Comparison of Capillary Versus Venous Blood for the Diagnosis of Plasmodium falciparum Malaria Using Rapid Diagnostic Tests.
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ABSTRACT:
SUBMITTER: Gorret AM
PROVIDER: S-EPMC8491838 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
Publications
Comparison of Capillary Versus Venous Blood for the Diagnosis of Plasmodium falciparum Malaria Using Rapid Diagnostic Tests.
Gorret Abalinda M AM Muhindo Rabbison R Baguma Emma E Ntaro Moses M Mulogo Edgar M EM Deutsch-Feldman Molly M Juliano Jonathan J JJ Nyehangane Dan D Boyce Ross M RM
The Journal of infectious diseases 20210701 1
We enrolled 250 febrile children in western Uganda to compare the results of malaria rapid diagnostic tests (RDTs) when using capillary vs venous blood. Participants were tested with 4 different RDT types. Polymerase chain reaction testing was performed as the reference standard. Sensitivity and specificity were broadly similar across RDT types and sampling method. Agreement between sample type was high, ranging from 0.95 to 0.99. When following the manufacturer's recommended interpretation, onl ...[more]
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Project description:In Africa, most rapid diagnostic tests (RDTs) for falciparum malaria recognize histidine-rich protein 2 antigen. Plasmodium falciparum parasites lacking histidine-rich protein 2 (pfhrp2) and 3 (pfhrp3) genes escape detection by these RDTs, but it is not known whether these deletions confer sufficient selective advantage to drive rapid population expansion. By studying blood samples from a cohort of 12,572 participants enroled in a prospective, cross-sectional survey along Ethiopia's borders with Eritrea, Sudan and South Sudan using RDTs, PCR, an ultrasensitive bead-based immunoassay for antigen detection and next-generation sequencing, we estimate that histidine-rich protein 2-based RDTs would miss 9.7% (95% confidence interval 8.5-11.1) of P. falciparum malaria cases owing to pfhrp2 deletion. We applied a molecular inversion probe-targeted deep sequencing approach to identify distinct subtelomeric deletion patterns and well-established pfhrp3 deletions and to uncover recent expansion of a singular pfhrp2 deletion in all regions sampled. We propose a model in which pfhrp3 deletions have arisen independently multiple times, followed by strong positive selection for pfhrp2 deletion owing to RDT-based test-and-treatment. Existing diagnostic strategies need to be urgently reconsidered in Ethiopia, and improved surveillance for pfhrp2 deletion is needed throughout the Horn of Africa.
| S-EPMC8478644 | biostudies-literature
Project description:BackgroundAccurate diagnosis and timely treatment are crucial in combating malaria.MethodsA total of 449 samples were screened for Plasmodium falciparum infection by expert microscopy, qPCR, and three RDTs, namely Rapigen Biocredit Malaria Ag Pf (detecting HRP2 and pLDH on separate bands), Abbott NxTek Eliminate Malaria Ag Pf (detecting HRP2), and SD Bioline Malaria Ag Pf (detecting HRP2). hrp2/3 deletion typing was done by digital PCR.Results45.7% (205/449) individuals tested positive by qPCR for P. falciparum with a mean parasite density of 12.5 parasites/μL. Using qPCR as reference, the sensitivity of microscopy was 28.3% (58/205), the Biocredit RDT was 52.2% (107/205), the NxTek RDT was 49.3% (101/205), and the Bioline RDT was 39.5% (81/205). When only samples with densities > 20 parasites/μL were included (n = 89), sensitivity of 62.9% (56/89) by microscopy, 88.8% (79/89) by Biocredit, 88.8% (79/89) by NxTek, and 78.7% (70/89) by Bioline were obtained. All three RDTs demonstrated specificities > 95%. The limits of detection (95% probability that a sample tested positive) was 4393 parasites/μL (microscopy), 56 parasites/μL (Biocredit, considering either HRP2 or pLDH), 84 parasites/μL (NxTek), and 331 parasites/μL (Bioline). None of the three qPCR-confirmed P. falciparum positive samples, identified solely through the pLDH target, or eight samples negative for all RDTs but qPCR-positive at densities > 20 parasites/µL carried hrp2/3 deletions.ConclusionThe Biocredit and NxTek RDTs demonstrated comparable diagnostic efficacies. All three RDTs performed better than microscopy.
| S-EPMC11363606 | biostudies-literature
Project description:BackgroundRapid diagnostic tests (RDTs) are central to fulfilling the WHO's recommendation for parasitologic confirmation of all suspected cases of malaria. RDT performance may be compromised when exposed to the high temperature conditions typical of most malaria endemic regions. However, a systematic method to monitor RDT quality and performance in endemic countries is lacking at the present time. Current methods to monitor RDT performance in the field include comparing results from RDTs to diagnoses made by light microscopy and observing health workers perform tests. These methods are not substitutes for direct quality control. In this study, the suitability of dried Plasmodium falciparum-infected blood as quality control samples for malaria RDTs was evaluated.MethodsThree cultured strains of P. falciparum at 200 and 2,000 parasites/μl were tested on 10 brands of RDT. After baseline testing to determine initial reactivity, aliquots of parasite-infected blood were air dried, stored at 35°C, room temperature (~25°C) or 4°C for one, four and 12 weeks and were then tested on the 10 RDTs after rehydration. Extended stability testing of dried blood stored at 4°C was done using P. falciparum strain 3D7 at 1,000 and 2,000 parasites/μl.ResultsAll dried blood samples at 2,000 parasites/μl retained reactivity (100% sensitivity) at all three temperatures and time points for all nine RDT brands that detect histidine-rich protein-2 (HRP2). The dried blood samples with 200 parasites/μl were detected by six of the nine HRP2-based RDTs at all storage temperatures and time points. The sensitivity for two of the three remaining HRP2-based RDTs was 100% up to four weeks of storage at all temperatures but dropped to 87.5% at week 12. Of the four RDTs that detect plasmodium lactate dehydrogenase (pLDH) in a pan-specific manner, alone or in combination with HRP2, the detection of pLDH in samples with 2,000 parasites/μL was 100% for two RDTs and 80% for the other two RDTs. The mean level for detection of pLDH at 200 parasites/μl was low (29%), with a range of 0% to100%, which was partly attributable to weak initial baseline reactivity. Reactivity of dried 3D7 at 1,000 and 2,000 parasites/μl stored at 4°C was retained at 100% for up to 52 weeks for both HRP2 and pLDH.ConclusionsIn the absence of native or recombinant positive control antigens, well-standardized P. falciparum-infected dried blood samples can be used as positive control samples for monitoring RDT performance, particularly with HRP2-detecting tests.
| S-EPMC3483274 | biostudies-literature
Project description:BackgroundPrompt, accurate diagnosis and treatment with artemisinin combination therapy remains vital to current malaria control. Blood film microscopy the current standard test for diagnosis of malaria has several limitations that necessitate field evaluation of alternative diagnostic methods especially in low income countries of sub-Saharan Africa where malaria is endemic.MethodsThe accuracy of axillary temperature, health centre (HC) microscopy, expert microscopy and a HRP2-based rapid diagnostic test (Paracheck) was compared in predicting malaria infection using polymerase chain reaction (PCR) as the gold standard. Three hundred patients with a clinical suspicion of malaria based on fever and or history of fever from a low and high transmission setting in Uganda were consecutively enrolled and provided blood samples for all tests. Accuracy of each test was calculated overall with 95% confidence interval and then adjusted for age-groups and level of transmission intensity using a stratified analysis. The endpoints were: sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). This study is registered with Clinicaltrials.gov, NCT00565071.ResultsOf the 300 patients, 88(29.3%) had fever, 56(18.7%) were positive by HC microscopy, 47(15.7%) by expert microscopy, 110(36.7%) by Paracheck and 89(29.7%) by PCR. The overall sensitivity >90% was only shown by Paracheck 91.0% [95%CI: 83.1-96.0]. The sensitivity of expert microscopy was 46%, similar to HC microscopy. The superior sensitivity of Paracheck compared to microscopy was maintained when data was stratified for transmission intensity and age. The overall specificity rates were: Paracheck 86.3% [95%CI: 80.9-90.6], HC microscopy 93.4% [95%CI: 89.1-96.3] and expert microscopy 97.2% [95%CI: 93.9-98.9]. The NPV >90% was shown by Paracheck 95.8% [95%CI: 91.9-98.2]. The overall PPV was <88% for all methods.ConclusionThe HRP2-based RDT has shown superior sensitivity compared to microscopy in diagnosis of malaria and may be more suitable for screening of malaria infection.
| S-EPMC3002380 | biostudies-literature
Project description:BACKGROUND: Malaria transmission in Ethiopia is unstable and variable, caused by both Plasmodium falciparum and Plasmodium vivax. The Federal Ministry of Health (FMoH) is scaling up parasitological diagnosis of malaria at all levels of the health system; at peripheral health facilities this will be through use of rapid diagnostic tests (RDTs). The present study compared three RDT products to provide the FMoH with evidence to guide appropriate product selection. METHODS: Performance of three multi-species (pf-HRP2/pan-pLDH and pf-HRP2/aldolase) RDTs (CareStart, ParaScreen and ICT Combo) was compared with 'gold standard' microscopy at three health centres in Jimma zone, Oromia Regional State. Ease of RDT use by health extension workers was assessed at community health posts. RDT heat stability was tested in a controlled laboratory setting according to WHO procedures. RESULTS: A total of 2,383 patients with suspected malaria were enrolled between May and July 2009, 23.2% of whom were found to be infected with Plasmodium parasites by microscopy. All three RDTs were equally sensitive in detecting P. falciparum or mixed infection: 85.6% (95% confidence interval 81.2-89.4). RDT specificity was similar for detection of P. falciparum or mixed infection at around 92%. For detecting P. vivax infection, all three RDTs had similar sensitivity in the range of 82.5 to 85.0%. CareStart had higher specificity in detecting P. vivax (97.2%) than both ParaScreen and ICT Combo (p < 0.001 and p = 0.05, respectively). Health extension workers preferred CareStart and ParaScreen to ICT Combo due to the clear labelling of bands on the cassette, while the 'lab in a pack' style of CareStart was the preferred design. ParaScreen and CareStart passed all heat stability testing, while ICT Combo did not perform as well. CONCLUSIONS: CareStart appeared to be the most appropriate option for use at health posts in Ethiopia, considering the combination of quantitative performance, ease of use and heat stability. When new products become available, the choice of multi-species RDT for Ethiopia should be regularly re-evaluated, as it would be desirable to identify a test with higher sensitivity than the ones evaluated here.
| S-EPMC2988036 | biostudies-other
Project description:BackgroundMalaria has a negative effect on the outcome of pregnancy. Pregnant women are at high risk of severe malaria and severe haemolytic anaemia, which contribute 60-70% of foetal and perinatal losses. Peripheral blood smear microscopy under-estimates sequestered placental infections, therefore malaria rapid diagnostic tests (RDTs) detecting histidine rich protein-2 antigen (HRP-2) in peripheral blood are a potential alternative.MethodsHRP-2 RDTs accuracy in detecting malaria in pregnancy (MIP >28 weeks gestation) and placental Plasmodium falciparum malaria (after childbirth) were conducted using Giemsa microscopy and placental histopathology respectively as the reference standard. The study was conducted in Mbale Hospital, using the midwives to perform and interpret the RDT results. Discordant results samples were spot checked using PCR techniques.ResultsAmong 433 febrile women tested, RDTs had a sensitivity of 96.8% (95% CI 92-98.8), specificity of 73.5% (95% CI 67.8-78.6), a positive predictive value (PPV) of 68.0% (95% CI 61.4-73.9), and negative predictive value (NPV) of 97.5% (95% CI 94.0-99.0) in detecting peripheral P. falciparum malaria during pregnancy. At delivery, in non-symptomatic women, RDTs had a 80.9% sensitivity (95% CI 57.4-93.7) and a 87.5% specificity (95%CI 80.9-92.1), PPV of 47.2% (95% CI 30.7-64.2) and NPV of 97.1% (95% CI 92.2-99.1) in detecting placental P. falciparum infections among 173 samples. At delivery, 41% of peripheral infections were detected by microscopy without concurrent placental infection. The combination of RDTs and microscopy improved the sensitivity to 90.5% and the specificity to 98.4% for detecting placental malaria infection (McNemar's X(2)> 3.84). RDTs were not superior to microscopy in detecting placental infection (McNemar's X(2)< 3.84). Presence of malaria in pregnancy and active placental malaria infection were 38% and 12% respectively. Placental infections were associated with poor pregnancy outcome [pre-term, still birth and low birth weight] (aOR = 37.9) and late pregnancy malaria infection (aOR = 20.9). Mosquito net use (aOR 2.1) and increasing parity (aOR 2.7) were associated with lower risk for malaria in pregnancy.ConclusionUse of HRP-2 RDTs to detect malaria in pregnancy in symptomatic women was accurate when performed by midwives. A combination of RDTs and microscopy provided the best means of detecting placental malaria. RDTs were not superior to microscopy in detecting placental infection. With a high sensitivity and specificity, RDTs could be a useful tool for assessing malaria in pregnancy, with further (cost-) effectiveness studies.
| S-EPMC3206496 | biostudies-literature
Project description:BACKGROUND: An accurate diagnosis is essential for the rapid and appropriate treatment of malaria. The accuracy of the histidine-rich protein 2 (PfHRP2)-based rapid diagnostic test (RDT) Palutop+4® was assessed here. One possible factor contributing to the failure to detect malaria by this test is the diversity of the parasite PfHRP2 antigens. METHODS: PfHRP2 detection with the Palutop+4® RDT was carried out. The pfhrp2 and pfhrp3 genes were amplified and sequenced from 136 isolates of Plasmodium falciparum that were collected in Dakar, Senegal from 2009 to 2011. The DNA sequences were determined and statistical analyses of the variation observed between these two genes were conducted. The potential impact of PfHRP2 and PfHRP3 sequence variation on malaria diagnosis was examined. RESULTS: Seven P. falciparum isolates (5.9% of the total isolates, regardless of the parasitaemia; 10.7% of the isolates with parasitaemia ?0.005% or ?250 parasites/?l) were undetected by the PfHRP2 Palutop+4® RDT. Low parasite density is not sufficient to explain the PfHRP2 detection failure. Three of these seven samples showed pfhrp2 deletion (2.4%). The pfhrp3 gene was deleted in 12.8%. Of the 122 PfHRP2 sequences, 120 unique sequences were identified. Of the 109 PfHRP3 sequences, 64 unique sequences were identified. Using the Baker's regression model, at least 7.4% of the P. falciparum isolates in Dakar were likely to be undetected by PfHRP2 at a parasite density of ?250 parasites/?l (slightly lower than the evaluated prevalence of 10.7%). This predictive prevalence increased significantly between 2009 and 2011 (P = 0.0046). CONCLUSION: In the present work, 10.7% of the isolates with a parasitaemia ?0.005% (?250 parasites/?l) were undetected by the PfHRP2 Palutop+4® RDT (7.4% by the predictive Baker'model). In addition, all of the parasites with pfhrp2 deletion (2.4% of the total samples) and 2.1% of the parasites with parasitaemia >0.005% and presence of pfhrp2 were not detected by PfHRP2 RDT. PfHRP2 is highly polymorphic in Senegal. Efforts should be made to more accurately determine the prevalence of non-sensitive parasites to pfHRP2.
| S-EPMC3571878 | biostudies-literature
Project description:BackgroundThe need for new malaria surveillance tools and strategies is critical, given improved global malaria control and regional elimination efforts. High quality Plasmodium falciparum DNA can reliably be extracted from malaria rapid diagnostic tests (RDTs). Together with highly sensitive molecular assays, wide scale collection of used RDTs may serve as a modern tool for improved malaria case detection and drug resistance surveillance. However, comparative studies of DNA extraction efficiency from RDTs and the field applicability are lacking. The aim of this study was to compare and evaluate different methods of DNA extraction from RDTs and to test the field applicability for the purpose of molecular epidemiological investigations.MethodsDNA was extracted from two RDT devices (Paracheck-Pf® and SD Bioline Malaria Pf/Pan®), seeded in vitro with 10-fold dilutions of cultured 3D7 P. falciparum parasites diluted in malaria negative whole blood. The level of P. falciparum detection was determined for each extraction method and RDT device with multiple nested-PCR and real-time PCR assays. The field applicability was tested on 855 paired RDT (Paracheck-Pf) and filter paper (Whatman® 3MM) blood samples (734 RDT negative and 121 RDT positive samples) collected from febrile patients in Zanzibar 2010. RDT positive samples were genotyped at four key single nucleotide polymorphisms (SNPs) in pfmdr1 and pfcrt as well as for pfmdr1 copy number, all associated with anti-malarial drug resistance.ResultsThe P. falciparum DNA detection limit varied with RDT device and extraction method. Chelex-100 extraction performed best for all extraction matrixes. There was no statistically significant difference in PCR detection rates in DNA extracted from RDTs and filter paper field samples. Similarly there were no significant differences in the PCR success rates and genotyping outcomes for the respective SNPs in the 121 RDT positive samples.ConclusionsThe results support RDTs as a valuable source of parasite DNA and provide evidence for RDT-DNA extraction for improved malaria case detection, molecular drug resistance surveillance, and RDT quality control.
| S-EPMC3605315 | biostudies-literature
Project description:BackgroundRapid diagnostic tests (RDTs) are becoming increasingly indispensable in malaria management, as a means of increasing the accuracy of diagnosis. The WHO has issued recommendations, but the selection of the most suitable RDT remains difficult for users in endemic countries. The genetic variability of the antigens detected with RDTs has been little studied, but may affect the sensitivity of RDTs. This factor has been studied by comparisons between countries at continental level, but little information is available concerning antigen variability within a given country.MethodsA country-wide assessment of polymorphism of the PfHRP2, PfHRP3, pLDH and aldolase antigens was carried out in 260 Plasmodium falciparum and 127 Plasmodium vivax isolates, by sequencing the genes encoding these antigens in parasites originating from the various epidemiological strata for malaria in Madagascar.ResultsHigher levels of polymorphism were observed for the pfhrp2 and pfhrp3 genes than for the P. falciparum and P. vivax aldolase and pldh genes. Pfhrp2 sequence analysis predicted that 9% of Malagasy isolates would not be detected at parasite densities < or = 250 parasites/mul (ranging from 6% in the north to 14% in the south), although RDTs based on PfHRP2 detection are now recommended in Madagascar.ConclusionThese findings highlight the importance of training of health workers and the end users of RDTs in the provision of information about the possibility of false-negative results for patients with clinical symptoms of malaria, particularly in the south of Madagascar.
| S-EPMC2582241 | biostudies-literature
Project description:BackgroundCurrent Uganda National Malaria treatment guidelines recommend parasitological confirmation either by microscopy or rapid diagnostic test (RDT) before treatment with artemether-lumefantrine (AL). However, the cost-effectiveness of these strategies has not been assessed at rural operational primary care centres.MethodsThree health centres (HCs) were randomized to three diagnostic arms (microscopy, RDT and presumptive diagnosis) in a district of low and another of high malaria transmission intensities in Uganda. Some 22,052 patients presenting with fever at outpatients departments were enrolled from March 2010 to February 2011. Of these, a random sample of 1,627 was selected to measure additional socio-economic characteristics. Costing was performed following the standard step-down cost allocation and the ingredients approach. Effectiveness was measured as the number and proportion of patients correctly diagnosed and treated. Incremental Cost-Effectiveness Ratios (ICERs) were estimated from the societal perspective (http://Clinicaltrials.gov, NCT00565071).ResultsOverall RDT was most cost-effective with lowest ICER US$5.0 compared to microscopy US$9.61 per case correctly diagnosed and treated. In the high transmission setting, ICER was US$4.38 for RDT and US$12.98 for microscopy. The corresponding ICERs in the low transmission setting were US$5.85 and US$7.63 respectively. The difference in ICERs between RDT and microscopy was greater in the high transmission area (US$8.9) than in low transmission setting (US$1.78). At a willingness to pay of US$2.8, RDT remained cost effective up to a threshold value of the cost of treatment of US$4.7.ConclusionRDT was cost effective in both low and high transmission settings. With a global campaign to reduce the costs of AL and RDT, the Malaria Control Programme and stakeholders need a strategy for malaria diagnosis because as the cost of AL decreases, presumptive treatment is likely to become more attractive.
| S-EPMC3266346 | biostudies-literature