Management of malaria with acute renal failure

This article has no abstract

Suppression of Plasmodium falciparum by serum collected from a case of Plasmodium vivax infection.

BACKGROUND: It has frequently been reported that Plasmodium vivax suppressed Plasmodium falciparum and ameliorated disease severity in patients infected with these two species simultaneously. The authors investigate the hypothesis that immunological responses stimulated by P. vivax may play a role in suppressing co-infecting P. falciparum. METHODS: Sera, taken sequentially from one of the authors (YN) during experimental infection with P. vivax, were added to in vitro cultures of P. falciparum. Cross-reactive antibodies against P. falciparum antigens, and cytokines were measured in the sera. RESULTS: Significant growth inhibitory effects upon P. falciparum cultures (maximally 68% inhibition as compared to pre-illness average) were observed in the sera collected during an acute episode. Such inhibitory effects showed a strong positive temporal correlation with cross-reactive antibodies, especially IgM against P. falciparum schizont extract and, to a lesser degree, IgM against Merozoite Surface Protein (MSP)-119. Interleukin (IL)-12 showed the highest temporal correlation with P. vivax parasitaemia and with body temperatures in the volunteer. CONCLUSION: These results suggest the involvement by cross-reactive antibodies, especially IgM, in the interplay between plasmodial species. IL-12 may be one of direct mediators of fever induction by rupturing P. vivax schizonts, at least in some subjects. Future studies, preferably of epidemiological design, to reveal the association between cross-reactive IgM and cross-plasmodial interaction, are warranted

Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>The efficacy of anti-malarial drugs is determined by the level of parasite susceptibility, anti-malarial drug bioavailability and pharmacokinetics, and host factors including immunity. Host immunity improves the <it>in vivo </it>therapeutic efficacy of anti-malarial drugs, but the mechanism and magnitude of this effect has not been characterized. This study characterized the effects of 'immune' plasma to <it>Plasmodium falciparum</it>on the <it>in vitro </it>susceptibility of <it>P. falciparum </it>to anti-malarial drugs.</p> <p>Methods</p> <p>Titres of antibodies against blood stage antigens (mainly the ring-infected erythrocyte surface antigen [RESA]) were measured in plasma samples obtained from Thai patients with acute falciparum malaria. 'Immune' plasma was selected and its effects on <it>in vitro </it>parasite growth and multiplication of the Thai <it>P. falciparum </it>laboratory strain TM267 were assessed by light microscopy. The <it>in vitro </it>susceptibility to quinine and artesunate was then determined in the presence and absence of 'immune' plasma using the ³H-hypoxanthine uptake inhibition method. Drug susceptibility was expressed as the concentrations causing 50% and 90% inhibition (IC₅₀and IC₉₀), of ³H-hypoxanthine uptake.</p> <p>Results</p> <p>Incubation with 'immune' plasma reduced parasite maturation and decreased parasite multiplication in a dose dependent manner. ³H-hypoxanthine incorporation after incubation with 'immune' plasma was decreased significantly compared to controls (median [range]; 181.5 [0 to 3,269] cpm versus 1,222.5 [388 to 5,932] cpm) (<it>p</it>= 0.001). As a result 'immune' plasma reduced apparent susceptibility to quinine substantially; median (range) IC₅₀6.4 (0.5 to 23.8) ng/ml versus 221.5 (174.4 to 250.4) ng/ml (<it>p </it>= 0.02), and also had a borderline effect on artesunate susceptibility; IC₅₀0.2 (0.02 to 0.3) ng/ml versus 0.8 (0.2 to 2.3) ng/ml (<it>p </it>= 0.08). Effects were greatest at low concentrations, changing the shape of the concentration-effect relationship. IC₉₀values were not significantly affected; median (range) IC₉₀448.0 (65 to > 500) ng/ml versus 368.8 (261 to 501) ng/ml for quinine (<it>p </it>> 0.05) and 17.0 (0.1 to 29.5) ng/ml versus 7.6 (2.3 to 19.5) ng/ml for artesunate (<it>p </it>= 0.4).</p> <p>Conclusions</p> <p>'Immune' plasma containing anti-malarial antibodies inhibits parasite development and multiplication and increases apparent <it>in vitro </it>anti-malarial drug susceptibility of <it>P. falciparum</it>. The IC₉₀was much less affected than the IC₅₀measurement.</p

RECRUDESCENCE IN ARTESUNATE-TREATED PATIENTS WITH FALCIPARUM MALARIA IS DEPENDENT ON PARASITE BURDEN NOT ON PARASITE FACTORS

Artemisinin derivatives are first-line antimalarial drugs in Thailand. No firm evidence of clinically relevant artemisinin resistance exists. When used as monotherapy, artesunate has been associated with a high treatment failure (recrudescence) rate, which could be due to low-level artemisinin resistance. To understand the causes of recrudescence, we retrospectively studied a cohort of 104 malaria patients treated with artesunate monotherapy, 32 of whom recrudesced. There was no difference in in vitro artesunate sensitivities between 6 nonrecrudescent isolates and 16 paired admission and recrudescent isolates. Paired admission and recrudescent isolates from 10 patients were genotyped; only 3 had pfmdr1 mutations. Patients with admission parasitemias >10,000 per µl had a 9-fold higher likelihood of recrudescence (adjusted odds ratio) compared with patients with lower parasitemias. This study suggests (1) recrudescence after treatment with artesunate is not the result of inherent parasite resistance, and (2) admission parasitemia may be useful in choosing therapeutic options

Antibacterial, antibiofilm, and anti-adhesion activities of Piper betle leaf extract against Avian pathogenic Escherichia coli

Piper betle leaves have traditionally been used to treat many diseases, including bacterial infections. The present studyaimed to investigate the antibacterial, antibiofilm, and anti-adhesion activities of P. betle extract against avian pathogenicEscherichia coli (APEC). The ethanol extract of P. betle leaves demonstrated strong antibacterial activity against clinicalisolates of APEC with MIC and MBC values ranging from 0.5 to 1.0 mg/mL as compared with 1% DMSO, a negative control.Disruption and breakdown of the bacterial cells were detected when the cells were challenged with the extract at 2 × MIC.Bacterial cells treated with the extract demonstrated longer cells without a septum, compared to the control. The extract at1/8, 1/4, and 1/2× MIC significantly inhibited the formation of the bacterial biofilm of all the tested isolates except the iso-late CH10 (P < 0.05) without inhibiting growth. At 1/2 × MIC, 55% of the biofilm inhibition was detected in APEC CH09,a strong biofilm producer. At 32 × MIC, 88% of the inhibition of viable cells embedded in the mature biofilm was detectedin APEC CH09. Reduction in the bacterial adhesion to surfaces was shown when APEC were treated with sub-MICs of theextract as observed by SEM. Hydroxychavicol was found to be the major compound presented in the leaf extract as detectedby GC–MS analysis. The information suggested potential medicinal benefits of P. betle extract to inhibit the growth, biofilm,and adhesion of avian pathogenic E. coli.publishe

Vascular endothelial cells cultured from patients with cerebral or uncomplicated malaria exhibit differential reactivity to TNF

Plasmodium falciparum malaria is a major cause of morbidity and mortality in African children, and factors that determine the development of uncomplicated (UM) versus cerebral malaria (CM) are not fully understood. We studied the ex vivo responsiveness of microvascular endothelial cells to pro-inflammatory stimulation and compared the findings between CM and UM patients. In patients with fatal disease we compared the properties of vascular endothelial cells cultured from brain tissue to those cultured from subcutaneous tissue, and found them to be very similar. We then isolated, purified and cultured primary endothelial cells from aspirated subcutaneous tissue of patients with CM (ECCM) or UM (ECUM) and confirmed the identity of the cells before analysis. Upon TNF stimulation in vitro, ECCM displayed a significantly higher capacity to upregulate ICAM-1, VCAM-1 and CD61 and to produce IL-6 and MCP-1 but not RANTES compared with ECUM. The shedding of endothelial microparticles, a recently described parameter of severity in CM, and the cellular level of activated caspase-3 were both significantly greater in ECCM than in ECUM. These data suggest that inter-individual differences in the endothelial inflammatory response to TNF may be an additional factor influencing the clinical course of malaria

Microbiomics for enhancing electron transfer in an electrochemical system

In microbial electrochemical systems, microorganisms catalyze chemical reactions converting chemical energy present in organic and inorganic molecules into electrical energy. The concept of microbial electrochemistry has been gaining tremendous attention for the past two decades, mainly due to its numerous applications. This technology offers a wide range of applications in areas such as the environment, industries, and sensors. The biocatalysts governing the reactions could be cell secretion, cell component, or a whole cell. The electroactive bacteria can interact with insoluble materials such as electrodes for exchanging electrons through colonization and biofilm formation. Though biofilm formation is one of the major modes for extracellular electron transfer with the electrode, there are other few mechanisms through which the process can occur. Apart from biofilm formation electron exchange can take place through flavins, cytochromes, cell surface appendages, and other metabolites. The present article targets the various mechanisms of electron exchange for microbiome-induced electron transfer activity, proteins, and secretory molecules involved in the electron transfer. This review also focuses on various proteomics and genetics strategies implemented and developed to enhance the exo-electron transfer process in electroactive bacteria. Recent progress and reports on synthetic biology and genetic engineering in exploring the direct and indirect electron transfer phenomenon have also been emphasized

The Role of Medicinal and Aromatic Plants against Obesity and Arthritis: A Review

Obesity is a significant health concern, as it causes a massive cascade of chronic inflammations and multiple morbidities. Rheumatoid arthritis and osteoarthritis are chronic inflammatory conditions and often manifest as comorbidities of obesity. Adipose tissues serve as a reservoir of energy as well as releasing several inflammatory cytokines (including IL-6, IFN-γ, and TNF-α) that stimulate low-grade chronic inflammatory conditions such as rheumatoid arthritis, osteoarthritis, diabetes, hypertension, cardiovascular disorders, fatty liver disease, oxidative stress, and chronic kidney diseases. Dietary intake, low physical activity, unhealthy lifestyle, smoking, alcohol consumption, and genetic and environmental factors can influence obesity and arthritis. Current arthritis management using modern medicines produces various adverse reactions. Medicinal plants have been a significant part of traditional medicine, and various plants and phytochemicals have shown effectiveness against arthritis and obesity; however, scientifically, this traditional plant-based treatment option needs validation through proper clinical trials and toxicity tests. In addition, essential oils obtained from aromatic plants are being widely used as for complementary therapy (e.g., aromatherapy, smelling, spicing, and consumption with food) against arthritis and obesity; scientific evidence is necessary to support their effectiveness. This review is an attempt to understand the pathophysiological connections between obesity and arthritis, and describes treatment options derived from medicinal, spice, and aromatic plants

Fitness Trade-Offs in the Evolution of Dihydrofolate Reductase and Drug Resistance in Plasmodium falciparum

Background: Patterns of emerging drug resistance reflect the underlying adaptive landscapes for specific drugs. In Plasmodium falciparum, the parasite that causes the most serious form of malaria, antifolate drugs inhibit the function of essential enzymes in the folate pathway. However, a handful of mutations in the gene coding for one such enzyme, dihydrofolate reductase, confer drug resistance. Understanding how evolution proceeds from drug susceptibility to drug resistance is critical if new antifolate treatments are to have sustained usefulness. Methodology/Principal Findings: We use a transgenic yeast expression system to build on previous studies that described the adaptive landscape for the antifolate drug pyrimethamine, and we describe the most likely evolutionary trajectories for the evolution of drug resistance to the antifolate chlorcycloguanil. We find that the adaptive landscape for chlorcycloguanil is multi-peaked, not all highly resistant alleles are equally accessible by evolution, and there are both commonalities and differences in adaptive landscapes for chlorcycloguanil and pyrimethamine. Conclusions/Significance: Our findings suggest that cross-resistance between drugs targeting the same enzyme reflect the fitness landscapes associated with each particular drug and the position of the genotype on both landscapes. The possibl