scholarly journals Peroxisome Proliferator-Activator Receptorγ: A Link between Macrophage CD36 and Inflammation in Malaria Infection

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Yi Ren

Severe malaria infection caused byPlasmodium falciparumis a global life-threatening disease and a leading cause of death worldwide. Intensive investigations have demonstrated that macrophages play crucial roles in control of inflammatory and immune responses and clearance ofPlasmodium-falciparum-parasitized erythrocytes (PE). This paper focuses on how macrophage CD36 recognizes and internalizes PE and participates the inflammatory signaling in response toPlasmodium falciparum. In addition, recent advances in our current understanding of the biological actions of PPARγ on CD36 and malaria clearance from the hosts are highlighted.

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Getachew Geleta ◽  
Tsige Ketema

Despite rigorous effort made to control malaria for more than a century, it is still among the main public health problems in least developed regions of the world. Majority of deaths associated with malaria occur in sub-Sahara Africa among biologically risked groups. Thus, this study was designed to assess the incidence of severe malaria syndromes among children in Pawe Hospital, Northwest Ethiopia. Children seeking medication for malaria infection in Pawe Hospital during the study period were recruited. Sociodemographic characteristics, physical, hematological, and clinical features of complicated malaria were assessed following standard parasitological and clinical procedures. A total of 263 children were found malaria positive. Among these, 200 were infected with Plasmodium falciparum. Most of the severe malaria symptoms were observed among children infected with P. falciparum and P. vivax. The study showed that significant number of the children developed severe life threatening malaria complications. This calls for prompt early diagnosis and effective treatment of patients to reduce mortality and complications associated with malaria in the study site.


2018 ◽  
Vol 3 ◽  
pp. 155 ◽  
Author(s):  
Melissa C. Kapulu ◽  
Patricia Njuguna ◽  
Mainga M. Hamaluba ◽  

Malaria remains a major public health burden despite approval for implementation of a partially effective pre-erythrocytic malaria vaccine. There is an urgent need to accelerate development of a more effective multi-stage vaccine. Adults in malaria endemic areas may have substantial immunity provided by responses to the blood stages of malaria parasites, but field trials conducted on several blood-stage vaccines have not shown high levels of efficacy.  We will use controlled human malaria infection (CHMI) studies with malaria-exposed volunteers to identify correlations between immune responses and parasite growth rates in vivo.  Immune responses more strongly associated with control of parasite growth should be prioritized to accelerate malaria vaccine development. We aim to recruit up to 200 healthy adult volunteers from areas of differing malaria transmission in Kenya, and after confirming their health status through clinical examination and routine haematology and biochemistry, we will comprehensively characterize immunity to malaria using >100 blood-stage antigens. We will administer 3,200 aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Challenge) by direct venous inoculation. Serial quantitative polymerase chain reaction to measure parasite growth rate in vivo will be undertaken. Clinical and laboratory monitoring will be undertaken to ensure volunteer safety. In addition, we will also explore the perceptions and experiences of volunteers and other stakeholders in participating in a malaria volunteer infection study. Serum, plasma, peripheral blood mononuclear cells and extracted DNA will be stored to allow a comprehensive assessment of adaptive and innate host immunity. We will use CHMI in semi-immune adult volunteers to relate parasite growth outcomes with antibody responses and other markers of host immunity. Registration: ClinicalTrials.gov identifier NCT02739763.


2020 ◽  
Author(s):  
DANIEL OSAGIE OKPOKOR ◽  
ASAGA MAC PETER ◽  
Ajibaye Olusola ◽  
Anthony Danaan Dakul

Abstract Background Available evidence indicates that the various stages of the malaria parasite life cycle have specific immune responses. The pro-inflammatory cytokines tend to play an important role in preventing malaria and killing the parasites. Furthermore, the relative levels of pro-and anti-inflammatory cytokines are essential mediators of malaria anemia production and outcomes. Natural human immune responses to malaria recognize extracellular sporozoites and merozoites, both of which have surface-exposed antigens, and which are currently being developed for various vaccines. Methods A total of four hundred sixty- two (462) participants were tested for Plasmodium falciparum. The procedure employed were parasite staining using World Health Organization parasitology laboratory protocol [Microscopy] of Giemsa staining and Enzyme linked immunosorbent assay [ELISA]. Results The subjects in this study showed high levels of INF-γ and TNF-α which decreases with increased malaria severity and high parasite density. These results suggest that INF-γ cytokine and TNF-α may contribute to protection against severe malaria anaemia and parasite clearance. Conversely, infected participants showed higher levels of IL-10, which decreases with severe malaria parasite, furthermore IL-10 levels correlated with parasite density. These findings suggest that higher levels of anti-inflammatory cytokines, especially IL-10 levels may contribute to pathogenesis of complicated malaria by inhibiting the INF-γ and TNF-α production. Conclusion Molecular biological and other serological analysis are needed to elucidate the implication of these cytokines and other pro-inflammatory cytokines as IL-17, IL-21 and IL-22 in the responses to malaria and consequently their involvement in malaria vaccine construct/development as well as other therapeutics for the treatment and elimination of the malaria parasite in our environment.


2019 ◽  
Author(s):  
Guyguy Kabundi Tshima ◽  
Paul Madishala Mulumba

AbstractObjectiveWe aimed to evaluate BMI changes in HIV adults’ subjects in the first year of ART in malaria endemic areas.MethodsWe used linear regression analysis showing that the change in weight at 12 months (y) in a malaria-endemic area is related to malaria infection at admission and its different episodes as illustrated by equation: y = a + bxi + ε, where x is malaria on admission, i refers to episodes of clinical malaria infection during the year, b is the slope, a is a constant and ε are confounding factors such as tuberculosis or poor eating habits.ResultsWe found a positive value for b (b = 0.697), and this shows that weight loss at 12 months is correlated with the diagnosis of severe malaria at admission. In other words, severe malaria eliminates the weight gained under ART.ConclusionsMalaria is the leading cause of weight loss under ART.Important recommendation for future:This study suggests nutritional education based on local foods containing antioxidants to fight the oxidative stress generated by HIV and stimulated by Plasmodium falciparum during febrile episodes. Oxidative stress is blocked by NADPHase which is a metalloenzyme based on selenium.Thus, to prevent a weight loss or the occurrence of the protein-energy malnutrition among people living with HIV, it is necessary to use the nutritional education.RésuméObjectifNous voulions évaluer les modifications de l’IMC chez les patients VIH adultes au cours de la première année du traitement antirétroviral dans une zone d’endémie palustreMatériel et MéthodesNous avons utilisé une analyse de régression linéaire montrant que la variation de poids à 12 mois (y) dans une zone d’endémie palustre est liée à l’infection palustre à l’admission et à ses différents épisodes, comme l’illustre l’équation suivante: y = a + bxi + ε, où x est le paludisme à l’admission, i les épisodes de paludisme clinique survenus au cours de l’année, b est la pente, a est une constante et ε sont des facteurs de confusion tels que la tuberculose ou de mauvaises habitudes alimentaires..RésultatsNous avons trouvé une valeur positive pour b (b = 0,697), ce qui montre que la perte de poids à 12 mois est en corrélation avec le diagnostic de paludisme grave à l’admission. En d’autres termes, le paludisme grave élimine le poids gagné sous traitement antirétroviral.ConclusionsLe paludisme est la principale cause de perte de poids sous ARV.Recommandation importante pour l’avenir : Cette étude suggère une éducation nutritionnelle basée sur des aliments locaux contenant des anti-oxydants pour lutter contre le stress oxydatif généré par le VIH et stimulé par le Plasmodium falciparum lors des poussées fébriles. Le stress oxydatif est bloqué par la NADPHase qui est une métalloenzyme à base de sélénium. Ainsi, il est nécessaire d’utiliser l’éducation nutritionnelle pour prévenir la perte du poids sous ARV.


2021 ◽  
Author(s):  
Amre Nasr ◽  
Ahmad Aljada ◽  
Osama Hamid ◽  
Hatim A. Elsheikh ◽  
Emad Masuadi ◽  
...  

Abstract Background: The FcyRs genotypes have been reported to play a key role in the defence against malaria parasites through both cellular and humoral immunity. This study aimed to investigate the possible correlation between FcγR (IIa, IIIa, and IIIb) genes polymorphism and the clinical outcome for anti‐malarial antibody response of Plasmodium falciparum infection among Saudi children. Material and methods: A 600 volunteers have been enrolled in this study, including 200 malaria-free control (MFC) subjects, 218 patients with uncomplicated malaria (UM) and 182 patients with severe malaria (SM). The FcγR genotypes was analysed using PCR amplification methods, and measurement of immunoglobulins were determine using ELISA. Results: The data revealed the FcγRIIa-R/R131 showed a statistically association with the increased susceptibility to SM when compared to UM patients. Furthermore, higher levels of IgG1, IgG2, and IgG4 were associated with the FcγRIIa-H/H131 genotypes among UM patients. Although the FcγRIIa-F/V176 genotype was not associated with UM, it showed a significant association with severe malaria. Interestingly, the FcγRIIa-V/V176 genotype was This study aimed to associated with protection against SM. Moreover, severe malaria patients carrying the FcγRIIa-F/F genotype showed higher levels of AMA-1-specific IgG2 and IgG4 antibodies. The FcγRIIIb NA1/NA1 and FcγRIIIb NA2/NA2 genotypes did not show significant differences between UM and the MFC. However, the genotype FcγRIIIb-NA2/NA2 was statistically associated with severe malaria. Conclusions: The data presented in this study strongly suggest the possible impact of FcyR (IIa, RIIIa and RIIIb) gene variants and anti-malaria IgG subclasses play a role in susceptibility to malaria infection and disease outcomes in Saudi children.


Author(s):  
Chunmei Cai ◽  
Zhiqiang Hu ◽  
Xiao Yu

Malaria is a life-threatening infectious disease, affecting over 250 million individuals worldwide each year, eradicating malaria has been one of the greatest challenges to public health for a century. Growing resistance to anti-parasitic therapies and lack of effective vaccines are major contributing factors in controlling this disease. However, the incomplete understanding of parasite interactions with host anti-malaria immunity hinders vaccine development efforts to date. Recent studies have been unveiling the complexity of immune responses and regulators against Plasmodium infection. Here, we summarize our current understanding of host immune responses against Plasmodium-derived components infection and mainly focus on the various regulatory mechanisms mediated by recent identified immune regulators orchestrating anti-malaria immunity.


2018 ◽  
Vol 219 (11) ◽  
pp. 1766-1776 ◽  
Author(s):  
Stije J Leopold ◽  
Aniruddha Ghose ◽  
Erik L Allman ◽  
Hugh W F Kingston ◽  
Amir Hossain ◽  
...  

AbstractBackgroundAcidosis in severe Plasmodium falciparum malaria is associated with high mortality, yet the pathogenesis remains incompletely understood. The aim of this study was to determine the nature and source of metabolic acids contributing to acidosis in patients with severe falciparum malaria.MethodsA prospective observational study was conducted to characterize circulating acids in adults with P. falciparum malaria (n = 107) and healthy controls (n = 45) from Bangladesh using high-resolution liquid chromatography–mass spectrometry metabolomics. Additional in vitro P. falciparum culture studies were performed to determine if parasites release the acids detected in plasma from patients with severe malaria acidosis.ResultsWe identified previously unmeasured plasma acids strongly associated with acidosis in severe malaria. Metabolomic analysis of P. falciparum parasites in vitro showed no evidence that these acids are released by the parasite during its life cycle. Instead, 10 of the plasma acids could be mapped to a gut microbial origin. Patients with malaria had low L-citrulline levels, a plasma marker indicating reduced gut barrier integrity. Longitudinal data showed the clearance of these newly identified acids was delayed in fatal cases.ConclusionsThese data suggest that a compromise in intestinal barrier function may contribute significantly to the pathogenesis of life-threatening acidosis in severe falciparum malaria.Clinical Trials RegistrationNCT02451904.


2011 ◽  
Vol 7 (12) ◽  
pp. e1002389 ◽  
Author(s):  
Anne C. Teirlinck ◽  
Matthew B. B. McCall ◽  
Meta Roestenberg ◽  
Anja Scholzen ◽  
Rob Woestenenk ◽  
...  

2019 ◽  
Vol 3 ◽  
pp. 155
Author(s):  
Melissa C. Kapulu ◽  
Patricia Njuguna ◽  
Mainga M. Hamaluba ◽  

Malaria remains a major public health burden despite approval for implementation of a partially effective pre-erythrocytic malaria vaccine. There is an urgent need to accelerate development of a more effective multi-stage vaccine. Adults in malaria endemic areas may have substantial immunity provided by responses to the blood stages of malaria parasites, but field trials conducted on several blood-stage vaccines have not shown high levels of efficacy.  We will use the controlled human malaria infection (CHMI) models with malaria-exposed volunteers to identify correlations between immune responses and parasite growth rates in vivo.  Immune responses more strongly associated with control of parasite growth should be prioritized to accelerate malaria vaccine development. We aim to recruit up to 200 healthy adult volunteers from areas of differing malaria transmission in Kenya, and after confirming their health status through clinical examination and routine haematology and biochemistry, we will comprehensively characterize immunity to malaria using >100 blood-stage antigens. We will administer 3,200 aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Challenge) by direct venous inoculation. Serial quantitative polymerase chain reaction to measure parasite growth rate in vivo will be undertaken. Clinical and laboratory monitoring will be undertaken to ensure volunteer safety. In addition, we will also explore the perceptions and experiences of volunteers and other stakeholders in participating in a malaria volunteer infection study. Serum, plasma, peripheral blood mononuclear cells and whole blood will be stored to allow a comprehensive assessment of adaptive and innate host immunity. We will use CHMI in semi-immune adult volunteers to relate parasite growth outcomes with antibody responses and other markers of host immunity. Registration: ClinicalTrials.gov identifier NCT02739763.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Amre Nasr ◽  
Ahmad Aljada ◽  
Osama Hamid ◽  
Hatim A. Elsheikh ◽  
Emad Masuadi ◽  
...  

Abstract Background The FcγRs genotypes have been reported to play a key role in the defence against malaria parasites through both cellular and humoral immunity. This study aimed to investigate the possible correlation between FcγR (IIa, IIIa, and IIIb) genes polymorphism and the clinical outcome for anti‐malarial antibody response of Plasmodium falciparum infection among Saudi children. Methods A total of 600 volunteers were enrolled in this study, including 200 malaria-free control (MFC) subjects, 218 patients with uncomplicated malaria (UM) and 182 patients with severe malaria (SM). The FcγR genotypes were analysed using PCR amplification methods, and measurements of immunoglobulin were determined using enzyme-linked immunosorbent assay (ELISA) technique. Results The data revealed that the FcγRIIa-R/R131 showed a statistically significant association with SM patients when compared to UM patients. Furthermore, higher levels of IgG1, IgG2, and IgG4 were associated with the FcγRIIa-H/H131 genotype among UM patients. Although the FcγRIIa-F/V176 genotype was not associated with UM, it showed a significant association with severe malaria. Interestingly, the FcγRIIIa-V/V176 genotype offered protection against SM. Moreover, SM patients carrying the FcγRIIIa-F/F genotype showed higher levels of AMA-1-specific IgG2 and IgG4 antibodies. The FcγRIIIb-NA1/NA1 and FcγRIIIb-NA2/NA2 genotypes did not show significant differences between the UM and the MFC groups. However, the genotype FcγRIIIb-NA2/NA2 was statistically significantly associated with SM patients. Conclusions The data presented in this study suggest that the influence of the FcγRIIa-R/R131, FcγRIIIa-F/F176 and FcγRIIIb-NA2/NA2 genotypes are statistically significantly associated with SM patients. However, the FcγRIIa-H/H13 and FcγRIIIa-V/V176 genotypes have demonstrated a protective effect against SM when compared to UM patients. The impact of the FcyR (IIa, IIIa and IIIb) gene variants and anti-malaria IgG subclasses play an important role in susceptibility to malaria infection and disease outcome in Saudi children.


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