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Transmission lines are most prone to faults in the transmission system, so high-precision fault diagnosis is very important for quick troubleshooting. There are some problems in current intelligent fault diagnosis research methods, such as difficulty in extracting fault features accurately, low fault recognition accuracy and poor fault tolerance. In order to solve these problems, this paper proposes an intelligent fault diagnosis method for high voltage direct current transmission lines (HVDC) based on Gramian angular difference field (GADF) domain and improved convolutional neural network (VGG16). This method first performs variational modal decomposition (VMD) on the original fault voltage signal, and then uses the correlation coefficient method to select the appropriate intrinsic mode function (IMF) component, and converts it into a two-dimensional image using the Gramian Angular Difference Field(GADF). Finally, the improved VGG16 network is used to extract and classify fault features adaptively to realize fault diagnosis. In order to improve the performance of the VGG16 fault diagnosis model, batch normalization, dense connection and global average pooling techniques are introduced. The comparative experimental results show that the model proposed in this paper can further identify fault features and has a high fault diagnosis accuracy. In addition, the method is not affected by fault type, transitional resistance and fault distance, has good anti-interference ability, strong fault tolerance, and has great potential in practical applications. [ABSTRACT FROM AUTHOR]

To accurately locate faulty components in analog circuits, an analog circuit fault diagnosis method based on Tunable Q-factor Wavelet Transform(TQWT) and Convolutional Neural Network (CNN) is proposed in this paper. Firstly, the Grey Wolf algorithm (GWO) is used to improve the TQWT. The improved TQWT can adaptively determine the parameters Q-factor and decomposition level. Secondly, The signal is decomposed, and single-branch reconstruction is conducted with TQWT to facilitate adequate feature extraction. Thirdly, to capture the time-frequency features in the signal, a CNN-LSTM network is built by combining CNN and LSTM for feature extraction. Finally, CNN, which introduces Fully Convolutional Network (FCN) layers and a Batch Normalization layer, is used to fault diagnosis. The method was comprehensively evaluated with a second-order bandpass filter circuit. The experimental results illustrate that the proposed fault diagnosis method can achieve excellent fault diagnosis accuracy, and the average accuracy is 98.96%. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the leading causes of cancer-related deaths worldwide. To reduce the mortality rate, early detection and proper treatment should be ensured. Computer-aided diagnosis methods analyze different modalities of medical images to increase diagnostic precision. In this paper, we propose an ensemble model, called the Mitscherlich function-based Ensemble Network (MENet), which combines the prediction probabilities obtained from three deep learning models, namely Xception, InceptionResNetV2, and MobileNetV2, to improve the accuracy of a lung cancer prediction model. The ensemble approach is based on the Mitscherlich function, which produces a fuzzy rank to combine the outputs of the said base classifiers. The proposed method is trained and tested on the two publicly available lung cancer datasets, namely Iraq-Oncology Teaching Hospital/National Center for Cancer Diseases (IQ-OTH/NCCD) and LIDC-IDRI, both of these are computed tomography (CT) scan datasets. The obtained results in terms of some standard metrics show that the proposed method performs better than state-of-the-art methods. The codes for the proposed work are available at https://github.com/SuryaMajumder/MENet. [ABSTRACT FROM AUTHOR]

Background: Like many infectious diseases, there is no practical gold standard for diagnosing clinical visceral leishmaniasis (VL). Latent class modeling has been proposed to estimate a latent gold standard for identifying disease. These proposed models for VL have leveraged information from diagnostic tests with dichotomous serological and PCR assays, but have not employed continuous diagnostic test information. Methods/Principal findings: In this paper, we employ Bayesian latent class models to improve the identification of canine visceral leishmaniasis using the dichotomous PCR assay and the Dual Path Platform (DPP) serology test. The DPP test has historically been used as a dichotomous assay, but can also yield numerical information via the DPP reader. Using data collected from a cohort of hunting dogs across the United States, which were identified as having either negative or symptomatic disease, we evaluate the impact of including numerical DPP reader information as a proxy for immune response. We find that inclusion of DPP reader information allows us to illustrate changes in immune response as a function of age. Conclusions/Significance: Utilization of continuous DPP reader information can improve the correct discrimination between individuals that are negative for disease and those with clinical VL. These models provide a promising avenue for diagnostic testing in contexts with multiple, imperfect diagnostic tests. Specifically, they can easily be applied to human visceral leishmaniasis when diagnostic test results are available. Also, appropriate diagnosis of canine visceral leishmaniasis has important consequences for curtailing spread of disease to humans. Author summary: Diagnostic tests often aid in diagnosis of infectious diseases, like the neglected tropical disease visceral leishmaniasis (VL). While such tests provide useful information, they are imperfect, so they can produce false positive or false negative results. Moreover, diagnostic tests for VL are often dichotomous, meaning they only provide positive or negative results. The Dual Path Platform (DPP) serology test has been used as a dichotomous assay, but can also yield numerical information via the DPP reader. Although we can only observe diagnostic test results, rather than the true disease status of an individual, we can use a set of statistical methods called latent class models to estimate the true disease status. We can also incorporate the numerical information from the DPP reader in latent class models. In this paper, we evaluate the impact of including this numerical information in a Bayesian latent class model to provide additional information about immune response. We compare this to a more traditional latent class model, which only incorporates dichotomized assay information. We fit these models to data collected from a cohort of hunting dogs across the United States. Incorporating DPP reader information allows us to illustrate changes in immune response for different ages. [ABSTRACT FROM AUTHOR]

Given fault false alarm and fault control failure caused by the decrease of fault identification accuracy and fault delay of Switched Reluctance Motor (SRM) power converter in complex working conditions, a method based on the Interactive Multi-Model (IMM) algorithm was proposed in this paper. Besides, the corresponding equivalent circuit models were established according to the different working states of the SRM power converter. The Kalman filter was employed to estimate the state of the model, and the fault detection and location were realized depending on the residual signal. Additionally, a transition probability correction function of the IMM was constructed using the difference of the n-th order to suppress the influence of external disturbance on the fault diagnosis accuracy. Concurrently, a model jump threshold was introduced to reduce delay when the matched model was switched, so as to realize the rapid separation of faults and effective fault control. The simulation and experiment results demonstrate that the IMM algorithm based on low delay anti-interference can effectively reduce the influence of complex working conditions, improve the anti-interference ability of SRM power converter fault diagnosis, and identify fault information accurately and quickly. [ABSTRACT FROM AUTHOR]

Over 71 million people are infected with hepatitis C virus (HCV) worldwide, and approximately 400,000 global deaths result from complications of untreated chronic HCV. Pan-genomic direct-acting antivirals (DAAs) have recently become widely available and feature high cure rates in less than 12 weeks of treatment. The rollout of DAAs is reliant on diagnostic tests for HCV RNA to identify eligible patients with viremic HCV infections. Current PCR-based HCV RNA assays are restricted to well-resourced central laboratories, and there remains a prevailing clinical need for expanded access to decentralized HCV RNA testing to provide rapid chronic HCV diagnosis and linkage to DAAs in outpatient clinics. This paper reports a rapid, highly accurate, and minimally instrumented assay for HCV RNA detection using reverse transcription recombinase polymerase amplification (RT-RPA). The assay detects all HCV genotypes with a limit of detection of 25 copies per reaction for genotype 1, the most prevalent in the United States and worldwide. The clinical sensitivity and specificity of the RT-RPA assay were both 100% when evaluated using 78 diverse clinical serum specimens. The accuracy, short runtime, and low heating demands of RT-RPA may enable implementation in a point-of-care HCV test to expand global access to effective treatment via rapid chronic HCV diagnosis. [ABSTRACT FROM AUTHOR]

The electrical control system of rapier weaving machines is susceptible to various disturbances during operation and is prone to failures. This will seriously affect the production and a fault diagnosis system is needed to reduce this effect. However, the existing popular fault diagnosis systems and methods need to be improved due to the limitations of rapier weaving machine process and electrical characteristics. Based on this, this paper presents an in-depth study of rapier loom fault diagnosis system and proposes a rapier loom fault diagnosis method combining edge expert system and cloud-based rough set and Bayesian network. By analyzing the process and fault characteristics of rapier loom, the electrical faults of rapier loom are classified into common faults and other faults according to the frequency of occurrence. An expert system is built in the field for edge computing based on knowledge fault diagnosis experience to diagnose common loom faults and reduce the computing pressure in the cloud. Collect loom fault data in the cloud, train loom fault diagnosis algorithms to diagnose other faults, and handle other faults diagnosed by the expert system. The effectiveness of loom fault diagnosis is verified by on-site operation and remote monitoring of the loom human-machine interaction system. Technical examples are provided for the research of loom fault diagnosis system. [ABSTRACT FROM AUTHOR]

Previous studies have shown that fetal abdominal obesity (FAO) was already observed at the time of gestational diabetes mellitus (GDM) diagnosis and persisted until delivery despite management in older and/or obese women. In this study, we investigated whether fetuses of women with milder hyperglycemia than GDM have accelerated abdominal growth, leading to adverse pregnancy outcomes. We retrospectively reviewed the medical records of 7,569 singleton pregnant women who were universally screened using a 50-g glucose challenge test (GCT) and underwent a 3-h 100-g oral glucose tolerance test (OGTT) if GCT result was ≥140mg/dL. GDM, one value abnormality (OVA), and normal glucose tolerance (NGT, NGT1: GCT negative, NGT2: GCT positive & OGTT negative) were diagnosed using Carpenter-Coustan criteria. With fetal biometry data measured simultaneously with 50-g GCT, relative fetal abdominal overgrowth was investigated by assessing the fetal abdominal overgrowth ratios (FAORs) of the ultrasonographically estimated gestational age (GA) of abdominal circumference(AC) per actual GA by the last menstruation period(LMP), biparietal diameter(BPD) or femur length(FL), respectively. FAO was defined as FAOR ≥90th percentile The FAORs of GA-AC/GA-LMP and GA-AC/GA-BPD were significantly higher in OVA subjects compared to NGT subjects but not in NGT2 subjects. Although the frequency of FAO in OVA (12.1%) was between that of NGT (9.6%) and GDM (18.3%) without statistically significant difference, the prevalence of large for gestational age at birth and primary cesarean delivery rates were significantly higher in OVA (9.8% and 29.7%) than in NGT (5.1% and 21.5%, p<0.05). Particularly, among OVA subjects with FAO, the prevalence (33.3% and 66.7%) was significantly higher than in those without FAO (9.7% and 24.2%, p<0.05). The degree of fetal abdominal growth acceleration in OVA subjects was intermediate between that of NGT and GDM subjects. OVA subjects with FAO at the time of GDM diagnosis were strongly associated with adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Intuitively, combining multiple sources of evidence should lead to more accurate decisions than considering single sources of evidence individually. In practice, however, the proper computation may be difficult, or may require additional data that are inaccessible. Here, based on the concept of conditional independence, we consider expressions that can serve either as recipes for integrating evidence based on limited data, or as statistical benchmarks for characterizing evidence integration processes. Consider three events, A, B, and C. We find that, if A and B are conditionally independent with respect to C, then the probability that C occurs given that both A and B are known, P(C|A, B), can be easily calculated without the need to measure the full three-way dependency between A, B, and C. This simplified approach can be used in two general ways: to generate predictions by combining multiple (conditionally independent) sources of evidence, or to test whether separate sources of evidence are functionally independent of each other. These applications are demonstrated with four computer-simulated examples, which include detecting a disease based on repeated diagnostic testing, inferring biological age based on multiple biomarkers of aging, discriminating two spatial locations based on multiple cue stimuli (multisensory integration), and examining how behavioral performance in a visual search task depends on selection histories. Besides providing a sound prescription for predicting outcomes, this methodology may be useful for analyzing experimental data of many types. [ABSTRACT FROM AUTHOR]

Diagnostic tests play a crucial role in establishing the presence of a specific disease in an individual. Receiver Operating Characteristic (ROC) curve analyses are essential tools that provide performance metrics for diagnostic tests. Accurate determination of the cutoff point in ROC curve analyses is the most critical aspect of the process. A variety of methods have been developed to find the optimal cutoffs. Although the R programming language provides a variety of package programs for conducting ROC curve analysis and determining the appropriate cutoffs, it typically needs coding skills and a substantial investment of time. Specifically, the necessity for data preprocessing and analysis can present a significant challenge, especially for individuals without coding experience. We have developed the CERA (ChatGPT-Enhanced ROC Analysis) tool, a user-friendly ROC curve analysis web tool using the shiny interface for faster and more effective analyses to solve this problem. CERA is not only user-friendly, but it also interacts with ChatGPT, which interprets the outputs. This allows for an interpreted report generated by R-Markdown to be presented to the user, enhancing the accessibility and understanding of the analysis results. [ABSTRACT FROM AUTHOR]

Background: The parasitic disease loiasis is associated with significant morbidity and mortality. Individuals with hyper-microfilaremia (greater than 20,000 microfilariae per mL of blood) may suffer from serious treatment-related or spontaneous adverse events. Diagnosing loiasis remains complex and primarily relies on direct parasite detection. In this study, we analyzed the performance of various diagnostic tests and the influence of parasitological and clinical factors on test outcomes in samples from individuals living in an endemic region. Methods: Data and samples were collected from rural Gabon. Loiasis was defined as either detectable microfilaremia, or a positive history of eyeworm as assessed by the RAPLOA questionnaire. Diagnostic testing included a quantitative PCR (qPCR) for detection of Loa loa DNA in blood samples, an in-house crude L. loa antigen IgG ELISA, and a rapid test for antibodies against the Ll-SXP-1 antigen (RDT). Sensitivity and specificity were determined for each test and factors potentially influencing outcomes were evaluated in an exploratory analysis. Results: ELISA, RDT and qPCR results were available for 99.8%, 78.5%, and 100% of the 1,232 participants, respectively. The ELISA and RDT had only modest diagnostic accuracy. qPCR was specific for L. loa microfilaremia and Cycle threshold values correlated with microfilarial density. Anti-L. loa IgG levels were highest in occult loiasis, and antibody levels correlated inversely with L. loa microfilarial density as did RDT line intensities. Only 84.6% and 16.7% of hyper-microfilaremic individuals tested positive by ELISA (11/13) and RDT (2/12), respectively. Conclusion: None of the tests demonstrated high sensitivity and specificity for loiasis. Indirect diagnostic assays were characterized by low specificity. Additionally, hyper-microfilaremic individuals often tested negative by RDT and ELISA, indicating that these tests are not suitable for individual case management in endemic populations. Author summary: Loiasis remains highly neglected despite recent evidence of significant loiasis-associated mortality and morbidity. This complex disease is difficult to diagnose, especially in endemic populations. Here, we assessed the performance of several diagnostic assays. In addition, an exploratory analysis of factors associated with the outcomes of indirect, serology-based tests was performed. The presented data show only moderate performance of indirect tests. Furthermore, amicrofilaremic loiasis was associated with higher quantitative serological test results. None of the indirect tests detected all cases of microfilaremic loiasis, including individuals with high and hyper-microfilaremia. As a negative test may not reliably exclude hyper-microfilaremic infections, these serological tests should not be used as screening tests in individual case management. This is important, as hyper-microfilaremic individuals are at increased risk of developing serious adverse events after treatment with drugs such as ivermectin or diethylcarbamazine. [ABSTRACT FROM AUTHOR]

Ocular toxoplasmosis (OT) is caused by protozoan T. gondii. Ophthalmological examination is considered the gold standard for OT diagnosis, and laboratory tests are used for diagnostic confirmation. However, these tests can present different results, which change depending on their basis, on sample type and on patients' clinical alteration. Thus, the aim of the present study is to assess immunodiagnostic and molecular techniques applied in blood, serum and tear fluid to diagnose T. gondii infection in patients seen at an Ophthalmology Clinic. In total, 160 patients were included in the study, 40 of them had OT with active lesions (G1); 40 had OT with healed lesions (G2), 40 had non-toxoplasmic uveitis (G3) and 40 had no ocular alterations (G4). Serum samples were subjected to Immunoenzymatic Assay (ELISA) and to Indirect Immunofluorescence Reaction (IFAT) to search for anti-T. gondii IgM and IgG. Tear fluid samples were analyzed through ELISA for IgA research. All blood and tear fluid samples were subjected to conventional polymerase chain reaction (cPCR) and in a Nested PCR model for T. gondii DNA amplification with targets B1, GRA7 and REP 529. IgG and IgM anti-T. gondii was detected in serum samples from 106 and 15 patients, respectively, when combining ELISA and IFAT results. Anti-T.gondii IgA antibodies were detected in 9.2% of the tear material. Nested PCR with GRA7 target showed higher positivity in blood samples (24.4%); Nested PCR with B1 target showed a higher frequency of positivity in tears (15%). Biological samples of patients with active lesions showed the highest positivity frequencies in all immunodiagnostic assays, as well as in most PCR models. The present results highlighted the need of associating techniques with different fundamentals to confirm OT diagnosis. Furthermore, further tear fluid analyses should be performed to validate this biological material as lesser invasive alternative for the more accurate OT diagnosis. [ABSTRACT FROM AUTHOR]

Background and objectives: Ischemic strokes in young adults have been a significant concern due to various potential etiologies and had substantial clinical and public health impacts. We aimed to study the diagnostic tests, etiologies, and functional outcomes of acute ischemic stroke (AIS) and transient ischemic attack (TIA) in young adult patients. Methods: The data were retrieved from the Chiang Mai University Hospital Stroke Registry between January 2018 and December 2021. Consecutive AIS or TIA patients were included if they were 18–50 years and had no stroke mimics. Study outcomes were proportions of positive diagnostic tests, and 90-day modified Rankin Scale (mRS). Results: Of 244 enrolled patients, 59.0% (n = 144) were male, and 38.1% (n = 93) were aged 18–40, classified as the younger age group. There was a high incidence of diabetes (24.5%) and dyslipidemia (54.3%) among patients aged 41–50, associated with small-vessel occlusion and large-artery atherosclerosis stroke classification in this age group. Patients aged 18–40 years had more other determined etiologies (39.8%), with hypercoagulability (8.2%), arterial dissection (7.8%), and cardiac sources (6.6%) being the first three causes, which were associated with higher anticoagulant treatment. The cerebrovascular study, cardiac evaluation using echocardiography, and antiphospholipid syndrome testing were commonly performed, of which computed tomography angiography provided a high proportion of positive results (80.3%). 76.3% of young adult patients had excellent functional outcomes (mRS 0–1) with a median mRS of 0 (interquartile range 0–1) at 90-day follow-up. Conclusions: Stroke of other determined etiology remained the common cause of stroke in young adults, and most affected individuals had excellent clinical outcomes. Blood tests for arterial hypercoagulability and noninvasive vascular and cardiac evaluations are encouraged in selected patients to determine the stroke etiology and guide for appropriate preventive strategies. [ABSTRACT FROM AUTHOR]

Background: Tata MD CHECK SARS-CoV-2 kit 1.0, a CRISPR based reverse transcription PCR (TMC-CRISPR) test was approved by Indian Council of Medical Research (ICMR) for COVID-19 diagnosis in India. To determine the potential for rapid roll-out of this test, we conducted performance characteristic and an operational feasibility assessment (OFA) at a tertiary care setting. Intervention: The study was conducted at an ICMR approved COVID-19 RT-PCR laboratory of King Edward Memorial (KEM) hospital, Mumbai, India. The TMC-CRISPR test was evaluated against the gold-standard RT-PCR test using the same RNA sample extracted from fresh and frozen clinical specimens collected from COVID-19 suspects for routine diagnosis. TMC-CRISPR results were determined manually and using the Tata MD CHECK application. An independent agency conducted interviews of relevant laboratory staff and supervisors for OFA. Results: Overall, 2,332 (fresh: 2,121, frozen: 211) clinical specimens were analysed of which, 140 (6%) were detected positive for COVID-19 by TMC-CRISPR compared to 261 (11%) by RT-PCR. Overall sensitivity and specificity of CRISPR was 44% (95% CI: 38.1%-50.1%) and 99% (95% CI: 98.2%-99.1%) respectively when compared to RT-PCR. Discordance between TMC-CRISPR and RT-PCR results increased with increasing Ct values and corresponding decreasing viral load (range: <20% to >85%). In the OFA, all participants indicated no additional requirements of training to set up RT PCR. However, extra post-PCR steps such as setting up the CRISPR reaction and handling of detection strips were time consuming and required special training. No significant difference was observed between manual and mobile app-based readings. However, issues such as erroneous results, difficulty in interpretation of faint bands, internet connectivity, data safety and security were highlighted as challenges with the app-based readings. Conclusion: The evaluated version-Tata MD CHECK SARS-CoV-2 kit 1.0 of TMC-CRISPR test cannot be considered as an alternative to the RT-PCR. There is a definite scope for improvement in this assay. [ABSTRACT FROM AUTHOR]

Though the traditional fault diagnosis method of T-connected transmission lines can identify the faults inside and outside the area, it can not identify the specific branches. To improve the accuracy and reliability of fault diagnosis of T-connection transmission lines, a new method is proposed to identify specific faulty branches of T-connection transmission lines based on multi-scale traveling wave reactive power and random forest. Based on the S-transform, the mean and sum ratios of the corresponding short-time series traveling wave reactive powers of each two traveling wave protection units at multiple frequencies are calculated respectively to form the fault feature vector sample set of the T-connection transmission line. A random forest fault branch identification model is established, and it is trained and tested by the fault feature sample set of T-connection transmission line to identify the fault branch. The simulation results show that the proposed algorithm can identify the branch where the fault is located inside and outside the protection zone of T-connection transmission line quickly and accurately under various working conditions. This method also shows good performance to identify faults even under the situation of CT saturation, noise influence and data loss. [ABSTRACT FROM AUTHOR]

In this review, we assessed the diagnostic efficiency of artificial intelligence (AI) models in detecting temporomandibular joint osteoarthritis (TMJOA) using radiographic imaging data. Based upon the PRISMA guidelines, a systematic review of studies published between January 2010 and January 2023 was conducted using PubMed, Web of Science, Scopus, and Embase. Articles on the accuracy of AI to detect TMJOA or degenerative changes by radiographic imaging were selected. The characteristics and diagnostic information of each article were extracted. The quality of studies was assessed by the QUADAS-2 tool. Pooled data for sensitivity, specificity, and summary receiver operating characteristic curve (SROC) were calculated. Of 513 records identified through a database search, six met the inclusion criteria and were collected. The pooled sensitivity, specificity, and area under the curve (AUC) were 80%, 90%, and 92%, respectively. Substantial heterogeneity between AI models mainly arose from imaging modality, ethnicity, sex, techniques of AI, and sample size. This article confirmed AI models have enormous potential for diagnosing TMJOA automatically through radiographic imaging. Therefore, AI models appear to have enormous potential to diagnose TMJOA automatically using radiographic images. However, further studies are needed to evaluate AI more thoroughly. [ABSTRACT FROM AUTHOR]

Background: In Myanmar, 1.3 million people have been exposed to hepatitis C (HCV). However, public sector access to viral load (VL) testing for HCV diagnosis remains limited; ten near-point-of-care (POC) devices are available nationally. Myanmar's National Health Laboratory (NHL) has surplus capacity on centralized molecular testing platforms used for HIV diagnostics, presenting an opportunity for integrating HCV testing to expand overall testing capacity. This pilot assessed the operational feasibility and acceptability of HCV/HIV integrated testing implemented with a comprehensive package of supportive interventions. Methods: HCV VL samples were collected prospectively from consenting participants at five treatment clinics and tested at Myanmar's NHL (October 2019-February 2020) on the Abbott m2000. To optimize integration, laboratory human resources were bolstered, staff trainings were offered, and existing laboratory equipment was serviced/repaired as needed. Diagnostics data during the intervention period were compared against HIV diagnostics data in the seven months prior. We conducted three time and motion analyses at the laboratory and semi-structured interviews with laboratory staff to assess time needs and program acceptability. Results: 715 HCV samples were processed during the intervention period with an average test processing time of 18 days (IQR: 8–28). Despite adding HCV testing, average monthly test volumes were 2,331 for HIV VL and 232 for early infant diagnosis (EID), comparable to the pre-intervention period. Processing times were 7 days for HIV VL and 17 days for EID, also comparable to the pre-intervention period. HCV test error rate was 4.3%. Platforms utilization increased from 18.4% to 24.6%. All staff interviewed were supportive of HCV and HIV diagnostics integration; suggestions were made for broader implementation and expansion. Conclusions: With a package of supportive interventions, integration of HCV and HIV diagnostics on a centralized platform was operationally feasible, did not adversely impact HIV testing, and was acceptable to laboratory staff. In Myanmar, integrated HCV VL diagnostic testing on centralized platforms may be an important addition to existing near-POC testing in expanding national testing capacity for HCV elimination. [ABSTRACT FROM AUTHOR]

The live attenuated tetravalent CYD-TDV vaccine (Dengvaxia) is effective but has scarcely been used due to safety concerns among seronegative recipients. Rapid diagnostic tests (RDTs) which can accurately determine individual dengue serostatus are needed for use in pre-vaccination screening. This study aimed to determine the performance of existing RDTs (which have been designed to detect levels of immunoglobulin G, IgG, associated with acute post-primary dengue) when repurposed for detection of previous dengue infection (where concentrations of IgG are typically lower). A convenience sample of four-hundred-and-six participants (including 217 children) were recruited in the community. Whole blood was collected by phlebotomy and tested using Bioline Dengue IgG/IgM (Abbott) and Standard Q Dengue IgM/IgG (SD Biosensor) RDTs in the field. Serum samples from the same individuals were also tested at National Health Laboratory. The Panbio indirect IgG ELISA was used as a reference test. Reference testing determined that 370 (91.1%) participants were dengue IgG seropositive. Both assays were highly specific (100.0%) but had low sensitivity (Bioline = 21.1% and Standard Q = 4.6%) when used in the field. Sensitivity was improved when RDTs were used under laboratory conditions, and when assays were allowed to run beyond manufacturer recommendations (and read at a delayed time-point), but specificity was reduced. Efforts to develop RDTs with high sensitivity and specificity for prior dengue infection which can be operationalised for pre-vaccination screening are ongoing. Performance of forthcoming candidate assays should be tested under field conditions with blood samples, as well as in the laboratory. Author summary: Dengvaxia is effective but has scarcely been used due to safety concerns among seronegative recipients. Rapid diagnostic tests (RDTs) which can accurately determine individual dengue serostatus are therefore needed for pre-vaccination screening. This study evaluated two commercially available RDTs during a community seroprevalence survey in Timor-Leste. Field conditions were intended to replicate a pre-vaccination screening setting. Both assays were specific but had low sensitivity, and performance was found to be inferior when compared to previous studies which were conducted in laboratories using stored serum samples. Future candidate assays must be evaluated under field conditions before they can safely be used in pre-vaccination screening. [ABSTRACT FROM AUTHOR]

Objective: To determine the diagnostic validity of the enzyme-linked immunosorbent assay (ELISA) and Rapid Diagnostic Tests (RDT) among individuals with suspected chronic Chagas Disease (CD). Methodology: A search was made for studies with ELISA and RDT assays validity estimates as eligibility criteria, published between 2010 and 2020 on PubMed, Web of Science, Scopus, and LILACS. This way, we extracted the data and assessed the risk of bias and applicability of the studies using the QUADAS-2 tool. The bivariate random effects model was also used to estimate the overall sensitivity and specificity through forest-plots, ROC space, and we visually assessed the heterogeneity between studies. Meta-regressions were made using subgroup analysis. We used Deeks' test to assess the risk of publication bias. Results: 43 studies were included; 27 assessed ELISA tests; 14 assessed RDTs; and 2 assessed ELISA and RDTs, against different reference standards. 51.2 % of them used a non-comparative observational design, and 46.5 % a comparative clinical design ("case-control" type). High risk of bias was detected for patient screening and reference standard. The ELISA tests had a sensitivity of 99% (95% CI: 98–99) and a specificity of 98% (95% CI: 97–99); whereas the Rapid Diagnostic Tests (RDT) had values of 95% (95% CI: 94–97) and 97% (95% CI: 96–98), respectively. Deeks' test showed asymmetry on the ELISA assays. Conclusions: ELISA and RDT tests have high validity for diagnosing chronic Chagas disease. The analysis of these two types of evidence in this systematic review and meta-analysis constitutes an input for their use. The limitations included the difficulty in extracting data due to the lack of information in the articles, and the comparative clinical-type design of some studies. Author summary: Chagas disease (CD), an infection caused by the Trypanosoma cruzi parasite, affects between 8 and 10 million people worldwide. It is considered one of the main problems of public health in Latin America, and the international migration has caused infected subjects to scatter through the rest of the world, making CD a global health problem. Therefore, it is important to diagnose this infection using laboratory tests, which sometimes becomes a problem due to lack of reference tests and the existence of different types of tests with different sensitivity and specificity values, added to the difficulty in detecting the parasite in its chronic phase. This systematic review and meta-analysis determined the diagnostic validity of the enzyme-linked immunosorbent assay (ELISA) and rapid diagnostic tests (RDT) among individuals with suspected chronic CD. It included 43 studies and concluded that both ELISA and RDTs had adequate diagnostic performance. It is necessary to better understand these two types of diagnostic tests to facilitate clinical decision making about the disease and improve access to treatment for the population at risk. [ABSTRACT FROM AUTHOR]

Background and aims: At present, it is difficult and risky to diagnose splenic lesions by conventional needle biopsy using computed tomography (CT) or ultrasound (US). Endoscopic ultrasound (EUS)-guided tissue acquisition is increasingly being used as a new technique to determine the tissue diagnosis of splenic lesions. Therefore, our goal was to determine the efficacy and safety of EUS-guided tissue acquisition for splenic lesions. Methods: We performed a systematic review and meta-analysis to evaluate the pooled sensitivity and specificity of EUS-guided tissue acquisition for the diagnosis of splenic lesions using Metadisc. The Quality Assessment of Diagnostic Accuracy Studies Questionnaire, a quality assessment tool, was used to scrutinize the quality of the studies. Results: Six eligible studies between January 2000 and June 2022 were identified, and a total number of 62 patients (aged range from 19 to 84) were enrolled. One patient was excluded because of insufficient specimens. The pooled sensitivity and specificity of included studies were 0.85 [95% confidence interval (CI), 0.73–0.93] and 0.77 (95% CI, 0.46–0.95), respectively. The pooled positive likelihood ratio (LR) was 2.38 (95% CI, 1.24–4.57), the pooled negative LR was 0.31 (95% CI, 0.17–0.55), the pooled diagnostic odds ratio (DOR) was 8.67 (95% CI, 2.80–26.82), the area under the summary receiver operating characteristic (SROC) curve was 0.8100 (Standard Error 0.0813). Conclusion: EUS-guided tissue acquisition is a safe technique with high sensitivity in the diagnosis of splenic lesions. However, because of the small sample sizes, more studies with more cases are needed to further validate these results. [ABSTRACT FROM AUTHOR]

Background: Rapid diagnostics are vital for curving the transmission and control of the COVID-19 pandemic. Although many commercially available antigen-based rapid diagnostic tests (Ag-RDTs) for the detection of SARS-CoV-2 are recommended by the WHO, their diagnostic performance has not yet been assessed in Ethiopia. So far, the vast majority of studies assessing diagnostic accuracies of rapid antigen tests considered RT-PCR as a reference standard, which inevitably leads to bias when RT-PCR is not 100% sensitive and specific. Thus, this study aimed to evaluate the diagnostic performance of Panbio™ jointly with the RT-PCR for the detection of SARS-CoV-2. Methods: A prospective cross-sectional study was done from July to September 2021 in Addis Ababa, Ethiopia, during the third wave of the pandemic involving two health centers and two hospitals. Diagnostic sensitivity and specificity of Panbio™ and RT-PCR were obtained using Bayesian Latent-Class Models (BLCM). Results: 438 COVID-19 presumptive clients were enrolled, 239 (54.6%) were females, of whom 196 (44.7%) had a positive RT-PCR and 158 (36.1%) were Panbio™ positive. The Panbio™ and RT-PCR had a sensitivity (95% CrI) of 99.6 (98.4–100) %, 89.3 (83.2–97.6) % and specificity (95% CrI) of 93.4 (82.3–100) %, and 99.1 (97.5–100) %, respectively. Most of the study participants, 318 (72.6%) exhibited COVID-19 symptoms; the most reported was cough 191 (43.6%). Conclusion: As expected the RT-PCR performed very well with a near-perfect specificity and a high, but not perfect sensitivity. The diagnostic performance of Panbio™ is coherent with the WHO established criteria of having a sensitivity ≥80% for Ag-RDTs. Both tests displayed high diagnostic accuracies in patients with and without symptoms. Hence, we recommend the use of the Panbio™ for both symptomatic and asymptomatic individuals in clinical settings for screening purposes. [ABSTRACT FROM AUTHOR]

Introduction: There is currently no test for pelvic inflammatory disease (PID) that is non-invasive and sufficiently sensitive and specific. Clinicians must therefore diagnose PID clinically, ruling out medical emergencies and conducting pelvic examinations where possible. While guidelines state that clinicians should be prepared to over-diagnose PID, it remains an under-diagnosed condition, with severe reproductive health impacts when left untreated. This research is the first to consider the perspectives of end-users on the development of a diagnostic test for PID. Methods: Semi-structured live video feed online (Zoom) interviews were conducted with 11 clinicians and nine women (aged 18–30 years) in Australia to understand how a diagnostic test might be used, and what characteristics a test would need for it to be acceptable to clinicians and young women. Participants were recruited via researcher and university student networks. Reflexive thematic analysis was used to identify key themes relating to the acceptability and characteristics of a diagnostic test for PID. Results: Seven general practitioners, four clinicians working in sexual health clinics, and nine young women (aged 21–27 years) were interviewed. Clinicians were aged between 31–58 years and were predominantly female. Clinicians recognised that the development of an accurate test to diagnose PID would be valuable to themselves and other clinicians, particularly those who lack experience diagnosing PID, and those working in certain settings, including emergency departments. They discussed how they might use a test to enhance their clinical assessment but highlighted that it would not replace clinical judgement. Clinicians also considered how a test would impact the patient experience and time to treatment, emphasising that it should be minimally invasive and have a quick turnaround time. Young women said a test would be acceptable if endorsed by a trustworthy clinician. Conclusions: PID remains a challenging diagnosis. Development of a minimally invasive and sufficiently accurate diagnostic test would be acceptable to young women and benefit some clinicians, although no test would completely replace an experienced clinician's judgement in making a PID diagnosis. [ABSTRACT FROM AUTHOR]

Background: Rapid Diagnostic Tests (RDTs) have become the cornerstone for the management of malaria in many endemic settings, but their use is constrained for several reasons: (i) persistent malaria antigen (histidine-rich protein 2; HRP2) leading to false positive test results; (ii) hrp2 deletions leading to false negative PfHRP2 results; and (iii) limited sensitivity with a detection threshold of around 100 parasites/μl blood (pLDH- and HRP2-based) leading to false negative tests. Microscopy is still the gold standard for malaria diagnosis, and allows for species determination and quantitation, but requires trained microscopists, maintained microscopes and has detection limit issues. Consequently, there is a pressing need to develop and evaluate more sensitive and accurate diagnostic tests. To address this need we have developed a direct on blood mini PCR-NALFIA test that combines the benefits of molecular biology with low infrastructural requirements and extensive training. Methods: This is a Phase 3 diagnostic evaluation in 5 African countries. Study sites (Sudan, Ethiopia, Burkina, Kenya and Namibia) were selected to ensure wide geographical coverage of Africa and to address various malaria epidemiological contexts ranging from high transmission to near elimination settings with different clinical scenarios and diagnostic challenges. Study participants will be enrolled at the study health facilities after obtaining written informed consent. Diagnostic accuracy will be assessed following the WHO/TDR guidelines for the evaluation of diagnostics and reported according to STARD principles. Due to the lack of a 100% specific and sensitive standard diagnostic test for malaria, the sensitivity and specificity of the new test will be compared to the available diagnostic practices in place at the selected sites and to quantitative PCR as the reference test. Discussion: This phase 3 study is designed to validate the clinical performance and feasibility of implementing a new diagnostic tool for the detection of malaria in real clinical settings. If successful, the proposed technology will improve the diagnosis of malaria. Enrolment started in November 2022 (Kenya) with assessment of long term outcome to be completed by 2023 at all recruitment sites. Trial registration: Pan African Clinical Trial Registry (www.pactr.org) PACTR202202766889963 on 01/02/2022 and ISCRTN (www.isrctn.com/) ISRCTN13334317 on 22/02/2022. [ABSTRACT FROM AUTHOR]

Computerized auscultation of lung sounds is gaining importance today with the availability of lung sounds and its potential in overcoming the limitations of traditional diagnosis methods for respiratory diseases. The publicly available ICBHI respiratory sounds database is severely imbalanced, making it difficult for a deep learning model to generalize and provide reliable results. This work aims to synthesize respiratory sounds of various categories using variants of Variational Autoencoders like Multilayer Perceptron VAE (MLP-VAE), Convolutional VAE (CVAE) Conditional VAE and compare the influence of augmenting the imbalanced dataset on the performance of various lung sound classification models. We evaluated the quality of the synthetic respiratory sounds' quality using metrics such as Fréchet Audio Distance (FAD), Cross-Correlation and Mel Cepstral Distortion. Our results showed that MLP-VAE achieved an average FAD of 12.42 over all classes, whereas Convolutional VAE and Conditional CVAE achieved an average FAD of 11.58 and 11.64 for all classes, respectively. A significant improvement in the classification performance metrics was observed upon augmenting the imbalanced dataset for certain minority classes and marginal improvement for the other classes. Hence, our work shows that deep learning-based lung sound classification models are not only a promising solution over traditional methods but can also achieve a significant performance boost upon augmenting an imbalanced training set. [ABSTRACT FROM AUTHOR]

Background: Chikungunya (CHIKV) is a reemerging arboviral disease and represents a global health threat because of the unprecedented magnitude of its spread. Diagnostics strategies rely heavily on reverse transcriptase-polymerase chain reaction (RT-PCR) and antibody detection by enzyme-linked Immunosorbent assay (ELISA). Rapid diagnostic tests (RDTs) are available and promise to decentralize testing and increase availability at lower healthcare system levels. Objectives: We aim to identify the extent of research on CHIKV RDTs, map the global availability of CHIKV RDTs, and evaluate the accuracy of CHIKV RDTs for the diagnosis of CHIKV. Eligibility criteria: We included studies reporting symptomatic individuals suspected of CHIKV, tested with CHIKV RDTs, against the comparator being a validated laboratory-based RT-PCR or ELISA assay. The primary outcome was the accuracy of the CHIKV RDT when compared with reference assays. Sources of evidence: Medline, EMBASE, and Scopus were searched from inception to 13 October 2021. National regulatory agencies (European Medicines Agency, US Food and Drug Administration, and the Brazilian National Health Surveillance Agency) were also searched for registered CHIKV RDTs. Results: Seventeen studies were included and corresponded to 3,222 samples tested with RDTs between 2005 and 2018. The most development stage of CHIKV RDTs studies was Phase I (7/17 studies) and II (7/17 studies). No studies were in Phase IV. The countries that manufacturer the most CHIKV RDTs were Brazil (n = 17), followed by the United States of America (n = 7), and India (n = 6). Neither at EMA nor FDA-registered products were found. Conversely, the ANVISA has approved 23 CHIKV RDTs. Antibody RDTs (n = 43) predominated and demonstrated sensitivity between 20% and 100%. The sensitivity of the antigen RDTs ranged from 33.3% to 100%. Conclusions: The landscape of CHIKV RDTs is fragmented and needs coordinated efforts to ensure that patients in CHIKV-endemic areas have access to appropriate RDTs. Further research is crucial to determine the impact of such tests on integrated fever case management and prescription practices for acute febrile patients. [ABSTRACT FROM AUTHOR]

Background: Cholera continues to pose a problem for low-resource, fragile and humanitarian contexts. Evidence suggests that 2.86 million cholera cases and 95,000 deaths due to cholera are reported annually. Without quick and effective diagnosis and treatment, case-fatality may be 50%. In line with the priorities of the Global Task Force on Cholera Control, we undertook a systematic review and meta-analysis of diagnostic test accuracy and other test characteristics of current tests for cholera detection in stool and water. Methods: We searched 11 bibliographic and grey literature databases. Data was extracted on test sensitivity, specificity and other product information. Meta-analyses of sensitivity and specificity were conducted for tests reported in three or more studies. Where fewer studies reported a test, estimates were summarised through narrative synthesis. Risk of Bias was assessed using QUADAS-2. Results: Searches identified 6,637 records; 41 studies reporting on 28 tests were included. Twenty-two tests had both sensitivities and specificities reported above 95% by at least one study, but there was, overall, wide variation in reported diagnostic accuracy across studies. For the three tests where meta-analyses were possible the highest sensitivity meta-estimate was found in the Cholera Screen test (98.6%, CI: 94.7%-99.7%) and the highest specificity meta-estimate in the Crystal VC on enriched samples (98.3%, CI: 92.8%-99.6%). There was a general lack of evidence regarding field use of tests, but where presented this indicated trends for lower diagnostic accuracy in field settings, with lesser-trained staff, and without the additional process of sample enrichment. Where reported, mean test turnaround times ranged from over 50% to 130% longer than manufacturer's specification. Most studies had a low to unclear risk of bias. Conclusions: Currently available Rapid Diagnostic Tests can potentially provide high diagnostic and detection capability for cholera. However, stronger evidence is required regarding the conditions required to secure these levels of accuracy in field use, particularly in low-resource settings. Registration: PROSPERO (CRD42016048428). [ABSTRACT FROM AUTHOR]

Background: Reliable and field-applicable diagnosis of schistosome infections in non-human animals is important for surveillance, control, and verification of interruption of human schistosomiasis transmission. This study aimed to summarize uses of available diagnostic techniques through a systematic review and meta-analysis. Methodology and principal findings: We systematically searched the literature and reports comparing two or more diagnostic tests in non-human animals for schistosome infection. Out of 4,909 articles and reports screened, 19 met our inclusion criteria, four of which were considered in the meta-analysis. A total of 14 techniques (parasitologic, immunologic, and molecular) and nine types of non-human animals were involved in the studies. Notably, four studies compared parasitologic tests (miracidium hatching test (MHT), Kato-Katz (KK), the Danish Bilharziasis Laboratory technique (DBL), and formalin-ethyl acetate sedimentation-digestion (FEA-SD)) with quantitative polymerase chain reaction (qPCR), and sensitivity estimates (using qPCR as the reference) were extracted and included in the meta-analyses, showing significant heterogeneity across studies and animal hosts. The pooled estimate of sensitivity was 0.21 (95% confidence interval (CI): 0.03–0.48) with FEA-SD showing highest sensitivity (0.89, 95% CI: 0.65–1.00). Conclusions/Significance: Our findings suggest that the parasitologic technique FEA-SD and the molecular technique qPCR, are the most promising techniques for schistosome diagnosis in non-human animal hosts. Future studies are needed for validation and standardization of the techniques for real-world field applications. Author summary: The diagnosis of schistosome infection in non-human hosts is important for control and elimination of human schistosomiasis. This study aimed to summarize effectiveness of available diagnostic techniques through a systematic review of the literature and reports comparing two or more diagnostic tests in non-human animals. Overall, 4,909 articles and reports were screened. Nineteen articles met our inclusion criteria and were analyzed in greater detail. A total of 14 techniques (parasitologic, immunologic, and molecular) and nine types of non-human animals were involved in the studies. Four studies comparing parasitologic tests (miracidium hatching test (MHT), Kato-Katz (KK), the Danish Bilharziasis Laboratory technique (DBL), and formalin-ethyl acetate sedimentation-digestion (FEA-SD)) with quantitative polymerase chain reaction (qPCR) were included in the meta-analyses. The findings suggest that the parasitologic technique FEA-SD and molecular techniques, especially qPCR, are the most promising techniques. However, further validation and standardization of the techniques under field conditions are much needed. [ABSTRACT FROM AUTHOR]

Background: Plasmodium vivax (Pv) infections were 68% of the total malaria burden in Laos in 2019. The parasite causes frequent relapses, which can be prevented by primaquine (PMQ). Testing for glucose-6-phosphate-dehydrogenase (G6PD) deficiency is recommended before giving PMQ to avoid haemolysis. Because of the risk of haemolysis in G6PD intermediate deficiencies among females, Laos uses the PMQ 14-days regimen only in G6PD normal females. Among G6PD point-of-care tests, qualitative tests cannot differentiate between G6PD normal and intermediate females. Quantitative tests are required to differentiate between G6PD normal and intermediate deficiencies. However, the quantitative test lacks the cost-effectiveness evidence necessary for decision-making for large-scale adoption. This study examined the cost-effectiveness of quantitative G6PD test, with either supervised PMQ treatment or unsupervised PMQ treatment, against the usual unsupervised PMQ 8-weeks strategy. Supervised PMQ 8-weeks strategy without G6PD testing was also compared against the unsupervised PMQ 8-weeks strategy since the former had recently been adopted in malaria high burden villages that had village malaria volunteers. A budget impact analysis was conducted to understand the incremental cost and effect needed for a nationwide scale-up of the chosen strategy. Methods: A decision tree model compared the cost-effectiveness of implementing four strategies at one health facility with an average of 14 Pv cases in one year. The strategies were unsupervised PMQ strategy, supervised PMQ strategy, G6PD test with unsupervised PMQ strategy, and G6PD test with supervised PMQ strategy. Disability Adjusted Life Years (DALYs) was the effect measure. Costs were calculated from a payer perspective, and sensitivity analyses were conducted. One Gross Domestic Product (GDP) per capita of Laos was set as the cost-effectiveness threshold. Budget impact analysis was conducted using the health facility wise Pv data in Laos in 2020. Findings: Supervised PMQ strategy was extendedly dominated by G6PD test strategies. When compared against the unsupervised PMQ strategy, both G6PD test strategies were more costly but more effective. Their Incremental Cost-Effectiveness Ratios (ICER) were 96.72US$ for the G6PD test with unsupervised PMQ strategy and 184.86US$ for the G6PD test with supervised PMQ strategy. Both ICERs were lower than one GDP per capita in Laos. Following the sensitivity analysis, low adherence for PMQ 14 days made both G6PD test strategies less cost-effective. The lower the Pv case number reported in a health facility, the higher the ICER was. In the budget impact analysis, the expected budget need was only half a million US$ when the G6PD test rollout was discriminately done depending on the Pv case number reported at the health facilities. Indiscriminate roll out of G6PD test to all health facilities was most expensive with least effect impact. [ABSTRACT FROM AUTHOR]

Background: Leptospirosis has globally significant human mortality and morbidity, yet estimating the clinical and public health burden of leptospirosis is challenging because timely diagnosis remains limited. The goal of the present study was to evaluate leptospirosis undercounting by current standard methods in both clinical and epidemiological study settings. Methodology/Principal findings: A prospective hospital-based study was conducted in multiple hospitals in Sri Lanka from 2016 to 2019. Culture, whole blood, and urine samples were collected from clinically suspected leptospirosis cases and patients with undifferentiated fever. Analysis of biological samples from 1,734 subjects confirmed 591 (34.1%) cases as leptospirosis and 297 (17.1%) were classified as "probable" leptospirosis cases. Whole blood quantitative PCR (qPCR) did identify the most cases (322/540(60%)) but missed 40%. Cases missed by each method include; urine qPCR, 70% (153/220); acute sample microscopic agglutination test (MAT), 80% (409/510); paired serum sample MAT, 58% (98/170); and surveillance clinical case definition, 53% (265/496). qPCR of negative culture samples after six months of observation was of diagnostic value retrospectively with but missed 58% of positives (109/353). Conclusion: Leptospirosis disease burden estimates should consider the limitations of standard diagnostic tests. qPCR of multiple sample types should be used as a leading standard test for diagnosing acute leptospirosis. Author summary: Diagnostics of leptospirosis have not been optimised yet and is considered as a significant limiting factor for estimating the disease burden. This prospective hospital-based study, including 1734 clinically suspected leptospirosis cases and undifferentiated febrile patients, revealed that a minimum of 40% of cases would be missed by using any of the following tests individually. (Whole blood qPCR, single or paired-sample MAT, Urine qPCR, culture, culture qPCR, surveillance case definition). Therefore, we conclude that whole blood qPCR should be the standard test for diagnosing leptospirosis for clinical purposes until day 10 of the reported disease. MAT should be limited to places where the serological diagnosis has an epidemiological interest. qPCR testing of microscopically-negative cultures should be done before discarding to increase the yield in research settings. [ABSTRACT FROM AUTHOR]

Background: Successful malaria treatment, control and elimination programs require accurate, affordable, and field-deployable diagnostic tests. A number of studies have directly compared diagnostic performance between the new ultrasensitive rapid diagnostic test (us-RDT) and conventional rapid diagnostic test (co-RDT) for detecting malaria. Thus, we undertook this review to directly compare pooled diagnostic performance of us-RDT and co-RDT for detection of malaria. Methods: PubMed, Web of Science, Scopus, Embase, and ProQuest were searched from their inception until 31 January 2021 accompanied by forward and backward citations tracking. Two authors independently assessed the quality of included studies by RevMan5 software (using the QUADAS-2 checklist). Diagnostic accuracy estimates (sensitivity and specificity and others) were pooled using a random-effect model and 95% confidence interval (CI) in Stata 15 software. Results: Fifteen studies with a total of 20,236 paired co-RDT and us-RDT tests were included in the meta-analysis. Molecular methods (15 studies) and immunoassay test (one study) were used as standard methods for comparison with co-RDT and us-RDT tests. The pooled sensitivity for co-RDT and us-RDT were 42% (95%CI: 25–62%) and 61% (95%CI: 47–73%), respectively, with specificity of 99% (95%CI: 98–100%) for co-RDT, and 99% (95%CI: 96–99%) for us-RDT. In asymptomatic individuals, the pooled sensitivity and specificity of co-RDT were 27% (95%CI: 8–58%) and 100% (95%CI: 97–100%), respectively, while us-RDT had a sensitivity of 50% (95%CI: 33–68%) and specificity of 98% (95%CI: 94–100%). In low transmission settings, pooled sensitivity for co-RDT was 36% (95%CI: 9 76%) and 62% (95%CI: 44 77%) for us RDT, while in high transmission areas, pooled sensitivity for co RDT and us RDT were 62% (95%CI: 39 80%) and 75% (95%CI: 57–87%), respectively. Conclusion: The us-RDT test showed better performance than co-RDT test, and this characteristic is more evident in asymptomatic individuals and low transmission areas; nonetheless, additional studies integrating a range of climate, geography, and demographics are needed to reliably understand the potential of the us-RDT. [ABSTRACT FROM AUTHOR]

Background: Respiratory tract infections (RTIs) are often inappropriately treated with antibiotics. Rapid diagnostic tests (RDTs) have been developed with the aim of improving antibiotic prescribing but uptake remains low. The aim of this study was to examine provider knowledge, attitudes and behaviors regarding RDT use and their relationship to antibiotic prescribing decisions across multiple clinical departments in an urban safety-net hospital. Methods: We conducted a mixed methods sequential explanatory study. Providers with prescribing authority (attending physicians, nurse practitioners and physician assistants) who had at least 20 RTI encounters from January 1, 2016 to December 31, 2018. Eighty-five providers completed surveys and 16 participated in interviews. We conducted electronic surveys via RedCap from April to July 2019, followed by semi-structured individual interviews from October to December 2019, to ascertain knowledge, attitudes and behaviors related to RDT use and antibiotic prescribing. Results: Survey findings indicated that providers felt knowledgeable about antibiotic prescribing guidelines. They reported high familiarity with the rapid streptococcus and rapid influenza tests. Familiarity with comprehensive respiratory panel PCR (RPP-respiratory panel PCR) and procalcitonin differed by clinical department. Qualitative interviews identified four main themes: providers trust their clinical judgment more than rapid test results; patient-provider relationships play an important role in prescribing decisions; there is patient demand for antibiotics and providers employ different strategies to address the demand and providers do not believe RDTs are implemented with sufficient education or evidence for clinical practice. Conclusion: Prescribers are knowledgeable about prescribing guidelines but often rely on clinical judgement to make final decisions. The utility of RDTs is specific to the type of RDT and the clinical department. Given the low familiarity and clinical utility of RPP and procalcitonin, providers may require additional education and these tests may need to be implemented differently based on clinical department. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic caused by the SARS-CoV-2 is a serious health threat causing worldwide morbidity and mortality. Real-time reverse transcription PCR (RT-qPCR) is currently the standard for SARS-CoV-2 detection. Although various nucleic acid-based assays have been developed to aid the detection of SARS-CoV-2 from COVID-19 patient samples, the objective of this study was to develop a diagnostic test that can be completed in 30 minutes without having to isolate RNA from the samples. Here, we present an RNA amplification detection method performed using reverse transcription loop-mediated isothermal amplification (RT-LAMP) reactions to achieve specific, rapid (30 min), and sensitive (<100 copies) fluorescent detection in real-time of SARS-CoV-2 directly from patient nasopharyngeal swab (NP) samples. When compared to RT-qPCR, positive NP swab samples assayed by fluorescent RT-LAMP had 98% (n = 41/42) concordance and negative NP swab samples assayed by fluorescent RT-LAMP had 87% (n = 59/68) concordance for the same samples. Importantly, the fluorescent RT-LAMP results were obtained without purification of RNA from the NP swab samples in contrast to RT-qPCR. We also show that the fluorescent RT-LAMP assay can specifically detect live virus directly from cultures of both SARS-CoV-2 wild type (WA1/2020), and a SARS-CoV-2 B.1.1.7 (alpha) variant strain with equal sensitivity to RT-qPCR. RT-LAMP has several advantages over RT-qPCR including isothermal amplification, speed (<30 min), reduced costs, and similar sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Background: Little is known about the diagnostic performance of rapid diagnostic tests (RDTs) for passive screening of human African trypanosomiasis (HAT) in Côte d'Ivoire. We determined HAT prevalence among clinical suspects, identified clinical symptoms and signs associated with HAT RDT positivity, and assessed the diagnostic tests' specificity, positive predictive value and agreement. Methods: Clinical suspects were screened with SD Bioline HAT, HAT Sero-K-Set and rHAT Sero-Strip. Seropositives were parasitologically examined, and their dried blood spots tested in trypanolysis, ELISA/Tbg, m18S-qPCR and LAMP. The HAT prevalence in the study population was calculated based on RDT positivity followed by parasitological confirmation. The association between clinical symptoms and signs and RDT positivity was determined using multivariable logistic regression. The tests' Positive Predictive Value (PPV), specificity and agreement were determined. Results: Over 29 months, 3433 clinical suspects were tested. The RDT positivity rate was 2.83%, HAT prevalence 0.06%. Individuals with sleep disturbances (p<0.001), motor disorders (p = 0.002), convulsions (p = 0.02), severe weight loss (p = 0.02) or psychiatric problems (p = 0.04) had an increased odds (odds ratios 1.7–4.6) of being HAT RDT seropositive. Specificities ranged between 97.8%-99.6% for individual RDTs, and 93.3–98.9% for subsequent tests on dried blood spots. The PPV of the individual RDTs was below 14.3% (CI 2–43), increased to 33.3% (CI 4–78) for serial RDT combinations, and reached 67% for LAMP and ELISA/Tbg on RDT positives. Agreement between diagnostic tests was poor to moderate (Kappa ≤ 0.60), except for LAMP and ELISA/Tbg (Kappa = 0.66). Conclusion: Identification of five key clinical symptoms and signs may simplify referral for HAT RDT screening. The results confirm the appropriateness of the diagnostic algorithm presently applied, with screening by SD Bioline HAT or HAT Sero-K-Set, supplemented with trypanolysis. ELISA/Tbg could replace trypanolysis and is simpler to perform. Trial registration: ClinicalTrials.gov ClinicalTrials.gov, ID NCT03356665 Author summary: As human African trypanosomiasis (HAT) or sleeping sickness is approaching elimination, case management is progressively transferred from specialized teams to front line health care centres. This approach raises practical questions. What clinical symptoms and signs should trigger HAT testing? What rapid diagnostic tests (RDT) are suitable for screening? Which unconfirmed serological suspects should be examined further? During this study conducted in Côte d'Ivoire, individuals with sleep disturbances, motor disorders, convulsions, severe weight loss, or psychiatric problems were more often positive in RDTs. These symptoms and signs should trigger referral for HAT screening. Our results confirm appropriateness of the existing HAT screening strategy with SD Bioline HAT or HAT Sero-K-Set having specificities of 97.8% and 98.9%. Subsequent tests on dried blood spots from RDT positives were 93.3% to 98.9% specific, and increased the positive predictive value from below 15% up to 67%. For selection of RDT seropositives for additional parasitological examinations, trypanolysis on dried blood spots is suitable, but could be replaced by ELISA, which can be performed locally. The optimal diagnostic test algorithm for Côte d'Ivoire, in terms of cost-effectiveness, remains to be determined. [ABSTRACT FROM AUTHOR]

Background: The 20-minute whole blood clotting test (20WBCT) has been used to detect coagulopathy following snakebite for almost 50 years. A systematic review and meta-analysis of the 20WBCT was conducted to evaluate the accuracy of the 20WBCT to detect coagulopathy, indicative of systemic envenoming. Methods and findings: Databases were searched from inception up to 09/12/2020 to identify studies that compared the 20WBCT and INR/fibrinogen on five or more subjects. Data was extracted from full-text articles by two reviewers using a predetermined form. Authors of 29 studies that lacked sufficient details in the manuscript were contacted and included if data meeting the inclusion criteria were provided. Included studies were evaluated for bias using a tailored QUADAS-2 checklist. The study protocol was prospectively registered on PROSPERO database (CRD42020168953). The searches identified 3,599 studies, 15 met the inclusion criteria and 12 were included in the meta-analysis. Data was reported from 6 countries and included a total of 2,270 patients. The aggregate weighted sensitivity of the 20WBCT at detecting INR >1.4 was 0.84 (CI 0.61 to 0.94), the specificity was 0.91 (0.76 to 0.97) and the SROC AUC was 0.94 (CI 0.91 to 0.96). The aggregate weighted sensitivity of the 20WBCT at detecting fibrinogen <100 mg/dL was 0.72 (CI 0.58 to 0.83), the specificity was 0.94 (CI 0.88 to 0.98) and the SROC AUC was 0.93 (0.91 to 0.95). Both analyses that used INR and fibrinogen as the reference test displayed considerable heterogeneity. Conclusions: In the absence of laboratory clotting assays, the 20WBCT remains a highly specific and fairly sensitive bedside test at detecting coagulopathy following snakebite. However, clinicians should be aware of the importance of operator training, standardized equipment and the lower sensitivity of the 20WBCT at detecting mild coagulopathy and resolution of coagulopathy following antivenom. Author summary: Snakebite is a neglected tropical disease and responsible for an estimated 130,000 deaths per year. Coagulopathy is the commonest clinical manifestation of systemic snakebite envenoming and is indicative of a need for antivenom. The 20WBCT is a simple, cheap and quick bedside clotting test devised to detect coagulopathy after snakebite. The test is used widely and is incorporated in multiple national and WHO guidelines. However, following a publication questioning its diagnostic accuracy, there is a lack of consensus regarding its diagnostic accuracy and utility. In this review, we conclude that the 20WBCT is capable of detecting coagulopathy following snakebite with high specificity and acceptable sensitivity. Diagnostic test accuracy of the 20WBCT is improved when assessing for the presence of severe coagulopathy. Inclusion of data in this analysis from a variety of countries, make the findings widely applicable. However, the heterogeneity in study findings indicates the need for local assessment of external validity. The results of this study support the WHO guidelines that recommend its continued use in the absence of conventional laboratory clotting assays. Urgent efforts are required to identify an optimal method of detecting systemic snakebite envenoming and the response to treatment through pharmacokinetic and pharmacodynamic studies of venom and antivenom. [ABSTRACT FROM AUTHOR]