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La gastroenteritis ocasionada por rotavirus se encuentra entre las principales causas de morbilidad y mortalidad infantil. En el Perú rotavirus representa el 30% de las muertes por diarrea y 4% del total de defunciones, afectando principalmente a niños menores de 5 años. Desde el año 2009 el Perú implementó la vacuna contra rotavirus en su programa de vacunación universal, sin embargo, debido a la aparición de genotipos emergentes, es importante monitorear la diversidad del virus para evaluar los posibles efectos sobre la eficacia de la vacuna. Pese a esto, existen escasos reportes de la epidemiología de rotavirus en nuestro país. El objetivo del presente estudio es determinar la presencia y los genotipos G y P de Rotavirus en muestras provenientes de niños con gastroenteritis aguda atendidos en un hospital de Lima entre Octubre del 2013 y Octubre del 2014. Como metodología se utilizó el RT-PCR en tiempo real (qRT- PCR) para la detección del rotavirus y el RT PCR convencional para la genotipificación de las muestras positivas, asimismo se secuenciaron algunas muestras para determinar los genotipos finales. De las 448 muestras analizadas en el estudio, 45 (10%) tuvieron resultado positivo para rotavirus. Entre los genotipos identificados, G12 (40.9%), G2 (25%) y P[8] (77.3%) fueron los más frecuentes y la combinación G/P más dominante fue G12P[8] (54.5%). Los resultados evidenciaron una alta prevalencia de G12P[8]entre los casos positivos, genotipo no reportado previamente en el Perú. Se recomienda realizar nuevos estudios para evaluar las variaciones en la diversidad de rotavirus circulantes en el Perú y los posibles efectos ante la presión selectiva de la vacuna.Rotavirus gastroenteritis is one of the leading causes of morbidity and mortality in children. In Peru rotavirus represents 30% of deaths due to diarrhea and is responsible of 4% of the total deaths, affecting mostly children under 5 years. Peru implemented the rotavirus vaccine in its universal vaccination program since 2009. Due to the appearance of emerging genotypes, it is important to evaluate the diversity of the virus in order to determine possible effects on vaccine efficacy. However there are few reports on the molecular epidemiology of rotavirus in our country. The aim of this study was to determine the presence and Rotavirus G and P genotypes in samples from children with acute gastroenteritis attended in a hospital in Lima between October 2013 and October 2014. The method usedfor the detection of rotavirus was real time RT-PCR (qPCR) and conventional RT-PCR to determine the genotype of positive samples. Additionally, sequencing was used to confirm the final genotype of some samples. Of the 448 samples analyzed, 45 (10%) were positive for rotavirus.G12 (40.9%), G2 (25%) and P[8] (77.3%) were the most frequent genotypes and the most prevalent G/P combination was G12P[8] (54.5%). The results showed a high prevalence of G12P[8] among the positive cases. G12P[8] has not been previously reported in Peru. We recommend more in deep studies to identify the diversity of circulating genotypes in Peru.

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 255-300).

Norovirus (NoV) and Sapovirus (SaV) are major causes of outbreak gastroenteritis worldwide. NoV and SaV are highly infectious, have multiple transmission routes and have a short incubation period, thereby facilitating rapid intercontinental spread of new variants. Consequently, a treatment would be advantageous for controlling them. However, currently little is known about the replication cycle and evolution of human NoV or SaV as neither are culturable. NoV and SaV are RNA viruses of the Caliciviridae family and have great genetic diversity which is thought to facilitate irnmune evasion. Consequently variants of NoV GI1.4 arose in 1996, 2002, 2004 and in 2006 and resulted in pandemics. Therefore, in this study, the role of the two main mechanisms associated with generating viral diversity; recombination, and point mutation were investigated for NoV and SaV. Physiological and kinetic properties of three NoV RdRps (genotypes, Gll.b, Gll.4, Gll.7) and two SaV RdRps (genogroups GI, GII) were also investigated. RNA recombination is a significant driving force in viral evolution. Increased awareness of recombination within the Calicivirus genus Norovirus (NoV) has led to a rise in the identification of NoV recombinants and they are now reported at high frequency. Despite this no classification system exists for recombinant NoVs As a result, there is duplication in reporting novel recombinants and the precise number of novel NoV recombinant types is unknown. Therefore, in order to elucidate thero!e of recombination in NoV evolution, 121 NoV nucleotide sequences, compiled from the GenBank database and published literature, were analysed for recombination events. NoV recombinants and their recombination breakpoint were identified using three methods: phylogenetic analysis, Simplot analysis and the Maximum Chi-Squared method. In total 19 unique NoV recombinant types were identified in circulation across the globe and they had a common recombination point near the ORF1/2 overlap. Recombination at the ORF1/0RF2 overlap could have important implications in NoV evolution as it enables a virus to swap its antigenic determinates (capsid) and thereby avoid immune clearance in an analogous manner to antigenic shift in influenza virus. This study also examined the role of NoV and SaV replication in generating viral diversity by comparing the physiological, kinetic and biochemical properties of five genotypically distinct RdRps from two different genera of the Caliciviridae. Genetically diverse HuCV RdRps were expressed in Escherichia coli and characterised in an in vitro assay designed for this study. The results indicated that despite high sequence variation between the five enzymes (between 6% and 71% amino acid difference) they shared similar physiological properties. Though there was some variation in their template usage and kinetic properties. SaV was able to perform primer dependent replication on homopolymeric A RNA whereas the NoV RdRps were not. Additionally, NoV RdRps had a higher incorporation rate and were more kinetically efficient than the two SaV RdRps. The incorporation fidelity of the five enzymes was similar (between 2.2x10-5 to 8.9x10-4 ), although interestingly the most prevalent strain, Gll.4, had the lowest fidelity of the caliciviruses. Therefore, suggesting that RdRp fidelity has an important role in NoV evolution. Overall, this study illustrated that NoV and SaV generate genetic diversity in a similar fashion to other RNA viruses, that is, a delicate combination of recombination, point mutation and replication efficiency. Understanding the mechanisms involved in viral replication and genomic diversity of the calicivirus RdRps is essential if a successful control strategy for the human caliciviruses is going to be developed.

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MSc (Med), Epidemiology and Biostatistics,University of the Witwatersrand, Faculty of Health Sciences / Introduction In developing countries, diarrhoea is a major cause of morbidity and mortality among children under five years of age. This study aimed to determine the effect of age and HIV infection status on incidence of acute gastroenteritis and to identify risk factors associated with death and prolonged hospitalisation. Methods A secondary data analysis was performed using an existing cohort of children enrolled on a pneumococcal vaccine efficacy study performed in 1998-2005 in Soweto. Results The incidence rate of acute gastroenteritis requiring hospitalisation was 10.13 (CI95% 9.68, 10.58) per 1000 person years. Incidence was highest in those under six months of age, decreased with increasing age, and was 5.42 times (CI95% 4.89, 6.01) higher in those infected with HIV compared to that in HIV-uninfected children. HIV-infected children were more likely to be malnourished, have severe dehydration and have a concomitant diagnosis of lower respiratory tract infection (LRTI). HIV-infected children were four times more likely to die in hospital (OR 3.99 CI95% 2.04, 7.81) and almost twice as likely to be hospitalized > 2 days (OR 1.81 CI95% 1.38, 2.38) compared to HIV-uninfected children. Presence of malnutrition, severe dehydration and a concomitant diagnosis of LRTI were also significant risk factors for death and prolonged hospitalisation. Conclusions Acute gastroenteritis is an important cause of hospitalisation in children under 2 years, especially among HIV-infected children. Prevention and management of severe dehydration, malnutrition, HIV infection and concomitant LRTI need to be targeted to decrease mortality and shorten the duration of hospitalisation in children admitted with acute gastroenteritis.

Norovirus (NoV) is a leading causative agent of non-bacterial gastroenteritis in humans worldwide. NoV is genetically classified into five distinct genogroups in which genogroups I (GI), II, and rarely IV infect humans. Each genogroup is further subdivided into different genotypes. Previous local surveillance studies demonstrated that NoV GII, in particular the genotype 4 (GII/4) strain, is the predominant genogroup circulating in Hong Kong since 2001. Similar epidemiologic observations were also reported in the US, Europe, UK, Australia, and Japan, highlighting the enormous pandemic and epidemic potential of this genogroup. However, explanation for its predominance has been lacking. In this study, we demonstrated that NoV GII, comprised mostly of the GII/4 strain, showed an increased median viral RNA level in fecal specimens which was at least 100-fold higher than that of GI. The high level of viral shedding may confer greater opportunity for transmission of GII strains through the fecal-oral route. We also demonstrated that fecal viral RNA level correlated positively and independently with diarrhea duration in NoV GII/4 infections. The median fecal viral level in patients with protracted (last for ≥4 days) diarrhea was 100-fold higher than that in patients with only limited diarrhea. Longer infectivity period may also confer greater opportunity for virus transmission through the fecal-oral route. Higher chance of transmission may result in more efficient person-to-person transmission and rapid dissemination, maintaining a high level of NoV GII persistence in the community. In summer 2006, a territory-wide gastroenteritis outbreak attributed to NoV has occurred with more than 3,000 cases of laboratory-confirmed NoV infections in Hong Kong. Phylogenetic analysis showed that the virus causing this unprecedented outbreak was a novel NoV GII/4 variant distinct from all previously reported global pandemic and local epidemic strains. In this 2006 variant, we identified two hypervariable regions when compared with previous local epidemic strains in 2005: protruding domain 2 (P2 domain) of viral protein 1 (VP1) and VP1-binding domain of VP2. We mapped frequent amino acid substitutions to the modeled antigenic loop regions of P2 domain. We also identified in carboxyl-terminus of VP1 an epidemiologically important, putative conformational epitope that alternates between two 3-amino acid signatures during pandemic NoV GII/4 strains evolution since 1995. Our findings reflect the rapid evolution of NoV GII/4 under immunological pressure and suggest that immune evasion might be a potential mechanism for pandemic NoV GII/4 strains emergence. Taken together, high level of fecal viral shedding, longer infectivity period, and periodic emergence of novel variant may underlie the global predominance of NoV GII. Further investigations are warranted to better understand the public health and biological importance of NoV GII. / Chan, Chi Wai. / Adviser: Wai K. Leung. / Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0818. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 124-143). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / School code: 1307.

Background: Rotavirus (RV) is the leading agent of acute gastroenteritis in children under five years old, especially in children of 6~24 months. RV can lead to serious complications or even death. RV can cause a heavy burden of disease particularly in developing countries such as China. To prevent or reduce rotavirus diarrhea (RVD) and RV infection related diseases, damages or complications in children is an important task of public health. RV can also cause extraintestinal damage and complications. The finding of elevated CK-MB has been reported in a couple of Chinese literatures, but the epidemiology and the potential implication of this phenomenon remain poorly understood. Objective: 1. To study the prevalence of elevated serum CK-MB level among children hospitalized with rotavirus gastroenteritis in Guangzhou. 2. To examine factors associated with an elevated CK-MB level 3. To examine the clinical implication of elevated serum CK-MB level with different clinical symptomatology, severity, and disease outcome of rotavirus gastroenteritis in children. Methods: Aretrospective analysis of hospital records had carried out in Guangzhou Women and Children’s Medical Centre (GZWCMC), China. Hospital records during the period from 1 January 2011 to 31 December 2011 of inpatients from GZWCMC were screened and all inpatients with a diagnosis of rotavirus gastroenteritis in GZWCMC were recruited. Result and conclusion: Our study included418 cases of rotavirus infection hospitalized in GZWCMC in Guangdong in 2011, we found elevation of CK-MB a common phenomenon among patients of RV gastroenteritis, and identified a number of risk factors for elevated CK-MB level. These included patients of aged between 6-24 months, cases occurring in autumn or winter, patients coming from low income families, had never been breast-fed, or having dehydration, vomiting, malnutrition, fever, or having an abnormal blood gas and electrolyte. The elevated CK-MB level was positively associated with a higher occurrence of complications, a longer duration of hospitalization, and higher hospital cost per day. / published_or_final_version / Public Health / Master / Master of Public Health