Chemistry and Pharmacology of Bergenin or Its Derivatives: A Promising Molecule.

Bergenin is a glycosidic derivative of trihydroxybenzoic acid that was discovered in 1880 by Garreau and Machelart from the rhizomes of the medicinal plant Bergenia crassifolia (currently: Saxifraga crassifolia-Saxifragaceae), though was later isolated from several other plant sources. Since its first report, it has aroused interest because it has several pharmacological activities, mainly antioxidant and anti-inflammatory. In addition to this, bergenin has shown potential antimalarial, antileishmanial, trypanocidal, antiviral, antibacterial, antifungal, antinociceptive, antiarthritic, antiulcerogenic, antidiabetic/antiobesity, antiarrhythmic, anticancer, hepatoprotective, neuroprotective and cardioprotective activities. Thus, this review aimed to describe the sources of isolation of bergenin and its in vitro and in vivo biological and pharmacological activities. Bergenin is distributed in many plant species (at least 112 species belonging to 34 families). Both its derivatives (natural and semisynthetic) and extracts with phytochemical proof of its highest concentration are well studied, and none of the studies showed cytotoxicity for healthy cells.

Is zoonotic Plasmodium vivax malaria an obstacle for disease elimination?

BACKGROUND: The groundwork for malaria elimination does not currently consider the potential of Plasmodium zoonotic cycles that involve non-human primates (NHPs) in sylvatic environments. Since vivax malaria is less responsive to control measures, finding Plasmodium vivax infected NHPs adds even more concern. METHODS: Both Free-living monkeys in forest fragments inside the urban area and captive monkeys from a local zoo had blood samples tested for Plasmodium species. RESULTS: In this study, among the Neotropical monkeys tested, three (4.4%), one captive and two free-living, were found to be naturally infected by P. vivax. CONCLUSION: This important finding indicates that it is necessary to estimate the extent to which P. vivax NHP infection contributes to the maintenance of malaria transmission to humans. Therefore, the discussion on wildlife conservation and management must be incorporated into the malaria elimination agenda.

Real-life implementation of a G6PD deficiency screening qualitative test into routine vivax malaria diagnostic units in the Brazilian Amazon (SAFEPRIM study).

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency greatly hinders Plasmodium vivax malaria radical cure and further elimination due to 8-aminoquinolines-associated hemolysis. Although the deleterious health effects of primaquine in G6PD deficient individuals have been known for over 50 years, G6PD testing is not routinely performed before primaquine treatment in most P. vivax endemic areas. METHOD/PRINCIPAL FINDINGS: The qualitative CareStart G6PD screening test was implemented in 12 malaria treatment units (MTUs) in the municipality of Rio Preto da Eva, Western Brazilian Amazon, a malaria endemic area, between February 2019 and early January 2020. Training materials were developed and validated; evaluations were conducted on the effectiveness of training health care professionals (HCPs) to perform the test, the interpretation and reliability of routine testing performed by HCPs, and perceptions of HCPs and patients. Most HCPs were unaware of G6PD deficiency and primaquine-related adverse effects. Most of 110 HCPs trained (86/110, 78%) were able to correctly perform the G6PD test after a single 4-hour training session. The test performed by HCPs during implementation showed 100.0% (4/4) sensitivity and 68.1% (62/91) specificity in identifying G6PD deficient patients as compared to a point-of-care quantitative test (Standard G6PD). CONCLUSIONS/SIGNIFICANCE: G6PD screening using the qualitative CareStart G6PD test performed by HCPs in MTUs of an endemic area showed high sensitivity and concerning low specificity. The amount of false G6PD deficiency detected led to substantial loss of opportunities for radical cure.

Influence of CYP2C8, CYP3A4, and CYP3A5 Host Genotypes on Early Recurrence of Plasmodium vivax.

Cytochrome P450 (CYP) enzymes are involved in the biotransformation of chloroquine (CQ), but the role of the different profiles of metabolism of this drug in relation to Plasmodium vivax recurrences has not been properly investigated. To investigate the influence of the CYP genotypes associated with CQ metabolism on the rates of P. vivax early recurrences, a case-control study was carried out. The cases included patients presenting with an early recurrence (CQ-recurrent individuals), defined as a recurrence during the first 28 days after initial infection and plasma concentrations of CQ plus desethylchloroquine (DCQ; the major CQ metabolite) higher than 100 ng/ml. A control group with no parasite recurrence over the follow-up (the CQ-responsive group) was also included. CQ and DCQ plasma levels were measured on day 28. CQ-metabolizing CYP (CYP2C8, CYP3A4, and CYP3A5) genotypes were determined by real-time PCR. An ex vivo study was conducted to verify the efficacy of CQ and DCQ against P. vivax isolates. The frequency of alleles associated with normal and slow metabolism was similar between the cases and the controls for the CYP2C8 (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 0.51 to 4.14, P = 0.570), CYP3A4 (OR = 2.38, 95% CI = 0.92 to 6.19, P = 0.105), and CYP3A5 (OR = 4.17, 95% CI = 0.79 to 22.04, P = 1.038) genes. DCQ levels were higher than CQ levels, regardless of the genotype. Regarding the DCQ/CQ ratio, there was no difference between groups or between those patients who had a normal genotype and those patients who had a mutant genotype. DCQ and CQ showed similar efficacy ex vivo CYP genotypes had no influence on early recurrence rates. The similar efficacy of CQ and DCQ ex vivo could explain the absence of therapeutic failure, despite the presence of alleles associated with slow metabolism.

An Ultra-Sensitive Technique: Using Pv-mtCOX1 qPCR to Detect Early Recurrences of Plasmodium vivax in Patients in the Brazilian Amazon.

BACKGROUND: Early recurrence of Plasmodium vivax is a challenge for malaria control in the field, particularly because this species is associated with lower parasitemia, which hinders diagnosis and monitoring through blood smear testing. Early recurrences, defined as the persistence of parasites in the peripheral blood despite adequate drug dosages, may arise from resistance to chloroquine. The objective of the study was to estimate early recurrence of P. vivax in the Brazilian Amazon by using a highly-sensitive detection method, in this case, PCR. METHODS: An ultra-sensitive qPCR that targeted mitochondrial DNA was used to compare a standard qPCR that targeted 18S rDNA to detect early recurrence of P. vivax in very low densities in samples from patients treated with chloroquine. RESULTS: Out of a total of 312 cases, 29 samples (9.3%) were characterized as recurrences, from which 3.2% (10/312) were only detected through ultra-sensitive qPCR testing. CONCLUSIONS: Studies that report the detection of P. vivax early recurrences using light microscopy may severely underestimate their true incidence.