Interpretation Of Diagnostic Tests Research Articles

Development of a clinical risk score for the prediction of Pneumocystis jirovecii pneumonia in hospitalised patients

BackgroundThe performance and availability of invasive and non-invasive investigations for the diagnosis of Pneumocystis jirovecii pneumonia (PCP) vary across clinical settings. Estimating the pre-test probability of PCP is essential to the optimal selection and interpretation of diagnostic tests, such as the 1,3-β-D-glucan assay (BDG), for the prioritization of bronchoscopy, and to guide empiric treatment decisions. We aimed to develop a multivariable risk score to estimate the pre-test probability of PCP.MethodsThe score was developed from a cohort of 626 individuals who underwent bronchoscopy for the purposes of identifying PCP in a Canadian tertiary-care centre, between 2015 and 2018. We conducted a nested case-control study of 57 cases and 228 unmatched controls. Demographic, clinical, laboratory, and radiological data were included in a multivariable logistic regression model to estimate adjusted odds ratios for PCP diagnosis. A clinical risk score was derived from the multivariable model and discrimination was assessed by estimating the score’s receiver operating characteristic curve.ResultsParticipants had a median age of 60 years (interquartile range [IQR] 49–68) and 115 (40%) were female; 40 (14%) had HIV and 49 (17%) had a solid organ transplant (SOT). The risk score included prior SOT or HIV with CD4 ≤ 200/µL (+ 2), serum lactate dehydrogenase ≥ 265.5 IU/mL (+ 2), radiological pattern typical of PCP on chest x-ray (+ 2) or CT scan (+ 2.5), and PCP prophylaxis with trimethoprim-sulfamethoxazole (-3) or other antimicrobials (-2). The median score was 4 points (IQR, 2-4.5) corresponding to a 28% probability of PCP. The risk prediction model had good discrimination with a c-statistic of 0.79 (0.71–0.84). Given the operating characteristics of the BDG assay, scores ≤ 3 in patients without HIV, and ≤ 5.5 in those with HIV, paired with a negative BDG, would be expected to rule out PCP with 95% certainty.ConclusionWe propose the PCP Score to estimate pre-test probability of PCP. Once validated, it should help clinicians determine which patients to refer for invasive investigations, when to rely on serological testing, and in whom to consider pre-emptive treatment.

IgG, IgM, and Nonstructural Protein 1 Response Profiles after Receipt of Tetravalent Dengue Vaccine TAK-003 in a Phase 2 Randomized Controlled Trial.

The profiles of vaccine-induced dengue antibodies may differ from those produced following natural infection and could potentially interfere with the interpretation of diagnostic tests. We assessed anti-dengue IgG and IgM antibodies, and nonstructural protein 1 antigen profiles in the serum of adults who received a single dose of the tetravalent dengue vaccine TAK-003 as either an initially developed high-dose formulation or the standard approved formulation in a phase 2 study in Singapore (#NCT02425098). Immunoglobulin G and IgM profiles during the first 30 days postvaccination varied by baseline serostatus (microneutralization assay). Nonstructural protein 1 antigen was not detected in the serum of any participants. Vaccine-induced IgG and IgM antibodies can affect serological confirmation of subsequent dengue infection in vaccinees. These results highlight the limitations of using serological tests for dengue diagnosis, particularly in a postvaccination setting, and emphasize the need for more sensitive antigen- and molecular-based testing for accurate dengue diagnosis.

Cushing's Syndrome in the Elderly.

Management of Cushing's syndrome (CS) can be particularly challenging in older patients, compared with younger individuals, due to the lack of several clinical features associated with cortisol excess along with a greater burden of associated comorbidities. Moreover, the interpretation of diagnostic tests could be influenced by age-related physiological changes in cortisol secretion. While mortality is higher and quality of life is more impaired in the elderly with CS as compared with the younger, there is currently no agreement on the most effective therapeutic options in aged individuals, and safety data concerning medical treatment are scanty. In this review, we summarize the current knowledge about age-related differences in CS etiology, clinical presentation, treatment, and outcomes and describe the potential underlying mechanisms.

Pitfalls in the Diagnostic Evaluation of Pheochromocytomas.

Pheochromocytomas and paragangliomas (PPGLs), rare neuroendocrine tumors arising from chromaffin cells, present a significant diagnostic challenge due to their clinical rarity and polymorphic symptomatology. The clinical cases demonstrate the importance of an integrated approach that combines clinical assessment, biochemical testing, and imaging to distinguish PPGLs from mimicking conditions, such as obstructive sleep apnea and interfering medication effects, which can lead to false-positive biochemical results. Although a rare condition, false-negative metanephrine levels can occur in pheochromocytomas, but imaging findings can give some clues and increase suspicion for a pheochromocytoma diagnosis. This expert endocrine consult underscores the critical role of evaluating preanalytical conditions and pretest probability in the biochemical diagnosis of PPGLs. Moreover, a careful differentiation of PPGLs from similar conditions and careful selection and interpretation of diagnostic tests, with focus on understanding and reducing false positives to enhance diagnostic accuracy and patient outcomes, is crucial.

How Outreach Training and Supportive Supervision (OTSS) Affect Health Facility Readiness and Health-Care Worker Competency to Prevent and Treat Malaria in Niger: A Secondary Analysis of OTSS Data.

The quality of health services is key to the goal of averting morbidity and mortality from malaria. From July 2020 to August 2021, PMI Impact Malaria supported the implementation of four rounds of Outreach Training and Supportive Supervision (OTSS) in 12 health districts in the two regions of Niger: Dosso and Tahoua. Through OTSS, trained supervisors conducted onsite visits to observe an average of 174 healthcare workers (HCWs) per round in 96 public primary health facilities, managing persons with fever or conducting antenatal care (ANC) consultations, and then provided instant and individualized feedback and onsite training. Data from health facility readiness, case management, and malaria in pregnancy (MiP) checklists across the four rounds were analyzed using Wilcoxon's and the χ2 tests. These analyses highlighted improved facility readiness, including an increased likelihood that HCWs had received classroom training, and facilities had increased availability of guidelines and algorithms by round 4 compared with round 1. Median HCW performance scores showed an improvement in the correct performance and interpretation of malaria rapid diagnostic tests, in classification of malaria as uncomplicated or severe, and in the management of uncomplicated malaria across the four rounds. For MiP services, malaria prevention and the management of pregnant women with malaria also improved from round 1 to round 4. These findings provide further evidence that OTSS can achieve rapid improvements in health facility readiness and HCW competency in managing outpatients and ANC clients.

Revisiting the Importance of Orthobunyaviruses for Animal Health: A Scoping Review of Livestock Disease, Diagnostic Tests, and Surveillance Strategies for the Simbu Serogroup.

Orthobunyaviruses (order Bunyavirales, family Peribunyaviridae) in the Simbu serogroup have been responsible for widespread epidemics of congenital disease in ruminants. Australia has a national program to monitor arboviruses of veterinary importance. While monitoring for Akabane virus, a novel orthobunyavirus was detected. To inform the priority that should be given to this detection, a scoping review was undertaken to (1) characterise the associated disease presentations and establish which of the Simbu group viruses are of veterinary importance; (2) examine the diagnostic assays that have undergone development and validation for this group of viruses; and (3) describe the methods used to monitor the distribution of these viruses. Two search strategies identified 224 peer-reviewed publications for 33 viruses in the serogroup. Viruses in this group may cause severe animal health impacts, but only those phylogenetically arranged in clade B are associated with animal disease. Six viruses (Akabane, Schmallenberg, Aino, Shuni, Peaton, and Shamonda) were associated with congenital malformations, neurological signs, and reproductive disease. Diagnostic test interpretation is complicated by cross-reactivity, the timing of foetal immunocompetence, and sample type. Serological testing in surveys remains a mainstay of the methods used to monitor the distribution of SGVs. Given significant differences in survey designs, only broad mean seroprevalence estimates could be provided. Further research is required to determine the disease risk posed by novel orthobunyaviruses and how they could challenge current diagnostic and surveillance capabilities.

Laboratory diagnosis of CNS infections in children due to emerging and re-emerging neurotropic viruses.

Recent decades have witnessed the emergence and re-emergence of numerous medically important viruses that cause central nervous system (CNS) infections in children, e.g., Zika, West Nile, and enterovirus/parechovirus. Children with immature immune defenses and blood-brain barrier are more vulnerable to viral CNS infections and meningitis than adults. Viral invasion into the CNS causes meningitis, encephalitis, brain imaging abnormalities, and long-term neurodevelopmental sequelae. Rapid and accurate detection of neurotropic viral infections is essential for diagnosing CNS diseases and setting up an appropriate patient management plan. The addition of new molecular assays and next-generation sequencing has broadened diagnostic capabilities for identifying infectious meningitis/encephalitis. However, the expansion of test menu has led to new challenges in selecting appropriate tests and making accurate interpretation of test results. There are unmet gaps in development of rapid, sensitive and specific molecular assays for a growing list of emerging and re-emerging neurotropic viruses. Herein we will discuss the advances and challenges in the laboratory diagnosis of viral CNS infections in children. This review not only sheds light on selection and interpretation of a suitable diagnostic test for emerging/re-emerging neurotropic viruses, but also calls for more research on development and clinical utility study of novel molecular assays. IMPACT: Children with immature immune defenses and blood-brain barrier, especially neonates and infants, are more vulnerable to viral central nervous system infections and meningitis than adults. The addition of new molecular assays and next-generation sequencing has broadened diagnostic capabilities for identifying infectious meningitis and encephalitis. There are unmet gaps in the development of rapid, sensitive and specific molecular assays for a growing list of emerging and re-emerging neurotropic viruses.

Isoniazid-Resistant Tuberculosis - A Series of Clinical Cases

Abstract The emergence of M. tuberculosis strains resistant to Isoniazid (INH) and Rifampicin (RIF), the two most potent drugs of first-line anti-TB treatment is termed multidrug drug-resistant TB (MDR-TB). Multidrug-resistant tuberculosis has been a severe medical and epidemic problem worldwide. We present a series of clinical cases consisting of two patients diagnosed with isoniazid-resistant tuberculosis. Histopathological examination supports the diagnosis of tuberculous granulomas. The pathology molecular examination revealed the presence of Isoniazid-resistant Mycobacterium tuberculosis 1, 2 via the following mutation c.947G>A; p. Gly316Asp. Isoniazid-resistance is associated with mutations in the furA-katG and fabG1-inhA operons and in the ahpC gene. 64% of the isoniazid-resistance phenotypes were associated with the kat G 315 mutation worldwide. The second most common mutation is inhA-15, reported in 19% of the Isoniazid-resistant isolates. The significant association between the two mutations, inhA c-15 and kat G 315 respectively, and the high-level resistance is of interest in the interpretation of current and future molecular diagnostic testing, as an early prediction of the level of Isoniazid-resistance is essential to decide the benefit of high-dose Isoniazid use.

Adquisición de competencias en ECV en el grado en Medicina: percepción de médicos residentes de cardiología

Introduction and objectivesUniversity education during the degree in Medicine must ensure the acquisition of essential knowledge and skills necessary for the performance of the medical profession. The objective of this study was to analyze the perception of Cardiology resident doctors in Spain regarding the acquisition of competencies in cardiovascular pathology during their university training, and its usefulness in daily clinical practice. MethodsA telematic questionnaire was developed targeting 814 cardiology residents in Spain between January and February 2023. The acquisition of competencies during the medicine degree and the implementation of teaching innovations in the subject of cardiovascular diseases were evaluated. ResultsThe survey was completed by 69 (8.5%) cardiology residents (mean age of 29, 43% women). The competencies that a larger number of respondents considered acquired during their university training were knowledge of cardiovascular risk factors (91.2%), while the interpretation of major diagnostic tests was considered acquired by a smaller number of respondents (27.9%). The majority of participants stated that university training was only useful for passing the subject. The most commonly implemented teaching innovations were clinical practices (96.2%), and their implementation received positive evaluations from the majority of participants. ConclusionsCardiology residents participating in the survey reflected that university education in cardiovascular pathology in Spain primarily emphasizes the acquisition of theoretical knowledge. However, the inclusion of teaching innovations could facilitate the development of practical competencies and skills, which are crucial in the foundational training of a physician.

When in doubt, return to fundamentals (seizure semiology).

This case of drug resistant focal epilepsy highlights several invaluable teaching points. Hypotheses grounded in seizure semiology provide the best framework to ensure accurate interpretation of diagnostic testing. Without a hypothesis, information gathered from tests can be difficult to linearly piece together and can lead to poor patient outcomes. The case also provides a real-world conundrum of discordant test results that were ultimately rectified by re-visiting the initial hypothesis and cross-testing. Perinatal stroke continues to be a common etiology of drug resistant epilepsy. Patients can achieve seizure freedom and good quality of life with appropriate workup and in appropriate cases, surgery.

Central Disorders of Hypersomnolence.

The goals of this article are to describe the clinical approach to and management of patients with central disorders of hypersomnolence, and to understand and differentiate available diagnostic tools. Updated clinical practice guidelines for the treatment of central disorders of hypersomnolence and narcolepsy specifically highlight new treatment options. Approval for a lower-sodium oxybate formulation that contains 92% less sodium than the standard sodium oxybate for the treatment of narcolepsy and idiopathic hypersomnia adds to the number of medications available for these disorders, allowing for a more tailored management of symptoms. Central disorders of hypersomnolence are characterized by excessive daytime sleepiness that impacts daily functions. These disorders can be differentiated by obtaining a detailed clinical sleep history and by a thoughtful interpretation of sleep diagnostic testing. Tailoring treatment approaches to meet the needs of individuals and accounting for medical and psychiatric comorbidities may improve quality of life.

Selection and interpretation of diagnostic testing

It has been said that making a diagnosis is the most difficult undertaking of humans. It can be easy with an overwhelming case to run a battery of diagnostic tests searching for an answer in a challenging case. Further, it can be tempting to enter into a herd-level diagnostic undertaking without a real plan for what to do with the results. As veterinarians, it is our responsibility to perform diagnostic tests with strategy and a plan for each of the possible outcomes. This is what separates us from layper­sons who submit samples directly to a diagnostic lab expecting a printout with a plan.

Rapidly adaptable automated interpretation of point-of-care COVID-19 diagnostics

BackgroundPoint-of-care diagnostic devices, such as lateral-flow assays, are becoming widely used by the public. However, efforts to ensure correct assay operation and result interpretation rely on hardware that cannot be easily scaled or image processing approaches requiring large training datasets, necessitating large numbers of tests and expert labeling with validated specimens for every new test kit format.MethodsWe developed a software architecture called AutoAdapt POC that integrates automated membrane extraction, self-supervised learning, and few-shot learning to automate the interpretation of POC diagnostic tests using smartphone cameras in a scalable manner. A base model pre-trained on a single LFA kit is adapted to five different COVID-19 tests (three antigen, two antibody) using just 20 labeled images.ResultsHere we show AutoAdapt POC to yield 99% to 100% accuracy over 726 tests (350 positive, 376 negative). In a COVID-19 drive-through study with 74 untrained users self-testing, 98% found image collection easy, and the rapidly adapted models achieved classification accuracies of 100% on both COVID-19 antigen and antibody test kits. Compared with traditional visual interpretation on 105 test kit results, the algorithm correctly identified 100% of images; without a false negative as interpreted by experts. Finally, compared to a traditional convolutional neural network trained on an HIV test kit, the algorithm showed high accuracy while requiring only 1/50th of the training images.ConclusionsThe study demonstrates how rapid domain adaptation in machine learning can provide quality assurance, linkage to care, and public health tracking for untrained users across diverse POC diagnostic tests.

COVID-19 Antigen Results Correlate with the Quantity of Replication-Competent SARS-CoV-2 in a Cross-Sectional Study of Ambulatory Adults during the Delta Wave.

Appropriate interpretation of various diagnostic tests for COVID-19 is critical, yet the association among rapid antigen tests, reverse transcription (RT)-PCR, and viral culture has not been fully defined. To determine whether rapid antigen testing correlates with the presence and quantity of replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in ambulatory adults, 626 adult participants were enrolled in a cross-sectional diagnostic study. Each participant had two anterior nasal swabs obtained for rapid antigen and RT-PCR testing and SARS-CoV-2 viral culture. The primary outcomes were the presence and quantification of SARS-CoV-2 growth in VeroE6-ACE2-TMPRSS2 cells in asymptomatic and symptomatic ambulatory adults. In this cross-sectional study of 626 adult outpatients, the sensitivity of a single positive antigen test to identify replication-competent SARS-CoV-2 was 63.6% in asymptomatic and 91.0% in symptomatic participants. Viral culture titers were the highest at the onset of symptoms and rapidly declined by 7 days after symptom onset. The positive agreement of the rapid antigen test with RT-PCR at a cycle threshold CT less than 30 was 66.7% in asymptomatic and 90.7% in symptomatic participants. Among symptomatic participants a with a CT less than 30, a single antigen test had a positive agreement of 90.7% (95% confidence interval [CI], 84.8% to 94.8%). There was 100% negative agreement as all 425 RT-PCR-negative participants had a negative antigen test. A positive antigen test in symptomatic adults with COVID-19 has a strong correlation with replication-competent SARS-CoV-2. Rapid antigen test results may be a suitable proxy for infectiousness. IMPORTANCE Do rapid antigen test results correlate with replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (i.e., infectious) virus? In this cross-sectional diagnostic study of 626 adults, the sensitivity of the antigen test to identify replication-competent SARS-CoV-2 was 63.6% in asymptomatic and 91.0% in symptomatic participants. Viral culture titers were the highest at the onset of symptoms and rapidly declined by 7 days after symptom onset. The positive agreement of the rapid antigen test with reverse transcription (RT)-PCR at a CT of less than 30 was 66.7% in asymptomatic participants and 90.7% in symptomatic participants. A positive antigen test may be an appropriate surrogate for identifying replication-competent virus in symptomatic individuals with COVID-19.

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The Diagnostic Test: Goodness, Characteristics, and Interpretation: Under the Impact of the Corona Pandemic and Different SARS-CoV-2 Tests

Many diagnostic tests are currently being performed around the world to detect SARS-CoV-2 infection. Positive and negative test results are not one hundred percent accurate, but have far-reaching consequences. There are false positives (test positive, uninfected) and false negatives (test negative, infected). A positive/negative result does not necessarily mean that the test subject is actually infected/non-infected. This article has two objectives: 1. to explain the most important characteristics of diagnostic tests with binary outcome 2. to point out problems and phenomena of interpretation of diagnostic tests, on the basis of different scenarios. Presentation of the basic concepts of the quality of a diagnostic test (sensitivity, specificity) and pre-test probability (prevalence of test group). Calculation (including formulas) of further important quantities. In the basic scenario, sensitivity is 100%, specificity 98.8%, and pre-test probability of 1.0% (10 infected persons per 1,000 tested). For 1,000 diagnostic tests, the statistical mean is 22 positive cases, 10 of which are true-positive. The positive predictive probability is 45.7%. The prevalence calculated from this (22/1,000 tests) overestimates the actual prevalence (10/1,000 tests) by a factor of 2.2. All cases with a negative test outcome are true negative. The prevalence has a strong influence on the positive and negative predictive value. This phenomenon occurs even with otherwise very good test values of sensitivity and specificity. At a prevalence of only 5 infected persons per 10,000 (0.05%), the positive predictive probability drops to 4.0%. Lower specificity amplifies this effect, especially with small numbers of infected persons. If the sensitivity or specificity is below 100%, diagnostic tests are always error-prone. If the prevalence of infected persons is low, a large number of false positive results are to be expected - even if the test is of good quality with a high sensitivity and especially a high specificity. This is accompanied by low positive predictive values, i. e. positive tested persons are not infected. A false positive test result in the first test can be clarified by carrying out a second test.

Digital Platform for Automatic Qualitative and Quantitative Reading of a Cryptococcal Antigen Point-of-Care Assay Leveraging Smartphones and Artificial Intelligence.

Cryptococcosis is a fungal infection that causes serious illness, particularly in immunocompromised individuals such as people living with HIV. Point of care tests (POCT) can help identify and diagnose patients with several advantages including rapid results and ease of use. The cryptococcal antigen (CrAg) lateral flow assay (LFA) has demonstrated excellent performance in diagnosing cryptococcosis, and it is particularly useful in resource-limited settings where laboratory-based tests may not be readily available. The use of artificial intelligence (AI) for the interpretation of rapid diagnostic tests can improve the accuracy and speed of test results, as well as reduce the cost and workload of healthcare professionals, reducing subjectivity associated with its interpretation. In this work, we analyze a smartphone-based digital system assisted by AI to automatically interpret CrAg LFA as well as to estimate the antigen concentration in the strip. The system showed excellent performance for predicting LFA qualitative interpretation with an area under the receiver operating characteristic curve of 0.997. On the other hand, its potential to predict antigen concentration based solely on a photograph of the LFA has also been demonstrated, finding a strong correlation between band intensity and antigen concentration, with a Pearson correlation coefficient of 0.953. The system, which is connected to a cloud web platform, allows for case identification, quality control, and real-time monitoring.

Using the theoretical domains framework to explore stakeholder perspectives of a “prescriber-ready pharmacist” to help develop the future workforce

Abstract Introduction The General Pharmaceutical Council’s (GPhC’s) revised standards for the Initial Education and Training of Pharmacists, enable pharmacists to prescribe on registration”.1 This major reform is transforming the education and training of ‘day-one pharmacist prescribers’ allowing them to play a greater role in patient care. Aim To explore stakeholder perspectives on a “prescriber-ready pharmacist” to help inform the initial education and training of the future pharmacy workforce. Methods Structured interviews with a diverse group of stakeholders, and an interview and focus groups with pharmacy students, took place in Autumn 2021. The schedule was developed using the Theoretical Domains Framework (TDF).2. Participants were identified and recruited via email by the investigators, who had legitimate access to their contact details. All were held and recorded on Microsoft Teams, then transcribed and analysed using Framework Method.3 Ethical approval from LJMU, School of Pharmacy, REC (PBS/2021-22/01). Results The study included 50 participants; interviews with six patients, eight community pharmacists (two independent prescribers (IPs)), 10 hospital pharmacists (six IPs), 12 primary care pharmacists (eight IPs), two nurses (one IP), five GPs, and one second year pharmacy student; and two focus groups, with three, final-year pharmacy students. Participants felt person-centred care, communication and consultation skills were very important for ‘day-one pharmacist prescribers’. Professional knowledge and clinical skills e.g., “interpretation of diagnostic tests” [Hospital Pharmacist_04], were cited by hospital and primary care pharmacists. Conversely, professionalism were more likely to be mentioned by community pharmacists, “General knowledge about legalities of prescribing” [Community Pharmacist_07] and understanding their limitations. Many felt the pharmacy degree needed to become more clinical with additional placement opportunities, which would be challenging in terms of time constraints and staff capacity “… have to provide training for a large number of students that [they] haven't had to train in that way before” [Primary Care Pharmacist_05]. Barriers to ‘day one’ pharmacists prescribing included a lack of experience and confidence and pharmacist respondents felt it was important for them to gain the trust of other health care professionals. Barriers specifically for community pharmacy were: a perceived lack of support and commercial pressures, along with logistical barriers including lack of space, equipment, IT issues and pharmacists sitting outside of the ‘parent team’ in hospitals. Discussion/Conclusion Hospital and primary care pharmacists in the study were more likely to mention professional knowledge and skills, for example clinical and diagnostic skills. This may be explained because many were qualified independent prescribers and so have a better understanding of the knowledge and skills to perform the role. The additional challenges faced by community pharmacy presented may be because of a lack of defined roles for independent prescribers working within this setting. A limitation of the study is a lack of stakeholder representation from medics and other health care professionals in secondary care. ‘Prescriber-ready pharmacists’ require appropriate professional knowledge and skills, and provide a person-centred service within their sphere of competence. Stakeholders need assurance that these pharmacists are competent as independent prescribers at the point of registration before, through changes to the undergraduate programme, in particular placement opportunities.

Protocols of Investigation of Neonatal Cholestasis-A Critical Appraisal.

Neonatal cholestasis (NC) starts during the first three months of life and comprises extrahepatic and intrahepatic groups of diseases, some of which have high morbimortality rates if not timely identified and treated. Prolonged jaundice, clay-colored or acholic stools, and choluria in an infant indicate the urgent need to investigate the presence of NC, and thenceforth the differential diagnosis of extra- and intrahepatic causes of NC. The differential diagnosis of NC is a laborious process demanding the accurate exclusion of a wide range of diseases, through the skillful use and interpretation of several diagnostic tests. A wise integration of clinical-laboratory, histopathological, molecular, and genetic evaluations is imperative, employing extensive knowledge about each evaluated disease as well as the pitfalls of each diagnostic test. Here, we review the difficulties involved in correctly diagnosing the cause of cholestasis in an affected infant.

Evaluation of the fluorescent-thin layer chromatography (f-TLC) for the diagnosis of Buruli ulcer disease in Ghana.

BackgroundBuruli ulcer is a tissue necrosis infection caused by an environmental mycobacterium called Mycobacterium ulcerans (MU). The disease is most prevalent in rural areas with the highest rates in West and Central African countries. The bacterium produces a toxin called mycolactone which can lead to the destruction of the skin, resulting in incapacitating deformities with an enormous economic and social burden on patients and their caregivers. Even though there is an effective antibiotic treatment for BU, the control and management rely on early case detection and rapid diagnosis to avert morbidities. The diagnosis of Mycobacterium ulcerans relies on smear microscopy, culture histopathology, and PCR. Unfortunately, all the current laboratory diagnostics have various limitations and are not available in endemic communities. Consequently, there is a need for a rapid diagnostic tool for use at the community health centre level to enable diagnosis and confirmation of suspected cases for early treatment. The present study corroborated the diagnostic performance and utility of fluorescent-thin layer chromatography (f-TLC) for the diagnosis of Buruli ulcer.Methodology/Principal findingsThe f-TLC method was evaluated for the diagnosis of Buruli ulcer in larger clinical samples than previously reported in an earlier preliminary study Wadagni et al. (2015). A total of 449 patients suspected of BU were included in the final data analysis out of which 122 (27.2%) were positive by f-TLC and 128 (28.5%) by PCR. Using a composite reference method generated from the two diagnostic methods, 85 (18.9%) patients were found to be truly infected with M. ulcerans, 284 (63.3%) were uninfected, while 80 (17.8%) were misidentified as infected or noninfected by the two methods. The data obtained was used to determine the discriminatory accuracy of the f-TLC against the gold standard IS2404 PCR through the analysis of its sensitivity, specificity, positive (+LR), and negative (–LR) likelihood ratio. The positive (PPV) and negative (NPV) predictive values, area under the receiver operating characteristic curve Azevedo et al. (2014), and diagnostic odds ratio were used to assess the predictive accuracy of the f-TLC method. The sensitivity of f-TLC was 66.4% (85/128), specificity was 88.5% (284/321), while the diagnostic accuracy was 82.2% (369/449). The AUC stood at 0.774 while the PPV, NPV, +LR, and–LR were 69.7% (85/122), 86.9% (284/327), 5.76, and 0.38, respectively. The use of the rule-of-thumb interpretation of diagnostic tests suggests that the method is good for use as a diagnostic tool.Conclusions/SignificanceLarger clinical samples than previously reported had been used to evaluate the f-TLC method for the diagnosis of Buruli ulcer. A sensitivity of 66.4%, a specificity of 88.5%, and diagnostic accuracy of 82.2% were obtained. The method is good for diagnosis and will help in making early clinical decisions about the patients as well as patient management and facilitating treatment decisions. However, it requires a slight modification to address the challenge of background interference and lack of automatic readout to become an excellent diagnostic tool.