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A Novel Malaria Pf/Pv Ab Rapid Diagnostic Test Using a Differential Diagnostic Marker Identified by Network Biology.

ABSTRACT: Rapid diagnostic tests (RDTs) can detect anti-malaria antibodies in human blood. As they can detect parasite infection at the low parasite density, they are useful in endemic areas where light infection and/or re-infection of parasites are common. Thus, malaria antibody tests can be used for screening bloods in blood banks to prevent transfusion-transmitted malaria (TTM), an emerging problem in malaria endemic areas. However, only a few malaria antibody tests are available in the microwell-based assay format and these are not suitable for field application. A novel malaria antibody (Ab)-based RDT using a differential diagnostic marker for falciparum and vivax malaria was developed as a suitable high-throughput assay that is sensitive and practical for blood screening. The marker, merozoite surface protein 1 (MSP1) was discovered by generation of a Plasmodium-specific network and the hierarchical organization of modularity in the network. Clinical evaluation revealed that the novel Malaria Pf/Pv Ab RDT shows improved sensitivity (98%) and specificity (99.7%) compared with the performance of a commercial kit, SD BioLine Malaria P.f/P.v (95.1% sensitivity and 99.1% specificity). The novel Malaria Pf/Pv Ab RDT has potential for use as a cost-effective blood-screening tool for malaria and in turn, reduces TTM risk in endemic areas.

SUBMITTER: Cho SJ

PROVIDER: S-EPMC4910601 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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A Novel Malaria Pf/Pv Ab Rapid Diagnostic Test Using a Differential Diagnostic Marker Identified by Network Biology.

Cho Sung Jin SJ Lee Jihoo J Lee Hyun Jae HJ Jo Hyun-Young HY Sinniah Mangalam M Kim Hak-Yong HY Chong Chom-Kyu CK Song Hyun-Ok HO

International journal of biological sciences 20160525 7

Rapid diagnostic tests (RDTs) can detect anti-malaria antibodies in human blood. As they can detect parasite infection at the low parasite density, they are useful in endemic areas where light infection and/or re-infection of parasites are common. Thus, malaria antibody tests can be used for screening bloods in blood banks to prevent transfusion-transmitted malaria (TTM), an emerging problem in malaria endemic areas. However, only a few malaria antibody tests are available in the microwell-based ...[more]

PMID: 27313496

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Project description:BackgroundThe present study evaluated CareStart pLDH Malaria, a three-band rapid diagnostic test detecting Plasmodium falciparum-specific parasite lactate dehydrogenase (Pf-pLDH) and pan Plasmodium-specific pLDH (pan-pLDH) in a reference setting.MethodsCareStart pLDH was retrospectively and prospectively assessed with a panel of stored (n=498) and fresh (n=77) blood samples obtained in international travelers suspected of malaria. Both panels comprised all four Plasmodium species; the retrospective panel comprised also Plasmodium negative samples. The reference method was microscopy corrected by PCR. The prospective panel was run side-to-side with OptiMAL (Pf-pLDH/pan-pLDH) and SDFK60 (histidine-rich protein-2 (HRP-2)/pan-pLDH).ResultsIn the retrospective evaluation, overall sensitivity for P. falciparum samples (n=247) was 94.7%, reaching 98.7% for parasite densities>1,000/μl. Most false negative results occurred among samples with pure gametocytaemia (2/12, 16.7%) and at parasite densities ≤ 100/μl (7/12, 58.3%). None of the Plasmodium negative samples (n=96) showed visible test lines. Sensitivities for Plasmodium vivax (n=70), Plasmodium ovale (n=69) and Plasmodium malariae (n=16) were 74.3%, 31.9% and 25.0% respectively. Wrong species identification occurred in 10 (2.5%) samples and was mainly due to P. vivax samples reacting with the Pf-pLDH test line. Overall, Pf-pLDH test lines showed higher line intensities compared to the pan-pLDH lines (67.9% and 23.0% medium and strong line intensities for P. falciparum). In the prospective panel (77 Plasmodium-positive samples), CareStart pLDH showed higher sensitivities for P. falciparum compared to OptiMAL (p=0.008), lower sensitivities for P. falciparum as compare to SDFK60 (although not reaching statistical significance, p=0.08) and higher sensitivities for P. ovale compared to both OptiMAL (p=0.03) and SDFK60 (p=0.01). Inter-observer and test reproducibility were good to excellent.ConclusionCareStart pLDH performed excellent for the detection of P. falciparum, well for P. vivax, but poor for P. ovale and P. malariae.

Project description:There was an increase in the number of malaria cases in Cameroon in 2018 that could reflect changes in provider practice, despite effective interventions. In this study, we assessed the diagnostic performance of two malaria rapid diagnostic tests (mRDTs) for diagnostic confirmation of suspected cases of malaria in public and private health facilities in two malaria transmission settings in Cameroon. We evaluated the diagnostic performance of CareStart pf and SD Bioline Pf/PAN mRDT and compared these parameters by RDT type and transmission setting. Nested PCR and blood film microscopy were used as references. The chi square test was used for independent sample comparisons, while the McNemar's test was used to test for the dependence of categorical data in paired sample testing. A p < 0.05 was considered significant in all comparisons. The R (v.4.0.2) software was used for analyses. A total of 1126 participants consented for the study in the four sites. The diagnostic accuracy of the CareStart Pf mRDT was 0.93.6% (0.911-0.961) in Yaoundé, 0.930% (0.90-0.960) in Ngounso, 0.84% (0.794-0.891) in St Vincent Catholic Hospital Dschang and 0.407 (0.345-0.468) in Dschang district hospital. For SD Bioline Pf/PAN the accuracy was 0.759 (0.738-0.846) for St Vincent Catholic Hospital Dschang and 0.426 (0.372-0.496) for the Dschang district hospital. The accuracy was slightly lower in each case but not statistically different when PCR was considered as the reference. The likelihood ratios of the positive and negative tests were high in the high transmission settings of Yaoundé (10.99 (6.24-19.35)) and Ngounso (14.40 (7.89-26.28)) compared to the low transmission settings of Dschang (0.71 (0.37-1.37)) and St Vincent Catholic hospital (7.37 (4.32-12.59)). There was a high degree of agreement between the tests in Yaoundé (Cohen's Kappa: 0.85 ± 0.05 (0.7-0.95)) and Ngounso (Cohen's Kappa: 0.86 ± 0.05 (0.74, 0.97)) and moderate agreement in St Vincent hospital Dschang (k: 0.58 ± 0.06 (0.44-0.71)) and poor agreement in the District Hospital Dschang (Cohen's Kappa: -0.11 ± 0.05 (-0.21-0.01)). The diagnostic indicators of the SD Bioline Pf/PAN were slightly better than for CareStart Pf mRDT in St Vincent Catholic hospital Dschang, irrespective of the reference test. Publicly procured malaria rapid diagnostic tests in Cameroon have maintained high accuracy (91-94%) in the clinical diagnosis of malaria in high malaria transmission regions of Cameroon, although they failed to reach WHO standards. We observed an exception in the low transmission region of Dschang, West region, where the accuracy tended to be lower and variable between facilities located in this town. These results underscore the importance of the routine monitoring of the quality and performance of malaria RDTs in diverse settings in malaria endemic areas.

Project description:BackgroundThe Gambia has successfully reduced malaria transmission. The human reservoir of infection could further decrease if malaria-infected individuals could be identified by highly sensitive, field-based, diagnostic tools and then treated.MethodsA cross-sectional survey was done at the peak of the 2017 malaria season in 47 Gambian villages. From each village, 100 residents were randomly selected for finger-prick blood samples to detect Plasmodium falciparum infections using highly sensitive rapid diagnostic tests (HS-RDT) and PCR. The sensitivity and specificity of the HS-RDT were estimated (assuming PCR as the gold standard) across varying transmission intensities and in different age groups. A deterministic, age-structured, dynamic model of malaria transmission was used to estimate the impact of mass testing and treatment (MTAT) with HS-RDT in four different scenarios of malaria prevalence by PCR: 5, 15, 30, and 60%, and with seasonal transmission. The impact was compared both to MTAT with conventional RDT and mass drug administration (MDA).ResultsMalaria prevalence by HS-RDT was 15% (570/3798; 95% CI 13.9-16.1). The HS-RDT sensitivity and specificity were 38.4% (191/497, 95% CI 34.2-42.71) and 88.5% (2922/3301; 95% CI 87.4-89.6), respectively. Sensitivity was the highest (50.9%, 95% CI 43.3-58.5%) in high prevalence villages (20-50% by PCR). The model predicted that in very low transmission areas (≤ 5%), three monthly rounds of MTAT with HS-RDT, starting towards the end of the dry season and testing 65 or 85% of the population for 2 consecutive years, would avert 62 or 78% of malaria cases (over 2 years), respectively. The effect of the intervention would be lower in a moderate transmission setting. In all settings, MDA would be superior to MTAT with HS-RDT which would be superior to MTAT with conventional RDT.ConclusionThe HS-RDT's field sensitivity was modest and varied by transmission intensity. In low to very low transmission areas, three monthly rounds per year of MTAT with HS-RDT at 85% coverage for 2 consecutive years would reduce malaria prevalence to such low levels that additional strategies may achieve elimination. The model prediction would need to be confirmed by cluster-randomized trials.

Project description:BackgroundPlasmodium falciparum strains with mutations/deletions of the genes encoding the histidine-rich proteins 2/3 (pfhrp2/3) have emerged during the last 10 years leading to false-negative results in HRP2-based rapid diagnostic tests (RDTs). This can lead to unrecognized infections in individuals and to setbacks in malaria control in endemic countries where RDTs are the backbone of malaria diagnostics and control.Case descriptionHere the detection of a pfhrp2/3-negative P. falciparum infection acquired in Ethiopia by a 63-year old female traveller is presented. After onset of symptoms during travel, she was first tested negative for malaria, most probably by RDT, at a local hospital in Harar, Ethiopia. Falciparum malaria was finally diagnosed microscopically upon her return to Germany, over 4 weeks after infection. At a parasite density of approximately 5387 parasites/µl, two different high-quality RDTs: Palutop + 4 OPTIMA, NADALRMalaria PF/pan Ag 4 Species, did not respond at their respective P. falciparum test lines. pfhrp2/3 deletion was confirmed by multiplex-PCR. The patient recovered after a complete course of atovaquone and proguanil. According to the travel route, malaria was acquired most likely in the Awash region, Central Ethiopia. This is the first case of imported P. falciparum with confirmed pfhrp2/3 deletion from Ethiopia.ConclusionHRP2-negative P. falciparum strains may not be recognized by the presently available HRP2-based RDTs. When malaria is suspected, confirmation by microscopy and/or qPCR is necessary in order to detect falciparum malaria, which requires immediate treatment. This case of imported P. falciparum, non-reactive to HRP2-based RDT, possibly underlines the necessity for standardized, nationwide investigations in Ethiopia and should alert clinicians from non-endemic countries to the possibility of false-negative RDT results which may increase in returning travellers with potentially life-threatening infections.

Project description:BackgroundAlthough malaria rapid diagnostic tests (RDTs) have been extensively evaluated since their introduction in the early 1990's, sensitivity and specificity vary widely limiting successful integration into clinical practice. This paper reviews specific issues surrounding RDT use in field settings and presents results of research investigating how to interpret "faint test bands" on ParaCheck Pf® in areas of low transmission in order to reduce malaria misdiagnosis.MethodsA multi-phase cross-sectional study was conducted at a remote hospital in the northern Tanzanian highlands. Capillary blood samples were taken from consenting participants (n = 319) for blood smear and ParaCheck Pf® testing. Primary outcome variables were sensitivity, specificity and proportion misdiagnosed by ParaCheck Pf® and local microscopy. ParaCheck Pf® "faint bands" were classified as both true positives or true negatives during evaluation to determine appropriate clinical interpretation. Multivariate logistic regression adjusted for age and gender was conducted to determine odds of misdiagnosis for local microscopy and ParaCheck Pf®.ResultsOverall, 23.71% of all ParaCheck Pf® tests resulted in a "faint band" and 94.20% corresponded with true negatives. When ParaCheck Pf® "faint bands" were classified as positive, specificity was 75.5% (95% CI = 70.3%-80.6%) as compared to 98.9% (95% CI = 97.0%-99.8%) when classified as negative. The odds of misdiagnosis by local microscopy for those > 5 years as compared to those ≤ 5 years are 0.370 (95% CI = 0.1733-0.7915, p = 0.010). In contrast, even when ParaCheck Pf® faint bands are considered positive, the odds of misdiagnosis by ParaCheck Pf® for those > 5 years as compared to those ≤ 5 years are 0.837 (95% CI = 0.459-1.547, p = 0.5383).ConclusionsWe provide compelling evidence that in areas of low transmission, "faint bands" should be considered a negative test when used to inform clinical decision-making. Correct interpretation of RDT test bands in a clinical setting plays a central role in successful malaria surveillance, appropriate patient management and most importantly reducing misdiagnosis.

Dataset Information

A Novel Malaria Pf/Pv Ab Rapid Diagnostic Test Using a Differential Diagnostic Marker Identified by Network Biology.

Publications

A Novel Malaria Pf/Pv Ab Rapid Diagnostic Test Using a Differential Diagnostic Marker Identified by Network Biology.

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