Metapneumovirus humano: epidemiología y posibles tratamientos profilácticos / Human Metapneumovirus: Epidemiology and Possible Prophylactic Treatments

Resumen En el 2001, se identificó en Holanda al metapneumovirus humano (hMPV) como un "nuevo" agente etiológico causante de infecciones respiratorias agudas en infantes menores de 5 años; sin embargo, también se ha aislado en personas de la tercera edad e inmunocomprometidos. Este virus se considera como el segundo agente etiológico en enfermedades agudas del tracto respiratorio. En la actualidad, el costo estimado de las infecciones respiratorias agudas (IRA) en nuestro país es de 9,000 dólares estadounidenses por paciente hospitalizado. El hMPV es un miembro del género Metapneumovirus, familia Pneumoviridae, que pertenece al orden de los Mononegavirales, correspondiente a virus de ácido ribonucleico (RNA) monocatenario negativo, que consta de 8 genes en el orden 3'-N-P-M-F-M2-SH-G-L-5', y que codifica para 9 proteínas. De estas proteínas, la glicoproteína de fusión F está altamente conservada en el género Metapneumovirus y es el mayor determinante antigénico, y al no existir aún vacuna aprobada para este virus, se ha utilizado como un epítopo candidato para el diseño de una vacuna que confiera inmunidad al hospedero o como un blanco terapéutico en la creación de péptidos antivirales que inhiban la fusión del virus a su célula blanco y se evite la infección en sujetos de alto riesgo de contagio, ya que en la actualidad no se ha aprobado por la COFEPRIS ningún tratamiento profiláctico contra hMPV.

Abstract In 2001 in the Netherlands, Human metapneumovirus (hMPV) was identified as a "new" etiologic agent causing acute respiratory infections in children younger than 5 years old; however, it has also been isolated in the elderly and immunocompromised people. This virus is considered the second etiological agent in acute diseases of the respiratory tract. Currently, the estimated cost of IRAs in our country is of 9,000 USD per inpatient. hMPV is a member of the genus Metapneumovirus, family Pneumoviridae, and it belongs to the order Mononegavirales that is part of the negative single-stranded ribonucleic acid (RNA) virus, consisting of eight genes ordered: 3'-N-P-M-F-M2-SH-G-L-5 ', and which encodes for 9 proteins. Of these proteins, the F fusion glycoprotein is highly conserved in the genus Metapneumovirus, and is the major antigenic determinant, and because an approved vaccine doesn't exist, it has been used as a candidate epitope for the design of a vaccine that confers host immunity or as a therapeutic target in the creation of antiviral peptides that inhibit the fusion of the virus to its target cell and to avoid infection in subjects at high risk of contagion since there is currently none accepted by COFEPRIS as a prophylactic treatment against hMPV.

Study on Causes of Respiratory Disease to the Middle East Respiratory Syndrome-negative Subjects

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe cases of human respiratory disease. The current outbreak of infection with this virus in South Korea, which began on May 20, 2015, has infected 186 patients and caused 36 deaths within 2 months. In this study, to investigate the viral pathogen causing acute respiratory infections, multiplex/RT-PCR was performed on were obtained from nucleic acid of the Middle East Respiratory Syndrome-negative subjects. Viruses and atypical bacteria were detected in 39 of 337 (11.6%). Frequent viruses were human rhinovirus (n=11, 3.3%), human metapneumovirus (n=9, 2.7%), parainfluenza (n=9, 2.7%) and adenovirus (n=4, 1.2%). Mycoplasma pneumonia (M. pneumonia) was detected in 1.8 % (n=6). Out of 9 human metapneumovirus (hMPV) positive samples, 6 samples were successfully sequenced using F gene. And M. pneumoniae was sequencing of a repetitive region of the P1 gene. Phylogenetic analysis revealed that hMPV clustered into A2b lineage (n=4), B2 lineage (n=2) and M. pneumoniae clustered into two genotypes: Type 1 (n=4), Type 2a (n=2).

Study on Causes of Respiratory Disease to the Middle East Respiratory Syndrome-negative Subjects

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe cases of human respiratory disease. The current outbreak of infection with this virus in South Korea, which began on May 20, 2015, has infected 186 patients and caused 36 deaths within 2 months. In this study, to investigate the viral pathogen causing acute respiratory infections, multiplex/RT-PCR was performed on were obtained from nucleic acid of the Middle East Respiratory Syndrome-negative subjects. Viruses and atypical bacteria were detected in 39 of 337 (11.6%). Frequent viruses were human rhinovirus (n=11, 3.3%), human metapneumovirus (n=9, 2.7%), parainfluenza (n=9, 2.7%) and adenovirus (n=4, 1.2%). Mycoplasma pneumonia (M. pneumonia) was detected in 1.8 % (n=6). Out of 9 human metapneumovirus (hMPV) positive samples, 6 samples were successfully sequenced using F gene. And M. pneumoniae was sequencing of a repetitive region of the P1 gene. Phylogenetic analysis revealed that hMPV clustered into A2b lineage (n=4), B2 lineage (n=2) and M. pneumoniae clustered into two genotypes: Type 1 (n=4), Type 2a (n=2).

The Burden of Influenza, Respiratory Syncytial Virus and Human Metapneumovirus in Infants and Young Children in N. Greece, 2004-2013.

Background: According to the World Health Organization (WHO), acute respiratory infections are a leading cause of morbidity and mortality in infants and children worldwide. The aetiology of many of these respiratory infections remains unknown, highlighting the potential role of unrecognized pathogens. The aim of the present study is to determine the contribution of hMPV, RSV and influenza virus infections to acute respiratory infections in children< 6 years old, during 2004- 2013 in northern Greece. Materials and Methods: During 2004-2013, a total of 949 pharyngeal swabs were collected from patients younger than 6 years old, who were presented as Influenza-Like Illness (ILI) or other respiratory infections. The clinical specimens were divided into three age groups (0-6 months-119 specimens, 7 months-2 years-377 specimens, 3-6 years-453 specimens). A real-time onestep RT-PCR protocol with specific primers and probes for matrix protein and haemagglutinin genes was used in order to type and subtype influenza A and B viruses. A multiplex real-time one-step RT-PCR was used to detect hMPV and RSV in the extracted RNA. Results: Influenza viruses were detected in 343 out of 949 specimens, RSV in 82 and hMPV in 50 specimens. Conclusion: Our results show the significant role of these pathogens in childhood respiratory disease. They require constant medical attention as they represent a substantial health care burden among inpatients and outpatients.

Detección de Metapneumovirus Humano en niños menores de 5 años hospitalizados en Paraguay / Detection of Human Metapneumovirus in Children under Age 5 Hospitalized in Paraguay

El Metapneumovirus humano (hMPV) constituye una importante causa de Infecciones Respiratorias Agudas (IRAs) en niños hospitalizados. En Paraguay, las IRAs están entre las primeras causas de hospitalización durante la infancia, siendo los virus los principales agentes causales. Sin embargo, aún persiste una alta proporción de casos sin etiología identificada. La pandemia de Influenza en el año 2009, condujo a una intensificación de la vigilancia de las infecciones respiratorias, lo cual permitió al mismo tiempo la búsqueda de otros virus como el hMPV. Nuestro objetivo fue detectar hMPV en niños hospitalizados por IRAs en Paraguay durante el año 2009. Fueron estudiadas 240 muestras respiratorias de niños < 5 años internados por IRAs en Paraguay durante el año 2009, que habían resultado negativas para otros virus respiratorios. Fue utilizado el reactivo LightMix Kit human MPV de TIBMOLBIOL, para la detección del gen N de hMPV por PCR en Tiempo Real, siguiendo el procedimiento indicado por el fabricante. De las 240 muestras estudiadas, 29 (12%) resultaron positivas para hMPV, con la mayor detección en julio y agosto; predominando en mayores de 1 año. Los principales signos y síntomas fueron tos, fiebre y dificultad respiratoria; y las complicaciones más frecuentes neumonía y bronquiolitis. Estos resultados proveen las primeras evidencias en Salud Pública, de la importancia del hMPV asociado a niños hospitalizados por IRAs en Paraguay.

Human metapneumovirus (hMPV) is a significant cause of acute respiratory infection (ARI) in hospitalized children. In Paraguay, ARI is one of the leading causes of childhood hospitalization, with viruses being the primary causal agents. However, a large number of cases of unknown etiology remain. The influenza pandemic of 2009 led to intensified vigilance concerning respiratory infections and more thorough efforts to confirm the presence of viruses such as hMPV. Our objective was to detect hMPV in children hospitalized for ARI in Paraguay during 2009. We studied respiratory samples from 240 children age < 5 years hospitalized for IRAs in Paraguay during 2009 who had tested negative for other respiratory viruses. We used the hMPV-reactive LightMix® kit from TIB MOLBIOL for the detection of the nucleoprotein (N) gene by real-time PCR according to manufacturer-specified procedures. Of the 240 samples studied, 29 (12%) were positive for hMPV, with the highest rates detected in July and August (winter) predominating in children over 1 year of age. The most common signs and symptoms were cough, fever, and respiratory distress; while the most common complications were pneumonia and bronchiolitis. These results provide the first evidence concerning the prevalence of hMPV in children hospitalized for ARI in Paraguay.

Observations on pathogenicity between A and B subtype of hMPV in mice / 中华微生物学和免疫学杂志

ObjectiveTo investigate the difference of pathogenicity between the two genotypes of human metapneumovirus(hMPV) for the further research.MethodsAt various time after hMPV infection in BALB/c mice,viral titers of lung tissue were measured by real-time RT-PCR,pathology was assessed by a histopathological scoring system,airway responsiveness was assayed by animal lung function monitoring equipment.Pathogenicity was then measured by detailed evaluation through the results above.Results There is no significant difference in weight of mice between control group and experimental group through dynamic monitoring ; though the difference was exists in airway responsiveness and pathological changes of mice between control group and experimental group,the differences were not statistically in airway reaction,pathological changes and virus drops among the three groups of experimental group.ConclusionThere is no difference in pathogenicity between the two subtypes of hMPV in infection of BALB/c mice,viral genotype do not appear to be associated with pathogenicity.

A Case of Human Metapneumovirus Pneumonia in an Immunocompetent Adult Patient Mimicking with Influenza (A/H1N1-2009) Pandemic / 감염과화학요법

The human metapneumovirus virus (hMPV) is a recently described human respiratory pathogen. The virus has usually been associated with upper and lower respiratory tract infections in children. Since most of the available data on the clinical manifestations come from observational studies on children, relatively little is known of emerging hMPV infections in the adult population in Korea. A 32-year old female patient, presenting fever, chills, cough and sputum for 3 days progressed to severe pneumonia during the season of pandemic influenza A/H1N1-2009. RT-PCR screening of viral pathogens revealed hMPV. Clinical improvement was achieved a week after illness. This case represents severe hMPV pneumonia developed in an immunocompetent adult.

Vírus respiratório sincicial humano e metapneumovírus humano / Human respiratory syncitial vírus and human metapneumovirus

O Vírus respiratório sincicial humano (hRSV - human respiratory syncytial virus) e o Metapneumovírus humano (hMPV - human metapneumovirus) são os principais agentes etiológicos identificados nas infecções respiratórias agudas (IRAs). As IRAs representam importante causa de morbidade e mortalidade em crianças no mundo todo. hRSV e hMPV são membros da família Paramyxoviridae. São vírus envelopados, não-segmentados dotados de genoma de RNA de fita simples com sentido negativo. O hRSV é o agente viral melhor caracterizado neste grupo, associado à doença do trato respiratório inferior. Recentemente foi identificado um novo patógeno humano pertencente à subfamília Pneumovirinae, o hMPV, o qual possui similaridades com o hRSV, na sua organização genômica, estrutura viral, antigenicidade e sintomas clínicos. A subfamília Pneumovirinae contém dois gêneros: gênero Pneumovirus que contêm o hRSV, o RSV bovino (bRSV - bovine RSV), bem como os RSV ovino, caprino e o vírus da pneumonia murina, o segundo gênero Metapneumovirus que consiste do MPV aviário (aMPV - avian MPV) e hMPV. Neste trabalho, apresentamos uma breve revisão narrativa da literatura sobre aspectos importantes da biologia, epidemiologia e manifestações clínicas das infecções por estes dois vírus respiratórios.

The human respiratory syncytial virus (hRSV) and the human metapneumovirus (hMPV) are the main etiological agents of acute respiratory infections (ARIs). ARIs are an important cause of childhood morbidity and mortality worldwide. The hRSV and hMPV are members of the Paramyxoviridae family. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. The respiratory syncytial virus (hRSV) is the best characterized viral agent of this group, associated with respiratory diseases in the lower respiratory tract. Recently, a new human pathogen belonging to the subfamily Pneumovirinae was identified, the human metapneumovirus (hMPV), which is structurally similar to the hRSV in terms of genomic organization, viral structure, antigenicity, and clinical symptoms. The subfamily Pneumovirinae contains two genera: genus Pneumovirus contains the hRSV, the bovine RSV (bRSV), as well as the ovine and caprine RSV and pneumonia virus of mice, the second genus Metapneumovirus, consists of the avian MPV (aMPV) and hMPV. In this study, we present a brief review of the literature on important aspects of the biology, epidemiology, and clinical manifestations of infections by two respiratory viruses.

Apnea como forma de presentación de una infección por metapneumovirus humano / Apnea as a presenting symptom in human metapneumovirus infection

Metapneumovirus humano (MPVh), agente de infección respiratoria aguda baja (IRAB) recientemente descrito, ha sido detectado en 5,4 por ciento de lactantes chilenos hospitalizados por IRAB, con estudio negativo para virus respiratorio sincicial, adenovirus, parain-fluenza e influenza. Puede determinar bronquiolitis o neumonía en hospitalizados, en ocasiones llega a requerir conexión a ventilación mecánica y tratamiento en una unidad de cuidados intensivos. En algunos casos se presenta como apnea, situación que es más frecuente en prematuros. Está descrita su transmisión nosocomial. Presentamos el caso de un lactante de un mes de edad, con apnea, antecedente de prematurez e infección por MPVh y una probable adquisición intrahospitalaria. Se revisan las características clínicas de la infección por este agente y se discute la asociación con apnea e infección nosocomial. El MPVh debiera ser incluido en el estudio etiológico de lactantes que presentan apnea con estudio viral convencional negativo y como agente respiratorio de infección nosocomial

Human metapneumovirus (hMPV), a recently described pathogen of lower respiratory tract infections (LRTI), has been detected in 5,4 percent of Chilean infants hospitalized for LRTI whom are negative for adenovirus, respiratory syncytial virus, influenza and parainfluenza viruses. hMPV may cause bronchiolitis or pneumonia in hospitalized patients, and ocassionally require admission to intensive care units and mechanical ventilation. The infection has been associated with apnea, especially in preterm infants. Nosocomial dissemination has also been described. We present the case of a one-month-of age premature infant with apnea, and infection caused by hMPV of probable nosocomial aquisition. Clinical features of hMPV infection are reviewed and its association with apnea and nosocomial transmission is discussed. hMPV should be included in the routine diagnosis of respiratory viruses in infants with apnea and should be considered among the respiratory pathogens associated with nosocomial transmission