scholarly journals The pitfalls of inferring virus–virus interactions from co-detection prevalence data: application to influenza and SARS-CoV-2

2022 ◽  
Vol 289 (1966) ◽  
Author(s):  
Matthieu Domenech de Cellès ◽  
Elizabeth Goult ◽  
Jean-Sebastien Casalegno ◽  
Sarah C. Kramer

There is growing experimental evidence that many respiratory viruses—including influenza and SARS-CoV-2—can interact, such that their epidemiological dynamics may not be independent. To assess these interactions, standard statistical tests of independence suggest that the prevalence ratio—defined as the ratio of co-infection prevalence to the product of single-infection prevalences—should equal unity for non-interacting pathogens. As a result, earlier epidemiological studies aimed to estimate the prevalence ratio from co-detection prevalence data, under the assumption that deviations from unity implied interaction. To examine the validity of this assumption, we designed a simulation study that built on a broadly applicable epidemiological model of co-circulation of two emerging or seasonal respiratory viruses. By focusing on the pair influenza–SARS-CoV-2, we first demonstrate that the prevalence ratio systematically underestimates the strength of interaction, and can even misclassify antagonistic or synergistic interactions that persist after clearance of infection. In a global sensitivity analysis, we further identify properties of viral infection—such as a high reproduction number or a short infectious period—that blur the interaction inferred from the prevalence ratio. Altogether, our results suggest that ecological or epidemiological studies based on co-detection prevalence data provide a poor guide to assess interactions among respiratory viruses.

2021 ◽  
Author(s):  
Matthieu Domenech de Cellès ◽  
Elizabeth Goult ◽  
Jean-Sébastien Casalegno ◽  
Sarah C Kramer

There is growing experimental evidence that many respiratory viruses—including influenza and SARS-CoV-2—can interact, such that their epidemiological dynamics may not be independent. To assess these interactions, standard statistical tests of independence suggest that the prevalence ratio—defined as the ratio of co-infection prevalence to the product of single-infection prevalences—should equal unity for non-interacting pathogens. As a result, earlier epidemiological studies aimed to estimate the prevalence ratio from co-detection prevalence data, under the assumption that deviations from unity implied interaction. To examine the validity of this assumption, we designed a simulation study that built on a broadly applicable epidemiological model of co-circulation of two respiratory viruses causing seasonal epidemics. By focusing on the pair influenza–SARS-CoV-2, we first demonstrate that the prevalence ratio systematically under-estimates the strength of interaction, and can even misclassify antagonistic or synergistic interactions that persist after clearance of infection. In a global sensitivity analysis, we further identify properties of viral infection—such as a high reproduction number or a short infectious period—that blur the interaction inferred from the prevalence ratio. Altogether, our results suggest that epidemiological studies based on co-detection prevalence data provide a poor guide to assess interactions among respiratory viruses.


2021 ◽  
Vol 149 ◽  
Author(s):  
Leeberk Raja Inbaraj ◽  
Sindhulina Chandrasingh ◽  
Nalini Arun Kumar ◽  
Jothi Suchitra ◽  
Abi Manesh

Abstract Varicella infection during pregnancy has serious and/or difficult implications and in some cases lethal outcome. Though epidemiological studies in developing countries reveal that a significant proportion of patients may remain susceptible during pregnancy, such an estimate of susceptible women is not known in India. We designed this study to study the prevalence and factors associated with susceptibility to varicella among rural and urban pregnant women in South India. We prospectively recruited 430 pregnant women and analysed their serum varicella IgG antibodies as surrogates for protection. We estimated seroprevalence, the validity of self-reported history of chickenpox and factors associated with varicella susceptibility. We found 23 (95% CI 19.1–27.3) of women were susceptible. Nearly a quarter (22.2%) of the susceptible women had a history of exposure to chickenpox anytime in the past or during the current pregnancy. Self-reported history of varicella had a positive predictive value of 82.4%. Negative history of chickenpox (adjusted prevalence ratio (PR) 1.85, 95% CI 1.15–3.0) and receiving antenatal care from a rural secondary hospital (adjusted PR 4.08, 95% CI 2.1–7.65) were significantly associated with susceptibility. We conclude that high varicella susceptibility rates during pregnancy were noted and self-reported history of varicella may not be a reliable surrogate for protection.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lize Hermans ◽  
Stephan Van den Broucke ◽  
Lydia Gisle ◽  
Stefaan Demarest ◽  
Rana Charafeddine

Abstract Background The importance of health literacy in dealing with the COVID-19 epidemic has been emphasized but scarcely addressed empirically. In this study, the association of health literacy with mental health, compliance with COVID-19 preventive measures and health prospects was assessed in a Belgian context. Methods Data were extracted from the third of a series of cross-sectional online COVID-related surveys (n = 32,794). Data collection took place for 1 week starting the 28th of May 2020. People residing in Belgium and aged 18 years or older could participate. Data were collected on sociodemographic background, health literacy, multimorbidity, mental health (depression, anxiety, sleeping disorder, vitality), knowledge about COVID-19, compliance with COVID-19 measures (hygiene, physical distance, covering mouth and nose on public transport and in places where physical distance cannot be respected), and health prospects (risk for health when returning to normal life and possibility of infection). Prevalence Ratio (PR) of poor mental health, non-compliance with the measures and health prospects in relation to health literacy were calculated using Poisson regressions. Results People showing sufficient health literacy were less likely to suffer from anxiety disorders (PR = 0.47, 95% CI = [0.42–0.53]), depression (PR = 0.46, 95% CI = [0.40–0.52]) and sleeping disorders (PR = 0.85, 95% CI = [0.82–0.87]), and more likely to have optimal vitality (PR = 2.41, 95% CI = [2.05–2.84]) than people with low health literacy. They were less at risk of not complying with the COVID-19 measures (PR between 0.60 and 0.83) except one (covering mouth and nose in places where physical distance cannot be respected). Finally, they were less likely to perceive returning to normal life as threatening (PR = 0.70, 95% CI = [0.65–0.77]) and to consider themselves at risk of an infection with COVID-19 (PR = 0.75, 95% CI = [0.67–0.84]). The associations remained significant after controlling for COVID-19 knowledge and multimorbidity. Conclusions These results suggest that health literacy is a crucial factor in managing the COVID-19 epidemic and offer a perspective for future studies that target health literacy in the context of virus outbreaks.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Simo Kitanovski ◽  
Gibran Horemheb-Rubio ◽  
Ortwin Adams ◽  
Barbara Gärtner ◽  
Thomas Lengauer ◽  
...  

Abstract Background Non-pharmaceutical measures to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be carefully tuned as they can impose a heavy social and economic burden. To quantify and possibly tune the efficacy of these anti-SARS-CoV-2 measures, we have devised indicators based on the abundant historic and current prevalence data from other respiratory viruses. Methods We obtained incidence data of 17 respiratory viruses from hospitalized patients and outpatients collected by 37 clinics and laboratories between 2010-2020 in Germany. With a probabilistic model for Bayes inference we quantified prevalence changes of the different viruses between months in the pre-pandemic period 2010-2019 and the corresponding months in 2020, the year of the pandemic with noninvasive measures of various degrees of stringency. Results We discovered remarkable reductions δ in rhinovirus (RV) prevalence by about 25% (95% highest density interval (HDI) [−0.35,−0.15]) in the months after the measures against SARS-CoV-2 were introduced in Germany. In the months after the measures began to ease, RV prevalence increased to low pre-pandemic levels, e.g. in August 2020 δ=−0.14 (95% HDI [−0.28,0.12]). Conclusions RV prevalence is negatively correlated with the stringency of anti-SARS-CoV-2 measures with only a short time delay. This result suggests that RV prevalence could possibly be an indicator for the efficiency for these measures. As RV is ubiquitous at higher prevalence than SARS-CoV-2 or other emerging respiratory viruses, it could reflect the efficacy of noninvasive measures better than such emerging viruses themselves with their unevenly spreading clusters.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Tiotrefis G Fernandes ◽  
Isabela M Bensenor ◽  
Paulo A Lotufo

There is a lack of epidemiological studies addressing cerebrovascular diseases in remote places as the Amazon river basin. We aimed to calculate the stroke prevalence rates among "ribeirinhos", rural inhabitants who living in riverbanks fishing and extracting fruit and nuts, in the rainforest comparing to townsmen in the same municipality. Methods: From May to October 2011, 6216 residents aged over 35 years in the of Coari, a municipality that is coverage by the Family Health Program with of 76 000 inhabitants, 35% of them are "ribeirinhos”. We trained all community health workers to carry out a door-to-door application of the “Stroke Symptom Questionnaire” for people over 35 years-old. This tool was applied first for the family for stroke screening and further for the index stroke case, including questions about six key functional impairment. It was previously translated to Portuguese and validated by a neurologist. Results: From a total of of 4897 respondents of urban area and 1028 "ribeirinhos", we calculated crude prevalence of stroke of 6.3% (95% CI; 5.0-7.7) among the "ribeirinhos" and of 3.7% (95% CI; 3.3-4.1) among townsmen. This difference was maintained after sex-age-adjustment. The female:male prevalence ratio was 1.37 (95% CI; 1.02-1.85) in urban area and the rural area of 0.93 (95% CI; 0.57-1.52). Among stroke suffers, the "ribeirinhos" were those with less access to medical care (32.1% vs. 52.5%, p=0.01) and a lower proportion of stroke survivors requiring help with least 1 activity of daily living (16.9% vs. 39.3%, p=0.001) in comparison to townsmen. Conclusion: To our knowledge it was the first study that provided a population-based stroke survey in the Amazon rainforest revealing a higher stroke prevalence among "ribeirinhos" compared to townsmen of the same municipality.


2020 ◽  
Vol 8 ◽  
Author(s):  
Cristina Galli ◽  
Laura Pellegrinelli ◽  
Gabriele Del Castillo ◽  
Giovanni Forni ◽  
Cecilia Eugenia Gandolfi ◽  
...  

This study aimed at assessing the validity of self-collected (self-sampled) oropharyngeal (OP) swabs among healthcare workers compared to those collected by trained sentinel general practitioners (GP-sampled) from individuals with influenza-like illness (ILI), to be implemented in epidemiological studies and/or surveillance programs of viral pathogens involved in community respiratory infections. In our study, OP swabs were collected from adults (>18 years) with ILI during the 2018–2019 influenza season. Two groups of samples were considered: group 1−131 self-sampled OP swabs collected by healthcare workers after being trained on the sampling procedure; group 2−131 GP-sampled OP swabs collected from outpatients by sentinel GPs operating within the Italian Influenza Surveillance Network. To assess swabbing quality, following RNA extraction, each sample was tested for the presence of the human ribonuclease P gene (RNP) by in-house real-time reverse transcriptase–polymerase chain reaction (RT-PCR). Samples with a cycle threshold (Ct) <35 were considered adequate for further virological analysis. Influenza viruses (IVs), respiratory syncytial virus (RSV), and rhinovirus (RV) genomes were detected by in-house real-time RT-PCR. All samples were positive to RNP detection with Ct <35. The mean Ct value was similar in the two groups (group 1 vs. group 2: 25.93 ± 2.22 vs. 25.46 ± 2.40; p = 0.10). IVs, RSV, and RV positivity rates were 26.7 vs. 52.7% (p < 0.01), 7.6 vs. 9.9% (p = 0.52), and 21.4 vs. 19.9% (p = 0.76), respectively. Self-sampled OP swabs resulted as valid as GP-sampled OP swabs for molecular detection of respiratory viruses. Self-swabbing can thus be a worthwhile strategy for sample collection to implement molecular surveillance of respiratory pathogens and carry out epidemiological studies, easily reaching a larger population size.


2020 ◽  
Vol 64 (2) ◽  
pp. 29-37
Author(s):  
A. N. Eleazar ◽  
M. I. Takeet ◽  
A. O. Sonibare ◽  
F. O. Olufemi ◽  
E. B. Otesile

AbstractPorcine circovirus type 2 (PCV2) associated diseases are a group of emerging devastating pig diseases worldwide. Due to a dearth of information on the virus in Nigeria, this study was carried out on 12 farms in Abeokuta Ogun State, Nigeria. Key production problems were identified through a questionnaire survey and direct field observations. The prevalence of the PCV2 was determined by the Polymerase Chain Reaction (PCR); 207 sera of pigs were obtained from the farms, DNAs extracted and amplified by the PCR. Based on gel results, the prevalence of PCV2 types were recorded and the effects of age, sex and geographic area determined. The observed production problems (and the percentage of farms suffering from such problems) were: runting (91.7 %), high piglet mortality (83.3 %), late term abortion (50 %), stillbirth (50 %) and anoestrous (41.7 %). The overall prevalence of 8.7 % of the PCV2 viral DNA was obtained. A single infection of PCV2b and PCV2a accounted for a prevalence of 5.3 % and 2.4 %, respectively, while a concurrent infection of both was found in only 1 % of the pigs. The prevalence of PCV2 was not significantly (P > 0.05) influenced by age or sex; with the rates in adults, growers and piglets being 9.9 %, 8.1 % and 8.1 %, respectively, while in males and females, the rates were 9.4 % and 9.0 %, respectively. The prevalence of PCV2 in high-density areas (13.2 %) was significantly (P < 0.05) higher than in low-density areas (4.0 %). It was concluded that PCV2a and PCV2b were present in pigs in Abeokuta, Nigeria and PCV2b was more prevalent. It was recommended that large-scale epidemiological studies covering all geographical regions be carried out with sequencing and phylogenetic analysis to characterize the PCV2 genotypes present in Nigeria.


2021 ◽  
Vol 9 ◽  
Author(s):  
Yan Mardian ◽  
Adhella Menur Naysilla ◽  
Dewi Lokida ◽  
Helmia Farida ◽  
Abu Tholib Aman ◽  
...  

Determining the causative pathogen(s) of community-acquired pneumonia (CAP) in children remains a challenge despite advances in diagnostic methods. Currently available guidelines generally recommend empiric antimicrobial therapy when the specific etiology is unknown. However, shifts in epidemiology, emergence of new pathogens, and increasing antimicrobial resistance underscore the importance of identifying causative pathogen(s). Although viral CAP among children is increasingly recognized, distinguishing viral from bacterial etiologies remains difficult. Obtaining high quality samples from infected lung tissue is typically the limiting factor. Additionally, interpretation of results from routinely collected specimens (blood, sputum, and nasopharyngeal swabs) is complicated by bacterial colonization and prolonged shedding of incidental respiratory viruses. Using current literature on assessment of CAP causes in children, we developed an approach for identifying the most likely causative pathogen(s) using blood and sputum culture, polymerase chain reaction (PCR), and paired serology. Our proposed rules do not rely on carriage prevalence data from controls. We herein share our perspective in order to help clinicians and researchers classify and manage childhood pneumonia.


2021 ◽  
Author(s):  
Sang Min Nam ◽  
Thomas A Peterson ◽  
Kyoung Yul Seo ◽  
Hyun Wook Han ◽  
Jee In Kang

BACKGROUND In epidemiological studies, finding the best subset of factors is challenging when the number of explanatory variables is large. OBJECTIVE Our study had two aims. First, we aimed to identify essential depression-associated factors using the extreme gradient boosting (XGBoost) machine learning algorithm from big survey data (the Korea National Health and Nutrition Examination Survey, 2012-2016). Second, we aimed to achieve a comprehensive understanding of multifactorial features in depression using network analysis. METHODS An XGBoost model was trained and tested to classify “current depression” and “no lifetime depression” for a data set of 120 variables for 12,596 cases. The optimal XGBoost hyperparameters were set by an automated machine learning tool (TPOT), and a high-performance sparse model was obtained by feature selection using the feature importance value of XGBoost. We performed statistical tests on the model and nonmodel factors using survey-weighted multiple logistic regression and drew a correlation network among factors. We also adopted statistical tests for the confounder or interaction effect of selected risk factors when it was suspected on the network. RESULTS The XGBoost-derived depression model consisted of 18 factors with an area under the weighted receiver operating characteristic curve of 0.86. Two nonmodel factors could be found using the model factors, and the factors were classified into direct (<i>P</i>&lt;.05) and indirect (<i>P</i>≥.05), according to the statistical significance of the association with depression. Perceived stress and asthma were the most remarkable risk factors, and urine specific gravity was a novel protective factor. The depression-factor network showed clusters of socioeconomic status and quality of life factors and suggested that educational level and sex might be predisposing factors. Indirect factors (eg, diabetes, hypercholesterolemia, and smoking) were involved in confounding or interaction effects of direct factors. Triglyceride level was a confounder of hypercholesterolemia and diabetes, smoking had a significant risk in females, and weight gain was associated with depression involving diabetes. CONCLUSIONS XGBoost and network analysis were useful to discover depression-related factors and their relationships and can be applied to epidemiological studies using big survey data.


2021 ◽  
Vol 15 (10) ◽  
pp. e0009877
Author(s):  
Sara Halili ◽  
Jessica R. Grant ◽  
Nils Pilotte ◽  
Catherine A. Gordon ◽  
Steven A. Williams

Background Elimination and control of Schistosoma japonicum, the most virulent of the schistosomiasis-causing blood flukes, requires the development of sensitive and specific diagnostic tools capable of providing an accurate measurement of the infection prevalence in endemic areas. Typically, detection of S. japonicum has occurred using the Kato-Katz technique, but this methodology, which requires skilled microscopists, has been shown to radically underestimate levels of infection. With the ever-improving capabilities of next-generation sequencing and bioinformatic analysis tools, identification of satellite sequences and other highly repetitive genomic elements for use as real-time PCR diagnostic targets is becoming increasingly common. Assays developed using these targets have the ability to improve the sensitivity and specificity of results for epidemiological studies that can in turn be used to inform mass drug administration and programmatic decision making. Methodology/Principal findings Utilizing Tandem Repeat Analyzer (TAREAN) and RepeatExplorer2, a cluster-based analysis of the S. japonicum genome was performed and a tandemly arranged genomic repeat, which we named SjTR1 (Schistosoma japonicum Tandem Repeat 1), was selected as the target for a real-time PCR diagnostic assay. Based on these analyses, a primer/probe set was designed and the assay was optimized. The resulting real-time PCR test was shown to reliably detect as little as 200 ag of S. japonicum genomic DNA and as little as 1 egg per gram of human stool. Based on these results, the index assay reported in this manuscript is more sensitive than previously published real-time PCR assays for the detection of S. japonicum. Conclusions/Significance The extremely sensitive and specific diagnostic assay described in this manuscript will facilitate the accurate detection of S. japonicum, particularly in regions with low levels of endemicity. This assay will be useful in providing data to inform programmatic decision makers, aiding disease control and elimination efforts.


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