Astrovirus Infection and Diarrhea in 8 Countries

Olórtegui, Maribel Paredes; Rouhani, Saba; Yori, Pablo Peñataro; Salas, Mery Siguas; Trigoso, Dixner Rengifo; Mondal, Dinesh; Bodhidatta, Ladaporn; Platts-Mills, James A; Samie, Amidou; Kabir, Furqan; Lima, Aldo A. M.; Babji, Sudhir; Shrestha, Sanjaya; Mason, C.; Kalam, Adil; Bessong, Pascal; Ahmed, Tahmeed; Mduma, Estomih; Bhutta, Zulfiqar A; Lima, Ila Fernanda Nunes; Ramdass, Rakhi; Moulton, Lawrence H.; Lang, Dennis; George, Ajila; Zaidi, Anita K. M.; Kang, Gagandeep; Houpt, Eric R.; Kosek, Margaret

doi:10.1542/peds.2017-1326

Cited by 55 publications

(44 citation statements)

References 38 publications

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“…In a related study, norovirus GII, rotavirus, and astrovirus exhibited the highest attributable burdens of diarrhea in the first 2 years of life (6). These studies show that HAstV is an overlooked cause of diarrhea among vulnerable children worldwide, and they highlight the need for future research as well as the importance of this virus as a target for vaccine development (5,6).…”

mentioning

confidence: 89%

“…middle-income countries with high prevalence of diarrhea and undernutrition was reported (5); the prevalence of HAstV in diarrheal stools was 5.6%, and remarkably, the disease severity exceeded that of all enteropathogens tested except rotavirus. In a related study, norovirus GII, rotavirus, and astrovirus exhibited the highest attributable burdens of diarrhea in the first 2 years of life (6).…”

mentioning

confidence: 96%

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Isolation of Neutralizing Monoclonal Antibodies to Human Astrovirus and Characterization of Virus Variants That Escape Neutralization

Espinosa

López

Bogdanoff

et al. 2019

J Virol

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Human astroviruses (HAstVs) cause severe diarrhea and represent an important health problem in children under two years of age. Despite their medical importance, the study of these pathogens has been neglected. To better understand the astrovirus antigenic structure and the basis of protective immunity, in this work we produced a panel of neutralizing monoclonal antibodies (Nt-MAbs) to HAstV serotypes 1, 2, and 8 and identified the mutations that allow the viruses to escape neutralization. We first tested the capacity of the recombinant HAstV capsid core and spike domains to elicit Nt-Abs. Hyperimmunization of animals with the two domains showed that although both induced a potent immune response, only the spike was able to elicit antibodies with neutralizing activity. Based on this finding, we used a mixture of the recombinant spike domains belonging to the three HAstV serotypes to immunize mice. Five Nt-MAbs were isolated and characterized; all of them were serotype specific, two were directed to HAstV-1, one was directed to HAstV-2, and two were directed to HAstV-8. These antibodies were used to select single and double neutralization escape variant viruses, and determination of the amino acid changes that allow the viruses to escape neutralization permitted us to define the existence of four potentially independent neutralization epitopes on the HAstV capsid. These studies provide the basis for development of subunit vaccines that induce neutralizing antibodies and tools to explore the possibility of developing a specific antibody therapy for astrovirus disease. Our results also establish a platform to advance our knowledge on HAstV cell binding and entry. IMPORTANCE Human astroviruses (HAstVs) are common etiological agents of acute gastroenteritis in children, the elderly, and immunocompromised patients; some virus strains have also been associated with neurological disease. Despite their medical importance, the study of these pathogens has advanced at a slow pace. In this work, we produced neutralizing antibodies to the virus and mapped the epitopes they recognize on the virus capsid. These studies provide the basis for development of subunit vaccines that induce neutralizing antibodies, as well as tools to explore the development of a specific antibody therapy for astrovirus disease. Our results also establish a platform to advance our knowledge on HAstV cell binding and entry.

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mentioning

confidence: 89%

mentioning

confidence: 96%

Isolation of Neutralizing Monoclonal Antibodies to Human Astrovirus and Characterization of Virus Variants That Escape Neutralization

Espinosa

López

Bogdanoff

et al. 2019

J Virol

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“…The research was carried out in compliance with the Helsinki Declaration. astrovirus in diarrheal stools was 5.6% according to a multiple-country study [9]. As previous research revealed, that the classic human astrovirus is highly diverse and consists of eight genotypes (genotype 1-8), while genotype 1 was the most prevalent genotype globally.…”

Section: Ethical Approvalmentioning

confidence: 86%

An Acute Gastroenteritis Outbreak Caused by Astrovirus Serotype 4 in a School of Shenzhen City, China, 2017

Luo¹,

Li²,

Gao³

et al. 2020

J Infect Dis Epidemiol

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Background: In November of 2017, a school outbreak of acute gastroenteritis was reported from Shenzhen City. Methods: A cohort study was conducted to describe the epidemiological characteristics of the outbreak. Data on demographic details, onset of clinical symptoms, food and water intake history, contact with ill person prior to illness were obtained. Results: 98 student-cases were identified. The main symptoms included vomiting (69%), abdominal pain (59%), nausea (47%), diarrhea (43%) and cough (38%) with the median duration of illness of 2 days (range: 1-8 days). The AR was 3.2% and involved 63% of the classes with the median age of 10 years (range 6-15 years). Based on epidemiological investigation, multivariate analysis showed that touching with ill students (RR = 3.95, 95% CI = 2.18-5.58) and touching the handles of faucet (RR = 4.18, 95% CI = 1.50-8.37) were associated with illness. Astrovirus serotype 4 was detected in 6 ill students and 1 asymptomatic cleaning staff. Conclusions: This outbreak was caused by astrovirus. The main exposure mode was likely person to person and touching a contaminated water faucet. Recommendations included immediate isolation of cases and daily disinfecting the drinking water faucet. In the future, surveillance for astrovirus should be strengthened by laboratory testing after other common pathogens are ruled out.

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“…Classical HAstV (serotypes 1‐8) are phylogenetically distant from novel HAstV (namely MLB and VA) with amino acid identities being as low as 23% to a maximum of 54.5% depending on the open reading frames 1. Although classical HAstV are a leading cause of viral gastroenteritis, especially in children, elderly, and immunocompromised patients,2, 3, 4 the clinical manifestations of novel HAstV have not been fully characterized 5, 6, 7, 8. The spectrum of human diseases for classical and novel HAstV is not restricted to the gastrointestinal tract: both have been reported as causal agents of central nervous system infections 1.…”

Section: Introductionmentioning

confidence: 99%

Novel human astroviruses in pediatric respiratory samples: A one‐year survey in a Swiss tertiary care hospital

Cordey

Zanella

Wagner

et al. 2018

Journal of Medical Virology

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Although classical human astroviruses (HAstV) are known to be a leading cause of viral gastroenteritis, the pathogenesis and clinical manifestations of novel HAstV remain largely unknown. There is mounting evidence that, in contrast to classical astroviruses, novel HAstV exhibit tropism for the upper respiratory tract. This one‐year period prevalence screened all available clinical nasopharyngeal swab samples collected from pediatric patients aged ≤5 years for novel and classical HAstV using real‐time reverse transcription polymerase chain reaction. A total of 205 samples were tested; two novel HAstV cases were detected for a prevalence of 1.3%, with viral loads suggesting active upper respiratory tract replication. No classical HAstV was detected.

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Astrovirus Infection and Diarrhea in 8 Countries

Abstract: Astrovirus is an overlooked cause of diarrhea among vulnerable children worldwide. With the evidence presented here, we highlight the need for future research as well as the potential for astrovirus to be a target for vaccine development.

Cited by 55 publications

References 38 publications

Isolation of Neutralizing Monoclonal Antibodies to Human Astrovirus and Characterization of Virus Variants That Escape Neutralization

Isolation of Neutralizing Monoclonal Antibodies to Human Astrovirus and Characterization of Virus Variants That Escape Neutralization

An Acute Gastroenteritis Outbreak Caused by Astrovirus Serotype 4 in a School of Shenzhen City, China, 2017

Novel human astroviruses in pediatric respiratory samples: A one‐year survey in a Swiss tertiary care hospital

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