Delayed Parasite Clearance Rates and Low Clinical and Parasitological Responses Following Treatment of Uncomplicated Falciparum Malaria With Artemether-lumefantrine in Ethiopian- Sudan Border, Western Ethiopia

BackgroundThe appearance of artemisinin-resistant parasites in Africa is catastrophic as many cases and deaths from malaria are usually reported in the continent. This study was the first to evaluate the status of artemether-lumefantrine (AL) efficacy, seventeen years after the introduction of this drug in the study area. This study aimed to assess PCR- corrected clinical and parasitological responses at 28 days following AL treatment.MethodsSixty uncomplicated falciparum malaria patients were enrolled, treated with standard doses of AL, and monitored for 28 days with clinical and parasitological assessments from September 15 to December 15, 2020. Molecular analysis was done on dried blood spots collected from each patient from day 0 and on follow-up days 1, 2, 3, 7, 14, 21, and 28. Descriptive statistics and binary logistic regressions were done using SPSS 20.0 statistical software. A p-value of less or equal to 0.05 was considered significant.ResultsSixty patients enrolled in the study, ten were lost to follow-up; and the results were analyzed for 50 patients. All of the patients were fever-free on day 3. But, two patients febrile on day 1 became febrile on day 7 of the follow-up period. Day 3 parasites positivity rate was zero and 60 % using microscopy and PCR, respectively. Parasite clearance on day 3 was more among patients ≥ 15 years as compared with < 15 years (AOR= 6.71, P=0.021). 14 of 50 patients tested were parasite positive on day 7 by PCR. In addition, 7 patients had persisted parasitemia by PCR from day 0 to day 28 of the follow-up. The PCR-corrected adequate clinical and parasitological response (ACPR) rate was 59.2 %. PCR adjusted AL treatment failures was 40.8% and it was noted as 0 early treatment failure, 10.2% late clinical failures, and 30.6% late parasitological failures. Recrudescence and new infection rate within 28 days was7/50(14%) and1/50 (2%) respectively.Conclusionartemisinin resistance is suspected in the study area as parasite positivity rate on day 3 was greater than 10%. A slow parasitological clearance was followed by low-density parasitemia persistence and recrudescences. AL treatment failure was greater than the 10% threshold for treatments in use as per WHO. These findings suggest probably a decreased sensitivity of the parasite for the artemisinin component and the partner drug and highlight the need for prompt reassessment of the efficacy of AL and other factors that may contribute to low parasite susceptibility to the drug.

Complications and dosing frequency of 5% imiquimod for genital warts in a young man

A clinical decision report using: Fife KH, Ferenczy A, Douglas JM Jr, et al. Treatment of external genital warts in men using 5% imiquimod cream applied three times a week, once daily, twice daily, or three times a day. Sex Transm Dis. 2001;28(4):226-231. https://doi.org/10.1097/00007435-200104000-00007 for a patient with genital warts and an unstable social support network.

Cultivar Differences in the Biochemical and Physiological Responses of Common Beans to Aluminum Stress

Soil conditions leading to high levels of available aluminum are detrimental to plant growth, but data are limited on genotypic differences in tolerance to aluminum stress in some crops. The aim of this study was to examine the morphological, biochemical, and physiological changes in roots and shoots of 25 common bean (Phaseolus vulgaris L.) cultivars (Pinto market class) under aluminum (Al) treatment. Additionally, this study aimed to assess the range of responses amongst the common bean cultivars relative to their Al toxicity tolerance and sensitivity. Plants were grown hydroponically using a simplified nutrient solution with or without 20 µM AlCl3. Reactive oxygen species (ROS), activities of the antioxidant enzymes superoxide dismutase (SOD) and guaiacol peroxidase (POD), and malondialdehyde (MDA) concentration, an indicator of lipid peroxidation, were measured to establish the effects of Al treatment on the plants. In addition, growth parameters such as shoot and root dry weight, root-to-shoot ratio, root elongation, and root volume changes were also investigated. The cultivar effect was significant for all the measured parameters, except for shoot dry weight. Inhibition of the root and shoot dry weight for selected common bean cultivars shows that the response of common bean to Al stress is genotype-specific. Additionally, Al-induced root elongation inhibition and root volume changes varied among the cultivars. Most cultivars had significantly higher SOD activity (20 of 25 cultivars) and POD activity (12 cultivars) under AlCl3 treatment compared to the controls. A positive significant correlation was observed between MDA and ROS, showing that Al stress induced the accumulation of ROS along with an increase in lipid peroxidation. According to the results of this study, Arapaho and AC Island cultivars could potentially be used in the future production of common beans under Al stress. Therefore, these two cultivars could also be included in Al tolerance breeding programs.

Quantitative and qualitative feed restriction for broilers

The objective of this study is to evaluate the influence of five feed restriction programs (FRP) on broiler performance and carcass yield. 425 Cobb 500® broilers were distributed in a completely randomized design with five FRPs and five replicates with 17 broilers. The FRPs were: Program 1 (P1): consumption ad libitum (AL) of control diet from 14 to 42 days; P2: quantitative restriction (QTR) of 10% of AL consumption from 14 to 28 days and AL consumption from 29 to 42 days; P3: AL consumption from 14 to 28 days and QTR from 29 to 42 days; P4: qualitative restriction (QLR) of 10% of the level of crude protein and essential amino acids from 14 to 28 days and AL consumption from 29 to 42 days; and P5: AL consumption from 14 to 28 days and QLR from 29 to 42 days. The broilers of the AL treatment gained more weight (p≤0.01), but had a similar FCR (P>0.05) compared to broilers submitted to QTR from 29 to 42 days. In addition, broilers fed QTR from 14 to 28 days presented a lower FI and a better FCR (p≤0.01) in relation to broilers fed QLR of 14 to 28 (P4) and 29 to 42 days (P5). The broilers fed QTR of 14 to 28 days diet presented a similar FCR as broilers fed AL. The 10% reduction in AL consumption of 14 to 28 d is a viable economical alternative to feed broilers up to 42 days of age.

Artemisinin-based combination therapy for uncomplicated Plasmodium falciparum malaria in Mali: a systematic review and meta-analysis

Background Artemisinin-based combination therapy (ACT) was deployed in 2005 as an alternative to chloroquine and is considered the most efficacious treatment currently available for uncomplicated falciparum malaria. While widespread artemisinin resistance has not been reported to date in Africa, recent studies have reported partial resistance in Rwanda. The purpose of this study is to provide a current systematic review and meta-analysis on ACT at Mali study sites, where falciparum malaria is highly endemic. Methods A systematic review of the literature maintained in the bibliographic databases accessible through the PubMed, ScienceDirect and Web of Science search engines was performed to identify research studies on ACT occurring at Mali study sites. Selected studies included trials occurring at Mali study sites with reported polymerase chain reaction (PCR)-corrected adequate clinical and parasite response rates (ACPRcs) at 28 days. Data were stratified by treatment arm (artemether–lumefantrine (AL), the first-line treatment for falciparum malaria in Mali and non-AL arms) and analysed using random-effects, meta-analysis approaches. Results A total of 11 studies met the inclusion criteria, and a risk of bias assessment carried out by two independent reviewers determined low risk of bias among all assessed criteria. The ACPRc for the first-line AL at Mali sites was 99.0% (95% CI (98.3%, 99.8%)), while the ACPRc among non-AL treatment arms was 98.9% (95% CI (98.3%, 99.5%)). The difference in ACPRcs between non-AL treatment arms and AL treatment arms was not statistically significant (p = .752), suggesting that there are potential treatment alternatives beyond the first-line of AL in Mali. Conclusions ACT remains highly efficacious in treating uncomplicated falciparum malaria in Mali. Country-specific meta-analyses on ACT are needed on an ongoing basis for monitoring and evaluating drug efficacy patterns to guide local malaria treatment policies, particularly in the wake of observed artemisinin resistance in Southeast Asia and partial resistance in Rwanda.

Effects of Calcium and Aluminum on Particle Settling in an Oil Sands End Pit Lake

Surface mining of oil sands ore in Alberta, Canada has generated fluid fine tailings (FFT) that must be reclaimed. End pit lakes (EPLs), which consist of thick deposits of FFT capped with water, have been proposed for FFT reclamation, and Base Mine Lake (BML) is the first full-scale demonstration EPL. However, FFT particle settling and resuspension contributes to high turbidity in the BML water cap, which may be detrimental to the development of an aquatic ecosystem. This study investigated the effect of Ca and Al treatments on turbidity mitigation. The initial turbidity was reduced from 20 NTU to less than 2 NTU in BML surface water treated with 54 mg/L of Ca or 1.1 mg/L of Al. At a concentration of 1.1 mg/L, Al reduced the initial turbidity to a greater extent, and in a shorter time, than 54 mg/L of Ca. Further, resuspended Al-treated FFT particles were 100–700 nm larger in diameter, and thus resettled faster than the resuspended untreated or Ca-treated FFT particles. The final turbidity values 21 days after resuspension of untreated and 1.7 mg/L Al-treated FFT particles in fresh BML surface water were 20.5 NTU and 2.5 NTU, respectively. Thus, Al treatment may be effective in mitigating turbidity in BML through both Al-induced coagulation and self-weight settling of the resuspended Al-treated FFT particles.

Opportunities and Challenges for Gut Microbiota in Acute Leukemia

Acute leukemia (AL) is a highly heterogeneous hematologic malignancy, and although great progress has been made in the treatment of AL with allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and new targeted drugs, problems such as infection and GVHD in AL treatment are still serious. How to reduce the incidence of AL, improve its prognosis and reduce the side effects of treatment is a crucial issue. The gut microbiota plays an important role in regulating disease progression, pathogen colonization, and immune responses. This article reviews recent advances in the gut microbiota and AL pathogenesis, infection, treatment and its role in allo-HSCT.

Therapeutic efficacy of artesunate-amodiaquine and artemether-lumefantrine and polymorphism in Plasmodium falciparum kelch13-propeller gene in Equatorial Guinea

Background Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the currently recommended first- and second-line therapies for uncomplicated Plasmodium falciparum infections in Equatorial Guinea. This study was designed to evaluate the efficacy of these artemisinin-based combinations and detect mutations in P. falciparum kelch13-propeller domain gene (Pfkelch13). Methods A single-arm prospective study evaluating the efficacy of ASAQ and AL at three sites: Malabo, Bata and Ebebiyin was conducted between August 2017 and July 2018. Febrile children aged six months to 10 years with confirmed uncomplicated P. falciparum infection and other inclusion criteria were sequentially enrolled first in ASAQ and then in AL at each site, and followed up for 28 days. Clinical and parasitological parameters were assessed. The primary endpoint was PCR-adjusted adequate clinical and parasitological response (ACPR). Samples on day-0 were analysed for mutations in Pfkelch13 gene. Results A total 264 and 226 patients were enrolled in the ASAQ and AL treatment groups, respectively. Based on per-protocol analysis, PCR-adjusted cure rates of 98.6% to 100% and 92.4% to 100% were observed in patients treated with ASAQ and AL, respectively. All study children in both treatment groups were free of parasitaemia by day-3. Of the 476 samples with interpretable results, only three samples carried non-synonymous Pfkelch13 mutations (E433D and A578S), and none of them is the known markers associated with artemisinin resistance. Conclusion The study confirmed high efficacy of ASAQ and AL for the treatment of uncomplicated falciparum infections as well as the absence of delayed parasite clearance and Pfkelch13 mutations associated with artemisinin resistance. Continued monitoring of the efficacy of these artemisinin-based combinations, at least every two years, along with molecular markers associated with artemisinin and partner drug resistance is imperative to inform national malaria treatment policy and detect resistant parasites early. Trial registration ACTRN12617000456358, Registered 28 March 2017; http://www.anzctr.org.au/trial/MyTrial.aspx

Distribution, Drivers, and Threats of Aluminum in Groundwater in Nova Scotia, Canada

Increased rates of acid deposition derived from the burning of fossil fuels over the last century have resulted in the acidification and increase in aluminum (Al) levels in freshwaters and soils in sensitive areas. While the acidification of surface waters such as lakes and rivers has been extensively studied, the acidification status and resulting Al concentrations in groundwater are poorly understood. Here we aim to describe the distribution of Al in groundwater across the province of Nova Scotia, Canada. We investigate the hydrogeological conditions that influence Al concentrations in groundwater and compare Al concentrations to legislated threshold levels for human and aquatic health. We found groundwater Al concentrations to be highest in areas underlain by plutonic and metamorphic bedrock types as well as surficial aquifers, with pH and organic carbon concentrations having the strongest correlation with groundwater Al concentrations. Few samples exceed the maximum acceptable concentration of 2900 µg/L released by Health Canada (2021), but these exceedances are important to highlight given the challenges with respect to Al treatment in private domestic wells and our evolving understanding of Al impacts to human health. High concentrations of Al in groundwater may also be exported to surface waters such as rivers and lakes, where they can be harmful to aquatic populations such as Atlantic salmon (Salmo salar). We recommend that private well owners test their water supplies for Al, and that further studies on Al export from groundwater to surface water be carried out in the most high-risk areas coincident with important Atlantic salmon river watersheds.