Post-marketing surveillance of intussusception after Rotarix administration in Afghanistan, 2018-2022.

BACKGROUND: In January 2018, Afghanistan introduced the monovalent oral rotavirus vaccine (Rotarix) nationwide, administered as a 2-dose series at six and ten weeks of age. We describe characteristics of intussusception cases and assess potential intussusception risk associated with Rotarix vaccination in Afghan infants. METHODS: Multi-center prospective active hospital-based surveillance for intussusception was conducted from May 2018 to March 2022 in four sentinel sites in Afghanistan. We applied the Brighton Level 1 criteria for intussusception and verified vaccination status by reviewing vaccine cards. We used the self-controlled case series (SCCS) methodology to compare intussusception incidence in the 1 to 21 days after each dose of Rotarix vaccination against non-risk periods. RESULTS: A total of 468 intussusception cases were identified in infants under 12 months, with 264 cases aged between 28 and 245 days having confirmed vaccination status contributing to the SCCS analysis. Most case-patients (98 %) required surgery for treatment, and over half (59 %) of those who underwent surgery required intestinal resection. Nineteen (7 %) case-patients died. Eighty-six percent of case-patients received the first dose of Rotarix, and 69 % received the second dose before intussusception symptom onset. There was no increased risk of intussusception in the 1-7 days (relative incidence: 0.9, 95 % CI: 0.1, 7.5), 8-21 days (1.3, 95 % CI: 0.4, 4.2), or 1-21 days (1.1, 95 % CI: 0.4, 3.4) following receipt of the first dose or in the 1-7 days (0.2, 95 % CI: 0.3, 1.8), 8-21 days (0.7, 95 % CI: 0.3, 1.5), or 1-21 days (0.6, 95 % CI: 0.3, 1.2) following the second dose. CONCLUSION: Rotarix vaccination was not associated with an increased intussusception risk, supporting its continued use in Afghanistan's immunization program. However, there was a high level of death and resection due to intussusception among Afghan infants.

Intussusception and Chronic Marijuana Use in a Young Adult.

BACKGROUND Intussusception is a common phenomenon in children, but it is rare in adults. In the pediatric population, the presentation is commonly primary, without a lead point. However, up to 90% of intussusception cases arise due to a secondary cause - a pathological lead point - which the most common etiology in adults being malignancy. Herein, we present a case report of adult intussusception without a known cause. CASE REPORT A 26-year-old woman presented to the hospital with severe abdominal pain. She admitted to not passing stool or gas for 2 days. The patient's social history was significant for chronic marijuana use. A computed tomography (CT) scan of the abdomen revealed a 6-cm in length intussuscepted segment of bowel in the descending colon distal to the splenic flexure with no obvious inciting mass. The patient was sent for emergent open abdominal surgery. Upon surgical exploration, the surgeons discovered that the intussusception had self-resolved. Aside from a small ball of stool, an intraoperative colonoscopy revealed no masses or polyps. CONCLUSIONS Marijuana use is known to disrupt gastrointestinal (GI) mobility through receptors in the GI tract nerve plexuses. The incidence of chronic marijuana use and adult intussusception is documented in the literature. Conservative management with bowel rest is confirmed to be a suitable treatment option with a favorable outcome. Therefore, we present this case to increase awareness of the potential adverse effects of chronic marijuana use, and to prevent invasive treatment.

Impact of rotavirus vaccination on intussusception hospital admissions in England.

BACKGROUND: An increased risk of intussusception has been reported following rotavirus vaccination. We sought to determine whether introduction of rotavirus vaccination in England in July 2013 was associated with a change in the burden of total and age group-specific childhood hospital admissions for intussusception. METHODS: We identified all children aged 0-36 months admitted to hospitals in England with intussusception using the Hospital Episode Statistics dataset. We performed a retrospective ecological analysis comparing hospital admission rates for intussusception during the periods before (2008/2009-2012/2013) and after (2014/2015-2017/2018) introduction of rotavirus vaccination using modified Poisson regression and interrupted time series analysis. Length of hospital stay and clinical outcomes were also examined. RESULTS: The mean annual admission rate for intussusception in infants over the ten-year study period was 31.5 per 100,000 person-years. An increase in the admission rate in the 8-16 weeks age group (RR 1.46, 95% CI 1.12-1.91), those receiving vaccination, was compensated for by decreases in the 17-24 weeks (RR 0.77, 0.63-0.94), 25-32 weeks (RR 0.71, 0.59-0.86) and 41-52 weeks (RR 0.80, 0.66-0.98) age groups. Using interrupted time series analysis, we observed a significant decrease in incidence in the 0-12 months age group (RR 0.80, 0.67-0.96), but not in the overall 0-36 months age group (RR 1.09, 0.98-1.20). There was no significant change in the proportion of children requiring surgical intervention or with major complications of intussusception. Length of hospital stay decreased among infants receiving surgery for intussusception. CONCLUSIONS: Our results suggest that introduction of rotavirus vaccination in England has resulted in a downward shift in the age at which intussusception occurs in infants, with no overall increase in hospital admission rate or disease severity. These findings support the view that the benefits of rotavirus vaccination outweigh the small increased risk of intussusception in the early post-vaccination period.

[A Case of Small Intestinal Metastasis with Intussusception Due to Barium].

A 48-year-old man noticed nausea and took health examination. After chest X-ray and gastrointestinal barium study was underwent, he was referred to our hospital because of abnormal shadow in the chest X-ray. CT scan revealed about 4 cm tumor in the hilum of left lung and target sign in the small intestine. He was diagnosed with intussusception and emergency operation was performed. During the laparotomy, we found 2 intussusceptions in the small intestine and we performed manual reduction using Hutchinson's maneuver. We confirmed the mass in oral side of the intussusception site but we did not confirmed any tumor in anal of the intussusception. This suggests the intussusception was caused by barium. Finally 3 small intestine tumor was observed and we resected and reconstructed each of the tumor. Histopathological examination showed small intestinal metastasis from pleomorphic carcinoma of the lung.

Leveraging the National Rotavirus Surveillance Network for Monitoring Intussusception.

OBJECTIVE: To assess feasibility of monitoring intussusception by hospitals participating in the National Rotavirus Surveillance Network. METHODS: Questionnaire-based survey in 28 hospitals. One hospital with electronic records selected for detailed data analysis. RESULTS: There was 75% response to the questionnaire. Few network hospitals were suitable for monitoring intussusception in addition to ongoing activities, but there was at least one potential sentinel hospital in each region. The hospital selected for detailed data analysis of cases of intussusception reported an incidence rate of 112 per 100,000 child years in infants. Over 90% of intussusceptions were managed without surgery. CONCLUSIONS: Selection of sentinel hospitals for intussusception surveillance is feasible and necessary, but will require training, increased awareness and referral.

Post-rotavirus vaccine intussusception in identical twins: A case report.

The intussusception is one of the most frequent causes of occlusive syndrome in infants and in children. (1) The mesenteric lymphadenopathy, wich is very rare post rotavirus vaccination, can cause intussusception, (2-5) especially in genetically predisposed individuals. (6) There is an association between intussusception and some classes of genotype. (7-9) Two infants aged 3 months, vaccinated against rotavirus. After about a week, one of the 2 identical infants presented inconsolable crying, vomiting, loose stools mixed with blood, and was diagnosed with bowel obstruction with intussusception. He was operated in urgency. After a few hours, his brother presented vomiting, and was admitted to our Hospital for suspected intussusception. The controls carried out have confirmed the presence of intussusception that was treated early, before the onset of severe symptoms. The incidence of post rotavirus vaccine intussusception is very low. The determining factor hypothetically might be linked to the presence of a genotype that exposes infants to a greater risk of developing mesenteric lymphadenitis and intussusception. In our case, the diagnosis of intussusception occurred in a twin, which allowed us to recognize early symptoms which accused the brother and schedule the surgery with less urgency. Our experience may want to sensitize families and pediatricians to report cases of intussusception given a theoretical familiar association. The study of the genotype could be decisive for or not to exclude the presence of a risk of invagination, thus avoiding vaccination.

Intussusception incidence rates in 9 Zambian hospitals, 2007-2011: prerotavirus vaccine introduction.

BACKGROUND: Intussusception, a rare adverse event associated with rotavirus vaccines in some settings, is a common cause of intestinal obstruction in infants and toddlers globally with a peak age of 4-6 months. This age group may overlap with the extended age of administering rotavirus vaccine. METHODS: A retrospective (January 2007 to June 2009) and prospective (July 2009 to June 2012) survey was conducted in 9 Zambian hospitals. Children between 0 and 24 months who were operated on for intestinal obstruction/intussusception were identified in theatre log books. In the latter part of the survey, patients were recruited prospectively. Demographic, clinical and surgical data from hospital files were collected for each patient. RESULTS: One-hundred and five children were identified to have undergone surgery for intussusceptions. Many were boys 57.6% (57/99). Of those with complete data, intussusception was common in infants 86.9% (86/99) and many children (68.0%) were between 3 and 8 months of age with a peak age of 5-6 months. Lusaka had the highest number of children with intussusception with an estimated annual incidence rate of 12/100,000 in children <2 years of age. The overall case fatality rate was very high 33.7% (31/92). CONCLUSION: Intussusception was common in infants with a peak age of 5-6 months, and of particular concern is the group of 2-4 months the age of rotavirus vaccination. The estimated incidence rate of 12/100,000 is an underestimate as many cases may not present for care. The high case fatality rate of 33.7% is due to both delayed presentation and diagnosis in hospital.

Workshop on intussusception in African countries--meeting report.

Rotavirus causes approximately 450,000 deaths annually among children less than 5 years of age worldwide, almost half of which occur in Africa. After the recent completion of successful trials of 2 new rotavirus vaccines, the World Health Organization has recommended these vaccines for all children worldwide. Because a previous rotavirus vaccine, Rotashield(®), was associated with intussusception, a form of intestinal obstruction among infants, the current rotavirus vaccines were tested in large clinical trials and found to be safe. However, due to the past Rotashield(®) experience, post licensure monitoring of intussusception is considered to be crucial after the introduction of future oral rotavirus vaccines. Thus, in planning for future introductions of rotavirus vaccine in Africa, a workshop of experts working on intussusception was convened by the World Health Organization in May 2004 in association with the Pan-African Association of Paediatric Surgeons (PAPSA) in Malawi. In brief, delegates from ten countries presented data from retrospective record reviews of intussusception events from 1993 to 2003 at selected hospitals in their respective countries. This review showed that age of intussusception onset during infancy varies markedly with peak prevalence between 4 and 6 months of life. Diagnostic modality (e.g., contrast enema, ultrasound) was employed in <20% of the events; nearly 70% of the intussusception events were diagnosed at the time of surgery. Overall, case-fatality was high, ~13%, in these African countries. The findings of this meeting highlight the challenges in implementing surveillance for intussusception after rotavirus vaccine introduction in Africa. The deliberations identified some concrete steps necessary to establish active surveillance at sentinel sites in African countries. This is becoming more urgent now that many countries are expressing interest in introducing rotavirus vaccines.

Safety of the pentavalent rotavirus vaccine (PRV), RotaTeq(®), in Kenya, including among HIV-infected and HIV-exposed infants.

Two multicenter Phase III trials were conducted in five countries from March 2007 to March 2009 to evaluate the safety and efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq(®), in Africa and Asia. In this report, we evaluate the safety of this vaccine, including among HIV-infected and HIV-exposed infants, in Kenya. 1308 Infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6, 10, and 14 weeks of age. HIV counseling and testing were offered to all participants. A positive PCR result indicated HIV infection; the presence of HIV antibody in PCR-negative children indicated HIV exposure without HIV infection. All serious adverse events (SAE) within 14 days of any dose, and vaccine-related SAEs, intussusception, and deaths occurring at any time during the study, were reported ("SAE surveillance"). In addition, 297 participants were followed for 42 days after any dose for any adverse event (AE), regardless of severity ("intensive safety surveillance"). The safety evaluation was stratified by HIV status. SAEs were reported in 20/649 vaccine recipients (3.1%) and 21/643 placebo recipients (3.3%) within 14 days following vaccination (p = 0.9). The most common SAE in the vaccinated group was pneumonia (1.7%). No individual SAE was significantly more common among vaccine vs. placebo recipients. Seventy-two deaths were reported, 38 (5.9%) and 34 (5.3%) among vaccine and placebo recipients, respectively (p = 0.66). No cases of intussusception were reported. During intensive safety surveillance, 137/147 (93.2%) vaccine recipients and 147/150 (98.0%) placebo recipients experienced one or more AEs (risk ratio = 0.95; 95% CI: 0.91-1.0; p = 0.05). 88.5% of the infants were tested for HIV infection; 21/581 (3.6%) children in the vaccine group and 17/577 (2.9%) in the placebo group were HIV-infected. Among the 37 HIV-infected infants with full safety follow-up, 5/21 (23.8%) vaccine recipients and 2/16 (12.5%) placebo recipients reported an SAE (p = 0.67). In total, 12 deaths occurred among identified HIV-infected infants: 8 (38%) receiving vaccine vs. 4 (23.5%) receiving placebo (RR = 1.6, 95% CI: 0.59-4.5). Among the 21 HIV-infected infants in the vaccine group, 2 of 8 deaths were gastroenteritis-related; among the 17 HIV-infected infants in the placebo group, 3 of 4 deaths were gastroenteritis-related. There were no significant differences in serious or non-serious AEs, including vaccine-related SAEs, between the 88 HIV-exposed vaccine recipients vs. the 89 HIV-exposed placebo recipients. PRV appears to be a safe intervention against rotavirus gastroenteritis among infants in Kenya. AEs, including serious AEs, were not associated with receipt of vaccine. Further, SAEs were not significantly more common among HIV-infected or HIV-exposed participants; however, the low number of HIV-infected infants did not provide sufficient power to fully assess safety in HIV-infected vaccine recipients.

Adult idiopathic intussusception: a case report and review of the literature.

Adult intussusception is a rare condition. Most of the cases are due to an organic lesion and unlike the incidence in children idiopathic forms are really exceptional, occurring at a rate of 5% of all cases. Whereas in children a main cause is seldom found, adult intussusception is usually characterised by the presence of a leading intraluminal benign or malignant lesion. The authors report their experience with a clinical case of ileocolic intussusception occurring in an 28-year-old white male. In spite of the patient's age, the clinical presentation was very typical with the classic triad of abdominal pain, blood per rectum and a palpable mass. Diagnostic tools, namely US and TC scan, together with colonoscopy confirmed the physical examination, so that surgery was initiated with a definite diagnosis of intussusception. A large polyp or a lymphoma were considered the possible leading causes. After right hemicolectomy, pathology revealed that there was no organic lesion and the bulging mass was caused only by oedema and haemorrhagic infiltration of the invaginated loop. The patient had been on antipsychotic drugs for several months and the possible explanation of the pathology was linked to altered peristalsis induced by the pharmacological agents he was taking. The authors compare their experience with the data reported in the literature, evaluating in particular the incidence, pathology, clinical presentation, diagnosis and treatment of adult intussusception.

Association of tumor necrosis factor, interleukin-6 and cyclooxygenase pathway with lipopolysaccharide-induced intussusception.

INTRODUCTION: Many factors and mechanisms have been proposed as causes for intussusception (IN); however, the etiology remains unclear. Inflammatory mediators such as tumor necrosis factor (TNF) and interleukin-6 (IL-6), which are elevated during infectious diseases, can significantly affect gastrointestinal motility. Motility changes caused by these agents might contribute to the development of IN. The aim of this experimental study was to determine the preventive effects of indomethacin on lipopolysaccharide (LPS)-induced IN in mice and to investigate the role of TNF and IL-6 on intussusception. MATERIALS AND METHODS: Seventy-eight mice were divided into five groups. In the Control group (n=6), no procedure was done. In the Sham group (n=6), 1 ml saline, in the Indomethacin group (n=6), 10 mg/kg of indomethacin, in the LPS group (n=30), 12 mg/kg of LPS was administered intraperitoneally (IP). In the Treatment group (n=30), 10 mg/kg of indomethacin was administered IP following 12 mg/kg of LPS. All animals were laparotomized 6 hours following IP injections. The existence of IN was noted and blood specimens were obtained. TNFalpha and IL-6 plasma level measurements were performed by standard ELISA for mice. The results were compared using the Mann-Whitney U test and one-way ANOVA test. A value of p<0.05 was considered significant. RESULTS: Five mice (1 in the control, 2 in the LPS, 2 in the Treatment group) were excluded from the study. IN was observed in 6 (20%) mice in the LPS group, whereas it was not found in any mice in the Treatment group. Mean TNFalpha and IL-6 levels were statistically higher in the LPS group (394.72+/-403.79; 195.18+/-218.37 pg/ml, respectively) compared to all other groups, including the Treatment group (p<0.05 for each comparison). Within the LPS group of mice, the levels were higher in animals with IN compared to the mice without IN. CONCLUSION: Increased TNFalpha and IL-6 levels induced by LPS correlated well with the occurrence of IN, and a decrease in these levels via cyclooxygenase (COX) inhibition by indomethacin prevented IN from forming in this experimental model.

Rotavirus infection enhances lipopolysaccharide-induced intussusception in a mouse model.

Unexpected reports of intussusception after vaccination with the live tetravalent rotavirus vaccine RotaShield resulted in voluntary withdrawal of the vaccine. Intussusception, a condition in which the intestine acutely invaginates upon itself, is the most common cause of intestinal obstruction in children. We report here the development of a mouse model to study rotavirus-induced intussusception. In this model, both homologous murine and heterologous simian rotavirus strains significantly enhanced the rate of lipopolysaccharide (LPS)-induced intussusception, and this enhancement was replication dependent, requiring rotavirus doses of greater than one 50% infectious dose. Rotavirus-induced intussusceptions did not have observable lymphoid lead points, despite the induction of intestinal lymphoid hyperplasia after rotavirus infection. Intussusceptions are also postulated to result from altered intestinal motility, but rotavirus infection had no effect on gastrointestinal transit. LPS-induced intussusception is associated with the induction of inflammatory mediators, and intussusception rates can be modified by inflammatory antagonists. We show that rotavirus infection significantly enhanced serum tumor necrosis factor alpha and gamma interferon cytokine levels after LPS treatment compared to uninfected mice. Together, these data suggest that rotavirus infection sensitized mice to the inflammatory effects of subsequent LPS treatment to enhance intussusception rates.

Intussusception of vermiform appendix with microscopic melanosis coli: a case report.

Intussusception of the appendix is a rare occurrence. Due to the similarity of its symptoms with appendicitis, preoperative diagnosis of this condition is extremely difficult. In this report, we present appendiceal intussusception with histological melanosis coli that occurred in a patient on long-term anthranoid laxative use for chronic constipation. Melanosis coli in the appendiceal tissue, as an indicator of chronic laxative intake, may be a clue implying that the appendical exposure to hyperperistalsis for a long time in our case led to the intussusception. We conclude that colonoscopy may help in preoperative diagnosis of appendiceal intussusception in patients with suspicious appendicitis, particularly in those using laxative medication.

Declaración del Comité Consultivo de Inmunizaciones (CCI) de la Sociedad Chilena de Infectología respecto a vacuna anti-rotavirus: Marzo 2006 / Rotavirus vaccine: statement of the Consultive Committee of Immunizations on behalf of The Chilean Infectious Diseases Society: March 2006

Se presenta una breve revisión de la epidemiología de la infección por rotavirus y de los antecedentes científicos de las vacunas Rotashield®, retirada del mercado luego de mostrar asociación con invaginación intestinal en EEUU, Rotateq® actualmente en fases finales de desarrollo y Rotarix®, recientemente licenciada en Chile. Considerando estos antecedentes, el Comité Consultivo de Inmunizaciones de la Sociedad Chilena de Infectología, indica sus conclusiones y recomendaciones en relación a la vacunación anti-rotavirus de lactantes en nuestro país.

Vacunas anti-rotavirus: al fin una realidad / New rotavirus vaccines: a reality at last

Rotavirus es la primera causa de diarrea aguda grave en niños bajo 3 años de edad en el mundo. Esta infección es responsable de 25 millones de consultas, 2 millones de hospitalizaciones y 440.000 muertes por año en niños con menos de 5 años. El desarrollo de vacunas anti-rotavirus ha sido un camino largo y tortuoso marcado por la abrupta caída de Rotashield® en 1999 debido a su asociación con invaginación intestinal. Luego de seis años de intensa investigación, el mundo celebra la licencia de dos nuevas vacunas que, a pesar de ser diferentes en su formulación y forma de administración, han demostrado ser seguras y no asociadas a invaginación intestinal, en estudios de Fase III de gran magnitud, que enrolaron más de 60.000 niños. Estas dos vacunas, Rotarix® de Glaxo SmithKline Biologicals y Rotateq® de Merck Sharp & Dohme son altamente eficaces contra diarrea grave causada por rotavirus de los serotipos más prevalentes en el mundo. La incorporación de estas vacunas, más temprano que tarde, especialmente en los países más pobres del mundo, requerirá de un esfuerzo conjunto de los gobiernos, laboratorios productores, organismos internacionales y no gubernamentales y fundaciones de beneficencia.

Intussusception in children with ALL receiving chemotherapy for acute lymphoblastic leukaemia.

Acute abdominal complications of chemotherapy are common but the differential diagnosis wide. We describe two cases of intussuception of the bowel in children receiving chemotherapy for acute lymphoblastic leukaemia (ALL) and discuss how a high clinical suspicion is critical for the correct diagnosis to be made rapidly.

Antibiotic-induced mesenteric adenopathy in an intussusception mouse model: a randomized, controlled trial.

BACKGROUND: Idiopathic intussusception is a leading cause of intestinal obstruction in young children. Although the etiology remains obscure, lymphoid hyperplasia is found in a majority of cases. Antibiotics, the most frequently prescribed medication class in the pediatric population, have been recently associated with intussusception. The authors sought to determine whether enteral antibiotic exposure influences the development of mesenteric adenopathy, bowel dilation or intussusception in an animal model. MATERIALS AND METHODS: The authors conducted a randomized, controlled animal trial using a previously described intussusception model. Mice were gavaged with normal saline, amoxicillin-clavulanate or azithromycin twice daily for 5 days to assess the influence of enteral antibiotic exposure on intussusception, mesenteric adenopathy and bowel dilation. One pediatric surgeon performed all laparotomies and was blinded to group designation. Chi2 and Fisher exact tests were used to evaluate differences between antibiotic exposed and control groups. RESULTS: Mesenteric adenopathy was identified in 4.1% of the normal saline controls compared with 54.1% (P < 0.01) and 38.9% (P < 0.01) of the amoxicillin-clavulanate and azithromycin exposed animals, respectively. A total of four intussusceptions were observed in the antibiotic-exposed groups combined whereas no intussusception cases were identified in the control group (P = 0.30). CONCLUSIONS: This is the first study to describe a significant association between antibiotic use and mesenteric adenopathy in any animal species.

Recombinant human erythropoietin induces intussusceptive microvascular growth in vivo.

The role of erythropoietin (Epo) in angiogenesis has not been completely clarified. Epo induces endothelial cell proliferation and migration and stimulates angiogenesis on rat aortic rings in vitro and in vivo in the chick embryo chorioallantoic membrane (CAM) assay. The aim of the present study was to evaluate the ultrastructural aspects of angiogenesis in the CAM vasculature after recombinant human Epo (rHuEpo) exposure. The results demonstrated that after rHuEpo stimulation, the generation of new blood vessels occurred more frequently following an intussusceptive microvascular growth (IMG) mechanism. We have performed our experiments between days 8 and 12 of incubation, that is, when in the normal condition the capillary network expands mainly by IMG, and because it is generally accepted that implants made from days 8 to 10 are strongly angiogenic. This response is peculiar of rHuEpo, because it is abolished when an Epo-blocking antibody was coadministered with Epo.

Intussusception among recipients of rotavirus vaccine: reports to the vaccine adverse event reporting system.

BACKGROUND: Rotavirus vaccine was licensed on August 31, 1998, and subsequently recommended for routine use among infants. To assess rare adverse events, postlicensure surveillance was conducted. OBJECTIVE: To describe the cases of intussusception among rotavirus vaccine recipients reported to the Vaccine Adverse Event Reporting System from October 1998 through December 1999. SETTING AND PARTICIPANTS: Infants vaccinated with rotavirus vaccine in the United States. OUTCOME MEASURES: Intussusception confirmed by radiology, surgery, or autopsy report with medical record documentation or confirmed by a primary health care provider. RESULTS: There were 98 confirmed cases of intussusception after vaccination with rotavirus vaccine reported to the Vaccine Adverse Event Reporting System; 60 of these developed intussusception within 1 week after vaccination. Based on calculations using vaccine distribution data and intussusception incidence rates from 2 separate databases, an estimated 7 to 16 cases would have been expected to occur in the week after vaccination by chance alone. CONCLUSION: Using a passive surveillance system for vaccine adverse events, we observed at least a fourfold increase over the expected number of intussusception cases occurring within 1 week of receipt of rotavirus vaccine. Other studies were initiated to further define the relationship between rotavirus vaccine and intussusception. In light of these and other data, the rotavirus vaccine manufacturer voluntarily removed its product from the market, and the recommendation for routine use of rotavirus vaccine among US infants has been withdrawn.