). Among the 60 cases detected by NGS, the main pathogens included Mycobacterium (12 cases), Streptococcus pneumoniae (5 cases), Klebsiella pneumoniae (3 cases), P. aeruginosa (3 cases), Haemophilus influenzae (3 cases), and S. aureus (3 cases), Aspergillus (9 cases), Pneumocystis jiroveci (5 cases), C. albicans (3 cases), Human Papilloma Virus (9 cases), Epstein-Barr virus (8 cases), and parvovirus (6 cases). In addition, 2 cases of chlamydia and 1 case of mycoplasma infection were detected by NGS. The time taken to perform the NGS tests was significantly shorter than that taken with the traditional method. NGS analysis of bronchoalveolar lavage fluid, in combination with traditional pathogen detection methods, can improve the efficiency of pathogen detection. More attention should be paid to the regional epidemic characteristics of infectious pathogens in LRTI.

94. Pooled analysis of nirsevimab resistance through 150 days post dose in preterm and term infants

Abstract Background Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infection (LRTI) and hospitalization in infants. In two global pivotal placebo-controlled studies, nirsevimab, a monoclonal antibody to the RSV prefusion (F) protein with extended half-life, reduced medically attended (MA) RSV LRTI versus placebo throughout the RSV season (MELODY (Primary Cohort)/Study 3 (Proposed Dose) Pool, 79.5% efficacy). Here we summarize resistance analyses of all RT-PCR-confirmed RSV isolates from healthy term and preterm infants through 150 days post dose. Methods Infants were randomized 2:1 to receive one intramuscular injection of nirsevimab or placebo, prior to their first RSV season. RT-PCR-confirmed RSV isolates were reflexed for genotypic analyses of RSV F and phenotypic analyses of identified substitutions in a recombinant RSV neutralization susceptibility assay. Results In the pooled proposed dose analysis of Study 3 (50 mg nirsevimab if &amp;lt; 5 kg at dosing) and MELODY (50 or 100 mg nirsevimab if &amp;lt; 5 kg or ≥5 kg at dosing, respectively), no subject with MA RSV LRTI had an RSV isolate containing nirsevimab resistance-associated substitutions in either treatment group (nirsevimab, RSV A: 0/14 and RSV B: 0/5; placebo, RSV A: 0/35 and RSV B: 0/16). In Study 3 (50 mg nirsevimab if ≥5 kg at dosing), 2/18 subjects in the nirsevimab group and 0/20 subjects in the placebo group with MA RSV LRTI had an RSV isolate harbouring nirsevimab binding site substitutions I64T+K68E+I206M+Q209R (&amp;gt;447-fold) or N208S (&amp;gt;387-fold) that conferred reduced susceptibility to nirsevimab neutralization (nirsevimab, RSV A: 0/9 and RSV B: 2/9; placebo, RSV A: 0/10 and RSV B: 0/10). Subjects with RSV isolates harboring F protein sequence variations that maintained susceptibility to nirsevimab neutralization were balanced between treatment groups with no association with RSV disease severity. No subjects with non-protocol defined MA RSV LRTI cases or hospitalization due to any RSV respiratory illness had an RSV isolate conferring nirsevimab resistance. Conclusion Lack of nirsevimab resistance following immunization at the proposed dose supports efficacy and neutralization activity of nirsevimab against both RSV A and B strains throughout the RSV season. Disclosures Michael E. Abram, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Bahar Ahani, BSC, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds David E. Tabor, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Fiona Fernandes, PhD, AstraZeneca: Stocks/Bonds Deidre Wilkins, BSC, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Anastasia A. Aksyuk, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Kevin M. Tuffy, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Hong Ji, BSc, AstraZeneca: Stocks/Bonds Christine Blaze, BSc, AstraZeneca: Stocks/Bonds Tyler Brady, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Pamela Griffin, MD, AstraZeneca: Stocks/Bonds Amanda Leach, MD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Tonya L. Villafana, PhD, MPH, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Mark T. Esser, PhD, AstraZeneca: Stocks/Bonds.

Indoor bacterial and fungal aerosols as predictors of lower respiratory tract infections among under-five children in Ibadan, Nigeria.

This study aimed to investigate the association between exposure to diverse indoor microbial aerosols and lower respiratory tract infections (LRTI) among children aged 1 to 59months in Ibadan, Nigeria. One hundred and seventy-eight (178) hospital-based LRTI cases among under-five children were matched for age (± 3months), sex and geographical location with 180 community-based controls (under-five children without LRTI). Following consent from caregivers of eligible participants, a child's health questionnaire, clinical proforma and standardized home-walkthrough checklist were used to collect data. Participant homes were visited and sampled for indoor microbial exposures using active sampling approach by Anderson sampler. Indoor microbial count (IMC), total bacterial count (TBC), and total fungal count (TFC) were estimated and dichotomized into high (> median) and low (≤ median) exposures. Alpha diversity measures including richness (R), Shannon (H) and Simpson (D) indices were also estimated. Conditional logistic regression models were used to test association between exposure to indoor microbial aerosols and LRTI risk among under-five children. Significantly higher bacterial and fungal diversities were found in homes of cases (R = 3.00; H = 1.04; D = 2.67 and R = 2.56; H = 0.82; D = 2.33) than homes of controls (R = 2.00; H = 0.64; D = 1.80 and R = 1.89; H = 0.55; D = 1.88) p < 0.001, respectively. In the multivariate models, higher categories of exposure to IMC (aOR = 2.67, 95% CI 1.44-4.97), TBC (aOR = 2.51, 95% CI 1.36-4.65), TFC (aOR = 2.75, 95% CI 1.54-4.89), bacterial diversity (aOR = 1.87, 95% CI 1.08-3.24) and fungal diversity (aOR = 3.00, 95% CI 1.55-5.79) were independently associated with LRTI risk among under-five children. This study suggests an increased risk of LRTI when children under the age of five years are exposed to high levels of indoor microbial aerosols.

Utility of a three-gene transcriptomic signature in the diagnosis of tuberculosis in a low-endemic hospital setting

Background Host transcriptomic blood signatures have demonstrated diagnostic potential for tuberculosis (TB), requiring further validation across different geographical settings. Discriminating TB from other diseases with similar clinical manifestations is crucial for the development of an accurate immunodiagnostic tool. In this exploratory cohort study, we evaluated the performance of potential blood-based transcriptomic signatures in distinguishing TB disease from non-TB lower respiratory tract infections in hospitalised patients in a TB low-endemic country. Method Quantitative real-time polymerase chain reaction qPCR) was used to evaluate 26 previously published genes in blood from 31 patients (14 TB and 17 lower respiratory tract infection cases) admitted to Oslo University Hospital in Norway. The diagnostic accuracies of differentially expressed genes were determined by receiver operating characteristic curves. Results A significant difference (p < .01) in the age distribution was observed between patients with TB (mean age, 40 ± 15 years) and lower respiratory tract infection (mean age 59 ± 12 years). Following adjustment for age, ETV7, GBP1, GBP5, P2RY14 and BLK were significantly differentially expressed between patients with TB and those with LRI. A general discriminant analysis generated a three-gene signature (BAFT2, ETV7 and CD1C), which diagnosed TB with an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI, 0.69 − 1.00), sensitivity of 69.23% (95% CI, 38.57%−90.91%) and specificity of 94.12% (95% CI, 71.31%−99.85%). Conclusion The three-genes signature may have potential to improve diagnosis of TB in a hospitalised low-burden setting. However, the influence of confounding variables or covariates such as age requires further evaluation in larger studies.