Cerebral malaria: a lethal complication of a common tropical infection

Cerebral malaria (CM) represents a deadly neurological complication associated with Plasmodium falciparum infection. It is defined as an unarousable coma or a deep level of unconsciousness in the presence of a P. falciparum parasitemia, the diagnosis confirmed after exclusion of other common causes of coma such as hypoglycemia, septicemia, metabolic derangements and bacterial and viral meningitis/encephalopathies. Mortality is high and some surviving patients sustain neuronal injury which manifests as long-term neuro-cognitive impairments. Microscopy of Giemsa-stained blood smears remains the gold standard for confirmation of malaria diagnosis. The purpose of this review was to summarize the updated knowledge on the disease, its presentation, complications and neurological sequelae and the presently available newer and experimental adjuvant therapies. For this review, a PubMed search was conducted for articles and case reports from 1968 to 2020 containing the keywords cerebral malaria, P. falciparum, neurological impairment, neurocognitive defects and artesunate combination therapy. The treatment includes specific antimalarial therapy, supportive therapy for multi-organ dysfunction and management of associated complications. Prompt and rapid stabilization of the patient, adequate fluid supplementation and correction of electrolyte imbalance remain the most vital supplementary interventions in these cases, along with early induction of primary parenteral antimalarial therapy in the form of artemisinin based combination therapy (ACT) or quinine. Neurological sequelae including seizures are frequently observed in many treated and recovered cases, with some patients having to endure long term neurocognitive defects.

Adverse reaction to Coartem (artemether/lumefantrine) resulting in oculogyric crisis

Background Artemether/lumefantrine (AL), sold under the brand name Coartem, is the most common artemisinin-based combination therapy for the treatment of malaria. Drug-induced oculogyric crisis is a neurological disorder characterized by frequent upward deviations of the eye. In the literature, no cases of Coartem-induced oculogyric crisis have been reported in Ghana. Case presentation A 19-year-old male patient, who presented fever measuring 37.9 °C, general body pains, and weakness was prescribed with antimalarial therapy artemether/lumefantrine, Coartem®, from a local pharmacy. Just after initiation of treatment, the patient complained of double vision, involuntary upward eye deviation, and inability to close both eyes. The patient was diagnosed with Coartem-induced oculogyric crisis and was treated with the cessation of the causing agent and intramuscular injection of promethazine hydrochloride. Conclusions When a patient exhibits a neurological disorder, such as oculogyric crisis, with normal conscious state and normal vital signs, special attention should be given to obtaining a history of recently administered medications. Clinicians should recognize adverse reactions to drugs based on a thorough patient history and examination. The goal of this report was to present Coartem-induced oculogyric crisis.

In vitro analyses of Artemisia extracts on Plasmodium falciparum suggest a complex antimalarial effect

Dried-leaf Artemisia annua L. (DLA) antimalarial therapy was shown effective in prior animal and human studies, but little is known about its mechanism of action. Here IC50s and ring-stage assays (RSAs) were used to compare extracts of A. annua (DLAe) to artemisinin (ART) and its derivatives in their ability to inhibit and kill Plasmodium falciparum strains 3D7, MRA1252, MRA1240, Cam3.11 and Cam3.11rev in vitro. Strains were sorbitol and Percoll synchronized to enrich for ring-stage parasites that were treated with hot water, methanol and dichloromethane extracts of DLA, artemisinin, CoArtem™, and dihydroartemisinin. Extracts of A. afra SEN were also tested. There was a correlation between ART concentration and inhibition of parasite growth. Although at 6 hr drug incubation, the RSAs for Cam3.11rev showed DLA and ART were less effective than high dose CoArtem™, 8 and 24 hr incubations yielded equivalent antiparasitic results. For Cam3.11, drug incubation time had no effect. DLAe was more effective on resistant MRA-1240 than on the sensitive MRA-1252 strain. Because results were not as robust as observed in animal and human studies, a host interaction was suspected, so sera collected from adult and pediatric Kenyan malaria patients was used in RSA inhibition experiments and compared to sera from adults naïve to the disease. The sera from both age groups of malaria patients inhibited parasite growth ≥ 70% after treatment with DLAe and compared to malaria naïve subjects suggesting some host interaction with DLA. The discrepancy between these data and in-vivo reports suggested that DLA’s effects require an interaction with the host to unlock their potential as an antimalarial therapy. Although we showed there are serum-based host effects that can kill up to 95% of parasites in vitro, it remains unclear how or if they play a role in vivo. These results further our understanding of how DLAe works against the malaria parasite in vitro.

Synthesis of Nanostructured Lipid Carriers Loaded Chitosan/ Carbopol Hybrid Nanocomposite Gel for Oral Delivery of Artemether and Curcumin

Background: Antimalarial therapy remains the utmost effective means for the management of malarial parasites in the liver and red blood cells. The application of these therapeutic agents is hampered by their improper application, hepato-toxicity caused by their continuous use, and degradation by hepatic enzymes. Methods: Recent advancements in drug delivery applications have shown potential in improving the pharmacological properties of artemether. Nanostructured lipid carriers (NLCs) loaded chitosan (CH)/Carbopol (CB) hybrid gel was prepared using glycerol monostearate (GMS) as solid lipid and clove oil as a liquid lipid for artemether (ART) and curcumin (CR) for its localized effect on the liver. Results: The smaller particle size (~118 ± 1.0 nm) and high zeta potential (- 41.1 ± 6.46 mV) confirm the formulation and stability of NLCs. On the other hand, the shape and morphology of prepared NLCs and gel showed a spherical and wrinkled surface with a size range of 150-250 nm. The release studies of the NLC’s showed a controlled release of artemether (~ 92%) and curcumin (~ 83%) for up to 30 h. Photostability data showed that, approximately, ~86.5 ± 0.3% and ~60 ± 0.9% of nanoencapsulated artemether and curcumin were still detected on exposure to sunlight, respectively. It has been found from the permeation study that 69.8% and 49.1% of the drug was permeated across the mucus membrane in 24 h with a significant increase (P < 0.05) in flux as well as permeability coefficients. Conclusion: The overall results showed that prepared CH/CB/NLCs hybrid gel could be a promising vehicle for the effective delivery of ART and CR for the management of malarial parasites. Lay Summary: Antimalarial therapy remains the utmost effective means for the management of malarial parasites in liver and red blood cells. Recent advancements in drug delivery applications have shown potential in improving the pharmacological properties of artemether. Application of these therapeutic agents hampered by their improper application, hepato-toxicity caused by their continuous use and degradation by hepatic enzymes. To manage the above issues, we synthesize nanostructured lipid carriers (NLC’s) loaded chitosan (CH)/Carbopol (CB) hybrid gel using glycerol monostearate (GMS) as solid lipid and clove oil as liquid lipid for artemether (ATR) and curcumin (CR) for its local action in liver and the major criteria were to find a protective barrier with hepatoprotective nature of the curcumin.

A STUDY ON LEVELS OF CHOLINESTERASE IN PLEURAL FLUIDS OF DIVERSE ETIOLOGIES

Introduction: Acetylcholinesterase , also known as true, specific, type I cholinesterase or RBC cholinesterase: It is found in nervous tissue, erythrocytes, lungs, spleen and grey matter. It is decreased in pernicious anaemia and after antimalarial therapy. Methodology: Patients participating in the study were explained about the procedure, technique and complications of pleural fluid aspiration. Pleural fluid aspiration was performed under strict aseptic precautions after analysing the fluid levels by percussion and chest x-rays. In few of the cases, ultrasonography-guided pleural fluid aspiration was performed. Results: The mean values of pleural fluid cholinesterase levels were 806.26 + 516.28 U/L in the transudates group and 3476.11 + 1250.17 U/L in the exudates group. The normal levels of cholinesterase varies between laboratories. The cut-off value is 1/10th of the upper limit of normal level of cholinesterase in the respective laboratory. Conclusion: In this study Light’s criteria had a sensitivity of 91.9% and specificity of 87.3% in comparison to pleural fluid to serum cholinesterase ratio that had a sensitivity of 96.8% and specificity of 95.2%.

Oral manifestations associated with antimalarial therapy in patients with systemic lupus erythematosus

Introduction Lupus erythematosus (LE) is an autoimmune disease often treated with antimalarial drugs. The prolonged use of chloroquine and hydroxychloroquine can cause hyperpigmentation in the skin, oral mucosa and retinal pigment epithelium, which in turn can trigger toxicity in this epithelium, which in some cases causes vision loss. The objective of the present work was to establish the association between the presence of oral pigmented macules by antimalarial and secondary retinal toxicity. Methods A total of 105 patients diagnosed with LE being treated with chloroquine/hydroxychloroquine were evaluated. All patients were ophthalmologically evaluated for retinopathy screening. When the patient showed oral hyperpigmented maculae, an incisional biopsy was performed with the corresponding histopathological study with informed consent. The variables were compared using the chi-square test for quantitative variables and the non-parametric Mann–Whitney U-test for categorical variables. The confidence level was established at 95%, and p-values of ≤0.005 were considered statistically significant. Results Only 9.5% of the patients showed oral brown spots. Histopathologically, 100% of the oral macules showed characteristics of oral pigmentation by drug and 100% ophthalmological parameters of normality. Two patients presented with a diagnosis of pre-retinopathy, but none showed oral lesions. Conclusion Hyperpigmented macules in the buccal mucosa in lupus patients receiving antimalarial treatment are not frequent and do not represent a predictive finding of toxicity of the drug.