Search

Copyright of Tropical Life Sciences Research is the property of Universiti Sains Malaysia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The digestive vacuole of the malaria parasite Plasmodium falciparum is the site of haemoglobin digestion and haem detoxification, and is the target of chloroquine and other antimalarials. The mechanisms for genesis of the digestive vacuole and transfer of haemoglobin from the host cytoplasm are still debated. Here, we use live-cell imaging and photobleaching to monitor the uptake of the pH-sensitive fluorescent tracer SNARF-1-dextran from the erythrocyte cytoplasm in ring-stage and trophozoite-stage parasites. We compare these results with electron tomography of serial sections of parasites at different stages of growth. We show that uptake of erythrocyte cytoplasm is initiated in mid-ring-stage parasites. The host cytoplasm is internalised via cytostome-derived invaginations and concentrated into several acidified peripheral structures. Haemoglobin digestion and haemozoin formation take place in these vesicles. The ring-stage parasites can adopt a deeply invaginated cup shape but do not take up haemoglobin via macropinocytosis. As the parasite matures, the haemozoin-containing compartments coalesce to form a single acidic digestive vacuole that is fed by haemoglobin-containing vesicles. There is also evidence for haemoglobin degradation in compartments outside the digestive vacuole. The work has implications for the stage specificity of quinoline and endoperoxide antimalarials. [ABSTRACT FROM AUTHOR]

Background: Malaria is one of the leading causes of death worldwide caused by parasites of the genus Plasmodium. The reduced efficacy of the mainstay antimalarial drugs due to the widespread of drug-resistant Plasmodium falciparum (P. falciparum) necessitates an effort to develop novel antimalarial drugs with new targets. The effects of a phenolic compound, ellagic acid, against the malaria parasite have previously been reported. This present study aimed to evaluate the effect of ellagic acid on pH of the P. falciparum digestive vacuole. Methods: The antimalarial potential of ellagic acid against the chloroquine-sensitive strain (3D7) of P. falciparum was assessed by using a malarial SYBR Green 1 fluorescence-based (MSF) assay. The effect of different concentrations of ellagic acid on the pH of the parasite's digestive vacuole at mid-trophozoite stage was examined by using a ratiometric pH indicator, fluorescein isothiocyanate (FITC)-dextran on the flow cytometry. Results: The result of the MSF assay showed that ellagic acid has an antimalarial activity (half-maximal inhibitory concentration [IC50] = 1.85 ± 4.57 nM) at par with a standard drug, artemisinin (IC50 = 1.91 ± 5.41 nM). The pH of the digestive vacuole of ellagic acid-treated parasites was significantly changed (pH values ranged from 6.11 to 6.74) in a concentration-dependent manner as compared to untreated parasites (P < 0.001). A similar effect was shown by the parasites treated with a standard proton pump inhibitor, concanamycin A. Conclusion: These findings suggest that ellagic acid might have altered the digestive vacuole pH through the inhibition of proton pumps that regulate the acidification of this organelle. Overall, this study provides a valuable insight into the potential of ellagic acid as a promising antimalarial candidate with a novel mechanism of action. [ABSTRACT FROM AUTHOR]

Background: The spread of Plasmodium falciparum resistance in common antimalarial drugs, including artemisinin-based combination therapies, has necessitated the discovery of new drugs with novel mechanisms of action. In the present study, the in vitro antimalarial and toxicological activities of acetone, methanol, ethanol and aqueous extracts of Quercus infectoria (Q. infectoria) galls were investigated. Methods: The extracts were assessed for the antimalarial potential using a malarial SYBR Green I fluorescence-based (MSF) assay, while the toxicity was screened by using brine shrimp lethality test (BSLT), haemolytic assay, and cytotoxicity assay against normal embryo fibroblast cell line (NIH/3T3) and normal kidney epithelial cell line (Vero). Results: The acetone extract showed the highest antimalarial activity (50% inhibitory concentration, IC50 = 5.85 ± 1.64 μg/mL), followed by the methanol extract (IC50 = 10.31 ± 1.90 μg/mL). Meanwhile, the ethanol and aqueous extracts displayed low antimalarial activity with IC50 values of 20.00 ± 1.57 and 30.95 μg/mL ± 1.27 μg/mL, respectively. The significant antimalarial activity was demonstrated in all extracts and artemisinin (P < 0.05). All extracts were non-toxic to brine shrimps (50% lethality concentration, LC50 > 1000 ppm). Furthermore, no occurrence of haemolysis (< 5%) was observed in normal erythrocytes when treated with all extracts compared to Triton X-100 that caused 100% haemolysis (P < 0.05). The acetone and methanol extracts were non-toxic to the normal cell lines and statistically significant to artemisinin (P < 0.05). Conclusion: Taken together with satisfactory selectivity index (SI) values, the acetone and methanol extracts of Q. infectoria galls could serve as an alternative, promising and safe antimalarial agents. [ABSTRACT FROM AUTHOR]

Background: The connection between malaria-associated morbidities and farming activities has not been succinctly reported. This study aimed to address the connectivity between farming activities and malaria transmission. Methods: The study took place in the agricultural setting of Nigeria Edu local government (9° N, 4.9° E) between March 2016 and December 2018. A pre-tested structured questionnaire was administered to obtain information on their occupation and malaria infection. Infection status was confirmed with blood film and microscopic diagnosis of Plasmodium falciparum was based on the presence of ring form or any other blood stages. Individuals who are either critically ill or lived in the community less than 3 months were excluded from the study. Results: Of the 341 volunteers, 58.1% (52.9% in Shigo and 61.4% in Sista) were infected (parasitaemia density of 1243.7 parasites/μL blood). The prevalence and intensity of infection were higher among farmers (71.3%, 1922.9 parasites/μL blood, P = 0.005), particularly among rice farmers (2991.6 parasites/μL blood) compared to non-farmer participants. The occurrence and parasite density follow the same pattern for sex and age (P < 0.05). Children in the age of 6 to 10 years (AOR: 2.168, CI: 1.63-2.19) and ≥ 11 years (AOR: 3.750, CI: 2.85-3.80) groups were twoand four-fold more likely to be infected with malaria. The analysis revealed that the proximity of bush and stagnant water to the farmer (73.9%, AOR: 3.242, CI: 2.57-3.61) and non-farmer (38.1%, AOR: 1.362, CI: 1.25-1.41) habitations influence malaria transmission. Conclusion: This study highlights farming activities as a risk factor for malaria infection in agro-communities. Integrated malaria control measures in agricultural communities should therefore include water and environmental management practices. [ABSTRACT FROM AUTHOR]

Background: The connection between malaria-associated morbidities and farming activities has not been succinctly reported. This study aimed to address the connectivity between farming activities and malaria transmission., Methods: The study took place in the agricultural setting of Nigeria Edu local government (9° N, 4.9° E) between March 2016 and December 2018. A pre-tested structured questionnaire was administered to obtain information on their occupation and malaria infection. Infection status was confirmed with blood film and microscopic diagnosis of Plasmodium falciparum was based on the presence of ring form or any other blood stages. Individuals who are either critically ill or lived in the community less than 3 months were excluded from the study., Results: Of the 341 volunteers, 58.1% (52.9% in Shigo and 61.4% in Sista) were infected (parasitaemia density of 1243.7 parasites/μL blood). The prevalence and intensity of infection were higher among farmers (71.3%, 1922.9 parasites/μL blood, P = 0.005), particularly among rice farmers (2991.6 parasites/μL blood) compared to non-farmer participants. The occurrence and parasite density follow the same pattern for sex and age ( P < 0.05). Children in the age of 6 to 10 years (AOR: 2.168, CI: 1.63-2.19) and ≥ 11 years (AOR: 3.750, CI: 2.85-3.80) groups were two-and four-fold more likely to be infected with malaria. The analysis revealed that the proximity of bush and stagnant water to the farmer (73.9%, AOR: 3.242, CI: 2.57-3.61) and non-farmer (38.1%, AOR: 1.362, CI: 1.25-1.41) habitations influence malaria transmission., Conclusion: This study highlights farming activities as a risk factor for malaria infection in agro-communities. Integrated malaria control measures in agricultural communities should therefore include water and environmental management practices., Competing Interests: Conflict of Interest None., (© Penerbit Universiti Sains Malaysia, 2020.)

Studies show that the pH of the malaria parasite's digestive vacuole (DV) plays a key role in the physiological functions of this organelle and antimalarial drug accumulation, and yet is technically difficult to measure. In this study, a flow cytometry-based technique was developed to measure the DV pH using a ratiometric pH indicator, FITC-dextran loaded into the DV of saponin-permeabilized parasites. To calculate the DV pH, a standard pH calibration curve was generated by incubating the saponin-permeabilized cells in buffers with different pH in the presence of an ionophore, CCCP. The measured average pH of the DV was 5.27 ± 0.03 that is approximately the same in the parasites observed microscopically by Hayward et al. (2006) (5.50 ± 0.14) using the same probe. The removal of glucose from the medium, causing a rapid depletion of parasite ATP, resulted in an alkalization of the DV. The DV was reacidified upon restoration of glucose to the medium. This technique provides a rapid, simple and quantitative measurement of the DV pH on a large number of cells. It will also be useful in future attempts to evaluate the effect of antimalarial drugs (i.e. chloroquine and artemisinin-based drugs) in pH changes of the DV.