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James Whitehorn,
Rosmari Rodriguez Roche,
Maria G Guzman, Eric Martinez,
Wilmar Villamil Gomez,
Leonard Nainggolan,
Ida Safitri Laksono,
Ajay Mishra,
Lucy Lum,
Abul Faiz, [......],
Axel Kroeger,
Olaf Horstick,
Guy Thwaites,
Heiman Wertheim,
Mattias Larsson,
Tran Tinh Hien,
Rosanna Peeling,
Bridget Wills,
Cameron Simmons,
Jeremy Farrar
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ABSTRACT: Dengue is the most important arboviral infection of humans. Thrombocytopenia is frequently observed in the course of infection and haemorrhage may occur in severe disease. The degree of thrombocytopenia correlates with the severity of infection, and may contribute to the risk of haemorrhage. As a result of this prophylactic platelet transfusions are sometimes advocated for the prevention of haemorrhage. There is currently no evidence to support this practice, and platelet transfusions are costly and sometimes harmful. We conducted a global survey to assess the different approaches to the use of platelets in dengue. Respondents were all physicians involved with the treatment of patients with dengue. Respondents were asked that their answers reflected what they would do if they were the treating physician. We received responses from 306 physicians from 20 different countries. The heterogeneity of the responses highlights the variation in clinical practice and lack of an evidence base in this area and underscores the importance of prospective clinical trials to address this key question in the clinical management of patients with dengue.
PLoS Neglected Tropical Diseases 06/2012; 6(6):e1716. · 4.69 Impact Factor
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Naeema A Akbar,
Iván Allende,
Angel Balmaseda,
Ivo C B Coelho,
Rivaldo V da Cunha,
Bibek Datta,
S Shamala Devi,
Jeremy Farrar,
Roger Gaczkowski,
Maria G Guzman, [......],
Gladys Ramirez,
Kerstin Rosenberger,
Cameron P Simmons,
Joao B Siqueira,
Carmen Soria,
Lian H Tan,
Tran T Thuy,
Iris Villalobos,
Elci Villegas,
Bridget Wills
Clinical Infectious Diseases 04/2012; 54(12):1820-1; author reply 1821-2. · 9.15 Impact Factor
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Neal Alexander,
Angel Balmaseda,
Ivo C B Coelho,
Efren Dimaano,
Tran T Hien,
Nguyen T Hung,
Thomas Jänisch,
Axel Kroeger,
Lucy C S Lum, Eric Martinez,
Joao B Siqueira,
Tran T Thuy,
Iris Villalobos,
Elci Villegas,
Bridget Wills
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ABSTRACT: To evaluate the existing WHO dengue classification across all age groups and a wide geographical range and to develop a revised evidence-based classification that would better reflect clinical severity.
We followed suspected dengue cases daily in seven countries across South-east Asia and Latin America and then categorised them into one of three intervention groups describing disease severity according to the overall level of medical and nursing support required. Using a pre-defined analysis plan, we explored the clinical and laboratory profiles characteristic of these intervention categories and presented the most promising options for a revised classification scheme to an independent group of WHO dengue experts for consideration. Potential warning signs were also evaluated by comparing contemporaneous data of patients who progressed to severe disease with the data of those who did not.
A total of 2259 patients were recruited during 2006-2007 and 230 (13%) of the 1734 laboratory-confirmed patients required major intervention. Applying the existing WHO system, 47/210 (22%) of patients with shock did not fulfil all the criteria for dengue haemorrhagic fever. However, no three-tier revision adequately described the different severity groups either. Inclusion of readily discernible complications (shock/severe vascular leakage and/or severe bleeding and/or severe organ dysfunction) was necessary to devise a system that identified patients requiring major intervention with sufficient sensitivity and specificity to be practically useful. Only a small number of subjects (5%) progressed to severe disease while under observation; several warning signs were identified, but much larger studies are necessary to fully characterize features associated with disease progression.
Based on these results, a revised classification system comprised of two entities, 'Dengue' and 'Severe Dengue', was proposed and has now been incorporated into the new WHO guidelines.
Tropical Medicine & International Health 05/2011; 16(8):936-48. · 2.80 Impact Factor
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Neal Alexander,
Angel Balmaseda,
Ivo C. B. Coelho,
Efren Dimaano,
Tran T. Hien,
Nguyen T. Hung,
Thomas Jänisch,
Axel Kroeger,
Lucy C. S. Lum, Eric Martinez,
Joao B. Siqueira,
Tran T. Thuy,
Iris Villalobos,
Elci Villegas,
Bridget Wills,
World Health Organization (WHO-TDR) supported DENCO Study Group on behalf of the European Union
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ABSTRACT: Objective To evaluate the existing WHO dengue classification across all age groups and a wide geographical range and to develop a revised evidence-based classification that would better reflect clinical severity.Methods We followed suspected dengue cases daily in seven countries across South-east Asia and Latin America and then categorised them into one of three intervention groups describing disease severity according to the overall level of medical and nursing support required. Using a pre-defined analysis plan, we explored the clinical and laboratory profiles characteristic of these intervention categories and presented the most promising options for a revised classification scheme to an independent group of WHO dengue experts for consideration. Potential warning signs were also evaluated by comparing contemporaneous data of patients who progressed to severe disease with the data of those who did not.Results A total of 2259 patients were recruited during 2006–2007 and 230 (13%) of the 1734 laboratory-confirmed patients required major intervention. Applying the existing WHO system, 47/210 (22%) of patients with shock did not fulfil all the criteria for dengue haemorrhagic fever. However, no three-tier revision adequately described the different severity groups either. Inclusion of readily discernible complications (shock/severe vascular leakage and/or severe bleeding and/or severe organ dysfunction) was necessary to devise a system that identified patients requiring major intervention with sufficient sensitivity and specificity to be practically useful. Only a small number of subjects (5%) progressed to severe disease while under observation; several warning signs were identified, but much larger studies are necessary to fully characterize features associated with disease progression.Conclusions Based on these results, a revised classification system comprised of two entities, ‘Dengue’ and ‘Severe Dengue’, was proposed and has now been incorporated into the new WHO guidelines.Objectif: Evaluer la classification actuelle de l’OMS pour la dengue dans tous les groupes d’âge et sur une vaste étendue géographique et élaborer une classification révisée, fondée sur des preuves permettant de mieux tenir compte de la sévérité clinique.Méthodes: Nous avons suivi quotidiennement des cas suspects de dengue dans 7 pays d’Asie du sud-est et d’Amérique latine, puis les avons classé en trois groupes d’intervention décrivant la sévérité de la maladie en fonction du niveau général du soutien médical et infirmier nécessaire. En utilisant un plan d’analyse prédéfini, nous avons exploré les profils cliniques et de laboratoire, caractéristiques de ces catégories d’intervention et avons soumis pour avis, les options les plus prometteuses pour un système révisé de classification, à un groupe d’experts indépendants de l’OMS pour la dengue. Les signes avant-coureurs potentiels ont également étéévalués en comparant les données contemporaines de patients qui ont évolué vers une maladie sévère avec les données de ceux qui n’ont pas évolué de cette façon.Résultats: 2259 patients ont été recrutés en 2006–2007 et 230 (13%) des 1734 patients avec une confirmation de laboratoire ont nécessité une intervention majeure. En appliquant le système actuel de l’OMS, 47/210 (22%) patients atteints de choc ne remplissaient pas tous les critères de dengue hémorragique. Toutefois, aucune révision tertiaire non plus n’a pu décrire adéquatement les différents groupes de sévérité. L’inclusion de complications facilement reconnaissables (choc/pertes vasculaires sévères et/ou saignements sévères et/ou dysfonctionnement sévère d’un organe) a été nécessaire pour concevoir un système permettant d’identifier les patients nécessitant une intervention majeure, avec une sensibilité et une spécificité suffisantes pour être utiles dans la pratique. Seul un petit nombre de sujets (5%) a progressé vers une maladie sévère alors qu’ils étaient sous observation; plusieurs signes d’alerte ont été identifiés, mais beaucoup plus d’études sont nécessaires pour caractériser complètement les caractéristiques associées à la progression de la maladie.Conclusions: Sur base de ces résultats, un système de classification révisé, composé de deux entités, “Dengue” et “ dengue sévère “, a été proposé et a été intégré dans les nouvelles directives de l’OMS.
Tropical Medicine & International Health 05/2011; 16(8):936 - 948. · 2.80 Impact Factor
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Maria G Guzman,
Thomas Jaenisch,
Roger Gaczkowski,
Vo Thi Ty Hang,
Shamala Devi Sekaran,
Axel Kroeger,
Susana Vazquez,
Didye Ruiz, Eric Martinez,
Juan C Mercado,
Angel Balmaseda,
Eva Harris,
Efren Dimano,
Prisca Susan A Leano,
Sutee Yoksan,
Elci Villegas,
Herminia Benduzu,
Iris Villalobos,
Jeremy Farrar,
Cameron P Simmons
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ABSTRACT: Early diagnosis of dengue can assist patient triage and management and prevent unnecessary treatments and interventions. Commercially available assays that detect the dengue virus protein NS1 in the plasma/serum of patients offers the possibility of early and rapid diagnosis.
The sensitivity and specificity of the Pan-E Dengue Early ELISA and the Platelia Dengue NS1 Ag assays were compared against a reference diagnosis in 1385 patients in 6 countries in Asia and the Americas. Platelia was more sensitive (66%) than Pan-E (52%) in confirmed dengue cases. Sensitivity varied by geographic region, with both assays generally being more sensitive in patients from SE Asia than the Americas. Both kits were more sensitive for specimens collected within the first few days of illness onset relative to later time points. Pan-E and Platelia were both 100% specific in febrile patients without evidence of acute dengue. In patients with other confirmed diagnoses and healthy blood donors, Platelia was more specific (100%) than Pan-E (90%). For Platelia, when either the NS1 test or the IgM test on the acute sample was positive, the sensitivity versus the reference result was 82% in samples collected in the first four days of fever. NS1 sensitivity was not associated to disease severity (DF or DHF) in the Platelia test, whereas a trend for higher sensitivity in DHF cases was seen in the Pan-E test (however combined with lower overall sensitivity).
Collectively, this multi-country study suggests that the best performing NS1 assay (Platelia) had moderate sensitivity (median 64%, range 34-76%) and high specificity (100%) for the diagnosis of dengue. The poor sensitivity of the evaluated assays in some geographical regions suggests further assessments are needed. The combination of NS1 and IgM detection in samples collected in the first few days of fever increased the overall dengue diagnostic sensitivity.
PLoS Neglected Tropical Diseases 01/2010; 4(8). · 4.69 Impact Factor
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ABSTRACT: To report the clinical, laboratory and sonographic findings in 76 adult cases of dengue hemorrhagic fever (DHF).
A dengue 3 epidemic occurred in Havana City from June 2001 to March 2002. 12,889 cases were reported, with 81 DHF cases. From this, 76 serologically confirmed cases were studied descriptively.
Bronchial asthma and white race were important risk factors for the severe form of the disease. Fever (100%), headache (92.1%), myalgia (76.3%), arthralgia (73.7%) and retro-orbital pain (57.7%) were the most frequent general symptoms. Vomiting and abdominal pain were observed in 59.2% and 48.6% of cases, respectively. The most common bleeding site was the vagina (64%), followed by the skin (55.2%). Eighteen patients (23.6%) had shock syndrome. Laboratory findings included thrombocytopenia (100%), hemoconcentration (93.4%), an increase in liver enzymes (82.8%), and leukopenia (71%). Ultrasound detected thickening of the gallbladder wall in 35.1%, pleural effusion in 20.3%, and splenomegaly in 12.9% of cases.
These findings contribute to a better understanding of the clinical aspects of DHF in adult patients due to the dengue 3 virus.
International Journal of Infectious Diseases 10/2005; 9(5):280-5. · 1.94 Impact Factor