Chapter 13: Rotavirus

Authors: Julia M. Baker, PhD, MPH; Jacqueline E. Tate, PhD, MPH; Rashi Gautam, PhD, MS; Umesh D. Parashar, MBBS, MPH

Key points

This chapter provides general guidance for vaccine-preventable disease surveillance, describing the disease background/epidemiology, case investigation and reporting/notification, disease case definitions, and activities for enhancing surveillance, case investigation, and outbreak control for rotavirus.

Disease Description

Before the advent of rotavirus vaccines, rotavirus was the most common cause of severe gastroenteritis in infants and young children and caused nearly 500,000 deaths among young children globally each year.1 Introduction of the rotavirus vaccine into national immunization programs of over 120 countries2 has resulted in dramatic decreases in rotavirus infections and transmission in those settings, including the United States.34 Rotavirus illness can range in severity from mild, watery diarrhea of limited duration to severe diarrhea with vomiting and fever that can result in dehydration with shock, electrolyte imbalance, and on very rare occasions for US children, death.567 Following an incubation period of 1–3 days, the illness often begins abruptly, and vomiting often precedes the onset of diarrhea. Gastrointestinal symptoms generally resolve in 3–7 days. Up to one-third of patients have a temperature of >102°F (>39°C). Severe, dehydrating rotavirus infection occurs primarily among children 3–35 months of age.567891011

Rotaviruses are shed in high concentrations in the stools of infected persons and are transmitted primarily by the fecal-oral route, both through close person-to-person contact and through fomites.12131415 Rotaviruses may also be transmitted by other modes, such as respiratory droplets and fecally contaminated food and water.81617 Rotavirus is highly communicable with a small infectious dose of <100 virus particles.1318 Prior to vaccine introduction, the proportion of severe diarrhea due to rotavirus was similar among children across geographic settings,1920 suggesting that improved hygienic measures and sanitation are not sufficient to lead to significant declines in rotavirus burden. For this reason, rotavirus vaccines have been identified as and remain the optimal strategy to decrease the burden associated with severe and fatal rotavirus diarrhea worldwide.21

Repeated rotavirus exposures occur throughout the human lifespan, however, birth cohort studies have demonstrated a progressive reduction in risk of symptomatic illness with subsequent infection.2223 Symptomatic illness is less common among older children and adults. Children who are immune compromised sometimes experience severe, prolonged, and even fatal rotavirus gastroenteritis.24252627 Rotavirus infections do occur among US adults but tend to be milder or even asymptomatic. In some adults, especially those who have underlying medical conditions or who are older adults, rotavirus can still cause severe gastroenteritis requiring medical care.28

Background

Rotaviruses are nonenveloped RNA viruses belonging to the Sedoreoviridae family.29 The viral nucleocapsid is composed of three concentric shells that enclose 11 segments of double-stranded RNA. The outermost layer contains two structural viral proteins (VPs): VP4, the protease-cleaved protein (P protein) and VP7, the glycoprotein (G protein).8 These two proteins define the serotype of the virus and are considered critical to vaccine development because they are targets for neutralizing antibodies that might be important for protection.30 Because the two gene segments that encode these proteins can segregate independently, a typing system consisting of both P and G types has been developed.3132

Rotavirus serotypes (as described above) are classified within groups. Nine groups (A-I) have been defined based on differences in the VP6 protein.[8] Group A rotaviruses are the most common cause of rotavirus-related illness in humans though groups B and C have also been identified in human epidemics or infections.333435363738 Although human rotavirus strains that possess a high degree of genetic homology with animal strains have been identified, animal-to-human transmission of whole virions appears to be uncommon. Most human rotaviruses having some genetic similarity to animal rotaviruses appear to be formed by reassortment of one or more animal rotavirus genes into a human rotavirus during a mixed infection in vivo.3940

Prior to rotavirus vaccine introduction, viruses containing five distinct G and P combinations were most prevalent: G1[P8], G2[P4], G3P[8], G4P[8], and G9P[8].3941424344 In recent years, G12P[8] has become a predominant strain among severe rotavirus gastroenteritis cases in the United States (Figure 1), although secular variation by geographic region is frequently observed.45464748

Figure 1. Genotype prevalence for rotavirus positive samples collected from 7 U.S. New Vaccine Surveillance Network Sites by season: (A) 2009-2013 seasons and (B) 2014-2016 seasons.45

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Figure 1. Genotype prevalence for rotavirus positive samples collected from 7 U.S. New Vaccine Surveillance Network Sites by season: (A) 2009-2013 seasons and (B) 2014-2016.[45]
Figure 1

Vaccination

RotaTeq

In 2006, RotaTeq, a live, oral, human-bovine reassortant rotavirus vaccine produced by Merck and Company (Whitehouse Station, New Jersey) was recommended by the Advisory Committee on Immunization Practices (ACIP) for routine vaccination of US infants. Three doses of this vaccine are recommended to be administered at 2, 4, and 6 months of age, concurrently with other vaccines given at this age. RotaTeq contains five reassortant rotaviruses developed from human and bovine parent rotavirus strains that express human outer capsid proteins of five common circulating strains (G1, G2, G3, G4, and P[8] [subgroup P1A]).49

RotaTeq was tested in two phase III trials,5051 including a large-scale clinical trial of more than 70,000 infants enrolled primarily in the United States and Finland. The efficacy of three doses of RotaTeq against G1-G4 rotavirus gastroenteritis of any severity was 74% (95% confidence interval [CI] = 67%, 80%) and against severe G1-G4 rotavirus gastroenteritis was 98% (95% CI = 88%, 100%). RotaTeq was observed to be effective against each targeted serotype and reduced the incidence of medical office visits by 86% (95% CI = 74%, 93%), emergency department (ED) visits by 94% (95% CI = 89%, 97%), and rotavirus gastroenteritis hospitalizations by 96% (95% CI = 91%, 98%). Efficacy against all gastroenteritis hospitalizations of any etiology was 59% (95% CI = 52%, 65%).50

Rotarix

In 2008, ACIP updated its rotavirus vaccination recommendation to include Rotarix (produced by GlaxoSmithKline Biologicals, Rixensart, Belgium). This live vaccine contains the attenuated monovalent G1P[8] human rotavirus strain and is recommended by the manufacturer to be orally administered in two doses to infants at 2 and 4 months of age.52

In a large clinical trial of more than 63,000 infants from 11 Latin American countries and Finland, Rotarix was found to be safe and highly immunogenic.53 During the first year after vaccination, the efficacy (as defined by the Vesikari 20-point scoring system) of two doses of Rotarix against hospitalization due to severe rotavirus was 85% and increased up to 100% against more severe rotavirus gastroenteritis. Rotarix was protective against hospitalizations due to all causes of gastroenteritis (42% protection for the first year, 95% CI=29%, 53%). Rotarix provided protection against a broad range of rotavirus serotypes during the 2-year study period, including against the less common G9P[8] strain.53 In a randomized, double-blind, placebo-controlled study conducted in six European countries, Rotarix was further confirmed to be highly protective.54 The efficacy of Rotarix through the first rotavirus season against any grade of severity of rotavirus gastroenteritis was 87% (95% CI = 80%, 92%) and against severe rotavirus gastroenteritis (as defined by a score ≥11 on the Vesikari scale) was 96% (95% CI=90%, 99%). Rotarix reduced hospitalizations for all-cause gastroenteritis regardless of presumed etiology by 75% (95% CI = 46%, 89%). The efficacy of Rotarix through two rotavirus seasons against severe rotavirus gastroenteritis was 90% (95% CI= 85%, 94%), and in reducing hospitalizations was 96% (95% CI= 84%, 100%).54

Further recommendations

While one study conducted among children in a high child mortality country found RotaTeq induces a stronger and longer-lasting immune response compared to Rotarix,55 no clinical trial has yet compared the efficacy of Rotarix against that of RotaTeq in the United States, and ACIP offers no vaccine preference. For harmonization of vaccination administration scheduling, the ACIP recommends that, for both vaccines, the maximum age for dose 1 is 14 weeks and six days, and the maximum age for the last dose of rotavirus vaccine is 8 months and 0 days.4952

The ACIP recommends that a child's rotavirus vaccine series be completed with the same product whenever possible but allows interchanging vaccine types if the product used for a previous dose(s) is not available or is unknown. In such situations, ACIP recommends that "If any dose in the series was RV5 (RotaTeq) or the vaccine product is unknown for any dose in the series, a total of three doses of rotavirus vaccine should be administered." In a study comparing these two vaccines concurrently administered in childhood populations, the complete 3-course rotavirus vaccination regimen with mixed RotaTeq and Rotarix vaccines retained a statistically significant level of protection against severe rotavirus gastroenteritis that was nearly identical to that observed for complete, single vaccine type regimens.56

Rotavirus vaccines are contraindicated for: 1) infants diagnosed with severe combined immunodeficiency, 2) infants with a history of intussusception, and 3) infants with a history of a severe allergic reaction to a previous rotavirus vaccine dose or to vaccine com­ponent. Infants with a severe allergy to latex should not receive Rotarix.5257

Furthermore, ACIP specifies that the vaccine should be administered to clinically stable preterm infants who fulfill the chronological age requirements (i.e., 6 weeks through 14 weeks and 6 days of age for dose 1) at or after discharge from the neonatal intensive care unit (or nursery).52 However, infants born prematurely or with underlying conditions are at increased risk of severe rotavirus disease and associated complications and may not be age-eligible for vaccination at the time of their discharge.58 Recent data found no evidence of nosocomial rotavirus vaccine-strain transmission in neonatal intensive care unit settings and suggest that risk in institutions with acceptable infection control standards is likely low.5960

International use

Rotavirus vaccines have been introduced into the national immunization programs of more than 120 countries.2 In the global setting, in addition to RotaTeq and Rotarix, two new live, oral rotavirus vaccines are increasingly being integrated into national immunization programs in Africa and Asia.61 Rotasiil (Serum Institute of India), a pentavalent vaccine (G1, G2, G3, G4, and G9),6263 and Rotavac (Bharat Biotech), a monovalent vaccine (G9P[11]),64 are administered in 3-dose series at 6, 10, and 14 weeks of age.61 Rotasiil and Rotavac demonstrate comparable efficacy to RotaTeq and Rotarix in African and Asian countries at 36-67%.626364 All four of these vaccines have been prequalified by the World Health Organization—RotaTeq in 2008, Rotarix in 2009, and Rotavac and Rotasiil in 2018.61

Vaccine coverage

Rotavirus vaccination rates among US children 19–35 months of age have been estimated using systematic sampling methods by the National Immunization Survey since 2009. Over the last several years, US rotavirus vaccine coverage has remained steady with approximately three-quarters of children completing the full vaccine course. This is notably lower than coverage of other routine childhood vaccinations such as DTaP (≥3-dose coverage of 94%) or poliovirus vaccine (≥3-dose coverage of 93%)65

Post-licensure vaccine impact

During the pre-rotavirus vaccine era, an estimated 410,000 physician visits, 205-272,000 ED visits, and 55,000–70,000 hospitalizations were attributable to rotavirus infections in US children, costing approximately $1 billion annually.66 The licensure and approval by ACIP of rotavirus vaccines brought dramatic overall declines in the rotavirus disease burden among US children, which have been consistently observed in various surveillance efforts.

Numerous post-licensure publications documenting rotavirus vaccine impact have demonstrated great declines in the incidence of rotavirus gastroenteritis. In an 18-state analysis of hospital discharge data (accounting for 49% of the US population) from 2000 to 2008, acute, all-cause gastroenteritis hospitalization rates for children <5 years of age were calculated. Compared with the median rate for the 2000–2006 rotavirus seasons, the rates for 2007 and 2008 were 16% and 45% lower, respectively. This analysis was among the first to find that RotaTeq vaccine introduction was associated with a dramatic reduction in rotavirus gastroenteritis among US children almost immediately following rotavirus vaccine introduction.38

Analyses in other databases and clinical settings have reinforced those findings. Laboratory-based data from the National Respiratory and Enteric Virus Surveillance System (NREVSS) (Figure 2),3 child hospitalization data from the State Inpatient Databases67,[ rotavirus gastroenteritis emergency department (ED) data from the State Emergency Department Visit database,68 and active surveillance from the New Vaccine Surveillance Network (NVSN)69 have all demonstrated dramatic declines in rotavirus-related illness since vaccine introduction. Combining these and other surveillance system evaluations, the median reduction in rotavirus associated hospitalizations since vaccine introduction is estimated to be 80% (Interquartile range: 63%-82%).66

Figure 2. Rotavirus testing and percent positivity from 2000-2018 using passively reported U.S. laboratory rotavirus test data (NREVSS).3

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Figure 2. Rotavirus testing and percent positivity from 2000-2018 using passively reported U.S. laboratory rotavirus test data (NREVSS).[3]
Figure 2

Each of these analyses also revealed an interesting biennial rotavirus disease trend, regardless of clinical setting. This biennial trend emerged immediately following rotavirus vaccine introduction with rotavirus incidence sharply curtailed during the winters of even-numbered years (e.g., 2008, 2010, 2012) and a slight increase during odd-numbered years (e.g., 2009, 2011, 2013), albeit to a level remaining below that observed during the prevaccine era. Predicted in rotavirus modeling analyses,70 this observed biennial trend in clinical and laboratory reports is believed to be due to annual fluctuations in susceptible children and the efficiency of rotavirus transmission. Rotavirus vaccination rates of eligible US children appear to be high enough to temporarily limit disease transmission, but since fewer than 80% have received vaccine, those unvaccinated children who remain susceptible to disease accumulate over time until a period when rotavirus transmission in a population can again occur with efficiency. Whether this pattern will continue if vaccine coverage increases will require ongoing surveillance of seasonal trends.667172

Rotavirus vaccines have been observed to provide indirect protective benefits, even among those who have not been vaccinated. Analyses of large hospital discharge databases have shown a statistically significantly lower rate of rotavirus- or unspecified-gastroenteritis hospitalization across age groups73 and among household members having a vaccinated child.74

In terms of direct medical costs, during the prevaccine era the median medical cost per hospitalized child was $3,581, from analyses of actively collected billing records of laboratory-confirmed US cases.75 The rotavirus hospitalization rate in 2006 was 22.1/10,000, with an estimated annual national cost of $91 million. Increased costs were associated with study site, age <3 months of age, underlying medical conditions, and an atypical acute gastroenteritis presentation. For ED visits, the prevaccine median medical cost per child was $574, and the ED visit rate was 291/10,000, resulting in an estimated annual national cost of $192 million (2009 dollars). In analyses of the Market Scan administrative database/Truven Commercial Claims database, NVSN, the State Inpatient Database and others, vaccine introduction is estimated to have reduced annual rotavirus and AGE-associated healthcare costs by $121–$231 million.66

Post-licensure vaccine effectiveness

Several studies have assessed vaccine performance using active, prospective surveillance in clinical settings with laboratory confirmation of rotavirus cases or large administrative databases. A meta-analysis of data from 2006–2017 found similar full-series VE for RotaTeq and Rotarix at 85% (95% CI = 80%, 87%) and 83% (95% CI = 72%, 89%), respectively. VE was high against both hospitalization (89%, 95% CI = 82%, 93%) and ED visits (79%, 95% CI = 75%, 83%).66 A more recent analysis of NVSN data spanning 2009 through 2022 found similarly high protection with any dose (≥1 dose) VE against rotavirus-associated ED visits or hospitalization of 78% (95% CI = 75%, 80%). VE ranged from 59% (95% CI = 49%, 67%) for mild rotavirus-associated acute gastroenteritis to 94% (95% CI = 90%, 97%) against very severe disease. The vaccines provide strong protection against commonly circulating genotypes. In age-stratified analyses, the highest VE was observed among children less than three years of age and decreased with increasing age (Figure 3).76

Figure 3. Rotavirus vaccine effectiveness against rotavirus-associated hospitalization or ED visit by age among children 8 months to 17 years, NVSN, 2010 to 2022.76

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Figure 3. Rotavirus vaccine effectiveness against rotavirus-associated hospitalization or ED visit by age among children 8 months to 17 years, NVSN, 2010 to 2022.[76]
Figure 3

Other benefits of rotavirus vaccination

Rotavirus infection is not limited to the intestine; antigenemia and viremia have been identified in children.777879 Wild-type rotavirus has been detected in cerebrospinal fluid (CSF) in cases of seizure occurring with diarrhea and neurologic illnesses have been attributed to rotavirus infection in multiple studies and case reports.80 Studies in some settings demonstrate that children vaccinated with rotavirus vaccine have a reduced risk of seizures compared with unvaccinated children.81 Several mechanisms may explain this protective association between rotavirus vaccination and seizures, although there is little clinical information to inform our understanding of this pathway. The most likely mechanism is that vaccination directly prevents systemic rotavirus infection, including extra-intestinal complications involving the central nervous system.82 Vaccination may also prevent secondary effects of rotavirus infection, including calcium channel fluctuations resulting in neurotransmitter dysregulation, elevation of nitric oxide in CSF that induces neurotoxicity, or changes in rotavirus enterotoxin NSP4.838485

Innate host factors influencing immunity to rotavirus

Histo-blood group antigens (HBGAs) are carbohydrates expressed on the mucosal epithelia of human respiratory, genitourinary, and digestive tracts that serve as host receptor sites necessary for bacterial/viral attachment and cellular entry and, therefore, infection. The expression of secretor antigen production (including FUT2) on HBGA's can be inactivated by single nucleotide polymorphisms (SNPs), and those individuals having genetically inactivated FUT2 production are termed nonsecretors.86 For rotaviruses, the association between secretor status and infection seems to be driven by increased likelihood of infection with P[8] rotaviruses among secretors (Figure 4).87 Emerging evidence suggests secretor-positive individuals may also have higher vaccine take.88

Figure 4. Susceptibility to rotavirus infection based on secretor status, by genotype.87

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Figure 4. Susceptibility to rotavirus infection based on secretor status, by genotype.[87]
Figure 4

Vaccine safety

A modestly elevated risk of intussusception (~1–6 cases per 100,000 vaccine recipients) among rotavirus vaccine recipients has been noted in some international settings and in the United States.899091929394 In the U.S. State Inpatient Database, an increase in the intussusception hospitalization rate was observed in children 8 to 11 weeks old, when the majority of first doses of vaccine are given.92 This finding is consistent with other US studies. The Vaccine Safety Datalink (VSD) analysis found the attributable risk of intussusception after the administration of two doses of Rotarix to be 5.3 per 100,000 infants vaccinated.93 VSD also found an upper limit for the attributable risk of one intussusception case per 65,287 RotaTeq dose-1 recipients.94 Given the magnitude of declines in rotavirus disease compared with this small increase in intussusception, the benefits of rotavirus vaccination are considered to outweigh the increased risk of intussusception.95

Importance of Surveillance

With rotavirus vaccines routinely used by the U.S. childhood immunization program, it remains important to conduct surveillance to:

  1. monitor the impact of vaccination in reducing morbidity and mortality from rotavirus disease over time;
  2. evaluate vaccine effectiveness in field use and identify and determine the causes of possible vaccine failure;
  3. monitor the possible emergence of rotavirus strains that might escape vaccination;
  4. identify population groups that might not be adequately covered by vaccination; and
  5. continue to monitor the safety of rotavirus vaccines.

Surveillance efforts should focus on monitoring trends of severe rotavirus disease, such as rotavirus hospitalizations or emergency room visits, at the national level and through more intensive efforts at sentinel sites. In addition to severe and medically-attended disease surveillance, viral strain surveillance is also important to evaluate whether strain variability is a secular phenomenon or whether it is the result of a potential selection of rotavirus serotypes through vaccine pressures.

Current active, passive, and laboratory-based national rotavirus surveillance includes the following:

  1. New Vaccine Surveillance Network (NVSN): Active rotavirus surveillance activities through NVSN began in the 2005–06 rotavirus season with three original sites and have continued prospectively with seven sites. Acute gastroenteritis cases are identified and additional epidemiological and clinical information is collected from parental interviews and medical chart reviews. Stool specimens are currently tested for rotavirus by RT-PCR at each study site, and CDC laboratories type all positive specimens. Analyses are conducted to estimate disease burden and to assess rotavirus vaccine effectiveness in field use.
  2. National Respiratory and Enteric Virus Surveillance System (NREVSS): Laboratory-based sentinel surveillance activities through the NREVSS monitor temporal and geographic patterns associated with the detection of several viruses, including rotavirus. Participating laboratories report the total number of fecal specimens submitted for rotavirus testing and the number that tested positive for rotavirus on a weekly basis to CDC. A subset of laboratories submits a representative sample of rotavirus-positive fecal specimens to CDC for strain characterization by molecular methods.
  3. Secondary analysis of national health utilization datasets: National estimates of the burden of rotavirus disease have been derived primarily through review of passive surveillance data on diarrhea mortality, hospitalizations, and ambulatory visits collected by the National Center for Health Statistics (e.g., the National Hospital Discharge Survey, the National Ambulatory Care Survey). In this approach, a set of International Classification of Diseases, Ninth and Tenth Volumes, Clinical Module (ICD–9 and 10–CM) codes have been first used to identify events attributable to acute gastroenteritis. Then, the unique epidemiologic characteristics of rotavirus gastroenteritis (i.e., predilection for children 4–35 months of age, marked winter seasonality) have been used to estimate the proportion of diarrhea events attributable to rotavirus. A rotavirus-specific ICD code was introduced in 1992. One validation study[96] found that this code had a high positive predictive value (i.e., coded events were highly likely to be true cases) but had a sensitivity of <50%. Nonetheless, by applying a variety of ICD codes related to acute gastroenteritis to these large databases and accounting for the seasonal and age-specific distributions of rotavirus incidence, it is possible to deduce large-scale rotavirus disease patterns and impacts.

Case Definitions

Definitive diagnosis of rotavirus gastroenteritis requires laboratory confirmation of infection. Currently, no case definition for rotavirus gastroenteritis is approved by the Council of State and Territorial Epidemiologists (CSTE; www.cste.org). Active surveillance being conducted at sentinel sites by CDC defines a confirmed case of rotavirus gastroenteritis as a child with diarrhea (≥3 loose stools in 24 hours) OR vomiting (≥1 episodes in 24 hours) and with detection of rotavirus in a fecal specimen by a standard assay (e.g., commercially available enzyme immunoassays).

Laboratory Testing

It is not possible to diagnose rotavirus infection by clinical presentation because the clinical features of rotavirus gastroenteritis do not differ from those of gastroenteritis caused by other pathogens. Confirmation of rotavirus infection by laboratory testing is necessary for reliable rotavirus surveillance and can be useful in clinical settings to avoid inappropriate use of antimicrobial therapy.6

Rotavirus is shed in high concentration in the stool of children with gastroenteritis and a fecal specimen is the preferred specimen for diagnosis.

Rotavirus detection assays

Rotavirus detection assays include electron microscopy (EM), cell culture isolation, polyacrylamide gel electrophoresis (PAGE) of viral segments, enzyme immunoassays (EIAs), latex agglutination tests, immunochromatographic tests, reverse transcription polymerase chain reaction (RT-PCR), real time or quantitative RT-PCR (qRT-PCR) and multi-pathogen diagnostic assays (Table 1).96 The most widely available method for detection of rotavirus antigen in stool is an enzyme immunoassay (EIA) directed at an antigen common to all group A rotaviruses. Several commercial EIA kits are available that are inexpensive, easy to use, rapid, and highly sensitive (approximately 90–100%), making them suitable for rotavirus surveillance and clinical diagnosis.9798 Polyacrylamide gel electrophoresis and silver staining is about as sensitive as EIA but is very labor intensive.99100 Latex agglutination is less sensitive and specific than EIA but is still used in some settings.101 Several multipathogen diagnostic kits are commercially available to rapidly detect enteric pathogens in a high throughput format, including the Luminex Gastrointestinal Pathogen Panel (xTAG GPP-Luminex Corporation) and Film Array Gastrointestinal Panel (Biofire Diagnostics).31 Other techniques including electron microscopy, RT-PCR and cell culture isolation for rotavirus detection are used primarily in research settings.

Serotyping and genotyping assays

Rotaviruses are traditionally classified based on the serologic/genetic characteristics of the aforementioned outer capsid proteins VP7 (G) and VP4 (P) that elicit neutralizing antibodies in the host. During rotavirus surveillance studies, both G and P serotypes/genotypes are monitored because they reassort independently from one another in vivo. Rotavirus strains can be characterized for VP7 and VP4 by molecular-based assays, including RT-PCR and qRT-PCR, which have increased sensitivity, higher throughput, and faster turnaround time31 (Table 1).

Sequencing assays

Sequence analysis is the definitive method for confirmation of rotavirus genotypes. Since the 1990s, the Sanger dye-termination sequencing method has been the most widely used method of automated DNA sequencing of VP7 and VP4 rotavirus genes. Currently, the genetic characterization of all 11 rotavirus genes is typically accomplished using next generation sequencing platforms such as the Illumina MiSeq (Illumina, San Diego, CA)[103,104] or the Nanopore MinION (Oxford Nanopore Technology, United Kingdom). Whole genome level characterization enables identification of reassortant strains beyond VP7 and VP4 genotyping102 (Table 1).

TABLE

Recommended chemoprophylaxis regimens for close contacts and persons with invasive meningococcal disease

Assay Method 

Assay Name

Cost

Time

Throughput

Sensitivity

Specificity

Advantages

Disadvantages

Reference

Detection

Electron Microscopy

High

Days

Low

Low

High

High specificity

Subjective interpretation of results

(Flewett, Davies et al. 1974)

Cell Culture Isolation

Low

Days

Low

Medium

Low

Low cost

Low throughput, prone to contamination

(Ward, Knowlton et al. 1984) (Arnold, Patton et al. 2009)

Poly Acrylamide Gel Electrophoresis (PAGE)

Low

Days

Low

Low

High

RV detection and electropherotype determination

Low throughput, labor intensive

(Herring, Inglis et al. 1982) (Matsui, Mackow et al. 1990)

Enzyme Immuno Assay (EIA)

Low

Hours

High

Medium

High

High throughput

Variable sensitivity and specificity of different EIA kits

(Dennehy, Gauntlett et al. 1988) (Gautam, Lyde et al. 2013)

Latex Agglutination

Low

Hours

High

Low

Low

Least complex

Low sensitivity and specificity

(Cevenini, Rumpianesi et al. 1983)

Immunochromatographic Tests

Low

Hours

High

Low

Low

Low cost and high throughput

Low sensitivity and specificity

(Lee, Hong et al. 2007)

Reverse transcription-polymerase chain reaction (RT-PCR)

Low

Hours

High

High

Medium

High throughput and high sensitivity

Cross reactivity of primers

(Wilde, Yolken et al. 1991)

Quantitative Reverse transcription-polymerase chain reaction (qRT-PCR-RVA)

Low

Hours

High

High

High

High throughput and high sensitivity

Cross reactivity of primers and probes

(Gutierrez-Aguirre, Steyer et al. 2008) (Kottaridi, Spathis et al. 2012) (Kang, Iturriza-Gomara et al. 2004) (Katz, Gautam et al. 2017) (Mijatovic-Rustempasic, Tam et al. 2013)

Multipathogen diagnostic assays

Low

Hours

High

High

High

High throughput and high sensitivity

Cross reactivity of primers and probes

(Gray and Coupland 2014) (Liu, Gratz et al. 2013) (Navidad, Griswold et al. 2013) (Reddington, Tuite et al. 2014)

Serotyping/
Genotyping

Serotyping

 Medium

Days

Low

Low

Low

Low cost

Low sensitivity and limited Mabs

(Gomara, Green et al. 2000)

RT-PCR

Low

Hours

High

High

Medium

High throughput and high sensitivity

Cross reactivity of primers

(Esona, Gautam et al. 2015)

qRT-PCR

Low

Hours

High

High

High

High throughput and high sensitivity

Cross reactivity of primers and probes

(Gautam, Mijatovic-Rustempasic et al. 2016) (Kottaridi, Spathis et al. 2012) (Liu, Lurain et al. 2015) (Podkolzin, Fenske et al. 2009)

TAC Card

Low

Hours

High

High

High

High throughput and high sensitivity

Cross reactivity of primers and probes

Unpublished

Sequencing

Sanger Sequencing

High

Days

High

Medium

Medium

High throughput and sequence availability

High cost and medium sensitivity/specificity

(Das, Gentsch et al. 1994) (Gentsch, Glass et al. 1992) (Iturriza-Gomara, Isherwood et al. 2001)

Next Generation Sequencing Using MiSeq

High

Days

High

Medium

Medium

High throughput and sequence availability

High cost and medium sensitivity/specificity

(Katz, Esona et al. 2019) (Sarkar, Esona et al. 2020)

Next Generation Sequencing Using MinION

High

Days

High

Medium

Medium

High throughput and sequence availability

High cost and medium sensitivity/specificity

(Kim, Yi et al. 2020)

Specimen collection

Specimen collection and shipping are important steps in obtaining laboratory diagnosis or disease confirmation. Guidelines have been published for specimen collection and handling for viral and microbiologic agents. Information is also available on using CDC laboratories as support for reference and disease surveillance; this includes

  • a central website for requesting lab testing;
  • the form required for submitting specimens to CDC (See Appendix 23, Form # CDC 50.34);
  • information on general requirements for shipment of etiologic agents (Appendix 24 [4 pages]) —although written to guide specimen submission to CDC, this information may be applicable to submission of specimens to other laboratories); and
  • the CDC Infectious Diseases Laboratories Test Directory, which contains not only a list of orderable tests for that institution, but also detailed information on appropriate specimen types, collection methods, specimen volume, shipping instructions and points of contact.

Reporting and Case Notification

Rotavirus gastroenteritis is not a nationally reportable disease and notification is not required by CDC. Contact the state health department for reporting requirements in your state.

Case Investigation

Case investigations are usually not warranted, except perhaps during outbreaks or in the case of deaths or other serious manifestations of rotavirus infections. Because diarrheal outbreaks can be caused by many pathogens, a laboratory investigation for the causative agent that includes viral, bacterial, and parasitic agents should be considered for gastroenteritis cases seeking medical attention.

Control

Routine immunization of infants is anticipated to be the most effective public health intervention for population-wide rotavirus infection control. Post-exposure vaccine prophylaxis is not a recommended strategy in response to an outbreak of rotavirus gastroenteritis.

Related

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  2. International Vaccine Access Center (IVAC), Johns Hopkins Bloomberg School of Public Health. Rotavirus vaccine (Rota) introduction & use [Internet]. VIEW-hub by IVAC. [cited 2024 May 14]. https://view-hub.org/vaccine/rota?set=current-program-type&group=vaccine-introduction&categor–y=rv
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