Massive elimination efforts have been done to control the malaria disease caused by the emergence of the fifth human malaria parasite known as Plasmodium knowlesi. Early detection of the parasite is important in treating malaria infection. Microscopic examination of Giemsa-stained thick and thin blood films is the gold standard for laboratory malaria diagnosis, while rapid diagnostic tests (RDTs), polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) are significant diagnostic techniques to detect acute infection. However, these methods have several limitations in which it could delay the treatment. The potential of lab-on-chip (LOC) as a point-of-care diagnostic tool for malaria fulfils the requirement of limitations where it is able to produce early detection of malaria infection. This review discusses advantages and disadvantages of malaria diagnostic methods as well as new approaches that could be used for high speed, sensitive and reliable malaria detection to prevent the disease from causing severe complications and even fatal if left untreated.
The discovery of new antimalarial drugs from medicinal plants is urgently neededdue to the development of multidrug-resistant Plasmodium falciparum. Therefore, Piper sarmentosum(kaduk), a commonly used as a herbal medicine to treat malarial symptoms was screened for antimalarial as well as toxicological activities of their methanol and water leaves extracts. The inhibitory concentration (IC50) of P. sarmentosum methanol and water extracts against a chloroquine-sensitive strain (3D7) of P. falciparumwas determined by using a malarial SYBR Green I-based fluorescence (MSF) assay. The lethal concentration (LC50) of the plant extracts was evaluated by using a brine shrimp lethality test (BSLT). The presence of heavy metal contents in the crude extract was alsodetected by using an atomic absorption spectrometry (AAS). Both methanol and water extracts showed an inactive antimalarial activity with an IC50value of 138.8 ± 0.122 μg/mL and 229.7 ± 0.125 μg/mL, respectively. The water extract was considered non-toxic (LC50= 2741.7 3.16 ppm), while the methanol extract was toxic (LC50= 894.94 0.018 ppm). The heavy metals such as plumbum (Pb), zinc (Zn), cadmium (Cd) and chromium (Cr) were identified in the crude extract but they were below the safety limits recommended except for arsenic (As). Further investigations are required to determine the toxicological profiles of P. sarmentosum extracts on mammalian models.
Pyrogallol has a capability of generating free radicals like other antimalarial drugs such as artemisinin, which is thought to inhibit the proton pump located in the membrane of the Plasmodium falciparum digestive vacuole, thus alkalinising this acidic organelle. This study aimed to determine pH changes of the malaria parasite’s digestive vacuole following treatment with pyrogallol. The antimalarial activity of this compound was evaluated by a malarial SYBR Green 1 fluorescence-based assay to determine the 50% inhibitory concentration (IC50). Based on the IC50 value, different concentrations of pyrogallol were selected to ensure changes of the digestive vacuole pH were not due to parasite death. This was measured by flow cytometry after 4-hour pyrogallol treatment on the fluorescein isothiocyanate-dextran-accumulated digestive vacuole of the mid-trophozoite stage parasites. Pyrogallol showed a moderate antimalarial activity with the IC50 of 2.84 ± 9.40 µM. The treatment of 1.42, 2.84 and 5.67 µM pyrogallol increased 2.9, 3.0 and 3.1 units of the digestive vacuole pH, respectively as compared with the untreated parasite (pH 5.6 ± 0.78). The proton pump, V-type H+-ATPase might be inhibited by pyrogallol, hence causing the digestive vacuole pH alteration, which is similar with the result shown by a standard V-type H+-ATPase inhibitor, concanamycin A. This study provides a fundamental understanding on the antimalarial activity and mechanism of action of pyrogallol that has a potential to be the antimalarial drug candidate.
Ferrocene plays an important role in chemistry and industry. The structure and bonding discovered in ferrocene has led to new developments in organometallic chemistry, and the discovery of entirely new organometallic compounds. The high stability of this compound is also related to its interesting electrochemical properties that makes it effective electrochemical, reduction and combustion catalysts. Nevertheless, ferrocenyl derivatives are also capable of enhancing the activity of certain biological compounds. Indeed, recently ferrocene and its derivatives have been incorporated into antimalarial agents. Therefore, the evaluation of the possible toxic effects of ferrocene derivative called ferrocenium tetrachloroantimonate (C10H10FeSbCl4 or FC) on acute and subchronic toxicity tests using different dose concentrations according to the body weight for different time interval was carried out in an in vivo model. Results showed that FC was acutely toxic with the LD50 value of 194.70 mg/kg body weight (BW) with signs of toxicity associated with respiratory depression. In the 28-day acute toxicity test, the dose of 100 mg/kg BW resulted in 60 % mortality with signs of gross toxicity, adverse pharmacological effects or abnormal behaviors during the 28 days observation. While in the 90-day subchronic toxicity test at the lower dose of 10 mg/kg BW, however, showed no significant differences (p>0.05) in the mortality rates, and showed no sign of toxicity. These results indicated that FC had different toxicity levels, and mice appeared to tolerate well at the lower dose of 10 mg/kg BW.
Introduction: Plasmodium falciparum (P. falciparum) is a deadly protozoan that is accountable for malaria and chloroquine was the first-line antimalarial drug before its withdrawal and replaced by artemisinin. To date, several studies showed that P. falciparum had regained its sensitivity towards chloroquine after its withdrawal for decades. By understanding the basic principle and mechanism of chloroquine resistance in P. falciparum, at the molecular level, it would be valuable prior to the re-introduction of chloroquine as a first-line anti-malarial drug for malaria treatment. Thus, this study was conducted to determine the chloroquine resistance level of long preserved lab-adapted P. falciparum strain. Methodology: By using 14 years (2006-2020) cryopreserved chloroquine-sensitive (3D7) and chloroquine-resistant (W2) lab-adapted P. falciparum strains, the strains were subjected to continuous culture for three months before in vitro drug susceptibility assay and single nucleotide polymorphisms (SNP) analysis on Pfcrt and Pfmdr-1 gene for both strains. Results: This study shows the IC50 chloroquine of lab-adapted P. falciparum 3D7 and W2 strains were at 32.98 nM and 691.21 nM, respectively and both strains showed 3-fold higher IC50 when compared to their susceptibility before cryopreserved (3D7; 13.84nM and W2; 208.27 nM). The SNPs result showed a consistent amino acid substitution at position 76 (K to T) on PfCRT and 86 (N to Y) in Pfmdr-1 gene which concordance with other studies before preservation. Conclusion: Thus, this study shows that long cryopreserved of lab-adapted P. falciparum increases the chloroquine resistance level but not exhibited any change in susceptibility.