Human metapneumovirus and respiratory syncytial virus, Brazil

We describe the epidemiologic and clinical characteristics of 111 children attending clinics and hospitals in Aracaju, northeast Brazil, with acute respiratory infections attributable to human metapneumovirus (HMPV), respiratory syncytial virus (RSV), or both in May and June 2002. Fifty-three (48%) children were infected with RSV alone, 19 (17%) with HMPV alone, and 8 (7%) had RSV/HMPV co-infections.     

RSV 2010: Recent advances in research on respiratory syncytial virus and other pneumoviruses

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are important causes of acute respiratory tract disease in infants, immunocompromised patients and the elderly. The Seventh International RSV symposium was held in Rotterdam, the Netherlands, from December 2-5, 2010. This symposium is the flagship event for leading investigators engaged in RSV and HMPV research around the world. The objective of the symposium was to provide a forum to review recent advances in research on RSV, HMPV and other pneumoviruses. More than 200 young and established investigators attended the meeting. Over a hundred papers were presented in 55 oral presentations and six poster sessions, providing all participants the opportunity to share and to discuss their work. The Chanock lecture, instituted in 2003 to acknowledge important contributors to RSV research, was presented by Peter Collins. As a preface to his lecture, he presented an in memoriam of the late Dr. Robert M. Chanock, who played a key role in the characterization of RSV as a human pathogen. The current report presents highlights of the meeting, covering topics from basic virology, pathogenesis and immunology to clinical studies, therapeutics and vaccine development.     

Modelling the impact of respiratory syncytial virus (RSV) vaccine and immunoprophylaxis strategies in New Zealand

BackgroundMathematical models of respiratory syncytial virus (RSV) transmission can help describe seasonal epidemics and assess the impact of potential vaccines and immunoprophylaxis with monoclonal antibodies (mAb).MethodsWe developed a deterministic, compartmental model for RSV transmission, which was fitted to population-based RSV hospital surveillance data from Auckland, New Zealand. The model simulated the introduction of either a maternal vaccine or a seasonal mAb among infants aged less than 6 months and estimated the reduction in RSV hospitalizations for a range of effectiveness and coverage values.ResultsThe model accurately reproduced the annual seasonality of RSV epidemics in Auckland. We found that a maternal vaccine with effectiveness of 30–40% in the first 90 days and 15–20% for the next 90 days could reduce RSV hospitalizations by 18–24% in children younger than 3 months, by 11–14% in children aged 3–5 months, and by 2–3% in children aged 6–23 months. A seasonal infant mAb with 40–60% effectiveness for 150 days could reduce RSV hospitalizations by 30–43%, 34–48% and by 14–21% in children aged 0–2 months, 3–5 months and 6–23 months, respectively.ConclusionsOur results suggest that either a maternal RSV vaccine or mAb would effectively reduce RSV hospitalization disease burden in New Zealand. Overall, a seasonal mAb resulted in a larger disease prevention impact than a maternal vaccine.     

Virus-like particle vaccine induces cross-protection against human metapneumovirus infections in mice

Human metapneumovirus (HMPV) is a paramyxovirus that causes acute respiratory-tract infections in children and adults worldwide. A safe and effective vaccine could decrease the burden of disease associated with this novel pathogen. We engineered HMPV viral-like particles (HMPV-VLPs) derived from retroviral core particles that mimic the properties of the viral surface of two HMPV viruses of either lineage A or B. These VLPs functionally display F and G HMPV surface glycoproteins. When injected in mice, HMPV-VLPs induce strong humoral immune response against both homologous and heterologous strains. Moreover, the induced neutralizing antibodies prevented mortality upon subsequent infection of the lungs with both homologous and heterologous viruses. Upon challenge, viral titers in the lungs of immunized animals were significantly reduced as compared to those of control animals. In conclusion, a HMPV-VLP vaccine that induces cross-protective immunity in mice is a promising approach to prevent HMPV infections.     

Rates of hospitalisation for influenza, respiratory syncytial virus and human metapneumovirus among infants and young children

To inform the development of a national influenza immunisation programme and the potential role of antiviral drugs in young children, we studied 613 children aged 71 months or younger who attended Leicester Childrens' Hospital during winter 2001-2002. During periods of respiratory syncytial virus (RSV), influenza, and human metapneumovirus activity, an estimated 12.2% (95% CI: 11.4-13.1), 7.1% (6.3-7.9), and 2.5% (2.1-2.9), respectively, of all medical cases assessed in the hospital were associated with these infections. The respective rates of hospital assessments for RSV, influenza, and human metapneumovirus (HMPV) were 1042 (95% CI: 967-1021), 394 (348-443), and 223 (189-262) per 100,000 children, and for admissions were 517 (465-574), 144 (117-175), and 126 (101-156) per 100,000. Few children with influenza had a prior risk factor. Children with influenza were admitted a median of 4 days after onset of illness and none was coded at discharge as influenza. We conclude that antivirals have little role in the hospital management of children with influenza. Our data provide health economists with information to evaluate the place of universal immunisation of young children against influenza. Hospitalisation rates decreased markedly with referral age, so vaccine would need to be given in early infancy for maximum benefit.     

Human metapneumovirus infections in hospitalized children

We evaluated the percentage of hospitalizations for acute respiratory tract infections in children < or =3 years of age attributable to human metapneumovirus (HMPV) and other respiratory viruses in a prospective study during winter and spring 2002. We used real-time polymerase chain assays and other conventional diagnostic methods to detect HMPV, human respiratory syncytial virus (HRSV), and influenza viruses in nasopharyngeal aspirates of children. HMPV was detected in 12 (6%) of the 208 children hospitalized for acute respiratory tract infections, HRSV in 118 (57%), and influenza A in 49 (24%). Bronchiolitis was diagnosed in 8 (68%) and pneumonitis in 2 (17%) of HMPV-infected children; of those with HRSV infection, bronchiolitiss was diagnosed in 99 (84%) and pneumonitis in 30 (25%). None of the HMPV-infected children was admitted to an intensive-care unit, whereas 15% of those with HRSV or influenza A infections were admitted. HMPV is an important cause of illness in young children with a similar, although less severe, clinical presentation to that of HRSV.     

Genetic variability of human metapneumovirus amongst an all ages population in Cambodia between 2007 and 2009

First identified in 2001, human metapneumovirus (HMPV) is a novel pathogen and causative agent of acute respiratory tract infection. Re-infection with HMPV is common, and currently there is no available vaccine against HMPV infection. Two genotypes of HMPV have been identified, A and B, both of which can be divided further into at least two distinct sub-genotypes. Here we report the results of the first study to investigate the genetic variability of HMPV strains circulating within Cambodia. The overall incidence of HMPV infection amongst an all-ages population of patients hospitalised with ALRI in Cambodia during 3 consecutive years, between 2007 and 2009, was 1.7%. The incidence of HMPV infection was highest amongst children less than 5 years of age, with pneumonia or bronchopneumonia the most frequent clinical diagnoses across all age groups. The incidence of HMPV infection varied annually. As anticipated, genetic diversity was low amongst the conserved F gene sequences but very high amongst G gene sequences, some strains sharing as little as 56.3% and 34.2% homology at the nucleotide and amino acid levels, respectively. Simultaneous co-circulation of strains belonging to the HMPV sub-genotypes B1, B2 and lineage A2b, amongst patients recruited at 2 geographically distinct provincial hospitals, was detected. Sub-genotype B2 strains were responsible for the majority of the infections detected, and a significant (p  =  0.013) association between infection with lineage A2b strains and disease severity was observed.     

WHO consultation on Respiratory Syncytial Virus Vaccine Development Report from a World Health Organization Meeting held on 23–24 March 2015

Respiratory syncytial virus (RSV) is a globally prevalent cause of lower respiratory infection in neonates and infants. Despite its disease burden, a safe and effective RSV vaccine has remained elusive. In recent years, improved understanding of RSV biology and innovations in immunogen design has resulted in the advancement of multiple vaccine candidates into the clinical development pipeline. Given the growing number of vaccines in clinical trials, the rapid pace at which they are being tested, and the likelihood that an RSV vaccine will reach the commercial market in the next 5–10 years, consensus and guidance on clinical development pathways and licensure routes are needed now, before large-scale efficacy trials commence. In pursuit of this aim, the World Health Organization convened the first RSV vaccine consultation in 15 years on the 23rd and 24th of March, 2015 in Geneva, Switzerland. The meeting's primary objective was to provide guidance on clinical endpoints and development pathways for vaccine trials with a focus on considerations of low- and middle-income countries. Meeting participants reached consensus on candidate case definitions for RSV disease, considerations for clinical efficacy endpoints, and the clinical development pathway for active and passive immunization trials in maternal and pediatric populations. The strategic focus of this meeting was on the development of high quality, safe and efficacious RSV preventive interventions for global use and included: (1) maternal/passive immunization to prevent RSV disease in infants less than 6 months; (2) pediatric immunization to prevent RSV disease in infants and young children once protection afforded by maternal immunization wanes.     

Invasive pneumococcal and meningococcal disease: association with influenza virus and respiratory syncytial virus activity?

Few studies have examined the relationship between viral activity and bacterial invasive disease, considering both influenza virus and respiratory syncytial virus (RSV). This study aimed to assess the potential relationship between invasive pneumococcal disease (IPD), meningococcal disease (MD), and influenza virus and RSV activity in The Netherlands. Correlations were determined between population-based data on IPD and MD during 1997-2003 and influenza virus and RSV surveillance data. Incidence rate ratios of disease during periods of high influenza virus and RSV activity over the peri-seasonal and summer baseline periods were calculated. The analyses comprised 7266 and 3072 cases of IPD and MD. When data from all seasons were included, the occurrence of pneumococcal bacteraemia and MD correlated significantly with influenza virus and RSV activity both in children and adults. Periods of increased influenza virus and RSV activity showed higher rates of pneumococcal bacteraemia in older children and adults than the peri-season period. Rates of MD in children were also higher during periods of increased influenza virus activity; the same appeared true for MD in older children during periods of increased RSV activity. Although no causal relationship may be inferred from these data, they support a role for influenza virus and RSV in the pathogenesis of IPD and MD.     

The absence of enhanced disease with wild type respiratory syncytial virus infection occurring after receipt of live, attenuated, respiratory syncytial virus vaccines

Early in the development of respiratory syncytial virus (RSV) vaccines severe disease occurred in children after receipt of formalin-inactivated RSV vaccine. Continuing efforts to develop an appropriately attenuated and immunogenic live RSV vaccine have given opportunities to assure that live vaccines are safe through surveillance of children after vaccination. In the present study, the rate of RSV-associated upper respiratory tract illness in 388 children was lower in RSV vaccinated children than in controls (14% versus 20% in a 6-24 month old group and 16% versus 25% in infants). Additionally, there was no evidence that vaccination predisposed to more severe lower respiratory tract illness. Thus infection with a series of live attenuated RSV vaccines did not result in enhanced disease upon infection with wild type RSV. The impact of RSV during this surveillance will inform the design of future efficacy studies with RSV vaccines.     

Emerging Human Metapneumovirus Gene Duplication Variants in Patients with Severe Acute Respiratory Infection,China, 2017–2019

We detected human metapneumovirus (HMPV) in 72 (7.1%) of 1,021 patients hospitalized with severe acute respiratory infection in Luohe, China, during 2017–2019. We detected HMPV most frequently in young children and less often in adults. HMPV genotype A2c variants 111 nt and 180 nt duplications predominated, demonstrating their continuing geographic spread.     

Human metapneumovirus infection among children, Bangladesh

We confirmed circulation of human metapneumovirus (HMPV) among children with febrile and respiratory illness in an urban slum in Dhaka, Bangladesh, during active surveillance in 2001. HMPV was the most common single virus identified among febrile children and appears to contribute to the high rates of illness in this population.     

湖南省2012-2014年发热呼吸道症候群哨点监测结果及分析

目的 通过“发热呼吸道症候群监测”了解湖南省主要呼吸道病毒流行情况及病原谱分布,为发热呼吸道症候群防控及临床诊疗提供科学依据。 方法 2012年1月-2014年12月,从符合发热呼吸道症候群定义的患者身上采集鼻/咽拭子、肺泡灌洗液、痰液样本。采用基于毛细管凝胶电泳的“9+7呼吸道病毒多重PCR检测法”对标本中流感病毒(Flu)、呼吸道腺病毒(AdV)、呼吸道合胞病毒(RSV)、人鼻病毒(hRV)、副流感病毒(PIV)、偏肺病毒(HMPV)、人博卡病毒(hBoV)和人冠状病毒(hCoV)共8种病毒的16个亚型进行核酸检测。使用SPSS17.0统计学软件对个案信息及检测结果进行统计学分析。 结果 2012年1月-2014年12月,从哨点医院采集各类呼吸道标本共961份,其中男性病例标本595份,占61.91%;女性病例标本366份,占38.09%。在961份已检测的标本中,通过PCR检出阳性标本456份,阳性检出率为47.45%。男、女病例标本的阳性检出率差异无统计学意义(P>0.05)。按年龄将病例分为7个年龄组,各年龄组的阳性检出率分别为 1岁以下(52.80%)、1~2岁(66.53%)、2~5岁(49.86%)、6~15岁(25.56%)、16~49岁(11.11%)、50~64岁(17.39%)和65岁以上(19.40%)。在456份病毒阳性的标本中,检出混合感染48例,非混合感染408例。在检出的呼吸道病毒中,AdV、RSV和Flu所占的比例最大(病原谱构成比分别为25.90%、21.31%和17.73%),其次为hRV(14.14%)和PIV(11.75%);HMPV(4.78%)和hBoV(3.98%)检出较少,而hCoV只有两例阳性被检出。男性、女性的病原构成差异无统计学意义(P>0.05)。各年龄段的病原构成差异有统计学意义(P<0.05),其中2岁以下的儿童病例中检出的病毒以RSV(29.36%)和AdV(23.02%)为主,其次为PIV(13.10%)、hRV(11.90%)和Flu(11.11%);2~5岁的儿童病例中,AdV所占比例最大(34.02%),其次为hRV(18.56%)、Flu(18.04%)和RSV(15.46%);6~15岁少儿病例中以Flu(31.43%)和PIV(34.29%)为主,其次为AdV(17.14%)和hRV(14.29%);在16~49岁的病例中,只有Flu检出;在50岁以上老年病例中,病原构成以Flu(68.41%)为主,其余为PIV(10.53%)、HMPV(10.53%)和RSV(10.53%)。监测还发现,Flu、AdV有夏季和冬春季两个流行高峰;RSV有冬春季流行高峰;hRV有秋冬季流行高峰。 结论 所监测的8种呼吸道病毒是引发严重急性呼吸道住院病例的重要病原。5岁以下儿童及65岁以上的老人可能是主要的易感人群。其中,RSV、AdV、 Flu可能是引发儿童病毒性呼吸道感染的主要病原,而Flu则可能是引发成人病毒性呼吸道感染的主要原因。因此,应将这几种病毒作为呼吸道病毒防控的重点,进行更多的监测和更深入的研究。     

Climatic, temporal, and geographic characteristics of respiratory syncytial virus disease in a tropical island population

Respiratory syncytial virus (RSV) is an important cause of morbidity in children worldwide, although data from equatorial regions are limited. We analysed climatic, spatial, and temporal data for children presenting to hospitals in Lombok island, Indonesia with clinical pneumonia. During the study period, 2878 children presented and 741 RSV cases were identified. In multivariate analysis with an 8-day lag, occurrence of rain was associated with 64% higher incidence of RSV disease [incidence rate ratio (IRR) 1.64, 95% confidence interval (CI) 1.13-2.38]. A 1% rise in mean relative humidity and 1 degree C increase in mean air temperature was associated with a 6% (IRR 1.06, 95% CI 1.03-1.10) and 44% (IRR 1.44, 95% CI 1.24-1.66) increase in RSV cases, respectively. Four statistically significant local clusters of RSV pneumonia were identified within the annual island-wide epidemics. This study demonstrates statistical association of monsoon-associated weather in equatorial Indonesia with RSV. Moreover, within the island-wide epidemics, localized RSV outbreaks suggest local factors influence RSV disease.     

Brief report: respiratory syncytial virus activity--United States, 2004-2005

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections (LRTIs) (e.g., bronchiolitis and pneumonia) among young children, resulting in an estimated 51,000-82,000 hospitalizations annually in the United States. RSV also causes severe disease and death among older persons and persons of all ages with compromised respiratory, cardiac, or immune systems and can exacerbate chronic cardiac and pulmonary conditions. In temperate climates, most RSV infections occur during a distinct seasonal peak. This report presents preliminary data from RSV activity reported to the National Respiratory and Enteric Virus Surveillance System (NREVSS) for the weeks ending July 2 through December 3, 2005, indicating the onset of the 2005-06 RSV season, and summarizes trends during July 2004-June 2005. Health-care providers should consider RSV in the differential diagnosis for persons of all ages with LRTIs, implement appropriate isolation precautions to prevent nosocomial transmission, and provide appropriate immune prophylaxis to eligible children, including certain premature infants or infants and children with chronic lung and heart disease.     

Brief report: respiratory syncytial virus activity--United States, 2005-2006

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections (LRTIs) (e.g., bronchiolitis and pneumonia) among young children in the United States. RSV also causes severe respiratory disease and a substantial number of deaths among older adults and persons with compromised respiratory, cardiac, or immune systems. RSV is transmitted person to person through close contact or inhalation of large droplets from a sneeze or cough; infection also can occur through contact with fomites (i.e., contaminated surfaces or objects). In temperate climates, peak RSV activity typically occurs during the winter. This report presents preliminary data on RSV activity reported to the National Respiratory and Enteric Virus Surveillance System (NREVSS) for the weeks ending July 8-November 18, 2006, indicating the onset of the 2006-2007 RSV season, and summarizes RSV trends during July 2005-June 2006. Health-care providers should consider RSV in the differential diagnosis for persons of all ages with LRTIs and implement appropriate isolation precautions to prevent nosocomial transmission from RSV-infected patients. Immune prophylaxis should be considered for certain infants and young children at high risk for complications from RSV infection (e.g., certain premature infants or infants and children with chronic lung and heart disease).     

Potential impact of a maternal vaccine for RSV: A mathematical modelling study

Respiratory syncytial virus (RSV) is a major cause of respiratory morbidity and one of the main causes of hospitalisation in young children. While there is currently no licensed vaccine for RSV, a vaccine candidate for pregnant women is undergoing phase 3 trials. We developed a compartmental age-structured model for RSV transmission, validated using linked laboratory-confirmed RSV hospitalisation records for metropolitan Western Australia. We adapted the model to incorporate a maternal RSV vaccine, and estimated the expected reduction in RSV hospitalisations arising from such a program. The introduction of a vaccine was estimated to reduce RSV hospitalisations in Western Australia by 6–37% for 0–2 month old children, and 30–46% for 3–5 month old children, for a range of vaccine effectiveness levels. Our model shows that, provided a vaccine is demonstrated to extend protection against RSV disease beyond the first three months of life, a policy using a maternal RSV vaccine could be effective in reducing RSV hospitalisations in children up to six months of age, meeting the objective of a maternal vaccine in delaying an infant’s first RSV infection to an age at which severe disease is less likely.