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1. International Consensus (ICON): allergic reactions to vaccines

Author

Antonella Muraro, James T. Li, Mario Sánchez-Borges, Pascal Demoly, Kathryn M. Edwards, Michael Gold, Neal A. Halsey, Jean-Christoph Roger J-P Caubet, Renata J.M. Engler, Robert A. Wood, John M. Kelso, Stephen C. Dreskin, Menachem Rottem, Claude Ponvert, Lanny J. Rosenwasser, Donna S. Hummell, Division of Allergy and Clinical Immunology [Aurora, CO, USA], University of Colorado Anschutz [Aurora], Department of International Health [Baltimore, MD, USA], Johns Hopkins University School of Medicine [Baltimore]-Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Division of Allergy, Asthma, and Immunology [San Diego, CA, USA], Scripps Clinic [San Diego, CA, USA], The Division of Pediatric Allergy and Immunology [Baltimore, USA], Johns Hopkins University School of Medicine [Baltimore], Division of Pediatric Allergy, Immunology, and Pulmonary Medicine [Nashville, TN, USA], Vanderbilt University School of Medicine [Nashville], Division of Pediatric Infectious Diseases [Nashville, TN, USA], Department of Pediatrics [Geneva, Switzerland], Hôpitaux Universitaires de Genève (HUG), Department of Medicine and Pediatrics [Bethesda, MD, USA] (Allergy-Immunology-Immunization), Uniformed Services University of the Health Sciences (USUHS)-Walter Reed Army Institute of Research, Disipline of Paediatrics [Adelaide SA, Australia], University of Adelaide, Service de Pneumologie Allergologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Department of Allergy and Clinical Immunology [Caracas, Venezuela], Centro Medico-Docente La Trinidad, Food Allergy Referral Centre Veneto Region [Padua, Italy], Universita degli Studi di Padova, Division of Allergic Diseases [Rochester, MN, USA], Mayo Clinic [Rochester], Allergy Asthma and Immunology [Haifa, Israel], Ha'Emek Medical Center, Afula-Rappaport Faculty of Medicine, Allergy-Immunology Division [Kansas City, MO, USA], Children's Mercy Hospital [Kansas City]-University of Missouri [Kansas City] (UMKC), University of Missouri System-University of Missouri System, Walter Reed Army Institute of Research-Uniformed Services University of the Health Sciences (USUHS), Centro Médico Docente La Trinidad, Università degli Studi di Padova = University of Padua (Unipd), University of Colorado Denver School of Medicine [Aurora, CO, USA], Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University ( JHU ) -Johns Hopkins University ( JHU ) -Institute for Vaccine Safety [Baltimore, MD, USA], Vanderbilt University School of Medicine [[Nashville, TN, USA]], Hôpitaux Universitaires de Genève ( HUG ), Department of Medicine and Pediatrics [Bethesda, MD, USA] ( Allergy-Immunology-Immunization ), Uniformed Services University of the Health Sciences [Bethesda, MD, USA]-Walter Reed Army Medical Center [Bethesda, MD, USA], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut Pierre Louis d'Epidémiologie et de Santé Publique ( iPLESP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Sorbonne Universités, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, University Hospital of Padua, Mayo Clinic Rochester [USA], Children's Mercy Hospital [Kansas City, MO, USA]-University of Missouri–Kansas City School of Medicine [USA], and BMC, BMC

Subjects
lcsh:Immunologic diseases. Allergy, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Allergy, Consensus, [SDV]Life Sciences [q-bio], Immunology, Alternative medicine, Vaccines Administered, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, medicine, Immunology and Allergy, 030212 general & internal medicine, Consensus Document, Anaphylaxis, Components, computer.programming_language, Asthma, ddc:618, [ SDV ] Life Sciences [q-bio], business.industry, Routine immunization, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Causality, Immunization, International, Family medicine, Allergic reactions, Icon, lcsh:RC581-607, business, Vaccine, computer
Abstract

Background Routine immunization, one of the most effective public health interventions, has effectively reduced death and morbidity due to a variety of infectious diseases. However, allergic reactions to vaccines occur very rarely and can be life threatening. Given the large numbers of vaccines administered worldwide, there is a need for an international consensus regarding the evaluation and management of allergic reactions to vaccines.Methods Following a review of the literature, and with the active participation of representatives from the World Allergy Organization (WAO), the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma, and Immunology (AAAAI), and the American College of Allergy, Asthma, and Immunology (ACAAI), the final committee was formed with the purpose of having members who represented a wide-range of countries, had previously worked on vaccine safety, and included both allergist/immunologists as well as vaccinologists.Results Consensus was reached on a variety of topics, including: definition of immediate allergic reactions, including anaphylaxis, approaches to distinguish association from causality, approaches to patients with a history of an allergic reaction to a previous vaccine, and approaches to patients with a history of an allergic reaction to components of vaccines.Conclusions This document provides comprehensive and internationally accepted guidelines and access to on-line documents to help practitioners around the world identify allergic reactions following immunization. It also provides a framework for the evaluation and further management of patients who present either following an allergic reaction to a vaccine or with a history of allergy to a component of vaccines. Keywords: Allergy, Allergic reactions, Anaphylaxis, Causality, Components, International, Consensus, Vaccine

Published
2016
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2. Reconstructing unseen transmission events to infer dengue dynamics from viral sequences

Author

Stefan Fernandez, Butsaya Thaisomboonsuk, Caroline O. Buckee, Kriangsak Ruchusatsawat, Richard G. Jarman, Mathew V. Kiang, Kenth Engø-Monsen, Chonticha Klungthong, Jonathan M. Read, Derek A. T. Cummings, Henrik Salje, Sopon Iamsirithaworn, Noémie Lefrancq, Tyler S. Brown, Warunee Punpanich Vandepitte, Simon Cauchemez, Irina Maljkovic Berry, Amy Wesolowski, Piyarat Suntarattiwong, Wesolowski, Amy [0000-0001-6320-3575], Kiang, Mathew V [0000-0001-9198-150X], Berry, Irina Maljkovic [0000-0001-8555-5352], Lefrancq, Noemie [0000-0001-5991-6169], Jarman, Richard G [0000-0002-5765-0173], Engø-Monsen, Kenth [0000-0003-1618-7597], Buckee, Caroline [0000-0002-8386-5899], Cauchemez, Simon [0000-0001-9186-4549], Cummings, Derek AT [0000-0002-9437-1907], Apollo - University of Cambridge Repository, Kiang, Mathew V. [0000-0001-9198-150X], Jarman, Richard G. [0000-0002-5765-0173], Cummings, Derek A. T. [0000-0002-9437-1907], University of Cambridge [UK] (CAM), Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Florida [Gainesville] (UF), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Harvard T.H. Chan School of Public Health, Stanford University, Walter Reed Army Institute of Research, Armed Forces Research Institute of Medical Sciences [Bangkok] (AFRIMS), Ministry of Public Health [Thailand], Queen Sirikit National Institute of Child Health [Bangkok], Lancaster University, Telenor Group, H.S. is funded by the European Research Council (No. 804744). H.S. and D.A.T.C. would like to recognise funding by The National Institutes of Health (R01AI114703). A.P.W. is funded by a Career Award at the Scientific Interface by the Burroughs Wellcome Fund, by the National Library of Medicine of the National Institutes of Health under Award Number DP2LM013102 and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R21Al151750., and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Population genetics, Population Dynamics, General Physics and Astronomy, MESH: Dengue, 631/208/457, Dengue virus, MESH: Dengue Virus, medicine.disease_cause, law.invention, Dengue fever, Dengue, 0302 clinical medicine, 631/114/2397, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], law, Aedes, MESH: Child, Computational models, MESH: Animals, MESH: Models, Theoretical, MESH: Phylogeny, Child, Phylogeny, education.field_of_study, Multidisciplinary, Phylogenetic tree, article, MESH: Aedes, Thailand, Phylogeography, Transmission (mechanics), MESH: Phylogeography, Susceptible individual, 631/326/596/1413, Host-Pathogen Interactions, MESH: Mosquito Vectors, MESH: Genome, Viral, Algorithms, Adult, Science, 030231 tropical medicine, Population, MESH: Algorithms, Genome, Viral, Mosquito Vectors, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 692/699/255/2514, medicine, Animals, Humans, MESH: Thailand, education, MESH: Humans, MESH: Host-Pathogen Interactions, MESH: Adult, General Chemistry, MESH: Population Dynamics, Dengue Virus, Models, Theoretical, medicine.disease, 030104 developmental biology, Viral infection, Evolutionary biology, Vector (epidemiology)
Abstract

For most pathogens, transmission is driven by interactions between the behaviours of infectious individuals, the behaviours of the wider population, the local environment, and immunity. Phylogeographic approaches are currently unable to disentangle the relative effects of these competing factors. We develop a spatiotemporally structured phylogenetic framework that addresses these limitations by considering individual transmission events, reconstructed across spatial scales. We apply it to geocoded dengue virus sequences from Thailand (N = 726 over 18 years). We find infected individuals spend 96% of their time in their home community compared to 76% for the susceptible population (mainly children) and 42% for adults. Dynamic pockets of local immunity make transmission more likely in places with high heterotypic immunity and less likely where high homotypic immunity exists. Age-dependent mixing of individuals and vector distributions are not important in determining spread. This approach provides previously unknown insights into one of the most complex disease systems known and will be applicable to other pathogens., Phylogeographic analyses can provide broad descriptions of the spread of pathogens between populations, but are limited by incomplete sampling. Here, the authors develop an inference framework that reconstructs sequential transmission events and use it to characterise dynamics of dengue in Thailand.

Published
2021
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3. Evaluation of the extended efficacy of the Dengvaxia vaccine against symptomatic and subclinical dengue infection

Author

Mary Noreen Chua, Derek A. T. Cummings, Damon Ellison, Anon Srikiatkhachorn, Richard G. Jarman, Maria Theresa Alera, Alan L. Rothman, Gregory D. Gromowski, Stefan Fernandez, Henrik Salje, In-Kyu Yoon, Isabel Rodriguez-Barraquer, Taweewun Hunsawong, Louis R. Macareo, Simon Cauchemez, University of Cambridge [UK] (CAM), University of Florida [Gainesville] (UF), Armed Forces Research Institute of Medical Sciences [Bangkok] (AFRIMS), Chong Hua Hospital [Cebu City, Philippines], Walter Reed Army Institute of Research, University of Rhode Island (URI), King Mongkut's University of Technology North Bangkok (KMUTNB), University of California [San Francisco] (UCSF), University of California, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Coalition for Epidemic Preparedness Innovations [Washington, DC, États-Unis] (CEPI), This work was supported by the National Institutes of Health and National Institute of Allergy and Infectious Diseases (grant numbers P01AI034533, 5R01AI114703-05), the US Military Infectious Diseases Research Program and the European Research Council (grant number. 804744)., University of California [San Francisco] (UC San Francisco), University of California (UC), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, and promotion of well-being, Dengue virus, medicine.disease_cause, Antibodies, Viral, Medical and Health Sciences, Dengue fever, Dengue, 0302 clinical medicine, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Risk Factors, Medicine, Viral, Child, Asymptomatic Infections, Subclinical infection, education.field_of_study, Antibody titer, General Medicine, 3. Good health, Vaccination, Infectious Diseases, 3.4 Vaccines, 6.1 Pharmaceuticals, 030220 oncology & carcinogenesis, Child, Preschool, Infection, Biotechnology, Adolescent, Clinical Trials and Supportive Activities, Immunology, Population, Dengue Vaccines, Antibodies, General Biochemistry, Genetics and Molecular Biology, Article, Vaccine Related, 03 medical and health sciences, Rare Diseases, Clinical Research, Biodefense, Humans, Preschool, education, Dengue vaccine, business.industry, Prevention, Evaluation of treatments and therapeutic interventions, Prevention of disease and conditions, medicine.disease, Vaccine efficacy, Vector-Borne Diseases, Emerging Infectious Diseases, Good Health and Well Being, 030104 developmental biology, Immunization, business
Abstract

More than half of the world’s population lives in areas at risk for dengue virus infection. A vaccine will be pivotal to controlling spread, however, the only licensed vaccine, Dengvaxia, has been shown to increase the risk of severe disease in a subset of individuals. Vaccine efforts are hampered by a poor understanding of antibody responses, including those generated by vaccines, and whether antibody titers can be used as a marker of protection from infection or disease. Here we present the results of an ancillary study to a phase III vaccine study (n = 611). All participants received three doses of either Dengvaxia or placebo and were followed for 6 years. We performed neutralization tests on annual samples and during confirmed dengue episodes (n = 16,508 total measurements). We use mathematical models to reconstruct long-term antibody responses to vaccination and natural infection, and to identify subclinical infections. There were 87 symptomatic infections reported, and we estimated that there were a further 351 subclinical infections. Cumulative vaccine efficacy was positive for both subclinical and symptomatic infection, although the protective effect of the vaccine was concentrated in the first 3 years following vaccination. Among individuals with the same antibody titer, we found no difference between the risk of subsequent infection or disease between placebo and vaccine recipients, suggesting that antibody titers are a good predictor of both protection and disease risk. Multiyear analysis of antibody responses in recipients of the dengue vaccine Dengvaxia in the Philippines supports their utility as a predictor of protection against disease, and reveals that Dengvaxia efficacy declines 3 years after complete vaccination.

Published
2021
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4. RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control study

Author

Núria Díez-Padrisa, Chenjerai Jairoce, Nana Aba Williams, Benoit Gamain, Ben Gyan, James G. Beeson, Alfons Jiménez, Evelina Angov, Kwaku Poku Asante, Rebeca Santano, Deepak Gaur, Ruth Aguilar, Aintzane Ayestaran, Clarissa Valim, Ross L. Coppel, David Dosoo, Seth Owusu-Agyei, Joseph J. Campo, David E. Lanar, Itziar Ubillos, Marta Vidal, David R. Cavanagh, Augusto Nhabomba, Virander S. Chauhan, Sheetij Dutta, Carlota Dobaño, Gemma Moncunill, Chetan E. Chitnis, Universitat de Barcelona (UB), Centro de Investigação em Saúde de Manhiça [Maputo, Mozambique] (CISM), University of Ghana, Kintampo Health Research Centre, Ghana, CIBER de Epidemiología y Salud Pública (CIBERESP), Walter Reed Army Institute of Research, International Centre for Genetic Engineering and Biotechnology [New Delhi] (ICGEB), Biologie de Plasmodium et Vaccins - Malaria Parasite Biology and Vaccines, Institut Pasteur [Paris], Jawaharlal Nehru University (JNU), Department of Immunology and Infectious Diseases (IID), Harvard T.H. Chan School of Public Health, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Monash University [Melbourne], University of Edinburgh, The Macfarlane Burnet Institute for Medical Research and Public Health [Melbourne], Funding was obtained from the NIH-NIAID (R01AI095789), PATH Malaria Vaccine Initiative (MVI), Ministerio de Economía y Competitividad (Instituto de Salud Carlos III, PI11/00423 and PI14/01422), and EVIMalaR and AGAUR-Catalonia (2014 SGR991). GM was a recipient of a Sara Borrell—ISCIII fellowship (CD010/00156) and had the support of the Department of Health, Catalan Government (SLT006/17/00109). ISGlobal is a member of the CERCA Program, Generalitat de Catalunya., Biologie de Plasmodium et Vaccins, Department of Immunology and Infectious Diseases, Harvard School of Public Health, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS), Institut Pasteur [Paris] (IP), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)

Subjects
Male, lcsh:Medicine, Antibodies, Protozoan, 0302 clinical medicine, Pre-erythrocytic antigens, antibody, RTS,S, Medicine, 030212 general & internal medicine, Malaria, Falciparum, Child, Children, Protection, biology, Malaria vaccine, Vaccination, General Medicine, Acquired immune system, protection, 3. Good health, Blood-stage antigens, Child, Preschool, Female, Infants, Research Article, Naturally acquired immunity, Plasmodium falciparum, malaria, Malària, Àfrica, Antigens, Protozoan, RTS, 03 medical and health sciences, Immune system, Antigen, parasitic diseases, Malaria Vaccines, Humans, Antibody, Maternal antibodies, business.industry, lcsh:R, Infant, biology.organism_classification, medicine.disease, Malaria, maternal antibodies, Case-Control Studies, Immunology, Africa, Antibody Formation, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, business, Vaccine, 030217 neurology & neurosurgery
Abstract

Background Vaccination and naturally acquired immunity against microbial pathogens may have complex interactions that influence disease outcomes. To date, only vaccine-specific immune responses have routinely been investigated in malaria vaccine trials conducted in endemic areas. We hypothesized that RTS,S/A01E immunization affects acquisition of antibodies to Plasmodium falciparum antigens not included in the vaccine and that such responses have an impact on overall malaria protective immunity. Methods We evaluated IgM and IgG responses to 38 P. falciparum proteins putatively involved in naturally acquired immunity to malaria in 195 young children participating in a case-control study nested within the African phase 3 clinical trial of RTS,S/AS01E (MAL055 NCT00866619) in two sites of different transmission intensity (Kintampo high and Manhiça moderate/low). We measured antibody levels by quantitative suspension array technology and applied regression models, multimarker analysis, and machine learning techniques to analyze factors affecting their levels and correlates of protection. Results RTS,S/AS01E immunization decreased antibody responses to parasite antigens considered as markers of exposure (MSP142, AMA1) and levels correlated with risk of clinical malaria over 1-year follow-up. In addition, we show for the first time that RTS,S vaccination increased IgG levels to a specific group of pre-erythrocytic and blood-stage antigens (MSP5, MSP1 block 2, RH4.2, EBA140, and SSP2/TRAP) which levels correlated with protection against clinical malaria (odds ratio [95% confidence interval] 0.53 [0.3–0.93], p = 0.03, for MSP1; 0.52 [0.26–0.98], p = 0.05, for SSP2) in multivariable logistic regression analyses. Conclusions Increased antibody responses to specific P. falciparum antigens in subjects immunized with this partially efficacious vaccine upon natural infection may contribute to overall protective immunity against malaria. Inclusion of such antigens in multivalent constructs could result in more efficacious second-generation multistage vaccines. Electronic supplementary material The online version of this article (10.1186/s12916-019-1378-6) contains supplementary material, which is available to authorized users.

Published
2019
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5. International AIDS Society global scientific strategy: towards an HIV cure 2016

Author

Deeks, Sg, Lewin, Sr, Ross, Al, Ananworanich, J, Benkirane, M, Cannon, P, Chomont, N, Douek, D, Lifson, Jd, Lo, Yr, Kuritzkes, D, Margolis, D, Mellors, J, Persaud, D, Tucker, Jd, Barre-Sinoussi, F, International Aids Society Towards a Cure Working Group, International Aids Society Towards a Cure Working Group, Alter, G, Auerbach, J, Autran, B, Barouch, Dh, Behrens, G, Cavazzana, M, Chen, Z, Cohen, Ea, Corbelli, Gm, Eholié, S, Eyal, N, Fidier, S, Garcia, L, Grossman, C, Henderson, G, Henrich, Tj, Jefferys, R, Kiem, Hp, Mccune, J, Moodley, K, Newman, Pa, Nijhuis, M, Nsubuga, Ms, Ott, M, Palmer, S, Richman, D, Saez-Cirion, A, Sharp, M, Siliciano, J, Silvestri, G, Singh, J, Spire, B, Taylor, J, Tolstrup, M, Valente, S, van Lunzen, J, Walensky, R, Wilson, I, Zack, J, Department of Medicine [San Francisco], University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), The Peter Doherty Institute for Infection and Immunity [Melbourne], University of Melbourne-The Royal Melbourne Hospital, Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia, International and Scientific Relations Office, ANRS, Paris, France, Walter Reed Army Institute of Research, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), University of Southern California (USC), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), National Institutes of Health [Bethesda] (NIH), Frederick National Laboratory for Cancer Research (FNLCR), World Health Organization Regional Office for the Western Pacific, Manila, Philippines, Brigham and Women's Hospital [Boston], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Institut Pasteur [Paris] (IP), Ragon Institute of MGH, MIT and Harvard, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Clinic for Immunology and Rhematology, Hannover Medical School, Hanover, Germany, Département de Biothérapie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AIDS Institute, The University of Hong Kong, Pok Fu Lam, Hong Kong, Institut de Recherches Cliniques de Montréal (IRCM), Université de Montréal (UdeM), European AIDS Treatment Group, Italy, Programme PAC-CI, Centre Hospitalier Universitaire de Treichville, Abidjan, Côte d'Ivoire, Harvard School of Public Health, Imperial College London, The B-Change Group, Manila, Philippines, Treatment Action Group (TAG), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Stellenbosch University, Factor-Inwentash Faculty of Social Work, University of Toronto, Toronto, Ontario, Canada, University Medical Center [Utrecht], Joint Clinical Research Centre, University of California (UC), The Westmead Institute for Medical Research, University of California [San Diego] (UC San Diego), Independent HIV Education and Advocacy Consultant, San Francisco, California, USA, Emory University [Atlanta, GA], Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CARE Collaboratory Community Advisory Board, Palm Springs, California, USA., Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark., The Scripps Research Institute [La Jolla, San Diego], ViiV Healthcare, London, United Kingdom., Massachusetts General Hospital [Boston], Brown University School of Public Health, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California [San Francisco] (UCSF), University of California-University of California, Institut Pasteur [Paris], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Department of Medicine, Imperial College London, London, United Kingdom, University of California, Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Scripps Research Institute, Imperial College Healthcare NHS Trust- BRC Funding, American Foundation for AIDS Research, Medical Research Council (MRC), MRC DCS, British HIV Association (BHIVA), and Larose, Catherine

Subjects
CD4(+) T-CELLS, 0301 basic medicine, International Cooperation, [SDV]Life Sciences [q-bio], VIRAL RESERVOIR, Human immunodeficiency virus (HIV), Stakeholder engagement, HIV Infections, [SDV.GEN] Life Sciences [q-bio]/Genetics, Research & Experimental Medicine, medicine.disease_cause, Medicine, Societies, Medical, IN-VIVO, ComputingMilieux_MISCELLANEOUS, HIGHLY PATHOGENIC SIV, virus diseases, LATENT HIV-1, 11 Medical And Health Sciences, General Medicine, TREATMENT INTERRUPTION, 3. Good health, [SDV] Life Sciences [q-bio], International AIDS Society Towards a Cure Working Group, Medicine, Research & Experimental, Goals, Life Sciences & Biomedicine, BROADLY NEUTRALIZING ANTIBODIES, Biochemistry & Molecular Biology, medicine.medical_specialty, RALTEGRAVIR INTENSIFICATION, Immunology, education, Article, General Biochemistry, Genetics and Molecular Biology, HISTONE DEACETYLASE INHIBITOR, 03 medical and health sciences, Global population, Acquired immunodeficiency syndrome (AIDS), SUPPRESSIVE ANTIRETROVIRAL THERAPY, Journal Article, Humans, Organizational Objectives, Acquired Immunodeficiency Syndrome, [SDV.GEN]Life Sciences [q-bio]/Genetics, Science & Technology, business.industry, Research, Cell Biology, medicine.disease, Antiretroviral therapy, 030104 developmental biology, Treatment interruption, Family medicine, business
Abstract

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy.

Published
2016
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6. Improving Dengue Virus Capture Rates in Humans and Vectors in Kamphaeng Phet Province, Thailand, Using an Enhanced Spatiotemporal Surveillance Strategy

Author

Louis Lambrechts, Thomas W. Scott, Robert V. Gibbons, Alongkot Ponlawat, Richard G. Jarman, Jared Aldstadt, Jason H. Richardson, Alan L. Rothman, Stephen J. Thomas, Sopon Iamsirithaworn, Timothy P. Endy, In-Kyu Yoon, Darunee Buddhari, Walter Reed Army Institute of Research, United States Army (U.S. Army), Ministry of Public Health - Thailande, University of California [Davis] (UC Davis), University of California (UC), University of Rhode Island (URI), Interactions Virus-Insectes (IVI), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), National Institutes of Health [Bethesda] (NIH), Funding sources for this project included National Institutes of Health grants R01 GM083224-01 and P01 AI034533. Additional funding was provided by the U.S. Military Infectious Diseases Research Program., University of California, and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]

Subjects
Male, viruses, MESH: Dengue, Dengue virus, MESH: Dengue Virus, medicine.disease_cause, Medical and Health Sciences, Dengue fever, Dengue, MESH: Aged, 80 and over, 0302 clinical medicine, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Child, 80 and over, 2.2 Factors relating to the physical environment, MESH: Animals, Viral, 030212 general & internal medicine, Aetiology, Child, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, biology, Reverse Transcriptase Polymerase Chain Reaction, Transmission (medicine), Articles, Middle Aged, Thailand, MESH: Infant, 3. Good health, Infectious Diseases, MESH: Young Adult, Child, Preschool, MESH: RNA, Viral, Epidemiological Monitoring, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, Female, Infection, Adult, Adolescent, 030231 tropical medicine, MESH: Insect Vectors, Disease cluster, Vaccine Related, Young Adult, 03 medical and health sciences, Rare Diseases, Spatio-Temporal Analysis, MESH: Spatio-Temporal Analysis, Clinical Research, Biodefense, Tropical Medicine, Virology, medicine, Animals, Humans, Preschool, MESH: Thailand, Aged, MESH: Adolescent, Aedes, Dengue polymerase chain reaction, MESH: Humans, Geographic area, Prevention, MESH: Child, Preschool, Infant, MESH: Adult, Dengue Virus, medicine.disease, biology.organism_classification, MESH: Male, Insect Vectors, Vector-Borne Diseases, Emerging Infectious Diseases, Good Health and Well Being, Culicidae, Vector (epidemiology), RNA, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Parasitology, MESH: Epidemiological Monitoring, MESH: Culicidae, MESH: Female
Abstract

International audience; Dengue is of public health importance in tropical and sub-tropical regions. Dengue virus (DENV) transmission dynamics was studied in Kamphaeng Phet Province, Thailand, using an enhanced spatiotemporal surveillance of 93 hospitalized subjects with confirmed dengue (initiates) and associated cluster individuals (associates) with entomologic sampling. A total of 438 associates were enrolled from 208 houses with household members with a history of fever, located within a 200-m radius of an initiate case. Of 409 associates, 86 (21%) had laboratory-confirmed DENV infection. A total of 63 (1.8%) of the 3,565 mosquitoes collected were dengue polymerase chain reaction positive (PCR+). There was a significant relationship between spatial proximity to the initiate case and likelihood of detecting DENV from associate cases and Aedes mosquitoes. The viral detection rate from human hosts and mosquito vectors in this study was higher than previously observed by the study team in the same geographic area using different methodologies. We propose that the sampling strategy used in this study could support surveillance of DENV transmission and vector interactions.

Published
2015
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7. Reconstruction of antibody dynamics and infection histories to evaluate dengue risk

Author

Justin Lessler, Timothy P. Endy, Alden L. Weg, Isabel Rodriguez-Barraquer, Louis R. Macareo, Henrik Salje, Butsaya Thaisomboonsuk, Leah C. Katzelnick, Alan L. Rothman, Chonticha Klungthong, Stephen J. Thomas, Richard G. Jarman, Ananda Nisalak, Derek A. T. Cummings, In-Kyu Yoon, Damon Ellison, Simon Cauchemez, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), University of Florida [Gainesville] (UF), University of California [San Francisco] (UCSF), University of California, Armed Forces Research Institute of Medical Sciences [Bangkok] (AFRIMS), International Vaccine Institute (IVI), Walter Reed Army Institute of Research, SUNY Upstate Medical University, State University of New York (SUNY), University of Rhode Island (URI), National Institutes of Health (R01AI114703-01), Salje, Henrik [0000-0003-3626-4254], Apollo - University of Cambridge Repository, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UC San Francisco), and University of California (UC)

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], MESH: Dengue, Dengue virus, medicine.disease_cause, Antibodies, Viral, MESH: Dengue Vaccines, Dengue fever, Cohort Studies, Dengue, MESH: Child, [MATH]Mathematics [math], Child, MESH: Cohort Studies, Subclinical infection, education.field_of_study, Multidisciplinary, MESH: Risk, 3. Good health, MESH: Hemagglutination Inhibition Tests, Cohort, Disease Susceptibility, Seasons, Blood drawing, Cohort study, Risk, Adolescent, MESH: Bayes Theorem, Population, MESH: Disease Susceptibility, Dengue Vaccines, Models, Biological, Article, Antibodies, 03 medical and health sciences, medicine, Humans, education, MESH: Adolescent, MESH: Humans, business.industry, MESH: Models, Biological, Bayes Theorem, Dengue Virus, Hemagglutination Inhibition Tests, medicine.disease, Confidence interval, 030104 developmental biology, Immunology, business, MESH: Seasons, MESH: Antibodies, Viral
Abstract

As with many pathogens, most dengue infections are subclinical and therefore unobserved 1 . Coupled with limited understanding of the dynamic behaviour of potential serological markers of infection, this observational problem has wide-ranging implications, including hampering our understanding of individual- and population-level correlates of infection and disease risk and how these change over time, between assay interpretations and with cohort design. Here we develop a framework that simultaneously characterizes antibody dynamics and identifies subclinical infections via Bayesian augmentation from detailed cohort data (3,451 individuals with blood draws every 91 days, 143,548 haemagglutination inhibition assay titre measurements)2,3. We identify 1,149 infections (95% confidence interval, 1,135–1,163) that were not detected by active surveillance and estimate that 65% of infections are subclinical. After infection, individuals develop a stable set point antibody load after one year that places them within or outside a risk window. Individuals with pre-existing titres of ≤1:40 develop haemorrhagic fever 7.4 (95% confidence interval, 2.5–8.2) times more often than naive individuals compared to 0.0 times for individuals with titres >1:40 (95% confidence interval: 0.0–1.3). Plaque reduction neutralization test titres ≤1:100 were similarly associated with severe disease. Across the population, variability in the size of epidemics results in large-scale temporal changes in infection and disease risk that correlate poorly with age. Analyses of antibody dynamics and subclinical infections show that across the population, variability in the infection strength of dengue viruses results in large-scale temporal changes in infection and disease risk that correlate poorly with age.

Published
2017
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8. Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1

Author

Xiaojiang Gao, Stephen A. Migueles, Steven G. Deeks, Bruce D. Walker, Florencia P Segal, Emma Gostick, Zabrina L. Brumme, Mary Carrington, James J. Goedert, Nelson L. Michael, Jonathan M. Carlson, Ying Qi, Patrick R. Shea, David Price, Steven M. Wolinsky, Vivek Naranbhai, Julian P. Vivian, Nicolas Vince, Rasmi Thomas, Sian Llewellyn-Lacey, Maureen P. Martin, Jacques Fellay, Bernard A. P. Lafont, Veron Ramsuran, Jamie Rossjohn, David W. Haas, Shu Cheng Wong, Andrew G. Brooks, Philippa M. Saunders, Mark Connors, Jacqueline M.L. Widjaja, Phillip Pymm, Cancer and Inflammation Program [Frederick, MD, USA] (Leidos Biomedical Research Inc.), Frederick National Laboratory for Cancer Research (FNLCR)-NCI-Frederick, Ragon Institute of MGH, MIT and Harvard, Centre for the AIDS Programme of Research [Durban, South Africa] (CAPRISA), University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN), Institute for Genomic Medicine [New York, NY, USA], Columbia University [New York], KwaZulu-Natal Research Innovation and Sequencing Platform [Durban, South Africa] (KRISP), University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN)-School of Laboratory Medicine and Medical Sciences [Durban, South Africa], Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Translational ImmunoGenetic in AutoImmunity and Transplantation (Team 5 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), US Military HIV Research Program [Silver Spring, MD, USA], Walter Reed Army Institute of Research, Henry M. Jackson Foundation for the Advancement of Military Medicine (HJM), Faculty of Health Sciences [Burnaby, BC, Canada], Simon Fraser University (SFU.ca), British Columbia Centre for Excellence in HIV/AIDS [Vancouver, BC, Canada], Microsoft Research [Redmond], Microsoft Corporation [Redmond, Wash.], Division of Infectious Diseases [Chicago, IL, USA], Northwestern University Feinberg School of Medicine, Infections and Immunoepidemiology Branch [Bethesda, MD, USA], National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), San Francisco General Hospital Medical Center [San Francisco, CA, USA], Vanderbilt University School of Medicine [Nashville], Laboratory of Immunoregulation [Bethesda, MD, USA], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), School of Life Sciences [Lausanne], Ecole Polytechnique Fédérale de Lausanne (EPFL), School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff], Non-Human Primate Immunogenetics and Cellular Immunology Unit [Bethesda, MD, USA], National Institutes of Health [Bethesda] (NIH)-National Institute of Allergy and Infectious Deseases (NIAID), Human Immunology Section [Bethesda, MD, USA] (Vaccine Research Center), Viral Immunology Section [Bethesda, MD, USA] (Office of the Scientific Director), Infection and Immunity Program [Victoria, Australia] (Department of Biochemistry and Molecular Biology), Monash University [Clayton]-Biomedicine Discovery Institute [Victoria, Australia]-Australian Research Council Centre of Excellence in Advanced Molecular Imaging [Victoria, Australia], Department of Microbiology and Immunology [Victoria, Australia], University of Melbourne-Peter Doherty Institute for Infection and Immunity [Victoria, Australia], This work was supported by federal funds from the NCI, NIH, under contract HHSN261200800001E., Le Bihan, Sylvie, University of KwaZulu-Natal (UKZN), University of KwaZulu-Natal (UKZN)-School of Laboratory Medicine and Medical Sciences [Durban, South Africa], Institute of Medical Genetics [Cardiff]-Cardiff University, and Monash University [Clayton]-Australian Research Council Centre of Excellence in Advanced Molecular Imaging [Victoria, Australia]-Biomedicine Discovery Institute [Victoria, Australia]

Subjects
0301 basic medicine, Adult, Male, T cell, Killer-cell immunoglobulin-like receptor, Immunology, HIV Infections, NK cells, Medical and Health Sciences, AIDS/HIV, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, KIR3DL1, Clinical Research, MHC class I, Receptors, medicine, HLA-B Antigens, 2.1 Biological and endogenous factors, Humans, Aetiology, Receptor, MHC class 1, Innate immunity, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Genetic Variation, Receptors, KIR3DL1, General Medicine, Middle Aged, Molecular biology, Allotype, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Good Health and Well Being, biology.protein, HIV-1, HIV/AIDS, Female, Infection, CD8, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, Research Article
Abstract

International audience; HLA-B*57 control of HIV involves enhanced CD8+ T cell responses against infected cells, but extensive heterogeneity exists in the level of HIV control among B*57+ individuals. Using whole-genome sequencing of untreated B*57+ HIV-1-infected controllers and noncontrollers, we identified a single variant (rs643347A/G) encoding an isoleucine-to-valine substitution at position 47 (I47V) of the inhibitory killer cell immunoglobulin-like receptor KIR3DL1 as the only significant modifier of B*57 protection. The association was replicated in an independent cohort and across multiple outcomes. The modifying effect of I47V was confined to B*57:01 and was not observed for the closely related B*57:03. Positions 2, 47, and 54 tracked one another nearly perfectly, and 2 KIR3DL1 allotypes differing only at these 3 positions showed significant differences in binding B*57:01 tetramers, whereas the protective allotype showed lower binding. Thus, variation in an immune NK cell receptor that binds B*57:01 modifies its protection. These data highlight the exquisite specificity of KIR-HLA interactions in human health and disease.

Published
2017

9. Clinical and public health implications of acute and early HIV detection and treatment: a scoping review

Author

Christopher D. Pilcher, Omar Sued, Christophe Fraser, Sarah Fidler, Myron S. Cohen, Marco Vitoria, Jintanat Ananworanich, Joseph D. Tucker, Cheryl Johnson, Sarah E. Rutstein, Meg Doherty, Asier Sáez-Cirión, Eduard J. Sanders, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Walter Reed Army Institute of Research, Henry M. Jackson Foundation for the Advancement of Military Medicine (HJM), Imperial College London, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), London School of Hygiene and Tropical Medicine (LSHTM), University of Amsterdam [Amsterdam] (UvA), Kenya Medical Research Institute (KEMRI), Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford, Fundación Huésped [Buenos Aires], HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP), University of California [San Francisco] (UC San Francisco), University of California (UC), EJS is supported by Wellcome Trust and the KWTRP at the Centre for Geographical Medicine Research‐Kilifi (supported by core funding from the Wellcome Trust (#203077/Z/16/Z)), with support from the International AIDS Vaccine Initiative. JDT is supported by NIAID R21AI20549. SF is supported by NIHR BRC. SER was supported by National Institutes of Health [R01 AI114320], [F30 MH098731] and [T32 GM008719]., University of Oxford [Oxford], HIV, Inflammation et persistance, Institut Pasteur [Paris], University of California [San Francisco] (UCSF), University of California, Imperial College Healthcare NHS Trust- BRC Funding, MRC DCS, Medical Research Council (MRC), and Merck Sharp & Dohme Ltd.

Subjects
0301 basic medicine, T-CELL COUNTS, [SDV]Life Sciences [q-bio], Human immunodeficiency virus (HIV), HIV Infections, Review Article, medicine.disease_cause, COST-EFFECTIVENESS, acute HIV infection, Pre-exposure prophylaxis, 0302 clinical medicine, MESH: Early Diagnosis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Behavior Therapy, diagnostics, 030212 general & internal medicine, Prospective Studies, guidelines, low- and middle-income countries, Prospective cohort study, SUB-SAHARAN AFRICA, ADULTS SEEKING CARE, Framingham Risk Score, Transmission (medicine), MESH: Behavior Therapy, MESH: HIV Infections, 3. Good health, MESH: Point-of-Care Systems, Infectious Diseases, Public Health, AG/AB COMBO TEST, VIRAL-LOAD, MESH: Public Health, Viral load, Life Sciences & Biomedicine, early HIV, medicine.medical_specialty, Point-of-Care Systems, 030106 microbiology, Immunology, antiretroviral therapy, primary HIV, UNITED-STATES, 03 medical and health sciences, medicine, Humans, Intensive care medicine, Science & Technology, MESH: Humans, business.industry, Public health, Public Health, Environmental and Occupational Health, 1199 Other Medical And Health Sciences, MESH: Prospective Studies, respiratory tract diseases, Early Diagnosis, EARLY ANTIRETROVIRAL THERAPY, Pre-Exposure Prophylaxis, Implementation research, business, SEXUALLY-TRANSMITTED INFECTION, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, PREEXPOSURE PROPHYLAXIS, MESH: Pre-Exposure Prophylaxis
Abstract

INTRODUCTION: The unchanged global HIV incidence may be related to ignoring acute HIV infection (AHI). This scoping review examines diagnostic, clinical, and public health implications of identifying and treating persons with AHI. METHODS: We searched PubMed, in addition to hand-review of key journals identifying research pertaining to AHI detection and treatment. We focused on the relative contribution of AHI to transmission and the diagnostic, clinical, and public health implications. We prioritized research from low- and middle-income countries (LMICs) published in the last fifteen years. RESULTS AND DISCUSSION: Extensive AHI research and limited routine AHI detection and treatment have begun in LMIC. Diagnostic challenges include ease-of-use, suitability for application and distribution in LMIC, and throughput for high-volume testing. Risk score algorithms have been used in LMIC to screen for AHI among individuals with behavioural and clinical characteristics more often associated with AHI. However, algorithms have not been implemented outside research settings. From a clinical perspective, there are substantial immunological and virological benefits to identifying and treating persons with AHI - evading the irreversible damage to host immune systems and seeding of viral reservoirs that occurs during untreated acute infection. The therapeutic benefits require rapid initiation of antiretrovirals, a logistical challenge in the absence of point-of-care testing. From a public health perspective, AHI diagnosis and treatment is critical to: decrease transmission via viral load reduction and behavioural interventions; improve pre-exposure prophylaxis outcomes by avoiding treatment initiation for HIV-seronegative persons with AHI; and, enhance partner services via notification for persons recently exposed or likely transmitting. CONCLUSIONS: There are undeniable clinical and public health benefits to AHI detection and treatment, but also substantial diagnostic and logistical barriers to implementation and scale-up. Effective early ART initiation may be critical for HIV eradication efforts, but widespread use in LMIC requires simple and accurate diagnostic tools. Implementation research is critical to facilitate sustainable integration of AHI detection and treatment into existing health systems and will be essential for prospective evaluation of testing algorithms, point-of-care diagnostics, and efficacious and effective first-line regimens.

Published
2017
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10. Prediction, Assessment of the Rift Valley Fever Activity in East and Southern Africa 2006–2008 and Possible Vector Control Strategies

Author

Patrick Nguku, Allen W. Hightower, Robert Swanepoel, Seth C. Britch, Jennifer Small, David Schnabel, Mohamed A. Mohamed, Mark D. Latham, Robert F. Breiman, Stephane de La Rocque, Salih Osman Magdi, Jean-Paul Chretien, Pierre Formenty, Jean-Marc Reynes, Edwin W. Pak, Henry B. Lewandowski, Compton J. Tucker, Kenneth J. Linthicum, Assaf Anyamba, Rosemary Sang, Karl A. Haagsma, NASA Goddard Space Flight Center (GSFC), USDA-ARS Center for Medical, Agricultural and Veterinary Entomology, USDA-ARS : Agricultural Research Service, EMPRES/Animal Production and Health Division (AGAH), Food and Agriculture Organization of the United Nations, Global Alert and Response Department (HSE/GAR), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Kenya Medical Research Unit (KEMRI-CDC), Kenya Medical Research Institute (KEMRI), Division of Preventive Medicine, Walter Reed Army Institute of Research, United States Army Medical Research Unit-Kenya, United States Army Medical Research Directorate [Kenya] (USAMRD-K), 757th Airlift Squadron, Youngstown Air Reserve Station, Manatee County Mosquito Control, Chatham County Mosquito Control, Federal Ministry of Health, Epidemiology Department, Ministry of Health and Social Welfare, Division of Communicable Disease Control, Ministry of Health [Mozambique], Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), National Institute for Communicable Diseases [Johannesburg] (NICD), Kenya Medical Research Unit, and National Institute for Communicable Diseases (NICD)

Subjects
Rift Valley Fever, Climate, Rain, MESH: Satellite Communications, MESH: Risk Assessment, Disease Outbreaks, 0302 clinical medicine, Aedes, MESH: Rift Valley Fever, MESH: Animals, MESH: Disease Outbreaks, Rift Valley fever, 0303 health sciences, Temperature, Articles, MESH: Aedes, Vegetation, Africa, Eastern, Satellite Communications, MESH: Climate, MESH: Temperature, Culex, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Geography, Habitat, Animals, Domestic, Livestock, MESH: Forecasting, 030231 tropical medicine, MESH: Culex, MESH: Insect Vectors, Risk Assessment, Africa, Southern, 03 medical and health sciences, Virology, parasitic diseases, medicine, Animals, Humans, MESH: Animals, Domestic, Epizootic, 030304 developmental biology, MESH: Africa, Eastern, MESH: Humans, business.industry, Outbreak, medicine.disease, Insect Vectors, El Niño, 13. Climate action, Vector (epidemiology), MESH: Rain, Parasitology, MESH: Africa, Southern, Physical geography, business, Forecasting
Abstract

International audience; Historical outbreaks of Rift Valley fever (RVF) since the early 1950s have been associated with cyclical patterns of the El Niño/Southern Oscillation (ENSO) phenomenon, which results in elevated and widespread rainfall over the RVF endemic areas of Africa. Using satellite measurements of global and regional elevated sea surface temperatures, elevated rainfall, and satellite derived-normalized difference vegetation index data, we predicted with lead times of 2-4 months areas where outbreaks of RVF in humans and animals were expected and occurred in the Horn of Africa, Sudan, and Southern Africa at different time periods from September 2006 to March 2008. Predictions were confirmed by entomological field investigations of virus activity and by reported cases of RVF in human and livestock populations. This represents the first series of prospective predictions of RVF outbreaks and provides a baseline for improved early warning, control, response planning, and mitigation into the future.

Published
2010
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11. Rationale for the coadministration of albendazole and ivermectin to humans for malaria parasite transmission control

Author

Haoues Alout, Archie C. A. Clements, Brian D. Foy, Jason H. Richardson, Brett E. Swierczewski, Poom Adisakwattana, Kevin C. Kobylinski, Walter Reed Army Institute of Research, Department of Microbiology, Immunology, and Pathology, Arthropod-borne and Infectious Diseases Laboratory, Colorado State University [Fort Collins] (CSU), Australian National University (ANU), Mahidol University [Bangkok], Armed Forces Pest Management Board, and Partenaires INRAE

Subjects
Anopheles gambiae, [SDV]Life Sciences [q-bio], 030231 tropical medicine, Plasmodium falciparum, Albendazole, Perspective Piece, 03 medical and health sciences, Soil, 0302 clinical medicine, Ivermectin, Virology, parasitic diseases, Anopheles, medicine, Animals, Humans, 030212 general & internal medicine, Malaria, Falciparum, Mass drug administration, Ascaris lumbricoides, biology, Antiparasitic Agents, Drug Synergism, medicine.disease, biology.organism_classification, Antiparasitic agent, 3. Good health, Insect Vectors, Infectious Diseases, Trichuris, Immunology, Coinfection, Parasitology, Drug Therapy, Combination, Malaria, medicine.drug
Abstract

Recently there have been calls for the eradication of malaria and the elimination of soil-transmitted helminths (STHs). Malaria and STHs overlap in distribution, and STH infections are associated with increased risk for malaria. Indeed, there is evidence that suggests that STH infection may facilitate malaria transmission. Malaria and STH coinfection may exacerbate anemia, especially in pregnant women, leading to worsened child development and more adverse pregnancy outcomes than these diseases would cause on their own. Ivermectin mass drug administration (MDA) to humans for malaria parasite transmission suppression is being investigated as a potential malaria elimination tool. Adding albendazole to ivermectin MDAs would maximize effects against STHs. A proactive, integrated control platform that targets malaria and STHs would be extremely cost-effective and simultaneously reduce human suffering caused by multiple diseases. This paper outlines the benefits of adding albendazole to ivermectin MDAs for malaria parasite transmission suppression.

Published
2014
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12. Specificity of resistance to dengue virus isolates is associated with genotypes of the mosquito antiviral gene Dicer-2

Author

Thomas W. Scott, Louis Lambrechts, Jason H. Richardson, Christine Chevillon, Valérie Noël, Richard G. Jarman, Elsa Quillery, Insectes et Maladies Infectieuses, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Evolution Théorique et Expérimentale (MIVEGEC-ETE), Perturbations, Evolution, Virulence (PEV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Entomology branch, Walter Reed Army Institute of Research, Viral Disease branch, Department of Entomology, University of California [Davis] (UC Davis), University of California-University of California, Evolution of host-microbe communities (MIVEGEC-EVCO), Processus Écologiques et Évolutifs au sein des Communautés (PEEC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and University of California (UC)-University of California (UC)

Subjects
0106 biological sciences, Ribonuclease III, Genotype, Population, Locus (genetics), Dengue virus, medicine.disease_cause, 010603 evolutionary biology, 01 natural sciences, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Virus, Dicer-2, 03 medical and health sciences, Aedes aegypti, RNA interference, Aedes, medicine, Animals, education, Research Articles, 030304 developmental biology, General Environmental Science, DNA Primers, Disease Resistance, Genetics, 0303 health sciences, education.field_of_study, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, General Immunology and Microbiology, biology, RNA virus, General Medicine, Dengue Virus, biology.organism_classification, Thailand, Virology, Immunity, Innate, 3. Good health, Genetics, Population, RNAi, Host-Pathogen Interactions, biology.protein, Female, RNA Interference, General Agricultural and Biological Sciences, genotype-by-genotype interaction, Dicer
Abstract

In contrast to the prevailing view that invertebrate immunity relies on broad-spectrum recognition and effector mechanisms, intrinsic genetic compatibility between invertebrate hosts and their pathogens is often highly specific in nature. Solving this puzzle requires a better understanding of the molecular basis underlying observed patterns of invertebrate host–pathogen genetic specificity, broadly referred to as genotype-by-genotype interactions. Here, we identify an invertebrate immune gene in which natural polymorphism is associated with isolate-specific resistance to an RNA virus.Dicer-2(dcr2) encodes a key protein upstream of the RNA interference (RNAi) pathway, a major antiviral component of innate immunity in invertebrates. We surveyed allelic polymorphism at thedcr2locus in a wild-type outbred population and in three derived isofemale families of the mosquitoAedes aegyptithat were experimentally exposed to several, genetically distinct isolates of dengue virus. We found thatdcr2genotype was associated with resistance to dengue virus in a virus isolate-specific manner. By contrast, no such association was found for genotypes at two control loci flankingdcr2, making it likely thatdcr2contains the yet-unidentified causal polymorphism(s). This result supports the idea that host–pathogen compatibility in this system depends, in part, on a genotype-by-genotype interaction betweendcr2and the viral genome, and points to the RNAi pathway as a potentially important determinant of intrinsic insect-virus genetic specificity.

Published
2012
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13. A commensal gone bad: Complete genome sequence of the prototypical enterotoxigenic Escherichia coli strain H10407

Author

Ian R. Henderson, A. Keith Turner, Jon L. Hobman, Scott A. Beatson, Vivienne Mahon, Julian Parkhill, Mark J. Pallen, Nicola K. Petty, Timothy J. Wells, Timothy J. Johnson, Carl Brinkley, Susan M. Turner, Roy R. Chaudhuri, Charles W. Penn, Adam F. Cunningham, Stephen G. J. Smith, Lisa Crossman, Stephen J. Savarino, Nicholas R. Thomson, Mickaël Desvaux, The Wellcome Trust Sanger Institute [Cambridge], Department of Veterinary Medicine, University of Cambridge [UK] (CAM), School of Chemistry & Molecular Biosciences, University of Queensland [Brisbane], School of Immunity and Infection, University of Birmingham [Birmingham], Trinity College Dublin, Walter Reed Army Institute of Research, School of Biosciences, University of Nottingham, UK (UON), Department of Enteric Diseases, Armed Forces Research Institute of Medical Sciences [Bangkok] (AFRIMS), Department of Veterinary and Biomedical Sciences, University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, and BBSRC BB/C510075/1

Subjects
Colonization, Identification, Genomics and Proteomics, medicine.disease_cause, Genome, sécrétion, Plasmid, Enterotoxigenic Escherichia coli, Epithelial-cell invasion, Genetics, 0303 health sciences, biology, Virulence, Escherichia coli Proteins, cellule épithéliale, Chromosomes, Bacterial, Enterobacteriaceae, 3. Good health, Plasmid stability, protéine, plasmide, Fimbriae Proteins, escherichia coli, Autre (Sciences du Vivant), Plasmids, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], colonisation, Characterization, Molecular Sequence Data, Context (language use), Microbiology, 03 medical and health sciences, entérotoxine thermostable, medicine, Amino Acid Sequence, Gene-cluster, Molecular Biology, Escherichia coli, Secretion, 030304 developmental biology, Heat-labile enterotoxin, Molecular, Protein, Whole genome sequencing, 030306 microbiology, Gene Expression Profiling, caractérisation, Gene Expression Regulation, Bacterial, biology.organism_classification, Genome, Bacterial
Abstract

In most cases, Escherichia coli exists as a harmless commensal organism, but it may on occasion cause intestinal and/or extraintestinal disease. Enterotoxigenic E. coli (ETEC) is the predominant cause of E. coli -mediated diarrhea in the developing world and is responsible for a significant portion of pediatric deaths. In this study, we determined the complete genomic sequence of E. coli H10407, a prototypical strain of enterotoxigenic E. coli , which reproducibly elicits diarrhea in human volunteer studies. We performed genomic and phylogenetic comparisons with other E. coli strains, revealing that the chromosome is closely related to that of the nonpathogenic commensal strain E. coli HS and to those of the laboratory strains E. coli K-12 and C. Furthermore, these analyses demonstrated that there were no chromosomally encoded factors unique to any sequenced ETEC strains. Comparison of the E. coli H10407 plasmids with those from several ETEC strains revealed that the plasmids had a mosaic structure but that several loci were conserved among ETEC strains. This study provides a genetic context for the vast amount of experimental and epidemiological data that have been published.

Published
2010
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14. Plasmodium falciparum liver stage antigen-1 is cross-linked by tissue transglutaminase

Author

William S. Nicoll, Christian Doerig, Michael R. Hollingdale, John B. Sacci, Carlo Rodolfo, David E. Lanar, Mauro Piacentini, Giuseppina Di Giacomo, Zoe Holland, BMC, Ed., U.S. Military Malaria Vaccine Program, Walter Reed Army Institute of Research-Division of Malaria Vaccine Development, Department of Microbiology and Immunology, University of Maryland School of Medicine, University of Maryland System-University of Maryland System, Department of Biology, Università degli Studi di Roma Tor Vergata [Roma], Controle de la Proliferation Cellulaire Chez Plasmodium Falciparum, Institut National de la Santé et de la Recherche Médicale (INSERM), Consultant to the USMMVP, and Malaria Department

Subjects
Tissue transglutaminase, MESH: Microscopy, Fluorescence, Mice, SCID, Schizogony, Mice, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Parasite hosting, MESH: Animals, MESH: Mice, SCID, Malaria, Falciparum, MESH: Plasmodium falciparum, 0303 health sciences, Microscopy, biology, MESH: Malaria, Falciparum, 3. Good health, Cell biology, medicine.anatomical_structure, Infectious Diseases, Liver, MESH: Transglutaminases, Hepatocyte, Protozoan, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Antibody, Falciparum, Settore BIO/06, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Plasmodium falciparum, Antigens, Protozoan, SCID, MESH: Host-Parasite Interactions, Fluorescence, lcsh:Infectious and parasitic diseases, Host-Parasite Interactions, 03 medical and health sciences, Antigen, medicine, Animals, Humans, lcsh:RC109-216, Protein Glutamine gamma Glutamyltransferase 2, Antigens, MESH: Mice, 030304 developmental biology, MESH: Humans, Transglutaminases, Research, biology.organism_classification, Virology, In vitro, Malaria, Microscopy, Fluorescence, biology.protein, Parasitology, MESH: Antigens, Protozoan, MESH: Liver
Abstract

Background Plasmodium falciparum sporozoites injected by mosquitoes into the blood rapidly enter liver hepatocytes and undergo pre-erythrocytic developmental schizogony forming tens of thousands of merozoites per hepatocyte. Shortly after hepatocyte invasion, the parasite starts to produce Liver Stage Antigen-1 (LSA-1), which accumulates within the parasitophorous vacuole surrounding the mass of developing merozoites. The LSA-1 protein has been described as a flocculent mass, but its role in parasite development has not been determined. Methods Recombinant N-terminal, C-terminal or a construct containing both the N- and C- terminal regions flanking two 17 amino acid residue central repeat sequences (LSA-NRC) were subjected to in vitro modification by tissue transglutaminase-2 (TG2) to determine if cross-linking occurred. In addition, tissue sections of P. falciparum-infected human hepatocytes were probed with monoclonal antibodies to the isopeptide ε-(γ-glutamyl)lysine cross-bridge formed by TG2 enzymatic activity to determine if these antibodies co-localized with antibodies to LSA-1 in the growing liver schizonts. Results This study identified a substrate motif for (TG2) and a putative casein kinase 2 phosphorylation site within the central repeat region of LSA-1. The function of TG2 is the post-translational modification of proteins by the formation of a unique isopeptide ε-(γ-glutamyl)lysine cross-bridge between glutamine and lysine residues. When recombinant LSA-1 protein was crosslinked in vitro by purified TG2 in a calcium dependent reaction, a flocculent mass of protein was formed that was highly resistant to degradation. The cross-linking was not detectably affected by phosphorylation with plasmodial CK2 in vitro. Monoclonal antibodies specific to the very unique TG2 catalyzed ε- lysine cross-bridge co-localized with antibodies to LSA-1 in infected human hepatocytes providing visual evidence that LSA-1 was cross-linked in vivo. Conclusions While the role of LSA-1 is still unknown these results suggest that it becomes highly cross-linked which may aid in the protection of the parasite as it develops.

Published
2010
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15. Parasite Load Decrease during Application of a Safe and Easily Applied Antileishmanial Aminoglycoside Cream

Author

Philip L. Smith, A. Kidar, Nathalie Ben Messaoud, Max Grogl, Anne Novitt-Moreno, Carl J. Nielsen, Afif Ben Salah, Amor Zaâtour, Gloria Morizot, Mara Kreishman-Deitrick, Janet Ransom, Karen M. Kopydlowski, Pierre Buffet, Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP), Regional Hospital of Gafsa, U.S. Army Medical Materiel Development Activity, Fort Detrick, Fast-Track Drugs and Biologics, North Potomac, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Walter Reed Army Institute of Research

Subjects
Male, Paromomycin, Administration, Topical, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Scars, Cryotherapy, Parasite load, Parasite Load, From Innovation to Application, Clinical trials, Medicine, ComputingMilieux_MISCELLANEOUS, biology, lcsh:Public aspects of medicine, Dermis, Middle Aged, Trypanocidal Agents, Drug Combinations, Infectious Diseases, Research Design, Leishmaniasis, Visceral, Female, medicine.symptom, Phase II clinical investigation, medicine.drug, Adult, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, Adolescent, Clinical Research Design, lcsh:RC955-962, Leishmania donovani, Research and Analysis Methods, Microbiology, Young Adult, Cutaneous leishmaniasis, Humans, Aged, Medicine and health sciences, business.industry, Public Health, Environmental and Occupational Health, Biology and Life Sciences, lcsh:RA1-1270, Papule, biology.organism_classification, Leishmania, medicine.disease, Surgery, Clinical medicine, Parasitology, Gentamicins, business
Abstract

Cutaneous leishmaniasis (CL) is a disfiguring illness caused by Leishmania species of protozoa, with over 350 million people at risk worldwide [1]. Leishmania parasites enter the skin through a sandfly bite, producing a papule or nodule that generally ulcerates [1]. Spontaneous resolution of CL ulcers may take months to years [2], and both active lesions and scars can engender stigma and cause disability [3]. There is no consensus regarding the optimum therapy for CL, and no single treatment approach fits all possible clinical presentations [1], [2]. However, because systemic treatments may produce considerable toxicity [1], [2], [4], localized therapy (e.g., intralesional antimonials, cryotherapy, thermotherapy, or intralesional injections plus cryotherapy) is now recommended in Old World CL (L. major, L. tropica) and in selected cases of New World CL [1], [2]. However, all present local therapy modalities have limitations, e.g., variable cure rates, pain, challenges and complexities associated with treatment administration (especially in children), and variable utility in patients with multiple lesions or lesions located on body areas where local treatment is impractical [1], [2], [5].

Published
2014
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