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Fulltext Dengue vaccine design: issues and challenges

Cardosa MJ

Br Med Bull, 1998;54(2):395-405.
PMID: 9830205 DOI: 10.1093/oxfordjournals.bmb.a011696

Dengue virus infection is now a global problem affecting tens of millions of people. The spread of the four dengue virus serotypes had led to increased incidence of dengue haemorrhagic fever (DHF) reported and with 2.5 billion people at risk, efforts towards the development of safe and effective vaccines against dengue must be accelerated. This chapter reviews some of the important lessons of pathogenesis which may be learnt from classical studies in the field and place these in the context of current knowledge about the molecular biology of the virus. The issues which have to be addressed in designing a safe vaccine against dengue are raised and the problems of designing subunit as well as whole virus vaccines are pointed out, particularly with regard to the phenomenon of antibody dependent enhancement and, more generally, the problem of immune potentiation of disease. More efforts must be made to understand the basis of pathogenesis in DHF and in finding out what nature has to teach about protection against and recovery from dengue virus infection.
Chemotherapy of malaria

Davey DG

Br Med Bull, 1951;8:37-46.
DOI: 10.1093/oxfordjournals.bmb.a074052

Until the early thirties the chemotherapy of malaria was comparatively simple, even if unsatisfactory. Quinine, inherited from the seventeenth century, still held sway, and directions for its use were fairly straightforward, although the experts, of course, each had a particularly favoured way of using it A second drug, plasmoquine (pamaquin)1, heralded with an appropriate fanfare because it was the first synthetic drug for malaria, appeared in 1926, but in the early thirties it was still in an experimental stage, and in any event no one suggested that it would rival quinine or that it would have more than special uses ancillary to quinine. Then, in 1931, atebrin (mepacrine) was announced, and as research with it proceeded, particularly by Field and his colleagues in Malaya, it became clear that the role of quinine was being challenged. If war had not broken out in 1939 the outcome of the challenge would, perhaps, never have been properly known, for the Germans had pushed on from atebrin and developed resochin (chloroquine) and sontochin (sontoquine) both of which were receiving field trials when war came. © 1951, Oxford University Press. All rights reserved.
Drug repurposing for COVID-19: current evidence from randomized controlled adaptive platform trials and living systematic reviews

Augustin Y, Staines HM, Velavan TP, Kamarulzaman A, Kremsner PG, Krishna S

Br Med Bull, 2023 Sep 12;147(1):31-49.
PMID: 37312588 DOI: 10.1093/bmb/ldac037

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic resulted in a race to develop effective treatments largely through drug repurposing via adaptive platform trials on a global scale. Drug repurposing trials have focused on potential antiviral therapies aimed at preventing viral replication, anti-inflammatory agents, antithrombotic agents and immune modulators through a number of adaptive platform trials. Living systematic reviews have also enabled evidence synthesis and network meta-analysis as clinical trial data emerge globally.
SOURCES OF DATA: Recent published literature.
AREAS OF AGREEMENT: Corticosteroids and immunomodulators that antagonize the interleukin-6 (IL-6) receptor have been shown to play a critical role in modulating inflammation and improving clinical outcomes in hospitalized patients. Inhaled budesonide reduces the time to recovery in older patients with mild-to-moderate COVID-19 managed in the community.
AREAS OF CONTROVERSY: The clinical benefit of remdesivir remains controversial with conflicting evidence from different trials. Remdesivir led to a reduction in time to clinical recovery in the ACTT-1 trial. However, the World Health Organization SOLIDARITY and DISCOVERY trial did not find a significant benefit on 28-day mortality and clinical recovery.
GROWING POINTS: Other treatments currently being investigated include antidiabetic drug empagliflozin, antimalarial drug artesunate, tyrosine kinase inhibitor imatinib, immunomodulatory drug infliximab, antiviral drug favipiravir, antiparasitic drug ivermectin and antidepressant drug fluvoxamine.
AREAS TIMELY FOR DEVELOPING RESEARCH: The timing of therapeutic interventions based on postulated mechanisms of action and the selection of clinically meaningful primary end points remain important considerations in the design and implementation of COVID-19 therapeutic trials.

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