How Important Is ‘Accuracy’ of Surrogate Decision-Making for Research Participation?

Background

There is a longstanding concern about the accuracy of surrogate consent in representing the health care and research preferences of those who lose their ability to decide for themselves. We sought informed, deliberative views of the older general public (≥50 years old) regarding their willingness to participate in dementia research and to grant leeway to future surrogates to choose an option contrary to their stated wishes.

Methodology/Principal Findings

503 persons aged 50+ recruited by random digit dialing were randomly assigned to one of three groups: deliberation, education, or control. The deliberation group attended an all-day education/peer deliberation session; the education group received written information only. Participants were surveyed at baseline, after the deliberation session (or equivalent time), and one month after the session, regarding their willingness to participate in dementia research and to give leeway to surrogates, regarding studies of varying risk-benefit profiles (a lumbar puncture study, a drug randomized controlled trial, a vaccine randomized controlled trial, and an early phase gene transfer trial). At baseline, 48% (gene transfer scenario) to 92% (drug RCT) were willing to participate in future dementia research. A majority of respondents (57–71% depending on scenario) were willing to give leeway to future surrogate decision-makers. Democratic deliberation increased willingness to participate in all scenarios, to grant leeway in 3 of 4 scenarios (lumbar puncture, vaccine, and gene transfer), and to enroll loved ones in research in all scenarios. On average, respondents were more willing to volunteer themselves for research than to enroll their loved ones.

Conclusions/Significance

Most people were willing to grant leeway to their surrogates, and this willingness was either sustained or increased after democratic deliberation, suggesting that the attitude toward leeway is a reliable opinion. Eliciting a person’s current preferences about future research participation should also involve eliciting his or her leeway preferences.     

Accuracy and precision of protein–ligand interaction kinetics determined from chemical shift titrations

NMR-monitored chemical shift titrations for the study of weak protein?Cligand interactions represent a rich source of information regarding thermodynamic parameters such as dissociation constants (K _D ) in the micro- to millimolar range, populations for the free and ligand-bound states, and the kinetics of interconversion between states, which are typically within the fast exchange regime on the NMR timescale. We recently developed two chemical shift titration methods wherein co-variation of the total protein and ligand concentrations gives increased precision for the K _D value of a 1:1 protein?Cligand interaction (Markin and Spyracopoulos in J Biomol NMR 53: 125?C138, 2012). In this study, we demonstrate that classical line shape analysis applied to a single set of ¹H?C¹⁵N 2D HSQC NMR spectra acquired using precise protein?Cligand chemical shift titration methods we developed, produces accurate and precise kinetic parameters such as the off-rate (k _off ). For experimentally determined kinetics in the fast exchange regime on the NMR timescale, k _off ?~?3,000?s^?1 in this work, the accuracy of classical line shape analysis was determined to be better than 5?% by conducting quantum mechanical NMR simulations of the chemical shift titration methods with the magnetic resonance toolkit GAMMA. Using Monte Carlo simulations, the experimental precision for k _off from line shape analysis of NMR spectra was determined to be 13?%, in agreement with the theoretical precision of 12?% from line shape analysis of the GAMMA simulations in the presence of noise and protein concentration errors. In addition, GAMMA simulations were employed to demonstrate that line shape analysis has the potential to provide reasonably accurate and precise k _off values over a wide range, from 100 to 15,000?s^?1. The validity of line shape analysis for k _off values approaching intermediate exchange (~100?s^?1), may be facilitated by more accurate K _D measurements from NMR-monitored chemical shift titrations, for which the dependence of K _D on the chemical shift difference (????) between free and bound states is extrapolated to ?????=?0. The demonstrated accuracy and precision for k _off will be valuable for the interpretation of biological kinetics in weakly interacting protein?Cprotein networks, where a small change in the magnitude of the underlying kinetics of a given pathway may lead to large changes in the associated downstream signaling cascade.     

Active Site Mutations in Mammalian DNA Polymerase δ Alter Accuracy and Replication Fork Progression

DNA polymerase δ (pol δ) is one of the two main replicative polymerases in eukaryotes; it synthesizes the lagging DNA strand and also functions in DNA repair. In previous work, we demonstrated that heterozygous expression of the pol δ L604G variant in mice results in normal life span and no apparent phenotype, whereas a different substitution at the same position, L604K, is associated with shortened life span and accelerated carcinogenesis. Here, we report in vitro analysis of the homologous mutations at position Leu-606 in human pol δ. Four-subunit human pol δ variants that harbor or lack 3′ → 5′-exonucleolytic proofreading activity were purified from Escherichia coli. The pol δ L606G and L606K holoenzymes retain catalytic activity and processivity similar to that of wild type pol δ. pol δ L606G is highly error prone, incorporating single noncomplementary nucleotides at a high frequency during DNA synthesis, whereas pol δ L606K is extremely accurate, with a higher fidelity of single nucleotide incorporation by the active site than that of wild type pol δ. However, pol δ L606K is impaired in the bypass of DNA adducts, and the homologous variant in mouse embryonic fibroblasts results in a decreased rate of replication fork progression in vivo. These results indicate that different substitutions at a single active site residue in a eukaryotic polymerase can either increase or decrease the accuracy of synthesis relative to wild type and suggest that enhanced fidelity of base selection by a polymerase active site can result in impaired lesion bypass and delayed replication fork progression.     

Are you looking at me? Accuracy in processing line-of-sight in Turner syndrome.

The behavioural phenotype of women with Turner syndrome (X-monosomy, 45,X) is poorly understood, but includes reports of some social development anomalies. With this in mind, accuracy of direction of gaze detection was investigated in women with Turner syndrome. Two simple experimental tasks were used to test the prediction that the ability to ascertain gaze direction from face photographs showing small lateral angular gaze deviations would be impaired in this syndrome, compared with a control population of men and women. The prediction was confirmed and was found to affect both the detection of egocentric gaze from the eyes (''is the face looking at me?'') and the detection of allocentric gaze, where the eyes in a photographed face inspected one of a number of locations of attention (''where is she looking?''). We suggest that dosage-sensitive X-linked genes contribute to the development of gaze-monitoring abilities.     

National Approaches to Monitoring Population Salt Intake: A Trade-Off between Accuracy and Practicality?

Aims

There is strong evidence that diets high in salt are bad for health and that salt reduction strategies are cost effective. However, whilst it is clear that most people are eating too much salt, obtaining an accurate assessment of population salt intake is not straightforward, particularly in resource poor settings. The objective of this study is to identify what approaches governments are taking to monitoring salt intake, with the ultimate goal of identifying what actions are needed to address challenges to monitoring salt intake, especially in low and middle-income countries.

Methods and Results

A written survey was issued to governments to establish the details of their monitoring methods. Of the 30 countries that reported conducting formal government salt monitoring activities, 73% were high income countries. Less than half of the 30 countries, used the most accurate assessment of salt through 24 hour urine, and only two of these were developing countries. The remainder mainly relied on estimates through dietary surveys.

Conclusions

The study identified a strong need to establish more practical ways of assessing salt intake as well as technical support and advice to ensure that low and middle income countries can implement salt monitoring activities effectively.     

Accuracy of StepWatch? and ActiGraph Accelerometers for Measuring Steps Taken among Persons with Multiple Sclerosis

Introduction

There has been increased interest in the objective monitoring of free-living walking behavior using accelerometers in clinical research involving persons with multiple sclerosis (MS). The current investigation examined and compared the accuracy of the StepWatch activity monitor and ActiGraph model GT3X+ accelerometer for capturing steps taken during various speeds of prolonged, over-ground ambulation in persons with MS who had mild, moderate, and severe disability.

Methods

Sixty-three persons with MS underwent a neurological examination for generation of an EDSS score and undertook two trials of walking on the GAITRite electronic walkway. Participants were fitted with accelerometers, and undertook three modified six-minute walk (6MW) tests that were interspersed with 10–15 minutes of rest. The first 6MW was undertaken at a comfortable walking speed (CWS), and the two remaining 6MW tests were undertaken above (faster walking speed; FWS) or below (slower walking speed; SWS) the participant''s CWS. The actual number of steps taken was counted through direct observation using hand-tally counters.

Results

The StepWatch activity monitor (99.8%–99.9%) and ActiGraph model GT3X+ accelerometer (95.6%–97.4%) both demonstrated highly accurate measurement of steps taken under CWS and FWS conditions. The StepWatch had better accuracy (99.0%) than the ActiGraph (95.5%) in the overall sample under the SWS condition, and this was particularly apparent in those with severe disability (StepWatch: 95.7%; ActiGraph: 87.3%). The inaccuracy in measurement for the ActiGraph was associated with alterations of gait (e.g., slower gait velocity, shorter step length, wider base of support).

Conclusions

This research will help inform the choice of accelerometer to be adopted in clinical trials of MS wherein the monitoring of free-living walking behavior is of particular value.     

Accuracy of malaria rapid diagnosis test Optimal-IT® in Kinshasa, the Democratic Republic of Congo

ABSTRACT: BACKGROUND: Despite some problems related to accuracy and applicability, malaria rapid diagnostic tests (RDTs), are currently considered the best option in areas with limited laboratory services for improving case management and reducing over-treatment. However, their performance must be established taking into the account the particularities of each endemic area. In the Democratic Republic of Congo, the validity of Optimal-IT(R) and Paracheck-Pf(R), respectively based on the detection of lactate dehydrogenase and histidine-rich protein-2, was assessed at primary health care level (PHC). METHODS: This was a two-stage cluster randomized survey, conducted in one health centre in 12 health zones in Kinshasa city. All patients with malaria presumptive diagnosis were eligible. Gold standard was microscopy performed by experts from the parasitology unit, Kinshasa University. RESULTS: 624 patients were enrolled. 53.4% (95% CI: 49.4-57.3) owed a bed net, obtained in 74.5% of cases (95% CI: 69.4-79.1) through community-based distribution by the National Malaria Control Programme. Microscopy expert reading confirmed 123 malaria cases (19.7%; 95% CI: 16.7-23.1). Overall sensitivity were 79.7% (95% CI: 72.4-86.8), 97.0% (95% CI: 95.5-98.5) and 87.8% (95% CI: 81.9-93.6), respectively, for Optimal-IT(R), Paracheck-Pf(R) and microscopy performed at PHC. Specificity was 91.6% (95% CI: 89.1-94.0). 86.2% (95% CI: 79.9-92.3) and 49.1% (95% CI: 44.7-53.4). The proportion of confirmed cases seemed similar in under-fives compared to others (p=0.131). Any treatment prior to the current visit was a predictor for malaria (AOR: 2.3; 95% CI: 1.5-3.5), but not malaria treatment (AOR: 0.87; 95% CI: 0.4-1.8). Bed net ownership tended to protect against malaria (AOR: 0.67; 95% CI: 0.45-1.00). CONCLUSION: Although microscopy is considered as the "gold standard" for malaria diagnosis at point of care level, this study showed that its accuracy may not always be satisfactory when performed in health centres.     

Effect of Supervised Students' Involvement on Diagnostic Accuracy in Hospitalized Medical Patients �� A Prospective Controlled Study

Background

During internships most medical students engage in history taking and physical examination during evaluation of hospitalized patients. However, the students'' ability for pattern recognition is not as developed as in medical experts and complete history taking is often not repeated by an expert, so important clues may be missed. On the other hand, students'' history taking is usually more extensive than experts'' history taking and medical students discuss their findings with a Supervisor. Thus the effect of student involvement on diagnostic accuracy is unclear. We therefore compared the diagnostic accuracy for patients in the medical emergency department with and without student involvement in the evaluation process.

Methodology/Principal Findings

Patients in the medical emergency department were assigned to evaluation by either a supervised medical student or an emergency department physician. We only included patients who were admitted to our hospital and subsequently cared for by another medical team on the ward. We compared the working diagnosis from the emergency department with the discharge diagnosis. A total of 310 patients included in the study were cared for by 41 medical students and 21 emergency department physicians. The working diagnosis was changed in 22% of the patients evaluated by physicians evaluation and in 10% of the patients evaluated by supervised medical students (p = .006). There was no difference in the expenditures for diagnostic procedures, length of stay in the emergency department or patient comorbidity complexity level.

Conclusion/Significance

Involvement of closely supervised medical students in the evaluation process of hospitalized medical patients leads to an improved diagnostic accuracy compared to evaluation by an emergency department physician alone.     

Is “Appearing Chronically Ill” a Sign of Poor Health? A Study of Diagnostic Accuracy

Objective

To determine the sensitivity and specificity of a physician’s assessment that a patient “appears chronically ill” for the detection of poor health status.

Methods

The health status of 126 adult outpatients was determined using the 12-Item Short Form Health Survey (SF-12). Physician participants (n = 111 residents and faculty) viewed photographs of each patient participant and assessed whether or not the patient appeared chronically ill. For the entire group of physicians, the median sensitivity and specificity of “appearing chronically ill” for the detection of poor health status (defined as SF-12 physical health score below age group norms by at least 1 SD) were calculated. The study took place from February 2009 to January 2011.

Results

Forty-two participants (33%) had an SF-12 physical health score ≥1 SD below age group norms, and 22 (18%) had a score ≥2 SD below age group norms. When poor health status was defined as an SF-12 physical score ≥1 SD below age group norms, the median sensitivity was 38.1% (IQR 28.6–47.6%), specificity 78.6% (IQR 69.0–84.0%), positive likelihood ratio 1.64 (IQR 1.42–2.15), and negative likelihood ratio 0.82 (IQR 0.74–0.87). For an SF-12 physical score ≥2 SD below age group norms, the median sensitivity was 45.5% (IQR 36.4–54.5%), specificity 76.9% (IQR 66.3–83.7%), positive likelihood ratio 1.77 (IQR 1.49–2.25), and negative likelihood ratio 0.75 (IQR 0.66–0.86).

Conclusions

Our study suggests that a physician’s assessment that a patient “appears chronically ill” has poor sensitivity and modest specificity for the detection of poor health status in adult outpatients. The associated likelihood ratios indicate that this assessment may have limited diagnostic value.     

Accuracy of the StressEraser<Superscript>®</Superscript> in the Detection of Cardiac Rhythms

StressEraser is a commercially marketed biofeedback device designed to enhance heart rate variability. StressEraser makes its internal calculations on beat-to-beat measures of finger pulse intervals. However, the accuracy and precision of StressEraser in quantifying interbeat intervals using finger pulse intervals has not been evaluated against standard laboratory equipment using R-R intervals. Accuracy was assessed by simultaneously recording interbeat intervals using StressEraser and a standard laboratory ECG system. The interbeat intervals were highly correlated between the systems. The average deviation in interbeat interval recordings between the systems was approximately 6 ms. Moreover, correlations approached unity between the systems on estimates of heart period, heart rate, and heart rate variability. Feedback from StressEraser is based on an interbeat time series that provides sufficient information to provide an excellent estimate of the dynamic changes in heart rate and heart rate variability. The slight variations between StressEraser and the laboratory equipment in quantifying heart rate and heart rate variability are due to features related to monitoring heart rate with finger pulse: (1) a lack in precision in the peak of the finger pulse relative to the clearly defined inflection point in the R-wave, and (2) contribution of variations in pulse transit time.     

Does Clinical Depression Affect the Accuracy of Self‐reported Height and Weight in Obese Women?

Objective: Recent research from a self‐report survey showed a strong association between obesity and clinical depression in women. The present analysis assessed whether differential bias in self‐reports of height and weight as a function of depression influences the apparent strength of the association. Methods: Accuracy of self‐reported height and weight was assessed in 250 obese (mean BMI=38.7 kg/m²) women, 135 of whom met the American Psychiatric Association DSM‐IV diagnostic criteria for clinical depression. Results: Depressed and non‐depressed women underreported their weight by 1.5 and 1.2 kg, respectively. They underreported their height by 0.002 and 0.003 m, respectively. Discussion: Bias in self‐reports of body weight and height is similar in depressed and non‐depressed obese women. The underreporting of weight in both groups is similar in magnitude to that seen in normal weight women. Thus, using self‐reports of height and weight seems unlikely to bias estimates of the association between obesity and clinical depression in women.     

Does Simplicity Compromise Accuracy in ACS Risk Prediction? A Retrospective Analysis of the TIMI and GRACE Risk Scores

Background

The Thrombolysis in Myocardial Infarction (TIMI) risk scores for Unstable Angina/Non-ST–elevation myocardial infarction (UA/NSTEMI) and ST-elevation myocardial infarction (STEMI) and the Global Registry of Acute Coronary Events (GRACE) risk scores for in-hospital and 6-month mortality are established tools for assessing risk in Acute Coronary Syndrome (ACS) patients. The objective of our study was to compare the discriminative abilities of the TIMI and GRACE risk scores in a broad-spectrum, unselected ACS population and to assess the relative contributions of model simplicity and model composition to any observed differences between the two scoring systems.

Methodology/Principal Findings

ACS patients admitted to the University of Michigan between 1999 and 2005 were divided into UA/NSTEMI (n = 2753) and STEMI (n = 698) subpopulations. The predictive abilities of the TIMI and GRACE scores for in-hospital and 6-month mortality were assessed by calibration and discrimination. There were 137 in-hospital deaths (4%), and among the survivors, 234 (7.4%) died by 6 months post-discharge. In the UA/NSTEMI population, the GRACE risk scores demonstrated better discrimination than the TIMI UA/NSTEMI score for in-hospital (C = 0.85, 95% CI: 0.81–0.89, versus 0.54, 95% CI: 0.48–0.60; p<0.01) and 6-month (C = 0.79, 95% CI: 0.76–0.83, versus 0.56, 95% CI: 0.52–0.60; p<0.01) mortality. Among STEMI patients, the GRACE and TIMI STEMI scores demonstrated comparably excellent discrimination for in-hospital (C = 0.84, 95% CI: 0.78–0.90 versus 0.83, 95% CI: 0.78–0.89; p = 0.83) and 6-month (C = 0.72, 95% CI: 0.63–0.81, versus 0.71, 95% CI: 0.64–0.79; p = 0.79) mortality. An analysis of refitted multivariate models demonstrated a marked improvement in the discriminative power of the TIMI UA/NSTEMI model with the incorporation of heart failure and hemodynamic variables. Study limitations included unaccounted for confounders inherent to observational, single institution studies with moderate sample sizes.

Conclusions/Significance

The GRACE scores provided superior discrimination as compared with the TIMI UA/NSTEMI score in predicting in-hospital and 6-month mortality in UA/NSTEMI patients, although the GRACE and TIMI STEMI scores performed equally well in STEMI patients. The observed discriminative deficit of the TIMI UA/NSTEMI score likely results from the omission of key risk factors rather than from the relative simplicity of the scoring system.     

Accuracy of coalescent likelihood estimates: do we need more sites, more sequences, or more loci?

A computer simulation study has been made of the accuracy of estimates of Theta = 4Nemu from a sample from a single isolated population of finite size. The accuracies turn out to be well predicted by a formula developed by Fu and Li, who used optimistic assumptions. Their formulas are restated in terms of accuracy, defined here as the reciprocal of the squared coefficient of variation. This should be proportional to sample size when the entities sampled provide independent information. Using these formulas for accuracy, the sampling strategy for estimation of Theta can be investigated. Two models for cost have been used, a cost-per-base model and a cost-per-read model. The former would lead us to prefer to have a very large number of loci, each one base long. The latter, which is more realistic, causes us to prefer to have one read per locus and an optimum sample size which declines as costs of sampling organisms increase. For realistic values, the optimum sample size is 8 or fewer individuals. This is quite close to the results obtained by Pluzhnikov and Donnelly for a cost-per-base model, evaluating other estimators of Theta. It can be understood by considering that the resources spent collecting larger samples prevent us from considering more loci. An examination of the efficiency of Watterson's estimator of Theta was also made, and it was found to be reasonably efficient when the number of mutants per generation in the sequence in the whole population is less than 2.5.     

Diagnostic Accuracy of Apparent Diffusion Coefficient and 123I-Metaiodobenzylguanidine for Differentiation of Multiple System Atrophy and Parkinson’s Disease

Background

It is often hard to differentiate Parkinson’s disease (PD) and parkinsonian variant of multiple system atrophy (MSA-P), especially in the early stages. Cardiac sympathetic denervation and putaminal rarefaction are specific findings for PD and MSA-P, respectively.

Purpose

We investigated diagnostic accuracy of putaminal apparent diffusion coefficient (ADC) test for MSA-P and ¹²³I-metaiodobenzylguanidine (MIBG) scintigram for PD, especially in early-stage patients.

Methods

The referral standard diagnosis of PD and MSA-P were the diagnostic criteria of the United Kingdom Parkinson’s Disease Society Brain Bank Criteria and the second consensus criteria, respectively. Based on the referral standard criteria, diagnostic accuracy [area under the receiver-operator characteristic curve (AUC), sensitivity and specificity] of the ADC and MIBG tests was estimated retrospectively. Diagnostic accuracy of these tests performed within 3 years of symptom onset was also investigated.

Results

ADC and MIBG tests were performed on 138 patients (20 MSA and 118 PD). AUC was 0.95 and 0.83 for the ADC and MIBG tests, respectively. Sensitivity and specificity were 85.0% and 89.0% for MSA-P diagnosis by ADC test and 67.0% and 80.0% for PD diagnosis by MIBG test. When these tests were restricted to patients with disease duration ≤3 years, the sensitivity and specificity were 75.0% and 91.4% for the ADC test (MSA-P diagnosis) and 47.7% and 92.3% for the MIBG test (PD diagnosis).

Conclusions

Both tests were useful in differentiating between PD and MSA-P, even in the early stages. In early-stage patients, elevated putaminal ADC was a diagnostic marker for MSA-P. Despite high specificity of the MIBG test, careful neurological history and examinations were required for PD diagnosis because of possible false-negative results.     

Accuracy of radio-tracking to estimate activity and distances walked by European bison in the Bialowieża Forest, Poland

To determine the accuracy of radio-tracking estimates of activity and distances walked by European bisonBison bonasus (Linnaeus, 1758), we observed bison while simultaneously conducting radio-tracking in the Bialowie?a Forest (Poland). Single radio-tracking estimates often did not represent the actual activity of the bison, but the mean time spent active calculated from radio-tracking and direct observations did not differ significantly. Radio-tracking provided overestimates of the distances walked by bison when the animals walked between 0 and 25 m and underestimated the distances walked by bison if they walked further than 25 m in a radio-tracking interval. Activity was best estimated when radio-trackers were between 200 and 300 m from the bison. The mean activity calculated with a sampling interval of 15 min needed about 8 days of radio-tracking and the mean of distances walked about 35 tracking days to stabilise. We concluded that collars without activity sensors can measure the mean activity of bison but cannot represent the length of their activity bouts or the type of their activity and that our radio-tracking estimates of distances walked by bison needed to be corrected before further analyses.     

When Do Latent Class Models Overstate Accuracy for Diagnostic and Other Classifiers in the Absence of a Gold Standard?

Latent class models are increasingly used to assess the accuracy of medical diagnostic tests and other classifications when no gold standard is available and the true state is unknown. When the latent class is treated as the true class, the latent class models provide measures of components of accuracy including specificity and sensitivity and their complements, type I and type II error rates. The error rates according to the latent class model differ from the true error rates, however, and empirical comparisons with a gold standard suggest the true error rates often are larger. We investigate conditions under which the true type I and type II error rates are larger than those provided by the latent class models. Results from Uebersax (1988, Psychological Bulletin 104, 405-416) are extended to accommodate random effects and covariates affecting the responses. The results are important for interpreting the results of latent class analyses. An error decomposition is presented that incorporates an error component from invalidity of the latent class model.     

Evaluation of the Accuracy of the EasyTest? Malaria Pf/Pan Ag,a Rapid Diagnostic Test,in Uganda

In recent years, rapid diagnostic tests (RDTs) have been widely used for malaria detection, primarily because of their simple operation, fast results, and straightforward interpretation. The Asan EasyTest™ Malaria Pf/Pan Ag is one of the most commonly used malaria RDTs in several countries, including Korea and India. In this study, we tested the diagnostic performance of this RDT in Uganda to evaluate its usefulness for field diagnosis of malaria in this country. Microscopic and PCR analyses, and the Asan EasyTest™ Malaria Pf/Pan Ag rapid diagnostic test, were performed on blood samples from 185 individuals with suspected malaria in several villages in Uganda. Compared to the microscopic analysis, the sensitivity of the RDT to detect malaria infection was 95.8% and 83.3% for Plasmodium falciparum and non-P. falciparum, respectively. Although the diagnostic sensitivity of the RDT decreased when parasitemia was ≤500 parasites/µl, it showed 96.8% sensitivity (98.4% for P. falciparum and 93.8% for non-P. falciparum) in blood samples with parasitemia ≥100 parasites/µl. The specificity of the RDT was 97.3% for P. falciparum and 97.3% for non-P. falciparum. These results collectively suggest that the accuracy of the Asan EasyTest™ Malaria Pf/Pan Ag makes it an effective point-of-care diagnostic tool for malaria in Uganda.     

Accuracy of Urine Circulating Cathodic Antigen (CCA) Test for Schistosoma mansoni Diagnosis in Different Settings of C?te d'Ivoire

Background

Promising results have been reported for a urine circulating cathodic antigen (CCA) test for the diagnosis of Schistosoma mansoni. We assessed the accuracy of a commercially available CCA cassette test (designated CCA-A) and an experimental formulation (CCA-B) for S. mansoni diagnosis.

Methodology

We conducted a cross-sectional survey in three settings of Côte d''Ivoire: settings A and B are endemic for S. mansoni, whereas S. haematobium co-exists in setting C. Overall, 446 children, aged 8–12 years, submitted multiple stool and urine samples. For S. mansoni diagnosis, stool samples were examined with triplicate Kato-Katz, whereas urine samples were tested with CCA-A. The first stool and urine samples were additionally subjected to an ether-concentration technique and CCA-B, respectively. Urine samples were examined for S. haematobium using a filtration method, and for microhematuria using Hemastix dipsticks.

Principal Findings

Considering nine Kato-Katz as diagnostic ‘gold’ standard, the prevalence of S. mansoni in setting A, B and C was 32.9%, 53.1% and 91.8%, respectively. The sensitivity of triplicate Kato-Katz from the first stool and a single CCA-A test was 47.9% and 56.3% (setting A), 73.9% and 69.6% (setting B), and 94.2% and 89.6% (setting C). The respective sensitivity of a single CCA-B was 10.4%, 29.9% and 75.0%. The ether-concentration technique showed a low sensitivity for S. mansoni diagnosis (8.3–41.0%). The specificity of CCA-A was moderate (76.9–84.2%); CCA-B was high (96.7–100%). The likelihood of a CCA-A color reaction increased with higher S. mansoni fecal egg counts (odds ratio: 1.07, p<0.001). A concurrent S. haematobium infection or the presence of microhematuria did not influence the CCA-A test results for S. mansoni diagnosis.

Conclusion/Significance

CCA-A showed similar sensitivity than triplicate Kato-Katz for S. mansoni diagnosis with no cross-reactivity to S. haematobium and microhematuria. The low sensitivity of CCA-B in our study area precludes its use for S. mansoni diagnosis.