Aedes aegypti is the vector of a wide range of diseases (e.g. yellow fever, dengue, Chikungunya and Zika) which impact on over half the world’s population. Entomopathogenic fungi such as Metarhizium anisopliae and Beauveria bassiana have been found to be highly efficacious in killing mosquito larvae but only now are the underlying mechanisms for pathogenesis being elucidated. Recently it was shown that conidia of M. anisopliae caused stress induced mortality in Ae. aegypti larvae, a different mode of pathogenicity to that normally seen in terrestrial hosts. Blastospores constitute a different form of inoculum produced by this fungus when cultured in liquid media and although blastospores are generally considered to be more virulent than conidia no evidence has been presented to explain why. In our study, using a range of biochemical, molecular and microscopy methods, the infection process of Metarhizium brunneum (formerly M. anisopliae) ARSEF 4556 blastospores was investigated. It appears that the blastospores, unlike conidia, readily adhere to and penetrate mosquito larval cuticle. The blastospores are readily ingested by the larvae but unlike the conidia are able infect the insect through the gut and rapidly invade the haemocoel. The fact that pathogenicity related genes were upregulated in blastospores exposed to larvae prior to invasion, suggests the fungus was detecting host derived cues. Similarly, immune and defence genes were upregulated in the host prior to infection suggesting mosquitoes were also able to detect pathogen-derived cues. The hydrophilic blastospores produce copious mucilage, which probably facilitates adhesion to the host but do not appear to depend on production of Pr1, a cuticle degrading subtilisin protease, for penetration since protease inhibitors did not significantly alter blastospore virulence. The fact the blastospores have multiple routes of entry (cuticle and gut) may explain why this form of the inoculum killed Ae. aegypti larvae in a relatively short time (12-24hrs), significantly quicker than when larvae were exposed to conidia. This study shows that selecting the appropriate form of inoculum is important for efficacious control of disease vectors such as Ae. aegypti.

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Dengue fever is one of the most important viral infections transmitted by Aedes mosquitoes and a major cause of morbidity and mortality globally. Accurate identification of cases and treatment of dengue patients at the early stages can reduce medical complications and dengue mortality rate. This survey aims to determine the knowledge, attitude, and practices (KAP) among physicians in dengue diagnosis and treatment. This study was conducted among physicians in Turkey as one nonendemic country and Bangladesh, India, and Malaysia as three dengue-endemic countries. The dosing frequencies, maximum doses, and contraindications in dengue fever were examined. The results found that physicians from Bangladesh, India, and Malaysia have higher KAP scores in dengue diagnosis and treatment compared to physicians in Turkey. This may be due to a lack of physician’s exposure to a dengue patient as Turkey is considered a nonendemic country. This assessment may help establish a guideline for intervention strategies among physicians to have successful treatment outcomes and reduce dengue mortality.

Is Coronavirus Disease 2019 (COVID-19) seen less in countries more exposed to Malaria? To the editor, The Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 and continues to spread worldwide with the increasing number of cases. The disease poses a major threat to public health worldwide. As of April 2, 2020, a total of 896.450 confirmed cases of COVID-19 and 45.526 deaths have been reported worldwide [1]. It is noteworthy that the number of confirmed cases is relatively low in countries such as Nigeria (n = 139), the Democratic Republic of the Congo (n = 22), Uganda (n = 44), Cote d' Ivoire (n = 190), Mozambique (n = 10), and Niger (n = 74), especially where malaria is common [1,2]. Nigeria (25%), Democratic Republic of the Congo (12%), Uganda (5%), Cote d' Ivoire (4%), Mozambique (4%) and Niger (4%) are accounted for more than half of all global malaria burden [2]. The World Health Organization is working hard on disease prevention, control, transportation of protective equipment and laboratory test kits. SARS-CoV-2 shares similar genetic sequences and viral structures with severe acute Respiratory Syndrome (SARS) coronavirus and Middle East Respiratory Syndrome (MERS) coronavirus [3]. The virus enters the cell via angiotensin-converting enzyme 2, the cellular receptor of SARS-CoV. They stimulate immune cells and lead to clinical manifestations resulting in ARDS by cytokine storms with overproduction of cytokines [4-6]. In this context, antiviral drugs and therapies that modulate the immune system are required to control the disease and reduce mortality. Many potentially effective treatments such as remdesivir, lopinavir/ritonavir, favipiravir, steroid, plasma transfusion, hydroxychloroquine (HCQ), and chloroquine (CQ) are used to control the COVID-19 [7,6]. Treatment responses for CQ such as fever reduction and improvement in CT imaging were obtained in patients [7,8]. In this context, clinical studies on CQ and HCQ are still ongoing for COVID-19 [9]. HCQ and CQ have metabolic, anti-tumoral, anti-microbial, and antithrombotic effects and used in rheumatology practice for patients with rheumatoid arthritis and systemic lupus erythematosus [10,11]. Quinacrine is beneficial for skin involvement of systemic lupus erythematosus, however, it is not widely used due to its side effects [10]. Although CQ and HCQ are structurally similar, the difference is in the hydroxyethyl group on the tertiary amino nitrogen side chain [10,12]. HCQ is less toxic of 4 amino quinolones and more soluble than CQ with more safety and low side effect profile. Cardiotoxicity, retinal toxicity, hypoglycemia, myopathy, hemolytic anemia, and hyperpigmentation are some of the reported side effects [12]. Toxicity varies depending on the high dose, long-term use, concomitant drug use, and kidney disease [13]. The risk of retinopathy, the most noticeable side effect, is below 1% for 5 years when used in appropriate doses [13]. Therefore, HCQ is considered to be a pri...

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