title: Population Impact and Effectiveness of Monovalent Rotavirus Vaccination in Urban Malawian Children 3 Years After Vaccine Introduction: Ecological and Case-Control Analyses.
abstract: BACKGROUND
  Rotavirus vaccines have been introduced in many low-income African countries including Malawi in 2012. Despite early evidence of vaccine impact, determining persistence of protection beyond infancy, the utility of the vaccine against specific rotavirus genotypes, and effectiveness in vulnerable subgroups is important.
  
  
  METHODS
  We compared rotavirus prevalence in diarrheal stool and hospitalization incidence before and following rotavirus vaccine introduction in Malawi. Using case-control analysis, we derived vaccine effectiveness (VE) in the second year of life and for human immunodeficiency virus (HIV)-exposed and stunted children.
  
  
  RESULTS
  Rotavirus prevalence declined concurrent with increasing vaccine coverage, and in 2015 was 24% compared with prevaccine mean baseline in 1997-2011 of 32%. Since vaccine introduction, population rotavirus hospitalization incidence declined in infants by 54.2% (95% confidence interval [CI], 32.8-68.8), but did not fall in older children. Comparing 241 rotavirus cases with 692 test-negative controls, VE was 70.6% (95% CI, 33.6%-87.0%) and 31.7% (95% CI, -140.6% to 80.6%) in the first and second year of life, respectively, whereas mean age of rotavirus cases increased from 9.3 to 11.8 months. Despite higher VE against G1P[8] than against other genotypes, no resurgence of nonvaccine genotypes has occurred. VE did not differ significantly by nutritional status (78.1% [95% CI, 5.6%-94.9%] in 257 well-nourished and 27.8% [95% CI, -99.5% to 73.9%] in 205 stunted children;P= .12), or by HIV exposure (60.5% [95% CI, 13.3%-82.0%] in 745 HIV-unexposed and 42.2% [95% CI, -106.9% to 83.8%] in 174 exposed children;P= .91).
  
  
  CONCLUSIONS
  Rotavirus vaccination in Malawi has resulted in reductions in disease burden in infants <12 months, but not in older children. Despite differences in genotype-specific VE, no genotype has emerged to suggest vaccine escape. VE was not demonstrably affected by HIV exposure or stunting.
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre Institute of Infection and Global Health, University of Liverpool, United Kingdom.
authors.forename: Naor
authors.initials: N
authors.lastname: Bar-Zeev
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre Institute of Infection and Global Health, University of Liverpool, United Kingdom.
authors.forename: Khuzwayo C
authors.initials: KC
authors.lastname: Jere
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre Institute of Infection and Global Health, University of Liverpool, United Kingdom.
authors.forename: Aisleen
authors.initials: A
authors.lastname: Bennett
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre Institute of Infection and Global Health, University of Liverpool, United Kingdom.
authors.forename: Louisa
authors.initials: L
authors.lastname: Pollock
authors.affiliation: Epidemiology Branch, Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Tate
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakagomi
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, United Kingdom.
authors.forename: Miren
authors.initials: M
authors.lastname: Iturriza-Gomara
authors.affiliation: Institute of Global Health, University College London, United Kingdom.
authors.forename: Anthony
authors.initials: A
authors.lastname: Costello
authors.affiliation: Ministry of Health, Lilongwe, Malawi.
authors.forename: Charles
authors.initials: C
authors.lastname: Mwansambo
authors.affiliation: Epidemiology Branch, Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Umesh D
authors.initials: UD
authors.lastname: Parashar
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre Liverpool School of Tropical Medicine Division of Infection and Immunity, University College London, United Kingdom.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre Institute of Infection and Global Health, University of Liverpool, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: French
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, United Kingdom.
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Cunliffe
mesh_terms: D016022:Case-Control Studies; D002675:Child, Preschool; D003967:Diarrhea / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D062665:Epidemiological Monitoring; D005243:Feces / Q000821:virology; D005260:Female; D005759:Gastroenteritis / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D005838:Genotype; D006130:Growth Disorders / Q000453:epidemiology; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology; D006760:Hospitalization; D006801:Humans; D007223:Infant; D008295:Malawi / Q000453:epidemiology; D015995:Prevalence; D012401:Rotavirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D012400:Rotavirus Infections / Q000453:epidemiology* / Q000517:prevention & control* / Q000821:virology; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014504:Urban Health / Q000706:statistics & numerical data / Q000639:trends*; D014611:Vaccination / Q000706:statistics & numerical data / Q000639:trends; D064166:Vaccine Potency; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D035862:Vulnerable Populations / Q000706:statistics & numerical data
chemical_list: C492457:RIX4414 vaccine; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated
keywords: case-control; developing countries; population impact; rotavirus vaccine; vaccine effectiveness