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1.
J Infect Dis ; 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32249284

RESUMO

Though the etiology of type 1 diabetes (T1D) is not well understood, it is believed to comprise both genetic and environmental factors. Viruses are the most well studied environmental trigger, and there is a small but growing body of research on the potential influence of rotavirus on T1D. Rotavirus infections were initially identified as possible triggers of T1D given similarities between viral peptide sequences and T1D autoantigen peptide sequences. Further, rotavirus infection has been shown to modify T1D risk in T1D-prone mice. However, research into associations of rotavirus infections with T1D development in humans have yielded mixed findings and suggested interactions with age and diet. As global availability of rotavirus vaccines increases, recent studies have assessed whether rotavirus vaccination modifies T1D development, finding null or protective associations. Overall, evidence to-date suggests a possible triggering relationship between some wild-type rotavirus infections and T1D, but the potential effect of rotavirus vaccination remains unclear.

2.
Clin Infect Dis ; 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32322882

RESUMO

BACKGROUND: Rotavirus is a common cause of severe pediatric acute gastroenteritis (AGE). Two vaccines are licensed in the United States and have demonstrated high effectiveness against moderate to severe disease. However, fewer data are available on rotavirus vaccine effectiveness (VE) against milder disease. METHODS: We leveraged active surveillance data from Kaiser Permanente Northwest (KPNW) to calculate rotavirus VE against medically attended rotavirus illness among age-eligible children. We utilized a test-negative case-control design and applied 4 distinct case definitions based on reverse-transcription-quantitative real-time PCR (qRT-PCR) assay and enzyme immunoassay (EIA) test results. VE was calculated as 100*(1 - Odds Ratio), and models were adjusted for age group. RESULTS: The VE analysis population comprised 842 children, 799 (95%) of which had mild disease requiring at most a clinic visit, and 698 (83%) of whom were fully vaccinated against rotavirus. Age-adjusted VE was 70% (95% confidence interval [CI]: 37 - 86%) against disease defined solely by qRT-PCR results, 72% (95% CI: 31 - 89%) against disease as defined by qRT-PCR with a quantification cycle (Cq) value <27, 73% (95% CI: 32 - 90%) against disease that was qRT-PCR positive but EIA negative, and 62% (95% CI: -20 - 88%) against disease defined solely by EIA. Results were similar when restricting to disease resulting in at most an ambulatory clinic or emergency department visit. CONCLUSIONS: These results support the effectiveness of rotavirus vaccination in protecting U.S. children from mild to moderate as well as severe disease. Our findings are also useful to show the effectiveness of rotavirus vaccination against qRT-PCR-defined illness.

3.
Clin Infect Dis ; 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32291450

RESUMO

BACKGROUND: Up-to-date estimates of the burden of norovirus, a leading cause of acute gastroenteritis (AGE) in the United States, are needed to assess the potential value of norovirus vaccines in development. We aimed to estimate the rates, annual counts, and healthcare charges of norovirus-associated ambulatory clinic encounters, Emergency Department (ED) visits, hospitalizations, and deaths in the United States. METHODS: We analyzed administrative data on AGE outcomes from July 1, 2001 through June 30, 2015. Data were sourced from IBM® MarketScan® Commercial and Medicare Supplemental Databases (ambulatory clinic and ED visits), the Healthcare Utilization Project National Inpatient Sample (NIS; hospitalizations), and the National Center for Health Statistics multiple-cause-of-mortality (MCM) data (deaths). Outcome data (ambulatory clinic and ED visits, hospitalizations, or deaths) were summarized by month, age group, and setting. Healthcare charges were estimated based on insurance claims. Monthly counts of cause-unspecified gastroenteritis-associated outcomes were modeled as functions of cause-specified outcomes, and model residuals were analyzed to estimate norovirus-associated outcomes. Healthcare charges were estimated by applying average charges per cause-unspecified gastroenteritis encounter to the estimated number of norovirus encounters. RESULTS: We estimate 900 deaths (95% Confidence Interval [CI]: 650 - 1100), 110,000 hospitalizations (95%CI: 80,000 - 145,000), 470,000 ED visits (95% CI: 348,000 - 610,000), and 2.3 million ambulatory clinic encounters (95% CI: 1.7 - 2.9 million) annually due to norovirus, with an associated $430 - 740 million in healthcare charges. CONCLUSIONS: Norovirus causes a substantial health burden in the United States each year, and an effective vaccine could have important public health impact.

5.
J Infect Dis ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32095831

RESUMO

Since 2006, more than 100 countries have introduced rotavirus vaccine into their immunization programs. We reviewed published data on relative reductions of rotavirus hospitalizations, acute gastroenteritis (AGE) hospitalizations, and AGE deaths among children <5 years old. Articles published from 1 January 2006 to 31 December 2019 with at least 12 months of data before and after rotavirus vaccine introduction were included. Relative reductions were abstracted into a standardized form. Descriptive statistics are presented as medians and interquartile ranges (IQR). We reviewed 1827 total records and included 105 articles from 49 countries. Among children <5 years old, there was a median reduction of 59% (IQR: 46, 74) in rotavirus hospitalizations, 36% (IQR: 23, 47) in AGE hospitalizations, and 36% (IQR: 28, 46) AGE mortality. Reductions were larger in countries with low child mortality, among younger age groups, and in countries with higher coverage. The median percentage of specimens that tested positive for rotavirus among children <5 years old hospitalized for diarrhea was 40% (IQR: 28, 45) before rotavirus vaccine introduction and 20% (IQR: 20, 20) 4 years after introduction. Overall, we found sustained impact on rotavirus and AGE hospitalizations and deaths. These results should encourage countries still considering rotavirus vaccine implementation.

6.
Clin Infect Dis ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32009161

RESUMO

BACKGROUND: Acute gastroenteritis(AGE) is a common reason for children to seek medical care. However, the viral etiology of AGE illness is not well described in the post-rotavirus vaccine era, particularly in the outpatient(OP) setting. METHODS: Between 2012 and 2015, children 15 days through 17 years old presenting to Vanderbilt Children's Hospital, Nashville, TN with AGE were enrolled prospectively from the inpatient, emergency department, and OP settings and stool specimens were collected. Healthy controls(HCs) were enrolled and frequency-matched for period, age group, race, and ethnicity. Stool specimens were tested by reverse-transcription real-time quantitative polymerase chain reaction for norovirus, sapovirus, and astrovirus RNA and by Rotaclone enzyme immunoassay for rotavirus antigen, followed by PCR verification of antigen detection. RESULTS: A total of 3705 AGE cases and 1563 HC were enrolled, among whom 2885 cases(78%) and 1110 HCs(71%) provided stool specimens that were tested. All four viruses were more frequently detected in AGE cases vs. HC: norovirus, 22% vs. 8%; rotavirus, 10% vs. 1%; sapovirus, 10% vs. 5%; and astrovirus, 5% vs. 2%(p<0.001 for each virus, respectively). AGE rates in the OP setting due to norovirus were highest compared to the other three viruses. Children under five years old had higher OP AGE rates compared to older children for all viruses. CONCLUSIONS: Norovirus remains the most common virus detected in all settings, occurring nearly twice as frequently as the next most common pathogens, sapovirus and rotavirus. Combined, these four viruses were associated with almost half of all AGE visits and therefore are an important reason for children to seek medical care.

7.
Clin Infect Dis ; 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32060546

RESUMO

BACKGROUND: Since 2006, the New Vaccine Surveillance Network has conducted active, population-based surveillance for acute gastroenteritis (AGE) hospitalizations and emergency department (ED) visits in three US counties. Trends in the epidemiology and disease burden of rotavirus hospitalizations and ED visits were examined from 2006-2016. METHODS: Children <3 years of age hospitalized or visiting the ED with AGE, were enrolled from January 2006-June 2016. Bulk stool specimens were collected and tested for rotavirus. Rotavirus-associated hospitalization and ED visit rates were calculated annually with 2006-2007 defined as pre-vaccine and 2008-2016 as post-vaccine periods. Rotavirus genotype trends were compared over time. RESULTS: Over 11 seasons, 6954 children with AGE were enrolled and submitted a stool specimen (2187 hospitalized and 4767 in the ED). Comparing pre- and post-vaccine periods, the proportion of children with rotavirus dramatically declined for hospitalization (49% vs 10%) and ED visits (49% vs 8%). In the post-vaccine era, a biennial pattern of rotavirus rates was observed, with a trend toward an older median age. G1P[8] (63%) was the predominant genotype in the pre-vaccine period with a significantly lower proportion (7%) in the post-vaccine period (p<.001). G2P[4] remained stable (8% to 14%) in both periods, while G3P[8] and G12P[8] increased in proportion from pre-to post-vaccine periods (1% to 25% and 17% to 40%) respectively. CONCLUSIONS: The epidemiology and disease burden of rotavirus has been altered by rotavirus vaccination with a biennial disease pattern, sustained low rates of rotavirus in children <3 years of age and a shift in the residual genotypes from G1P[8] to other genotypes.

9.
Transbound Emerg Dis ; 67(1): 442-449, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31469933

RESUMO

Group A rotavirus (RVA) associated diarrhoea in piglets represents one of the major causes of morbidity and mortality in pig farms worldwide. A diarrhoea outbreak occurred among nomadic piglets in north-western district of Bangladesh in February 2014. Outbreak investigation was performed to identify the cause, epidemiologic and clinical features of the outbreak. Rectal swabs and clinical information were collected from diarrhoeic piglets (n = 36). Rectal swabs were tested for RVA RNA by real-time reverse transcription polymerase chain reaction (rRT-PCR) using NSP3-specific primers. The G (VP7) and P (VP4) genes were typed by conventional RT-PCR and sanger sequencing and full genome sequences were determined using next-generation sequencing. We found the attack rate was 61% (50/82) among piglets in the nomadic pig herd, and the case fatality rate was 20% (10/50) among piglets with diarrhoea. All study piglets cases had watery diarrhoea, lack of appetite or reluctance to move. A novel RVA strain with a new P[49] genotype combined with G4 was identified among all piglets with diarrhoea. The genome constellation of the novel RVA strains was determined to be G4-P[49]-I1-R1-C1-M1-A8-N1-T7-E1-H1. Genetic analysis shows that the novel G4P[49] strain is similar to Indian and Chinese porcine or porcine-like G4 human strains and is genetically distant from Bangladeshi human G4 strains. Identification of this novel RVA strain warrants further exploration for disease severity and zoonotic potential.

10.
J Pediatr Gastroenterol Nutr ; 70(1): 20-24, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31517717

RESUMO

OBJECTIVES: Morbidity and mortality from intussusception, the leading cause of bowel obstruction in infants, is higher in Africa than in other regions of the world, but the reasons have not been well examined. We sought to identify risk and protective factors associated with death or intestinal resection following intussusception. METHODS: Infants with intussusception from 7 sub-Saharan African countries (Ethiopia, Ghana, Kenya, Malawi, Tanzania, Zambia, and Zimbabwe) were enrolled through active, hospital-based surveillance from February 2012 to December 2016. We examined demographic, clinical, and socioeconomic factors associated with death or intestinal resection following intussusception, using multivariable logistic regression. RESULTS: A total of 1017 infants <1 year of age with intussusception were enrolled. Overall, 13% of children (133/1017) died during the hospitalization, and 48% (467/966) required intestinal resection. In multivariable analyses, female sex [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.2-3.3], longer duration of symptoms before presentation (OR 1.1; 95% CI 1.0-1.2), and undergoing intestinal resection (OR 3.4; 95% CI 1.9-6.1) were associated with death after intussusception. Diagnosis by ultrasound or enema (OR 0.4; 95% CI 0.3-0.7), and employment of a household member (OR 0.7; 95% CI 0.4-1.0) were protective against intestinal resection. CONCLUSIONS: Delays in hospital presentation and female sex were significantly associated with death, whereas higher socioeconomic status and availability of radiologic diagnosis reduced likelihood of undergoing resection. Efforts should be intensified to improve the awareness, diagnosis, and management of intussusception in sub-Saharan African countries to reduce morbidity and mortality from intussusception in these resource-limited settings.

11.
Clin Infect Dis ; 70(1): 40-48, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30901024

RESUMO

BACKGROUND: Norovirus is an important cause of epidemic acute gastroenteritis (AGE), yet the burden of endemic disease in adults has not been well documented. We estimated the prevalence and incidence of outpatient and community-acquired inpatient norovirus AGE at 4 Veterans Affairs Medical Centers (VAMC) (Atlanta, Georgia; Bronx, New York; Houston, Texas; and Los Angeles, California) and examined trends over 4 surveillance years. METHODS: From November 2011 to September 2015, stool specimens collected within 7 days of AGE symptom onset for clinician-requested diagnostic testing were tested for norovirus, and positive samples were genotyped. Incidence was calculated by multiplying norovirus prevalence among tested specimens by AGE-coded outpatient encounters and inpatient discharges, and dividing by the number of unique patients served. RESULTS: Of 1603 stool specimens, 6% tested were positive for norovirus; GII.4 viruses (GII.4 New Orleans [17%] and GII.4 Sydney [47%]) were the most common genotypes. Overall prevalence and outpatient and inpatient community-acquired incidence followed a seasonal pattern, with higher median rates during November-April (9.2%, 376/100 000, and 45/100 000, respectively) compared to May-October (3.0%, 131/100 000, and 13/100 000, respectively). An alternate-year pattern was also detected, with highest peak prevalence and outpatient and inpatient community-acquired norovirus incidence rates in the first and third years of surveillance (14%-25%, 349-613/100 000, and 43-46/100 000, respectively). CONCLUSIONS: This multiyear analysis of laboratory-confirmed AGE surveillance from 4 VAMCs demonstrates dynamic intra- and interannual variability in prevalence and incidence of outpatient and inpatient community-acquired norovirus in US Veterans, highlighting the burden of norovirus disease in this adult population.

13.
Lancet Glob Health ; 7(12): e1664-e1674, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31708147

RESUMO

BACKGROUND: Previous studies have found rotavirus vaccination to be highly cost-effective in low-income countries. However, updated evidence is now available for several inputs (ie, rotavirus disease mortality rates, rotavirus age distributions, vaccine timeliness, and vaccine efficacy by duration of follow-up), new rotavirus vaccines have entered the market, vaccine prices have decreased, and cost-effectiveness thresholds have been re-examined. We aimed to provide updated cost-effectiveness estimates to inform national decisions about the new introduction and current use of rotavirus vaccines in Gavi countries. METHODS: We calculated the potential costs and effects of rotavirus vaccination for ten successive birth cohorts in 73 countries previously and currently eligible for Gavi support, compared with no vaccination. We used a deterministic cohort model to calculate numbers of rotavirus gastroenteritis cases, outpatient visits, hospitalisations, and deaths between birth and 5 years, with and without rotavirus vaccination. We calculated treatment costs from the government and societal perspectives. The primary outcome measure was the incremental cost-effectiveness ratio (discounted US$ per disability-adjusted life-year averted). Country-specific model input parameters were based on the scientific literature, published meta-analyses, and international databases. We ran deterministic and probabilistic uncertainty analyses. FINDINGS: Over the period 2018-27, rotavirus vaccination has the potential to prevent nearly 600 000 deaths in Gavi countries. Averted outpatient visits and hospitalisations could lead to treatment savings of approximately $484·1 million from the government perspective and $878·0 million from the societal perspective. The discounted dollars per disability-adjusted life-year averted has a very high probability (>90%) of being less than 0·5 times the gross domestic product per capita in 54 countries, and less than 1·0 times gross domestic product per capita in 63 countries. INTERPRETATION: Rotavirus vaccination continues to represent good value for money across most Gavi countries despite lower rotavirus mortality estimates and more stringent willingness-to-pay thresholds. FUNDING: Bill & Melinda Gates Foundation.

14.
J Infect Dis ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31754717

RESUMO

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 a slightly increased risk of intussusception with rotavirus vaccination has been found in several countries. 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 2015-2017, we enrolled one-to-one matched intussusception cases and hospital controls; 249 pairs are included. Stool specimens were tested for 37 infectious agents using TaqMan Array technology. We used conditional logistic regression to estimate the odds ratio and 95% confidence interval (CI) of each pathogen associated with intussusception in a pooled analysis and in quantitative sub-analyses. 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.

15.
Lancet Glob Health ; 7(11): e1541-e1552, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31607466

RESUMO

BACKGROUND: Infant rotavirus vaccines have led to substantial reductions in hospital admissions and deaths due to gastroenteritis, but some studies have reported an elevated risk of intussusception, a rare bowel disorder. This analysis aimed to provide evidence on the potential mortality reduction benefits and intussusception risks of current rotavirus vaccination schedules, and to explore whether alternative schedules could have advantages. METHODS: All 135 low-income and middle-income countries, defined by gross national income per capita of less than US$12 236 in the 2018 fiscal year, were included in the model. Mortality reduction benefits and intussusception risks of rotavirus vaccination were modelled by use of an Excel-based static cohort model with a finely disaggregated age structure. Numbers of rotavirus gastroenteritis deaths and intussusception deaths in each week of age were calculated for all infants born in the year 2015 between birth and age 5·0 years, with and without restrictions on age at administration. Benefit-risk ratios (rotavirus gastroenteritis deaths prevented per excess intussusception death) and other indicators were calculated for two vaccination schedules currently recommended by WHO and 16 alternative schedules. Of these schedules, it was assumed that between one and three doses would be given; the first dose of the rotavirus vaccine would be co-administered with either BCG or diphtheria-tetanus-pertussis (DTP)1; and the second or third dose would be co-administered with either DTP1, DTP2, DTP3, or measles (Meas)1. FINDINGS: A three-dose schedule co-administered with DTP (without age restrictions) could prevent about 74 000 (95% uncertainty interval 59 000-100 000) rotavirus gastroenteritis deaths (38% reduction) and could lead to 201 (77-550) excess intussusception deaths (1·4% increase) compared with no vaccination, resulting in a benefit-risk ratio of 369:1 (160:1-895:1). The benefit-risk ratio was most favourable when the relative risk of intussusception was assumed to decline with the national under-5 mortality rate (2386:1) and least favourable with pessimistic assumptions about access to hospital for intussusception treatment (168:1). Schedules that involve giving the first dose with BCG and the second with DTP1 had the fewest excess intussusception deaths and most favourable benefit-risk ratios. INTERPRETATION: Rotavirus vaccines have a favourable benefit-risk profile in LMICs. Neonatal schedules have the potential to prevent more rotavirus gastroenteritis deaths and cause fewer excess intussusception deaths than the schedules currently recommended by WHO, but more efficacious rotavirus vaccines would be needed to achieve more substantial mortality reduction benefits. FUNDING: Bill & Melinda Gates Foundation.

16.
BMC Public Health ; 19(1): 1340, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640646

RESUMO

BACKGROUND: Diarrhea is a major cause of morbidity and mortality, yet incidence and etiology data are limited. We conducted laboratory-based diarrhea surveillance in Guatemala. METHODS: A diarrhea case was defined as ≥3 loose stools in a 24-h period in a person presenting to the surveillance facilities. Epidemiologic data and stool specimens were collected. Specimens were tested for bacterial, parasitic, and viral pathogens. Yearly incidence was adjusted for healthcare seeking behaviors determined from a household survey conducted in the surveillance catchment area. RESULTS: From November 2008 to December 2012, the surveillance system captured 5331 diarrhea cases; among these 1381 (26%) had specimens tested for all enteric pathogens of interest. The adjusted incidence averaged 659 diarrhea cases per 10,000 persons per year, and was highest among children aged < 5 years, averaging 1584 cases per 10,000 children per year. Among 1381 (26%) specimens tested for all the pathogens of interest, 235 (17%) had a viral etiology, 275 (20%) had a bacterial, 50 (4%) had parasites, and 86 (6%) had co-infections. Among 827 (60%) specimens from children aged < 5 years, a virus was identified in 196 (23%) patients; 165 (20%) had norovirus and 99 (12%) rotavirus, including co-infections. Among 554 patients aged ≥5 years, 103 (19%) had a bacterial etiology, including diarrheagenic Escherichia coli in 94 (17%) cases, Shigella spp. in 31 (6%), Campylobacter spp. in 5 (1%), and Salmonella spp. in 4 (1%) cases. Detection of Giardia and Cryptosporidium was infrequent (73 cases; 5%). CONCLUSIONS: There was a substantial burden of viral and bacterial diarrheal diseases in Guatemala, highlighting the importance of strengthening laboratory capacity for rapid detection and control and for evaluation of public health interventions.


Assuntos
Disenteria/epidemiologia , Disenteria/etiologia , Vigilância em Saúde Pública/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Fezes/microbiologia , Fezes/parasitologia , Fezes/virologia , Feminino , Guatemala/epidemiologia , Humanos , Incidência , Lactente , Laboratórios , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Clin Infect Dis ; 2019 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-31626687

RESUMO

International Classification of Diseases diagnostic codes are used to estimate acute gastroenteritis (AGE) disease burden. We validated AGE-related codes in pediatric and adult populations using 2 multiregional active surveillance platforms. The sensitivity of AGE codes was similar (54% and 58%) in both populations and increased with addition of vomiting-specific codes.

18.
JAMA Netw Open ; 2(9): e1912242, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31560386

RESUMO

Importance: Rotavirus vaccines have been recommended for universal US infant immunization for more than 10 years, and understanding their effectiveness is key to the continued success of the US rotavirus vaccine immunization program. Objective: To assess the association of RotaTeq (RV5) and Rotarix (RV1) with inpatient and emergency department (ED) visits for rotavirus infection. Design, Setting, and Participants: This case-control vaccine effectiveness study was performed at inpatient and ED clinical settings in 7 US pediatric medical institutions from November 1, 2009, through June 30, 2016. Children younger than 5 years seeking medical care for acute gastroenteritis were enrolled. Clinical and epidemiologic data, vaccination verification, and results of stool sample tests for laboratory-confirmed rotavirus were collected. Data were analyzed from November 1, 2009, through June 30, 2016. Main Outcomes and Measures: Rotavirus vaccine effectiveness for preventing rotavirus-associated inpatient and ED visits over time for each licensed vaccine, stratified by clinical severity and age. Results: Among the 10 813 children included (5927 boys [54.8%] and 4886 girls [45.2%]; median [range] age, 21 [8-59] months), RV5 and RV1 analyses found that compared with controls, rotavirus-positive cases were more often white (RV5, 535 [62.2%] vs 3310 [57.7%]; RV1, 163 [43.1%] vs 864 [35.1%]), privately insured (RV5, 620 [72.1%] vs 4388 [76.5%]; RV1, 305 [80.7%] vs 2140 [87.0%]), and older (median [range] age for RV5, 26 [8-59] months vs 21 [8-59] months; median [range] age for RV1, 22 [8-59] months vs 19 [8-59] months) but did not differ by sex. Among 1193 rotavirus-positive cases and 9620 rotavirus-negative controls, at least 1 dose of any rotavirus vaccine was 82% (95% CI, 77%-86%) protective against rotavirus-associated inpatient visits and 75% (95% CI, 71%-79%) protective against rotavirus-associated ED visits. No statistically significant difference during this 7-year period was observed for either rotavirus vaccine. Vaccine effectiveness against inpatient and ED visits was 81% (95% CI, 78%-84%) for RV5 (3 doses) and 78% (95% CI, 72%-82%) for RV1 (2 doses) among the study population. A mixed course of both vaccines provided 86% (95% CI, 74%-93%) protection. Rotavirus patients who were not vaccinated had severe infections 4 times more often than those who were vaccinated (74 of 426 [17.4%] vs 28 of 605 [4.6%]; P < .001), and any dose of rotavirus vaccine was 65% (95% CI, 56%-73%) effective against mild infections, 81% (95% CI, 76%-84%) against moderate infections, and 91% (95% CI, 85%-95%) against severe infections. Conclusions and Relevance: Evidence from this large postlicensure study of rotavirus vaccine performance in the United States from 2010 to 2016 suggests that RV5 and RV1 rotavirus vaccines continue to perform well, particularly in preventing inpatient visits and severe infections and among younger children.

19.
Clin Infect Dis ; 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31544211

RESUMO

INTRODUCTION: Monovalent rotavirus vaccine, RotarixTM, was introduced in Kenya in July 2014, is recommended to infants as oral doses at ages 6 and 10 weeks. A multi-site study was established in two population based surveillance sites to evaluate vaccine impact on the incidence of rotavirus-associated hospitalisations (RVH). METHODS: Hospital-based surveillance was conducted from January 2010 to June 2017 for acute diarrhoea hospitalisations among children aged <5 years in two health facilities in Kenya. A controlled interrupted time series analysis was undertaken to compare RVH pre and post vaccine introduction using rotavirus negative cases as a control series.  The change in incidence post vaccine introduction was estimated from a negative binomial model that adjusted for secular trend, seasonality and multiple health worker industrial actions (strikes). RESULTS: Between January 2010 and June 2017 there were 1513 and 1652 diarrhoea hospitalisations in Kilifi and Siaya; among those tested for rotavirus, 28% (315/1142) and 23% (197/877) were positive, respectively.  There was a 57% (95% CI: 8 to 80) reduction in RVH observed in the first year post vaccine introduction in Kilifi and a 59% (95% CI: 20 to 79) reduction in Siaya. In the second year, RVH decreased further at both sites, 80% (95% CI: 46 to 93) reduction in Kilifi and 82% reduction in Siaya (95% CI: 61 to 92), and this reduction was sustained at both sites into the third year. CONCLUSIONS: A substantial reduction of RVH and all-cause diarrhoea has been observed in two demographic surveillance sites in Kenya within 3 years of vaccine introduction.

20.
Sci Transl Med ; 11(505)2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31413144

RESUMO

Rotavirus vaccination has substantially reduced the incidence of rotavirus-associated gastroenteritis (RVGE) in high-income countries, but vaccine impact and estimated effectiveness are lower in low-income countries for reasons that are poorly understood. We used mathematical modeling to quantify rotavirus vaccine impact and investigate reduced vaccine effectiveness, particularly during the second year of life, in Malawi, where vaccination was introduced in October 2012 with doses at 6 and 10 weeks. We fitted models to 12 years of prevaccination data and validated the models against postvaccination data to evaluate the magnitude and duration of vaccine protection. The observed rollout of vaccination in Malawi was predicted to lead to a 26 to 77% decrease in the overall incidence of moderate-to-severe RVGE in 2016, depending on assumptions about waning of vaccine-induced immunity and heterogeneity in vaccine response. Vaccine effectiveness estimates were predicted to be higher among 4- to 11-month-olds than 12- to 23-month-olds, even when vaccine-induced immunity did not wane, due to differences in the rate at which vaccinated and unvaccinated individuals acquire immunity from natural infection. We found that vaccine effectiveness during the first and second years of life could potentially be improved by increasing the proportion of infants who respond to vaccination or by lowering the rotavirus transmission rate. An additional dose of rotavirus vaccine at 9 months of age was predicted to lead to higher estimated vaccine effectiveness but to only modest (5 to 16%) reductions in RVGE incidence over the first 3 years after introduction, regardless of assumptions about waning of vaccine-induced immunity.

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