Global burden of acute lower respiratory infection associated with human metapneumovirus in children under 5 years in 2018: a systematic review and modelling study.

BACKGROUND: Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs associated with human metapneumovirus in children, and no licensed vaccines or drugs exist for human metapneumovirus infections. We aimed to estimate the age-stratified human metapneumovirus-associated ALRI global incidence, hospital admissions, and mortality burden in children younger than 5 years. METHODS: We estimated the global burden of human metapneumovirus-associated ALRIs in children younger than 5 years from a systematic review of 119 studies published between Jan 1, 2001, and Dec 31, 2019, and a further 40 high quality unpublished studies. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We estimated incidence, hospital admission rates, and in-hospital case-fatality ratios (hCFRs) of human metapneumovirus-associated ALRI using a generalised linear mixed model. We applied incidence and hospital admission rates of human metapneumovirus-associated ALRI to population estimates to yield the morbidity burden estimates by age bands and World Bank income levels. We also estimated human metapneumovirus-associated ALRI in-hospital deaths and overall human metapneumovirus-associated ALRI deaths (both in-hospital and non-hospital deaths). Additionally, we estimated human metapneumovirus-attributable ALRI cases, hospital admissions, and deaths by combining human metapneumovirus-associated burden estimates and attributable fractions of human metapneumovirus in laboratory-confirmed human metapneumovirus cases and deaths. FINDINGS: In 2018, among children younger than 5 years globally, there were an estimated 14·2 million human metapneumovirus-associated ALRI cases (uncertainty range [UR] 10·2 million to 20·1 million), 643 000 human metapneumovirus-associated hospital admissions (UR 425 000 to 977 000), 7700 human metapneumovirus-associated in-hospital deaths (2600 to 48 800), and 16 100 overall (hospital and community) human metapneumovirus-associated ALRI deaths (5700 to 88 000). An estimated 11·1 million ALRI cases (UR 8·0 million to 15·7 million), 502 000 ALRI hospital admissions (UR 332 000 to 762 000), and 11 300 ALRI deaths (4000 to 61 600) could be causally attributed to human metapneumovirus in 2018. Around 58% of the hospital admissions were in infants under 12 months, and 64% of in-hospital deaths occurred in infants younger than 6 months, of which 79% occurred in low-income and lower-middle-income countries. INTERPRETATION: Infants younger than 1 year have disproportionately high risks of severe human metapneumovirus infections across all World Bank income regions and all child mortality settings, similar to respiratory syncytial virus and influenza virus. Infants younger than 6 months in low-income and lower-middle-income countries are at greater risk of death from human metapneumovirus-associated ALRI than older children and those in upper-middle-income and high-income countries. Our mortality estimates demonstrate the importance of intervention strategies for infants across all settings, and warrant continued efforts to improve the outcome of human metapneumovirus-associated ALRI among young infants in low-income and lower-middle-income countries. FUNDING: Bill & Melinda Gates Foundation.

Results from the WHO external quality assessment for the respiratory syncytial virus pilot, 2016-17.

BACKGROUND: External quality assessments (EQAs) for the molecular detection of respiratory syncytial virus (RSV) are necessary to ensure the provision of reliable and accurate results. One of the objectives of the pilot of the World Health Organization (WHO) Global RSV Surveillance, 2016-2017, was to evaluate and standardize RSV molecular tests used by participating countries. This paper describes the first WHO RSV EQA for the molecular detection of RSV. METHODS: The WHO implemented the pilot of Global RSV Surveillance based on the WHO Global Influenza Surveillance and Response System (GISRS) from 2016 to 2018 in 14 countries. To ensure standardization of tests, 13 participating laboratories were required to complete a 12 panel RSV EQA prepared and distributed by the Centers for Disease Control and Prevention (CDC), USA. The 14th laboratory joined the pilot late and participated in a separate EQA. Laboratories evaluated a RSV rRT-PCR assay developed by CDC and compared where applicable, other Laboratory Developed Tests (LDTs) or commercial assays already in use at their laboratories. RESULTS: Laboratories performed well using the CDC RSV rRT-PCR in comparison with LDTs and commercial assays. Using the CDC assay, 11 of 13 laboratories reported correct results. Two laboratories each reported one false-positive finding. Of the laboratories using LDTs or commercial assays, results as assessed by Ct values were 100% correct for 1/5 (20%). With corrective actions, all laboratories achieved satisfactory outputs. CONCLUSIONS: These findings indicate that reliable results can be expected from this pilot. Continued participation in EQAs for the molecular detection of RSV is recommended.

Burden of influenza-associated respiratory hospitalizations in the Americas, 2010-2015.

BACKGROUND: Despite having influenza vaccination policies and programs, countries in the Americas underutilize seasonal influenza vaccine, in part because of insufficient evidence about severe influenza burden. We aimed to estimate the annual burden of influenza-associated respiratory hospitalizations in the Americas. METHODS: Thirty-five countries in the Americas with national influenza surveillance were invited to provide monthly laboratory data and hospital discharges for respiratory illness (International Classification of Diseases 10th edition J codes 0-99) during 2010-2015. In three age-strata (<5, 5-64, and ≥65 years), we estimated the influenza-associated hospitalizations rate by multiplying the monthly number of respiratory hospitalizations by the monthly proportion of influenza-positive samples and dividing by the census population. We used random effects meta-analyses to pool age-group specific rates and extrapolated to countries that did not contribute data, using pooled rates stratified by age group and country characteristics found to be associated with rates. RESULTS: Sixteen of 35 countries (46%) contributed primary data to the analyses, representing 79% of the America's population. The average pooled rate of influenza-associated respiratory hospitalization was 90/100,000 population (95% confidence interval 61-132) among children aged <5 years, 21/100,000 population (13-32) among persons aged 5-64 years, and 141/100,000 population (95-211) among persons aged ≥65 years. We estimated the average annual number of influenza-associated respiratory hospitalizations in the Americas to be 772,000 (95% credible interval 716,000-829,000). CONCLUSIONS: Influenza-associated respiratory hospitalizations impose a heavy burden on health systems in the Americas. Countries in the Americas should use this information to justify investments in seasonal influenza vaccination-especially among young children and the elderly.

Estimating the burden of influenza-associated hospitalizations and deaths in Chile during 2012-2014.

BACKGROUND: Influenza is a vaccine preventable disease that causes important morbidity and mortality worldwide. Estimating the burden of influenza disease is difficult. However, there are some methods based in surveillance data and laboratory testing that can be used for this purpose. OBJECTIVES: Estimating the burden of serious illness from influenza by means of hospitalization and death records during the period between 2012 and 2014, and using information from Severe Acute Respiratory Illness (SARI) surveillance. METHODS: To estimate the Chilean rate of influenza-associated hospitalizations and deaths, we applied the influenza positivity of respiratory samples tested in six SARI surveillance sentinel hospitals to the hospitalizations and deaths from the records with ICD-10 codes from influenza and pneumonia. RESULTS: Annually, 5320 people are hospitalized for influenza and 447 die for this cause. The annual influenza-associated hospitalization rate for the period was 71.5/100 000 person-year for <5 years old, 11.8/100 000 person-year for people between 5 and 64 years old; and 156.0/100 000 person-year for ≥65 years. The annual mortality rate for the period was 0.08/100 000 person-year for <5 years; 0.3/100 000 person-year for people between 5 and 64 years; and 22.8/100 000 person-year for ≥65 years. CONCLUSIONS: This is the first study of influenza burden in Chile. Every year an important quantity of hospitalizations and deaths result from influenza infection. In countries in temperate zones, it is important to know the burden of influenza in order to prepare the health care network and to assess preventive intervention currently in practice and the new ones to implementing.

Morbilidad y mortalidad asociada a hospitalizaciones por influenza pandémica A (H1N1) 2009 en dos hospitales de la Región Metropolitana y evaluación de su impacto económico / Morbidity and mortality associated to influenza A (H1N1) 2009 admissions in two hospitals of the Metropolitan area and analysis of its economic impact

Influenza A (H1N1) 2009 infection was an important cause of morbidity and mortality in Chile. Aim: To characterize the clinical pattern of hospitalized patients, identify risk factors associated with ICU admission or death, and evaluate its economic impact. Patients and Methods: Twenty five adult patients admitted to 2 hospitals in the Metropolitan Area from May 2009 to December 2010 with PCR confirmed H1N1 infection were analyzed. Total hospital charges were obtained and, using data of registered cases, expenses for the whole country during the first epidemic wave were estimated. Results: Aill cases presented a risk factor: age over 60 years old (n = 13, 52%), co-morbid conditions (n = 24, 96%) or pregnancy (n = 1, 4%). Pneumonia was present in 64% (n = 16) and 16% (n = 4) had hypotension. Only 6 patients (24%) had a CURB-65 score ≥ 2 and 36% (n = 9) requiring ICU admission. Case fatality rate was 16% (n = 4). By multivariate analysis, diabetes mellitus type 2 was independently associated with ICU admission or death (OR 8.12; IC95 1.11-59.2, p < 0.05). Hospital charges for those admitted to ICU or the intermediate care unit reached US$ 20,304, and US$ 1,262 for those admitted in general wards. We estimated US$ 20 million in hospital charges for influenza related hospitalizations during the first wave for the whole country. Conclusions: A high proportion of patients affected by influenza A (H1N1) 2009 infection required ICU admission during 2009-2010. Case fatality rate associated to this infection was high, and diabetes mellitus type 2 was a risk factor for ICU admission or death. Hospital charges were higher for those admitted in critical care units and represented an important expenditure for Chile during the first wave. The CURB-65 score was inappropriate to recognize patients at risk of hospitalization or ICU admission.

Introducción: La infección por influenza A (H1N1) pandémica representó una importante carga de morbilidad y mortalidad en Chile. Objetivo: Caracterización clínica de pacientes hospitalizados durante los años 2009 y 2010, identificar factores de riesgo asociados con ingreso a UCI o muerte y determinar el impacto económico de esta enfermedad. Pacientes y Métodos: Análisis de las características clínicas y evolución en un grupo de 25 pacientes adultos ingresados a dos hospitales institucionales en la Región Metropolitana confirmados por RPC desde mayo de 2009 a diciembre de 2010. Estudio de gastos hospitalarios y estimación de gasto nacional según registro de casos atendidos desde mayo a agosto de 2009. Resultados. Todos los pacientes presentaron una condición de riesgo: edad > 60 años (n: 13, 52%), co-morbilidad (n: 24, 96%) o embarazo ((n: 1, 4%). El 64% (n: 16) presentó neumonía y 16% tuvieron hipotensión arterial (n: 4). Sólo 6 pacientes (24%) tuvieron puntuación CURB-65 ≥ 2. Un 36% (n: 9) requirió manejo en Unidad de Cuidados Intensivos (UCI) y 4 pacientes fallecieron (16%). Por análisis multivariado, el antecedente de diabetes mellitus tipo 2 se asoció en forma significativa e independiente al ingreso a UCI o a un desenlace fatal (OR 8,12; IC95 1,11-59,2, p < 0,05). El gasto por paciente en aquellos que ingresaron a la UCI o Intermedio alcanzó los US$ 20.304 y US$ 1.262, para los que no ingresaron a estas unidades. Para Chile, se estimó un gasto mínimo de 20 millones de dólares por concepto de hospitalización para los primeros cuatro meses de la pandemia el 2009, asumiendo que 60% ingresó a UCI o Unidades Intermedias. Conclusiones: Una alta proporción de los pacientes afectados por influenza A (H1N1) 2009 requirió ingreso a UCI durante los años 2009-2010. La letalidad de esta infección fue elevada y la diabetes mellitus tipo 2 fue un factor de riesgo para ingreso a UCI o muerte. Los gastos hospitalarios fueron elevados, especialmente en los que ingresaron a unidades críticas. El sistema CURB-65 tiene una baja capacidad para reconocer riesgo de hospitalización o muerte en estos pacientes.

[Morbidity and mortality associated to influenza A (H1N1) 2009 admissions in two hospitals of the Metropolitan area and analysis of its economic impact]. / Morbilidad y mortalidad asociada a hospitalizaciones por influenza pandémica A (H1N1) 2009 en dos hospitales de la Región Metropolitana y evaluación de su impacto económico.

UNLABELLED: Influenza A (H1N1) 2009 infection was an important cause of morbidity and mortality in Chile. AIM: To characterize the clinical pattern of hospitalized patients, identify risk factors associated with ICU admission or death, and evaluate its economic impact. PATIENTS AND METHODS: Twenty five adult patients admitted to 2 hospitals in the Metropolitan Area from May 2009 to December 2010 with PCR confirmed H1N1 infection were analyzed. Total hospital charges were obtained and, using data of registered cases, expenses for the whole country during the first epidemic wave were estimated. RESULTS: Aill cases presented a risk factor: age over 60 years old (n = 13, 52%), co-morbid conditions (n = 24, 96%) or pregnancy (n = 1, 4%). Pneumonia was present in 64% (n = 16) and 16% (n = 4) had hypotension. Only 6 patients (24%) had a CURB-65 score ≥ 2 and 36% (n = 9) requiring ICU admission. Case fatality rate was 16% (n = 4). By multivariate analysis, diabetes mellitus type 2 was independently associated with ICU admission or death (OR 8.12; IC95 1.11-59.2, p < 0.05). Hospital charges for those admitted to ICU or the intermediate care unit reached US$ 20,304, and US$ 1,262 for those admitted in general wards. We estimated US$ 20 million in hospital charges for influenza related hospitalizations during the first wave for the whole country. CONCLUSIONS: A high proportion of patients affected by influenza A (H1N1) 2009 infection required ICU admission during 2009-2010. Case fatality rate associated to this infection was high, and diabetes mellitus type 2 was a risk factor for ICU admission or death. Hospital charges were higher for those admitted in critical care units and represented an important expenditure for Chile during the first wave. The CURB-65 score was inappropriate to recognize patients at risk of hospitalization or ICU admission.

Epidemiologic and virologic assessment of the 2009 influenza A (H1N1) pandemic on selected temperate countries in the Southern Hemisphere: Argentina, Australia, Chile, New Zealand and South Africa.

UNLABELLED: INTRODUCTION AND SETTING: Our analysis compares the most comprehensive epidemiologic and virologic surveillance data compiled to date for laboratory-confirmed H1N1pdm patients between 1 April 2009 - 31 January 2010 from five temperate countries in the Southern Hemisphere-Argentina, Australia, Chile, New Zealand, and South Africa. OBJECTIVE: We evaluate transmission dynamics, indicators of severity, and describe the co-circulation of H1N1pdm with seasonal influenza viruses. RESULTS: In the five countries, H1N1pdm became the predominant influenza strain within weeks of initial detection. South Africa was unique, first experiencing a seasonal H3N2 wave, followed by a distinct H1N1pdm wave. Compared with the 2007 and 2008 influenza seasons, the peak of influenza-like illness (ILI) activity in four of the five countries was 3-6 times higher with peak ILI consultation rates ranging from 35/1,000 consultations/week in Australia to 275/100,000 population/week in New Zealand. Transmission was similar in all countries with the reproductive rate ranging from 1.2-1.6. The median age of patients in all countries increased with increasing severity of disease, 4-14% of all hospitalized cases required critical care, and 26-68% of fatal patients were reported to have ≥1 chronic medical condition. Compared with seasonal influenza, there was a notable downward shift in age among severe cases with the highest population-based hospitalization rates among children <5 years old. National population-based mortality rates ranged from 0.8-1.5/100,000. CONCLUSIONS: The difficulty experienced in tracking the progress of the pandemic globally, estimating its severity early on, and comparing information across countries argues for improved routine surveillance and standardization of investigative approaches and data reporting methods.