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Background: Anhui Province is currently facing an increase in imported malaria cases as a result of globalization and international travel. In response, Anhui Province has implemented a comprehensive adaptive framework to effectively address this threat., Methods: This study collected surveillance data from 2012 to 2022 in Anhui Province. Descriptive statistics were used to analyze the epidemiological characteristics of imported malaria cases. Additionally, multivariate logistic regression was employed to identify factors associated with severe malaria. Documents were reviewed to document the evolution of the adaptive framework designed to combat imported malaria. The effectiveness of the adaptive framework was evaluated based on the rates of timely medical visits, timely diagnosis, and species identification., Results: During the study period, a total of 1008 imported malaria cases were reported across 77 out of 105 counties in Anhui Province, representing a coverage of 73.33%. It was found that 10.52% of imported cases went undiagnosed for more than seven days after onset. The multivariate analysis revealed several potential risk factors for severe malaria, including increasing age (OR = 1.049, 95%CI:1.015-1.083), occupation (waitperson vs. worker, OR = 2.698, 95%CI:1.054-6.906), a longer time interval between onset and the initial medical visit (OR = 1.061, 95%CI:1.011-1.114), and misdiagnosis during the first medical visit (OR = 5.167, 95%CI:2.535-10.533). Following the implementation of the adaptive framework, the rates of timely medical visits, timely diagnosis, and species identification reached 100.00%, 78.57%, and 100.00%, respectively., Conclusions: Anhui Province has successfully developed and implemented an adaptive framework for addressing imported malaria, focusing on robust surveillance, prompt diagnosis, and standardized treatment. The experiences gained from this initiative can serve as a valuable reference for other non-endemic areas., (© 2024. The Author(s).)

Introduction: The provincial malaria diagnosis reference laboratories review and assess malaria cases diagnosed in health facilities for supporting the malaria elimination efforts and preventing re-transmission of imported malaria. The study aimed to evaluate the detection capability of malaria diagnosis in China from 2014 to 2021., Methods: Data on malaria cases reported in the provincial-level administrative divisions (PLADs) of Anhui, Henan, Hubei, Guangxi, and Zhejiang from 2014 to 2021 were collected and analyzed., Results: In total, 5,770 malaria cases were reported from 2014 to 2021, and 99.05% (5,715/5,770) were submitted to the provincial malaria diagnosis reference laboratories. The median time between malaria cases being reported and the samples being received by reference laboratories was 6 days (Interquartile range, IQR:3-12 days) from 2017 to 2021. Diagnosis of 5,680 samples in the laboratory were confirmed by provincial reference laboratories, including 3,970 cases of Plasmodium falciparum , 414 of P. vivax , 1,055 of P. ovale , 158 of P. malariae , 1 of P. knowlesi , and 82 of mixed infections. Plasmodium species of 5,141 confirmed cases were consistent with the initial diagnosis, with a species accuracy rate of 90.53% (5,141/5,679). The accuracy of P. falciparum diagnosis in health facilities was higher than that of non-falciparum species. The inconsistency between microscopy and nested polymerase chain reaction (nPCR) results of confirmatory diagnosis was mainly in malaria-positive versus malaria-negative cases, as well as in mixed versus single infection cases., Conclusion: The provincial malaria diagnosis reference laboratories have played an important role in ensuring the accuracy and reliability of Plasmodium diagnosis in health facilities. However, the results of this study imply that capacity training for the identification of Plasmodium species in health facilities is warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Jiang, Sui, Yan, Xia, Liu, Sun, Wang, Marfurt, Lu, Li, Ruan and Wang.)

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., (© 2023. The Author(s).)

Background: In areas where malaria has been eliminated, delayed care-seeking and diagnosis of imported malaria are constant threats. This study aimed to describe the profile and determinants of delayed care-seeking and diagnosis among patients with imported malaria in China., Methods: This retrospective study assessed surveillance data obtained from 2014 to 2021 in the Chinese provincial-level administrative divisions (PLADs) of Anhui, Henan, Hubei, and Zhejiang, and Guangxi. Epidemiological characteristics were analyzed using descriptive statistics. Furthermore, factors associated with delayed care-seeking and diagnosis among imported malaria cases were identified using multivariate logistic regression., Results: Overall, 11.81% and 30.08% of imported malaria cases had delays in seeking care and diagnosis, respectively. During the study period, there was a decreasing trend in the proportion of imported malaria cases with delayed care-seeking (χ 2  = 36.099, P < 0.001) and diagnosis (χ 2  = 11.395, P = 0.001). In multivariate analysis, independent risk factors associated with delayed care-seeking include PLADs (Guangxi as reference), consultations in high-level facilities for the first medical visit, infections with non-Plasmodium falciparum species, and older age. However, PLADs (Guangxi as reference), the purpose of traveling (labour as reference), and infections with non-P. falciparum species increased the risk of delayed diagnosis. Delayed care-seeking (adjusted odds ratio: 1.79, P = 0.001) and diagnosis (adjusted odds ratio: 1.62, P = 0.004) were risk factors for severe disease development., Conclusions: Based on this study's findings, we strongly advocate for improved access to quality healthcare to reduce the rate of misdiagnosis at the first visit. Infections caused by non-P. falciparum species should be highlighted, and more sensitive and specific point-of-care detection methods for non-P. falciparum species should be developed and implemented. In addition, education programs should be enhanced to reach target populations at risk of malaria infection. All these factors may reduce delayed care-seeking and diagnosis of imported malaria., (© 2022. The Author(s).)

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., (Copyright © 2021. Published by Elsevier B.V.)

Background: Although autochthonous malaria cases are no longer reported in Anhui Province, China, imported malaria has become a major health concern. The proportion of reported malaria cases caused by Plasmodium ovale spp. increased to levels higher than expected during 2012 to 2019, and showed two peaks, 19.69% in 2015 and 19.35% in 2018., Methods: A case-based retrospective study was performed using data collected from the China Information System for Disease Control and Prevention (CISDCP) and Information System for Parasitic Disease Control and Prevention (ISPDCP) from 2012 to 2019 to assess the trends and differences between Plasmodium ovale curtisi (P. o. curtisi) and Plasmodium ovale wallikeri (P. o. wallikeri). Epidemiological characteristics were analyzed using descriptive statistics., Results: Plasmodium o. curtisi and P. o. wallikeri were found to simultaneously circulate in 14 African countries. Among 128 patients infected with P. ovale spp., the proportion of co-infection cases was 10.16%. Six cases of co-infection with P. ovale spp. and P. falciparum were noted, each presenting with two clinical attacks (the first attack was due to P. falciparum and the second was due to P. ovale spp.) at different intervals. Accurate identification of the infecting species was achieved among only 20.00% of cases of P. ovale spp. infection. At the reporting units, 32.17% and 6.96% of cases of P. ovale spp. infection were misdiagnosed as P. vivax and P. falciparum infections, respectively., Conclusion: The present results indicate that the potential of P. ovale spp. to co-infect with other Plasmodium species has been previously underestimated, as is the incidence of P. ovale spp. in countries where malaria is endemic. P. o. curtisi may have a long latency period of > 3 years and potentially cause residual foci, thus posing challenges to the elimination of malaria in P. ovale spp.-endemic areas. Considering the low rate of species identification, more sensitive point-of-care detection methods need to be developed for P. ovale spp. and introduced in non-endemic areas.

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: IC 50 = 0.0066 μM; Dd2: IC 50 = 0.0056 μM). In P. berghei-infected mice, oral administration effectively suppressed parasitemia (ED 50 = 0.52 mg·kg -1 ·day -1 ) and cured the established infection (CD 50 = 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 (PCT 99 = 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., (© 2020 The British Pharmacological Society.)