Genomics and Epidemiology of Protozoan Parasites

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Parasitic Pathogens".

Deadline for manuscript submissions: 30 November 2024 | Viewed by 16161

Special Issue Editors


E-Mail Website
Guest Editor
Institute of Tropical Medicine, University of Tuebingen, 72074 Tuebingen, Germany
Interests: malaria; neglected tropical diseases; diagnostics; clinical studies

E-Mail Website
Guest Editor
Institute of Tropical Medicine, University of Tuebingen, 72074 Tuebingen, Germany
Interests: malaria; infectious diseases; clinical trials; vaccines; chemotherapies

Special Issue Information

Dear Colleagues, 

Globally, more than 1 billion people are at risk of infectious diseases caused by protozoan parasites. Protozoan parasites are a large and highly diverse group of unicellular eukaryotes infecting humans and animals. The most important parasitic diseases in humans include malaria, as well as African trypanosomiasis, Chagas disease, and leishmaniasis, which are considered neglected tropical diseases. Gastroenteric diseases such as cryptosporidiosis and giardiasis are also caused by protozoan parasites. These diseases are considered poverty-related and are a significant health burden particularly in poor, tropical and subtropical countries. However, they occasionally occur in industrialized countries, as do toxoplasmosis and babesiosis. Infection with Toxoplasma gondii during pregnancy is a serious risk to the unborn baby, and Naegleria fowleri is a free-living, rare but emerging protozoon causing severe disease.

Efficacious treatments and prevention measures are available for some of these parasitic diseases. Malaria can effectively be cured with artemisinin-based combination therapies, and even a malaria vaccine is on the horizon. Human African trypanosomiasis is reaching the elimination phase, and a new drug has recently been developed. In contrast, cure from Chagas remains difficult, as is the case for many other protozoan infections. Overall, there is a lack of safe and effective antiparasitic vaccines and treatments, and the development of resistance in parasites is worsening the situation. Apart from the overall limited efforts and financial investment, there are many reasons for this deficit. Compared to viruses and bacteria, protozoan parasites have more complex genomes, cellular structure, life cycle and biology; host–parasite interactions are not well understood; and many parasites evade the host´s immune response.

Genome-scale sequencing approaches can be applied to all areas of biological investigations, including understanding of gene function and of parasite biology, as well as a tool for epidemiological investigations such as the identification of new parasite strains, parasite transmission and spread, parasite evolution and spread of drug resistance. In this Special Issue we will provide a collection of in-depth, up-to-date genome-scale investigations on several protozoan parasites. 

We invite original research and review articles reporting on protozoan parasites infective to humans. Potential topics include but are not limited to:

  • Functional genomics to understand parasite biology.
  • Evolutionary and comparative genomics to understand evolutionary relationships and phylogeny.
  • Genomic variations in parasite populations (including resistance markers).
  • Genomics epidemiology (including prevalence, geographic distribution, and transmission patterns).

Dr. Andrea Kreidenweiss
Prof. Dr. Peter G. Kremsner
Guest Editors

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Keywords

  • protozoa
  • parasite
  • human pathogenic
  • genomics
  • epidemiology

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Published Papers (5 papers)

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Research

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12 pages, 1304 KiB  
Article
Comparative study of Plasmodium falciparum msp-1 and msp-2 Genetic Diversity in Isolates from Rural and Urban Areas in the South of Brazzaville, Republic of Congo
by Marcel Tapsou Baina, Abel Lissom, Naura Veil Assioro Doulamo, Jean Claude Djontu, Dieu Merci Umuhoza, Jacques Dollon Mbama-Ntabi, Steve Diafouka-Kietela, Jolivet Mayela, Georges Missontsa, Charles Wondji, Ayola Akim Adegnika, Etienne Nguimbi, Steffen Borrmann and Francine Ntoumi
Pathogens 2023, 12(5), 742; https://doi.org/10.3390/pathogens12050742 - 22 May 2023
Cited by 2 | Viewed by 1885
Abstract
Polymorphisms in the genes encoding the merozoite surface proteins msp-1 and msp-2 are widely used markers for characterizing the genetic diversity of Plasmodium falciparum. This study aimed to compare the genetic diversity of circulating parasite strains in rural and urban settings in the [...] Read more.
Polymorphisms in the genes encoding the merozoite surface proteins msp-1 and msp-2 are widely used markers for characterizing the genetic diversity of Plasmodium falciparum. This study aimed to compare the genetic diversity of circulating parasite strains in rural and urban settings in the Republic of Congo after the introduction of artemisinin-based combination therapy (ACT) in 2006. A cross-sectional survey was conducted from March to September 2021 in rural and urban areas close to Brazzaville, during which Plasmodium infection was detected using microscopy (and nested-PCR for submicroscopic infection). The genes coding for merozoite proteins-1 and -2 were genotyped by allele-specific nested PCR. Totals of 397 (72.4%) and 151 (27.6%) P. falciparum isolates were collected in rural and urban areas, respectively. The K1/msp-1 and FC27/msp-2 allelic families were predominant both in rural (39% and 64%, respectively) and urban (45.4% and 54.5% respectively) areas. The multiplicity of infection (MOI) was higher (p = 0.0006) in rural areas (2.9) compared to urban settings (2.4). The rainy season and the positive microscopic infection were associated with an increase in MOI. These findings reveal a higher P. falciparum genetic diversity and MOI in the rural setting of the Republic of Congo, which is influenced by the season and the participant clinical status. Full article
(This article belongs to the Special Issue Genomics and Epidemiology of Protozoan Parasites)
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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 6 | Viewed by 2325
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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16 pages, 1649 KiB  
Article
In Vitro Cytopathogenic Activities of Acanthamoeba T3 and T4 Genotypes on HeLa Cell Monolayer
by Rosnani Hanim Mohd Hussain, Mohamed Kamel Abdul Ghani, Naveed Ahmed Khan, Ruqaiyyah Siddiqui, Shafiq Aazmi, Hasseri Halim and Tengku Shahrul Anuar
Pathogens 2022, 11(12), 1474; https://doi.org/10.3390/pathogens11121474 - 5 Dec 2022
Cited by 1 | Viewed by 1843
Abstract
Amoebic keratitis and encephalitis are mainly caused by free-living amoebae of the genus Acanthamoeba, which consists of both pathogenic and nonpathogenic species. The global distribution, amphizoic properties and the severity of the disease caused by Acanthamoeba species have inspired the scientific community [...] Read more.
Amoebic keratitis and encephalitis are mainly caused by free-living amoebae of the genus Acanthamoeba, which consists of both pathogenic and nonpathogenic species. The global distribution, amphizoic properties and the severity of the disease caused by Acanthamoeba species have inspired the scientific community to put more effort into the isolation of Acanthamoeba, besides exploring the direct and indirect parameters that could signify a pathogenic potential. Therefore, this study was performed to characterize the pathogenic potential of Acanthamoeba isolated from contact lens paraphernalia and water sources in Malaysia. Various methodologies were utilized to analyze the thermotolerance and osmotolerance, the secretion level of proteases and the cytopathic effect of trophozoites on the cell monolayer. In addition, the in vitro cytopathogenicity of these isolates was assessed using the LDH-release assay. A total of 14 Acanthamoeba isolates were classified as thermo- and osmotolerant and had presence of serine proteases with a molecular weight of 45–230 kDa. Four T4 genotypes isolated from contact lens paraphernalia recorded the presence of serine-type proteases of 107 kDa and 133 kDa. In contrast, all T3 genotypes isolated from environmental samples showed the presence of a 56 kDa proteolytic enzyme. Remarkably, eight T4 and a single T3 genotype isolates demonstrated a high adhesion percentage of greater than 90%. Moreover, the use of the HeLa cell monolayer showed that four T4 isolates and one T3 isolate achieved a cytopathic effect in the range of 44.9–59.4%, indicating an intermediate-to-high cytotoxicity level. Apart from that, the LDH-release assay revealed that three T4 isolates (CL5, CL54 and CL149) and one T3 isolate (SKA5-SK35) measured an exceptional toxicity level of higher than 40% compared to other isolates. In short, the presence of Acanthamoeba T3 and T4 genotypes with significant pathogenic potential in this study reiterates the essential need to reassess the functionality of other genotypes that were previously classified as nonpathogenic isolates in past research. Full article
(This article belongs to the Special Issue Genomics and Epidemiology of Protozoan Parasites)
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Review

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19 pages, 1703 KiB  
Review
Distribution and Current State of Molecular Genetic Characterization in Pathogenic Free-Living Amoebae
by Alejandro Otero-Ruiz, Leobardo Daniel Gonzalez-Zuñiga, Libia Zulema Rodriguez-Anaya, Luis Fernando Lares-Jiménez, Jose Reyes Gonzalez-Galaviz and Fernando Lares-Villa
Pathogens 2022, 11(10), 1199; https://doi.org/10.3390/pathogens11101199 - 18 Oct 2022
Cited by 14 | Viewed by 4812
Abstract
Free-living amoebae (FLA) are protozoa widely distributed in the environment, found in a great diversity of terrestrial biomes. Some genera of FLA are linked to human infections. The genus Acanthamoeba is currently classified into 23 genotypes (T1-T23), and of these some (T1, T2, [...] Read more.
Free-living amoebae (FLA) are protozoa widely distributed in the environment, found in a great diversity of terrestrial biomes. Some genera of FLA are linked to human infections. The genus Acanthamoeba is currently classified into 23 genotypes (T1-T23), and of these some (T1, T2, T4, T5, T10, T12, and T18) are known to be capable of causing granulomatous amoebic encephalitis (GAE) mainly in immunocompromised patients while other genotypes (T2, T3, T4, T5, T6, T10, T11, T12, and T15) cause Acanthamoeba keratitis mainly in otherwise healthy patients. Meanwhile, Naegleria fowleri is the causative agent of an acute infection called primary amoebic meningoencephalitis (PAM), while Balamuthia mandrillaris, like some Acanthamoeba genotypes, causes GAE, differing from the latter in the description of numerous cases in patients immunocompetent. Finally, other FLA related to the pathologies mentioned above have been reported; Sappinia sp. is responsible for one case of amoebic encephalitis; Vermamoeba vermiformis has been found in cases of ocular damage, and its extraordinary capacity as endocytobiont for microorganisms of public health importance such as Legionella pneumophila, Bacillus anthracis, and Pseudomonas aeruginosa, among others. This review addressed issues related to epidemiology, updating their geographic distribution and cases reported in recent years for pathogenic FLA. Full article
(This article belongs to the Special Issue Genomics and Epidemiology of Protozoan Parasites)
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Other

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14 pages, 760 KiB  
Systematic Review
Systematic Review and Meta-Analysis on Human African Trypanocide Resistance
by Keneth Iceland Kasozi, Ewan Thomas MacLeod and Susan Christina Welburn
Pathogens 2022, 11(10), 1100; https://doi.org/10.3390/pathogens11101100 - 25 Sep 2022
Cited by 6 | Viewed by 2379
Abstract
Background Human African trypanocide resistance (HATr) is a challenge for the eradication of Human African Trypansomiaisis (HAT) following the widespread emergence of increased monotherapy drug treatment failures against Trypanosoma brucei gambiense and T. b. rhodesiense that are associated with changes in pathogen [...] Read more.
Background Human African trypanocide resistance (HATr) is a challenge for the eradication of Human African Trypansomiaisis (HAT) following the widespread emergence of increased monotherapy drug treatment failures against Trypanosoma brucei gambiense and T. b. rhodesiense that are associated with changes in pathogen receptors. Methods: Electronic searches of 12 databases and 3 Google search websites for human African trypanocide resistance were performed using a keyword search criterion applied to both laboratory and clinical studies. Fifty-one publications were identified and included in this study using the PRISMA checklist. Data were analyzed using RevMan and random effect sizes were computed for the statistics at the 95% confidence interval. Results: Pentamidine/melarsoprol/nifurtimox cross-resistance is associated with loss of the T. brucei adenosine transporter 1/purine 2 gene (TbAT1/P2), aquaglyceroporins (TbAQP) 2 and 3, followed by the high affinity pentamidine melarsoprol transporter (HAPT) 1. In addition, the loss of the amino acid transporter (AAT) 6 is associated with eflornithine resistance. Nifurtimox/eflornithine combination therapy resistance is associated with AAT6 and nitroreductase loss, and high resistance and parasite regrowth is responsible for treatment relapse. In clinical studies, the TbAT1 proportion of total random effects was 68% (95% CI: 38.0–91.6); I2 = 96.99% (95% CI: 94.6–98.3). Treatment failure rates were highest with melarsoprol followed by eflornithine at 41.49% (95% CI: 24.94–59.09) and 6.56% (3.06–11.25) respectively. HATr-resistant phenotypes used in most laboratory experiments demonstrated significantly higher pentamidine resistance than other trypanocides. Conclusion: The emergence of drug resistance across the spectrum of trypanocidal agents that are used to treat HAT is a major threat to the global WHO target to eliminate HAT by 2030. T. brucei strains were largely resistant to diamidines and the use of high trypanocide concentrations in clinical studies have proved fatal in humans. Studies to develop novel chemotherapeutical agents and identify alternative protein targets could help to reduce the emergence and spread of HATr. Full article
(This article belongs to the Special Issue Genomics and Epidemiology of Protozoan Parasites)
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