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Recent Advances in Malaria Diagnosis
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Recent Advances in Malaria Diagnosis

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Diagnostic Microbiology and Infectious Disease".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 45307

Special Issue Editors

Prof. Dr. Weng Kung Peng

E-Mail Website
Guest Editor
Spin Dynamics in Health Engineering, Songshan Lake Materials Laboratory, Building A1, University Innovation Park, Songshan Lake, Dongguan 523808, China
Interests: precision medicine; NMR-based PoCT; machine learning
Special Issues, Collections and Topics in MDPI journals
Dr. Maria Isabel Veiga

E-Mail Website
Guest Editor
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
Interests: malaria; plasmodium falciparum; antimalarial drugs; resistance; epidemiology; diagnostics; molecular markers; hemozoin; drug transporters
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

On behalf of Diagnostics, we cordially invite you to submit a manuscript to our Special Issue entitled “Recent Advances in Malaria Diagnosis”.

Malaria is a major public health concern which continues to claim the lives of more than 435,000 people each year. The challenges with antimalarial drug resistance and detection of low parasitaemia form an immediate barrier to achieving the United Nations Sustainable Development Goals of ending malaria epidemics by the fast-approaching deadline of 2030. With the increasing human mobility (e.g., travel, migration), the threat of resurgence in traditionally non-endemic countries (e.g., United States, Europe) remains high.

This Special Issue discusses the recent advances of emerging technologies/methodologies in malaria diagnostics. Submissions can be original research articles, reviews, or commentaries/perspectives.

Prof. Dr. Weng Kung Peng
Dr. Maria Isabel Veiga
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Malaria
  • Diagnostic
  • Asymptomatic
  • Sensitive
  • Specific

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Related Special Issue

Published Papers (10 papers)

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Research

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19 pages, 4577 KiB  
Article
Diagnosis of Indigenous Non-Malarial Vector-Borne Infections from Malaria Negative Samples from Community and Rural Hospital Surveillance in Dhalai District, Tripura, North-East India
by Ipsita Pal Bhowmick, Apoorva Pandey, Sarala K. Subbarao, Rocky Pebam, Tapan Majumder, Aatreyee Nath, Diptarup Nandi, Analabha Basu, Apurba Sarkar, Saikat Majumder, Jotish Debbarma, Dipanjan Dasgupta, Arup Borgohain, Rajdeep Chanda, Mandakini Das, Karuna Gogoi, Kongkona Gogoi, Pyare Laal Joshi, Harpreet Kaur, Biswajyoti Borkakoti, Dibya Ranjan Bhattacharya, Abdul Mamood Khan, Satyajit Sen and Kanwar Narainadd Show full author list remove Hide full author list
Diagnostics 2022, 12(2), 362; https://doi.org/10.3390/diagnostics12020362 - 1 Feb 2022
Cited by 3 | Viewed by 3882
Abstract
The aetiology of non-malaria vector-borne diseases in malaria-endemic, forested, rural, and tribal-dominated areas of Dhalai, Tripura, in north-east India, was studied for the first time in the samples collected from malaria Rapid Diagnostic Kit negative febrile patients by door-to-door visits in the villages [...] Read more.
The aetiology of non-malaria vector-borne diseases in malaria-endemic, forested, rural, and tribal-dominated areas of Dhalai, Tripura, in north-east India, was studied for the first time in the samples collected from malaria Rapid Diagnostic Kit negative febrile patients by door-to-door visits in the villages and primary health centres. Two hundred and sixty serum samples were tested for the Dengue NS1 antigen and the IgM antibodies of Dengue, Chikungunya, Scrub Typhus (ST), and Japanese Encephalitis (JE) during April 2019–March 2020. Fifteen Dengue, six JE, twelve Chikungunya, nine ST and three Leptospirosis, and mixed infections of three JE + Chikungunya, four Dengue + Chikungunya, three Dengue + JE + Chikungunya, one Dengue + Chikungunya + ST, and one Dengue + ST were found positive by IgM ELISA tests, and four for the Dengue NS1 antigen, all without any travel history. True prevalence values estimated for infections detected by Dengue IgM were 0.134 (95% CI: 0.08–0.2), Chikungunya were 0.084 (95% CI: 0.05–0.13), Scrub were 0.043 (95% CI: 0.01–0.09), and Japanese Encephalitis were 0.045 (95% CI: 0.02–0.09). Dengue and Chikungunya were associated significantly more with a younger age. There was a lack of a defined set of symptoms for any of the Dengue, Chikungunya, JE or ST infections, as indicated by the k-modes cluster analysis. Interestingly, most of these symptoms have an overlapping set with malaria; thereby, it becomes imperative that malaria and these non-malaria vector-borne disease diagnoses are made in a coordinated manner. Findings from this study call for advances in routine diagnostic procedures and the development of a protocol that can accommodate, currently, in practicing the rapid diagnosis of malaria and other vector-borne diseases, which is doable even in the resource-poor settings of rural hospitals and during community fever surveillance. Full article
(This article belongs to the Special Issue Recent Advances in Malaria Diagnosis)
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13 pages, 4963 KiB  
Article
Advanced Multiplex Loop Mediated Isothermal Amplification (mLAMP) Combined with Lateral Flow Detection (LFD) for Rapid Detection of Two Prevalent Malaria Species in India and Melting Curve Analysis
by Supriya Sharma, Sandeep Kumar, Md Zohaib Ahmed, Nitin Bhardwaj, Jaskirat Singh, Sarita Kumari, Deepali Savargaonkar, Anupkumar R. Anvikar and Jyoti Das
Diagnostics 2022, 12(1), 32; https://doi.org/10.3390/diagnostics12010032 - 24 Dec 2021
Cited by 12 | Viewed by 4828
Abstract
Isothermal techniques with lateral flow detection have emerged as a point of care (POC) technique for malaria, a major parasitic disease in tropical countries such as India. Plasmodium falciparum and Plasmodium vivax are the two most prevalent malaria species found in the country. [...] Read more.
Isothermal techniques with lateral flow detection have emerged as a point of care (POC) technique for malaria, a major parasitic disease in tropical countries such as India. Plasmodium falciparum and Plasmodium vivax are the two most prevalent malaria species found in the country. An advanced multiplex loop-mediated isothermal amplification (mLAMP) combined with a lateral flow dipstick (LFD) technique was developed for the swift and accurate detection of P. falciparum and P. vivax, overcoming the challenges of the existing RDTs (rapid diagnostic tests). A single set of LAMP primers with a biotinylated backward inner primer (BIP primer) was used for DNA amplification of both malaria species in a single tube. The amplified DNA was hybridized with fluorescein isothiocyanate (FITC) and digoxigenin-labelled DNA probes, having a complemented sequence for the P. falciparum and P. vivax genomes, respectively. A colour band appeared on two separate LFDs for P. falciparum and P. vivax upon running the hybridized solution over them. In total, 39 clinical samples were collected from ICMR-NIMR, New Delhi. Melting curve analysis, with cross primers for both species, was used to ascertain specificity, and the sensitivity was equated with a polymerase chain reaction (PCR). The results were visualized on the LFD for both species within 60 min. We found 100% sensitivity and specificity, when compared with a traditional PCR. Melting curve analysis of mLAMP revealed the lowest detection limit of 0.15 pg/μL from sample genomic DNA. The mLAMP-LFD assays could be a potential point of care (POC) tool for early diagnosis in non-laboratory conditions, with the convenience of a reduced assay time and the simple interpretation of results. Full article
(This article belongs to the Special Issue Recent Advances in Malaria Diagnosis)
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11 pages, 1865 KiB  
Article
Development of a Multiplex Loop-Mediated Isothermal Amplification Assay for Diagnosis of Plasmodium spp., Plasmodium falciparum and Plasmodium vivax
by Woong Sik Jang, Da Hye Lim, YoungLan Choe, Hyunseul Jee, Kyung Chul Moon, Chaewon Kim, Minkyeong Choi, In Su Park and Chae Seung Lim
Diagnostics 2021, 11(11), 1950; https://doi.org/10.3390/diagnostics11111950 - 20 Oct 2021
Cited by 5 | Viewed by 2526
Abstract
Malaria, caused by the parasite Plasmodium and transmitted by mosquitoes, is an epidemic that mainly occurs in tropical and subtropical regions. As treatments differ across species of malarial parasites, there is a need to develop rapid diagnostic methods to differentiate malarial species. Herein, [...] Read more.
Malaria, caused by the parasite Plasmodium and transmitted by mosquitoes, is an epidemic that mainly occurs in tropical and subtropical regions. As treatments differ across species of malarial parasites, there is a need to develop rapid diagnostic methods to differentiate malarial species. Herein, we developed a multiplex malaria Pan/Pf/Pv/actin beta loop-mediated isothermal amplification (LAMP) to diagnose Plasmodium spp., P. falciparum, and P. vivax, as well as the internal control (IC), within 40 min. The detection limits of the multiplex malaria Pan/Pf/Pv/IC LAMP were 1 × 102, 1 × 102, 1 × 102, and 1 × 103 copies/µL for four vectors, including the 18S rRNA gene (Plasmodium spp.), lactate dehydrogenase gene (P. falciparum), 16S rRNA gene (P. vivax), and human actin beta gene (IC), respectively. The performance of the LAMP assay was compared and evaluated by evaluating 208 clinical samples (118 positive and 90 negative samples) with the commercial RealStar® Malaria S&T PCR Kit 1.0. The developed multiplex malaria Pan/Pf/Pv/IC LAMP assay showed comparable sensitivity (100%) and specificity (100%) with the commercial RealStar® Malaria S&T PCR Kit 1.0 (100%). These results suggest that the multiplex malaria Pan/Pf/Pv/IC LAMP could be used as a point-of-care molecular diagnostic test for malaria. Full article
(This article belongs to the Special Issue Recent Advances in Malaria Diagnosis)
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14 pages, 7012 KiB  
Article
An Optimized Real-Time qPCR Method for the Effective Detection of Human Malaria Infections
by Saiful Arefeen Sazed, Mohammad Golam Kibria and Mohammad Shafiul Alam
Diagnostics 2021, 11(5), 736; https://doi.org/10.3390/diagnostics11050736 - 21 Apr 2021
Cited by 13 | Viewed by 5410
Abstract
Polymerase chain reaction, although an expensive method for the detection of human Plasmodium spp., is still considered the finest for the diagnosis of malaria. The conventional diagnostic PCR is an inexpensive process but consumes a lot of time, reagents and lacks sensitivity. On [...] Read more.
Polymerase chain reaction, although an expensive method for the detection of human Plasmodium spp., is still considered the finest for the diagnosis of malaria. The conventional diagnostic PCR is an inexpensive process but consumes a lot of time, reagents and lacks sensitivity. On the other hand, real-time PCR assays currently being used are mostly probe-based expensive methods and sometimes not feasible to detect all the species in a single amplification reaction condition. Here we have established a real-time PCR method that is time and cost effective with a single protocol to detect and distinguish five human Plasmodium species using the existing primers efficiently. The primers used here are being used in the conventional method and the sensitivity as well as specificity of this method has also been immensely improved (100%). The lower limit of detection for Plasmodium falciparum, Plasmodium vivax and Plasmodium malariae are 0.064 parasites/µL, 1.6 parasites/µL, and 0.32 parasites/µL respectively and no cross reactivity was observed. Besides, we have analyzed melt curves that can be used for further species confirmation and validation purposes using multiplex systems. This method, therefore, can be considered as an alternative to the existing lineup for molecular diagnosis of malaria in endemic countries. Full article
(This article belongs to the Special Issue Recent Advances in Malaria Diagnosis)
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11 pages, 1612 KiB  
Article
Validation of PfSNP-LAMP-Lateral Flow Dipstick for Detection of Single Nucleotide Polymorphism Associated with Pyrimethamine Resistance in Plasmodium falciparum
by Suganya Yongkiettrakul, Fassou René Kolié, Darin Kongkasuriyachai, Jetsumon Sattabongkot, Wang Nguitragool, Namfon Nawattanapaibool, Chayanut Suansomjit, Saradee Warit, Niwat Kangwanrangsan and Sureemas Buates
Diagnostics 2020, 10(11), 948; https://doi.org/10.3390/diagnostics10110948 - 13 Nov 2020
Cited by 6 | Viewed by 3044
Abstract
The loop-mediated isothermal amplification coupled with lateral flow dipstick (PfSNP-LAMP-LFD) was recently developed to detect single nucleotide polymorphism (AAT → ATT), corresponding to substitution of asparagine to isoleucine at amino acid position 51 in the P. falciparum [...] Read more.
The loop-mediated isothermal amplification coupled with lateral flow dipstick (PfSNP-LAMP-LFD) was recently developed to detect single nucleotide polymorphism (AAT → ATT), corresponding to substitution of asparagine to isoleucine at amino acid position 51 in the P. falciparumdhfr-ts gene associated with antifolate resistance. In this present study, the PfSNP-LAMP-LFD was validated on 128 clinical malaria samples of broad ranged parasite densities (10 to 87,634 parasites per microliter of blood). The results showed 100% accuracy for the detection of single nucleotide polymorphism for N51I mutation. Indeed, the high prevalence of N51I in the Pfdhfr-ts gene detected in the clinical samples is in line with reports of widespread antifolate resistant P. falciparum in Thailand. The relationship between enzyme choice and reaction time was observed to have an effect on PfSNP-LAMP-LFD specificity; however, the method yielded consistent results once the conditions have been optimized. The results demonstrate that PfSNP-LAMP-LFD is a simple method with sufficient sensitivity and specificity to be deployed in routine surveillance of antifolate resistance molecular marker and inform antimalarial management policy. Full article
(This article belongs to the Special Issue Recent Advances in Malaria Diagnosis)
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Review

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11 pages, 276 KiB  
Review
The Potential Use of Volatile Biomarkers for Malaria Diagnosis
by Hwa Chia Chai and Kek Heng Chua
Diagnostics 2021, 11(12), 2244; https://doi.org/10.3390/diagnostics11122244 - 30 Nov 2021
Cited by 5 | Viewed by 2307
Abstract
Pathogens may change the odor and odor-related biting behavior of the vector and host to enhance pathogen transmission. In recent years, volatile biomarker investigations have emerged to identify odors that are differentially and specifically released by pathogens and plants, or the pathogen-infected or [...] Read more.
Pathogens may change the odor and odor-related biting behavior of the vector and host to enhance pathogen transmission. In recent years, volatile biomarker investigations have emerged to identify odors that are differentially and specifically released by pathogens and plants, or the pathogen-infected or even cancer patients. Several studies have reported odors or volatile biomarkers specifically detected from the breath and skin of malaria-infected individuals. This review will discuss the potential use of these odors or volatile biomarkers for the diagnosis of malaria. This approach not only allows for the non-invasive mean of sample collection but also opens up the opportunity to develop a biosensor for malaria diagnosis in low-resource settings. Full article
(This article belongs to the Special Issue Recent Advances in Malaria Diagnosis)
17 pages, 1044 KiB  
Review
Multi-Omics Advancements towards Plasmodium vivax Malaria Diagnosis
by Shalini Aggarwal, Weng Kung Peng and Sanjeeva Srivastava
Diagnostics 2021, 11(12), 2222; https://doi.org/10.3390/diagnostics11122222 - 28 Nov 2021
Cited by 14 | Viewed by 4254
Abstract
Plasmodium vivax malaria is one of the most lethal infectious diseases, with 7 million infections annually. One of the roadblocks to global malaria elimination is the lack of highly sensitive, specific, and accurate diagnostic tools. The absence of diagnostic tools in particular has [...] Read more.
Plasmodium vivax malaria is one of the most lethal infectious diseases, with 7 million infections annually. One of the roadblocks to global malaria elimination is the lack of highly sensitive, specific, and accurate diagnostic tools. The absence of diagnostic tools in particular has led to poor differentiation among parasite species, poor prognosis, and delayed treatment. The improvement necessary in diagnostic tools can be broadly grouped into two categories: technologies-driven and omics-driven progress over time. This article discusses the recent advancement in omics-based malaria for identifying the next generation biomarkers for a highly sensitive and specific assay with a rapid and antecedent prognosis of the disease. We summarize the state-of-the-art diagnostic technologies, the key challenges, opportunities, and emerging prospects of multi-omics-based sensors. Full article
(This article belongs to the Special Issue Recent Advances in Malaria Diagnosis)
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10 pages, 290 KiB  
Review
Epidemiological, Physiological and Diagnostic Comparison of Plasmodium ovale curtisi and Plasmodium ovale wallikeri
by Joseph Hawadak, Rodrigue Roman Dongang Nana and Vineeta Singh
Diagnostics 2021, 11(10), 1900; https://doi.org/10.3390/diagnostics11101900 - 14 Oct 2021
Cited by 5 | Viewed by 2228
Abstract
Nowadays, Plasmodium ovale is divided into two non-recombinant sympatric species: Plasmodium ovale wallikeri and Plasmodium ovale curtisi. In this mini review, we summarize the available knowledge on the clinical/biological aspects of P. ovale spp. malaria and current techniques for the diagnosis/characterisation of [...] Read more.
Nowadays, Plasmodium ovale is divided into two non-recombinant sympatric species: Plasmodium ovale wallikeri and Plasmodium ovale curtisi. In this mini review, we summarize the available knowledge on the clinical/biological aspects of P. ovale spp. malaria and current techniques for the diagnosis/characterisation of P. ovale curtisi and P. ovale wallikeri. P. ovale wallikeri infections are characterized by a deeper thrombocytopenia and shorter latency compared to P. ovale curtisi infections, indicating that P. ovale wallikeri is more pathogenic than P. ovale curtisi. Rapid diagnosis for effective management is difficult for P. ovale spp., since specific rapid diagnostic tests are not available and microscopic diagnosis, which is recognized as the gold standard, requires expert microscopists to differentiate P. ovale spp. from other Plasmodium species. Neglect in addressing these issues in the prevalence of P. ovale spp. represents the existing gap in the fight against malaria. Full article
(This article belongs to the Special Issue Recent Advances in Malaria Diagnosis)
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 34 | Viewed by 10108
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)
18 pages, 367 KiB  
Review
Performance and Application of Commercially Available Loop-Mediated Isothermal Amplification (LAMP) Kits in Malaria Endemic and Non-Endemic Settings
by Ulrika Morris and Berit Aydin-Schmidt
Diagnostics 2021, 11(2), 336; https://doi.org/10.3390/diagnostics11020336 - 18 Feb 2021
Cited by 23 | Viewed by 3885
Abstract
Loop-mediated isothermal amplification (LAMP) is a sensitive molecular tool suitable for use as a near point-of-care test for the diagnosis of malaria. Recent meta-analyses have detailed high sensitivity and specificity of malaria LAMP when compared to microscopy, rapid diagnostic tests, and polymerase chain [...] Read more.
Loop-mediated isothermal amplification (LAMP) is a sensitive molecular tool suitable for use as a near point-of-care test for the diagnosis of malaria. Recent meta-analyses have detailed high sensitivity and specificity of malaria LAMP when compared to microscopy, rapid diagnostic tests, and polymerase chain reaction in both endemic and non-endemic settings. Despite this, the use of malaria LAMP has primarily been limited to research settings to date. In this review, we aim to assess to what extent commercially available malaria LAMP kits have been applied in different settings, and to identify possible obstacles that may have hindered their use from being adopted further. In order to address this, we conducted a literature search in PubMed.gov using the search terms (((LAMP) OR (Loop-mediated isothermal amplification)) AND ((Malaria) OR (Plasmodium))). Focusing primarily on studies employing one of the commercially available kits, we then selected three key areas of LAMP application for further review: the performance and application of LAMP in malaria endemic settings including low transmission areas; LAMP for malaria screening during pregnancy; and malaria LAMP in returning travelers in non-endemic settings. Full article
(This article belongs to the Special Issue Recent Advances in Malaria Diagnosis)
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