scholarly journals Antiplasmodial Activity of p-Substituted Benzyl Thiazinoquinone Derivatives and Their Potential against Parasitic Infections

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1530 ◽  
Author(s):  
Marcello Casertano ◽  
Marialuisa Menna ◽  
Caterina Fattorusso ◽  
Nicoletta Basilico ◽  
Silvia Parapini ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Mammalian Cells ◽  
Resonance Effect ◽  
Child Survival ◽  
Plasmodium Falciparum Malaria ◽  
Antiplasmodial Activity ◽  
Parasitic Infections ◽  
Current Survey ◽  
Life Threatening ◽  
Benzyl Substituent

Malaria is a life-threatening disease and, what is more, the resistance to available antimalarial drugs is a recurring problem. The resistance of Plasmodium falciparum malaria parasites to previous generations of medicines has undermined malaria control efforts and reversed gains in child survival. This paper describes a continuation of our ongoing efforts to investigate the effects against Plasmodium falciparum strains and human microvascular endothelial cells (HMEC-1) of a series of methoxy p-benzyl-substituted thiazinoquinones designed starting from a pointed antimalarial lead candidate. The data obtained from the newly tested compounds expanded the structure–activity relationships (SARs) of the thiazinoquinone scaffold, indicating that antiplasmodial activity is not affected by the inductive effect but rather by the resonance effect of the introduced group at the para position of the benzyl substituent. Indeed, the current survey was based on the evaluation of antiparasitic usefulness as well as the selectivity on mammalian cells of the tested p-benzyl-substituted thiazinoquinones, upgrading the knowledge about the active thiazinoquinone scaffold.

scholarly journals Anti-Plasmodium falciparum Activity of Extracts from 10 Cameroonian Medicinal Plants

Medicines ◽  
2018 ◽  
Vol 5 (4) ◽  
pp. 115 ◽  
Author(s):  
Toghueo Rufin Marie ◽  
Heroine Mbetyoumoun Mfouapon ◽  
Eugenie Madiesse Kemgne ◽  
Cedric Jiatsa Mbouna ◽  
Patrick Tsouh Fokou ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Medicinal Plants ◽  
Mammalian Cells ◽  
Cold Water ◽  
Public Health Problem ◽  
New Drugs ◽  
Antiplasmodial Activity ◽  
Major Public Health Problem ◽  
Drug Resistant ◽  
Isolation And Identification

Background: In the midst of transient victories by way of insecticides against mosquitoes or drugs against malaria, the most serious form of malaria, caused by Plasmodium falciparum, continues to be a major public health problem. The emergence of drug-resistant malaria parasites facilitated by fake medications or the use of single drugs has worsened the situation, thereby emphasizing the need for a continued search for potent, safe, and affordable new antimalarial treatments. In line with this need, we have investigated the antiplasmodial activity of 66 different extracts prepared from 10 different medicinal plants that are native to Cameroon. Methods: Extracts were evaluated for their capacity to inhibit the growth of the chloroquine-sensitive (Pf3D7) and resistant (PfINDO) strains of P. falciparum using the SYBR green fluorescence method. The cytotoxicity of promising extracts against human embryonic kidney cells (HEK293T) mammalian cells was assessed by MTT assay. Results: The antiplasmodial activity (50% inhibitory concentration, IC50) of plant extracts ranged from 1.90 to >100 μg/mL against the two strains. Six extracts exhibited good activity against both Pf3D7 and PfINDO strains, including cold water, water decoction, and ethyl acetate extracts of leaves of Drypetes principum (Müll.Arg.) Hutch. (IC503D7/INDO = 4.91/6.64 μg/mL, 5.49/5.98 μg/mL, and 6.49/7.10 μg/mL respectively), water decoction extract of leaves of Terminalia catappa L. (IC503D7/INDO = 6.41/8.10 μg/mL), and water decoction extracts of leaves and bark of Terminalia mantaly H.Perrier (IC503D7/INDO = 2.49/1.90 μg/mL and 3.70/2.80 μg/mL respectively). These promising extracts showed no cytotoxicity against HEK293T up to 200 μg/mL, giving selectivity indices (SIs) in the range of >31.20–80.32. Conclusions: While providing credence to the use of D. principum, T. catappa, and T. mantaly in the traditional treatment of malaria, the results achieved set the stage for isolation and identification of active principles and ancillary molecules that may provide us with new drugs or drug combinations to fight against drug-resistant malaria.

scholarly journals Splenic Infarction in Plasmodium Falciparum Malaria: Case Report and Review of Literature

2016 ◽  
Vol 35 (3) ◽  
pp. 298-300
Author(s):  
Deepak Dwivedi ◽  
Jyoti Singh
Keyword(s):  
Plasmodium Falciparum ◽  
Abdominal Pain ◽  
Case Report ◽  
Malaria Case ◽  
Plasmodium Falciparum Malaria ◽  
Splenic Infarction ◽  
Review Of Literature ◽  
Splenic Enlargement ◽  
Splenic Involvement ◽  
Life Threatening

Splenic involvement is frequently observed during malarial episode. This involvement may vary from simple asymptomatic splenic enlargement to serious complication such as hematoma, rupture, or infarction. Very few cases of splenic infarction in paediatric patients are reported in literature. This case report suggests that if a patient with malaria is complaining of left upper quadrant abdominal pain, and/or enlarging tender splenomegaly is observed during treatment, splenic infarct should be suspected and managed accordingly to avoid further life-threatening complications.J Nepal Paediatr Soc 2015;35(3):298-300

scholarly journals Identifying the Components of Acidosis in Patients With Severe Plasmodium falciparum Malaria Using Metabolomics

2018 ◽  
Vol 219 (11) ◽  
pp. 1766-1776 ◽  
Author(s):  
Stije J Leopold ◽  
Aniruddha Ghose ◽  
Erik L Allman ◽  
Hugh W F Kingston ◽  
Amir Hossain ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Severe Malaria ◽  
Falciparum Malaria ◽  
Intestinal Barrier ◽  
Plasmodium Falciparum Malaria ◽  
Intestinal Barrier Function ◽  
Life Threatening ◽  
Plasma Marker ◽  
Severe Falciparum Malaria

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.

Ineffectiveness of Continuous Quinidine Gluconate Infusion in the Treatment of Severe Chloroquine-Resistant Plasmodium Falciparum Malaria

1988 ◽  
Vol 22 (11) ◽  
pp. 883-885 ◽  
Author(s):  
Gary K. Matsuura ◽  
Lucinda A. Chan
Keyword(s):  
Plasmodium Falciparum ◽  
Disease Control ◽  
Continuous Infusion ◽  
Falciparum Malaria ◽  
Plasmodium Falciparum Malaria ◽  
Viable Alternative ◽  
Loading Dose ◽  
Drug Of Choice ◽  
Life Threatening ◽  
The U.S

The drug of choice in the treatment of chloroquine-resistant Plasmodium falciparum malaria is parenteral quinine dihydrochloride. Due to limited use, the drug is not commercially available in the U.S. and must be obtained through the Centers for Disease Control (CDC) in Atlanta, Georgia. As an alternative, the CDC has developed a protocol to treat P. falciparum malaria with parenteral quinidine gluconate. Following this protocol, a 10 mg/kg loading dose of quinidine gluconate followed by a 0.02 mg/kg/min continuous infusion was administered to a 53-year-old man with severe life-threatening chloroquine-resistant P. falciparum malaria. Although the patient described did not survive, the use of parenteral quinidine gluconate still appears to be a viable alternative to parenteral quinine dihydrochloride in the treatment of severe chloroquine-resistant P. falciparum malaria.

scholarly journals Rapid diagnostic test negative Plasmodium falciparum malaria in a traveller returning from Ethiopia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Stefan Schlabe ◽  
Ingrid Reiter-Owona ◽  
Tamara Nordmann ◽  
Ramona Dolscheid-Pommerich ◽  
Egbert Tannich ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
False Negative ◽  
Plasmodium Falciparum Malaria ◽  
Negative Results ◽  
First Case ◽  
False Negative Results ◽  
Genes Encoding ◽  
Life Threatening ◽  
And Control

Abstract Background Plasmodium falciparum strains with mutations/deletions of the genes encoding the histidine-rich proteins 2/3 (pfhrp2/3) have emerged during the last 10 years leading to false-negative results in HRP2-based rapid diagnostic tests (RDTs). This can lead to unrecognized infections in individuals and to setbacks in malaria control in endemic countries where RDTs are the backbone of malaria diagnostics and control. Case description Here the detection of a pfhrp2/3-negative P. falciparum infection acquired in Ethiopia by a 63-year old female traveller is presented. After onset of symptoms during travel, she was first tested negative for malaria, most probably by RDT, at a local hospital in Harar, Ethiopia. Falciparum malaria was finally diagnosed microscopically upon her return to Germany, over 4 weeks after infection. At a parasite density of approximately 5387 parasites/µl, two different high-quality RDTs: Palutop + 4 OPTIMA, NADALRMalaria PF/pan Ag 4 Species, did not respond at their respective P. falciparum test lines. pfhrp2/3 deletion was confirmed by multiplex-PCR. The patient recovered after a complete course of atovaquone and proguanil. According to the travel route, malaria was acquired most likely in the Awash region, Central Ethiopia. This is the first case of imported P. falciparum with confirmed pfhrp2/3 deletion from Ethiopia. Conclusion HRP2-negative P. falciparum strains may not be recognized by the presently available HRP2-based RDTs. When malaria is suspected, confirmation by microscopy and/or qPCR is necessary in order to detect falciparum malaria, which requires immediate treatment. This case of imported P. falciparum, non-reactive to HRP2-based RDT, possibly underlines the necessity for standardized, nationwide investigations in Ethiopia and should alert clinicians from non-endemic countries to the possibility of false-negative RDT results which may increase in returning travellers with potentially life-threatening infections.

scholarly journals The Use of Activated Protein C in Severe Plasmodium Falciparum Malaria

2007 ◽  
Vol 35 (3) ◽  
pp. 428-432 ◽  
Author(s):  
L. G. Rankin ◽  
D. L. H. Austin
Keyword(s):  
Plasmodium Falciparum ◽  
Severe Sepsis ◽  
Falciparum Malaria ◽  
Protein C ◽  
Multiorgan Failure ◽  
Activated Protein C ◽  
Severe Infection ◽  
Plasmodium Falciparum Malaria ◽  
Peripheral Hospital ◽  
Life Threatening

A 56-year-old man presented to a peripheral hospital in New Zealand with severe Plasmodium falciparum malaria with cerebral involvement and subsequently developed multi-system organ failure. Activated protein C was used in an attempt to stop the cascade of events into multiorgan failure. Severe infection with P. falciparum is life-threatening and appears to activate a hypercoagulable state similar to that of severe sepsis. Activated protein C is currently used in the treatment of severe sepsis and may provide a new adjuvant therapy for severe P. falciparum malaria.

scholarly journals Malaria in the Time of COVID-19: Do Not Miss the Real Cause of Illness

2021 ◽  
Vol 6 (2) ◽  
pp. 40
Author(s):  
Johannes Jochum ◽  
Benno Kreuels ◽  
Egbert Tannich ◽  
Samuel Huber ◽  
Julian Schulze zur Wiesch ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Severe Acute Respiratory Syndrome ◽  
Falciparum Malaria ◽  
Medical Management ◽  
Cognitive Biases ◽  
Plasmodium Falciparum Malaria ◽  
Current Situation ◽  
The Real ◽  
Life Threatening

We report a case of Plasmodium falciparum malaria in a patient asymptomatically co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the current ongoing coronavirus pandemic, co-infections with unrelated life-threatening febrile conditions may pose a particular challenge to clinicians. The current situation increases the risk for cognitive biases in medical management.

scholarly journals Targets and Mechanisms Associated with Protection from Severe Plasmodium falciparum Malaria in Kenyan Children

2016 ◽  
Vol 84 (4) ◽  
pp. 950-963 ◽  
Author(s):  
Linda M. Murungi ◽  
Klara Sondén ◽  
David Llewellyn ◽  
Josea Rono ◽  
Fatuma Guleid ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Rank Correlation ◽  
Plasmodium Falciparum Malaria ◽  
Cell Surface Antigens ◽  
Immunological Parameters ◽  
Content Type ◽  
Merozoite Antigens ◽  
Life Threatening ◽  
Matched Case ◽  
Functional Mechanisms

Severe malaria (SM) is a life-threatening complication of infection withPlasmodium falciparum. Epidemiological observations have long indicated that immunity against SM is acquired relatively rapidly, but prospective studies to investigate its immunological basis are logistically challenging and have rarely been undertaken. We investigated the merozoite targets and antibody-mediated mechanisms associated with protection against SM in Kenyan children aged 0 to 2 years. We designed a unique prospective matched case-control study of well-characterized SM clinical phenotypes nested within a longitudinal birth cohort of children (n= 5,949) monitored over the first 2 years of life. We quantified immunological parameters in sera collected before the SM event in cases and their individually matched controls to evaluate the prospective odds of developing SM in the first 2 years of life. Anti-AMA1 antibodies were associated with a significant reduction in the odds of developing SM (odds ratio [OR] = 0.37; 95% confidence interval [CI] = 0.15 to 0.90;P= 0.029) after adjustment for responses to all other merozoite antigens tested, while those against MSP-2, MSP-3,Plasmodium falciparumRh2 [PfRh2], MSP-119, and the infected red blood cell surface antigens were not. The combined ability of total IgG to inhibit parasite growth and mediate the release of reactive oxygen species from neutrophils was associated with a marked reduction in the odds of developing SM (OR = 0.07; 95% CI = 0.006 to 0.82;P= 0.03). Assays of these two functional mechanisms were poorly correlated (Spearman rank correlation coefficient [rs] = 0.12;P= 0.07). Our data provide epidemiological evidence that multiple antibody-dependent mechanisms contribute to protective immunity via distinct targets whose identification could accelerate the development of vaccines to protect against SM.

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