ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Rotavirus vaccines for infants

Rotavirus vaccines for infants
Literature review current through: Jan 2024.
This topic last updated: Mar 02, 2023.

INTRODUCTION — Rotavirus was the most common cause of severe, acute gastroenteritis in infants and children worldwide in the prevaccine era, during which it was estimated to cause approximately 440,000 deaths, 2 million hospitalizations, and 25 million outpatient visits per year worldwide among children <5 years of age [1-3]. More than 120 countries have introduced national rotavirus vaccination programs, and approximately 15 additional countries are planning to introduce them [4].

Rotavirus vaccination of infants will be discussed below. The pathogenesis, clinical presentation, and diagnosis of rotavirus gastroenteritis are discussed separately, as are general measures to prevent viral gastroenteritis in children. (See "Clinical manifestations and diagnosis of rotavirus infection" and "Acute viral gastroenteritis in children in resource-abundant countries: Management and prevention".)

MICROBIOLOGY — Rotavirus is a double-stranded RNA virus in the Reoviridae family [5]. The outer capsid contains two proteins that define rotavirus serotypes: a G protein (VP7) and a P protein (VP4) (figure 1). Five G-P combinations accounted for approximately 90 percent of human rotaviruses circulating worldwide: G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8] in the prevaccine era [3]. However, in countries in Africa and Asia, strain diversity is greater; within one geographic area, multiple types may circulate simultaneously, and the prevalent strains may vary from season to season. During 2014 to 2016, genotype G12P[8] predominated in the United States [6]. The effects of infant immunization on rotavirus serotype prevalence are discussed below. (See 'Serotype selection' below.)

ROTAVIRUS VACCINES

Vaccine development — Rotavirus vaccines have been developed from animal rotavirus strains, human-animal rotavirus reassortants (genes from human and animal strains), attenuated human rotaviruses, subunits of rotavirus virions, and virus-like particles [7-13]. For live virus-based vaccines, reassortants are necessary because most human rotaviruses grow too poorly in cell culture for production of standard vaccine lots for large-scale immunization programs. Monovalent vaccines prepared from animal rotaviruses have not been promising in humans. Assessment of rotavirus subunit vaccine candidates has reached human studies [14].

Vaccines licensed in the United States — Two live, attenuated oral rotavirus vaccines are licensed for use in the United States and many other countries (table 1). The vaccines have similar efficacy and safety, and no preference for one over the other vaccine exists [1,3,5,15]. (See 'Contraindications' below and 'Efficacy/effectiveness' below and 'Adverse events and safety' below.)

Pentavalent human-bovine rotavirus reassortant vaccine (RV5, PRV, RotaTeq) is based upon the bovine strain, WC3, which is naturally attenuated for humans but not broadly cross-protective. Each reassortant component contains a single gene derived from a human rotavirus strain encoding a major outer capsid protein from the most common human serotypes: G1, G2, G3, G4, and P1[8] (figure 2). This vaccine induces homologous (ie, serotype-specific) protection against the common types of exposure, as well as the nonvaccine type G9 [16].

Attenuated human rotavirus vaccine (RV1, HRV, Rotarix) is a monovalent vaccine derived from the most common human rotavirus serotype combination (G1P[8]) that has been attenuated by serial passage in cell culture (figure 2) [10]. Observational studies of natural rotavirus infection suggest that infection with one serotype provides at least partial cross-protection against most other serotypes [17].

Other vaccines

Human-bovine reassortant vaccine (116E, Rotavac) and oral bovine rotavirus pentavalent vaccine (BRV-PV, Rotasiil) – These vaccines are licensed for use in India and have World Health Organization (WHO) prequalification for use in resource-limited countries [18-21].

116E – The 116E rotavirus vaccine is a nonpathogenic strain (G9P[11]) that occurs naturally in India. It contains a virus reassortant strain in which one gene was from a rotavirus strain naturally occurring in bovines (P[11]) and 10 genes were from a rotavirus strain naturally occurring in humans. Phase 3 clinical trials in India have been completed (demonstrating efficacy of 56 percent against severe rotavirus gastroenteritis and 34 percent against rotavirus gastroenteritis in the first year of follow-up) [12,22]. The 116E vaccine is licensed for use in India and has World Health Organization (WHO) prequalification for use in resource-limited countries [18-20].

BRV-PV – BRV-PV is a heat-stable bovine-human reassortant vaccine that contains serotypes G1, G2, G3, G4, and G9 [23,24]. It is administered in three doses at 6, 10, and 14 weeks.

A randomized trial compared BRV-PV with placebo in 3508 Nigerian infants [23,24]. Four weeks after the third dose, infants who received BRV-PV had fewer episodes of laboratory-confirmed, severe rotavirus gastroenteritis than those who received placebo (31 versus 87 episodes; efficacy of 67 percent, 95% CI 50-78 percent). The rates of adverse events were similar between groups. None of the participants had confirmed intussusception. In a multicenter randomized trial in 7500 infants in India, the efficacy of BRV-PV in preventing severe rotavirus gastroenteritis before age two years was 39 percent (95% CI 26-49 percent) [25].

BRV-PV is less expensive than RV5 and RV1 and may be more suitable for vaccination programs in remote areas where cold-chain capacity is limited [23]. It is licensed for use in India and has WHO prequalification for use in resource-limited countries [20].

In a multicenter, open-label, randomized trial, a mixed schedule of116E and BRV-PV was safe and immunogenic, suggesting that the two vaccines can be used interchangeably for routine immunization [26].

Lanzhou lamb rotavirus vaccine – A monovalent, G10P[12] oral lamb rotavirus vaccine is licensed in China. In a randomized trial in China, the efficacy of the lamb rotavirus vaccine was 57 percent efficacious in reducing rotavirus gastroenteritis and 70 percent efficacious in reducing severe rotavirus gastroenteritis [27]. However, a mouse study suggests that monovalent rotavirus vaccines may not be sufficiently immunogenic against heterotypic strains for protection against rotavirus disease in China [19]. Previous studies indicate that strain variation and induction of antibody response is well correlated in mice and humans [28].

Oral human neonatal rotavirus vaccine (RV3-BB) – RV3-BB is a naturally attenuated oral vaccine developed from a strain initially recovered from an outbreak in a nursery in which infections were asymptomatic (G3P[6]) [29]. In a phase 2 randomized trial in Indonesia, RV3-BB was efficacious in preventing severe rotavirus gastroenteritis before age 18 months when administered to neonates (at age 0 to 5 days, 8 weeks, and 14 weeks) and infants (at age 8, 14, and 18 weeks). RV3-BB also appears to be safe and immunogenic [29-31].

Human attenuated rotavirus vaccine (G1P[8]) in lyophilized (Rotavin-M1) and liquid formulation (Rotavin) A lyophilized human attenuated rotavirus vaccine (G1P[8]) was licensed in Vietnam in 2012. Although the lyophilized formulation and a liquid formulation appear to be safe and immunogenic [32], additional data from phase 3 trials are necessary before use of these vaccines can be expanded.

Tetravalent human-rhesus reassortant vaccine – An oral tetravalent human-rhesus rotavirus reassortant vaccine (RRV-TV, RotaShield) was licensed in 1998 and recommended for universal immunization of term infants in the United States, but was withdrawn from the market in 1999 because of an epidemiologic link to intussusception occurring within two weeks after vaccine administration [33-37]. (See 'Intussusception' below.)

INDICATIONS — We recommend universal immunization of infants against rotavirus, as recommended by the Centers for Disease Control and Prevention [1], the World Health Organization [38], the American Academy of Pediatrics [5], the American Academy of Family Physicians, the European Society for Pediatric Infectious Diseases, and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition [15].

In randomized trials and meta-analyses, rotavirus vaccines are highly efficacious in preventing rotavirus gastroenteritis and rotavirus gastroenteritis-associated hospitalization and health care utilization [39-41]. (See 'Efficacy/effectiveness' below.)

CONTRAINDICATIONS — Rotavirus vaccines are contraindicated in those infants [1,5,15,42-44]:

Who are allergic to any of the ingredients of the vaccine

The oral dose applicator presentations of the attenuated human rotavirus vaccine (RV1) are contraindicated in infants with severe (anaphylactic) allergy to latex because the applicator contains latex; the squeezable tube presentation of RV1 or the pentavalent human-bovine rotavirus reassortant vaccine can be administered to such infants [45,46] (see "Allergic reactions to vaccines", section on 'Latex')

Who had a severe (anaphylactic) allergic reaction after a previous dose

With severe combined immunodeficiency (SCID) – Vaccine-acquired rotavirus disease has been reported in infants who subsequently were diagnosed with SCID [42,47-52] (see "Severe combined immunodeficiency (SCID): An overview")

With a history of intussusception – Fatal intussusception after the second dose has been reported in infants with a history of intussusception after the first dose [43,53]

Although few data exist upon which to base recommendations, the 2013 Infectious Diseases Society of America guidelines on vaccination of the immunocompromised host consider the following conditions to also be contraindications to rotavirus vaccination because of the potential risk of serious adverse effects [44]:

Combined immunodeficiencies – Di George syndrome and other combined immunodeficiencies with a CD3 count <500 cells/microL, Wiskott-Aldrich syndrome, X-linked lymphoproliferative disease, and familial disorders that predispose to hemophagocytic lymphohistiocytosis (eg, Griscelli syndrome, Chediak-Higashi syndrome, Hermansky-Pudlak syndrome) (see "Combined immunodeficiencies: An overview")

Certain phagocytic cell deficiencies – Leukocyte adhesion deficiency, defects of cytotoxic granule release (eg, Chediak-Higashi), and other undefined phagocytic cell defects (see "Leukocyte-adhesion deficiency" and "Chediak-Higashi syndrome")

Major antibody deficiencies treated with immunoglobulin therapy (see "Primary humoral immunodeficiencies: An overview")

Planned or status-post hematopoietic stem cell transplant

Planned or current receipt of cancer chemotherapy

Status-post solid organ transplant

Chronic inflammatory disease treated with immunosuppressive medications (ie, prednisone, azathioprine, 6-mercaptopurine, biologic agents [eg, tumor necrosis factor antagonists, rituximab])

These conditions are uncommon to rare among infants in the age group for rotavirus vaccine administration (six weeks to eight months). (See 'Schedule' below.)

The following conditions are not contraindications to rotavirus vaccination [1,5,44]:

Immunocompromised family member or household member (see 'Immunocompromised household contact' below)

Breastfeeding (efficacy trials included breastfeeding infants, with no alteration in normal breastfeeding patterns) [54,55]

Pregnant family member or household contact

PRECAUTIONS

Immunodeficiency other than severe combined immunodeficiency – Decisions regarding immunization of children with known or suspected immunodeficiency other than severe combined immunodeficiency (SCID) (which is a contraindication to rotavirus vaccine) should be made on a case-by-case basis after considering the risks and benefits. Although there are few data regarding the efficacy or safety of rotavirus vaccine in infants who are potentially immunocompromised, systemic infections or severe mucosal infections due to a rotavirus vaccine have been extremely rare [50].

In this setting, the United States Advisory Committee on Immunization Practices (ACIP) advises consultation with an immunologist or infectious disease specialist and the American Academy of Pediatrics (AAP) advises precaution for administration of rotavirus vaccine for manifestations of altered immunocompetence other than SCID [1,5,42].

Consultation with an expert in pediatric infectious diseases is also warranted for infants born to women who received certain biologic response modifiers (eg, adalimumab, golimumab) other than certolizumab during pregnancy [5]. Although data are limited, these infants may have detectable drug concentrations for months after delivery, which may increase their risk of vaccine-type rotavirus disease [56-59]. Certolizumab is an exception because it does not cross the placenta. Rotavirus vaccine should be avoided for up to 12 months after the last in utero exposure; the duration of avoidance varies with the agent but is usually at least 6 months. (Refer to the drug interactions program included within UpToDate for details.) In resource-abundant countries where rotavirus gastroenteritis is rarely life threatening and there is evidence of community ("herd") immunity to rotavirus infection, the risk of developing vaccine-type rotavirus disease with prenatal exposure to biologic response modifiers is greater than the risk of developing severe wild-type rotavirus disease without vaccination.

The Infectious Diseases Society of America (IDSA) guidelines on vaccination of the immunocompromised host suggest that rotavirus vaccine may be administered to infants with the following conditions [44]:

HIV exposure or infection – Rotavirus gastroenteritis may be particularly severe in children with HIV infection. In a prospective study in South Africa, children with HIV infection were more likely to have a prolonged hospitalization and had a fourfold increased mortality rate compared with children without HIV infection admitted to the same hospital [60]. The AAP also supports administration of rotavirus vaccine to infants with HIV exposure or infection, regardless of the CD4+ T-lymphocyte percentage or count [5].

Rotavirus vaccine trials that included infants with HIV infection have found no evidence of enhanced disease associated with HIV infection [44]. In randomized trials, administration of attenuated human rotavirus vaccine (RV1) and pentavalent human-bovine rotavirus reassortant vaccine (RV5) was safe and immunogenic when administered to infants with HIV infection in a three-dose schedule [61,62].

Groups other than the IDSA (eg, the Department of Health and Human Services, Centers for Disease Control and Prevention) suggest that the potential risks and benefits of rotavirus vaccination be considered before vaccination [63]; however, they suggest that the potential delay in establishment of definitive diagnosis of HIV infection beyond the recommended age for the first dose of rotavirus vaccine and considerable attenuation of rotavirus vaccine strains support vaccination of infants with suspected HIV infection or exposure.

Primary (congenital) complement deficiencies. (See "Inherited disorders of the complement system".)

Chronic granulomatous disease. (See "Chronic granulomatous disease: Pathogenesis, clinical manifestations, and diagnosis".)

Congenital or cyclic neutropenia. (See "Congenital neutropenia" and "Cyclic neutropenia".)

Immunoglobulin A deficiency, provided that all other components of the immune system are normal. (See "Selective IgA deficiency: Clinical manifestations, pathophysiology, and diagnosis".)

Specific polysaccharide antibody deficiency provided that all other components of the immune system are normal. (See "Specific antibody deficiency".)

For infants with innate immune defects that result in defects of cytokine generation or response or cellular activation (eg, defects of the interferon-gamma/interleukin-12 axis), the IDSA recommends consultation with a specialist before administration of live vaccines [44].

Other precautions – The ACIP and AAP suggest the following conditions are precautions for the administration of rotavirus vaccines, because the safety and efficacy of the vaccine were not specifically evaluated in infants with these conditions [1,5]:

Acute moderate-to-severe gastroenteritis – Immunization of infants with acute, moderate-to-severe gastroenteritis should be deferred until the illness resolves. A concern is that the antibody response may be diminished.

Moderate-to-severe febrile illness – Immunization of infants with moderate to severe illness of any type should be deferred until the illness resolves. Deferral of the immunization makes it easier to differentiate possible adverse effects related to the vaccine from manifestations of the underlying disease.

Pre-existing or acquired chronic gastrointestinal disease excluding intussusception – Infants with pre-existing or acquired gastrointestinal conditions (eg, congenital malabsorption syndromes, Hirschsprung disease, short-bowel syndrome, some forms of cystic fibrosis-related gastrointestinal disease) who are not receiving immunosuppressive therapy should benefit from rotavirus vaccines, and the benefits outweigh the theoretic risks. In a pilot study, RV1 appeared to be safe and immunogenic in 14 children with early intestinal failure [64]. In another small study, RV5 appeared to be safe and immunogenic in five infants with a history of bowel resection [65]. There is one case report of pneumatosis intestinalis following rotavirus vaccination in a three-month-old with short bowel syndrome [66].

Spina bifida or bladder exstrophy – Infants with spina bifida or bladder exstrophy have a high risk of developing latex allergy. To minimize latex exposure, some experts suggest that RV5 or the latex-free presentation of RV1 (table 1) be used for such infants. The ACIP recommends rotavirus vaccination even if latex-free presentations are not available because the benefit of vaccination is greater than the risk of sensitization [1].

SCHEDULE

Routine schedule — The recommended routine schedules for pentavalent human-bovine rotavirus reassortant vaccine (RV5) and attenuated human rotavirus vaccine (RV1) differ [1,5]:

RV5 is administered in three oral doses at two, four, and six months of age.

RV1 is administered in two oral doses at two and four months.

Whenever possible, the rotavirus vaccine series should be completed with the same vaccine product [1]; however, vaccination should not be deferred if the product used for previous doses is not known. A total of three doses of vaccine should be given to infants who received RV5 for any dose and infants in whom the vaccine product for previous dose(s) is unknown.

An open-label, multicenter randomized trial confirmed that completion of rotavirus immunization using a combination of RV5 and RV1 was as immunogenic as completion with RV5 or RV1 and was well tolerated [67]. In postlicensure surveillance, completion of immunization with a combination of RV5 and RV1 (eg, two doses of RV5 and one dose of RV1 or two doses of RV1 and one dose of RV5) was 80 percent (95% CI 51-92 percent) effective in preventing rotavirus gastroenteritis [68]. Although mixed schedules and single formulation schedules were not directly compared, this is similar to published rates of effectiveness for three doses of RV5 or two doses of RV1 in the same population [69].

Catch-up schedule — The catch-up schedules for RV5 and RV1 differ:

RV5 – In the United States, the first dose of RV5 should be given between 6 and 15 weeks of age [1,5]. Two subsequent doses are administered with a minimum interval of four weeks between doses. The third dose should not be administered after eight months, zero days of age.

The vaccine series should not be initiated in infants who are older than 14 weeks, 6 days of age [1]. The safety of the first dose of rotavirus vaccine in older infants was not studied in the prelicensure trials; however, for infants in whom the first dose is inadvertently administered at 15 weeks or older, the rest of the rotavirus immunization series should be completed as described above [1]. The timing of the first dose should not affect the safety and efficacy of the second and third dose.

In Europe, the first dose of RV5 should be given between 6 and 12 weeks, preferably at 6 to 8 weeks, and the full schedule completed by 24 weeks of age, but preferably earlier [15].

For resource-limited countries, to avoid missed opportunities, the World Health Organization (WHO) loosened the age restriction to permit completion of the three-dose RV5 schedule by age 24 months (although earlier completion is preferred) [3]. This recommendation has not been fully adopted [70].

RV1 – In the United States, the first dose of RV1 should be given between 6 and 15 weeks of age and the full schedule completed by eight months, zero days of age [1,5].

In Europe, the first dose of RV1 should be given between 6 and 12 weeks, preferably at 6 to 8 weeks, and the full schedule completed by 24 weeks of age, but preferably earlier [15].

For resource-limited countries, to avoid missed opportunities, the WHO loosened the age restriction to permit completion of the two-dose RV1 schedule by age 24 months (although earlier completion is preferred) [3]. This recommendation has not been fully adopted [70].

There is no maximum interval between doses.

Special circumstances

Preterm infants — In the United States, rotavirus vaccines can be administered to preterm infants who are clinically stable and at least six weeks old [1,5,71,72]. For hospitalized infants who are due for rotavirus vaccine during admission, individual institutions may choose to administer the vaccine during admission or at the time of discharge [5]. The European Society for Paediatric Infectious Diseases and the Australian government recommend rotavirus vaccination of preterm infants according to their chronologic age, whether or not they have been discharged from the nursery, with appropriate precautions to prevent transmission to high-risk contacts [15,73]. (See 'Shedding and transmission of vaccine virus' below.)

In retrospective reviews, age-appropriate administration of RV5 to preterm enterally-fed infants in the neonatal intensive care unit was well tolerated and did not appear to be associated with transmission [74,75]. Subsequent prospective studies support the low risk of transmission [76,77]. The larger prospective study evaluated rotavirus shedding and transmission among infants age <15 weeks admitted to an intensive care unit with single or double room assignments of an academic medical center that permitted RV5 administration during hospitalization [76]. Rotavirus was detected in 13 of 1192 stool specimens (1.1 percent) collected weekly: one wild-type strain from an unvaccinated infant and 12 vaccine-type strains from nine vaccinated infants. No vaccine-type rotavirus cases were observed among unvaccinated infants during 1952 days of potential exposure, and no reassortants were identified. These findings suggest that delaying RV5 vaccination until hospital discharge may be unnecessary in hospitals with comparable infection control standards. In making decisions for individual infants, attending clinicians must consider the benefit of vaccination with possible asymptomatic transmission and the risk of missed opportunity for rotavirus vaccination in an infant who may be at increased risk of severe rotavirus disease [78].

Infants with rotavirus gastroenteritis — The rotavirus vaccine series should be initiated or completed in infants who have had rotavirus gastroenteritis before receiving the full two- or three-dose series because natural first infections do not provide complete immunity against subsequent severe disease and multiple serotypes of rotavirus usually are present in any community [1,5,79].

Receipt of blood products — Rotavirus vaccines may be administered at any time in relation to the receipt of blood products, including antibody-containing products [1,80].

Hospitalization of vaccinated infant — In the event that an infant requires hospitalization after administration of rotavirus vaccine, standard precautions should be used to prevent the spread of vaccine virus in the hospital setting [5]. No additional infection control measures are necessary. Co-rooming with children with severe combined immunodeficiency or suspected severe immunodeficiency is not recommended. (See "Infection prevention: Precautions for preventing transmission of infection", section on 'Standard precautions' and 'Shedding and transmission of vaccine virus' below.)

Immunocompromised household contact — Rotavirus vaccines can be administered to infants living in households with immunocompromised persons [1,5,44]. (See 'Shedding and transmission of vaccine virus' below.)

Resource-poor countries with high child mortality — The World Health Organization recommends routine rotavirus vaccination for all its member countries [24]. Rotavirus vaccine effectiveness varies among the countries that have introduced a rotavirus vaccine into the routine infant immunization schedule [81-92]. Although poverty is a surrogate marker for poorer population vaccine effectiveness [93-96], rotavirus vaccine remains effective in reducing rotavirus-related hospitalization and emergency department visits in resource-poor countries with high child mortality [92,97-99]. (See 'Efficacy/effectiveness' below.)

Factors that may explain variation in vaccine effectiveness include:

Greater portion of missed vaccination opportunities, related to the narrow age range for administration [87,89]

Failure to adopt a universal recommendation for rotavirus vaccination (which may prevent or reduce herd immunity) [100,101]

Variation in herd effect with increasing interval from initiation of universal vaccination with high uptake [83,102,103]

Relatively increased natural, wild-type rotavirus circulation, reducing rotavirus vaccine effectiveness with increasing interval from initiation of universal vaccination [85,104-106]

Naturally acquired rotavirus disease in infants too young to be vaccinated [82]

Attenuation of vaccine response by transplacental maternal antibody [107] or in infants who are exclusively breast-fed [108]

Coinfection with another diarrheal pathogen (eg, adenovirus 40/41, Shigella, norovirus) [109]

Malnutrition or poor diet (which may affect the intestinal biome) [82,91,110-112]

Immunogenic competition with simultaneous administration of oral polio vaccine, discussed below (see 'Administration with other vaccines' below)

Infant histo-blood group antigens and infant or maternal secretor status [113-116]

ADMINISTRATION — The licensed rotavirus vaccines are administered orally [1]. The dose varies with the vaccine and vaccine presentation (table 1) [1,45,46]:

Pentavalent human-bovine rotavirus reassortant vaccine (RV5) – 2 mL

Attenuated human rotavirus vaccine (RV1)

Ready-to-use presentations (squeezable tube or oral dose applicator without vial) – 1.5 mL

Presentation requiring reconstitution (oral dose applicator with vial) – 1 mL

To avoid loss of a portion of the dose and of splashes into the eyes of infants, caregivers, or health care providers, the vaccine should be administered gently inside the cheek [117].

Dietary restriction, including breastfeeding, is not needed before or after rotavirus vaccine is administered. Doses that are regurgitated, spit out, or vomited should not be repeated (they were not repeated in prelicensure studies of efficacy) [1,5,80]. Multiple randomized trials have demonstrated that breastfeeding does not affect rotavirus vaccine efficacy; normal breastfeeding was not altered in the prelicensure trials [39,40,54,55]. In randomized trials that specifically evaluated this issue, immune response was not affected by abstaining from breastfeeding for ≥1 hour before and after each dose of rotavirus vaccine [118-120].

In the event that rotavirus vaccine is injected rather than administered orally, the dose is not considered valid and should be repeated within the appropriate age and dosing schedule [117]. In a review of reports to the Vaccine Adverse Reporting System, adverse reactions to intramuscular injection were uncommon and mild (eg, local reactions, brief irritability).

ADMINISTRATION WITH OTHER VACCINES — Rotavirus vaccines can be administered at the same visit as the other routine infant immunizations [1,5,121,122].

Simultaneous administration of oral polio vaccine (OPV) may be associated with decreased immune response to the first dose of rotavirus vaccine, but this interference does not persist after subsequent doses [123-128]. OPV is not used in the United States. In countries where OPV continues to be used, the European Society for Pediatric Infectious Disease and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition suggest that rotavirus vaccines and OPV not be administered at the same visit [15].

EFFICACY/EFFECTIVENESS

Rotavirus gastroenteritis — The protection against rotavirus gastroenteritis provided by the licensed vaccines is similar to that observed following natural infection [79].

Overall effectiveness – The effectiveness of rotavirus immunization is difficult to determine because many children with rotavirus gastroenteritis do not seek medical attention; however, the number of stool samples sent for rotavirus testing and the number of positive samples can serve as a marker of vaccine effectiveness. Such laboratory surveillance indicates that during each rotavirus season since reintroduction of rotavirus vaccine in the United States in 2006, rotavirus activity was delayed in onset and diminished in magnitude compared with the 2000-2006 rotavirus seasons (figure 3) [129-131]. A pattern of alternating reduced and markedly reduced seasonality occurred from 2007-2008 through the 2017-2018 rotavirus seasons [131].

In an impact analysis of surveillance data from 198 sites in 69 predominantly low- and middle-income countries participating in the Global Rotavirus Surveillance Network, introduction of rotavirus vaccine was associated with a 40 percent relative reduction (95% CI 35-44 percent) in rotavirus-associated hospitalizations among children <5 year of age [90]. A similar decline in rotavirus hospitalizations among children <5 years of age following implementation of rotavirus vaccine was noted in the World Health African Region [132].

Efficacy and effectiveness of RV5 – In randomized trials and meta-analyses, pentavalent human-bovine rotavirus reassortant vaccine (RV5) was efficacious in preventing rotavirus gastroenteritis, rotavirus gastroenteritis hospitalization, and rotavirus gastroenteritis-associated health care utilization in infants [39,41,133,134]. RV5 protection appears to be sustained through the first four years of life [135-137].

A systematic review identified 15 randomized trials (88,934 participants) comparing RV5 with placebo [41]. Meta-analyses assessed vaccine efficacy separately for countries with low, medium, and high levels of child mortality:

In low-child-mortality countries, RV5 prevented 97 percent of cases of severe rotavirus gastroenteritis in the first year (risk ratio [RR] 0.03, 95% CI 0.01-0.11; five trials, 7688 participants) and 96 percent of cases in the second year (RR 0.04, 95% CI 0.01-0.11; two trials, 5442 participants).

In medium-child-mortality countries, RV5 prevented 79 percent of cases of severe rotavirus gastroenteritis at two years (RR 0.21, 95% CI 0.11-0.41; 1 trial, 1937 participants).

In high-child-mortality countries, RV5 prevented 57 percent of cases of severe rotavirus gastroenteritis in the first year (RR 0.43, 95% CI 0.29-0.64; two trials, 6775 participants) and 44 percent of cases in the second year (RR 0.56, 95% CI 0.41-0.77; two trials, 6744 participants). (See 'Resource-poor countries with high child mortality' above.)

The largest trial (the Rotavirus Efficacy and Safety Trial), which included 68,038 infants from both low- and high-child mortality countries, also noted protection against rotavirus gastroenteritis of any severity, reduced rotavirus gastroenteritis-associated hospitalization and emergency department visits, and reduced hospitalization for gastroenteritis from any cause [39].

In a systematic review of rotavirus vaccine effectiveness from 2006 to 2016, the median effectiveness of RV5 in preventing rotavirus hospitalizations, emergency department visits, and outpatient visits was 90 percent (range 63 to 100 percent) in 20 studies from countries with low child mortality and 45 percent (range 43 to 92 percent) in seven studies from countries with high child mortality [98].

Efficacy and effectiveness of RV1 – In randomized trials and meta-analyses, attenuated human rotavirus vaccine (RV1) is efficacious in preventing rotavirus gastroenteritis, rotavirus gastroenteritis hospitalizations, and rotavirus-gastroenteritis-associated health care utilization in infants [40,41,99,138,139].

A systematic review identified 36 randomized trials (119,114 participants) comparing RV1 with placebo [41]. Meta-analyses assessed vaccine efficacy separately for countries with low, medium, and high levels of child mortality:

In low-child-mortality countries, RV1 prevented 93 percent of cases of severe rotavirus gastroenteritis after one year (RR 0.07, 95% CI 0.03-0.18; four trials, 14,976 participants) and 90 percent of cases in the second year (RR 0.10, 95% CI 0.07-0.14; six trials, 18,145 participants). RV1 also prevented severe diarrhea from any cause.

In medium-child-mortality countries, RV1 prevented 79 percent of cases of severe rotavirus gastroenteritis in the first year (RR 0.21, 95% CI 0.16-0.29; four trials, 31,671 participants) and 78 percent of cases in the second year (RR 0.23, 95% CI 0.17-0.29; three trials, 23,834 participants).

In high-child-mortality countries, RV1 prevented 58 percent of cases of severe rotavirus gastroenteritis in the first year (RR 0.42, 95% CI 0.28-0.61; four trials, 9951 participants) and 35 percent of cases in the second year (RR 0.65, 95% CI 0.51-0.83; two trials, 7113 participants). (See 'Resource-poor countries with high child mortality' above.)

The largest trial comparing RV1 with placebo, which included 63,225 infants from both low- and high-child-mortality countries, also noted protection against rotavirus gastroenteritis of any severity and reduced rotavirus gastroenteritis-associated hospitalization and emergency department visits [40].

In a systematic review of rotavirus vaccine effectiveness from 2006 to 2016, the median effectiveness of RV1 in preventing rotavirus hospitalizations, emergency department visits, and outpatient visits was 84 percent (range 19 to 97 percent) in 13 studies from countries with low child mortality, 75 percent (range -2 to 94 percent) in eight studies from countries with medium child mortality, and 57 percent (range 18 to 69 percent) in nine studies from countries with high child mortality [98]. Protection appears to be sustained through the first four years of life [98,136,137]. A before-after cohort study from the Netherlands suggests that the effectiveness of RV1 may be reduced in infants with high-risk medical conditions (preterm birth, low birth weight, severe congenital disorders) [38].

In pooled analysis of phase 2 and 3 clinical trials, genotype-specific efficacy of RV1 was 92 percent against genotypes containing either the G1 or the P[8] antigen and 83 percent against genotypes containing neither the G1 nor the P[8] antigen [140].

Efficacy of Rotavac – A systematic review identified four randomized trials (8432 participants) comparing Rotavac with placebo in high-child-mortality countries [41]. Rotavac prevented 57 percent of cases of severe rotavirus gastroenteritis in the first year (RR 0.43, 95% CI 0.30-0.60; one trial, 6799 participants) and 54 percent by up to two years (RR 0.46, 95% CI 0.35-0.60; one trial, 6541 participants).

Efficacy of Rotasiil – In a meta-analysis of two trials (11,008 participants) comparing Rotasiil with placebo in high-child-mortality countries, Rotasiil prevented 48 percent of cases of severe rotavirus gastroenteritis in the first year (RR 0.52, 95% CI 0.33-0.81) and 44 percent of cases in the second year (RR 0.56, 95% CI 0.42-0.74) [41].

Incomplete immunization – A systematic review of postlicensure studies (2006 to 2016) found that incomplete immunization with RV5 or RV1 was effective in preventing rotavirus health care utilization but less effective than complete immunization [98].

Community ("herd") immunity — Rotavirus immunization in infants is associated with reduced rotavirus morbidity among unvaccinated neonates and young infants too young for vaccination, older children, and adults (ie, indirect protection or community ["herd"] immunity) [141-148]. Seventy percent vaccine uptake by 2010 significantly altered natural rotavirus disease peaks in most of the United States [142,149]. Even partial (approximately 50 percent) uptake of RV5 under a recommendation for universal immunization of infants with rotavirus vaccine was associated with reduced rotavirus disease in unvaccinated older children and adults [143-145,150,151]. As an example, compared with 2006, rates of hospitalization for rotavirus infection in 2008 were reduced among children younger than three years, whether or not they were vaccinated [151]. An 87 percent reduction occurred in the 6- to 11-month age group (with vaccine coverage 77 percent), a 96 percent reduction occurred in the 12- to 23-month age group (vaccine coverage 46 percent), and a 92 percent reduction occurred in the 24- to 35-month age group (vaccine coverage 1 percent). Similar results were observed at several and widely dispersed sites in North America [142,145,146,150,151]. Protection in older nonvaccinated children indicating community immunity has also been reported in England [152].

Other potential benefits — Rotavirus vaccine appears to reduce the risk of seizures [153-157]. In a cohort of >1.7 million commercially insured children in the United States, complete rotavirus vaccination was associated with a decreased risk of hospitalization for seizure before age five years compared with no vaccination (adjusted hazard ratio 0.76, 95% CI 0.67-0.87) [157]. The differential effects of febrile versus afebrile seizures could not be determined because of rarity of seizure hospitalization (estimated five-year risk of 0.35 percent).

In some observational studies, universal infant immunization against rotavirus has been associated with decreased incidence of type 1 diabetes mellitus [158-160], but this finding is inconsistent [161-164].

ADVERSE EVENTS AND SAFETY

Overview — Rotavirus immunization is safe. In prelicensure studies, the rates of death (<0.1 percent) and serious adverse events (approximately 2.5 percent) were similar among vaccine and placebo recipients [39,40]. Vaccine and placebo recipients also reported similar rates of solicited events, including of fever (approximately 42 percent), vomiting (approximately 13 percent), and diarrhea (approximately 19 percent), all of which were mild [39].

Intussusception

Risk with RV5, RV1, and Rotavac – Intussusception is a rare potential adverse effect of oral rotavirus vaccination, estimated to occur in approximately 1 in 20,000 to 1 in 100,000 vaccine recipients in high- and middle-income countries [165-171].

A history of intussusception is a contraindication to rotavirus vaccination [43], yet for infants without a history of intussusception, the risk of intussusception after rotavirus vaccination is much lower than the risk of severe rotavirus gastroenteritis in children who do not receive rotavirus vaccine [172-177].

Caregivers should contact their child's health care provider if the child develops signs of intussusception (ie, stomach pain, vomiting, diarrhea, blood in the stool, or change in bowel habits) any time after vaccination, but especially within the first 14 days after a dose was given [178]. (See "Intussusception in children", section on 'Clinical manifestations'.)

Prelicensure studies of pentavalent human-bovine rotavirus reassortant vaccine (RV5) and attenuated human rotavirus vaccine (RV1) found no increased risk of intussusception among vaccine recipients compared with placebo recipients [39,40]. Although postlicensure studies suggested a rare association between RV5 and RV1 vaccination and intussusception within 21 days of the first dose in high- and middle income countries [165-171,179,180], in two meta-analyses of pre- and postlicensure randomized trials from low-, middle-, and high-income countries, no differences in the rates of intussusception were detected between rotavirus vaccine (RV5, RV1, or Rotavac) and placebo groups [41,181]. In active surveillance, the risk of intussusception following RV1 administration was not increased in lower-income sub-Saharan African countries or following Rotavac administration in India [182,183]. Despite the small potential risk of intussusception, the absolute number of estimated rotavirus hospitalizations prevented by rotavirus vaccines far exceeds that of cases of intussusception associated with rotavirus vaccine (eg, 65,000 hospitalizations prevented and 40 to 120 cases of intussusception per year in the United States) [172]. The Centers for Disease Control and Prevention and World Health Organization Global Advisory Committee on Vaccine Safety continue to recommend universal rotavirus vaccine for infants [184,185].

Risk with RRV-TV – In 1999, just over a year after human-rhesus rotavirus reassortant vaccine (RRV-TV, RotaShield) was licensed, it was withdrawn from the market because of a strong epidemiologic link to intussusception [34-37]. The increased risk was estimated to be approximately 22-fold over the background risk within five to seven days of vaccination and overall approximately one excess case for every 10,000 to 12,000 infants vaccinated [36,186].

The mechanism of this association is unclear. One hypothesis is that vaccination triggered intussusception in infants who were likely to develop intussusception with any enteric infection, based upon the observation that rates of intussusception were actually lower among vaccine recipients than nonvaccinees in the period 4 to 12 weeks after vaccination [37]. Thus, RRV-TV may have caused intussusception in infants who otherwise would not have experienced intussusception, but it also may have protected against natural rotavirus infection-induced intussusception in others.

Rotavirus strain differences appear to make a difference in intussusception risk, as demonstrated by the reduced intussusception risk after RV5 or RV1 compared with RRV, and supported by results in a mouse model [187].

Kawasaki disease — Although cases of Kawasaki disease were reported during clinical trials of rotavirus vaccines and in postmarketing surveillance [45,46,188,189], no evidence of an association was identified in surveillance of >2 million doses of rotavirus vaccine administered to infants born from 2006 to 2017 [190].

Caregivers should contact their child's health care provider if the child develops signs of Kawasaki disease (eg, fever, conjunctivitis, erythema of the lips and oral mucosa, rash, swelling of the hands and feet, cervical lymphadenopathy), whether or not the child recently received rotavirus vaccine. (See "Kawasaki disease: Clinical features and diagnosis".)

Shedding and transmission of vaccine virus — Rotavirus shedding in the stool peaks within approximately seven days of administration and is most common after the first dose [45,46,191-194]. Viral shedding may be prolonged in infants with immunodeficiency [48,52,195].

Transmission of vaccine virus resulting in symptomatic gastroenteritis is known from three case reports [196-198]; separately, zero of 100 participants in a placebo-controlled twin study experienced symptomatic transmission of RV1 [199].

To minimize the risk of vaccine-derived rotavirus infections transmitted by the fecal-oral route, individuals who care for infants should wash their hands after changing a diaper. Particular care should be taken with this precaution for at least one week after the first dose. Highly immunocompromised individuals should avoid handling diapers of infants who have received rotavirus vaccine for at least four weeks after vaccination [44]. Highly immunocompromised individuals include (but are not limited to) those with combined primary immunodeficiency; receiving cancer chemotherapy; within two months of solid organ transplant; with HIV infection and CD4 count <200 cells/microL (adults and adolescents) or CD4 percentage <15 percent (infants and children); receiving daily glucocorticoid therapy for ≥14 days at a dose equivalent to prednisone ≥20 mg/day or >2 mg/kg per day, if they weigh <10 kg.

In the phase 3 prelicensure trial of RV5, 9 percent of subjects who were evaluated had fecal shedding of vaccine virus, detected by polymerase chain reaction (PCR), four to six days after the first dose [191,193]. None and 0.3 percent of recipients shed vaccine virus four to six days after the second and third dose, respectively. In studies of RV1, 50 to 80 percent of infants shed vaccine virus (PCR detection) at approximately one week and 24 percent at approximately one month after the first dose [200]. After the second dose, between 4 and 18 percent of recipients shed virus at one week and 1.2 percent at approximately one month. Because vaccine virus detection relies on PCR (a highly sensitive gene amplification method), the exact correlation between shedding of vaccine virus and viability/transmission is uncertain.

Transmission of vaccine virus has not been well studied; it appears to occur more frequently among recipients of RV1 than RV5 [192]; however, it rarely results in symptoms. In a randomized trial, in which one twin in each of 100 twin pairs received two doses of RV1 and the other twin received placebo, transmission of vaccine virus occurred in 15 of 80 evaluable cases (18.8 percent) but was not associated with symptomatic gastroenteritis [199]. In an observational study in Malawi, RV1 fecal shedding was detected in 68 percent of 60 vaccinated infants but only 1.4 percent of 147 household contacts, indicating that horizontal transmission of vaccine virus is also uncommon [201]. Asymptomatic transmission may contribute to community ("herd") immunity [192]. (See 'Community ("herd") immunity' above.)

Serotype selection — RV5 was first introduced into a national vaccine program in 2006. After introduction of RV5 (and subsequently of RV1), surveillance of rotavirus genotypes and rotavirus disease prevalence in countries with and without rotavirus vaccine programs has not demonstrated sustained selection of one or more serotypes due to vaccine selective pressure [202], although transient increases of a given serotype and decreased incidence of simultaneous infections with multiple rotavirus types (ie, "mixed infections") have been documented [88,203-206].

After nearly 15 years of rotavirus vaccine use, vaccine-related serotype selection/replacement seems to be at most a limited phenomenon, although continued surveillance is necessary to understand the epidemiologic significance of potential genetic/antigenic modifications in novel circulating strains for which licensed rotavirus vaccines may not be effective [87,88,205,207-212]. (See 'Microbiology' above.)

Reporting adverse events — In the United States, any clinically significant or unexpected adverse events that occur after administration of rotavirus vaccine (including intussusception and Kawasaki disease) should be reported to the Vaccine Adverse Event Reporting System (telephone number 1-800-822-7967) [1]. (See "Standard immunizations for children and adolescents: Overview", section on 'Reporting adverse events'.)

Porcine circovirus contamination — In 2010, an academic group using a novel technique found components of porcine circovirus (PCV1) in RV1 and the US Food and Drug Administration (FDA) temporarily suspended use of RV1 [213]. Additional review by the FDA and vaccine manufacturers determined that PCV1 components were present from the early stages of RV1 development, including during the prelicensure clinical trials, and that RV5 contained components of PCV1 and PCV2 [213,214].

Given that PCV1 and PCV2 are not known to cause illness in humans, and the absence of any evidence that millions of rotavirus vaccine recipients suffered adverse effects related to PCV, the FDA recommended resumption of use of RV1 and continued use of RV5 [214,215]. In a subsequent observational study, PCV1 did not appear to replicate in RV1 recipients [216].

The known benefits of the oral vaccination outweigh the theoretic risk related to PCV1 or PCV2 [217].

RESOURCES — Resources related to immunization in infants include:

The American Academy of Pediatrics

The Centers for Disease Control and Prevention

The Immunize.org

The Vaccine Information Statement for Rotavirus vaccine

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Immunizations in children and adolescents".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

Basics topic (see "Patient education: Rotavirus infection (The Basics)")

Beyond the Basics topic (see "Patient education: Vaccines for infants and children age 0 to 6 years (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Introduction – Rotavirus is the most common cause of severe gastroenteritis in infants and children around the world. (See 'Introduction' above.)

Rotavirus vaccines – Two oral vaccines are globally available for the prevention of rotavirus disease: pentavalent human-bovine reassortant rotavirus vaccine (RV5, PRV, RotaTeq) and attenuated human rotavirus vaccine (RV1, HRV, Rotarix) (table 1 and figure 2). The vaccines have similar efficacy and safety, and neither vaccine is preferred over the other. Two other vaccines are used in more restricted settings, and novel vaccine candidates, including parenteral vaccines, are under investigation. (See 'Rotavirus vaccines' above.)

Indications – We recommend universal immunization of infants against rotavirus (Grade 1A). Rotavirus vaccines are highly effective in preventing rotavirus gastroenteritis and rotavirus gastroenteritis-associated hospitalization and health care utilization. (See 'Indications' above and 'Efficacy/effectiveness' above.)

Contraindications and precautions – Contraindications to rotavirus vaccine include allergy to any of the vaccine ingredients, severe allergic reaction (anaphylaxis) to a previous dose, severe combined immunodeficiency (SCID), certain other primary and secondary immunodeficiencies, and history of intussusception. Latex-free presentations of RV1 and RV5 are available for infants with a history of severe allergic reaction to latex (table 1). (See 'Contraindications' above.)

Conditions that are precautions for administration of rotavirus vaccine include immunodeficiency other than SCID, acute moderate or severe illness, certain pre-existing or acquired gastrointestinal conditions (eg, congenital malabsorption syndromes, Hirschsprung disease, short-bowel syndrome, previous bowel surgery), and spina bifida or bladder exstrophy. (See 'Precautions' above.)

Schedule – The recommended dose and schedule for RV5 and RV1 differ (table 1). Whenever possible, the vaccine series should be completed with the same product; however, vaccination should not be deferred if the product used for previous doses is not known. (See 'Schedule' above.)

Adverse events and safety – Intussusception is a rare potential adverse effect of oral rotavirus vaccination in some settings; however, the risk of intussusception after rotavirus vaccination is much lower than the risk of severe rotavirus gastroenteritis in children who do not receive rotavirus vaccine. (See 'Adverse events and safety' above.)

Continued surveillance of rotavirus genotypes and rotavirus disease prevalence in countries with and without rotavirus vaccine programs is necessary to understand the epidemiologic significance of potential genetic/antigenic modifications in novel circulating strains for which licensed rotavirus vaccines may not be effective. (See 'Serotype selection' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate would like to acknowledge David O Matson, MD, PhD, who contributed to an earlier version of this topic review.

  1. Cortese MM, Parashar UD, Centers for Disease Control and Prevention (CDC). Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2009; 58:1.
  2. Parashar UD, Hummelman EG, Bresee JS, et al. Global illness and deaths caused by rotavirus disease in children. Emerg Infect Dis 2003; 9:565.
  3. Rotavirus vaccines. WHO position paper - July 2021. Wkly Epidemiol rec 2021:96:301. Available at: https://www.who.int/publications/i/item/WHO-WER9628 (Accessed on January 03, 2023).
  4. International Vaccine Access Center. Available at: http://view-hub.org (Accessed on January 03, 2023).
  5. American Academy of Pediatric. Rotavirus infections. In: Red Book: 2021-2024 Report of the Committee on Infectious Diseases, 32nd ed, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (Eds), American Academy of Pediatric, Itasca, IL 2021. p.644.
  6. Esona MD, Ward ML, Wikswo ME, et al. Rotavirus Genotype Trends and Gastrointestinal Pathogen Detection in the United States, 2014-2016: Results From the New Vaccine Surveillance Network. J Infect Dis 2021; 224:1539.
  7. Cunliffe NA, Bresee JS, Hart CA. Rotavirus vaccines: development, current issues and future prospects. J Infect 2002; 45:1.
  8. Conner ME, Matson DO, Estes MK. Rotavirus vaccines and vaccination potential. Curr Top Microbiol Immunol 1994; 185:285.
  9. Vesikari T. Rotavirus vaccines: development and use for the prevention of diarrhoeal disease. Ann Med 1999; 31:79.
  10. Glass RI, Parashar UD. The promise of new rotavirus vaccines. N Engl J Med 2006; 354:75.
  11. Clark HF, Bernstein DI, Dennehy PH, et al. Safety, efficacy, and immunogenicity of a live, quadrivalent human-bovine reassortant rotavirus vaccine in healthy infants. J Pediatr 2004; 144:184.
  12. Bhandari N, Rongsen-Chandola T, Bavdekar A, et al. Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial. Lancet 2014; 383:2136.
  13. Changotra H, Vij A. Rotavirus virus-like particles (RV-VLPs) vaccines: An update. Rev Med Virol 2017; 27.
  14. Groome MJ, Koen A, Fix A, et al. Safety and immunogenicity of a parenteral P2-VP8-P[8] subunit rotavirus vaccine in toddlers and infants in South Africa: a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis 2017; 17:843.
  15. Vesikari T, Van Damme P, Giaquinto C, et al. European Society for Paediatric Infectious Diseases consensus recommendations for rotavirus vaccination in Europe: update 2014. Pediatr Infect Dis J 2015; 34:635.
  16. RotaTeq (Rotavirus vaccine, live, oral, pentavalent). United States Prescribing Information. Revised February 2017, US Food & Drug Administration. Available online at: https://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm094063.htm (Accessed on March 07, 2017).
  17. De Vos B, Han HH, Bouckenooghe A, et al. Live attenuated human rotavirus vaccine, RIX4414, provides clinical protection in infants against rotavirus strains with and without shared G and P genotypes: integrated analysis of randomized controlled trials. Pediatr Infect Dis J 2009; 28:261.
  18. Santosham M, Steele D. Rotavirus Vaccines - A New Hope. N Engl J Med 2017; 376:1170.
  19. Mi K, Ou X, Guo L, et al. Comparative analysis of the immunogenicity of monovalent and multivalent rotavirus immunogens. PLoS One 2017; 12:e0172156.
  20. Kirkwood CD, Steele AD. Rotavirus Vaccines in China: Improvement Still Required. JAMA Netw Open 2018; 1:e181579.
  21. World Health Organization. Rotasiil. Available at: https://extranet.who.int/pqweb/content/rotasiil (Accessed on March 02, 2023).
  22. Sun ZW, Fu Y, Lu HL, et al. Association of Rotavirus Vaccines With Reduction in Rotavirus Gastroenteritis in Children Younger Than 5 Years: A Systematic Review and Meta-analysis of Randomized Clinical Trials and Observational Studies. JAMA Pediatr 2021; 175:e210347.
  23. Isanaka S, Guindo O, Langendorf C, et al. Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger. N Engl J Med 2017; 376:1121.
  24. Loharikar A, Dumolard L, Chu S, et al. Status of New Vaccine Introduction - Worldwide, September 2016. MMWR Morb Mortal Wkly Rep 2016; 65:1136.
  25. Kulkarni PS, Desai S, Tewari T, et al. A randomized Phase III clinical trial to assess the efficacy of a bovine-human reassortant pentavalent rotavirus vaccine in Indian infants. Vaccine 2017; 35:6228.
  26. Kanungo S, Chatterjee P, Bavdekar A, et al. Safety and immunogenicity of the Rotavac and Rotasiil rotavirus vaccines administered in an interchangeable dosing schedule among healthy Indian infants: a multicentre, open-label, randomised, controlled, phase 4, non-inferiority trial. Lancet Infect Dis 2022; 22:1191.
  27. Xia S, Du J, Su J, et al. Efficacy, immunogenicity and safety of a trivalent live human-lamb reassortant rotavirus vaccine (LLR3) in healthy Chinese infants: A randomized, double-blind, placebo-controlled trial. Vaccine 2020; 38:7393.
  28. Desselberger U, Huppertz HI. Immune responses to rotavirus infection and vaccination and associated correlates of protection. J Infect Dis 2011; 203:188.
  29. Bines JE, At Thobari J, Satria CD, et al. Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth. N Engl J Med 2018; 378:719.
  30. Bines JE, Danchin M, Jackson P, et al. Safety and immunogenicity of RV3-BB human neonatal rotavirus vaccine administered at birth or in infancy: a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis 2015; 15:1389.
  31. Witte D, Handley A, Jere KC, et al. Neonatal rotavirus vaccine (RV3-BB) immunogenicity and safety in a neonatal and infant administration schedule in Malawi: a randomised, double-blind, four-arm parallel group dose-ranging study. Lancet Infect Dis 2022; 22:668.
  32. Thiem VD, Anh DD, Ha VH, et al. Safety and immunogenicity of two formulations of rotavirus vaccine in Vietnamese infants. Vaccine 2021; 39:4463.
  33. Recommended childhood immunization schedule-United States, January-December 1999. American Academy of Pediatrics Committee on Infectious Diseases. Pediatrics 1999; 103:182.
  34. Peter G, Myers MG, National Vaccine Advisory Committee, National Vaccine Program Office. Intussusception, rotavirus, and oral vaccines: summary of a workshop. Pediatrics 2002; 110:e67.
  35. Centers for Disease Control and Prevention (CDC). Intussusception among recipients of rotavirus vaccine--United States, 1998-1999. MMWR Morb Mortal Wkly Rep 1999; 48:577.
  36. Murphy TV, Gargiullo PM, Massoudi MS, et al. Intussusception among infants given an oral rotavirus vaccine. N Engl J Med 2001; 344:564.
  37. Murphy BR, Morens DM, Simonsen L, et al. Reappraisal of the association of intussusception with the licensed live rotavirus vaccine challenges initial conclusions. J Infect Dis 2003; 187:1301.
  38. van Dongen JAP, Rouers EDM, Schuurman R, et al. Rotavirus Vaccine Safety and Effectiveness in Infants With High-Risk Medical Conditions. Pediatrics 2021; 148.
  39. Vesikari T, Matson DO, Dennehy P, et al. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N Engl J Med 2006; 354:23.
  40. Ruiz-Palacios GM, Pérez-Schael I, Velázquez FR, et al. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med 2006; 354:11.
  41. Bergman H, Henschke N, Hungerford D, et al. Vaccines for preventing rotavirus diarrhoea: vaccines in use. Cochrane Database Syst Rev 2021; 11:CD008521.
  42. Centers for Disease Control and Prevention (CDC). Addition of severe combined immunodeficiency as a contraindication for administration of rotavirus vaccine. MMWR Morb Mortal Wkly Rep 2010; 59:687.
  43. Centers for Disease Control and Prevention (CDC). Addition of history of intussusception as a contraindication for rotavirus vaccination. MMWR Morb Mortal Wkly Rep 2011; 60:1427.
  44. Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014; 58:e44.
  45. Rotarix (oral dosing applicator). US Food and Drug Administration (FDA) approved product information. Revised November 2022. Available online at https://www.fda.gov/media/163009/download (Accessed on January 03, 2023).
  46. Rotarix (squeezable tube). US Food and Drug Administration (FDA) approved product information. Revised December 2022. Available online at https://www.fda.gov/media/163010/download (Accessed on January 03, 2023).
  47. Patel NC, Hertel PM, Estes MK, et al. Vaccine-acquired rotavirus in infants with severe combined immunodeficiency. N Engl J Med 2010; 362:314.
  48. Werther RL, Crawford NW, Boniface K, et al. Rotavirus vaccine induced diarrhea in a child with severe combined immune deficiency. J Allergy Clin Immunol 2009; 124:600.
  49. Bakare N, Menschik D, Tiernan R, et al. Severe combined immunodeficiency (SCID) and rotavirus vaccination: reports to the Vaccine Adverse Events Reporting System (VAERS). Vaccine 2010; 28:6609.
  50. Kaplon J, Cros G, Ambert-Balay K, et al. Rotavirus vaccine virus shedding, viremia and clearance in infants with severe combined immune deficiency. Pediatr Infect Dis J 2015; 34:326.
  51. Morillo-Gutierrez B, Worth A, Valappil M, et al. Chronic Infection with Rotavirus Vaccine Strains in UK Children with Severe Combined Immunodeficiency. Pediatr Infect Dis J 2015; 34:1040.
  52. Gower CM, Dunning J, Nawaz S, et al. Vaccine-derived rotavirus strains in infants in England. Arch Dis Child 2020; 105:553.
  53. MedWatch. The FDA safety information and adverse event reporting program. Drug safety labeling changes. Rotarix (rotavirus vaccine, live, oral) oral suspension. http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm230397.htm (Accessed on April 18, 2011).
  54. Goveia MG, DiNubile MJ, Dallas MJ, et al. Efficacy of pentavalent human-bovine (WC3) reassortant rotavirus vaccine based on breastfeeding frequency. Pediatr Infect Dis J 2008; 27:656.
  55. Vesikari T, Prymula R, Schuster V, et al. Efficacy and immunogenicity of live-attenuated human rotavirus vaccine in breast-fed and formula-fed European infants. Pediatr Infect Dis J 2012; 31:509.
  56. Nguyen GC, Seow CH, Maxwell C, et al. The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy. Gastroenterology 2016; 150:734.
  57. Mahadevan U, Wolf DC, Dubinsky M, et al. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2013; 11:286.
  58. Julsgaard M, Christensen LA, Gibson PR, et al. Concentrations of Adalimumab and Infliximab in Mothers and Newborns, and Effects on Infection. Gastroenterology 2016; 151:110.
  59. Beaulieu DB, Ananthakrishnan AN, Martin C, et al. Use of Biologic Therapy by Pregnant Women With Inflammatory Bowel Disease Does Not Affect Infant Response to Vaccines. Clin Gastroenterol Hepatol 2018; 16:99.
  60. Groome MJ, Madhi SA. Five-year cohort study on the burden of hospitalisation for acute diarrhoeal disease in African HIV-infected and HIV-uninfected children: potential benefits of rotavirus vaccine. Vaccine 2012; 30 Suppl 1:A173.
  61. Steele AD, Madhi SA, Louw CE, et al. Safety, Reactogenicity, and Immunogenicity of Human Rotavirus Vaccine RIX4414 in Human Immunodeficiency Virus-positive Infants in South Africa. Pediatr Infect Dis J 2011; 30:125.
  62. Levin MJ, Lindsey JC, Kaplan SS, et al. Safety and immunogenicity of a live attenuated pentavalent rotavirus vaccine in HIV-exposed infants with or without HIV infection in Africa. AIDS 2017; 31:49.
  63. Department of Health and Human Services. Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children. Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children. Available at: aidsinfo.nih.gov/contentfiles/lvguidelines/oi_guidelines_pediatrics.pdf (Accessed on May 02, 2019).
  64. Javid PJ, Sanchez SE, Jacob S, et al. The Safety and Immunogenicity of Rotavirus Vaccination in Infants With Intestinal Failure. J Pediatric Infect Dis Soc 2014; 3:57.
  65. McGrath EJ, Thomas R, Duggan C, Asmar BI. Pentavalent rotavirus vaccine in infants with surgical gastrointestinal disease. J Pediatr Gastroenterol Nutr 2014; 59:44.
  66. Lopez RN, Krishnan U, Ooi CY. Enteritis with pneumatosis intestinalis following rotavirus immunisation in an infant with short bowel syndrome. BMJ Case Rep 2017; 2017.
  67. Libster R, McNeal M, Walter EB, et al. Safety and Immunogenicity of Sequential Rotavirus Vaccine Schedules. Pediatrics 2016; 137:e20152603.
  68. Payne DC, Sulemana I, Parashar UD, New Vaccine Surveillance Network. Evaluation of Effectiveness of Mixed Rotavirus Vaccine Course for Rotavirus Gastroenteritis. JAMA Pediatr 2016; 170:708.
  69. Payne DC, Selvarangan R, Azimi PH, et al. Long-term Consistency in Rotavirus Vaccine Protection: RV5 and RV1 Vaccine Effectiveness in US Children, 2012-2013. Clin Infect Dis 2015; 61:1792.
  70. Mandomando I, Mumba M, Nsiari-Muzeyi Biey J, et al. Implementation of the World Health Organization recommendation on the use of rotavirus vaccine without age restriction by African countries. Vaccine 2021; 39:3111.
  71. Goveia MG, Rodriguez ZM, Dallas MJ, et al. Safety and efficacy of the pentavalent human-bovine (WC3) reassortant rotavirus vaccine in healthy premature infants. Pediatr Infect Dis J 2007; 26:1099.
  72. Dahl RM, Curns AT, Tate JE, Parashar UD. Effect of Rotavirus Vaccination on Acute Diarrheal Hospitalizations Among Low and Very Low Birth Weight US Infants, 2001-2015. Pediatr Infect Dis J 2018; 37:817.
  73. Rotavirus. In Australian Immunisation Handbook, 10th edition. Available at: http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home~handbook10part4~handbook10-4-17#4.17.6 (Accessed on January 08, 2018).
  74. Monk HM, Motsney AJ, Wade KC. Safety of rotavirus vaccine in the NICU. Pediatrics 2014; 133:e1555.
  75. Thrall S, Doll MK, Nhan C, et al. Evaluation of pentavalent rotavirus vaccination in neonatal intensive care units. Vaccine 2015; 33:5095.
  76. Hofstetter AM, Lacombe K, Klein EJ, et al. Risk of Rotavirus Nosocomial Spread After Inpatient Pentavalent Rotavirus Vaccination. Pediatrics 2018; 141.
  77. Hiramatsu H, Suzuki R, Nagatani A, et al. Rotavirus Vaccination Can Be Performed Without Viral Dissemination in the Neonatal Intensive Care Unit. J Infect Dis 2018; 217:589.
  78. Burke RM, Tate JE, Han GS, et al. Rotavirus Vaccination Coverage During a Rotavirus Outbreak Resulting in a Fatality at a Subacute Care Facility. J Pediatric Infect Dis Soc 2020; 9:287.
  79. Velázquez FR, Matson DO, Calva JJ, et al. Rotavirus infection in infants as protection against subsequent infections. N Engl J Med 1996; 335:1022.
  80. Centers for Disease Control and Prevention. General best practice guidelines for immunization. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/index.html (Accessed on May 16, 2019).
  81. Abeid KA, Jani B, Cortese MM, et al. Monovalent Rotavirus Vaccine Effectiveness and Impact on Rotavirus Hospitalizations in Zanzibar, Tanzania: Data From the First 3 Years After Introduction. J Infect Dis 2017; 215:183.
  82. Narváez J, Osorio MB, Castañeda-Orjuela C, et al. Is Colombia reaching the goals on infant immunization coverage? A quantitative survey from 80 municipalities. Vaccine 2017; 35:1501.
  83. Bennett A, Bar-Zeev N, Cunliffe NA. Measuring indirect effects of rotavirus vaccine in low income countries. Vaccine 2016; 34:4351.
  84. Madhi SA, Cunliffe NA, Steele D, et al. Effect of human rotavirus vaccine on severe diarrhea in African infants. Malawi Med J 2016; 28:108.
  85. Velázquez RF, Linhares AC, Muñoz S, et al. Efficacy, safety and effectiveness of licensed rotavirus vaccines: a systematic review and meta-analysis for Latin America and the Caribbean. BMC Pediatr 2017; 17:14.
  86. Gruber JF, Hille DA, Liu GF, et al. Heterogeneity of Rotavirus Vaccine Efficacy Among Infants in Developing Countries. Pediatr Infect Dis J 2017; 36:72.
  87. Wylie KM, Stanley KM, TeKippe EM, et al. Resurgence of Rotavirus Genotype G12 in St. Louis During the 2014-2015 Rotavirus Season. J Pediatric Infect Dis Soc 2017; 6:346.
  88. Muhsen K, Kassem E, Rubenstein U, et al. Incidence of rotavirus gastroenteritis hospitalizations and genotypes, before and five years after introducing universal immunization in Israel. Vaccine 2016; 34:5916.
  89. Lo Vecchio A, Liguoro I, Dias JA, et al. Rotavirus immunization: Global coverage and local barriers for implementation. Vaccine 2017; 35:1637.
  90. Aliabadi N, Antoni S, Mwenda JM, et al. Global impact of rotavirus vaccine introduction on rotavirus hospitalisations among children under 5 years of age, 2008-16: findings from the Global Rotavirus Surveillance Network. Lancet Glob Health 2019; 7:e893.
  91. Khagayi S, Omore R, Otieno GP, et al. Effectiveness of Monovalent Rotavirus Vaccine Against Hospitalization With Acute Rotavirus Gastroenteritis in Kenyan Children. Clin Infect Dis 2020; 70:2298.
  92. Otieno GP, Bottomley C, Khagayi S, et al. Impact of the Introduction of Rotavirus Vaccine on Hospital Admissions for Diarrhea Among Children in Kenya: A Controlled Interrupted Time-Series Analysis. Clin Infect Dis 2020; 70:2306.
  93. Tissera MS, Cowley D, Bogdanovic-Sakran N, et al. Options for improving effectiveness of rotavirus vaccines in developing countries. Hum Vaccin Immunother 2017; 13:921.
  94. Al-Aidaroos AYA, Standaert B, Meszaros K, Shibl AM. Economic assessment of rotavirus vaccination in Saudi Arabia. J Infect Public Health 2017; 10:564.
  95. Hill HA, Elam-Evans LD, Yankey D, et al. Vaccination Coverage Among Children Aged 19-35 Months - United States, 2015. MMWR Morb Mortal Wkly Rep 2016; 65:1065.
  96. Gosselin V, Petit G, Gagneur A, Généreux M. Trends in severe gastroenteritis among young children according to socio-economic characteristics before and after implementation of a rotavirus vaccination program in Quebec. Can J Public Health 2016; 107:e161.
  97. Burnett E, Jonesteller CL, Tate JE, et al. Global Impact of Rotavirus Vaccination on Childhood Hospitalizations and Mortality From Diarrhea. J Infect Dis 2017; 215:1666.
  98. Jonesteller CL, Burnett E, Yen C, et al. Effectiveness of Rotavirus Vaccination: A Systematic Review of the First Decade of Global Postlicensure Data, 2006-2016. Clin Infect Dis 2017; 65:840.
  99. Mujuru HA, Burnett E, Nathoo KJ, et al. Monovalent Rotavirus Vaccine Effectiveness Against Rotavirus Hospitalizations Among Children in Zimbabwe. Clin Infect Dis 2019; 69:1339.
  100. Loganathan T, Jit M, Hutubessy R, et al. Rotavirus vaccines contribute towards universal health coverage in a mixed public-private healthcare system. Trop Med Int Health 2016; 21:1458.
  101. Santos VS, Marques DP, Martins-Filho PR, et al. Effectiveness of rotavirus vaccines against rotavirus infection and hospitalization in Latin America: systematic review and meta-analysis. Infect Dis Poverty 2016; 5:83.
  102. Holubar M, Stavroulakis MC, Maldonado Y, et al. Impact of vaccine herd-protection effects in cost-effectiveness analyses of childhood vaccinations. A quantitative comparative analysis. PLoS One 2017; 12:e0172414.
  103. Markkula J, Hemming-Harlo M, Salminen MT, et al. Rotavirus epidemiology 5-6 years after universal rotavirus vaccination: persistent rotavirus activity in older children and elderly. Infect Dis (Lond) 2017; 49:388.
  104. da Silva MF, Fumian TM, de Assis RM, et al. VP7 and VP8* genetic characterization of group A rotavirus genotype G12P[8]: Emergence and spreading in the Eastern Brazilian coast in 2014. J Med Virol 2017; 89:64.
  105. Asada K, Kamiya H, Suga S, et al. Rotavirus vaccine and health-care utilization for rotavirus gastroenteritis in Tsu City, Japan. Western Pac Surveill Response J 2016; 7:28.
  106. Rogawski ET, Platts-Mills JA, Colgate ER, et al. Quantifying the Impact of Natural Immunity on Rotavirus Vaccine Efficacy Estimates: A Clinical Trial in Dhaka, Bangladesh (PROVIDE) and a Simulation Study. J Infect Dis 2018; 217:861.
  107. Mwila K, Chilengi R, Simuyandi M, et al. Contribution of Maternal Immunity to Decreased Rotavirus Vaccine Performance in Low- and Middle-Income Countries. Clin Vaccine Immunol 2017; 24.
  108. Bautista-Marquez A, Velasquez DE, Esparza-Aguilar M, et al. Breastfeeding linked to the reduction of both rotavirus shedding and IgA levels after Rotarix® immunization in Mexican infants. Vaccine 2016; 34:5284.
  109. Praharaj I, Platts-Mills JA, Taneja S, et al. Diarrheal Etiology and Impact of Coinfections on Rotavirus Vaccine Efficacy Estimates in a Clinical Trial of a Monovalent Human-Bovine (116E) Oral Rotavirus Vaccine, Rotavac, India. Clin Infect Dis 2019; 69:243.
  110. Becker-Dreps S, Vilchez S, Bucardo F, et al. The Association Between Fecal Biomarkers of Environmental Enteropathy and Rotavirus Vaccine Response in Nicaraguan Infants. Pediatr Infect Dis J 2017; 36:412.
  111. Harris VC, Armah G, Fuentes S, et al. Significant Correlation Between the Infant Gut Microbiome and Rotavirus Vaccine Response in Rural Ghana. J Infect Dis 2017; 215:34.
  112. Burnett E, Parashar UD, Tate JE. Rotavirus Infection, Illness, and Vaccine Performance in Malnourished Children: A Review of the Literature. Pediatr Infect Dis J 2021; 40:930.
  113. Armah GE, Cortese MM, Dennis FE, et al. Rotavirus Vaccine Take in Infants Is Associated With Secretor Status. J Infect Dis 2019; 219:746.
  114. Kazi AM, Cortese MM, Yu Y, et al. Secretor and Salivary ABO Blood Group Antigen Status Predict Rotavirus Vaccine Take in Infants. J Infect Dis 2017; 215:786.
  115. Pollock L, Bennett A, Jere KC, et al. Nonsecretor Histo-blood Group Antigen Phenotype Is Associated With Reduced Risk of Clinical Rotavirus Vaccine Failure in Malawian Infants. Clin Infect Dis 2019; 69:1313.
  116. Williams FB, Kader A, Colgate ER, et al. Maternal Secretor Status Affects Oral Rotavirus Vaccine Response in Breastfed Infants in Bangladesh. J Infect Dis 2021; 224:1147.
  117. Hibbs BF, Miller ER, Shimabukuro T, Centers for Disease Control and Prevention (CDC). Notes from the field: rotavirus vaccine administration errors--United States, 2006-2013. MMWR Morb Mortal Wkly Rep 2014; 63:81.
  118. Groome MJ, Moon SS, Velasquez D, et al. Effect of breastfeeding on immunogenicity of oral live-attenuated human rotavirus vaccine: a randomized trial in HIV-uninfected infants in Soweto, South Africa. Bull World Health Organ 2014; 92:238.
  119. Rongsen-Chandola T, Strand TA, Goyal N, et al. Effect of withholding breastfeeding on the immune response to a live oral rotavirus vaccine in North Indian infants. Vaccine 2014; 32 Suppl 1:A134.
  120. Ali A, Kazi AM, Cortese MM, et al. Impact of withholding breastfeeding at the time of vaccination on the immunogenicity of oral rotavirus vaccine--a randomized trial. PLoS One 2015; 10:e0127622.
  121. Rodriguez ZM, Goveia MG, Stek JE, et al. Concomitant use of an oral live pentavalent human-bovine reassortant rotavirus vaccine with licensed parenteral pediatric vaccines in the United States. Pediatr Infect Dis J 2007; 26:221.
  122. Ciarlet M, He S, Lai S, et al. Concomitant use of the 3-dose oral pentavalent rotavirus vaccine with a 3-dose primary vaccination course of a diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-Haemophilus influenzae type b vaccine: immunogenicity and reactogenicity. Pediatr Infect Dis J 2009; 28:177.
  123. Ramani S, Mamani N, Villena R, et al. Rotavirus Serum IgA Immune Response in Children Receiving Rotarix Coadministered With bOPV or IPV. Pediatr Infect Dis J 2016; 35:1137.
  124. Tregnaghi MW, Abate HJ, Valencia A, et al. Human rotavirus vaccine is highly efficacious when coadministered with routine expanded program of immunization vaccines including oral poliovirus vaccine in Latin America. Pediatr Infect Dis J 2011; 30:e103.
  125. Ciarlet M, Sani-Grosso R, Yuan G, et al. Concomitant use of the oral pentavalent human-bovine reassortant rotavirus vaccine and oral poliovirus vaccine. Pediatr Infect Dis J 2008; 27:874.
  126. Steele AD, De Vos B, Tumbo J, et al. Co-administration study in South African infants of a live-attenuated oral human rotavirus vaccine (RIX4414) and poliovirus vaccines. Vaccine 2010; 28:6542.
  127. Zaman K, Sack DA, Yunus M, et al. Successful co-administration of a human rotavirus and oral poliovirus vaccines in Bangladeshi infants in a 2-dose schedule at 12 and 16 weeks of age. Vaccine 2009; 27:1333.
  128. Baker JM, Tate JE, Leon J, et al. Antirotavirus IgA seroconversion rates in children who receive concomitant oral poliovirus vaccine: A secondary, pooled analysis of Phase II and III trial data from 33 countries. PLoS Med 2019; 16:e1003005.
  129. Leshem E, Tate JE, Steiner CA, et al. Acute gastroenteritis hospitalizations among US children following implementation of the rotavirus vaccine. JAMA 2015; 313:2282.
  130. Kaufman HW, Chen Z. Trends in Laboratory Rotavirus Detection: 2003 to 2014. Pediatrics 2016; 138.
  131. Hallowell BD, Parashar UD, Curns A, et al. Trends in the Laboratory Detection of Rotavirus Before and After Implementation of Routine Rotavirus Vaccination - United States, 2000-2018. MMWR Morb Mortal Wkly Rep 2019; 68:539.
  132. Mwenda JM, Hallowell BD, Parashar U, et al. Impact of Rotavirus Vaccine Introduction on Rotavirus Hospitalizations Among Children Under 5 Years of Age-World Health Organization African Region, 2008-2018. Clin Infect Dis 2021; 73:1605.
  133. Grant LR, Watt JP, Weatherholtz RC, et al. Efficacy of a pentavalent human-bovine reassortant rotavirus vaccine against rotavirus gastroenteritis among American Indian children. Pediatr Infect Dis J 2012; 31:184.
  134. Lamberti LM, Ashraf S, Walker CL, Black RE. A Systematic Review of the Effect of Rotavirus Vaccination on Diarrhea Outcomes Among Children Younger Than 5 Years. Pediatr Infect Dis J 2016; 35:992.
  135. Leshem E, Moritz RE, Curns AT, et al. Rotavirus vaccines and health care utilization for diarrhea in the United States (2007-2011). Pediatrics 2014; 134:15.
  136. Getachew HB, Dahl RM, Lopman BA, Parashar UD. Rotavirus Vaccines and Health Care Utilization for Diarrhea in US Children, 2001 to 2015. Pediatr Infect Dis J 2018; 37:943.
  137. Payne DC, Englund JA, Weinberg GA, et al. Association of Rotavirus Vaccination With Inpatient and Emergency Department Visits Among Children Seeking Care for Acute Gastroenteritis, 2010-2016. JAMA Netw Open 2019; 2:e1912242.
  138. Vesikari T, Karvonen A, Prymula R, et al. Efficacy of human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in European infants: randomised, double-blind controlled study. Lancet 2007; 370:1757.
  139. Linhares AC, Velázquez FR, Pérez-Schael I, et al. Efficacy and safety of an oral live attenuated human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in Latin American infants: a randomised, double-blind, placebo-controlled phase III study. Lancet 2008; 371:1181.
  140. Amin AB, Tate JE, Waller LA, et al. Monovalent Rotavirus Vaccine Efficacy Against Different Rotavirus Genotypes: A Pooled Analysis of Phase II and III Trial Data. Clin Infect Dis 2023; 76:e1150.
  141. Atchison CJ, Stowe J, Andrews N, et al. Rapid Declines in Age Group-Specific Rotavirus Infection and Acute Gastroenteritis Among Vaccinated and Unvaccinated Individuals Within 1 Year of Rotavirus Vaccine Introduction in England and Wales. J Infect Dis 2016; 213:243.
  142. Tate JE, Haynes A, Payne DC, et al. Trends in national rotavirus activity before and after introduction of rotavirus vaccine into the national immunization program in the United States, 2000 to 2012. Pediatr Infect Dis J 2013; 32:741.
  143. Dey A, Wang H, Menzies R, Macartney K. Changes in hospitalisations for acute gastroenteritis in Australia after the national rotavirus vaccination program. Med J Aust 2012; 197:453.
  144. Lopman BA, Payne DC, Tate JE, et al. Post-licensure experience with rotavirus vaccination in high and middle income countries; 2006 to 2011. Curr Opin Virol 2012; 2:434.
  145. Anderson EJ, Shippee DB, Weinrobe MH, et al. Indirect protection of adults from rotavirus by pediatric rotavirus vaccination. Clin Infect Dis 2013; 56:755.
  146. Gastañaduy PA, Curns AT, Parashar UD, Lopman BA. Gastroenteritis hospitalizations in older children and adults in the United States before and after implementation of infant rotavirus vaccination. JAMA 2013; 310:851.
  147. Prelog M, Gorth P, Zwazl I, et al. Universal Mass Vaccination Against Rotavirus: Indirect Effects on Rotavirus Infections in Neonates and Unvaccinated Young Infants Not Eligible for Vaccination. J Infect Dis 2016; 214:546.
  148. Baker JM, Tate JE, Steiner CA, et al. Longer-term Direct and Indirect Effects of Infant Rotavirus Vaccination Across All Ages in the United States in 2000-2013: Analysis of a Large Hospital Discharge Data Set. Clin Infect Dis 2019; 68:976.
  149. Aliabadi N, Tate JE, Haynes AK, et al. Sustained decrease in laboratory detection of rotavirus after implementation of routine vaccination—United States, 2000-2014. MMWR Morb Mortal Wkly Rep 2015; 64:337.
  150. Lopman BA, Curns AT, Yen C, Parashar UD. Infant rotavirus vaccination may provide indirect protection to older children and adults in the United States. J Infect Dis 2011; 204:980.
  151. Payne DC, Staat MA, Edwards KM, et al. Direct and indirect effects of rotavirus vaccination upon childhood hospitalizations in 3 US Counties, 2006-2009. Clin Infect Dis 2011; 53:245.
  152. Thomas SL, Walker JL, Fenty J, et al. Impact of the national rotavirus vaccination programme on acute gastroenteritis in England and associated costs averted. Vaccine 2017; 35:680.
  153. Payne DC, Baggs J, Zerr DM, et al. Protective association between rotavirus vaccination and childhood seizures in the year following vaccination in US children. Clin Infect Dis 2014; 58:173.
  154. Pardo-Seco J, Cebey-López M, Martinón-Torres N, et al. Impact of Rotavirus Vaccination on Childhood Hospitalization for Seizures. Pediatr Infect Dis J 2015; 34:769.
  155. Sheridan SL, Ware RS, Grimwood K, Lambert SB. Febrile Seizures in the Era of Rotavirus Vaccine. J Pediatric Infect Dis Soc 2016; 5:206.
  156. Pringle KD, Burke RM, Steiner CA, et al. Trends in Rate of Seizure-Associated Hospitalizations Among Children <5 Years Old Before and After Rotavirus Vaccine Introduction in the United Sates, 2000-2013. J Infect Dis 2018; 217:581.
  157. Burke RM, Tate JE, Dahl RM, et al. Rotavirus Vaccination Is Associated With Reduced Seizure Hospitalization Risk Among Commercially Insured US Children. Clin Infect Dis 2018; 67:1614.
  158. Rogers MAM, Basu T, Kim C. Lower Incidence Rate of Type 1 Diabetes after Receipt of the Rotavirus Vaccine in the United States, 2001-2017. Sci Rep 2019; 9:7727.
  159. Perrett KP, Jachno K, Nolan TM, Harrison LC. Association of Rotavirus Vaccination With the Incidence of Type 1 Diabetes in Children. JAMA Pediatr 2019; 173:280.
  160. Blumenfeld O, Lawrence G, Shulman LM, Laron Z. Use of the Whole Country Insulin Consumption Data in Israel to Determine the Prevalence of Type 1 Diabetes in Children <5 Years of Age Before and During Rotavirus Vaccination. Pediatr Infect Dis J 2021; 40:771.
  161. Glanz JM, Clarke CL, Xu S, et al. Association Between Rotavirus Vaccination and Type 1 Diabetes in Children. JAMA Pediatr 2020; 174:455.
  162. Vaarala O, Jokinen J, Lahdenkari M, Leino T. Rotavirus Vaccination and the Risk of Celiac Disease or Type 1 Diabetes in Finnish Children at Early Life. Pediatr Infect Dis J 2017; 36:674.
  163. Burke RM, Tate JE, Dahl RM, et al. Rotavirus Vaccination and Type 1 Diabetes Risk Among US Children With Commercial Insurance. JAMA Pediatr 2020; 174:383.
  164. Hemming-Harlo M, Lähdeaho ML, Mäki M, Vesikari T. Rotavirus Vaccination Does Not Increase Type 1 Diabetes and May Decrease Celiac Disease in Children and Adolescents. Pediatr Infect Dis J 2019; 38:539.
  165. Patel MM, López-Collada VR, Bulhões MM, et al. Intussusception risk and health benefits of rotavirus vaccination in Mexico and Brazil. N Engl J Med 2011; 364:2283.
  166. Velázquez FR, Colindres RE, Grajales C, et al. Postmarketing surveillance of intussusception following mass introduction of the attenuated human rotavirus vaccine in Mexico. Pediatr Infect Dis J 2012; 31:736.
  167. Haber P, Patel M, Pan Y, et al. Intussusception after rotavirus vaccines reported to US VAERS, 2006-2012. Pediatrics 2013; 131:1042.
  168. Carlin JB, Macartney KK, Lee KJ, et al. Intussusception risk and disease prevention associated with rotavirus vaccines in Australia's National Immunization Program. Clin Infect Dis 2013; 57:1427.
  169. Weintraub ES, Baggs J, Duffy J, et al. Risk of intussusception after monovalent rotavirus vaccination. N Engl J Med 2014; 370:513.
  170. Yih WK, Lieu TA, Kulldorff M, et al. Intussusception risk after rotavirus vaccination in U.S. infants. N Engl J Med 2014; 370:503.
  171. Leino T, Ollgren J, Strömberg N, Elonsalo U. Evaluation of the Intussusception Risk after Pentavalent Rotavirus Vaccination in Finnish Infants. PLoS One 2016; 11:e0144812.
  172. Centers for Disease Control and Prevention. Vaccine Safety. Rotavirus. http://www.cdc.gov/vaccinesafety/vaccines/rotavsb.html (Accessed on September 04, 2013).
  173. Centers for Disease Control and Prevention. Rotarix® rotavirus vaccine: Rare side effect possible. Questions and answers for parents and caregivers. http://www.cdc.gov/vaccines/vpd-vac/rotavirus/Vac-label-parents.htm (Accessed on September 23, 2010).
  174. Desai R, Cortese MM, Meltzer MI, et al. Potential intussusception risk versus benefits of rotavirus vaccination in the United States. Pediatr Infect Dis J 2013; 32:1.
  175. Glass RI, Parashar UD. Rotavirus vaccines--balancing intussusception risks and health benefits. N Engl J Med 2014; 370:568.
  176. Buttery JP, Standish J, Bines JE. Intussusception and rotavirus vaccines: consensus on benefits outweighing recognized risk. Pediatr Infect Dis J 2014; 33:772.
  177. Meissner HC. Complexity in Assessing the Benefit vs Risk of Vaccines: Experience With Rotavirus and Dengue Virus Vaccines. JAMA 2019; 322:1861.
  178. U.S. Food and Drug Administration. Information on Rotarix--Labeling revision pertaining to intussusception. http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm226690.htm (Accessed on September 23, 2010).
  179. Shui IM, Baggs J, Patel M, et al. Risk of intussusception following administration of a pentavalent rotavirus vaccine in US infants. JAMA 2012; 307:598.
  180. Tate JE, Yen C, Steiner CA, et al. Intussusception Rates Before and After the Introduction of Rotavirus Vaccine. Pediatrics 2016; 138.
  181. Lu HL, Ding Y, Goyal H, Xu HG. Association Between Rotavirus Vaccination and Risk of Intussusception Among Neonates and Infants: A Systematic Review and Meta-analysis. JAMA Netw Open 2019; 2:e1912458.
  182. Tate JE, Mwenda JM, Armah G, et al. Evaluation of Intussusception after Monovalent Rotavirus Vaccination in Africa. N Engl J Med 2018; 378:1521.
  183. Reddy SN, Nair NP, Tate JE, et al. Intussusception after Rotavirus Vaccine Introduction in India. N Engl J Med 2020; 383:1932.
  184. Global Advisory Committee on Vaccine Safety, 11–12 December 2013. Wkly Epidemiol Rec 2014; 89:53.
  185. Wodi AP, Murthy N, McNally V, et al. Advisory Committee on Immunization Practices Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger - United States, 2023. MMWR Morb Mortal Wkly Rep 2023; 72:137.
  186. DeStefano F, Vaccine Safety Datalink Research Group. The Vaccine Safety Datalink project. Pharmacoepidemiol Drug Saf 2001; 10:403.
  187. Warfield KL, Blutt SE, Crawford SE, et al. Rotavirus infection enhances lipopolysaccharide-induced intussusception in a mouse model. J Virol 2006; 80:12377.
  188. RotaTeq® [Rotavirus Vaccine, Live, Oral, Pentavalent] product label http://www.merck.com/product/usa/pi_circulars/r/rotateq/rotateq_pi.pdf (Accessed on August 02, 2011).
  189. Information pertaining to labeling revision for RotaTeq http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm142393.htm (Accessed on August 02, 2011).
  190. Kamidani S, Panagiotakopoulos L, Licata C, et al. Kawasaki Disease Following the 13-valent Pneumococcal Conjugate Vaccine and Rotavirus Vaccines. Pediatrics 2022; 150.
  191. Dennehy PH, Goveia MG, Dallas MJ, Heaton PM. The integrated phase III safety profile of the pentavalent human-bovine (WC3) reassortant rotavirus vaccine. Int J Infect Dis 2007; 11 Suppl 2:S36.
  192. Anderson EJ. Rotavirus vaccines: viral shedding and risk of transmission. Lancet Infect Dis 2008; 8:642.
  193. Matson DO, Vesikari T, Dennehy P, et al. Analysis by rotavirus gene 6 reverse transcriptase-polymerase chain reaction assay of rotavirus-positive gastroenteritis cases observed during the vaccination phase of the Rotavirus Efficacy and Safety Trial (REST). Hum Vaccin Immunother 2014; 10:2267.
  194. Ye S, Whiley DM, Ware RS, et al. Multivalent Rotavirus Vaccine and Wild-type Rotavirus Strain Shedding in Australian Infants: A Birth Cohort Study. Clin Infect Dis 2018; 66:1411.
  195. Uygungil B, Bleesing JJ, Risma KA, et al. Persistent rotavirus vaccine shedding in a new case of severe combined immunodeficiency: A reason to screen. J Allergy Clin Immunol 2010; 125:270.
  196. Payne DC, Edwards KM, Bowen MD, et al. Sibling transmission of vaccine-derived rotavirus (RotaTeq) associated with rotavirus gastroenteritis. Pediatrics 2010; 125:e438.
  197. Hemming M, Vesikari T. Detection of rotateq vaccine-derived, double-reassortant rotavirus in a 7-year-old child with acute gastroenteritis. Pediatr Infect Dis J 2014; 33:655.
  198. Sakon N, Miyamoto R, Komano J. An infant with acute gastroenteritis caused by a secondary infection with a Rotarix-derived strain. Eur J Pediatr 2017; 176:1275.
  199. Rivera L, Peña LM, Stainier I, et al. Horizontal transmission of a human rotavirus vaccine strain--a randomized, placebo-controlled study in twins. Vaccine 2011; 29:9508.
  200. Centers for Disease Control and Prevention. Rotavirus. In: Epidemiology and Prevention of Vaccine-Preventable Diseases. The Pink Book: Course Textbook, 13th ed, Hamborsky J, Kroger A, Wolfe S, (Eds). Public Health Foundation, Washington, DC 2015. http://www.cdc.gov/vaccines/pubs/pinkbook/index.html (Accessed on July 09, 2015).
  201. Bennett A, Pollock L, Jere KC, et al. Infrequent Transmission of Monovalent Human Rotavirus Vaccine Virus to Household Contacts of Vaccinated Infants in Malawi. J Infect Dis 2019; 219:1730.
  202. Leshem E, Lopman B, Glass R, et al. Distribution of rotavirus strains and strain-specific effectiveness of the rotavirus vaccine after its introduction: a systematic review and meta-analysis. Lancet Infect Dis 2014; 14:847.
  203. Roczo-Farkas S, Kirkwood CD, Cowley D, et al. The Impact of Rotavirus Vaccines on Genotype Diversity: A Comprehensive Analysis of 2 Decades of Australian Surveillance Data. J Infect Dis 2018; 218:546.
  204. Reyes JF, Wood JG, Beutels P, et al. Beyond expectations: Post-implementation data shows rotavirus vaccination is likely cost-saving in Australia. Vaccine 2017; 35:345.
  205. Bowen MD, Mijatovic-Rustempasic S, Esona MD, et al. Rotavirus Strain Trends During the Postlicensure Vaccine Era: United States, 2008-2013. J Infect Dis 2016; 214:732.
  206. Maguire JE, Glasgow K, Glass K, et al. Rotavirus Epidemiology and Monovalent Rotavirus Vaccine Effectiveness in Australia: 2010-2017. Pediatrics 2019; 144.
  207. Bernstein DI. Rotavirus Vaccines: Mind Your Ps and Gs. J Infect Dis 2018; 218:519.
  208. Hungerford D, Allen DJ, Nawaz S, et al. Impact of rotavirus vaccination on rotavirus genotype distribution and diversity in England, September 2006 to August 2016. Euro Surveill 2019; 24.
  209. Al-Ayed MS, Asaad AM, Qureshi MA, Hawan AA. Epidemiology of group A rotavirus infection after the introduction of monovalent vaccine in the National Immunization Program of Saudi Arabia. J Med Virol 2017; 89:429.
  210. Zeller M, Heylen E, Tamim S, et al. Comparative analysis of the Rotarix™ vaccine strain and G1P[8] rotaviruses detected before and after vaccine introduction in Belgium. PeerJ 2017; 5:e2733.
  211. Mukhopadhya I, Murdoch H, Berry S, et al. Changing molecular epidemiology of rotavirus infection after introduction of monovalent rotavirus vaccination in Scotland. Vaccine 2017; 35:156.
  212. Roczo-Farkas S, Kirkwood CD, Bines JE, and the Australian Rotavirus Surveillance Group. Australian Rotavirus Surveillance Program annual report, 2015. Commun Dis Intell Q Rep 2016; 40:E527.
  213. US Food and Drug Administration. Components of extraneous virus detected in Rotarix vaccine; no known safety risk www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm205625.htm (Accessed on March 22, 2010).
  214. U.S. Food and Drug Administration. Update on recommendations for the use of rotavirus vaccines. www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm212140.htm (Accessed on May 17, 2010).
  215. Victoria JG, Wang C, Jones MS, et al. Viral nucleic acids in live-attenuated vaccines: detection of minority variants and an adventitious virus. J Virol 2010; 84:6033.
  216. Mijatovic-Rustempasic S, Immergluck LC, Parker TC, et al. Shedding of porcine circovirus type 1 DNA and rotavirus RNA by infants vaccinated with Rotarix®. Hum Vaccin Immunother 2017; 13:928.
  217. Kuehn BM. FDA: Benefits of rotavirus vaccination outweigh potential contamination risk. JAMA 2010; 304:30.
Topic 6023 Version 76.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟