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.

Multicountry Analysis of Spectrum of Clinical Manifestations of Children <5 Years of Age Hospitalized with Diarrhea.

After introduction of rotavirus vaccine, other pathogens might become leading causes of hospitalizations for severe diarrhea among children <5 years of age. Our study in 33 hospitals in 7 countries found acute gastroenteritis accounted for most (84%) reported hospitalizations of children with diarrhea. Bloody and persistent diarrhea each accounted for <1%.

Rotavirus Vaccination Is Associated With Reduced Seizure Hospitalization Risk Among Commercially Insured US Children.

Rotavirus commonly causes diarrhea but can also cause seizures. Analysis of insurance claims for 1773295 US children with 2950 recorded seizures found that, compared to rotavirus-unvaccinated children, seizure hospitalization risk was reduced by 24% (95% confidence interval [CI], 13%-33%) and 14% (95% CI, 0%-26%) among fully and partially rotavirus-vaccinated children, respectively.

Ebola Virus Persistence in Breast Milk After No Reported Illness: A Likely Source of Virus Transmission From Mother to Child.

A 9-month-old infant died from Ebola virus (EBOV) disease with unknown epidemiological link. While her parents did not report previous illness, laboratory investigations revealed persisting EBOV RNA in the mother's breast milk and the father's seminal fluid. Genomic analysis strongly suggests EBOV transmission to the child through breastfeeding.

Implementation of Rotavirus Surveillance and Vaccine Introduction - World Health Organization African Region, 2007-2016.

Rotavirus is a leading cause of severe pediatric diarrhea globally, estimated to have caused 120,000 deaths among children aged <5 years in sub-Saharan Africa in 2013 (1). In 2009, the World Health Organization (WHO) recommended rotavirus vaccination for all infants worldwide (2). Two rotavirus vaccines are currently licensed globally: the monovalent Rotarix vaccine (RV1, GlaxoSmithKline; 2-dose series) and the pentavalent RotaTeq vaccine (RV5, Merck; 3-dose series). This report describes progress of rotavirus vaccine introduction (3), coverage (using estimates from WHO and the United Nations Children's Fund [UNICEF]) (4), and impact on pediatric diarrhea hospitalizations in the WHO African Region. By December 2016, 31 (66%) of 47 countries in the WHO African Region had introduced rotavirus vaccine, including 26 that introduced RV1 and five that introduced RV5. Among these countries, rotavirus vaccination coverage (completed series) was 77%, according to WHO/UNICEF population-weighted estimates. In 12 countries with surveillance data available before and after vaccine introduction, the proportion of pediatric diarrhea hospitalizations that were rotavirus-positive declined 33%, from 39% preintroduction to 26% following rotavirus vaccine introduction. These results support introduction of rotavirus vaccine in the remaining countries in the region and continuation of rotavirus surveillance to monitor impact.

Acute Flaccid Myelitis in the United States, August-December 2014: Results of Nationwide Surveillance.

BACKGROUND: During late summer/fall 2014, pediatric cases of acute flaccid myelitis (AFM) occurred in the United States, coincident with a national outbreak of enterovirus D68 (EV-D68)-associated severe respiratory illness. METHODS: Clinicians and health departments reported standardized clinical, epidemiologic, and radiologic information on AFM cases to the Centers for Disease Control and Prevention (CDC), and submitted biological samples for testing. Cases were ≤21 years old, with acute onset of limb weakness 1 August-31 December 2014 and spinal magnetic resonance imaging (MRI) showing lesions predominantly restricted to gray matter. RESULTS: From August through December 2014, 120 AFM cases were reported from 34 states. Median age was 7.1 years (interquartile range, 4.8-12.1 years); 59% were male. Most experienced respiratory (81%) or febrile (64%) illness before limb weakness onset. MRI abnormalities were predominantly in the cervical spinal cord (103/118). All but 1 case was hospitalized; none died. Cerebrospinal fluid (CSF) pleocytosis (>5 white blood cells/µL) was common (81%). At CDC, 1 CSF specimen was positive for EV-D68 and Epstein-Barr virus by real-time polymerase chain reaction, although the specimen had >3000 red blood cells/µL. The most common virus detected in upper respiratory tract specimens was EV-D68 (from 20%, and 47% with specimen collected ≤7 days from respiratory illness/fever onset). Continued surveillance in 2015 identified 16 AFM cases reported from 13 states. CONCLUSIONS: Epidemiologic data suggest this AFM cluster was likely associated with the large outbreak of EV-D68-associated respiratory illness, although direct laboratory evidence linking AFM with EV-D68 remains inconclusive. Continued surveillance will help define the incidence, epidemiology, and etiology of AFM.

Enterovirus D68 Infection in Children with Acute Flaccid Myelitis, Colorado, USA, 2014.

During August 8, 2014-October 14, 2014, a total of 11 children with acute flaccid myelitis and distinctive neuroimaging changes were identified near Denver, Colorado, USA. A respiratory prodrome was experienced by 10, and nasopharyngeal specimens were positive for enterovirus D68 (EV-D68) for 4. To determine whether an association exists between EV-D68 infection and acute flaccid myelitis, we conducted a retrospective case-control study comparing these patients with 2 groups of outpatient control children (1 group tested for acute respiratory illness and 1 for Bordetella pertussis infection). Adjusted analyses indicated that, for children with acute flaccid myelitis, the odds of having EV-D68 infection were 10.3 times greater than for those tested for acute respiratory infection and 4.5 times greater than for those tested for B. pertussis infection. No statistical association was seen between acute flaccid myelitis and non-EV-D68 enterovirus or rhinovirus infection. These findings support an association between EV-D68 infection and acute flaccid myelitis.

Sustained decrease in laboratory detection of rotavirus after implementation of routine vaccination­United States, 2000-2014.

Rotavirus infection is the leading cause of severe gastroenteritis among infants and young children worldwide. Before the introduction of rotavirus vaccine in the United States in 2006, rotavirus infection caused significant morbidity among U.S. children, with an estimated 55,000-70,000 hospitalizations and 410,000 clinic visits annually. The disease showed a characteristic winter-spring seasonality and geographic pattern, with annual seasonal activity beginning in the West during December-January, extending across the country, and ending in the Northeast during April-May. To characterize changes in rotavirus disease trends and seasonality following introduction of rotavirus vaccines in the United States, CDC compared data from CDC's National Respiratory and Enteric Virus Surveillance System (NREVSS), a passive laboratory reporting system, for prevaccine (2000-2006) and postvaccine (2007-2014) years. National declines in rotavirus detection were noted, ranging from 57.8%-89.9% in each of the 7 postvaccine years compared with all 7 prevaccine years combined. A biennial pattern of rotavirus activity emerged in the postvaccine era, with years of low activity and highly erratic seasonality alternating with years of moderately increased activity and seasonality similar to that seen in the prevaccine era. These results demonstrate the substantial and sustained effect of rotavirus vaccine in reducing the circulation and changing the epidemiology of rotavirus among U.S. children.

Acute neurologic illness of unknown etiology in children - Colorado, August-September 2014.

On September 12, 2014, CDC was notified by the Colorado Department of Public Health and Environment of a cluster of nine children evaluated at Children's Hospital Colorado with acute neurologic illness characterized by extremity weakness, cranial nerve dysfunction (e.g., diplopia, facial droop, dysphagia, or dysarthria), or both. Neurologic illness onsets occurred during August 8-September 15, 2014. The median age of the children was 8 years (range = 1-18 years). Other than neck, back, or extremity pain in some patients, all had normal sensation. All had a preceding febrile illness, most with upper respiratory symptoms, occurring 3-16 days (median = 7 days) before onset of neurologic illness. Seven of eight patients with magnetic resonance imaging of the spinal cord had nonenhancing lesions of the gray matter of the spinal cord spanning multiple levels, and seven of nine with magnetic resonance imaging of the brain had nonenhancing brainstem lesions (most commonly the dorsal pons). Two of five with magnetic resonance imaging of the lumbosacral region had gadolinium enhancement of the ventral nerve roots of the cauda equina. Eight children were up to date on polio vaccination. Eight have not yet fully recovered neurologically.

Equivalent immunogenicity across three RSVpreF vaccine lots in healthy adults 18-49 years of age: Results of a randomized phase 3 study.

BACKGROUND: Bivalent RSV prefusion F subunit vaccine (RSVpreF), comprised of equal quantities of stabilized prefusion F antigens from the major circulating subgroups (RSV A, RSV B), is licensed for prevention of RSV-associated lower respiratory tract illness (LRTI) in older adults and for maternal vaccination for prevention of RSV-associated LRTI in infants. To support licensure and large-scale manufacturing, this lot consistency study was conducted to demonstrate equivalence in immunogenicity across 3 RSVpreF lots. METHODS: This phase 3, multicenter, parallel-group, placebo-controlled, randomized (1:1:1:1), double-blind study evaluated immunogenicity, safety, and tolerability of RSVpreF in healthy 18-49-year-old adults. Participants received a single 120-µg injection of 1 of 3RSVpreF lots or placebo. Geometric mean ratio (GMR) of RSV serum 50 % neutralizing geometric mean titers obtained 1 month after vaccination were compared between each vaccine lot for RSV A and RSV B, separately. Equivalence between lots was defined using a 1.5-fold criterion (GMR 95 % CIs for every lot pair within the 0.667-1.5 interval). Safety and tolerability were assessed. RESULTS: Of 992participants vaccinated, 948 were included in the evaluable immunogenicity population. All 3 RSVpreF lots elicited strong immune responses, meeting the 1.5-fold equivalence criterion for all between-lot comparisons for both RSV A and RSV B. Across the 3 lots, RSV A and RSV B 50 % neutralizing geometric mean titers substantially increased from baseline (RSV A, 1671-1795; RSV B 1358-1429) to 1 month after RSVpreF vaccination (RSV A, 24,131-25,238; RSV B, 19,238-21,702), corresponding to ≥14-fold increases in 50 % neutralizing titers for both RSV A and RSV B from before to 1 month after vaccination. Single doses of RSVpreF were safe and well tolerated, with similar safety profiles across the 3 RSVpreF lots. CONCLUSIONS: These findings support the reproducibility of RSVpreF vaccine manufacturing with similar safety and reactogenicity profiles (NCT05096208).

Impact of rotavirus vaccine introduction in Abidjan, Côte d'Ivoire.

Côte d'Ivoire introduced rotavirus vaccine in March 2017. Rotavirus surveillance is conducted at Centre Hospitalier Universitaire de Yopougon in Abidjan, the capital city. Children <5 years of age are enrolled in rotavirus surveillance if admitted to the hospital with acute gastroenteritis. We used sentinel surveillance data from 2014 through mid-2019 to compare trends in rotavirus pediatric gastroenteritis hospitalizations before and after rotavirus vaccine introduction. We used Poisson regression to analyze changes in rotavirus prevalence, adjusting for calendar month and accounting for total monthly admissions; January 2014 - December 2016 was considered "pre-vaccine," and January 2017 - June 2019 was considered "post-vaccine." Age distribution and severity were compared between periods using the Mann-Whitney U test. Rotavirus-positive admissions declined 51% (95% CI: 28%-67%), from 31.5% pre-vaccine to 14.9% afterward. The median age of rotavirus-positive children increased from 7 months (interquartile range [IQR]: 5-11) in the pre-vaccine period to 11 months (IQR: 7-18, p = .005) in the post-vaccine period. The median severity score decreased from 11 to 9 (p = .008) among all children, and from 12 pre- to 10.5 post-vaccine (p = .35) among rotavirus-positive children. Our findings suggest that rotavirus vaccine introduction contributed to reduced rotavirus hospitalization in Abidjan and possibly more broadly.

Diversity of rotavirus strains circulating in Haiti before and after introduction of monovalent vaccine.

Background: Haiti introduced a monovalent human group A rotavirus (RVA) vaccine (Rotarix) into its routine infant immunization program in April 2014. The goal of the surveillance program was to characterize RVA strains circulating in Haiti before and after RVA vaccine introduction. Methods: Stool samples were collected from children <5 years old presenting with acute gastroenteritis at 16 hospitals in Haiti. RVA antigen enzyme immunoassay (EIA) testing was performed, and G and P genotypes were determined for positive specimens. In this study, genotype data for samples collected from May 2012 through April 2014 (the pre-vaccine introduction era) and May 2014 through July 2019 (post-vaccine introduction era) were analyzed. Results: A total of 809 specimens were tested by the Centers for Disease Control and Prevention. During the pre-vaccine introduction era (May 2012 through April 2014), G12P[8] was the predominant genotype, detected in 88-94% of specimens. There was a high prevalence of the equine-like G3P[8] genotype among Haitian children with RVA after vaccine introduction. Conclusions: The predominance of equine-like G3P[8] in three of five RVA seasons post-vaccine introduction suggests possible vaccine-specific selection pressure in Haiti. These temporal variations in RVA genotype predominance will require continued monitoring in Haiti as the vaccination program continues.

Acute intestinal intussusception among children under five years of age admitted in an Ouagadougou hospital, Burkina Faso, 2008-2013: epidemiological, clinical and therapeutic aspects.

INTRODUCTION: acute intestinal intussusception is a life-threatening surgical condition. In some settings, rotavirus vaccines have been associated with a low-level increased risk of intussusception. We describe the epidemiology, clinical manifestations and management of intussusception in a tertiary referral hospital in Burkina Faso prior to the introduction of rotavirus vaccine in October 2013. METHODS: we retrospectively reviewed medical records of all children under 5 years of age treated at the Charles de Gaulle Pediatric Hospital for intussusception meeting the Brighton level 1 diagnostic criteria, from October 31st, 2008 to October 30th, 2013. We report the incidence of intussusception as well as descriptive characteristics of these cases. RESULTS: a total of 107 Brighton level 1 intussusception cases were identified, representing a hospital incidence of 21.4 cases / year. There were 69 males and 38 females (sex ratio of 1.8), with a median age of 8 months (range 2 months to 4 years). Sixty-two percent of intussusception cases occurred among infants (n = 67 cases). The average time from symptom onset to seeking medical consultation was 3.8 days +/- 2.7 (range 0 to 14 days). Treatment was mainly surgical (105 patients, 98.1%) with 35 patients (32.7%) undergoing intestinal resection. Thirty-seven patients (35.5%) experienced post-operative complications. The mortality rate was 9.3%. Intestinal resection was a risk factor for death from intussusception. CONCLUSION: in this review of intussusception hospitalizations prior to rotavirus vaccine introduction in Burkina Faso, delays in seeking care were common and were associated with mortality.

Effectiveness of monovalent rotavirus vaccine against hospitalizations due to all rotavirus and equine-like G3P[8] genotypes in Haiti 2014-2019.

BACKGROUND: Rotavirus vaccines are effective in preventing severe rotavirus. Haiti introduced 2-dose monovalent (G1P[8]) rotavirus vaccine recommended for infants at 6 and 10 weeks of age in 2014. We calculated the effectiveness of rotavirus vaccine against hospitalization for acute gastroenteritis in Haiti. METHODS: We enrolled children 6-59 months old admitted May 2014-September 2019 for acute watery diarrhea at any sentinel surveillance hospital. Stool was tested for rotavirus using enzyme immunoassay (EIA) and genotyped with multiplex one-step RT-PCR assay and Sanger sequencing for stratification by genotype. We used a case-negative design where cases were children positive for rotavirus and controls were negative for rotavirus. Only children eligible for vaccination were included and a child was considered vaccinated if vaccine was given ≥ 14 days before enrollment. We used unconditional logistic regression to calculate odds ratios and calculated 2-dose and 1-dose vaccine effectiveness (VE) as (1 - odds ratio) * 100. RESULTS: We included 129 (19%) positive cases and 543 (81%) negative controls. Among cases, 77 (60%) were positive for equine-like G3P[8]. Two doses of rotavirus vaccine were 66% (95% CI: 44, 80) effective against hospitalizations due to any strain of rotavirus and 64% (95% CI: 33, 81) effective against hospitalizations due to the equine-like G3P[8] genotype. CONCLUSIONS: These findings are comparable to other countries in the Americas region. To the best of our knowledge, this is the first VE estimate both against the equine-like G3P[8] genotype and from a Caribbean country. Overall, these results support rotavirus vaccine use and demonstrate the importance of complete vaccination.

Impact of Monovalent Rotavirus Vaccine on Rotavirus Hospitalizations among Children Younger Than 5 Years of Age in the Ouest and Artibonite Departments, Haiti, 2013 to 2019.

Rotavirus is responsible for 26% of diarrheal deaths in Latin America and the Caribbean. Haiti introduced the monovalent rotavirus vaccine in April 2014. The objective of this analysis is to describe the impact of the rotavirus vaccine on hospitalizations among Haitian children younger than 5 years old during the first 5 years after introduction. This analysis includes all children with diarrhea who were enrolled as part of a sentinel surveillance system at two hospitals from May 2013 to April 2019. We compare the proportion of rotavirus-positive specimens in each post-vaccine introduction year to the pre-vaccine period. To account for the potential dilution of the proportion of rotavirus-positive specimens from a waning cholera outbreak, we also analyzed annual trends in the absolute number of positive stools, fit a two-component finite-mixture model to the negative specimens, and fit a negative binomial time series model to the pre-vaccine rotavirus-positive specimens to predict the number of rotavirus diarrhea hospital admissions in the absence of rotavirus vaccination. The overall percentage of rotavirus-positive specimens declined by 22% the first year after introduction, increased by 17% the second year, and declined by 33% to 50% the subsequent 3 years. All sensitivity analyses confirmed an overall decline. We observed a clear annual rotavirus seasonality before and after vaccine introduction, with the greatest activity in December through April, and a biennial pattern, with high sharp peaks and flatter longer periods of increased rotavirus activity in alternating years, consistent with suboptimal vaccination coverage. Overall, our study shows evidence that the introduction of the rotavirus vaccine reduced the burden of severe rotavirus diarrhea.

Does Rotavirus Vaccination Affect Longer-Term Intussusception Risk in US Infants?

Rotavirus vaccination has been associated with a short-term increased risk of intussusception. Our analysis of insurance claims for 1 858 827 US children with 544 recorded cases of intussusception found a nonsignificant decrease in intussusception (hazard ratio, 0.79 [95% confidence interval, 0.57-1.09]) in fully rotavirus-vaccinated children followed up to the age of 2 years.

Cost of pediatric hospitalizations in Burkina Faso: A cross-sectional study of children aged <5 years enrolled through an acute gastroenteritis surveillance program.

INTRODUCTION: Diarrheal illness is a leading cause of hospitalizations among children <5 years. We estimated the costs of inpatient care for rotavirus and all-cause acute gastroenteritis (AGE) in two Burkina Faso hospitals. METHODS: We conducted a cross-sectional study among children <5 years from December 2017 to June 2018 in one urban and one rural pediatric hospital. Costs were ascertained through caregiver interview and chart abstraction. Direct medical, non-medical, and indirect costs per child incurred are reported. Costs were stratified by rotavirus results. RESULTS: 211 children <5 years were included. AGE hospitalizations cost 161USD (IQR 117-239); 180USD (IQR 121-242) at the urban and 154USD (IQR 116-235) at the rural site. Direct medical costs were higher in the urban compared to the rural site (140USD (IQR 102-182) vs. 90USD (IQR 71-108), respectively). Direct non-medical costs were higher at the rural versus urban site (15USD (IQR 10, 15) vs. 11USD (IQR 5-20), respectively). Indirect costs were higher at the rural versus urban site (35USD (IQR 8-91) vs. 0USD (IQR 0-26), respectively). Rotavirus hospitalizations incurred less direct medical costs as compared to non-rotavirus hospitalizations at the rural site (79USD (IQR 64-103) vs. 95USD (IQR 80-118)). No other differences by rotavirus testing status were observed. The total median cost of a hospitalization incurred by households was 24USD (IQR 12-49) compared to 75USD for government (IQR 59-97). Direct medical costs for households were higher in the urban site (median 49USD (IQR 31-81) versus rural (median 14USD (IQR 8-25)). Households in the lowest wealth quintiles at the urban site expended 149% of their monthly income on the child's hospitalization, compared to 96% at the rural site. CONCLUSIONS: AGE hospitalization costs differed between the urban and rural hospitals and were most burdensome to the lowest income households. Rotavirus positivity was not associated with greater household costs.

Bilateral choroidal osteoma associated with langerhans cell histiocytosis, a coincidence?

PURPOSE: To describe a case of bilateral choroidal osteoma (CO) in a patient with a history of langerhans cell histiocytosis (LCH). METHODS: A 24-year-old man complaining of gradually decreasing visual acuity in both eyes is presented. He had a history of lymphadenopathy, respiratory symptoms, and pathology-proven diagnosis of LCH. RESULTS: Ophthalmic clinical and imaging studies revealed bilateral CO. CONCLUSION: In this patient, we suggest a possible relationship between LCH and CO.

Diarrhea-Associated Mortality in Children Less Than 5 Years of Age in the United States, 2005-2016.

Diarrheal disease morbidity decreased after the 2006 US introduction of rotavirus vaccine. We calculated diarrheal death rates for children who were <5 years of age during 2005-2016. Death rates declined from 2.3/100,000 (2005-2006) to 1.7/100,000 (2014-2016). Declines were seen among 1- to 23-month olds, white and black children. Further exploration of the role of rotavirus vaccine in decreasing deaths among children is warranted.

Factors Associated With Rotavirus Vaccine Coverage.

BACKGROUND: Rotavirus vaccines (RVVs) were included in the US immunization program in 2006 and are coadministered with the diphtheria-tetanus-acellular pertussis (DTaP) vaccine, yet their coverage lags behind DTaP. We assessed timing, initiation, and completion of the RVV series among children enrolled in active gastroenteritis surveillance at 7 US medical institutions during 2014-2016. METHODS: We compared coverage and timing of each vaccine series and analyzed characteristics associated with RVV initiation and completion. We report odds ratios (ORs) and 95% confidence intervals (CIs) from multivariable logistic regression models. RESULTS: We enrolled 10 603 children. In 2015, ≥1 dose coverage was 91% for RVV and 97% for DTaP. Seven percent of children received their first DTaP vaccine at age ≥15 weeks versus 4% for RVV (P ≤ .001). Recent birth years (2013-2016) were associated with higher odds of RVV initiation (OR = 5.72; 95% CI 4.43-7.39), whereas preterm birth (OR = 0.32; 95% CI 0.24-0.41), older age at DTaP initiation (OR 0.85; 95% CI 0.80-0.91), income between $50 000 and $100 000 (OR = 0.56; 95% CI 0.40-0.78), and higher maternal education (OR = 0.52; 95% CI 0.36-0.74) were associated with lower odds. Once RVV was initiated, recent birth years (2013-2016; OR = 1.57 [95% CI 1.32-1.88]) and higher maternal education (OR = 1.31; 95% CI 1.07-1.60) were associated with higher odds of RVV completion, whereas preterm birth (OR = 0.76; 95% CI 0.62-0.94), African American race (OR = 0.82; 95% CI 0.70-0.97) and public or no insurance (OR = 0.75; 95% CI 0.60-0.93) were associated with lower odds. Regional differences existed. CONCLUSIONS: RVV coverage remains lower than that for the DTaP vaccine. Timely DTaP administration may help improve RVV coverage.