Performance Of Rapid Diagnostic Tests Research Articles

Comparison of malaria diagnostic methods for detection of asymptomatic Plasmodium infections among pregnant women in northwest Ethiopia

BackgroundMalaria in pregnancy remains a major public health problem in the globe, especially in sub-Saharan Africa. In malaria endemic areas, most pregnant women remain asymptomatic, but malaria could still cause complications on the mother and her offspring; as well as serve as reservoirs to transmit infection. Despite these effects, no attention is given to the diagnosis of asymptomatic Plasmodium infections (APIs) using highly sensitive and specific laboratory diagnostic tools in Ethiopia. Therefore, the goal of this study was to compare the performance of Rapid Diagnostic Test (RDT), microscopy and real-time polymerase chain reaction (RT-PCR) to detect APIs among pregnant women.MethodsA health facility based cross -sectional study was conducted among pregnant women attending antenatal care at Fendeka town health facilities Jawi district, northwest Ethiopia from February to March, 2019. A total of 166 participants were enrolled by using convenient sampling technique. Socio-demographic features were collected using a semi structured questionnaire. Dried blood spot (DBS) samples were collected for molecular analysis. Asymptomatic Plasmodium infection on pregnant women was diagnosed using RDT, microscopy and RT-PCR. Descriptive statistics were used to determine the prevalence of APIs. Method comparison was performed, and Cohen’s kappa coefficient (k) was used to determine the degree of agreement among the diagnostic methods. Parasite densities were also calculated.ResultsThe prevalence of API was 9.6%, 11.4% and 18.7% using RDT, microscopy and RT-PCR, respectively. The overall proportion of API was 19.3%. Sensitivity of the RDT was 83.3% as compared with microscopy. Rapid Diagnostic Test and microscopy also showed sensitivity of 50% and 60%, respectively, as compared with RT-PCR. The mean parasite density was 3213 parasites/µl for P falciparum and 1140 parasites/µl of blood for P. vivax.ConclusionPrevalence of API in the study area was high. Both RDT and microscopy had lower sensitivity when compared with RT-PCR. Therefore, routine laboratory diagnosis of API among pregnant women should be given attention and done with better sensitive and specific laboratory diagnostic tools.

Evaluation of Malaria Rapid Diagnostic Test Performance and pfhrp2 Deletion in Tanzania School Surveys, 2017.

As part of malaria nationwide monitoring and evaluation initiatives, there is an increasing trend of incorporating malaria rapid diagnostic tests (mRDTs) in surveys conducted within primary schools to detect malaria parasites. However, mRDTs based on the detection of histidine-rich protein 2 (HRP2) are known to yield false-positive results due to persistent antigenemia, and false-negative results may result from low parasitemia or Plasmodium falciparum hrp2/3 gene deletion. We evaluated diagnostic performance of an HRP2 and pan-parasite lactate dehydrogenase (HRP2/pLDH) mRDT against polymerase chain reaction (PCR) for detection of P. falciparum among 17,051 primary school-age children from eight regions of Tanzania in 2017. According to PCR, the prevalence of P. falciparum was 19.2% (95% CI: 18.6-19.8). Using PCR as reference, the sensitivity and specificity of mRDT was 76.2% (95% CI: 74.7-77.7) and 93.9% (95% CI: 93.5-94.3), respectively. Test agreement was lowest in low transmission areas, where true-positive mRDTs were outnumbered by false-negatives due to low parasitemia. Discordant samples (mRDT-negative but PCR-positive) were screened for pfhrp2/3 deletion by real-time PCR. Among those with a parasite density sufficient for analysis, pfhrp2 deletion was confirmed in 60 samples, whereas pfhrp3 deletion was confirmed in two samples; one sample had both pfhrp2 and pfhrp3 deletions. The majority of samples with gene deletions were detected in the high-transmission Kagera region. Compared with mRDTs, PCR and other molecular methods offer increased sensitivity and are not affected by pfhrp2/3 deletions, making them a useful supplement to mRDTs in schools and other epidemiological surveys.

Comparison of SD Bioline Malaria Ag Pf/Pan and Acro Malaria P.f./P.v./Pan with Microscopy and Real Time PCR for the Diagnosis of Human Plasmodium Species.

The early diagnosis of malaria is crucial to controlling morbidity and mortality. The World Health Organization (WHO) recommends diagnosing malaria either using light microscopy or a malaria rapid diagnostic test (RDT). Most RDTs use antibodies to detect two P. falciparum histidine-rich proteins named PfHRP2 and PfHRP3. However, false-negative results are known to occur due to the poor performance of RDTs depending on the species and the deletion of the Pfhrp2 and Pfhrp3 genes. This study evaluated new malaria RDTs for the detection of the human Plasmodium species. The Acro Malaria P.f./P.v./Pan Rapid Test Cassette allows the qualitative detection of parasite antigens, such as PfHRP2 specific to Plasmodium falciparum, PvLDH specific to Plasmodium vivax, and/or panLDH Plasmodium genus lactate dehydrogenase, in the blood of infected individuals. This RDT was assessed against 229 samples collected from imported malaria cases, mainly from Africa. The samples were previously diagnosed using light microscopy and RDT (SD Malaria Ag P.f./Pan, SD Bioline Alere Abbott), then confirmed using real time PCR. The two RDTs were evaluated using a comparison with real time PCR as the reference method, and their performances were compared with each other. Compared to SD RDT, the Acro RDT showed a better sensitivity to P. falciparum (96.8% vs. 89.8%), P. vivax (78.6% vs. 64.3%), P. ovale (73.7% vs. 5.3%), and P. malariae (20.0% vs. 0%). The respective specificities of the Acro RDT and SD RDT are 90.7% vs. 95.3% to P. falciparum, 100% to P. vivax, and 100% vs. 100% to Plasmodium genus. Therefore, Acro RDT showed better performance in the identification of P. ovale and low parasitaemia of P. falciparum. In addition, Acro RDT has the advantage of detecting PvLDH-specific antigens. The Acro Malaria RDT presents the benefits of detecting a P. falciparum antigen (PfHRP2) and a P. vivax antigen (PvLDH) with high sensitivity (96.8% and 73.7%, respectively) and specificity (90.7% and 100%, respectively). Acro Malaria P.f./P.v./Pan rapid diagnostic tests could be effectively used in endemic areas, especially when microscopic examination cannot be performed.

Conducting active screening for human African trypanosomiasis with rapid diagnostic tests: The Guinean experience (2016-2021).

Strategies to detect Human African Trypanosomiasis (HAT) cases rely on serological screening of populations exposed to trypanosomes. In Guinea, mass medical screening surveys performed with the Card Agglutination Test for Trypanosomiasis have been progressively replaced by door-to-door approaches using Rapid Diagnostic Tests (RDTs) since 2016. However, RDTs availability represents a major concern and medical teams must often adapt, even in the absence of prior RDT performance evaluation. For the last 5 years, the Guinean HAT National Control Program had to combine three different RDTs according to their availability and price: the SD Bioline HAT (not available anymore), the HAT Sero-K-SeT (most expensive), and recently the Abbott Bioline HAT 2.0 (limited field evaluation). Here, we assess the performance of these RDTs, alone or in different combinations, through the analysis of both prospective and retrospective data. A parallel assessment showed a higher positivity rate of Abbott Bioline HAT 2.0 (6.0%, n = 2,250) as compared to HAT Sero-K-SeT (1.9%), with a combined positive predictive value (PPV) of 20.0%. However, an evaluation of Abbott Bioline HAT 2.0 alone revealed a low PPV of 3.9% (n = 6,930) which was surpassed when using Abbott Bioline HAT 2.0 in first line and HAT Sero-K-SeT as a secondary test before confirmation, with a combined PPV reaching 44.4%. A retrospective evaluation of all 3 RDTs was then conducted on 189 plasma samples from the HAT-NCP biobank, confirming the higher sensitivity (94.0% [85.6-97.7%]) and lower specificity (83.6% [76.0-89.1%]) of Abbott Bioline HAT 2.0 as compared to SD Bioline HAT (Se 64.2% [52.2-74.6%]-Sp 98.4% [94.2-99.5%]) and HAT Sero-K-SeT (Se 88.1% [78.2-93.8%]-Sp 98.4% [94.2-99.5%]). A comparison of Abbott Bioline HAT 2.0 and malaria-RDT positivity rates on 479 subjects living in HAT-free malaria-endemic areas further revealed that a significantly higher proportion of subjects positive in Abbott Bioline HAT 2.0 were also positive in malaria-RDT, suggesting a possible cross-reaction of Abbott Bioline HAT 2.0 with malaria-related biological factors in about 10% of malaria cases. This would explain, at least in part, the limited specificity of Abbott Bioline HAT 2.0. Overall, Abbott Bioline HAT 2.0 seems suitable as first line RDT in combination with a second HAT RDT to prevent confirmatory lab overload and loss of suspects during referral for confirmation. A state-of-the-art prospective comparative study is further required for comparing all current and future HAT RDTs to propose an optimal combination of RDTs for door-to-door active screening.

Evaluation of the Performance of Rapid Diagnostic Tests for Malaria Diagnosis and Mapping of Different Plasmodium Species in Mali.

The first-line diagnosis of malaria in Mali is based on the use of rapid diagnostic tests (RDT) that detect the Histidin Rich Protein 2 (HRP2) antigen specific to Plasmodium falciparum. Our study, based on a real-time polymerase chain reaction (qPCR) gold standard, aimed to describe the distribution of the Plasmodium species in each administrative region of Mali and to assess the performance of RDTs. We randomly selected 150 malaria-negative and up to 30 malaria-positive RDTs in 41 sites distributed in 9 regions of Mali. DNA extracted from the RDT nitrocellulose strip was assayed with a pan-Plasmodium qPCR. Positive samples were then analyzed with P. falciparum-, P. malariae-, P. vivax-, or P. ovale-specific qPCRs. Of the 1496 RDTs, 258 (18.6%) were positive for Plasmodium spp., of which 96.9% were P. falciparum. The P. vivax prevalence reached 21.1% in the north. RDT displayed acceptable diagnostic indices; the lower CI95% bounds of Youden indices were all ≥0.50, except in the north (Youden index 0.66 (95% CI [0.44-0.82]) and 0.63 (95% CI [0.33-0.83]. Overall, RDT diagnostic indices are adequate for the biological diagnosis of malaria in Mali. We recommend the use of RDTs detecting P. vivax-specific antigens in the north.

Benefits of Lot Testing to Improve the Quality of Malaria Rapid Diagnostic Tests in India.

Since 2010, malaria rapid diagnostic tests (RDTs) are widely used to detect malaria. The Indian Council of Medical Research-National Institute of Malaria Research performed lot testing (LT) according to WHO procedures since 2016. Lot testing is performed to evaluate the lot-to-lot variation in performance of malaria RDTs. Four sets of positive quality control (QC) panels for P. falciparum (Pf) and P. vivax (Pv) and 10 negative panels tested RDTs. RDTs were reported as pass, failed, or deferred on the basis of WHO criteria. In the past 5 years, 275 lots containing 15,488 RDT kits for malaria diagnosis were subjected to LT. The monovalent RDTs (n = 1,216), based on either Pf histidine rich protein 2 (HRP2) or Pan-Plasmodium lactate dehydrogenase (Pan-pLDH) antigens, showed 90.4% sensitivity and 100% specificity, whereas RDTs based on HRP2 + Pan-pLDH or HRP2 + pLDH (n = 13,924) had sensitivity 95.6% and specificity 99.5%, respectively. RDTs based on PfHRP2 + Pv-pLDH + Pan-pLDH (n = 348) had 100% sensitivity and specificity. In a comparison between HRP2 + pLDH or HRP2 + Pan-pLDH to HRP2 + pLDH + Pan-pLDH RDTs, it was found that the sensitivity of PfHRP2 with Pan-pLDH RDTs (n = 2,382) was only 83%. Of the 275 lots analyzed, 15 lots of PfHRP2 with Pan-pLDH were deferred. The QC panel for Pf revealed a faint Pan band in the tested lots, which is a cause for concern. The results of deferred lots were reported to concerned government agencies. Quality-compromised RDTs may lead to an incorrect diagnosis. It is critical to have a QC system in place for effective malaria management.

Prevalence of malaria and comparative diagnostic performance of malaria rapid diagnostic test against microscopy in Nasarawa-west senatorial District, Nasarawa, Nigeria

Malaria is a vector-borne parasitic disease caused by Plasmodium species, and transmitted by the bite of an infected female anopheles mosquito. It remains a major public health challenge in Sub-Saharan Africa, a major cause of mortality and morbidity, especially in children and pregnant women. This study evaluated the prevalence of malaria and the comparative performance of rapid diagnostic test (RDT) against Microcopy, the gold standard. A total of 385 febrile consenting patients attending randomly selected health facilities in Nasarawa-West Senatorial District were recruited using simple random sampling technique. Malaria parasite tests were conducted using RDT and microscopy technique. Of the 385 samples tested, 115 (29.9%; 95% CI = 25.34 to 34.71%) were positive by microscopy and 103 (26.8%) were positive by RDT. The RDT had a sensitivity of 89.6% (95% CI = 82.48% to 94.49%), specificity of 100.00% (95% CI = 98.64% to 100.00%), Positive Predictive Value (PPV) of 100.00% (95% CI = 96.48% to 100.00%); and Negative Predictive Value (NPV) of 95.8% (95% CI = 92.94% to 97.46%). The accuracy of the RDT was 96.88% (95% CI = 94.62 to 98.38%). Thus, the high diagnostic performance of SD Bioline indicates that it can be effectively used for the diagnosis of malaria. Microscopy however, was able to detect a higher number of positive malaria cases thus implying that microscopy remains a better diagnostic tool for malaria parasite detection than the RDTs.

Assessment of the Performance of Lactate Dehydrogenase-Based Rapid Diagnostic Test for Malaria in Djibouti in 2022–2023

Until 2020, Djiboutian health authorities relied on histidine-rich protein-2 (HRP2)-based rapid diagnostic tests (RDTs) to establish the diagnosis of Plasmodium falciparum. The rapid spread of P. falciparum histidine-rich protein-2 and -3 (pfhrp2/3) gene-deleted parasite strains in Djibouti has led the authorities to switch from HRP2-based RDTs to lactate dehydrogenase (LDH)-based RDTs targeting the plasmodial lactate dehydrogenase (pLDH) specific for P. falciparum and P. vivax (RapiGEN BIOCREDIT Malaria Ag Pf/Pv pLDH/pLDH) in 2021. This study was conducted with the primary objective of evaluating the diagnostic performance of this alternative RDT. Operational constraints related, in particular, to the implementation of this RDT during the COVID-19 pandemic were also considered. The performance of BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH) RDT was also compared to our previously published data on the performance of two HRP2-based RDTs deployed in Djibouti in 2018–2020. The diagnosis of 350 febrile patients with suspected malaria in Djibouti city was established using two batches of RapiGEN BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH) RDT over a two-year period (2022 and 2023) and confirmed by real-time quantitative polymerase chain reaction. The sensitivity and specificity for the detection of P. falciparum were 88.2% and 100%, respectively. For P. vivax, the sensitivity was 86.7% and the specificity was 100%. Re-training and closer supervision of the technicians between 2022 and 2023 have led to an increased sensitivity to detect P. falciparum (69.8% in 2022 versus 88.2% in 2023; p < 0.01). The receiver operating characteristic curve analysis highlighted a better performance in the diagnosis of P. falciparum with pLDH-based RDTs compared with previous HRP2-based RDTs. In Djibouti, where pfhrp2-deleted strains are rapidly gaining ground, LDH-based RDTs seem to be more suitable for diagnosing P. falciparum than HRP2-based RDTs. Awareness-raising and training for technical staff have also been beneficial.

Comparative evaluation of traditional and molecular diagnostic methods for malaria: An analysis of performance.

As we edge closer to the eradication of malaria, several methods for detecting Plasmodium species have been developed, including peripheral blood smear examination (PBS), rapid diagnostic tests (RDTs), serological evaluations, fluorescent microscopy, polymerase chain reactions (PCRs), fluorescent in situ hybridization, and flow cytometry. The suitability of these tools for routine diagnosis requires evaluation, considering both their diagnostic accuracy and cost-effectiveness. Our study compared four diagnostic techniques for malaria: PBS, quantitative buffy coat (QBC), RDT, and PCR. We used PCR as the benchmark standard and statistically assessed the performance of PBS, QBC, and RDT against PCR in detecting malaria. Adopting a prospective observational approach, we collected blood samples from 117 patients exhibiting the symptoms suggestive of malaria. The findings from our study showed that PBS had a positivity rate of 93.4%, with a 95% confidence interval (CI) of 0.881-0.987, indicating reliable results for a similar population. The QBC assay demonstrated an elevated positivity rate of 96.7% with a solid 95% CI of 0.930-1.000. Although the RDT had a slightly lower rate of 92.4%, it still delivered dependable results, presenting a significant 95% CI of 0.868-0.980, ensuring a robust diagnostic performance compared to PCR. PCR is a reliable test when the identification of the specific species is inconclusive. Conversely, the commonly used PBS occasionally overlooks positive malaria cases due to the specialized skills needed for accurate reading. The cost-effective RDT is feasible for field operations without the need for expert knowledge. However, it fails to differentiate between old and new infections. Meanwhile, the QBC test, known for its sensitivity and speed, can be consistently employed for malaria diagnosis in a tertiary care settings.

Lesson Learned from Mass Antibody Rapid Diagnostic Used in the Early COVID-19 Pandemic in Indonesia Contributors.

Laboratory examination is extremely important in handling the COVID-19 pandemic. In the first era of the pandemic, the molecular and antigen tests were limited. Hence, at that time, it was necessary to carry out antibody Rapid Diagnostic Tests (RDT). However, many antibody RDTs were yet to obtain Food and Drug Authorization (FDA)'s approval. Therefore, The Indonesian Association of Clinical Pathology and Medical Laboratory (PDS PatKLIn) decided to conduct a validity test of RDT antibodies to find out the quality of SARS-CoV-2 diagnosis performance based on these RDTs used. This is a descriptive observational design with diagnostic analysis. The retrospective secondary data were collected from 34 provinces in Indonesia from May to June 2020. Data analysis was carried out on the sensitivity and specificity values of each antibody RDT brand to the RT-PCR result and analyzed descriptive data. The amount of secondary data of antibody RDT and RT-PCR results collected was 139,908, consisting of 59 RDT brands of which 44% were authorized by The Indonesian COVID-19 Response Acceleration Task Force (Gugus Tugas Percepatan Penanganan COVID-19 Indonesia). There were huge variations of SARS-CoV-2 antibody RDT performance between total antibody types (sensitivity 59.18%, specificity 62%), IgM RDT (sensitivity 16-100%, specificity 7-97%), and RDT IgG (sensitivity 33-96%, specificity 19-100%). The variations in the RDT antibodies'performance can cause errors in diagnosis leading to significant material and immaterial losses. Therefore, cooperation from various parties is needed for the pre- and post-marketing surveillance process to assess the performance and the characteristics of each RDT kit and other diagnostic methods to assist the rapid pandemic response process.

Sensitivity and specificity of a syphilis rapid diagnostic test in blood donors’ samples

Rapid Diagnostic Tests (RDT) are useful to identify syphilis cases, particularly for hard-to-reach populations and if laboratory services are scarce. However, RDT performance may be suboptimal. We aimed to assess the sensitivity and specificity of a syphilis RDT using well-characterized blood donors’ samples. We categorized samples from 811 blood donors into five groups: 1 - Samples with reactive Chemiluminescence (QML), FTA-Abs, and VDRL; 2 - Samples with reactive QML and FTA-Abs, and nonreactive VDRL; 3 - Samples with reactive QML, and nonreactive for other markers (false-positives); 4 - Controls with nonreactive QML; and 5 - Samples reactive for HIV, with nonreactive QML. Sensitivity was tested in groups 1 (overall and according to VDRL titers) and 2; specificity was tested in groups 3‒5. The RDT had high specificity, even in samples reactive for HIV. The sensitivity was high (91.9%) in samples with reactive VDRL but varied between 75.0%‒100% according to VDRL titers. The overall sensitivity was lower (81.3%) in samples with reactive FTA-Abs and nonreactive VDRL. The RDT is a useful tool to detect active syphilis but may be more limited for cases with very early or remote infection, or those with prior treatment. When higher sensitivity is needed, additional strategies including recurrent testing or laboratory-based tests may be required.

Laboratory evaluation of eleven rapid diagnostic tests for serological diagnosis of Chagas disease in Colombia.

Chagas disease is a public health challenge in Colombia, where only an estimated 1.2% of people at risk have accessed diagnosis, while less than 0.5% of affected people have obtained treatment. The development of simplified diagnostic algorithms would enable progress in access to diagnosis; however, the current diagnostic algorithm relies on at least two laboratory-based tests that require qualified personnel, processing equipment, and infrastructure, which are still generally lacking at the primary care level. Rapid diagnostic tests (RDTs) for Chagas disease could simplify diagnosis, but their performance in the epidemiological context of Colombia is not well known. A retrospective analytical observational study of RDTs was performed to estimate the operational characteristics of 11 commercially available RDTs designed for in vitro detection of anti-T. cruzi IgG antibodies. The study was performed under controlled laboratory conditions using human serum samples. Eleven RDTs were assessed, ten using 585 serum samples and one using 551 serum samples. Employing the current national diagnostic algorithm as a reference standard for serological diagnosis of chronic infection, the sensitivity of the assessed RDTs ranged from 75.5% to 99.0% (95% CI 70.5-100), while specificity ranged from 70.9% to 100% (95% CI 65.3-100). Most tests (7/11, 63.6%) had sensitivity above 90%, and almost all (10/11, 90.9%) had specificity above 90%. Five RDTs had both sensitivity and specificity above 90%. The evaluation of these 11 commercially available RDTs under controlled laboratory conditions is a first step in the assessment of the diagnostic performance of RDTs in Colombia. As a next step, field studies will be conducted on available RDTs with sensitivity and specificity greater than 90% in this study, to evaluate performance in real world conditions, with the final goal to allow simplified diagnostic algorithms.

Antigen concentration, viral load, and test performance for SARS-CoV-2 in multiple specimen types.

The relationship between N-antigen concentration and viral load within and across different specimens guides the clinical performance of rapid diagnostic tests (RDT) in different uses. A prospective study was conducted in Porto Velho, Brazil, to investigate RDT performance in different specimen types as a function of the correlation between antigen concentration and viral load. The study included 214 close contacts with recent exposures to confirmed cases, aged 12 years and older and with various levels of vaccination. Antigen concentration was measured in nasopharyngeal swab (NPS), anterior nares swab (ANS), and saliva specimens. Reverse transcriptase (RT)-PCR was conducted on the NPS and saliva specimens, and two RDTs were conducted on ANS and one RDT on saliva. Antigen concentration correlated well with viral load when measured in the same specimen type but not across specimen types. Antigen levels were higher in symptomatic cases compared to asymptomatic/oligosymptomatic cases and lower in saliva compared to NPS and ANS samples. Discordant results between the RDTs conducted on ANS and the RT-PCR on NPS were resolved by antigen concentration values. The analytical limit-of-detection of RDTs can be used to predict the performance of the tests in populations for which the antigen concentration is known. The antigen dynamics across different sample types observed in SARS-CoV-2 disease progression support use of RDTs with nasal samples. Given lower antigen concentrations in saliva, rapid testing using saliva is expected to require improved RDT analytical sensitivity to achieve clinical sensitivity similar to rapid testing of nasal samples.

Diagnostic performance of PfHRP2/pLDH malaria rapid diagnostic tests in elimination setting, northwest Ethiopia.

Accurate diagnosis of malaria is vital for the effectiveness of parasite clearance interventions in elimination settings. Thus, evaluating the diagnostic performance of rapid diagnostic tests (RDTs) used in malaria parasite clearance interventions in elimination settings is essential. Therefore, this study aimed to evaluate the diagnostic performance of rapid diagnostic tests recently used in detecting malaria parasites in northwest Ethiopia. A facility-based cross-sectional study was conducted from November 2020 to February 2021 comparing PfHRP2/pLDH CareStart malaria RDTs with light microscopy and polymerase chain reaction (PCR). Blood samples were collected from 310 febrile patients who attended the outpatient department and examined using CareStart RDTs, light microscopy, and PCR. Statistical analyses were performed using STATA/SE version 17.0. The sensitivity of PfHRP2/pLDH CareStart malaria RDTs, regardless of species, was 81.0% [95% CI, 75.3, 86.7] and 75.8% [95% CI, 69.6, 82.0] compared to light microscopy and PCR, while the specificity was 96.8% [95% CI, 93.7, 99.9] and 93.2% [95% CI, 88.6, 97.8], respectively. The false-negative rate of CareStart malaria RDTs in comparison with light microscopy and PCR was 19.0% and 24.2%, respectively. The level of agreement beyond chance between tests was substantial, RDT versus microscopy was 75.0% and RDT versus PCR was 65.1%. The diagnostic performance of PfHRP2/pLDH CareStart RDTs in detecting malaria parasites among febrile patients in the study area was below the recommended WHO standard. The limited diagnostic performance of RDTs in the malaria elimination area undoubtedly affects the impact of malaria parasite clearance interventions. Therefore, parasite clearance intervention like targeted mass drug administration with antimalarial drugs is recommended to back up the limited diagnostic performance of the RDT or replace the existing malaria RDTs with more sensitive, field-deployable, and affordable diagnostic tests.

Comparative Study of Rapid Diagnostic Test (RDT) and Microscopic Diagnosis of Malaria Infection among Patients Attending General Hospital Minna, Niger State

Malaria is a global public health problem known to be a common cause of under five children mortality in the tropical area of Africa. The aim of this study was to compare rapid diagnostic test (RDT) and microscopy technique of malaria infection among patients attending General Hospital Minna, Niger State. A convenience sampling qualitative study was carried out on 300 consenting outpatients of general hospital, Minna in Niger state. Results of the study showed that most of the respondents were females 212(71%) and Most of the participants were within the age bracket of 11-20 years (41%). This demonstrated that transmission was higher among the young age than the elderly. Microscopy was positive in 179(59%) patients and RDT was positive in 185(61%) of the total study population while 6(3%) of those negative by microscopy were also positive with RDT. There was no significant difference when the efficacy of both tests was compared. The RDT used had a sensitivity of 87%, a specificity of 98% while microscopy had sensitivity of 95% and specificity of 72%. The RDT performance was extremely high compared to microscopy in this study. RDT can still serve as the first screening test for malaria diagnosis. However, the gold standard for confirmation of clinical diagnosis for malaria is microscopy examination. Rapid diagnostic test (RDT) offers rapid, timely, accurate and accessible detection of malaria parasites which is important for prevention and treatment. Keywords: Rapid diagnostic test, microscopic diagnosis of Malaria, Malaria fever.

Poor performance of malaria rapid diagnostic tests for the detection of Plasmodium malariae among returned international travellers in China

BackgroundMalaria is a worldwide infectious disease. For countries that have achieved malaria elimination, the prevention of re-establishment due to infections in returned travellers has become important. The accurate and timely diagnosis of malaria is the key in preventing re-establishment, and malaria rapid diagnostic tests (RDTs) are frequently used due to their convenience. However, the RDT performance in Plasmodium malariae (P. malariae) infection diagnosis remains unknown.MethodsThis study analysed epidemiological features and diagnosis patterns of imported P. malariae cases from 2013 to 2020 in Jiangsu Province and evaluated the sensitivity of four parasite enzyme lactate dehydrogenase (pLDH)-targeting RDTs (Wondfo, SD BIONLINE, CareStart and BioPerfectus) and one aldolase-targeting RDT(BinaxNOW) for P. malariae detection. Furthermore, influential factors were investigated, including parasitaemia load, pLDH concentration and target gene polymorphisms.ResultsThe median duration from symptom onset to diagnosis among patients with P. malariae infection was 3 days, which was longer than that with Plasmodium falciparum (P. falciparum) infection. The RDTs had a low detection rate (39/69, 56.5%) among P. malariae cases. All tested RDT brands had poor performance in P. malariae detection. All the brands except the worst-performing SD BIOLINE, achieved 75% sensitivity only when the parasite density was higher than 5000 parasites/μL. Both pLDH and aldolase showed relatively conserved and low gene polymorphism rates.ConclusionsThe diagnosis of imported P. malariae cases was delayed. The RDTs had poor performance in P. malariae diagnosis and may threaten the prevention of malaria re-establishment from returned travellers. The improved RDTs or nucleic acid tests for P. malariae cases are urgently needed for the detection of imported cases in the future.

Development of an approach to monitor the manufacturing consistency of HIV rapid diagnostic tests: Panel qualification and potential impact on country programs.

Although regulatory bodies have standards that manufacturers of rapid diagnostic tests (RDTs) must meet for market approval, RDTs have no specific sampling and testing standards to monitor ongoing lot production, unlike pharmaceuticals and certain devices. With the importance of accurate diagnosis for improved health outcomes, independent quality assurance testing is key to ensuring the availability of high-quality RDTs, particularly in low-resource settings. This work develops an approach for HIV RDT lot testing, involving qualification of specimens to enable testing across various RDTs (namely Determine HIV-1/2, OraQuick HIV-1/2, Bioline HIV-1/2 3.0, UniGold HIV, and HIV Ag/Ab Combo). A sampling plan and acceptance criteria were developed per lot (approximating sensitivity and specificity) based on ISO 2859-1: 1999, using the test line response to a qualified panel (disease-positive and negative specimens) as the attribute. Based on general performance of HIV RDTs, an average % defective tests allowed per lot (acceptance quality limit) of 0.65% within ISO 2859-1: 1999 was selected, where RDTs are tested with 80 positives (accept 1 / reject 2 defective results) and 80 negatives (accept 1 / reject 2 defective results) per lot. Panel qualification was conducted with 83 positive and 84 negative serum specimens to select specimens that consistently provided expected results when tested in quadruplicate with three lots per product. While all products yielded consistent results with at least 80 negative specimens, only 4 products did the same for positive specimens. With this approach, each of these 4 RDT products can be tested with the qualified 80-positive specimen panel, requiring the other product to be tested with 20 specimens in quadruplicate. Additionally, this approach was adapted to evaluate HIV antibody/antigen combination tests with Ag panel qualification using p24 samples. While panels were qualified to monitor ongoing lot consistency of HIV RDTs, this approach could be mimicked with other types of diagnostics for monitoring manufacturing consistency, field investigation, small-scale stability checks, and proficiency testing.

Laboratory Evaluation and Field Testing of Dengue NS1 and IgM/IgG Rapid Diagnostic Tests in an Epidemic Context in Senegal.

In Senegal, the burden of dengue is increasing and expanding. As case management and traditional diagnostic techniques can be difficult to implement, rapid diagnostic tests (RDTs) deployed at point of care are ideal for investigating active outbreaks. The aim of this study was to evaluate the diagnostic performance of the Dengue NS1 and Dengue IgM/IgG RDTs on the serum/plasma samples in a laboratory setting and in the field. During laboratory evaluation, performance of the NS1 RDT was assessed using NS1 ELISA as the gold standard. Sensitivity and specificity were 88% [75-95%] and 100% [97-100%], respectively. Performance of the IgM/IG RDT was assessed using the IgM Antibody Capture (MAC) ELISA, indirect IgG, and PRNT as gold standards. The IgM and IgG test lines respectively displayed sensitivities of 94% [83-99%] and 70% [59-79%] and specificities of 91% [84-95%] and 91% [79-98%]. In the field, the Dengue NS1 RDT sensitivity and specificity was 82% [60-95%] and 75% [53-90%], respectively. The IgM and IgG test lines displayed sensitivities of 86% [42-100%] and 78% [64-88%], specificities of 85% [76-92%] and 55% [36-73%], respectively. These results demonstrate that RDTs are ideal for use in a context of high prevalence or outbreak setting and can be implemented in the absence of a confirmatory test for acute and convalescent patients.

Early diagnosis of dengue: Diagnostic utility of the SD BIOLINE Dengue Duo rapid test in Reunion Island.

In Reunion Island, dengue outbreaks have been occurring since 2018. The healthcare facilities are facing the problem of managing a massive influx of patients and a growing care burden. The aim of this study was to evaluate the performance of the SD Bioline Dengue Duo rapid diagnostic test in adults consulting at an emergency department during the 2019 epidemic. This retrospective study of diagnostic accuracy included patients over 18 years old, suspected of dengue, who were admitted to emergency units of the University Hospital of Reunion between the 1st of January and 30th of June, 2019, and were tested for dengue fever with the SD Bioline Dengue Duo rapid diagnostic test and reverse transcriptase polymerase chain reaction. Over the study period, 2099 patients were screened retrospectively. Of them, 671 patients matched the inclusion criteria. The overall rapid diagnostic test performance was 42% for sensitivity and 15% for specificity. The non-structural 1 antigen component had a good specificity of 82% but a low sensitivity of 12%. The immunoglobulin M component had a sensitivity of 28% and a specificity of 33%. Sensitivities were slightly improved beyond the 5th day of illness compared to the early stage for all components, but only the non-structural 1 antigen component had a better specificity of 91%. Furthermore, predictive values were low and post-test probabilities never improved pre-test probabilities in our setting. These results suggest that the SD Bioline Dengue Duo RDT did not achieve sufficient performance levels to rule in, or discard, an early point of care dengue diagnosis in the emergency department during the 2019 epidemic in Reunion.

Accuracy of diagnosis among clinical malaria patients: comparing microscopy, RDT and a highly sensitive quantitative PCR looking at the implications for submicroscopic infections

BackgroundThe World Health Organization recommends parasitological confirmation of all suspected malaria cases by microscopy or rapid diagnostic tests (RDTs) before treatment. These conventional tools are widely used for point-of-care diagnosis in spite of their poor sensitivity at low parasite density. Previous studies in Ghana have compared microscopy and RDT using standard 18S rRNA PCR as reference with varying outcomes. However, how these conventional tools compare with ultrasensitive varATS qPCR has not been studied. This study, therefore, sought to investigate the clinical performance of microscopy and RDT assuming highly sensitive varATS qPCR as gold standard.Methods1040 suspected malaria patients were recruited from two primary health care centers in the Ashanti Region of Ghana and tested for malaria by microscopy, RDT, and varATS qPCR. The sensitivity, specificity, and predictive values were assessed using varATS qPCR as gold standard.ResultsParasite prevalence was 17.5%, 24.5%, and 42.1% by microscopy, RDT, and varATS qPCR respectively. Using varATS qPCR as the standard, RDT was more sensitive (55.7% vs 39.3%), equally specific (98.2% vs 98.3%), and reported higher positive (95.7% vs 94.5%) and negative predictive values (75.3% vs 69.0%) than microscopy. Consequently, RDT recorded better diagnostic agreement (kappa = 0.571) with varATS qPCR than microscopy (kappa = 0.409) for clinical detection of malaria.ConclusionsRDT outperformed microscopy for the diagnosis of Plasmodium falciparum malaria in the study. However, both tests missed over 40% of infections that were detected by varATS qPCR. Novel tools are needed to ensure prompt diagnosis of all clinical malaria cases.