Clinical and parasitological response to oral chloroquine and primaquine in uncomplicated human Plasmodium knowlesi infections

Background: Plasmodium knowlesi is a cause of symptomatic and potentially fatal infections in humans. There are no studies assessing the detailed parasitological response to treatment of knowlesi malaria infections in man and whether antimalarial resistance occurs. Methods: A prospective observational study of oral chloroquine and primaquine therapy was conducted in consecutive patients admitted to Kapit Hospital, Sarawak, Malaysian Borneo with PCR-confirmed single P. knowlesi infections. These patients were given oral chloroquine for three days, and at 24 hours oral primaquine was administered for two consecutive days, primarily as a gametocidal agent. Clinical and parasitological responses were recorded at 6-hourly intervals during the first 24 hours, daily until discharge and then weekly to day 28. Vivax malaria patients were studied as a comparator group. Results: Of 96 knowlesi malaria patients who met the study criteria, 73 were recruited to an assessment of the acute response to treatment and 60 completed follow-up over 28 days. On admission, the mean parasite stage distributions were 49.5%, 41.5%, 4.0% and 5.6% for early trophozoites, late trophozoites, schizonts and gametocytes respectively. The median fever clearance time was 26.5 [inter-quartile range 16-34] hours. The mean times to 50% (PCT50) and 90% (PCT90) parasite clearance were 3.1 (95% confidence intervals [CI] 2.8-3.4) hours and 10.3 (9.4-11.4) hours. These were more rapid than in a group of 23 patients with vivax malaria 6.3 (5.3-7.8) hours and 20.9 (17.6-25.9) hours; P = 0.02). It was difficult to assess the effect of primaquine on P. knowlesi parasites, due to the rapid anti-malarial properties of chloroquine and since primaquine was administered 24 hours after chloroquine. No P. knowlesi recrudescences or re-infections were detected by PCR. Conclusions: Chloroquine plus primaqine is an inexpensive and highly effective treatment for uncomplicated knowlesi malaria infections in humans and there is no evidence of drug resistance. Further studies using alternative anti-malarial drugs, including artemisinin derivatives, would be desirable to define optimal management strategies for P. knowlesi.Publisher PDFPeer reviewe

Plasmodium knowlesi Malaria in Malaysia

Plasmodium knowlesi, a simian malaria parasite, is now recognised as the fifth cause of human malaria and can lead to fatal infections in humans. Knowlesi malaria cases are widely distributed in East and West Malaysia and account for more than 50% of admissions for malaria in certain hospitals in the state of Sarawak. This paper will begin with a description of the early studies on P. knowlesi, followed by a review of the epidemiology, diagnosis, clinical and laboratory features, and treatment of knowlesi malaria

Training, experience, and perceptions of chest tube insertion by higher speciality trainees: implications for training, patient safety, and service delivery

Abstract Background Seldinger Chest Tube Insertion (CTI) is a high acuity low occurrence procedure and remains a core capability for UK physician higher speciality trainee’s (HST). A multitude of factors have emerged which may affect the opportunity of generalists to perform CTI. In view of which, this paper sought to establish the current experiences, attitudes, training, and knowledge of medical HST performing Seldinger CTI in acute care hospitals in the Peninsula deanery. Methods A Scoping review was performed to establish the UK medical HST experience of adult seldinger CTI. Synonymous terms for CTI training were searched across Cochrane, ERIC, Pubmed and British education index databases. Following which, a regional survey was constructed and completed by HST and pleural consultants from five hospitals within the Peninsula deanery between April–July 2022. Data collected included participants demographics, attitudes, training, experience, and clinical knowledge. Outcomes were collated and comparisons made across groups using SPSS. A p-value of &lt; 0.05 was defined as significant. Results The scoping review returned six papers. Salient findings included low self-reported procedural confidence levels, poor interventional selection for patient cases, inadequate site selection for CTI and 1 paper reported only 25% of respondents able to achieve 5–10 CTI annually. However, all papers were limited by including grades other than HST in their responses. The regional survey was completed by 87 HST (12 respiratory, 63 non-respiratory medical HST and 12 intensivists/anaesthetists HST). An additional seven questionnaires were completed by pleural consultants. Respiratory HSTs performed significantly more Seldinger CTI than general and ICM/anaesthetic registrars (p &lt; 0.05). The percentage of HST able to achieve a self-imposed annual CTI number were 81.8, 12.9 and 41.7% respectively. Self-reported transthoracic ultrasound competence was 100, 8 and 58% respectively (p &lt; 0.001). The approach to clinical management significantly differed with national guidance with pleural consultants showing an agreement of 89%, respiratory HST 75%, general HST 52% and ICM/anaesthetic HST 54% (p = 0.002). Conclusion Compared to respiratory trainees, non-respiratory trainees perform lower numbers of Seldinger CTI, with lower confidence levels, limited knowledge, and a reduced perceived relevance of the skill set. This represents a significant training and service challenge, with notable patient safety implications. </jats:sec

The Effect of Walnut (<i>Juglans regia</i>) Leaf Extract on Glycemic Control and Lipid Profile in Patients With Type 2 Diabetes Mellitus:A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Numerous clinical trials have examined the beneficial effects of Juglans regia leaf extract (JRLE) in patients with type 2 diabetes mellitus (T2DM); however, the results of these studies are inconsistent. Therefore, we conducted the current systematic review and meta-analysis to evaluate the effect of JRLE on glycemic control and lipid profile in T2DM patients. We searched online databases including PubMed, Scopus, EMBASE, and Web of Science for randomized controlled clinical trials that examined the effect of JRLE on glycemic and lipid indices in T2DM patients. Data were pooled using both fixed and random-effect models and weighted mean difference (WMD) was considered as the overall effect size. Of the total records, 4 eligible studies, with a total sample size of 195 subjects, were included. The meta-analysis revealed that JRLE supplementation significantly reduces fasting blood glucose (WMD, −18.04; 95% confidence interval [CI], −32.88 mg/dL, −3.21 mg/dL; p = 0.017) and significantly increases fasting insulin level (WMD, 1.93; 95% CI, 0.40 U/L, 3.45 U/L; p = 0.014). Although the overall effect of JRLE supplementation on hemoglobin A1c was not significant, a significant reduction was seen in studies with an intervention duration of > 8 weeks (WMD, −0.64; 95% CI, −1.16%, −0.11%; p = 0.018). Moreover, we also found no significant change in lipid parameters. Our findings revealed a beneficial effect of JRLE supplementation on glycemic indices in T2DM patients, but no significant improvement was found for lipid profile parameters

Unusual conductance collapse in one-dimensional quantum structures

We report an unusual insulating state in one-dimensional quantum wires with a non-uniform confinement potential. The wires consist of a series of closely spaced split gates in high mobility GaAs/AlGaAs heterostructures. At certain combinations of wire widths, the conductance abruptly drops over three orders of magnitude, to zero on a linear scale. Two types of collapse are observed, one occurring in multi-subband wires in zero magnetic field and one in single subband wires in an in-plane field. The conductance of the wire in the collapse region is thermally activated with an energy of the order of 1 K. At low temperatures, the conductance shows a steep rise beyond a threshold DC source-drain voltage of order 1 mV, indicative of a gap in the density of states. Magnetic depopulation measurements show a decrease in the carrier density with lowering temperature. We discuss these results in the context of many-body effects such as charge density waves and Wigner crystallization in quantum wires.Comment: 5 pages, 5 eps figures, revte

Efficient Surveillance of Plasmodium knowlesi Genetic Subpopulations, Malaysian Borneo, 2000-2018.

Population genetic analysis revealed that Plasmodium knowlesi infections in Malaysian Borneo are caused by 2 divergent parasites associated with long-tailed (cluster 1) and pig-tailed (cluster 2) macaques. Because the transmission ecology is likely to differ for each macaque species, we developed a simple genotyping PCR to efficiently distinguish between and survey the 2 parasite subpopulations. This assay confirmed differences in the relative proportions in areas of Kapit division of Sarawak state, consistent with multilocus microsatellite analyses. Analyses of 1,204 human infections at Kapit Hospital showed that cluster 1 caused approximately two thirds of cases with no significant temporal changes from 2000 to 2018. We observed an apparent increase in overall numbers in the most recent 2 years studied, driven mainly by increased cluster 1 parasite infections. Continued monitoring of the frequency of different parasite subpopulations and correlation with environmental alterations are necessary to determine whether the epidemiology will change substantially

Anti-Inflammatory Cytokines Predominate in Acute Human Plasmodium knowlesi Infections

Plasmodium knowlesi has entered the human population of Southeast Asia. Naturally acquired knowlesi malaria is newly described with relatively little available data, including data on the host response to infection. Therefore pre-treatment cytokine and chemokine profiles were determined for 94 P. knowlesi, and for comparison, 20, P. vivax and 22 P. falciparum, patients recruited in Malaysian Borneo. Nine, five and one patient with P. knowlesi, P. falciparum and P. vivax respectively had complicated malaria as defined by World Health Organisation. Patients with uncomplicated P. knowlesi had lower levels of the pro-inflammatory cytokines IL-8 and TNFα than those with complicated disease (both p<0.05, Dunn's post test, DPT). The anti-inflammatory cytokines IL-1ra and IL-10 were detected in all patients in the study. IL-1ra, the most abundant cytokine measured, correlated with parasitaemia in P. knowlesi (rs = 0.47, p =  <0.0001), P. vivax (rs = 0.61, p = 0.0042) and P. falciparum (rs = 0.57,p = 0.0054) malaria. IL-10 correlated with parasitaemia in both P. knowlesi (rs = 0.54, p =  <0.0001) and P. vivax (rs = 0.78, p =  <0.0001) infections. There were between group differences in soluble markers of macrophage activation (MIP-1β and MCP-1). P. knowlesi patients had significantly lower levels of MIP-1β than P. falciparum (DPT, p =  <0.01). Uncomplicated P. knowlesi patients had significantly lower levels of MCP-1 than uncomplicated P. falciparum patients (DPT, p =  <0.001). There was no significant difference between complicated and uncomplicated P. knowlesi infections. MCP-1, MIP-1β, IL-8 and TNFα increased in complicated P. knowlesi but decreased in complicated P. falciparum infections. Descriptions of human knowlesi malaria provide a comparative means to discover mediators of pathophysiology in severe P. knowlesi as well as P. falciparum malaria. Crucially, P. knowlesi may be the disease and experimental primate model for severe malaria