Aplicación universal de la vacuna de rotavirus: impacto en la mortalidad y hospitalizaciones por diarrea / Worldwide application of the rotavirus vaccine: impact on mortality and hospitalizations due to diarrhea

En EE.UU., Australia y algunos países latinoamericanos y europeos en donde se ha incorporado la vacuna de rotavirus a los programas nacionales de inmunización, se ha observado una reducción significativa de las tasas de mortalidad y hospitalización por diarrea. Además, pareciera que la vacuna confiere protección a los niños no vacunados, lo que sugiere que sería capaz de inducir un beneficio indirecto a la población (inmunidad de rebaño). En este artículo se hace una revisión de la información publicada, recientemente, con respecto al impacto de la inmunización con rotavirus en la carga de la diarrea en la niñez.

In the United States, Australia and some Latin-American and European countries where the rotavirus vaccine has been incorporated into the national immunization programs, a significant reduction of mortality and hospitalization rates due to diarrhea have been seen. It would also seem that the vaccine confers protection to non vaccinated children, which suggests that it might be able to induce an indirect benefit to the population (herd immunity). This paper presents a review of the recently published information regarding the impact of rotavirus immunization on the childhood diarrhea load.

Inmunizaciones: [revisión] / Immunizations: [review]

Los avances en la prevención de la enfermedad diarreica aguda con el uso de vacunas orales están presentes gracias a las investigaciones en el área de los trabajos realizados en cólera, fiebre tifoidea y con más éxito en la prevención de la diarrea por rotavirus. en este consenso desarrollamos los elementos actualizados en la inmunización contra cólera, fiebre tifoidea, indicaciones y futuras vacunas. en especial, se hace referencia a la vacunación contra rotavirus, sus estudios iniciales, evaluación de la investigación en fase III (realizada en Venezuela), las características particulares de cada vacuna desarrollada y en uso hoy en día, su aplicación y seguimiento una vez iniciado el plan nacional de vacunación, finalizando con los estudios de impacto económico y costo-efectividad.

Advances in prevention of acute diarrheal disease with the use of oral vaccines have been accomplished thanks to research in cholera, typhoid fever and, with more success, in the prevention of rotavirus diarrhea. This consensus addresses updates in immunization against cholera, typhoid fever, indications and future vaccines. In particular, we refer to vaccinations against rotavirus, their initial studies, research evaluation in phase III (held in Venezuela), particular characteristics of each vaccine developed and in use today, and the follow up of its implementation once the national vaccination plan is initiated. Final considerations in relation to the economic impact and cost effectiveness studies are stated.

Estudio epidemiológico y clínico de las diarreas por rotavirus en niños menores de 5 años atendidos en centros asistenciales del estado Miranda-Venezuela / Epidemiological and clinical study of diarrhea by rotavirus in children 5 years of age attended in medical centers of the Miranda State Venezuela

Con el objeto de conocer la epidemiología y clínica de la infección por rotavirus (RV) tratada de forma ambulatoria, se realizó un estudio en 5 centros (un hospital tipo I y 4 ambulatorios) del estado Miranda, entre febrero 2006 y enero 2007. Se evaluaron 194 niños menores de 5 años con diarrea aguda y se analizaron las siguientes variables: género, edad, estrato socioeconómico, alimentación, estado nutricional, clínica, diagnóstico de RV por Ensayo Inmuno Enzimático (ELISA) y su tipificación G por RT-PCR. La población presentó las siguientes características: 53 por ciento de varones, 17,6 ± 14,05 meses de edad (media), 68 por ciento de clase obrera y marginal (Graffar 4 y 5), 59 por ciento de lactancia materna en el primer año de vida, 13 por ciento de desnutrición, 40 por ciento de deshidratación y 19 por ciento de infección por RV. Los episodios RV positivos se asociaron significativamente a vómitos (94 por ciento, P < 0,0001) y a desnutrición (30 por ciento, P = 0,0010) al compararlos con los RV negativos. En los casos deshidratados fue mayor significativamente la desnutrición (21 por ciento, P = 0,00232) y la presencia de RV (28 por ciento, P = 0,0407). Encontramos entre la población del hospital y los ambulatorios diferencias respecto al graffar 4 y 5 (90 por ciento vs 53 por ciento, P < 0,0001), desnutrición (23 por ciento vs 6 por ciento, P = 0,006), deshidratación (63 por ciento vs 24 por ciento, P<0,0001) y RV (27 por ciento vs 13 por ciento, P = 0,027). Se tipificaron 14 cepas RV positivos resultando el 29 por ciento de tipo G1, 21 por ciento de G3 y 14 por ciento de G4. Este estudio sugiere que los RV, en la región estudiada, son causa de diarreas severas asociadas a desnutrición, pobreza y afectan significativamente a la población mayor de un año.

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.

BACKGROUND: Peak incidence of rotavirus gastroenteritis is seen in infants between 6 and 24 months of age. We therefore aimed to assess the 2-year efficacy and safety of an oral live attenuated human rotavirus vaccine for prevention of severe gastroenteritis in infants. METHODS: 15 183 healthy infants aged 6-13 weeks from ten Latin American countries randomly assigned in a 1 to 1 ratio to receive two oral doses of RIX4414 or placebo at about 2 and 4 months of age in a double-blind, placebo-controlled phase III study were followed up until about 2 years of age. Primary endpoint was vaccine efficacy from 2 weeks after dose two until 1 year of age. Treatment allocation was concealed from investigators and parents of participating infants. Efficacy follow-up for gastroenteritis episodes was undertaken from 2 weeks after dose two until about 2 years of age. Analysis was according to protocol. This study is registered with ClinicalTrials.gov, number NCT00140673 (eTrack444563-023). FINDINGS: 897 infants were excluded from the according-to-protocol analysis. Fewer cases (p<0.0001) of severe rotavirus gastroenteritis were recorded for the combined 2-year period in the RIX4414 group (32 [0.4%] of 7205; 95% CI 0.3-0.6) than in the placebo group (161 [2.3%] of 7081; 1.9-2.6), resulting in a vaccine efficacy of 80.5% (71.3-87.1) to 82.1% (64.6-91.9) against wild-type G1, 77.5% (64.7-86.2) against pooled non-G1 strains, and 80.5% (67.9-88.8) against pooled non-G1 P[8] strains. Vaccine efficacy for hospital admission for rotavirus gastroenteritis was 83.0% (73.1-89.7) and for admission for diarrhoea of any cause was 39.3% (29.1-48.1). No cases of intussusception were reported during the second year of follow-up. INTERPRETATION: Two doses of RIX4414 were effective against severe rotavirus gastroenteritis during the first 2 years of life in a Latin American setting. Inclusion of RIX4414 in routine paediatric immunisations should reduce the burden of rotavirus gastroenteritis worldwide.

[Epidemiological and clinical study of diarrhea by rotavirus in children <5 years of age attended in medical centers of the Miranda State, Venezuela]. / Estudio epidemiológico y clinico de las diarreas por rotavirus en niños menores de 5 años atendidos en centros asistenciales del estado Miranda-Venezuela.

To have a better knowledge of the epidemiological and clinical aspects of rotavirus (RV) infection treated at out-patient clinics, we carried out a study in five centers (one hospital type I, and four out-patient clinics) of Miranda state, between february 2006 and january 2007. We evaluated 194 children <5 years old with acute diarrhea and analyzed the following characteristics: gender, age, socioeconomic condition, breastfeeding, nutritional status, clinical characteristics, rotavirus diagnosis and typing by Enzyme Linked immuno Sorbent Asssay (EISA) and G typing by RT-PCR, respectively. The population presented the following characteristics: 53% males; mean age, 17.6 +/- 14.05 months; 68% belonged to worker and marginal class (Graffar 4 and 5); 59% were breast-fed during their first year of life; 13% were malnourished; 40% were dehydrated and 19% were infected with RV. RV infection was significantly and more frequently associated with vomiting (94%, P<0.0001) and malnourishment (30%, P=0.0010) than the episodes negative for rotavirus. In dehydrated cases, significantly greater malnourishment (21%, P=0.0232) and RV (28%, P=0.0407). We found significant differences between the hospital and out-patient clinics, in terms of Graffar 4 and 5 (90% vs .53%, P<0.0001), malnourished (23% vs. 6%, P=0.006), dehydration (63% vs 24%, P<0.0001) and RV (27% vs. 13%, P=0.027). Fourteen samples RV positive were genotyped and the G types were 29% G1, 21% G3 and 14% G4 types. This study suggests that RV cause severe diarrhea associated to malnutrition and poverty and significantly affect the population older than one year of age in the region studied.

Efficacy of the human rotavirus vaccine RIX4414 in malnourished children.

UNLABELLED: The effect of nutritional status on protective efficacy of a live attenuated human rotavirus vaccine (RIX4414) was studied. Vaccine protection was evaluated through a secondary analysis of data from an efficacy study conducted in Brazil, Mexico, and Venezuela. Vaccine efficacy against rotavirus gastroenteritis (RVGE) was similar in well-nourished and malnourished infants: 74.1% (95% confidence interval [CI], 52.2%-86.2%) and 73% (95% CI, 11.2%-92.3%) for severe RVGE and 60.9% (95% CI, 37.4%-75.4%) and 61.2% (95% CI, 10.4%-83.1%) for RVGE of any severity, respectively. RIX4414 significantly decreased the rate of RVGE regardless of nutritional status, which suggests that this patient group can also benefit from rotavirus vaccination. CLINICAL TRIALS REGISTRY: e-Track 444563-006, NCT00385320 (http://www.clinicaltrials.gov).

Rotavirus mortality confirmed by etiologic identification in Venezuelan children with diarrhea.

BACKGROUND: Hospital-based studies to determine the etiology of deaths from diarrhea are scarce. In this study, we specifically analyzed deaths due to rotavirus to assess the rotavirus impact on diarrhea mortality. METHODS: To determine the rotavirus proportion contributing to mortality due to diarrhea, we analyzed data obtained from a hospital-based mortality surveillance, conducted over 7 years, in the Ciudad Hospitalaria Dr. Enrique Tejera, Valencia, Venezuela. Rotavirus was identified in stool samples collected from children who died of diarrhea, by a confirmatory ELISA and/or reverse transcription polymerase chain reaction. RESULTS: Our results show that rotavirus (21%; 21/100) is the leading cause of death due to diarrhea among children <5 years of age; rotavirus also has an important impact (2%; 21/1336) on deaths from all causes in this age group. Shigella spp. (19%; 13/69) was the second most important cause of death, followed by calicivirus (6%; 3/53). Furthermore, this study documents a seasonal pattern in the deaths due to rotavirus (odds ratio 3.28; 95% confidence interval 1.13-9.76). CONCLUSIONS: For Venezuela, it is estimated that approximately 300 children <5 years of age die of rotavirus each year, which means that 1 in 1800 children die by the age of 5. Rotavirus was found to be the main cause of death due to diarrhea, which supports previous estimations. This is the first study to present data of cause-specific mortality due to diarrhea based on hospital surveillance of diarrhea etiologies.

Evaluación del impacto económico de la vacuna antirrotavírica en Venezuela / Assessment of the economic impact of the antiretroviral vaccine in Venezuela

En Venezuela existe un interés creciente por los estudios de impacto económico y de costo-efectividad, y se reconoce que estos últimos son esenciales para la toma de decisiones en materia de salud. La principal dificultad para realizar estos estudios es la disponibilidad de la información necesaria para alimentar el modelo de análisis.

Evaluación del impacto económico de la vacuna antirrotavírica en Venezuela / Assessment of the economic impact of the antiretroviral vaccine in Venezuela

OBJETIVO: El objetivo de este estudio fue evaluar el costo de la atención médica de la gastroenteritis por rotavirus y la relación costo-efectividad de la vacuna antirrotavírica en la población venezolana menor de 5 años de edad. MÉTODOS: Se utilizó un modelo económico que integra la información epidemiológica, la eficacia de la vacuna y los costos de atención médica de la gastroenteritis por rotavirus, desde la perspectiva de la sociedad. Para determinar la efectividad de la vacuna, se estimó el número de casos de hospitalización, de consultas médicas y de muertes evitados después de su administración. La relación costo-efectividad de la vacuna se evaluó partiendo del número de años de vida ajustados por discapacidad (AVAD) y de casos evitados. RESULTADOS: En Venezuela, los servicios de salud invierten, aproximadamente, 4,2 millones de dólares estadounidenses (US$) por año para cubrir los costos de atención médica causados por el rotavirus. Un programa de vacunación antirrotavírica evitaría aproximadamente el 52 por ciento (186) de las muertes, el 54 por ciento (7 232) de las hospitalizaciones y el 50 por ciento (55 168) de las consultas ambulatorias durante los primeros cinco años de vida, en una cohorte vacunada. Para un precio estimado de US$ 24 por régimen de vacuna, se genera una relación costo-efectividad de US$ 1 352 por AVAD. CONCLUSIONES: Los resultados de este estudio apuntan a que la vacunación antirrotavírica es una estrategia costoefectiva en la prevención de la gastroenteritis por rotavirus en Venezuela, ya que puede evitar muertes y años de vida ajustados por discapacidad en la población menor de cinco años de edad.

OBJECTIVE: To assess the cost of medical care for rotavirus gastroenteritis and the cost-effectiveness of the antiretroviral vaccine in Venezuelan children under five. METHODS: We used an economic model that comprises epidemiologic information, vaccine efficacy, and the cost of medical care in connection with rotavirus gastroenteritis, viewed from a social perspective. In order to determine the effectiveness of the vaccine, we estimated the number of hospitalized cases, of medical visits, and of deaths averted after vaccination. The cost-effectiveness of the vaccine was determined on the basis of the number of disability-adjusted life years (DALYs) and cases averted. RESULTS: In Venezuela, health services spend approximately US$ 4.2 million yearly on covering the costs of medical care for rotavirus-related disease. In a vaccinated cohort, an antiretroviral vaccination program would prevent around 52 percent (186) of the deaths, 54 percent (7 232) of the hospitalizations, and 50 percent (55 168) of the ambulatory visits that take place during the first five years of life. For an estimated cost of approximately US$ 24 per individual vaccination schedule, the cost-effectiveness ratio obtained is US$ 1 352 per DALY. CONCLUSIONS: The results of this study suggest that antiretroviral vaccination is a cost-effective strategy for preventing rotavirus gastroenteritis in Venezuela, since it can prevent deaths and DALYs in the population under five years of age.

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

BACKGROUND: The safety and efficacy of an attenuated G1P[8] human rotavirus (HRV) vaccine were tested in a randomized, double-blind, phase 3 trial. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.)

[Assessment of the economic impact of the antiretroviral vaccine in Venezuela]. / Evaluación del impacto económico de la vacuna antirrotavírica en Venezuela.

OBJECTIVE: To assess the cost of medical care for rotavirus gastroenteritis and the cost-effectiveness of the antiretroviral vaccine in Venezuelan children under five. METHODS: We used an economic model that comprises epidemiologic information, vaccine efficacy, and the cost of medical care in connection with rotavirus gastroenteritis, viewed from a social perspective. In order to determine the effectiveness of the vaccine, we estimated the number of hospitalized cases, of medical visits, and of deaths averted after vaccination. The cost-effectiveness of the vaccine was determined on the basis of the number of disability-adjusted life years (DALYs) and cases averted. RESULTS: In Venezuela, health services spend approximately 4.2 million US$ yearly on covering the costs of medical care for rotavirus-related disease. In a vaccinated cohort, an antiretroviral vaccination program would prevent around 52% (186) of the deaths, 54% (7,232) of the hospitalizations, and 50% (55,168) of the ambulatory visits that take place during the first five years of life. For an estimated cost of approximately 24 US$ per individual vaccination schedule, the cost-effectiveness ratio obtained is 1,352 US$ per DALY. CONCLUSIONS: The results of this study suggest that antiretroviral vaccination is a cost-effective strategy for preventing rotavirus gastroenteritis in Venezuela, since it can prevent deaths and DALYs in the population under five years of age.

Evaluation of serum antibody responses against the rotavirus nonstructural protein NSP4 in children after rhesus rotavirus tetravalent vaccination or natural infection.

The immune response elicited by the rotavirus nonstructural protein NSP4 and its potential role in protection against rotavirus disease are not well understood. We investigated the serological response to NSP4 and its correlation with disease protection in sera from 110 children suffering acute diarrhea, associated or not with rotavirus, and from 26 children who were recipients of the rhesus rotavirus tetravalent (RRV-TV) vaccine. We used, as antigens in an enzyme-linked immunosorbent assay (ELISA), affinity-purified recombinant NSP4 (residues 85 to 175) from strains SA11, Wa, and RRV (genotypes A, B, and C, respectively) fused to glutathione S-transferase. Seroconversion to NSP4 was observed in 54% (42/78) of the children who suffered from natural rotavirus infection and in 8% (2/26) of the RRV-TV vaccine recipients. Our findings indicate that NSP4 evokes significantly (P < 0.05) higher seroconversion rates after natural infection than after RRV-TV vaccination. The serum antibody levels to NSP4 were modest (titers of < or = 200) in most of the infected and vaccinated children. A heterotypic NSP4 response was detected in 48% of the naturally rotavirus-infected children with a detectable response to NSP4. Following natural infection or RRV-TV vaccination, NSP4 was significantly less immunogenic than the VP6 protein when these responses were independently measured by ELISA. A significant (P < 0.05) proportion of children who did not develop diarrhea associated with rotavirus had antibodies to NSP4 in acute-phase serum, suggesting that serum antibodies against NSP4 might correlate with protection from rotavirus diarrhea. In addition, previous exposures to rotavirus did not affect the NSP4 seroconversion rate.

Evaluation of safety, immunogenicity and efficacy of an attenuated rotavirus vaccine, RIX4414: A randomized, placebo-controlled trial in Latin American infants.

BACKGROUND: A live attenuated monovalent rotavirus vaccine RIX4414 was developed with a human strain of G1P1A P[8] specificity to reduce the rotavirus burden in children. METHODS: A double blind, randomized, placebo-controlled study evaluated the efficacy, immunogenicity, safety and reactogenicity of 2 oral doses of RIX4414 (10(4.7), 10(5.2) or 10(5.8) focus-forming units) at 2 and 4 months coadministered with routine vaccinations and oral poliovirus vaccine given for study purposes at least 14 days apart. The 2155 infants (1618 vaccine/537 placebo) enrolled in Brazil, Mexico and Venezuela were followed until 1 year of age. RESULTS: Antirotavirus IgA seroconversion rates 2 months after dose 2 ranged between 61% (10(4.7) ffu group) and 65% (10(5.8) ffu group), and most of the infants had seroprotective levels of antibodies to coadministered routine vaccinations. The reactogenicity profile of RIX4414 was similar to that of the placebo, and no vaccination-related serious adverse events were reported. Protective efficacy against severe and any rotavirus gastroenteritis from 15 days post-dose 2 was highest in the 10(5.8) ffu group [86%; 95% confidence interval (95% CI), 63-96% and 70% (95% CI 46-84%), P < 0.001, 2-sided Fisher's exact test]. The efficacy against hospitalization was 79% (95% CI 48-92%) for pooled vaccine groups. Multiple rotavirus serotypes [G1 (50%), G9 (40%), G2, G3 and G4] were identified from gastroenteritis stools (enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction) during the study period. For severe gastroenteritis caused by G9 serotypes, the protection reached 77% (95% CI 18-96%) in the 10(5.8) ffu group, providing proof of concept that the monovalent G1P1A P[8] human rotavirus vaccine elicits cross-protection against the G9 strain. A reduction in any and severe rotavirus gastroenteritis was already observed at post-dose 1 (period: day of dose 1 to 14 days post-dose 2) in vaccinees compared with placebo recipients. CONCLUSIONS: Two doses of RIX4414 are highly efficacious, providing cross-protection (G1 and G9 strains, prevalent during this study) and early protection against any and severe rotavirus gastroenteritis and hospitalization to infants in Latin America.

Factores de virulencia asociados a la enteropatogenicidad en cepas de Aeromonas spp. aisladas de niños con diarrea en Mérida, Venezuela / Factors of virulence associated with entero-pathogenicity in strains of Aeromonas spp isolated from children with diarrhea in Mérida, Venezuela

Se estudiaron las heces de 397 pacientes con enfermedad diarreica aguda, y las de 121 pacientes sin diarrea que conformaron el grupo control , en el estado de Mérida, Venezuela , entre junio de 1993 y diciembre de 1994. El género Aeromonas fue identificado en los pacientes con enfermedad diarreica aguda en 11,83 por ciento y 5,78 por ciento se identificó en los pacientes del grupo control. Al estudiar los factores de virulencia descritos para Aeromonas (enterotoxina, citotoxina, hemaglutininas, hidrofobicidad celular y actividad hemolítica) en las cepas aisladas, se detectó que todas poseían al menos uno de los factores investigados asociados a la enteropatogenicidad. De las especies aisladas, Aeromonas caviae resultó ser la que se identificó con mayor frecuencia. Todos estos resultados sugieren que las especies de Aeromonas son patógenos entéricos potenciales en esta población

Factores de virulencia asociados a la enteropatogenicidad en cepas de Aeromonas spp. aisladas de niños con diarrea en Mérida, Venezuela / Factors of virulence associated with entero-pathogenicity in strains of Aeromonas spp isolated from children with diarrhea in Mérida, Venezuela

Se estudiaron las heces de 397 pacientes con enfermedad diarreica aguda, y las de 121 pacientes sin diarrea que conformaron el grupo control , en el estado de Mérida, Venezuela , entre junio de 1993 y diciembre de 1994. El género Aeromonas fue identificado en los pacientes con enfermedad diarreica aguda en 11,83 por ciento y 5,78 por ciento se identificó en los pacientes del grupo control. Al estudiar los factores de virulencia descritos para Aeromonas (enterotoxina, citotoxina, hemaglutininas, hidrofobicidad celular y actividad hemolítica) en las cepas aisladas, se detectó que todas poseían al menos uno de los factores investigados asociados a la enteropatogenicidad. De las especies aisladas, Aeromonas caviae resultó ser la que se identificó con mayor frecuencia. Todos estos resultados sugieren que las especies de Aeromonas son patógenos entéricos potenciales en esta población(AU)

[Factors of virulence associated with enteropathogenicity in strains of Aeromonas spp. isolated from children with diarrhea in Mérida, Venezuela]. / Factores de virulencia asociados a la enteropatogenicidad en cepas Aeromonas spp. aisladas de niños con diarrea en Mérida, Venezuela.

The feces of 397 patients with acute diarrheal disease (ADD) and of other 121 patients without diarrea (control group) were studied in the state of Mérida, Venezuela, from June 1993 to December 1994. The genus Aeromonas was identified in patients with ADD in 11.83% and in 5.78% of the patients from the control group. On studying the virulence factors described for Aeromonas (enterotoxin, cytotoxin, hemaglutinins, cellular hydrofibrosity, and hemolytic activity) in the isolated strains, it was detected that all presented at least one of the factors investigated associated with enteropathogenicity. Of the isolated species, Aeromonas caviae was the most frequently identified. All these results suggest that the Aeromonas species are potential enteric pathogens in this population.

A rotavirus vaccine for prophylaxis of infants against rotavirus gastroenteritis.

The need for safe and effective vaccines to reduce morbidity and mortality caused by rotavirus gastroenteritis in children is well-known. A live attenuated monovalent rotavirus vaccine (Rotarix) containing human rotavirus strain RIX4414 of G1P1A P[8] specificity is being developed to meet the global need. An overview of RIX4414 trials in developed and developing settings is presented for 3 selected trials conducted in Finland (pilot study), Latin America (Brazil, Mexico and Venezuela) and Singapore involving 5024 infants. The vaccine was well-tolerated, with no increase in any solicited symptoms as compared with the placebo. After 2 doses, 61-91% of vaccinated infants developed rotavirus-specific IgA antibodies. There was no interference with immunogenicity of coadministered routine pediatric vaccines. Rotarix significantly reduced rotavirus gastroenteritis episodes and rotavirus-related hospitalizations in vaccinated infants compared with placebo recipients (P < 0.05). Vaccine efficacy was observed against severe rotavirus gastroenteritis caused by G1 and non-G1 types including the emerging G9 type (P < 0.05) in Latin America. These results show prospects for widespread use of Rotarix to reduce rotavirus disease burden and warrant continued worldwide evaluation.

Human rotavirus specific T cells: quantification by ELISPOT and expression of homing receptors on CD4+ T cells.

Using an intracellular cytokine assay, we recently showed that the frequencies of rotavirus (RV)-specific CD4(+) and CD8(+) T cells secreting INFgamma, circulating in RV infected and healthy adults, are very low compared to the frequencies of circulating cytomegalovirus (CMV) reactive T cells in comparable individuals. In children with acute RV infection, these T cells were barely or not detectable. In the present study, an ELISPOT assay enabled detection of circulating RV-specific INFgamma-secreting cells in children with RV diarrhea but not in children with non-RV diarrhea without evidence of a previous RV infection. Using microbead-enriched CD4(+) and CD8(+) T cell subsets, IFNgamma-secreting RV-specific CD8(+) but not CD4(+) T cells were detected in recently infected children. Using the same approach, both CD4(+) and CD8(+) RV-specific T cells were detected in healthy adults. Furthermore, stimulation of purified subsets of PBMC that express lymphocyte homing receptors demonstrated that RV-specific INFgamma-secreting CD4(+) T cells from adult volunteers preferentially express the intestinal homing receptor alpha4beta7, but not the peripheral lymph node homing receptor L-selectin. In contrast, CMV-specific INFgamma-secreting CD4(+) T cells preferentially express L-selectin but not alpha4beta7. These results suggest that the expression of homing receptors on virus-specific T cells depends on the organ where these cells were originally stimulated and that their capacity to secrete INFgamma is independent of the expression of these homing receptors.