Modeling of rotavirus transmission dynamics and impact of vaccination in Ghana

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

Science Translational Medicine ◽

10.1126/scitranslmed.aav6419 ◽

2019 ◽

Vol 11 (505) ◽

pp. eaav6419 ◽

Cited By ~ 6

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.

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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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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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Vaccine waning and mumps re-emergence in the USA

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx162.063 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S25-S25

Author(s):

Joseph Lewnard ◽

Yonatan H Grad

Keyword(s):

Vaccine Coverage ◽

Age Distribution ◽

Booster Vaccination ◽

Vaccine Effectiveness ◽

Vaccine Introduction ◽

Mumps Vaccine ◽

Population Immunity ◽

Clinical Protection ◽

The Usa ◽

History Of

Abstract Background Following decades of declining mumps incidence amid widespread vaccination, the US has experienced a resurgence in mumps cases since 2006 driven largely by outbreaks on college campuses. The occurrence of cases among previously-vaccinated individuals and in communities with high vaccine coverage has prompted concerns about performance of the live attenuated mumps vaccine (Jeryl Lynn strain) currently included in the measles-mumps-rubella (MMR) series. It is unclear whether the resurgence is due to antigenic changes in circulating mumps virus, which would warrant consideration of a new vaccine, or to waning vaccine-derived protection, necessitating additional booster doses. Methods We pooled data from studies of vaccine effectiveness to test for waning of protection. We used mathematical models to measure changes in population immunity since mumps vaccine introduction and to assess whether recent mumps transmission dynamics are consistent with hypotheses of waning immunity or vaccine escape. Results We estimate that vaccine-derived protection persists, on average, 29 (95% CI: 17–54) years after receipt of the last dose (Fig. 1). This waning accounts for 66.4% of unexplained variation in estimates of mumps vaccine effectiveness across published studies. Changes in age-specific susceptibility due to vaccine waning and declining transmission track with the current resurgence in cases among young adults in the USA, and explain outbreaks reported among vaccinated adolescents during the late 1980s (Fig. 2). In contrast, vaccine escape would not be expected to result in cases following the observed age distribution (Fig. 3). Routine adult booster vaccination is needed to sustain mumps elimination. Conclusion The resurgence of mumps in the USA since 2006 is attributable to waning of vaccine-derived immunity, suggesting the need for booster doses in adulthood. Trials are needed to assess clinical protection afforded by booster doses in individuals with a history of MMR vaccination. Disclosures J. Lewnard, Pfier: Grant Investigator, Research grant

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Monovalent Rotavirus Vaccine Effectiveness Against Rotavirus Hospitalizations Among Children in Zimbabwe

Clinical Infectious Diseases ◽

10.1093/cid/ciy1096 ◽

2018 ◽

Vol 69 (8) ◽

pp. 1339-1344 ◽

Cited By ~ 4

Author(s):

Hilda A Mujuru ◽

Eleanor Burnett ◽

Kusum J Nathoo ◽

Ismail Ticklay ◽

Nhamo A Gonah ◽

...

Keyword(s):

Vaccine Effectiveness ◽

Vaccination Status ◽

Watery Diarrhea ◽

Rotavirus Vaccine ◽

Normal Height ◽

Severe Diarrhea ◽

Vaccine Introduction ◽

Rotavirus Vaccines ◽

Negative Case ◽

Acute Watery Diarrhea

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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