Differentiation between Wild-Type Group A Rotaviruses and Vaccine Strains in Cases of Suspected Horizontal Transmission and Adverse Events Following Vaccination
Human group A rotaviruses (RVA) are important enteric pathogens, as they are a leading cause of acute gastroenteritis (AGE) in children worldwide. Since 2013, the German Standing Committee on vaccination recommended the routine rotavirus vaccination for infants in Germany. While vaccination has sign...
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| Format: | Article |
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MDPI AG
2022-07-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/8/1670 |
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| author | Sonja Jacobsen Sandra Niendorf Roswitha Lorenz C.-Thomas Bock Andreas Mas Marques |
| author_facet | Sonja Jacobsen Sandra Niendorf Roswitha Lorenz C.-Thomas Bock Andreas Mas Marques |
| author_sort | Sonja Jacobsen |
| collection | DOAJ |
| description | Human group A rotaviruses (RVA) are important enteric pathogens, as they are a leading cause of acute gastroenteritis (AGE) in children worldwide. Since 2013, the German Standing Committee on vaccination recommended the routine rotavirus vaccination for infants in Germany. While vaccination has significantly decreased RVA cases and worldwide mortality, in some cases, infants can develop acute gastroenteritis as an adverse reaction after immunization with an attenuated live vaccine. Pediatricians, as well as clinicians and diagnostic laboratories, contacted the Consultant Laboratory for Rotaviruses and inquired whether cases of RVA-positive AGE after vaccination were associated with vaccine or with wild-type RVA strains. A testing algorithm based on distinguishing PCRs and confirmative sequencing was designed, tested, and applied. Diagnostic samples from 68 vaccinated children and six cases where horizontal transmission was suspected were investigated in this study. Using a combination of real-time PCR, fragment-length analysis of amplicons from multiplex PCRs and confirmative sequencing, vaccine-like virus was detected in 46 samples and wild-type RVA was detected in 6 samples. Three mixed infections of vaccine and wild-type RVA were detectable, no RVA genome was found in 19 samples. High viral loads (>1.0 × 10<sup>7</sup> copies/g stool) were measured in most RVA-positive samples. Furthermore, information on co-infections with other AGE pathogens in the vaccinated study population was of interest. A commercial multiplex PCR and in-house PCRs revealed three co-infections of vaccinated infants with bacteria (two samples with <i>Clostridioides difficile</i> and one sample with enteropathogenic <i>E. coli</i>) and six co-infections with norovirus in a subset of the samples. Human astrovirus was detected in one sample, with suspected horizontal transmission. The cases of suspected horizontal transmission of vaccine RVA strains could not be confirmed, as they either involved wild-type RVA or were RVA negative. This study shows that RVA-positive AGE after vaccination is not necessarily associated with the vaccine strain and provides a reliable workflow to distinguish RVA vaccine strains from wild-type strains. |
| first_indexed | 2024-03-09T03:42:07Z |
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| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T03:42:07Z |
| publishDate | 2022-07-01 |
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| spelling | doaj.art-1224980a5bed4c43a14eb3c4b95543ad2023-12-03T14:38:59ZengMDPI AGViruses1999-49152022-07-01148167010.3390/v14081670Differentiation between Wild-Type Group A Rotaviruses and Vaccine Strains in Cases of Suspected Horizontal Transmission and Adverse Events Following VaccinationSonja Jacobsen0Sandra Niendorf1Roswitha Lorenz2C.-Thomas Bock3Andreas Mas Marques4Unit Gastroenteritis and Hepatitis Viruses and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, Seestraße 10, 13353 Berlin, GermanyUnit Gastroenteritis and Hepatitis Viruses and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, Seestraße 10, 13353 Berlin, GermanyUnit Gastroenteritis and Hepatitis Viruses and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, Seestraße 10, 13353 Berlin, GermanyUnit Gastroenteritis and Hepatitis Viruses and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, Seestraße 10, 13353 Berlin, GermanyUnit Gastroenteritis and Hepatitis Viruses and Enteroviruses, Department of Infectious Diseases, Robert Koch Institute, Seestraße 10, 13353 Berlin, GermanyHuman group A rotaviruses (RVA) are important enteric pathogens, as they are a leading cause of acute gastroenteritis (AGE) in children worldwide. Since 2013, the German Standing Committee on vaccination recommended the routine rotavirus vaccination for infants in Germany. While vaccination has significantly decreased RVA cases and worldwide mortality, in some cases, infants can develop acute gastroenteritis as an adverse reaction after immunization with an attenuated live vaccine. Pediatricians, as well as clinicians and diagnostic laboratories, contacted the Consultant Laboratory for Rotaviruses and inquired whether cases of RVA-positive AGE after vaccination were associated with vaccine or with wild-type RVA strains. A testing algorithm based on distinguishing PCRs and confirmative sequencing was designed, tested, and applied. Diagnostic samples from 68 vaccinated children and six cases where horizontal transmission was suspected were investigated in this study. Using a combination of real-time PCR, fragment-length analysis of amplicons from multiplex PCRs and confirmative sequencing, vaccine-like virus was detected in 46 samples and wild-type RVA was detected in 6 samples. Three mixed infections of vaccine and wild-type RVA were detectable, no RVA genome was found in 19 samples. High viral loads (>1.0 × 10<sup>7</sup> copies/g stool) were measured in most RVA-positive samples. Furthermore, information on co-infections with other AGE pathogens in the vaccinated study population was of interest. A commercial multiplex PCR and in-house PCRs revealed three co-infections of vaccinated infants with bacteria (two samples with <i>Clostridioides difficile</i> and one sample with enteropathogenic <i>E. coli</i>) and six co-infections with norovirus in a subset of the samples. Human astrovirus was detected in one sample, with suspected horizontal transmission. The cases of suspected horizontal transmission of vaccine RVA strains could not be confirmed, as they either involved wild-type RVA or were RVA negative. This study shows that RVA-positive AGE after vaccination is not necessarily associated with the vaccine strain and provides a reliable workflow to distinguish RVA vaccine strains from wild-type strains.https://www.mdpi.com/1999-4915/14/8/1670rotavirus Aacute gastroenteritisvaccinationvirus sheddingdiagnostic workflowmolecular diagnostics |
| spellingShingle | Sonja Jacobsen Sandra Niendorf Roswitha Lorenz C.-Thomas Bock Andreas Mas Marques Differentiation between Wild-Type Group A Rotaviruses and Vaccine Strains in Cases of Suspected Horizontal Transmission and Adverse Events Following Vaccination Viruses rotavirus A acute gastroenteritis vaccination virus shedding diagnostic workflow molecular diagnostics |
| title | Differentiation between Wild-Type Group A Rotaviruses and Vaccine Strains in Cases of Suspected Horizontal Transmission and Adverse Events Following Vaccination |
| title_full | Differentiation between Wild-Type Group A Rotaviruses and Vaccine Strains in Cases of Suspected Horizontal Transmission and Adverse Events Following Vaccination |
| title_fullStr | Differentiation between Wild-Type Group A Rotaviruses and Vaccine Strains in Cases of Suspected Horizontal Transmission and Adverse Events Following Vaccination |
| title_full_unstemmed | Differentiation between Wild-Type Group A Rotaviruses and Vaccine Strains in Cases of Suspected Horizontal Transmission and Adverse Events Following Vaccination |
| title_short | Differentiation between Wild-Type Group A Rotaviruses and Vaccine Strains in Cases of Suspected Horizontal Transmission and Adverse Events Following Vaccination |
| title_sort | differentiation between wild type group a rotaviruses and vaccine strains in cases of suspected horizontal transmission and adverse events following vaccination |
| topic | rotavirus A acute gastroenteritis vaccination virus shedding diagnostic workflow molecular diagnostics |
| url | https://www.mdpi.com/1999-4915/14/8/1670 |
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