Neonatal hand, foot, and mouth disease due to Coxsackievirus A6 in Shanghai

Abstract Background: Evidence of hand, foot, and mouth disease (HFMD) in neonates is limited. The aim of this study was to evaluate the clinical symptoms, pathogens, possible transmission routes, and prognosis of neonatal HFMD in Shanghai. Methods: This was a case-control study based on the HFMD registry surveillance system. All neonates and infected family members were enrolled between 2016 and 2017 in Shanghai. Neonates with HFMD were followed for at least half a year. Detailed questionnaires, medical history, and physical examination were recorded. Routine blood examination, liver and renal function, immunophenotypes of peripheral blood lymphocytes (CD3, CD4, and CD8 T-cells; NK cells), immunoglobulin (Ig) M, IgG, and IgA, and cytokine interleukin (IL-1β, IL-2R, IL-6, IL-8, IL-10, and TNF-α) levels were measured. All rectal swab specimens were collected and genotyped for enterovirus, and phylogenetic analysis based on the VP1 sequences of coxsackievirus A6 (CV-A6) was performed to investigate molecular and evolutionary characteristics. T-test or nonparametric test was used to evaluate the differences. Logistic analysis was applied to calculate the risk of clinical manifestations in the group of HFMD neonates and their paired siblings. Results: There were 16 neonates among the 12608 diagnosed patients with HFMD, accounting for 0.13%. All neonatal infections were transmitted by other members of the family, mainly the elder siblings, and were caused by CV-A6. CV-A6 was the emerging and predominant causative agent of HFMD in Shanghai. None of the neonates with HFMD experienced fever, onychomadesis, or severe complications. However, two elder sibling patients showed lethargy, and one developed hypoperfusion. In the elder siblings with HFMD, the proportion of white blood cells was generally higher than in neonates with HFMD. The immunologic function of the neonates with HFMD was basically normal. The levels of inflammatory markers were higher in both neonates and elder siblings with HFMD compared to age-matched controls. The clinical symptoms receded about one week after onset. None of the neonates had sequelae. Conclusions: In our study, CV-A6 infection in neonates was benign, but had the character of family clustering. Due to the two-child policy in China, elder siblings may be the main route of HFMD transmission.

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Neonatal hand, foot, and mouth disease due to Coxsackievirus A6 in Shanghai

10.21203/rs.2.14800/v2 ◽

2019 ◽

Author(s):

Shanshan Xu ◽

Huajun Li ◽

Peng Qiao ◽

Guofeng Xu ◽

Dongying Zhao ◽

...

Keyword(s):

Clinical Symptoms ◽

White Blood Cells ◽

Foot And Mouth Disease ◽

Nonparametric Test ◽

Peripheral Blood Lymphocytes ◽

Mouth Disease ◽

Mild Disease ◽

Logistic Analysis ◽

Coxsackievirus A6 ◽

Foot And Mouth

Abstract Background: Evidence of hand, foot, and mouth disease (HFMD) in neonates is limited. The aim of this study was to evaluate the clinical symptoms, possible transmission routes, and prognosis of neonatal HFMD in Shanghai. Methods: This was a case-control study based on the HFMD registry surveillance system. All neonates and infected family members were enrolled between 2016 and 2017 in Shanghai. Neonates with HFMD were followed for at least half a year. Detailed questionnaires, medical history, and physical examination were recorded. Routine blood examination, liver and renal function, immunophenotypes of peripheral blood lymphocytes (CD3, CD4, and CD8 T-cells; NK cells), immunoglobulin (Ig) M, IgG, and IgA, and cytokine interleukin (IL-1β, IL-2R, IL-6, IL-8, IL-10, and TNF-α) levels were measured. All rectal swab specimens were collected and genotyped for enterovirus. T-test or nonparametric test was used to evaluate the differences. Logistic analysis was applied to calculate the risk of clinical symptoms in the group of HFMD neonates and their paired siblings. Results: There were 16 neonates among the 12608 diagnosed patients with HFMD, accounting for 1.3‰. All neonatal infections were transmitted by other members of the family, mainly the elder siblings, and involved different types of coxsackievirus A6. Coxsackievirus A6 is also the emerging and predominant causative agent of HFMD in Shanghai. None of the neonates with HFMD suffered fever, onychomadesis, or severe complications. However, two elder sibling patients showed lethargy, and one developed hypoperfusion. In the elder siblings with HFMD, the proportion of white blood cells was generally higher than in neonates with HFMD. The immunologic function of the neonates with HFMD was basically normal. The levels of inflammatory markers were higher in both neonates and elder siblings with HFMD compared to their age-matched controls. The clinical symptoms receded after about one week of onset. None of the neonates had sequelae. Conclusions: All neonates with coxsackievirus A6 HFMD had mild disease with no complications or sequelae. Notably, due to the two-child policy in China, elder siblings may be the main route of HFMD transmission.

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Neonatal hand, foot, and mouth disease due to Coxsackievirus A6 in Shanghai

10.21203/rs.2.14800/v3 ◽

2020 ◽

Author(s):

Shanshan Xu ◽

Huajun Li ◽

Peng Qiao ◽

Guofeng Xu ◽

Dongying Zhao ◽

...

Keyword(s):

Clinical Symptoms ◽

White Blood Cells ◽

Foot And Mouth Disease ◽

Nonparametric Test ◽

Peripheral Blood Lymphocytes ◽

Mouth Disease ◽

Mild Disease ◽

Logistic Analysis ◽

Coxsackievirus A6 ◽

Foot And Mouth

Abstract Background: Evidence of hand, foot, and mouth disease (HFMD) in neonates is limited. The aim of this study was to evaluate the clinical symptoms, possible transmission routes, and prognosis of neonatal HFMD in Shanghai. Methods: This was a case-control study based on the HFMD registry surveillance system. All neonates and infected family members were enrolled between 2016 and 2017 in Shanghai. Neonates with HFMD were followed for at least half a year. Detailed questionnaires, medical history, and physical examination were recorded. Routine blood examination, liver and renal function, immunophenotypes of peripheral blood lymphocytes (CD3, CD4, and CD8 T-cells; NK cells), immunoglobulin (Ig) M, IgG, and IgA, and cytokine interleukin (IL-1β, IL-2R, IL-6, IL-8, IL-10, and TNF-α) levels were measured. All rectal swab specimens were collected and genotyped for enterovirus. T-test or nonparametric test was used to evaluate the differences. Logistic analysis was applied to calculate the risk of clinical symptoms in the group of HFMD neonates and their paired siblings. Results: There were 16 neonates among the 12608 diagnosed patients with HFMD, accounting for 0.1%. All neonatal infections were transmitted by other members of the family, mainly the elder siblings, and involved different types of coxsackievirus A6. Coxsackievirus A6 is also the emerging and predominant causative agent of HFMD in Shanghai. None of the neonates with HFMD suffered fever, onychomadesis, or severe complications. However, two elder sibling patients showed lethargy, and one developed hypoperfusion. In the elder siblings with HFMD, the proportion of white blood cells was generally higher than in neonates with HFMD. The immunologic function of the neonates with HFMD was basically normal. The levels of inflammatory markers were higher in both neonates and elder siblings with HFMD compared to their age-matched controls. The clinical symptoms receded after about one week of onset. None of the neonates had sequelae. Conclusions: All neonates with coxsackievirus A6 HFMD had mild disease with no complications or sequelae. Notably, due to the two-child policy in China, elder siblings may be the main route of HFMD transmission.

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Neonatal hand, foot, and mouth disease: a case-control study in Shanghai

10.21203/rs.2.14800/v1 ◽

2019 ◽

Author(s):

Shanshan Xu ◽

Huajun Li ◽

Peng Qiao ◽

Guofeng Xu ◽

Dongying Zhao ◽

...

Keyword(s):

Case Control Study ◽

Clinical Symptoms ◽

White Blood Cells ◽

Foot And Mouth Disease ◽

Case Control ◽

Peripheral Blood Lymphocytes ◽

Mouth Disease ◽

Coxsackievirus A6 ◽

Foot And Mouth ◽

Control Study

Abstract Background Evidence of hand, foot, and mouth disease (HFMD) in neonates is limited. This study aimed to report the clinical symptoms, possible transmission routes, and prognosis of neonatal HFMD in Shanghai. Methods This was a case-control study based on registry system of HFMD. All neonates and infected family members were enrolled between 2016 and 2017 in Shanghai. Neonates with HFMD were followed for at least half a year. The detailed questionnaires, medical history and physical examination were recorded. Routine blood examination, liver and renal function, immunophenotypes of peripheral blood lymphocytes (CD3, CD4, and CD8 T-cells; NK cells), immunoglobulin (Ig) M, IgG, and IgA and cytokine interleukin (IL-1β, IL-2R, IL-6, IL-8, IL-10, and TNF-α) levels were detected. All rectal swab specimens were collected and genotyped for enterovirus. T-test or nonparametric test was used to evaluate the differences. Logistic analysis was applied to find the risk of clinical symptoms in the group of neonates and their HFMD paired siblings.Results There were 16 neonates among the 12608 diagnosed patients with HFMD, accounting for 1.3‰. All the neonates were transmitted within-family, mainly by the elder sibling, with different types of coxsackievirus A6 infection. Coxsackievirus A6 was also the emerging and predominant causative agent of HFMD in Shanghai. None of the neonates with HFMD suffered fever, onychomadesis, or severe complications. However, two elder sibling patients showed lethargy, and one developed hypoperfusion. The white blood cells in the elder siblings with HFMD were generally higher than the neonates with HFMD. The immunologic function of the neonates was basically normal. The inflammatory response was high regardless of the neonates or elder siblings. The clinical symptoms receded at about one week. None of the neonates had sequalae.Conclusions The severity of neonates infected with HFMD may vary with pathogen. With the two-child policy in China, it should be noticed that elder siblings may be the main route of HFMD transmission.

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Clinical Manifestations of Coxsackievirus A6 Infection Associated with a Major Outbreak of Hand, Foot, and Mouth Disease in Japan

Japanese Journal of Infectious Diseases ◽

10.7883/yoken.66.260 ◽

2013 ◽

Vol 66 (3) ◽

pp. 260-261 ◽

Cited By ~ 18

Author(s):

Masaaki Kobayashi ◽

Tomohiko Makino ◽

Nozomu Hanaoka ◽

Hiroyuki Shimizu ◽

Miki Enomoto ◽

...

Keyword(s):

Clinical Manifestations ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Coxsackievirus A6 ◽

Foot And Mouth ◽

Major Outbreak

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Characterization of oral virome and microbiome revealed distinctive microbiome disruptions in paediatric patients with hand, foot and mouth disease

npj Biofilms and Microbiomes ◽

10.1038/s41522-021-00190-y ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Si Xian Ho ◽

Nyo Min ◽

Emmerie Phaik Yen Wong ◽

Chia Yin Chong ◽

Justin Jang Hann Chu

Keyword(s):

Wide Spectrum ◽

Clinical Manifestations ◽

Human Microbiome ◽

Foot And Mouth Disease ◽

Critical Factor ◽

Mouth Disease ◽

Oral Microbiome ◽

Coxsackievirus A6 ◽

Foot And Mouth

AbstractWhile the underlying determinants are unclear, hand, foot and mouth disease (HFMD) presents a wide spectrum of clinical manifestations with varying severity in different individuals. Recently, many studies identified the human microbiome as a critical factor in the pathogenesis of various diseases. Therefore, we here investigated the ecological dynamics of the oral microbiome changes during the HFMD infection. After targeted enrichment of all known vertebrate viruses, the virome profiles of symptomatic and asymptomatic HFMD patients were examined and revealed to be significantly altered from those of healthy individuals, with nine discriminative viruses detected. Further characterization of the prokaryotic microbiome revealed an elevated level of Streptococcus sp. as the most important signature of the symptomatic HFMD cohort, positively correlating to the level of enterovirus A RNA. In addition, we found that while coxsackievirus A5 is detected in saliva RNA of all asymptomatic cases, coxsackievirus A6 dominates the majority of the symptomatic cohort.

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Simultaneous enterovirus EV-D68 and CVA6 infections causing acute respiratory distress syndrome and hand, foot and mouth disease

Virology Journal ◽

10.1186/s12985-021-01560-w ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Ivanildo Pedro de Sousa ◽

Heloísa Ihle Giamberardino ◽

Sonia Mara Raboni ◽

Maria Carmo Debur ◽

Maria de Lourdes Aguiar Oliveira ◽

...

Keyword(s):

Respiratory Distress ◽

Clinical Symptoms ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Rt Pcr ◽

Double Infection ◽

Chinese Strain ◽

Case Presentation ◽

Foot And Mouth ◽

Shed Light

Abstract Background Although most enterovirus (EV) infections can be asymptomatic, these viral agents can cause serious conditions associated with central nervous system, respiratory disease and uncommon manifestations of hand, foot and mouth disease (HFMD). EV-coinfections have been rarely reported with development of complications and severe clinical outcome. An atypical case of a child presenting HFMD and severe acute respiratory syndrome, co-infected with EV-D68 and CVA6, is reported herein. Case presentation A 3-year-old boy was admitted in the emergency department unit showing fever, abdominal pain and tachycardia. Twenty-four hours after hospitalization the child developed severe clinical symptoms associated with HFMD and was discharged after recovery. Two days later, the child was readmitted with fever, cough and respiratory distress. RT-PCR and Sanger sequencing confirmed positivity for EV-D68 and CVA6 in oro and nasopharynges swabs and vesicles fluid, respectively. Phylogenetic analysis based on VP1 gene sequences suggested that CVA6 was closely related with HFMD viruses circulating in Turkey, while EV-D68 was genetically related to a Chinese strain. Conclusions To the best of our knowledge, this case is the first report of a double infection caused by CVA6 and EV-D68, which shed light on the pathogenesis of enterovirus infections. Further studies must be conducted to ascertain the role and clinical significance of EV co-infections, as well as a potential synergistic pathway between these viruses.

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