Evaluation Of Rapid Diagnostic Test Research Articles

Performance and Comparison of two Malaria Rapid Diagnostic Tests among Symptomatic Patients in Lagos, Southwest Nigeria

Malaria remains a public health problem in Sub Saharan Africa. Microscopic identification of Plasmodium spp. is the gold standard for malaria diagnosis. However, malaria rapid diagnostic test kits are also available for prompt diagnosis, effective treatment and are important in reducing morbidity and mortality associated with malaria especially among high-risk groups. The use of malaria rapid diagnostic tests (RDTs) has improved Plasmodium falciparum diagnosis, especially in settings where quality microscopy is not available. Field evaluation of RDTs would assist in confirming the potency, performance of the RDTs and in ruling out or confirming malaria parasite. In this study, the performance of two RDTs were assessed for malaria diagnosis, using thick and thin blood smears as the gold standard. A total of 1,271 patients suspected to have malaria who gave consent were enrolled in the study within six months at St Matthew”s Primary Health Center Amukoko in Ajeromi Ifelodun LGA of Lagos state. The study population age range between 2-67years. This is a cross-sectional study involving patients with history of malaria symptoms. The SD Bioline and First Response HRP2 based MRDTs were evaluated in this study. Of the patients 1,271 screened for malaria, 185 were slide positive for malaria parasites. Blood smears and HRP2 First response RDT showed malaria prevalence rate of 14.6%, while the HRP2 SD Bioline RDT showed prevalence rate of 15.5%. The SD Bioline HRP2 RDTs showed a sensitivity of 61.1%, specificity of 92.3%, PPV of 57.4% and NPV of 93.3%, while the First response RDT showed a sensitivity of 58.9%, specificity of 93.1%, PPV of 59.6% and NPV of 92.9%. In this study, the sensitivity of the RDT increased with parasite density (>1000p/µl showed sensitivity >90%). All the malaria rapid diagnostic test kits performed relatively well and can be used in emergencies. Concerning cost-effectiveness, using the malaria RDTs at the hospital is cheaper than light microscopy for diagnosing malaria. However, for malaria diagnosis, malaria RDT kits cannot be relied upon alone; hence, microscopic confirmation is always required.

Field evaluation of rapid diagnostic tests to determine dengue serostatus in Timor-Leste.

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 during a community serosurvey. 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.

Comparison of two malaria multiplex immunoassays that enable quantification of malaria antigens

BackgroundImmunoassay platforms that simultaneously detect malaria antigens including histidine-rich protein 2 (HRP2)/HRP3 and Plasmodium lactate dehydrogenase (pLDH), are useful epidemiological tools for rapid diagnostic test evaluation. This study presents the comparative evaluation of two multiplex platforms in identifying Plasmodium falciparum with presence or absence of HRP2/HRP3 expression as being indicative of hrp2/hrp3 deletions and other Plasmodium species. Moreover, correlation between the malaria antigen measurements performed at these platforms is assessed after calibrating with either assay standards or international standards and the cross-reactivity among Plasmodium species is examined.MethodsA 77-member panel of specimens composed of the World Health Organization (WHO) international Plasmodium antigen standards, cultured parasites for P. falciparum and Plasmodium knowlesi, and clinical specimens with mono-infections for P. falciparum, Plasmodium vivax, and Plasmodium malariae was generated as both whole blood and dried blood spot (DBS) specimens. Assays for HRP2, P. falciparum–specific pLDH (PfLDH), P. vivax–specific pLDH (PvLDH), and all human Plasmodium species Pan malaria pLDH (PanLDH) on the Human Malaria Array Q-Plex and the xMAP platforms were evaluated with these panels.ResultsThe xMAP showed a higher percent positive agreement for identification of hrp2-deleted P. falciparum and Plasmodium species in whole blood and DBS than the Q-Plex. For whole blood samples, there was a highly positive correlation between the two platforms for PfLDH (Pearson r = 0.9926) and PvLDH (r = 0. 9792), moderate positive correlation for HRP2 (r = 0.7432), and poor correlation for PanLDH (r = 0.6139). In Pearson correlation analysis between the two platforms on the DBS, the same assays were r = 0.9828, r = 0.7679, r = 0.6432, and r = 0.8957, respectively. The xMAP HRP2 assay appeared to cross-react with HRP3, while the Q-Plex did not. The Q-Plex PfLDH assay cross-reacted with P. malariae, while the xMAP did not. For both platforms, P. knowlesi was detected on the PvLDH assay. The WHO international standards allowed normalization across both platforms on their HRP2, PfLDH, and PvLDH assays in whole blood and DBS.ConclusionsQ-Plex and xMAP show good agreement for identification of P. falciparum mutants with hrp2/hrp3 deletions, and other Plasmodium species. Quantitative results from both platforms, normalized into international units for HRP2, PfLDH, and PvLDH, showed good agreement and should allow comparison and analysis of results generated by either platform.

Microbiology Assessments in Critically Ill Patients.

The prevalence of suspected or proven infections in critically ill patients is high, with a substantial attributable risk to in-hospital mortality. Coordinated guidance and interventions to improve the appropriate microbiological assessment for diagnostic and therapeutic decisions are therefore pivotal. Conventional microbiology follows the paradigm of "best practice" of specimen selection and collection, governed by laboratory processing and standard operating procedures, and informed by the latest developments and trends. In this regard, the preanalytical phase of a microbiological diagnosis is crucial since inadequate sampling may result in the incorrect diagnosis and inappropriate management. In addition, the isolation and detection of contaminants interfere with multiple intensive care unit (ICU) processes, which confound the therapeutic approach to critically ill patients. To facilitate bedside enablement, the microbiology laboratory should provide expedited feedback, reporting, and interpretation of results. Compared with conventional microbiology, novel rapid and panel-based diagnostic strategies have the clear advantages of a rapid turnaround time, the detection of many microorganisms including antimicrobial resistant determinants and thus promise substantial improvements in health care. However, robust data on the clinical evaluation of rapid diagnostic tests in presumed sepsis, sepsis and shock are extremely limited and more rigorous intervention studies, focusing on direct benefits for critically ill patients, are pivotal before widespread adoption of their use through the continuum of ICU stay. Advocating the use of these diagnostics without firmly establishing which patients would benefit most, how to interpret the results, and how to treat according to the results obtained, could in fact be counterproductive with regards to diagnostic "best practice" and antimicrobial stewardship. Thus, for the present, they may supplement but not yet supplant conventional microbiological assessments.

Comparative evaluation of rapid diagnostic test and real-time PCR in clinically suspected malaria

Background: India represents 3% related to the global malaria problem. Early diagnosis and treatment that are complete alongside preventive measures are modalities essential to managing the situation. Rapid diagnostic tests (RDTs) and polymerase chain reaction (PCR) that are malaria that is real-time be used to obtain an exceedingly really very early diagnosis in acutely febrile customers. Aims and Objectives: This study aims to gauge the effectiveness of RDT bloodstream that is utilized entire from clients clinically suspected of malaria and compare it with real-time PCR. Materials and Methods: The cross-sectional study is observationally done and made up of 158 patients admitted to Index Hospital, Indore, having a serious illness that is febrile and medical suspicion of malaria. RDT for malaria antigen and PCR that are real-time done in the bloodstream that is whole examples depending on kit guidelines. Results: There exists a difference that is significant the nice and examples which are negative by both techniques. Fast P = test is diagnostic PCR that is real-time RDT has been good in 62 (44%) clients, whereas, real-time PCR detected the parasite in 136 (91%) customers. RDT was in reality negative for malaria antigen in 16 (12.8%) consumers, in whom RT-PCR was good. RDT failed to identify Plasmodium falciparum antigen in RT-PCR samples that can be good. RT-PCR indicates basic greater sensitiveness (82.4–95% CI 79.2–84.5%) in diagnosing malaria set alongside the quick test is an antigen. The sensitiveness of RT-PCR in detecting P. falciparum had been also high (74.2%, 95% CI 71.4–77.2). This has greater specificity than RDT in detecting P. falciparum disease (91.3%, 95% CI 89.4–95.4) in detecting P. falciparum than RDT. Conclusion: RT-PCR has better efficacy to look for the presence of malaria parasites in acutely clients being febrile remain undiscovered by RDT. Therefore, it might be helpful for the verification of diagnoses and studies which are epidemiological.

Evaluation of rapid diagnostic test compared with ELISA for detection of hepatitis B surface antigen

Hepatitis B is a serious type of viral infection affecting millions of people throughout the world. Some of those who become Chronic carriers may progress to develop hepatocellular carcinoma and end stage liver disease. Therefore, early diagnosis and management is the need of time. Present study was aimed to compare the relative sensitivity and specificity of rapid ICT with ELISA for the detection of HBsAg.: One step rapid test for detection of HBsAg was performed on samples by Meriscreen HBsAg test from Meril Diagnostics. HbsAg ELISA was done by using SD HBsAg ELISA 3.0 from SD Biostandard diagnostics Private Ltd. This is assay for qualitative detection of HBsAg from human serum and plasma. Total 526 samples were analysed. Out of 64 positive samples, 62 were positive by rapid card test, and 2 were negative. Out of 462 negative samples, 461 were negative by rapid card test, and one was positive. We found the sensitivity and specificity of rapid ICT was 96.8% and 99.7% as compared to ELISA. The results are very much similar to several previous studies done in India and other parts of world. It would be wise to validate this point of care tests with a standard ELISA or other specific tests whenever feasible.

Evaluation of rapid diagnostic tests and Enzyme Linked Immunoassay in the detection of malaria in ancient human remains

Malaria has had a significant impact on humans for millennia, yet it has proved difficult to conclusively identify. To-date, there is no absolute way to quantify and confirm the presence of malaria in ancient human remains. Clinically, rapid diagnostic tests (RDTs) are regularly used as a cost-effective and efficient method of identifying the presence of Plasmodium parasite antigens (i.e. malaria) in blood samples. In this study, we evaluate two different immunoassay methods used in the detection of malaria antigens on ancient human skeletal remains, utilising the current generation of RDTs, as well as a highly sensitive histidine rich protein 2 double-site sandwich Enzyme Linked Immunoassay (HRP2-ELISA). Our investigation using RDTs and ELISA immunoassay has produced mixed results, providing new input into, and raising questions regarding, the efficacy and reliability of these immunoassays in the detection of the Plasmodium parasite antigens in ancient bones. Specific protocols to adapt the tests to bone samples must be adhered to, and the sensitivity of the test is crucial to identification. Further optimization of these methods would provide a cost effective avenue of conclusively identifying malaria in the past, and should continue to be pursued. We found that the QDx Malaria Card tests DiaSys produced the highest number of positive results, with 50% of the samples testing positive for malaria with these particular tests.

Evaluation of rapid diagnostic tests and assessment of risk factors in drug-resistant pulmonary tuberculosis.

Background:Early diagnosis and treatment of drug-resistant tuberculosis (TB) is crucial to halt the spread of drug resistance in the community.Aim:The aim of the study was to compare rapid diagnostic tests (GeneXpert and line probe assay, LPA) with conventional liquid culture for the diagnosis of drug-resistant TB and to assess the risk factors for it.Method:This cross-sectional study recruited 229 multidrug-resistant TB suspects who were sputum smear positive. They were evaluated by the rapid diagnostic tests and sensitivity, specificity, positive predictive value and negative predictive value were calculated for drug resistance detection as compared to liquid culture drug susceptibility testing. The risk factors for the development of drug resistance were also assessed and the P value of < 0.05 was considered significant.Results:In the final comparison, 193 samples were included. The sensitivity and specificity of GeneXpert for detection of drug resistance (rifampicin) was 100% (95% confidence interval, CI: 88.8–100%) and 99.4% (95% CI: 96.6–99.9%), respectively. Whereas sensitivity and specificity of LPA was 94.3% (95% CI: 80.8–99.3%) and 100% (95% CI: 97.7–100%), respectively. Only three discordant samples were observed. Defaulting to antitubercular therapy, contact with resistant TB, and disseminated disease were found to be significant risk factors for the development of drug-resistant TB with high statistical significance (P value < 0.05).Conclusion:Both rapid diagnostic tests have very high sensitivity and specificity for detection of drug resistance in sputum smear positive with the advantage of short turn-around time. Defaulting to antitubercular therapy, contact with resistant TB, and disseminated disease are significant risk factors for drug resistance.

English

English

Deletions of pfhrp2 and pfhrp3 genes of Plasmodium falciparum from Honduras, Guatemala and Nicaragua

BackgroundMalaria remains a public health problem in some countries of Central America. Rapid diagnostic tests (RDTs) are one of the most useful tools to assist in the diagnosis of malaria in remote areas. Since its introduction, a wide variety of RDTs have been developed for the detection of different parasite antigens. PfHRP2 is the most targeted antigen for the detection of Plasmodium falciparum infections. Genetic mutations and gene deletions are important factors influencing or affecting the performance of rapid diagnostic tests.MethodsIn order to demonstrate the presence or absence of the pfhrp2 and pfhrp3 genes and their flanking regions, a total of 128 blood samples from patients with P. falciparum infection from three Central American countries were analysed through nested or semi-nested PCR approaches.ResultsIn total, 25.8 and 91.4% of the isolates lacked the region located between exon 1 and exon 2 of pfhrp2 and pfhrp3 genes, respectively. Parasites from the three countries showed deletions of one or both genes. The highest proportion of pfhrp2 deletions was found in Nicaragua while the isolates from Guatemala revealed the lowest number of pfhrp2 deletions. Parasites collected from Honduras showed the highest proportion of phfrp3 absence (96.2%). Twenty-one percent of isolates were double negative mutants for the exon 1–2 segment of both genes, and 6.3% of isolates lacked the full-length coding region of both genes.ConclusionsThis study provides molecular evidence of the existence of P. falciparum isolates lacking the pfhrp2 and pfhrp3 genes, and their flanking regions, in Honduras, Guatemala and Nicaragua. This finding could hinder progress in the control and elimination of malaria in Central America. Continuous evaluation of RDTs and molecular surveillance would be recommended.

A diagnostic performance evaluation of rapid diagnostic tests and microscopy for malaria diagnosis using nested polymerase chain reaction as reference standard in a tertiary hospital in Jos, Nigeria.

Rapid diagnostic tests are frequently used in healthcare settings across Nigeria for diagnosis of Plasmodium falciparum malaria, which is the commonest form of malaria in the country. In this study, the performance of a rapid diagnostic test (RDT) was compared with expert microscopy using the polymerase chain reaction (PCR) as the reference standard in a tertiary hospital in Jos, Nigeria. This study was a prospective, cross-sectional, hospital-based study. A total of 200 participants of all ages presenting to Jos University Teaching Hospital with a history of fever or an axillary temperature of >37.5°C were recruited. Blood specimens were collected and malaria testing was done using RDT, microscopy and PCR. The prevalence of malaria in this study was 17%, 15% and 13% by PCR, microscopy and RDT, respectively. Compared with microscopy, RDT had lower sensitivity of 75% (95% CI: 56.60-88.54) vs 88.24% (95% CI: 72.55-96.70), lower specificity of 98.80% (95% CI: 95.72-99.85) vs 100.0% (95% CI: 97.80-100.0), lower positive predictive value 92.31 (95% CI: 74.89-97.97) vs 100 (95% CI: 98.0-100.0), and lower negative predictive value 95.35 (95% CI: 91.83-97.39) versus 97.65 (95% CI: 94.30-99.05). The diagnostic performance of expert microscopy was better than RDT in the diagnosis of Plasmodium falciparum malaria. Quality assurance procedures such as using expert microscopy to cross-check a proportion of RDT negative results in patients with clinical features of malaria is desirable.

Malaria in children of Tshimbulu (Western Kasai, Democratic Republic of the Congo): epidemiological data and accuracy of diagnostic assays applied in a limited resource setting.

BackgroundThe literature data on malaria in Western Kasai, DRC, are limited and inadequate. A recent molecular survey there has detected Plasmodium ovale and Plasmodium malariae as mixed infections with Plasmodium falciparum. In Tshimbulu, Western Kasai, during a humanitarian initiative designed to provide children with free preventive screening and to reduce the local high malaria death rate, accurate species identification was performed, in order to collect unambiguous epidemiological data and to evaluate the reliability of locally applied diagnostics.MethodsFinger pricks provided fresh blood for microscopic analysis (MA), for rapid diagnostic test (RDT) and for molecular diagnostics (MD). MA and RDT were first performed by the local team and then a re-interpretation of the results (on the same slides and on RDT’s taken pictures) was conducted in Italy, where MD were performed.ResultsThe analysis was conducted on 306 children; RDT found 80.9 % as P. falciparum-positive (37.4 % as two-band positive, P. falciparum single infection). MA identified a further four children as positive to P. falciparum and six co-infections with P. ovale. The second RDT evaluation confirmed a similar infection rate (78.2 %) but interpreted as two-band positive a significantly higher share of tests (56.8 %). MA confirmed 80.0 % of the children as malaria positive and, in addition to P. falciparum, identified P. malariae (13.8 %), P. vivax (3.4 %) and P. ovale (2.4 %), and detected Babesia microti in 19 smears. MD confirmed all of the species found (Babesia microti included), classified as mono-infection with P. falciparum a rate of spots comparable to MA revision, and identified all P. ovale as Plasmodium ovale wallikeri. The RDT used locally proved 93.1 % sensitive and 92.1 % specific for P. falciparum.ConclusionsThe malaria prevalence among the children and the presence of four Plasmodium species, highlighted in this study, identified a sanitary issue which proved to be more alarming than expected, as it was worsened by the unpredictable presence of P. vivax and Babesia microti (never before reported in DRC). Each diagnostic tool showed its point of weakness. Therefore, the most correct approach is by the combined use of different, locally available, diagnostic tools.

Performance evaluation of rapid diagnostic test for malaria in high malarious districts of Amhara region, Ethiopia

Performance evaluation of rapid diagnostic test for malaria in high malarious districts of Amhara region, Ethiopia

Evaluating the use of microscopic examination and rapid diagnostic tests to diagnose malaria in North Central Nigeria

The global impact of malaria has spurred interest in developing prompt and accurate diagnostic strategies to provide an effective management of the disease. The aim of this study was to compare rapid diagnostic tests (RDTs) for malaria with routine microscopy. Samples were collected randomly from 364 febrile out-patients with clinical suspicion of malaria from four hospitals in North Central Nigeria. Results from the rapid diagnostic kits were analysed and compared to those obtained by general microscopy. Of the 364 out-patients involved in the study, 218 (59.89%) tested positive for &lt;em&gt;Plasmodium falciparum&lt;/em&gt; by RDTs, whereas 263 (72.256%) tested positive by microscopy. There are significant differences (P&amp;lt;0.05) in infection rates between RDT and microscopy. The sensitivity, specificity and negative predictive values of RDTs compared to microscopy are low, while the positive predictive value is high. Evaluation of RDTs against the parasite-positive panel with parasite densities of &amp;lt;1000 parasites/μL, between 1000-5000 parasites/μL and above 5000 parasites/ μL was 11.73, 30.61, 57.65% for RDTs compared to 6.11, 27.95 and 65.94% for microscopy, respectively. Test line intensity increases with increase in parasite densities for both methods.

A country-wide field evaluation of rapid diagnostic test for meningococcal meningitis

We comment on a unique country-wide scale field evaluation of rapid diagnostic test (RDT) for meningococcal meningitis in Niger. The authors reported the good sensitivity and specificity of the test, and the reliability of results obtained in the field by non-specialized health staff. This finding allows us to consider RDT as a good candidate laboratory tool to be used for the case-based surveillance system, post introduction of the new conjugate A vaccine (MenAfriVac) in the African meningitis belt countries. In addition, RDT is also a potential point of care test to improve the management of meningitis patients.

Evaluation of Rapid Diagnostic Tests for Rabies Diagnosis in Nigeria

Evaluation of Rapid Diagnostic Tests for Rabies Diagnosis in Nigeria

Reliability of rapid diagnostic test for diagnosing peripheral and placental malaria in an area of unstable malaria transmission in Eastern Sudan

BackgroundDiagnosing Plasmodium falciparum malaria during pregnancy is a great challenge for clinicians because of the low density of parasites in the peripheral blood and parasite sequestration in the placenta. Nevertheless, few data on the use of malaria rapid diagnostic test (RDT) during pregnancy have been published.MethodsP. falciparum infections were assessed in 156 febrile pregnant women by microscopic examination of their blood smears and by RDT and polymerase chain reactions (PCR). In addition, 150 women were assessed at the time of delivery by microscopy, RDT, PCR and placental histology investigations. The study was conducted at the Gadarif Hospital, Eastern Sudan. The SD Bioline P. f / P. v (Bio Standard Diagnostics, Gurgaon, Korea) RDT kit was evaluated in this study.ResultsAmong the febrile pregnant women, 17 (11.0%), 26 (16.7%) and 18 (11.5%) positive cases of P. falciparum were detected by microscopy, RDT, and PCR, respectively. The sensitivity and specificity of the microscopy was 94.4% and 100%, respectively. The corresponding values for RDT evaluation were 83.3% and 92.0%, as compared with PCR as the gold standard.While there were no detected cases of malaria by microscopic examination of blood smears, 27 (18.0%), 21(14.0%) and 46 (30.7%) out of the 150 placentae investigated had P. falciparum as determined by RDT, PCR, and histology, respectively. The sensitivity and specificity for RDT was 17.4% and 81.7%, respectively. The corresponding values for PCR were 6.5% and 82.7%, where histology was used as the gold standard.ConclusionsThe RDT kit used in this study has poor performance for peripheral and placental P. falciparum malaria detection in this setting.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1092363465928479

Comparative Evaluation of Bivalent Malaria Rapid Diagnostic Tests versus Traditional Methods in Field with Special Reference to Heat Stability Testing in Central India

BackgroundMalaria presents a diagnostic challenge in areas where both Plasmodium falciparum and P.vivax are co-endemic. Bivalent Rapid Diagnostic tests (RDTs) showed promise as diagnostic tools for P.falciparum and P.vivax. To assist national malaria control programme in the selection of RDTs, commercially available seven malaria RDTs were evaluated in terms of their performance with special reference to heat stability.Methodology/Principal FindingsThis study was undertaken in four forested districts of central India (July, 2011– March, 2012). All RDTs were tested simultaneously in field along with microscopy as gold standard. These RDTs were stored in their original packing at 25°C before transport to the field or they were stored at 35°C and 45°C upto 100 days for testing the performance of RDTs at high temperature. In all 2841 patients with fever were screened for malaria of which 26% were positive for P.falciparum, and 17% for P.vivax. The highest sensitivity of any RDT for P.falciparum was 98% (95% CI; 95.9–98.8) and lowest sensitivity was 76% (95% CI; 71.7–79.6). For P.vivax highest and lowest sensitivity for any RDT was 80% (95% CI; 94.9 - 83.9) and 20% (95% CI; 15.6–24.5) respectively. Heat stability experiments showed that most RDTs for P.falciparum showed high sensitivity at 45°C upto 90 days. While for P.vivax only two RDTs maintained good sensitivity upto day 90 when compared with RDTs kept at room temperature. Agreement between observers was excellent for positive and negative readings for both P.falciparum and P.vivax (Kappa >0.6–0.9).ConclusionThis is first field evaluation of RDTs regarding their temperature stability. Although RDTs are useful as diagnostic tool for P.falciparum and P.vivax even at high temperature, the quality of RDTs should be regulated and monitored more closely.

Estimating the True Accuracy of Diagnostic Tests for Dengue Infection Using Bayesian Latent Class Models

BackgroundAccuracy of rapid diagnostic tests for dengue infection has been repeatedly estimated by comparing those tests with reference assays. We hypothesized that those estimates might be inaccurate if the accuracy of the reference assays is not perfect. Here, we investigated this using statistical modeling.Methods/Principal FindingsData from a cohort study of 549 patients suspected of dengue infection presenting at Colombo North Teaching Hospital, Ragama, Sri Lanka, that described the application of our reference assay (a combination of Dengue IgM antibody capture ELISA and IgG antibody capture ELISA) and of three rapid diagnostic tests (Panbio NS1 antigen, IgM antibody and IgG antibody rapid immunochromatographic cassette tests) were re-evaluated using Bayesian latent class models (LCMs). The estimated sensitivity and specificity of the reference assay were 62.0% and 99.6%, respectively. Prevalence of dengue infection (24.3%), and sensitivities and specificities of the Panbio NS1 (45.9% and 97.9%), IgM (54.5% and 95.5%) and IgG (62.1% and 84.5%) estimated by Bayesian LCMs were significantly different from those estimated by assuming that the reference assay was perfect. Sensitivity, specificity, PPV and NPV for a combination of NS1, IgM and IgG cassette tests on admission samples were 87.0%, 82.8%, 62.0% and 95.2%, respectively.ConclusionsOur reference assay is an imperfect gold standard. In our setting, the combination of NS1, IgM and IgG rapid diagnostic tests could be used on admission to rule out dengue infection with a high level of accuracy (NPV 95.2%). Further evaluation of rapid diagnostic tests for dengue infection should include the use of appropriate statistical models.

Field evaluation of rapid diagnostic tests for malaria in Yaounde, Cameroon

Rapid diagnostic tests (RDTs) are affordable, alternative diagnostic tools. The present study aimed to evaluate RDTs available in Cameroon and compare their characteristics to follow the parasitological response of patients for 28 days. Malaria diagnosis was assessed in 179 febrile patients using conventional microscopy as the reference method. Parascreen detects both Plasmodium falciparum-specific histidine-rich protein 2 (Pf HRP-2) and Pan-specific plasmodial lactate dehydrogenase (pLDH) in all four human Plasmodium spp. Diaspot is based on the detection of Pf HRP-2. OptiMAL-IT (pLDH specific for P. falciparum and pLDH for all four human Plasmodium spp.) was assessed for comparison. The reliability of RDTs was evaluated by calculating the sensitivity, specificity, positive predictive value, negative predictive value, false-positive rate, false-negative rate, and likelihood ratio. The clinical outcome of 18 children treated with atovaquone–proguanil and followed for 28 days was evaluated using microscopy and RDTs. Of 179 samples, 133 (74.3%) were pure P. falciparum-positive smears, 4 (2.2%) pure P. malariae-positive smears, and 42 (23.5%) negative smears. Parascreen and Diaspot had high sensitivity (>92%) and positive predictive values (>94%). The specificities for Parascreen and Diaspot were 81.0% and 90.5%, respectively. The false-positive rates and the false-negative rates were 19.0% and 4.5% for Parascreen and 9.5% and 8.3% for Diaspot, respectively. Most false-negatives occurred in samples with low parasitaemia (<500 asexual parasites/μL). The performance of RDTs was better at higher parasitaemia (>500 asexual parasites/μL). Four pure P. malariae were only detected by the pan-Plasmodium bands of Parascreen and OptiMAL-IT. In blood samples from patients treated and followed-up for 28 days, HRP2-based RDTs remained positive in most samples until Day 28. Despite negative smears, OptiMAL-IT remained positive in several patients until Day 7 but was negative in all patients from Day 14 onwards. RDTs can improve the management of febrile patients. The validity, ease of use, and cost of HRP2-based tests were comparable. However, one of the current weaknesses of the RDT-based strategy using the tests available in Cameroon is inadequate sensitivity for low parasitaemia. In some cases, RDT results may require correct interpretation based on clinical history, clinical examination, and microscopic diagnosis.