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Displaying publications 41 - 44 of 44 in total

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Adjunctive pascolizumab in rifampicin-susceptible pulmonary tuberculosis: proof-of-concept, partially-randomised, double-blind, placebo-controlled, dose-escalation trial

Paton NI, Gurumurthy M, Lu Q, Leek F, Kwan P, Koh HWL, et al.

J Infect Dis, 2024 Mar 25.
PMID: 38527849 DOI: 10.1093/infdis/jiae104

BACKGROUND: Interleukin-4 (IL-4), increased in tuberculosis infection, may impair bacterial killing. Blocking IL-4 confers benefit in animal models. We evaluated safety and efficacy of pascolizumab (humanised anti-IL-4 monoclonal antibody) as adjunctive tuberculosis treatment.
METHODS: Participants with rifampicin-susceptible pulmonary tuberculosis received a single intravenous infusion of pascolizumab or placebo; and standard 6-month tuberculosis treatment. Pascolizumab dose increased in successive cohorts: [1] non-randomised 0.05 mg/kg (n = 4); [2] non-randomised 0.5 mg/kg (n = 4); [3] randomised 2.5 mg/kg (n = 9) or placebo (n = 3); [4] randomised 10 mg/kg (n = 9) or placebo (n = 3). Co-primary safety outcome was study-drug-related grade 4 or serious adverse event (G4/SAE); in all cohorts (1-4). Co-primary efficacy outcome was week-8 sputum culture time-to-positivity (TTP); in randomised cohorts (3-4) combined.
RESULTS: Pascolizumab levels exceeded IL-4 50% neutralising dose for 8 weeks in 78-100% of participants in cohorts 3-4. There were no study-drug-related G4/SAEs. Median week-8 TTP was 42 days in pascolizumab and placebo groups (p = 0.185). Rate of TTP increase was greater with pascolizumab (difference from placebo 0.011 [95% Bayesian credible interval 0.006 to 0.015] log10TTP/day.
CONCLUSIONS: There was no evidence to suggest blocking IL-4 was unsafe. Preliminary efficacy findings are consistent with animal models. This supports further investigation of adjunctive anti-IL-4 interventions for tuberculosis in larger phase 2 trials.
A cohort study of health care workers to assess nosocomial transmissibility of Nipah virus, Malaysia, 1999

Mounts AW, Kaur H, Parashar UD, Ksiazek TG, Cannon D, Arokiasamy JT, et al.

J Infect Dis, 2001 Mar 1;183(5):810-3.
PMID: 11181159 DOI: 10.1086/318822

During 1998-1999, an outbreak of Nipah virus encephalitis occurred in Malaysia. To assess the possibility of nosocomial transmission, 338 health care workers (HCWs) exposed and 288 HCWs unexposed to outbreak-related patients were surveyed, and their serum samples were tested for anti-Nipah virus antibody. Needlestick injuries were reported by 12 (3%) HCWs, mucosal surface exposure to body fluids by 39 (11%), and skin exposure to body fluids by 89 (25%). No encephalitis occurred in either group. Three exposed and no unexposed HCWs tested positive by EIA for IgG antibodies. It is likely that these 3 were false positives; no IgM response occurred, and the serum samples were negative for anti-Nipah virus neutralizing antibodies. The risk of nosocomial transmission of Nipah virus appears to be low; however, given the high case-fatality rate and the presence of virus in respiratory secretions and urine of some patients, standard and droplet infection-control practices should be maintained with these patients.
A Lethal Aerosol Exposure Model of Nipah Virus Strain Bangladesh in African Green Monkeys

Prasad AN, Agans KN, Sivasubramani SK, Geisbert JB, Borisevich V, Mire CE, et al.

J Infect Dis, 2020 05 11;221(Suppl 4):S431-S435.
PMID: 31665351 DOI: 10.1093/infdis/jiz469

The high case-fatality rates and potential for use as a biological weapon make Nipah virus (NiV) a significant public health concern. Previous studies assessing the pathogenic potential of NiV delivered by the aerosol route in African green monkeys (AGMs) used the Malaysia strain (NiVM), which has caused lower instances of respiratory illness and person-to-person transmission during human outbreaks than the Bangladesh strain (NiVB). Accordingly, we developed a small particle aerosol model of NiVB infection in AGMs. Consistent with other mucosal AGM models of NiVB infection, we achieved uniform lethality and disease pathogenesis reflective of that observed in humans.
Fulltext A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609

Zhang R, Suwanarusk R, Malleret B, Cooke BM, Nosten F, Lau YL, et al.

J Infect Dis, 2016 Jan 1;213(1):100-4.
PMID: 26136472 DOI: 10.1093/infdis/jiv358

Recent clinical trials revealed a surprisingly rapid clearance of red blood cells (RBCs) infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite-infected RBCs exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent to the disruption of the parasite's sodium efflux pump (adenosine triphosphate 4). We also show that this peculiar drug effect is likely to cause accelerated splenic clearance of the rheologically impaired Plasmodium vivax- and Plasmodium falciparum-infected RBCs.