Evaluation of PfHRP2 and PfLDH Malaria Rapid Diagnostic Test Performance in Assosa Zone, Ethiopia.
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ABSTRACT:
SUBMITTER: Alemayehu GS
PROVIDER: S-EPMC7646789 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC10332618 | biostudies-literature
Project description:BackgroundRapid diagnostic tests (RDTs) are widely used for malaria diagnosis of both symptomatic and asymptomatic infections. Although RDTs are a reliable and practical diagnostic tool, the sensitivity of histidine-rich protein 2 (HRP2)-based RDTs can be reduced if pfhrp2 or pfhrp3 (pfhrp2/3) gene deletions exist in the Plasmodium falciparum parasite population. This study evaluated dried blood spot (DBS) samples collected from a national household survey to investigate the presence of pfhrp2/3 deletions and the performance of the RDT used in the cross-sectional survey in a low transmission setting.MethodsThe 2015 Ethiopia Malaria Indicator Survey tested household members by RDT and collected DBS samples. DBS (n = 2648) from three regions in northern Ethiopia were tested by multiplex bead-based antigen detection assay after completion of the survey. The multiplex assay detected pan-Plasmodium lactate dehydrogenase (LDH), pAldolase, and HRP2 antigens in samples. Samples suspected for pfhrp2/3 gene deletions (pLDH and/or pAldolase positive but low or absent HRP2) were further investigated by molecular assays for gene deletions. Antigen results were also compared to each individual's RDT results. Dose-response logistic regression models were fit to estimate RDT level of detection (LOD) antigen concentrations at which 50, 75, 90, and 95% of the RDTs returned a positive result during this survey.ResultsOut of 2,648 samples assayed, 29 were positive for pLDH or pAldolase antigens but low or absent for HRP2 signal, and 15 of these samples (51.7%) were successfully genotyped for pfhrp2/3. Of these 15 P. falciparum infections, eight showed single deletions in pfhrp3, one showed a single pfhrp2 deletion, and six were pfhrp2/3 double-deletions. Six pfhrp2 deletions were observed in Tigray and one in Amhara. Twenty-five were positive for HRP2 by the survey RDT while the more sensitive bead assay detected 30 HRP2-positive samples. A lower concentration of HRP2 antigen generated a positive test result by RDT compared to pLDH (95% LOD: 16.9 ng/mL vs. 319.2 ng/mL, respectively).ConclusionsThere is evidence of dual pfhrp2/3 gene deletions in the Tigray and Amhara regions of Ethiopia in 2015. As the prevalence of malaria was very low (< 2%), it is difficult to make strong conclusions on RDT performance, but these results challenge the utility of biomarkers in household surveys in very low transmission settings.
| S-EPMC8895513 | biostudies-literature
Project description:Lateral flow immunochromatographic rapid diagnostic tests (RDTs) are the primary form of medical diagnostic used for malaria in underdeveloped nations. Unfortunately, many of these tests do not detect asymptomatic malaria carriers. In order for eradication of the disease to be achieved, this problem must be solved. In this study, we demonstrate enhancement in the performance of six RDT brands when a simple sample-processing step is added to the front of the diagnostic process. Greater than a 4-fold RDT signal enhancement was observed as a result of the sample processing step. This lowered the limit of detection for RDT brands to submicroscopic parasitemias. For the best performing RDTs the limits of detection were found to be as low as 3 parasites per μL. Finally, through individual donor samples, the correlations between donor source, WHO panel detection scores and RDT signal intensities were explored.
| S-EPMC5098896 | biostudies-literature
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.
| S-EPMC7952815 | biostudies-literature
Project description:The aim of this study was to evaluate the diagnostic performance of Simtomax® CoronaCheck, a serology rapid diagnostic test (RDT) for the detection of IgG and IgM against SARS-CoV-2. 48 plasma samples positive for SARS-CoV-2 based on RT-PCR and 98 negative control samples were studied. Diagnostic performance of the IgG/IgM RDT was assessed against RT-PCR and the electro-chemiluminescence immunoassay (ECLIA) Elecsys® Anti-SARS-CoV-2 total Ig. Overall, the RDT sensitivity was 92 % (95 % confidence interval [95 %CI]: 79-97), specificity 97 % (95 % CI: 91-99 %), PPV 94 % (95 % CI: 81-98) and the NPV 96 % (95 % CI: 89-99). When considering only samples collected ≥ 15 days post-symptoms (DPS), the sensitivity increased to 98 % (95 %CI: 86-100) and the specificity was 97 % (95 % CI: 91-99 %). Two samples with 180 DPS were still positive for IgG. Globally, this IgG/IgM RDT displayed a high diagnostic accuracy for SARS-CoV-2 IgG/IgM detection in plasma samples in high COVID-19 prevalence settings. It could be effectively used, in absence of facilities for routine diagnostic serology, for samples with a DPS between 15 and 180 days.
| S-EPMC8095018 | biostudies-literature
Project description:BACKGROUND:Malaria is endemic in all regions where gambiense or rhodesiense human African trypanosomiasis (HAT) is reported, and both diseases have similarities in their symptomatology. A combined test could be useful for both diseases and would facilitate integration of the screening for gambiense HAT (gHAT) and malaria diagnosis. This study aimed to evaluate a combined prototype rapid diagnostic test (RDT) for gHAT and malaria. METHODS:Blood samples were collected in the Democratic Republic of the Congo and in Uganda to evaluate the performance of a prototype HAT/Malaria Combined RDT in comparison to an individual malaria RDT based on Plasmodium falciparum (P.f.) Histidine Rich Protein II (HRP-II or HRP2) antigen (SD BIOLINE Malaria Ag P.f. RDT) for malaria detection and an individual gHAT RDT based on recombinant antigens, the SD BIOLINE HAT 2.0 RDT for HAT screening. Due to the current low prevalence of gHAT in endemic regions, the set of blood samples that were collected was used to evaluate the specificity of the RDTs for gHAT, and additional archived plasma samples were used to complete the evaluation of the HAT/Malaria Combined RDT in comparison to the HAT 2.0 RDT. RESULTS:Frozen whole blood samples from a total of 486 malaria cases and 239 non-malaria controls, as well as archived plasma samples from 246 gHAT positive and 246 gHAT negative individuals were tested. For malaria, the sensitivity and specificity of the malaria band in the HAT/Malaria Combined RDT were 96.9% (95% CI: 95.0-98.3) and 97.1% (95% CI: 94.1-98.8) respectively. The sensitivity and specificity of the SD BIOLINE malaria Ag P.f. RDT were 97.3% (95% CI: 95.5-98.6) and 97.1% (95% CI: 94.1-98.8) respectively. For gHAT, using archived plasma samples, the sensitivity and specificity were respectively 89% (95% CI: 84.4-92.6) and 93.5% (95% CI: 89.7-96.2) with the HAT/Malaria Combined RDT, and 88.2% (95% CI: 83.5-92) and 94.7% (95% CI: 91.1-97.2) with the HAT 2.0 RDT. Using the whole blood samples that were collected during the study, the specificity of the HAT/Malaria Combined RDT for gHAT was 95.8% (95% CI: 94.3-97.0). CONCLUSION:The HAT/Malaria Combined prototype RDT was as accurate as the individual malaria or gHAT RDTs. The HAT/Malaria Combined prototype RDT is therefore suitable for both malaria diagnosis and gHAT screening. However, there is a need to assess its accuracy using fresh samples in prospective clinical trials.
| S-EPMC7162526 | biostudies-literature
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.
| S-EPMC6712604 | biostudies-literature
Project description:BackgroundWith the documentation of cases of falciparum malaria negative by rapid diagnostic tests (RDT), though at low frequency from natural isolates in a small pocket of Odisha, it became absolutely necessary to investigate the status of HRP-2 based RDT throughout the state and in different seasons of the year.MethodsSuspected individuals were screened for malaria infection by microscopy and RDT in 25/30 districts of Odisha, India. Discrepancies in results were confirmed by PCR. False negative RDT samples for Plasmodium falciparum mono-infection were evaluated for detection of HRP2 antigen in ELISA and genotyped for pfhrp2, pfhrp3 and their flanking genes. Multiplicity of infection was ascertained based on msp1 and msp2 genotyping and parasitaemia level was determined by microscopy.ResultsOf the total 1058 patients suspected for malaria, 384 were microscopically confirmed for P. falciparum mono-infection and RDT failure was observed in 58 samples at varying proportion in different regions of the state. The failure in detection was due to undetectable level of HRP-2. Although most of these samples were screened during rainy season (45/345), significantly high proportion (9/17) of RDT negative samples were obtained during the summer compared to rainy season (P = 0.0002; OR = 7.5). PCR genotyping of pfhrp2 and pfhrp3 in RDT negative samples showed 38/58 (65.5) samples to be pfhrp2 negative and 24/58 (41.4) to be pfhrp3 negative including dual negative in 17/58 (29.3). Most of the RDT negative samples (39/58) were with single genotype infection and high proportions of pfhrp2 deletion (7/9) was observed in summer. No difference in parasitaemia level was observed between RDT positive and RDT negative patients.ConclusionHigh prevalence of parasites with pfhrp2 deletion including dual deletions (pfhrp2 and pfhrp3) is a serious cause of concern, as these patients could not be given a correct diagnosis and treatment. Therefore, HRP2-based RDT for diagnosing P. falciparum infection in Odisha is non-reliable and must be performed in addition to or replaced by other appropriate diagnostic tools for clinical management of the disease.
| S-EPMC6206925 | biostudies-literature
Project description:BackgroundRapid diagnostic tests (RDT) for malaria are the primary tool for malaria diagnosis in sub-Saharan Africa but the utility of the most commonly used histidine-rich protein 2 (HRP2) antigen-based tests is limited in high transmission settings due to the long duration of positivity after successful malaria treatment. HRP2 tests are also threatened by the emergence of Plasmodium that do not carry pfhrp2 or pfhrp 3 genes. Plasmodium lactate dehydrogenase (pLDH)-based tests are promising alternatives, but less available. This study assessed the performances of HRP2 and pLDH(pan) tests under field conditions.MethodsThe study performed a prospective facility-based diagnostic evaluation of two malaria RDTs in Aweil, South Sudan, during the high transmission season. Capillary blood by fingerprick was collected from 800 children under 15 years of age with fever and no signs of severity. SD Bioline HRP2 and CareStart pLDH(pan) RDTs were performed in parallel, thick and thin smears for microscopy were examined, and dried blood was used for PCR testing.ResultsUsing microscopy as the gold standard, the sensitivity of both tests was estimated at > 99%, but the specificity of each was lower: 55.0% for the pLDH test and 61.7% for the HRP2 test. When using PCR as the gold standard, the sensitivity of both tests was lower than the values assessed using microscopy (97.0% for pLDH and 96.5% for HRP2), but the specificity increased (65.1% for pLDH and 72.9% for HRP2). Performance was similar across different production lots, sex, and age. Specificity of both the pLDH and HRP2 tests was significantly lower in children who reported taking a therapeutic course of anti-malarials in the 2 months prior to enrollment. The prevalence of pfhrp2/3 deletions in the study population was 0.6%.ConclusionsThe low specificity of the pLDH RDT in this setting confirms previous results and suggests a problem with this specific test. The prevalence of pfhrp2/3 deletions in the study area warrants continued monitoring and underscores the relevance of assessing deletion prevalence nationally. Improved malaria RDTs for high-transmission environments are needed.
| S-EPMC9461093 | biostudies-literature
Project description:BackgroundRapid diagnostic tests (RDT) are commonly used for the diagnosis of malaria caused by Plasmodium falciparum. However, false negative results of RDT caused by genetic variation of P. falciparum histidine-rich protein 2 and 3 genes (pfhrp2/3) threaten existing malaria case management and control efforts. The main objective of this study was to investigate the genetic variations of the pfhrp2/3 genes.MethodsA cross-sectional study was conducted from malaria symptomatic individuals in 2018 in Assosa zone, Ethiopia. Finger-prick blood samples were collected for RDT and microscopic examination of thick and thin blood films. Dried blood spots (DBS) were used for genomic parasite DNA extraction and molecular detection. Amplification of parasite DNA was made by quantitative PCR. DNA amplicons of pfhrp2/3 were purified and sequenced.ResultsThe PfHRP2 amino acid repeat type isolates were less conserved compared to the PfHRP3 repeat type. Eleven and eight previously characterized PfHRP2 and PfHRP3 amino acid repeat types were identified, respectively. Type 1, 4 and 7 repeats were shared by PfHRP2 and PfHRP3 proteins. Type 2 repeats were found only in PfHRP2, while types 16 and 17 were found only in PfHRP3 with a high frequency in all isolates. 18 novel repeat types were found in PfHRP2 and 13 novel repeat types were found in PfHRP3 in single or multiple copies per isolate. The positivity rate for PfHRP2 RDT was high, 82.9% in PfHRP2 and 84.3% in PfHRP3 sequence isolates at parasitaemia levels > 250 parasites/µl. Using the Baker model, 100% of the isolates in group A (If product of types 2 × type 7 repeats ≥ 100) and 73.7% of the isolates in group B (If product of types 2 × type 7 repeats 50-99) were predicted to be detected by PfHRP2 RDT at parasitaemia level > 250 parasite/μl.ConclusionThe findings of this study indicate the presence of different PfHRP2 and PfHRP3 amino acid repeat including novel repeats in P. falciparum from Ethiopia. These results indicate that there is a need to closely monitor the performance of PfHRP2 RDT associated with the genetic variation of the pfhrp2 and pfhrp3 gene in P. falciparum isolates at the country-wide level.
| S-EPMC8502267 | biostudies-literature