Effectiveness of Antibiotic Prophylaxis for Leptospirosis among Adults: A Systematic Review

Leptospirosis is one of the most widespread re-emerging zoonoses in the world. Malaysia is known to be an endemic country for human leptospirosis, with a case fatality rate of 2.11%, and an average annual incidence rate of 7.80 cases per 100,000 individuals. This systematic review is conducted to determine the effectiveness of antibiotic prophylaxis for leptospirosis among the adult populations who are highly at risk of getting infected. A systematic search was performed for the relevant titles, abstracts and keywords on PubMed, Scopus, Cochrane and Google Scholar from inception to November 2017 based on the PICO strategy; which returned 126 studies. Screening of abstracts had shortlisted 19 studies and data extraction was conducted for 8 studies which had been accepted after review of the full text. For the evaluation of antibiotics prophylaxis effectiveness against leptospirosis, only trials and cohort studies with risk ratio (RR) were selected. The articles were analyzed from the viewpoint of the dosage, adverse effects, study settings and effectiveness of the antibiotic prophylaxis. Using fixed effects model, pooled RR showed protective association between antibiotic prophylaxis use against the incidence of leptospirosis (RR = 0.31; 95% CI: 0.20, 0.48). Antibiotic prophylaxis for leptospirosis had been shown to be effective in preventing the incidence of the disease among high-risk populations and carries minimal adverse effects. It is recommended that the practice of antibiotic prophylaxis for leptospirosis is included in the standard protocol for leptospirosis prevention among people at high-risk, including disaster response teams and patrons of eco-sports tourism activities; with the drug of choice being doxycycline, either as a single 200 mg dose or weekly dose of 200 mg for the duration of exposure, based on the setting, duration of event and resources available

Phase I clinical study of the recombinant antibody toxin scFv(FRP5)-ETA specific for the ErbB2/HER2 receptor in patients with advanced solid malignomas

INTRODUCTION: ScFv(FRP5)-ETA is a recombinant antibody toxin with binding specificity for ErbB2 (HER2). It consists of an N-terminal single-chain antibody fragment (scFv), genetically linked to truncated Pseudomonas exotoxin A (ETA). Potent antitumoral activity of scFv(FRP5)-ETA against ErbB2-overexpressing tumor cells was previously demonstrated in vitro and in animal models. Here we report the first systemic application of scFv(FRP5)-ETA in human cancer patients. METHODS: We have performed a phase I dose-finding study, with the objective to assess the maximum tolerated dose and the dose-limiting toxicity of intravenously injected scFv(FRP5)-ETA. Eighteen patients suffering from ErbB2-expressing metastatic breast cancers, prostate cancers, head and neck cancer, non small cell lung cancer, or transitional cell carcinoma were treated. Dose levels of 2, 4, 10, 12.5, and 20 μg/kg scFv(FRP5)-ETA were administered as five daily infusions each for two consecutive weeks. RESULTS: No hematologic, renal, and/or cardiovascular toxicities were noted in any of the patients treated. However, transient elevation of liver enzymes was observed, and considered dose limiting, in one of six patients at the maximum tolerated dose of 12.5 μg/kg, and in two of three patients at 20 μg/kg. Fifteen minutes after injection, peak concentrations of more than 100 ng/ml scFv(FRP5)-ETA were obtained at a dose of 10 μg/kg, indicating that predicted therapeutic levels of the recombinant protein can be applied without inducing toxic side effects. Induction of antibodies against scFv(FRP5)-ETA was observed 8 days after initiation of therapy in 13 patients investigated, but only in five of these patients could neutralizing activity be detected. Two patients showed stable disease and in three patients clinical signs of activity in terms of signs and symptoms were observed (all treated at doses ≥ 10 μg/kg). Disease progression occurred in 11 of the patients. CONCLUSION: Our results demonstrate that systemic therapy with scFv(FRP5)-ETA can be safely administered up to a maximum tolerated dose of 12.5 μg/kg in patients with ErbB2-expressing tumors, justifying further clinical development

Proceedings of Abstracts, School of Physics, Engineering and Computer Science Research Conference 2022

© 2022 The Author(s). This is an open-access work distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. For further details please see https://creativecommons.org/licenses/by/4.0/. Plenary by Prof. Timothy Foat, ‘Indoor dispersion at Dstl and its recent application to COVID-19 transmission’ is © Crown copyright (2022), Dstl. This material is licensed under the terms of the Open Government Licence except where otherwise stated. To view this licence, visit http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3 or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email: [email protected] present proceedings record the abstracts submitted and accepted for presentation at SPECS 2022, the second edition of the School of Physics, Engineering and Computer Science Research Conference that took place online, the 12th April 2022