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IJCRR - 6(15), August, 2014

Pages: 10-14

Date of Publication: 10-Aug-2014


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Immune mechanisms involved in malaria: A review

Author: Anil Pawar

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Abstract:Despite extensive research, malaria is still very rampant and unrestrained. The complexity of Plasmodium parasite's life cycle,its intracellular nature, and its ability to evade the innate and adaptive immune responses make our efforts incompetent. Understanding the induction pathways of immune responses during malaria infection is crucial for the development of an effective vaccine. Present review explains the various aspects of immune mechanisms involved in fortification against malaria infection.

Keywords: Plasmodium, innate, acquired, immunity, malaria

Full Text:

INTRODUCTION
Malaria is one of the most prevalent and devastating of all human parasitic diseases, and is closely associated with socioeconomic burden in many temperate and most tropical countries. As a result of a massive scale-up in malaria control programs by the World Health Organizations (WHO) as part of the Millennium Development Goals, the estimated incidence of malaria globally has reduced by 17% and malaria-specific mortality rates by 26% between 2000 and 20101 . Although this represents some progress in reducing the disease burden, malaria still remains a major global health threat and continues to cause high morbidity and mortality, especially in subSaharan Africa, where almost 600 million people are at risk2 . Together, the Congo, India and Nigeria account for 40% of estimated malaria cases, and the Congo and Nigeria account for over 40% of the estimated total of malaria deaths globally in 20103 . Malaria is caused by a protozoan parasite of genus Plasmodium and is transmitted by female Anopheles mosquitoes. There are five species that infect humans, namely, Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale and Plasmodium knowlesi. P. falciparum is the causative agent of 90% of infections and is the target of the vaccine trials of the different initiatives and programs. Immunity to malaria has a major role in controlling disease and pathogenesis. For malaria, partial antiparasite immunity develops only after several years of endemic exposure. Evidences suggest that this inefficient induction of immunity is partly a result of antigenic polymorphism, poor immunogenicity of individual antigens, the ability of the parasite to interfere with the development of immune responses and to cause apoptosis of effector and memory B and T cells, and the interaction of maternal and neonatal immunity4. Studies of the immune responses of naive animals to malaria parasites indicate that the host response varies depending on the strain of parasite and genetic background of the host5,6,7. Both innate as well as adaptive immune responses play an important role in parasite suppression.

INNATE IMMUNITY
In both human infections as well as experimental malaria models, survival appears to be critically linked to the ability of the host to control blood-stage parasite replication within the first 7–14 days of infection8 . It is noteworthy that the parasite-specific antibodies and cellular responses are basically absent during the acute stage of infection; innate immune mechanisms seem to be vital in controlling early parasite replication and decreasing the risk of advancement to severe and fatal disease. Interferon gamma (IFN-γ) is a macrophage-activating factor involved in the innate immune response to malaria. It is mainly produced by CD4+ and CD8+ T lymphocytes in a specific immune response and by natural killer (NK) cells in a non-specific response. Early production of IFN-γ is critical since it directly mediates anti-parasitic effects and hence helps to limit progression from mild malaria to severe and life-threatening complications. Augmented release of IFN-γ stimulates monocytes/macrophage and γδ-T cells to secrete tumor necrosis factor-alpha (TNF-α), which can further promote anti-plasmodial properties through formation of toxic free radicals, such as nitric oxide9 . Interleukin (IL)-6 and IL1-β, like TNF-α, are other inflammatory cytokines that also play a role in limiting parasite replication but are involved in induction of fever and acute phase response10. The ability to balance effectively the anti-parasitic and immunopathogenic effects of these cytokines is a hallmark of clinical immunity to malaria. As a central component of the innate immune response, complement plays a critical role in neutralizing invading parasites; however, excessive activation of this system has the potential to mediate disease pathogenesis11. Clearance of infected erythrocytes by monocytes/macrophages is important for control of infection and in limiting excessive inflammation induced by the rupture of infected cells. Blocking complement deposition has been shown to prevent nearly 80–95% of phagocytosis of erythrocytes harboring immature (ring-stage) parasites in vitro12. Macrophages contribute in the control of the infection through both antibody-dependent and -independent phagocytosis, and secretion of soluble factors directly or indirectly toxic to the parasite, such as IL-1, TNF-α, granulocytes-macrophage colony stimulating factor (GM-CSF), reactive nitrogen and oxygen radicals13. CD36, a member of the class B family of scavenger receptors, was primarily expressed on dermal microvascular endothelium that supported adhesion of most natural isolates of P. falciparum malaria. It has been demonstrated that it performs dual function in mediating phagocytosis as well as produces cytokine responses to malaria, and helps in innate host defence to P. chabaudi chabaudi AS (PCCAS) malaria in vivo. Phagocytosis of microbial pathogens is linked to innate sensing and cytokine response mediated via cooperation between pattern recognition receptors such as scavenger receptors and toll-like receptors (TLRs)14. Production of IL-12 from activated macrophages is also crucial to early activation of γδ-T cells, resulting in additional production of IFN-γ15. γδ-T cells represent the interface between innate and adaptive immune response and together with NK cells, contribute to a rapid resolution of clinical malaria. Though, the innate effector mechanisms that actually regulate the blood stage parasitemia during acute infection are not fully understood.

ACQUIRED IMMUNITY
The acquired immunity to malaria involves activation of both humoral as well as cellular immune responses8,16. Dendritic cells (DCs) are supposed to play a crucial role, both as highly efficient presenters of antigen to helper T cells and in determining the balance of cell-mediated immunity and antibody-mediated immunity by steering the T cell population towards a Th1 or Th2 response17,18. The influence of environment, genetic background and nutritional status cannot be ruled out to explain the disparity of specific immunity.

Natural acquired immunity Contrasting to many acute viral diseases that produce life-long resistance to reinfection, Plasmodium provokes immunity only after several years of continuous exposure, during which recurring infections and illness occur. Robert Koch first reported a scientific basis for naturally acquired protection against malaria. By cross-sectional studies of stained blood films, Koch inferred that protection against malaria was acquired only after heavy and uninterrupted exposure to the parasite. But it is not clear that as to how this protection comes about, and there is only little knowledge on the key determinants of protection19. Natural immunity against malaria develops only gradually over many years of repeated and multiple infections in endemic areas20,21. The identification of immune correlates of protection among the abundant non-protective host responses remains a research priority. While evasion and modulation of the host immune response clearly occurs throughout the Plasmodium life cycle, immune mechanisms to control blood-stage parasites are acquired and maintained by individuals living in malaria endemic areas, allowing parasite densities to be kept below the threshold for the induction of acute disease and providing protection against severe malaria pathology22.

In human host, it appears that natural immunity is acquired only to blood stages. Conversely, naturally acquired immunity to pre-erythrocytic stages is not believed to occur and this is likely due to the small infectious load, the immunotolerant state of the liver as well as host impairment of the liver-stage infection in individuals with blood stage disease23. Once established, anti-malarial immunity appears to be a ‘regional phenomenon’, as seen in labor migrants or refugees, who lose protection against re-infection when moving to geographically separate places24. The concept of ‘P. falciparum diversity’ postulates a rationale for the detected slow acquisition of natural immunity.

Immunity in infants Infants seem to be relatively protected from malaria infection and its consequences for initial six months of their life. When infants become susceptible, their infection tends to be of low parasite density, asymptomatic and is cleared within a month25. Simister (1988)26 reported that in humans, systematic transfer of maternal antibodies of IgG isotype occurs across the placenta. P. falciparum specific IgG1 and IgG3 are more reliably transferred from mother to child as compared to IgG2 and IgG427. It is crucial to know about the period during which infants lose their maternally derived antibodies to malaria and instigate to acquire naturally their own immune responses against parasite antigens, so that malaria vaccines may be best administered. Duah et al. (2010)28 investigated the rates of decline and acquisition of serum antibody isotypes IgG1, IgG2, IgG3, IgG4, IgM and IgA to P. falciparum antigens; apical membrane antigen (AMA1), merozoite surface proteins (MSP1-19, MSP2 and MSP3) in a birth cohort of 53 children living in an urban area in the Gambia, followed over the first 3 years of life (sampled at birth, 4, 9, 18 and 36 months). Antigen-specific maternally transferred antibody isotypes of all immunoglobulin G (IgG) subclasses were detected at birth and were almost totally depleted by the age of 4 months. Attainment of specific antibody isotypes to the antigens began with IgM, followed by IgG1 and IgA. Against the MSP2 antigen, IgG1 responses were observed in the children, in contrast with the maternally derived antibodies to this antigen that were mostly IgG3. This confirms that IgG subclass responses to MSP2 are strongly dependent on age or previous malaria experience, polarized towards IgG1 early in life and to IgG3 in older exposed individuals28. STAGE-SPECIFIC ACQUIRED IMMUNITY Acquired immunity against the Plasmodium parasite is complex and stage-specific. By convention, immune responses in malaria are dichotomized into pre-erythrocytic responses (directed against sporozoites and liver-stage parasites) and erythrocytic responses (directed against merozoites and intra-erythrocytic parasites). Pre-erythrocytic stage immunity After their inoculation into the skin, some sporozoites get associate with Dendritic cells (DCs) in the draining lymph nodes. These cells present sporozoite antigens to naive T cells, and hence T cells get activated. Activated T cells enter the circulation and traffic to the liver, help in obliteration of the infected hepatocytes that display antigen-MHC complexes on their surface, reducing liverstage parasite load29. Pre-erythrocytic immunity generally consists of cellular responses against infected hepatocytes, which inhibit intracellular parasite development through the induction of reactive nitrogen intermediates. Various antigens, specific to the liver stage, have been identified and it has been suggested that these antigens, along with those brought in with the invading sporozoites, are rapidly processed by the host cell and presented on the surface of infected hepatocytes in combination with MHC class I 30. This presentation leads to recognition by cytotoxic T lymphocytes (CTLs) and killing of the infected cell, or stimulation of NK and CD4+ T cells to produce IFN-γ. This can trigger a cascade of immune reactions and ultimately can lead to the death of intracellular parasite30,31. The CTLs may be directly cytolytic against malaria-infected hepatocytes by releasing perforin and granzyme or by binding to apoptosis-inducing receptors on the infected cells32.

Plasmodium sporozoites suppress the respiratory burst and antigen presentation of Kupffer cells, which are regarded as the portal of invasion into hepatocytes. It is not known whether immune modulation of Kupffer cells can affect the liver stage. In a study, it was observed that sporozoites inoculated into wistar rats could be detected in the liver, spleen, and lungs; however, most of the sporozoites were arrested in the liver. Sporozoites were captured by Kupffer cells lined with endothelial cells in the liver sinusoid before hepatocyte invasion. Pre-treatment with TLR3 agonist poly (I:C) and TLR2 agonist BCG primarily activated the Kupffer cells, inhibiting the sporozoite development into the exoerythrocytic form, whereas, Kupffer cell antagonists dexamethasone and cyclophosphamide promoted development of the liver stage. Present data implies that sporozoite development into its exo-erythrocytic form may be associated with Kupffer cell functional status. Immune modulation of Kupffer cells could be a promising strategy to prevent Plasmodium infection33.

Erythrocytic stage immunity Merozoites that survive to the pre-erythocytic stage are responsible for the modification of infected red blood cells in terms of parasite proteins expressed on the cell surface and the concomitant immune response to the Plasmodium parasite, resulting in the clinical manifestations of malaria34. The pathogenic manifestations during a malaria crisis are due to proinflammatory cytokines released by T cells and macrophages in response to malaria parasites and their products, including glycosylphosphatidyl-inositol (GPI) moieties35, malaria pigment36 and Plasmodium-derived nitric oxide synthase (NOS)-inducing factor37.

Humoral responses against extracellular merozoites and intraerythrocytic parasites have traditionally been considered the most important component of blood-stage immunity. An antibody binding to the surface of the merozoite, and to proteins that are externalised from the apical complex of organelles involved in erythrocyte recognition and invasion, seems to have an important role in immunity to asexual blood stages. This antibody could neutralize parasites or lead to Fc dependent mechanisms of parasite killing by macrophages38. T cell responses against pRBC remain less well understood, partly because erythrocytes lack MHC class I or class II presentation capacity. Nevertheless, cellular responses against pRBC have been suggested to contribute to protection in humans in the absence of antibodies39,40. Finally, monocyte/macrophage-mediated responses, in particular phagocytosis and antibody-dependent cellular inhibition (ADCI) also form an important component of bloodstage immunity41. Immunity to blood-stage Plasmodium parasites is critically dependent on the type 1 cytokine IFN-γ and requires coordinate and timely innate and adaptive immune responses involving dendritic cells (DC), NK cells, CD4+ T helper cells, and B cells8,41. Moreover, a balance between pro-inflammatory and anti-inflammatory responses is essential to limit the development of life-threatening immune-mediated pathology such as CM and SMA. Although a better understanding of the mechanisms involved in protective immunity and immunopathology is emerging, still the understanding of regulatory mechanisms required to maintain the balance between beneficial and deleterious responses during blood-stage malaria infection remains limited42. IMMUNE EVASION BY PLASMODIUM Despite the presence of various immune mechanisms, the parasite is adept at evading immunity by a variety of mechanisms, which help its survival in the host. Possible mechanisms of interference in the activation of T cells and B cells, and the generation of immunological memory by the parasite have been described by many workers21,43. The parasite modulates the immune mechanism either by interfering with presentation or processing and cause apoptosis of T cells and other effector cells or mutates the sequence of epitopes critical for B or T cell recognition44. Furthermore, because malaria is a chronic infection, it is possible that B and T cell exhaustion may contribute to the suboptimal host immunity that is inadequate to control the parasite. Data from a longitudinal study in Mali has shown that exhausted B cells comprise 20-60% of that circulating B cell pool as compared with 1–2% of the B cell pool in people from non-endemic areas45. Understanding the immunological and molecular mechanisms of the crosstalk between the host and parasite is a pre-requisite for the rational discovery and development of a safe, affordable, and protective anti-malaria vaccine46. CONCLUSIONS Immunity contributes an essential role in controlling the disease, but partial immunity develops only after several years of endemic exposure. Innate immunity, involving complement system, macrophages and various cytokines, is vital in controlling early infection. The adaptive immunity is complex and stage-specific, and includes activation of both humoral as well as cellular immune responses. Plasmodium evades the immune mechanisms by interfering the activation of B and T cells, and the generation of immunological memory. Overall, a better understanding of the immunopathology and immunoregulatory pathways involved both in experimental malaria models as well as in individuals is essential for the development of an effective vaccine so that this fatal disease can be controlled.

ACKNOWLEDGEMENTS
Author is thankful to University Grants Commission (UGC), New Delhi for providing financial assistance to him in the form of Research Fellowship in Science for Meritorious students (RFSMS) under UGC-CAS programme. At the same time, he acknowledges all the scholars, whose articles are cited for preparation of this manuscript.

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A Study by Kholis Ernawati et al. entitled "The Utilization of Mobile-Based Information Technology in the Management of Dengue Fever in the Community Year 2019-2020: Systematic Review" is awarded Best Article for Vol 13 issue 18
A Study by Bhat Asifa et al. entitled "Efficacy of Modified Carbapenem Inactivation Method for Carbapenemase Detection and Comparative Evaluation with Polymerase Chain Reaction for the Identification of Carbapenemase Producing Klebsiella pneumonia Isolates" is awarded Best Article for Vol 13 issue 17
A Study by Gupta R. et al. entitled "A Clinical Study of Paediatric Tracheostomy: Our Experience in a Tertiary Care Hospital in North India" is awarded Best Article for Vol 13 issue 16
A Study by Chandran Anand et al. entitled "A Prospective Study on Assessment of Quality of Life of Patients Receiving Sorafenib for Hepatocellular Carcinoma" is awarded Best article for Vol 13 issue 15
A Study by Rosa PS et al. entitled "Emotional State Due to the Covid – 19 Pandemic in People Residing in a Vulnerable Area in North Lima" is awarded Best Article for Vol 13 issue 14
A Study by Suvarna Sunder J et al. entitled "Endodontic Revascularization of Necrotic Permanent Anterior Tooth with Platelet Rich Fibrin, Platelet Rich Plasma, and Blood Clot - A Comparative Study" is awarded Best Article for Vol 13 issue 13
A Study by Mona Isam Eldin Osman et al. entitled "Psychological Impact and Risk Factors of Sexual Abuse on Sudanese Children in Khartoum State" is awarded Best Article for Vol 13 issue 12
A Study by Khaw Ming Sheng & Sathiapriya Ramiah entitled "Web Based Suicide Prevention Application for Patients Suffering from Depression" is awarded Best Article for Vol 13 issue 11
A Study by Purushottam S. G. et al. entitled "Development of Fenofibrate Solid Dispersions for the Plausible Aqueous Solubility Augmentation of this BCS Class-II Drug" is awarded Best article for Vol 13 issue 10
A Study by Kumar S. et al. entitled "A Study on Clinical Spectrum, Laboratory Profile, Complications and Outcome of Pediatric Scrub Typhus Patients Admitted to an Intensive Care Unit from a Tertiary Care Hospital from Eastern India" is awarded Best Article for Vol 13 issue 09
A Study by Mardhiah Kamaruddin et al. entitled "The Pattern of Creatinine Clearance in Gestational and Chronic Hypertension Women from the Third Trimester to 12 Weeks Postpartum" is awarded Best Article for Vol 13 issue 08
A Study by Sarmila G. B. et al. entitled "Study to Compare the Efficacy of Orally Administered Melatonin and Clonidine for Attenuation of Hemodynamic Response During Laryngoscopy and Endotracheal Intubation in Gastrointestinal Surgeries" is awarded Best Article for Vol 13 issue 07
A Study by M. Muthu Uma Maheswari et al. entitled "A Study on C-reactive Protein and Liver Function Tests in Laboratory RT-PCR Positive Covid-19 Patients in a Tertiary Care Centre – A Retrospective Study" is awarded Best Article of Vol 13 issue 06 Special issue Modern approaches for diagnosis of COVID-19 and current status of awareness
A Study by Gainneos PD et al. entitled "A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study" is awarded Best Article of Vol 13 issue 05 Special issue on Recent Advances in Dentistry for better Oral Health
A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" is awarded Best Article of Vol 13 issue 06
A Study by Chen YY and Ghazali SRB entitled "Lifetime Trauma, posttraumatic stress disorder Symptoms and Early Adolescence Risk Factors for Poor Physical Health Outcome Among Malaysian Adolescents" is awarded Best Article of Vol 13 issue 04 Special issue on Current Updates in Plant Biology to Medicine to Healthcare Awareness in Malaysia
A Study by Kumari PM et al. entitled "Study to Evaluate the Adverse Drug Reactions in a Tertiary Care Teaching Hospital in Tamilnadu - A Cross-Sectional Study" is awarded Best Article for Vol 13 issue 05
A Study by Anu et al. entitled "Effectiveness of Cytological Scoring Systems for Evaluation of Breast Lesion Cytology with its Histopathological Correlation" is awarded Best Article of Vol 13 issue 04
A Study by Sharipov R. Kh. et al. entitled "Interaction of Correction of Lipid Peroxidation Disorders with Oxibral" is awarded Best Article of Vol 13 issue 03
A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02
A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01
A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24
A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22
A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


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International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal

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