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Whole-genome Sequencing for Tracing the Transmission Link between Two ARD Outbreaks Caused by a Novel HAdV Serotype 7 Variant, China.

Qiu S, Li P, Liu H, Wang Y, Liu N, Li C, Li S, Li M, Jiang Z, Sun H, Li Y, Xie J, Yang C, Wang J, Li H, Yi S, Wu Z, Jia L, Wang L, Hao R, Sun Y, Huang L, Ma H, Yuan Z, Song H - Sci Rep (2015)

Bottom Line: WGS analyses showed that the HAdV-7 isolates from the two outbreaks were genetically indistinguishable; however, a 12 bp deletion in the virus-associated RNA gene distinguished the outbreak isolates from other HAdV-7 isolates.Outbreak HAdV-7 isolates demonstrated increased viral replication compared to non-outbreak associated HAdV-7 isolate.Our findings imply that in-hospital contact investigations should be encouraged to reduce or interrupt further spread of infectious agents when treating outbreak cases, and WGS can provide useful information guiding infection-control interventions.

View Article: PubMed Central - PubMed

Affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing 100071, China.

ABSTRACT
From December 2012 to February 2013, two outbreaks of acute respiratory disease caused by HAdV-7 were reported in China. We investigated possible transmission links between these two seemingly unrelated outbreaks by integration of epidemiological and whole-genome sequencing (WGS) data. WGS analyses showed that the HAdV-7 isolates from the two outbreaks were genetically indistinguishable; however, a 12 bp deletion in the virus-associated RNA gene distinguished the outbreak isolates from other HAdV-7 isolates. Outbreak HAdV-7 isolates demonstrated increased viral replication compared to non-outbreak associated HAdV-7 isolate. Epidemiological data supported that the first outbreak was caused by introduction of the novel HAdV-7 virus by an infected recruit upon arrival at the training base. Nosocomial transmission by close contacts was the most likely source leading to onset of the second HAdV-7 outbreak, establishing the apparent transmission link between the outbreaks. Our findings imply that in-hospital contact investigations should be encouraged to reduce or interrupt further spread of infectious agents when treating outbreak cases, and WGS can provide useful information guiding infection-control interventions.

No MeSH data available.


Related in: MedlinePlus

Timeline of critical events and nosocomial transmission for the index cases.Index case C was hospitalized due to a training injury from February 3 to 8, 2013. During his hospitalization, there were also about 70 patients hospitalized in the Xiangyang affiliated hospital from the Base A outbreak (Xiangyang). All cases were housed in the same in-patient building. Index case C had close contact with Index case B, a confirmed HAdV-7 case from the Xiangyang outbreak. They reported verbal contact twice for about half an hour on February 5 and 7, 2013, respectively. After 5 days of hospitalization, he returned to the training base B (Jingmen) on February 8, 2013, and took part in the normal training without isolation for medical observation. On February 11, 2013, he developed symptoms of ARD with fever (maximum temperature 39·0 °C), sore throat, cough and headache. A nasopharyngeal sample collected from this patient was detected positive for HAdV-7 by PCR sequencing on February 22, 2013. Thereafter, 5 roommates consecutively had ARD symptoms. These investigations revealed that nosocomial transmission by close contact contributed to the introduction of HAdV-7 into the training base B (Jingmen), indicating the potential transmission link between the two outbreaks. This figure including the drawings of people was drawn by the author Shaofu Qiu.
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f2: Timeline of critical events and nosocomial transmission for the index cases.Index case C was hospitalized due to a training injury from February 3 to 8, 2013. During his hospitalization, there were also about 70 patients hospitalized in the Xiangyang affiliated hospital from the Base A outbreak (Xiangyang). All cases were housed in the same in-patient building. Index case C had close contact with Index case B, a confirmed HAdV-7 case from the Xiangyang outbreak. They reported verbal contact twice for about half an hour on February 5 and 7, 2013, respectively. After 5 days of hospitalization, he returned to the training base B (Jingmen) on February 8, 2013, and took part in the normal training without isolation for medical observation. On February 11, 2013, he developed symptoms of ARD with fever (maximum temperature 39·0 °C), sore throat, cough and headache. A nasopharyngeal sample collected from this patient was detected positive for HAdV-7 by PCR sequencing on February 22, 2013. Thereafter, 5 roommates consecutively had ARD symptoms. These investigations revealed that nosocomial transmission by close contact contributed to the introduction of HAdV-7 into the training base B (Jingmen), indicating the potential transmission link between the two outbreaks. This figure including the drawings of people was drawn by the author Shaofu Qiu.

Mentions: Based on the similar demographic characteristics, clinical presentations, laboratory and radiographic findings, possible epidemiological associations that might link the outbreaks was explored. Preliminary investigations identified a 22-year-old male recruit (Index case A) who had ARD symptoms before reporting to Base A (Xiangyang) on December 6, 2012 (Fig. 2). He arrived at the training base on December 10, 2012. During the next one month, he was treated in the clinic of Base A by empirical administration of roxithromycin, lincomycin, ceftriaxone and ribavirin, however his condition did not resolve and by January 10, 2013 had worsened to persistent high fever (39–39.9 °C) and shortness of breath. The case was admitted to Xiangyang affiliated hospital on January 11, 2013 where he was diagnosed as a severe pneumonia case with multiorgan damage. He had an elevated WBC count (12.5 × 109 cells/liter), creatine kinase (56867 U/liter), lactate dehydrogenase (348 U/liter), aspartate aminotransferase (687 U/liter), alanine aminotransferase (303 U/liter) and C-reactive protein (28.16 mg/liter), and decreased level of potassium (3.39 μmol/liter). He was treated with additional antimicrobial and antiviral agents including azithromycin, levofloxacin, cefepime and ribavirin, and methylprednisolone was intravenously administered (range, 40–320 mg per day). Liver-protective and myocardial nutritional drugs were also prescribed. After 25 days of hospitalization the case made a full recovery. A serum sample collected on January 10, 2013 was positive for HAdV IgA, and a HAdV-7 isolate was identified from a nasopharyngeal sample collected on January 17, 2013 by PCR and viral culture, suggesting that the case had prolonged shedding of adenovirus (Fig. 2). From December to January, this case was not quarantined at Base A, and he participated in normal training and educational activities including the training course opening ceremony on December 20, 2012. During this period, 9 recruits living in the same dormitory (9/12) with the index case successively showed ARD symptoms; HAdV-7 was detected in 7 (77.8%) by PCR analysis of nasopharyngeal samples.


Whole-genome Sequencing for Tracing the Transmission Link between Two ARD Outbreaks Caused by a Novel HAdV Serotype 7 Variant, China.

Qiu S, Li P, Liu H, Wang Y, Liu N, Li C, Li S, Li M, Jiang Z, Sun H, Li Y, Xie J, Yang C, Wang J, Li H, Yi S, Wu Z, Jia L, Wang L, Hao R, Sun Y, Huang L, Ma H, Yuan Z, Song H - Sci Rep (2015)

Timeline of critical events and nosocomial transmission for the index cases.Index case C was hospitalized due to a training injury from February 3 to 8, 2013. During his hospitalization, there were also about 70 patients hospitalized in the Xiangyang affiliated hospital from the Base A outbreak (Xiangyang). All cases were housed in the same in-patient building. Index case C had close contact with Index case B, a confirmed HAdV-7 case from the Xiangyang outbreak. They reported verbal contact twice for about half an hour on February 5 and 7, 2013, respectively. After 5 days of hospitalization, he returned to the training base B (Jingmen) on February 8, 2013, and took part in the normal training without isolation for medical observation. On February 11, 2013, he developed symptoms of ARD with fever (maximum temperature 39·0 °C), sore throat, cough and headache. A nasopharyngeal sample collected from this patient was detected positive for HAdV-7 by PCR sequencing on February 22, 2013. Thereafter, 5 roommates consecutively had ARD symptoms. These investigations revealed that nosocomial transmission by close contact contributed to the introduction of HAdV-7 into the training base B (Jingmen), indicating the potential transmission link between the two outbreaks. This figure including the drawings of people was drawn by the author Shaofu Qiu.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4559894&req=5

f2: Timeline of critical events and nosocomial transmission for the index cases.Index case C was hospitalized due to a training injury from February 3 to 8, 2013. During his hospitalization, there were also about 70 patients hospitalized in the Xiangyang affiliated hospital from the Base A outbreak (Xiangyang). All cases were housed in the same in-patient building. Index case C had close contact with Index case B, a confirmed HAdV-7 case from the Xiangyang outbreak. They reported verbal contact twice for about half an hour on February 5 and 7, 2013, respectively. After 5 days of hospitalization, he returned to the training base B (Jingmen) on February 8, 2013, and took part in the normal training without isolation for medical observation. On February 11, 2013, he developed symptoms of ARD with fever (maximum temperature 39·0 °C), sore throat, cough and headache. A nasopharyngeal sample collected from this patient was detected positive for HAdV-7 by PCR sequencing on February 22, 2013. Thereafter, 5 roommates consecutively had ARD symptoms. These investigations revealed that nosocomial transmission by close contact contributed to the introduction of HAdV-7 into the training base B (Jingmen), indicating the potential transmission link between the two outbreaks. This figure including the drawings of people was drawn by the author Shaofu Qiu.
Mentions: Based on the similar demographic characteristics, clinical presentations, laboratory and radiographic findings, possible epidemiological associations that might link the outbreaks was explored. Preliminary investigations identified a 22-year-old male recruit (Index case A) who had ARD symptoms before reporting to Base A (Xiangyang) on December 6, 2012 (Fig. 2). He arrived at the training base on December 10, 2012. During the next one month, he was treated in the clinic of Base A by empirical administration of roxithromycin, lincomycin, ceftriaxone and ribavirin, however his condition did not resolve and by January 10, 2013 had worsened to persistent high fever (39–39.9 °C) and shortness of breath. The case was admitted to Xiangyang affiliated hospital on January 11, 2013 where he was diagnosed as a severe pneumonia case with multiorgan damage. He had an elevated WBC count (12.5 × 109 cells/liter), creatine kinase (56867 U/liter), lactate dehydrogenase (348 U/liter), aspartate aminotransferase (687 U/liter), alanine aminotransferase (303 U/liter) and C-reactive protein (28.16 mg/liter), and decreased level of potassium (3.39 μmol/liter). He was treated with additional antimicrobial and antiviral agents including azithromycin, levofloxacin, cefepime and ribavirin, and methylprednisolone was intravenously administered (range, 40–320 mg per day). Liver-protective and myocardial nutritional drugs were also prescribed. After 25 days of hospitalization the case made a full recovery. A serum sample collected on January 10, 2013 was positive for HAdV IgA, and a HAdV-7 isolate was identified from a nasopharyngeal sample collected on January 17, 2013 by PCR and viral culture, suggesting that the case had prolonged shedding of adenovirus (Fig. 2). From December to January, this case was not quarantined at Base A, and he participated in normal training and educational activities including the training course opening ceremony on December 20, 2012. During this period, 9 recruits living in the same dormitory (9/12) with the index case successively showed ARD symptoms; HAdV-7 was detected in 7 (77.8%) by PCR analysis of nasopharyngeal samples.

Bottom Line: WGS analyses showed that the HAdV-7 isolates from the two outbreaks were genetically indistinguishable; however, a 12 bp deletion in the virus-associated RNA gene distinguished the outbreak isolates from other HAdV-7 isolates.Outbreak HAdV-7 isolates demonstrated increased viral replication compared to non-outbreak associated HAdV-7 isolate.Our findings imply that in-hospital contact investigations should be encouraged to reduce or interrupt further spread of infectious agents when treating outbreak cases, and WGS can provide useful information guiding infection-control interventions.

View Article: PubMed Central - PubMed

Affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing 100071, China.

ABSTRACT
From December 2012 to February 2013, two outbreaks of acute respiratory disease caused by HAdV-7 were reported in China. We investigated possible transmission links between these two seemingly unrelated outbreaks by integration of epidemiological and whole-genome sequencing (WGS) data. WGS analyses showed that the HAdV-7 isolates from the two outbreaks were genetically indistinguishable; however, a 12 bp deletion in the virus-associated RNA gene distinguished the outbreak isolates from other HAdV-7 isolates. Outbreak HAdV-7 isolates demonstrated increased viral replication compared to non-outbreak associated HAdV-7 isolate. Epidemiological data supported that the first outbreak was caused by introduction of the novel HAdV-7 virus by an infected recruit upon arrival at the training base. Nosocomial transmission by close contacts was the most likely source leading to onset of the second HAdV-7 outbreak, establishing the apparent transmission link between the outbreaks. Our findings imply that in-hospital contact investigations should be encouraged to reduce or interrupt further spread of infectious agents when treating outbreak cases, and WGS can provide useful information guiding infection-control interventions.

No MeSH data available.


Related in: MedlinePlus