Sensitivity and Specificity of Immunocytochemical Assay for Detection of Dengue Virus 3 Infection in Mosquito

Background: Virological surveillance provides an early warning sign for the risk of transmission in an area. Laboratory tests for dengue virus infection on mosquitoes include isolation of the virus, Polymerase Chain Reaction (PCR) and Direct Fluorescent-Antibody (DFA) requires a high level of technical skill, expensive equipment, and time-consuming. A method based on immunocytochemical (IC) using monoclonal antibody DSSE10 has several advantages. This study aimed to evaluate sensitivity and specificity IC assay compared with Reverse Transcription-Polymerase Chain Reaction (RT-PCR) as gold standard to detect Dengue Virus (DENV)-3 infections in mosquito Aedes aegypti.Methods: An experimental study was conducted in laboratory of Medical Parasitology, Faculty of Medicine, Universitas Gadjah Mada (UGM) in May 2009 until October 2010. A total of 22 artificially-infected adult Ae. aegypti mosquitoes of DENV 3 were used as infectious samples and 35 non-infected adult Ae. aegypti mosquitoes were used as normal ones. The IC Streptavidin Biotin Peroxidase Complex (SBPC) assay using monoclonal antibody DSSE10 was applied in mosquito head squash to detect Dengue virus antigen. RT-PCR as a gold standard was applied in mosquito thorax.Results: The kappa value showed a good agreement between two observers (kappa value 0.63). IC could detect dengue virus antigen as sensitive as RT-PCR (sensitivity 100%). But IC was less specific than RT-PCR (specificity 91%) because some false positive results were found in this method.Conclusion: The IC method has a high sensitivity and high specificity compared with RT-PCR. This IC method may be useful for virological surveillance of dengue infected Aedes mosquitoes. (Health Science Indones 2011;2:87-91)

Sensitivity and specificity of point-of-care circulating Cathodic antigen test before and after praziquantel treatment in diagnosing Schistosoma mansoni infection in adult population co-infected with human immunodeficiency virus-1, North-Western Tanzania.

BACKGROUND: The effect of Human Immunodeficiency Virus-1 (HIV-1) on CD4+ Th2 cells is hypothesized to affect parasitological diagnosis of Schistosoma mansoni using Kato Katz technique. Thus, the use of more sensitive technique such as Point-of-Care Circulating Cathodic Antigen (POC-CCA) test is recommended. However, the sensitivity of this diagnostic test in diagnosing S.mansoni infection and the usefulness of it in monitoring efficacy of praziquantel drug in presence of HIV-1 co-infection remains inconclusive. The Primary objective of the present study was to assess accuracy of the POC-CCA test in diagnosing S.mansoni infection before and after praziquantel treatment in adult population co-infected with HIV -1. METHODS: A prospective longitudinal study was conducted among individuals aged 15-55 years at Igalagala village, north-western Tanzania. At baseline and 4 weeks after treatment, a single stool and urine samples were collected from each participants. Kato Katz (KK) technique and Point-of-Care Circulating Cathodic Antigen tests were used for diagnosis of Schistosoma mansoni. RESULTS: At baseline, based on KK and POC-CCA, the prevalence of S.mansoni was 57.8% (95%CI: 52.9-62.4) and 87.5% (95%CI: 83.9-90.4). Based on KK technique and POC-CCA test, 3.6% and 5.7% of the study participants were co-infected with S.mansoni and HIV-1. At baseline, in the general population, the sensitivities of POC-CCA test using KK technique and combine gold standard were 96.3%(95%CI: 93.1-98.3) and 97.6%(95%CI:95.5-98.9) respectively. In the HIV-1 seropositive group, at baseline, the sensitivities of POC-CCA test using KK technique and combined gold standards, were 93.3%(95%CI:68.1-99.8) and 96%(95CI%:79.6-99.9). Four weeks after treatment, in general population, the sensitivities of POC-CCA test using KK technique and combined gold standards were 47.8%(95%CI:26.8-69.4) and 84.4%(95%CI:74.4-91.7). In the HIV-1 seropositive group, using KK technique, the sensitivity was 100% (95%CI:2.5-100). CONCLUSION: The sensitivity of POC-CCA in diagnosing S.mansoni infection was higher than KK technique in adult individuals likely to have low infection intensity and co-infected with HIV-1. However, its sensitivity decreases following praziquantel treatment but remained higher than Kato Katz technique. If the goal of the post-treatment is to identify uncured individuals, then POC-CCA test offers the best choice

Sensitivity and specificity of diagnostic tests for Lassa fever: a systematic review.

BACKGROUND: Lassa fever virus has been enlisted as a priority pathogen of epidemic potential by the World Health organization Research and Development (WHO R & D) Blueprint. Diagnostics play a crucial role in epidemic preparedness. This systematic review was conducted to determine the sensitivity and specificity of Lassa fever diagnostic tests for humans. METHODS: We searched OVID Medline, OVID Embase, Scopus and Web of Science for laboratory based and field studies that reported the performance of diagnostic tests for Lassa fever in humans from 1 January 1990 to 25 January 2019. Two reviewers independently screened all the studies and included only studies that involved the evaluation of a Lassa fever diagnostic test and provided data on the sensitivity and specificity. The quality of the studies was assessed using the QUADAS-2 criteria. Data on the study location, study design, type of sample, index test, reference tests and diagnostic performance were extracted from the studies. RESULTS: Out of a total of 1947 records identified, 1245 non-duplicate citations were obtained. Twenty-six (26) full-text articles examined which identified 08 studies meeting pre-defined criteria. Only one study was a field evaluation study. The sensitivity and specificity of the point of care (RDT) against the Nikisins qPCR were 91.2%(95% CI:75.2-97.7) and 86%(95% CI: 71.4-94.2) at temperatures 18-30 °C, while the sensitivity and specificity of the single IgM ELISA assay against standard RT-PCR were 31.1%(95%CI: 25.6-37) and 95.7%(95%CI:92.8-97.7). The sensitivity of the combined ELISA Antigen/IgM assay(against virus isolation), the recombinant IgM/IgG ELISA(against standard RT-PCR), and the IgM/IgG immunoblot(against IFA) were 88%(95%CI:77-95), 25.9%(95%CI:20.8-31.6), and 90.7%(95%CI:84.13-97.27) respectively. The specificity of the combined ELISA Antigen/IgM assay(against virus isolation), the recombinant IgM/IgG ELISA(against standard RT-PCR), and the IgM/IgG immunoblot(against IFA) were 90%(95%CI:88-91), 100%(95%CI:98.2-100), and 96.3%(95%CI:92.2-100) respectively. CONCLUSION: Lassa fever has assays for antigenaemia, IgM, IgG and PCR detection. The RDT reportedly performed well but more data are needed from other countries and at temperatures above 30 °C. Most combined immunoassays perform better than the single IgM. Multiplex and pan-Lassa assays are needed. More well conducted field studies are needed. TRIAL REGISTRATION: Prospero registration number: CRD42018091585

Estimating sensitivity and specificity of diagnostic tests using latent class models that account for conditional dependence between tests: a simulation study

BACKGROUND: Latent class models are increasingly used to estimate the sensitivity and specificity of diagnostic tests in the absence of a gold standard, and are commonly fitted using Bayesian methods. These models allow us to account for 'conditional dependence' between two or more diagnostic tests, meaning that the results from tests are correlated even after conditioning on the person's true disease status. The challenge is that it is not always clear to researchers whether conditional dependence exists between tests and whether it exists in all or just some latent classes. Despite the increasingly widespread use of latent class models to estimate diagnostic test accuracy, the impact of the conditional dependence structure chosen on the estimates of sensitivity and specificity remains poorly investigated. METHODS: A simulation study and a reanalysis of a published case study are used to highlight the impact of the conditional dependence structure chosen on estimates of sensitivity and specificity. We describe and implement three latent class random-effect models with differing conditional dependence structures, as well as a conditional independence model and a model that assumes perfect test accuracy. We assess the bias and coverage of each model in estimating sensitivity and specificity across different data generating mechanisms. RESULTS: The findings highlight that assuming conditional independence between tests within a latent class, where conditional dependence exists, results in biased estimates of sensitivity and specificity and poor coverage. The simulations also reiterate the substantial bias in estimates of sensitivity and specificity when incorrectly assuming a reference test is perfect. The motivating example of tests for Melioidosis highlights these biases in practice with important differences found in estimated test accuracy under different model choices. CONCLUSIONS: We have illustrated that misspecification of the conditional dependence structure leads to biased estimates of sensitivity and specificity when there is a correlation between tests. Due to the minimal loss in precision seen by using a more general model, we recommend accounting for conditional dependence even if researchers are unsure of its presence or it is only expected at minimal levels

Optimal group testing designs for estimating prevalence with uncertain testing errors

We construct optimal designs for group testing experiments where the goal is to estimate the prevalence of a trait by using a test with uncertain sensitivity and specificity. Using optimal design theory for approximate designs, we show that the most efficient design for simultaneously estimating the prevalence, sensitivity and specificity requires three different group sizes with equal frequencies. However, if estimating prevalence as accurately as possible is the only focus, the optimal strategy is to have three group sizes with unequal frequencies. On the basis of a chlamydia study in the U.S.A., we compare performances of competing designs and provide insights into how the unknown sensitivity and specificity of the test affect the performance of the prevalence estimator. We demonstrate that the locally D- and Ds-optimal designs proposed have high efficiencies even when the prespecified values of the parameters are moderately misspecified

Evaluation of updated sepsis scoring systems and systemic inflammatory response syndrome criteria and their association with sepsis in equine neonates

BackgroundThe original equine sepsis score provided a method of identifying foals with sepsis. New variables associated with sepsis have been evaluated, but the sepsis score has not been updated.ObjectivesTo evaluate the sensitivity and specificity of 2 updated sepsis scores and the systemic inflammatory response syndrome (SIRS) criteria in regard to detecting sepsis in foals.AnimalsTwo-hundred and seventy-three ill foals and 25 healthy control foals.MethodsHistorical, physical examination, and clinicopathologic findings were used to calculate the original sepsis score and 2 updated sepsis scores. SIRS criteria were also evaluated. Sepsis scores and positive SIRS scores were statistically compared to foals with sepsis.ResultsOne-hundred and twenty-six foals were septic and 147 sick-nonseptic. The original and updated sepsis scores were significantly higher in septic foals as compared to sick-nonseptic and healthy foals. The sensitivity and specificity of the updated sepsis scores to predict sepsis were not significantly better than those of the original sepsis score. One-hundred and twenty-seven of 273 (46.5%) foals met the original SIRS criteria and 88/273 (32%) foals met the equine neonatal SIRS criteria. The original SIRS criteria had similar sensitivity and specificity for predicting sepsis as did the 3 sepsis scores in our study.Conclusions and clinical importanceThe updated sepsis scores did not provide improved ability in predicting sepsis. Fulfilling the original SIRS criteria provided similar sensitivity and specificity in predicting sepsis as the modified sepsis score and might serve as a diagnostic aid in identifying foals at risk for sepsis

Comparison of reproducibility, accuracy, sensitivity, and specificity of miRNA quantification platforms

Given the increasing interest in their use as disease biomarkers, the establishment of reproducible, accurate, sensitive, and specific platforms for microRNA (miRNA) quantification in biofluids is of high priority. We compare four platforms for these characteristics: small RNA sequencing (RNA-seq), FirePlex, EdgeSeq, and nCounter. For a pool of synthetic miRNAs, coefficients of variation for technical replicates are lower for EdgeSeq (6.9%) and RNA-seq (8.2%) than for FirePlex (22.4%); nCounter replicates are not performed. Receiver operating characteristic analysis for distinguishing present versus absent miRNAs shows small RNA-seq (area under curve 0.99) is superior to EdgeSeq (0.97), nCounter (0.94), and FirePlex (0.81). Expected differences in expression of placenta-associated miRNAs in plasma from pregnant and non-pregnant women are observed with RNA-seq and EdgeSeq, but not FirePlex or nCounter. These results indicate that differences in performance among miRNA profiling platforms impact ability to detect biological differences among samples and thus their relative utility for research and clinical use