Determining the effectiveness of the pentavalent rotavirus vaccine against rotavirus hospitalizations and emergency department visits using two study designs
Introduction
Rotavirus is the most common cause of diarrhea-related illness and death among infants and young children [1]. Prior to the introduction of a rotavirus vaccine in the United States (US), nearly all children were infected with rotavirus during the first five years of life [2], [3], [4], [5]. The introduction of a three dose, oral, pentavalent, human-bovine reassortant vaccine (RV5) (RotaTeq, Merck and Co. Inc., Whitehouse Station, NJ), in the US led to significant reductions in rotavirus hospitalizations and emergency department (ED) visits [6], [7], [8], [9], [10], [11], [12]. RV5, which contains G1–G4 and P8 strains, was licensed for use in the US in February 2006 and subsequently recommended by the Centers for Disease Control and Prevention (CDC)’s Advisory Committee on Immunization Practices and the American Academy of Pediatrics for routine use in infants [13], [14]. RV5 is recommended for infants at 2, 4 and 6 months of age, and all doses should be administered before a child reaches 32 weeks of age [15]. Coverage with ≥1 dose of RV5 reached 50–60% during the first year following its introduction in 2006 and increased steadily (2.7% per quarter on average) to 74% by mid-2009 [6].
Because vaccine effectiveness (VE) may be reduced under field conditions [16], post-licensure evaluation of VE is important. Different study designs have been used to estimate post-licensure VE and each has advantages and disadvantages. While case-control studies are most frequently used to determine post-licensure VE [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], the case-cohort design is also used for this purpose [28], [29], [30], [31], [32], [33]. The vaccination status of diseased cases is compared to disease-free controls with the traditional case-control design, and to a representative subcohort from the community regardless of disease status that produced the cases with the case-cohort design. A direct comparison of these designs for rotavirus VE has not been done.
As part of the CDC-funded New Vaccine Surveillance Network (NVSN), seasonal, population-based acute gastroenteritis (AGE) surveillance was conducted to determine the burden and epidemiology of rotavirus disease and to monitor the impact of the rotavirus vaccine program. This system provided a unique opportunity to determine the effectiveness of RV5 for preventing rotavirus-associated hospitalizations and ED visits using two different study designs.
Section snippets
Materials and methods
Active, prospective, population-based surveillance for hospitalizations and ED visits due to AGE in non-immunocompromised children <3 years was conducted during two rotavirus seasons: 2007 (December 2006–June 2007) and 2008 (December 2007–June 2008). Surveillance sites included University of Rochester Medical Center (Monroe County, New York), Cincinnati Children's Hospital Medical Center (Hamilton County, Ohio) and Vanderbilt University Medical Center (Davidson County, Tennessee), hereafter
Cases
Seventy-six cases met the surveillance enrollment inclusion criteria, and had verified vaccination status; 21 from Rochester, 39 from Cincinnati, and 16 from Nashville. Table 1 displays the characteristics of the cases compared to each of the comparison groups.
Comparison group #1: subcohort comparison group (case-cohort design)
The subcohort consisted of 21 clusters (10 children each) from Rochester, 39 clusters from Cincinnati, and 16 clusters from Nashville. After removing subcohort members not meeting inclusion criteria and/or those excluded due to a missing
Discussion
This is the first study to evaluate the VE of RV5 using two study designs and three comparison groups with the same set of rotavirus-positive cases. Each of the VE methods found three doses of RV5 to be 92% effective in preventing rotavirus-related hospitalizations and ED visits with similar point estimates for partial doses. Our three-dose VE estimates were comparable to the pre-licensure efficacy trial (94.5%) [45], and similar to other post-licensure RV5 VE studies using case-control designs
References (51)
- et al.
Measles in the United Kingdom 1990–2008 and the effectiveness of measles vaccines
Vaccine
(2010) - et al.
The effectiveness of the mumps component of the MMR vaccine: a case control study
Vaccine
(2005) - et al.
Effectiveness of seven-valent pneumococcal conjugate vaccine against invasive pneumococcal disease: a matched case-control study
Lancet
(2006) - et al.
Use of the state immunization information system to assess rotavirus vaccine effectiveness in Connecticut, 2006–2008
Vaccine
(2011) - et al.
Effectiveness of hexavalent vaccines against invasive Haemophilus influenzae type b disease: Germany's experience after 5 years of licensure
Vaccine
(2008) - et al.
The pregnancy and influenza project: design of an observational case-cohort study to evaluate influenza burden and vaccine effectiveness among pregnant women and their infants
Am J Obstet Gynecol
(2011) - et al.
Characterization of nontypeable rotavirus strains from the United States: identification of a new rotavirus reassortant (P2A[6],G12) and rare P3[9] strains related to bovine rotaviruses
Virology
(2002) - et al.
Global illness and deaths caused by rotavirus disease in children
Emerg Infect Dis
(2003) - et al.
Hospitalizations and deaths from diarrhea and rotavirus among children <5 years of age in the United States, 1993–2003
J Infect Dis
(2007) - et al.
Hospitalizations associated with rotavirus diarrhea in the United States, 1993 through 1995: surveillance based on the new ICD-9-CM rotavirus-specific diagnostic code
J Infect Dis
(1998)