Immunogenicity of RV1 and RV5 vaccines administered in standard and interchangeable mixed schedules: a randomized, double-blind, non-inferiority clinical trial in Mexican infants.

Introduction: Rotavirus-associated diarrheal diseases significantly burden healthcare systems, particularly affecting infants under five years. Both Rotarix™ (RV1) and RotaTeq™ (RV5) vaccines have been effective but have distinct application schedules and limited interchangeability data. This study aims to provide evidence on the immunogenicity, reactogenicity, and safety of mixed RV1-RV5 schedules compared to their standard counterparts. Methods: This randomized, double-blind study evaluated the non-inferiority in terms of immunogenicity of mixed rotavirus vaccine schedules compared to standard RV1 and RV5 schedules in a cohort of 1,498 healthy infants aged 6 to 10 weeks. Participants were randomly assigned to one of seven groups receiving various combinations of RV1, and RV5. Standard RV1 and RV5 schedules served as controls of immunogenicity, reactogenicity, and safety analysis. IgA antibody levels were measured from blood samples collected before the first dose and one month after the third dose. Non-inferiority was concluded if the reduction in seroresponse rate in the mixed schemes, compared to the standard highest responding scheme, did not exceed the non-inferiority margin of -0.10. Reactogenicity traits and adverse events were monitored for 30 days after each vaccination and analyzed on the entire cohort. Results: Out of the initial cohort, 1,365 infants completed the study. Immunogenicity analysis included 1,014 infants, considering IgA antibody titers ≥20 U/mL as seropositive. Mixed vaccine schedules demonstrated non-inferiority to standard schedules, with no significant differences in immunogenic response. Safety profiles were comparable across all groups, with no increased incidence of serious adverse events or intussusception. Conclusion: The study confirms that mixed rotavirus vaccine schedules are non-inferior to standard RV1 and RV5 regimens in terms of immunogenicity and safety. This finding supports the flexibility of rotavirus vaccination strategies, particularly in contexts of vaccine shortage or logistic constraints. These results contribute to the global effort to optimize rotavirus vaccination programs for broader and more effective pediatric coverage.Clinical trial registration: ClinicalTrials.gov, NCT02193061.

Post-marketing surveillance of intussusception after Rotarix administration in Afghanistan, 2018-2022.

BACKGROUND: In January 2018, Afghanistan introduced the monovalent oral rotavirus vaccine (Rotarix) nationwide, administered as a 2-dose series at six and ten weeks of age. We describe characteristics of intussusception cases and assess potential intussusception risk associated with Rotarix vaccination in Afghan infants. METHODS: Multi-center prospective active hospital-based surveillance for intussusception was conducted from May 2018 to March 2022 in four sentinel sites in Afghanistan. We applied the Brighton Level 1 criteria for intussusception and verified vaccination status by reviewing vaccine cards. We used the self-controlled case series (SCCS) methodology to compare intussusception incidence in the 1 to 21 days after each dose of Rotarix vaccination against non-risk periods. RESULTS: A total of 468 intussusception cases were identified in infants under 12 months, with 264 cases aged between 28 and 245 days having confirmed vaccination status contributing to the SCCS analysis. Most case-patients (98 %) required surgery for treatment, and over half (59 %) of those who underwent surgery required intestinal resection. Nineteen (7 %) case-patients died. Eighty-six percent of case-patients received the first dose of Rotarix, and 69 % received the second dose before intussusception symptom onset. There was no increased risk of intussusception in the 1-7 days (relative incidence: 0.9, 95 % CI: 0.1, 7.5), 8-21 days (1.3, 95 % CI: 0.4, 4.2), or 1-21 days (1.1, 95 % CI: 0.4, 3.4) following receipt of the first dose or in the 1-7 days (0.2, 95 % CI: 0.3, 1.8), 8-21 days (0.7, 95 % CI: 0.3, 1.5), or 1-21 days (0.6, 95 % CI: 0.3, 1.2) following the second dose. CONCLUSION: Rotarix vaccination was not associated with an increased intussusception risk, supporting its continued use in Afghanistan's immunization program. However, there was a high level of death and resection due to intussusception among Afghan infants.

No sign of Rotavirus co-infection in COVID-19 patients with gastrointestinal symptoms.

Background and aims: The main goal of the present study is to investigate the incidence of Rotavirus co-infection in COVID-19 patients. Methods and Results: Fecal samples of COVID-19 patients with gastrointestinal symptoms which had positive PCR- were collected from Abadan's hospital, Iran during the period December 2020 to January 2021. Samples were analyzed by RT-PCR to determine the presence of Rotavirus. Finally, the total samples size of 37 were included in this study. The mean age of patients was 48.22 years. Abdominal pain alone was detected in 48.65% of the patients. At least one gastrointestinal symptom was detected in all of the patients. Diarrhea and fever were seen in 13.51% and 59.46% of patients, respectively. Nausea and vomiting were seen in 5.41% of the patients. RT-PCR showed no infection of Rotavirus among the patients. Conclusion: Gastrointestinal symptoms related to COVID-19 are common. More studies is need among these patients groups for investigate co-infection with other fecal viral shedding carries, due to a worse prognosis and its association with disease severity.

Intussusception risk following oral monovalent rotavirus vaccination in 3 Asian countries: A self-control case series evaluation.

Rotavirus vaccines have substantially decreased rotavirus hospitalizations in countries where they have been implemented. In some high- and middle-income countries, a low-level of increased risk of intussusception, a type of acute bowel obstruction, has been detected following rotavirus vaccination. However, no increased risk of intussusception was found in India, South Africa, or a network of 7 other African countries. We assessed the association between a 2-dose monovalent rotavirus vaccine (Rotarix) and intussusception in 3 early-adopter low-income Asian countries -- Afghanistan, Myanmar, and Pakistan. Children <12 months of age admitted to a sentinel surveillance hospital with Brighton level 1 intussusception were eligible for enrollment. We collected information about each child's vaccination status and used the self-controlled case series method to calculate the relative incidence of intussusception 1-7 days, 8-21 days, and 1-21 days following each dose of vaccine and derived confidence intervals with bootstrapping. Of the 585 children meeting the analytic criteria, the median age at intussusception symptom onset was 24 weeks (IQR: 19-29). Overall, 494 (84 %) children received the first Rotarix dose and 398 (68 %) received the second dose. There was no increased intussusception risk during any of the risk periods following the first (1-7 days: 1.01 (95 %CI: 0.39, 2.60); 8-21 days: 1.37 (95 %CI: 0.81, 2.32); 1-21 days: 1.28 (95 %CI: 0.78, 2.11)) or second (1-7 days: 0.81 (95 %CI: 0.42, 1.54); 8-21 days: 0.77 (95 %CI: 0.53, 1.16); 1-21 days: 0.78 (95 %CI: 0.53, 1.16)) rotavirus vaccine dose. Our findings are consistent with other data showing no increased intussusception risk with rotavirus vaccination in low-income countries and add to the growing body of evidence demonstrating safety of rotavirus vaccines.

Severe Adult Rotavirus Gastroenteritis: A Rare Case with Multi-Organ Failure and Critical Management.

BACKGROUND Infectious diarrheal illnesses such as rotavirus gastroenteritis are significant contributors to childhood morbidity and mortality, especially in low socio-demographic index regions. Major advances in addressing this issue include sanitation and clean water initiatives, as well as rotavirus immunization. In Australia, a robust vaccination program has significantly reduced childhood rotavirus infections, leading to decreased hospitalizations and mortality. However, cases of adult rotavirus still occur, and although these adult patients usually do not require interventional management, it is possible for them to present critically unwell and require resuscitation. CASE REPORT A previously well 65-year-old man presented to the Emergency Department febrile and hypotensive with severe diarrhea attributed to rotavirus. Clinically, he presented with mixed hypovolemic and septic shock. Despite initial resuscitation, he had multiple severe acute end-organ complications, secondary to poor perfusion. He acquired an acute kidney injury, type-2 myocardial infarction, and ischemic hepatic injury. The mainstay of management was rapid fluid resuscitation, continuous renal replacement therapy, and monitoring in the Intensive Care Unit; however, it was crucial to empirically treat for other causes of shock. CONCLUSIONS To the best of our knowledge, there is a scarcity of reports documenting the management of severe rotavirus gastroenteritis in adults. We recommend advising elderly patients to avoid contact with individuals with diarrheal illnesses, especially rotavirus gastroenteritis. Clinicians should also promote awareness regarding the potential severity of a disease that is typically managed conservatively, and be aware that intervention can be required in severe gastroenteritis.

Rotavirus and bacterial diarrhoea among children in Ile-Ife, Nigeria: Burden, risk factors and seasonality.

BACKGROUND: Diarrhoea is a leading cause of death among under-five children globally, with sub-Saharan Africa alone accounting for 1/3 episodes yearly. Viruses, bacteria and parasites may cause diarrhoea. Rotavirus is the most common viral aetiology of diarrhoea in children less than five years globally. In Nigeria, there is scarce data on the prevalence/importance, burden, clinical/risk factors and seasonality of rotavirus and bacteria and this study aims to determine the role of rotavirus and bacteria on diarrhoea cases in children less than five years in Ile-Ife, Nigeria. METHODS: Socio-demographic data, environmental/risk factors and diarrhoiec stool samples were collected from children less than five years presenting with acute diarrhoea. Rotavirus was identified using ELISA. Bacteria pathogens were detected using cultural technique and typed using PCR. Diarrhoeagenic E. coli (DEC) isolates were subjected to antimicrobial susceptibility testing. Pathogen positive and negative samples were compared in terms of gender, age-group, seasonal distribution, and clinical/risk factors using chi-square with two-tailed significance. SPSS version 20.0.1 for Windows was used for statistical analysis. RESULTS: At least one pathogen was detected from 63 (60.6%) children having gastroenteritis while 28 (44.4%) had multiple infections. Rotavirus was the most detected pathogen. Prevalence of rotavirus mono-infection was 22%, multiple infection with bacteria was 45%. Mono-infection prevalence of DEC, Shigella spp., and Salmonella spp. were 5.8% (6/104), 5.8% (6/104), and 2.9% (3/104) and co-infection with RVA were 23.1% (24/104), 21.2% (22/104) and 10.6% (11/104) respectively. All rotaviral infections were observed in the dry season. The pathotypes of DEC detected were STEC and EAEC. Parent earnings and mid-upper arm circumference measurement have statistical correlation with diarrhoea (p = 0.034; 0.035 respectively). CONCLUSION: In this study, rotavirus was more prevalent than bacteria and occurred only in the dry season. Among bacteria aetiologies, DEC was the most common detected. Differences in seasonal peaks of rotavirus and DEC could be employed in diarrhoea management in Nigeria and other tropical countries to ensure optimal limited resources usage in preventing diarrhoea transmission and reducing indiscriminate use of antibiotics.

Clinical characteristics and influencing factors of infectious diarrhea in preschool children: An observational study.

Infectious diarrhea is a common disease in preschool children, but the pathogenic species, origins, and influencing factors remain debatable. Therefore, more studies are required to solve these debatable topics. A number of 260 eligible preschool children diagnosed with infectious diarrhea in our hospital were enrolled in the infection group. Meanwhile, a number of 260 matched healthy children from the health center were enrolled in the control group. The pathogenic species and origins, the time of onset of infectious diarrhea in the infection group, demographic data, exposure history, hygiene habits, dietary habits, and other variables in both groups were initially collected from medical documents. In addition, a questionnaire was used to complete and confirm study variables through face-to-face or telephone interviews. Then, the univariate and multivariate regression analyses were used to screen the influencing factors of infectious diarrhea. Among 260 infected children, salmonella (15.77%), rotavirus (13.85%), shigella (11.54%), vibrio (10.38%), and norovirus (8.85%) were the top 5 common pathogens; January (13.85%), December (12.69%), August (12.31%), February (11.92%), and July (8.46%) were the top 5 frequent times of infectious diarrhea. The distribution of onset time for infectious diarrhea was commonly found in winter and summer, and the pathogens always originated from foods. The results of multivariate regression analysis showed that recent exposure to diarrhea, flies, and/or cockroaches indoors were the 2 risk factors for infectious diarrhea; Meanwhile, rotavirus vaccination, regular hand-washing, tableware disinfection, separate preparation of cooked and raw foods, and regular intake of lactobacillus products were the 5 protective factors for infectious diarrhea in preschool children. Infectious diarrhea has a diversity of pathogenic species, origins, and influencing factors in preschool children. Activities focusing on these influencing factors such as rotavirus vaccination, consumption of lactobacillus products, and other conventional factors would be beneficial to preschool children's health.

Drivers of Decline in Diarrhea Mortality Between GEMS and VIDA Studies.

BACKGROUND: Statistical modeling suggests that decreasing diarrhea-associated mortality rates in recent decades are largely attributed to improved case management, rotavirus vaccine, and economic development. METHODS: We examined data collected in 2 multisite population-based diarrhea case-control studies, both conducted in The Gambia, Kenya, and Mali: the Global Enteric Multicenter Study (GEMS; 2008-2011) and Vaccine Impact on Diarrhea in Africa (VIDA; 2015-2018). Population-level diarrhea mortality and risk factor prevalence, estimated using these study data, were used to calculate the attribution of risk factors and interventions for diarrhea mortality using a counterfactual framework. We performed a decomposition of the effects of the changes in exposure to each risk factor between GEMS and VIDA on diarrhea mortality for each site. RESULTS: Diarrhea mortality among children under 5 in our African sites decreased by 65.3% (95% confidence interval [CI]: -80.0%, -45.0%) from GEMS to VIDA. Kenya and Mali had large relative declines in diarrhea mortality between the 2 periods with 85.9% (95% CI: -95.1%, -71.5%) and 78.0% (95% CI: -96.0%, 36.3%) reductions, respectively. Among the risk factors considered, the largest declines in diarrhea mortality between the 2 study periods were attributed to reduction in childhood wasting (27.2%; 95% CI: -39.3%, -16.8%) and an increased rotavirus vaccine coverage (23.1%; 95% CI: -28.4%, -19.4%), zinc for diarrhea treatment (12.1%; 95% CI: -16.0%, -8.9%), and oral rehydration salts (ORS) for diarrhea treatment (10.2%). CONCLUSIONS: The VIDA study sites demonstrated exceptional reduction in diarrhea mortality over the last decade. Site-specific differences highlight an opportunity for implementation science in collaboration with policymakers to improve the equitable coverage of these interventions globally.

Norovirus Disease Among Children <5 Years in 3 Sub-Saharan African Countries: Findings From the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015-2018.

BACKGROUND: To address a paucity of data from sub-Saharan Africa, we examined the prevalence, severity, and seasonality of norovirus genogroup II (NVII) among children <5 years old in The Gambia, Kenya, and Mali following rotavirus vaccine introduction. METHODS: Population-based surveillance was conducted to capture medically-attended moderate-to-severe diarrhea (MSD) cases, defined as a child 0-59 months old passing ≥3 loose stools in a 24-hour period with ≥1 of the following: sunken eyes, poor skin turgor, dysentery, intravenous rehydration, or hospitalization within 7 days of diarrhea onset. Diarrhea-free matched controls randomly selected from a censused population were enrolled at home. Stools from cases and controls were tested for enteropathogens, including norovirus and rotavirus, by TaqMan quantitative polymerase chain reaction (PCR) and conventional reverse transcription PCR. We used multiple logistic regression to derive adjusted attributable fractions (AFe) for each pathogen causing MSD, which takes into consideration the prevalence in both cases and controls, for each site and age. A pathogen was considered etiologic if AFe was ≥0.5. In further analyses focusing on the predominant NVII strains, we compared rotavirus and NVII severity using a 20-point modified Vesikari score and examined seasonal fluctuations. RESULTS: From May 2015 to July 2018, we enrolled 4840 MSD cases and 6213 controls. NVI was attributed to only 1 MSD episode. NVII was attributed to 185 (3.8%) of all MSD episodes and was the sole attributable pathogen in 139 (2.9%); peaking (36.0%) at age 6-8 months with majority (61.2%) aged 6-11 months. MSD cases whose episodes were attributed to NVII alone compared with rotavirus alone were younger (median age, 8 vs 12 months, P < .0001) and had less severe illness (median Vesikari severity score, 9 vs 11, P = .0003) but equally likely to be dehydrated. NVII occurred year-round at all study sites. CONCLUSIONS: Infants aged 6-11 months bear the greatest burden of norovirus disease, with NVII predominating. An early infant vaccine schedule and rigorous adherence to guidelines recommended for management of dehydrating diarrhea may offer substantial benefit in these African settings.

Neurologic Complications of Rotavirus Infections in Children.

BACKGROUND: Rotavirus is the leading cause of complicated gastroenteritis in children younger than 5 years in countries where rotavirus vaccination is not implemented as a routine vaccination. Besides the intestinal symptoms that are associated with ordinary gastroenteritis, rotavirus can cause neurological complications. The aim of this study is to describe the clinical characteristics of complicated rotavirus infections. METHODS: From January 1, 2016 to January 31, 2022, all children (below the age of 18 years) with a positive rotavirus test in feces that were either hospitalized or presented at the outpatient clinic or emergency department of a large pediatric hospital in the Netherlands were included. Rotavirus was only tested in case of a severe or abnormal disease course. We described the clinical characteristics and outcomes with a particular focus on neurological manifestations. RESULTS: In total, 59 patients with rotavirus were included of whom 50 (84.7%) were hospitalized and 18 (30.5%) needed intravenous rehydration. Ten patients (16.9%) had neurologic complications, of whom 6 patients (60.0%) presented encephalopathy. Two patients (20.0%) with neurological symptoms showed abnormalities on diagnostic imaging. CONCLUSIONS: Rotavirus can cause gastroenteritis with severe, but apparently self-limiting, neurological manifestations. Considering rotavirus in pediatric patients with neurological symptoms such as encephalopathy and encephalitis is therefore important. Early detection of rotavirus infection may predict a favorable course of the disease and may thereby prevent unnecessary treatment and should be further investigated.

Interferon-λ3 alleviates intestinal epithelium injury induced by porcine rotavirus in mice.

Interferons are a group of glycoproteins that are expressed in various cell types in their inflammatory responses to infections. In this study, we explored the protective effects of porcine interferon-λ3 (PIFN-λ3) on intestinal inflammation and injury in mice induced by porcine rotavirus (PRV). BALB/c mice were administrated by PIFN-λ3 or phosphate buffer solution (PBS) for three days prior to PRV infection. We show that PRV infection caused acute inflammatory responses in mice, as indicated by increases in serum concentrations of inflammatory cytokines such as the interlukin-1ß (IL-1ß), interlukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) (P < 0.05). However, PIFN-λ3 administration not only decreased their concentrations but also elevated the concentrations of immunoglobulin (Ig) M and IgG in the PRV challenged mice (P < 0.05). PRV infection significantly decreased the jejunal villus height and the ratio of villus height to crypt depth (V/C); however, PIFN-λ3 treatment significantly elevated the villus height and the abundance of tight junction protein ZO-1 in the jejunum (P < 0.05). Moreover, PIFN-λ3 decreased the replication of PRV in the jejunal epithelium, but significantly increased the abundance of sIgA and the activities of maltase and sucrase in the PRV-challenged mice (P < 0.05). Interestingly, PIFN-λ3 elevated the expression levels of sodium/glucose cotransporter 1 (SGLT1) and mucin 2 (MUC2) in the PRV-challenged mice (P < 0.05). Moreover, PIFN-λ3 significantly increased the expression levels of IL-10, signal transducer and activator of transcription 1 (STAT1), and critical interferon-stimulated genes such as the 2'-5' oligoadenylate synthetase-like 1 (OASL1), interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) and radical S-adenosyl methionine domain containing 2 (RSAD2) in the jejunum upon PRV infection (P < 0.05). The anti-virus and anti-inflammatory effect of PIFN-λ3 should make it an attractive candidate to prevent various pathogen-induced bowel diseases.

Neurological complications of rotavirus infection in children: A systematic review and meta-analysis.

AIM: To systematically review the clinical features and outcomes of paediatric patients developing neurological complications associated with a rotavirus infection. METHODS: A systematic literature review and meta-analysis was performed, including articles published from 1984 to 2020. Neurological complications were classified into four groups: encephalitis, cerebellitis, encephalo-cerebellitis and benign convulsions with mild gastroenteritis (CwG). RESULTS: Out of 68 reports that fulfilled the research criteria, 99 cases of CwG, 39 cases of encephalitis, 18 cases of encephalo-cerebellitis and five cases of cerebellitis were collected. Ninety-five patients were from Asia. Median age was 22 (IQR 14-29) months, and the children who developed CwG were significantly younger (19, IQR 12-24 months, p < 0.0001) than the others. Status epilepticus was observed in 23% and 5% of the encephalitis and CwG groups respectively. The most frequently described neuroimaging finding were lesions of the splenium of corpus callosum. Four deaths were reported in the encephalitis group, whereas no fatal events were described in the other groups. Among the surviving children, the encephalo-cerebellitis group showed the most severe long-term outcome. All cases of CwG recovered completely. CONCLUSION: Older age at diagnosis and the development of encephalo-cerebellitis are associated with a higher risk of long-term complications.

N-Glycosylation of Rotavirus NSP4 Protein Affects Viral Replication and Pathogenesis.

Rotavirus (RV), the most common cause of gastroenteritis in children, carries a high economic and health burden worldwide. RV encodes six structural proteins and six nonstructural proteins (NSPs) that play different roles in viral replication. NSP4, a multifunctional protein involved in various viral replication processes, has two conserved N-glycosylation sites; however, the role of glycans remains elusive. Here, we used recombinant viruses generated by a reverse genetics system to determine the role of NSP4 N-glycosylation during viral replication and pathogenesis. The growth rate of recombinant viruses that lost one glycosylation site was as high as that of the wild-type virus. However, a recombinant virus that lost both glycosylation sites (glycosylation-defective virus) showed attenuated replication in cultured cell lines. Specifically, replications of glycosylation-defective virus in MA104 and HT29 cells were 10- and 100,000-fold lower, respectively, than that of the wild-type, suggesting that N-glycosylation of NSP4 plays a critical role in RV replication. The glycosylation-defective virus showed NSP4 mislocalization, delay of cytosolic Ca2+ elevation, and less viroplasm formation in MA104 cells; however, these impairments were not observed in HT29 cells. Further analysis revealed that assembly of glycosylation-defective virus was severely impaired in HT29 cells but not in MA104 cells, suggesting that RV replication mechanism is highly cell type dependent. In vivo mouse experiments also showed that the glycosylation-defective virus was less pathogenic than the wild-type virus. Taken together, the data suggest that N-glycosylation of NSP4 plays a vital role in viral replication and pathogenicity. IMPORTANCE Rotavirus is the main cause of gastroenteritis in young children and infants worldwide, contributing to 128,500 deaths each year. Here, we used a reverse genetics approach to examine the role of NSP4 N-glycosylation. An N-glycosylation-defective virus showed attenuated and cell-type-dependent replication in vitro. In addition, mice infected with the N-glycosylation-defective virus had less severe diarrhea than mice infected with the wild type. These results suggest that N-glycosylation affects viral replication and pathogenesis. Considering the reduced pathogenicity in vivo and the high propagation rate in MA104 cells, this glycosylation-defective virus could be an ideal live attenuated vaccine candidate.

Association between nurse staffing levels and rotavirus infection in neonatal intensive care units: A retrospective observational study.

OBJECTIVES: To explore the relationship between nurse staffing levels and rotavirus infection in neonatal intensive care units. RESEARCH METHODOLOGY: This study adopted a retrospective observational design with data from the Health Insurance Review and Assessment Service (2018) database in South Korea. Participants were 35,308 infants in neonatal intensive care units. Multiple logistic regression analyses were employed to examine the association between nurse staffing levels and rotavirus infection in neonatal intensive care units after adjusting for confounding variables such as patient and hospital-related characteristics. RESULTS: A total of 1,514 (4.3%) infants developed rotavirus infection. Among the confounding variables, infectious disease, and being admitted from January to March and in December significantly increased the risk of rotavirus infection, whereas low birth weight, cardiovascular disorders, neonatal jaundice, receiving breastmilk, central line insertion, and ventilator usage significantly decreased the risk. Neonatal intensive care units with a grade 5 nurse staffing level (compared with grades 1-4) had a higher risk of rotavirus infection. CONCLUSIONS: The results suggest that neonatal intensive care units with higher (vs lower) nurse staffing levels are associated with lower rotavirus infection rates among infants. High-risk infants are extremely susceptible to hospital-acquired infections, and more intensive nursing care that differs from that provided to adult or paediatric patients is required. Therefore, nurse staffing levels with less than a 2:1 patient-to-nurse ratio are needed to control and prevent rotavirus infection in neonatal intensive care units.

Increased Risk of Neurological Disease Following Pediatric Rotavirus Infection: A Two-Center Case-Control Study.

BACKGROUND: Whether pediatric rotavirus infection is associated with extraintestinal complications remains unknown. METHODS: We conducted a case-control study to investigate the incidences and risks of rotavirus-associated extraintestinal complications in hospitalized newborns, infants, and children younger than 5 years. RESULTS: A total of 1325 young inpatients with rotavirus infection (754 male and 539 newborns) and 1840 controls without rotavirus infection (1035 male and 836 newborns) were included. The incidences of neurological disease were higher among rotavirus individuals compared with controls: newborns, 7.24% (39/539) versus 2.87% (24/836), P < .001; infants and young children, 19.59% (154/786) versus 12.35% (124/1004), P < .001. The associated odd ratios (ORs) for neurological disease frequency following rotavirus infection was 2.64 (95% confidence interval [CI], 1.57-4.44) for newborns and 1.73 (95% CI, 1.34-2.24) for infants and young children, which increased to 2.56 (95% CI, 1.57-4.18) in case-control (1:1) matching analysis and 1.85 (95% CI, 1.41-2.42) in confounder adjustment. Rotavirus infection was associated with other extraintestinal complications, depending on study population and disease severity. Outcome analysis revealed rotavirus infection and its consequences had a significant impact on hospitalization and discharge. CONCLUSIONS: Rotavirus exposure was associated with a spectrum of extraintestinal complications, particularly neurological disease. Rotavirus infection and subsequent consequences resulted in poor clinical outcomes.

Prolonged diarrhea among under-five children in Bangladesh: Burden and risk factors.

INTRODUCTION & BACKGROUND: Prolonged (duration >7 to 13 days) diarrhea (ProD) in under-five children is a universal health problem including Bangladesh. Data on epidemiology and associated or risk factors of ProD are limited, particularly in Bangladesh where a high burden of ProD is reported. This study intended to assess the case load of ProD and its associated or risk factors compared to acute diarrhea (AD, duration ≤7 days). METHODS: We analyzed the data collected between 1996-2014 from a hospital-based Diarrheal-Disease-Surveillance-System (DDSS) in the 'Dhaka Hospital' of International Centre for Diarrhoeal Diseases, Bangladesh (icddr,b). The DDSS enrolled a 2% systematic sample, regardless of age, sex, and diarrhea severity. The data included information on socio-demographic factors, environmental history, clinical characteristics, nutritional status, and diarrhea-pathogens. After cleaning of data, relevant information of 21,566 under-five children were available who reported with ≤13 days diarrhea (including AD and ProD), and their data were analyzed. Variables found significantly associated with ProD compared to AD in bi-variate analysis were used in logistic regression model after checking the multicollinearity between independent variables. RESULTS: The mean±SD age of the children was 14.9±11.7 months and 40.4% were female; 7.6% had ProD and 92.4% had AD. Age <12 months, mucoid- or bloody-stool, warmer months (April-September), drug used at home before seeking care from hospital, and history of diarrhea within last one month were found associated with ProD (p<0.05); however, rotavirus infection was less common in children with ProD (p<0.05). ProD children more often needed inpatient admission than AD children (14.4 vs. 6.3, p<0.001). Case fatality rate of ProD vs. AD was 0.3% (n = 5) vs. 0.1% (n- = 22) respectively (p = 0.051). CONCLUSION: A considerable proportion (7.6%) of under-five children reporting to icddr,b hospital suffered from ProD. Understanding the above-mentioned associated or risk factors is likely to help policy makers formulating appropriate strategies for alleviating the burden and effectively managing ProD in under-five children.