[Investigation of the Efficacy of Cinnamaldehyde, Cannabidiol and Eravacycline in a Malaria Model]. / Sitma Modelinde Cinnamaldehyde, Cannabidiol ve Eravacycline'in Etkinliginin Arastirilmasi.

In this study, it was aimed to investigate the antimalarial activity of cinnamaldehyde (CIN) and cannabidiol (CBD) which have shown various biological activities such as potent antimicrobial activity and eravacycline (ERA), a new generation tetracycline derivative, in an in vivo malaria model. The cytotoxic activities of the active substances were determined by the MTT method against L929 mouse fibroblasts and their antimalarial activity were determined by the four-day test in an in vivo mouse model. In this study, five groups were formed: the CIN group, the CBD group, the ERA group, the chloroquine group (CQ) and the untreated group (TAG). 2.5 x 107 parasites/mL of P.berghei-infected erythrocyte suspension was administered IP to all mice. The determined doses of active substances were given to the mice by oral gavage in accordance with the four-day test and the parasitemia status in the mice was controlled for 21 days with smear preparations made from the blood taken from the tail end of the mice. The IC50 values, which express the cytotoxic activity values of the active substances were determined as 27.55 µg/mL, 16.40 µM and 48.82 µg/mL for CIN, CBD and ERA, respectively. The mean parasitemia rate in untreated mice was 33% on day nine and all mice died on day 11. On the ninth day, when compared with the TAG group, no parasites were observed in the CIN group, while the average parasitemia was 0.08% in the CBD group and 17.8% in the ERA group. Compared to the mice in the TAG group, the life expectancy of the other groups was prolonged by eight days in the CIN group, 12 days in the CBD group and eight days in the ERA group. It has been determined that all three active subtances tested in this study suppressed the development of Plasmodium parasites in an in vivo mouse model and prolonged the life span of the mice. It is thought that the strong antimalarial activity of CIN and CBD shown in the study and the possible positive effect of ERA on the clinical course can be improved by combining them with the existing and potential antimalarial molecules.

Association between malaria and undernutrition among pregnant women at presentation for antenatal care in health facilities in the Mount Cameroon region.

In resource limited settings, malaria and undernutrition are major public health problems in pregnancy. Therefore, this study assessed the association between malaria infection and undernutrition among pregnant women in the Mount Cameroon area. This cross-sectional study enrolled 1,014 pregnant women consecutively over a year. A structured questionnaire was used to collect socio-demographic information and clinical data. Maternal nutrition was assessed using dietary diversity (DD). Peripheral blood samples collected were used for the diagnosis of malaria parasitaemia by microscopy whereas haemoglobin (Hb) levels were determined using an Hb meter. Logistic regression was used to determine factors associated with malaria and dietary diversity. The prevalence of malaria infection and undernutrition was 17.8% and 89.6% respectively. In addition, of those infected with malaria, geometric mean parasite density was 301/µL of blood (range: 40-9280) while mean DD score was 3.57±0.82 (range: 1-7). The odds of being infected with malaria parasitaemia was highest among women enrolled in the rainy season (OR = 1.58, P = 0.043), who were farmers (OR = 2.3, P = 0.030), had a household size of < 4 individuals (OR = 1.48, P = 0.026) and who were febrile (OR = 1.87, P < 0.001). Also, attending clinic visits in Mutengene Medical Centre (OR = 2.0, P = 0.012) or Buea Integrated Health Centre (OR = 2.9, P = < 0.001), being < 25 years (OR = 2.4, P = 0.002) and a farmer (OR = 10.6, P = 0.024) as well as < 4 clinic visits (OR = 1.62, P = 0.039) were identified as predictors of undernutrition. Furthermore, the association between malaria and DD was statistically significant (P = 0.015). In this study, undernutrition was highly frequent than malaria infection. Thus, there is an urgent need to improve maternal awareness through nutritional counselling and health campaigns on the benefits of consuming at least five food groups. Besides, improved maternal dietary nutrient intake is likely to have impact on the burden of malaria parasite infection.

Ursolic acid-rich extract presents trypanocidal action in vitro but worsens mice under experimental acute Chagas disease.

Chagas disease is a neglected tropical disease with only two drugs available for treatment and the plant Cecropia pachystachya has several compounds with antimicrobial and anti-inflammatory activities. This study aimed to evaluate a supercritical extract from C. pachystachya leaves in vitro and in vivo against Trypanosoma cruzi. A supercritical CO2 extraction was used to obtain the extract (CPE). Cytotoxicity and immunostimulation ability were evaluated in macrophages, and the in vitro trypanocidal activity was evaluated against epimastigotes and trypomastigotes forms. In vivo tests were done by infecting BALB/c mice with blood trypomastigotes forms and treating animals orally with CPE for 10 days. The parasitemia, survival rate, weight, cytokines and nitric oxide dosage were evaluated. CPE demonstrated an effect on the epi and trypomastigotes forms of the parasite (IC50 17.90 ± 1.2 µg/mL; LC50 26.73 ± 1.2 µg/mL) and no changes in macrophages viability, resulting in a selectivity index similar to the reference drug. CPE-treated animals had a worsening compared to non-treated, demonstrated by higher parasitemia and lower survival rate. This result was attributed to the anti-inflammatory effect of CPE, demonstrated by the higher IL-10 and IL-4 values observed in the treated mice compared to the control ones. CPE demonstrated a trypanocidal effect in vitro and a worsening in the in vivo infection due to its anti-inflammatory activity.

Vitamin C-rich juice co-administration with artemether-lumefantrine ameliorates oxido-inflammatory responses in Plasmodium berghei-infected mice.

This study investigated the effects of co-administration of a commercial juice rich in vitamin C (Vit C) on the antimalarial efficacy of artemether-lumefantrine (AL) in Plasmodium berghei-infected mice. Fifty Balb/c mice were infected with Plasmodium berghei NK65 strain from a donor mouse. Parasitemia was established after 72 h. Animals were grouped into 6 (n = 10) and treated daily for 3 days with normal saline, chloroquine, artemether-lumefantrine (AL), AL plus 50% commercial juice (CJ), and AL plus 50% Vit C supplementation in drinks ad libitum, respectively. Body weight, parasitemia levels, and mean survival time were determined. Tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), nitrite, malondialdehyde, reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) were determined in the serum and liver tissues. Spleen histopathological changes were determined by H&E staining. Parasitemia was cleared by administration of AL and was not affected by Vit C and CJ supplementation. Vit C significantly prevented body weight reduction in AL-treated mice. CJ and Vit C supplementation to AL-treated mice significantly improved survival proportion compared with AL alone animals. Vit C and CJ supplementation significantly improved reduction of TNF-α, IL-6, and malondialdehyde, and increased GSH, CAT, and SOD in AL-treated mice. Spleen cell degeneration and presence of malaria pigment were reduced in AL-treated animals. The results suggest that ad libitum co-administration of commercial juice and vitamin C with artemether-lumefantrine does not impair its antimalarial efficacy but rather improved antioxidant and anti-inflammatory effects in mice.

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

BACKGROUND: Description of the condition Malaria, an infectious disease transmitted by the bite of female mosquitoes from several Anopheles species, occurs in 87 countries with ongoing transmission (WHO 2020). The World Health Organization (WHO) estimated that, in 2019, approximately 229 million cases of malaria occurred worldwide, with 94% occurring in the WHO's African region (WHO 2020). Of these malaria cases, an estimated 409,000 deaths occurred globally, with 67% occurring in children under five years of age (WHO 2020). Malaria also negatively impacts the health of women during pregnancy, childbirth, and the postnatal period (WHO 2020). Sulfadoxine/pyrimethamine (SP), an antifolate antimalarial, has been widely used across sub-Saharan Africa as the first-line treatment for uncomplicated malaria sTo examine the effects of folic acid supplementation, at various doses, on malaria susceptibility (risk of infection) and severity among people living in areas with various degrees of malaria endemicity. We will examine the interaction between folic acid supplements and antifolate antimalarial drugs. Specifically, we will aim to answer the following. Among uninfected people living in malaria endemic areas, who are taking or not taking antifolate antimalarials for malaria prophylaxis, does taking a folic acid-containing supplement increase susceptibility to or severity of malaria infection? Among people with malaria infection who are being treated with antifolate antimalarials, does folic acid supplementation increase the risk of treatment failure?Criteria for considering studies for this review Types of studies Inclusion criteria Randomized controlled trials (RCTs) Quasi-RCTs with randomization at the individual or cluster level conducted in malaria-endemic areas (areas with ongoing, local malaria transmission, including areas approaching elimination, as listed in the World Malaria Report 2020) (WHO 2020) Exclusion criteria Ecological studies Observational studies In vivo/in vitro studies Economic studies Systematic literature reviews and meta-analyses (relevant systematic literature reviews and meta-analyses will be excluded but flagged for grey literature screening) Types of participants Inclusion criteria Individuals of any age or gender, living in a malaria endemic area, who are taking antifolate antimalarial medications (inclu

Medicinal plants used in traditional treatment of malaria in Ethiopia: a review of ethnomedicine, anti-malarial and toxicity studies.

BACKGROUND: Malaria is extremely common in Ethiopia, and it is one of the country's most serious public health and economic problems. Traditional medicines have long been utilized in Ethiopia by people of various ethnic groups. As a result, the goal of this study is to record the use of Ethiopian medicinal herbs that have been used to treat malaria. Also, a critical review of the literature on the therapeutic properties of these and other Ethiopian medicinal plants that have been tested against Plasmodium spp. parasites was conducted with the goal of highlighting neglected studies and fostering further research in this area. METHODS: A comprehensive literature search was performed in Scopus, Web of Science Core Collection, PubMed, Science Direct, Google Scholar, and Scientific Electronic Library Online (SciELO) from August 2021 to October 2021. The study databases included original articles published in peer reviewed journals covering anti-malarial plants, dated until October 2021. RESULTS: The review looked at 51 plant species (28 families) that have been used to treat malaria in Ethiopia. The most often used ethnobotanical plant species for the treatment of malaria were Allium sativum, Croton macrostachyus, Carica papaya, and Lepidium sativum. Leaves were used more frequently as a therapeutic preparation than other parts. Plant extracts were found to have very good, good, and moderate anti-malarial activity in mice with rodent Plasmodium species. The most active species were Ajuga remota and Capsicum frufescens, which suppressed parasitaemia by 77.34% and 72.65%, respectively, at an oral dose of 100 mg/kg and an LD50 of above 2000 mg/kg. The compound Aloinoside reported from Aloe macrocarpa leave latex was the most potent; it suppressed parasitaemia by 100% at 400 mg/kg oral dose of Plasmodium berghei infected mice, and its LD50 was above 2000 mg/kg. Toxicity was shown to be safe in 84% of the plant extracts. CONCLUSION: In Ethiopia, medicinal plants have a significant part in reducing the severity of malaria due to their widespread use. As a result, more studies are needed to identify and develop effective novel drugs that could be employed in broader malaria eradication efforts.

Hydroethanolic Extracts of Senna alata Leaves Possess Antimalarial Effects and Reverses Haematological and Biochemical Pertubation in Plasmodium berghei-infected Mice.

The current work investigated the chemical profile, antimalarial potential and capacity of hydroethanolic Senna alata extract (SAE) to reverse hematological and biochemical pertubation in Plasmodium berghei infected mice. Results of the phytochemical analysis revealed the presence of alkaloids, flavonoids, phenolics, tannins, terpenoids, saponins, steroids and cardiac glycosides. Total phenolic and flavonoid content was estimated to be 45.29 ± 2.34 mg GAE/g and 25.22 ± 2.26 mg QE/g respectively. In vitro analysis of the extract also confirmed its antioxidant property. Results of the test for prophylaxis of P. berghei indicated that SAE suppressed parasitemia significantly in treated groups in a dose dependent manner when compared with negative control group. Similarly, SAE improved the mean survival time (MST) and packed cell volume (PCV) of infected mice. The test for curative effect showed that SAE significantly suppressed parasitemia to 4.50 ± 1.05% compared to untreated group 29.83 ± 3.49%. Results of liver and kidney functions indices of treated animals indicated that whereas infection with P. berghei caused increase in the levels of AST, ALT, ALP, urea and creatinine, treatment with SAE significantly reversed the perturbation. Similarly, infected mice were dyslipidemic with concomitant increased activity of HMG CoA reductase and decreased activity of antioxidant enzymes with increase in lipid peroxides levels. However, these alterations were significantly reversed by administration of SAE. Results of this study shows that Senna alata possess antimalarial activity and therefore justify the traditional use of plant for the treatment of malaria.

Hepatoprotective activity of Eucalyptus camaldulensis extract in murine malaria mediated by suppression of oxidative and inflammatory processes.

Herbal extracts are promising agents against various parasitic diseases, such as malaria. This study aimed to evaluate the ameliorative action of Eucalyptus camaldulensis extract (ECE) against hepatic damage caused by Plasmodium chabaudi infection. Mice were allocated into five groups as follows: two groups served as the control non-infected groups that received distilled water and ECE, respectively; subsequent three groups were infected with 106 P. chabaudi parasitized erythrocytes; the last two groups were infected with the parasite and then treated with ECE and chloroquine. On day 8 post-infection, the parasite count increased inside erythrocytes (59.4% parasitemia in the infected group). Parasitemia was successfully reduced to 9.4% upon ECE treatment. Phytochemical screening using GC mass spectrometry revealed that ECE contained 23 phytochemical components. Total phenolics and flavonoids in ECE were 104 ± 2 and 7.1± 3 µg/mL, respectively, with 57.2% antioxidant activity. ECE ameliorated changes in liver histopathology and enzymatic activity of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. In addition, ECE prevented oxidative damage induced by the parasite in the liver, as evidenced by the change in the liver concentrations of glutathione, nitric oxide, malondialdehyde, and catalase. Moreover, ECE was able to regulate the expression of liver cytokines, interleukins-1ß and 6, as well as IFN-γ mRNA. ECE possesses antiplasmodial, antioxidant, and anti-inflammatory activity against liver injury induced by the parasite P. chabaudi.

Antimalarial activity of solvent fractions of a leaf of Eucalyptus globulus labill against Plasmodium berghei infected mice.

INTRODUCTION: The leaf of Eucalyptus globulus is commonly used in the traditional management of malaria. However, the efficacy of solvent fractions are didn't study yet scientifically. Thus, this study aimed to investigate the antimalarial efficacy of the solvent fractions of the leaf of Eucalyptus globulus in mice against P.berghei. METHODS: The antimalarial activity of the fractions was tested in a 4-day suppressive test, Rane's test, and prophylactic test models within P.berghei infected mice. The results were analyzed using a one-way analysis of variance (ANOVA) followed by a post hoc Tukey's test in version 20 SPSS. RESULTS: All fractions at all test doses in the three test models suppressed parasitemia (p < 0.001) compared to the negative controls. In addition, the CF and EA at all three test doses and the AF at 400 mg/kg in three antimalarial test models showed 50% and above parasitemia suppression. In compliance with this, all fractions at all test doses in all test models prolonged the mean survival time of the mice greater than 12 days, except the AF at a lower dose. All fractions at 400 mg/kg in the three test models prevented (p < 0.001) loss of body weight and rectal temperature compared to the negative controls. Furthermore, all fractions in all test models and doses prevented packed cell volume reduction (p < 0.05 to p < 0.001) compared to the negative controls.. CONCLUSION: The findings of this study showed that CF and EAF had greater antimalarial activity compared to AF. This could be attributed to the presence of few phytochemicals in the AF in contrast to the CF and EAF. Overall, the results of this study further support the in vitro antimalarial activity study and the traditional use of the leaf in the management of malaria.

Administration of L-citrulline prevents Plasmodium growth by inhibiting/ modulating T-regulatory cells during malaria pathogenesis.

BACKGROUND & OBJECTIVES: Malaria affects around 228 million people all over the globe. Malaria causing parasite Plasmodium infection leads to activation of immune responses. The growth of parasite and immune activation requires semi essential amino acids like L-arginine. Malaria infection leads to condition of hyperargininemia and low availability of nitric oxide. However, the effect of L-arginine supplementation in malaria infected mice has not been explored in in-vivo studies. In this study we have compared the effect of oral supplementation of nitric oxide donor, L-arginine and L-citrulline, in malaria infected mice Methods: To examine the effect of oral supplementation of L-arginine and L-citrulline, Plasmodium berghei infected mice were divided in different groups and respective groups were fed with L- arginine and L-citrulline, parasitemia was measured on different days. Mice was sacrificed and immunophenotyping was done on 10 days post infection. RESULTS: our results show that supplementation of L-arginine induces conducive environment for Plasmodium growth due to which the infected mice dies earlier than control wild type infected mice whereas L-citrulline supplementation inhibits parasite growth and mice survives for longer period of time. Flow cytometric analysis shows that supplementation of L-arginine increases cTLA-4 on T cell population, increases Treg cells leading to immunosuppression while supplementation of L-citrulline does not have effect on T cells population and number of Treg cell decrease compared to P. berghei infected mice. INTERPRETATION & CONCLUSION: our results show that L-citrulline can be a better alternative than L-arginine because of lower expression of inhibitory molecules and lower parasitemia as well as increased survival of infected mice.

Probiotic administration enhanced antitrypanosomal effects of diminazene aceturate in dogs experimentally infected with Trypanosoma brucei brucei.

OBJECTIVES: This study demonstrated the enhancing actions of probiotic on the antitrypanosomal effects of diminazene aceturate in dogs experimentally infected with Trypanosoma brucei brucei. METHODS: Twenty (20) apparently healthy adult local dogs of both sexes were randomly divided into five groups each containing four dogs. Group I were uninfected and untreated while groups III, IV and V were infected. Groups II, III, IV and V were administered multispecies probiotic (MSP) and/or diminazene aceturate (DA). Parasitaemia was determined, clinical signs recorded and blood collected for haematology. RESULTS: Results revealed T. b. brucei prepatent periods of 4.75 ± 0.25, (4-5) days and significant decrease of parasitaemia, clinical signs and mortality in groups IV and V compared to group III. Mortalities of 100% (group III), 25% (group IV) and 0% (group V) were recorded. Mean packed cells volume, haemoglobin concentration and red blood cells count showed no significant difference in groups I, II, and V, but were significantly decreased in groups III and IV post-treatment. CONCLUSIONS: The administration of MSP to infected dogs enhanced the antitrypanosomal effects of diminazene aceturate.

Associations of maternal iron deficiency with malaria infection in a cohort of pregnant Papua New Guinean women.

BACKGROUND: Iron deficiency (ID) is common in malaria-endemic settings. Intermittent preventative treatment of malaria in pregnancy (IPTp) and iron supplementation are core components of antenatal care in endemic regions to prevent adverse pregnancy outcomes. ID has been associated with reduced risk of malaria infection, and correspondingly, iron supplementation with increased risk of malaria infection, in some studies. METHODS: A secondary analysis was conducted amongst 1888 pregnant women enrolled in a malaria prevention trial in Papua New Guinea. Maternal ID was defined as inflammation-corrected plasma ferritin levels < 15 µg/L at antenatal enrolment. Malaria burden (Plasmodium falciparum, Plasmodium vivax) was determined by light microscopy, polymerase chain reaction, and placental histology. Multiple logistic and linear regression analyses explored the relationship of ID or ferritin levels with indicators of malaria infection. Models were fitted with interaction terms to assess for modification of iron-malaria relationships by gravidity or treatment arm. RESULTS: Two-thirds (n = 1226) and 13.7% (n = 258) of women had ID and peripheral parasitaemia, respectively, at antenatal enrolment (median gestational age: 22 weeks), and 18.7% (120/1,356) had evidence of malaria infection on placental histology. Overall, ID was associated with reduced odds of peripheral parasitaemia at enrolment (adjusted odds ratio [aOR] 0.50; 95% confidence interval [95% CI] 0.38, 0.66, P < 0.001); peripheral parasitaemia at delivery (aOR 0.68, 95% CI 0.46, 1.00; P = 0.050); and past placental infection (aOR 0.35, 95% CI 0.24, 0.50; P < 0.001). Corresponding increases in the odds of infection were observed with two-fold increases in ferritin levels. There was effect modification of iron-malaria relationships by gravidity. At delivery, ID was associated with reduced odds of peripheral parasitaemia amongst primigravid (AOR 0.44, 95% CI 0.25, 0.76; P = 0.003), but not multigravid women (AOR 1.12, 95% CI 0.61, 2.05; P = 0.720). A two-fold increase in ferritin associated with increased odds of placental blood infection (1.44, 95% CI 1.06, 1.96; P = 0.019) and active placental infection on histology amongst primigravid women only (1.24, 95% CI 1.00, 1.54; P = 0.052). CONCLUSIONS: Low maternal ferritin at first antenatal visit was associated with a lower risk of malaria infection during pregnancy, most notably in primigravid women. The mechanisms by which maternal iron stores influence susceptibility to infection with Plasmodium species require further investigation.

The Role of MIF and IL-10 as Molecular Yin-Yang in the Modulation of the Host Immune Microenvironment During Infections: African Trypanosome Infections as a Paradigm.

African trypanosomes are extracellular flagellated unicellular protozoan parasites transmitted by tsetse flies and causing Sleeping Sickness disease in humans and Nagana disease in cattle and other livestock. These diseases are usually characterized by the development of a fatal chronic inflammatory disease if left untreated. During African trypanosome infection and many other infectious diseases, the immune response is mediating a see-saw balance between effective/protective immunity and excessive infection-induced inflammation that can cause collateral tissue damage. African trypanosomes are known to trigger a strong type I pro-inflammatory response, which contributes to peak parasitaemia control, but this can culminate into the development of immunopathologies, such as anaemia and liver injury, if not tightly controlled. In this context, the macrophage migration inhibitory factor (MIF) and the interleukin-10 (IL-10) cytokines may operate as a molecular "Yin-Yang" in the modulation of the host immune microenvironment during African trypanosome infection, and possibly other infectious diseases. MIF is a pleiotropic pro-inflammatory cytokine and critical upstream mediator of immune and inflammatory responses, associated with exaggerated inflammation and immunopathology. For example, it plays a crucial role in the pro-inflammatory response against African trypanosomes and other pathogens, thereby promoting the development of immunopathologies. On the other hand, IL-10 is an anti-inflammatory cytokine, acting as a master regulator of inflammation during both African trypanosomiasis and other diseases. IL-10 is crucial to counteract the strong MIF-induced pro-inflammatory response, leading to pathology control. Hence, novel strategies capable of blocking MIF and/or promoting IL-10 receptor signaling pathways, could potentially be used as therapy to counteract immunopathology development during African trypanosome infection, as well as during other infectious conditions. Together, this review aims at summarizing the current knowledge on the opposite immunopathological molecular "Yin-Yang" switch roles of MIF and IL-10 in the modulation of the host immune microenvironment during infection, and more particularly during African trypanosomiasis as a paradigm.

Randomized clinical trial to assess the protective efficacy of a Plasmodium vivax CS synthetic vaccine.

A randomized, double-blind, controlled vaccine clinical trial was conducted to assess, as the primary outcome, the safety and protective efficacy of the Plasmodium vivax circumsporozoite (CS) protein in healthy malaria-naïve (phase IIa) and semi-immune (phase IIb) volunteers. Participants (n = 35) were randomly selected from a larger group (n = 121) and further divided into naïve (n = 17) and semi-immune (n = 18) groups and were immunized at months 0, 2, and 6 with PvCS formulated in Montanide ISA-51 adjuvant or placebo (adjuvant alone). Specific antibodies and IFN-γ responses to PvCS were determined as secondary outcome; all experimental volunteers developed specific IgG and IFN-γ. Three months after the last immunization, all participants were subjected to controlled human malaria infection. All naive controls became infected and drastic parasitemia reduction, including sterile protection, developed in several experimental volunteers in phase IIa (6/11) (54%, 95% CI 0.25-0.84) and phase IIb (7/11) (64%, 95% CI 0.35-0.92). However, no difference in parasitemia was observed between the phase IIb experimental and control subgroups. In conclusion, this study demonstrates significant protection in both naïve and semi-immune volunteers, encouraging further PvCS vaccine clinical development. Trial registration number NCT02083068. This trial was funded by Colciencias (grant 529-2009), NHLBI (grant RHL086488 A), and MVDC/CIV Foundation (grant 2014-1206).

C57BL/6 Mice Pretreated With Alpha-Tocopherol Show a Better Outcome of Trypanosoma cruzi Infection With Less Tissue Inflammation and Fibrosis.

Chagas disease is accompanied by a multisystem inflammatory disorder that follows Trypanosoma cruzi infection. Alpha-tocopherol has been described as an antioxidant and a potential adjuvant to enhance immune responses to vaccines. Therefore, we have evaluated the immune response to T. cruzi infection upon alpha-tocopherol pre-administration. The results show that administration of alpha-tocopherol before the infection results in lower parasitemia and lower mortality of C57BL/6 mice infected with the Tulahuen T. cruzi strain. Alpha-tocopherol administration in normal C57BL/6 mice resulted in higher levels of IFN-γ production by T and NK cells before and after the infection with T. cruzi. More importantly, previous administration of alpha-tocopherol increased the production of IL-10 by T and myeloid suppressor cells and the formation of effector memory T cells while decreasing the expression of PD-1 on T cells. These results suggest that alpha-tocopherol may limit the appearance of dysfunctional T cells during the acute and early chronic phases of T. cruzi infection, contributing to control infection. In addition, alpha-tocopherol could diminish tissue inflammation and fibrosis in late acute disease. These results strongly suggest that alpha-tocopherol may be a helpful agent to be considered in Chagas disease.

Antitrypanosomal activity of hydromethanol extract of leaves of Cymbopogon citratus and seeds of Lepidium sativum: in-vivo mice model.

BACKGROUND: Trypanosomiasis is one of the neglected tropical diseases of both humans and animals which decreases their productivity and causes death in the worst scenario. Unavailability of vaccines, the low therapeutic index of trypanocidal drugs, and the development of resistance lead to the need for research focused on developing alternative treatment options especially from medicinal plants. The present study was aimed to investigate antitrypanosomal activities of leaves of Cymbopogon citratus and seeds of Lepidium sativum in in-vivo mice model. METHODS: The plant extracts were prepared by maceration using 80% methanol and reconstituted with 10% dimethyl sulfoxide (DMSO) to have the desired concentration. The test doses were adjusted to 100, 200 and 400 mg/kg based on the toxicity profile. The plants extracts were administered to the respective groups of mice after the 12th day of field isolate T. congolense inoculation for seven consecutive days. The level of parasitemia, bodyweight, packed cell volume (PCV), and differential white blood cell counts were measured. RESULTS: The in -vivo test results revealed that both plant extracts had dose-dependent antitrypanosomal activity. Both crude extracts showed a significant reduction in parasite load (P < 0.05), increased or prevent the fall of PCV value (P < 0.05), decreased lymphocytosis and increased neutrophil counts (p < 0.05) and improved bodyweight but significant bodyweight increment (P < 0.05) was observed only in C. citratus treated mice compared to the negative and positive controls. CONCLUSION: The present study concluded that the crude extracts of leaves of C. citratus and seeds of L. sativum had antitrypanosomal effects. Both plants extracts reduced parasitemia level, prevented anemia and improved bodyweight of treated mice. Comparative results from all tested parameters showed that the best activities were observed with C. citratus treated groups of mice.

Annona muricata Linn and Khaya grandifoliola C.DC. Reduce Oxidative Stress In Vitro and Ameliorate Plasmodium berghei-Induced Parasitemia and Cytokines in BALB/c Mice.

BACKGROUND: Annona muricata and Khaya grandifoliola are ethnomedicinally used for the treatment of malaria and have been experimentally shown to have an anti-plasmodial effect, but the mechanisms involved are not fully understood. This study investigated the effect of the ethanol extracts of their leaves on parasitemia, radical scavenging and cytokines in Plasmodium berghei ANKA-infected BALB/c mice. METHODS: BALB/c mice were infected with P. berghei and treated with chloroquine, A. muricata or K. grandifoliola extract for 4 days. The percentage of parasitemia and the level of cytokine expression were determined after treatment. Trace element, phytochemical and nitric oxide (NO) scavenging activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging properties assays were done to study the antioxidant effects of AN and KG in vitro. RESULTS: P. berghei consistently increased parasitemia in BALB/c mice. The tested doses (100-, 200-, and 400 mg/kg) of A. muricata and K. grandifoliola attenuated the P. berghei-induced elevation of parasitemia and cytokines (TNF-α, IL-5, and IL-6) in vivo during the experimental period, though not as much as chloroquine. Moreover, both extracts scavenged the DPPH and NO radicals, though A. muricata had more anti-oxidant effect than K. grandifoliola in-vitro. CONCLUSION: The ethanol extracts of A. muricata and K. grandifoliola reduce parasitemia in P. berghei-treated mice BALB/c by scavenging free radicals and reducing cytokines, though the extracts were not as effective as chloroquine.

Delayed reduction of Anaplasma marginale parasitemia and packed cell volume normalization despite prolonged enrofloxacin treatment of cattle co-infected with Trypanosoma vivax.

Although co-infections of Trypanosoma vivax, Anaplasma spp., and Babesia spp. have been reported, knowledge gaps remain that need to be addressed. The present study evaluated the efficacy of enrofloxacin (7.5 mg/kg) against A. marginale in naturally infected cattle and cattle experimentally co-infected with T. vivax by observation of the variation in A. marginale parasitemia and packed cell volume (PCV) for 39 days. Bovines were distributed into two groups, each with six calves: T01 = animals immunosuppressed with dexamethasone and with latent anaplasmosis; T02 = animals immunosuppressed with dexamethasone, with latent anaplasmosis and experimentally co-infected with T. vivax on day 0 (D0). Animals of both groups were immunosuppressed with dexamethasone and received enrofloxacin (7.5 mg/kg) whenever mean values of parasitemia for A. marginale were ≥ 5% per group. Cattle of group T02 were also treated with isometamidium chloride (0.5 mg/kg) on D25. On D17 and D22 to D28 of the study, there was a higher (P ≤ 0.05) A. marginale parasitemia in animals of T02 than in those of T01. Animals of T01 required one enrofloxacin treatment to decrease A. marginale parasitemia, while those from T02 needed five treatments. From D5 to D37 of study, the mean values of PCV for calves from T02 were lower (P ≤ 0.05) than that for calves from T01. In conclusion, bovines co-infected T. vivax needed four more treatments with enrofloxacin to reduce A. marginale parasitemia and keep PCV values within reference standards.

In vivo antimalarial activity of a probiotic bacterium Lactobacillus sakei isolated from traditionally fermented milk in BALB/c mice infected with Plasmodium berghei ANKA.

ETHNOPHARMACOLOGICAL RELEVANCE: Milk production, processing and consumption are integral part of traditional practices in Fulani tribe of Cameroon. It has been observed that Fulani are resistant to malaria. Dairy products traditionally processed by Fulani are intensively used in the ritual treatment of malarial, inflammations and behavioural disorders. Many studies have demonstrated that fermented milk is a rich source of probiotic bacteria. However, the antimalarial activity of probiotics isolated from this natural source has not been experimentally tested. AIM OF THE STUDY: Hence, this study was therefore aimed at evaluating the antimalarial activity of a probiotic bacterium Lactobacillus sakei isolated from traditionally fermented milk in mice infected with chloroquine sensitive Plasmodium berghei ANKA. MATERIALS AND METHODS: The probiotic bacterium was isolated from the Cameroonian Mborro Fulani's traditionally fermented milk and identified using the 16S r RNA gene sequencing. The schizontocidal activity of Lactobacillus sakei on established malaria infection was evaluated. Eighty-four healthy young adult Balb/c mice infected with Plasmodium berghei parasite were randomly divided into two sets of seven group of six mice each, and were given three different doses of Lactobacillus sakei, chloroquine and sulfadoxine/pyrimethamine for seven and fourteen days respectively. The level of parasitaemia, body temperature, survival time and haematological parameters were evaluated. RESULTS: The parasite growth inhibition was observed to increase with increasing dose of probiotic bacterium with maximum suppression being 100 % at dose 3 on day 20. Also, the probiotic bacterium significantly prevented body weight loss and was associated with body temperature reduction and prevented (p<0.05) a decrease in haematological parameters compared to that untreated malaria infected mice. CONCLUSION: The results obtained suggest that Lactobacillus sakei is a probiotic bacterium with antimalarial activity in mice infected with chloroquine sensitive Plasmodium berghei.

Developmental stages influence in vivo antimalarial activity of aerial part extracts of Schkuhria pinnata.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria remains a dire health challenge, particularly in sub-Saharan Africa. In Uganda, it is the most ordinary condition in hospital admission and outpatient care. The country's meager health services compel malaria patients to use herbal remedies such as Schkuhria pinnata (Lam.) Kuntze ex Thell (Asteraceae). Although in vivo studies tested the antimalarial activity of S. pinnata extracts, plant developmental stages and their effect at different doses remain unknown. AIM OF THE STUDY: This study aims to determine the effect of the plant developmental stage on the antimalarial activity of S. pinnata in mice and to document the acute oral toxicity profile. METHODS: Seeds of S. pinnata were grown, and aerial parts of each developmental stage were harvested. Extraction was done by maceration in 70% methanol. The antimalarial activity was evaluated using chloroquine-sensitive Plasmodium berghei on swiss albino mice, in a chemosuppressive test, at 150, 350, and 700 mg/kg, p.o. Standard drugs used were artemether-lumefantrine (0.57 + 3.43) mg/kg and chloroquine (10 mg/kg) as positive controls. Distilled water at 1 mL/100g was used as a negative control. The Lorke method was adopted to determine the acute toxicity of extracts. RESULTS: The flowering stage extract had a maximum suppression of parasitemia at 700 mg/kg (68.83 ± 4.49%). Extract at other developmental stages also significantly suppressed the parasitemia (in the ascending order) fruiting (50.71 ± 1.87%), budding (54.92 ± 7.56%), vegetative (55.39 ± 2.01%) compared to the negative control (24.7 ± 2.7%), p < 0.05. Extracts from all developmental stages increased survival time, with the flowering stage having the highest survival time at 20.33 ± 0.88 days. All extracts had an LD50 of 2157 mg/kg, implying that extracts are safe at lower doses. CONCLUSION: Together, our findings revealed that the S. pinnata extracts at the flowering stage had superior antimalarial activity compared to other plant developmental stages. Extracts from all developmental stages have demonstrated a dose-dependent suppression of malarial parasites and increased survival time with an LD50 of 2157 mg/kg. Thus, for better antimalarial activity, local communities could consider harvesting S. pinnata at the flowering stage. Further studies are needed to isolate pure compounds from S. pinnata and determine their antimalarial activity.