Severe Diarrhea In Children Research Articles

Bfp Adhesions and EspA Filament by Enteropathogenic E.Coli in Relation to Pathogenesis of Infantile Diarrhea in Children Under 5 Years in Mansoura University Children Hospital

Background: Our study was applied aiming to detect the biofilm formation by the Enteropathogenic E. coli causing diarrhea and to investigate the relation between the Bfp adhesions and EspA filament containing strains with the severity of diarrhea in children under 5 years in Mansoura University Children Hospital, Egypt. Methods: It was carried out by identification of EPEC, Serological agglutination test, Biofilm Formation under static condition at 3,6,9,24 hours. Results: Out of 103 children with diarrhea, 50 E. coli were isolated, 16 (32%) were EPEC and 34 (68%) were non-EPEC. The CFU mean± SD of biofilm of 16 EPEC isolates at 4 time points 3, 6, 9, 24h are 108- 1013, 69.5910±24.9310, 106-109, 20.2948±3.96778, 107-1011, 13.92×1010±3.376×1010, 109-1015, 6.402×1013± 2.496×1013. The relation of the biofilm formation and the severity of diarrhea in 16 EPEC isolates including 5 typical EPEC isolates and11 atypical EPEC reveals significant relation between the duration of the diarrhea and biofilm formation P=0.001**. Conclusion: EPEC is capable of forming biofilms on plastic under static and flow through-continuous conditions which correlate to the severity of the diarrhea in children under 5 years.

Disease burden and seasonal impact of improving rotavirus vaccine coverage in the United States: A modeling study

Prior to vaccine introduction in 2006, rotavirus was the leading cause of severe diarrhea in children under five years of age in the U.S. Vaccination of infants has led to major reductions in disease burden, a shift in the seasonal peak and the emergence of a biennial pattern of disease. However, rotavirus vaccine coverage has remained relatively low (70-75%) compared to other infant immunizations in the U.S. Part of the reason for this lower coverage is that children whose care is provided by family practitioners (FP) have considerably lower probability of being vaccinated compared to those seen be pediatricians (PE). We used a dynamic transmission model to assess the impact of improving rotavirus vaccine coverage by FP and/or PE on rotavirus gastroenteritis (RVGE) incidence and seasonal patterns. A deterministic age-structured dynamic model with susceptible, infectious, and recovered compartments (SIRS model) was used to simulate rotavirus transmission and vaccination. We estimated the reduction of RVGE cases by 2 doses of rotavirus vaccine with three vaccination scenarios: (Status Quo: 85% coverage by pediatricians and 45% coverage by family practitioners; Improved FP: 85% coverage by pediatricians and family practitioners; Improved FP+PE: 95% coverage by pediatricians and family practitioners). In addition, we tested the sensitivity of the model to the assumption of random mixing patterns between children visiting pediatricians and children visiting family practitioners. In this model, higher vaccine coverage provided by family practitioners and pediatricians leads to lower incidence of severe RVGE cases (23% averted in Improved FP and 57% averted in Improved FP+PE compared to Status Quo) including indirect effects. One critical impact of higher total vaccine coverage is the effect on rotavirus epidemic patterns in the U.S.; the biennial rotavirus epidemic patterns shifted to reduced annual epidemic patterns. Additionally, assortative mixing patterns in children visiting pediatricians and family practitioners amplify the impact of increasing vaccine coverage. Other high-income countries that introduced vaccine have not experienced biennial patterns, like the U.S. Our results suggest that increasing overall vaccine coverage to 85% among infants would lead to an overall reduction in incidence with annual epidemic patterns.

HBGA binding modes and selectivity in noroviruses upon mutation: a docking and molecular dynamics study.

Norovirus, also called winter vomiting bug, is the most common cause for gastroenteritis and severe childhood diarrhea disease. High mutation rates cause drug resistance and thus complicate the development of an effective therapeutics against virus infection. The virus protein enters the host cell via the interaction with histo-blood group antigens (HBGAs), formed by oligosaccharides. To date, the crystal structures of numerous complexes of virus proteins with different antigens have been reported. The HBGAs bind to the two distinct regions of the virus proteins. Herein, the affinity of different variants of virus protein to some common glycans has been computationally analyzed. Molecular docking studies as combination of docking scores and rmsd values revealed that the binding region 1 is more attractive for the ligands in variants of categories 1-5, but selectivity is drastically shifted to region 2 due to in category 6. In addition, molecular dynamics simulations were unraveled when the region 1 is hindered (in category 6); the blocking loop has less fluctuation than that of unblocked in other categories.

The Guanine Nucleotide Exchange Factor GBF1 Participates in Rotavirus Replication.

Cellular and viral factors participate in the replication cycle of rotavirus. We report that the guanine nucleotide exchange factor GBF1, which activates the small GTPase Arf1 to induce COPI transport processes, is required for rotavirus replication since knocking down GBF1 expression by RNA interference or inhibiting its activity by treatment with brefeldin A (BFA) or Golgicide A (GCA) significantly reduces the yield of infectious viral progeny. This reduction in virus yield was related to a block in virus assembly, since in the presence of either BFA or GCA, the assembly of infectious mature triple-layered virions was significantly prevented and only double-layered particles were detected. We report that the catalytic activity of GBF1, but not the activation of Arf1, is essential for the assembly of the outer capsid of rotavirus. We show that both BFA and GCA, as well as interfering with the synthesis of GBF1, alter the electrophoretic mobility of glycoproteins VP7 and NSP4 and block the trimerization of the virus surface protein VP7, a step required for its incorporation into virus particles. Although a posttranslational modification of VP7 (other than glycosylation) could be related to the lack of trimerization, we found that NSP4 might also be involved in this process, since knocking down its expression reduces VP7 trimerization. In support, recombinant VP7 protein overexpressed in transfected cells formed trimers only when cotransfected with NSP4.IMPORTANCE Rotavirus, a member of the family Reoviridae, is the major cause of severe diarrhea in children and young animals worldwide. Despite significant advances in the characterization of the biology of this virus, the mechanisms involved in morphogenesis of the virus particle are still poorly understood. In this work, we show that the guanine nucleotide exchange factor GBF1, relevant for COPI/Arf1-mediated cellular vesicular transport, participates in the replication cycle of the virus, influencing the correct processing of viral glycoproteins VP7 and NSP4 and the assembly of the virus surface proteins VP7 and VP4.

Reduction in hospitalisations for acute gastroenteritis-associated childhood seizures since introduction of rotavirus vaccination: a time-series and change-point analysis of hospital admissions in England

IntroductionThe incidence of severe childhood diarrhoea has fallen substantially following the introduction of rotavirus vaccine in the UK in July 2013. Since children with rotavirus infection may experience febrile and...

Prevalence and Genetic Characterization of Rotavirus Infections Among Children Under Five Years in Mutaho Health District, Gitega Province and Bujumbura Municipality, Burundi

Rotavirus is the leading cause of severe diarrhea in children under five years worldwide. It is ranked as a priority for vaccine. In Burundi, vaccine against rotavirus was implemented in 2013. The impact of recent rotavirus vaccination on morbidities in Burundi is not well established. Moreover, no study has been carried out to document the genetic diversity of rotavirus strains circulating in Burundi. This cross-sectional health facility-based study aimed at determining the prevalence and molecular characteristics of rotavirus infections among children under five years of age in Mutaho Health District and the Municipality of Bujumbura, in Burundi. Stool specimens were collected from children presenting with acute diarrhea. These specimens were tested for rotavirus antigen using Diagnostar ® rapid test kit. Positive stool samples were confirmed at the Kenya Medical Research Institute (KEMRI) by ELISA. Positive confirmed samples underwent RT-PCR, G and P genotyping by multiplex semi-nested PCR using a cocktail of type specific primers or by sequencing. A total of 646 participants were enrolled in this study. The overall prevalence of rotavirus was 6.2% (40/646) with 4.0% (16/400) in Mutaho health district and 9.7% (24/246) in the Municipality of Bujumbura. Rotavirus detection rate tended to increase as the level of precipitation went down, showing a significant negative association between the two variables. (OR = 15.2; P = 0.0001). In addition, rotavirus detection rate was higher in Bujumbura Municipality than in Mutaho health district (OR = 2.6; P = 0.005). Two G genotypes were identified, G1 the predominating G genotype accounted for 53.8% (14/26) followed by G12 (46.2%, 12/26). The prevalence of the genotype G1 of Group A rotavirus was significantly higher in Bujumbura Municipality than in Mutaho health district while G12 predominated in Mutaho health district (OR = 7.33; P = 0.026). Rotavirus strains from pigs might have contributed to the high prevalence of human G12 rotavirus in that area. Three different P types were identified P[8] the most common, followed by P[6] and P[4]. The most common G/P combination genotype was G1P[8] which accounted for 45.5% of all rotavirus genotypes identified, followed by G12 P [8] (41.0%), G1P [6] (4.5%), G12 P [6] (4.5%) and G12 P [4] (4.5%). The emergence of G12 rotavirus strains which share neither G nor P genotypes with currently used rotavirus vaccines raises public health concerns as they have the potential to challenge their efficacy. Therefore, we recommend to initiate and maintain a continuous rotavirus strain surveillance in Burundi so as to monitor trends in the occurrence of these prevailing and potentially emerging new strains. Keywords : Rotavirus, diarrhea, genetic diversity, prevalence, Mutaho, Bujumbura, children DOI : 10.7176/JBAH/9-10-04 Publication date :May 31 st 2019

The curse of dimensionality: Animal-related risk factors for pediatric diarrhea in western Kenya, and methods for dealing with a large number of predictors.

BackgroundPediatric diarrhea, a leading cause of under-five mortality, is predominantly infectious in etiology. As many putative causal agents are zoonotic, animal exposure is a likely risk factor. To evaluate the effect of animal-related factors on moderate to severe childhood diarrhea in rural Kenya, where animal contact is common, Conan et al. studied 73 matched case-control pairs from 2009-2011, collecting rich exposure data on many dimensions of animal contact. We review the challenges associated with analyzing moderately-sized datasets with a large number of predictors and present two alternative methodological approaches.Methodology/Principal findingsWe conducted a simulation study to demonstrate that forward stepwise selection results in overfit models when data are high-dimensional, and that p values reported directly from the data used to train these models are misleading. We described how automated methods of variable selection, attractive when the number of predictors is large, can result in overadjustment bias. We proposed an alternative a priori regression approach not subject to this bias. Applied to Conan et al.’s data, this approach found a non-significant but positive trend for household’s sharing of water sources with livestock or poultry, child’s presence for poultry slaughter, and child’s habit of playing where poultry sleep or defecate. For many predictors evaluated few pairs were discordant, suggesting matching compromised the power of this analysis. Finally, we proposed latent variable modeling as a complimentary approach and performed Item Response Theory modeling on Conan et al.’s data, with animal contact as the latent trait. We found a moderate but non-significant effect (OR 1.21, 95% CI 0.78, 1.87, unit = 1 standard deviation).Conclusions/SignificanceAutomated methods of model selection are appropriate for prediction models when fit and evaluated on separate samples. However when the goal is inference, these methods can produce misleading results. Furthermore, case-control matching should be done with caution.

Optimization of Methionyl tRNA-Synthetase Inhibitors for Treatment of Cryptosporidium Infection.

Cryptosporidiosis is one of the leading causes of moderate to severe diarrhea in children in low-resource settings. The therapeutic options for cryptosporidiosis are limited to one drug, nitazoxanide, which unfortunately has poor activity in the most needy populations of malnourished children and HIV-infected persons. We describe here the discovery and early optimization of a class of imidazopyridine-containing compounds with potential for treating Cryptosporidium infections. The compounds target the Cryptosporidium methionyl-tRNA synthetase (MetRS), an enzyme that is essential for protein synthesis. The most potent compounds inhibited the enzyme with Ki values in the low picomolar range. Cryptosporidium cells in culture were potently inhibited with 50% effective concentrations as low as 7 nM and >1,000-fold selectivity over mammalian cells. A parasite persistence assay indicates that the compounds act by a parasiticidal mechanism. Several compounds were demonstrated to control infection in two murine models of cryptosporidiosis without evidence of toxicity. Pharmacological and physicochemical characteristics of compounds were investigated to determine properties that were associated with higher efficacy. The results indicate that MetRS inhibitors are excellent candidates for development for anticryptosporidiosis therapy.

The role of zinc supplementation for diarrhoea in children: a critical review

Background: Nearly 1.7 million children suffer from diarrhoea and around 760,000 die each year. The high prevalence of diarrhoea in the developing countries is closely related to lack of safe drinking water, inadequate sanitation and hygiene, and poor health and nutritional status. These environmental conditions facilitate the spread of infectious disease easily. The great morbidity and mortality of this preventable and treatable disease raise concern on how to save children from this fatal disease by improving management of diarrhoea. Several studies suggest that zinc deficiency contribute towards high morbidity and mortality in diarrhoea. Further, there is an area of uncertainty regarding how significant zinc supplementation will help to reduce the duration and severity of diarrhoea in children compared to the diarrhoea management without zinc?
 Objective: To critically analyse the current evidences of zinc supplementation in diarrhoea.
 Data Sources: Keywords searching through MEDLINE Ovid database and additional references from retrieved articles. Study Selection: Limited to randomized controlled trial(RCT) study design and systematic review studies which were conducted from 2006 to 2016. However, there is one prospective cohort study included as it is a follow-up of subjects who participated in the previous double-blind randomized placebo-controlled trial.
 Data Synthesis: This review involves a summary of 10 articles that have been appraised on their relevance in evaluating the role of zinc in reducing severity and duration of diarrhoea in children. Further, the literature found is synthesised through method used in the studies and the effectiveness of zinc therapy
 Conclusion: Zinc is relatively safe to be used and it can improve diarrhoea management especially in developing countries.
 Bangladesh Journal of Medical Science Vol.18(2) 2019 p.190-195

Etiology and severity of diarrheal diseases in infants at the semiarid region of Brazil: A case-control study

BackgroundDiarrheal diseases are an important cause of morbidity and mortality among children in developing countries. We aimed to study the etiology and severity of diarrhea in children living in the low-income semiarid region of Brazil.MethodologyThis is a cross-sectional, age-matched case-control study of diarrhea in children aged 2–36 months from six cities in Brazil’s semiarid region. Clinical, epidemiological, and anthropometric data were matched with fecal samples collected for the identification of enteropathogens.ResultsWe enrolled 1,200 children, 596 cases and 604 controls. By univariate analysis, eight enteropathogens were associated with diarrhea: Norovirus GII (OR 5.08, 95% CI 2.10, 12.30), Adenovirus (OR 3.79, 95% CI 1.41, 10.23), typical enteropathogenic Escherichia coli (tEPEC), (OR 3.28, 95% CI 1.39, 7.73), enterotoxigenic E. coli (ETEC LT and ST producing toxins), (OR 2.58, 95% CI 0.99, 6.69), rotavirus (OR 1.91, 95% CI 1.20, 3.02), shiga toxin-producing E. coli (STEC; OR 1.77, 95% CI 1.16, 2.69), enteroaggregative E. coli (EAEC), (OR 1.45, 95% CI 1.16, 1.83) and Giardia spp. (OR 1.39, 95% CI 1.05, 1.84). By logistic regression of all enteropathogens, the best predictors of diarrhea were norovirus, adenovirus, rotavirus, STEC, Giardia spp. and EAEC. A high diarrhea severity score was associated with EAEC.ConclusionsSix enteropathogens: Norovirus, Adenovirus, Rotavirus, STEC, Giardia spp., and EAEC were associated with diarrhea in children from Brazil’s semiarid region. EAEC was associated with increased diarrhea severity.

Realizing the need of inclusion of rotavirus vaccine in expanded program on immunization in Sindh, Pakistan

The basic goal of the expanded program on immunization (EPI) is to assure the proper immunization services that aids in preserving and promoting the health of children. The foundation of EPI in Pakistan was prompted and initiated by the World Health Organization (WHO) in 19781. The current EPI of Pakistan has vaccines for Tuberculosis, Poliomyelitis, Diphtheria, Tetanus, Pertussis, Hepatitis B, Haemophilus Influenza-b (Hib) Pneumonia, Meningitis, and Measles. However, it doesn't include the most important Rotavirus vaccine which is internationally included in EPI of other 90 countries. Despite the advent of Rotavirus vaccine a decade ago, it is the most common cause of severe childhood diarrhea. Globally it results in more than half a million deaths among children of less than 5 years of age per annum. In 2006 first rotavirus vaccine was introduced in Finland (US) in 2 forms, Rotarix and Rotteq. Both had the maximum potential effect if given before 8 months of age. In the United States, studies depicted that after the introduction of the vaccine in 2006 mortality has reduced by more than two thirds. According to WHO, diarrhea has the 3rd highest rates of mortality in children amongst all infectious diseases.

Rotavirus Outbreaks in the Postvaccine Era

Before the advent of rotavirus vaccination in 2006, this reovirus was the most common cause of severe childhood diarrhea in the U.S. The use of either

Development of novel in vitro and in vivo models to evaluate antibiotic efficacy against shigellosis

Shigellosis is caused by oral ingestion of the gram‐negative bacteria Shigella. Symptoms of the disease include severe diarrhea and dysentery, and the impact of the disease disproportionately affects children and those in low‐income countries such as sub‐Saharan Africa, Asia, and Latin America. According to a reanalysis of the Global Enteric Multicenter Study (GEMS), Shigella has the highest attributable incidence of pathogen specific moderate to severe diarrhea in children between 12–59 months of age. Recent studies have estimated approximately 90 million shigellosis cases annually, and the Global Burden of Disease 2015 analysis suggests at least 164,000 deaths per year are due to Shigella. Interspecies‐variation with lack of cross‐protection may challenge the development of a broadly‐protective vaccine and no human vaccine candidates are currently approved for treatment. Therapeutic options for shigellosis are limited and globally emerging drug resistance to sulfonamides, tetracyclines, ampicillin, and TMP‐SMX has been reported. With resistance to many “first‐line” antibiotics, ciprofloxacin, azithromycin, and ceftriaxone have been recommended for treatment of shigellosis. However, rapidly evolving resistance has been reported for these antibiotics as well. While there is a clear need for novel therapeutics to treat this disease, current drug development efforts are hindered by a lack of fundamental in vitro and in vivo tools to assess the efficacy of pre‐clinical candidates. We have focused our efforts on establishing in vitro co‐culture systems and in vivo mouse models to evaluate small molecule therapeutics. Our aim is to use these tools to identify PK/PD relationships for established and novel therapeutics to treat Shigella infection. The gastrointestinal localization of the parasite generates a unique challenge for establishing a pharmacokinetic‐pharmacodynamic (PK/PD) relationship for an anti‐Shigella drug candidate. We have previously reported on our use of physiology based pharmacokinetic (PBPK) modeling to identify an association between gastrointestinal drug concentrations and in vivo efficacy for anti‐Cryptosporidium drugs and we plan to use a similar technique for the antibiotics used to treat Shigella infection. The presented work will be valuable for the entire research community currently engaged in the development of therapeutics for enteric diseases.Support or Funding InformationThis work was supported by the Tres Cantos Open Lab Foundation Award: TC246This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impact of pentavalent rotavirus vaccine against severe rotavirus diarrhoea in The Gambia

IntroductionRotavirus vaccines protect against the leading cause of severe childhood diarrhoea, and have been introduced in many low-income African countries. The Gambia introducedRotateq® (RV5) into their national immunization program in 2013. We revieweddata from an active rotavirus sentinel surveillancesitefor early evidence of vaccine impact. MethodsWe compared rotavirus prevalence in diarrhoeal stool in children< 5 years of age admittedat the Edward Francis Small Teaching Hospital sentinel surveillance site before (2013) andafterRV5 introduction (2015–2016) in the Gambia. The rotavirus-percent positive was separately compared for all diarrhoealhospitalizations and for hospitalizations with severe symptoms. Rotavirus prevalence was compared annually for the pre-vaccine year of 2013 with post-vaccine years of 2015 and 2016 using chi-square or Fisher’s exact tests and the p-value to establish significant relationship was set at p < 0.05. All analyses were completed in SAS 9.3 (SAS Analytics, North Carolina). ResultsRotavirus prevalence among all diarrhoeahospitalizations decreased from 22% in 2013 to 11% in 2015 (p = 0.04), while remaining unchanged in 2016 (18%, p = 0.56). For hospitalizations that were clinically severe and/or treated with intravenous fluids (mean of 46 per year), the rotavirus prevalence decreased from 33% in 2013 to 8% in 2015 (p = 0.04), and to 15% in 2016 (p = 0.08). The children with age <1 year accounted for 45% the population infected with rotavirus in both pre and post rotavirus vaccination periods. ConclusionsRotavirus vaccine introduction in the Gambia could be among factors resulting in decreased diarrhea hospitalizations among children at the Edward Francis Small Teaching Hospital, particularly those with severe disease. These results support the continuation of rotavirus vaccine and additional monitoring of rotavirus hospitalization trends in the country.

Update on Epidemiology and Circulating Genotypes of Rotavirus in Iranian Children With Severe Diarrhea: 1986-2015

Rotaviruses are the most common cause of severe diarrhea in children under 5 years of age worldwide with a higher prevalence in developing countries. In accordance with the World Health Organization (WHO) recommendations for the global use of rotavirus vaccines, it is important to review trends of rotavirus epidemiology, distribution and diversity of rotavirus strains in the pre-vaccine period. In Iran, the average rotavirus positivity rate is 40.04% in all patients under 5 years of age hospitalized for acute gastroenteritis (AGE). Studies have shown a substantial increase in the rotavirus detection rate over time from 1986 to 2013. Moreover, there has been continued predominance of G (G1) and P (P[8]) genotypes, although the peak prevalence of G1 appeared to decline in 2007-2011 compared to 2001-2006. The data presented in this review, which suggests a change in the pattern of rotavirus genotypes in the Iranian population, further highlights the important role of continuous monitoring of rotavirus genotypes before starting any national rotavirus vaccination program.

The other Campylobacters: Not innocent bystanders in endemic diarrhea and dysentery in children in low-income settings.

BackgroundCampylobacter is one of the main causes of gastroenteritis worldwide. Most of the current knowledge about the epidemiology of this food-borne infection concerns two species, C. coli and C. jejuni. Recent studies conducted in developing countries and using novel diagnostic techniques have generated evidence of the increasing burden and importance of other Campylobacter species, i.e. non-C. coli/jejuni. We performed a nested case-control study to compare the prevalence of C. coli/jejuni and other Campylobacter in children with clinical dysentery and severe diarrhea as well as without diarrhea to better understand the clinical importance of infections with Campylobacter species other than C. coli/jejuni.Methodology/Principal findingsOur nested case-control study of 439 stool samples included dysenteric stools, stools collected during severe diarrhea episodes, and asymptomatic stools which were systematically selected to be representative of clinical phenotypes from 9,160 stools collected during a birth cohort study of 201 children followed until two years of age. Other Campylobacter accounted for 76.4% of the 216 Campylobacter detections by qPCR and were more prevalent than C. coli/jejuni across all clinical groups. Other Campylobacter were also more prevalent than C. coli/jejuni across all age groups, with older children bearing a higher burden of other Campylobacter. Biomarkers of intestinal inflammation and injury (methylene blue, fecal occult test, myeloperoxidase or MPO) showed a strong association with dysentery, but mixed results with infection. MPO levels were generally higher among children infected with C. coli/jejuni, but Shigella-infected children suffering from dysentery recorded the highest levels (26,224 ng/mL); the lowest levels (10,625 ng/mL) were among asymptomatic children infected with other Campylobacter. Adjusting for age, sex, and Shigella infection, dysentery was significantly associated with C. coli/jejuni but not with other Campylobacter, whereas severe diarrhea was significantly associated with both C. coli/jejuni and other Campylobacter. Compared to asymptomatic children, children suffering from dysentery had a 14.6 odds of C. coli/jejuni infection (p-value < 0.001, 95% CI 5.5–38.7) but were equally likely to have other Campylobacter infections–odds ratio of 1.3 (0.434, 0.7–2.4). Children suffering from severe diarrhea were more likely than asymptomatic children to test positive for both C. coli/jejuni and other Campylobacter–OR of 2.8 (0.034, 1.1–7.1) and 1.9 (0.018, 1.1–3.1), respectively. Compared to the Campylobacter-free group, the odds of all diarrhea given C. coli/jejuni infection and other Campylobacter infection were 8.8 (<0.001, 3.0–25.7) and 2.4 (0.002, 1.4–4.2), respectively. Eliminating other Campylobacter in this population would eliminate 24.9% of the diarrhea cases, which is almost twice the population attributable fraction of 15.1% due to C. coli/jejuni.Conclusions/SignificanceEighty-seven percent of the dysentery and 59.5% of the severe diarrhea samples were positive for Campylobacter, Shigella, or both, emphasizing the importance of targeting these pathogens to limit the impact of dysentery and severe diarrhea in children. Notably, the higher prevalence of other Campylobacter compared to C. coli/jejuni, their increasing burden during early childhood, and their association with severe diarrhea highlight the importance of these non-C. coli/jejuni Campylobacter species and suggest a need to clarify their importance in the etiology of clinical disease across different epidemiological contexts.

Incidence and clinical profile of rotaviral infection among children below 5 years of age admitted with acute diarrhea in a tertiary care hospital of Tripura

Background: Acute diarrheal disease is a major cause of childhood morbidity and mortality. Rotavirus has been recognized as the most common cause of severe diarrhea in children. Data on rotaviral disease burden are needed across India to support reasonable, evidence-based decision regarding any intervention. Objectives: The objectives of the study were to study the incidence of rotavirus infection in acute diarrhea among children below 5 years and clinical profile of rotaviral diarrhea. Materials and Methods: This cross-sectional study was conducted in a teaching institution of Tripura from November 1, 2014, to April 30, 2016. Stool samplesfrom 460 hospitalized children below 5 years admitted with acute diarrhea were tested for rotaviral antigen by ELISA method. Caregivers were interviewed, physical examination was conducted, assessment of dehydration was done, and cases were managed as per the WHO Guideline. Results: Out of 460 cases of acute diarrhea, 290 (63%) were male and 170 (37%) were female. In infants, 240 (52%) diarrheal cases were observed. Out of total 460 stool samples, 166 (36%) were rotavirus positive, and of these, 100 (60.24%) rotavirus positive cases were infant, and 102 (61.44%) were male children. Rotavirus infection was observed throughout the year, with peak (54.21%) during January–March (winter season). Clinically, 110 (66.26%) children had fever, 94% (156) cases had vomiting, and 63.25% (105) children of rotaviral diarrheal cases were admitted with some dehydration, and 33.13% (55) patients were admitted with severe dehydration. The mean duration of diarrhea (4.97 days) and mean duration of hospital stay (3.71 days) were significantly higher in rotaviral diarrhea as compared with non-rotaviral diarrhea. No death was observed. Out of 460 cases of acute diarrhea, only 6 (1.3%) cases had received rotaviral vaccine, and only one case (0.6%) among 166 rotaviral diarrhea cases had received rotaviral vaccine. Conclusion: This study highlights that rotavirus is a significant cause of acute diarrhea in this part of the country and mainly affects children below 12 months age.

English

Group A rotaviruses are the major viral agent of acute gastroenteritis and severe diarrhea in children <5 years old. The World Health Organization (WHO) recommends surveillance of circulating strains before and after introduction of vaccination in countries. However, the diversity of circulating strains in developing countries is a major challenge to the vaccination programs. This study, carried out in furtherance of the sentinel surveillance, aims to identify the different genotypes circulating before the introduction of the Rotavirus vaccine. All children with acute gastroenteritis aged 0 to 5 years, admitted in one of the sentinel surveillance collection sites were included in the study. The study period was from January 2010 to December 2016. Rotavirus was detected in stool specimens by enzyme-linked immunosorbent assay (ELISA). Rotavirus G and P types were determined by real-time polymerase chain reaction (RT-PCR). A total of 1472 stool samples were collected during this period. 31.8% of the stools were rotavirus positive by ELISA test. G1 was predominant with 39.6% followed by G12 (27%). P [8] was 50.4%. The predominant genotype combinations were G1P [8] with 26.1%; G12P [8], 15%; G1P [6], 11.3% and G12P [6], 10.8%. Genotyping of circulating rotavirus strains is important in monitoring strains before and after the introduction of the vaccine. With previous observations, these findings will contribute to baseline data to further monitor the impact of rotavirus immunization in Cote d’Ivoire. Key words: Rotavirus, Cote d’Ivoire, diarrhea, vaccination, acute gastroenteritis.

Rotavirus Vaccines: New Strategies and Approaches

Rotaviruses cause an infectious disease that is the main cause of severe diarrhea in children all over the world and one of the factors that determine the level of child mortality. Only live attenuated vaccines are currently used against rotavirus infection. These vaccines are efficient, but a range of side effects, including intussusception risk, is characteristic of them. Complications associated with the use of existing vaccines usually occur in the case of oral administration and develop as the attenuated live vaccines start to replicate in the human intestine. Thus, there is a need for development of modern, efficient, and safe preparations for the prevention of rotavirus infection. These preparations should be incapable of reproduction (replication) in the organism after vaccination. Recombinant vaccines represent a new generation of vaccines against rotavirus infection, and the development and testing of such vaccines, including those intended for parenteral administration, has progressed considerably during recent years. The complex antigenic structure of the rotavirus is one of the problems associated with the production of these vaccines. The present review summarizes published data on genetic and antigenic diversity of rotavirus strains and geographic localization of epidemiologically significant virus variants. The role of capsid proteins in the emergence of immune response against the virus and the current state of research on new candidate recombinant vaccines against rotavirus infection are discussed.

Rotavirus genotypes as etiological agents of diarrhoea in general populations of two geographic regions of Brazil.

ABSTRACTRotavirus is the main global cause of severe childhood diarrhoea among children. In 2006, Rotarix® (G1P[8]) was introduced into Brazil’s National Immunization Program. The vaccine coverage rate was 84.4% in 2009. Evidences of increasing G2P[4] after 2006 opened up the discussion about the vaccine effectiveness to non-G1 strains. The aim of this study was to identify the circulating rotavirus genotypes in two Brazilian regions during 2009. A total of 223 positive samples by immunochromatography and latex agglutination assay from the Northeast (Bahia/Pernambuco States) and Southeast (São Paulo/Rio de Janeiro States) regions were included in the study. The samples were submitted to genotyping by nested-PCR according to VP7(G) and VP4(P) and 175 samples (78.5%) were able to be characterized. Considering the characterization of VP7, the G-types detected were G1, G2, and G4 in the Northeast, and G2, G3, G5, and G9 in the Southeast. Considering the characterization of VP4, the P-types detected were P[4], P[8], and P[6]/P[9] in the Northeast and the Southeast. The most frequent mixed types found were G2P[4]/G2P[NT](81.4%), G2P[6](5.2%), G1P[6](5.2%) in the Northeast, and G2P[4]/G2P[NT](78.8%), G2P[6](8.2%), G9P[8](4.7%) in the Southeast. Among immunized individuals whose age ranged from 0-4 years, the G2P[4]/G2P[NT] genotype was identified in 91,0% of cases, and among non-immunized individuals of the same age, the G2P[4]/G2P[NT] genotype was identified in 85.7% of the cases. In accordance with the high level of vaccine coverage, the data suggest that the circulation of G2P[4] in these regions had a considerable increase after the introduction of Rotarix®.