Our objective was to evaluate the performance of HIV testing algorithms based on WHO recommendations, using data from specimens collected at six HIV testing and counseling sites in sub-Saharan Africa ...(Conakry, Guinea; Kitgum and Arua, Uganda; Homa Bay, Kenya; Douala, Cameroon; Baraka, Democratic Republic of Congo). A total of 2,780 samples, including 1,306 HIV-positive samples, were included in the analysis. HIV testing algorithms were designed using Determine as a first test. Second and third rapid diagnostic tests (RDTs) were selected based on site-specific performance, adhering where possible to the WHO-recommended minimum requirements of ≥99% sensitivity and specificity. The threshold for specificity was reduced to 98% or 96% if necessary. We also simulated algorithms consisting of one RDT followed by a simple confirmatory assay. The positive predictive values (PPV) of the simulated algorithms ranged from 75.8% to 100% using strategies recommended for high-prevalence settings, 98.7% to 100% using strategies recommended for low-prevalence settings, and 98.1% to 100% using a rapid test followed by a simple confirmatory assay. Although we were able to design algorithms that met the recommended PPV of ≥99% in five of six sites using the applicable high-prevalence strategy, options were often very limited due to suboptimal performance of individual RDTs and to shared falsely reactive results. These results underscore the impact of the sequence of HIV tests and of shared false-reactivity data on algorithm performance. Where it is not possible to identify tests that meet WHO-recommended specifications, the low-prevalence strategy may be more suitable.
Creatinine is a parameter that is required to monitor renal function and is important to follow in patients under treatment with potentially toxic renal drugs, such as the anti-HIV drug Tenofovir. A ...point of care instrument to measure creatinine would be useful for patients monitoring in resource-limited settings, where more instruments that are sophisticated are not available. The StatSensor Xpress Creatinine (Nova Biomedical Cooperation, Waltham, MA, USA) point of care analyzer was evaluated for its diagnostic performance in indicating drug therapy change. Creatinine was measured in parallel using the Nova StatSensor Xpress Creatinine analyzer and the Vitros 5,1FS (Ortho Clinical Diagnostics, Inc, Rochester, USA), which served as reference standard. The precision (i.e., repeatability and reproducibility) and accuracy of the StatSensor Xpress Creatinine analyzer were calculated using a panel of specimens with normal, low pathological and high pathological values. Two different Nova StatSensor Xpress Creatinine analyzers were used for the assessment of accuracy using repeated measurements. The coefficient of variation of the StatSensor Xpress Creatinine analyzers ranged from 2.3 to 5.9% for repeatability and from 4.2 to 9.0% for between-run reproducibility. The concordance correlation agreement was good except for high values (>600 µmol/L). The Bland-Altman analysis in high pathological specimens suggests that the Nova StatSensor Xpress Creatinine test tends to underestimate high creatinine values (i.e., >600 µmol/L). The Nova StatSensor Xpress Creatinine analyzers showed acceptable to good results in terms of repeatability, inter-device reproducibility and between-run reproducibility over time using quality control reagents. The analyzer was found sufficiently accurate for detecting pathological values in patients (age >10 year) and can be used with a moderate risk of misclassification.
To estimate the proportion of invalid results generated by a CD4+ T-lymphocyte analyser used by Médecins Sans Frontières (MSF) in field projects and identify factors associated with invalid results.
...We collated 25,616 CD4+ T-lymphocyte test results from 39 sites in nine countries for the years 2011 to 2013. Information about the setting, user, training, sampling technique and device repair history were obtained by questionnaire. The analyser performs a series of checks to ensure that all steps of the analysis are completed successfully; if not, an invalid result is reported. We calculated the proportion of invalid results by device and by operator. Regression analyses were used to investigate factors associated with invalid results.
There were 3354 invalid test results (13.1%) across 39 sites, for 58 Alere PimaTM devices and 180 operators. The median proportion of errors per device and operator was 12.7% (interquartile range, IQR: 10.3-19.9) and 12.1% (IQR: 7.1-19.2), respectively. The proportion of invalid results varied widely by country, setting, user and device. Errors were not associated with settings, user experience or the number of users per device. Tests performed on capillary blood samples were significantly less likely to generate errors compared to venous whole blood.
The Alere Pima CD4+ analyser generated a high proportion of invalid test results, across different countries, settings and users. Most error codes could be attributed to the operator, but the exact causes proved difficult to identify. Invalid results need to be factored into the implementation and operational costs of routine CD4+ T-lymphocyte testing.
Creatinine is a parameter that is required to monitor renal function and is important to follow in patients under treatment with potentially toxic renal drugs, such as the anti-HIV drug Tenofovir. A ...point of care instrument to measure creatinine would be useful for patients monitoring in resource-limited settings, where more instruments that are sophisticated are not available. The StatSensor Xpress Creatinine (Nova Biomedical Cooperation, Waltham, MA, USA) point of care analyzer was evaluated for its diagnostic performance in indicating drug therapy change. Creatinine was measured in parallel using the Nova StatSensor Xpress Creatinine analyzer and the Vitros 5,1FS (Ortho Clinical Diagnostics, Inc, Rochester, USA), which served as reference standard. The precision (i.e., repeatability and reproducibility) and accuracy of the StatSensor Xpress Creatinine analyzer were calculated using a panel of specimens with normal, low pathological and high pathological values. Two different Nova StatSensor Xpress Creatinine analyzers were used for the assessment of accuracy using repeated measurements. The coefficient of variation of the StatSensor Xpress Creatinine analyzers ranged from 2.3 to 5.9% for repeatability and from 4.2 to 9.0% for between-run reproducibility. The concordance correlation agreement was good except for high values (>600 µmol/L). The Bland-Altman analysis in high pathological specimens suggests that the Nova StatSensor Xpress Creatinine test tends to underestimate high creatinine values (i.e., >600 µmol/L). The Nova StatSensor Xpress Creatinine analyzers showed acceptable to good results in terms of repeatability, inter-device reproducibility and between-run reproducibility over time using quality control reagents. The analyzer was found sufficiently accurate for detecting pathological values in patients (age >10 year) and can be used with a moderate risk of misclassification.
Thyroid-stimulating hormone (TSH) promotes expression of thyroid hormones which are essential for metabolism, growth, and development. Second-line drugs to treat tuberculosis (TB) can cause ...hypothyroidism by suppressing thyroid hormone synthesis. Therefore, TSH levels are routinely measured in TB patients receiving second-line drugs, and thyroxin treatment is initiated where indicated. However, standard TSH tests are technically demanding for many low-resource settings where TB is prevalent; a simple and inexpensive test is urgently needed.
As a proof of concept study TSH was measured in routinely collected sera at the University Medical Center Utrecht, Netherlands, using the TSH-CHECK-1 (VEDALAB, Alençon, France), a lateral-flow rapid immunochromatographic assay with a TSH cut-off value of 10 µIU/mL, the standard threshold for initiating treatment. These results were compared with TSH levels measured by a reference standard (UniCel DXi 800 imunoassay system, Beckman Coulter, USA). Sensitivity, specificity, and likelihood ratios were then calculated.
A total of 215 serum samples were evaluated: 107 with TSH values <10 µIU/mL and 108 with values ≥10 µIU/mL. TSH-CHECK-1 test sensitivity was found to be 100.0% (95% CI: 96.6-100.0) and specificity was 76.6% (95% CI: 67.5-84.3). Predictive values (PV) were modelled for different levels of prevalence. For a prevalence of 10% and 50%, the positive PV was 32.2% (95% CI: 25.0-39.7%) and 81.1% (95% CI: 75.0-85.5%), respectively; the negative PV was 100% (95% CI: 98.9-100%) and 100% (95% CI: 91.3-100%) respectively.
The TSH-CHECK-1 rapid test was practical and simple to perform but difficult to interpret on weak positive results. All sera with TSH≥10 µIU/mL were correctly identified, but the test lacked sufficient specificity. Given its excellent negative PV in this evaluation, the test shows promise for ruling out hypothyroidism. However, so far it appears that samples testing positive with TSH-CHECK-1 would require confirmation using another method.
Introduction: Although individual HIV rapid diagnostic tests (RDTs) show good performance in evaluations conducted by WHO, reports from several African countries highlight potentially significant ...performance issues. Despite widespread use of RDTs for HIV diagnosis in resource‐constrained settings, there has been no systematic, head‐to‐head evaluation of their accuracy with specimens from diverse settings across sub‐Saharan Africa. We conducted a standardized, centralized evaluation of eight HIV RDTs and two simple confirmatory assays at a WHO collaborating centre for evaluation of HIV diagnostics using specimens from six sites in five sub‐Saharan African countries.
Methods: Specimens were transported to the Institute of Tropical Medicine (ITM), Antwerp, Belgium for testing. The tests were evaluated by comparing their results to a state‐of‐the‐art reference algorithm to estimate sensitivity, specificity and predictive values.
Results: 2785 samples collected from August 2011 to January 2015 were tested at ITM. All RDTs showed very high sensitivity, from 98.8% for First Response HIV Card Test 1–2.0 to 100% for Determine HIV 1/2, Genie Fast, SD Bioline HIV 1/2 3.0 and INSTI HIV‐1/HIV‐2 Antibody Test kit. Specificity ranged from 90.4% for First Response to 99.7% for HIV 1/2 STAT‐PAK with wide variation based on the geographical origin of specimens. Multivariate analysis showed several factors were associated with false‐positive results, including gender, provider‐initiated testing and the geographical origin of specimens. For simple confirmatory assays, the total sensitivity and specificity was 100% and 98.8% for ImmunoComb II HIV 12 CombFirm (ImmunoComb) and 99.7% and 98.4% for Geenius HIV 1/2 with indeterminate rates of 8.9% and 9.4%.
Conclusions: In this first systematic head‐to‐head evaluation of the most widely used RDTs, individual RDTs performed more poorly than in the WHO evaluations: only one test met the recommended thresholds for RDTs of ≥99% sensitivity and ≥98% specificity. By performing all tests in a centralized setting, we show that these differences in performance cannot be attributed to study procedure, end‐user variation, storage conditions, or other methodological factors. These results highlight the existence of geographical and population differences in individual HIV RDT performance and underscore the challenges of designing locally validated algorithms that meet the latest WHO‐recommended thresholds.
Introduction: We evaluated the diagnostic accuracy of HIV testing algorithms at six programmes in five sub‐Saharan African countries.
Methods: In this prospective multisite diagnostic evaluation ...study (Conakry, Guinea; Kitgum, Uganda; Arua, Uganda; Homa Bay, Kenya; Doula, Cameroun and Baraka, Democratic Republic of Congo), samples from clients (greater than equal to five years of age) testing for HIV were collected and compared to a state‐of‐the‐art algorithm from the AIDS reference laboratory at the Institute of Tropical Medicine, Belgium. The reference algorithm consisted of an enzyme‐linked immuno‐sorbent assay, a line‐immunoassay, a single antigen‐enzyme immunoassay and a DNA polymerase chain reaction test.
Results: Between August 2011 and January 2015, over 14,000 clients were tested for HIV at 6 HIV counselling and testing sites. Of those, 2786 (median age: 30; 38.1% males) were included in the study. Sensitivity of the testing algorithms ranged from 89.5% in Arua to 100% in Douala and Conakry, while specificity ranged from 98.3% in Doula to 100% in Conakry. Overall, 24 (0.9%) clients, and as many as 8 per site (1.7%), were misdiagnosed, with 16 false‐positive and 8 false‐negative results. Six false‐negative specimens were retested with the on‐site algorithm on the same sample and were found to be positive. Conversely, 13 false‐positive specimens were retested: 8 remained false‐positive with the on‐site algorithm.
Conclusions: The performance of algorithms at several sites failed to meet expectations and thresholds set by the World Health Organization, with unacceptably high rates of false results. Alongside the careful selection of rapid diagnostic tests and the validation of algorithms, strictly observing correct procedures can reduce the risk of false results. In the meantime, to identify false‐positive diagnoses at initial testing, patients should be retested upon initiating antiretroviral therapy.
Regarding the query around whether the specimens were characterized correctly and whether this can be assessed from the information in our article, the characterization of specimens was done at the ...National HIV Reference Laboratory at the Institute of Tropical Medicine, Antwerp, Belgium, using the algorithm described in Figure 1. Some differences between our evaluation and that of the WHO prequalification remain: we collected samples prospectively versus WHO use of stored, well‐characterized samples; the reference standard differed slightly (e.g. we used only one enzyme‐linked immunosorbent as screening assay); our samples originated only from sub‐Saharan Africa; and we did not attempt to evaluate performance for HIV‐2 or during seroconversion, but had an overall larger sample size. The 2015 consolidated guidelines state that the testing strategies for diagnosis described have been developed assuming that all HIV serological assays used should have a sensitivity of >99% and specificity of >98% (lower bounds of the confidence interval) 5, which is why we used this indication as a benchmark in our discussion.
This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows:
To assess the diagnostic accuracy of commercial NS1 antigen detecting assays for acute dengue ...infection.
National guidance from the United Kingdom and the United States on community-acquired pneumonia in children states that chest radiographs are not recommended routinely in uncomplicated cases. The ...main reason in the ambulatory setting is that there is no evidence of a substantial impact on clinical outcomes. However clinical practice and adherence to guidance is multifactorial and includes the clinical context (developed vs. developing world), the confidence of the attending physician, the changing incidence of complications (according to the success of immunisation programs), the availability of alternative imaging (and its relationship to perceived risks of radiation) and the reliability of the interpretation of imaging. In practice, chest radiographs are performed frequently for suspected pneumonia in children. Time pressures facing clinicians at the front line, difficulties in distinguishing which children require admission, restricted bed numbers for admissions, imaging-resource limitations, perceptions regarding risk from procedures, novel imaging modalities and the probability of other causes for the child’s presentation all need to be factored into a guideline. Other drivers that often weigh in, depending on the setting, include cost-effectiveness and the fear of litigation. Not all guidelines designed for the developed world can therefore be applied to the developing world, and practice guidelines require regular review in the context of new information. In addition, radiologists must improve radiographic diagnosis of pneumonia, reach consensus on the interpretive terminology that clarifies their confidence regarding the presence of pneumonia and act to replace one imaging technique with another whenever there is proof of improved accuracy or reliability.
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