[Show abstract][Hide abstract] ABSTRACT: A humanitarian emergency involves a complete breakdown of authority that often disrupts routine health care delivery, including immunization. Diarrheal diseases are a principal cause of morbidity and mortality among children during humanitarian emergencies. The objective of this study was to assess if vaccination against rotavirus, the most common cause of severe diarrhea among children, either as an addition to routine immunization program (RI) or supplemental immunization activity (SIA) would be cost-effective during a humanitarian emergency to decrease diarrhea morbidity and mortality, using Somalia as a case study.
An impact and cost-effectiveness analysis was performed comparing no vaccine; two-dose rotavirus SIA and two-dose of RI for the 424,592 births in the 2012 Somali cohort. The main summary measure was the incremental cost per disability-adjusted life-year (DALY) averted. Univariate sensitivity analysis examined the extent to which the uncertainty in the variables affected estimates.
If introduced in Somalia, a full-series rotavirus RI and SIA would save 908 and 359 lives, respectively, and save US$63,793 and US$25,246 in direct medical costs, respectively. The cost of a RI strategy would be US$309,458. Because of the high operational costs, a SIA strategy would cost US$715,713. US$5.30 per DALY would be averted for RI and US$37.62 per DALY averted for SIA. Variables that most substantially influenced the cost-effectiveness for both RI and SIA were vaccine program costs, mortality rate, and vaccine effectiveness against death.
Based on our model, rotavirus vaccination appears to be a cost-effective intervention as either RI or SIA, as defined by the World Health Organization as one to three times the per capita Gross Domestic Product (Somalia $112 in 2011). RI would have greater health impact and is more cost effective than SIA, assuming feasibility of reaching the target population. However, given the lack of infrastructure, whether RI is realistic in this setting remains unanswered, and alternative approaches like SIA should be further examined.
Conflict and Health 12/2015; 9(1):5. DOI:10.1186/s13031-015-0032-y
[Show abstract][Hide abstract] ABSTRACT: During the 2008-2009 rotavirus season of the CDC New Vaccine Surveillance Network, one case of pediatric acute gastroenteritis associated with a rotavirus G14P strain was identified. This was the first detection of the genotype G14 and P in humans and the first detection of the G14P combination. To gain an insight into the origins and the evolution of this strain, we determined the complete open reading frame sequences of all 11 genes. A majority of the genes identified were similar to the simian strain TUCH, except for the VP1 and VP7 genes that cluster only distantly with the bovine and equine strains, respectively. In addition, this strain carries an AU-1-like NSP2 and NSP4 genes. Using codon-partitioning and protein-based phylogenetic approaches, we determined that the VP7 genotype of strain 2009727118 is actually G3; therefore, the proposed full genomic classification of the 2009727118 strain is G3-P-I9-R2-C3-M3-A9-N3-T3-E3-H6. These findings indicate the possibility that the 2009727118 strain originated by interspecies transmission and multiple reassortment events involving human, bovine and equine rotaviruses, resulting in the introduction of some genes into the genome of simian rotaviruses. Additionally, we found evidence of mutational saturation in the 3rd codon position of the VP7 ORF which presented an issue with homoplasy in phylogenetic analyses.
Journal of General Virology 11/2015; DOI:10.1099/jgv.0.000349 · 3.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Using a multi-center, active surveillance network from two rotavirus seasons (2012 and 2013), we assessed the vaccine effectiveness of RV5 (RotaTeq) and RV1 (Rotarix) rotavirus vaccines in preventing rotavirus gastroenteritis hospitalizations and emergency department (ED) visits for numerous demographic and secular strata.
We enrolled children hospitalized or visiting the ED with acute gastroenteritis (AGE) for the 2012 and 2013 seasons at 7 medical institutions. Stool specimens were tested for rotavirus by enzyme immunoassay and genotyped, and rotavirus vaccination histories were compared for rotavirus-positive cases and rotavirus-negative AGE controls. We calculated the VE for preventing rotavirus associated hospitalizations and ED visits for each vaccine, stratified by vaccine dose, season, clinical setting, age, predominant genotype, and ethnicity.
RV5-specific VE analyses included 2,961 subjects, 402 rotavirus cases (14%) and 2,559 rotavirus-negative AGE controls. RV1-specific VE analyses included 904 subjects, 100 rotavirus cases (11%) and 804 rotavirus-negative AGE controls. Over the two rotavirus seasons, the VE for a complete 3-dose vaccination with RV5 was 80% (CI= 74% - 84%), and VE for a complete 2-dose vaccination with RV1 was 80% (CI= 68% - 88%).Statistically significant VE was observed for each year of life for which sufficient data allowed analysis (7 years for RV5 and 3 years for RV1). Both vaccines provided statistically significant genotype-specific protection against predominant circulating rotavirus strains.
In this large, geographically and demographically diverse sample of US children, we observed that RV5 and RV1 rotavirus vaccines each provided a lasting, and broadly heterologous protection against rotavirus gastroenteritis.
[Show abstract][Hide abstract] ABSTRACT: Background:
Live oral rotavirus (RV) vaccines have shown modest efficacy among children in African countries for reasons that are not completely understood. We examined the possible inhibitory effect of pre-existing anti-rotavirus antibodies on immunogenicity of monovalent rotavirus vaccine (RV1).
Mother-infant pairs were enrolled at presentation for their routine immunization visit in Soweto, South Africa at 5-8 weeks age. Infant serum samples were obtained before each of the first and second doses of RV1, and one month after the second dose. Maternal serum and breast milk samples were obtained prior to administration of each dose of RV1 to infants. RV-specific IgG, IgA and neutralizing activity in sera of infants and serum or breast milk samples of mothers were measured by enzyme-linked immunosorbent assays or a microneutralization test.
Of the 107 serum pairs from infants who were seronegative for RV IgA at enrollment, we observed a strong positive association between IgG titers in pre-dose 1 sera of infants and mothers and significant negative associations between IgG titers in pre dose 1 sera of infants and seroconversion to RV1 post dose 1. Similarly, mothers whose infants IgA seroconverted after RV1 had significantly lower pre-dose 1 IgG titers in sera than those whose infants did not seroconvert.
High levels of pre-existing serum IgG, including transplacentally acquired maternal IgG, appeared to have an inhibitory effect on the immunogenicity of RV1 among infants and may, in part, contribute to lower efficacy of RV vaccines in this and other low income settings.
[Show abstract][Hide abstract] ABSTRACT: Importance:
A genetic polymorphism affecting FUT2 secretor status in approximately one-quarter of humans of European descent affects the expression of histo-blood group antigens on the mucosal epithelia of human respiratory, genitourinary, and digestive tracts. These histo-blood group antigens serve as host receptor sites necessary for attachment and infection of some pathogens, including norovirus.
We investigated whether an association exists between FUT2 secretor status and laboratory-confirmed rotavirus infections in US children.
Design, setting, and participants:
Multicenter case-control observational study involving active surveillance at 6 US pediatric medical institutions in the inpatient and emergency department clinical settings. We enrolled 1564 children younger than 5 years with acute gastroenteritis (diarrhea and/or vomiting) and 818 healthy controls frequency matched by age and month, from December 1, 2011, through March 31, 2013.
Main outcomes and measures:
Paired fecal-saliva specimens were tested for rotavirus and for secretor status. Comparisons were made between rotavirus test-positive cases and healthy controls stratified by ethnicity and vaccination status. Adjusted multivariable analyses assessed the preventive association of secretor status against severe rotavirus gastroenteritis.
One (0.5%) of 189 rotavirus test-positive cases was a nonsecretor, compared with 188 (23%) of 818 healthy control participants (P < .001). Healthy control participants of Hispanic ethnicity were significantly less likely to be nonsecretors (13%) compared with healthy children who were not of Hispanic ethnicity (25%) (P < .001). After controlling for vaccination and other factors, children with the nonsecretor FUT2 polymorphism appeared statistically protected (98% [95% CI, 84%-100%]) against severe rotavirus gastroenteritis.
Conclusions and relevance:
Severe rotavirus gastroenteritis was virtually absent among US children who had a genetic polymorphism that inactivates FUT2 expression on the intestinal epithelium. We observed a strong epidemiologic association among children with rotavirus gastroenteritis compared with healthy control participants. The exact cellular mechanism behind this epidemiologic association remains unclear, but evidence suggests that it may be rotavirus genotype specific. The lower prevalence of nonsecretors among Hispanic children may translate to an enhanced burden of rotavirus gastroenteritis among this group. Our findings may have bearing on our full understanding of rotavirus infections and the effects of vaccination in diverse populations.
[Show abstract][Hide abstract] ABSTRACT: Background:
Trivalent oral poliovirus vaccine (tOPV) is known to interfere with monovalent rotavirus vaccine (RV1) immunogenicity. Interference with bivalent and monovalent OPV formulations, which will be increasingly used globally in coming years, has not been examined. We conducted a post-hoc analysis to assess the interference of co-administration of different OPV formulations on RV1 immunogenicity.
Healthy infants in Matlab, Bangladesh were randomized to receive 3 doses of monovalent OPV type 1 (mOPV1) or bivalent OPV 1+3 (bOPV) at 6, 8 and 10 weeks or at 6, 10, 14 weeks of age; or tOPV at 6, 10 and 14 weeks of age. All infants received two doses of RV1 at around 6 and 10 weeks of age. Concomitant administration was defined as RV1 and OPV given on the same day; staggered administration as RV1 and OPV given ≥1 day apart. Rotavirus seroconversion was defined as a 4-fold rise in IgA titer from before the 1(st) RV1 dose to ≥3 weeks after 2(nd) RV1 dose.
There were no significant differences in baseline RV1 immunogenicity among the 409 infants included in the final analysis. Infants who received RV1 and OPV concomitantly, regardless of OPV formulation, were less likely to seroconvert (47% [95% CI: 39-54%]) compared to those that received both vaccines staggered ≥1 day (63% [95% CI: 57%-70%], p<0.001). For staggered administration, we found no evidence that the length of interval between RV1 and OPV administration affected RV1 immunogenicity.
Co-administration of mOPV1, bOPV or tOPV appears to lower RV1 immunogenicity.
[Show abstract][Hide abstract] ABSTRACT: To describe the epidemiology of intussusception before introduction of the rotavirus vaccine, we reviewed the records of 280 patients younger than 5 years who were hospitalized in Kenya between 2002 and 2013. The patients who died (18 [6.4%]) had sought care later after symptom onset than the patients who survived (median, 5 vs 3 days, respectively; P = .04). Seeking prompt care may improve therapeutic outcomes.
[Show abstract][Hide abstract] ABSTRACT: In 2006 and 2008, two new rotavirus vaccines (RotaTeq [RV5] and Rotarix [RV1]) were introduced in the United States. US data on intussusception have been mostly related to RV5, with limited data on RV1.
We assessed intussusception events following RV1 reported to the Vaccine Adverse Event Reporting System (VAERS), a US national passive surveillance system, during February 2008-December 2014. We conducted a self-controlled risk interval analysis using Poisson regression to estimate the daily reporting ratio (DRR) of intussusception after the first 2 doses of RV1 comparing average daily reports 3-6 versus 0-2 days after vaccination. We calculated the excess risk of intussusception per 100,000 vaccinations based on DRRs and background rates of intussusception. Sensitivity analyses were conducted to assess effects of differential reporting completeness and inaccuracy of baseline rates.
VAERS received 108 confirmed insusceptible reports after RV1. A significant clustering was observed on days 3-8 after does1 (p=0.001) and days 2-7 after dose 2 (p=0.001). The DRR comparing the 3-6 day and the 0-2 day periods after RV1 dose 1 was 7.5 (95% CI=2.3, 24.6), translating to an excess risk of 1.6 (95% CI=0.3, 5.8) per 100,000 vaccinations. The DRR was elevated but not significant after dose 2 (2.4 [95% CI=0.8,7.5]). The excess risk ranged from 1.2 to 2.8 per 100,000 in sensitivity analysis.
We observed a significant increased risk of intussusception 3-6 days after dose 1 of RV1. The estimated small number of intussusception cases attributable to RV1 is outweighed by the benefits of rotavirus vaccination.
Published by Elsevier Ltd.
[Show abstract][Hide abstract] ABSTRACT: Respiratory and diarrheal diseases are leading causes of morbidity and mortality among children under 5 years of age in developing countries. Data on the burden of these diseases in Haiti are scarce.
We conducted a retrospective review of hospital admission registries during January 1, 2011-December 31, 2013 for children under 5 years of age in six hospitals in Haiti. We recorded the number of all-cause, respiratory and diarrheal disease admissions and deaths by epidemiologic week and age.
A total of 31,565 hospital admissions and 1763 deaths were recorded among children aged <5 years during the study period. Respiratory diseases accounted for 9183 (29%) hospitalizations and 301 (17%) deaths. Children aged 6-23 months had the highest percentage of hospitalizations attributable to respiratory diseases (38%), while children aged 36-47 months had the highest proportion of deaths attributable to respiratory diseases (37%). Respiratory disease hospitalizations followed a bimodal seasonal pattern, with peaks during May-June and October-December. Diarrheal diseases accounted for 8063 (26%) hospitalizations and 224 (13%) deaths. Children aged 6-11 months had the highest percentage of diarrhea-associated hospitalizations (39%) and deaths (29%). Diarrheal disease admissions peaked in January-April prior to the rainy season.
Respiratory and diarrheal diseases contributed to more than half of hospitalizationsand almost a third of deaths in children under 5 years of age in Haiti. These data are essential to assess the impact of pneumococcal and rotavirus vaccinesand other interventions in Haiti.
[Show abstract][Hide abstract] ABSTRACT: Human norovirus infection causes significant medical and financial costs in the USA and abroad. Some populations, including young children, the elderly, and the immunocompromised, are at heightened risk of infection with this virus and subsequent complications, while others, such as healthcare workers and food handlers are at increased risk of transmitting it, and some are at risk of both. Human noroviruses are heterogeneous with new strains emerging periodically. In addition to viral diversity, incompletely understood characteristics, such as virus-host cell binding and duration of immunity after infection add to the challenges of creating a norovirus vaccine. Although much progress has been made in recent years, many questions remain to be answered. In this review, we discuss the important areas and relevant literature in considering human norovirus vaccine development and potential targets for implementation.
[Show abstract][Hide abstract] ABSTRACT: In 1999, the first rhesus-human reassortant rotavirus vaccine licensed in the United States was withdrawn within a year of its introduction after it was linked with intussusception at a rate of ∼1 excess case per 10,000 vaccinated infants. While clinical trials of 60,000-70,000 infants of each of the two current live oral rotavirus vaccines, RotaTeq (RV5) and Rotarix (RV1), did not find an association with intussusception, post-licensure studies have documented a risk in several high and middle income countries, at a rate of ∼1-6 excess cases per 100,000 vaccinated infants. However, considering this low risk against the large health benefits of vaccination that have been observed in many countries, including in countries with a documented vaccine-associated intussusception risk, policy makers and health organizations around the world continue to support the routine use of RV1 and RV5 in national infant immunization programs. Because the risk and benefit data from affluent settings may not be directly applicable to developing countries, further characterization of any associated intussusception risk following rotavirus vaccination as well as the health benefits of vaccination is desirable for low income settings.
Published by Elsevier Ltd.
[Show abstract][Hide abstract] ABSTRACT: Population-based surveillance during 2006-2013 showed that norovirus hospitalization rates among Bedouin (low-middle income settings) children <5 years old were 13.9/10,000 person-years compared with 7.1/10,000 among Jewish (high-income settings) children who were <5 years (rate ratio: 2.0, 95% confidence interval: 1.6-2.3). Differences were most prominent among infants (59.7 vs. 19.7/10,000, respectively; rate ratio: 3.0, 95% confidence interval: 2.5-3.8). GII.3 and GII.4 strains dominated (67%) in both populations.
[Show abstract][Hide abstract] ABSTRACT: We studied the transmission of norovirus infection in households in Quininde, Ecuador. Among household contacts of norovirus positive children with diarrhea, norovirus negative children with diarrhea, and asymptomatic controls, infection attack rates (iARs) were 33%, 8%, and 18%, respectively (N= 45, 36, 83). iARs were higher when index children had a higher viral load.
[Show abstract][Hide abstract] ABSTRACT: During the last decade, substantial declines in overall childhood mortality from diarrhea have been documented among Chinese children, but the last detailed assessment of rotavirus-specific mortality in China was conducted in 2002. To provide policy makers with up-to-date information, we examined rotavirus-related mortality in children >5 years of age in China during 2003-2012.
We obtained mortality rates for children <5 years of age from the Chinese Health Statistic Yearbook; these figures were multiplied by the proportion of deaths in this age group attributable to diarrhea from the Chinese Maternal and Child Mortality Surveillance (MCMS) to obtain estimates of diarrhea deaths in children <5 years of age. To estimate rotavirus deaths, diarrhea death estimates were multiplied by the detection rate of rotavirus in children hospitalized with diarrhea from the Viral Diarrhea Surveillance System (VDSS) in China and from peer-reviewed literature.
From 2003 to 2012, a total of 127,539 deaths from diarrhea were reported among Chinese children <5 years of age, of which an estimated 53,559 (42%) had illness attributable to rotavirus. Comparing 2003 to 2012, the annual number of deaths from rotavirus diarrhea decreased by 74% (from 10,531 to 2,791, respectively) and the mortality rate fell 74% (from 0.66 to 0.17 deaths per 1,000 live births, respectively). Ninety-three percent of all rotavirus deaths occurred in rural areas, where mortality rates (0.33 deaths per 1,000 live births in 2012) were 11 times greater than in urban areas (0.03 deaths per 1,000 live births in 2012).
Rotavirus diarrhea mortality has substantially declined in the past decade in Chinese children. The vast majority of rotavirus deaths occurred in rural areas. There is potential value in using rotavirus vaccine interventions in rural areas to further reduce mortality from this disease.
[Show abstract][Hide abstract] ABSTRACT: 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.
MMWR. Morbidity and mortality weekly report 04/2015; 64(13):337-42.