Archive for December 13, 2014

Sex Differences in Pediatric Infectious Diseases

Journal of Infectious Diseases July 15, 2014 V.209 SUPL.3 S120-S126

Maximilian Muenchhoff1 and Philip J. R. Goulder1,2

1Department of Paediatrics, University of Oxford, United Kingdom

2HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa

Correspondence: Prof Philip J. R. Goulder, Department of Paediatrics, University of Oxford, Peter Medawar Bldg for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK v(philip.goulder@paediatrics.ox.ac.uk).

Abstract

The success of the immune response is finely balanced between, on the one hand, the need to engage vigorously with, and clear, certain pathogens; and, on the other, the requirement to minimize immunopathology and autoimmunity.

Distinct immune strategies to achieve this balance have evolved in females and males and also in infancy through to adulthood. Sex differences in outcome from a range of infectious diseases can be identified from as early as fetal life, such as in congenital cytomegalovirus infection.

The impact of sex hormones on the T-helper 1/T-helper 2 cytokine balance has been proposed to explain the higher severity of most infectious diseases in males. In the minority where greater morbidity and mortality is observed in females, this is hypothesized to arise because of greater immunopathology and/or autoimmunity.

However, a number of unexplained exceptions to this rule are described. Studies that have actually measured the sex differences in children in the immune responses to infectious diseases and that would further test these hypotheses, are relatively scarce.

PDF

http://jid.oxfordjournals.org/content/209/suppl_3/S120.full.pdf+html

 

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December 13, 2014 at 5:43 pm

Dengue Human Infection Models Supporting Drug Development

Journal of Infectious Diseases June 15, 2014 V.209 SUPPL.2 S66-S70

James Whitehorn1,3, Vinh Chau Nguyen Van4 and Cameron P. Simmons2,3,5

1Department of Clinical Research, London School of Hygiene and Tropical Medicine

2Centre for Tropical Medicine, Oxford University, United Kingdom

3Oxford University Clinical Research Unit, Hospital for Tropical Diseases

4Directorate, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

5Nossal Institute for Global Health and Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia

Correspondence: Cameron P. Simmons, BSC (Hons), PhD, (csimmons@oucru.org).

Abstract

Dengue is a arboviral infection that represents a major global health burden. There is an unmet need for effective dengue therapeutics to reduce symptoms, duration of illness and incidence of severe complications. Here, we consider the merits of a dengue human infection model (DHIM) for drug development.

A DHIM could allow experimentally controlled studies of candidate therapeutics in preselected susceptible volunteers, potentially using smaller sample sizes than trials that recruited patients with dengue in an endemic country. In addition, the DHIM would assist the conduct of intensive pharmacokinetic and basic research investigations and aid in determining optimal drug dosage.

Furthermore, a DHIM could help establish proof of concept that chemoprophylaxis against dengue is feasible.

The key challenge in developing the DHIM for drug development is to ensure the model reliably replicates the typical clinical and laboratory features of naturally acquired, symptomatic dengue.

PDF

http://jid.oxfordjournals.org/content/209/suppl_2/S66.full.pdf+html

December 13, 2014 at 5:41 pm

PlasmoView: A Web-based Resource to Visualise Global Plasmodium falciparum Genomic Variation

Journal of Infectious Diseases June 1, 2014 V.209 N.11 P.1808-1815

Mark D. Preston1, Samuel A. Assefa1, Harold Ocholla2,3, Colin J. Sutherland1, Steffen Borrmann4,5, Alexis Nzila6,7, Pascal Michon8, Tran Tinh Hien9, Teun Bousema1, Christopher J. Drakeley1, Issaka Zongo10, Jean-Bosco Ouédraogo11, Abdoulaye A. Djimde12,13, Ogobara K. Doumbo14, Francois Nosten15,16,17, Rick M. Fairhurst18, David J. Conway1, Cally Roper1 and Taane G. Clark1

1Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom

2Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre 3, Malawi

3Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom

4KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya

5Department of Infectious Diseases, Heidelberg University School of Medicine, Heidelberg 69120, Germany

6KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya

7King Fahd University of Petroleum and Minerals, PO Box 468, Dhahran 31262, Kingdom of Saudi Arabia

8Papua New Guinea Institute of Medical Research, PO Box 483, Madang, Papua New Guinea

9Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Hospital for Tropical Diseases, District 5, Ho Chi Minh City, Vietnam

10Institut de Recherche en Sciences de la Sant, Bobo–Dioulasso, Burkina Faso

11Institut de Recherche en Sciences de la Sant, BP 545, Bobo-Dioulasso 01, Burkina Faso

12Malaria Research and Training Centre, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali

13Wellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom

14Malaria Research and Training Centre, Faculty of Medicine, Pharmacy and Dentistry, University of Bamako, Bamako, Mali

15Mahidol-Oxford Tropical Medicine Research Unit, Bangkok 10400, Thailand

16Centre for Tropical Medicine, University of Oxford, Oxford OX3 7LJ, United Kingdom

17Shoklo Malaria Research Unit, Mae Sot TAK 63110, Thailand

18Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA

Correspondence: Dr Mark D. Preston, Department of Pathogen Molecular Biology, LSHTM, Keppel Street, London, UK (mark.preston@lshtm.ac.uk).

Abstract

Malaria is a global public health challenge, with drug resistance a major barrier to disease control and elimination. To meet the urgent need for better treatments and vaccines, a deeper knowledge of Plasmodium biology and malaria epidemiology is required.

An improved understanding of the genomic variation of malaria parasites, especially the most virulent Plasmodium falciparum (Pf) species, has the potential to yield new insights in these areas. High-throughput sequencing and genotyping is generating large amounts of genomic data across multiple parasite populations.

The resulting ability to identify informative variants, particularly single-nucleotide polymorphisms (SNPs), will lead to the discovery of intra- and inter-population differences and thus enable the development of genetic barcodes for diagnostic assays and clinical studies. Knowledge of genetic variability underlying drug resistance and other differential phenotypes will also facilitate the identification of novel mutations and contribute to surveillance and stratified medicine applications.

The PlasmoView interactive web-browsing tool enables the research community to visualise genomic variation and annotation (eg, biological function) in a geographic setting. The first release contains over 600 000 high-quality SNPs in 631 Pf isolates from laboratory strains and four malaria-endemic regions (West Africa, East Africa, Southeast Asia and Oceania).

PDF

http://jid.oxfordjournals.org/content/209/11/1808.full.pdf+html

 

December 13, 2014 at 5:38 pm


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