Dataset Information

Individualized Transcriptional Resolution of Complicated Malaria in a Colombian Study.

ABSTRACT: To evaluate whether recovery from complicated malaria follows a common trajectory in terms of immunological mechanism or, rather, is highly individualized for each patient, we performed longitudinal gene expression profiling of whole blood. RNA sequencing (RNAseq) was performed on blood samples obtained from eight patients on four consecutive days between hospital admission and discharge. Six patients were infected with Plasmodium falciparum, and two with Plasmodium vivax; one patient was a pregnant woman infected with P. falciparum, who was hospitalized for several weeks. The characterization of blood transcript modules (BTM) and blood informative transcripts (BIT) revealed that patients' responses showed little commonality, being dominated by the balance of gene activity relating to lymphocyte function, inflammation, and interferon responses specific to each patient. Only weak correlations with specific complicated malaria symptoms such as jaundice, thrombocytopenia, or anemia were observed. The differential expression of individual genes, including transcripts derived from the human leukocyte antigen (HLA) complex, generally reflected differences in the underlying immune processes. Although the results of this pilot study do not point to any single process that might provide a target for complicated malaria treatment or prevention or personalized medical strategies, larger patient series and more extensive blood sampling may allow the classification of patients according to their type of response in order to develop novel therapeutic approaches.

SUBMITTER: Rojas-Pena ML

PROVIDER: S-EPMC6163772 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Individualized Transcriptional Resolution of Complicated Malaria in a Colombian Study.

Rojas-Peña Mónica L ML Duan Meixue M Arafat Dalia D Rengifo Lina L Herrera Socrates S Arévalo-Herrera Myriam M Gibson Greg G

Journal of personalized medicine 20180914 3

To evaluate whether recovery from complicated malaria follows a common trajectory in terms of immunological mechanism or, rather, is highly individualized for each patient, we performed longitudinal gene expression profiling of whole blood. RNA sequencing (RNAseq) was performed on blood samples obtained from eight patients on four consecutive days between hospital admission and discharge. Six patients were infected with <i>Plasmodium falciparum</i>, and two with <i>Plasmodium vivax;</i> one pati ...[more]

PMID: 30223463

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Project description:BackgroundMalaria primarily affects populations living in poor socioeconomic conditions, with limited access to basic services, deteriorating environmental conditions, and barriers to accessing health services. Control programmes are designed without participation from the communities involved, ignoring local knowledge and sociopolitical and cultural dynamics surrounding their main health problems, which implies imposing decontextualized control measures that reduce coverage and the impact of interventions. The objective of this study was to determine the community perception of malaria in the municipality of Olaya Herrera in the Colombian Pacific.MethodsA 41-question survey on knowledge, attitudes, and practices (KAP) related to malaria, the perception of actions by the Department of Health, and access to the health services network was conducted.ResultsA total of 134 adults were surveyed, in whose households a total of 671 people lived. According to the survey data, about 80% of the household members included teenagers and children, out of which 61% had malaria at one time, and for 75.3%, this disease is a persistent problem. In spite of this, 57.2% of people who fell ill due to malaria were never visited by health personnel for a follow up. This population claimed that responsibility for who should prevent the disease is shared between each person and the Department of Health. However, personal actions were focused on using mosquito nets, ignoring other important practices to prevent bites. Despite campaigns by the Department of Health, 11.9% of respondents did not know how malaria was transmitted, and 8.96% thought it was transmitted through water. Also, 43.5% said that the Department of Health did not do any work to control malaria and 16% did not know if any action was taken.ConclusionsIn spite of the knowledge about malaria and the efforts of the Department of Health to prevent it, the community actions do not seem to be consistent with this knowledge, as the number of cases of malaria is still high in the area.

Project description:In temperate and sub-tropical regions of Latin America, complicated malaria manifested as hepatic dysfunction or renal dysfunction is seen in all age groups. There has been a concerted focus on understanding the patho-physiological and molecular basis of complicated malaria in children, much less is known about it in adults. This can be attributed to many factors: one of which is the expression of clonally variant families of adhesion proteins: PfEMP1 on the iRBC surface. We report here, the analysis of data from a custom, cross strain microarray (Agilent Platform) using material from patient samples, showing hepatic dysfunction or renal failure. These are the most common manifestations seen in adults along with cerebral malaria. The data has been analyzed with reference to variable surface antigens, encoded by the var, rifin and stevor gene families. The differential regulation profiles of key genes (comparison of PFC and PFU) have been observed. The exportome has been analyzed using similar parameters. GO term based functional enrichment of differentially regulated genes identified, up-regulated genes stastically enriched (p<0.5) to critical biological processes. Systems network based functional enrichment of overall differentially regulated genes yielded a similar result. We are reporting here, up-regulation of var group A and B genes whose proteins are predicted to interact with CD36 receptor in the host as also the up-regulation of group A rifins and many of the stevors. This is contrary to most other reports from pediatric patients, with cerebral malaria where the up-regulation of var A group genes have been seen. A protein-protein interaction based network has been created and analysis performed. This co-expression and text mining based network has shown overall connectivity between the variable surface antigens and the exportome. The up-regulation of var group B and C genes encoding PfEMP1 with different domain architecture would be important for deciding strategies for disease prevention. Plasmodium falciparum isolates were collected from patients (n=12) with differing clinical conditions. The patients exhibited symptoms categorized as uncomplicated (n=5) or complicated malaria (n=7). Criteria for determination of complicated disease were based on World Health Organization year 2000 guidelines. Microarray array based transcriptional profiling was carried out to find out differentailly expressed genes in complicated malaria isolates (non-cerebral malaria) compared to un-complicated malaria isolates.

Dataset Information

Individualized Transcriptional Resolution of Complicated Malaria in a Colombian Study.

Publications

Individualized Transcriptional Resolution of Complicated Malaria in a Colombian Study.

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