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Narra J Apr 2024In Indonesia, malaria remains a problem, with 94,610 active cases in 2021 and its current therapy includes chloroquine and artemisinin; however, resistance has been...
In Indonesia, malaria remains a problem, with 94,610 active cases in 2021 and its current therapy includes chloroquine and artemisinin; however, resistance has been commonly reported. To overcome this problem, studies about potential medicinal plants that can be used as antimalaria, such as moringa () started to receive more attention. The aim of this study was to investigate the effects of moringa in parasitemia, monocyte activation, and organomegaly on animal model malaria. This experimental study used male , infected by ANKA, as an animal malaria model. The extract was made by maceration of dry moringa leaves, which were then divided into three concentrations: 25%, 50%, and 75%. Dihydroartemisinin-piperazine was used as a positive control treatment, and distilled water as a negative control treatment. The animals were observed for six days to assess the parasitemia count and the number of monocyte activation. On day 7, the animals were terminated, and the liver, spleen, and kidney were weighed. The results showed that the effective concentrations in reducing parasitemia and inducing monocyte activation were 50% and 25% of moringa leaf extract, respectively. The smallest liver and spleen enlargement was observed among animals within the group treated with a 50% concentration of extract. In contrast, the smallest kidney enlargement was observed in the group treated with 25% of extract. Further analysis is recommended to isolate compounds with antimalarial properties in moringa leaves.
Topics: Animals; Mice; Plasmodium berghei; Plant Extracts; Male; Malaria; Monocytes; Parasitemia; Disease Models, Animal; Antimalarials; Moringa; Moringa oleifera; Plant Leaves; Spleen; Organ Size
PubMed: 38798832
DOI: 10.52225/narra.v4i1.653 -
Pathogens (Basel, Switzerland) May 2024The murine model of experimental cerebral malaria (ECM) induced by ANKA was used to investigate the relationship among pro-inflammatory cytokines, alterations in renal...
The murine model of experimental cerebral malaria (ECM) induced by ANKA was used to investigate the relationship among pro-inflammatory cytokines, alterations in renal function biomarkers, and the induction of the TRAIL apoptosis pathway during malaria-associated acute kidney injury (AKI). Renal function was evaluated through the measurement of plasma creatinine and blood urea nitrogen (BUN). The mRNA expression of several cytokines and NaPi-IIa was quantified. Kidney sections were examined and cytokine levels were assessed using cytometric bead array (CBA) assays. The presence of glomerular IgG deposits and apoptosis-related proteins were investigated using in situ immunofluorescence assays and quantitative real-time PCR, respectively. NaPi-IIa downregulation in the kidneys provided novel insights into the pathogenesis of hypophosphatemia during CM. Histopathological analysis revealed characteristic features of severe malaria-associated nephritis, including glomerular collapse and tubular alterations. Pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, were upregulated. The TRAIL apoptosis pathway was significantly activated, implicating its role in renal apoptosis. The observed alterations in renal biomarkers and the downregulation of NaPi-IIa shed light on potential mechanisms contributing to renal dysfunction in ECM. The intricate balance between pro- and anti-inflammatory cytokines, along with the activation of the TRAIL apoptosis pathway, highlights the complexity of malaria-associated AKI and provides new therapeutic targets.
PubMed: 38787228
DOI: 10.3390/pathogens13050376 -
Ethiopian Journal of Health Sciences Sep 2023The increasing resistance to most antimalarial drugs suggests a need for better alternatives. This study evaluated in vivo antimalarial and liver antioxidant profile of...
BACKGROUND
The increasing resistance to most antimalarial drugs suggests a need for better alternatives. This study evaluated in vivo antimalarial and liver antioxidant profile of dry plantain leaf extract (Musa paradisiaca) on mice infected with Plasmodium berghei.
METHODS
Six groups of ten mice each grouped as control, P. berghei, artesunate, and P. berghei infected mice were orally administered 250,500 and 1000mg/kg Musa paradisiaca leaf extract for 5 days. Blood smears were evaluated for parasitaemia on the 10 day and the mice sacrificed. Catalase, Malondialdehyde, protein, Glutathione peroxidase and reduced glutathione was estimated using Colorimetric, Biuret and spectrophotometric methods respectively with data analyzed using SPSS version 21.
RESULTS
Catalase activity (umol/ml/mins) was 24.62 ± 0.99, 10.04 ± 0.50, 19.35 ± 0.38, 22.13 ± 0.00, 22.79 ± 0.00 and 23.66 ± 0.20 while Glutathione Peroxidase(u/l) was 332.34± 0.64, 205.22± 4.61, 218.26± 0.63, 310.59± 0.00, 305.20± 0.00. and 295.97± 0.02 at Control, P.berghei, artesunate, 250mg, 500mg and1000mg extracts. Glutathione (mM) was 1.60 ± 0.12, 0.64 ± 0.09, 1.06 ± 0.16, 0.72 ± 0.00, 0.92 ± 0.00 and 1.26 ± 0.08 while Malondialdehye (uM) was 16.93 ± 3.59, 61.65 ± 1.72, 27.80 ± 0.26, 36.90 ± 0.00, 34.30 ± 0.00 and 32.68 ± 0.27 and Protein(g/dl) was 22.37 ± 1.87, 7.91 ± 0.13, 11.78 ± 1.19, 11.79 ± 0.00, 13.20 ± 0.00 and 17.04 ±0.03 at control, P.berghei, artesunate, 250mg, 500mg and1000mg respectively.
CONCLUSION
The study suggested that ethanolic extract of Musa paradisiaca reduced liver oxidative stress caused by P.berghei.
Topics: Animals; Plant Extracts; Mice; Plasmodium berghei; Malaria; Liver; Plant Leaves; Antioxidants; Antimalarials; Musa; Malondialdehyde; Glutathione; Glutathione Peroxidase; Male; Catalase; Ethanol
PubMed: 38784501
DOI: 10.4314/ejhs.v33i5.6 -
Parasites & Vectors May 2024Like other oviparous organisms, the gonotrophic cycle of mosquitoes is not complete until they have selected a suitable habitat to oviposit. In addition to the...
BACKGROUND
Like other oviparous organisms, the gonotrophic cycle of mosquitoes is not complete until they have selected a suitable habitat to oviposit. In addition to the evolutionary constraints associated with selective oviposition behavior, the physiological demands relative to an organism's oviposition status also influence their nutrient requirement from the environment. Yet, studies that measure transmission potential (vectorial capacity or competence) of mosquito-borne parasites rarely consider whether the rates of parasite replication and development could be influenced by these constraints resulting from whether mosquitoes have completed their gonotrophic cycle.
METHODS
Anopheles stephensi mosquitoes were infected with Plasmodium berghei, the rodent analog of human malaria, and maintained on 1% or 10% dextrose and either provided oviposition sites ('oviposited' herein) to complete their gonotrophic cycle or forced to retain eggs ('non-oviposited'). Transmission potential in the four groups was measured up to 27 days post-infection as the rates of (i) sporozoite appearance in the salivary glands ('extrinsic incubation period' or EIP), (ii) vector survival and (iii) sporozoite densities.
RESULTS
In the two groups of oviposited mosquitoes, rates of sporozoite appearance and densities in the salivary glands were clearly dependent on sugar availability, with shorter EIP and higher sporozoite densities in mosquitoes fed 10% dextrose. In contrast, rates of appearance and densities in the salivary glands were independent of sugar concentrations in non-oviposited mosquitoes, although both measures were slightly lower than in oviposited mosquitoes fed 10% dextrose. Vector survival was higher in non-oviposited mosquitoes.
CONCLUSIONS
Costs to parasite fitness and vector survival were buffered against changes in nutritional availability from the environment in non-oviposited but not oviposited mosquitoes. Taken together, these results suggest vectorial capacity for malaria parasites may be dependent on nutrient availability and oviposition/gonotrophic status and, as such, argue for more careful consideration of this interaction when estimating transmission potential. More broadly, the complex patterns resulting from physiological (nutrition) and evolutionary (egg-retention) trade-offs described here, combined with the ubiquity of selective oviposition behavior, implies the fitness of vector-borne pathogens could be shaped by selection for these traits, with implications for disease transmission and management. For instance, while reducing availability of oviposition sites and environmental sources of nutrition are key components of integrated vector management strategies, their abundance and distribution are under strong selection pressure from the patterns associated with climate change.
Topics: Animals; Oviposition; Anopheles; Mosquito Vectors; Female; Malaria; Plasmodium berghei; Salivary Glands; Sporozoites; Sugars; Mice
PubMed: 38783366
DOI: 10.1186/s13071-024-06317-2 -
Journal of Parasitology Research 2024Comorbidities that involve infectious and noninfectious diseases, such as malaria and cancer, have been described. Cancer and malaria induce changes in the nociceptive...
Comorbidities that involve infectious and noninfectious diseases, such as malaria and cancer, have been described. Cancer and malaria induce changes in the nociceptive and inflammatory responses through similar pathophysiological mechanisms. However, it is unclear whether malaria and antimalarial treatment can change the inflammatory and nociceptive responses induced by solid cancer. Therefore, the present study experimentally evaluated the effect of infection by strain ANKA and chloroquine treatment on the nociceptive and inflammatory responses induced by the solid Ehrlich tumor in male BALB/c mice. On the 1 experimental day, mice were infected with and injected with tumor cells in the left hind paw. From the 7 to the 9 experimental day, mice were treated daily with chloroquine. The parasitemia was evaluated on the 7 and 10 days after infection. On the 11 experimental day, mice were evaluated on the von Frey filament test, the hot plate test, and the paw volume test. At the end of the experimental tests on the 11th day, the peripheral blood of all mice was collected for dosing of IL-1 and TNF-. The blood parasitemia significantly increased from the 7 to the 10 day. The chloroquine treatment significantly decreased the parasitemia on the 10 day. The presence of the tumor did not significantly change the parasitemia on the 7 and 10 days in mice treated and nontreated with chloroquine. On the 11 day, the mechanical and thermal nociceptive responses significantly increased in mice with tumors. The treatment with antimalarial significantly reduced the mechanical nociceptive response induced by tumors. The hyperalgesia induced by tumors did not change with malaria. The mechanical and thermal hyperalgesia induced by the tumor was significantly reduced in mice treated and healed from malaria. On the 11 day, the volume of the paw injected by the tumor was significantly increased. The mice treated with chloroquine, infected with malaria, or healed of malaria showed reduced paw edema induced by the tumor. Mice with tumors did not show a change in IL- and TNF- serum levels. Mice with tumors showed a significant increase in serum levels of IL-1 but not TNF- when treated with chloroquine, infected with malaria, or healed of malaria. In conclusion, the results show that malaria infection and chloroquine treatment can influence, in synergic form, the nociceptive and inflammatory responses induced by the solid tumor. Moreover, the mechanical antinociception, the thermal hyperalgesia, and the antiedema effect observed in mice treated with chloroquine and healed from malaria can be related to the increase in the serum level of IL-1.
PubMed: 38774541
DOI: 10.1155/2024/3771926 -
International Journal For Parasitology May 2024Malaria remains the most important arthropod-borne infectious disease globally. The causative agent, Plasmodium, is a unicellular eukaryote that develops inside red...
Malaria remains the most important arthropod-borne infectious disease globally. The causative agent, Plasmodium, is a unicellular eukaryote that develops inside red blood cells. Identifying new Plasmodium parasite species that infect mammalian hosts can shed light on the complex evolution and diversity of malaria parasites. Bats feature a high diversity of microorganisms including seven separate genera of malarial parasites. Three species of Plasmodium have been reported so far, for which scarce reports exist. Here we present data from an investigation of Plasmodium infections in bats in the western Guinean lowland forest in Sierra Leone. We discovered a new Plasmodium parasite in the horseshoe bat Rhinolophus landeri. Plasmodium cyclopsi infections in a member of leaf-nosed bats, Doryrhina cyclops, exhibited a high prevalence of 100%. Phylogenetic analysis of complete mitochondrial genomes and nine nuclear markers recovered a close relationship between P. cyclopsi and the new Plasmodium parasite with the rodent species Plasmodium berghei, a widely used in vivo model to study malaria in humans. The data suggests that the "rodent/bat" Plasmodium (Vinckeia) clade represents a diverse group of malarial parasites that would likely expand with a systematic sampling of small mammals in tropical Africa. Identifying the bat Plasmodium repertoire is central to our understanding of the evolution of Plasmodium parasites in mammals.
PubMed: 38762159
DOI: 10.1016/j.ijpara.2024.05.002 -
Phytomedicine : International Journal... Jul 2024A global death toll of 608,000 in 2022 and emerging parasite resistance to artemisinin, the mainstay of antimalarial chemotherapy derived from the Chinese herb Artemisia...
BACKGROUND
A global death toll of 608,000 in 2022 and emerging parasite resistance to artemisinin, the mainstay of antimalarial chemotherapy derived from the Chinese herb Artemisia annua, urge the development of novel antimalarials. A clinical trial has found high antimalarial potency for aqueous extracts of A. annua as well as its African counterpart Artemisia afra, which contains only trace amounts of artemisinin. The artemisinin-independent antimalarial activity of A. afra points to the existence of other antimalarials present in the plant. However, the publication was retracted due to ethical and methodological concerns in the trial, so the only evidence for antimalarial activity of A. afra is built on in vitro studies reporting efficacy only in the microgram per milliliter range.
HYPOTHESIS
Our study aims to shed more light on the controversy around the antimalarial activity of A. afra by assessing its efficacy in mice. In particular, we are testing the hypothesis that A. afra contains a pro-drug that is inactive in vitro but active in vivo after metabolization by the mammalian host.
METHODS
Plasmodium berghei-infected mice were treated once or thrice (on three consecutive days) with various doses of A. afra, A. annua, or pure artemisinin.
RESULTS
Aqueous powder suspensions of A. annua but not A. afra showed antimalarial activity in mice.
CONCLUSION
Our experiments conducted in mice do not support the pro-drug hypothesis.
Topics: Antimalarials; Animals; Artemisia; Malaria; Plasmodium berghei; Artemisinins; Mice; Plant Extracts; Powders; Artemisia annua; Suspensions; Male
PubMed: 38761524
DOI: 10.1016/j.phymed.2024.155644 -
Frontiers in Immunology 2024Among spp. responsible for human malaria, ranks as the second most prevalent and has the widest geographical range; however, vaccine development has lagged behind that...
Among spp. responsible for human malaria, ranks as the second most prevalent and has the widest geographical range; however, vaccine development has lagged behind that of , the deadliest species. Recently, we developed a multistage vaccine for based on a heterologous prime-boost immunization regimen utilizing the attenuated vaccinia virus strain LC16m8Δ (m8Δ)-prime and adeno-associated virus type 1 (AAV1)-boost, and demonstrated 100% protection and more than 95% transmission-blocking (TB) activity in the mouse model. In this study, we report the feasibility and versatility of this vaccine platform as a multistage vaccine, which can provide 100% sterile protection against sporozoite challenge and >95% TB efficacy in the mouse model. Our vaccine comprises m8Δ and AAV1 viral vectors, both harboring the gene encoding two circumsporozoite (PvCSP) protein alleles (VK210; PvCSP-Sal and VK247; -PNG) and P25 (Pvs25) expressed as a Pvs25-PvCSP fusion protein. For protective efficacy, the heterologous m8Δ-prime/AAV1-boost immunization regimen showed 100% (short-term; Day 28) and 60% (long-term; Day 242) protection against PvCSP VK210 transgenic sporozoites. For TB efficacy, mouse sera immunized with the vaccine formulation showed >75% TB activity and >95% transmission reduction activity by a direct membrane feeding assay using isolates in blood from an infected patient from the Brazilian Amazon region. These findings provide proof-of-concept that the m8Δ/AAV1 vaccine platform is sufficiently versatile for vaccine development. Future studies are needed to evaluate the safety, immunogenicity, vaccine efficacy, and synergistic effects on protection and transmission blockade in a non-human primate model for Phase I trials.
Topics: Animals; Malaria Vaccines; Plasmodium vivax; Malaria, Vivax; Mice; Genetic Vectors; Dependovirus; Female; Protozoan Proteins; Antibodies, Protozoan; Disease Models, Animal; Vaccinia virus; Humans; Mice, Inbred BALB C; Immunization, Secondary; Vaccine Efficacy
PubMed: 38745665
DOI: 10.3389/fimmu.2024.1372584 -
Cell Reports May 2024While brain swelling, associated with fluid accumulation, is a known feature of pediatric cerebral malaria (CM), how fluid and macromolecules are drained from the brain...
While brain swelling, associated with fluid accumulation, is a known feature of pediatric cerebral malaria (CM), how fluid and macromolecules are drained from the brain during recovery from CM is unknown. Using the experimental CM (ECM) model, we show that fluid accumulation in the brain during CM is driven by vasogenic edema and not by perivascular cerebrospinal fluid (CSF) influx. We identify that fluid and molecules are removed from the brain extremely quickly in mice with ECM to the deep cervical lymph nodes (dcLNs), predominantly through basal routes and across the cribriform plate and the nasal lymphatics. In agreement, we demonstrate that ligation of the afferent lymphatic vessels draining to the dcLNs significantly impairs fluid drainage from the brain and lowers anti-malarial drug recovery from the ECM syndrome. Collectively, our results provide insight into the pathways that coordinate recovery from CM.
Topics: Animals; Malaria, Cerebral; Brain Edema; Mice; Disease Models, Animal; Lymphatic Vessels; Mice, Inbred C57BL; Brain; Lymph Nodes; Plasmodium berghei; Female; Male
PubMed: 38728141
DOI: 10.1016/j.celrep.2024.114217 -
Current Research in Pharmacology and... 2024infection is a health challenge. Although, antiplasmodial drugs kill the parasites, information on the effects of infection and drugs on the expression of some genes is...
infection is a health challenge. Although, antiplasmodial drugs kill the parasites, information on the effects of infection and drugs on the expression of some genes is limited. Malaria was induced in two different studies using NK65 (chloroquine-susceptible, study 1), and ANKA (chloroquine-resistant, study 2) strains of in 30 male Swiss mice (n = 5) in each study. Mice orally received 10 mL/kg distilled water, (infected control), Mefloquine (MF) (10 mg/kg), MF and Curcumin (CM) (25 mg/kg), MF and CM (50 mg/kg), CM (25 mg/kg) and CM (50 mg/kg). Five mice (un-infected) were used as the control. After treatment, total Ribonucleic acid (RNA) was isolated from liver and erythrocytes while Deoxyribonucleic acid (DNA)-free RNA were converted to cDNA. Polymerase Chain Reaction (PCR) amplification was performed and relative expressions of oxidoreductase, and cytochrome oxidase expressions were determined. Markers of glycolysis, toxicity and antioxidants were determined using ELISA assays. While the expression of was blunted by MF in the susceptible study, co-treatment with curcumin (25 mg/kg) yielded the same results in the chloroquine-resistant study. Similar results were obtained on in both studies. Curcumin decreased in both studies. infection decreased oxidoreductase and cytochrome oxidase but mefloquine-curcumin restored the expression of these genes. While glycolysis and toxicity were inhibited, antioxidant systems improved in the treated groups. Curcumin is needed for effective therapeutic efficacy and prevention of toxicity. infection and treatment modulate the expressions of some genes in the host. Curcumin combination with mefloquine modulates the expression of some genes in the host.
PubMed: 38725654
DOI: 10.1016/j.crphar.2024.100180