Respiratory infections and coinfections: geographical and population patterns / Infecciones y coinfecciones respiratorias: patrón geográfico y de circulación poblacional

Abstract Introduction: Acute respiratory infections are the second cause of mortality in children younger than five years, with 150.7 million episodes per year. Human orthopneumovirus (hOPV) and metapneumovirus (hMPV) are the first and second causes of bronchiolitis; type 2 human orthorubulavirus (hORUV) has been associated with pneumonia in immunocompromised patients. Objective: To define hOPV, hMPV and hORUV geographical distribution and circulation patterns. Method: An observational, prospective cross-sectional pilot study was carried out. Two-hundred viral strains obtained from pediatric patients were genotyped by endpoint reverse transcription polymerase chain reaction (RT-PCR). Results: One-hundred and eighty-six positive samples were typed: 84 hOPV, 43 hMPV, two hORUV and 57 co-infection specimens. Geographical distribution was plotted. hMPV, hOPV, and hORUV cumulative incidences were 0.215, 0.42, and 0.01, respectively. Cumulative incidence of hMPV-hORUV and hMPV-hOPV coinfection was 0.015 and 0.23; for hOPV-hMPV-hORUV, 0.035; and for hORUV-hOPV, 0.005. The largest number of positive cases of circulating or co-circulating viruses occurred between January and March. Conclusions: This study successfully identified circulation and geographical distribution patterns of the different viruses, as well as of viral co-infections.

Resumen Introducción: Las infecciones respiratorias agudas constituyen la segunda causa de mortalidad en los niños menores de cinco años, con 150.7 millones de episodios anuales. Entre los principales agentes etiológicos están Orthopneumovirus (hOPV) y metapneumovirus (hMPV) humanos como primera y segunda causa de bronquiolitis, respectivamente; Orthorubulavirus humano tipo 2 (hORUV) se ha asociado a neumonía en pacientes inmunocomprometidos. Objetivo: Definir patrones de distribución geográfica y de circulación de hOPV, hMPV y hORUV. Método: Se llevó a cabo un estudio piloto transversal prospectivo observacional. Se genotipificaron 200 aislamientos virales de pacientes pediátricos mediante transcripción inversa seguida de reacción en cadena de la polimerasa en punto final (RT-PCR). Resultados: Se tipificaron 186 muestras positivas: 84 de hOPV, 43 de hMPV, dos de hORUV y 57 de coinfecciones. Se trazó la distribución geográfica. Las incidencias acumuladas de hMPV, hOPV y hORUV fueron de 0.215, 0.42 y 0.01, respectivamente. Las incidencias acumuladas de la coinfección de hMPV-hORUV y hMPV-hOPV fueron de 0.015 y 0.23; de hOPV-hMPV-hORUV, de 0.035; y de hORUV-hOPV, de 0.005. El mayor número de casos positivos de virus circulantes o cocirculantes se presentó entre enero y marzo. Conclusiones: Fue posible identificar patrones de circulación y distribución geográfica de los diferentes virus, así como de las coinfecciones virales.

Human metapneumovirus in Southern Brazil

INTRODUCTION Infections caused by respiratory viruses are important problems worldwide, especially in children. Human metapneumovirus (hMPV) is a respiratory pathogen and causes severe infections with nonspecific symptoms. This study reports the hMPV occurrence and dissemination in southern Brazil and compares the frequency of occurrence of this virus and the human respiratory syncytial virus (hRSV) in the epidemiological weeks in a three-year period (2009-2011). METHODS: In total, 545 nasopharyngeal (NP) specimens from individuals with Severe Acute Respiratory Syndrome (SARS) who were negative for other seven respiratory viruses were analyzed for the presence of hMPV. Human metapneumovirus was detected by direct immunofluorescence and real-time reverse transcription polymerase chain reaction. RESULTS: hMPV was detected in 109 patients from the main geographic regions of the southernmost state of Brazil, presenting similar overall prevalence in males (46.8%) and females (53.2%). Among children who were less than six years old, hMPV was detected in 99 samples of all age groups, with a higher frequency in infants who were less than one year old (45.7%) compared to all other age groups until six years. hMPV and hRSV infection occurred in almost the same epidemiological weeks (EWs) of each year, with peaks of incidence between EW 31/37 and EW 26/38 for the years 2009 and 2011, respectively. hMPV was further detected in several cases of SARS and it was the only virus detected in three deaths. CONCLUSIONS These findings indicate that hMPV is in circulation in southern Brazil and highlight the importance of diagnosing hMPV for influenza-like illness in the population. (AU)

Detección de virus parainfluenza en pacientes inmunocomprometidos e inmunocompetentes atendidos en un hospital terciario de la Ciudad de São Paulo, Brasil / Detection of parainfluenza virus in immunocompromised and immunocompetent patients in a tertiary hospital in Sao Paulo, Brazil

Parainfluenza virus infections (PIV) were evaluated in patients with mild and severe infections through real time PCR. One thousand and sixty-seven samples were collected from subjects as follows: 233 adult renal transplanted outpatients, 129 children with congenital heart disease, 381 with adult hematopoietic stem cell patients and 324 hospitalized patients suspected of influenza A (H1N1) pdm09 infection. PIV was detected in 74 (6.9%) samples. VPI-3 was the most frequent (60.8%) and a higher risk was observed for older adults (p = 0.018) and for those who were hematopoietic stem cell transplanted. Further studies are needed to understand the VPI role in patients' at risk for developing serious illness.

Se evaluó la infección por virus parainfluenza (VPI) en pacientes con infecciones leves y graves mediante RPC en tiempo real. Se analizó un total de 1.067 muestras: 233 provenían de pacientes ambulatorios adultos receptores de trasplantes renales, 129 de niños con cardiopatía congénita, 381 de pacientes receptores de trasplantes de precursores hematopoyéticos adultos y 324 de pacientes hospitalizados con sospecha de influenza A (H1N1) pdm09. Se detectó VPI en 74 muestras (6,9%). Siendo VPI-3 el virus más frecuente (60,8%), se observó un mayor riesgo para los adultos mayores (p = 0,018) y para aquellos que fueron receptores de precursores hematopoyéticos. Son necesarios estudios adicionales para entender el papel del VPI en pacientes de riesgo para desarrollar enfermedad grave.

Sentinel surveillance of influenza and other respiratory viruses, Brazil, 2000-2010

There are scanty data on the epidemiology of influenza and other respiratory viruses in South America and Brazil. The aim of this study was to summarize the data from the Brazilian surveillance system of influenza and other respiratory viruses and discuss the patterns of viral circulation. The system is based on detecting cases of influenza-like illness in sentinel sites and weekly collection of five nasopharyngeal secretions samples, which are processed in state public health laboratories for respiratory viruses by indirect immunofluorescence assay. Data from 2000 to 2010 were described over time, by region, gender, and age group, and an analysis of Spearman correlation was performed between monthly influenza detection and rainfall and temperature data in two state capitals with the highest number of positive samples, one from the northeast region (Maceió) and other from the southern region (Curitiba). There were 3,291,946 visits for influenza-like illness; of these, 37,120 had samples collected and 6421 tested positive: 1690 (26%) influenza A, 567 (9%) influenza B, 277 (4%) parainfluenza 1, 571 (9%) parainfluenza 2, 589 (9%) parainfluenza 3, 742 (12%) adenovirus, and 1985 (31%) respiratory syncytial virus. Overall, increased activity of respiratory syncytial virus was observed from March to June, preceding the peak of influenza activity, from May to August, but with regional differences. In Maceió, there was a weak correlation between temperature and influenza detection (ρ = 0.05), but a moderate positive correlation between rainfall and influenza detection (ρ = 0.36). In Curitiba, a high correlation was observed between the decrease in temperature and rainfall and the increase in influenza detection (ρ = -0.83 and -0.78 respectively). These data are important to guide public health control measures as the best time for influenza vaccination and use of antivirals.

Metaneumovirus humano en niños: primeros casos en Colombia / Human metapneumovirus in children: first cases in Colombia

El metaneumovirus humano es un nuevo patógeno asociado a infecciones respiratorias, principalmente en niños, que produce cuadros clínicos que van desde leves hasta graves, los cuales pueden incluso requerir tratamiento en unidades de cuidados intensivos. Hasta el momento, la reacción en cadena de la polimerasa con transcripción inversa y el cultivo celular son los métodos más usados para su diagnóstico. Se presentan los seis primeros casos de metapneumovirus humano en niños de Medellín, Colombia.

Human metapneumovirus is a newly discovered pathogen associated with respiratory disease and occurring mainly in children. It produces an acute viral respiratory disease picture that varies from mild disease to severe, and which can require strict surveillance in intensive care units. Currently, reverse transcriptase polymerase chain reaction and cell culture are the most common methods for its diagnosis. The first six cases of human metapneumovirus in Colombia are presented from Medellín.

Infección respiratoria por metapneumovirus humano en pacientes adultos mayores / Respiratory infections caused by metapneumovirus in elderly patients

Human metapneumovirus infections are increasingly recognized among adult patients and the aim of this report is to present a series of 4 cases admitted during the winter of 2010. All were detected by direct fluorescence anti-bodies assay of respiratory samples and all were female patients with an age range of 79 to 95 years, including two bedridden cases, one with dementia and three with chronic obstructive pulmonary disease. One patient presented with parainfluenza 3 virus coinfection. Patients presented with pneumonía in 3 cases (interstitial pattern in 2 and lobar consolidation in the other) or acute exacerbation of chronic bronchitis in the remaining case. Symptoms were present for 3 to 7 days before admission and 3 have wheezing. All had hypoxemic or global respiratory failure and lymphopenia (< 1.000/mm³). Hospitalization lasted for 5 to 20 days, marked in the 3 cases that survived by prolonged bronchial obstructive manifestations. Two cases required non invasive mechanical ventilation. Human metapneumovirus infections can decompensate elderly patients with chronic respiratory diseases generating hospital admission and a prolonged morbidity marked by obstructive manifestations and sometimes can become into death.

Las infecciones por metapneumovirus (MPVH) son poco conocidas en pacientes adultos y el objetivo de esta publicación es presentar una serie de 4 casos observados en pacientes hospitalizados durante el invierno de 2010. Los casos se identificaron por inmunofluorescencia directa en muestras respiratorias. Todos los pacientes fueron de sexo femenino con un rango de edad 79 a 95 años, dos de ellos postrados, uno con demencia y 3 con enfermedad pulmonar obstructiva crónica. La manifestación clínica correspondió a neumonía en 3 casos (2 de tipo intersticial y una con consolidación lobar) y bronquitis crónica reagudizada en el caso restante, con una duración sintomática de 3 a 7 días antes de la hospitalización. Un caso presentó co-infección con virus parainfiuenza 3. Las sibilancias estuvieron presentes en 3 casos y todos presentaron falla respiratoria hipoxémica o global con linfopenia (< 1.000/mm³). La hospitalización tuvo una duración de 5 a 20 días, marcada en los 3 casos que sobrevivieron por una signología obstructiva prolongada. Dos pacientes requirieron ventilación mecánica no invasora. Las infecciones por MPVH representan una causa de hospitalización por descompensación de patologías respiratorias crónicas en pacientes adultos ancianos, tienen una morbilidad prolongada con signología obstructiva marcada y pueden ocasionar la muerte.

Genotypes and clinical data of respiratory syncytial virus and metapneumovirus in brazilian infants: a new perspective

The aim of this study was to determine if there was a correlation between respiratory syncytial virus (RSV) and metapneumovirus (MPV) genotypes and clinical data of Brazilian infants hospitalized for acute lower respiratory infection. The viruses in the patients' nasopharyngeal secretions were studied using the polymerase chain reaction and phylogenetic analysis. The study assessed 144 infants; 31.9 percent were RSV positive and 5.6 percent were MPV positive. Statistical analysis was performed using the chi-squared test, Fisher's test, Odds ratio, univariate logistic regression, non-conditional multivariate logistic regression and the forward - stepwise method. Multivariate analysis confirmed a significant relationship between a positive PCR test for RSV and hospitalization during the month of May and with pulse oximetry less than 90 percent. The phylogenetic analysis indicated the genotypes GA2, GA5, SAA1 (Group A), SAB1, SAB3 and BA (Group B) for RSV and Group B, subgroup B1, for MPV.

Virus Respiratorios en Menores de Diez Años con Infección Respiratoria en el Hospital Militar Central de Bogotá 2000-2001 / Respiratory virus in children aged less than 10 years old suffering from respiratory infection in the Hospital Militar Central in Bogota from 2000-2001

Objetivo: Se llevo a cabo un estudio en niños que consultaban por infección respiratoria aguda al Hospital Militar (Hosmil) de Bogota, Colombia, con el objetivo de estimar la frecuencia de enfermedad respiratoria aguda en esa institución producida por algunos virus respiratorios. Métodos: Durante 18 meses, de Marzo de 2000 a Septiembre de 2001, se seleccionaron semanalmente tres a cinco niños con infección respiratoria de aquellos que consultaban al servicio de emergencia o de consulta ambulatoria del Hospital. De cada uno de ellos se obtuvo muestras nasofaringeas que fueron examinadas por inmunofluorescencia para virus sincitial respiratorio (VSR), influenza, adenovirus y parainfluenza. Resultados: Se estudiaron 139 niños de los cuales el 40 por ciento fue positivo para alguno de los virus estudiados. El agente viral mas frecuentemente encontrado fue el VSR (27 por ciento), seguido por el virus de la influenza (5 por ciento) y adenovirus (3 por ciento). La circulación de VSR coincidía con los picos de hospitalizaciones por IRA y por neumonía y del hospital, era mas frecuente en los niños menores de 3 años y se encontraba presente durante todo el año. Conclusiones: Los virus respiratorios causan gran parte de la enfermedad respiratoria moderada o severa en el Hosmil y el VSR es el agente más importante entre ellos.

Objective: A study was carried out on children seeking medical care at the Hospital Militar (Hosmil) in Bogota due to acute respiratory infection; it was aimed at estimating the frequency of respiratory virus-associated acute respiratory disease (ARD) in children aged under 10. Methods: Three to five children aged less than 10 years old were selected every week from the hospital's emergency ward or ambulatory services over an 18-month period from March 2000 to September 2001. Nasopharyngeal samples were obtained from them and processed using indirect immunofluorescence. The relative frequency of respiratory syncytial virus (RSV), influenza, adenovirus and parainfluenza were calculated. Results: Around 40 percent of the 139 children examined proved positive for at least one respiratory virus. RSV was the most frequently found virus (27 percent positivity: 38 patients) followed by influenza (5 percent: 7 patients) and adenovirus (3 percent: 4 patients). RSV circulation peaks coincided with peaks related to ARD and pneumonia in the hospital: it was found most frequently in children aged less than 3 and was present throughout the year. Conclusion: Respiratory viruses were an important cause of moderate to severe respiratory illness in children seeking health care at Hosmil; RSV was the leading agent amongst such viruses.

Metapneumovirus humano como causa de hospitalización en niños bajo 3 años de edad, con infección respiratoria aguda, durante el año 2004 / Human metapneumovirus as hospitalization cause in children under 3 years old with acute respiratory infections during 2004

Metapneumovirus humano (MPVh) fue detectado entre julio y noviembre en 15 de 123 niños bajo 3 años de edad hospitalizados por infección respiratoria aguda (12 por ciento). Las muestras fueron estudiadas mediante técnicas de biología molecular (RPC-TR de muestra de hisopado nasofaríngeo y/o de sobrenadante de cultivo). El 67 por ciento de los niños hospitalizados con MPVh tenían menos de 1 año de edad, todos ellos presentaron tos y fiebre y el principal motivo de hospitalización fue el requerimiento de oxígeno en 73 por ciento de los casos. Si bien un tercio de los pacientes tenía patología previa, su evolución clínica no fue diferente respecto de los niños previamente sanos. El patrón radiológico mostró aumento de la trama intersticial, con focos de consolidación en 6 casos (40 por ciento). El diagnóstico más frecuente fue síndrome bronquial obstructivo o bronquiolitis, asociado o no a neumonía. Destaca la necesidad de un método de diagnóstico rápido para optimizar el diagnóstico diferencial, manejo y control de infecciones en estos pacientes.

Human metapneumovirus was detected in 15 of 123 children (12 percent) younger than 3 years of age hospitalized for treatment of acute respiratory infection between July and November 2004. The virus was detected by RT-PCR directly from nasopharyngeal swabs and/or from supernatants after cell culture. Children infected with hMPV were mostly younger than one year of age (67 percent), all presenting with fever and cough. The main cause for hospitalization was the need for oxygen therapy (73 percent). Four hMPV positive children had an identifiable co-morbid condition but had a similar clinical evolution when compared to previously healthy infants. Chest radiography showed an increase in interstitial infiltrates with focal consolidation in 6 children. Obstructive bronchial syndrome and bronchiolitis, with or without pneumonia, were the most frequent diagnosis associated with hMPV positivity. A rapid and sensitive diagnostic method is required to improve diagnosis and treatment of these patients.

Virological studies on para-influenza virus isolated from Kafr El-Sheikh governorate

In the present study, 250 swabs [174 nasal and 76 ocular] and 510 serum samples were collected from different farms at Kafr El-Sheikh Governorate from calves, feed lot and adult cattle of different ages for P1-3 isolation, identification and seroprevalence. Some of the animals were suffering from the disease. The results indicated that 15 and 12 samples idenified as P13 positive by FAT and 12 VNT, respectively. The serodiagnosis results of 510 examined serum samples by HI and SNT revealed that the P13 anti bodies were detected in diseased animals at percentages of 32% and 23.4%, respectively. While in apparently healthy animals in percentages of 31% and 13.1%, respectively

Serologic evidence of human metapneumovirus circulation in Uruguay

First identified in 2001, the human metapneumovirus (hMPV), is a respiratory tract pathogen that affects young children, elderly, and immunocompromised patients. The present work represents the first serologic study carried out in Uruguay. It was performed with the purpose of obtaining serological evidence of hMPV circulation in Uruguay and to contribute to the few serologic reports described until now. Sixty nine serum samples collected between 1998 and 2001 by vein puncture from patients without respiratory symptoms or underlying pathology aged 6 days to 60 years were examined using an indirect immunofluorescence assay (IFA). The global seropositivity rate of the samples was 80 percent (55/69). Rates of 60 percent (15/25) and 91 percent (40/44) were observed for the pediatric and adult cohorts, respectively. Results obtained from a longitudinal analysis of 6 children aged 6 days to 18 months are discussed. These results are a clear evidence of hMPV circulation in Uruguay, at least since 1998, and reinforce the previous data on worldwide circulation of this virus.