| 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. |
- Bucardo, Filemón, et al.
(författare)
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Association of Genetic Polymorphisms in DC-SIGN, Toll-Like Receptor 3, and Tumor Necrosis Factor a Genes and the Lewis-Negative Phenotype With Chikungunya Infection and Disease in Nicaragua
- 2021
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 223:2, s. 278-286
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChikungunya infections range from subclinical infection to debilitating arthralgia and to chronic inflammatory rheumatism. Tumor necrosis factor (TNF) α, DC-SIGN (dendritic cell–specific intercellular adhesion molecule 3–grabbing nonintegrin), Toll-like receptor (TLR) 3, and blood groups have been directly or indirectly implicated in the susceptibility and pathogenesis of chikungunya.MethodsTo test the hypothesis that polymorphisms in genes coding for these molecules determine clinical outcomes of chikungunya infection, a retrospective case-control study was performed in León, Nicaragua. The study included 132 case patients and 132 controls, matched for age, sex and neighborhood. Case patients had clinical symptoms of chikungunya, which was diagnosed by means of polymerase chain reaction. Controls were individuals not reporting abrupt presentation of clinical chikungunya-like symptoms. Polymorphisms were identified by TaqMan single-nucleotide polymorphism genotyping assays.ResultsAfter adjustment for sociodemographic risk factors, chikungunya disease was associated with polymorphism in DC-SIGN and TLR3 genes (odds ratios, 5.2 and 3.3, respectively), and TNF-α with reduced persistent joint pain (0.24). Persistent joint pain was also associated with age, female sex and other comorbid conditions. Most interestingly, the Lewis-negative phenotype was strongly associated with both symptomatic chikungunya and immunoglobulin G seropositivity (odds ratios, 2.7, and 3.3, respectively).ConclusionThis study identified polymorphisms in DC-SIGN, TLR3, and TNF-α genes as well as Lewis-negative phenotype as risk factors for chikungunya infection and disease progression.
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| 3. |
- Vielot, Nadja A., et al.
(författare)
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First Episodes of Norovirus and Sapovirus Gastroenteritis Protect Against Subsequent Episodes in a Nicaraguan Birth Cohort
- 2022
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Ingår i: Epidemiology. - 1044-3983 .- 1531-5487. ; 33:5, s. 650-653
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Tidskriftsartikel (refereegranskat)abstract
- Background: Norovirus and sapovirus cause a large burden of acute gastroenteritis (AGE) in young children. We assessed protection conferred by norovirus and sapovirus AGE episodes against future episodes.Methods: Between June 2017 and July 2018, we recruited 444 newborns in León, Nicaragua. Weekly household surveys identified AGE episodes over 36 months, and AGE stools were tested by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) for norovirus genogroup (G)I/GII and sapovirus. We used recurrent-event Cox models and negative control methods to estimate protection conferred by first episodes, controlling for observed and unobserved risk factors, respectively.Results: Sapovirus episodes conferred a 69% reduced hazard of subsequent episodes using the negative control method. Norovirus GI (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.31, 1.3) and GII (HR = 0.20; 95% CI = 0.04, 0.44) episodes also appeared highly protective. Protection against norovirus GII was enhanced following two episodes.Conclusions: Evidence of natural immunity in early childhood provides optimism for the future success of pediatric norovirus and sapovirus vaccines.
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| 4. |
- 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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| 5. |
- Becker-Dreps, Sylvia, et al.
(författare)
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Etiology of Childhood Diarrhea After Rotavirus Vaccine Introduction A Prospective, Population-based Study in Nicaragua
- 2014
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Ingår i: The Pediatric Infectious Disease Journal. - : Lippincott, Williams andamp; Wilkins. - 0891-3668 .- 1532-0987. ; 33:11, s. 1156-1163
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nicaragua was the first developing nation to implement routine immunization with the pentavalent rotavirus vaccine (RV5). In this RV5-immunized population, understanding infectious etiologies of childhood diarrhea is necessary to direct diarrhea treatment and prevention efforts. Methods: We followed a population-based sample of children less than5 years in Leon, Nicaragua for diarrhea episodes through household visits. Information was obtained on RV5 history and sociodemographics. Stool samples collected during diarrhea episodes and among healthy children underwent laboratory analysis for viral, bacterial and parasitic enteropathogens. Detection frequency and incidence of each enteropathogen was calculated. Results: The 826 children in the cohort experienced 677 diarrhea episodes during 607.5 child-years of exposure time (1.1 episodes per child-year). At least 1 enteropathogen was detected among 61.1% of the 337 diarrheal stools collected. The most common enteropathogens among diarrheal stools were: norovirus (20.4%), sapovirus (16.6%), enteropathogenic Escherichia coli (11.3%), Entamoeba histolytica/dispar (8.3%), Giardia lamblia (8.0%) and enterotoxigenic E. coli (7.7%), with rotavirus detected among 5.3% of diarrheal stools. Enteropathogenic Escherichia coli and enterotoxigenic E. coli were frequently detected among stools from healthy children. Among children with diarrhea, norovirus was more commonly detected among younger children (less than2 years) and G. lamblia was more commonly detected among older children (2-4 years). The mean age of rotavirus detection was 34.6 months. Conclusions: In this Central American community after RV5 introduction, rotavirus was not commonly detected among children with diarrhea. Prevention and appropriate management of norovirus and sapovirus should be considered to further reduce the burden of diarrheal disease.
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| 6. |
- Bowman, Natalie M., et al.
(författare)
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Clinical and Epidemiological Features of Acute Zika Virus Infections in Leon, Nicaragua
- 2021
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Ingår i: American Journal of Tropical Medicine and Hygiene. - : AMER SOC TROP MED & HYGIENE. - 0002-9637 .- 1476-1645. ; 105:4, s. 924-930
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Tidskriftsartikel (refereegranskat)abstract
- The American Zika virus (ZIKV) epidemic has highlighted the need to gain a better understanding of this emerging virus. The goal of this study was to describe the clinical symptoms, laboratory findings, and risk factors for symptomatic ZIKV infection in an area with ongoing transmission of other arboviral infections. We recruited patients at least 2 years of age seeking care at public health centers in Leon, Nicaragua, between January 2016 and August 2017, for fever, maculopapular rash, and/or nonsuppurative conjunctivitis with a duration of less than 1 week. A laboratory diagnosis of ZIKV was established using a combination of molecular and serological tests. Clinical and laboratory findings and potential risk factors were compared between participants with and without acute ZIKV infection. Fifty-eight (26%) of the 225 participants included in the analysis were found to have acute ZIKV infection. Pregnancy and reports of previous arboviral infection were associated with a higher risk of ZIKV infection. Rash, conjunctivitis, sore throat, and lower absolute neutrophil counts were associated with acute ZIKV infection. The clinical characteristics and risk factors identified were consistent with those identified by previous studies; however, we found sore throat to be a feature of ZIKV infection. We also found that neutrophil counts were lower in ZIKV-infected subjects. These clinical symptoms and laboratory datamay help clinicians suspect ZIKV infection during future outbreaks.
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| 7. |
- Bucardo, Filemon, et al.
(författare)
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Pediatric norovirus GII.4 infections in Nicaragua, 1999-2015
- 2017
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Ingår i: Infection, Genetics and Evolution. - : ELSEVIER SCIENCE BV. - 1567-1348 .- 1567-7257. ; 55, s. 305-312
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Investigate clinical and epidemiological factors of pediatric GII.4 norovirus infections in children with acute gastroenteritis (AGE) in Nicaragua between 1999 and 2015. Methods: We retrospectively analyzed laboratory and epidemiologic data from 1,790 children amp;lt;= 7 years with AGE from 6 hospitals in Nicaragua (n = 538), and 3 community clinics (n = 919) and households (n = 333) in Leon, between 1999 and 2015. Moreover, asymptomatic children from community clinics (n = 162) and households (n = 105) were enrolled. Norovirus was detected by real-time PCR and genotyped by sequencing the N-terminal and shell region of the capsid gene. Results: Norovirus was found in 19% (n = 338) and 12% (n = 32) of children with and without AGE, respectively. In total, 20 genotypes including a tentatively new genotype were detected. Among children with AGE, the most common genotypes were GII.4 (53%), GII.14 (7%), GII.3 (6%) and GI.3 (6%). In contrast, only one (1.4%) GII.4 was found in asymptomatic children. The prevalence of GII.4 infections was significantly higher in children between 7 and 12 months of age. The prevalence of GII.4 was lowest in households (38%), followed by community clinics (50%) and hospitals (75%). Several different GII.4 variants were detected and their emergence followed the global temporal trend. Conclusions: Overall our study found the predominance of pediatric GII.4 norovirus infections in Nicaragua mostly occurring in children between 7 and 12 months of age, implicating GII.4 as the main norovirus vaccine target.
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| 8. |
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| 9. |
- Bucardo-Rivera, Filemón
(författare)
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Pediatric rotavirus and norovisrus diarrhea in Nicaragua
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diarrheal diseases are still one of the major health problems in developing countries with rotavirus (RV) being the most important pathogen of severe diarrhea in young children. Norovirus (NoV), a common cause of gastroenteritis is now recognized as an important cause of sporadic diarrhea and hospitalization in children worldwide. Estimates of the disease burden indicate that every year, RV causes approximately 111 million episodes of gastroenteritis, 2 million of hospitalizations and approximately 600,000 deaths in children <5 years of age, with most of the mortality in developing countries. Likewise, recent estimations indicate that NoV cause 900,000 clinical visits among children in industrialized countries, and up to 200,000 deaths of children <5 years of age in developing countries. Thus viral intestinal pathogens are associated with approximately 800.000 deaths in young children every year predominantly in developing countries. In, this thesis the importance, molecular epidemiology and host genetic factors associated with RV and NoV diarrhea in Nicaraguan children have been investigated. Between February and March 2005 a nationwide outbreak of acute gastroenteritis associated with an exaggerated increase in mortality in children <2 years of age was observed in Nicaragua. A total of 108 stool samples from children and adults of 13 towns or major cities of the country were investigated. RV was detected in 72 (67%) of the 108 samples examined. Surprisingly, most (85%) of the RVpositive samples were typed as P[8]G4, a virus not previously observed in Nicaragua. This viral strain was found to have several amino acid mutations that modified antigenic sites and the secondary structure of VP7. The structural changes observed in this virus may have increased virulence and enable this particular virus strain to escape neutralization. Following the nationwide outbreak of rotavirus, a diarrhea surveillance study was conducted in the city of León between March 2005 and February 2006 to investigate the role of NoVs infections in pediatric diarrhea. NoV was detected in 12% (65/542) of the children; of these, 11% (45/409) were in the community and 15% (20/133) among hospitalized children, with most strains (88%) belonging to genogroup (G) II. 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). GII.4 virus infected predominantly young children (<2 years old) and was the most common strain found among hospitalized cases. Molecular epidemiological analysis revealed circulation of NoV genotypes with significant diversity (GII.2, GII.4, GII.17 and GII.18-Nica) in April followed by decreased diversity (GI.4, GII.4 and GII.18-Nica) in May-June and restriction mainly to GII.4 in July. Our findings suggests that NoV is an important etiological agent of acute diarrhea among children of <2 years of age in Nicaragua. Host genetic resistance to NoV has been observed in challenge and outbreak studies in populations from Europe, Asia and USA. This, thesis also include an study to investigate if histoblood group antigens (HBGA) and secretor status (defined by a nonsense G428A mutation in FUT2 gene) are associated with NoV susceptibility in the Nicaraguan population. A subset of 28 NoV-positive patients and 131 healthy population controls were investigated in relation to blood types, Lewis phenotypes (Lea+b-, Lea-b+ and Lea-b-), secretor status and NoV antibody prevalence and titers. Similar to reports from Europe, none of the nonsecretor or Lea+b- individuals was symptomatically infected. Moreover, only 3% of the Nicaraguan population was nonsecretor in contrast to 20% in Europe. The globally dominating GII.4 virus was found to infect all blood groups except AB, nonsecretors and Lea+b- individuals. AB individuals were found to have significantly lower antibody-prevalence than both A and O individuals (P < 0.05) and also significantly lower antibody-titers than blood group A, B and O (P < 0.05) further suggesting that, AB individuals are highly resistant to NoV infection. The Lewis investigation revealed not only that Lewis status (Lea+b-, Lea-b+ and Lea-b-) is not a predictive marker for NoV infection, an observation consistent with a previous report but also that the Lea-b-individuals can be infected with both GI and GII viruses, an observation not previously made. Furthermore, no significant difference in antibody-prevalence was observed between different Lewis phenotypes. Surprisingly, 25% of the Nicaraguan population was Lea-b- as compared with the 5.7% and 10% observed in Sweden and Spain, respectively. This study extended previous knowledge about the role of HBGAs in NoV disease in a population with different genetic background than North America and Europe. The recognition of NoV as an important cause of gastroenteritis is in part due to recent development of sensitive and specific diagnostic methods. In, this thesis I describe a sensitive and specific LUX real-time PCR assay for detection and quantification of NoV. The LUX system uses a fluorophore attached to one primer having a self-quenching hairpin structure, making it cost-effective and specific. The assay simultaneously detected and distinguished between GI and GII NoV by using genogroup specific primers and melting temperature analysis. Quantification limit per real-time PCR reaction was 10 and 20 gene copies for GII and GI, respectively. The assay correctly identified all (n = 11) coded control specimens in a reference panel containing various NoV genogroups and genotypes. Of the clinical specimens from Nicaragua the LUX real-time PCR assay identified NoV in 29/42 samples which correlated with TaqMan assay, but not with a commercial ELISA (24/42) or a conventional PCR (targeting the RdRp) (25/42). One possible reason why the conventional PCR method failed to detect certain NoV-positive specimens might be that viral RNA concentration was too low. Another reason might be that the sites targeted (RdRp) with the conventional PCR primers are less conserved.
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| 10. |
- Bucardo, Filemon, et al.
(författare)
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Vaccine-derived NSP2 segment in rotaviruses from vaccinated children with gastroenteritis in Nicaragua
- 2012
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Ingår i: Infection, Genetics and Evolution. - : Elsevier. - 1567-1348 .- 1567-7257. ; 12:6, s. 1282-1294
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Tidskriftsartikel (refereegranskat)abstract
- Rotavirus (RV) vaccination programs have been established in several countries using the human-attenuated G1P[8] monovalent vaccine Rotarix (TM) (GlaxoSmithKline) and/or the human-bovine reassortant G1, G2, G3, G4, P[8] pentavalent vaccine Rotaleq (TM) (Merck). The efficacy of both vaccines is high (similar to 90%) in developed countries, but can be remarkably lower in developing countries. For example, a vaccine efficacy against severe diarrhea of only 58% was observed in a 2007-2009 Nicaraguan study using RotaTeq. To gain insight into the significant level of vaccine failure in this country, we sequenced the genomes of RVs recovered from vaccinated Nicaraguan children with gastroenteritis. The results revealed that all had genotype specificities typical for human RVs (11G1P[8], 1G3P[8]) and that the sequences and antigenic epitopes of the outer capsid proteins (VP4 and VP7) of these viruses were similar to those reported for RVs isolated elsewhere in the world. As expected, nine of the G1 P[8] viruses and the single G3P[8] virus had genome constellations typical of human G1 P[8] and G3P[8] RVs: G1/3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. However, two of the G1P[8] viruses had atypical constellations, G1-P[8]-I1-R1-C1-M1-A1-N2-T1-E1-H1, due to the presence of a genotype-2 NSP2 (N2) gene. The sequence of the N2 NSP2 gene was identical to the bovine N2 NSP2 gene of RotaTeq, indicating that the two atypical viruses originated via reassortment of human G1P[8] RVs with RotaTeq viruses. Together, our data suggest that the high level of vaccine failure in Nicaraguan is probably not due to antigenic drift of commonly circulating virus strains nor the emergence of new antigenetically distinct virus strains. Furthermore, our data suggest that the widespread use of the RotaTeq vaccine has led to the introduction of vaccine genes into circulating human RVs.
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