| 1. |
- Bucardo, Filemon, et al.
(författare)
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Genetic susceptibility to symptomatic norovirus infection in Nicaragua. : norovirus susceptibility in Nicaragua
- 2009
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Ingår i: Journal of medical virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 81:4, s. 728-35
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Tidskriftsartikel (refereegranskat)abstract
- Host genetic resistance to Norovirus (NoV) has been observed in challenge and outbreak studies in populations from Europe, Asia, and USA. In this study, we have investigated if histo-blood group antigens can predict susceptibility to diarrhea caused by NoV in Nicaragua, Central America, and if this can be reflected in antibody-prevalence and titer to NoV among individuals with different histo-blood group antigen phenotypes. Investigation of 28 individuals infected with NoV and 131 population controls revealed 6% of non-secretors in the population and nil non-secretors among patients infected with NoV, suggesting that non-secretors may be protected against NoV disease in Nicaragua. Surprisingly, 25% of the population was Lewis negative (Le(a-b-)). NoV infections with genogroup I (GI) and GII occurred irrespective of Lewis genotype, but none of the Lewis a positive (Le(a + b-)) were infected. The globally dominating GII.4 virus infected individuals of all blood groups except AB (n = 5), while the GI viruses (n = 4) infected only blood type O individuals. Furthermore, O blood types were susceptible to infections with GI.4, GII.4, GII.7, GII.17, and GII.18-Nica viruses, suggesting that secretors with blood type O are susceptible (OR = 1.52) and non-secretors resistant. The overall antibody-prevalence to NoV GII.3 VLP was 62% with the highest prevalence among blood type B carriers (70%) followed by A (68%) and O (62%). All four investigated individuals carrying blood type AB were antibody-negative. Among secretors, 63% were antibody-positive compared to 33% among non-secretors (P = 0.151). This study extends previous knowledge about the histo-blood group antigens role in NoV disease in a population with different genetic background than North American and European.
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| 2. |
- Espinoza, F., et al.
(författare)
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Shifts of rotavirus G and P types in Nicaragua - 2001-2003
- 2006
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Ingår i: The Pediatric Infectious Disease Journal. - : Ovid Technologies (Wolters Kluwer Health). - 0891-3668 .- 1532-0987. ; 25:11, s. 1078-1080
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Tidskriftsartikel (refereegranskat)abstract
- The present study reports the diversity of rotavirus strains circulating in León, Nicaragua during three years. There was a shift of G and P genotypes with increment of one specific genotype during the second most important peak of diarrhea occurring in the beginning of every year. © 2006 Lippincott Williams & Wilkins, Inc.
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| 3. |
- Bucardo, Filemon, et al.
(författare)
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Pediatric norovirus diarrhea in Nicaragua
- 2008
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Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 46:8, s. 2573-2580
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Tidskriftsartikel (refereegranskat)abstract
- Information about norovirus (NoV) infections in Central America is limited. Through a passive community and hospital pediatric diarrhea surveillance program, a total of 542 stool samples were collected between March 2005 and February 2006 in León, Nicaragua. NoV was detected in 12% (65/542) of the children; of these, 11% (45/409) were in the community and 15% (20/133) were in the hospital, with most strains (88%) belonging to genogroup II. NoV infections were age and gender associated, with children of <2 years of age (P < 0.05) and girls (P < 0.05) being most affected. Breast-feeding did not reduce the number of NoV infections. An important proportion (57%) of NoV-infected children were coinfected with diarrheagenic Escherichia coli. A significant proportion (18/31) of NoV-positive children with dehydration required intravenous rehydration. Nucleotide sequence analysis (38/65) of the N-terminal and shell region in the capsid gene revealed that at least six genotypes (GI.4, GII.2, GII.4, GII.7, GII.17, and a potentially novel cluster termed "GII.18-Nica") circulated during the study period, with GII.4 virus being predominant (26/38). The majority (20/26) of those GII.4 strains shared high nucleotide homology (99%) with the globally emerging Hunter strain. The mean viral load was approximately 15-fold higher in children infected with GII.4 virus than in those infected with other G.II viruses, with the highest viral load observed for the group of children infected with GII.4 and requiring intravenous rehydration. This study, the first of its type from a Central American country, suggests that NoV is an important etiological agent of acute diarrhea among children of <2 years of age in Nicaragua.
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| 4. |
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| 5. |
- Bucardo, Filemon, et al.
(författare)
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Genetic susceptibility to symptomatic norovirus infection in Nicaragua
- 2009
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Ingår i: Journal of Medical Virology. - : John Wiley & Sons. - 0146-6615 .- 1096-9071. ; 81:4, s. 728-735
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Tidskriftsartikel (refereegranskat)abstract
- Host genetic resistance to Norovirus (NoV) has been observed in challenge and outbreak studies in populations from Europe, Asia, and USA. In this study, we have investigated if histo-blood group antigens can predict susceptibility to diarrhea caused by NoV in Nicaragua, Central America, and if this can be reflected in antibody-prevalence and titer to NoV among individuals with different histo-blood group antigen phenotypes. Investigation of 28 individuals infected with NoV and 131 population controls revealed 6% of non-secretors in the population and nil non-secretors among patients infected with NoV, suggesting that non-secretors may be protected against NoV disease in Nicaragua. Surprisingly, 25% of the population was Lewis negative (Le(a-b-)). NoV infections with genogroup I (GI) and GII occurred irrespective of Lewis genotype, but none of the Lewis a positive (Le(a + b-)) were infected. The globally dominating GII.4 virus infected individuals of all blood groups except AB (n = 5), while the GI viruses (n = 4) infected only blood type O individuals. Furthermore, O blood types were susceptible to infections with GI.4, GII.4, GII.7, GII.17, and GII.18-Nica viruses, suggesting that secretors with blood type O are susceptible (OR = 1.52) and non-secretors resistant. The overall antibody-prevalence to NoV GII.3 VLP was 62% with the highest prevalence among blood type B carriers (70%) followed by A (68%) and O (62%). All four investigated individuals carrying blood type AB were antibody-negative. Among secretors, 63% were antibody-positive compared to 33% among non-secretors (P = 0.151). This study extends previous knowledge about the histo-blood group antigens role in NoV disease in a population with different genetic background than North American and European.
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| 6. |
- Bucardo, F, et al.
(författare)
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Mutated G4P[8] rotavirus associated with a nationwide outbreak of gastroenteritis in Nicaragua in 2005
- 2007
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Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 45:3, s. 990-997
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Tidskriftsartikel (refereegranskat)abstract
- During February and March 2005, one of the largest national recorded outbreaks of severe acute gastroenteritis occurred in Nicaragua, affecting ≥64,000 individuals and causing ≥56 deaths, predominantly in children under 5 years of age. Through a nationwide laboratory-based study, stool samples were collected and investigated for rotavirus. Of 108 stool samples examined, 72 (67%) were positive for rotavirus. While 69% (50/72) of the positive samples were found in children less than 2 years of age, 50% (6/12) of the adult samples were positive. A mutated G4P[8] strain was the most commonly recognized strain (85%), followed by mixed G strains (8%) and G9P[8] (7%) strains. Phylogenetic analysis of the VP7 gene revealed that the G4 strains belonged to the emerging lineage Ic and was distantly related to the ST3 and VA70 G4 strains. Secondary structure predictions of the VP7 G4 protein revealed an insert of an asparagine residue in position 76, which, combined with additional mutations, surprisingly modified two downstream β-sheets at amino acid positions 80 to 85 and 115 to 119. The 2005 G4P[8] strain compared to a G4P[8] strain from 2002 had a substitution of an asparagine residue for threonine (Asn→Thr) at position 96 within antigenic region A, thus eliminating a potential glycosylation site. The mutated G4 virus was introduced in Nicaragua after 2002 and probably emerged from Brazil, Argentina, or Uruguay. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
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| 7. |
- Nordgren, Johan, 1980-, et al.
(författare)
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Novel light-upon-extension real-time PCR assays for detection and quantification of genogroup I and II noroviruses in clinical specimens
- 2008
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Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 46:1, s. 164-170
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Tidskriftsartikel (refereegranskat)abstract
- Norovirus is now recognized as the leading cause of nonbacterial acute gastroenteritis in adults, causing numerous outbreaks worldwide. We have developed two novel light-upon-extension (LUX) real-time PCR assays for detection and quantification of norovirus genogroups I and II. The LUX system uses a fluorophore attached to one primer having a self-quenching hairpin structure, making it cost-effective and specific. The assays were evaluated against clinical stool specimens (n = 103) from Sweden and Nicaragua and compared to established methods. The norovirus assay detected more positive stool specimens (47/103) than conventional PCR (39/103) and corresponded to a TaqMan real-time PCR, with the exception of one specimen. Furthermore, the assays correctly identified all (n = 11) coded control specimens in a reference panel containing various genogroups and genotypes. Both LUX real-time PCR assays had a wide dynamic range, detecting from < or = 10(1) to 10(7) genes per reaction, resulting in a theoretical lower limit of < or = approximately 20,000 viruses per gram of stool. No cross-reactivity was noticed with specimens containing other enteric viruses, and by using melting curve analysis we could differentiate between norovirus genogroups I and II.
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| 8. |
- Nordgren, Johan, 1980-
(författare)
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Norovirus Epidemiology : Prevalence, transmission, and determinants of disease susceptibility
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Norovirus (NoV) is today recognized as the most important agent of acute human gastroenteritis, causing a high number of diarrheal episodes in both adults and children. Outbreaks in hospitals, nursing homes, day-care centers, and from consumption of contaminated food and drinking water are common. Wastewater can be a source of NoV dissemination, e.g. when used for irrigation of crops, or due to shellfish cultivation near the outlet of wastewater treatment plants. Today, at least 25 different genotypes of NoV belonging to two major genogroups (GG) have been observed in humans. These genotypes are associated with different transmission patterns and disease severity in humans. Also host genetic factors, such as presence of ABO antigens and mutations in the FUT2 gene affect susceptibility, and can even render complete resistance to symptomatic infections, but only the most common NoV genotypes have been studied regarding this.In this thesis, we wanted to find prevention strategies for NoV disease through four studies of NoV epidemiology: Development of a sensitive real-time PCR assay for detection and quantification of human NoVs, characterization of NoV in children with diarrhea in Nicaragua, investigation of the prevalence and parameters influencing NoV concentration in a wastewater treatment plant in Gothenburg, Sweden, and studying host susceptibility factors in a foodborne NoV outbreak in Jönköping, Sweden.First we developed a real-time PCR assay which can detect and quantify NoV in various settings, both in stool samples of patients, and in wastewater samples from which virus was first concentrated using ultracentrifugation. This assay was found to be more sensitive than commercial immunological assays and conventional PCR methods. The assay is furthermore able to differentiate between the two major human genogroups of NoV using melting curve analysis, which provides valuable information about the circulating NoV strains.The survey of NoV in pediatric diarrhea in Nicaragua revealed a large impact of NoV, both in community and hospital based settings, with 15% of the severe diarrhea cases attributed to NoV. Peaks of clinically diagnosed NoV gastroenteritis were associated with emerging variants of genotype GGII.4, largely replacing the many different NoV genotypes circulating before the peak of diarrheal cases. Children infected with the GGII.4 genotype were found to shed more virus compared to children infected with other genotypes, which could partly explain the high transmission of GGII.4.At the wastewater treatment plant in Gothenburg, both NoV GGI and GGII were detected during a whole year, not only during the winter season when clinical cases are common. This indicates that NoV infections are frequently occurring at clinical and/or sub-clinical levels in the community. During winter, GGII was present in high concentrations, whereas GGI concentration increased to higher levels than GGII in summer, possibly due to the emergence of new genotypes following the winter outbreaks. The levels of NoV GGI were stable during the year, and hence incoming concentrations were affected by dilution factors such as rain. Primary treatment and treatment in a conventional, non-nitrifying activated sludge system reduced the NoV concentration by a factor of about 30. The detection of NoV in outgoing water, together with the low reduction and lack of correlation to indicator bacteria, suggest that better monitoring tools for virus in wastewater are warranted to reduce environmental contamination.A foodborne NoV outbreak in Jönköping in October 2007, by a NoV GGI.3 strain, revealed a surprising pattern of host susceptibility. In contrast to previous findings, this strain infected individuals irrespective of secretor status and Lewis (Le) phenotype, with non-secretors and Lea+bindividuals having a higher risk of disease. Individuals with blood group B had a partial protection to symptomatic infection, but none of the host factors investigated mediated complete resistance. Furthermore, we observed differences in susceptibility regarding homozygosity and heterozygosity in the FUT2 gene, with heterozygous secretor-positive individuals being more susceptible to symptomatic NoV infection than homozygous secretors.In summary, the developed LUX real-time PCR assay was successfully used in all studies in this thesis, which yielded important information about the prevalence and transmission of NoV. We observed the emergence of GGII.4 variants, causing the majority of diarrheal cases in children, largely replacing the other circulating genotypes, possibly due to better replication leading to a higher viral shedding. After the peak of NoV-induced diarrheal episodes, the incidence of GGII.4 decrease and other strains emerge which can infect people not previously exposed. This was observed in the foodborne outbreak in Jönköping, where individuals expected to be resistant to NoV were infected, and indeed had a higher risk of developing disease. A similar seasonal pattern was also indirectly observed in wastewater, with high levels of GGII in winter, which subsequently declined, followed by an increase of GGI in summer. Taken together, these results provide a better insight into the epidemiology of the virus, which hopefully can lead to better preventive measures for NoV gastroenteritis.
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