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ABSTRACTChildren have elevated fever risk 1 to 2 weeks after the first dose of a measles-containing vaccine (MCV), which is likely affected by genetic, immunologic, and clinical factors. Fever after MCV is associated with febrile seizures, though may also be associated with higher measles antibody titers. This exploratory study investigated genetic and immunologic associations with a fever after MCV. Concurrent with a randomized Phase 3 clinical trial of 12–15-month-olds who received their first measles-mumps-rubella (MMR) vaccine in which parents recorded post-vaccination temperatures daily, we consented a subset to collect additional blood and performed human leukocyte antigens (HLA) typing. Association between fever 5–12 days after MMR (“MMR-associated”) and HLA type was assessed using logistic regression. We compared 42-day post-vaccination geometric mean titers (GMT) to measles between children who did and did not have fever using a t-test. We enrolled 86 children and performed HLA typing on 82; 13 (15.1%) had MMR-associated fever. Logistic regressions identified associations between MMR-associated fever and HLA Class I loci A-29:02 (P= .036), B-57:01 (P= .018), C-06:02 (P= .006), C-14:02 (P= .022), and Class II loci DRB1-15 (P= .045). However, Bonferroni's adjustment for multiple comparisons suggests that these associations could have been due to chance. Ninety-eight percent of children had protective antibody titers to measles; however, GMT was higher among those with fever compared with children without fever (P= .006). Fever after the measles vaccine correlated with genetic factors and higher immune response. This study suggests a possible genetic susceptibility to MMR-associated fever.

ABSTRACTWe evaluated whether parental clinical conditions were associated with fever after a first dose of measles-containing vaccine (MCV) in the child in a cohort study including 244,125 children born in Kaiser Permanente Northern California between 2009 and 2016 who received MCV between ages 1 and 2 years. Each child was linked with his/her mother and father when possible. Parental clinical conditions present before and after their child’s birth were identified. We defined fever in the children as clinic and emergency department visits with a fever code 7–10 days after a first dose of MCV (“MCV-associated fever”). We evaluated parental clinical conditions associated with MCV-associated fever using multivariate logistic regression analyses. After adjusting for multiple factors, including healthcare utilization, maternal fever [odds ratio (OR) = 1.19, 95% confidence interval (CI) 1.06–1.32], fever after MCV (OR = 5.90, 95% CI 1.35–25.78), respiratory infections (OR = 1.20, 95% CI 1.10–1.31), migraine (OR = 1.14, 95% CI 1.05–1.24), syncope (OR 1.14, 95% CI 1.01–1.27), and essential thrombocythemia (OR = 1.93, 95% CI 1.15–3.25) were significantly associated with MCV-associated fever. Paternal respiratory infections (OR = 1.15, 95% CI 1.05–1.27), fever associated with respiratory infections (OR = 1.47, 95% CI 1.23–1.76), and vitiligo (OR = 1.63, 95% CI 1.06–2.53) were significantly associated with MCV-associated fever. Parental clinical conditions, specifically fever alone and fever associated with respiratory infection, are associated with fever in their child 7–10 days after MCV.

Pathogenic caliciviruses of the genus Vesiviruscirculate in oceanic ecosystems and spread to and among terrestrial mammals. Isolation of Vesivirusfrom natural and laboratory infections in humans led to this investigation of Vesivirusseroprevalence and viremia. Sera from four groups were tested for antibodies to Vesivirusas follows: blood donors whose units were cleared for donation, blood donors whose units were not accepted for donation solely because of elevated blood liver alanine aminotransferase (ALT) concentrations, patients with clinical hepatitis of unknown but suspected infectious cause, and patients with clinical hepatitis of unknown cause but associated with blood transfusion or dialysis. Additionally, sera were tested for Vesivirusgenome by three methods: dot‐blot and two reverse transcription‐polymerase chain reaction (RT‐PCR) methods. The calculated seroprevalence against Vesivirusvirions within these groups (N = 765) was 12%, 21%, 29%, and 47%, respectively (P< 0.001 for group differences). Additionally, 11 (9.8%) of 112 sera tested yielded RT‐PCR amplicons that by nucleotide sequence were distinct from each other and related to known Vesivirus. These data indicate that some blood donors in the population tested have serologic evidence of previous Vesivirusinfection and some also have Vesivirusviremia. These results justify further investigation of an association between Vesivirusinfection and illness in humans. J. Med. Virol.78:693–701, 2006. © 2006 Wiley‐Liss, Inc.

Rotavirus is the main cause of acute diarrhea in infants and young children worldwide. In Paraguay, acute diarrhea ranks fourth among the causes of mortality in children under 4 years of age. Rotavirus was detected in 93 out of 410 patients admitted to three main hospitals in Asunción, Paraguay from August 1998 to August 2000. Samples from 64 patients were analyzed by RT‐PCR for G and P typing. G4P[8] (46.9%; 30/64) was the most common strain detected, followed by G9P[8] (17.2%; 11/64) and G1P[8] (10,9%; 7/64). Since G4 was predominant during the epidemiological peaks of 1998 and 1999, four samples were sequenced and all grouped into sublineage Ic. This sublineage was reported for the first time in 1998 in Argentina, southern border of Paraguay, and it was shown to be responsible for the increased prevalence of G4 during the epidemiological season of 1998 in that country. In addition, Paraguayan G1 strains grouped in different lineages (I and II). However, G9 was predominant during the rotavirus epidemiological peak of 2000, and phylogenetic analysis of five samples grouped into a common emergent/reemergent lineage that circulates worldwide. Since vaccination could reduce the severity and the number of cases of rotavirus disease, this study suggests that a vaccine containing recently isolated variants of the most prevalent types (G1–G4) together with the emerging G9 type, might be sufficient to elicit a protective immune response against the rotavirus types circulating currently in Paraguay. J. Med. Virol.77:579–586, 2005. © 2005 Wiley‐Liss, inc.

ABSTRACTRotavirus is the most-common cause of severe diarrhea in young children. Complete rotavirus characterization includes determination of the antigenic type of the two outer capsid proteins, VP7 and VP4, designated G and P types, respectively. During a nationwide rotavirus surveillance study, genotype G4 frequency increased during the second year. To evaluate further the mechanism of emergence and the relationship among G4 strains, the genetic diversity of VP7 capsid protein in these samples was studied in detail. Overall nucleotide sequence divergence ranged from less than 0.1 to 19.5%, a higher divergence than that observed for other rotavirus G types (0.1 to 9%). Sequences were classified into two major lineages (designated I and II) based on their nucleotide distances. The most heterogeneous lineage was further subdivided into four sublineages (designated Ia to Id). Most Argentine sequences were of sublineages Ib and Ic, which were confirmed to be independent sequence clusters by parsimony analysis. This study describes different lineages and sublineages within G4 strains and shows that Argentine strains are distantly related to reference strain ST3. The appearance of at least two G4 genotype (sub)lineages during 1998 demonstrates that the increased frequency of these strains was due to the synchronized emergence of different groups of strains.

ABSTRACTBecause rotavirus diarrhea can be reduced through vaccination and because current vaccine candidates provide protection against only the most common G antigenic types (G1 to G4), detection of uncommon G types is one of the main goals of rotavirus surveillance. After a 2-year nationwide rotavirus surveillance study in Argentina concluded, surveillance was continued and an increase of G9 prevalence in several Argentine cities was detected. During this period G9 strains predominated in the south, and a gradient of decreasing G9 prevalence was observed from south to north (41 to 0%). Sequence analysis of gene 9, encoding the G antigen, showed that Argentine strains cluster with most G9 isolates from other countries, showing less than 2% nucleotide divergence among them, but are distinctive from them in that they present some unique amino acid changes. Our results agree with reports of increased G9 prevalence in other parts of the world, suggesting the need to incorporate G9 into candidate rotavirus vaccines.

Group A rotaviruses are the major cause of severe gastroenteritis in young children worldwide. Because rotavirus vaccination appeared imminent, a nationwide surveillance program was organized between October 1996 and October 1998 in the largest Argentine cities. Surveillance for disease burden, rotavirus detection, and rotavirus typing was undertaken at nine locations. Results showed rotavirus to be associated with 42% of diarrhea admissions. Although the prevalent G types changed from year to year, common G types were found in 96% of the cases and were usually associated with common P types. Uncommon G types, G9 and G5, were found at low prevalence and uncommon G/P combinations occurred at almost every study site. These data suggest that a rotavirus vaccine could substantially decrease the rotavirus disease burden in Argentina, but that introduction of a vaccine should be accompanied by a concurrent surveillance system. J. Med. Virol. 65:190–198, 2001. © 2001 Wiley‐Liss, Inc.