Search

Background: Since August 2017, Myanmar nationals from Rakhine state have crossed the border into Bangladesh and settled in Cox's Bazar, the World's largest refugee camp. Due to overcrowding, poor sanitation, and hygienic practices they have been under significant health risks including diarrheal diseases. The objective of this study is to determine the viral etiology of acute gastroenteritis (AGE) among forcibly displaced Myanmar nationals (FDMN) and adjacent Bangladeshi local host population (AHP)., Methods: From April 2018 to April 2019, we collected stool specimens from 764 FDMN and 1159 AHP of all ages. We tested 100 randomly selected specimens from each group for the most common AGE viruses., Results: Among 200 diarrhea patients, 55% and 64% of FDMN and AHP patients, respectively, had viral infections; the most common viruses were rotavirus (29% vs 44%), adenovirus (24% vs 31%), and norovirus (14% vs 10%). In both populations, viral infections were significantly higher in children less than 5 years of age, compared with bacterial infections that were higher in patients older than 5 years of age (P ≤ .05)., Conclusions: Disparities in viral and bacterial prevalence among various age groups warrant careful antibiotic usage, especially in children less than 5 years of age., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Noroviruses are the most common cause of epidemic and endemic acute gastroenteritis (AGE) worldwide. The burden of norovirus disease in low-income settings is poorly understood., Methods: We tested stool samples from children less than 5 years of age with diarrhea who were admitted in a rural hospital in Bangladesh from 2010-2012 and from matched, healthy controls from the same catchment area., Results: Norovirus was detected in 109 (18%) of 613 children with diarrhea and in 30 (15%) of 206 healthy controls. Most (n = 118; 85%) norovirus infections belonged to genogroup II (GII). Of these, GII.4 viruses were identified in 36 (33%) of the cases and in 6 (21%) of the controls. Other major genotypes included GII.3 (13%), GII.6 (11%), and GII.13 (11%) in the cases and GII.6 (17%) and GII.2 (14%) in the controls. The greatest risk of severe norovirus disease (Vesikari score ≥11) was associated with GII.4 infections. GII.4 viruses were the predominant genotype detected during the winter (55%) and rainy season (23%), while GII.3 (19%) and GII.13 (19%) viruses were the most prevalent genotypes during the summer. Vomiting was significantly associated with GII.4 infections, while longer durations of diarrhea were associated with GI.3 infections., Conclusions: Future studies are needed to understand the high rates of virus shedding in children without AGE symptoms., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Globally, noroviruses are among the foremost causes of acute diarrheal disease, yet there are many unanswered questions on norovirus immunity, particularly following natural infection in young children during the first 2 years of life when the disease burden is highest. We conducted a literature review on birth cohort studies assessing norovirus infections in children from birth to early childhood. Data on infection, immunity, and risk factors are summarized from 10 community-based birth cohort studies conducted in low- and middle-income countries. Up to 90% of children experienced atleast one norovirus infection and up to 70% experienced norovirus-associated diarrhea, most often affecting children 6 months of age and older. Data from these studies help to fill critical knowledge gaps for vaccine development, yet study design and methodological differences limit comparison between studies, particularly for immunity and risk factors for disease. Considerations for conducting future birth cohort studies on norovirus are discussed., (Published by Oxford University Press for the Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Noroviruses are a leading cause of diarrhea in children aged <5 years worldwide. We genotyped 88 viruses collected by active surveillance in a birth cohort of children <2 years of age in Dhaka, Bangladesh, during 2010-2013. Twenty-five of 31 (81%) established GI and GII genotypes were detected, with GII.4 as the predominant genotype (20%). Our results show that children in Bangladesh are infected with a great diversity of norovirus strains. Reinfections are common, but not with closely related genotypes. Birth cohort studies are critical to understand cross-protective immunity and advance the development of pediatric norovirus vaccines.

Background: Nonsevere diarrheal disease in Nepal represents a large burden of illness. Identification of the specific disease-causing pathogens will help target the appropriate control measures., Methods: Infants aged 6 weeks to 12 months were recruited from 5 health facilities in eastern, central, and western Nepal between August 2012 and August 2013. The diarrhea arm included infants with mild or moderate diarrhea treatable in an outpatient setting; the nondiarrhea arm included healthy infants who presented for immunization visits or had a mild nondiarrheal illness. Stool samples were tested for 15 pathogens with a multiplex polymerase chain reaction (PCR) assay and real-time reverse-transcription (RT)-PCR assays for rotavirus and norovirus. Rotavirus- and norovirus-positive specimens were genotyped. We calculated attributable fractions (AFs) to estimate the pathogen-specific burden of diarrhea and adjusted for facility, age, stunting, wasting, and presence of other pathogens., Results: We tested 307 diarrheal and 358 nondiarrheal specimens. Pathogens were detected more commonly in diarrheal specimens (164 of 307 [53.4%]) than in nondiarrheal specimens (113 of 358 [31.6%]) (P < .001). Rotavirus (AF, 23.9% [95% confidence interval (CI), 14.9%-32.8%]), Salmonella (AF, 12.4% [95% CI, 6.6%-17.8%]), and Campylobacter (AF, 5.6% [95% CI, 1.3%-9.8%]) contributed most to the burden of disease. In these diarrheal specimens, the most common genotypes for rotavirus were G12P[6] (27 of 82 [32.9%]) and G1P[8] (16 of 82 [19.5%]) and for norovirus were GII.4 Sydney (9 of 26 [34.6%]) and GII.7 (5 of 26 [19.2%])., Conclusions: The results of this study indicate that the introduction of a rotavirus vaccine in Nepal will likely decrease outpatient diarrheal disease burden in infants younger than 1 year, but interventions to detect and target other pathogens, such as Salmonella and Campylobacter spp, should also be considered., (Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Norovirus and sapovirus are important causes of acute gastroenteritis (AGE) among American Indian infants. We investigated the prevalence and molecular epidemiology of norovirus and sapovirus in American Indian infants who have historically experienced a high burden of AGE compared to other US populations. Stool samples were collected from 241 children with AGE (cases) and from 343 infants without AGE (controls) ≤9 months of age from 2002-2004. Cases experienced forceful vomiting and/or 3 or more watery or looser-than-normal stools in 24 hours. Stools were tested by real-time RT-PCR for norovirus GI, GII and GIV and sapovirus GI, GII, GIV and GV. Positive samples were genotyped after sequencing conventional RT-PCR products. Norovirus was identified in 76 (31.5%) of the cases and 70 (20.4%) of the controls (p<0.001). GII.3 and GII.4 Farmington Hills were the most frequently identified genotypes in 14.5% and 30.3% of cases and 17.1% and 27.1% of controls, respectively. Sapovirus GI and GII genotypes were identified in 8 (3.3%) of cases and 8 (2.3%) of controls and a single GIV virus was detected in a control. The same norovirus and sapovirus genotypes were circulating in the general U.S. population in the same time period. The high detection rate of norovirus in healthy controls suggests significant asymptomatic transmission in young infants in these communities., Competing Interests: The authors have declared that no competing interests exist.

Background: During 8-20 April 2012, an outbreak of gastrointestinal illness occurred among guests and employees of a resort hotel in St. Thomas, US Virgin Islands. We describe outbreak characteristics, and estimate indirect (non-medical) costs to travellers., Methods: Employees who met the case definition were interviewed and provided stool samples. Samples were tested for norovirus by real-time reverse-transcription polymerase chain reaction. Guests were asked to complete a survey aimed to identify and characterize cases, and to estimate quality adjusted vacation days (QAVD) lost., Results: Overall, 66 persons (20 employees and 46 guests) met the probable case definition. The first reported illness onset occurred in a hotel employee on 8 April, while the first reported onset in a guest occurred on 13 April. An employee suffered a public diarrhoea incident on 13 April in the central kitchen, followed by illness onset in the next day among employees that assisted with the clean-up. On 15 April, after 10 guests reported ill, the hotel implemented an outbreak response protocol instructing ill employees to take a 3-day leave, and obtain medical clearance prior to resuming work. Ill guests were advised to self-isolate, and rapid cleaning of public areas and guest rooms where suspected contamination occurred was implemented. We estimated that 65 QAVDs were lost by 43 guests (1.5 days/guest). Using an approximate cost of $450 per vacation day, we estimated indirect illness cost at $675 per guest case. Seven (64%) of 11 cases' stool specimens were positive for norovirus genotype GII.4 Den Haag., Conclusions: A norovirus outbreak in a resort hotel resulted in substantial indirect costs and loss of vacation days to ill travellers. We recommend outbreak control measures including exclusion of ill employees, until ≥48-72 h after resolution of symptoms, self-isolation of ill guests and appropriate cleaning in hotel-associated norovirus outbreaks., (Published by Oxford University Press on behalf of the International Society of Travel Medicine, 2016. This work is written by US Government employees and is in the public domain in the United States.)

Background: A globally-coordinated phase out of all type 2 containing oral polio vaccine (OPV) is planned for April 2016 during which bivalent 1+3 OPV (bOPV) will replace trivalent OPV (tOPV) in routine immunization schedules and campaigns. Diarrhea impairs the immune response to tOPV, but the effect of diarrhea on bOPV is unknown., Methods: Infants aged 6 weeks to 11 months, who had received <3 doses of OPV and had mild-moderate diarrhea or no diarrhea, were recruited at five health facilities in Nepal. Neutralizing antibody titers to poliovirus types 1 and 3 were measured before and 28 days after bOPV administration. The effect of diarrhea and other factors on seroconversion or boosting in antibody titers to poliovirus was assessed by multivariable analysis., Results: Infants with diarrhea, versus those without diarrhea, had reduced response for poliovirus types 1 (56% [87/156] vs 66% [109/164]) and 3 (34% [70/209] vs 52% [122/236]). After adjusting for other factors, infants with diarrhea had significantly reduced response for type 3 (odds ratio [OR]=0.44, 95% CI 0.29-0.68), as did infants with >5 loose stools per day (OR=0.36, 95% CI 0.21-0.62)., Conclusions: Diarrhea reduced the immune response to bOPV. Provision of additional doses of polio vaccine is necessary to maintain high population immunity in areas with high prevalence of diarrheal disease., Clinical Trial Registry: This study is registered at clinicaltrials.gov as NCT01559636., (Published by Elsevier Ltd.)

Background: Diarrheal diseases remain a major cause of mortality in Africa and worldwide. While the burden of rotavirus is well described, population-based rates of disease caused by norovirus, sapovirus, and astrovirus are lacking, particularly in developing countries., Methods: Data on diarrhea cases were collected through a population-based surveillance platform including healthcare encounters and household visits in Kenya. We analyzed data from June 2007 to October 2008 in Lwak, a rural site in western Kenya, and from October 2006 to February 2009 in Kibera, an urban slum. Stool specimens from diarrhea cases of all ages who visited study clinics were tested for norovirus, sapovirus, and astrovirus by RT-PCR., Results: Of 334 stool specimens from Lwak and 524 from Kibera, 85 (25%) and 159 (30%) were positive for norovirus, 13 (4%) and 31 (6%) for sapovirus, and 28 (8%) and 18 (3%) for astrovirus, respectively. Among norovirus-positive specimens, genogroup II predominated in both sites, detected in 74 (87%) in Lwak and 140 (88%) in Kibera. The adjusted community incidence per 100,000 person-years was the highest for norovirus (Lwak: 9,635; Kibera: 4,116), followed by astrovirus (Lwak: 3,051; Kibera: 440) and sapovirus (Lwak: 1,445; Kibera: 879). For all viruses, the adjusted incidence was higher among children aged <5 years (norovirus: 22,225 in Lwak and 17,511 in Kibera; sapovirus: 5,556 in Lwak and 4,378 in Kibera; astrovirus: 11,113 in Lwak and 2,814 in Kibera) compared to cases aged ≥5 years., Conclusion: Although limited by a lack of controls, this is the first study to estimate the outpatient and community incidence rates of norovirus, sapovirus, and astrovirus across the age spectrum in Kenya, suggesting a substantial disease burden imposed by these viruses. By applying adjusted rates, we estimate approximately 2.8-3.3 million, 0.45-0.54 million, and 0.77-0.95 million people become ill with norovirus, sapovirus, and astrovirus, respectively, every year in Kenya.

Unlabelled: Noroviruses are the leading cause of acute gastroenteritis outbreaks worldwide. The majority of norovirus outbreaks are caused by genogroup II.4 (GII.4). Novel GII.4 strains emerge every 2 to 4 years and replace older variants as the dominant norovirus. Novel variants emerge through a combination of recombination, genetic drift, and selection driven by population immunity, but the exact mechanism of how or where is not known. We detected two previously unknown novel GII.4 variants, termed GII.4 UNK1 and GII.4 UNK2, and a diverse norovirus population in fecal specimens from immunocompromised individuals with diarrhea after they had undergone bone marrow transplantation. We hypothesized that immunocompromised individuals can serve as reservoirs for novel norovirus variants. To test our hypothesis, metagenomic analysis of viral RNA populations was combined with a full-genome bioinformatic analysis of publicly available GII.4 norovirus sequences from 1974 to 2014 to identify converging sites. Variable sites were proportionally more likely to be within two amino acids (P < 0.05) of positively selected sites. Further analysis using a hypergeometric distribution indicated that polymorphic site distribution was random and its proximity to positively selected sites was dependent on the size of the norovirus genome and the number of positively selected sites.In conclusion, random mutations may have a positive impact on driving norovirus evolution, and immunocompromised individuals could serve as potential reservoirs for novel GII.4 strains., Importance: Norovirus is the most common cause of viral gastroenteritis in the United States. Every 2 to 3 years novel norovirus variants emerge and replace dominant strains. The continual emergence of novel noroviruses is believed to be caused by a combination of genetic drift, population immunity, and recombination, but exactly how this emergence occurs remains unknown. In this study, we identified two novel GII.4 variants in immunocompromised bone marrow transplant patients. Using metagenomic and bioinformatic analysis, we showed that most genetic polymorphisms in the novel variants occur near 0 to 2 amino acids of positively selected sites, but the distribution of mutations was random; clustering of polymorphisms with positively selected sites was a result of genome size and number of mutations and positively selected sites. This study shows that immunocompromised patients can harbor infectious novel norovirus variants, and although mutations in viruses are random, they can have a positive effect on viral evolution., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Background: Nicaragua was the first developing nation to implement routine immunization with the pentavalent rotavirus vaccine (RV5). In this RV5-immunized population, understanding infectious etiologies of childhood diarrhea is necessary to direct diarrhea treatment and prevention efforts., Methods: We followed a population-based sample of children <5 years in León, Nicaragua for diarrhea episodes through household visits. Information was obtained on RV5 history and sociodemographics. Stool samples collected during diarrhea episodes and among healthy children underwent laboratory analysis for viral, bacterial and parasitic enteropathogens. Detection frequency and incidence of each enteropathogen was calculated., Results: The 826 children in the cohort experienced 677 diarrhea episodes during 607.5 child-years of exposure time (1.1 episodes per child-year). At least 1 enteropathogen was detected among 61.1% of the 337 diarrheal stools collected. The most common enteropathogens among diarrheal stools were: norovirus (20.4%), sapovirus (16.6%), enteropathogenic Escherichia coli (11.3%), Entamoeba histolytica/dispar (8.3%), Giardia lamblia (8.0%) and enterotoxigenic E. coli (7.7%), with rotavirus detected among 5.3% of diarrheal stools. Enteropathogenic Escherichia coli and enterotoxigenic E. coli were frequently detected among stools from healthy children. Among children with diarrhea, norovirus was more commonly detected among younger children (< 2 years) and G. lamblia was more commonly detected among older children (2-4 years). The mean age of rotavirus detection was 34.6 months., Conclusions: In this Central American community after RV5 introduction, rotavirus was not commonly detected among children with diarrhea. Prevention and appropriate management of norovirus and sapovirus should be considered to further reduce the burden of diarrheal disease.

Noroviruses (NoVs) are a leading cause of acute gastroenteritis outbreaks and sporadic cases of diarrhea in industrialized countries. To study the prevalence and genetic diversity of NoVs in Guatemala, stool specimens were collected from hospitalized and ambulatory patients presenting with diarrhea (≥3 loose or liquid stools in a 24-hr period) who were enrolled in a prospective surveillance system in the Departments of Santa Rosa (October 2007 to August 2010) and Quetzaltenango (August 2009 to August 2010), Guatemala. Specimens were tested for rotavirus, enteric bacteria, and parasites by routine methods and for genogroups I and II NoV by real-time reverse transcription-PCR. A total of 2,403 stool specimens were collected from hospitalized (n = 528) and ambulatory patients (n = 1,875). Overall, 341 (14%) samples tested positive for NoVs including 114 (22%) hospitalized and 227 (12%) ambulatory patients. NoVs disease peaked during the winter (November-January) months. Among the 341 NoVs-positive patients, 32 (9%) were also positive for rotavirus, 32 (9%) for bacteria, and 9 (3%) for protozoa. Nucleotide sequences were obtained from 84 samples collected from hospitalized children aged <5 years of age, which could be grouped into nine GII and three GI genotypes with GII.4 (74%) and GI.8 (10%) being the most common. This is the first study on the prevalence of NoVs among hospitalized and ambulatory patients with diarrhea in Guatemala. The findings highlight the need to implement laboratory diagnostics for NoVs to improve appropriate clinical management of diarrheal diseases and guide vaccine development., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Diarrhea is a leading cause of childhood morbidity and mortality in sub-Saharan Africa. Data on risk factors for mortality are limited. We conducted hospital-based surveillance to characterize the etiology of diarrhea and identify risk factors for death among children hospitalized with diarrhea in rural western Kenya., Methods and Findings: We enrolled all children <5 years old, hospitalized with diarrhea (≥3 loose stools in 24 hours) at two district hospitals in Nyanza Province, western Kenya. Clinical and demographic information was collected. Stool specimens were tested for bacterial and viral pathogens. Bivariate and multivariable logistic regression analyses were carried out to identify risk factors for death. From May 23, 2005 to May 22, 2007, 1,146 children <5 years old were enrolled; 107 (9%) children died during hospitalization. Nontyphoidal Salmonella were identified in 10% (118), Campylobacter in 5% (57), and Shigella in 4% (42) of 1,137 stool samples; rotavirus was detected in 19% (196) of 1,021 stool samples. Among stools from children who died, nontyphoidal Salmonella were detected in 22%, Shigella in 11%, rotavirus in 9%, Campylobacter in 5%, and S. Typhi in <1%. In multivariable analysis, infants who died were more likely to have nontyphoidal Salmonella (adjusted odds ratio [aOR] = 6·8; 95% CI 3·1-14·9), and children <5 years to have Shigella (aOR = 5·5; 95% CI 2·2-14·0) identified than children who survived. Children who died were less likely to be infected with rotavirus (OR = 0·4; 95% CI 0·2-0·8). Further risk factors for death included being malnourished (aOR = 4·2; 95% CI 2·1-8·7); having oral thrush on physical exam (aOR = 2·3; 95% CI 1·4-3·8); having previously sought care at a hospital for the illness (aOR = 2·2; 95% CI 1·2-3·8); and being dehydrated as diagnosed at discharge/death (aOR = 2·5; 95% CI 1·5-4·1). A clinical diagnosis of malaria, and malaria parasites seen on blood smear, were not associated with increased risk of death. This study only captured in-hospital childhood deaths, and likely missed a substantial number of additional deaths that occurred at home., Conclusion: Nontyphoidal Salmonella and Shigella are associated with mortality among rural Kenyan children with diarrhea who access a hospital. Improved prevention and treatment of diarrheal disease is necessary. Enhanced surveillance and simplified laboratory diagnostics in Africa may assist clinicians in appropriately treating potentially fatal diarrheal illness.

To identify the prevalence and genetic variability of noroviruses in dogs, we tested fecal samples by using reverse transcription-PCR. We found canine norovirus in 40% and 9% of dogs with and without diarrhea, respectively. The virus was genetically unrelated to other noroviruses and constitutes a tentative new genogroup.

During a 2-year period in 2005-2007, we conducted surveillance of group A rotaviruses and other enteric agents among patients hospitalized with acute gastroenteritis in 8 different cities of the Russian Federation. Fecal specimens were gathered from 3208 children (including 2848 children aged <5 years) and 1354 adults who were admitted to hospitals in Moscow, St. Petersburg, Chelyabinsk, Nizhnii Novgorod, Tyumen, Khabarovsk, Makhachkala, and Yakutsk. Polymerase chain reaction was performed to detect rotaviruses of groups A and C, noroviruses of genogroups I and II, astrovirus, sapovirus, and enteric adenoviruses (group F). Group A rotavirus was the most common viral pathogen detected among children aged <5 years (43.6%), followed by norovirus (12.5%), whereas norovirus was the pathogen most commonly detected in adults (11.9%). P and G genotypes were determined for 515 rotavirus specimens, and the most prevalent genotypes were G1P[8] (44.9%), G4P[8] (40.0%), G2P[4] (8.5%), and G3P[8] (6.6%). This study is the first multicenter study of rotaviruses in the Russian Federation and documents the important burden of disease caused by this pathogen, which soon may be preventable by vaccination.

Background: Norovirus causes a majority of outbreaks of gastrointestinal (GI) illness on cruise ships calling on the United States. Control measures include patient isolation, hand washing, and facility closure. Little is known about the behaviors and practices of people who have become ill with norovirus GI illness compared to those who remained well during an outbreak., Methods: Passenger surveys were distributed during three cruise ship outbreaks caused by norovirus. Surveys inquired about illness symptoms, ill contacts, illness reporting status, hand sanitation beliefs and practices, and availability of public hand sanitizer. A case was a passenger reporting three or more episodes of loose stool in a 24-hour period, three or more episodes of vomiting in a 24-hour period, or one or more episodes each of loose stool and vomiting in a 24-hour period. Controls reported that they were not ill during the cruise., Results: In total, 1,323 responses were compared. All ships had passengers who were ill prior to embarkation. Most cases delayed or did not report their illness to the ship's infirmary because they did not believe it was serious (43%-70% of responses). Cases were less likely to believe that isolation was effective in preventing disease spread [Mann-Whitney-Wilcoxon (MWW) p value <0.0001]. Cases were less likely to believe that hand washing or hand sanitizer are effective means of preventing disease spread (MWW p values 0.002 and 0.04, respectively), wash their hands after restroom use (MWW p value 0.02), or believe that hand sanitizer was available for public use prior to/after knowing about an outbreak (MWW p values 0.002 and 0.03, respectively)., Conclusions: Prevention and control of norovirus GI illness may be improved by routine screening of embarking passengers, education about GI illness and its impact on public health, a focus on improving hand-washing practices, and identification of public hand sanitizer dispensing locations.

The incidence and aetiology of acute diarrhoea in 60 adult allogeneic or autologous stem cell transplant (SCT) recipients was determined in a prospective study. Stool specimens were obtained prior to SCT and on days +20, +40, +60 and +100 post transplant. Microbiological evaluation was performed for pathogenic bacteria, fungi, parasites and viruses. Forty-seven patients were evaluable of whom 31 had a total of 48 acute diarrhoeal episodes. Diarrhoea occurred in 79% of allogeneic and 47% of autologous SCT recipients (P < 0.05). Intestinal infections were found in three of 48 (6%) diarrhoeal episodes. Clostridium difficile with positive toxin was cultured twice and one stool specimen was positive for cryptosporidium. Intestinal pathogens were identified in 13 out of 172 stool specimens from asymptomatic patients and included: rotavirus (4), adenovirus (3), C. difficile, toxin positive (2), and others (4). Graft-versus-host disease was confirmed by biopsy in two of 36 episodes of diarrhoea in allogeneic patients, and in three patients a relationship between reactivation of cytomegalovirus and diarrhoea was suspected. In 40 of 48 (83%) episodes of diarrhoea no clear aetiology could be found.