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10 pages, 784 KiB  
Article
Severity of Vessel Color Changes and Macular and Peripheral Whitening in Malarial Retinopathy Are Associated with Higher Total Body and Sequestered Parasite Burdens
by Chiadika Nwanze, Daniel Muller, Priscilla Suleman, Mrinmayee Takle, John R. Barber, Kyle J. Wilson, Nicholas A. V. Beare, Karl B. Seydel and Douglas G. Postels
Trop. Med. Infect. Dis. 2024, 9(11), 279; https://doi.org/10.3390/tropicalmed9110279 - 16 Nov 2024
Viewed by 1081
Abstract
Two-thirds of children with cerebral malaria (CM) exhibit retinopathy characterized by whitening, vessel color changes, and/or hemorrhages. The pathogenesis of malarial retinopathy is not fully understood. This study aimed to assess the relationship between malarial retinopathy and the severity of its components (macular [...] Read more.
Two-thirds of children with cerebral malaria (CM) exhibit retinopathy characterized by whitening, vessel color changes, and/or hemorrhages. The pathogenesis of malarial retinopathy is not fully understood. This study aimed to assess the relationship between malarial retinopathy and the severity of its components (macular whitening, retinal hemorrhages, and vessel color changes) with the total, circulating, or sequestered parasite load in children with CM. Total parasite burden was estimated by measuring plasma levels of Plasmodium falciparum histidine-rich protein 2 (PfHRP2), while the sequestered load was calculated as the difference between the total burden and circulating parasitemia. Children with retinopathy-positive CM (n = 172) had higher total and sequestered parasite burdens compared to retinopathy-negative children (n = 42) (both p = 0.049). In a subgroup with detailed retinopathy grading (n = 52), more extensive vessel color changes correlated with higher total, sequestered, and circulating parasite loads (p = 0.0057, p = 0.0068, and p = 0.0433, respectively). Peripheral retinal whitening was also associated with increased total and sequestered loads (p = 0.0017 and p = 0.0012). No association was found between retinal hemorrhages and parasite burden, indicating that other factors may influence their pathogenesis. Full article
(This article belongs to the Special Issue Recent Progress in Mosquito-Borne Diseases)
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11 pages, 554 KiB  
Article
High Frequency of Deletions in the pfhrp2 and pfhrp3 Genes of Plasmodium falciparum in the Middle Rio Negro Region of the Brazilian Amazon
by Daniela Romero Bally, Simone da Silva Santos, Diego Calafate Arregue, Mariana Kelly de Mattos and Martha C. Suárez-Mutis
Trop. Med. Infect. Dis. 2024, 9(7), 149; https://doi.org/10.3390/tropicalmed9070149 - 2 Jul 2024
Cited by 2 | Viewed by 1864
Abstract
Several countries are reporting natural populations of P. falciparum with deletions in the pfhrp2/3 genes that can lead to false-negative results in rapid diagnostic tests. To investigate the prevalence of deletion in the pfhrp2/3 genes in the Rio Negro basin in [...] Read more.
Several countries are reporting natural populations of P. falciparum with deletions in the pfhrp2/3 genes that can lead to false-negative results in rapid diagnostic tests. To investigate the prevalence of deletion in the pfhrp2/3 genes in the Rio Negro basin in the Brazilian Amazon and identify whether there is clinical differentiation between individuals infected by these parasites, clinical samples collected from 2003 to 2016 were analyzed from symptomatic and asymptomatic P. falciparum-infected individuals. The molecular deletion of pfhrp2 and pfhrp3 genes was evaluated using the protocols recommended by the WHO. From 82 samples used, 28 (34.2%) had a single deletion in pfhrp2, 19 (23.2%) had a single deletion in pfhrp3, 15 (18.3%) had a double deletion (pfhrp2/3), and 20 (24.4%) did not have a deletion in either gene. In total, 29.3% of individuals had an asymptomatic plasmodial infection and were 3.64 times more likely to have parasites with a double deletion (pfhrp2/3) than patients with clinical malaria (p = 0.02). The high prevalence of parasites with pfhrp2/3 deletions shows the need to implement a surveillance program in this area. Deletions in parasites may be associated with the clinical pattern of the disease in this area. More studies must be carried out to elucidate these findings. Full article
(This article belongs to the Special Issue Advances in Molecular Diagnosis of Malaria)
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12 pages, 971 KiB  
Article
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
by Marylin Madamet, Isabelle Fonta, Joel Mosnier, Nicolas Benoit, Rémy Amalvict, Sébastien Briolant, French National Reference Centre for Imported Malaria Study Group and Bruno Pradines
Diagnostics 2024, 14(7), 721; https://doi.org/10.3390/diagnostics14070721 - 29 Mar 2024
Viewed by 2544
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Laboratory Diagnosis in Microbial Diseases, 2nd Edition)
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12 pages, 1377 KiB  
Article
Assessment of the Performance of Lactate Dehydrogenase-Based Rapid Diagnostic Test for Malaria in Djibouti in 2022–2023
by Rahma Abdi Moussa, Nasserdine Papa Mze, Houssein Yonis Arreh, Aicha Abdillahi Hamoud, Kahiya Mohamed Alaleh, Fatouma Mohamed Aden, Abdoul-Razak Yonis Omar, Warsama Osman Abdi, Samatar Kayad Guelleh, Abdoul-Ilah Ahmed Abdi, Leonardo K. Basco, Bouh Abdi Khaireh and Hervé Bogreau
Diagnostics 2024, 14(3), 262; https://doi.org/10.3390/diagnostics14030262 - 25 Jan 2024
Cited by 8 | Viewed by 2508
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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12 pages, 3529 KiB  
Article
Identification of Growth-Related SNPs and Genes in the Genome of the Pearl Oyster (Pinctada fucata) Using GWAS
by Mingming Zhao, Wipavee Thaimuangphol, Yujie Hong, Ziqi Yan, Zongfa Chen, Minxuan Jin, Anna Zheng, Bei Wang and Zhongliang Wang
Fishes 2023, 8(6), 296; https://doi.org/10.3390/fishes8060296 - 1 Jun 2023
Cited by 2 | Viewed by 2319
Abstract
Pinctada fucata, the pearl oyster, is a bivalve primarily cultivated for the production of saltwater pearls. In this study, the genome-wide association study (GWAS) for the growth-related traits and a principal components analysis (PCA) in P. fucata were performed. Genomic parameters of [...] Read more.
Pinctada fucata, the pearl oyster, is a bivalve primarily cultivated for the production of saltwater pearls. In this study, the genome-wide association study (GWAS) for the growth-related traits and a principal components analysis (PCA) in P. fucata were performed. Genomic parameters of 6 growth-related traits in 60 individuals were estimated by using 4,937,162 single-nucleotide polymorphisms (SNPs). A total of 45 SNPs associated with growth traits were thus identified. Furthermore, 165 candidate genes were identified, including collagen alpha-3 (VI), serine/threonine-protein kinase mos-like harboring significant markers, and histidine-rich protein PFHRP-III-like, which may influence growth-related traits associated with various biological processes. The results of this study can facilitate marker-assisted selection and breeding programs designed to enhance growth and also offer a theoretical foundation for the further development and utilization of genomic resources in P. fucata. Full article
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14 pages, 3149 KiB  
Article
Low Prevalence of Plasmodium falciparum Histidine-Rich Protein 2 and 3 Gene Deletions—A Multiregional Study in Central and West Africa
by Tina Krueger, Moses Ikegbunam, Abel Lissom, Thaisa Lucas Sandri, Jacques Dollon Mbama Ntabi, Jean Claude Djontu, Marcel Tapsou Baina, Roméo Aimé Laclong Lontchi, Moustapha Maloum, Givina Zang Ella, Romuald Agonhossou, Romaric Akoton, Luc Djogbenou, Steffen Borrmann, Jana Held, Francine Ntoumi, Ayola Akim Adegnika, Peter Gottfried Kremsner and Andrea Kreidenweiss
Pathogens 2023, 12(3), 455; https://doi.org/10.3390/pathogens12030455 - 14 Mar 2023
Cited by 9 | Viewed by 3320
Abstract
Plasmodium falciparum parasites carrying deletions of histidine-rich protein 2 and 3 genes, pfhrp2 and pfhrp3, respectively, are likely to escape detection via HRP2-based rapid diagnostic tests (RDTs) and, consequently, treatment, posing a major risk to both the health of the infected individual [...] Read more.
Plasmodium falciparum parasites carrying deletions of histidine-rich protein 2 and 3 genes, pfhrp2 and pfhrp3, respectively, are likely to escape detection via HRP2-based rapid diagnostic tests (RDTs) and, consequently, treatment, posing a major risk to both the health of the infected individual and malaria control efforts. This study assessed the frequency of pfhrp2- and pfhrp3-deleted strains at four different study sites in Central Africa (number of samples analyzed: Gabon N = 534 and the Republic of Congo N = 917) and West Africa (number of samples analyzed: Nigeria N = 466 and Benin N = 120) using a highly sensitive multiplex qPCR. We found low prevalences for pfhrp2 (1%, 0%, 0.03% and 0) and pfhrp3 single deletions (0%, 0%, 0.03% and 0%) at all study sites (Gabon, the Republic of Congo, Nigeria and Benin, respectively). Double-deleted P. falciparum were only found in Nigeria in 1.6% of all internally controlled samples. The results of this pilot investigation do not point towards a high risk for false-negative RDT results due to pfhrp2/pfhrp3 deletions in Central and West African regions. However, as this scenario can change rapidly, continuous monitoring is essential to ensure that RDTs remain a suitable tool for the malaria diagnostic strategy. Full article
(This article belongs to the Special Issue Genomics and Epidemiology of Protozoan Parasites)
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8 pages, 258 KiB  
Article
Diagnostic Performance of Plasmodium falciparum Histidine-Rich Protein-2 Antigen-Specific Rapid Diagnostic Test in Children at the Peripheral Health Care Level in Nanoro (Burkina Faso)
by Massa dit Achille Bonko, Marc Christian Tahita, Francois Kiemde, Palpouguini Lompo, Petra F. Mens, Halidou Tinto and Henk. D. F. H. Schallig
Trop. Med. Infect. Dis. 2022, 7(12), 440; https://doi.org/10.3390/tropicalmed7120440 - 15 Dec 2022
Cited by 3 | Viewed by 2058
Abstract
(1) Background: Malaria control has strongly benefited from the implementation of rapid diagnostic tests (RDTs). The malaria RDTs used in Burkina Faso, as per the recommendation of the National Malaria Control Program, are based on the detection of histidine-rich protein-2 (PfHRP2) [...] Read more.
(1) Background: Malaria control has strongly benefited from the implementation of rapid diagnostic tests (RDTs). The malaria RDTs used in Burkina Faso, as per the recommendation of the National Malaria Control Program, are based on the detection of histidine-rich protein-2 (PfHRP2) specific to Plasmodium falciparum, which is the principal plasmodial species causing malaria in Burkina Faso. However, there is increasing concern about the diagnostic performance of these RDTs in field situations, and so constant monitoring of their accuracy is warranted. (2) Methods: A prospective study was performed in the health district of Nanoro, where 391 febrile children under 5 years with an axillary temperature ≥37.5 °C presenting at participating health facilities were subjected to testing for malaria. The HRP2-based RDT and expert microscopy were used to determine the diagnostic performance of the former. Retrospectively, the correctness of the antimalaria prescriptions was reviewed. (3) Results: Taking expert malaria microscopy as the gold standard, the sensitivity of the employed RDT was 98.5% and the specificity 40.5%, with a moderate agreement between the RDT testing and microscopy. In total, 21.7% of cases received an inappropriate antimalarial treatment based on a retrospective assessment with expert microscopy results. (4) Conclusion: Malaria remains one of the principal causes of febrile illness in Burkina Faso. Testing with HRP2-based RDTs is inaccurate, in particular, due to the low specificity, which results in an over-prescription of antimalarials, with emerging antimalarial drug resistance as an important risk and many children not being treated for potential other causes of fever. Full article
(This article belongs to the Section One Health)
15 pages, 867 KiB  
Article
Performance Evaluation of Nested Polymerase Chain Reaction (Nested PCR), Light Microscopy, and Plasmodium falciparum Histidine-Rich Protein 2 Rapid Diagnostic Test (PfHRP2 RDT) in the Detection of Falciparum Malaria in a High-Transmission Setting in Southwestern Nigeria
by Oluwaseun Bunmi Awosolu, Zary Shariman Yahaya, Meor Termizi Farah Haziqah and Titus Adeniyi Olusi
Pathogens 2022, 11(11), 1312; https://doi.org/10.3390/pathogens11111312 - 9 Nov 2022
Cited by 8 | Viewed by 2692
Abstract
Malaria remains a major public health challenge worldwide. In order to ensure a prompt and accurate malaria diagnosis, the World Health Organization recommended the confirmatory parasitological diagnosis of malaria by microscopy and malaria rapid diagnostic test (RDT) prior to antimalarial administration and treatment. [...] Read more.
Malaria remains a major public health challenge worldwide. In order to ensure a prompt and accurate malaria diagnosis, the World Health Organization recommended the confirmatory parasitological diagnosis of malaria by microscopy and malaria rapid diagnostic test (RDT) prior to antimalarial administration and treatment. This study was designed to evaluate the performance of nested polymerase chain reaction (nested PCR), light microscopy, and Plasmodium falciparum histidine-rich protein 2 rapid diagnostic test (PfHRP2 RDT) in the detection of falciparum malaria in Akure, Nigeria. A cross-sectional and hospital-based study involving 601 febrile volunteer participants was conducted in Akure, Nigeria. Approximately 2–3 mL venous blood samples were obtained from each study participant for parasitological confirmation by microscopy and PfHRP2-based malaria RDT. Thick and thin films were prepared and viewed under the light microscope for parasite detection, parasite density quantification, and species identification, respectively. Dry blood spot samples were prepared on 3MM Whatman filter paper for nested PCR. The overall prevalence of microscopy, PfHRP2 RDT, and nested PCR were 64.89% (390/601), 65.7% (395/601), and 67.39% (405/601), respectively. The estimates of sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and Youden’s j index of microscopy and RDT were 96.30, 100.00, 100.00, 92.89, 97.50, 0.963, and 95.06, 94.90, 97.47, 90.29, 95.01, and 0.899, respectively. Malaria RDT recorded higher false negativity, compared microscopy (4.94% vs. 3.70%). A near perfect agreement was reported between microscopy and nested PCR, and between PfHRP2 RDT and nested PCR with Cohen’s kappa (k) values of 0.94 and 0.88, respectively. This study revealed that PfHRP2 RDT and microscopy continues to remain sensitive and specific for falciparum malaria diagnosis in the study area. Full article
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11 pages, 968 KiB  
Article
Genetic Sequence Variation in the Plasmodium falciparum Histidine-Rich Protein 2 Gene from Field Isolates in Tanzania: Impact on Malaria Rapid Diagnosis
by Robert D. Kaaya, Caroline Amour, Johnson J. Matowo, Franklin W. Mosha, Reginald A. Kavishe and Khalid B. Beshir
Genes 2022, 13(9), 1642; https://doi.org/10.3390/genes13091642 - 13 Sep 2022
Cited by 1 | Viewed by 2476
Abstract
Malaria rapid diagnosis test (RDT) is crucial for managing the disease, and the effectiveness of detection depends on parameters such as sensitivity and specificity of the RDT. Several factors can affect the performance of RDT. In this study, we focused on the pfhrp2 [...] Read more.
Malaria rapid diagnosis test (RDT) is crucial for managing the disease, and the effectiveness of detection depends on parameters such as sensitivity and specificity of the RDT. Several factors can affect the performance of RDT. In this study, we focused on the pfhrp2 sequence variation and its impact on RDTs targeted by antigens encoded by Plasmodium falciparum histidine-rich protein 2 (pfhrp2). Field samples collected during cross-sectional surveys in Tanzania were sequenced to investigate the pfhrp2 sequence diversity and evaluate the impact on HRP2-based RDT performance. We observed significant mean differences in amino acid repeats between current and previous studies. Several new amino acid repeats were found to occur at different frequencies, including types AAY, AHHAHHAAN, and AHHAA. Based on the abundance of types 2 and 7 amino acid repeats, the binary predictive model was able to predict RDT insensitivity by about 69% in the study area. About 85% of the major epitopes targeted by monoclonal antibodies (MAbs) in RDT were identified. Our study suggested that the extensive sequence variation in pfhrp2 can contribute to reduced RDT sensitivity. The correlation between the different combinations of amino acid repeats and the performance of RDT in different malaria transmission settings should be investigated further. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
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23 pages, 426 KiB  
Review
Malaria Rapid Diagnostic Tests: Literary Review and Recommendation for a Quality Assurance, Quality Control Algorithm
by Michael J. Kavanaugh, Steven E. Azzam and David M. Rockabrand
Diagnostics 2021, 11(5), 768; https://doi.org/10.3390/diagnostics11050768 - 25 Apr 2021
Cited by 50 | Viewed by 13060
Abstract
Malaria rapid diagnostic tests (RDTs) have had an enormous global impact which contributed to the World Health Organization paradigm shift from empiric treatment to obtaining a parasitological diagnosis prior to treatment. Microscopy, the classic standard, requires significant expertise, equipment, electricity, and reagents. Alternatively, [...] Read more.
Malaria rapid diagnostic tests (RDTs) have had an enormous global impact which contributed to the World Health Organization paradigm shift from empiric treatment to obtaining a parasitological diagnosis prior to treatment. Microscopy, the classic standard, requires significant expertise, equipment, electricity, and reagents. Alternatively, RDT’s lower complexity allows utilization in austere environments while achieving similar sensitivities and specificities. Worldwide, there are over 200 different RDT brands that utilize three antigens: Plasmodium histidine-rich protein 2 (PfHRP-2), Plasmodium lactate dehydrogenase (pLDH), and Plasmodium aldolase (pALDO). pfHRP-2 is produced exclusively by Plasmodium falciparum and is very Pf sensitive, but an alternative antigen or antigen combination is required for regions like Asia with significant Plasmodium vivax prevalence. RDT sensitivity also decreases with low parasitemia (<100 parasites/uL), genetic variability, and prozone effect. Thus, proper RDT selection and understanding of test limitations are essential. The Center for Disease Control recommends confirming RDT results by microscopy, but this is challenging, due to the utilization of clinical laboratory standards, like the College of American Pathologists (CAP) and the Clinical Lab Improvement Act (CLIA), and limited recourses. Our focus is to provide quality assurance and quality control strategies for resource-constrained environments and provide education on RDT limitations. Full article
(This article belongs to the Special Issue Recent Advances in Malaria Diagnosis)
19 pages, 6062 KiB  
Review
Field Performances of Rapid Diagnostic Tests Detecting Human Plasmodium Species: A Systematic Review and Meta-Analysis in India, 1990–2020
by Loick Pradel Kojom Foko, Veena Pande and Vineeta Singh
Diagnostics 2021, 11(4), 590; https://doi.org/10.3390/diagnostics11040590 - 25 Mar 2021
Cited by 21 | Viewed by 3540
Abstract
Rapid diagnostic tests (RDTs) have become a mainstay of malaria diagnosis in endemic countries since their implementation in the 1990s. We conducted a 30-year systematic review and meta-analysis on malaria RDTs performance in India. Outcomes of interest were sensitivity (Se), specificity (Sp), positive/negative [...] Read more.
Rapid diagnostic tests (RDTs) have become a mainstay of malaria diagnosis in endemic countries since their implementation in the 1990s. We conducted a 30-year systematic review and meta-analysis on malaria RDTs performance in India. Outcomes of interest were sensitivity (Se), specificity (Sp), positive/negative likelihood ratio (PLR/NLR), and diagnostic odd ratio (DOR). Among the 75 studies included, most of the studies were cross-sectional (65.3%), hospital-based (77.3%), and targeted febrile patients (90.6%). Nearly half of RDTs were designed for detecting Plasmodium falciparum only (47.5%) while the rest were for P. falciparum and P. vivax (11.9%), and P. falciparum/Pan-Plasmodium except for P. knowlesi (32.3%). When compared to light microscopy (gold standard), pooled estimates of performances were: Se = 97.0%, Sp = 96.0%, PLR = 22.4, NLR = 0.02 and DOR = 1080. In comparison to polymerase chain reaction, the RDTs showed Se = 89.0% and Sp = 99.0%. Performance outcomes (Se and Sp) were similar for RDT targeting P. falciparum only, but decreased for mixed and non-falciparum infections. Performances of malaria RDTs are still high India. However, there is a need for developing RDTs with regard to targeting minor malarial species, individuals carrying only mature gametocytes, and pfhrp2-deleted parasites. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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9 pages, 1360 KiB  
Article
Evaluation of Histidine-Rich Proteins 2 and 3 Gene Deletions in Plasmodium falciparum in Endemic Areas of the Brazilian Amazon
by Leandro Góes, Nathália Chamma-Siqueira, José Mário Peres, José Maria Nascimento, Suiane Valle, Ana Ruth Arcanjo, Marcus Lacerda, Liana Blume, Marinete Póvoa and Giselle Viana
Int. J. Environ. Res. Public Health 2021, 18(1), 123; https://doi.org/10.3390/ijerph18010123 - 26 Dec 2020
Cited by 14 | Viewed by 3372
Abstract
Histidine-rich proteins 2 and 3 gene (pfhrp2 and pfhrp3) deletions affect the efficacy of rapid diagnostic tests (RDTs) based on the histidine-rich protein 2 (HRP2), compromising the correct identification of the Plasmodium falciparum species. Therefore, molecular surveillance is necessary for the [...] Read more.
Histidine-rich proteins 2 and 3 gene (pfhrp2 and pfhrp3) deletions affect the efficacy of rapid diagnostic tests (RDTs) based on the histidine-rich protein 2 (HRP2), compromising the correct identification of the Plasmodium falciparum species. Therefore, molecular surveillance is necessary for the investigation of the actual prevalence of this phenomenon and the extent of the disappearance of these genes in these areas and other South American countries, thus guiding national malaria control programs on the appropriate use of RDTs. This study aimed to evaluate the pfhrp2 and pfhrp3 gene deletion in P. falciparum in endemic areas of the Brazilian Amazon. Aliquots of DNA from the biorepository of the Laboratory of Basic Research in Malaria, Evandro Chagas Institute, with a positive diagnosis for P. falciparum infection as determined by microscopy and molecular assays, were included. Monoinfection was confirmed by nested-polymerase chain reaction assay, and DNA quality was assessed by amplification of the merozoite surface protein-2 gene (msp2). The pfhrp2 and pfhrp3 genes were amplified using primers for the region between exons 1 and 2 and for all extension of exon 2. Aliquots of DNA from 192 P. falciparum isolates were included in the study, with 68.7% (132/192) from the municipality of Cruzeiro do Sul (Acre) and 31.3% (60/192) from Manaus (Amazonas). Of this total, 82.8% (159/192) of the samples were considered of good quality. In the state of Acre, 71.7% (71/99) showed pfhrp2 gene deletion and 94.9% (94/99) showed pfhrp3 gene deletion, while in the state of Amazonas, 100.0% (60/60) of the samples showed pfhrp2 gene deletion and 98.3% (59/60) showed pfhrp3 gene deletion. Moreover, 79.8% (127/159) of isolates displayed gene deletion. Our findings confirm the presence of a parasite population with high frequencies of pfhrp2 and pfhrp3 gene deletions in the Brazilian Amazon region. This suggests reconsidering the use of HRP2-based RDTs in the Acre and Amazonas states and calls attention to the importance of molecular surveillance and mapping of pfhrp2/pfhrp3 deletions in this area and in other locations in the Amazon region to guarantee appropriate patient care, control and ultimately contribute to achieving P. falciparum malaria elimination. Full article
(This article belongs to the Special Issue Geo-Epidemiology of Malaria)
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19 pages, 5212 KiB  
Review
Plasmodium falciparum Histidine-Rich Protein 2 and 3 Gene Deletions and Their Implications in Malaria Control
by Josphat Nyataya, John Waitumbi, Victor A. Mobegi, Ayman Noreddin and Mohamed E. El Zowalaty
Diseases 2020, 8(2), 15; https://doi.org/10.3390/diseases8020015 - 20 May 2020
Cited by 23 | Viewed by 6125
Abstract
Malaria remains the biggest threat to public health, especially among pregnant women and young children in sub-Saharan Africa. Prompt and accurate diagnosis is critical for effective case management and detection of drug resistance. Conventionally, microscopy and rapid diagnostic tests (RDTs) are the tools [...] Read more.
Malaria remains the biggest threat to public health, especially among pregnant women and young children in sub-Saharan Africa. Prompt and accurate diagnosis is critical for effective case management and detection of drug resistance. Conventionally, microscopy and rapid diagnostic tests (RDTs) are the tools of choice for malaria diagnosis. RDTs are simple to use and have been extensively used in the diagnosis of malaria among travelers to malaria-endemic regions, routine case management, and surveillance studies. Most RDTs target the histidine-rich protein (PfHRP) which is exclusively found in Plasmodium falciparum and a metabolic enzyme Plasmodium lactate dehydrogenase (pLDH) which is common among all Plasmodium species. Other RDTs incorporate the enzyme aldolase that is produced by all Plasmodium species. Recently, studies have reported false-negative RDTs primarily due to the deletion of the histidine-rich protein (pfhrp2 and pfhrp3) genes in field isolates of P. falciparum. Herein, we review published literature to establish pfhrp2/pfhrp3 deletions, the extent of these deletions in different geographical regions, and the implication in malaria control. We searched for publications on pfhrp2/pfhrp3 deletions and retrieved all publications that reported on this subject. Overall, 20 publications reported on pfhrp2/pfhrp3 deletions, and most of these studies were done in Central and South America, with very few in Asia and Africa. The few studies in Africa that reported on the occurrence of pfhrp2/pfhrp3 deletions rarely evaluated deletions on the flanking genes. More studies are required to evaluate the existence and extent of these gene deletions, whose presence may lead to delayed or missed treatment. This information will guide appropriate diagnostic approaches in the respective areas. Full article
(This article belongs to the Section Infectious Disease)
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21 pages, 2486 KiB  
Review
Recent Advances in the Development of Biosensors for Malaria Diagnosis
by Francis D. Krampa, Yaw Aniweh, Prosper Kanyong and Gordon A. Awandare
Sensors 2020, 20(3), 799; https://doi.org/10.3390/s20030799 - 1 Feb 2020
Cited by 47 | Viewed by 11499
Abstract
The impact of malaria on global health has continually prompted the need to develop more effective diagnostic strategies that could overcome deficiencies in accurate and early detection. In this review, we examine the various biosensor-based methods for malaria diagnostic biomarkers, namely; Plasmodium falciparum [...] Read more.
The impact of malaria on global health has continually prompted the need to develop more effective diagnostic strategies that could overcome deficiencies in accurate and early detection. In this review, we examine the various biosensor-based methods for malaria diagnostic biomarkers, namely; Plasmodium falciparum histidine-rich protein 2 (PfHRP-2), parasite lactate dehydrogenase (pLDH), aldolase, glutamate dehydrogenase (GDH), and the biocrystal hemozoin. The models that demonstrate a potential for field application have been discussed, looking at the fabrication and analytical performance characteristics, including (but not exclusively limited to): response time, sensitivity, detection limit, linear range, and storage stability, which are first summarized in a tabular form and then described in detail. The conclusion summarizes the state-of-the-art technologies applied in the field, the current challenges and the emerging prospects for malaria biosensors. Full article
(This article belongs to the Section Biosensors)
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14 pages, 3237 KiB  
Article
Development of an Immunosensor for PfHRP 2 as a Biomarker for Malaria Detection
by Aver Hemben, Jon Ashley and Ibtisam E. Tothill
Biosensors 2017, 7(3), 28; https://doi.org/10.3390/bios7030028 - 18 Jul 2017
Cited by 39 | Viewed by 10687
Abstract
Plasmodium falciparum histidine-rich protein 2 (PfHRP 2) was selected in this work as the biomarker for the detection and diagnosis of malaria. An enzyme-linked immunosorbent assay (ELISA) was first developed to evaluate the immunoreagent’s suitability for the sensor’s development. A gold-based [...] Read more.
Plasmodium falciparum histidine-rich protein 2 (PfHRP 2) was selected in this work as the biomarker for the detection and diagnosis of malaria. An enzyme-linked immunosorbent assay (ELISA) was first developed to evaluate the immunoreagent’s suitability for the sensor’s development. A gold-based sensor with an integrated counter and an Ag/AgCl reference electrode was first selected and characterised and then used to develop the immunosensor for PfHRP 2, which enables a low cost, easy to use, and sensitive biosensor for malaria diagnosis. The sensor was applied to immobilise the anti-PfHRP 2 monoclonal antibody as the capture receptor. A sandwich ELISA assay format was constructed using horseradish peroxidase (HRP) as the enzyme label, and the electrochemical signal was generated using a 3, 3′, 5, 5′tetramethyl-benzidine dihydrochloride (TMB)/H2O2 system. The performance of the assay and the sensor were optimised and characterised, achieving a PfHRP 2 limit of detection (LOD) of 2.14 ng·mL−1 in buffer samples and 2.95 ng∙mL−1 in 100% spiked serum samples. The assay signal was then amplified using gold nanoparticles conjugated detection antibody-enzyme and a detection limit of 36 pg∙mL−1 was achieved in buffer samples and 40 pg∙mL−1 in serum samples. This sensor format is ideal for malaria detection and on-site analysis as a point-of-care device (POC) in resource-limited settings where the implementation of malaria diagnostics is essential in control and elimination efforts. Full article
(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)
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