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1. Deaths from symptomatically identifiable furious rabies in India: a nationally representative mortality survey.

Author

Wilson Suraweera, Shaun K Morris, Rajesh Kumar, David A Warrell, Mary J Warrell, Prabhat Jha, and Million Death Study Collaborators

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

It is estimated that India has more deaths from rabies than any other country. However, existing estimates are indirect and rely on non-representative studies.We examined rabies deaths in the ongoing Million Death Study (MDS), a representative survey of over 122,000 deaths in India that uses enhanced types of verbal autopsy. We estimated the age-specific mortality rates of symptomatically identifiable furious rabies and its geographic and demographic distributions. A total of 140 deaths in our sample were caused by rabies, suggesting that in 2005 there were 12,700 (99% CI 10,000 to 15,500) symptomatically identifiable furious rabies deaths in India. Most rabies deaths were in males (62%), in rural areas (91%), and in children below the age of 15 years (50%). The overall rabies mortality rate was 1.1 deaths per 100,000 population (99%CI 0.9 to 1.4). One third of the national rabies deaths were found in Uttar Pradesh (4,300) and nearly three quarters (8,900) were in 7 central and south-eastern states: Chhattisgarh, Uttar Pradesh, Odisha, Andhra Pradesh, Bihar, Assam, and Madhya Pradesh.Rabies remains an avoidable cause of death in India. As verbal autopsy is not likely to identify atypical or paralytic forms of rabies, our figure of 12,700 deaths due to classic and clinically identifiable furious rabies underestimates the total number of deaths due to this virus. The concentrated geographic distribution of rabies in India suggests that a significant reduction in the number of deaths or potentially even elimination of rabies deaths is possible.

Published
2012
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2. A simplified 4-site economical intradermal post-exposure rabies vaccine regimen: a randomised controlled comparison with standard methods.

Author

Mary J Warrell, Anna Riddell, Ly-Mee Yu, Judith Phipps, Linda Diggle, Hervé Bourhy, Jonathan J Deeks, Anthony R Fooks, Laurent Audry, Sharon M Brookes, François-Xavier Meslin, Richard Moxon, Andrew J Pollard, and David A Warrell

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

The need for economical rabies post-exposure prophylaxis (PEP) is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID) vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods.Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90); or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available.All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method.This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be introduced without further studies.Controlled-Trials.com ISRCTN 30087513.

Published
2008
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3. Rabies post-exposure vaccination in 2 visits within a week: A 4-site intradermal regimen

Author

Mary J. Warrell

Subjects
Pediatrics, medicine.medical_specialty, Injections, Intradermal, Rabies, 030231 tropical medicine, Context (language use), World Health Organization, Off-label use, Vial, Drug Administration Schedule, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, Bites and Stings, 030212 general & internal medicine, Immunization Schedule, General Veterinary, General Immunology and Microbiology, business.industry, Vaccination, Public Health, Environmental and Occupational Health, medicine.disease, Regimen, Infectious Diseases, Rabies Vaccines, Immunization, Rabies virus, Practice Guidelines as Topic, Molecular Medicine, Post-Exposure Prophylaxis, business, Encephalitis
Abstract

Rabies is fatal in all unvaccinated patients bitten by dogs, and so post-exposure vaccine regimens must be robust enough to ensure their survival under all conditions. Treatment tends to be excessive for most people, but there is justified anxiety about reducing vaccine dosage and shortening regimens. Recently, World Health Organisation (WHO) recommended one week primary post-exposure intradermal regimens requiring 3 clinic visits, but these are unlikely to prove economical where rabies vaccination is most needed, in deprived rural areas of Africa and Asia. A highly immunogenic regimen involving two doses of intradermal vaccine given one week apart has advantages over other regimens. Anyone exposed to a possibly rabid animal would be given intradermal (ID) injections at 4 sites using a whole vial of vaccine. Those who had not been previously vaccinated would be given 2-site ID injections using half a vial one week later. Those who might be immunosuppressed could be given an optional single ID dose on day 28. The rationale for this regimen is discussed in the context of the recently revised WHO recommendations for rabies prophylaxis.

Published
2019

4. Time to revise the strategy for Gavi funding of rabies vaccine?

Author

Mary J. Warrell

Subjects
2019-20 coronavirus outbreak, medicine.medical_specialty, Asia, Coronavirus disease 2019 (COVID-19), Rabies, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Health Services Accessibility, Rabies vaccine, Pandemic, Medicine, Humans, Pandemics, business.industry, Immunization Programs, SARS-CoV-2, Public health, COVID-19, General Medicine, medicine.disease, Virology, Rabies Vaccines, Africa, Public Health, business, medicine.drug
Published
2020

5. Colorado tick fever and other arthropod-borne reoviruses

Author

Mary J. Warrell and David A. Warrell

Abstract

Human pathogens are found in six genera of Reoviridae: Reovirus, Rotavirus, Orthoreovirus, and three arthropod-borne genera: Coltivirus (Colorado tick fever, Salmon River virus, and Eyach viruses); Orbivirus (Kemerovo, Changuinola, Orungo, and Lebombo); and Seadornavirus (Banna virus). Colorado tick fever is common in parts of north-western North America; acquired from tick (ixodid) bites, most often by hikers and campers, presenting 3–6 days later with sudden fever, rigors, generalized aches, myalgia, headache and backache, rashes (12%), and gastrointestinal symptoms (20%). Diagnosis is confirmed by detection of viral antigen in erythrocytes or serum, or by serodiagnosis. Management is symptomatic. Illness usually resolves in 10–14 days, but convalescence may be prolonged. Prevention is by avoiding, repelling, and rapidly removing ticks; no vaccines are available.

Published
2020

6. Rhabdoviruses: Rabies and rabies-related lyssaviruses

Author

David A. Warrell and Mary J. Warrell

Subjects
medicine, Rabies, Biology, medicine.disease, Virology
Abstract

The Rhabdoviridae are a large family of RNA viruses, two genera of which infect animals: the genus Lyssavirus contains rabies and rabies-related viruses that cause at least 55,000 deaths annually in Asia and Africa. The risks and problems posed by rabies and other lyssaviruses vary across the world. Viruses can penetrate broken skin and intact mucosae. Humans are usually infected when virus-laden saliva is inoculated through the skin by the bite of a rabid animal, usually a dog. Although the greatest threat to man is the persistent cycle of infection in stray dogs, several other terrestrial mammal species are reservoirs of infection. In the Americas, bat viruses and also classic type 1 rabies and insectivorous bats have become the principal vectors of infection to humans in the United States of America. Elsewhere in the world, there is increasing evidence of widespread rabies-related lyssavirus infection of bats.

Published
2020

7. Simplification of Rabies Postexposure Prophylaxis: A New 2-Visit Intradermal Vaccine Regimen

Author

Mary J. Warrell

Subjects
Pediatrics, medicine.medical_specialty, Asia, Injections, Intradermal, Rabies, 030231 tropical medicine, World Health Organization, Vial, Rabies vaccination, Perspective Piece, 03 medical and health sciences, 0302 clinical medicine, Who recommendations, Virology, medicine, Humans, Rabies prophylaxis, Immunization Schedule, Clinical Trials as Topic, business.industry, medicine.disease, Vaccination, Regimen, Infectious Diseases, Immunization, Rabies Vaccines, Rabies virus, Africa, Parasitology, business, Post-Exposure Prophylaxis
Abstract

A 2-visit multiple-site intradermal (ID) vaccine protocol would be the most economical, immunogenic, and practicable regimen for postexposure rabies prophylaxis (PEP) in clinics seeing few patients a month. This regimen with an additional day 28 dose is now recommended by the WHO. The difficulties surrounding ID rabies vaccination have hindered progress in provision of prophylaxis, especially in rural Asia and Africa. Although the latest WHO recommendations include 1-week ID postexposure vaccine regimens, these are unlikely to prove economical where rabies vaccination is presently unavailable. The new protocol uses a whole vial of vaccine divided between 4-sites ID on the first day and half a vial at 2-sites ID on day 7. Gavi has recently approved support for rabies PEP. This 2-visit 4-site ID regimen, with or without a day 28 dose, should be considered for implementation in this remarkable new initiative.

Published
2019

8. The imperative of palliation in the management of rabies encephalomyelitis

Author

Arnaud Tarantola, David A. Warrell, Mary J. Warrell, University of Oxford, Oxford Vaccine Group, John Radcliffe Hospital [Oxford University Hospital], Institut Pasteur de Nouvelle-Calédonie, and Réseau International des Instituts Pasteur (RIIP)

Subjects
medicine.medical_specialty, Palliative care, palliation, diagnosis, Encephalomyelitis, [SDV]Life Sciences [q-bio], 030231 tropical medicine, lcsh:Medicine, rabies, Disease, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Public health surveillance, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Intensive care, medicine, 030212 general & internal medicine, Intensive care medicine, General Immunology and Microbiology, treatment, business.industry, lcsh:R, Rabies virus, Public Health, Environmental and Occupational Health, medicine.disease, Surgery, Vaccination, Infectious Diseases, encephalomyelitis, Rabies, business
Abstract

International audience; The aim of this review is to guide clinicians in the practical management of patients suffering from rabies encephalomyelitis. This condition is eminently preventable by modern post-exposure vaccination, but is virtually always fatal in unvaccinated people. In the absence of any proven effective antiviral or other treatment, palliative care is an imperative to minimise suffering. Suspicion of rabies encephalomyelitis depends on recognising the classic symptomatology and eliciting a history of exposure to a possibly rabid mammal. Potentially treatable differential diagnoses must be eliminated, notably other infective encephalopathies. Laboratory confirmation of suspected rabies is not usually possible in many endemic areas, but is essential for public health surveillance. In a disease as agonising and terrifying as rabies encephalomyelitis, alleviation of distressing symptoms is the primary concern and overriding responsibility of medical staff. Calm, quiet conditions should be created, allowing relatives to communicate with the dying patient in safety and privacy. Palliative management must address thirst and dehydration, fever, anxiety, fear, restlessness, agitation, seizures, hypersecretion, and pain. As the infection progresses, coma and respiratory, cardiovascular, neurological, endocrine, or gastrointestinal complications will eventually ensue. When the facilities exist, the possibility of intensive care may arise, but although some patients may survive, they will be left with severe neurological sequelae. Recovery from rabies is extremely rare, and heroic measures with intensive care should be considered only in patients who have been previously vaccinated, develop rabies antibody within the first week of illness, or were infected by an American bat rabies virus. However, in most cases, clinicians must have the courage to offer compassionate palliation whenever the diagnosis of rabies encephalomyelitis is inescapable.

Published
2018

9. Rabies and Rabies-Related Viruses

Author

David A. Warrell and Mary J. Warrell

Subjects
business.industry, medicine, Rabies, medicine.disease, business, Virology
Published
2017

10. List of Contributors

Author

Fredrick M. Abrahamian, Michael J. Aldape, Edelweiss Aldasoro, Upton D. Allen, Hythem Al-Sum, Milan J. Anadkat, Katherine Anders, Emmanouil Angelakis, Brian John Angus, Anastasia Antoniadou, Fabio Arena, Joop E. Arends, Jose R. Arribas, Andrew W. Artenstein, John C. Atherton, John N. Aucott, Tar-Ching Aw, Hilary M. Babcock, Robin Bailey, Thomas C. Bailey, Adam Z. Banks, David J. Barillo, Ernie-Paul Barrette, Martijn P. Bauer, Roger Bayston, C. Ben Beard, Justin Beardsley, Nick J. Beeching, Rodolfo E. Bégué, Guido Beldi, Constance A. Benson, Elie F. Berbari, Jean-Michel Berenger, Christoph Berger, Jose I. Bernardino, Jacques Bille, Alexander C. Billioux, Ari Bitnun, Iain Blair, Stéphane Blanche, Thomas P. Bleck, Chantal P. Bleeker-Rovers, Gijs Bleijenberg, Karen C. Bloch, Johannes Blum, Emily A. Blumberg, Robert A. Bonomo, Marc J.M. Bonten, Rafik Bourayou, Emilio Bouza, K. Ashley Brandt, Florence Bretelle, Sylvain Brisse, Warwick J. Britton, Itzhak Brook, Matthijs C. Brouwer, Sarah K. Browne, Amy E. Bryant, Silja Bühler, Eileen M. Bulger, R. Mark L. Buller, Leah A. Burke, Christian Burri, Marcus W. Butler, Thierry Calandra, David P. Calfee, Antonia Calvo-Cano, D. William Cameron, Joseph A. Carcillo, Gail Carson, Stephen T. Chambers, Remi N. Charrel, Vinh Chau Van Nguyen, Stéphane Chevaliez, Tom M. Chiller, Eirini Christaki, Kevin K. Chung, David B. Clifford, Nathan Clumeck, Jonathan Cohen, John Collinge, Christopher P. Conlon, Curdin Conrad, Fiona J. Cooke, Jennifer Rittenhouse Cope, G. Ralph Corey, John H. Cross, Burke A. Cunha, Cheston B. Cunha, Benoit D'Journo, George L. Daikos, Johannes M.A. Daniels, Robert N. Davidson, Nicholas P.J. Day, Kevin M. De Cock, Thushan I. de Silva, Henry J.C. de Vries, Stéphane de Wit, Julie Delaloye, David W. Denning, David T. Dennis, Shireesha Dhanireddy, Elodi J. Dielubanza, David J. Diemert, Mehmet Doganay, Tom Doherty, Christiane Dolecek, Arjen M. Dondorp, Abby Douglas, Michel Drancourt, Grégory Dubourg, Michael N. Dudley, Guillaume Durand, Benjamin J. Eckhardt, Androulla Efstratiou, Miquel B. Ekkelenkamp, Ambika Eranki, Hakan Erdem, Gerome V. Escota, Heather L. Evans, Alice Chijioke Eziefula, Florence Fenollar, Alan Fenwick, Joshua Fierer, Roger G. Finch, James M. Fleckenstein, Christina Forstner, Federico Foschi, Pierre-Edouard Fournier, Martyn A. French, Kenneth L. Gage, Lynne S. Garcia, Joaquim Gascon, Arturo S. Gastañaduy, Philippe Gautret, William M. Geisler, Khalil G. Ghanem, Tommaso Giani, Maddalena Giannella, Bruce L. Gilliam, Michel Gilliet, Carol A. Glaser, Youri Glupczynski, John W. Gnann, Ellie J.C. Goldstein, Bruno Gottstein, Frederique Gouriet, Patti E. Gravitt, Michael D. Green, Stephen T. Green, Andreas H. Groll, Roy M. Gulick, Arjun Gupta, Gilbert Habib, Stephan Harbarth, Marianne Harris, Frederick G. Hayden, David J. Hetem, Philip C. Hill, Bernard Hirschel, Aimee C. Hodowanec, Louis Hoffart, Christian Hoffmann, Steven M. Holland, Peter W. Horby, David J. Horne, Sami Hraiech, Mark W. Hull, Angela Huttner, Richard J.M. Ingram, Jasmin Islam, Michael G. Ison, Scott H. James, Claire Jenkins, Stephen G. Jenkins, Jørgen Skov Jensen, Christine Johnston, Theodore B. Jones, Stephen J. Jordan, Kathleen G. Julian, Yasuyuki Kato, Carol A. Kauffman, Keith S. Kaye, Michael P. Keane, James Keeney, Paul Kelly, Stephen J. Kent, Winfried V. Kern, Yoav Keynan, Andrea A. Kim, Isabelle Koné-Paut, Chris Kosmidis, Aloys C.M. Kroes, Frank P. Kroon, Thomas G. Ksiazek, F. Matthew Kuhlmann, Ed J. Kuijper, Jennie H. Kwon, George B. Kyei, Karine Lacombe, Philippe Lagacé-Wiens, Jean-Christophe Lagier, Theresa Lamagni, Luce Landraud, Fanny Lanternier, Kerry L. LaPlante, Stephen D. Lawn, Steven J. Lawrence, Hakan Leblebicioglu, Nelson Lee, James E. Leggett, Philippe Lehours, Pierre-Yves Levy, Rainer G. Leyh, Rebecca A. Lillis, Direk Limmathurotsakul, Jennifer Lin, H.D. Alan Lindquist, Benjamin A. Lipsky, Christina Liscynesky, David Looney, Olivier Lortholary, Franklin D. Lowy, Benjamin J. Luft, Philip A. Mackowiak, Paul A. MacPherson, Valérie Maghraoui-Slim, Patrick W. Mallon, Julie E. Mangino, Oriol Manuel, Oscar Marchetti, Kristen M. Marks, Kieren A. Marr, Jeanne Marrazzo, Jonas Marschall, David H. Martin, Frédéric Matonti, Richard S. Matulewicz, Kenneth H. Mayer, Russell J. McCulloh, Rose McGready, Rennatus Mdodo, Simon Mead, Francis Mégraud, Graeme Meintjes, Sarah C. Metcalf, Marian G. Michaels, Giovanni Battista Migliori, Michael A. Miles, Alastair Miller, Matthew J. Mimiaga, Marie-Paule Mingeot-Leclercq, Elizabeth Ann Misch, Makedonka Mitreva, Julio S.G. Montaner, Caroline B. Moore, Patricia Muñoz, Jose Muñoz, Clinton K. Murray, Didier Musso, Mable Mutengo, Misha M. Mutizwa, Kurt G. Naber, Pavithra Natarajan, Santiago Neme, Paul N. Newton, Ronald A. Nichols, Lindsay E. Nicolle, François Nosten, Luigi D. Notarangelo, Thomas B. Nutman, Paul Nyirjesy, P. Ronan O'Connell, Steven M. Opal, L. Peter Ormerod, Douglas R. Osmon, Marie Boulze Pankert, Giuseppe Pantaleo, Laurent Papazian, Diane M. Parente, Philippe Parola, Shadi Parsaei, Manuel A. Pascual, Rupa Patel, Eleni Patrozou, Jean-Michel Pawlotsky, Sharon J. Peacock, Jean-Claude Pechère, Ivan Pelegrin, Barry S. Peters, Edgar J.G. Peters, Jeannine M. Petersen, Lyle R. Petersen, Vidmantas Petraitis, Luu-Ly Pham, Albert Picado, Adrian Pilatz, Benoit Pilmis, María-Jesús Pinazo, Mathias W. Pletz, Jason M. Pogue, Evelyn L. Polgreen, Philip M. Polgreen, Klara M. Posfay-Barbe, William G. Powderly, Rachel Presti, Guy Prod'hom, Mirja Puolakkainen, Thomas C. Quinn, Didier Raoult, Raymund R. Razonable, Robert C. Read, Robert R. Redfield, Rob J. Rentenaar, Steven J. Reynolds, Camillo Ribi, Malcolm D. Richardson, Michele L. Ritter, Antoine Roch, Jürgen Kurt Rockstroh, Amanda Rojek, José R. Romero, Suzan H.M. Rooijakkers, Daniel Rosenbluth, Sergio D. Rosenzweig, Gian Maria Rossolini, Ethan Rubinstein, Greg Ryan, Steven A. Safren, Vikrant V. Sahasrabuddhe, Pekka A.I. Saikku, Mohammad M. Sajadi, Michelle R. Salvaggio, Carlos A.Q. Santos, Michael J. Satlin, Anthony J. Schaeffer, Christoph Schimmer, Robert T. Schooley, Richard F. Schumacher, Beverly E. Sha, Daniel S. Shapiro, Gerard Sheehan, David M. Shlaes, Shmuel Shoham, Cameron P. Simmons, Dennis W. Simon, Matthew S. Simon, Kari A. Simonsen, Mary P.E. Slack, Tyrel T. Smith, Jack D. Sobel, Maria Souli, Shruti Sridhar, James M. Steckelberg, Dennis L. Stevens, Heather Strah, A. Willem Sturm, Somnuek Sungkanuparph, Sarah J. Tabrizi, Evelina Tacconelli, Chen Sabrina Tan, Randy A. Taplitz, Guillemette Thomas, Lora D. Thomas, Franck Thuny, Guy Thwaites, Frederic Tissot, Tone Tønjum, Francesca J. Torriani, Christian Toso, Paul M. Tulkens, Allan R. Tunkel, Claire E. Turner, Andrew P. Ustianowski, Françoise van Bambeke, Reinout van Crevel, Diederik van de Beek, Christian van Delden, Menno M. van der Eerden, Jos W.M. van der Meer, Tom van der Poll, Jakko van Ingen, Jos van Putten, Bernard P. Vaudaux, Sten H. Vermund, Raphael P. Viscidi, Kumar Visvanathan, Govinda S. Visvesvara, Lorenz von Seidlein, Florian M.E. Wagenlehner, Anna Wald, Thomas J. Walsh, David C. Warhurst, David W. Warnock, David A. Warrell, Mary J. Warrell, Adilia Warris, Richard R. Watkins, David J. Weatherall, Rainer Weber, Wolfgang Weidner, Jonathan R. White, Peter J. White, James Whitehorn, Richard J. Whitley, Christopher J.M. Whitty, Willem Joost Wiersinga, Mark H. Wilcox, Thomas N. Williams, Cara C. Wilson, Mary Elizabeth Wilson, Hilmar Wisplinghoff, Robin Wood, Richard G. Wunderink, David Wyles, Zhi-Tao Yang, Jonathan S. Yoder, Najam A. Zaidi, Andrea J. Zimmer, Jane N. Zuckerman, and Alimuddin Zumla

Published
2017

11. Neurological manifestations of dengue infection

Author

Nguyen Minh Dung, Khin S. A. Myint, Tom Solomon, Jeremy Farrar, William James, Boonyos Raengsakulrach, Le Thi Thu Thao, Mary J. Warrell, Nicholas P. J. Day, Nicholas J. White, Rachel Kneen, Ha Thi Loan, David W. Vaughn, and Amanda Nisalak

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Encephalopathy, Disease, Polymerase Chain Reaction, Serology, Dengue fever, Dengue, Internal medicine, Epidemiology, medicine, Humans, Encephalitis, Viral, Severe Dengue, Child, Neurologic Examination, business.industry, Infant, General Medicine, Dengue Virus, medicine.disease, Vietnam, Child, Preschool, Immunology, Female, Viral disease, business, Complication, Encephalitis
Abstract

Summary Background Severe forms of dengue, the most important arboviral infection of man, are associated with haemorrhagic disease and a generalised vascular leak syndrome. The importance of dengue as a cause of neurological disease is uncertain. Methods During 1995, all patients with suspected CNS infections admitted to a referral hospital in southern Vietnam were investigated by culture, PCR, and antibody measurement in serum and CSF for dengue and other viruses. Findings Of 378 patients, 16 (4·2%) were infected with dengue viruses, compared with four (1·4%) of 286 hospital controls (odds ratio [95% CI] 3·1 [1·7–5·8]). Five additional dengue positive patients with CNS abnormalities were studied subsequently. No other cause of CNS infection was identified. Seven infections were primary dengue, 13 secondary, and one was not classified. Ten patients had dengue viruses isolated or detected by PCR, and three had dengue antibody in the CSF. 12 of the 21 had no characteristic features of dengue on admission. The most frequent neurological manifestations were reduced consciousness and convulsions. Nine patients had encephalitis. No patient died, but six had neurological sequelae at discharge. Phylogenetic analysis of the four DEN-2 strains isolated mapped them with a DEN-2 strain isolated from a patient with dengue haemorhagic fever, and with other strains previously isolated in southern Vietnam. Interpretation In dengue endemic areas patients with encephalitis and encephalopathy should be investigated for this infection, whether or not they have other features of the disease.

Published
2016

12. A simplified 4-site economical intradermal post-exposure rabies vaccine regimen: a randomised controlled comparison with standard methods

Author

Ly-Mee Yu, Andrew J. Pollard, Laurent Audry, Sharon M. Brookes, David A. Warrell, François-Xavier Meslin, Judith Phipps, Linda Diggle, Richard Moxon, Anthony R. Fooks, Hervé Bourhy, Jonathan J Deeks, Mary J. Warrell, and Anna Riddell

Subjects
Male, medicine.medical_treatment, 0302 clinical medicine, Rabies vaccine, 030212 general & internal medicine, Virology/Vaccines, Confusion, Viral Vaccine, lcsh:Public aspects of medicine, Standard methods, Middle Aged, 3. Good health, Vaccinology, Infectious Diseases, Female, medicine.symptom, medicine.drug, Research Article, Infectious Diseases/Tropical and Travel-Associated Diseases, Adult, medicine.medical_specialty, Post exposure, lcsh:Arctic medicine. Tropical medicine, Adolescent, Injections, Intradermal, lcsh:RC955-962, Rabies, Immunology, 030231 tropical medicine, Public Health and Epidemiology/Immunization, 03 medical and health sciences, Young Adult, Infectious Diseases/Viral Infections, medicine, Humans, Post-exposure prophylaxis, Intensive care medicine, Neurological Disorders/Infectious Diseases of the Nervous System, Infectious Diseases/Infectious Diseases of the Nervous System, business.industry, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, medicine.disease, Regimen, Infectious Diseases/Neglected Tropical Diseases, Rabies Vaccines, Public Health and Epidemiology/Preventive Medicine, business
Abstract

Background The need for economical rabies post-exposure prophylaxis (PEP) is increasing in developing countries. Implementation of the two currently approved economical intradermal (ID) vaccine regimens is restricted due to confusion over different vaccines, regimens and dosages, lack of confidence in intradermal technique, and pharmaceutical regulations. We therefore compared a simplified 4-site economical PEP regimen with standard methods. Methods Two hundred and fifty-four volunteers were randomly allocated to a single blind controlled trial. Each received purified vero cell rabies vaccine by one of four PEP regimens: the currently accepted 2-site ID; the 8-site regimen using 0.05 ml per ID site; a new 4-site ID regimen (on day 0, approximately 0.1 ml at 4 ID sites, using the whole 0.5 ml ampoule of vaccine; on day 7, 0.1 ml ID at 2 sites and at one site on days 28 and 90); or the standard 5-dose intramuscular regimen. All ID regimens required the same total amount of vaccine, 60% less than the intramuscular method. Neutralising antibody responses were measured five times over a year in 229 people, for whom complete data were available. Findings All ID regimens showed similar immunogenicity. The intramuscular regimen gave the lowest geometric mean antibody titres. Using the rapid fluorescent focus inhibition test, some sera had unexpectedly high antibody levels that were not attributable to previous vaccination. The results were confirmed using the fluorescent antibody virus neutralisation method. Conclusions This 4-site PEP regimen proved as immunogenic as current regimens, and has the advantages of requiring fewer clinic visits, being more practicable, and having a wider margin of safety, especially in inexperienced hands, than the 2-site regimen. It is more convenient than the 8-site method, and can be used economically with vaccines formulated in 1.0 or 0.5 ml ampoules. The 4-site regimen now meets all requirements of immunogenicity for PEP and can be introduced without further studies. Trial Registration Controlled-Trials.com ISRCTN 30087513, Author Summary All human deaths from rabies result from failure to give adequate prophylaxis. After a rabid animal bite, immediate wound cleaning, rabies vaccine and immunoglobulin injections effectively prevent fatal infection. Immunoglobulin is very rarely available in developing countries, where prevention relies on efficacious vaccine. WHO approved vaccines are prohibitively expensive, but 2 economical regimens (injecting small amounts of vaccine intradermally, into the skin, at 2 or 8 sites on the first day of the course) have been used for many years in a few places. Practical or perceived difficulties have restricted widespread uptake of economical methods. These could largely be overcome by introducing a new, simpler regimen, involving 4 site injections on the first day. We vaccinated volunteers to compare the antibody levels induced by the 4-site intradermal regimen with those induced by the current 2-site and 8-site regimens and the “gold standard” intramuscular regimen favoured internationally. All the economical intradermal regimens were at least as immunogenic as the intramuscular method. The results provide sufficient evidence that the 4-site regimen meets the criteria necessary for its recommendation for use wherever the cost of vaccine is prohibitive and especially where 2 or more patients are treated on the same day.

Published
2016

13. Human rabies and its prevention: an overview

Author

David A. Warrell and Mary J. Warrell

Subjects
Microbiology (medical), medicine.medical_specialty, Rabies, medicine.medical_treatment, medicine.disease_cause, law.invention, law, Intensive care, medicine, Humans, Post-exposure prophylaxis, Encephalomyelitis, Intensive care medicine, business.industry, Rabies virus, Immunization, Passive, medicine.disease, Virology, Intensive care unit, Kidney cell, Regimen, Infectious Diseases, Encephalitis, business
Abstract

Human rabies is underreported, but it clearly is still a frequent medical problem that is virtually confined to tropical countries. Rabies encephalitis remains essentially incurable, and most patients die at home, their terrible symptoms unpalliated by sedatives or analgesics. Recent attempts to cure rabies in well-equipped intensive care units have failed, a situation reemphasizing the importance of preventive measures. The great advances that have been made in understanding the rabies virus and the associated improvements in rabies vaccines have had little or no impact in the tropical endemic zone. Most patients who have been exposed to rabies are still given nervous tissue vaccines for postexposure prophylaxis. An urgent priority is the development of a regimen using tissue culture vaccine that is sufficiently economical to replace nervous tissue vaccine. This has been achieved in China with primary hamster kidney cell vaccine.

Published
2016

14. Is there a future for mRNAs as viral vaccines?

Author

Mary J. Warrell

Subjects
0301 basic medicine, business.industry, Viral Vaccine, RNA, Viral Vaccines, General Medicine, Virology, Viral Proteins, 03 medical and health sciences, 030104 developmental biology, Protein Biosynthesis, Protein biosynthesis, RNA, Viral, Medicine, RNA, Messenger, business
Published
2017

15. Rabies and African bat lyssavirus encephalitis and its prevention

Author

Mary J. Warrell

Subjects
Microbiology (medical), Rabies, medicine.disease_cause, Dogs, Chiroptera, Zoonoses, medicine, Animals, Humans, Pharmacology (medical), Encephalitis, Viral, Mononegavirales, Lyssavirus, biology, business.industry, Vaccination, Rabies virus, General Medicine, Rhabdoviridae, medicine.disease, biology.organism_classification, Virology, Infectious Diseases, Rabies Vaccines, Immunization, Africa, business, Encephalitis
Abstract

Unlike any other human infection, encephalitis caused by dog rabies virus is always fatal. Rabies and other lyssaviruses have been found in unexpected places, and human disease, especially paralytic rabies, has gone unrecognised. Evidence is emerging that rabies-related bat lyssaviruses are enzootic across Europe, Africa, Asia and Australia, but none has been detected in the Americas. The epidemiology and origins of African lyssaviruses are discussed. Ideal rabies prophylaxis (pre-exposure immunisation followed by post-exposure booster vaccination) has proved 100% effective; hence all human deaths result from failure of prevention. Rabies vaccines of known quality are unaffordable for the majority in Africa. Although intradermal regimens requiring

Published
2010

16. Emerging aspects of rabies infection: with a special emphasis on children

Author

Mary J. Warrell

Subjects
Microbiology (medical), medicine.medical_specialty, Rabies, Malaria, Cerebral, Immunoglobulins, medicine.disease_cause, Organ transplantation, Diagnosis, Differential, Dogs, Chiroptera, Rhabdoviridae Infections, Epidemiology, medicine, Animals, Humans, Encephalitis, Viral, Child, Intensive care medicine, Animal Bites, business.industry, Rabies virus, medicine.disease, Virology, Substance abuse, Infectious Diseases, Rabies Vaccines, Cerebral Malaria, Lyssavirus infection, Child, Preschool, Lyssavirus, business
Abstract

PURPOSE OF REVIEW Increased awareness of the long-neglected rabies virus could promote the highly effective methods of preventing human deaths. Rabies and rabies-related lyssaviruses have recently been appearing in unexpected places, sometimes with dire consequences. Although rabies of canine origin remains 100% fatal in human beings, should the surprising recovery of a single unvaccinated child influence treatment now? RECENT FINDINGS Evidence of rabies-related lyssavirus infection of bats is increasing across continents and with new virus types. Human rabies has been misdiagnosed as cerebral malaria, or even drug abuse. Organ transplant recipients have been infected. The first unvaccinated patient, a teenager, bitten by a bat, recovered from rabies encephalitis, but why might this be? Highly effective control and prevention of infection is possible. Preexposure prophylaxis for schoolchildren could now become routine. Improved economical intradermal postexposure vaccine regimens could increase the availability of affordable treatment in developing countries. Controlling dog rabies could prevent 95% of human deaths, but education and resources are lacking. SUMMARY The risks and problems of rabies and other lyssaviruses vary greatly across the world. Knowledge of epidemiology and prevention could save the lives of victims of animal bites and promote efforts to control and even eliminate dog rabies.

Published
2008

17. Rabies

Author

Mary J. Warrell

Published
2015

18. Rabies

Author

Mary J. Warrell

Published
2014

19. Contributors

Author

Steven Abrams, Adekunle M. Adesina, Dwomoa Adu, Sitara S.R. Ajjampur, Voahangy Andrianaivoarimanana, Angelakis Emmanouil, Jeffrey K. Aronson, Inoshi Atukorala, Guy Baily, Till Bärnighausen, Buddha Basnyat, Andrew Bastawrous, Imelda Bates, Daniel G. Bausch, Nicholas A.V. Beare, Raman Bedi, Nick J. Beeching, Nicholas J. Bennett, Anita Berlin, Ahmed I. Bhigjee, Zulfiqar A. Bhutta, David E. Bloom, Lucille Hellen Blumberg, Marleen Boelaert, Francis J. Bowden, Bernard J. Brabin, Freddie Bray, Rodney A. Bray, Simon J. Brooker, Matthijs C. Brouwer, Reto Brun, Enrico Brunetti, Susan Bull, Donald A.P. Bundy, Christian Burri, Amaya Bustinduy, Thashi Chang, François Chappuis, Wirongrong Chierakul, Peter L. Chiodini, John D. Clemens, Gordon C. Cook, Mark F. Cotton, John B.S. Coulter, Nigel A. Cunliffe, Bart J. Currie, Marian J. Currie, David A.B. Dance, Nicholas P.J. Day, Kevin DeCock, Jacqueline Deen, Sarah R Doffman, Arjen Dondorp, H. Rogier van Doorn, Martin W. Dünser, Edward M. Eitzen, Delia A. Enria, Jeremy Farrar, Christina Faust, Nicholas A. Feasey, Abebaw Fekadu, Günther Fink, Peter U. Fischer, Carlos Franco-Paredes, Neil French, Hector H. Garcia, Roger I. Glass, Melita A. Gordon, Stephen B. Gordon, Bruno Gottstein, Stephen M. Graham, Andy Haines, Roy A. Hall, Charlotte Hanlon, The late C. Anthony Hart, Melissa R. Haswell, Sophie Hawkesworth, Roderick J. Hay, Jeannine M. Heckmann, Markus M. Heimesaat, Anselm J.M. Hennis, Tran Tinh Hien, Achim Hoerauf, Peter J. Hotez, Salal Humair, Cheryl A. Johansen, Roch Christian Johnson, Malcolm K. Jones, Thomas Junghanss, Sasithorn Kaewkes, Gagandeep Kang, Paul Kelly, Charles H. King, Sandeep P. Kishore, Patricia Kissinger, David Lalloo, Trudie Lang, Oliver Liesenfeld, Diana N.J. Lockwood, David C.W. Mabey, The late M. Monir Madkour, Barbara J. Marston, Refiloe Masekela, Philippe Mayaud, James S. McCarthy, Rose McGready, Paul S. McNamara, Laura Merson, Robert F. Miller, Glen D. Liddell, Kevin Mortimer, Ayesha A. Motala, Kosta Y. Mumcuoglu, Flor M. Munoz, Melba Munoz Roldan, Theonest Mutabingwa, Osamu Nakagomi, Yukifumi Nawa, Robert Newton, Lisa F.P. Ng, François H. Nosten, Jennifer O’Hea, Shirley Owusu-Ofori, Daniel H. Paris, Michael Parker, Philip J. Peters, Fraser J. Pirie, Gerd Pluschke, Andrew M. Prentice, Thomas C. Quinn, Minoarisoa Esther Rajerison, Didier Raoult, Maherisoa Ratsitorahina, K. Srinath Reddy, Steven J. Reynolds, John Richens, Marcus J. Rijken, Sara Ritchie, Janet Robinson, Angela M.C. Rose, Juan C. Salazar, T. Alafia Samuels, Marcus J. Schultz, Crispian Scully, Paul Shears, Paul E. Simonsen, Paiboon Sithithaworn, David W. Smith, Tom Solomon, Vaughan R. Southgate, Banchob Sripa, M. Leila Srour, Marija Stojkovic, Shyam Sundar, Jecko Thachil, Raj Thuraisingham, C. Louise Thwaites, Guy Thwaites, M. Estée Török, Nigel Unwin, Diederik van de Beek, Francisco Vega-Lopez, Govinda S. Visvesvara, Lorenz von Seidlein, Katie Wakeham, Stephen L. Walker, Honorine Ward, Mary J. Warrell, David A. Warrell, Gary J. Weil, Graham B. White, Nicholas J. White, Stephen G. Withington, Vanessa Wong, Robin Wood, Sarah Wyllie, Lam Minh Yen, Paul R. Young, Sophie Yacoub, and Ken Zafren

Published
2014

20. Systems thinking needed for rabies control - Authors' reply

Author

Elizabeth Molyneux, Mary J. Warrell, Sarita Depani, Macpherson Mallewa, and Neil Kennedy

Subjects
medicine.medical_specialty, Rabies, Neglected Disease, Developing country, General Medicine, medicine.disease, Vaccination, Nursing, Research community, Immunology, medicine, Humans, Systems thinking, Rabies control, Outcomes research, Psychology
Abstract

200 www.thelancet.com Vol 381 January 19, 2013 1 Bainbridge D, Martin J, Arango M, Cheng D, for the Evidence-based Peri-operative Clinical Outcomes Research (EPiCOR) Group. Perioperative and anaesthetic-related mortality in developed and developing countries: a systematic review and meta-analysis. Lancet 2012; 380: 1075–81. vaccination is not expected to aff ect the number of dog bites. In conclusion, we support Depani and colleagues’ contention that rabies is an important, but neglected disease. Additionally, however, we emphasise the need for the research community to understand the systemic challenges facing the development of eff ective and practical solutions for rabies.

Published
2013

21. Rabies

Author

David A. Warrell and Mary J. Warrell

Subjects
medicine.medical_specialty, Post exposure, biology, business.industry, biology.organism_classification, medicine.disease, Virology, Wound cleaning, Tanzania, Rabies vaccine, Duvenhage virus, Family medicine, medicine, East africa, Rabies, business, medicine.drug
Published
2013

22. Viral CNS Infections

Author

David A. Warrell and Mary J. Warrell

Subjects
business.industry, Viral CNS Infections, Medicine, business, Virology
Published
2013

23. List of Contributors

Author

Jose M Acuin, Rodney D Adam, Tsiri Agbenyega, AM Shamsir Ahmed, Tahmeed Ahmed, S Asad Ali, Gregory M Anstead, George E Armah, Stephen J Aston, Ronald C Ballard, Elizabeth D Barnett, Imelda Bates, Charles W Beadling, Nicholas J Beeching, Michael L Bennish, Caryn Bern, Frank J Bia, Brian H Bird, Allyson K Bloom, Gerard Bodeker, Robert W Bradsher, Nynke van den Broek, Simon Brooker, John T Brooks, W Abdullah Brooks, Philippe Brouqui, Michael Brown, Fabrizio Bruschi, Donald AP Bundy, Danai Bunnag, Benjamin Caballero, Michael V Callahan, Aulasa J Camerlin, Grant L Campbell, Jonathan R Carapetis, Enitan D Carrol, Eric Caumes, Remi N Charrel, Anna M Checkley, Mala Chhabra, Tepirou Chher, Charlotte M Chiong, M Jobayer Chisti, David C Christiani, Bradley A Connor, Edward S Cooper, Philip J Cooper, R Richard Coughlin, John H Cross, Nigel N Cunliffe, Mark Danta, Nicholas PJ Day, Paron Dekumyoy, Nilanthi deSilva, Gregory Deye, Rebecca Dillingham, H Rogier van Doorn, Barbara Doudier, Michel Drancourt, Françoise Dromer, Michael Eddleston, Samer S El-Kamary, Jeremy Farrar, Wafaie Fawzi, Nicholas A Feasey, Vanessa Field, Marc Fischer, Susan Fisher-Hoch, Kevin Forsyth, LeAnne M Fox, Arthur M Friedlander, Gerson Galdos-Cardenas, Hector H Garcia, Lynne S Garcia, Anna-Maria Geretti, Achilleas Gikas, Robert H Gilman, Victor Javier Sanchez Gonzalez, Melita A Gordon, Richard A Gosselin, Stephen M Graham, Alison D Grant, James J Gray, John R Graybill, Bertrand Graz, Stephen Green, Jeffrey K Griffiths, Bruno Gryseels, Duane J Gubler, Rathi Guhadasan, Aron J Hall, Davidson Hamer, David Harley, Jason B Harris, Amy L Hartman, Oliver Hassall, Roderick J Hay, Chris F Heyns, David R Hill, Martin H Hobdell, Caroline M den Hoed, Meredith L Holtz, M Iqbal Hossain, Peter J Hotez, Eric R Houpt, Cynthia R Howard, Chien-Ching Hung, Munirul Islam, Elizabeth Joekes, Victoria Johnston, Sam Kampondeni, Gagandeep Kang, Powel Kazanjian, Jay S Keystone, Wasif Ali Khan, Arthur Y Kim, Christopher L King, Amy D Klion, Richard Knight, Peter James Krause, Sanjeev Krishna, Ernst J Kuipers, Angelle D LaBeaud, David G Lalloo, Xavier De Lamballerie, Saba Lambert, Regina C LaRocque, John Lawrenson, Myron M Levine, Daniel H Libraty, Diana NJ Lockwood, Kinke M Lommerse, Olivier Lortholary, Rogelio López-Vélez, Benjamin A Lopman, David Mabey, Alan J. Magill, Ciro Maguiña, Syed Faisal Mahmood, Kathryn Maitland, Hadi Manji, Barbara J Marston, Anu Mathew, Christine E Mathews, Max Maurin, Paola J Maurtua-Neumann, Philippe Mayaud, Bongani M Mayosi, Joseph B McCormick, Stephen McKew, Susan LF McLellan, Peter C McMinn, Joseph D Mega, Donald E Meier, Matthieu Million, Veena Mittal, Elizabeth M Molyneux, Susan P Montgomery, Pedro Morera, Pedro L Moro, William J Moss, K Darwin Murrell, Osamu Nakagomi, Toyoko Nakagomi, Neha Nanda, James P Nataro, Eileen E Navaro, Ronald C Neafie, Ricardo Negroni, Ann M Nelson, Paul N Newton, Robert Newton, Stuart T Nichol, Francesca F Norman, Marcio RT Nunes, Thomas B Nutman, Richard A Oberhelman, Edward C Oldfield, Eloy E Ordaya, Christopher D Paddock, Slobodan Paessler, Ilias C Papanikolaou, Georgios Pappas, Luc Paris, Philippe Parola, Christopher M Parry, Manish M Patel, Sharon J Peacock, Rosanna Peeling, Hans Persson, Philip J Peters, Jonathan J Phillips, Richard O Phillips, Farah Naz Qamar, Atif Rahman, Jamilla Rajab, Didier Raoult, Michael F Rein, Aurélié Renvoisé, Jean-Marc Reynes, Frank O Richards, John Richens, Anne W Rimoin, Robert Riviello, Ema G Rodrigues, Allan R Ronald, Benjamin M Rosenthal, David Rosmarin, Ernesto Ruiz-Tiben, Edward T Ryan, Debasish Saha, Arturo Saavedra, Peter M Schantz, Tony Schountz, Sandra K Schumacher, James J Sejvar, Aisha Sethi, Kwonjune J Seung, Om Prakash Sharma, Trueman W Sharp, Anuraj H Shankar, Sonya S Shin, David R Shlim, Nicholas J van Sickels, Freddy Sitas, Thomas L Snelling, Cristina Socolovschi, Tom Solomon, J Erin Staples, Robert C Stewart, August Stich, G Thomas Strickland, Kathryn N Suh, Andreas Suhrbier, Khuanchai Supparatpinyo, Catherine G Sutcliffe, Brett E Swierczewski, John L Tarpley, Hugh R Taylor, Terrie Taylor, Harry J Thomas, C Louise Thwaites, Guy E Thwaites, Tejpratap SP Tiwari, Phan Van Tu, Angus W Turner, Edouard Vannier, Pedro FC Vasconcelos, Fransisco Vega-López, Jorge J Velarde, Nicholas J Vietri, Govinda S Visvesvara, Keyur S Vyas, Katie Wakeham, Thomas J Walsh, Mark H Wansbrough-Jones, David A Warrell, Mary J Warrell, Haider J Warraich, George Watt, Yupaporn Wattanagoon, Dorn Watthanakulpanich, Scott C Weaver, Rachel B Webman, Paul J Weidle, Louis M Weiss, Nicholas J White, Christopher JM Whitty, Dana M Woodhall, Stephen G Wright, Ramnik J Xavier, Lihua Xiao, Hongjie Yu, and Anita KM Zaidi

Published
2013

24. Trend of human rabies prophylaxis in developing countries: Toward optimal rabies immunization

Author

Mary J. Warrell

Subjects
Post exposure, General Veterinary, General Immunology and Microbiology, Rabies, Rabies immunization, business.industry, Public Health, Environmental and Occupational Health, Developing country, medicine.disease, Virology, Infectious Diseases, Rabies vaccine, Rabies Vaccines, medicine, Humans, Molecular Medicine, business, Rabies prophylaxis, medicine.drug, Duck embryo vaccine
Published
2014

25. Contributors

Author

George J. Alangaden, Michael J. Aldape, Jérôme Allardet-Servent, Upton D. Allen, Heidi S.M. Ammerlaan, Emmanouil Angelakis, Andrew Artenstein, David Asboe, Kingsley B. Asiedu, John C. Atherton, Tar-Ching Aw, Seema Baid-Agrawal, Robin Bailey, Christopher Bandel, Philip S. Barie, David J. Barillo, Pierre-Alexandre Bart, Roger Bayston, C. Ben Beard, Nick J. Beeching, Rodolfo E. Bégué, Yves Benhamou, Constance A. Benson, Elie F. Berbari, Anthony R. Berendt, Madhav P. Bhatta, Jacques Bille, Ari Bitnun, Finn T. Black, Iain Blair, Stéphane Blanche, Thomas P. Bleck, Chantal P. Bleeker-Rovers, Gijs Bleijenberg, Karen C. Bloch, Marc J.M. Bonten, Charles A.B. Boucher, Rafik Bourayou, Emilio S. Bouza, William R. Bowie, Barry D. Brause, Sylvain Brisse, Warwick Britton, Itzhak Brook, David W.G. Brown, Christian Brun-Buisson, James C.M. Brust, Amy E. Bryant, André Bryskier, R. Mark L Buller, Karen Bush, Thierry Calandra, D. William Cameron, Michel Caraël, Michael J. Carr, Inmaculada Casas, Stephen T. Chambers, Katarina G. Chiller, Tom M. Chiller, Peter L. Chiodini, Ian Chopra, Anthony C. Chu, Kevin K. Chung, Benjamin M. Clark, Nathan Clumeck, Clay J. Cockerell, Jonathan Cohen, John Collinge, Christopher P. Conlon, G. Ralph Corey, Alan Cross, John H. Cross, Judith Currier, Carmel M. Curtis, Gina Dallabetta, Robert N. Davidson, Jane Davies, Jeremy Day, Nicholas P.J. Day, Cillian F. De Gascun, Stéphane de Wit, Jean Delmont, David T. Dennis, David J. Diemert, Mehmet Doganay, Tom Doherty, Christiane Dolecek, Stéphane Y. Donati, Arjen M. Dondorp, Barbara Doudier, Michel Drancourt, Dimitri M. Drekonja, Richard H. Drew, Jay S. Duker, J. Stephen Dummer, Charles N. Edwards, Miquel B. Ekkelenkamp, Mark C. Enright, Paul R. Epstein, Veronique Erard, Alice Chijioke Eziefula, Mark B. Feinberg, Florence Fenollar, Alan Fenwick, Luis Fernandez, Joshua Fierer, Roger G. Finch, Charles W. Flexner, Ad C. Fluit, Elizabeth Lee Ford-Jones, Pierre-Edouard Fournier, Victoria Fraser, Martyn A. French, Jon S. Friedland, Joseph M. Fritz, E. Yoko Furuya, Kenneth L. Gage, Lynne S. Garcia, Arturo S. Gastañaduy, Khalil G. Ghanem, Maddalena Giannella, Carol A. Glaser, Marshall J. Glesby, Sarah Glover, Youri Glupczynski, John W. Gnann, Andrew F. Goddard, Ellie J.C. Goldstein, Iveth J. González, Sherwood L. Gorbach, Bruno Gottstein, Ravi Gowda, John D. Grabenstein, John M. Grange, Michael D. Green, Stephen T. Green, Danielle T. Greenblatt, Brian Greenwood, Aric L. Gregson, Andreas H. Groll, Aditya K. Gupta, Kok-Ann Gwee, William Hall, Scott M. Hammer, Sajeev Handa, Diane Hanfelt-Goade, Alexandre Harari, Marianne Harris, Barry J. Hartman, Roderick J. Hay, David K. Henderson, Lisa E. Hensley, Luke Herbert, David R. Hill, Timothy J. Hills, John David Hinze, Hans H. Hirsch, Bernard Hirschel, Andy I.M. Hoepelman, Steven M. Holland, Mary M. Horgan, Robin Howe, James M. Hughes, Mark W. Hull, Clark B. Inderlied, Michael G. Ison, Peter J. Jenks, James R. Johnson, Theodore Jones, Mettassebia Kanno, Carol Kauffman, Patrick Kelly, Jason S. Kendler, Yoav Keynan, Ali S. Khan, Grace T. Kho, George R. Kinghorn, Paul E. Klapper, Jan AJW Kluytmans, Menno Kok, Isabelle Koné-Paut, John N. Krieger, Aloys C.M. Kroes, Frank P. Kroon, Christine J. Kubin, Alberto M. La Rosa, Tahaniyat Lalani, David G. Lalloo, Harold Lambert, Luce Landraud, Stephen D. Lawn, Phillipe Lehours Pharm, Marc Leone, Itzchak Levi, Alexandra M. Levitt, H. D. Alan Lindquist, Graham Lloyd, David J. Looney, Franklin D. Lowy, Benjamin J. Luft, William A. Lynn, Mark J. Macielag, Philip A. Mackowiak, Paul A. MacPherson, Valérie Maghraoui-Slim, Janice Main, Vincent Mallet, Julie E. Mangino, Oriol Manuel, Oscar Marchetti, Kristen Marks, Kieren A. Marr, Claude Martin, Pablo Martín-Rabadán, Augusto Julio Martinez, Ellen M. Mascini, Kenneth H. Mayer, Joseph B. McCormick, Rose McGready, Michael W. McKendrick, Simon Mead, Francis Mégraud, André Z. Meheus, Graeme Meintjes, Marian G. Michaels, Michael Miles, Alastair Miller, Matthew J. Mimiaga, Marie-Paule Mingeot-Leclercq, Thomas G. Mitchell, Pamela A. Moise, Julio Montaner, Caroline B. Moore, Philippe Moreillon, Peter Morgan-Capner, Valentina Montessori, Peter Moss, Patricia Muñoz, Kurt G. Naber, Sammy Nakhla, Jai P. Narain, Dilip Nathwani, Paul Newton, Chinh Nguyen, Lindsay E. Nicolle, Michael S. Niederman, Gary J. Noel, S. Ragnar Norrby, François Nosten, Luigi Daniele Notarangelo, Paul Nyirjesy, P. Ronan O'Connell, Jon S. Odorico, Edmund L.C. Ong, Steven M. Opal, L. Peter Ormerod, Douglas R. Osmon, Eric A. Ottesen, Gustavo Palacios, Giuseppe Pantaleo, Laurent Papazian, Philippe Parola, Manuel A. Pascual, Eleni Patrozou, Carlos Paya, Sharon J. Peacock, Jean-Claude Pechère, Mark D. Perkins, Barry Peters, Gaby E. Pfyffer, Paul A. Pham, Peter Piot, Geraldine Placko-Parola, Stainslas Pol, Klara M. Posfay-Barbe, William G. Powderly, Anton Pozniak, Guy Prod'hom, Thomas C. Quinn, Daniel W. Rahn, Aadia I. Rana, Didier Raoult, Raul Raz, Raymund Razonable, Robert C. Read, Stephen J. Reynolds, Malcolm D. Richardson, Christopher C. Robinson, Suzan H.M. Rooijakkers, Daniel Rosenbluth, Sergio D. Rosenzweig, Clarisse Rovery, Robert H. Rubin, Bina Rubinovitch, Kathleen H. Rubins, Ethan Rubinstein, Greg Ryan, Stephen Ryder, Steven Safren, Vikrant V. Sahasrabuddhe, Pekka A.I. Saikku, George Sakoulas, Juan Carlos Salazar, Michelle R. Salvaggio, Kirsten Schaffer, Franz-Josef Schmitz, Robert T. Schooley, Richard-Fabian Schumacher, Euan M. Scrimgeour, James Seddon, Harald Seifert, Graham R. Serjeant, Beverly E. Sha, Keerti V. Shah, Daniel S. Shapiro, Gerard Sheehan, Shmuel Shoham, Cameron P. Simmons, Kari A. Simonsen, Neeraj Singh, Mary P.E. Slack, Jack D. Sobel, Madhuri M. Sopirala, Lisa A. Spacek, Shiranee Sriskandan, Samuel L. Stanley, James M. Steckelberg, Iain Stephenson, Dennis L. Stevens, Walter L. Straus, Willem Sturm, Richard C. Summerbell, Joseph S. Susa, Sarah J. Tabrizi, Marc A. Tack, Randy Taplitz, Pablo Tebas, Marleen Temmerman, Steven F.T. Thijsen, Lora D. Thomas, Gail Thomson, Guy E. Thwaites, Umberto Tirelli, Nina E. Tolkoff-Rubin, Tone Tønjum, Francesca J. Torriani, Gregory C. Townsend, Gloria Trallero Masó, Paul M. Tulkens, Allan R. Tunkel, Emanuela Vaccher, Anaïs Vallet-Pichard, Françoise Van Bambeke, Diederik van de Beek, Jos W.M. van der Meer, Anton M. van Loon, Jos van Putten, Bernard P. Vaudaux, Sten H. Vermund, Hans Verstraelen, Paul Verweij, Raphael P. Viscidi, Kumar Visvanathan, Govinda S. Visvesvara, Lorenz von Seidlein, Florian M.E. Wagenlehner, Victoria Wahl-Jensen, Thomas J. Walsh, David C. Warhurst, David W. Warnock, David A. Warrell, Mary J. Warrell, Adilia Warris, Rainer Weber, Wolfgang Weidner, Vivienne C. Weston, Estella Whimbey, Michael Whitby, Peter J. White, Christopher J.M. Whitty, Rob J.L. Willems, Emrys Williams, Cara Wilson, Mary E. Wilson, Richard E. Winn, Kevin L. Winthrop, Martin J. Wiselka, Hilmar Wisplinghoff, Cameron R. Wolfe, Robin Wood, Natalie Wright, James R. Yankaskas, Najam A. Zaidi, Jonathan M. Zenilman, Yaobi Zhang, Arie J. Zuckerman, Jane Nicola Zuckerman, and Alimuddin Zumla

Published
2010

27. List of Contributors

Author

Adewale O. Adebajo, Dwomoa Adu, Yusuf Ahmed, Sandra Amor, Felix I. Anjorin, Jeffrey K. Aronson, Masharip Atadzhanov, Guy Baily, John R. Baker, Imelda Bates, Raman Bedi, Ronald H. Behrens, Solomon R. Benatar, Gerard C. Bodeker, Bernard J. Brabin, Rodney A. Bray, Simon Brooker, Annette K. Broom, Reto Brun, James E.G. Bunn, Donald A.P. Bundy, Christian Burri, Ana-Maria Cevallos, Richard E. Chaisson, Peter L. Chiodini, Sunil Chopra, Timothy J. Coleman, Kenneth J. Collins, Gordon C. Cook, John B.S. Coulter, George O. Cowan, Dorothy H. Crawford, Julia A. Critchley, Luis E. Cuevas, Nigel A. Cunliffe, David A.B. Dance, Andrew Davis, P. Shanthamali de Silva, Jean-Pierre Dedet, Mohammed R. Essop, Alice E. Eyers, John E. Eyers, Michael J.G. Farthing, Alan F. Fleming, Neil French, Göran Friman, Stephen H. Gillespie, Catherine Goodman, Stephen B. Gordon, Bruno Gottstein, Stephen M. Graham, John M. Grange, Goran Günther, Roy A. Hall, C. Anthony Hart, Melissa Haswell-Elkins, Alan Haworth, Roderick J. Hay, Tran Tinh Hien, Christopher J. Hoffman, Richard E. Holliman, John E. Jellis, Claire Jenkins, Cheryl A. Johansen, Sasithorn Kaewkes, Moses Kapembwa, Michael G. Kawooya, Paul Kelly, Mario A. Knight, Dominic Kwiatkowski, Gary Maartens, David C.W. Mabey, John S. Mackenzie, Charles R. Madeley, M. Monir Madkour, D.D. Murray McGavin, Michael A. Miles, Robert F. Miller, Alan E. Mills, Anthony Moody, Ayesha A. Motala, Zeridah Muyinda, Peter Mwaba, Datshana P. Naidoo, Osamu Nakagomi, Suchitra Nimmannitya, Stephen Owens, Shirley Owusu-Ofori, Joseph S.M. Peiris, Fraser J. Pirie, Francine Pratlong, Jürg Reichen, John Richens, Ivan M. Roitt, Dirk Schoonbaert, Geoffrey M. Scott, Crispian Scully, Paul Shears, Nandini P. Shetty, Prakash S. Shetty, Paul E. Simonsen, Paiboon Sithithaworn, Michael D. Smith, David W. Smith, Eugene Sobngwi, Tom Solomon, Vaughan R. Southgate, Banchob Sripa, Robert Steffen, John R. Sullivan, Gail Thomson, Eric John Threlfall, Raj C. Thuraisingham, Catherine L. Thwaites, Eli Tumba Tshibwabwa, Nigel Unwin, Francisco Vega-López, Damian G. Walker, David C. Warhurst, David A. Warrell, Mary J. Warrell, Nicholas J. White, Graham B. White, Hilary Williams, Stephen G. Withington, Sarah Wyllie, Lam Mihn Yen, David Yorston, Arie J. Zuckerman, Jane N. Zuckerman, and Alimuddin I. Zumla

Published
2009

29. [Untitled]

Author

Mary J. Warrell

Subjects
Infectious Diseases, Geography, Perspective (graphical), Public Health, Environmental and Occupational Health, medicine, Ethnology, Parasitology, Rabies, Environmental ethics, General Medicine, medicine.disease, Mediterranean Basin
Published
2005

30. Quinine Loading Dose in Cerebral Malaria *

Author

Sornchai Looareesuwan, Nicholas J. White, Mary J. Warrell, Danai Bunnag, David A. Warrell, Pornthep Chanthavanich, and Tranakchit Harinasuta

Subjects
Adult, Male, Adolescent, Plasmodium falciparum, Quinine dihydrochloride, Pharmacology, Loading dose, Virology, parasitic diseases, Humans, Medicine, Infusions, Parenteral, Brain Diseases, Quinine, biology, business.industry, biology.organism_classification, Malaria, Infectious Diseases, Cerebral Malaria, Anesthesia, Plasma concentration, Female, Parasitology, business, Mathematics, medicine.drug
Abstract

In cerebral malaria, the use of currently recommended doses of intravenous quinine may result in subtherapeutic plasma concentrations during the critical first 24 hours of treatment. A loading dose of quinine (20 mg/kg quinine dihydrochloride, equivalent to 16.7 mg/kg base, infused over 4 hours) proved a rapid and safe method of achieving plasma concentrations above the high minimum inhibitory concentrations for Plasmodium falciparum prevalent in Eastern Thailand.

Published
1983

31. Function of the Blood-Cerebrospinal Fluid Barrier in Human Cerebral Malaria: Rejection of the Permeability Hypothesis

Author

Helen Chapel, Suvit Areekul, Rodney E. Phillips, Mary J. Warrell, Savanat Tharavanij, David A. Warrell, Nicholas J. White, and Sornchai Looareesuwan

Subjects
Bromides, Male, medicine.medical_specialty, media_common.quotation_subject, Plasmodium falciparum, Serum albumin, Blood–brain barrier, Gastroenterology, Dexamethasone, Cerebral edema, Cerebrospinal fluid, Virology, Internal medicine, medicine, Humans, Insulin, alpha-Macroglobulins, Serum Albumin, media_common, Coma, Brain Diseases, biology, business.industry, Convalescence, medicine.disease, Malaria, Infectious Diseases, medicine.anatomical_structure, Blood-Brain Barrier, Cerebral Malaria, Anesthesia, biology.protein, Female, Parasitology, medicine.symptom, business, medicine.drug
Abstract

We tested the hypothesis that cerebral malaria is caused by blood-brain barrier inflammation and cerebral edema. In a group of 157 Thai patients with strictly defined cerebral malaria, cerebrospinal fluid (CSF) opening pressures were normal in 79% and were lower in fatal cases than in survivors (means +/- 1 SD, 144 +/- 58 and 167 +/- 51 mm CSF, respectively, P = 0.051). CSF: serum albumin ratios (X 10(3)) in 39 of them were significantly higher than in 61 British controls (medians 8.5 and 5.5, respectively, P = 0.04), but were no higher in 7 fatal cases. In a group of 12 patients this ratio was not significantly higher during coma than after full recovery (means +/- 1 SD, 9.0 +/- 6.2 and 6.7 +/- 4.2, respectively, P greater than 0.1). CSF alpha 2-macroglobulin concentrations were always normal. CSF : serum 77Br- ratios were elevated in 11/19 comatose cases but fell to normal 4 to 9 days later in 11/11 cases. Dexamethasone treatment had no significant effect on bromide partition. The percentage of an intravenously administered dose of 125I-human serum albumin detectable per ml of CSF 6 hr after intravenous injection was 2.4 +/- 1.3 X 10(-5) in 14 comatose patients and 4.4 +/- 4.0 X 10(-5) in 9 of them during convalescence (P greater than 0.1). These results demonstrate that the blood-CSF barrier is essentially intact in patients with cerebral malaria and give no support to the idea that cerebral edema is the cause of coma.

Published
1986

32. Quinine pharmacokinetics and toxicity in cerebral and uncomplicated falciparum malaria

Author

Nicholas J. White, Harinasuta T, Sornchai Looareesuwan, Mary J. Warrell, David A. Warrell, and Damnai Bunnag

Subjects
Adult, Male, medicine.medical_specialty, Metabolic Clearance Rate, Plasmodium falciparum, Every Eight Hours, Gastroenterology, Pharmacokinetics, Internal medicine, medicine, Humans, Infusions, Parenteral, Child, Cerebrospinal Fluid, Brain Diseases, Quinine, biology, business.industry, Brain, Liter, General Medicine, medicine.disease, biology.organism_classification, Malaria, Spectrometry, Fluorescence, Cerebral Malaria, Anesthesia, Acute Disease, Urinary Tract Infections, Toxicity, business, medicine.drug
Abstract

Acute pharmacokinetics of intravenously infused quinine were studied in 25 patients with cerebral malaria and 13 with uncomplicated falciparum malaria. In patients with cerebral malaria receiving the standard dose of 10 mg/kg every eight hours, plasma quinine concentrations consistently exceeded 10 mg/liter, reaching a peak 60 +/- 25 hours (mean +/- 1 S.D.) after treatment was begun and then declining. Quinine total clearances (Cl) and total apparent volumes of distribution (Vd) were significantly lower than in uncomplicated malaria (Cl, 0.92 +/- 0.42 compared with 1.35 +/- 0.6 ml/min/kg, p = 0.03; Vd, 1.18 +/- 0.37 compared with 1.67 +/- 0.34 liter/kg, p = 0.0013). There was no significant difference between the two groups in elimination half-times (t/2) or renal clearances (Cu) (t/2, 18.2 +/- 9.7 compared with 16 +/- 7.0 hours; Cu, 0.21 +/- 0.16 compared with 0.21 +/- 0.08 ml/min/kg). In nine patients studied following recovery, Cl (3.09 +/- 1.18 ml/min), Vd (2.74 +/- 0.47 liter/kg), and Cu (0.53 +/- 0.22 ml/min/kg) were significantly greater (p less than or equal to 0.0004), and t/2 was significantly shorter (11.1 +/- 4.1 hours, p = 0.006) than during the acute illness. Cu accounted for approximately 20 percent of Cl in all groups. Renal failure did not alter the disposition kinetics in cerebral malaria. There was no clinical or electrocardiographic evidence of cardiotoxicity and no permanent neurotoxicity. Quinine toxicity in cerebral malaria has probably been overemphasized. The benefits of high plasma concentrations in the acute phase of this life-threatening disease appear to outweigh the risks, particularly in view of the increasing resistance of Plasmodium falciparum to quinine in Southeast Asia.

Published
1982

33. Antibody response to suckling mouse brain rabies vaccines for post exposure treatment

Author

Juntra Karbwang, Pravan Suntharasamai, Rodney E. Phillips, Abha Sinhaseni, Sornchai Looareesuwan, Pierre Sureau, Mary J. Warrell, Chaisin Viravan, David A. Warrell, Wichai Supanaranond, Por Boonyarataphan, and Pornthep Chanthavanich

Subjects
Adult, Male, Post exposure, Rabies, Antibodies, Viral, medicine.disease_cause, Humans, Potency, Medicine, Neutralizing antibody, Aged, biology, business.industry, Rabies virus, Public Health, Environmental and Occupational Health, General Medicine, Middle Aged, medicine.disease, Regimen, Infectious Diseases, Antibody response, Rabies Vaccines, Immunology, biology.protein, Female, Parasitology, Antibody, business
Abstract

A new suckling mouse brain vaccine (SMBV) against rabies, produced by the Thai Red Cross Society, was compared with the well established Institut Pasteur SMBV in patients with very low risk rabies contact. The 4 regimens used were the standard daily injections with booster doses of Thai Red Cross vaccine (TRCV) and Institut Pasteur Vaccine (IPV), and a reduced dose scheme of 6 injections as used for tissue culture vaccines. The effect of 20 IU/kg of human rabies immune globulin (HRIG) was tested on each regimen, making 8 groups, a total of 122 patients. Blood samples taken on days 0, 7, 14, 28 and 91 were tested for neutralizing antibody. Only the standard IPV regimen produced antibody in every patient; all had levels greater than 0.5 IU at some stage. Two people (13%) given the standard TRCV produced no detectable antibody (less than or equal to 0.1 IU) throughout the study. The reduced dose regimens gave very low antibody levels. 7% of the IPV and 76% of the TRCV groups failed to produce antibody on any occasion. The antibody response was significantly suppressed by the administration of HRIG. Compared to the original South American SMBV, the vaccines tested induced low levels of short lived antibody. No reduction in the dosage of SMBV should be considered unless the potency of the product is adequate.

Published
1987

34. ELISA Confirmation of Acute and Past Envenoming by the Monocellate Thai Cobra (Naja kaouthia) *

Author

Chaisin Viravan, Mary J. Warrell, David A. Warrell, R.D.G. Theakston, and Udom Veeravat

Subjects
medicine.medical_specialty, Antivenom, Snake Bites, Poison control, Enzyme-Linked Immunosorbent Assay, Venom, Cobra, complex mixtures, Bungarus, Banded krait, Virology, Animals, Humans, Medicine, Naja kaouthia, Antigens, computer.programming_language, Elapid Venoms, biology, Antivenins, business.industry, Thailand, biology.organism_classification, Surgery, Infectious Diseases, Immunology, biology.protein, Parasitology, Antibody, business, computer
Abstract

The monocellate Thai cobra (Naja kaouthia) is a major cause of snake bite mortality and morbidity throughout Thailand, but neither the local nor the systemic effects of its venom are diagnostic. Species diagnosis is important because only monospecific antivenoms are available for treatment in Thailand. We tested the ability of the ELISA technique to detect venom antigen in the sera of 58 acute snake bite cases including 4 fatalities, and venom antibody in 51 patients bitten between 1 month and 19 years previously. N. kaouthia venom antigen was found in 8 of 33 patients with only local envenoming and in 14 of 20 with local plus systemic (neurotoxic) envenoming, but the mean venom concentration was 33 times greater in the latter group. The serum of 1 fatal case contained banded krait (Bungarus fasciatus) but no cobra venom antigen. N. kaouthia venom antibody was present in sera of patients bitten between 1 month and 7 years previously. Antibody was found in 6 of 8 patients who had had local envenoming alone but in only 19 of 41 who had had systemic envenoming treated by antivenom. The titer of antibody declined with an approximate half time of 2-3 years. One patient had a significant titer of B. fasciatus venom antibody. This study confirms the value of ELISA-immunodiagnosis and the predominance of N. kaouthia as a cause of neurotoxic envenoming in the Bang Phli area. However, the attribution of 1 fatal case to B. fasciatus bite suggests that patients with neurotoxic signs should be given B. fasciatus antivenom if they fail to respond to cobra antivenom.

Published
1986

35. A high rate of neurological complications following Semple anti-rabies vaccine

Author

Bruce G. Weniger, Witaya Swaddiwuthipong, Mary J. Warrell, and Somsak Wattanasri

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, Cohort Studies, Rabies vaccine, Meningoencephalitis, Case fatality rate, medicine, Humans, Child, Index case, business.industry, Encephalomyelitis, Acute Disseminated, Public Health, Environmental and Occupational Health, General Medicine, Thailand, medicine.disease, Surgery, Vaccination, Infectious Diseases, Rabies Vaccines, Parasitology, Rabies, Complication, business, Meningitis, Encephalitis, medicine.drug
Abstract

A fatal case of encephalitis due to Semple (phenolized sheep-brain) anti-rabies vaccine prompted a search for neurological complications among 722 recipients of 2 vaccine batches administered in Bangkok, Thailand in June and July 1984. A review of all patients admitted with neurological symptoms from June through August 1984 to the 5 major teaching hospitals in Bangkok found 6 cases (0·83%), including the index case, who had received the vaccine. Rabies infection was ruled out in all 6 cases. 4 patients had meningitis, and 2 had meningo-encephalitis. Only the index case was fatal; the other patients recovered without neurological sequelae. The rate of neurological complications after receiving Semple vaccine was therefore a minimum of 8·31 cases per 1000 persons vaccinated (1:120). This complication rate was about 25 times higher than the overall complication rate of 0·33 per 1000 (1:3018) determined from 14 previous reports. The fatality rate was 1·39 per 1000 (1:722), about 15 times higher than the rate of 0·09 per 1000 (1:10805) calculated from the previous studies. It is urgent to find economically feasible alternatives to Semple vaccine.

Published
1988

36. Intragastric Mefloquine is Absorbed Rapidly in Patients with Cerebral Malaria

Author

David A. Warrell, Pornthep Chanthavanich, J. von Bredow, Sornchai Looareesuwan, Mary J. Warrell, Nicholas J. White, and J. H. Digiovanni

Subjects
Adult, Male, Adolescent, medicine.medical_treatment, Absorption, Antimalarials, Chloroquine, Virology, parasitic diseases, medicine, Humans, Child, Intubation, Gastrointestinal, Brain Diseases, Quinine, Chemotherapy, business.industry, Mefloquine, Middle Aged, medicine.disease, Mefloquine Hydrochloride, Malaria, Bioavailability, Kinetics, Infectious Diseases, Cerebral Malaria, Anesthesia, Quinolines, Female, Parasitology, business, medicine.drug
Abstract

Mefloquine has proved effective in chloroquine- and quinine-resistant falciparum malaria, but it cannot be given parenterally. We have measured the absorption of mefloquine hydrochloride suspension (mean 15.6, range 9.7-28.6 mg/kg) given by nasogastric tube to 19 cerebral malaria patients already receiving intravenous quinine. Absorption was rapid with both dose schedules used; mean absorption half-times were 1.5 and 1.8 hr, and plasma mefloquine concentrations exceeded 200 ng/g within 3 hr of completing administration in all but one exceptionally ill patient who died 40 hr later. Steady state plasma concentrations over 7 days ranged from 300 to 1,050 (mean 561) ng/g. Bioavailability of mefloquine suspension in cerebral malaria therefore appears to be adequate for treatment in all but the most severely ill patients. Although intragastric mefloquine cannot now be recommended as an alternative to intravenous quinine for the treatment of severe chloroquine-resistant falciparum malaria, this situation could change if quinine resistance increases further.

Published
1985

37. Impaired cell-mediated immunity in Plasmodium falciparum-infected patients with high-parasitemia and cerebral malaria

Author

Ballet Jj, Savanat Tharavanis, Mary J. Warrell, Ph. Brasseur, Monique Agrapart, and Pierre Druilhe

Subjects
Adult, Male, Adolescent, Lymphocyte, Plasmodium falciparum, Immunology, Polyenes, Unconsciousness, Parasitemia, Lymphocyte Activation, Pathology and Forensic Medicine, Leukocyte Count, Immune system, Antigen, Pregnancy, In vivo, parasitic diseases, medicine, Humans, Immunology and Allergy, Child, Skin Tests, Immunity, Cellular, biology, Streptodornase and Streptokinase, Middle Aged, medicine.disease, biology.organism_classification, Virology, Anti-Bacterial Agents, Malaria, medicine.anatomical_structure, Cerebral Malaria, Acute Disease, Female, Macrolides, Mitogens
Abstract

Several cell-mediated functions were studied in vivo and in vitro in 63 Thai patients with acute falciparum malaria, including 21 cases with cerebral manifestations and 10 cases with initial parasitemia over 10%. Initial delayed cutaneous reactions to phytohemagglutinin and soluble protein antigens were negative in most cerebral malaria cases. In other patients, skin reactions were impaired or abolished as a direct function of parasitemia. No major alteration in the numbers of blood T and B lymphocytes was found. In lymphocyte cultures, proliferative responses to lectins were generally found within normal ranges; in contrast, proliferative responses to candidin were suppressed in parallel with delayed cutaneous responses to the same antigen. From these data, it can be concluded that the alteration of specific cell-mediated responses are predominantly detectable in acute cases with major parasite invasion, i.e., high parasitemia and/or cerebral manifestations. A direct role of Plasmodium falciparum was further suggested by the rapid restoration of cell-mediated functions observed in several cases under successful antimalarial therapy. These results do not support any evidence in favor of a preexisting cellular immune deficiency in relation with the occurrence of cerebral or high-parasitemia acute malaria in these patients.

Published
1983

38. A critical reappraisal of the use of enzyme-linked immunosorbent assays in the study of snake bite

Author

M. Ho, David A. Warrell, D. E. Bidwell, A. Voller, and Mary J. Warrell

Subjects
Antivenins, Cross reactions, Snake Bites, Enzyme-Linked Immunosorbent Assay, Elisa assay, Biology, Cross Reactions, Toxicology, medicine.disease_cause, Cross-reactivity, Predictive value, Animal origin, Antibodies, Body Fluids, Immunology, medicine, Immunoassay technique, Humans, Indicators and Reagents, Antibody detection, Snake Venoms
Abstract

The enzyme-linked immunosorbent assay (ELISA) has been the most widely used serological test in snake bite immunodiagnosis and epidemiology. The technique has been applied, however, without due consideration of the many factors which would affect an inherently sensitive test system, especially in tropical rural areas where large scale snake bite studies are usually carried out. This review discusses the effects of non-specific reactivity, cross reactivity and the quality of reagents on both the sensitivity and specificity of venom antigen and antibody detection assays. Simple laboratory modifications to optimize the assays are described. The importance of using the predictive value to assess the validity of applying the same test system in different circumstances is stressed. To fulfil its potential as the most versatile immunoassay technique in snake bite research, the test conditions of the ELISA will have to be much more stringently controlled in future.

Published
1986

39. The Importance of Anaemia in Cerebral and Uncomplicated Falciparum Malaria: Role of Complications, Dyserythropoiesis and Iron Sequestration

Author

Juntra Karbwang, S H Lee, David A. Warrell, Sornchai Looareesuwan, Mary J. Warrell, C Swasdichai, Rodney E. Phillips, D J Weatherall, and Nicholas J. White

Subjects
Creatinine, Pregnancy, medicine.medical_specialty, Blood transfusion, medicine.diagnostic_test, business.industry, Anemia, medicine.medical_treatment, Convalescence, media_common.quotation_subject, General Medicine, Hematocrit, medicine.disease, Gastroenterology, Surgery, chemistry.chemical_compound, chemistry, Cerebral Malaria, Internal medicine, medicine, Serum iron, business, media_common
Abstract

Ninety-four per cent of 169 patients with cerebral malaria developed anaemia (haematocrit less than 35 per cent) and 30 per cent required blood transfusion to maintain the haematocrit at more than 21 per cent. Anaemia was at its worst on admission in 58 patients (34 per cent); in the rest the haematocrit fell further, reaching its nadir one to 17 days later (mean 2.3 days). The mean lowest haematocrit was 24.3 +/- 7.2 per cent (+/- 1 SD) and the mean maximum fall was 7.9 +/- 5.6 per cent. Anaemia was more severe in patients with bacterial infection, retinal haemorrhages, schizontaemia and in pregnancy. The lowest haematocrit correlated with admission parasitaemia (r = -0.33, p less than 0.001), total serum bilirubin (r = -0.25, p less than 0.01) and serum creatinine (r = -0.22, p less than 0.01). In 23 patients with uncomplicated falciparum malaria the mean serum iron on admission was 53 micrograms/dl (range 16-157) and the mean serum ferritin 1773 ng/ml (range 170-10 000). There was a significant (p less than 0.001) rise in serum iron 96 h after starting antimalarial treatment; the serum ferritin declined slowly over several weeks. Stainable iron was present in all marrows examined and in eight patients the characteristic pattern of the anaemia of chronic disorders was seen. Seventy-three per cent of patients had dyserythropoiesis which was moderate to gross in 36 per cent. Dyserythropoiesis and erythrophagocytosis were often present on admission but sometimes appeared after the parasitaemia had cleared and persisted for at least three weeks into convalescence. These disturbances in iron metabolism and haemopoiesis are not completely explicable by red blood cell parasitisation. They may contribute more to the anaemia than has previously been recognised.

Published
1986

40. T-cell responsiveness in severe Plasmodium falciparum malaria

Author

Mary J. Warrell, Nicholas J. White, Monique Agrapart, Sornchai Looareesuwan, David A. Warrell, Savanat Tharavanij, Ballet Jj, Pierre Druilhe, Marc Gentilini, Philippe Brasseur, and Pornthep Chanthavanich

Subjects
biology, business.industry, T cell, T-Lymphocytes, Plasmodium falciparum, Public Health, Environmental and Occupational Health, General Medicine, T lymphocyte, biology.organism_classification, medicine.disease, Lymphocyte Activation, Virology, Malaria, Infectious Diseases, medicine.anatomical_structure, Cerebellar Diseases, Medicine, Humans, Parasitology, business
Published
1983

41. One year booster vaccination with purified vero cell rabies vaccine

Author

Wichai Supanaranond, Pravan Suntharasamai, Mary J. Warrell, and Pornthep Chanthavanich

Subjects
Booster vaccination, Rabies, business.industry, Immunization, Secondary, Public Health, Environmental and Occupational Health, General Medicine, Antibodies, Viral, Virology, Infectious Diseases, Rabies vaccine, Rabies Vaccines, Rabies virus, medicine, Vero cell, Animals, Humans, Parasitology, business, Vero Cells, medicine.drug, Duck embryo vaccine
Published
1988

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