| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- Bucardo, Filemon, et al.
(författare)
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Susceptibility of Children to Sapovirus Infections, Nicaragua, 2005–2006
- 2012
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Ingår i: Emerging Infectious Diseases. - Atlanta, GA, USA : U.S. Department of Health and Human Services * Centers for Disease Control and Prevention. - 1080-6040 .- 1080-6059. ; 18:11, s. 1875-1878
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Tidskriftsartikel (refereegranskat)abstract
- We describe the genetic diversity of sapovirus (SaV) in children in Nicaragua and investigate the role of host genetic factors and susceptibility to SaV infections. Our results indicate that neither ABO blood group, Lewis phenotype, nor secretor status affects susceptibility to SaV infection in Nicaragua.
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| 6. |
- Vielot, Nadja Alexandra, et al.
(författare)
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Association between breastfeeding, host genetic factors, and calicivirus gastroenteritis in a Nicaraguan birth cohort
- 2022
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- Background Norovirus and sapovirus are important causes of childhood acute gastroenteritis (AGE). Breastfeeding prevents AGE generally; however, it is unknown if breastfeeding prevents AGE caused specifically by norovirus and sapovirus. Methods We investigated the association between breastfeeding and norovirus or sapovirus AGE episodes in a birth cohort. Weekly data on breastfeeding and AGE episodes were captured during the first year of life. Stools were collected from children with AGE and tested by RT-qPCR for norovirus and sapovirus. Time-dependent Cox models estimated associations between weekly breastfeeding and time to first norovirus or sapovirus AGE. Findings From June 2017 to July 2018, 444 newborns were enrolled in the study. In the first year of life, 69 and 34 children experienced a norovirus and a sapovirus episode, respectively. Exclusive breastfeeding lasted a median of 2 weeks, and any breastfeeding lasted a median of 43 weeks. Breastfeeding in the last week did not prevent norovirus (HR: 1.09, 95% CI: 0.62, 1.92) or sapovirus (HR: 1.00, 95% CI: 0.82, 1.21) AGE in a given week, adjusting for household sanitation, consumption of high-risk foods, and mothers and childs histo-blood group phenotypes. Maternal secretor-positive phenotype was protective against norovirus AGE, whereas childs secretor-positive phenotype was a risk factor for norovirus AGE. Interpretation Exclusive breastfeeding in this population was short-lived, and no conclusions could be drawn about its potential to prevent norovirus or sapovirus AGE. Non-exclusive breastfeeding did not prevent norovirus or sapovirus AGE in the first year of life. However, maternal secretor-positive phenotype was associated with a reduced hazard of norovirus AGE.
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| 7. |
- Bucardo, F., et al.
(författare)
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Seroprevalence in Household Raised Pigs Indicate High Exposure to GII Noroviruses in Rural Nicaragua
- 2016
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Ingår i: Zoonoses and Public Health. - : WILEY-BLACKWELL. - 1863-1959 .- 1863-2378. ; 63:8, s. 600-607
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Tidskriftsartikel (refereegranskat)abstract
- Information about porcine norovirus (PoNoV), genetically similar to human NoV (HuNoV), is limited from rural areas where household-raised pigs are heavily exposed to faecal material which could facilitate transmission. Histoblood group antigens (HBGAs) are known susceptibility factors to NoV in humans and in a germfree piglet model but their role in susceptibility in the porcine population remains unknown. This study reports: (i) the seroprevalence and antibody titres to human norovirus (NoV) VLPs in household raised pigs; (ii) the distribution of HBGAs in relation to NoV IgG antibody titres and further characterization by blocking of GII. 4 VLP binding to pig gastric mucins (PGM). The majority of pigs were seropositive to all three VLPs tested (58-70%) with seropositivity and cross-reactivity increasing significantly with age. However, pig sera could not block the binding of NoV GII. 4 VLPs (Dijon) to PGM suggesting no previous infection with this genotype. The majority of the pigs were H-positive (84%), a susceptibility factor for human infections. IgG antibody titres were however higher in H-negative (GMT = 247) as compared with H-positive (GMT = 57) pigs, but after age stratification, this difference in antibody titres was only observed in pigs = 1 month of age. In conclusion, serological data show that the porcine population of Nicaragua is highly exposed to NoV infections, and the association to HBGAs warrants further investigation.
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| 8. |
- Bucardo, Filemon, et al.
(författare)
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Predominance of Norovirus and Sapovirus in Nicaragua after Implementation of Universal Rotavirus Vaccination
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 9:5, s. e0098201-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite significant reduction of rotavirus (RV) infections following implementation of RotaTeq vaccination in Nicaragua, a large burden of patients with diarrhea persists. Methods: We conducted a community-and hospital-based study of the burden of RV, norovirus (NV) and sapovirus (SV) infections as cause of sporadic acute gastroenteritis (GE) among 330 children less than= 5 years of age between September 2009 and October 2010 in two major cities of Nicaragua with a RotaTeq coverage rate of 95%. Results: We found that NV, SV and RV infections altogether accounted for 45% of cases of GE. Notably, NV was found in 24% (79/330) of the children, followed by SV (17%, 57/330) and RV (8%, 25/330). The detection rate in the hospital setting was 27%, 15% and 14% for NV, SV and RV respectively, whereas in the community setting the detection rate of RV was less than 1%. Among each of the investigated viruses one particular genogroup or genotype was dominant; GII.4 (82%) for NV, GI (46%) for SV and G1P[8] (64%) in RV. These variants were also found in higher proportions in the hospital setting compared to the community setting. The GII.4.2006 Minerva strain circulating globally since 2006 was the most common among genotyped NV in this study, with the GII.4-2010 New Orleans emerging in 2010. Conclusions: This study shows that NV has become the leading viral cause of gastroenteritis at hospital and community settings in Nicaragua after implementation of RV vaccination.
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| 9. |
- Bucardo, F., et al.
(författare)
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Large increase of rotavirus diarrhoea in the hospital setting associated with emergence of G12 genotype in a highly vaccinated population in Nicaragua.
- 2015
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Ingår i: Clinical Microbiology and Infection. - : Elsevier. - 1198-743X .- 1469-0691. ; 21:6, s. 603.e1-603.e7
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Tidskriftsartikel (refereegranskat)abstract
- Rotaviruses (RVs) are a major cause of severe diarrhoea in young children. Nicaragua introduced routine immunization with the pentavalent RV vaccine (RV5) in 2006, which greatly reduced the incidence of diarrhoea. A remaining concern has been the possible emergence of new RV strains to which the vaccination has less effect. In this study, 837 children with diarrhoea in hospital settings were investigated for RV between May 2011 and July 2013. RVs were subsequently typed by multiplex PCR and/or sequencing. Fecal anti-RV IgA titres for a subset of RV-infected (n = 137) and noninfected children (n = 52) were determined with an in-house enzyme-linked immunosorbent assay. The RV detection rate was 8% in 2011, followed by a sharp increase to 29% in 2012 and 19% in 2013. This was associated with emergence and predominance of genotype G12 RV, from 0% in 2011 to 66% in 2012 and 82% in 2013, infecting children from 1 month to 10 years of age. Two sequenced G12 strains showed a Wa-like genome with genotype G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1, similar to the globally emerging G12 strains. Fecal anti-RV IgA analysis showed that most G12-infected and noninfected children had been in contact with either vaccine or wild RV strains, but such antibodies did not prevent symptomatic G12 infection. A marked increase of RV was evident in the hospital setting associated with a nationwide emergence and predominance of RV G12 genotype in a population with high RV5 vaccine coverage.
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| 10. |
- Bucardo, Filemon, et al.
(författare)
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Histo-blood group antigens and rotavirus vaccine shedding in Nicaraguan infants
- 2019
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- ABO, Lewis and secretor histo-blood group antigens (HBGA) are susceptibility factors for rotavirus in a P-genotype dependent manner and can influence IgA seroconversion rates following rotavirus vaccination. To investigate the association between HBGA phenotypes and rotavirus vaccine shedding fecal samples (n = 304) from a total of 141 infants vaccinated with Rotarix (n = 71) and RotaTeq (n = 70) were prospectively sampled in three time frames (= 3, 4-7 and = 8 days) after first vaccination dose. Rotavirus was detected with qPCR and genotypes determined by G/P multiplex PCR and/or sequencing. HBGAs were determined by hemagglutination and saliva based ELISA. Low shedding rates were observed, with slightly more children vaccinated with RotaTeq (19%) than Rotarix (11%) shedding rotavirus at = 4 days post vaccination (DPV). At = 4 DPV no infant of Lewis A (n = 6) or nonsecretor (n = 9) phenotype in the Rotarix cohort shed rotavirus; the same observation was made for Lewis A infants (n = 7) in the RotaTeq cohort. Putative in-vivo gene reassortment among RotaTeq strains occurred, yielding mainly G1P[8] strains. The bovine derived P[5] genotype included in RotaTeq was able to replicate and be shed at long time frames (amp;gt;13 DPV). The results of this study are consistent with that HBGA phenotype influences vaccine strain shedding as similarly observed for natural infections. Due to the low overall shedding rates observed, additional studies are however warranted.
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