Seasonal diarrhea appeared to be more pronounced in older children in 2015 than in previous years.
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Additionally, a progressive delay in the rotavirus season was observed after vaccine introduction, from approximately May–July in 2010–2012 to August–October in 2013–2015 ( Figure 2). As expected, both the seasonality and the reduction after vaccine introduction were most striking in younger children. Testing during the seasonal peaks in 20 for all children enrolled in the vaccine effectiveness study confirmed that rotavirus was the primary etiology of the seasonal peaks ( Figure 1 inset).
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Diarrhea admissions showed a striking seasonal pattern, with a clear reduction after vaccine introduction ( Figure 1). We recorded discharge diagnoses from 11258 hospital admissions of children <5 years of age from 1 January 2010 to 31 December 2015, of which 2971 (26.4%) were for diarrhea. The 95% confidence intervals (CIs) were derived from the 2.5th and 97.5th quantiles of the AF distribution, and the point estimate of the AF was calculated using the original model coefficients.
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To estimate the variance for the model-based attribution, the odds ratios were estimated 1000 times using random perturbations of the model coefficients in accordance with their sampling variance-covariance these coefficients were drawn equally from each of the 7 GEMS sites. We then calculated AFs by summing pathogen attributions across each of j cases, that is, ∑ 1 j AF i, where AF i = 1 / j × ( 1 – 1 / OR i ), and OR i is the quantity-specific odds ratio derived from the regression model. Specifically, using qPCR data from 5304 cases of moderate-to-severe acute diarrhea and age-, sex-, and village-matched controls, we fit a multivariable conditional logistic regression model to describe the association between pathogen quantity and diarrhea while adjusting for the presence of other pathogens. First, we used models from the qPCR reanalysis of the GEMS study to derive quantity-specific odds ratios. To estimate pathogen-specific burdens of diarrhea, we calculated an adjusted attributable fraction (AF) for each pathogen. Vaccine effectiveness was calculated as (1 – adjusted odds ratio) × 100%. To examine the impact of vaccine introduction on diarrhea admissions to HLH, we obtained data on all admissions for children 5%. The monovalent rotavirus vaccine was introduced to the national immunization program on 1 January 2013 for administration at 6 and 10 weeks of age. The national immunization program is administered to this population through reproductive child health system clinics coordinated by HLH, which reach approximately 8000 new children per year. The study was performed at Haydom Lutheran Hospital (HLH), a 450-bed referral hospital situated in a rural area in northern Tanzania, with a catchment area of approximately 2 million people. We performed a study of the impact and effectiveness of vaccine introduction on all-cause and rotavirus diarrhea admissions to a rural African hospital, as well as a nested etiologic study using qPCR. The relative importance of specific enteropathogens after rotavirus vaccine has been introduced is not known. In particular, they have increased burden estimates for some pathogens, including Shigella, heat-stable enterotoxin-producing Escherichia coli (ST-ETEC), and adenovirus 40/41, but not others, including rotavirus and Cryptosporidium.
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īecause most prior etiologic studies have used a diverse group of diagnostic modalities, the advent of quantitative polymerase chain reaction (qPCR) diagnostics for enteropathogens has helped reveal an unbiased picture of the etiology of diarrhea in children in low-resource settings. Despite clinical trials and real-world effectiveness studies demonstrating reduced performance of these vaccines in sub-Saharan Africa, a profound impact of vaccine introduction has been observed, with the majority of the impact seen by the third year after introduction. The ongoing worldwide introduction of rotavirus vaccines is expected to have a substantial impact on the burden of rotavirus diarrhea. Rotavirus remains the leading etiology of severe and fatal diarrhea worldwide, responsible for approximately 40% of diarrheal deaths. Rotavirus vaccine, effectiveness, diarrhea, children, PCR