The Journal of infectious diseases
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Human noroviruses are a leading cause of gastroenteritis worldwide, yet there are no licensed antivirals. There is an urgent need for norovirus therapeutics, particularly for chronic infections in immunocompromised individuals, but also a potential need for prophylactic use in epidemics. Continued research has led to the identification of compounds that inhibit norovirus replication in vitro and, at least in some cases, are also effective in vivo against murine norovirus. Progress has included classical approaches targeting viral proteins and harnessing the antiviral action of interferon, strategies targeting essential host cell factors, and novel strategies exploiting the high mutation rate of noroviruses.
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This paper describes patient characteristics, including Ebola viral load, associated with mortality in a Médecins Sans Frontières Ebola case management centre (CMC). Out of 780 admissions between June and October 2014, 525 (67%) were positive for Ebola with a known outcome. The crude mortality rate was 51% (270/525). ⋯ The multivariable model predicted mortality in those with a viral load at admission greater than 10 million copies per milliliter (P < .05, odds ratio >10), aged ≥ 50 years (P = .08, odds ratio = 2) and symptom duration prior to admission less than 5 days (P = .14). The presence of confusion, diarrhea, and conjunctivitis were significantly higher (P < .05) in Ebola patients who died. These findings highlight the importance viral load at admission has on mortality outcomes and could be used to cohort cases with viral loads greater than 10 million copies into dedicated wards with more intensive medical support to further reduce mortality.
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Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and poses a threat to malaria control and elimination. Mutations in a P. falciparum gene encoding a kelch protein on chromosome 13 have been associated with delayed parasite clearance following artemisinin treatment elsewhere in the region, but not yet in China. ⋯ Plasmodium falciparum infections in southern China displayed markedly delayed clearance following artemisinin treatment. F446I was the predominant K13 mutation and was associated with delayed parasite clearance.
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A major barrier to effective tuberculosis control is our limited understanding of risk factors for tuberculosis disease progression. This study examined the role of apoptosis in immunity to tuberculosis. ⋯ While T cells are clearly able to mount a robust immune response to Mycobacterium tuberculosis, there are increased levels of apoptosis seen in effector T cells from tuberculosis patients. Dysregulation of several apoptotic genes suggest that apoptosis is a major functional pathway that could be targeted for future host-directed therapeutics.