Global Reports of Intussusception in Infants With SARS-CoV-2 Infection.

Idiopathic intussusception is a common cause of bowel obstruction in infants, presenting as refractory abdominal pain or mass, vomiting, lethargy, and currant jelly stool. Coronavirus disease 2019 is not well characterized in children, especially infants, but symptoms in children have included nausea, vomiting, diarrhea, and abdominal pain. From January to July 2020, intussusception was reported in 5 infants 4-10 months of age who had laboratory-confirmed SARS-CoV-2 infection. All 5 infants presented with currant jelly stool and at least 1 other abdominal symptom, and none presented with respiratory symptoms. Four infants recovered but the fifth infant progressed to a critical illness and death. While an association between SARS-CoV-2 infection and intussusception has not been established, infants with symptoms consistent with intussusception may warrant testing for viral pathogens, including SARS-CoV-2, especially if presenting to healthcare with a history of SARS-CoV-2 exposure or with signs and symptoms of COVID-19. More investigation is needed to determine whether intussusception is part of the clinical spectrum of COVID-19 in infants or a coincidental finding among infants with SARS-CoV-2 infection.

Intussusception in a child with COVID-19 in the USA.

COVID-19, caused by the novel coronavirus strain SARS-CoV-2 that emerged in late 2019, has resulted in a global pandemic. COVID-19 was initially believed to occur less frequently in children with relatively mild disease. However, severe disease and varied presentations have been reported in infected children, one of such being intussusception. There have only been three reported cases of intussusception in the pediatric population infected with COVID-19. In this paper, we will discuss the management and treatment of a novel fourth case of COVID-19-associated intussusception. This case is the first reported in the USA and suggests that COVID-19 may be implicated in the development of intussusception. Pediatricians should consider the possibility of intussusception when a child with COVID-19 presents with abdominal pain.

Intussusceptive angiogenesis in Covid-19: hypothesis on the significance and focus on the possible role of FGF2.

The interest on the role of angiogenesis in the pathogenesis and progression of human interstitial lung diseases is growing, with conventional sprouting (SA) and non-sprouting intussusceptive angiogenesis (IA) being differently represented in specific pulmonary injury patterns. The role of viruses as key regulators of angiogenesis is known for several years. A significantly enhanced amount of new vessel growth, through a mechanism of IA, has been reported in lungs of patients who died from Covid-19; among the angiogenesis-related genes, fibroblast growth factor 2 (FGF2) was found to be upregulated. These findings are intriguing. FGF2 plays a role in some viral infections: the upregulation is involved in the MERS-CoV-induced strong apoptotic response crucial for its highly lytic replication cycle in lung cells, whereas FGF2 is protective against the acute lung injury induced by H1N1 influenza virus, improving the lung wet-to-dry weight ratio. FGF2 plays a role also in regulating IA, acting on pericytes (crucial for the formation of intraluminal pillars), and endothelium, and FGF2-induced angiogenesis may be promoted by inflammation and hypoxia. IA is a faster and probably more efficient process than SA, able to modulate vascular remodeling through pruning of redundant or inefficient blood vessels. We can speculate that IA might have the function of restoring a functional vascular plexus consequently to extensive endothelialitis and alveolar capillary micro-thrombosis observed in Covid-19. Anti-Vascular endothelial growth factor (anti-VEGF) strategies are currently investigated for treatment of severe and critically ill Covid-19 patients, but also FGF2, and its expression and/or signaling, might represent a promising target.

Intussusception in 2 Children With Severe Acute Respiratory Syndrome Coronavirus-2 Infection.

We note that intussusception was likely associated with severe acute respiratory syndrome coronavirus-2 infection in 2 infants in Wuhan and London. The intussusception was reduced by enemas in Wuhan; the outcome was fatal. The intussusception was not reduced by enemas in London and required surgery; the outcome was favorable.

Infectious Etiologies of Intussusception Among Children <2 Years Old in 4 Asian Countries.

BACKGROUND: The etiology of intussusception, the leading cause of bowel obstruction in infants, is unknown in most cases. Adenovirus has been associated with intussusception and slightly increased risk of intussusception with rotavirus vaccination has been found. We conducted a case-control study among children <2 years old in Bangladesh, Nepal, Pakistan, and Vietnam to evaluate infectious etiologies of intussusception before rotavirus vaccine introduction. METHODS: From 2015 to 2017, we enrolled 1-to-1 matched intussusception cases and hospital controls; 249 pairs were included. Stool specimens were tested for 37 infectious agents using TaqMan Array technology. We used conditional logistic regression to estimate odds ratio (OR) and 95% confidence interval (CI) of each pathogen associated with intussusception in a pooled analysis and quantitative subanalyses. RESULTS: Adenovirus (OR, 2.67; 95% CI, 1.75-4.36) and human herpes virus 6 (OR, 3.50; 95% CI, 1.15-10.63) were detected more frequently in cases than controls. Adenovirus C detection <20 quantification cycles was associated with intussusception (OR, 18.59; 95% CI, 2.45-140.89). Wild-type rotavirus was not associated with intussusception (OR, 1.07; 95% CI, 0.52-2.22). CONCLUSIONS: In this comprehensive evaluation, adenovirus and HHV-6 were associated with intussusception. Future research is needed to better understand mechanisms leading to intussusception, particularly after rotavirus vaccination.

Simultaneous intussusception associated with adenovirus infection in monozygotic twins: A case report.

RATIONALE: Intussusception, a common cause of intestinal obstruction in children, typically requires medical reduction. Here, we describe the case of a pair of twins who had simultaneous intussusception and were positive for fecal adenovirus-strongly indicating that adenovirus infection may be a main cause of the intussusception. PATIENT CONCERNS: Two 1-year-old twin girls were brought to Cathay General Hospital one after another on the same day. Both presented with intermittent abdominal pain, abdominal distension, diarrhea, and loss of appetite. DIAGNOSES: Their laboratory data were adenovirus positivity in rectal swab culture. Intussusception was diagnosed through a lower gastrointestinal series. INTERVENTIONS: The twins were treated with reduction for intussusception. OUTCOMES: Both patients recovered well, without recurrence. LESSONS: Most cases of intussusception are idiopathic. However, some potential risk factors-as strongly suggested by the current cases-are genetic factors and adenovirus infection.

Epidemiology of intussusception before and after rotavirus vaccine introduction in Fiji.

In 2012, Fiji introduced rotavirus vaccine (Rotarix, GSK) into the national immunisation schedule. We describe the intussusception epidemiology prior to rotavirus vaccine, temporal association of intussusception cases to administration of rotavirus vaccine, and estimate the additional number of intussusception cases that may be associated with rotavirus vaccine. A retrospective review of intussusception cases for children aged <24 months old was undertaken between January 2007 and October 2012 pre-vaccine. All admissions and deaths with a discharge diagnosis of intussusception, bowel obstruction, paralytic ileus, or intussusception ICD10-AM codes were extracted from national databases and hospital records. Nationwide active intussusception surveillance was established for three years post-vaccine (2013-2015). There were 24 definite intussusception cases in the pre-rotavirus vaccine period, 96% were confirmed by surgery. The median age was 6.5 months. The incidence rate was 22.2 (95% CI: 13.9-33.7) per 100,000 infants. There were no deaths. Active surveillance identified 25 definite intussusception cases, 96% of which were among children who were age-eligible for rotavirus vaccine. None were potentially vaccine related. We estimated one to five additional  cases of intussusception every five years. The incidence of intussusception pre-rotavirus vaccine in Fiji is low. Intussusception associated with rotavirus vaccine is likely a rare event in Fiji.

Epidemiological Correlation between Fecal Adenovirus Subgroups and Pediatric Intussusception in Korea.

We investigated the adenoviral etiology and seasonal epidemic trends in intussusception and each adenoviral subgroup. Also we confirmed whether we can use the adenovirus data of Acute Infectious Agents Laboratory Surveillance Report (AIALSR) as an epidemic predictor of intussusception. Patients with intussusception (n = 126), < 5 years old, were enrolled and matched by age and sex with controls suffering acute gastroenteritis without intussusception (n = 106), all recruited at 8 centers. All fecal specimens were assayed for adenovirus, including subgroups A, B, C, E, and F, with reverse transcriptase-polymerase chain reaction (RT-PCR). Adenovirus was detected in 53 cases and 13 controls (P < 0.001). Nonenteric adenoviruses (NEAds) were detected in 51 cases and four controls (P < 0.001). We used Spearman's correlation analysis to analyze the incidence of intussusception and adenoviral epidemic trends, and compared them with fecal and respiratory adenoviral epidemic trends in the AIALSR. The trend of intussusception correlated with total NEAds (r = 0.635; P = 0.011), as did the fecal AIALSR adenovirus trends (r = 0.572; P = 0.026). Among the NEAd subgroups, subgroup C was dominant (P < 0.001), but subgroups B (P = 0.007) and E (P = 0.013) were also significant to intussusception. However, only subgroup C showed a significant epidemic correlation (r = 0.776; P = 0.001) with intussusception. Not respiratory but fecal AIALSR adenovirus trends correlated with the incidence of NEAds and intussusception. We suggest the possibility of using fecal AIALSR adenovirus data as an approximate epidemic predictor of intussusception.

Associations of Adenovirus Genotypes in Korean Acute Gastroenteritis Patients with Respiratory Symptoms and Intussusception.

Human adenoviruses (HAdVs) cause a wide range of diseases, including respiratory infections and gastroenteritis, and have more than 65 genotypes. To investigate the current genotypes of circulating HAdV strains, we performed molecular genotyping of HAdVs in the stool from patients with acute gastroenteritis and tried to determine their associations with clinical symptoms. From June 2014 to May 2016, 3,901 fecal samples were tested for an AdV antigen, and 254 samples (6.5%) yielded positive results. Genotyping using PCR and sequencing of the capsid hexon gene was performed for 236 AdV antigen-positive fecal specimens. HAdV-41, of species F, was the most prevalent genotype (60.6%), followed by HAdV-2 of species C (13.8%). Other genotypes, including HAdV-3, HAdV-1, HAdV-5, HAdV-6, HAdV-31, HAdV-40, HAdV-12, and HAdV-55, were also detected. Overall, 119 patients (50.4%) showed concomitant respiratory symptoms, and 32 patients (13.6%) were diagnosed with intussusception. HAdV-1 and HAdV-31 were significantly associated with intussusception (P < 0.05). Our results demonstrate the recent changes in trends of circulating AdV genotypes associated with gastroenteritis in Korea, which should be of value for improving the diagnosis and developing new detection, treatment, and prevention strategies for broad application in clinical laboratories.

Unparalleled patterns of intussusception and rotavirus gastroenteritis hospitalization rates among children younger than six years in Italy.

BACKGROUND: No nationwide studies are available so far in Italy to analyze the annual trend of hospitalizations for intussusception (IS) comparing it with that of rotavirus gastroenteritis (GARV), therefore a survey was undertaken to assess the incidence rates of IS and GARV in children hospitalized between 2005 and 2014 in Italy. STUDY DESIGN: A retrospective observational study was conducted analyzing the Italian Hospital Discharge Database (HDD), including a study on all hospitalizations bearing a primary or secondary diagnoses coded as 560.0 along the decade 2005-2014. METHODS: The trend and seasonality of hospitalizations rates (HRs) for IS were analyzed stratifying by gender and age groups. The statistical significance of temporal trend was determined using the analysis of the slope of the regression line. For the same period, data related to national hospitalizations for GARV (code 008.61 in any diagnosis) were analyzed for comparative purpose. RESULTS: A total of 6,074 hospitalizations for IS in children aged <6 years were recorded. A statistically significant increase of HRs was seen for male, female, 12-23 months and 24-71 months age groups. However, in children within the first year of life there was a downward trend. The analysis of the distribution of the HRs by months of hospitalization showed the absence of seasonality, in contrast to HRs for GARV. CONCLUSION: Our analysis confirmed the occurrence of the incidence peak of IS hospitalizations in children aged seven months. HRs decreased after the first year of life, replicating an age distribution that is also observed for other paediatric infectious diseases. Nevertheless, the total trend of HR was increasing. In Italy, IS HRs in the pre-vaccination era resulted in line with those described for other European countries, with an increasing trend and the annual slope of IS hospitalization turned out to unparallel the GARV HRs.

Adenovirus infection: A potential risk for developing intussusception in pediatric patients.

The pathogenesis of intussusception without obvious anatomical leading points remains unclear. The objective of this study was to determine a feasibility of association between certain gastroenteritis viruses and intussusception. This was a prospective cohort study. Forty intussusception cases and 136 acute gastroenteritis controls with comparable age and gender were separately consecutively enrolled and relevant clinical data of both groups were recorded. The clinical specimens collected from all patients were screened for adenovirus, rotavirus, norovirus, and astrovirus by PCR and RT-PCR using specific primers. The genomes of detected viruses were characterized further to identify their genotypes by nucleotide sequencing. In 40 intussusception cases, adenovirus, rotavirus, and norovirus were detected in 12 (30.0%), 2 (5.0%), and 2 (5.0%), respectively while astrovirus was undetectable. In contrast, 136 acute gastroenteritis patients, adenovirus, rotavirus, and norovirus were detected in 11 (8.1%), 24 (17.7%), and 24 (17.7%) patients, respectively and again astrovirus was undetectable. The detection of adenovirus in intussusception patients was significantly higher than those in the control group (P < 0.001) with an odd ratio of 4.87 (95%CI: 1.95, 12.16). Interestingly, molecular analysis of adenovirus genome demonstrated that all of adenovirus detected in intussusception patients belonged to adenovirus C. This could be a potential risk factor or pathogenesis for developing intussusception in the cases of those without apparent anatomical leading points. J. Med. Virol. 88:1930-1935, 2016. © 2016 Wiley Periodicals, Inc.

The effectiveness of a rotavirus vaccine in preventing hospitalizations and deaths presumably due to acute infectious diarrhea in Brazilian children: a quasi-experimental study.

INTRODUCTION: Rotavirus is the main etiologic agent of acute infectious diarrhea in children worldwide. Considering that a rotavirus vaccine (G1P8, strain RIX4414) was added to the Brazilian vaccination schedule in 2006, we aimed to study its effectiveness and safety regarding intestinal intussusception. METHODS: A quasi-experimental trial was performed in which the primary outcome was the number of hospitalizations that were presumably due to acute infectious diarrhea per 100,000 children at risk (0-4 years old). The secondary outcomes included mortality due to acute infectious diarrhea and the intestinal intussusception rates in children in the same age range. We analyzed three scenarios: Health Division XIII of the State of São Paulo (DRS XIII) from 2002 to 2008, the State of São Paulo, and Brazil from 2002 to 2012. RESULTS: The averages of the hospitalization rates for 100,000 children in the pre- and post-vaccination periods were 1,413 and 959, respectively, for DRS XIII (RR=0.67), 312 and 249, respectively, for the State of São Paulo (RR=0.79), and 718 and 576, respectively, for Brazil (RR=0.8). The mortality rate per 100,000 children in the pre- and post-vaccination periods was 2.0 and 1.3, respectively, for DRS XIII (RR=0.66), 5.5 and 2.5, respectively, for the State of São Paulo (RR=0.47), and 15.0 and 8.0, respectively, for Brazil (RR=0.53). The average annual rates of intussusception for 100,000 children in DRS XIII were 28.0 and 22.0 (RR=0.77) in the pre- and post-vaccination periods, respectively. CONCLUSIONS: A monovalent rotavirus vaccine was demonstrated to be effective in preventing the hospitalizations and deaths of children that were presumably due to acute infectious diarrhea, without increasing the risk of intestinal intussusception.

The effectiveness of a rotavirus vaccine in preventing hospitalizations and deaths presumably due to acute infectious diarrhea in Brazilian children: a quasi-experimental study

INTRODUCTION: Rotavirus is the main etiologic agent of acute infectious diarrhea in children worldwide. Considering that a rotavirus vaccine (G1P8, strain RIX4414) was added to the Brazilian vaccination schedule in 2006, we aimed to study its effectiveness and safety regarding intestinal intussusception. METHODS: A quasi-experimental trial was performed in which the primary outcome was the number of hospitalizations that were presumably due to acute infectious diarrhea per 100,000 children at risk (0-4 years old). The secondary outcomes included mortality due to acute infectious diarrhea and the intestinal intussusception rates in children in the same age range. We analyzed three scenarios: Health Division XIII of the State of São Paulo (DRS XIII) from 2002 to 2008, the State of São Paulo, and Brazil from 2002 to 2012. RESULTS: The averages of the hospitalization rates for 100,000 children in the pre- and post-vaccination periods were 1,413 and 959, respectively, for DRS XIII (RR=0.67), 312 and 249, respectively, for the State of São Paulo (RR=0.79), and 718 and 576, respectively, for Brazil (RR=0.8). The mortality rate per 100,000 children in the pre- and post-vaccination periods was 2.0 and 1.3, respectively, for DRS XIII (RR=0.66), 5.5 and 2.5, respectively, for the State of São Paulo (RR=0.47), and 15.0 and 8.0, respectively, for Brazil (RR=0.53). The average annual rates of intussusception for 100,000 children in DRS XIII were 28.0 and 22.0 (RR=0.77) in the pre- and post-vaccination periods, respectively. CONCLUSIONS: A monovalent rotavirus vaccine was demonstrated to be effective in preventing the hospitalizations and deaths of children that were presumably due to acute infectious diarrhea, without increasing the risk of intestinal intussusception. .

Intussusception is associated with the detection of adenovirus C, enterovirus B and rotavirus in a rotavirus vaccinated population.

BACKGROUND: Intussusception, a condition where one segment of intestine invaginates into another, occurs predominantly in infants and young children. A number of potential causes have been identified including infectious agents and rotavirus vaccination. Following the introduction of rotavirus vaccination of infants in Western Australia, a laboratory surveillance programme testing notified intussusception cases for infectious agents was commenced. This led to a PCR-based study of the association between gastrointestinal viruses and intussusception. OBJECTIVES: Conduct viral testing on stool samples from intussusception patients to determine viruses that may have an association with intussusception. STUDY DESIGN: A retrospective case-control study was conducted using stool samples collected from children with intussusception (n=74) and matched controls (n=289) between 2008 and 2011. Samples were tested for rotavirus, norovirus, adenovirus, enterovirus, rhinovirus, astrovirus, parechovirus and bocavirus. Adenovirus, enterovirus and rhinovirus species were determined by DNA sequencing. RESULTS: Human adenovirus C was detected in significantly more cases than controls with 31/74 (41.9%) cases testing positive compared to 39/289 (13.49%) controls (OR=4.38, p<0.001). A significant difference was seen in Enterovirus B detections with 11/74 (14.9%) cases testing positive compared to 21/289 (7.3%) controls (OR=2.24, p=0.04). Rotavirus was detected in 7/74 (9.46%) cases and 11/289 (3.81%) controls, which was also a significant difference (OR=2.88, p=0.045). CONCLUSIONS: Our results show that intussusception is associated with non-enteric adenovirus infections, and Enterovirus B infections. While a statistical association was seen with rotavirus and intussusception, we were not able to determine if this was related to vaccine strain or wild type rotavirus.

[Post-licensure passive safety surveillance of rotavirus vaccines: reporting sensitivity for intussusception]. / Vigilancia pasiva de la seguridad postautorización de las vacunas frente a rotavirus: sensibilidad de la notificación de invaginación intestinal.

INTRODUCTION: The aims of this study were to describe the reports of suspected adverse events due to rotavirus vaccines, and assess the reporting sensitivity for intussusception. MATERIAL AND METHODS: Descriptive study performed using the reports of suspected adverse events following rotavirus vaccination in infants aged less than 10 months, as registered in the Pharmacovigilance Centre of the Valencian Community during 2007-2011. The reporting rate for intussusception was compared to the intussusception rate in vaccinated infants obtained using the hospital discharge database (CMBD), and the regional vaccine registry. RESULTS: The adverse event reporting rate was 20 per 100,000 administered doses, with the majority (74%) of the reports being classified as non-serious. Fever, vomiting, and diarrhea were the adverse events reported more frequently. Two intussusception cases, which occurred within the first seven days post-vaccination, were reported as temporarily associated to vaccination. The reporting sensitivity for intussusception at the Pharmacovigilance Centre in the 1-7 day interval following rotavirus vaccination was 50%. CONCLUSIONS: Our results suggest that rotavirus vaccines have, in general, a good safety profile. Intussusception reporting to the Pharmacovigilance Centre shows sensitivity similar to other passive surveillance systems. The intussusception risk should be further investigated using well-designed epidemiological studies, and evaluated in comparison with the well-known benefits provided by these vaccines.

Descriptive epidemiology of rotavirus infection in a community in North India.

In India, rotavirus infections cause the death of 98621 children each year. In urban neighbourhoods in Delhi, children were followed up for 1 year to estimate the incidence of rotavirus gastroenteritis and common genotypes. Infants aged f1 week were enrolled in cohort 1 and infants aged 12 months (up to +14 days) in cohort 2. Fourteen percent (30/210) gastroenteritis episodes were positive for rotavirus. Incidence rates of rotavirus gastroenteritis episodes in the first and second year were 0.18 [95% confidence interval (CI) 0.10­0.27] and 0.14 (95% CI 0.07­0.21) episodes/child-year, respectively. The incidence rate of severe rotavirus gastroenteritis in the first year of life was 0.05 (95% CI 0.01­0.10) episodes/child-year. There were no cases in the second year. The common genotypes detected were G1P[8] (27%) and G9P[4] (23%). That severe rotavirus gastroenteritis is common in the first year of life is relevant for planning efficacy trials.

Potential intussusception risk versus benefits of rotavirus vaccination in the United States.

BACKGROUND: International data show a low-level increased risk of intussusception associated with rotavirus vaccination. Although US data have not documented a risk, we assumed a risk similar to international settings and compared potential vaccine-associated intussusception cases with benefits of prevention of rotavirus gastroenteritis by a fully implemented US rotavirus vaccine program. METHODS: To calculate excess intussusception cases, we used national data on vaccine coverage and baseline intussusception rates, and assumed a vaccine-associated intussusception relative risk of 5.3 (95% confidence interval [CI]: 3.0-9.3) in the first week after the first vaccine dose, the risk seen in international settings. We used postlicensure vaccine effectiveness data to calculate rotavirus disease burden averted. RESULTS: For a US birth cohort of 4.3 million infants, vaccine-associated intussusception could cause an excess 0.2 (range: 0.1-0.3) deaths, 45 (range: 21-86) hospitalizations and 13 (range: 6-25) cases managed in short-stay or emergency department settings. Vaccination would avert 14 (95% CI: 10-19) rotavirus-associated deaths, 53,444 (95% CI: 37,622-72,882) hospitalizations and 169,949 (95% CI: 118,161-238,630) emergency department visits. Summary benefit-risk ratios for death and hospitalization are 71:1 and 1093:1, respectively. CONCLUSIONS: The burden of severe rotavirus disease averted due to vaccination compared with the vaccine-associated intussusception events offers a side-by-side analysis of the benefits and potential risks. If an intussusception risk similar to that seen internationally exists in the United States, it is substantially exceeded by the benefits of rotavirus disease burden averted by vaccination.

Impact of rotavirus vaccines on rotavirus disease.

Rotaviruses are the most common cause of acute gastroenteritis in young children worldwide. Both licensed rotavirus vaccines (Rotarix™ [RV1] and RotaTeq™ [RV5]) are effective and safe. Studies from countries that have included RV1 or RV5 in the national immunization programs have demonstrated their safety and sustained efficacy under real-life circumstances. A significant decline in acute gastroenteritis-related deaths among Latin American children was observed after the introduction of RV1 and RV5 vaccines. Both vaccines were able to decrease the number of cases of rotavirus acute gastroenteritis and of severe rotavirus diseases. Vaccination was also associated with a dramatic reduction in hospitalizations and outpatient visits for all-cause acute gastroenteritis. Indirect protection after infant mass vaccination has been strongly suggested. Moreover, postlicensure safety studies assessed rare adverse events (rates <1 in 50,000), such as intussusception.

Trends in intussusception hospitalizations among US infants before and after implementation of the rotavirus vaccination program, 2000-2009.

BACKGROUND: Although US data have not documented an intussusception risk with current rotavirus vaccines, international data indicate a possible low risk, primarily after the first dose. METHODS: Among infants in 26 US states comprising 75% of the birth cohort, we examined age-specific trends in population-level intussusception hospitalization rates before (2000-2005) and after (2007-2009) rotavirus vaccine introduction. RESULTS: Compared with 2000-2005 (35.3 per 100,000), the rate was greater in 2007 (39.0 per 100,000; rate ratio [RR], 1.10; 95% confidence interval [CI], 1.04-1.18), similar in 2008 (33.4 per 100,000; RR, 0.95; 95% CI, .89-1.01), and lower in 2009 (32.9 per 100,000; RR, 0.93; 95% CI, .87-.99). Among infants aged 8-11 weeks, compared with 2000-2005 (6.9 per 100,000), a small, significant increase was observed in each of 2007 (11.4 per 100,000; RR, 1.64; 95% CI, 1.08-2.50), 2008 (12.2 per 100,000; RR, 1.76; 95% CI, 1.17-2.65), and 2009 (11.0 per 100,000; RR, 1.59; 95% CI, 1.04-2.44). CONCLUSIONS: Following rotavirus vaccine introduction, a small increase in intussusception rates was seen among US infants aged 8-11 weeks, to whom most first doses of vaccine are given; no sustained population-level change in overall rates was observed.