Prof Jeremy Farrar
| Research Area: | Global Health |
|---|---|
| Keywords: | influenza, dengue and tuberculous |
Jeremy Farrar's research interests include the interplay between infections and the immune system as well as the pathophysiology and treatment of bacterial meningitis, tuberculous meningitis, tetanus, malaria, influenza, dengue haemorrhagic fever and Japanese B encephalitis.
There are no collaborations listed for this principal investigator.
2005. The clinical benefit of adjunctive dexamethasone in tuberculous meningitis is not associated with measurable attenuation of peripheral or local immune responses. Journal of immunology (Baltimore, Md. : 1950), 175 (1), pp. 579-90. Read abstract | View on PubMed
Outcome from tuberculous meningitis (TBM) is believed to be dependent on the severity of the intracerebral inflammatory response. We have recently shown that dexamethasone improved survival in adults with TBM and postulated that the clinical effect would be associated with a measurable systemic and intracerebral impact on immunological markers of inflammation. Prolonged inflammatory responses were detected in all TBM patients irrespective of treatment assignment (placebo or dexamethasone). The inflammatory response in the cerebrospinal fluid was characterized by a leukocytosis (predominantly CD3(+)CD4(+) T lymphocytes, phenotypically distinct from those in the peripheral blood), elevated concentrations of inflammatory and anti-inflammatory cytokines, chemokines, and evidence of prolonged blood-brain barrier dysfunction. Dexamethasone significantly modulated acute cerebrospinal fluid protein concentrations and marginally reduced IFN-gamma concentrations; other immunological and routine biochemical indices of inflammation were unaffected. Peripheral blood monocyte and T cell responses to Mycobacterium tuberculosis Ags were also unaffected. Dexamethasone does not appear to improve survival from TBM by attenuating immunological mediators of inflammation in the subarachnoid space or by suppressing peripheral T cell responses to mycobacterial Ags. These findings challenge previously held theories of corticosteroid action in this disease. An understanding of how dexamethasone acts in TBM may suggest novel and more effective treatment strategies. Hide abstract
2004. Comparative pharmacokinetics of intramuscular artesunate and artemether in patients with severe falciparum malaria. Antimicrobial agents and chemotherapy, 48 (11), pp. 4234-9. Read abstract | View on PubMed
The first-dose pharmacokinetic properties of intramuscular (i.m.) artesunate (ARTS; 2.4 mg/kg immediately [stat], followed by 1.2 mg/kg i.m. daily) and artemether (ARM; 3.2 mg/kg i.m. stat, followed by 1.6 mg/kg i.m. daily) were compared in Vietnamese adults with severe falciparum malaria. A total of 19 patients were studied; 9 received ARTS, and 10 received ARM. ARTS was absorbed very rapidly; concentrations in plasma peaked between 1,362 and 8,388 nmol/liter (median, 5,710 nmol/liter) within 20 min of injection and then declined with a median (range) half-life (t(1/2)) of 30 (3 to 67) min. ARTS was hydrolyzed rapidly and completely to the biologically active metabolite dihydroartemisinin (DHA). Peak DHA concentrations in plasma ranged between 1,718 and 7,080 nmol/liter (median, 3,060 nmol/liter) and declined with a t(1/2) of 52 (26 to 69) min. In contrast, ARM was slowly and erratically absorbed. The absorption profile appeared biphasic. Maximum ARM concentrations in plasma ranged between 67 nmol/liter (a value close to the 50% inhibitory concentration for some Plasmodium falciparum isolates) and 1,631 nmol/liter (median, 574 nmol/liter) and occurred at a median (range) of 10 (1.5 to 24) h. There was relatively little conversion to DHA. After i.m. injection in cases of severe malaria, absorption of the water-soluble ARTS is rapid and extensive, whereas the oil-based ARM is slowly and erratically absorbed, with relatively little conversion to the more active DHA. On the basis of this pharmacological study, parenteral ARTS is preferable to ARM as an initial antimalarial therapy, particularly in the most seriously ill patients. These findings should be formally assessed by a randomized clinical trial. Hide abstract
2005. Diarrhoea as a presentation of bird flu infection: a summary on its correlation to outcome in Thai cases. Gut, 54 (10), pp. 1506. View on PubMed
2004. Crossing the species barrier--one small step to man, one giant leap to mankind. The New England journal of medicine, 350 (12), pp. 1171-2. View on PubMed
2005. Avian influenza A (H5N1) infection in humans. The New England journal of medicine, 353 (13), pp. 1374-85. View on PubMed
2004. Drug combinations for malaria: time to ACT? Lancet, 363 (9402), pp. 3-4. View on PubMed
2006. Pretreatment intracerebral and peripheral blood immune responses in Vietnamese adults with tuberculous meningitis: diagnostic value and relationship to disease severity and outcome. Journal of immunology (Baltimore, Md. : 1950), 176 (3), pp. 2007-14. Read abstract | View on PubMed
Tuberculous meningitis (TBM) is the most devastating form of tuberculosis. Both intracerebral and peripheral blood immune responses may be relevant to pathogenesis, diagnosis, and outcome. In this study, the relationship between pretreatment host response, disease phenotype, and outcome in Vietnamese adults with TBM was examined. Before treatment, peripheral blood IFN-gamma ELISPOT responses to the Mycobacterium tuberculosis Ags ESAT-6, CFP-10, and purified protein derivative (PPD) were a poor diagnostic predictor of TBM. Cerebrospinal fluid IL-6 concentrations at presentation were independently associated with severe disease presentation, suggesting an immunological correlate of neurological damage before treatment. Surprisingly however, elevated cerebrospinal fluid inflammatory cytokines were not associated with death or disability in HIV-negative TBM patients at presentation. HIV coinfection attenuated multiple cerebrospinal fluid inflammatory indices. Low cerebrospinal fluid IFN-gamma concentrations were independently associated with death in HIV-positive TBM patients, implying that IFN-gamma contributes to immunity and survival. Collectively, these results reveal the effect of HIV coinfection on the pathogenesis of TBM and suggest that intracerebral immune responses, at least in HIV-negative cases, may not be as intimately associated with disease outcome as previously thought. Hide abstract
2005. Oseltamivir resistance--disabling our influenza defenses. The New England journal of medicine, 353 (25), pp. 2633-6. View on PubMed
Population Genetics of Influenza Surveillance in Vietnam
Surveillance for potentially pandemic influenza viruses requires an understanding the avian reservoir of the influenza virus, the population-genetic structure of the virus in birds, and the possibilities for viral transmission from birds to humans. One of the most important genetic processes that needs to be understood and made rapidly identifiable from influenza samples is the reassortment of influenza’s RNA segments which can create a virus with partially avian and partially human genes. ...
Evolutionary Epidemiology of Influenza
A PhD student position is available at the Oxford University Clinical Research Unit in Viet Nam (www.oucru.org) under the joint supervision of Jeremy Farrar and Maciej Boni. The student should have a background in one or some of mathematical modeling, evolutionary biology, ecology, bioinformatics, population genetics, and/or computer science. The evolutionary biology of influenza is a rich field covering a variety of short-term and long-term processes that drive the virus’ evolution. ...
Theoretical Population Genetics, Theoretical Population Dynamics, and Disease
A PhD student position is available at the Oxford University Clinical Research Unit (www.oucru.org), under the joint supervision of Peter Horby, Maciej Boni and Jeremy Farrar. The student should have a background in one or some of mathematics, dynamical systems theory, stochastic processes, mathematical modeling, population genetics, evolutionary biology, ecology, and/or computer science. Mathematical modeling in population biology and population genetics can provide critical insight into ...
