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.

Impact of the Covid-19 Pandemic on Malaria Services in Uganda: A Time Series Analysis

Background: Pregnancy is both a risk factor for P. falciparum infection and development of severe malaria and, in Uganda, its control relies heavily in the administration of intermittent preventive treatment with sulfadoxinepyrimethamine (SP-IPTp) during antenatal care visits (ANC). COVID-19 pandemic severely impacted health systems globally. This study aims to assess trends in delivering malaria in pregnancy related healthcare services before and during Covid-19 in thirty health facilities in Northern Uganda. Method(s): Interrupted time series study comparing two periods: I) pre- Covid-19 (January 2018 to February 2020) and II) Covid-19 (from March 2020 to December 2021) period. Data were sourced from the District Health Information Management System II (DHIMS2) routinely collected indicators. Comparisons between the two periods were computed with a jointpoint regression model and Annual Average Percentage Changes (AAPC) were calculated. Result(s): The study involved data collected by 30 health facilities, 30 health facilities in Northern Uganda - including one hospital - with a catchment area of 506,276 inhabitants and an estimated number of pregnancies ranging from 21,440 to 23,315. Covid cumulative cases and deaths for Oyam districs are reported in Figure 1. As shown in Figure 2, during COVID period we found a significant reduction in the number of women accessing to at least 4 antenatal care (ANC) visits and taking at least three doses of intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine. The total number of pregnant women receiving Artemether-Lumefantrine for nonsevere malaria or being hospitalized for severe malaria, along with the total number of institutional deliveries and stillbirths followed kept following the trend recorded prior to the pandemic. Conclusion(s): The present study shows that, despite the international call for prioritization of maternal and reproductive health service delivery during COVID-19 pandemic, in Uganda, the essential care for malaria in pregnancy have been disrupted. This is concerning, as the failure to increase the delivery of SP-IPTp may impact malaria-related mortality.

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.

ARTEMISIA SPECIES AND ARTEMISININ DERIVATIVES AS ANTIVIRAL AGENTS AGAINST COVID-19. CURRENT KNOWLEDGE: CHEMISTRY, PHARMACOLOGY AND CLINICAL EVIDENCE

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the reason behind the third zoonotic outbreak from the Coronaviridae family during the 21st century. COVID-19 was declared a pandemic by the WHO on 11 March 2020, and it has been posing a challenge for the health care system all around the world. Research groups worldwide are trying to find potential leads for drugs against SARS-CoV-2. Investigating natural products and extracts from known medicinal plants has been one area of focus in searching for potential inhibitors of SARS-CoV-2. This review aims to highlight the importance of including natural plants and plants derived compounds in this investigation. We particularly focused on compounds from Artemisia species (artemisinin and its derivatives), as this plant is highly valuable and has various pharmacological profiles.

Role of Corticosteroids in Dengue Fever in Pakistan

Aim: To compare and evaluate clinical efficacy of corticosteroids in thrombocytopenia in patients suffering from moderate to severe Dengue. Methods: This randomized single blinded study was conducted at Furqan Clinic Gulbahar Peshawar from August 2021 to October 2021. 100 individuals of ages between 20 to 60 years irrespective of gender, with positive NS1 antigen test and no co-morbidities were included in study by convenient sampling technique. Patients with dengue and Covid-19 were excluded from the study. Randomization was done in four treatment groups. Consent was taken from all patients prior treatment with Cefixime, artemether/lumefantrine, IV Dexamethasone in adjunct to oral papaya leaf extracts. Duration of study was 3 months. Statistical analysis done using SPSS software version 24. Results: Group C and D showed the significant increase in platelet count as compared to group A and B. Pronounced effect was observed in group D. Conclusion: Intravenous Dexamethasone produced more beneficial effects in adjunct to oral carica papaya leaf extracts on thrombocytopenia with reduced risk of bleeding.

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.

First principle study of silver nanoparticle interactions with antimalarial drugs extracted from Artemisia annua plant.

Silver nanoparticles have a great potential in a broad range of applications such as drug-delivery carriers because of their antiviral and antibacterial properties. In this study, the coating properties of silver nanoparticle (size range of 1.6 nm) with three common anti-malarial drugs, Artemisinin, Artemether, and Artesunate have been studied by using the quantum mechanical and classical atomistic molecular dynamics simulation in order to use as the drug delivery to treat malaria and COVID-19 diseases. The optimized structure, frequencies, charge distribution, and the electrostatic potential maps of the three drug molecules were simulated by using the density functional theory (DFT) at the B3LYP/6-311++g(d,p) level of theory. Then, molecular dynamics simulation was used to study the coating of AgNP with each of these drugs. The affinity of interaction was obtained as Artesunate > Artemether > Artemisinin which is in agreement with the DFT results on the adsorption of drugs on the Ag(111) slab.