scholarly journals Evaluating strategies to improve rotavirus vaccine impact during the second year of life in Malawi

2019 ◽  
Vol 11 (505) ◽  
pp. eaav6419 ◽  
Author(s):  
Virginia E. Pitzer ◽  
Aisleen Bennett ◽  
Naor Bar-Zeev ◽  
Khuzwayo C. Jere ◽  
Benjamin A. Lopman ◽  
...  
Keyword(s):  
Low Income ◽  
Transmission Rate ◽  
Natural Infection ◽  
Vaccine Effectiveness ◽  
Low Income Countries ◽  
Rotavirus Vaccine ◽  
Second Year Of Life ◽  
Vaccine Impact ◽  
Second Year ◽  
Induced Immunity

Rotavirus vaccination has substantially reduced the incidence of rotavirus-associated gastroenteritis (RVGE) in high-income countries, but vaccine impact and estimated effectiveness are lower in low-income countries for reasons that are poorly understood. We used mathematical modeling to quantify rotavirus vaccine impact and investigate reduced vaccine effectiveness, particularly during the second year of life, in Malawi, where vaccination was introduced in October 2012 with doses at 6 and 10 weeks. We fitted models to 12 years of prevaccination data and validated the models against postvaccination data to evaluate the magnitude and duration of vaccine protection. The observed rollout of vaccination in Malawi was predicted to lead to a 26 to 77% decrease in the overall incidence of moderate-to-severe RVGE in 2016, depending on assumptions about waning of vaccine-induced immunity and heterogeneity in vaccine response. Vaccine effectiveness estimates were predicted to be higher among 4- to 11-month-olds than 12- to 23-month-olds, even when vaccine-induced immunity did not wane, due to differences in the rate at which vaccinated and unvaccinated individuals acquire immunity from natural infection. We found that vaccine effectiveness during the first and second years of life could potentially be improved by increasing the proportion of infants who respond to vaccination or by lowering the rotavirus transmission rate. An additional dose of rotavirus vaccine at 9 months of age was predicted to lead to higher estimated vaccine effectiveness but to only modest (5 to 16%) reductions in RVGE incidence over the first 3 years after introduction, regardless of assumptions about waning of vaccine-induced immunity.

scholarly journals Modeling of rotavirus transmission dynamics and impact of vaccination in Ghana

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

scholarly journals Community transmission of rotavirus infection in a vaccinated population in Malawi: a prospective household cohort study

2020 ◽  
Author(s):  
Aisleen Bennett ◽  
Louisa Pollock ◽  
Naor Bar-Zeev ◽  
Joseph A. Lewnard ◽  
Khuzwayo C. Jere ◽  
...  
Keyword(s):  
Low Income ◽  
Asymptomatic Infection ◽  
Vaccine Effectiveness ◽  
Low Income Countries ◽  
Rotavirus Vaccine ◽  
Rotavirus Infection ◽  
Indirect Transmission ◽  
Household Contacts ◽  
Asymptomatic Children ◽  
Increased Risk

AbstractBackgroundRotavirus vaccine effectiveness (VE) is reduced among children in low-income countries (LICs). Indirect (transmission-mediated) effects of rotavirus vaccine may contribute to the total population impact of vaccination. We estimated the effectiveness of rotavirus vaccine in preventing transmission of rotavirus to household contacts in Blantyre, Malawi.MethodsWe recruited vaccine-age-eligible children with acute rotavirus gastroenteritis (case-children), together with their household contacts. Clinical data and stool samples were collected from case-children at presentation, and prospectively from household contacts over 14 days. A single stool sample was collected from control households containing asymptomatic children age-matched to case-children. Samples were tested for rotavirus using real-time PCR. Risk factors for household transmission of rotavirus infection and clinical rotavirus disease were identified using logistic regression. Vaccine effectiveness against transmission (VET) was estimated as one minus the ratio of secondary attack rates (SAR) in vaccinated and unvaccinated populations, using VE estimates from the associated diarrhoeal surveillance platform to estimate the counterfactual SAR without vaccination.FindingsA total of 196 case-households and 55 control-households were recruited. Household SAR for rotavirus infection was high (65%); SAR for clinical disease was much lower (5%). Asymptomatic infection in control households was common (28%). Increasing disease severity was associated with increased risk of transmission of both rotavirus infection and disease to household contacts. Estimated VET was 39% (95% confidence interval 16-57%).InterpretationRotavirus vaccine has the potential to substantially reduce household rotavirus transmission. This should be considered in clinical and health economic assessments of vaccine impact.FundingWellcome Trust and NIH/NIAID.

scholarly journals The Rotavirus Vaccine Landscape, an Update

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 520
Author(s):  
Roberto Cárcamo-Calvo ◽  
Carlos Muñoz ◽  
Javier Buesa ◽  
Jesús Rodríguez-Díaz ◽  
Roberto Gozalbo-Rovira
Keyword(s):  
Developing Countries ◽  
Mortality Rate ◽  
Low Income ◽  
State Of The Art ◽  
The State ◽  
Cold Chain ◽  
Low Income Countries ◽  
Rotavirus Vaccine ◽  
Oral Vaccines

Rotavirus is the leading cause of severe acute childhood gastroenteritis, responsible for more than 128,500 deaths per year, mainly in low-income countries. Although the mortality rate has dropped significantly since the introduction of the first vaccines around 2006, an estimated 83,158 deaths are still preventable. The two main vaccines currently deployed, Rotarix and RotaTeq, both live oral vaccines, have been shown to be less effective in developing countries. In addition, they have been associated with a slight risk of intussusception, and the need for cold chain maintenance limits the accessibility of these vaccines to certain areas, leaving 65% of children worldwide unvaccinated and therefore unprotected. Against this backdrop, here we review the main vaccines under development and the state of the art on potential alternatives.

scholarly journals Rotavirus vaccine effectiveness in low-income settings: An evaluation of the test-negative design

Vaccine ◽  
2017 ◽  
Vol 35 (1) ◽  
pp. 184-190 ◽  
Author(s):  
Lauren M. Schwartz ◽  
M. Elizabeth Halloran ◽  
Ali Rowhani-Rahbar ◽  
Kathleen M. Neuzil ◽  
John C. Victor
Keyword(s):  
Low Income ◽  
Vaccine Effectiveness ◽  
Rotavirus Vaccine

scholarly journals Infrequent Transmission of Monovalent Human Rotavirus Vaccine Virus to Household Contacts of Vaccinated Infants in Malawi

2019 ◽  
Vol 219 (11) ◽  
pp. 1730-1734 ◽  
Author(s):  
Aisleen Bennett ◽  
Louisa Pollock ◽  
Khuzwayo C Jere ◽  
Virginia E Pitzer ◽  
Benjamin Lopman ◽  
...  
Keyword(s):  
Low Income ◽  
Indirect Effects ◽  
Horizontal Transmission ◽  
Vaccine Virus ◽  
Low Income Countries ◽  
Rotavirus Vaccine ◽  
Fecal Shedding ◽  
Household Contacts ◽  
Human Rotavirus ◽  
Stool Samples

Abstract Horizontal transmission of rotavirus vaccine virus may contribute to indirect effects of rotavirus vaccine, but data are lacking from low-income countries. Serial stool samples were obtained from Malawian infants who received 2 doses of monovalent human rotavirus vaccine (RV1) (days 4, 6, 8, and 10 after vaccination) and from their household contacts (8–10 days after vaccine). RV1 vaccine virus in stool was detected using semiquantitative real-time reverse-transcription polymerase chain reaction. RV1 fecal shedding was detected in 41 of 60 vaccinated infants (68%) and in 2 of 147 household contacts (1.4%). Horizontal transmission of vaccine virus within households is unlikely to make a major contribution to RV1 indirect effects in Malawi.

scholarly journals Parallel deficits in linear growth and mental development in low-income Mexican infants in the second year of life

2006 ◽  
Vol 9 (2) ◽  
pp. 178-186 ◽  
Author(s):  
Lia C Fernald ◽  
Lynnette M Neufeld ◽  
Lauren R Barton ◽  
Lourdes Schnaas ◽  
Juan Rivera ◽  
...  
Keyword(s):  
Low Income ◽  
Infant Development ◽  
Mental Development ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Targeted Interventions ◽  
Parental Characteristics ◽  
Second Year Of Life ◽  
Second Year ◽  
Height For Age

AbstractObjectiveTo explore anthropometric indicators and mental development in very-low-income children in the second year of life.DesignCross-sectional survey.SettingLow-income areas (income <20th percentile) in semi-urban Mexico (defined as towns or cities with 2500–50 000 inhabitants).SubjectsEight hundred and ninety-six children aged 12.5–23.5 months surveyed from September to December 2001.MethodsQuestionnaire survey and anthropometric survey of households. Multivariate regression models evaluated differences across age in anthropometry (height-for-age Z-score (HAZ) and weight-for-height Z-score) and cognitive function (Mental Development Index (MDI) of the Bayley Scales of Infant Development) while controlling for socio-economic and parental characteristics.ResultsThere was a significant decline in HAZ and in age-adjusted MDI score across the second year of life. Although the children showed MDI scores close to the mean, normed US values at 13–14 months, the scores were significantly lower than expected in older children (P < 0.0001), even after controlling for socio-economic status and parental characteristics. At 13–14 months, only 3% of children received scores below 70 (less than minus two standard deviations), whereas by 19–20 months, almost 17% of children were performing below this level. No socio-economic or parental characteristics were significant predictors of HAZ or MDI.ConclusionsParallel deficits are evident in both height-for-age and cognitive functioning during the second year of life in low-income Mexican infants. The consistency of these growth and development findings further stresses the need for targeted interventions to reduce the vulnerability of low-income Mexican children very early in life.

scholarly journals Impact of maternal antibodies and microbiota development on the immunogenicity of oral rotavirus vaccine in African, Indian, and European infants

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Edward P. K. Parker ◽  
Christina Bronowski ◽  
Kulandaipalayam Natarajan C. Sindhu ◽  
Sudhir Babji ◽  
Blossom Benny ◽  
...  
Keyword(s):  
Low Income ◽  
Early Life ◽  
Maternal Antibodies ◽  
Low Income Countries ◽  
Rotavirus Vaccine ◽  
Specific Antibodies ◽  
Environmental Enteric Dysfunction ◽  
The Uk ◽  
Antibody Levels ◽  
Microbiota Diversity

AbstractIdentifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. In this prospective cohort study, we measure maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India (n = 307), Malawi (n = 119), and the UK (n = 60), using standardised methods across cohorts. We observe ORV shedding and seroconversion rates to be significantly lower in Malawi and India than the UK. Maternal rotavirus-specific antibodies in serum and breastmilk are negatively correlated with ORV response in India and Malawi, mediated partly by a reduction in ORV shedding. In the UK, ORV shedding is not inhibited despite comparable maternal antibody levels to the other cohorts. In both India and Malawi, increased microbiota diversity is negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy.

scholarly journals Impact of maternal antibodies and microbiota development on the immunogenicity of oral rotavirus vaccine in African, Indian, and European infants: a prospective cohort study

2020 ◽  
Author(s):  
Edward P. K. Parker ◽  
Christina Bronowski ◽  
Kulandaipalayam Natarajan C. Sindhu ◽  
Sudhir Babji ◽  
Blossom Benny ◽  
...  
Keyword(s):  
Low Income ◽  
Early Life ◽  
Maternal Antibodies ◽  
Low Income Countries ◽  
Rotavirus Vaccine ◽  
Specific Antibodies ◽  
Environmental Enteric Dysfunction ◽  
The Uk ◽  
Antibody Levels ◽  
Microbiota Diversity

Identifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. We measured maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India (n = 307), Malawi (n = 119), and the UK (n = 60), using standardised methods across cohorts. ORV shedding and seroconversion rates were significantly lower in Malawi and India than the UK. Maternal rotavirus-specific antibodies in serum and breastmilk were negatively correlated with ORV response in India and Malawi, and this was mediated partly by a reduction in ORV replication. In the UK, ORV replication was not inhibited despite comparable maternal antibody levels. In both India and Malawi, pre-vaccination microbiota diversity was negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy.

scholarly journals 1170. Do Rotavirus Strains Affect Vaccine Effectiveness? A Systematic Review And Meta-analysis

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S676-S676
Author(s):  
Jordan Cates ◽  
Avnika Amin ◽  
Jacqueline Tate ◽  
Ben Lopman ◽  
Umesh D Parashar
Keyword(s):  
Systematic Review ◽  
Low Income ◽  
Random Effect ◽  
Income Level ◽  
Vaccine Effectiveness ◽  
Low Income Countries ◽  
P Value ◽  
Case Control Studies ◽  
Rotavirus Vaccines ◽  
Strain Type

Abstract Background Rotavirus causes 215,000 deaths from severe childhood diarrhea annually. Two rotavirus vaccines – a monovalent vaccine containing a single rotavirus strain (RV1) and a pentavalent vaccine containing 5 rotavirus strains (RV5) – are used in routine immunization programs of nearly 100 countries. Concerns exist that rotavirus vaccines may be less effective against rotavirus strains not contained in the vaccines which could subsequently cause selective pressure and strain replacement. We estimated the vaccine effectiveness (VE) of RV1 and RV5 against vaccine (homotypic) and non-vaccine (partially and fully heterotypic) strains. Methods After conducting a systematic review, we meta-analyzed 31 case-control studies (N=27,293) conducted between 2006 and 2020 using a random-effect regression model. Results In high-income countries, RV1 VE was 10% lower against partially heterotypic (p-value=0.04) and fully heterotypic (p-value=0.10) compared to homotypic strains (homotypic VE: 90% [95% CI: 82, 94]; partially heterotypic VE: 79% [95% CI: 71, 85]; fully heterotypic VE: 80% [95% CI: 65, 88]; Figure 1). In middle-income countries, RV1 VE was 14 to 16% lower against partially heterotypic (p-value=0.06) and fully heterotypic (p-value=0.04) compared to homotypic strains (homotypic VE: 81% [95% CI: 69, 88]; partially heterotypic VE: 67% [95% CI: 54, 76]; fully heterotypic VE: 65% [95% CI: 52, 75]; Figure 1). Strain-specific RV5 VE differences were less pronounced (Figure 2). Limited data were available from low-income countries. Figure 1. Vaccine effectiveness by country income level and strain type, for RV1. Figure 2. Vaccine effectiveness by country income level and strain type, for RV5. Conclusion Vaccine effectiveness of RV1 and RV5 was somewhat lower VE against non-vaccine than vaccine strains. Ongoing surveillance is crucial to continue long-term monitoring for strain replacement, particularly in low-income settings where data are limited. Disclosures All Authors: No reported disclosures

scholarly journals Measuring indirect effects of rotavirus vaccine in low income countries

Vaccine ◽  
2016 ◽  
Vol 34 (37) ◽  
pp. 4351-4353 ◽  
Author(s):  
Aisleen Bennett ◽  
Naor Bar-Zeev ◽  
Nigel A. Cunliffe
Keyword(s):  
Low Income ◽  
Indirect Effects ◽  
Low Income Countries ◽  
Rotavirus Vaccine
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