Outbreak Of Acute Respiratory Disease Research Articles

Genomic and Bioinformatics Analysis of HAdV-4, a Human Adenovirus Causing Acute Respiratory Disease: Implications for Gene Therapy and Vaccine Vector Development

Human adenovirus serotype 4 (HAdV-4) is a reemerging viral pathogenic agent implicated in epidemic outbreaks of acute respiratory disease (ARD). This report presents a genomic and bioinformatics analysis of the prototype 35,990-nucleotide genome (GenBank accession no. AY594253). Intriguingly, the genome analysis suggests a closer phylogenetic relationship with the chimpanzee adenoviruses (simian adenoviruses) rather than with other human adenoviruses, suggesting a recent origin of HAdV-4, and therefore species E, through a zoonotic event from chimpanzees to humans. Bioinformatics analysis also suggests a pre-zoonotic recombination event, as well, between species B-like and species C-like simian adenoviruses. These observations may have implications for the current interest in using chimpanzee adenoviruses in the development of vectors for human gene therapy and for DNA-based vaccines. Also, the reemergence, surveillance, and treatment of HAdV-4 as an ARD pathogen is an opportunity to demonstrate the use of genome determination as a tool for viral infectious disease characterization and epidemic outbreak surveillance: for example, rapid and accurate low-pass sequencing and analysis of the genome. In particular, this approach allows the rapid identification and development of unique probes for the differentiation of family, species, serotype, and strain (e.g., pathogen genome signatures) for monitoring epidemic outbreaks of ARD.

Concurrent Summer Influenza and Pertussis Outbreaks in a Nursing Home in Sydney, Australia

To report on the investigation of a summer outbreak of acute respiratory illness among residents of a Sydney nursing home. An epidemiologic and microbiological investigation of the resident cohort at the time of the outbreak and medical record review 5 months later. A nursing home located in Sydney, Australia, during February to July 1999. The cohort of residents present in the nursing home at the time of the outbreak. Public health interventions included recommendations regarding hygiene, cohorting of residents and staff, closure to further admissions, and prompt reporting of illness; and virologic and serologic studies of residents. Of the 69 residents (mean age, 85.1 years), 35 fulfilled the case definition of acute respiratory illness. Influenza A infection was confirmed in 19 residents, and phylogenetic analysis of the resulting isolate, designated H3N2 A/Sydney/203/99, showed that it differed from strains isolated in eastern Australia during the same period. Serologic evidence of Bordetella infection was also found in 10 residents; however, stratified epidemiologic analysis pointed to influenza A as the cause of illness. The investigation revealed an unusual summer outbreak of influenza A concurrent with subclinical pertussis infection. Surveillance of acute respiratory illness in nursing homes throughout the year, rather than solely during epidemic periods, in combination with appropriate public health laboratory support, would allow initiation of a timely public health response to outbreaks of acute respiratory illness in this setting.

Coccidioidomycosis among workers at an archeological site, northeastern Utah.

In 2001, an outbreak of acute respiratory disease occurred among persons working at a Native American archeological site at Dinosaur National Monument in northeastern Utah. Epidemiologic and environmental investigations were undertaken to determine the cause of the outbreak. A clinical case was defined by the presence of at least two of the following symptoms: self-reported fever, shortness of breath, or cough. Ten workers met the clinical case definition; 9 had serologic confirmation of coccidioidomycosis, and 8 were hospitalized. All 10 were present during sifting of dirt through screens on June 19; symptoms began 9–12 days later (median 10). Coccidioidomycosis also developed in a worker at the site in September 2001. A serosurvey among 40 other Dinosaur National Monument workers did not find serologic evidence of recent infection. This outbreak documents a new endemic focus of coccidioidomycosis, extending northward its known geographic distribution in Utah by approximately 200 miles.

Large summertime influenza A outbreak among tourists in Alaska and the Yukon Territory.

We investigated a large summertime outbreak of acute respiratory illness during May-September 1998 in Alaska and the Yukon Territory, Canada. Surveillance for acute respiratory illness (ARI), influenza-like illness (ILI), and pneumonia conducted at 31 hospital, clinic, and cruise ship infirmary sites identified 5361 cases of ARI (including 2864 cases of ILI [53%] and 171 cases of pneumonia [3.2%]) occurring primarily in tourists and tourism workers (from 18 and 37 countries, respectively). Influenza A viruses were isolated from 41 of 210 patients with ILI at 8 of 14 land sites and 8 of 17 cruise ship infirmaries. Twenty-two influenza isolates were antigenically characterized, and all were influenza A/Sydney/05/97-like (H3N2) viruses. No other predominant pathogens were identified. We estimated that >33,000 cases of ARI might have occurred during this protracted outbreak, which was attributed primarily to influenza A/Sydney/05/97-like (H3N2) viruses. Modern travel patterns may facilitate similar outbreaks, indicating the need for increased awareness about influenza by health care providers and travelers and the desirability of year-round influenza surveillance in some regions.

Isolation of H3N2 Swine Influenza Virus in South Korea

Swine influenza is a significant respiratory disease causing occasional reproductive problems in naïve swine herds. Although different subtypes of swine influenza virus (SIV) have been implicated in clinical outbreaks of swine influenza in Asian countries, no virus isolation has been made to identify SIV of subtypes other than the H1N1 subtype in the Korean swine population. In December 1998, an outbreak of acute respiratory disease was identified in a commercial swine farm located in the Kyunggi province of South Korea. A causative agent, which agglutinated rooster red blood cells, was detected from the lungs of 3 piglets from the index herd and was determined to be type A influenza virus using a commercial influenza virus typing kit. Hemagglutination activity (HA) of the isolates was completely inhibited by a swine antiserum against a recent US H3N2 SIV isolate (A/Sw/IA/41305/1998) but not by H1N1 swine antiserum (A/Sw/IA/1979). Reverse transcription-polymerase chain reaction (RT-PCR) revealed all 3 isolates were H3 SIV subtypes. Sequence analysis of hemagglutinin gene PCR products supported the belief that the Korean H3 SIV isolates were genetically similar to the known mammalian H3 influenza viruses. This is the first report on a clinical outbreak of swine influenza caused by the H3N2 virus in Korea.

Outbreak of influenza type A (H1N1) in Iporanga, São Paulo State, Brazil.

From June to July 1999 an outbreak of acute respiratory illness occurred in the town of Iporanga. Out of a total of 4,837 inhabitants, 324 cases were notified to the Regional Surveillance Service. Influenza virus was isolated from 57.1% of the collected samples and 100% seroconversion to influenza A (H1N1) was obtained in 20 paired sera tested. The isolates were related to the A/Bayern/07/95 strain (H1N1). The percentages of cases notified during the outbreak were 28.4%, 29.0%, 20.7%, 6.2% and 15.7% in the age groups of 0-4, 5-9, 10-14, 15-19 and older than 20 years, respectively. The highest proportion of positives was observed among children younger than 14 years and no cases were notified in people older than 65 years, none of whom had been recently vaccinated against influenza. These findings suggest a significant vaccine protection against A/Bayern/7/95, the H1 component included in the 1997-98 influenza vaccine for elderly people. This viral strain is antigenically and genetically related to A/Beijing/262/95, the H1 component of the 1999 vaccine. Vaccines containing A/Beijing/262/95 (H1N1) stimulated post-immunization hemagglutination inhibition antibodies equivalent in frequency and titre to both A/Beijing/262/95-like and A/Bayern/7/95-like viruses. Thus, this investigation demonstrates the effectiveness of vaccination against influenza virus in the elderly.

The effect of an outbreak of respiratory disease on herd-level milk production of Norwegian dairy farms

This study was done to evaluate the effect of an outbreak of acute respiratory disease associated with bovine respiratory syncytial virus (BRSV) on the daily milk yield per cow in Norwegian dairy-cattle farms. Retrospective data from 184 dairy herds located in two neighbouring veterinary districts during the study period (December 1994–May 1995, during which an epidemic of acute respiratory disease associated with BRSV occurred in this area) were analysed. Data on the bulk-milk deliveries and the date of the outbreak were collected at herd level, whereas information on calving dates and parity was collected at cow-level. The effect of the herd outbreaks on the daily milk yield was analysed with a repeated-measurement approach. The average daily milk loss was estimated to be 0.70 kg per cow for 7 days after a herd outbreak (compared with the period >1 week prior to an outbreak), adjusted for the herd-level lactation stage, parity and their interaction term. We consider the estimated milk loss associated with a herd outbreak of epidemic respiratory disease to be of minor importance.

The exceptionally large genome of Hendra virus: support for creation of a new genus within the family Paramyxoviridae.

An outbreak of acute respiratory disease in Hendra, a suburb of Brisbane, Australia, in September 1994 resulted in the deaths of 14 racing horses and a horse trainer. The causative agent was a new member of the family Paramyxoviridae. The virus was originally called Equine morbillivirus but was renamed Hendra virus (HeV) when molecular characterization highlighted differences between it and members of the genus Morbillivirus. Less than 5 years later, the closely related Nipah virus (NiV) emerged in Malaysia, spread rapidly through the pig population, and caused the deaths of over 100 people. We report the characterization of the HeV L gene and protein, the genome termini, and gene boundary sequences, thus completing the HeV genome sequence. In the highly conserved region of the L protein, the HeV sequence GDNE differs from the GDNQ found in almost all other nonsegmented negative-strand (NNS) RNA viruses. HeV has an absolutely conserved intergenic trinucleotide sequence, 3'-GAA-5', and highly conserved transcription initiation and termination sequences similar to those of respiroviruses and morbilliviruses. The large genome size (18,234 nucleotides), the unique complementary genome terminal sequences of HeV, and the limited homology with other members of the Paramyxoviridae suggest that HeV, together with NiV, should be classified in a new genus in this family. The large genome of HeV also fills a gap in the spectrum of genome sizes observed with NNS RNA virus genomes. As such, it provides a further piece in the puzzle of NNS RNA virus evolution.

A space–time cluster investigation of an outbreak of acute respiratory disease in Norwegian cattle herds

Outbreaks of acute respiratory disease occurred in several cattle herds in the south-east regions of Norway during the winter and spring of 1995. The present study was conducted to investigate the temporal and spatial dynamics of the occurrence of acute respiratory disease between January and April 1995 in the affected cattle herds, in two neighbouring counties in Norway. This was done to assess the possible role of an infectious agent in these outbreaks, as well as to investigate the possibility of transmission between neighbouring herds. During the study period, a total of 190 (19.8%) outbreaks occurred in 955 cattle herds located in the defined study area. Descriptive maps of the spatial and spatio-temporal patterns of the outbreak were generated, and two different statistical tests of space–time interaction (the Knox test and k-nearest neighbour test) and a cluster-detection test (the space–time scan statistic) were used. The results of all the space–time interaction tests strongly suggested that the case herds were clustered in time as well as in space. In addition, the space–time scan statistic defined the most-likely cluster to be located within the second veterinary district (Toten where the disease occurred) during 9–15 weeks in 1995. The relative risk of a herd being infected inside the most-likely cluster compared with the surrounding study area was estimated to be 3.59 ( p=0.001). The transmission rate between neighbouring farms therefore appeared to have been higher within this cluster than in the surrounding study area. This study supports the hypothesis that one common source of infection was involved in the outbreaks during the study period.

Detection of adenoviruses (AdV) in culture-negative environmental samples by PCR during an AdV-associated respiratory disease outbreak.

Since 1954, adenoviruses (AdV) have been recognized as an important cause of acute respiratory disease (ARD) among U.S. military recruits. Until recently, routine oral vaccination for AdV serotypes 4 and 7 eliminated epidemic AdV-associated ARD in this population. Now that the manufacturer has ceased production, vaccination has ended and AdV epidemics have reappeared. As part of a prospective epidemiological study during the high-risk ARD season, serial samples were obtained from ventilation system filters and tested for AdV by culture and PCR. An outbreak occurred during this surveillance. Of 59 air filters, 26 (44%) were AdV positive only by PCR. Sequence analysis confirmed the presence of AdV serotype 4, the implicated outbreak serotype. The number of AdV-related hospitalizations was directly correlated with the proportion of filters containing AdV; correlation coefficients were 0.86 (Pearson) and 0.90 (Spearman's rho). This is the first report describing a PCR method to detect airborne AdV during an ARD outbreak. It suggests that this technique can detect and quantify AdV-associated ARD exposure and may enable further definition of environmental effects on AdV-associated ARD spread.

Risk factors for epidemic respiratory disease in Norwegian cattle herds

An epidemic of acute respiratory disease associated with bovine respiratory syncytial virus (BRSV) occurred during the winter and spring of 1995 in two neighbouring veterinary districts in the south-eastern part of Norway. The objective of this study was to describe the time course of the outbreak associated with BRSV in the cattle herds, and to determine the association between selected herd factors and the risk of experiencing a herd outbreak of acute respiratory disease. Data from 431 cattle herds on the dates of disease occurrence, location of the farms, herd size, age profile and production type were collected retrospectively for 1995. The risk of acute respiratory disease occurring in a cattle herd was related to the herd size as well as the type of production, with an expressed interaction between these two variables. From the Cox proportional-hazards model, the risk of a herd outbreak in a mixed herd of 20 animals was estimated to be 1.7-times greater than in a dairy herd and 3.3-times greater than a beef herd (reference category) of a comparable size. On increasing the herd size to 50 animals, the risk increased 1.3-fold for a mixed herd, 3.3-fold for a dairy herd, and 2.1-fold for a beef herd, compared to the risk for a corresponding type of herd of 20 animals.

An outbreak of acute respiratory disease caused by Mycoplasma pneumoniae and adenovirus at a federal service training academy: new implications from an old scenario.

Outbreaks of Mycoplasma pneumoniae and adenovirus have been reported in military institutions for several decades. During a recent outbreak in a federal service training academy, we performed an epidemiological and laboratory investigation to better characterize and control the outbreak. Of 586 students responding to a questionnaire, 317 (54%) reported having a respiratory illness during the outbreak period. Among 42 students who underwent complete laboratory testing, 24 (57%) had evidence of M. pneumoniae infection, 8 (19%) had evidence of adenovirus infection, and 4 (10%) had evidence of both. Polymerase chain reaction testing of oropharyngeal swabs revealed more acute M. pneumoniae infections (57% positive) than did serology or culture. Multivariate analysis revealed that visiting the campus health clinic >3 times for a nonrespiratory condition, such as injury, was a significant risk factor for illness among freshmen early in the course of the outbreak, whereas having an ill roommate was a risk factor throughout the duration of the outbreak.

Reemergence of adenovirus type 4 acute respiratory disease in military trainees: report of an outbreak during a lapse in vaccination.

From 23 April to 13 May 1995, an outbreak of acute respiratory disease (ARD) hospitalizations occurred in basic training soldiers at Fort Jackson, South Carolina. Weekly hospitalization rates for the most affected military unit reached 11.6%. Virus isolation and serologic studies from a sample of patients identified the agent as adenovirus type 4. Prior to starting vaccinations against adenovirus types 4 and 7 in 1971, these serotypes were the major causes of ARD in basic trainees. No outbreaks were reported when the vaccines were used. A logistical error temporarily interrupted vaccine production, and newly arriving trainees received no adenovirus vaccines from the summer of 1994 through late March 1995. This outbreak occurred in unvaccinated soldiers. The sole manufacturer has permanently stopped adenovirus vaccine production. All type 4 vaccine supplies are now depleted. This outbreak demonstrates continued susceptibility of military recruits to adenovirus type 4 and warns of future outbreaks.

Strain variation in adenovirus serotypes 4 and 7a causing acute respiratory disease.

In order to determine the suitability of vaccine strains established in the 1960s for a new vaccine, a comprehensive study of strain variation of adenovirus serotype 4 (AV 4) and AV 7 was undertaken. A 1,500-bp region of the hexon gene containing the AV neutralization epitopes from prototype, vaccine, and community-acquired strains and from wild-type strains from military personnel that cause acute respiratory disease (ARD) was sequenced and analyzed. The whole hexon gene from prototype strains, vaccine strains, and selected isolates was sequenced. AV 7 and AV 7a were found to have distinct genotypes, and all vaccine and wild-type strains recovered from 1963 to 1997 had the AV 7a genotype. There was no significant strain variation in the neutralization epitopes of the AV 7a genotype over a 42-year period. The evolution of AV 4 was more complex, with continuous genetic drift punctuated by replacement with a new strain. The current strain of AV 4, which has been in circulation since 1995, is significantly different from the AV 4 prototype and the vaccine strains. Genetic differences were confirmed to be antigenic differences by neutralization tests, which define the new strain as an AV 4 variant. A type-specific PCR for AV 4, AV 7/7a, and AV 21 was developed, and this PCR facilitated the rapid identification of isolates from outbreaks of ARD.

Health effects resulting from nitrogen dioxide exposure in an indoor ice arena.

We investigated an outbreak of acute respiratory illness among adolescent ice-hockey players in an indoor ice arena in Stockholm that had a propane-powered ice-resurfacing machine. We administered questionnaires to all players, as well as to a reference group that had played ice hockey in indoor arenas with electric ice-resurfacing machines. In the exposed group, 55 subjects (55.6%) experienced acute respiratory symptoms, compared with 4 (7.1%) in the reference group (relative risk = 7.8; 95% confidence interval = 3.0, 20.3). The risk for pulmonary symptoms increased as time spent on the ice increased. Levels of nitrogen dioxide up to 2358 microg/m3 (1250 ppb) were detected during simulated conditions of the incident. The most likely cause of the outbreak was the high level of nitrogen dioxide that resulted from poor ventilation and a malfunctioning ice-resurfacing machine. Propane-fueled ice-resurfacing machines should not be used in indoor ice arenas.

Civilian Outbreak of Adenovirus Acute Respiratory Disease--South Dakota, 1997

Adenoviruses are human pathogens that commonly infect the respiratory and gastrointestinal tracts. Adenovirus infections are endemic, particularly among children, but also may cause epidemics of pharyngoconjunctival fever, keratoconjunctivitis, gastroenteritis, and acute respiratory disease (ARD) among military trainees. Outbreaks of ARD among adults in the civilian sector are rare. In March 1997, an outbreak of acute respiratory disease (ARD) caused by adenovirus serotype 11 occurred among students at a job training facility in South Dakota. This report summarizes the epidemiologic and clinical features of this outbreak and discusses the change in availability of adenovirus vaccines for military use.

Update: Respiratory Syncytial Virus Activity--United States, 1997-98 Season

Respiratory syncytial virus (RSV), a common cause of winter outbreaks of acute respiratory disease, results in an estimated 90,000 hospitalizations and 4500 deaths each year from lower respiratory tract disease among infants and young children in the United States. Outbreaks occur annually throughout the country. RSV activity in the United States is monitored by the National Respiratory and Enteric Virus Surveillance System (NREVSS), a voluntary, laboratory-based system. This report summarizes trends in RSV reported by NREVSS for July 1992-June 1997 and presents provisional surveillance results for July-November 1997. These data indicate onset of widespread RSV activity for the 1997-98 season.

Outbreak of adenovirus 35 pneumonia among adult residents and staff of a chronic care psychiatric facility.

Outbreaks of acute respiratory disease caused by adenovirus are rarely documented in civilian populations, and adenovirus 35 is an uncommon serotype best recognized as a cause of serious disease in immunocompromised patients. An outbreak of adenovirus 35 pneumonia among residents and staff of a chronic care psychiatric facility was investigated. Fourteen (26%) of 53 residents and 4 (2%) of approximately 200 staff had radiographically confirmed pneumonia. Thirteen (93%) of 14 residents with pneumonia were hospitalized, 5 (36%) required mechanical ventilation, and 1 (7%) died. One staff member was hospitalized. Adenovirus infection was diagnosed in 17 (94%) persons with pneumonia by culture or serology and was confirmed as adenovirus 35 infection in 8 persons. Residents with pneumonia had resided at the facility longer than other residents. Chronic illness was not a risk factor for severe disease. Crowding and poor hygienic behaviors probably facilitated transmission among residents.

Update: Respiratory Syncytial Virus Activity— United States, 1996-97 Season

Respiratory syncytial virus (RSV), a common cause of winter outbreaks of acute respiratory disease, causes an estimated 90,000 hospitalizations and 4500 deaths each year from lower respiratory tract disease in both infants and young children in the United States. Outbreaks occur annually throughout the United States, and community activity usually peaks within 1 month of the national peak. RSV activity in the United States is monitored by the National Respiratory and Enteric Virus Surveillance System (NREVSS), a voluntary, laboratory-based system. This report presents provisional surveillance results from the NREVSS for RSV during July 2-December 9, 1994, and summarizes trends in RSV from July 1, 1990, through July 1, 1994.

Value of influenza vaccine during an outbreak of influenza A in a nursing home, Pyrenees Atlantiques, France, November-December 1995.

A public health officer of the Direction Departementale de l'Action Sanitaire et Sociale des Pyrenees Atlantiques in France was notified of an outbreak of acute respiratory illness among residents of a nursing home on 4 December, 1995. Over 50 of the 69 r