Browsing by Author "Simon L. Croft"

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Case study for a vaccine against leishmaniasis
(2013) Jorge Alvar; Simon L. Croft; Paul Kaye; Ali Khamesipour; Shyam Sundar; Steven G. Reed
Leishmaniasis in many ways offers a unique vaccine case study. Two reasons for this are that leishmaniasis is a disease complex caused by several different species of parasite that are highly related, thus raising the possibility of developing a single vaccine to protect against multiple diseases. Another reason is the demonstration that a leishmaniasis vaccine may be used therapeutically as well as prophylactically. Although there is no registered human leishmaniasis vaccine today, immunization approaches using live or killed organisms, as well as defined vaccine candidates, have demonstrated at least some degree of efficacy in humans to prevent and to treat some forms of leishmaniasis, and there is a vigorous pipeline of candidates in development. Current approaches include using individual or combined antigens of the parasite or of salivary gland extract of the parasites' insect vector, administered with or without formulation in adjuvant. Animal data obtained with several vaccine candidates are promising and some have been or will be entered into clinical testing in the near future. There is sufficient scientific and epidemiological justification to continue to invest in the development of vaccines against leishmaniasis. © 2012 Elsevier Ltd.
Drug resistance in leishmaniasis
(2006) Simon L. Croft; Shyam Sundar; Alan H. Fairlamb
Leishmaniasis is a complex disease, with visceral and cutaneous manifestations, and is caused by over 15 different species of the protozoan parasite genus Leishmania. There are significant differences in the sensitivity of these species both to the standard drugs, for example, pentavalent antimonials and miltefosine, and those on clinical trial, for example, paromomycin. Over 60% of patients with visceral leishmaniasis in Bihar State, India, do not respond to treatment with pentavalent antimonials. This is now considered to be due to acquired resistance. Although this class of drugs has been used for over 60 years for leishmaniasis treatment, it is only in the past 2 years that the mechanisms of action and resistance have been identified, related to drug metabolism, thiol metabolism, and drug efflux. With the introduction of new therapies, including miltefosine in 2002 and paromomycin in 2005-2006, it is essential that there be a strategy to prevent the emergence of resistance to new drugs; combination therapy, monitoring of therapy, and improved diagnostics could play an essential role in this strategy. Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Leishmaniasis: New approaches to disease control
(BMJ Publishing Group, 2003) Clive R. Davies; Paul Kaye; Simon L. Croft; Shyam Sundar
Leishmaniasis is one of the major infectious diseases affecting the poorest regions of the world, but new developments in diagnosis, treatment, and control offer some fresh hope.
Mechanisms of experimental resistance of Leishmania to miltefosine: Implications for clinical use
(2006) F. Javier Pérez-Victoria; María P. Sánchez-Cañete; Karin Seifert; Simon L. Croft; Shyam Sundar; Santiago Castanys; Francisco Gamarro
Miltefosine (hexadecylphosphocholine, MIL), registered as Impavido®, has become the first oral drug for the treatment of visceral and cutaneous leishmanasis. MIL is a simple molecule, very stable, relatively safe and highly efficient in clinical trials. However, MIL requires a long treatment course (28 days) and has a long half-life (around 150 h), which might accelerate the emergence of drug resistance in case of inadequate use. The mechanisms of MIL resistance have been studied in vitro with experimental resistant lines. Resistance was shown to develop quickly in Leishmania promastigotes. Interestingly, a decreased MIL accumulation has always accounted for the resistance phenotype. The lower MIL accumulation can be achieved by two independent mechanisms: (i) an increase in drug efflux, mediated by the overexpression of the ABC transporter P-glycoprotein, and (ii) a decrease in drug uptake, which is easily achieved by the inactivation of any one of the two proteins known to be responsible for the MIL uptake, the MIL transporter LdMT and its beta subunit LdRos3. Policies concerning a proper use of this drug should be followed and supervised by health authorities of endemic areas to minimalize the risk for the appearance of drug failures and to ensure a long life span for this effective oral drug. © 2006 Elsevier Ltd. All rights reserved.
The development of a global research agenda and individual participant data platform for visceral leishmaniasis: challenges and future opportunities
(BioMed Central Ltd, 2025) Sauman Singh-Phulgenda; Prabin Dahal; Brittany J. Maguire; Jorge Alvar; Fabiana Piovesan Alves; Mitali Chatterjee; Carlos Henrique Nery Costa; Simon L. Croft; Philippe Jean Jean Guérin; Dinesh K. Mondal; Ahmed Mudawi Musa; Krishna Pandey; Koert Ritmeijer; G. A.s. Romero; Santhanam Sundar
Background: Visceral leishmaniasis (VL) is one of the neglected tropical diseases (NTDs) listed by the World Health Organization (WHO). The disease is currently in the elimination phase in the Indian subcontinent (ISC) and being targeted for elimination by 2030 in East Africa (EA). Maintaining the necessary financial and political commitments to achieve and sustain the current elimination efforts remains challenging. As with other NTDs, VL research is constrained by limited funding, and drug development has relied largely on partnerships between not-for-profit organisations and the pharmaceutical industry. Conducting robust clinical studies remains difficult, and therapeutic innovations have been limited. However, re-use of existing data offers an untapped opportunity to generate new evidence. Methods: We describe the process of developing a global VL research agenda and the establishment of an individual participant data (IPD) platform at the Infectious Diseases Data Observatory (IDDO). Key steps included a systematic scoping review of VL clinical trials, consultations with the Scientific Advisory Committee, expert and public reviews, and implementation of an equitable governance framework to harmonise and share IPD. Results: The VL research agenda, finalised in 2019, identified priority methodological and clinical questions suited to IPD analyses. The IDDO VL platform currently hosts harmonised data from nearly 15,000 patients across more than 50 studies (VL and post-kala-azar dermal leishmaniasis, PKDL). The platform is an inclusive resource guided by an equitable governance framework and provides a critical asset to support new evidence generation and can serve as a historical data to support accelerated drug development. Conclusions: The development of a global VL research agenda has provided an inventory of priority research questions of public health importance. A shared IPD platform aligned with this agenda was developed to complement ongoing global efforts. In addition, such a platform can accelerate secondary evidence generation, support methodological innovation and inform future trial designs and policy. Sustained collaboration and investment are needed to maximise the scientific and public health value of data re-use in VL and PKDL. © The Author(s) 2025.