Evaluation of Intussusception Following Pentavalent Rotavirus Vaccine (RotaTeq) Administration in 5 African Countries.

BACKGROUND: A low-level risk of intussusception following rotavirus vaccination has been observed in some settings and may vary by vaccine type. We examined the association between RotaTeq vaccination and intussusception in low-income settings in a pooled analysis from 5 African countries that introduced RotaTeq into their national immunization program. METHODS: Active surveillance was conducted at 20 hospitals to identify intussusception cases. A standard case report form was completed for each enrolled child, and vaccination status was determined by review of the child's vaccination card. The pseudo-likelihood adaptation of self-controlled case-series method was used to assess the association between RotaTeq administration and intussusception in the 1-7, 8-21, and 1-21 day periods after each vaccine dose in infants aged 28-245 days. RESULTS: Data from 318 infants with confirmed rotavirus vaccination status were analyzed. No clustering of cases occurred in any of the risk windows after any of the vaccine doses. Compared with the background risk of naturally occurring intussusception, no increased risk was observed after dose 1 in the 1-7 day (relative incidence = 2.71; 95% confidence interval [CI] = 0.47-8.03) or the 8-21 day window (relative incidence = 0.77; 95%CI = 0.0-2.69). Similarly, no increased risk of intussusception was observed in any risk window after dose 2 or 3. CONCLUSIONS: RotaTeq vaccination was not associated with increased risk of intussusception in this analysis from 5 African countries. This finding mirrors results from similar analyses with other rotavirus vaccines in low-income settings and highlights the need for vaccine-specific and setting-specific risk monitoring.

Intussusception after Rotavirus Vaccine Introduction in India.

BACKGROUND: A three-dose, oral rotavirus vaccine (Rotavac) was introduced in the universal immunization program in India in 2016. A prelicensure trial involving 6799 infants was not large enough to detect a small increased risk of intussusception. Postmarketing surveillance data would be useful in assessing whether the risk of intussusception would be similar to the risk seen with different rotavirus vaccines used in other countries. METHODS: We conducted a multicenter, hospital-based, active surveillance study at 27 hospitals in India. Infants meeting the Brighton level 1 criteria of radiologic or surgical confirmation of intussusception were enrolled, and rotavirus vaccination was ascertained by means of vaccination records. The relative incidence (incidence during the risk window vs. all other times) of intussusception among infants 28 to 365 days of age within risk windows of 1 to 7 days, 8 to 21 days, and 1 to 21 days after vaccination was evaluated by means of a self-controlled case-series analysis. For a subgroup of patients, a matched case-control analysis was performed, with matching for age, sex, and location. RESULTS: From April 2016 through June 2019, a total of 970 infants with intussusception were enrolled, and 589 infants who were 28 to 365 days of age were included in the self-controlled case-series analysis. The relative incidence of intussusception after the first dose was 0.83 (95% confidence interval [CI], 0.00 to 3.00) in the 1-to-7-day risk window and 0.35 (95% CI, 0.00 to 1.09) in the 8-to-21-day risk window. Similar results were observed after the second dose (relative incidence, 0.86 [95% CI, 0.20 to 2.15] and 1.23 [95% CI, 0.60 to 2.10] in the respective risk windows) and after the third dose (relative incidence, 1.65 [95% CI, 0.82 to 2.64] and 1.08 [95% CI, 0.69 to 1.73], respectively). No increase in intussusception risk was found in the case-control analysis. CONCLUSIONS: The rotavirus vaccine produced in India that we evaluated was not associated with intussusception in Indian infants. (Funded by the Bill and Melinda Gates Foundation and others.).

The Rotavirus Vaccine Story: From Discovery to the Eventual Control of Rotavirus Disease.

Worldwide, rotavirus is the leading pathogen causing severe diarrhea in children and a major cause of under 5 years mortality. In 1998, the first rotavirus vaccine, RotaShield, was licensed in the United States but a rare adverse event, intussusception, led to its withdrawal. Seven years passed before the next generation of vaccines became available, Rotarix (GSK) and Rotateq (Merck), and 11 years later, 2 additional vaccines from India, Rotavac (Bharat) and Rotasiil (Serum Institute), were recommended by World Health Organization for all children. Today, these vaccines are used in more than 100 countries and have contributed to marked decreases in hospitalizations and deaths from diarrhea. However, these live oral vaccines are less effective in low-income countries with high under 5 years mortality for reasons that are not understood. Efforts to develop new vaccines that avoid the oral route are in progress and will likely be needed to ultimately control rotavirus disease.

Evaluation of Intussusception after Monovalent Rotavirus Vaccination in Africa.

BACKGROUND: Postlicensure evaluations have identified an association between rotavirus vaccination and intussusception in several high- and middle-income countries. We assessed the association between monovalent human rotavirus vaccine and intussusception in lower-income sub-Saharan African countries. METHODS: Using active surveillance, we enrolled patients from seven countries (Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia, and Zimbabwe) who had intussusception that met international (Brighton Collaboration level 1) criteria. Rotavirus vaccination status was confirmed by review of the vaccine card or clinic records. The risk of intussusception within 1 to 7 days and 8 to 21 days after vaccination among infants 28 to 245 days of age was assessed by means of the self-controlled case-series method. RESULTS: Data on 717 infants who had intussusception and confirmed vaccination status were analyzed. One case occurred in the 1 to 7 days after dose 1, and 6 cases occurred in the 8 to 21 days after dose 1. Five cases and 16 cases occurred in the 1 to 7 days and 8 to 21 days, respectively, after dose 2. The risk of intussusception in the 1 to 7 days after dose 1 was not higher than the background risk of intussusception (relative incidence [i.e., the incidence during the risk window vs. all other times], 0.25; 95% confidence interval [CI], <0.001 to 1.16); findings were similar for the 1 to 7 days after dose 2 (relative incidence, 0.76; 95% CI, 0.16 to 1.87). In addition, the risk of intussusception in the 8 to 21 days or 1 to 21 days after either dose was not found to be higher than the background risk. CONCLUSIONS: The risk of intussusception after administration of monovalent human rotavirus vaccine was not higher than the background risk of intussusception in seven lower-income sub-Saharan African countries. (Funded by the GAVI Alliance through the CDC Foundation.).

Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth.

BACKGROUND: A strategy of administering a neonatal rotavirus vaccine at birth to target early prevention of rotavirus gastroenteritis may address some of the barriers to global implementation of a rotavirus vaccine. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine (RV3-BB) in preventing rotavirus gastroenteritis. Healthy newborns received three doses of RV3-BB, administered according to a neonatal schedule (0 to 5 days, 8 weeks, and 14 weeks of age) or an infant schedule (8 weeks, 14 weeks, and 18 weeks of age), or placebo. The primary analysis was conducted in the per-protocol population, which included only participants who received all four doses of vaccine or placebo within the visit windows, with secondary analyses performed in the intention-to-treat population, which included all participants who underwent randomization. RESULTS: Among the 1513 participants in the per-protocol population, severe rotavirus gastroenteritis occurred up to the age of 18 months in 5.6% of the participants in the placebo group (28 of 504 babies), in 1.4% in the neonatal-schedule vaccine group (7 of 498), and in 2.7% in the infant-schedule vaccine group (14 of 511). This resulted in a vaccine efficacy of 75% (95% confidence interval [CI], 44 to 91) in the neonatal-schedule group (P<0.001), 51% (95% CI, 7 to 76) in the infant-schedule group (P=0.03), and 63% (95% CI, 34 to 80) in the neonatal-schedule and infant-schedule groups combined (combined vaccine group) (P<0.001). Similar results were observed in the intention-to-treat analysis (1649 participants); the vaccine efficacy was 68% (95% CI, 35 to 86) in the neonatal-schedule group (P=0.001), 52% (95% CI, 11 to 76) in the infant-schedule group (P=0.02), and 60% (95% CI, 31 to 76) in the combined vaccine group (P<0.001). Vaccine response, as evidenced by serum immune response or shedding of RV3-BB in the stool, occurred in 78 of 83 participants (94%) in the neonatal-schedule group and in 83 of 84 participants (99%) in the infant-schedule group. The incidence of adverse events was similar across the groups. No episodes of intussusception occurred within the 21-day risk period after administration of any dose of vaccine or placebo, and one episode of intussusception occurred 114 days after the third dose of vaccine in the infant-schedule group. CONCLUSIONS: RV3-BB was efficacious in preventing severe rotavirus gastroenteritis when administered according to a neonatal or an infant schedule in Indonesia. (Funded by the Bill and Melinda Gates Foundation and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612001282875 .).

Combined use of lactic-acid-producing bacteria as probiotics and rotavirus vaccine candidates expressing virus-specific proteins.

Due to the lower efficacy of currently approved live attenuated rotavirus (RV) vaccines in developing countries, a new approach to the development of safe mucosally administered live bacterial vectors is being considered, using probiotic bacteria as an efficient delivery platform for heterologous RV antigens. Lactic acid bacteria (LAB), which are considered food-grade bacteria and normal microbiota, have been utilized throughout history as probiotics and developed since the 1990s as a delivery system for recombinant heterologous proteins. Over the last decade, LAB have frequently been used as a platform for the delivery of various RV antigens to the mucosa. Given the appropriate safety profile for neonates and providing the benefits of probiotics, recombinant LAB-based vaccines could potentially address the need for a subunit RV vaccine. The present review focuses mainly on different recombinant LAB vaccine constructs for RV and their potential as an alternative recombinant vaccine against RV disease.

Clinical Tolerance of In-Neonatal Intensive Care Unit Administration of Rotavirus Vaccine.

OBJECTIVE: This article determines the tolerance of neonatal intensive care unit (NICU)-based administration of RV5 in premature infants. This article also aims to compare the rate of clinically significant adverse events after RV5 immunization to the standard 2-month shot series and to historical controls who were not immunized. STUDY DESIGN: This is a retrospective case-control study of 201 premature infants immunized with RV5. Infants were evaluated for clinically significant events 7 days before and after immunization and were compared with events after the 2-month shot series and to 189 historical controls. Wilcoxon signed rank test and McNemar's test were used for all paired analysis. RESULTS: There was no increase in number of infants with clinically significant adverse events when comparing after RV5 to prior to RV5, after the 2-month shot series, or to the historical controls. CONCLUSION: RV5 is well tolerated in premature infants and does not result in clinically significant adverse events when administered in NICU-hospitalized infants.

Persistent infection with a rotavirus vaccine strain in a child suffering from Severe Combined Immunodeficiency in Argentina.

Due to the high burden of disease associated with rotavirus, the massive vaccination in children before six months of age has been encouraged. Currently licensed oral live vaccines have shown low risk of associated adverse events in the general population. Noteworthy, postmarketing reports of severe gastroenteritis with persistent vaccine viral shedding in children with severe combined immunodeficiency (SCID) have led companies to include this inborn error of immunity as an additional contraindication. SCID is not usually screened in newborns from developing countries. Therefore, the administration of live attenuated vaccines represents the first contact of these patients with life-threatening pathogens. We describe a clinical case of an infant with SCID who suffered from persistent rotavirus symptomatic diarrhea after receiving the rotavirus oral vaccine and was found to be infected with the vaccine strain. This case attempts to contribute to the discussion of those diseases that need to be incorporated into a screening program since an early diagnosis permits clinicians to withhold live attenuated immunization.

Evaluation of Intussusception After Oral Monovalent Rotavirus Vaccination in South Africa.

BACKGROUND: Postlicensure studies have shown an association between rotavirus vaccination and intussusception. We assessed the risk of intussusception associated with Rotarix (RV1) administration, at 6 and 14 weeks of age, in an upper-middle-income country, South Africa. METHODS: Active prospective surveillance for intussusception was conducted in 8 hospitals from September 2013 through December 2017. Retrospective case enrollment was done at 1 hospital from July 2012 through August 2013. Demographic characteristics, symptom onset, and rotavirus vaccine status were ascertained. Using the self-controlled case-series method, we estimated age-adjusted incidence rate ratios within 1-7, 8-21, and 1-21 days of rotavirus vaccination in children aged 28-275 days at onset of symptoms. In addition, age-matched controls were enrolled for a subset of cases (n = 169), and a secondary analysis was performed. RESULTS: Three hundred forty-six cases were included in the case-series analysis. Post-dose 1, there were zero intussusception cases within 1-7 days, and 5 cases within 8-21 days of vaccination. Post-dose 2, 15 cases occurred within 1-7 days, and 18 cases within 8-21 days of vaccination. There was no increased risk of intussusception 1-7 days after dose 1 (no cases observed) or dose 2 (relative incidence [RI], 1.71 [95% confidence interval {CI} .83-3.01]). Similarly, there was no increased risk 8-21 days after the first (RI, 4.01 [95% CI, .87-10.56]) or second dose (RI, .96 [95% CI, .52-1.60]). Results were similar for the case-control analysis. CONCLUSIONS: The risk of intussusception in the 21 days after the first or second dose of RV1 was not higher than the background risk among South Africa infants. CLINICAL TRIALS REGISTRATION: South African National Clinical Trial Register (DOH-27-0913-4183).

Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger.

BACKGROUND: Each year, rotavirus gastroenteritis is responsible for about 37% of deaths from diarrhea among children younger than 5 years of age worldwide, with a disproportionate effect in sub-Saharan Africa. METHODS: We conducted a randomized, placebo-controlled trial in Niger to evaluate the efficacy of a live, oral bovine rotavirus pentavalent vaccine (BRV-PV, Serum Institute of India) to prevent severe rotavirus gastroenteritis. Healthy infants received three doses of the vaccine or placebo at 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and were graded on the basis of the score on the Vesikari scale (which ranges from 0 to 20, with higher scores indicating more severe disease). The primary end point was the efficacy of three doses of vaccine as compared with placebo against a first episode of laboratory-confirmed severe rotavirus gastroenteritis (Vesikari score, ≥11) beginning 28 days after dose 3. RESULTS: Among the 3508 infants who were included in the per-protocol efficacy analysis, there were 31 cases of severe rotavirus gastroenteritis in the vaccine group and 87 cases in the placebo group (2.14 and 6.44 cases per 100 person-years, respectively), for a vaccine efficacy of 66.7% (95% confidence interval [CI], 49.9 to 77.9). Similar efficacy was seen in the intention-to-treat analyses, which showed a vaccine efficacy of 69.1% (95% CI, 55.0 to 78.7). There was no significant between-group difference in the risk of adverse events, which were reported in 68.7% of the infants in the vaccine group and in 67.2% of those in the placebo group, or in the risk of serious adverse events (in 8.3% in the vaccine group and in 9.1% in the placebo group); there were 27 deaths in the vaccine group and 22 in the placebo group. None of the infants had confirmed intussusception. CONCLUSIONS: Three doses of BRV-PV, an oral rotavirus vaccine, had an efficacy of 66.7% against severe rotavirus gastroenteritis among infants in Niger. (Funded by Médecins sans Frontières Operational Center and the Kavli Foundation; ClinicalTrials.gov number, NCT02145000 .).

Rotavirus vaccination in the neonatal intensive care units: where are we? A rapid review of recent evidence.

PURPOSE OF REVIEW: Rotavirus is a leading cause of viral acute gastroenteritis in infants. Neonates hospitalized in neonatal intensive care units (NICUs) are at risk of rotavirus infections with severe outcomes. The administration of rotavirus vaccines is only recommended, in the United States and Canada, upon discharge from the NICU despite rotavirus vaccines being proven well tolerated and effective in these populations, because of risks of live-attenuated vaccine administration in immunocompromised patients and theoretical risks of rotavirus vaccine strains shedding and transmission.We aimed to summarize recent evidence regarding rotavirus vaccine administration in the NICU setting and safety of rotavirus vaccines in preterm infants. METHODS: We conducted a rapid review of the literature from the past 10 years, searching Medline and Embase, including all study types except reviews, reporting on rotavirus vaccines 1 and 5; NICU setting; shedding or transmission; safety in preterm. One reviewer performed data extraction and quality assessment. RECENT FINDINGS: Thirty-one articles were analyzed. Vaccine-derived virus shedding following rotavirus vaccines existed for nearly all infants, mostly during the first week after dose 1, but with rare transmission only described in the household setting. No case of transmission in the NICU was reported. Adverse events were mild to moderate, occurring in 10-60% of vaccinated infants. Extreme premature infants or those with underlying gastrointestinal failure requiring surgery presented with more severe adverse events. SUMMARY: Recommendations regarding rotavirus vaccine administration in the NICU should be reassessed in light of the relative safety and absence of transmission of rotavirus vaccine strains in the NICU.

Rotavirus group A genotype circulation patterns across Kenya before and after nationwide vaccine introduction, 2010-2018.

BACKGROUND: Kenya introduced the monovalent G1P [8] Rotarix® vaccine into the infant immunization schedule in July 2014. We examined trends in rotavirus group A (RVA) genotype distribution pre- (January 2010-June 2014) and post- (July 2014-December 2018) RVA vaccine introduction. METHODS: Stool samples were collected from children aged < 13 years from four surveillance sites across Kenya: Kilifi County Hospital, Tabitha Clinic Nairobi, Lwak Mission Hospital, and Siaya County Referral Hospital (children aged < 5 years only). Samples were screened for RVA using enzyme linked immunosorbent assay (ELISA) and VP7 and VP4 genes sequenced to infer genotypes. RESULTS: We genotyped 614 samples in pre-vaccine and 261 in post-vaccine introduction periods. During the pre-vaccine introduction period, the most frequent RVA genotypes were G1P [8] (45.8%), G8P [4] (15.8%), G9P [8] (13.2%), G2P [4] (7.0%) and G3P [6] (3.1%). In the post-vaccine introduction period, the most frequent genotypes were G1P [8] (52.1%), G2P [4] (20.7%) and G3P [8] (16.1%). Predominant genotypes varied by year and site in both pre and post-vaccine periods. Temporal genotype patterns showed an increase in prevalence of vaccine heterotypic genotypes, such as the commonly DS-1-like G2P [4] (7.0 to 20.7%, P < .001) and G3P [8] (1.3 to 16.1%, P < .001) genotypes in the post-vaccine introduction period. Additionally, we observed a decline in prevalence of genotypes G8P [4] (15.8 to 0.4%, P < .001) and G9P [8] (13.2 to 5.4%, P < .001) in the post-vaccine introduction period. Phylogenetic analysis of genotype G1P [8], revealed circulation of strains of lineages G1-I, G1-II and P [8]-1, P [8]-III and P [8]-IV. Considerable genetic diversity was observed between the pre and post-vaccine strains, evidenced by distinct clusters. CONCLUSION: Genotype prevalence varied from before to after vaccine introduction. Such observations emphasize the need for long-term surveillance to monitor vaccine impact. These changes may represent natural secular variation or possible immuno-epidemiological changes arising from the introduction of the vaccine. Full genome sequencing could provide insights into post-vaccine evolutionary pressures and antigenic diversity.

Prospective surveillance for intussusception in Indian children aged under two years at nineteen tertiary care hospitals.

BACKGROUND: India introduced rotavirus vaccines (RVV, monovalent, Rotavac™ and pentavalent, Rotasiil™) in April 2016 with 6, 10 and 14 weeks schedule and expanded countrywide in phases. We describe the epidemiology of intussusception among children aged 2-23 months in India. METHODS: The prospective surveillance at 19 nationally representative sentinel hospitals from four regions recruited children with intussusception from April 2016 to September 2017. Data on sociodemography, immunization, clinical, treatment and outcome were collected. Along with descriptive analysis, key parameters between four regions were compared using Chi-Square/Fisher's exact/Mann-Whitney U/Kruskal-Wallis tests. The pre- and post-RVV periods were compared to estimate the risk ratios. RESULTS: Six hundred twenty-one children with intussusception from South (n = 262), East (n = 190), North (n = 136) and West (n = 33) regions were recruited. Majority (n = 465, 74.8%) were infants (40.0% aged 4-7 months) with median age 8 months (IQR 5, 13 months), predominantly males (n = 408, 65.7%) and half (n = 311, 50.0%) occurred during March-June months. A shorter interval between weaning and intussusception was observed for ragi based food (median 1 month, IQR 0-4.2 months) compared to rice (median 4 months, IQR 1-9 months) and wheat (median 3 months, IQR 1-7 months) based food (p < 0.01). Abdominal pain or excessive crying (82.8%), vomiting (72.6%), and bloody stool (58.1%) were the leading symptoms. Classical triad (abdominal pain, vomiting and bloody stool) was observed in 34.8% cases (24.4 to 45.8% across regions). 95.3% of the cases were diagnosed by ultrasound. 49.3% (10.5 to 82.4% across regions) cases were managed by reduction, 39.5% (11.5 to 71.1% across regions) cases underwent surgery and 11.1% spontaneously resolved. Eleven (1.8%) cases died. 89.1% cases met Brighton criteria level 1 and 7.6% met Level 2. RVV was received by 12 cases within 1-21 days prior to intussusception. No increase in case load (RR = 0.44; 95% CI 0.22-1.18) or case ratio (RR = 0.5; 95% CI 0.3-1.2) was observed after RVV introduction in select sites. CONCLUSIONS: Intussusception cases were observed across all sites, although there were variations in cases, presentation and mode of management. The high case load age coincided with age of the RVV third dose. The association with ragi based weaning food in intussusception needs further evaluation.

Accounting for indirect protection in the benefit-risk ratio estimation of rotavirus vaccination in children under the age of 5 years, France, 2018.

Background Rotavirus is a major cause of severe gastroenteritis in children worldwide. The disease burden has been substantially reduced in countries where rotavirus vaccines are used. Given the risk of vaccine-induced intussusception, the benefit­risk balance of rotavirus vaccination has been assessed in several countries, however mostly without considering indirect protection effects. Aim We performed a benefit­risk analysis of rotavirus vaccination accounting for indirect protection in France among the 2018 population of children under the age of 5 years. Methods To incorporate indirect protection effects in the benefit formula, we adopted a pseudo-vaccine approach involving mathematical approximation and used a simulation design to provide uncertainty intervals. We derived background incidence distributions from quasi-exhaustive health claim data. We examined different coverage levels and assumptions regarding the waning effects and intussusception case fatality rate. Results With the current vaccination coverage of < 10%, the indirect effectiveness was estimated at 6.4% (+/− 0.4). For each hospitalisation for intussusception, 277.0 (95% uncertainty interval: (165.0­462.1)) hospitalisations for rotavirus gastroenteritis were prevented. Should 90% of infants be vaccinated, indirect effectiveness would reach 57.9% (+/− 3.7) and the benefit­risk ratio would be 192.4 (95% uncertainty interval: 116.4­321.3). At a coverage level of 50%, indirect protection accounted for 27% of the prevented rotavirus gastroenteritis cases. The balance remained in favour of the vaccine even in a scenario with a high assumption for intussusception case fatality. Conclusions These findings contribute to a better assessment of the rotavirus vaccine benefit­risk balance.

[Historical overview of acute infectious diarrhea in Mexico and future preventive strategies]. / Panorama histórico de la enfermedad diarreica aguda en México y el futuro de su prevención.

OBJECTIVE: To analyze the epidemiological aspects of AID through Mexican history and the potential strategies to pre- vent AID in Mexican population. MATERIALS AND METHODS: A systematic review was performed exploring the key words, diarrhea, morbidity, mortality, Mexico, health promotion for the last 20 years (1978-2018). RESULTS: Over 8 600 articles were obtained; all of them were evaluated to consider those follow the aim of the present work. CONCLUSIONS: The result of the performed systematic review denoted the influence of AID in Mexican public health policy; the adopted actions diminished the AID's associated risks and allowed future strategies to prevent it; those actions must include hygienic and dietetic measures, pharmaceutical innovations and technological tools applied to health policies.

OBJETIVO: Revisar los aspectos epidemiológicos de la enfermedad diarreica aguda (EDA) a través de la historia de México y analizar las estrategias que potencialmente podrán prevenir su aparición en la población mexicana. MATERIAL Y MÉTODOS: Se realizó una búsqueda sistematizada utilizando los siguientes descriptores de las ciencias de la salud: diarrea, morbilidad, mortalidad, México y promoción de la salud de los últimos 20 años (1878-2018). RESULTADOS: Se obtuvieron más de 8 600 artículos que fueron evaluados en función de los objetivos de la presente publicación. CONCLUSIONES: Como resultado de una revisión sistemática se observó que, gracias a las estrategias implementadas a lo largo del tiempo, se ha logrado graduar los matices de riesgo de la EDA; ello permite ahora plantear estrategias que guiarán a la prevención de ese padecimiento, de la mano de políticas que incluyan aspectos higiénico-dietéticos, innovaciones farmacéuticas y aplicaciones tecnológicas en medidas sanitarias.

Current and new rotavirus vaccines.

PURPOSE OF REVIEW: As of 2019, four rotavirus vaccines have been prequalified by the WHO for use worldwide. This review highlights current knowledge regarding rotavirus vaccines available, and provides a brief summary of the rotavirus vaccine pipeline. RECENT FINDINGS: Data generated from use of currently available products supports their effectiveness and impact in diverse settings. Rotavirus vaccines have a favorable risk-benefit profile, but previous associations of rotavirus vaccination with intussusception necessitate continued monitoring for this rare but serious adverse event. Implementation of rotavirus vaccines was jeopardized in late 2018 and 2019 by a shortage of vaccine supply. Fortunately, with the prequalification of two additional vaccines in 2018, countries have increased choice in products with different characteristics, pricing, and implementation strategies. Other vaccines currently in development may open up further immunization strategies, such as neonatal vaccination schedules or parenteral administration. SUMMARY: Rotavirus vaccines have demonstrated impact in reducing diarrheal morbidity and mortality worldwide. As countries begin to introduce the newly prequalified vaccines, additional data will become available on the safety and effectiveness of those products. Products in the pipeline have distinct profiles and could be an essential part of the expansion of rotavirus vaccine use worldwide.

Persistent systemic rotavirus vaccine infection in a child with X-linked severe combined immunodeficiency.

OBJECTIVE: The main aims of the present study were to elucidate the systemic group A rotavirus (RVA) infection and to clarify the genetic changes of persistent virus in the X-linked severe combined immunodeficiency (SCID) patient. METHODS: RotaTeq vaccine (RV5) genotype-specific real-time reverse transcription polymerase chain reaction was used to monitor viral RNA load in serially collected serum and stool samples. Next-generation sequence analysis was used to determine the genotype of the virus by sequencing 11 gene segments. Polyacrylamide gel electrophoresis (PAGE) analysis was used to identify rearrangement of viral genes. The gene rearrangement was examined in NSP5 gene by using Sanger sequence. RESULTS: A 7-month-old boy demonstrated chronic diarrhea following the third administration of RV5 and failure to thrive. He was diagnosed with X-linked SCID and successfully underwent cord blood transplantation. High copy numbers of RV5 genotype G1 RNA were detected in serially collected stool and serum samples and the kinetics of viral RNA loads were correlated with the degree of clinical disease. Next-generation sequence analysis revealed genetic reassortment at least between the strains WI79-9/G1P7[5] and WI79-4/G6P1A[8] in the VP7 gene and the VP4 gene among the vaccine-derived rotavirus strains. In addition, PAGE analysis suggested genetic rearrangements in several genes, and it was confirmed in the NSP5 gene by sequence analysis. CONCLUSIONS: The kinetics of RVA RNA load in serum and stool samples was consistent with the clinical course of the patient. Among five genotypes of RV5 vaccine, G1 genotype replicated well in this patient. Reassortment and rearrangements were demonstrated in persistently infected G1 genotype of RV5.

[False beliefs about vaccines]. / Falsas creencias sobre las vacunas.

Vaccines are an essential tool for the prevention of infectious diseases. However, false ideas and rumours with no scientific foundation about their possible negative effects may dissuade people from being vaccinated, with the consequent risks for the health of the population. The objective of this article is to evaluate the origin and the arguments of some of the most frequent mistaken ideas and rumours about the possible adverse effects of vaccines. Some clearly established adverse effects are presented, as well as false beliefs about various vaccines and potential harm to health. Vaccines, like any drug, can cause adverse effects, but the possible adverse effects of vaccination programs are clearly lower than their individual (vaccinated) and collective benefits (those vaccinated and those who cannot be vaccinated for medical reasons). The possible adverse effects attributable to vaccines should be detected by powerful and well-structured pharmacovigilance systems.

Trends in Rate of Seizure-Associated Hospitalizations Among Children <5 Years Old Before and After Rotavirus Vaccine Introduction in the United Sates, 2000-2013.

Background: Rotavirus is a common cause of acute gastroenteritis and has also been associated with generalized tonic-clonic afebrile seizures. Since rotavirus vaccine introduction, hospitalizations for treatment of acute gastroenteritis have decreased. We assess whether there has been an associated decrease in seizure-associated hospitalizations. Methods: We used discharge codes to abstract data on seizure hospitalizations among children <5 years old from the State Inpatient Databases of the Healthcare Cost and Utilization Project. We compared seizure hospitalization rates before and after vaccine introduction, using Poisson regression, stratifying by age and by month and year of admission. We performed a time-series analysis with negative binomial models, constructed using prevaccine data from 2000 to 2006 and controlling for admission month and year. Results: We examined 962899 seizure hospitalizations among children <5 years old during 2000-2013. Seizure rates after vaccine introduction were lower than those before vaccine introduction by 1%-8%, and rate ratios decreased over time. Time-series analyses demonstrated a decrease in the number of seizure-coded hospitalizations in 2012 and 2013, with notable decreases in children 12-17 months and 18-23 months. Conclusions: Our analysis provides evidence for a decrease in seizure hospitalizations following rotavirus vaccine introduction in the United States, with the greatest impact in age groups with a high rotavirus-associated disease burden and during rotavirus infection season.

Epidemiology of rotavirus gastroenteritis and need of high rotavirus vaccine coverage with early completion of vaccination schedule for protection against rotavirus diarrhea in India: A narrative review.

Rotavirus is a leading cause of severe pediatric diarrhea worldwide, with about 199,000 childhood deaths in 2015, of which 90% in low-income countries. India alone accounts for 22% of the global rotavirus gastroenteritis (RVGE)-related deaths among children below 5 years of age. The World Health Organization recommends introducing rotavirus vaccines (RVVs) as a priority in developing countries where high rates of RVGE are observed. To have the desired impact, RVV should be administered the earliest possible, ideally before the first episode of RVGE. In India, four RVVs are available for use in infants ≥6 weeks of age: the single-strain, two-dose, live-attenuated human RVV Rotarix; the five-strain, three-dose, human-bovine reassortant RVV Rotateq; the single-strain, three-dose, naturally reassortant human-bovine RVV Rotavac; and the five-strain, three-dose, human-bovine RVV Rotasiil; all of them proven to be efficacious and well tolerated. Whereas Rotarix and Rotateq have shown high efficacy/effectiveness against severe RVGE in developed countries (≥90%), they have been observed to be lower in developing countries (~40%-70%). Rotavac and Rotasiil have shown similar efficacy in low-income settings, but further studies are needed to assess their effectiveness. Rotarix and Rotateq have not shown increased intussusception (IS) risk in clinical trials. Postmarketing surveillances were able to show a very tiny increased risk of IS after the first dose of vaccine, but the extensive benefits of rotavirus vaccination far outweigh the low-level risk of IS. In India, where the disease is a major problem and occurs in very early months of life, RVVs should have high coverage and vaccination schedule should be completed as early as possible (≥6 weeks of age) to maximize the vaccine impact.