Cytoadherence and Severe Malaria
Journal name: The Malaysian Journal of Medical Sciences
Original article title: Cytoadherence and Severe Malaria
The Malaysian Journal of Medical Sciences (MJMS) is a peer-reviewed, open-access journal published online at least six times a year. It covers all aspects of medical sciences and prioritizes high-quality research.
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Original source:
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G Craig Alister, Khairul Mohd Fadzli Mustaffa, R Patil Pradeep
The Malaysian Journal of Medical Sciences:
(A peer-reviewed, open-access journal)
Full text available for: Cytoadherence and Severe Malaria
Year: 2012
Copyright (license): CC BY 4.0
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Summary of article contents:
Introduction
Malaria remains a significant cause of morbidity and mortality worldwide, particularly in low- and middle-income countries. The disease is primarily caused by various species of the Plasmodium parasite, with Plasmodium falciparum being the most lethal. Cytoadherence of infected red blood cells (pRBC) to the endothelium is a critical feature of severe malaria, particularly cerebral malaria, as it leads to blockage of microvasculature and contributes to disease severity. Understanding the mechanisms behind this phenomenon is pivotal for developing effective treatments for malaria. This review evaluates existing knowledge linking cytoadherence to severe malaria and discusses ongoing debates regarding its essential role in the pathophysiology of the disease.
Summary of One Important Concept: Cytoadherence Mechanisms and Their Role in Severe Malaria
Cytoadherence is heavily mediated by interactions between pRBC and various adhesion receptors on endothelial cells, such as CD36 and ICAM-1, which facilitate the sequestration of pRBC in tissues, particularly in the brain during cerebral malaria. This adhesion alters the physical characteristics of the pRBC, making them more rigid and less deformable, which impedes their passage through small blood vessels and leads to blockage or ischemia. The presence of cytokines also influences cytoadherence, as pro-inflammatory mediators like TNF can upregulate adhesion molecules on endothelial cells. Furthermore, the process generates a feedback loop that exacerbates tissue damage and inflammation, leading to severe clinical manifestations. Therefore, cytoadherence is not merely a passive phenomenon; it actively contributes to the progression of severe malaria through complex host-parasite interactions.
Conclusion
In summary, the cytoadherence of Plasmodium falciparum-infected erythrocytes plays a crucial role in the development and severity of malaria, particularly in cases of cerebral malaria. The persistence of this condition even after treatment underscores the need for adjunct therapies targeting cytoadherence and its effects on the host. As research continues to unfold, a clearer understanding of cytoadherence mechanisms will be instrumental in developing more effective interventions to combat severe malaria cases and improve patient outcomes. The pursuit of therapies that inhibit or reverse the detrimental effects of cytoadherence is essential to mitigate the burden of severe malaria in affected populations.
FAQ section (important questions/answers):
What role does cytoadherence play in severe malaria pathology?
Cytoadherence is thought to contribute to severe malaria by promoting the adhesion of infected red blood cells (pRBC) to the microvasculature, leading to blockage, increased morbidity, and mortality due to compromised blood flow and organ dysfunction.
How do different Plasmodium species exhibit cytoadherence?
While Plasmodium falciparum is well-known for strong cytoadherence, recent studies suggest that P. vivax and P. knowlesi also have adhesive properties, though their timing and extent of cytoadherence differ significantly from P. falciparum.
What are some potential adjunct therapies for severe malaria?
Potential adjunct therapies include N-acetylcysteine to reduce pRBC binding, L-arginine to enhance endothelial function, and statins to restore endothelial integrity. Research is ongoing to evaluate these therapies' effectiveness in combination with standard antiparasitic treatment.
What factors regulate the pathogenicity of malaria cytoadherence?
Pathogenicity is influenced by several factors, including pro-inflammatory cytokine levels, expression of adhesion molecules on endothelial cells, and the specific PfEMP-1 variants expressed by the malaria parasites, which vary among cases of severe and uncomplicated malaria.
Glossary definitions and references:
Scientific and Ayurvedic Glossary list for “Cytoadherence and Severe Malaria”. This list explains important keywords that occur in this article and links it to the glossary for a better understanding of that concept in the context of Ayurveda and other topics.
1) Disease:
Disease refers to any abnormal condition affecting the body or mind, often caused by infections, genetic defects, or environmental factors. In the context of malaria, the disease is caused by the Plasmodium parasite, leading to severe health complications and high morbidity and mortality rates, especially in vulnerable populations.
2) Blood:
Blood is the fluid that circulates through the body's cardiovascular system, supplying oxygen and nutrients while removing waste products. In malaria, infected red blood cells (RBCs) can accumulate in the microvasculature, causing cytoadherence, which is associated with severe symptoms and complications like cerebral malaria.
3) Fever:
Fever is a common symptom of malaria, often characterized by elevated body temperature due to the body's response to infection. In Plasmodium infections, the febrile response can influence cytoadherence of infected RBCs to endothelial cells, contributing to disease severity and complications such as cerebral malaria.
4) Surface:
Surface refers to the outer layer of cells or organisms. For malaria-infected RBCs, surface proteins, such as PfEMP-1, play a crucial role in cytoadherence to endothelial cells. Changes in the cell surface contribute to the ability of parasites to escape immune responses and establish pathogenic interactions.
5) Study (Studying):
Study denotes systematic investigation intended to discover or interpret facts. Research on malaria pathology focuses on understanding the mechanisms behind cytoadherence and its implications for severe malaria. Various studies have attempted to correlate specific adhesion characteristics with disease outcomes, elucidating pathways for potential therapies.
6) Drug:
Drug refers to any substance used to treat, cure, or prevent diseases. In malaria treatment, antimalarial drugs like artemisinin and quinine are essential. However, resistance to drugs has been increasing, necessitating the development of new therapies and adjunct treatments to improve outcomes in severe malaria.
7) Species:
Species refers to a group of organisms that can interbreed. In malaria, six distinct Plasmodium species infect humans: P. falciparum, P. vivax, P. malariae, P. ovale, and P. knowlesi. Understanding the biological behaviors of these species is crucial for developing targeted treatments and understanding their pathogenicity.
8) Accumulation (Accumulating, Accumulate):
Accumulation refers to the buildup of substances in a specific location. In the context of malaria, the accumulation of parasitized red blood cells (pRBCs) in the microvasculature contributes to severe malaria due to microvascular obstruction and organ dysfunction, ultimately influencing disease severity and patient outcomes.
9) Death:
Death signifies the end of life and can result from various causes including severe disease. In malaria, mortality is a significant concern, particularly in severe cases where complications arise from cytoadherence and microvascular blockages, highlighting the need for effective treatment options to reduce mortality rates.
10) Kumar:
Kumar could refer to a researcher or an author in the field of malaria research. He commonly collaborates on studies aiming to understand malaria's pathology, its effects on human health, and potential treatment avenues. His contributions would be relevant in elucidating factors impacting malaria severity.
11) Observation:
Observation is a critical aspect of scientific research, involving the careful monitoring of phenomena. In malaria research, observations often include the behavior of infected RBCs, the effects of treatment strategies, and the responses of the immune system to infections, all integral to understanding disease pathogenesis.
12) Activity:
Activity refers to the execution of tasks or functions. In malaria, the activity of parasites within hosts and the immune response to the infection are essential research focuses. Understanding these activities can lead to insights about the pathology of severe malaria and potential interventions.
13) Patel:
Patel may refer to a researcher in the context of malaria studies. Contributions from individuals with this surname often explore malaria's interaction with host systems or the effectiveness of treatments, helping to enhance the understanding of malaria's pathology and aiding in developing more effective therapies.
14) Table:
Table refers to a systematic arrangement of data. In this context, tables summarizing clinical studies highlight the associations between cytoadherence of Plasmodium falciparum and disease severity, providing a visual representation of research findings and aiding in the understanding of complex interactions in malaria pathogenesis.
15) Post:
Post often signifies a position or publication after an event. In malaria research, it may refer to post-mortem analyses or studies examining the aftermath of malaria infections, which can provide vital insights into the disease's effects on human health that impact ongoing research and treatment strategies.
16) Transmission:
Transmission describes the process by which a disease spreads from one host to another. In malaria, understanding the modes of transmission (e.g., through mosquitoes) helps in designing effective control strategies and preventive measures to reduce the incidence of malaria infections in vulnerable populations.
17) Developing:
Developing refers to the process of progressing towards a particular state. In the context of malaria, developing new treatment strategies, vaccines, and public health interventions are essential. Efforts focus on understanding the disease better in low and middle-income countries impacted heavily by malaria.
18) Family:
Family refers to a group of related organisms. In malaria research, the Plasmodium genus belongs to the larger Apicomplexa family. Understanding the relationships within this family helps elucidate specific traits, such as virulence factors in different Plasmodium species, which infect humans and other hosts.
19) Animal:
Animal refers to living organisms within the kingdom Animalia. In malaria research, animal models, particularly murine models, are widely utilized to study the disease's pathophysiology, testing potential therapeutic interventions, and understanding host-parasite interactions, which inform treatment and prevention strategies.
20) Chang:
Chang may refer to a researcher involved in malaria studies. Contributions by individuals with this name, particularly in the context of malaria, could include investigations into the pathology of malaria, cytoadherence mechanisms, and innovative treatment approaches aimed at reducing mortality and disease severity.
21) Field:
Field relates to a specific area of study or work. In malaria research, the field encompasses various disciplines such as epidemiology, immunology, and vertical integration of treatments into public health systems. Advancements in the field aim to lessen the burden of malaria worldwide.
22) Pur:
Poor is often used to describe inadequate conditions or socioeconomic status impacting health outcomes. In the context of malaria, poor populations in low and middle-income countries are disproportionately affected, emphasizing the need for targeted public health interventions to minimize morbidity and mortality associated with malaria.
23) Inflammation:
Inflammation is the body’s immune response to infection or injury, characterized by redness, swelling, and pain. In severe malaria, inflammation is complexly interlinked with cytoadherence, potentially leading to organ dysfunction, and plays a significant role in disease pathogenesis which is important for treatment strategies.
24) Substance:
Substance denotes any material with a definite composition. In malaria research, understanding the various substances involved (e.g., cytokines, adhesion molecules) can clarify their roles in the disease process. Identifying these substances is essential for developing specific treatment strategies to mitigate severe malaria pathology.
25) Relative:
Relative refers to the comparative relation between entities. In the context of malaria, relative risk and outcomes help in understanding the severity of the disease and mortality associated with different Plasmodium species or specific patient demographics, aiding in public health planning and response strategies.
26) Pregnant:
Pregnant refers to the state of carrying a developing embryo or fetus. Malaria during pregnancy poses unique risks, such as maternal morbidity and adverse outcomes for the fetus. Understanding these dynamics is crucial for targeted intervention strategies in pregnant women, especially in endemic regions.
27) Krishna (Krsna):
Krishna may refer to a researcher in malaria studies. Contributions by such individuals often focus on the complexities of malaria infection, addressing various challenges related to pathogenesis, host interactions, and treatment outcomes, which are crucial in the global fight against malaria.
28) Killing (Killed):
Killed refers to the goal of treating malaria, where the objective is to eradicate the parasite within the human host. Antimalarial treatments aim to disrupt various stages of the Plasmodium lifecycle, thereby reducing morbidity, mortality, and the potential for further transmission.
29) Science (Scientific):
Science refers to the systematic study of the natural world through observation and experimentation. In malaria research, scientific inquiry drives understanding of parasite biology, disease mechanisms, and the development of effective treatments and preventive measures, contributing to public health achievements and strategies.
30) Autumn:
Autumn, as a seasonal reference, does not have direct relevance to malaria's pathology but may imply changes in vector behavior or transmission dynamics. Seasonal variations can influence malaria transmission patterns, which are crucial for the planning of control strategies in endemic regions.
31) Edema (Oedema):
Oedema refers to the accumulation of fluid in tissues, causing swelling. In severe malaria, oedema, especially cerebral oedema, can lead to increased intracranial pressure and complications. Understanding the mechanisms underlying oedema formation is crucial for managing severe malaria cases effectively.
32) Sharman (Sarma, Sharma, Sarman):
Sharma may refer to a researcher in malaria studies. Individuals with this surname likely contribute significantly to understanding malaria epidemiology, the biology of Plasmodium species, clinical presentation, and innovative strategies for treatment, thus aiding the broader effort to combat malaria globally.
33) Nature:
Nature refers to the intrinsic qualities or characteristics of organisms or systems. In malaria research, understanding the nature of disease progression, parasite-host interactions, and responses to treatment is essential for elucidating mechanisms behind malaria's pathogenicity and developing effective therapeutic strategies.
34) Debate:
Debate refers to discussions or arguments on specific topics. In malaria research, there may be ongoing debates regarding the mechanisms of severe disease, such as the role of cytoadherence. Engaging in scientific debate helps refine hypotheses and foster new ideas for research and treatment advancements.
35) Summer:
Summer, like autumn, is a seasonal term that influences environmental conditions, including mosquito activity and malaria transmission rates. Understanding seasonal patterns of malaria can inform public health strategies, ensuring timely interventions when transmission risk is highest.
36) India:
India is a malaria-endemic country where the disease poses significant public health challenges. Research and preventive measures in India contribute to the global understanding of malaria transmission, treatment, and the socio-economic impact of the disease, influencing policy and intervention strategies.
37) Divi:
Divi may refer to a researcher involved in malaria studies. Contributions from individuals with this name can include insights into malaria transmission, pathophysiology, and the molecular interactions between Plasmodium species and their human hosts, enhancing understanding of the disease.
38) Beta:
Beta often denotes a second position in a series. In scientific research, beta forms of proteins or drugs may signify variations that can affect function. Understanding these variations is essential in malaria research to identify therapeutic targets or potential drug candidates.
39) Chau:
Chau may refer to a researcher or author in the field of malaria. Individuals with this name may contribute to studies on malaria's biology, epidemiology, or treatment options, adding valuable insights to the collective understanding of this disease.
40) Sign:
Sign refers to an indicator, symptom, or evidence of a condition. In malaria research, signs such as fever or specific symptoms help clinicians assess disease severity and guide treatment decisions. Identifying these signs is crucial for timely intervention and management.
41) Rich (Rch):
Rich indicates a substantial amount or resource. In the context of malaria, rich knowledge can pertain to the understanding of the disease's complexity and the resources needed for effective control strategies. Malaria-rich regions may face unique challenges in managing outbreaks.
42) Line:
Line may refer to a lineage or specific group of organisms. In malaria research, studying particular parasite lines aids in understanding virulence, resistance patterns, and epidemiological differences. This knowledge is crucial for developing targeted interventions and public health strategies.
43) Pain:
Pain represents a symptom indicating distress or injury. In malaria, pain can manifest through fever, joint pain, or severe complications. Understanding the pain pathways associated with malaria helps healthcare providers manage symptoms effectively and improve patient comfort during treatment.
44) Ter:
Ther refers to therapies or treatment modalities. In malaria, various therapeutic approaches aim to eliminate the Plasmodium parasite and alleviate symptoms. The development of new therapies is ongoing, focused on enhancing effectiveness and reducing resistance in endemic regions.
45) Chan:
Chan may refer to a researcher in the context of malaria studies. Contributions from individuals with this surname could involve exploring malaria's mechanisms or treatment strategies, enriching the broader scientific understanding required to combat malaria effectively.
46) Life:
Life encompasses the biological existence and functioning of organisms. In malaria research, understanding how the Plasmodium parasite interacts with human hosts throughout the lifecycle is crucial for developing effective treatments and interventions aimed at mitigating malaria's impact on human health.
Other Science Concepts:
Discover the significance of concepts within the article: ‘Cytoadherence and Severe Malaria’. Further sources in the context of Science might help you critically compare this page with similair documents:
Quinine, Malaria, Blood flow, High fever, Blood transfusion, Central nervous system, Clinical trial, Malaria Cases, Clinical studies, Oxidative stress, Clinical trial study, Blood brain barrier, Morbidity and Mortality, In vitro, Severe Anaemia, Endothelial damage, Endothelial dysfunction, Molecular basis, Immune response, Apoptosis, Drug resistance, Blood coagulation, Epidemiological studies, Antioxidant, Recombinant Human Erythropoietin, Nitric oxide, Cytokine expression, Proinflammatory response, Atorvastatin, Cytokine production, Clinical implication, Green tea, Adhesive Interactions, Sickle Cell Disease, Metabolic disturbance, Levamisole, Chloroquine, Antimalarial activity, Adjunctive therapy, N-acetylcysteine, N-acetylcysteine (NAC), Molecular mechanism, Clinical isolate, Severe malaria, Uncomplicated malaria, Anti-malarial activity, Intercellular adhesion molecule-1, Malaria treatment, Erythropoietin injection, Endoplasmic reticulum stress, Blood coagulation cascade, Vascular endothelial cells, Red Blood Cell, Plasmodium Falciparum, P. falciparum, Cell Adhesion Molecule, Blood cell, Artemisinin combination therapy, Cerebral malaria, Macrophages and dendritic cells, Pro-inflammatory cytokine, Antimalarial properties, Blood Brain Barrier (BBB), Antimalarial, Combination therapies, Caspase activation, Blood cholesterol level, L-arginine, Endothelial cells, Erythropoietin, Tumor necrosis factor, Multi organ-dysfunction, Coagulation cascade, Tissue factor, Artesunate, Disease severity, Monoclonal antibody, Von Willebrand Factor, Plasmodium vivax, Serum Lactate, Host response, Microcirculatory Dysfunction, Falciparum malaria, Endothelial activation, Cerebral vessels, Oxidative cascade, Vascular obstruction, Organ Dysfunction, Clinical disease, Malaria parasite, Artemisinin derivative, Free oxygen radicals, P selectin, Weibel-Palade bodies, Host inflammatory response, Red blood cell deformability, Apoptosis inhibition, Anti-TNF therapy, Statin, Cell surface, Parasite clearance, Peripheral circulation, Apoptotic cell, Clinical malaria, Adhesion molecule, Tumour necrosis factor, Vascular cell adhesion molecule, Intercellular adhesion.
Concepts being referred in other categories, contexts and sources.