Advances in Molecular Diagnosis of Malaria

A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366). This special issue belongs to the section "Vector-Borne Diseases".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 7144

Special Issue Editors


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Guest Editor
Sao Paulo State Health Department and School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
Interests: molecular diagnosis; genomic surveillance; Plasmodium; transfusional malaria; antimalarial drug resistance

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Guest Editor
Laboratory of Parasitic Diseases, Institute Oswaldo Cruz/Fiocruz, Rio de Janeiro, Brazil
Interests: malaria; epidemiology; molecular diagnosis; genomic surveillance

Special Issue Information

Dear Colleagues,

Despite efforts to control and eliminate malaria, the disease is still one of the most serious public health problems worldwide, with an estimated 241 million cases in 2020 in 85 endemic countries and 627,000 deaths. Malaria is the most frequent cause of fever among travelers returning from endemic areas. Malaria is a vector-borne disease caused by five species of Plasmodium in humans, P. falciparum, P. vivax, P. malariae, P. ovale and P. knowlesi. One of the pillars of the Global Technical Strategy for Malaria is ensuring access to malaria prevention, diagnosis, and treatment. Although the thick blood smear is still considered to be the best reference test, the detection limit is 100 parasites/µL and is not adequate for detecting low parasitemias in malaria elimination areas. Rapid diagnostic tests are especially useful in remote areas. However, sensitivity is low at parasite densities below 100 parasites/µL. In addition, isolates with a deletion in the antigen most targeted for detection of P. falciparum, histidine-rich protein 2 (PFHRP2), have been widely reported, leading to false-negative results. In this scenario, new molecular diagnostic tools with greater sensitivity are essential, as most have a detection limit of 1 parasite/µL. Furthermore, molecular tools targeting conservative genes are useful for species differentiation, including zoonotic malaria infections. This Special Issue focuses on the molecular diagnosis of malaria, including well-known tests and new platforms for use in reference centers or remote areas, such as LAMP point-of-care technologies. Asymptomatic infections play an important role in control and elimination goals, as low-density parasitemias below the threshold of detection by microscopy or rapid diagnostic tests are transmissible to the Anopheles vector. In addition, asymptomatic carriers pose a risk to blood banks and transplant procedures. We intend for this Special Issue of Tropical Medicine and Infectious Disease to broadly address recent advances in molecular tools applied to the diagnosis of malaria, aiming to contribute to the control, surveillance, and elimination of this life-threatening disease.

Dr. Silvia Maria Fatima Di Santi
Dr. Martha Cecilia Suárez-Mutis
Guest Editors

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Keywords

  • malaria
  • Plasmodium
  • molecular diagnosis
  • malaria elimination
  • nucleic acid amplification test

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Published Papers (3 papers)

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Research

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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
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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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10 pages, 1267 KiB  
Article
Evaluation of A Simple DNA Extraction Method and Its Combination with Loop-Mediated Isothermal Amplification Assays for Rapid Plasmodium knowlesi Diagnosis
by Meng-Yee Lai, Mohd Hafizi Abdul Hamid, Jenarun Jelip, Rose Nani Mudin and Yee-Ling Lau
Trop. Med. Infect. Dis. 2023, 8(8), 389; https://doi.org/10.3390/tropicalmed8080389 - 29 Jul 2023
Cited by 2 | Viewed by 1788
Abstract
The initial and vital stage in the diagnosis of malaria involves extracting DNA. The efficiency of malaria testing is restricted by the multiple steps involved in commercial DNA extraction kits. We attempted to improve an existing loop-mediated isothermal amplification (LAMP) for the detection [...] Read more.
The initial and vital stage in the diagnosis of malaria involves extracting DNA. The efficiency of malaria testing is restricted by the multiple steps involved in commercial DNA extraction kits. We attempted to improve an existing loop-mediated isothermal amplification (LAMP) for the detection of Plasmodium knowlesi by using a simple DNA extraction approach, making it a feasible option for mass screening. We utilized a simple nucleic acid extraction method directly from whole blood for the detection of P. knowlesi, taking only 5 min to complete. The extracted DNA was evaluated by two fluorescent-based LAMP and one colorimetric-based LAMP assay. The detection limit for both SYTO-LAMP and SYBR green-LAMP was 0.00001% and 0.0001% parasitemia, respectively. Meanwhile, neutral red-LAMP had a detection limit of 0.01% parasitemia. Combining this simple and inexpensive DNA extraction method, SYTO-LAMP could serve as an alternative molecular diagnosis for the detection of P. knowlesi and other human Plasmodium spp. Full article
(This article belongs to the Special Issue Advances in Molecular Diagnosis of Malaria)
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16 pages, 680 KiB  
Systematic Review
Relationship between Duffy Genotype/Phenotype and Prevalence of Plasmodium vivax Infection: A Systematic Review
by Yelson Alejandro Picón-Jaimes, Ivan David Lozada-Martinez, Javier Esteban Orozco-Chinome, Jessica Molina-Franky, Domenica Acevedo-Lopez, Nicole Acevedo-Lopez, Maria Paz Bolaño-Romero, Fabriccio J. Visconti-Lopez, D. Katterine Bonilla-Aldana and Alfonso J. Rodriguez-Morales
Trop. Med. Infect. Dis. 2023, 8(10), 463; https://doi.org/10.3390/tropicalmed8100463 - 30 Sep 2023
Cited by 2 | Viewed by 3343
Abstract
The Duffy protein, a transmembrane molecule, functions as a receptor for various chemokines and facilitates attachment between the reticulocyte and the Plasmodium Duffy antigen-binding protein. Duffy expression correlates with the Duffy receptor gene for the chemokine, located on chromosome 1, and exhibits geographical [...] Read more.
The Duffy protein, a transmembrane molecule, functions as a receptor for various chemokines and facilitates attachment between the reticulocyte and the Plasmodium Duffy antigen-binding protein. Duffy expression correlates with the Duffy receptor gene for the chemokine, located on chromosome 1, and exhibits geographical variability worldwide. Traditionally, researchers have described the Duffy negative genotype as a protective factor against Plasmodium vivax infection. However, recent studies suggest that this microorganism’s evolution could potentially diminish this protective effect. Nevertheless, there is currently insufficient global data to demonstrate this phenomenon. This study aimed to evaluate the relationship between the Duffy genotype/phenotype and the prevalence of P. vivax infection. The protocol for the systematic review was registered in PROSPERO as CRD42022353427 and involved reviewing published studies from 2012 to 2022. The Medline/PubMed, Web of Science, Scopus, and SciELO databases were consulted. Assessments of study quality were conducted using the STROBE and GRADE tools. A total of 34 studies were included, with Africa accounting for the majority of recorded studies. The results varied significantly regarding the relationship between the Duffy genotype/phenotype and P. vivax invasion. Some studies predominantly featured the negative Duffy genotype yet reported no malaria cases. Other studies identified minor percentages of infections. Conversely, certain studies observed a higher prevalence (99%) of Duffy-negative individuals infected with P. vivax. In conclusion, this systematic review found that the homozygous Duffy genotype positive for the A allele (FY*A/*A) is associated with a higher incidence of P. vivax infection. Furthermore, the negative Duffy genotype does not confer protection against vivax malaria. Full article
(This article belongs to the Special Issue Advances in Molecular Diagnosis of Malaria)
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