Investigation of imported malaria cases at a COVID-19 isolation point in Qingdao

The epidemiological data were collected from travellers who returned from Guinea on the 23rd of September, 2020 and were diagnosed with malaria at a C OVID -19 quarantine site in Qingdao, Shandong Province. The epidemiological characteristics, diagnosis and treatment of the cases and the epidemiology investigation and the rapid test screening results for other travellers on from the same flight and the interventions in reaction to the imported malaria cases were analyzed. The results showed that 4 out of 231 Guinean returned travellers had developed malaria symptoms, including chills and fever, during the isolation period. Rapid diagnostic test (RDT) indicated Plasmodium falciparum infection. Considering the patients ' travel history, clinical manifestations, and laboratory RDT test results, a confirmed diagnosis of imported P. falciparum malaria was made. The four malaria cases, who are male workers aged 29 to 55, were transferred to Jiaozhou People ' s Hospital for treatment. All four patients were administrated of artemether tablets upon diagnosis. One of the cases experienced severe malaria complications and were administrated with 12 doses (60 mg/dose) of artesunate intravenously for five days. The other three patients were treated with dihydroartemisinin and piperaquine phosphate tablets for one course of 8 tablets in 2 days (40 mg dihydroartemisinin and 320 mg piperaquine phosphate), respectively. Among the 231 returned travellers, 111 (48.1 %) had a history of malaria overseas. There were 23 positive cases detected by RDT, including the four symptomatic cases. The other 19 cases were asymptomatic. One of the asymptomatic cases became symptomatic three months later and was diagnosed as an imported P. malariae infection. Laboratory blood smear microscopic tests at the Jiaozhou City and Qingdao Municipal Center For Disease Control and Prevention showed negative results for the four malaria cases and the 19 RDT positive case. The samples from the four malaria cases were rechecked by the provincial reference laboratory of Shandong Institute of parasitic Disease. The results were negative for malaria infection by microscopic examination but positive for P. falciparum infection by nucleic acid test. It is suggested that during the routine control of COVID-19, the awareness of COVID-19 and malaria should be established among the returned travellers from high malaria-endemic areas. The health education "gate" should be moved forward to improve the treatment compliance for malaria cases and reduce the relapse or recrudescence caused by sub-optimal treatment.Copyright © 2022, Chin J Parasitol Parasit Dis. All rights reserved.

An imported case of ovale malaria in Xinjiang during the epidemic period of COVID-19.

On December 13, 2020, Yutian County People's hospital reported one imported malaria case in Hotan, Xinjiang. The patient had worked and lived in Yaounde, Cameroon, from January to September 2020. He was infected with malaria twice in March and May 2020. Antimalarial treatment was administrated by the team doctor for 2-3 days in each treatment. The treatment was stopped after the symptoms improved. The patient returned to China on September 16 and was hospitalized on December 13 due to a high fever of 39! and upper respiratory symptoms. Multiple detections of COVID-19 nucleic acid showed negative results. Peripheral blood from the patient was taken for Plasmodium rapid diagnostic test (RDT), which showed a positive result suggesting non Plasmodium falciparum infection. Ring stage P. ovale was found in the blood smear. Nested PCR showed positive for P. ovale. A diagnosis of imported ovale malaria was made. The patient was administrated with 4 dihydroartemisinin piperaquine tablets and 3 primaquine phosphate tablets daily. The malaria parasite test became negative after 8 days of treatment. The patient was followed up for 3 months after discharge and had no symptoms of chills or fever.Copyright © 2022, National Institute of Parasitic Diseases. All rights reserved.

In-silico Discovery of Fungal Metabolites Bergenin, Quercitrin and Dihy-droartemisinin as Potential Inhibitors against Main Protease of SARS-CoV-2

Background: Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has given rise to COVID-19 pandemic, which has become a wreaking havoc worldwide. Therefore, there is an urgent need to find out novel drugs to combat SARS-CoV-2 in-fection. In this backdrop, the present study aimed to assess potent bioactive compounds from different fungi as potential inhibitors of SARS-CoV-2 main protease (Mpro) using an in-silico analysis. Method(s): High-Resolution Liquid Chromatography Mass Spectrometry analysis (HR-LCMS) was used for the bioactive profiling of ethanolic crude extract of Dictyophora indusiata, Geastrum tri-plex and Cyathus stercoreus. Of which, only bergenin (D. indusiata), quercitrin (G. triplex) and di-hydroartemisinin (C. stercoreus) were selected based on their medicinal uses, binding score and the active site covered. The 6LU7, a protein crystallographic structure of SARS-CoV-2 Mpro, was docked with bergenin, quercitrin and dihydroartemisinin using Autodock 4.2. Result(s): A total of 118 bioactive compounds were analyzed from the crude extract of used fungi and identified using HR LC/MS analysis. The binding energies obtained were-7.86,-10.29 and-7.20 kcal/mol, respectively, after docking analysis. Bergenin, quercitrin and dihydroartemisinin formed hydrogen bond, electrostatic interactions and hydrophobic interactions with foremost active site amino acids THR190, GLU166, GLN189, GLY143, HIS163, HIS164, CYS145 and PHE140. Conclusion(s): Present investigation suggests that these three compounds may be used as alternative inhibitors against SARS-CoV-2 Mpro. However, further research is necessary to assess in vitro potential of these compounds. To the best of our knowledge, the present investigation reported these three bioactive compounds of fungal origin for the first time.Copyright © 2021 Bentham Science Publishers.

Investigation of imported malaria cases at a COVID-19 isolation point in Qingdao

The epidemiological data were collected from travellers who returned from Guinea on the 23rd of September, 2020 and were diagnosed with malaria at a COVID-19 quarantine site in Qingdao, Shandong Province. The epidemiological characteristics, diagnosis and treatment of the cases and the epidemiology investigation and the rapid test screening results for other travellers on from the same flight and the interventions in reaction to the imported malaria cases were analyzed. The results showed that 4 out of 231 Guinean returned travellers had developed malaria symptoms, including chills and fever, during the isolation period. Rapid diagnostic test (RDT) indicated Plasmodium falciparum infection. Considering the patients' travel history, clinical manifestations, and laboratory RDT test results, a confirmed diagnosis of imported P. falciparum malaria was made. The four malaria cases, who are male workers aged 29 to 55, were transferred to Jiaozhou People's Hospital for treatment. All four patients were administrated of artemether tablets upon diagnosis. One of the cases experienced severe malaria complications and were administrated with 12 doses (60 mg/dose) of artesunate intravenously for five days. The other three patients were treated with dihydroartemisinin and piperaquine phosphate tablets for one course of 8 tablets in 2 days (40 mg dihydroartemisinin and 320 mg piperaquine phosphate), respectively. Among the 231 returned travellers, 111(48.1%) had a history of malaria overseas. There were 23 positive cases detected by RDT, including the four symptomatic cases. The other 19 cases were asymptomatic. One of the asymptomatic cases became symptomatic three months later and was diagnosed as an imported P. malariae infection. Laboratory blood smear microscopic tests at the Jiaozhou City and Qingdao Municipal Center For Disease Control and Prevention showed negative results for the four malaria cases and the 19 RDT positive case. The samples from the four malaria cases were rechecked by the provincial reference laboratory of Shandong Institute of parasitic Disease. The results were negative for malaria infection by microscopic examination but positive for P. falciparum infection by nucleic acid test. It is suggested that during the routine control of COVID-19, the awareness of COVID-19 and malaria should be established among the returned travellers from high malaria-endemic areas. The health education "gate" should be moved forward to improve the treatment compliance for malaria cases and reduce the relapse or recrudescence caused by sub-optimal treatment.

Anti-malarial drug, artemisinin and its derivatives for the treatment of respiratory diseases.

Artemisinins are sesquiterpene lactones with a peroxide moiety that are isolated from the herb Artemisia annua. It has been used for centuries for the treatment of fever and chills, and has been recently approved for the treatment of malaria due to its endoperoxidase properties. Progressively, research has found that artemisinins displayed multiple pharmacological actions against inflammation, viral infections, and cell and tumour proliferation, making it effective against diseases. Moreover, it has displayed a relatively safe toxicity profile. The use of artemisinins against different respiratory diseases has been investigated in lung cancer models and inflammatory-driven respiratory disorders. These studies revealed the ability of artemisinins in attenuating proliferation, inflammation, invasion, and metastasis, and in inducing apoptosis. Artemisinins can regulate the expression of pro-inflammatory cytokines, nuclear factor-kappa B (NF-κB), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), promote cell cycle arrest, drive reactive oxygen species (ROS) production and induce Bak or Bax-dependent or independent apoptosis. In this review, we aim to provide a comprehensive update of the current knowledge of the effects of artemisinins in relation to respiratory diseases to identify gaps that need to be filled in the course of repurposing artemisinins for the treatment of respiratory diseases. In addition, we postulate whether artemisinins can also be repurposed for the treatment of COVID-19 given its anti-viral and anti-inflammatory properties.

Artemisia annua L. extracts inhibit the in vitro replication of SARS-CoV-2 and two of its variants.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia annua L. has been used for millennia in Southeast Asia to treat "fever". Many infectious microbial and viral diseases have been shown to respond to A. annua and communities around the world use the plant as a medicinal tea, especially for treating malaria. AIM OF THE STUDY: SARS-CoV-2 (the cause of Covid-19) globally has infected and killed millions of people. Because of the broad-spectrum antiviral activity of artemisinin that includes blockade of SARS-CoV-1, we queried whether A. annua suppressed SARS-CoV-2. MATERIALS AND METHODS: Using Vero E6 and Calu-3 cells, we measured anti SARS-CoV-2 activity against fully infectious virus of dried leaf extracts of seven cultivars of A. annua sourced from four continents. IC50s were calculated and defined as the concentrations that inhibited viral replication by 50%; CC50s were also calculated and defined as the concentrations that kill 50% of cells. RESULTS: Hot-water leaf extracts based on artemisinin, total flavonoids, or dry leaf mass showed antiviral activity with IC50 values of 0.1-8.7 µM, 0.01-0.14 µg, and 23.4-57.4 µg, respectively. Antiviral efficacy did not correlate with artemisinin or total flavonoid contents of the extracts. One dried leaf sample was >12 years old, yet its hot-water extract was still found to be active. The UK and South African variants, B1.1.7 and B1.351, were similarly inhibited. While all hot water extracts were effective, concentrations of artemisinin and total flavonoids varied by nearly 100-fold in the extracts. Artemisinin alone showed an estimated IC50 of about 70 µM, and the clinically used artemisinin derivatives artesunate, artemether, and dihydroartemisinin were ineffective or cytotoxic at elevated micromolar concentrations. In contrast, the antimalarial drug amodiaquine had an IC50 = 5.8 µM. Extracts had minimal effects on infection of Vero E6 or Calu-3 cells by a reporter virus pseudotyped by the SARS-CoV-2 spike protein. There was no cytotoxicity within an order of magnitude above the antiviral IC90 values. CONCLUSIONS: A. annua extracts inhibit SARS-CoV-2 infection, and the active component(s) in the extracts is likely something besides artemisinin or a combination of components that block virus infection at a step downstream of virus entry. Further studies will determine in vivo efficacy to assess whether A. annua might provide a cost-effective therapeutic to treat SARS-CoV-2 infections.