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Malaria and schistosomiasis are two of the most socioeconomically devastating parasitic diseases in tropical and subtropical countries. Since current chemotherapeutic options are limited and defective, there is an urgent need to develop novel antiplasmodials and antischistosomals. Hemozoin is a disposal product formed from the hemoglobin digestion by some blood-feeding parasites. Hemozoin formation is an essential process for the parasites to detoxify free heme, which is a reliable therapeutic target for identifying novel antiparasitic agents. A series of novel carbazole aminoalcohols were designed and synthesized as potential antiplasmodial and antischistosomal agents, and several compounds showed potent in vitro activities against Plasmodium falciparum 3D7 and Dd2 strains and adult and juvenile Schistosoma japonicum. Investigations on the dual antiparasitic mechanisms showed the correlation between inhibitory activity of β-hematin formation and antiparasitic activity. Inhibiting hemozoin formation was identified as one of the mechanisms of action of carbazole aminoalcohols. Compound 7 displayed potent antiplasmodial (Pf3D7 IC 50  = 0.248 μM, PfDd2 IC 50  = 0.091 μM) and antischistosomal activities (100% mortality of adult and juvenile schistosomes at 5 and 10 μg/mL, respectively) and exhibited low cytotoxicity (CC 50  = 7.931 μM), which could be considered as a promising lead for further investigation. Stoichiometry determination and molecular docking studies were also performed to explain the mode of action of compound 7., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The global battle against malaria is facing formidable challenges, particularly in controlling Plasmodium vivax and Plasmodium ovale, whose cases have not been reduced as effectively as Plasmodium falciparum because of their relapse. This study investigates the current situation and underlying factors contributing to relapse or recrudescence of imported cases of P. vivax and P. ovale, and seeks to provide a reference for reducing relapse or recrudescence in malaria-free areas and offers a scientific basis for designing strategies to prevent imported re-transmission. Methods: This study analysed imported P. vivax and P. ovale in Anhui, Zhejiang, Henan, Hubei, and Guangxi provinces during 2014–2021 by retrospective analysis. A case–control study was conducted on patients who experienced relapse or recrudescence. Results: From 2014 to 2021, 306 cases of P.vivax and 896 cases of P.ovale were included in the study, while 75 cases had relapse or recrudescence, including 49 cases of P. ovale (65.33%) and 26 cases of P. vivax (34.67%). Within less than 5 weeks after returning to the country, 122 cases of P. vivax (39.87%, 122/306) and 265 cases of P. ovale (29.58%, 265/896) occurred. Within less than 53 weeks, the ratio of P. vivax was 94.77% (290/306), and that of P. ovale was 89.96% (806/896). Among the cases experiencing relapse or recrudescence, only 1 case of P. vivax (1/26 3.85%) and 3 cases of P. ovale (3/49 6.12%) occurred within less than 5 weeks after the first onset, whereas 21 cases of P. vivax (21/26 80.77%) and 42 cases of P. ovale (42/49 85.71%) occurred within less than 53 weeks after the first onset. The difference in relapse or recrudescence due to different drugs and medication regimens and medical activities at various levels of medical institutions was statistically significant. Conclusion: In areas where malaria has been eliminated, routine health screening in a scientific time frame for people returning from at-risk areas can effectively improve the efficiency of preventing re-transmission, thereby reducing prevention costs and disease burden. Preventing patients from self-treating and strengthening medication regulations in health facilities are key measures to reduce relapse or recrudescence. [ABSTRACT FROM AUTHOR]

Background and Purpose: Malaria is one of the deadliest diseases in the world. Novel chemotherapeutic agents are urgently required to combat the widespread Plasmodium resistance to frontline drugs. Here, we report the discovery of a novel benzonaphthyridine antimalarial, methnaridine, which was identified using a structural optimization strategy.Experimental Approach: An integrated pharmacological approach was used to evaluate the antimalarial profile of methnaridine. The pharmacokinetic properties of methnaridine were investigated along with the associated safety profile. Host immune response patterns were also analysed.Key Results: Methnaridine exhibited potent antimalarial activity against P. falciparum (3D7: IC50 = 0.0066 μM; Dd2: IC50 = 0.0056 μM). In P. berghei-infected mice, oral administration effectively suppressed parasitemia (ED50 = 0.52 mg·kg-1 ·day-1 ) and cured the established infection (CD50 = 10.13 mg·kg-1 ·day-1 ). These results are equivalent to or better than those of other antimalarial agents in clinical use. Notably, a four-dose oral regimen at a dosage of 25 mg·kg-1 achieved a complete cure of P. berghei infection in mice. Methnaridine exhibited a rapid parasiticidal profile (PCT99 = 36.0 h) and showed no cross-resistance to chloroquine. Pharmacokinetic studies revealed that methnaridine is readily absorbed, long-lasting and slowly cleared. The safety profile of methnaridine is also satisfactory (maximum tolerated dose = 1,125 mg·kg-1 ). In addition, following methnaridine treatment, infection-induced Th1 immune response was almost fully alleviated in mice.Conclusion and Implications: Methnaridine is an orally bioavailable, fast-acting and long-lasting agent with excellent antimalarial properties. Our study highlights the potential of methnaridine for clinical development as a promising antimalarial candidate. [ABSTRACT FROM AUTHOR]

• The combined toolbox (Wondfo RDTs plus microscopy) improved the surveillance system sensitivity for malaria in Anhui province. • The improvement was mainly attributed to the excellent ability of RDTs to detect P. falciparum infections. On the other hand, microscopy compensates for some limitations of the use of RDTs in field practice. • Using more than one diagnostic tool to strengthen the surveillance system was effective in the post-elimination stage. Background: In the Anhui Province, China, efforts to interrupt the local malaria transmission were successful, with no endemic cases reported since 2014. Contrastingly, imported malaria cases are still being reported, indicating a disease reintroduction risk after years of elimination. A good surveillance system is key for avoiding the risk, detecting imported cases and possible cases associated with local transmission early. Therefore, rapid diagnostic tests (RDTs) were combined with microscopy to strengthen malaria surveillance in the province. Herein, we aimed to evaluate the efficacy of this surveillance strategy. Methods: We conducted a retrospective study using malaria surveillance data from January 2016 to June 2020. Epidemiological characteristics and diagnostic information were analysed using descriptive and comparative statistics. The diagnostic performance of the combined toolbox (Wondfo RDTs plus microscopy) was evaluated based on its sensitivity, specificity, positive and negative predictive values, and Cohen's kappa coefficient, using real-time polymerase chain reaction as the gold standard. Results: The combined toolbox displayed a higher overall sensitivity for malaria cases than that of microscopy alone (93.74% vs 89.37%; p adj <0.05), which could detect 94.65%, 88.16%, 95.00%, and 100.00% of Plasmodium falciparum, P. ovale, P. vivax , and P. malariae infections, respectively. In clinical practice, Wondfo RDTs ability to detect P. falciparum infections was better than that of microscopy (97.55% vs 89.67%, p adj < 0.05). In contrast, microscopy displayed a higher specificity than that of Wondfo RDTs (81.82% vs 63.28%, p adj <0.05). Moreover, the consistency between microscopy and the gold standard results was also better than that of RDTs (Kappa value:0.669 vs 0.596). Conclusions: The combination of microscopy and RDTs is an effective strategy for malaria surveillance because it possibly detected more P. falciparum infections due to the introduction of RDTs. In contrast, microscopy is complementary to some limitations related to the use of RDTs in field practice. Thus, monitoring malaria cases in non-endemic areas may require employing more than one diagnostic tool in surveillance strategies. Moreover, further understanding of the advantages and disadvantages of different detection methods is necessary for applying optimum combinations in field settings. [ABSTRACT FROM AUTHOR]