scholarly journals The Plasmodium falciparum transcriptome in severe malaria reveals altered expression of genes involved in important processes including surface antigen–encoding var genes

PLoS Biology ◽  
2018 ◽  
Vol 16 (3) ◽  
pp. e2004328 ◽  
Author(s):  
Gerry Q. Tonkin-Hill ◽  
Leily Trianty ◽  
Rintis Noviyanti ◽  
Hanh H. T. Nguyen ◽  
Boni F. Sebayang ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Severe Malaria ◽  
Surface Antigen ◽  
Altered Expression ◽  
Var Genes ◽  
Expression Of Genes

scholarly journals Genetic diversity of expressed Plasmodium falciparum var genes from Tanzanian children with severe malaria

2012 ◽  
Vol 11 (1) ◽  
pp. 230 ◽  
Author(s):  
Joseph Mugasa ◽  
Weihong Qi ◽  
Sebastian Rusch ◽  
Matthias Rottmann ◽  
Hans-Peter Beck
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Severe Malaria ◽  
Var Genes

scholarly journals Antibodies to Peptides in Semiconserved Domains of RIFINs and STEVORs Correlate with Malaria Exposure

mSphere ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Albert E. Zhou ◽  
Andrea A. Berry ◽  
Jason A. Bailey ◽  
Andrew Pike ◽  
Antoine Dara ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Severe Malaria ◽  
Surface Antigen ◽  
Immune Evasion ◽  
Clinical Malaria ◽  
Malaria Episode ◽  
Natural Immunity ◽  
Content Type ◽  
Variant Surface Antigen ◽  
Malaria Exposure

ABSTRACT The repetitive interspersed family (RIFIN) and the subtelomeric variable open reading frame (STEVOR) family represent two of three major Plasmodium falciparum variant surface antigen families involved in malaria pathogenesis and immune evasion and are potential targets in the development of natural immunity. Protein and peptide microarrays populated with RIFINs and STEVORs associated with severe malaria vulnerability in Malian children were probed with adult and pediatric sera to identify epitopes that reflect malaria exposure. Adult sera recognized and reacted with greater intensity to all STEVOR proteins than pediatric sera did. Serorecognition of and seroreactivity to peptides within the semiconserved domain of STEVORs increased with age and seasonal malaria exposure, while serorecognition and seroreactivity increased for the semiconserved and second hypervariable domains of RIFINs only with age. Serologic responses to RIFIN and STEVOR peptides within the semiconserved domains may play a role in natural immunity to severe malaria. IMPORTANCE Malaria, an infectious disease caused by the parasite Plasmodium falciparum, causes nearly 435,000 deaths annually worldwide. RIFINs and STEVORs are two variant surface antigen families that are involved in malaria pathogenesis and immune evasion. Recent work has shown that a lack of humoral immunity to these proteins is associated with severe malaria vulnerability in Malian children. This is the first study to have compared serologic responses of children and adults to RIFINs and STEVORs in settings of malaria endemicity and to examine such serologic responses before and after a clinical malaria episode. Using microarrays, we determined that the semiconserved domains in these two parasite variant surface antigen families harbor peptides whose seroreactivity reflects malaria exposure. A similar approach has the potential to illuminate the role of variant surface antigens in the development of natural immunity to clinical malaria. Potential vaccines for severe malaria should include consideration of peptides within the semiconserved domains of RIFINs and STEVORs.

scholarly journals Homology blocks of Plasmodium falciparum var genes and clinically distinct forms of severe malaria in a local population

2013 ◽  
Vol 13 (1) ◽  
pp. 244 ◽  
Author(s):  
Mary M Rorick ◽  
Thomas S Rask ◽  
Edward B Baskerville ◽  
Karen P Day ◽  
Mercedes Pascual
Keyword(s):  
Plasmodium Falciparum ◽  
Severe Malaria ◽  
Local Population ◽  
Var Genes

scholarly journals Plasmodium falciparum var genes expressed in children with severe malaria encode CIDR α1 domains

2016 ◽  
Vol 8 (8) ◽  
pp. 839-850 ◽  
Author(s):  
Jakob S Jespersen ◽  
Christian W Wang ◽  
Sixbert I Mkumbaye ◽  
Daniel TR Minja ◽  
Bent Petersen ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Severe Malaria ◽  
Var Genes

scholarly journals An ApiAP2 transcription factor influencing virulence gene transcription and sexual development in Plasmodium falciparum

2020 ◽  
Author(s):  
Eliana Cubillos ◽  
Isadora Prata ◽  
Wesley Fotoran ◽  
Nicolas Cardenas ◽  
Diego Alonso ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Transcription Factor ◽  
Severe Malaria ◽  
Virulence Gene ◽  
Human Malaria Parasite ◽  
Var Genes ◽  
Anopheles Mosquitoes ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Transcriptional Memory

Abstract The human malaria parasite Plasmodium falciparum expresses variant PfEMP1 proteins on the infected erythrocyte, which function as ligands for endothelial receptors in capillary vessels, leading to erythrocyte sequestration and severe malaria. The factors that orchestrate the mono-allelic expression of the 50-60 PfEMP1-encoding var genes within each parasite genome are still not fully identified. Here, we show that the transcription factor PfAP2-O influences the transcription of var genes and other multigenic families. The temporary knockdown of PfAP2-O leads to a complete loss of var transcriptional memory and a decrease in cytoadherence. AP2-O-knocked down parasites exhibited also significant reductions in transmission through Anopheles mosquitoes. We propose that PfAP2-O is one of the major virulence gene transcriptional regulators and may, therefore, be exploited as an important target to disrupt severe malaria and block parasite transmission.

scholarly journals Predictors of treatment failures of plasmodium falciparum malaria in Vietnam: a 4-year single‐centre retrospective study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Minh Cuong Duong ◽  
Oanh Kieu Nguyet Pham ◽  
Phong Thanh Nguyen ◽  
Van Vinh Chau Nguyen ◽  
Phu Hoan Nguyen
Keyword(s):  
Plasmodium Falciparum ◽  
Treatment Failure ◽  
Severe Malaria ◽  
Falciparum Malaria ◽  
Control Strategies ◽  
Artemisinin Resistance ◽  
Plasmodium Falciparum Malaria ◽  
Molecular Technique ◽  
Drug Resistant ◽  
Public Health Burden

Abstract Background Drug-resistant falciparum malaria is an increasing public health burden. This study examined the magnitude of Plasmodium falciparum infection and the patterns and predictors of treatment failure in Vietnam. Methods Medical records of all 443 patients with malaria infection admitted to the Hospital for Tropical Diseases between January 2015 and December 2018 were used to extract information on demographics, risk factors, symptoms, laboratory tests, treatment, and outcome. Results More than half (59.8%, 265/443, CI 55.1–64.4%) of patients acquired Plasmodium falciparum infection of whom 21.9% (58/265, CI 17.1–27.4%) had severe malaria, while 7.2% (19/265, CI 4.6–10.9%) and 19.2% (51/265, CI 14.7–24.5%) developed early treatment failure (ETF) and late treatment failure (LTF) respectively. Among 58 patients with severe malaria, 14 (24.1%) acquired infection in regions where artemisinin resistance has been documented including Binh Phuoc (11 patients), Dak Nong (2 patients) and Gia Lai (1 patient). Under treatment with intravenous artesunate, the median (IQR) parasite half-life of 11 patients coming from Binh Phuoc was 3 h (2.3 to 8.3 h), two patients coming from Dak Nong was 2.8 and 5.7 h, and a patient coming from Gia Lai was 6.5 h. Most patients (98.5%, 261/265) recovered completely. Four patients with severe malaria died. Severe malaria was statistically associated with receiving treatment at previous hospitals (P < 0.001), hepatomegaly (P < 0.001) and number of inpatient days (P < 0.001). Having severe malaria was a predictor of ETF (AOR 6.96, CI 2.55–19.02, P < 0.001). No predictor of LTF was identified. Conclusions Plasmodium falciparum remains the prevalent malaria parasite. Despite low mortality rate, severe malaria is not rare and is a significant predictor of ETF. To reduce the risk for ETF, studies are needed to examine the effectiveness of combination therapy including parenteral artesunate and a parenteral partner drug for severe malaria. The study alerts the possibility of drug-resistant malaria in Africa and other areas in Vietnam, which are known as non-endemic areas of anti-malarial drug resistance. A more comprehensive study using molecular technique in these regions is required to completely understand the magnitude of drug-resistant malaria and to design appropriate control strategies.

Herpesvirus-Associated Proliferative Skin Disease in Frogs and Toads: Proposed Pathogenesis

2021 ◽  
pp. 030098582110063
Author(s):  
Francesco C. Origgi ◽  
Patricia Otten ◽  
Petra Lohmann ◽  
Ursula Sattler ◽  
Thomas Wahli ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Rana Temporaria ◽  
Skin Lesions ◽  
Bufo Bufo ◽  
Careful Examination ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Cell Remodeling ◽  
Tissue Changes

A comparative study was carried out on common and agile frogs ( Rana temporaria and R. dalmatina) naturally infected with ranid herpesvirus 3 (RaHV3) and common toads ( Bufo bufo) naturally infected with bufonid herpesvirus 1 (BfHV1) to investigate common pathogenetic pathways and molecular mechanisms based on macroscopic, microscopic, and ultrastructural pathology as well as evaluation of gene expression. Careful examination of the tissue changes, supported by in situ hybridization, at different stages of development in 6 frogs and 14 toads revealed that the skin lesions are likely transient, and part of a tissue cycle necessary for viral replication in the infected hosts. Transcriptomic analysis, carried out on 2 naturally infected and 2 naïve common frogs ( Rana temporaria) and 2 naturally infected and 2 naïve common toads ( Bufo bufo), revealed altered expression of genes involved in signaling and cell remodeling in diseased animals. Finally, virus transcriptomics revealed that both RaHV3 and BfHV1 had relatively high expression of a putative immunomodulating gene predicted to encode a decoy receptor for tumor necrosis factor in the skin of the infected hosts. Thus, the comparable lesions in infected frogs and toads appear to reflect a concerted epidermal and viral cycle, with presumptive involvement of signaling and gene remodeling host and immunomodulatory viral genes.

scholarly journals Allelic diversity of merozoite surface protein genes (msp1 and msp2) and clinical manifestations of Plasmodium falciparum malaria cases in Aceh, Indonesia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Kurnia Fitri Jamil ◽  
Nandha Rizki Pratama ◽  
Sylvia Sance Marantina ◽  
Harapan Harapan ◽  
Muhammad Riza Kurniawan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Liver Function ◽  
Severe Malaria ◽  
Clinical Manifestation ◽  
Allelic Diversity ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Malaria Control Programme ◽  
Co Morbidity ◽  
Aceh Province

Abstract Background The malaria control programme in Indonesia has successfully brought down malaria incidence in many parts in Indonesia, including Aceh Province. Clinical manifestation of reported malaria cases in Aceh varied widely from asymptomatic, mild uncomplicated to severe and fatal complications. The present study aims to explore the allelic diversity of merozoite surface protein 1 gene (msp1) and msp2 among the Plasmodium falciparum isolates in Aceh Province and to determine their potential correlation with the severity of malaria clinical manifestation. Methods Screening of over 500 malaria cases admitted to the hospitals in 11 districts hospital within Aceh Province during 2013–2015, identified 90 cases of P. falciparum mono-infection without any co-morbidity. The subjects were clinically phenotyped and parasite DNA was extracted and polymerase chain reaction (PCR) amplified for the msp1 and msp2 allelic subfamilies. Results Analysis of clinical manifestation revealed that fever-chill is the most frequent symptom. Based on WHO criteria showed 19 cases were classified as severe and 71 as mild malaria. Analysis of msp1 gene revealed the presence of K1 allele subfamily in 34 subjects, MAD20 in 42 subjects, RO33 in 1 subject, and mixed allelic of K1 + MAD20 in 5 subjects, K1 + RO33 in 4 subjects, and MAD20 + RO33 in 4 subjects. Analysis of msp2 gene revealed 34 subjects carried the FC27 allelic subfamily, 37 subjects carried the 3D7 and 19 subjects carried the mixed FC27 + 3D7. Analysis of multiplicity of infection revealed that msp1 alleles is slightly higher than msp2 with the mean of MOI were 2.69 and 2.27, respectively. Statistical analysis to determine the association between each clinical manifestation and msp1 and msp2 alleles revealed that liver function abnormal value was associated with the msp2 mixed alleles (odds ratio (OR):0.13; 95%CI: 0.03–0.53). Mixed msp1 of K1 + RO33 was associated with severe malaria (OR: 28.50; 95%CI: 1.59–1532.30). Conclusion This study found a strong association between severe malaria in Aceh with subjects carrying the msp1 mixed alleles of K1 and RO33. The liver function abnormal value associated with the msp2 mixed allelic subfamilies. Further study in different geographic areas is recommended.

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