scholarly journals Uses of pathogen detection data to estimate vaccine direct effects in case–control studies

2020 ◽  
Vol 17 (169) ◽  
pp. 20200161
Author(s):  
Joseph A. Lewnard

The fact that many pathogens can be carried or shed without causing symptoms complicates the interpretation of microbiological data when diagnosing certain infectious disease syndromes. Diagnostic criteria that attribute symptoms to a pathogen which is detectable, whether it is or is not the aetiological agent of disease, may lead to outcome misclassification in epidemiological studies. Case–control studies are commonly undertaken to estimate vaccine effectiveness (VE) and present an opportunity to compare pathogen detection among individuals with and without clinically relevant symptoms. Considering this study context, we present a mathematical framework yielding simple estimators for the direct effects of vaccination on various aspects of host susceptibility. These include protection against acquisition of the pathogen of interest and protection against progression of this pathogen to disease following acquisition. We assess the impact of test sensitivity on these estimators and extend our framework to identify a ‘vaccine probe’ estimator for pathogen-specific aetiological fractions. We also derive biases affecting VE estimates under the test-negative design, a special case enrolling only symptomatic persons. Our results provide strategies for estimating pathogen-specific VE in the absence of a diagnostic gold standard. These approaches can inform the design and analysis of studies addressing numerous pathogens and vaccines.

2020 ◽  
Author(s):  
Joseph A. Lewnard

ABSTRACTThe diagnosis of infectious disease syndromes such as fever, diarrhea, and pneumonia is complicated by the potential for shedding or carriage of putatively etiologic pathogens among individuals experiencing symptoms due to other causes. Symptomatic individuals among whom a pathogen is detected, but whose symptoms are caused by other factors, may be misclassified by diagnostic criteria based on pathogen detection. Case-control studies are commonly undertaken to estimate vaccine effectiveness, and present an opportunity to compare pathogen detection among individuals with and without clinically-relevant symptoms. Considering this study context, we derive simple estimators for the direct effects of vaccination on various aspects of host susceptibility. These include protection against acquisition of the pathogen of interest, and protection against progression of this pathogen to disease following acquisition. We assess the impact of test sensitivity on these estimators, and extend our framework to identify a “vaccine probe” estimator for pathogen-specific etiologic fractions. We also derive biases affecting vaccine effectiveness estimates under the test-negative design, an alternative approach using similar data. Our results provide strategies for estimation of pathogen-specific vaccine effectiveness in the absence a diagnostic gold standard. These approaches can inform the design and analysis of studies addressing numerous pathogens and vaccines.


2000 ◽  
Vol 125 (3) ◽  
pp. 713-718 ◽  
Author(s):  
P. R. HUNTER

Cryptosporidiosis is the most common cause of outbreaks of disease linked to mains water supply in the United Kingdom and the second commonest in the United States. Recent evidence has suggested that prior population immunity may have an impact on the epidemiology of waterborne outbreaks and in particular prior immunity may reduce the power of case-control studies for demonstrating association between disease and water consumption behaviour. However, the degree of impact of prior immunity on the power of epidemiological studies is not yet clear. This paper reports the results of some simple mathematical models of outbreaks of waterborne disease in populations with varying levels of immunity due to prior water and non-water exposure. The basic outbreak model was run on a spreadsheet. To determine the impact of prior immunity on case-control studies, further analysis was done using a Monte Carlo method to simulate sampling from cases and controls. It was found that moderate degrees of prior immunity due to water associated disease could markedly reduce the relative risk of water consumption on illness in waterborne outbreaks. In turn this would reduce the power of case-control studies. In addition, this model was used to demonstrate the impact of case misclassification and recall bias on case-control studies. Again it was found that within the model, the results of case-control studies could be significantly affected by both these sources of error. Anyone conducting epidemiological investigations of potentially waterborne outbreaks of disease should be aware of the epidemiological problems. Mistakes from case-control studies will be minimized if the outbreak team pays considerable attention to the descriptive phase of the investigation and if case-control studies are conducted as soon as possible after an outbreak is detected.


2015 ◽  
Vol 114 (9) ◽  
pp. 1341-1359 ◽  
Author(s):  
Míriam Rodríguez-Monforte ◽  
Gemma Flores-Mateo ◽  
Emília Sánchez

AbstractEpidemiological studies show that diet is linked to the risk of developing CVD. The objective of this meta-analysis was to estimate the association between empirically derived dietary patterns and CVD. PubMed was searched for observational studies of data-driven dietary patterns that reported outcomes of cardiovascular events. The association between dietary patterns and CVD was estimated using a random-effects meta-analysis with 95 % CI. Totally, twenty-two observational studies met the inclusion criteria. The pooled relative risk (RR) for CVD, CHD and stroke in a comparison of the highest to the lowest category of prudent/healthy dietary patterns in cohort studies was 0·69 (95 % CI 0·60, 0·78; I2=0 %), 0·83 (95 % CI 0·75, 0·92; I2=44·6 %) and 0·86 (95 % CI 0·74, 1·01; I2=59·5 %), respectively. The pooled RR of CHD in a case–control comparison of the highest to the lowest category of prudent/healthy dietary patterns was 0·71 (95 % CI 0·63, 0·80; I2=0 %). The pooled RR for CVD, CHD and stroke in a comparison of the highest to the lowest category of western dietary patterns in cohort studies was 1·14 (95 % CI 0·92, 1·42; I2=56·9 %), 1·03 (95 % CI 0·90, 1·17; I2=59·4 %) and 1·05 (95 % CI 0·91, 1·22; I2=27·6 %), respectively; in case–control studies, there was evidence of increased CHD risk. Our results support the evidence of the prudent/healthy pattern as a protective factor for CVD.


2019 ◽  
Vol 76 (Suppl 1) ◽  
pp. A21.1-A21
Author(s):  
Susan Peters ◽  
Jerome Lavoue ◽  
Marissa Baker ◽  
Hans Kromhout

Exposure assessment quality is a fundamental consideration in the design and evaluation of observational studies. High quality exposure assessment is particularly relevant for outcomes with long latency, such as cancer, where detailed information on past exposures are often missing and must therefore be estimated.For the IARC Monograph on welding, the exposure group provided an overview of assessment methods used in the key epidemiological studies. Strengths and weaknesses of each study were assessed, along with their potential effects on interpretation of risk estimates.For the association between lung cancer and welding fume exposure, 9 cohort and 10 case-control studies were reviewed. For ocular melanoma and ultraviolet radiation (UVR) from welding, 7 case-control studies were reviewed. Quality criteria were: full occupational histories, and standardized, blinded and quantitative exposure assessment. Additional criteria for lung cancer: specifically assessing welding fumes and using information on welding tasks. For ocular melanoma: assessing artificial and solar radiation separately, taking into account eye burns, eye protection and welding type.Exposure assessment of welding fumes by applying a ‘welding-exposure matrix’ (n=2) or welding-specific questionnaires (n=3) were considered highest quality, followed by case-by-case expert assessment (n=5) or general job-exposure matrices (JEMs, n=4). Job title alone was considered less informative (n=5). For exposure to UVR, JEMs were most informative (n=2), followed by self-reported eye burns and self-reported exposure from specific welding types (n=2), although caution is advised regarding recall bias. Assessing welding fume exposure or ever exposure to welding arcs as proxy for UVR was considered less informative. For both exposures, ever versus never welder, or assessments based on data collected from proxies, were considered least informative.The overall evaluation was that there is sufficient evidence in humans for the carcinogenicity of welding fumes and ultraviolet radiation from welding.


Biostatistics ◽  
2016 ◽  
Vol 17 (3) ◽  
pp. 499-522 ◽  
Author(s):  
Ying Huang

Abstract Two-phase sampling design, where biomarkers are subsampled from a phase-one cohort sample representative of the target population, has become the gold standard in biomarker evaluation. Many two-phase case–control studies involve biased sampling of cases and/or controls in the second phase. For example, controls are often frequency-matched to cases with respect to other covariates. Ignoring biased sampling of cases and/or controls can lead to biased inference regarding biomarkers' classification accuracy. Considering the problems of estimating and comparing the area under the receiver operating characteristics curve (AUC) for a binary disease outcome, the impact of biased sampling of cases and/or controls on inference and the strategy to efficiently account for the sampling scheme have not been well studied. In this project, we investigate the inverse-probability-weighted method to adjust for biased sampling in estimating and comparing AUC. Asymptotic properties of the estimator and its inference procedure are developed for both Bernoulli sampling and finite-population stratified sampling. In simulation studies, the weighted estimators provide valid inference for estimation and hypothesis testing, while the standard empirical estimators can generate invalid inference. We demonstrate the use of the analytical variance formula for optimizing sampling schemes in biomarker study design and the application of the proposed AUC estimators to examples in HIV vaccine research and prostate cancer research.


2019 ◽  
Author(s):  
Chukwuemeka Onwuchekwa ◽  
Edem Bassey ◽  
Victor Williams ◽  
Emmanuel Oga

AbstractBackgroundThe impact of pneumococcal conjugate vaccine introduction in reducing the incidence of childhood pneumonia has not been well documented in sub-Saharan Africa. Many studies evaluating vaccine impact have used invasive pneumococcal disease or pneumococcal pneumonia as an outcome.ObjectiveTo estimate the impact of routine administration of 10-valent and 13-valent PCV on the incidence of pneumonia in children under five years of age in sub-Saharan Africa.Data sourcesA systematic review was conducted between 16 and 31 July 2019. The review was registered on PROSPERO with registration number CRD42019142369. The literature search was conducted in indexed databases including Medline and Embase, grey literature databases and online libraries of two universities. Manual search of the references of included studies was performed to identify additional relevant studies. The search strategy combined pneumococcal conjugate vaccine, pneumonia and child as search concepts.Study selectionStudies investigating the impact of 10- or13-valent PCV on childhood pneumonia in a sub-Saharan African country were eligible for inclusion. Case-control, cohort, pre-post and time-series study designs were eligible for inclusion. Exclusion criteria were use of 7- or 9-valent PCV, systematic review studies, clinical trials and record publication prior to 2009.Data extractionIndependent data extraction was conducted. Key variables include year study conducted, type of study design, type of PCV used and year of introduction, reported PCV coverage, outcome measure evaluated and the effect measure.Data synthesisEight records were included in the final analysis, 6 records were pre-post or time-series studies, 1 was a case-control study and 1 report combined pre-post and case-control studies. Vaccine impact measured as percentage reduction in risk (%RR) of clinical pneumonia was mostly small and non-significant. The risk reduction was more significant and consistent on radiological and pneumococcal pneumonia. Vaccine effectiveness reported in case-control studies was mostly non-significant.ConclusionEvidence of the positive impact of routine infant pneumococcal vaccination on pneumonia in sub-Saharan Africa is weak. There is a need for more research in this area to evaluate the influence of pathogen or serotype replacement in pneumonia after PCV introduction. Ongoing surveillance is also required to establish the long term trend in pneumonia epidemiology after PCV introduction.


2020 ◽  
Vol 3 (2) ◽  
pp. 25-30
Author(s):  
Renata Zunec

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is reported to vary across different populations in the prevalence of infection, in the death rate of patients, in the severity of symptoms and in the drug response of patients. Among host genetic factors that can influence all these attributes human leukocyte antigen (HLA) genetic system stands out as one of the leading candidates. Case-control studies, large-scale population-based studies, as well as experimental bioinformatics studies are of utmost importance to confirm HLA susceptibility spectrum of COVID-19. This review presents the results of the first case-control and epidemiological studies performed in several populations, early after the pandemic breakout. The results are pointing to several susceptible and protective HLA alleles and haplotypes associations with COVID-19, some of which might be of interest for the future studies in Croatia, due to its common presence in the population. However, further multiple investigations from around the world, as numerous as possible, are needed to confirm or deteriorate these preliminary results.


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