A young male returned from the Democratic Republic of the Congo (DRC) to India after four months during his official work. Within a week of his arrival, he developed a high-grade fever with nausea and was hospitalized in a private hospital in New Delhi. He was diagnosed with malaria, treated with an artesunate injection as antimalarial, and discharged on day 5th from the hospital. A week later, he was diagnosed with malaria and dengue positive at ICMR-National Institute of Malaria Research, New Delhi. Artesunate with sulphadoxine and pyrimethamine (AS+SP) was administered following India's malaria treatment policy. However, high-grade fever, along with the asexual stage of the parasite, was observed within 28 days of treatment with AS+SP, signifying late treatment failure (LTF). Further, the molecular analysis from both the days of episodes was analyzed using genomic DNA from dried blood spots, revealing resistance to sulphadoxine-pyrimethamine with mutations at codons 51I, 59 R, 108 N, 437 A, 581 G. No functional mutation associated was found in 13, but interestingly the sensitive codons to chloroquine (CQ) (wild type K76 and N86) revealed the probably reversible CQ sensitivity in the sample from DRC.
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http://dx.doi.org/10.1016/j.idcr.2022.e01653 | DOI Listing |
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Department of Orthopedic Surgery, Hotel Dieu de France Hospital, Beirut, LEBANON.
Study Design: Meta-Analysis.
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Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.
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Department of Molecular and Life Science, Hanyang University, Ansan 15588, Republic of Korea.
The pathophysiology of sepsis is characterized by a systemic inflammatory response to infection; however, the cytokine blockade that targets a specific early inflammatory mediator, such as tumor necrosis factor, has shown disappointing results in clinical trials. During sepsis, excessive endotoxins are internalized into the cytoplasm of immune cells, resulting in dysregulated pyroptotic cell death, which induces the leakage of late mediator alarmins such as HMGB1 and PTX3. As late mediators of lethal sepsis, overwhelming amounts of alarmins bind to high-affinity TLR4/MD2 and low-affinity RAGE receptors, thereby amplifying inflammation during early-stage sepsis.
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Department of Surgical Oncology, Erasmus MC Cancer Institute Erasmus University Medical Center Rotterdam The Netherlands.
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