Diversidad genotípica de rotavirus grupo A: correlación entre el tipo G3 y severidad de la infección. Valencia, Venezuela

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Abstract

La variabilidad genética y antigénica de los rotavirus (RV) parece tener implicaciones en la severidad de la infección, pero los estudios no son concluyentes. Por este motivo, en el presente trabajo se compararon las medias de severidad entre los episodios de diarrea causados por RV tipo G1 y G3, durante el período 2001-2005, en la Ciudad Hospitalaria “Dr. Enrique Tejera” de Valencia, Venezuela. RV se detectó por ELISA, los tipos G y P por RT-PCR. La severidad de la infección se estimó utilizando el sistema de Ruuska-Vesikari, las medias de severidad se compararon mediante la prueba t de Student (2 colas, 95%IC). RV se detectó en 24,5% (3.193/13.026) de los pacientes. G3 fue más frecuente (50,3%), seguido por G1 (39,2%), G9 (6,2%), G2 (0,6%), G4 (0,6%) y 3,1% mixtos (G1+G3). El 87,3% de las muestras resultaron P[8], 10,9% P[4] y 1,8% P[6]. Al comparar los episodios G1 y G3, no se observaron diferencias significativas (P>0,05) entre los grupos etarios, frecuencia de desnutridos, deshidratación y lactancia materna. Sin embargo, el grupo G3 se caracterizó por presencia significativa (P< 0,05) de fiebre, episodios con una duración ≥ 6 días, 6 o más evacuaciones en 24 horas y 3 o más días con vómitos. La media de severidad para los episodios G3 (11,1) fue mayor significativamente (P<0,05) a la G1 (7,8). Estos resultados muestran la asociación de G3 con diarreas severas y apoyan la importancia de conocer la variabilidad y frecuencia de los tipos virales para medir el impacto de las vacunas antirotavirus.

Translated abstract

Genetic and antigenic rotavirus (RV) variabilities may have implications in the severity of the infection caused by these agents; however the studies are not conclusive. For that purpose, the mean severity scores of diarrhea episodes caused by RV types G1 and G3 were compared, at Ciudad Hospitalaria “Dr. Enrique Tejera” in Valencia, Venezuela, between 2001- 2005. RV were identified by ELISA, G and P types by RT-PCR. The severity of infection was determined using the Ruuska-Vesikari system and the mean severity values were compared using the Student’s t-test (two-tailed, 95%CI). RV were detected in 24.5% of patients (3193/13026), being G3 the most common (50.3%), followed by G1 (39.2%), G9 (6.2%), G2 (0.6%), G4 (0.6%) and of mixed infection 3.1% (G1+G3). Type P[8] was present in 87.3% of samples, 10.9% P[4] and 1.8% P[6]. There were not statistically significant differences (P≥0.05) observed between the episodes caused by G1 and G3 when age, breast feeding, and degrees of malnutrition and dehydration were considered. Nevertheless, in the G3 positive group, fever, episodes of more than 6 days, 6 or more evacuations in 24 hours and 3 or more days with vomit, were observed. The mean severity score for the G3 episodes (11.1) was significantly higher (P< 0.05) than for G1 (7.8). These results show that G3 was associated with severe diarrhea, supporting the hypothesis that the knowledge of the variability and frequency of viral types is essential to measure the impact of an anti-rotavirus vaccine.

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Most cited references 75

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Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis.

Guillermo Ruiz-Palacios, Irene Pérez-Schael, F Velázquez … (2006)

The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial. We studied 63,225 healthy infants from 11 Latin American countries and Finland who received two oral doses of either the HRV vaccine (31,673 infants) or placebo (31,552 infants) at approximately two months and four months of age. Severe gastroenteritis episodes were identified by active surveillance. The severity of disease was graded with the use of the 20-point Vesikari scale. Vaccine efficacy was evaluated in a subgroup of 20,169 infants (10,159 vaccinees and 10,010 placebo recipients). The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P<0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P<0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, -0.32 per 10,000 infants; 95 percent confidence interval, -2.91 to 2.18; P=0.78). Two oral doses of the live attenuated G1P[8] HRV vaccine were highly efficacious in protecting infants against severe rotavirus gastroenteritis, significantly reduced the rate of severe gastroenteritis from any cause, and were not associated with an increased risk of intussusception. (ClinicalTrials.gov numbers, NCT00139347 and NCT00263666.) Copyright 2006 Massachusetts Medical Society.

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Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine.

Timo Vesikari, David Matson, Penelope H Dennehy … (2006)

Rotavirus is a leading cause of childhood gastroenteritis and death worldwide. We studied healthy infants approximately 6 to 12 weeks old who were randomly assigned to receive three oral doses of live pentavalent human-bovine (WC3 strain) reassortant rotavirus vaccine containing human serotypes G1, G2, G3, G4, and P[8] or placebo at 4-to-10-week intervals in a blinded fashion. Active surveillance was used to identify subjects with serious adverse and other events. The 34,035 infants in the vaccine group and 34,003 in the placebo group were monitored for serious adverse events. Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose (relative risk, 1.6; 95 percent confidence interval, 0.4 to 6.4). The vaccine reduced hospitalizations and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent (95 percent confidence interval, 91.2 to 96.6 percent). In a nested substudy, efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to 79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95 percent confidence interval, 88.3 to 100 percent). The vaccine reduced clinic visits for G1-G4 rotavirus gastroenteritis by 86.0 percent (95 percent confidence interval, 73.9 to 92.5 percent). This vaccine was efficacious in preventing rotavirus gastroenteritis, decreasing severe disease and health care contacts. The risk of intussusception was similar in vaccine and placebo recipients. (ClinicalTrials.gov number, NCT00090233.) Copyright 2006 Massachusetts Medical Society.

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Rotavirus infections in infants as protection against subsequent infections.

F Velazquez, D Matson, J Calva … (1996)

Rotavirus is the leading cause of severe diarrhea in infants. To provide a base line for assessing the efficacy of rotavirus vaccines, we evaluated the protection that is conferred by natural rotavirus infection. We monitored 200 Mexican infants from birth to two years of age by weekly home visits and stool collections. A physician assessed the severity of any episodes of diarrhea and collected additional stool specimens for testing by enzyme immunoassay and typing of strains. Serum collected during the first week of life and every four months thereafter was tested for antirotavirus IgA and IgG. A total of 316 rotavirus infections were detected on the basis of the fecal excretion of virus (56 percent) or a serologic response (77 percent), of which 52 percent were first and 48 percent repeated infections. Children with one, two, or three previous infections had progressively lower risks of both subsequent rotavirus infection (adjusted relative risk, 0.62, 0.40, and 0.34, respectively) and diarrhea (adjusted relative risk, 0.23, 0.17, and 0.08) than children who had no previous infections. No child had moderate-to-severe diarrhea after two infections, whether symptomatic or asymptomatic. Subsequent infections were significantly less severe than first infections (P=0.024), and second infections were more likely to be caused by another G type (P=0.054). In infants, natural rotavirus infection confers protection against subsequent infection. This protection increases with each new infection and reduces the severity of the diarrhea.