ABSTRACT Background: The risk of possible cross-reactions between serological tests, together with the clinical similarities between dengue fever and COVID-19, can delay diagnosis and increase the risk of both COVID-19 transmission and worsening. The present study aimed to determine the possibility of cross-reactions among rapid serological tests based on clinical symptoms. Methods: Patients with COVID-19, confirmed by RT-PCR and clinical criteria for diagnosing dengue, were recruited consecutively between September 2020 and August 2021 and underwent rapid immunochromatographic diagnostic (RID) tests for AgNS1, IgM, and IgG. Patients who tested positive for acute-phase dengue IgM and AgNS1 underwent a follow-up test after 12-30 days for diagnostic confirmation. Results: A total of 43 patients were included, 38 of whom required hospital admission, and 8 received intensive care. Seven patients tested positive on the RID tests, comprising 2 NS1 positive (coinfection), one reactive for IgM and IgG (coinfection), three reactive for IgM not confirmed (false-positive), and one reactive for IgG due to previous infection. Two of the 3 patients with coinfection died. Fever, myalgia, headache, and cough were the most common clinical symptoms, while lymphopenia was the most prevalent laboratory finding. Conclusions: Cross-reactivity was found in only three patients and coinfection in another three patients, two of whom died of severe COVID-19 manifestations.

Farnesyl diphosphate synthase/geranylgeranyl diphosphate synthase (FPPS/GGPPS) is a key enzyme in the synthesis of isoprenic chains. Risedronate, a bisphosphonate containing nitrogen (N-BP), is a potent inhibitor of blood stage Plasmodium. Here, we show that P. falciparum parasites overexpressing FPPS/GGPPS are more resistant to risedronate, suggesting that this enzyme is an important target, and bisphosphonate analogues can be used as potential antimalarial drugs.

The development of new drugs is one strategy for malaria control. Biochemical pathways localised in the apicoplast of the parasite, such as the synthesis of isoprenic precursors, are excellent targets because they are different or absent in the human host. Isoprenoids are a large and highly diverse group of natural products with many functions and their synthesis is essential for the parasite's survival. During the last few years, the genes, enzymes, intermediates and mechanisms of this biosynthetic route have been elucidated. In this review, we comment on some aspects of the methylerythritol phosphate pathway and discuss the presence of diverse isoprenic products such as dolichol, ubiquinone, carotenoids, menaquinone and isoprenylated proteins, which are biosynthesised during the intraerythrocytic stages of Plasmodium falciparum.

In Plasmodium falciparum, the formation of isopentenyl diphosphate and dimethylallyl diphosphate, central intermediates in the biosynthesis of isoprenoids, occurs via the methylerythritol phosphate (MEP) pathway. Fosmidomycin is a specific inhibitor of the second enzyme of the MEP pathway, 1-deoxy-D-xylulose-5-phosphate reductoisomerase. We analyzed the effect of fosmidomycin on the levels of each intermediate and its metabolic requirement for the isoprenoid biosynthesis, such as dolichols and ubiquinones, throughout the intraerythrocytic cycle of P. falciparum. The steady-state RNA levels of the MEP pathway-associated genes were quantified by real-time polymerase chain reaction and correlated with the related metabolite levels. Our results indicate that MEP pathway metabolite peak precede maximum transcript abundance during the intraerythrocytic cycle. Fosmidomycin-treatment resulted in a decrease of the intermediate levels in the MEP pathway as well as in ubiquinone and dolichol biosynthesis. The MEP pathway associated transcripts were modestly altered by the drug, indicating that the parasite is not strongly responsive at the transcriptional level. This is the first study that compares the effect of fosmidomycin on the metabolic and transcript profiles in P. falciparum, which has only the MEP pathway for isoprenoid biosynthesis.