Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-30 (of 47 Records) |
Query Trace: Mijatovic-Rustempasic S[original query] |
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Rotavirus vaccine effectiveness against severe acute gastroenteritis: 2009-2022
Diallo AO , Wikswo ME , Sulemana I , Sahni LC , Boom JA , Ramani S , Selvarangan R , Moffatt ME , Harrison CJ , Halasa N , Chappell J , Stewart L , Staat MA , Schlaudecker E , Quigley C , Klein EJ , Englund JA , Zerr DM , Weinberg GA , Szilagyi PG , Albertin C , Johnston SH , Williams JV , Michaels MG , Hickey RW , Curns AT , Honeywood M , Mijatovic-Rustempasic S , Esona MD , Bowen MD , Parashar UD , Gautam R , Mirza SA , Tate JE . Pediatrics 2024 BACKGROUND: Rotavirus was the leading cause of acute gastroenteritis among US children until vaccine introduction in 2006, after which, substantial declines in severe rotavirus disease occurred. We evaluated rotavirus vaccine effectiveness (VE) over 13 years (2009-2022). METHODS: We analyzed data from the New Vaccine Surveillance Network using a test-negative case-control design to estimate rotavirus VE against laboratory-confirmed rotavirus infections among children seeking care for acute gastroenteritis (≥3 diarrhea or ≥1 vomiting episodes within 24 hours) in the emergency department (ED) or hospital. Case-patients and control-patients were children whose stool specimens tested rotavirus positive or negative, respectively, by enzyme immunoassay or polymerase chain reaction assays. VE was calculated as (1-adjusted odds ratio)×100%. Adjusted odds ratios were calculated by multivariable unconditional logistic regression. RESULTS: Among 16 188 enrolled children age 8 to 59 months, 1720 (11%) tested positive for rotavirus. Case-patients were less often vaccinated against rotavirus than control-patients (62% versus 88%). VE for receiving ≥1 dose against rotavirus-associated ED visits or hospitalization was 78% (95% confidence interval [CI] 75%-80%). Stratifying by a modified Vesikari Severity Score, VE was 59% (95% CI 49%-67%), 80% (95% CI 77%-83%), and 94% (95% CI 90%-97%) against mild, moderately severe, and very severe disease, respectively. Rotavirus vaccines conferred protection against common circulating genotypes (G1P[8], G2P[4], G3P[8], G9P[8], and G12[P8]). VE was higher in children <3 years (73% to 88%); protection decreased as age increased. CONCLUSIONS: Rotavirus vaccines remain highly effective in preventing ED visits and hospitalizations in US children. |
Correlates of rotavirus vaccine shedding and seroconversion in a U.S. cohort of healthy infants
Burke RM , Payne DC , McNeal M , Conrey SC , Burrell AR , Mattison CP , Casey-Moore MC , Mijatovic-Rustempasic S , Gautam R , Esona MD , Thorman AW , Bowen MD , Parashar UD , Tate JE , Morrow AL , Staat MA . J Infect Dis 2024 BACKGROUND: Rotavirus is a leading cause of severe pediatric gastroenteritis; two highly effective vaccines are used in the US. We aimed to identify correlates of immune response to rotavirus vaccination in a US cohort. METHODS: PREVAIL is a birth cohort of 245 mother-child pairs enrolled 2017-2018 and followed for 2 years. Infant stool samples and symptom information were collected weekly. Shedding was defined as RT-PCR detection of rotavirus vaccine virus in stools collected 4-28 days after dose one. Seroconversion was defined as a threefold rise in IgA between the six-week and six-month blood draws. Correlates were analyzed using generalized estimating equations and logistic regression. RESULTS: Pre-vaccination IgG (OR=0.84, 95% CI [0.75-0.94] per 100-unit increase) was negatively associated with shedding. Shedding was also less likely among infants with a single-nucleotide polymorphism inactivating FUT2 antigen secretion ("non-secretors") with non-secretor mothers, versus all other combinations (OR 0.37 [0.16-0.83]). Of 141 infants with data, 105 (74%) seroconverted; 78 (77%) had shed vaccine virus following dose one. Pre-vaccination IgG and secretor status were significantly associated with seroconversion. Neither shedding nor seroconversion significantly differed by vaccine product. DISCUSSION: In this US cohort, pre-vaccination IgG and maternal and infant secretor status were associated with rotavirus vaccine response. |
Coding-complete genome sequences of rotavirus A reference strains EDIM, Ph158, and CC425
Casey-Moore MC , Katz E , Mijatovic-Rustempasic S , Jaimes J , Gautam R , Bowen MD . Microbiol Resour Announc 2023 12 (11) e0063023 This study reports the coding-complete genome sequences of three rotavirus A (RVA) reference strains previously adapted in tissue culture: RVA/Mouse-tc/USA/EDIM/XXXX/G16P[16] with a G16-P[16]-I7-R7-C7-M8-A7-N7-T10-E7-H9 genotype constellation, RVA/Human-tc/USA/Ph158/1998/G9P[6] with a G9-P[6]-I2-R2-C2-M2-A2-N2-T2-E2-H2 genotype constellation, and RVA/Human-tc/USA/CC425/1998/G3P[9] with a G3-P[9]-I2-R2-C2-M2-A3-N2-T1-E2-H3 genotype constellation. |
Non-secretor phenotype is associated with less risk of rotavirus-associated acute gastroenteritis in a vaccinated Nicaraguan birth cohort
Reyes Y , St Jean DT , Bowman NM , González F , Mijatovic-Rustempasic S , Becker-Dreps S , Svensson L , Nordgren J , Bucardo F , Vielot NA . J Infect Dis 2023 228 (12) 1739-1747 BACKGROUND: Histo-blood group antigens (HBGAs) have been associated with rotavirus vaccine take; but the effect of these HBGAs on rotavirus incidence and risk remains poorly explored in vaccinated populations. METHODS: Rotavirus-associated acute gastroenteritis (AGE) was assessed in 444 Nicaraguan children followed from birth until 3 years of age. AGE episodes were tested for rotavirus by RT-qPCR and saliva or blood were used to determine the HBGAs phenotypes. Cox proportional hazards models were used to estimate the relative hazard of rotavirus AGE by HBGA phenotypes. RESULTS: Rotavirus was detected in 109 (7%) stool samples from 1,689 AGE episodes over 36 months of observation between June 2017 and July 2021. Forty-six samples were successfully genotyped. Of these, 15 (35%) were rotavirus vaccine strain G1P[8], followed by G8P[8] or G8P[nt] (11, 24%) and equine-like G3P[8] (11, 24%). The overall incidence of rotavirus-associated AGE was 9.2/100 child-years, and was significantly higher in secretor compared to non-secretor children (9.8 vs. 3.5/100 child-years, P = 0.002). CONCLUSION: The non-secretor phenotype was associated with decreased risk of clinical rotavirus vaccine failure in a vaccinated Nicaraguan birth cohort. These results show the importance of secretor status on rotavirus risk, even in vaccinated children. |
Coding-complete genome sequences of G6P[14] rotavirus strain detected in a human stool specimen within the United States
Casey-Moore MC , Mijatovic-Rustempasic S , Jaimes J , Perkins C , Riley AM , Cortese MM , Gautam R , Bowen MD . Microbiol Resour Announc 2023 12 (6) e0000823 In this study, we report the detection of a G6P[14] rotavirus strain from a human stool sample within the United States. The full genotype constellation of the G6P[14] strain was identified as G6-P[14]-I2-R2-C2-M2-A11-N2-T6-E2-H3. |
Genotypic investigation of a rotavirus cluster at a quaternary-care pediatric hospital.
Kitt EM , Yoon HW , Comar CE , Smith KP , Harris RM , Esona MD , Gautam R , Mijatovic-Rustempasic S , Hopkins AL , Jaimes J , Handy LK . Infect Control Hosp Epidemiol 2023 44 (10) 1-3 Rotavirus (RV) was a common healthcare-associated infection prior to the introduction of the RV vaccine. Following widespread RV vaccination, healthcare-associated rotavirus cases are rare. We describe an investigation of a cluster of rotavirus infections in a pediatric hospital in which an uncommon genotype not typically circulating in the United States was detected. |
Rotavirus Strain Trends in United States, 2009-2016: Results from the National Rotavirus Strain Surveillance System (NRSSS).
Mijatovic-Rustempasic S , Jaimes J , Perkins C , Ward ML , Esona MD , Gautam R , Lewis J , Sturgeon M , Panjwani J , Bloom GA , Miller S , Reisdorf E , Riley AM , Pence MA , Dunn J , Selvarangan R , Jerris RC , DeGroat D , Parashar UD , Cortese MM , Bowen MD . Viruses 2022 14 (8) Before the introduction of vaccines, group A rotaviruses (RVA) were the leading cause of acute gastroenteritis in children worldwide. The National Rotavirus Strain Surveillance System (NRSSS) was established in 1996 by the Centers for Disease Control and Prevention (CDC) to perform passive RVA surveillance in the USA. We report the distribution of RVA genotypes collected through NRSSS during the 2009-2016 RVA seasons and retrospectively examine the genotypes detected through the NRSSS since 1996. During the 2009-2016 RVA seasons, 2134 RVA-positive fecal specimens were sent to the CDC for analysis of the VP7 and VP4 genes by RT-PCR genotyping assays and sequencing. During 2009-2011, RVA genotype G3P[8] dominated, while G12P[8] was the dominant genotype during 2012-2016. Vaccine strains were detected in 1.7% of specimens and uncommon/unusual strains, including equine-like G3P[8] strains, were found in 1.9%. Phylogenetic analyses showed limited VP7 and VP4 sequence variation within the common genotypes with 1-3 alleles/lineages identified per genotype. A review of 20 years of NRSSS surveillance showed two changes in genotype dominance, from G1P[8] to G3P[8] and then G3P[8] to G12P[8]. A better understanding of the long-term effects of vaccine use on epidemiological and evolutionary dynamics of circulating RVA strains requires continued surveillance. |
Cross-sectional study and genotyping of rotavirus-A infections in ruminants in Kuwait.
Abdou NMI , Majeed QAH , Saad AA , Mijatovic-Rustempasic S , Bowen MD , Samy A . BMC Vet Res 2021 17 (1) 245 BACKGROUND: Group A rotaviruses (RVA) are zoonotic pathogens responsible for acute enteritis in human and neonatal ruminants. This research aimed to determine the prevalence of RVA in ruminants (cattle, sheep, and goats) and investigate the circulating RVA genotypes in these animals in Kuwait. We conducted a cross-sectional study to detect RVA in ruminants, using an immunochromatography test (IC), direct sandwich ELISA test, and real-time RT-PCR (RT-qPCR) assay using fecal samples. RESULTS: A total of 400 cattle, 334 sheep, and 222 goats were examined. The prevalence of RVA was 5.3, 1.2, and 2.3%, respectively, using IC. The ELISA test detected RVA from 4.3% of cattle, 0.9% of sheep, and 1.8% of goats. There was a significant association between the occurrence of diarrhea and the presence of RVA in bovine fecal samples (p-value = 0.0022), while no statistical association between diarrhea and the presence of RVA in fecal samples of sheep and goats was observed (p-value = 0.7250; p-value = 0.4499, respectively). Twenty-three of the IC-positive samples (17 from cattle, two from sheep, and four from goats) were tested using a RT-qPCR RVA detection assay targeting the NSP3 gene. The results showed that 21 of 23 IC-positive samples tested positive by RT-qPCR. Detection of RVA genotypes revealed that G10P[11] was the predominant strain in cattle (58.8%), followed by G8P[1] (11.7%). One sheep sample was genotyped as G8P[1]. In addition, G6P[1] and G6P[14] were detected in goat samples. CONCLUSION: The present study revealed that the IC was more sensitive in detecting RVA antigen in fecal samples than the ELISA test. A higher occurrence of RVA infection was observed in cattle than in sheep and goats. This study suggests that RVA might be a risk factor of diarrhea in bovine calves less than 2 weeks old. This research also demonstrates the circulation of RVA in sheep and goat populations in Kuwait. Finally, the G10P[11] RVA genotype was the most prevalent genotype identified from cattle samples. |
Rotavirus vaccine effectiveness and impact in Uzbekistan, the first country to introduce in central Asia.
Eraliev U , Latipov R , Tursunova D , Wasley A , Daniels D , Ismoilov U , Akramova M , Sultanova M , Yuldashova D , Barakaev B , Mutalova V , Tuychiev L , Musabaev E , Sharapov S , Pleshkov B , Videbaek D , Huseynov S , Safaeva K , Mijatovic-Rustempasic S , Bowen MD , Parashar UD , Cortese MM . Hum Vaccin Immunother 2020 17 (2) 1-7 Uzbekistan, the most populous country in central Asia, was the first in the region to introduce rotavirus vaccine into its national immunization program. Rotarix (GlaxoSmithKline Biologicals, RV1) was introduced in June 2014, with doses recommended at age 2 and 3 months. To evaluate vaccine impact, active surveillance for rotavirus diarrhea was reestablished in 2014 at 2 hospitals in Tashkent and Bukhara which had also performed surveillance during the pre-vaccine period 2005-2009. Children aged <5 y admitted with acute diarrhea had stool specimens collected and tested for rotavirus by enzyme immunoassay. Proportions testing rotavirus-positive in post-vaccine years were compared with the pre-vaccine period. Vaccine records were obtained and effectiveness of 2 RV1 doses vs 0 doses was estimated using rotavirus-case and test-negative design among children enrolled from Bukhara city. In 2015 and 2016, 8%-15% of infants and 10%-16% of children aged<5 y hospitalized with acute diarrhea at the sites tested rotavirus-positive, compared with 26% of infants and 27% of children aged<5 y in pre-vaccine period (reductions in proportion positive of 42%-68%, p <.001). Vaccine effectiveness of 2 RV1 doses vs 0 doses in protecting against hospitalization for rotavirus disease among those aged ≥6 months was 51% (95% CI 2-75) and is based on cases predominantly of genotype G2P[4]. Vaccine effectiveness point estimates tended to be higher against cases with higher illness severity (e.g., clinical severity based on modified Vesikari score ≥11). Our data demonstrate that the monovalent rotavirus vaccine is effective in reducing the likelihood of hospitalization for rotavirus disease in young children in Uzbekistan. |
Association of rotavirus vaccination with inpatient and emergency department visits among children seeking care for acute gastroenteritis, 2010-2016
Payne DC , Englund JA , Weinberg GA , Halasa NB , Boom JA , Staat MA , Selvarangan R , Azimi PH , Klein EJ , Szilagyi PG , Chappell J , Sahni LC , McNeal M , Harrison CJ , Moffatt ME , Johnston SH , Mijatovic-Rustempasic S , Esona MD , Tate JE , Curns AT , Wikswo ME , Sulemana I , Bowen MD , Parashar UD . JAMA Netw Open 2019 2 (9) e1912242 Importance: Rotavirus vaccines have been recommended for universal US infant immunization for more than 10 years, and understanding their effectiveness is key to the continued success of the US rotavirus vaccine immunization program. Objective: To assess the association of RotaTeq (RV5) and Rotarix (RV1) with inpatient and emergency department (ED) visits for rotavirus infection. Design, Setting, and Participants: This case-control vaccine effectiveness study was performed at inpatient and ED clinical settings in 7 US pediatric medical institutions from November 1, 2009, through June 30, 2016. Children younger than 5 years seeking medical care for acute gastroenteritis were enrolled. Clinical and epidemiologic data, vaccination verification, and results of stool sample tests for laboratory-confirmed rotavirus were collected. Data were analyzed from November 1, 2009, through June 30, 2016. Main Outcomes and Measures: Rotavirus vaccine effectiveness for preventing rotavirus-associated inpatient and ED visits over time for each licensed vaccine, stratified by clinical severity and age. Results: Among the 10 813 children included (5927 boys [54.8%] and 4886 girls [45.2%]; median [range] age, 21 [8-59] months), RV5 and RV1 analyses found that compared with controls, rotavirus-positive cases were more often white (RV5, 535 [62.2%] vs 3310 [57.7%]; RV1, 163 [43.1%] vs 864 [35.1%]), privately insured (RV5, 620 [72.1%] vs 4388 [76.5%]; RV1, 305 [80.7%] vs 2140 [87.0%]), and older (median [range] age for RV5, 26 [8-59] months vs 21 [8-59] months; median [range] age for RV1, 22 [8-59] months vs 19 [8-59] months) but did not differ by sex. Among 1193 rotavirus-positive cases and 9620 rotavirus-negative controls, at least 1 dose of any rotavirus vaccine was 82% (95% CI, 77%-86%) protective against rotavirus-associated inpatient visits and 75% (95% CI, 71%-79%) protective against rotavirus-associated ED visits. No statistically significant difference during this 7-year period was observed for either rotavirus vaccine. Vaccine effectiveness against inpatient and ED visits was 81% (95% CI, 78%-84%) for RV5 (3 doses) and 78% (95% CI, 72%-82%) for RV1 (2 doses) among the study population. A mixed course of both vaccines provided 86% (95% CI, 74%-93%) protection. Rotavirus patients who were not vaccinated had severe infections 4 times more often than those who were vaccinated (74 of 426 [17.4%] vs 28 of 605 [4.6%]; P < .001), and any dose of rotavirus vaccine was 65% (95% CI, 56%-73%) effective against mild infections, 81% (95% CI, 76%-84%) against moderate infections, and 91% (95% CI, 85%-95%) against severe infections. Conclusions and Relevance: Evidence from this large postlicensure study of rotavirus vaccine performance in the United States from 2010 to 2016 suggests that RV5 and RV1 rotavirus vaccines continue to perform well, particularly in preventing inpatient visits and severe infections and among younger children. |
Multiple introductions and antigenic mismatch with vaccines may contribute to increased predominance of G12P[8] rotaviruses in the United States.
Ogden KM , Tan Y , Akopov A , Stewart LS , McHenry R , Fonnesbeck CJ , Piya B , Carter MH , Fedorova NB , Halpin RA , Shilts MH , Edwards KM , Payne DC , Esona MD , Mijatovic-Rustempasic S , Chappell JD , Patton JT , Halasa NB , Das SR . J Virol 2018 93 (1) Rotavirus is the leading global cause of diarrheal mortality for unvaccinated children under five years of age. The outer capsid of rotavirus virions consists of VP7 and VP4 proteins, which determine viral G and P types, respectively, and are primary targets of neutralizing antibodies. Successful vaccination depends upon generating broadly protective immune responses following exposure to rotaviruses presenting a limited number of G and P type antigens. Vaccine introduction resulted in decreased rotavirus disease burden but also coincided with emergence of uncommon G and P genotypes, including G12. To gain insight into the recent predominance of G12P[8] rotaviruses in the U.S., we evaluated 142 complete rotavirus genome sequences and metadata from 151 clinical specimens collected in Nashville, TN from 2011-2013 through the New Vaccine Surveillance Network. Circulating G12P[8] strains were found to share many segments with other locally circulating strains but to have distinct constellations. Phylogenetic analyses of G12 sequences and their geographic sources provided evidence for multiple separate introductions of G12 segments into Nashville, TN. Antigenic epitopes of VP7 proteins of G12P[8] strains circulating in Nashville, TN differ markedly from those of vaccine strains. Fully vaccinated children were found to be infected with G12P[8] strains more frequently than with other rotavirus genotypes. Multiple introductions and significant antigenic mismatch may in part explain the recent predominance of G12P[8] strains in the U.S. and emphasize need for continued monitoring of rotavirus vaccine efficacy against emerging rotavirus genotypes.IMPORTANCERotavirus is an important cause of childhood diarrheal disease worldwide. Two immunodominant proteins of rotavirus, VP7 and VP4, determine G and P genotypes, respectively. Recently, G12P[8] rotaviruses have become increasingly predominant. By analyzing rotavirus genome sequences from stool specimens obtained in Nashville, TN from 2011-2013 and globally circulating rotaviruses, we found evidence of multiple introductions of G12 genes into the area. Based on sequence polymorphisms, VP7 proteins of these viruses are predicted to present themselves very differently to the immune system compared to those of vaccine strains. Many of the sick children with G12P[8] rotavirus in their diarrheal stools also were fully vaccinated. Our findings emphasize the need for continued monitoring of circulating rotaviruses and the effectiveness of the vaccines against strains with emerging G and P genotypes. |
Risk of rotavirus nosocomial spread after inpatient pentavalent rotavirus vaccination
Hofstetter AM , Lacombe K , Klein EJ , Jones C , Strelitz B , Jacobson E , Ranade D , Ward ML , Mijatovic-Rustempasic S , Evans D , Wikswo M , Bowen MD , Parashar UD , Payne DC , Englund JA . Pediatrics 2017 141 (1) BACKGROUND: Infants born prematurely or with underlying conditions are at increased risk of severe rotavirus disease and associated complications. Given the theoretical risk of nosocomial transmission of vaccine-type rotavirus, rotavirus vaccination is recommended for infants at or after discharge from neonatal care settings. Because the first dose should be administered by 104 days of age, some infants may be age-ineligible for vaccination if delayed until discharge. METHODS: This prospective cohort included infants admitted to an urban academic medical center between birth and 104 days who received care in intensive care settings. Pentavalent human-bovine reassortant rotavirus vaccine (RV5) was used, per routine clinical care. Stool specimens were collected weekly (February 2013-April 2014) and analyzed for rotavirus strains using real-time reverse transcription-polymerase chain reaction. Demographic and vaccine data were collected. RV5 safety was not assessed. RESULTS: Of 385 study infants, 127 were age-eligible for routine vaccinations during hospitalization. At discharge, 32.7% were up-to-date for rotavirus vaccination, compared with 82.7% for other vaccinations. Of rotavirus-unvaccinated infants, 42.6% were discharged at age >104 days and thus vaccination-ineligible. Of 1192 stool specimens collected, rotavirus was detected in 13 (1.1%): 1 wild-type strain from an unvaccinated infant; 12 vaccine-type strains from 9 RV5-vaccinated infants. No vaccine-type rotavirus cases were observed among unvaccinated infants (incidence rate: 0.0 [95% confidence interval: 0.0-1.5] cases per 1000 patient days at risk). CONCLUSIONS: These data suggest that delaying rotavirus vaccination until discharge from the hospital could lead to missed vaccination opportunities and may be unnecessary in institutions using RV5 with comparable infection control standards. |
Genomic Characterization of the First Equine-Like G3P[8] Rotavirus Strain Detected in the United States.
Perkins C , Mijatovic-Rustempasic S , Ward ML , Cortese MM , Bowen MD . Genome Announc 2017 5 (47) We report here the full coding region sequences for all 11 segments of the first equine-like G3P[8] rotavirus strain detected in the United States, strain RVA/Human-wt/USA/3000390639/2015/G3P[8]. The full genotype constellation of this strain is G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. |
Comparison of three multiplex gastrointestinal platforms for the detection of gastroenteritis viruses.
Chhabra P , Gregoricus N , Weinberg GA , Halasa N , Chappell J , Hassan F , Selvarangan R , Mijatovic-Rustempasic S , Ward ML , Bowen M , Payne DC , Vinje J . J Clin Virol 2017 95 66-71 BACKGROUND: Viruses are major etiological agents of childhood gastroenteritis. In recent years, several molecular platforms for the detection of viral enteric pathogens have become available. OBJECTIVE/STUDY DESIGN: We evaluated the performance of three multiplex platforms including Biofire's Gastrointestinal Panel (FilmArray), Luminex xTAG(R) Gastrointestinal Pathogen Panel (GPP), and the TaqMan Array Card (TAC) for the detection of five gastroenteritis viruses using a coded panel of 300 archived stool samples. RESULTS: The FilmArray detected a virus in 199 (96.1%) and the TAC in 172 (83.1%) of the 207 samples (187 samples positive for a single virus and 20 samples positive for more than one virus) whereas the GPP detected a virus in 100 (78.7%) of the 127 (97 positive for one virus and three positive for more than one virus) samples. Overall the clinical accuracy was highest for the FilmArray (98%) followed by TAC (97.2%) and GPP (96.9%). The sensitivity of the FilmArray, GPP and TAC platforms was highest for rotavirus (100%, 95.8%, and 89.6%, respectively) and lowest for adenovirus type 40/41 (97.4%, 57.9% and 68.4%). The specificity of the three platforms ranged from 95.6% (rotavirus) to 99.6% (norovirus/sapovirus) for the FilmArray, 99.6% (norovirus) to 100% (rotavirus/adenovirus) for GPP, and 98.9% (astrovirus) to 100% (rotavirus/sapovirus) for TAC. CONCLUSION: The FilmArray demonstrated the best analytical performance followed by TAC. In recent years, the availability of multi-enteric molecular testing platforms has increased significantly and our data highlight the strengths and weaknesses of these platforms. |
Shedding of porcine circovirus type 1 DNA and rotavirus RNA by infants vaccinated with Rotarix®.
Mijatovic-Rustempasic S , Immergluck LC , Parker TC , Laghaie E , Mohammed A , McFadden T , Parashar UD , Bowen MD , Cortese MM . Hum Vaccin Immunother 2016 13 (4) 0 Thirty-three infants aged approximately 2 months had serial stool samples collected after receipt of Rotarix(R) vaccine dose 1, and assessed for shedding of porcine circovirus type 1 DNA and Rotavirus group A RNA by molecular methods. We did not find strong evidence that porcine circovirus type 1 replication occurred. Porcine circovirus type 1 genome with the same sequence as that in Rotarix(R) was detected in a few infants as late as day ≥13; while this timing could suggest there may have been replication and not just transient passage through the gastrointestinal tract, the lack of increase in copy numbers in any infant supports transient passage and there are inherent limitations to the results. We found that 21% of infants did not shed Rotarix(R) RVA RNA beyond the day 3 sample, which may suggest lack of vaccine virus replication. Of the infants in whom Rotarix RVA RNA shedding continued, peak copy numbers were reached on days 3-5 for approximately 40%, and after day 5 in approximately 60%, and shedding can be prolonged (≥45 days). |
Ebola Virus Disease Diagnostics, Sierra Leone: Analysis of Real-time Reverse Transcription-Polymerase Chain Reaction Values for Clinical Blood and Oral Swab Specimens.
Erickson BR , Sealy TK , Flietstra T , Morgan L , Kargbo B , Matt-Lebby VE , Gibbons A , Chakrabarti AK , Graziano J , Presser L , Flint M , Bird BH , Brown S , Klena JD , Blau DM , Brault AC , Belser JA , Salzer JS , Schuh AJ , Lo M , Zivcec M , Priestley RA , Pyle M , Goodman C , Bearden S , Amman BR , Basile A , Bergeron E , Bowen MD , Dodd KA , Freeman MM , McMullan LK , Paddock CD , Russell BJ , Sanchez AJ , Towner JS , Wang D , Zemtsova GE , Stoddard RA , Turnsek M , Guerrero LW , Emery SL , Stovall J , Kainulainen MH , Perniciaro JL , Mijatovic-Rustempasic S , Shakirova G , Winter J , Sexton C , Liu F , Slater K , Anderson R , Andersen L , Chiang CF , Tzeng WP , Crowe SJ , Maenner MJ , Spiropoulou CF , Nichol ST , Stroher U . J Infect Dis 2016 214 S258-S262 During the Ebola virus outbreak of 2013-2016, the Viral Special Pathogens Branch field laboratory in Sierra Leone tested approximately 26 000 specimens between August 2014 and October 2015. Analysis of the B2M endogenous control Ct values showed its utility in monitoring specimen quality, comparing results with different specimen types, and interpretation of results. For live patients, blood is the most sensitive specimen type and oral swabs have little diagnostic utility. However, swabs are highly sensitive for diagnostic testing of corpses. |
Sensitive and specific nested PCR assay for detection of rotavirus A in samples with a low viral load.
Mijatovic-Rustempasic S , Esona MD , Williams AL , Bowen MD . J Virol Methods 2016 236 41-46 Techniques such as the real-time reverse transcription-polymerase chain reaction (qRT-PCR) can detect RNA in samples with a low viral load. However, these amplicons typically are either too short or at insufficient concentrations for use in subsequent sequencing reactions for genotyping and detection confirmation. The assay developed in this study detects rotavirus G genotypes and P genotypes with viral loads as low as 6.2 and 8.2 copies per reaction, respectively. The assay was validated using a panel of 91 stool samples, 32 reference rotavirus strains, and 6 non-target enteric virus samples. |
Rotavirus Strain Trends During the Postlicensure Vaccine Era: United States, 2008-2013.
Bowen MD , Mijatovic-Rustempasic S , Esona MD , Teel EN , Gautam R , Sturgeon M , Azimi PH , Baker CJ , Bernstein DI , Boom JA , Chappell J , Donauer S , Edwards KM , Englund JA , Halasa NB , Harrison CJ , Johnston SH , Klein EJ , McNeal MM , Moffatt ME , Rench MA , Sahni LC , Selvarangan R , Staat MA , Szilagyi PG , Weinberg GA , Wikswo ME , Parashar UD , Payne DC . J Infect Dis 2016 214 (5) 732-8 BACKGROUND: Group A rotaviruses (RVA) are a significant cause of pediatric gastroenteritis worldwide. The New Vaccine Surveillance Network (NVSN) has conducted active surveillance for RVA at pediatric hospitals and emergency departments at three to seven geographically diverse sites in the U.S. since 2006. METHODS: Over six consecutive years, from 2008 to 2013, 1,523 samples from NVSN sites that were test-positive by Rotaclone(R) enzyme immunoassay were submitted to the CDC for genotyping. RESULTS: In the 2009, 2010, and 2011 seasons, genotype G3P[8] was the predominant genotype throughout the network with 46-84% prevalence. In the 2012 season, G12P[8] replaced G3P[8] as the most common genotype with 70% prevalence and this trend persisted in 2013 (68.0% prevalence). Vaccine (RotaTeq(R), Rotarix(R)) strains were detected in 0.6-3.4% of genotyped samples each season. Uncommon and unusual strains (e.g., G8P[4], G3P[24], G2P[8], G3P[4], G3P[6], G24P[14], G4P[6], G9P[4]) were detected sporadically over the study period. Year, study site, and race were found to be significant predictors of genotype. CONCLUSION: Continued active surveillance is needed to monitor RVA genotypes in the U.S. and to detect potential changes since vaccine licensure. |
Molecular characterization of the first G24P[14] rotavirus strain detected in humans.
Ward ML , Mijatovic-Rustempasic S , Roy S , Rungsrisuriyachai K , Boom JA , Sahni LC , Baker CJ , Rench MA , Wikswo ME , Payne DC , Parashar UD , Bowen MD . Infect Genet Evol 2016 43 338-42 Here we report the genome of a novel rotavirus A (RVA) strain detected in a stool sample collected during routine surveillance by the Centers for Disease Control and Prevention's New Vaccine Surveillance Network. The strain, RVA/human-wt/USA/2012741499/2012/G24P[14], has a genomic constellation of G24-P[14]-I2-R2-C2-M2-A3-N2-T9-E2-H3. The VP2, VP3, VP7 and NSP3 genes cluster phylogenetically with bovine strains. The other genes occupy mixed clades containing animal and human strains. Strain RVA/human-wt/USA/2012741499/2012/G24P[14] most likely is the product of interspecies transmission and reassortment events. This is the second report of the G24 genotype and the first report of the G24P[14] genotype combination in humans. |
Full genome characterization of the first G3P[24] rotavirus strain detected in humans provides evidence of interspecies reassortment and mutational saturation in the VP7 gene.
Mijatovic-Rustempasic S , Roy S , Teel EN , Weinberg GA , Payne DC , Parashar UD , Bowen MD . J Gen Virol 2016 97 (2) 389-402 During the 2008-2009 rotavirus season of the Centers for Disease Control and Prevention New Vaccine Surveillance Network, one case of paediatric acute gastroenteritis associated with a rotavirus G14P[24] strain was identified. This was the first detection of the genotype G14 and P[24] in humans, and the first detection of the G14P[24] combination. To gain an insight into the origins and the evolution of this strain, we determined the complete ORF sequences of all 11 genes. A majority of the genes identified were similar to the simian strain TUCH, except for the VP1 and VP7 genes that clustered only distantly with the bovine and equine strains, respectively. In addition, this strain carried AU-1-like NSP2 and NSP4 genes. Using codon-partitioning and protein-based phylogenetic approaches, we determined that the VP7 genotype of strain 2009727118 was actually G3; therefore, the proposed full genomic classification of the 2009727118 strain is G3-P[24]-I9-R2-C3-M3-A9-N3-T3-E3-H6. These findings indicate the possibility that the 2009727118 strain originated by interspecies transmission and multiple reassortment events involving human, bovine and equine rotaviruses, resulting in the introduction of some genes into the genome of simian rotaviruses. Additionally, we found evidence of mutational saturation in the third codon position of the VP7 ORF which presented an issue with homoplasy in phylogenetic analyses. |
One-step multiplex real-time RT-PCR assay for detecting and genotyping wild-type group A rotavirus strains and vaccine strains (Rotarix® and RotaTeq®) in stool samples.
Gautam R , Mijatovic-Rustempasic S , Esona MD , Tam KI , Quaye O , Bowen MD . PeerJ 2016 4 e1560 BACKGROUND: Group A rotavirus (RVA) infection is the major cause of acute gastroenteritis (AGE) in young children worldwide. Introduction of two live-attenuated rotavirus vaccines, RotaTeq(R) and Rotarix(R), has dramatically reduced RVA associated AGE and mortality in developed as well as in many developing countries. High-throughput methods are needed to genotype rotavirus wild-type strains and to identify vaccine strains in stool samples. Quantitative RT-PCR assays (qRT-PCR) offer several advantages including increased sensitivity, higher throughput, and faster turnaround time. METHODS: In this study, a one-step multiplex qRT-PCR assay was developed to detect and genotype wild-type strains and vaccine (Rotarix(R) and RotaTeq(R)) rotavirus strains along with an internal processing control (Xeno or MS2 RNA). Real-time RT-PCR assays were designed for VP7 (G1, G2, G3, G4, G9, G12) and VP4 (P[4], P[6] and P[8]) genotypes. The multiplex qRT-PCR assay also included previously published NSP3 qRT-PCR for rotavirus detection and Rotarix(R) NSP2 and RotaTeq(R) VP6 qRT-PCRs for detection of Rotarix(R) and RotaTeq(R) vaccine strains respectively. The multiplex qRT-PCR assay was validated using 853 sequence confirmed stool samples and 24 lab cultured strains of different rotavirus genotypes. By using thermostable rTth polymerase enzyme, dsRNA denaturation, reverse transcription (RT) and amplification (PCR) steps were performed in single tube by uninterrupted thermocycling profile to reduce chances of sample cross contamination and for rapid generation of results. For quantification, standard curves were generated using dsRNA transcripts derived from RVA gene segments. RESULTS: The VP7 qRT-PCRs exhibited 98.8-100% sensitivity, 99.7-100% specificity, 85-95% efficiency and a limit of detection of 4-60 copies per singleplex reaction. The VP7 qRT-PCRs exhibited 81-92% efficiency and limit of detection of 150-600 copies in multiplex reactions. The VP4 qRT-PCRs exhibited 98.8-100% sensitivity, 100% specificity, 86-89% efficiency and a limit of detection of 12-400 copies per singleplex reactions. The VP4 qRT-PCRs exhibited 82-90% efficiency and limit of detection of 120-4000 copies in multiplex reaction. DISCUSSION: The one-step multiplex qRT-PCR assay will facilitate high-throughput rotavirus genotype characterization for monitoring circulating rotavirus wild-type strains causing rotavirus infections, determining the frequency of Rotarix(R) and RotaTeq(R) vaccine strains and vaccine-derived reassortants associated with AGE, and help to identify novel rotavirus strains derived by reassortment between vaccine and wild-type strains. |
Long-term consistency in rotavirus vaccine protection: RV5 and RV1 vaccine effectiveness in US children, 2012-2013
Payne DC , Selvarangan R , Azimi PH , Boom JA , Englund JA , Staat MA , Halasa NB , Weinberg GA , Szilagyi PG , Chappell J , McNeal M , Klein EJ , Sahni LC , Johnston SH , Harrison CJ , Baker CJ , Bernstein DI , Moffatt ME , Tate JE , Mijatovic-Rustempasic S , Esona MD , Wikswo ME , Curns AT , Sulemana I , Bowen MD , Gentsch JR , Parashar UD . Clin Infect Dis 2015 61 (12) 1792-9 BACKGROUND: Using a multi-center, active surveillance network from two rotavirus seasons (2012 and 2013), we assessed the vaccine effectiveness of RV5 (RotaTeq) and RV1 (Rotarix) rotavirus vaccines in preventing rotavirus gastroenteritis hospitalizations and emergency department (ED) visits for numerous demographic and secular strata. METHODS: We enrolled children hospitalized or visiting the ED with acute gastroenteritis (AGE) for the 2012 and 2013 seasons at 7 medical institutions. Stool specimens were tested for rotavirus by enzyme immunoassay and genotyped, and rotavirus vaccination histories were compared for rotavirus-positive cases and rotavirus-negative AGE controls. We calculated the VE for preventing rotavirus associated hospitalizations and ED visits for each vaccine, stratified by vaccine dose, season, clinical setting, age, predominant genotype, and ethnicity. RESULTS: RV5-specific VE analyses included 2,961 subjects, 402 rotavirus cases (14%) and 2,559 rotavirus-negative AGE controls. RV1-specific VE analyses included 904 subjects, 100 rotavirus cases (11%) and 804 rotavirus-negative AGE controls. Over the two rotavirus seasons, the VE for a complete 3-dose vaccination with RV5 was 80% (CI= 74% - 84%), and VE for a complete 2-dose vaccination with RV1 was 80% (CI= 68% - 88%).Statistically significant VE was observed for each year of life for which sufficient data allowed analysis (7 years for RV5 and 3 years for RV1). Both vaccines provided statistically significant genotype-specific protection against predominant circulating rotavirus strains. CONCLUSION: In this large, geographically and demographically diverse sample of US children, we observed that RV5 and RV1 rotavirus vaccines each provided a lasting, and broadly heterologous protection against rotavirus gastroenteritis. |
Epidemiologic Association Between FUT2 Secretor Status and Severe Rotavirus Gastroenteritis in Children in the United States.
Payne DC , Currier RL , Staat MA , Sahni LC , Selvarangan R , Halasa NB , Englund JA , Weinberg GA , Boom JA , Szilagyi PG , Klein EJ , Chappell J , Harrison CJ , Davidson BS , Mijatovic-Rustempasic S , Moffatt MD , McNeal M , Wikswo M , Bowen MD , Morrow AL , Parashar UD . JAMA Pediatr 2015 169 (11) 1-6 IMPORTANCE: A genetic polymorphism affecting FUT2 secretor status in approximately one-quarter of humans of European descent affects the expression of histo-blood group antigens on the mucosal epithelia of human respiratory, genitourinary, and digestive tracts. These histo-blood group antigens serve as host receptor sites necessary for attachment and infection of some pathogens, including norovirus. OBJECTIVE: We investigated whether an association exists between FUT2 secretor status and laboratory-confirmed rotavirus infections in US children. DESIGN, SETTING, AND PARTICIPANTS: Multicenter case-control observational study involving active surveillance at 6 US pediatric medical institutions in the inpatient and emergency department clinical settings. We enrolled 1564 children younger than 5 years with acute gastroenteritis (diarrhea and/or vomiting) and 818 healthy controls frequency matched by age and month, from December 1, 2011, through March 31, 2013. MAIN OUTCOMES AND MEASURES: Paired fecal-saliva specimens were tested for rotavirus and for secretor status. Comparisons were made between rotavirus test-positive cases and healthy controls stratified by ethnicity and vaccination status. Adjusted multivariable analyses assessed the preventive association of secretor status against severe rotavirus gastroenteritis. RESULTS: One (0.5%) of 189 rotavirus test-positive cases was a nonsecretor, compared with 188 (23%) of 818 healthy control participants (P < .001). Healthy control participants of Hispanic ethnicity were significantly less likely to be nonsecretors (13%) compared with healthy children who were not of Hispanic ethnicity (25%) (P < .001). After controlling for vaccination and other factors, children with the nonsecretor FUT2 polymorphism appeared statistically protected (98% [95% CI, 84%-100%]) against severe rotavirus gastroenteritis. CONCLUSIONS AND RELEVANCE: Severe rotavirus gastroenteritis was virtually absent among US children who had a genetic polymorphism that inactivates FUT2 expression on the intestinal epithelium. We observed a strong epidemiologic association among children with rotavirus gastroenteritis compared with healthy control participants. The exact cellular mechanism behind this epidemiologic association remains unclear, but evidence suggests that it may be rotavirus genotype specific. The lower prevalence of nonsecretors among Hispanic children may translate to an enhanced burden of rotavirus gastroenteritis among this group. Our findings may have bearing on our full understanding of rotavirus infections and the effects of vaccination in diverse populations. |
Multiplexed one-step RT-PCR VP7 and VP4 genotyping assays for rotaviruses using updated primers.
Esona MD , Gautam R , Tam KI , Williams A , Mijatovic-Rustempasic S , Bowen MD . J Virol Methods 2015 223 96-104 The current two-step VP7 and VP4 genotyping RT-PCR assays for rotaviruses have been linked consistently to genotyping failure in an estimated 30% of RVA positive samples worldwide. We have developed a VP7 and VP4 multiplexed one-step genotyping assays using updated primers generated from contemporary VP7 and VP4 sequences. To determine assay specificity and sensitivity, 17 reference virus strains, 6 non-target gastroenteritis viruses and 725 clinical samples carrying the most common VP7 (G1, G2, G3, G4, G9, and G12) and VP4 (P[4], P[6], P[8], P[9] and P[10]) genotypes were tested in this study. All reference RVA strain targets yielded amplicons of the expected sizes and non-target genotypes and gastroenteritis viruses were not detected by either assay. Out of the 725 clinical samples tested, the VP7 and VP4 assays were able to assigned specific genotypes to 711 (98.1%) and 714 (98.5%), respectively. The remaining unassigned samples were re-tested for RVA antigen using EIA and qRT-PCR assays and all were found to be negative. The overall specificity, sensitivity and limit of detection of the VP7 assay were in the ranges of 99.0-100%, 94.0-100% and 8.6x101 - 8.6x102 copies of RNA/reaction, respectively. For the VP4 assay, the overall specificity, sensitivity and limit of detection assay were in the ranges of 100%, 94.0-100% and ≤ 1 - 8.6x102 copies of RNA/reaction, respectively. Here we report two highly robust, accurate, efficient, affordable and documentable gel-based genotyping systems which are capable of genotyping 97.8% of the six common VP7 and 98.3% of the five common VP4 genotypes of RVA strains which are responsible for approximately 88.2% of all RVA infections worldwide. |
Full-Genome Sequence of the First G8P[14] Rotavirus Strain Detected in the United States.
Mijatovic-Rustempasic S , Roy S , Sturgeon M , Rungsrisuriyachai K , Reisdorf E , Cortese MM , Bowen MD . Genome Announc 2015 3 (3) This is a report of the complete genomic sequence of a rare rotavirus group A G8-P[14]-I2-R3-C2-M2-A3-N2-T6-E2-H3 strain detected in a stool sample from a 57-year-old subject. |
Full genomic characterization and phylogenetic analysis of a zoonotic human G8P[14] rotavirus strain detected in a sample from Guatemala.
Gautam R , Mijatovic-Rustempasic S , Roy S , Esona MD , Lopez B , Mencos Y , Rey-Benito G , Bowen MD . Infect Genet Evol 2015 33 206-11 We report the genomic characterization of a rare human G8P[14] rotavirus strain, identified in a stool sample from Guatemala (GTM) during routine rotavirus surveillance. This strain was designated as RVA/Human-wt/GTM/2009726790/2009/G8P[14], with a genomic constellation of G8-P[14]-I2-R2-C2-M2-A13-N2-T6-E2-H3. The VP4 gene occupied lineage VII within the P[14] genotype. Phylogenetic analysis of each genome segment revealed close relatedness to several zoonotic simian, guanaco and bovine strains. Our findings suggest that strain RVA/Human-wt/GTM/2009726790/2009/G8P[14] is an example of a direct zoonotic transmission event. The results of this study reinforce the potential role of interspecies transmission and reassortment in generating novel and rare rotavirus strains which infect humans. |
Full Genome Sequence of a Reassortant Human G9P[4] Rotavirus Strain.
Lewis J , Roy S , Esona MD , Mijatovic-Rustempasic S , Hardy C , Wang Y , Cortese M , Bowen MD . Genome Announc 2014 2 (6) This is a report of the complete genomic sequence of a reassortant rotavirus group A G9-P[4]-I2-R2-C2-M2-A2-N2-T2-E6-H2 strain designated RVA/Human-wt/USA/ LB1562/2010/G9P[4]. |
Rotavirus genotypes in Belarus, 2008-2012.
Semeiko G , Yermalovich M , Poliakova N , Mijatovic-Rustempasic S , Kerin T , Wasley A , Videbaek D , Gentsch JR , Bowen MD , Samoilovich E . Infect Genet Evol 2014 28 480-5 This study describes group A rotavirus (RVA) genotype prevalence in Belarus from 2008 to 2012. In 2008, data from 3 sites in Belarus (Brest, Mogilev, Minsk) indicated that G4P[8] was the predominant genotype. Data from Minsk (2008-2012) showed that G4P[8] was the predominant RVA genotype in all years except in 2011 when G3P[8] was most frequently detected. Other RVA genotypes common in Europe (G1P[8], G2P[4]) were detected each year of the study. This study reveals the dominance of genotype G4P[8] in Belarus and helps to establish the baseline genotype prevalence prior to RVA vaccine introduction in the country. |
Molecular epidemiology of contemporary G2P[4] human rotaviruses cocirculating in a single U.S. community: footprints of a globally transitioning genotype.
Dennis AF , McDonald SM , Payne DC , Mijatovic-Rustempasic S , Esona MD , Edwards KM , Chappell JD , Patton JT . J Virol 2014 88 (7) 3789-801 Group A rotaviruses (RVs) remain a leading cause of childhood gastroenteritis worldwide. Although the G/P types of locally circulating RVs can vary from year to year and differ depending upon geographical location, those with G1P[8], G2P[4], G3P[8], G4P[8], G9P[8], and G12P[8] specificities typically dominate. Little is known about the evolution and diversity of G2P[4] RVs and the possible role that widespread vaccine use has had on their increased frequency of detection. To address these issues, we analyzed the 12 G2P[4] RV isolates associated with a rise in RV gastroenteritis cases at Vanderbilt University Medical Center (VUMC) during the 2010-2011 winter season. Full-genome sequencing revealed that the isolates had genotype 2 constellations typical of DS-1-like viruses (G2P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2). Phylogenetic analyses showed that the genome segments of the isolates were comprised of two or three different subgenotype alleles; this enabled recognition of three distinct clades of G2P[4] viruses that caused disease at VUMC in the 2010-2011 season. Although the three clades cocirculated in the same community, there was no evidence of interclade reassortment. Bayesian analysis of 328 VP7 genes of G2 viruses isolated in the last 39 years indicate that existing G2 VP7 gene lineages continue to evolve and that novel lineages, as represented by the VUMC isolates, are constantly being formed. Moreover, G2 lineages are characteristically shaped by lineage turnover events that introduce new globally dominant strains every 7 years, on average. The ongoing evolution of G2 VP7 lineages may give rise to antigenic changes that undermine vaccine effectiveness in the long term. IMPORTANCE: Little is known about the diversity of cocirculating G2 rotaviruses and how their evolution may undermine the effectiveness of rotavirus vaccines. To expand our understanding of the potential genetic range exhibited by rotaviruses circulating in postvaccine communities, we analyzed part of a collection of rotaviruses recovered from pediatric patients in the United States from 2010 to 2011. Examining the genetic makeup of these viruses revealed they represented three segregated groups that did not exchange genetic material. The distinction between these three groups may be explained by three separate introductions. By comparing a specific gene, namely, VP7, of the recent rotavirus isolates to those from a collection recovered from U.S. children between 1974 and 1991 and other globally circulating rotaviruses, we were able to reconstruct the timing of events that shaped their ancestry. This analysis indicates that G2 rotaviruses are continuously evolving, accumulating changes in their genetic material as they infect new patients. |
Full-Genome Sequence of a Rare Human G3P[9] Rotavirus Strain.
Mijatovic-Rustempasic S , Roy S , Sturgeon M , Rungsrisuriyachai K , Esona MD , Degroat D , Qin X , Cortese MM , Bowen MD . Genome Announc 2014 2 (2) This is a report of the complete genomic sequence of a rare rotavirus group A G3-P[9]-I2-R2-C2-M2-A3-N2-T1-E2-H3 strain designated RVA/Human-wt/USA/12US1134/2012/G3P[9]. |
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