Monovalent Rotavirus Vaccine Effectiveness Against Rotavirus Hospitalizations Among Children in Zimbabwe

Abstract Background Rotavirus is a leading cause of mortality among children <5 years old. We evaluated monovalent rotavirus vaccine effectiveness (VE) under conditions of routine use at 2 surveillance sites in Harare, Zimbabwe, after vaccine introduction in May 2014. Methods Children aged <5 years hospitalized or treated in the accident and emergency department (A&E) for acute watery diarrhea were enrolled for routine surveillance. Copies of vaccination cards were collected to document vaccination status. Among children age-eligible to receive rotavirus vaccine, we estimated VE, calculated as 1 – odds ratio, using a test-negative case-control design Results We included 903 rotavirus-positive cases and 2685 rotavirus-negative controls in the analysis; 99% had verified vaccination status. Rotavirus-positive children had more severe diarrhea than rotavirus-negative children; 61% of cases and 46% of controls had a Vesikari score ≥11 (P < .01). Among cases and controls, 31% and 37%, respectively, were stunted for their age (P < .01). Among children 6–11 months old, adjusted 2-dose VE against hospitalization or treatment in A&E due to rotavirus of any severity was 61% (95% confidence interval [CI], 21%–81%) and 68% (95% CI, 13%–88%) against severe rotavirus disease. Stratified by nutritional status, adjusted VE was 45% (95% CI, –148% to 88%) among stunted infants and 71% (95% CI, 29%–88%) among infants with a normal height for age Conclusions Monovalent rotavirus vaccine is effective in preventing hospitalizations due to severe rotavirus diarrhea among infants in Zimbabwe, providing additional evidence for countries considering rotavirus vaccine introduction that live, oral rotavirus vaccines are effective in high-child-mortality settings.

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Emergence of Double- and Triple-Gene Reassortant G1P[8] Rotaviruses Possessing a DS-1-Like Backbone after Rotavirus Vaccine Introduction in Malawi

Journal of Virology ◽

10.1128/jvi.01246-17 ◽

2017 ◽

Vol 92 (3) ◽

Cited By ~ 15

Author(s):

Khuzwayo C. Jere ◽

Chrispin Chaguza ◽

Naor Bar-Zeev ◽

Jenna Lowe ◽

Chikondi Peno ◽

...

Keyword(s):

Amino Acid ◽

Vaccine Effectiveness ◽

Recent Common Ancestor ◽

Rotavirus Vaccine ◽

Careful Evaluation ◽

African Countries ◽

Vaccine Introduction ◽

Rotavirus Gastroenteritis ◽

Structural Conformation ◽

Rotavirus Vaccines

ABSTRACT To combat the high burden of rotavirus gastroenteritis, multiple African countries have introduced rotavirus vaccines into their childhood immunization programs. Malawi incorporated a G1P[8] rotavirus vaccine (Rotarix) into its immunization schedule in 2012. Utilizing a surveillance platform of hospitalized rotavirus gastroenteritis cases, we examined the phylodynamics of G1P[8] rotavirus strains that circulated in Malawi before (1998 to 2012) and after (2013 to 2014) vaccine introduction. Analysis of whole genomes obtained through next-generation sequencing revealed that all randomly selected prevaccine G1P[8] strains sequenced ( n = 32) possessed a Wa-like genetic constellation, whereas postvaccine G1P[8] strains ( n = 18) had a DS-1-like constellation. Phylodynamic analyses indicated that postvaccine G1P[8] strains emerged through reassortment events between human Wa- and DS-1-like rotaviruses that circulated in Malawi from the 1990s and hence were classified as atypical DS-1-like reassortants. The time to the most recent common ancestor for G1P[8] strains was from 1981 to 1994; their evolutionary rates ranged from 9.7 × 10 −4 to 4.1 × 10 −3 nucleotide substitutions/site/year. Three distinct G1P[8] lineages chronologically replaced each other between 1998 and 2014. Genetic drift was the likely driver for lineage turnover in 2005, whereas replacement in 2013 was due to reassortment. Amino acid substitution within the outer glycoprotein VP7 of G1P[8] strains had no impact on the structural conformation of the antigenic regions, suggesting that it is unlikely that they would affect recognition by vaccine-induced neutralizing antibodies. While the emergence of DS-1-like G1P[8] rotavirus reassortants in Malawi was therefore likely due to natural genotype variation, vaccine effectiveness against such strains needs careful evaluation. IMPORTANCE The error-prone RNA-dependent RNA polymerase and the segmented RNA genome predispose rotaviruses to genetic mutation and genome reassortment, respectively. These evolutionary mechanisms generate novel strains and have the potential to lead to the emergence of vaccine escape mutants. While multiple African countries have introduced a rotavirus vaccine, there are few data describing the evolution of rotaviruses that circulated before and after vaccine introduction. We report the emergence of atypical DS-1-like G1P[8] strains during the postvaccine era in Malawi. Three distinct G1P[8] lineages circulated chronologically from 1998 to 2014; mutation and reassortment drove lineage turnover in 2005 and 2013, respectively. Amino acid substitutions within the outer capsid VP7 glycoprotein did not affect the structural conformation of mapped antigenic sites, suggesting a limited effect on the recognition of G1-specific vaccine-derived antibodies. The genes that constitute the remaining genetic backbone may play important roles in immune evasion, and vaccine effectiveness against such atypical strains needs careful evaluation.

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1491. Active Norovirus Surveillance in Children Under 5 Years with Diarrhea after Rotavirus Vaccine Introduction in Argentina (2017–2019)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1355 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S543-S543

Author(s):

Angela Gentile ◽

Juan Stupka ◽

Juan I Degiuseppe ◽

María del Valle Juárez ◽

Maria Florencia Lucion ◽

...

Keyword(s):

Acute Diarrhea ◽

Epidemiological Data ◽

Cross Sectional Study ◽

Epidemiological Surveillance ◽

Watery Diarrhea ◽

Rotavirus Vaccine ◽

Cross Sectional ◽

Vaccine Introduction ◽

Rotavirus Vaccination ◽

Children Under 5

Abstract Background Acute diarrhea is one of the leading causes of infant morbidity and mortality. Argentina introduced massive rotavirus vaccination in 2015. In several countries, this introduction has changed the distribution of enteropathogens. The decrease in the prevalence of rotavirus has been described at the expense of an increase in Norovirus (NoV) activity worldwide. The aim of this study was to analyze the role of NoV in acute diarrhea cases in outpatient children under 5 years of age and their epidemiological profile. Methods A prospective and cross-sectional study in <5 years outpatients attended for acute diarrhea in Children’s Hospital “Dr. Ricardo Gutiérrez” in Buenos Aires, Argentina, between July 2017 and March 2019 was conducted. Active epidemiological surveillance was performed with a specific case reporting form. Stool samples were tested for NoV (RT-qPCR). Clinical and epidemiological data were recorded. Results A total of 252 patients were enrolled and 235 stools samples were tested. Median of age was 22.3 months (IQR: 11–30), 58.7% were male. The most frequent symptoms were fever and vomiting in 63.1% and 53%, respectively; 52% had watery diarrhea, 45.2% had moderate diarrhea according to Vesikari Scale, 95.6% were normohydrated and 22% had a household member with diarrhea. There were no immunocompromised children. A 72% had received rotavirus vaccine, 86% of them with full scheme. From samples tested, 27% (n = 63) were NoV positive. NoV was found throughout the year and the frequency of detection was higher in January and June (summer and winter in Argentina). Regarding genetic diversity the most frequent genogroup was GII (65%; 41/63) and genotype GII.P16-GII.4 Sydney (48%; 20/41). Bacterial co-infection was observed in 35%. Compared with negative cases, NoV were younger (18 vs. 20 months; P < 0.001) and were associated with higher prevalence of rotavirus vaccination (88% vs. 66%; P = 0.001). No statistically difference was found regarding to gender, clinical outcome and severity. Conclusion NoV was detected at high frequency (27%) in children presenting moderate acute diarrhea, mainly in those who received rotavirus vaccine. Regarding sporadic acute diarrhea cases in children, it is important to consider NoV as a frequent etiological agent. Disclosures All authors: No reported disclosures.

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Detection of rotavirus before and after monovalent rotavirus vaccine introduction and vaccine effectiveness among children in mainland Tanzania

Vaccine ◽

10.1016/j.vaccine.2018.01.071 ◽

2018 ◽

Vol 36 (47) ◽

pp. 7149-7156 ◽

Cited By ~ 9

Author(s):

Bhavin Jani ◽

Adolfine Hokororo ◽

Jackson Mchomvu ◽

Margaret M. Cortese ◽

Christopher Kamugisha ◽

...

Keyword(s):

Vaccine Effectiveness ◽

Rotavirus Vaccine ◽

Vaccine Introduction ◽

Before And After

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Rotavirus Vaccines: an Overview

Clinical Microbiology Reviews ◽

10.1128/cmr.00029-07 ◽

2008 ◽

Vol 21 (1) ◽

pp. 198-208 ◽

Cited By ~ 192

Author(s):

Penelope H. Dennehy

Keyword(s):

Developing Countries ◽

Control Measure ◽

The United States ◽

Rotavirus Vaccine ◽

Industrialized Countries ◽

Severe Diarrhea ◽

Rotavirus Vaccines ◽

Childhood Morbidity ◽

Human Rotavirus ◽

Increased Risk

SUMMARY Rotavirus infection is the most common cause of severe diarrhea disease in infants and young children worldwide and continues to have a major global impact on childhood morbidity and mortality. Vaccination is the only control measure likely to have a significant impact on the incidence of severe dehydrating rotavirus disease. In 1999, a highly efficacious rotavirus vaccine licensed in the United States, RotaShield, was withdrawn from the market after 14 months because of its association with intussusception. Two new live, oral, attenuated rotavirus vaccines were licensed in 2006: the pentavalent bovine-human reassortant vaccine (RotaTeq) and the monovalent human rotavirus vaccine (Rotarix). Both vaccines have demonstrated very good safety and efficacy profiles in large clinical trials in western industrialized countries and in Latin America. Careful surveillance has not revealed any increased risk of intussusception in the vaccinated groups with either vaccine. The new rotavirus vaccines are now introduced for routine use in a number of industrialized and developing countries. These new safe and effective rotavirus vaccines offer the best hope of reducing the toll of acute rotavirus gastroenteritis in both developed and developing countries.

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Rotavirus disease burden pre-vaccine introduction in young children in Rural Southern Mozambique, an area of high HIV prevalence

PLoS ONE ◽

10.1371/journal.pone.0249714 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0249714

Author(s):

Sozinho Acácio ◽

Tacilta Nhampossa ◽

Llorenç Quintò ◽

Delfino Vubil ◽

Marcelino Garrine ◽

...

Keyword(s):

Risk Factors ◽

Disease Burden ◽

Conditional Logistic Regression ◽

Epidemiological Data ◽

Daily Basis ◽

African Countries ◽

Severe Diarrhea ◽

Vaccine Introduction ◽

Rotavirus Vaccines ◽

The Impact

Background Rotavirus vaccines have been adopted in African countries since 2009, including Mozambique (2015). Disease burden data are needed to evaluate the impact of rotavirus vaccine. We report the burden of rotavirus-associated diarrhea in Mozambique from the Global Enteric Multicenter Study (GEMS) before vaccine introduction. Methods A case-control study (GEMS), was conducted in Manhiça district, recruiting children aged 0–59 months with moderate-to-severe diarrhea (MSD) and less-severe-diarrhea (LSD) between December 2007 and November 2012; including 1–3 matched (age, sex and neighborhood) healthy community controls. Clinical and epidemiological data and stool samples (for laboratory investigation) were collected. Association of rotavirus with MSD or LSD was determined by conditional logistic regression and adjusted attributable fractions (AF) calculated, and risk factors for rotavirus diarrhea assessed. Results Overall 915 cases and 1,977 controls for MSD, and 431 cases and 430 controls for LSD were enrolled. Rotavirus positivity was 44% (217/495) for cases and 15% (160/1046) of controls, with AF = 34.9% (95% CI: 32.85–37.06) and adjusted Odds Ratio (aOR) of 6.4 p< 0.0001 in infants with MSD compared to 30% (46/155) in cases and 14% (22/154) in controls yielding AF = 18.7%, (95% CI: 12.02–25.39) and aOR = 2.8, p = 0.0011 in infants with LSD. The proportion of children with rotavirus was 32% (21/66) among HIV-positive children and 23% (128/566) among HIV-negative ones for MSD. Presence of animals in the compound (OR = 1.9; p = 0.0151) and giving stored water to the child (OR = 2.0, p = 0.0483) were risk factors for MSD; while animals in the compound (OR = 2.37, p = 0.007); not having routine access to water on a daily basis (OR = 1.53, p = 0.015) and washing hands before cooking (OR = 1.76, p = 0.0197) were risk factors for LSD. Conclusion The implementation of vaccination against rotavirus may likely result in a significant reduction of rotavirus-associated diarrhea, suggesting the need for monitoring of vaccine impact.

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Modeling of rotavirus transmission dynamics and impact of vaccination in Ghana

10.1101/2020.03.12.20034801 ◽

2020 ◽

Author(s):

Ernest O. Asare ◽

Mohammad A. Al-Mamun ◽

George E. Armah ◽

Benjamin A. Lopman ◽

Umesh D. Parashar ◽

...

Keyword(s):

Teaching Hospital ◽

Response Rate ◽

Transmission Rate ◽

Age Distribution ◽

Vaccine Effectiveness ◽

Rotavirus Vaccine ◽

Vaccine Response ◽

Maternal Immunity ◽

Vaccine Introduction ◽

Vaccine Impact

AbstractBackgroundRotavirus incidence remains relatively high in low-income countries (LICs) compared to high-income countries (HICs) after vaccine introduction. Ghana introduced monovalent rotavirus vaccine in April 2012 and despite the high coverage, vaccine performance has been modest compared to developed countries. The predictors of low vaccine effectiveness in LICs are poorly understood, and the drivers of subnational heterogeneity in rotavirus vaccine impact are unknown.MethodsWe used mathematical models to investigate variations in rotavirus incidence in children <5 years old in Ghana. We fit models to surveillance and case-control data from three different hospitals: Korle-Bu Teaching Hospital in Accra, Komfo Anokye Teaching Hospital in Kumasi, and War Memorial Hospital in Navrongo. The models were fitted to both pre- and post-vaccine data to estimate parameters describing the transmission rate, waning of maternal immunity, and vaccine response rate.ResultsThe seasonal pattern and age distribution of rotavirus cases varied among the three study sites in Ghana. Our model was able to capture the spatio-temporal variations in rotavirus incidence across the three sites and showed good agreement with the age distribution of observed cases. The rotavirus transmission rate was highest in Accra and lowest in Navrongo, while the estimated duration of maternal immunity was longer (∼5 months) in Accra and Kumasi and shorter (∼3 months) in Navrongo. The proportion of infants who responded to the vaccine was estimated to be high in Accra and Kumasi and low in Navrongo.ConclusionsRotavirus vaccine impact varies within Ghana. A low vaccine response rate was estimated for Navrongo, where rotavirus is highly seasonal and incidence limited to a few months of the year. Our findings highlight the need to further explore the relationship between rotavirus seasonality, maternal immunity, and vaccine response rate to determine how they influence vaccine effectiveness and to develop strategies to improve vaccine impact.HighlightsMarked variations in rotavirus incidence and vaccine impact within GhanaSimilar rotavirus seasonality before and after vaccine introductionA shift in age distribution occurred following vaccine introductionThe models provide satisfactory predictions of rotavirus outbreaks and vaccine impact

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2746. Effectiveness of Influenza Vaccine for Prevention of Influenza-associated Hospitalizations Among Immunocompromised Adults—2017–2018

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2423 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S967-S967

Author(s):

Fernanda P Silveira ◽

Kailey L Hughes ◽

G K Balasubramani ◽

Donald Middleton ◽

Mary Patricia Nowalk ◽

...

Keyword(s):

Radiation Therapy ◽

Stem Cell ◽

Influenza Vaccine ◽

Stem Cell Transplant ◽

Organ Transplant ◽

Vaccine Effectiveness ◽

Vaccination Status ◽

Cell Transplant ◽

Negative Case ◽

Reduced Risk

Abstract Background Immunocompromised (IC) individuals are at higher risk for severe complications of influenza. Little literature describes vaccine effectiveness (VE) in this population. We evaluated VE for prevention of influenza-associated hospitalization among IC adults. Methods We analyzed data from adults hospitalized with acute respiratory illness (ARI) during the 2017–2018 FLU season at 9 hospitals participating in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) study. Details of disease severity, underlying health status, and vaccination status were obtained through enrollment interviews and medical records. Prior year clinical encounter diagnoses and enrollment interviews were used to define IC groups. IC groups were mutually exclusive. VE was evaluated with a test-negative case–control design using multivariate logistic regression with PCR-confirmed influenza as the outcome and vaccination status as the exposure, adjusting for age, race, and other factors, and stratifying by immunocompromising conditions. Results Of 3524 adults hospitalized with ARI, 1210 (34%) had an immunocompromising condition. Chronic steroid (n = 397), chemo/radiation therapy (n = 242), hematologic condition (n = 175), and organ transplant (n = 144) were most common. HIV (n = 45) and stem cell transplant (SCT) (n = 28) were least common. IC patients were more likely to be vaccinated than non-IC (60% vs. 55%, P = 0.002). Overall, vaccination reduced risk of influenza hospitalization by 36% (95% CI: 24,46). Among IC adults, VE was 9% (95% CI: −25,34). VE was 32% (95% CI: 5,51) for chemo/radiation therapy, 29% (95% CI: 6,47) for chronic steroids, 29% (95% CI: -6,52) for hematologic conditions, −1% (95% CI: −50,32) for organ transplant, −48% (95% CI: −190,25) for HIV, and −154% (95% CI = −458,−15) for SCT (Figure 1). Conclusion Vaccination reduced risk of influenza hospitalization among adults with the most prevalent immunocompromising conditions in our cohort; however, it had little to no effect in other groups, such as in HIV and organ and stem cell transplant recipients. Results support using other preventative strategies in addition to vaccinating adults with immunocompromising conditions, such as vaccination of close contacts. Disclosures All authors: No reported disclosures.

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2731. Does Last Season’s Influenza Vaccination Affect Current Season’s Vaccine Effectiveness in Young Children?

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2409 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S961-S961

Author(s):

Suchitra Rao ◽

Molly Lamb ◽

Angela Moss ◽

Edwin J Asturias

Keyword(s):

Medical Condition ◽

Vaccine Effectiveness ◽

Vaccination Status ◽

Urgent Care ◽

Control Analysis ◽

Current Season ◽

Logistic Regression Models ◽

Negative Case ◽

Influenza Illness ◽

Case Control Analysis

Abstract Background We evaluated influenza VE over two consecutive years vs. the current season against influenza illness during two H3N2-predominant seasons in children receiving care at emergency/urgent care (ED/UC) facilities in metropolitan Colorado. Methods We conducted a test-negative case–control analysis of 1478 children aged 6 months to 8 years enrolled at Children’s Hospital Colorado ED/UC with influenza like illness during the 2016–2017 and 2017–2018 influenza seasons. The primary outcome was PCR-confirmed influenza and vaccination status was confirmed using electronic medical record and parental interviews. Vaccination status was defined as completely vaccinated (all doses of influenza vaccine according to child’s age); partially or not vaccinated children were defined as unvaccinated. Multivariable logistic regression models adjusted for high-risk medical condition, age, race and insurance status were used to calculate odds ratios (OR) and 95% confidence intervals. Vaccine effectiveness was calculated as (1 − OR) × 100. Results Of the 1224 (82.8%) children enrolled in the study with known vaccination status for both seasons, 361 (29%) tested positive for influenza. Overall, VE against influenza was 49% (95% CI, 33–61%) after adjusting for other covariates in the model. VE did not differ significantly between those vaccinated in both seasons and those vaccinated in only the current season (VE 69%, 95% CI 41–115) (Table 1). Conclusion Our estimates of influenza VE for two predominantly H3N2-influenza seasons in Colorado are comparable to the CDC -VE for children 6 months to 8 years. VE against ED or UC-attended influenza illness in children did not vary significantly by prior seasons’ vaccination status. Disclosures All authors: No reported disclosures.

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Comparison of Local Influenza Vaccine Effectiveness Using Two Methods

10.1101/2020.09.14.20194449 ◽

2020 ◽

Author(s):

Goundappa K Balasubramani ◽

Richard K Zimmerman ◽

Heather Eng ◽

Jason Lyons ◽

Lloyd G Clarke ◽

...

Keyword(s):

Influenza Vaccine ◽

Research Methods ◽

Influenza A ◽

Vaccine Effectiveness ◽

Vaccination Status ◽

Administrative Databases ◽

Administrative Database ◽

Point Estimate ◽

Research Database ◽

Negative Case

Background: In some settings, research methods to determine influenza vaccine effectiveness (VE) may not be appropriate because of cost, time constraints, or other factors. Administrative database analysis of viral testing results and vaccination history may be a viable alternative. This study compared VE estimates from outpatient research and administrative databases. Methods: Using the test-negative, case-control design, data for 2017-2018 and 2018-2019 influenza seasons, were collected using: 1) research methods including consent, specimen collection, RT-PCR testing and vaccine verification using multiple methods; and 2) an administrative database of outpatients with a clinical respiratory viral panel combined with electronic immunization records. Odds ratios for likelihood of influenza infection by vaccination status were calculated using multivariable logistic regression. VE = (1 - OR) X 100. Results: Research participants were significantly younger (P<0.001), more often white (69% vs. 59%; P<0.001) than non-white and less frequently enrolled through the emergency department (ED) (35% vs. 72%; P<0.001) than administrative database participants. VE was significant against all influenza and influenza A in each season and both seasons combined (37%-49%). Point estimate differences between methods were evident, with higher VE in the research database, but insignificant due to low sample sizes. When enrollment sites were separately analyzed, there were significant differences in VE estimates for all influenza (66% research vs. 46% administrative P<0.001) and influenza A (67% research vs. 49% administrative; P<0.001) in the ED. The selection of the appropriate method for determining influenza vaccine effectiveness depends on many factors, including sample size, subgroups of interest, etc., suggesting that research estimates may be more generalizable. Other advantages of research databases for VE estimates include lack of clinician-related selection bias for testing and less misclassification of vaccination status. The advantages of the administrative databases are potentially shorter time to VE results and lower cost.

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