The Tucson Children's Respiratory Study. II. Lower respiratory tract illness in the first year of life

Lower respiratory tract illnesses occurring during the first year of life in 1,179 healthy infants enrolled in the Children's Respiratory Study, Tucson, Arizona, are described. The children, who use the pediatricians of a health maintenance organization, were enrolled into the study between May 1980 and January 1984. Data were collected on signs, symptoms, and diagnosis for each illness; nasopharyngeal and throat swabs were collected at the acute visit for viral, chlamydial, and mycoplasmal cultures. The cumulative incidence of illness in the first year of life was 32.88 per 100 children. Of the 348 initial lower respiratory tract illnesses occurring in these infants, 60% were diagnosed as bronchiolitis. At least one infecting agent was identified in 66% of the specimens collected at the time of the first illness. Respiratory syncytial virus was the most common isolate; 12 other agents were also identified. There was a strong (p less than 0.0001) relation between agent identified, symptoms reported, and diagnosis; bronchiolitis was predominantly associated with respiratory syncytial virus and croup with parainfluenza viruses. Sex and ethnicity were unrelated to illness experience or to characteristics of the first illness. Lower respiratory tract illness occurrence in the Children's Respiratory Study appears to be similar to patterns observed elsewhere, suggesting that diagnoses (and infecting agents) have changed little over the past decades.     

A study of acute respiratory disease in the community of Port Chalmers. I. Illnesses within a group of selected families and the relative incidence of respiratory pathogens in the whole community.

A study of respiratory diseases in the semi-isolated community of Port Chamlers, New Zealand, began in April 1973. The intensive surveillance of a selected group fo 26 families involved the weekly reporting of illness, the collection of specimens for virus, Group A streptococci and Mycoplasma pneumoniae isolation and the collection of sera at 6-month intervals. A total of 956 illnesses were reported during 32 months. The median number of illnesses per year were: infants 4.4, children 2.5, female adults 2.4 and male adults 2.0. Of all these illnesses, 57% were upper respiratory, 31% were lower respiratory and 9% were enteric. The severity of these illnesses was not greater than would be expected in open communities. Surveillance by pathogen isolation only of the whole community through the patients in the general practice was carried out concurrently. A total of 640 nasopharyngeal swab specimens were collected from which 161 viruses, 47 Group A streptococci and 2 M. pneumoniae were isolated. The overall isolation rate was 33%. The similarities between the epidemiological patterns of respiratory disease in the open community and the isolated community are discussed.     

Protection against bovine respiratory syncytial virus in calves vaccinated with adjuvanted modified live vaccine administered in the face of maternal antibody

Bovine respiratory syncytial virus (BRSV) is major viral contributor to bovine respiratory disease (BRD). BRD is a major cause of morbidity and mortality in all classes of cattle but particularly young beef and dairy calves. Passive antibodies not only help protect the calf against infection, but may interfere with the immune responses following vaccination. The purpose of this study was to evaluate the efficacy of an adjuvanted modified live virus (MLV) vaccine in the presence of well-defined maternal passive immunity. Calves were vaccinated at approximately 1 month of age and challenged ~90 days later when BRSV systemic antibodies were ≤1:4. Body temperature was lower at 6 and 7 days post challenge and other clinical signs were also lower in the vaccinates. Nasal viral shed was 3–4 times lower in the vaccinated animals as measured by virus isolation and polymerase chain reaction (PCR) and peaked 5 days post challenge compared to the controls (who peaked at days 6 and 7). On day 8 following challenge, animals were necropsied, and lung lobes were scored and tested for virus by PCR and indirect fluorescent assay (IFA). There was a 25-fold reduction in PCR virus detection in vaccinates and two of the vaccinated calves’ lungs were PCR negative. Only 29.4% of vaccinated calves were BRSV positive on IFA testing at necropsy, while 87.5% of control calves were BRSV positive. Vaccinated calves developed a mucosal BRSV IgA response with over 50% of the vaccinated calves having IgA prior to challenge and all vaccinated calves were positive following challenge. Additionally, vaccination stimulated the production of Interferon gamma (IFN-γ) in mononuclear cells to prime the immune system. This study established that an adjuvanted MLV vaccine could provide protection against BRSV as measured by clinical, virological, and pathological parameters while also activating both mucosal and systemic immunity.     

The Tecumseh study of respiratory illness. X. Relation of acute infections to smoking, lung function and chronic symptoms

The relationship of acute respiratory illness and infection to chronic bronchitis was investigated in the community of Tecumseh, Michigan. Families were randomly selected for study from among all those in the community and they were followed for periods of one year. Occurrence of acute respiratory illnesses was identified on a weekly basis. Frequency of chronic symptoms of cough and sputum production was separately ascertained. Lung function studies were performed three times during the course of the surveillance year and blood specimens were collected at those times. The blood specimens were tested for rise in antibody titer with antigens of type A and B influenza, respiratory syncytial virus and Mycoplasma pneumoniae. Adults with mild or intermittent chronic symptoms of cough and sputum production experienced more acute respiratory illness than those without these symptoms. This finding was present at different levels of smoking frequency. A similar relationship was present when serologic infection rates were used in the analysis instead of acute illness incidence. When the population was dichotomized on the basis of lung function data, the segment of the population with more depressed values was found to have experienced higher infection rates. The results suggest that acute infection may play an independent role in the pathogenesis of chronic respiratory disease.     

Delays in the application of outbreak control prophylaxis for influenza A in a nursing home.

OBJECTIVE: To identify delayed prophylaxis from a pre-existing database and strategies to improve performance. SETTING: A skilled nursing facility with 14 floors (4 buildings). The "outbreak unit" was a 50- to 60-bed floor. METHODS: We performed surveillance during six seasons using one protocol. Prophylaxis was started when influenza was cultured in the building and 10% of residents on the floor had a new respiratory illness within 7 days. We defined delayed prophylaxis as four or more residents on a floor with positive cultures whose specimens had been collected within 5 days before the application of prophylaxis. RESULTS: We identified 14 examples of delayed prophylaxis. In three, delayed prophylaxis was related to the 3.9-day delay between culture collection and culture report There was a high degree of commonality among building attack rates within a season. During six seasons, the first case in the last building occurred 27 to 64 days after the first case in the facility. The two seasons with the greatest activity (68 and 154 cases, respectively) began with explosive, multi-floor outbreaks in a single building. The match between the circulating strain and the vaccine was good, except in 1997-1998 when there were seven examples of delayed prophylaxis. CONCLUSIONS: Influenza may involve buildings sequentially with a commonality of building attack rates. Explosive, multi-floor outbreaks early in the season could lead to a lower threshold for prophylaxis within a larger area when initial cases are encountered later in the season. This strategy could have prevented five examples of delayed prophylaxis. Rapid testing of multiple specimens while waiting for culture confirmation could have prevented three examples of delayed prophylaxis.     

2017—2019年孝感市儿童呼吸道病毒感染流行病学特征

目的 对湖北省孝感市0~13岁呼吸道感染患儿进行病毒病原学检测,分析呼吸道病毒感染病原学特点,为0~13岁儿童呼吸道感染的预防、诊断和治疗提供科学依据。 方法 通过采集2017年1月1日—2019年12月31日,在湖北省孝感市中心医院就诊的呼吸道感染患儿的咽拭子标本,采用实时荧光定量 PCR,进行七项呼吸道病毒检测。 结果 共采集12 486例标本,其中3 309例标本为阳性,总阳性率为26.5%。其中呼吸道合胞病毒 (respiratory syncytial virus, RSV) 阳性率最高,为1 574 例 (12.6%)。阳性率随着年龄的增加而下降,各年龄组间病毒阳性率差异有统计学意义(χ²=318.972,P<0.001)。0~1岁组病毒阳性率最高(32.1%)。0~1岁组和~3岁组,RSV检出率最高分别为18.7%和9.4%。~6岁组和~13岁组,腺病毒(adenovirus, ADV)检出率最高分别为8.1%和4.6%。各季节间,病毒阳性率差异有统计学意义(χ²=822.421,P<0.001)。春季,副流感病毒Ⅲ (parainfluenza virus Ⅲ, PIV Ⅲ)检出率最高;夏季,ADV检出率最高;秋、冬季,RSV检出率最高。 结论 对于0~1岁的婴幼儿,冬、春季,应重点预防RSV感染,而夏季应重点预防PIVⅢ感染。而对于>1岁的儿童,在春、夏两季应注意ADV的感染,冬季应注意预防FluA、FluB的感染。     

新兵急性呼吸道疾病病原体检测结果分析

目的调查入伍新兵急性呼吸道疾病的常见病原体,为预防控制呼吸道传染病提供科学依据。方法留取40例老兵、204例新兵和40例急性呼吸道疾病新兵咽拭子,提取DNA和RNA,检测15种病原体的核酸,并留取急性呼吸道疾病新兵双份血清检测抗病原体抗体。结果老兵组咽拭子流感病毒、肺炎支原体和肺炎链球菌核酸的检出率分别为32.5%、25.0%和15.0%,高于新兵组的2.5%、2.5%和2.9%(P<0.05);在40例散发的患有急性呼吸道疾病的新兵中,甲型和乙型流感病毒核酸阳性率分别为5.0%和55.0%,肺炎支原体、肺炎链球菌和嗜肺军团菌的阳性率分别为20.0%、7.5%和15.0%,与老兵组(分别为25.0%、15.0%和17.5%)或新兵入营时(分别为2.5%、2.9%和7.4%)相比,差异均无统计学意义(均有P>0.05);对患有急性呼吸道疾病的新兵急性期和恢复期双份血清检测发现,乙型流感病毒感染发生率为65.0%(26/40),甲型流感病毒感染率为5.0%(2/40),无甲型流感病毒H5N1等感染病例发生。结论入伍新兵在入训期间散发的急性呼吸道疾病以流感病毒感染为主。     

Can routinely collected laboratory and health administrative data be used to assess influenza vaccine effectiveness? Assessing the validity of the Flu and Other Respiratory Viruses Research (FOREVER) Cohort

BackgroundLinking data on laboratory specimens collected during clinical practice with health administrative data permits highly powered vaccine effectiveness (VE) studies to be conducted at relatively low cost, but bias from using convenience samples is a concern. We evaluated the validity of using such data for estimating VE.MethodsWe created the Flu and Other Respiratory Viruses Research (FOREVER) Cohort by linking individual-level data on respiratory virus laboratory tests, hospitalizations, emergency department visits, and physician services. For community-dwelling adults aged > 65 years, we assessed the presence and magnitude of information and selection biases, generated VE estimates under various conditions, and compared our VE estimates with those from other studies.ResultsWe included 65,648 unique testing episodes obtained from 54,434 individuals during the 2010–11 to 2015–16 influenza seasons. To examine information bias, we found the proportion testing positive for influenza for patients with unknown interval from illness onset to specimen collection was more similar to patients for whom illness onset date was ≤ 7 days before specimen collection than to patients for whom illness onset was > 7 days before specimen collection. To assess the presence of selection bias, we found the likelihood of influenza testing was comparable between vaccinated and unvaccinated individuals, although the adjusted odds ratios were significantly greater than 1 for some healthcare settings and during some influenza seasons. Over 6 seasons, VE estimates ranged between 36% (95%CI, 27–44%) in 2010–11 and 5% (95%CI, –2, 11%) in 2014–15. VE estimates were similar under a range of conditions, but were consistently higher when accounting for misclassification of vaccination status through a quantitative sensitivity analysis. VE estimates from the FOREVER Cohort were comparable to those from other studies.ConclusionsRoutinely collected laboratory and health administrative data contained in the FOREVER Cohort can be used to estimate influenza VE in community-dwelling older adults.     

Co-infections of adenovirus species in previously vaccinated patients

Despite the success of the adenovirus vaccine administered to US military trainees, acute respiratory disease (ARD) surveillance still detected breakthrough infections (respiratory illnesses associated with the adenovirus serotypes specifically targeted by the vaccine). To explore the role of adenoviral co-infection (simultaneous infection by multiple pathogenic adenovirus species) in breakthrough disease, we examined specimens from patients with ARD by using 3 methods to detect multiple adenoviral species: a DNA microarray, a polymerase chain reaction (PCR)-enzyme-linked immunosorbent assay, and a multiplex PCR assay. Analysis of 52 samples (21 vaccinated, 31 unvaccinated) collected from 1996 to 2000 showed that all vaccinated samples had co-infections. Most of these co-infections were community-acquired serotypes of species B1 and E. Unvaccinated samples primarily contained only 1 species (species E) associated with adult respiratory illness. This study highlights the rarely reported phenomenon of adenoviral co-infections in a clinically relevant environment suitable for the generation of new recombinational variants.     

Studies on the virus content of mouth washings in the acute phase of smallpox

Epidemiological observations suggest that smallpox is not highly infectious in the febrile pre-eruptive period of illness. As virus is first discharged by most patients from lesions in the mouth or upper respiratory passages, mouth washings or garglings from smallpox patients in the acute stage of the disease were examined for virus. Only five specimens were obtained in the first two days of illness but no virus was recovered from them. Virus was most frequently found in specimens collected from the sixth to the ninth day of illness inclusive—a period when lesions in the mouth were breaking down and discharging virus. The results are in conformity with the view that the smallpox patient is most infective in the first few days of the eruptive phase of his illness.     

Impact of genetic diversity of European-type porcine reproductive and respiratory syndrome virus strains on vaccine efficacy

The aim of this study was to find out how efficiently pigs that are vaccinated with an attenuated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine based on a virus from the Lelystad cluster are protected against a European wild-type strain from the same or another genetic cluster. Two experiments were performed. In each experiment, 5-week-old PRRSV-seronegative pigs were vaccinated intramuscularly with 10(4.5) TCID50 of a commercial vaccine based on a European virus strain from the Lelystad cluster. Non-vaccinated pigs were included as controls. At 5, 9, 15, 20, 28, 35 and 42 days post vaccination (PV), broncho-alveolar lavage (BAL) fluids and blood were collected to determine vaccine virus quantities. Forty-nine days PV, pigs were challenged intranasally with 10(6.0) TCID50 of a European wild-type strain, belonging either to the Lelystad cluster (98% nucleotide identity in ORF5 with vaccine strain) (experiment A) or to an Italian cluster (84% nucleotide identity in ORF5 with vaccine strain) (experiment B). At 5, 9, 15, 20 and 27 days post challenge (PC), BAL fluids and blood were collected to determine virus quantities. Vaccine virus was first detected in BAL fluids and blood at 5 days PV and reached highest quantities between 9 and 15 days PV. One pig was positive in its BAL fluid until 42 days PV. After challenge, virus was isolated from BAL fluids and blood of all non-vaccinated control pigs. All vaccinated pigs challenged with the Lelystad strain remained negative for virus, while virus was present in BAL fluids and blood of all vaccinated pigs after challenge with the Italian strain. Mean virus titres of the vaccinated pigs challenged with the Italian strain were significantly lower than those of the non-vaccinated control pigs (P <0.05) at 9, 15 and 20 days PC. Thus, the genetic diversity within European-type PRRSV may affect the efficacy of the current European-type vaccines.     

Evaluation of Efficacy Endpoints for a Phase IIb Study of a Respiratory Syncytial Virus Vaccine in Older Adults Using Patient-Reported Outcomes With Laboratory Confirmation

ObjectivesThere are no approved vaccines for respiratory syncytial virus (RSV), and consensus on methods to assess RSV vaccine efficacy has not been established. In this study of an adjuvanted RSV vaccine, we evaluated an RSV disease endpoint using a patient-reported outcome instrument (the inFLUenza Patient-Reported Outcome instrument [FLU-PRO]) and molecular testing for virologic confirmation.MethodsIn a randomized, blinded efficacy study (NCT02508194), 1900 adult participants aged ≥60 years who had any respiratory symptom lasting ≥24 hours recorded symptoms in a FLU-PRO–based workbook for 21 days, self-collected nasal swabs on illness days 2 to 4, and had a site-collected swab obtained on (approximately) day 4. The endpoint, acute RSV-associated respiratory illness (ARA-RI), required specific symptoms with virologic confirmation.ResultsThe FLU-PRO demonstrated reliability, ability to detect change, and validity and had high participant adherence and acceptable patient burden in the setting of an RSV prevention trial. The ARA-RI endpoint definition captured all 33 virologically confirmed RSV illnesses for which symptom data were provided, and in 32 of these, at least 1 lower respiratory symptom was reported. Sensitivity analysis with an endpoint requiring ≥2 lower respiratory symptoms captured greater symptom severity but fewer cases. Results of self- and site-collected swabs were highly correlated. Self-swabbing detected 9 additional cases that would have been missed by site swabbing only.ConclusionsThese results demonstrated the reliability and validity of the ARA-RI definition and of the FLU-PRO for use in RSV studies. Self-swabbing improved RSV detection.     

应用PCR对呼吸道感染患者咽拭子样本肺炎衣原体DNA的检测

目的了解呼吸道感染患者肺炎衣原体感染状况,为临床诊断和治疗提供依据。方法 采集2006年1月在北京友谊医院发热门诊就诊的呼吸道患者的咽拭子样本88例,用肺炎衣原体种特异性引物对其进行PCR检测,阳性产物经基因测序,结果采用SPSS 10.0软件包进行数据统计分析,计数资料比较用χ2检验。结果 88例呼吸道感染患者的咽拭子样本中阳性者为28例,阳性率为31.82%。男性和女性阳性率差异无统计学意义。不同年龄组阳性率差异无统计学意义。结论 在有呼吸道症状的病例中,肺炎衣原体感染率较高,应对肺炎衣原体感染加以重视。PCR法是一简便、敏感和特异的诊断方法,值得在临床上进行应用和推广。     

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。     

2016—2019年杭州市余杭区973例严重急性呼吸道感染病例呼吸道合胞病毒检测结果

收集2016年1月至2019年12月杭州市余杭区第一人民医院的严重急性呼吸道感染病例鼻咽分泌物标本,采用荧光定量PCR方法进行RSV病毒核酸检测;检测后分析不同年龄组、不同月份RSV阳性检出情况。结果显示,共收集并检测973份鼻咽拭子标本中,63份标本RSV核酸检测阳性,阳性检出率为6.47%;核酸检出率男性大于女性,...     

2013年度贵州省发热呼吸道症候群病毒感染状况调查

摘要:目的　了解贵州省发热呼吸道症候群病毒性疾病的感染状况。方法　调查贵州省2013年度发热呼吸道症候群病例432例,采集呼吸道标本421份,通过相应试剂盒提取核酸,进行实时荧光定量（Real-Time）PCR检测流感病毒、副流感病毒、冠状病毒、呼吸道合胞病毒、腺病毒、博卡病毒,鼻病毒及偏肺病毒。结果　从421份标本中检测出阳性标本128份,阳性率为30.41%。其中流感病毒60份,阳性率为14.25%;冠状病毒8份,阳性率为1.90%;博卡病毒3份,阳性率为0.71%;腺病毒10份,阳性率为2.38%;偏肺病毒9份,阳性率为2.14%;鼻病毒38份,阳性率为9.03%;未检出呼吸道合胞病毒和副流感病毒。检出3例流感病毒和鼻病毒混合感染。结论　呼吸道病毒是导致发热呼吸道症候群的重要病原体,其中以流感病毒最为常见,鼻病毒其次,腺病毒、偏肺病毒等检出率较低。     

A review of vaccine research and development: human acute respiratory infections

Worldwide, acute respiratory infections (ARIs) constitute the leading cause of acute illnesses, being responsible for nearly 4 million deaths every year, mostly in young children and infants in developing countries. The main infectious agents responsible for ARIs include influenza virus, respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV-3), Streptococcus pneumoniae and Haemophilus influenzae. While effective vaccines against influenza, H. influenzae type b (Hib) and S. pneumoniae infections have been available for several years, no vaccine is available at present against illnesses caused by RSV, PIV-3, metapneumovirus or any of the three novel coronaviruses. In addition, the threat constituted by the multiple outbreaks of avian influenza during the last few years is urgently calling for the development of new influenza vaccines with broader spectrum of efficacy, which could provide immunity against an avian influenza virus pandemic. This article reviews the state of the art in vaccine R&D against ARIs and attempts to address these basic public health questions.