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Meeting of the Strategic Advisory Group of Experts on immunization, April 2013 - conclusions and recommendations.
Releve Epidemiologique Hebdomadaire. 2013 May 17; 88(20):201-6.Add to my documents.
Lancet. 2006 Dec 23; 368(9554):2193-2195.The global incidence of dengue has increased exponentially over past decades. Fuelled by conditioning factors such as rapid urbanisation, demographic change, large-scale migration, and travel, the disease is now endemic in most countries of the tropics, and about 925 million people now live in urban areas that are at risk of dengue infection. The increasing incidence, intensity, and geographical expansion of dengue epidemics pose a growing threat to the health and economic well-being of populations living in endemic areas, where the introduction of new virus strains to regions affected by existing serotypes is a risk factor for outbreaks and severe disease. Dengue is a major international public-health concern, as expressed in World Health Assembly resolution WHA 55.17 and in the 2005 revision of the International Health Regulations (WHA 58.3). We do have strategies, methods, and guidelines with which we can greatly reduce dengue case-fatality rates and virus transmission, but weak implementation of these plans and an inability to respond effectively to conditioning factors (such as those mentioned above) outside the health sector is causing concern. (excerpt)
The WHO dengue classification and case definitions: time for a reassessment. [Clasificación del dengue y definición de casos de la OMS: tiempo de una nueva evaluación]
Lancet. 2006 Jul 8; 368(9530):170-173.Dengue is the most prevalent mosquito-borne viral disease in people. It is caused by four dengue virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4), of the genus Flavivirus, and transmitted by Aedes aegypti mosquitoes. Infection provides life-long immunity against the infecting viral serotype, but not against the other serotypes. Although most of the estimated 100 million dengue virus infections each year do not come to the attention of medical staff , of those that do, the most common clinical manifestation is non-specific febrile illness or classic dengue fever. About 250 000--500 000 patients developing more severe disease. The risk of severe disease is several times higher in sequential than in primary dengue virus infections. Despite the large numbers of people infected with the virus each year, the existing WHO dengue classification scheme and case definitions have some drawbacks. In addition, the widely used guidelines are not always reproducible in different countries--a quality that is crucial to effective surveillance and reporting as well as global disease comparisons. And, as dengue disease spreads to different parts of the globe, several investigators have reported difficulties in using the system, and some have had to create new categories or new case definitions to represent the observed patterns of disease more accurately. (excerpt)
Classifying dengue: a review of the difficulties in using the WHO case classification for dengue haemorrhagic fever.
Tropical Medicine and International Health. 2006 Aug; 11(8):1238-1255.The current World Health Organisation (WHO) classification of dengue includes two distinct entities: dengue fever (DF) and dengue haemorrhagic fever (DHF)/dengue shock syndrome; it is largely based on pediatric cases in Southeast Asia. Dengue has extended to different tropical areas and older age groups. Variations from the original description of dengue manifestations are being reported. The objectives were to analyse the experience of clinicians in using the dengue case classification and identify challenges in applying the criteria in routine clinical practice. Systematic literature review of post-1975 English-language publications on dengue classification. Thirty-seven papers were reviewed. Several studies had strictly applied all four WHO criteria in DHF cases; however, most clinicians reported difficulties in meeting all four criteria and used a modified classification. The positive tourniquet test representing the minimum requirement of a haemorrhagic manifestation did not distinguish between DHF and DF. In cases of DHF thrombocytopenia was observed in 8.6--96%, plasma leakage in 6--95% and haemorrhagic manifestations in 22--93%. The low sensitivity of classifying DHF could be due to failure to repeat the tests or physical examinations at the appropriate time, early intravenous fluid therapy, and lack of adequate resources in an epidemic situation and perhaps a considerable overlap of clinical manifestations in the different dengue entities. A prospective multi-centre study across dengue endemic regions, age groups and the health care system is required which describes the clinical presentation of dengue including simple laboratory parameters in order to review and if necessary modify the current dengue classification. (author's)
Strengthening Implementation of the Global Strategy on Dengue Fever / Dengue Haemorrhagic Fever Prevention and Control. Report of the informal consultation, 18-20 October 1999, WHO HQ, Geneva.
Geneva, Switzerland, World Health Organization [WHO], 2000.  p. (WHO/CDS/(DEN)/IC/2000.1)Dengue fever and dengue haemorrhagic fever are becoming increasingly important public health problems in the tropics and sub-tropics. Exacerbated by urbanisation, increasing population movement, and lifestyles that contribute to the proliferation of man-made larval habitats of the mosquito vector, the worsening epidemiological trends appear likely to continue. The situation warranted an urgent review of the Global Strategy, the available tools and the partners, and to learn from and consider how relevant advances among other health and development, communications and commercial sector programmes can be applied to dengue. The Informal Consultation on Strengthening Implementation of the Global Strategy on Dengue Fever/Dengue Haemorrhagic Fever Prevention and Control was held in Geneva from 18 to 20 October 1999. It brought together specialists and scientists with public health expertise in dengue and other related disciplines including epidemiology, clinical management, vector control, behaviour change, the Integrated Management of Childhood Illness, public-commercial sector partnerships, non-government organisations and other disease control programmes. Developed in 1995, the Global Strategy for Prevention and Control of Dengue Fever and Dengue Haemorrhagic Fever comprises of five major components: selective integrated vector control, with community and intersectoral participation; active disease surveillance based on a strong health information system; emergency preparedness, capacity building and training; and vector control research. (excerpt)
DengueNet Implementation in the Americas. Report of a WHO / PAHO / CDC Meeting, San Juan, Puerto Rico, 9-11 July 2002.
Geneva, Switzerland, World Health Organization [WHO], Department of Communicable Disease Surveillance and Response, 2003.  p. (Global Health Security. Epidemic Alert and Response; WHO/CDS/CSR/GAR/2003.8; PAHO/HCP/HCT/V/230/03)The geographical spread of both the mosquito vectors and the viruses has led to the global resurgence of epidemic dengue fever/dengue haemorrhagic fever (dengue/DHF) in the past 25 years with the development of hyperendemicity in many urban centres of the tropics. Globally, 2.5 billion people live in areas where dengue viruses can be transmitted. The number of countries with epidemic DHF is continuing to rise. A pandemic in 1998, in which 1.2 million cases of dengue fever and DHF were reported from 56 countries, was unprecedented. Data for 2001-2002 indicate a situation of comparable magnitude. It is estimated that 50 million dengue infections occur each year with 500 000 cases of DHF and at least 12 000 deaths, mainly among children. Only a small proportion of cases are reported to WHO. The challenge for national and international health agencies is to reverse the trend of increased epidemic dengue activity and increased incidence of DHF. Epidemiological and laboratory-based surveillance is required to monitor and guide dengue/DHF prevention and control programmes, regardless of whether the form of control used is mosquito control or possible vaccination if an effective and safe vaccine becomes available. The reporting of dengue/DHF however is not standardized. Epidemiological and laboratory data are often collected by different institutions and reported in different formats, resulting in delay and comparability problems at regional and international levels. To address these problems WHO has created DengueNet, an Internet-based central data management system to collect and analyse standardized epidemiological and virological data for the global surveillance of dengue/DHF and to provide national and international public health authorities with epidemiological and virological indicators by place and time that can guide public health prevention and control actions. (excerpt)
2003 report of the Steering Committee on Dengue and other Flaviviruses Vaccines, including minutes of the SC Meeting, WHO, Geneva, 2-3 April 2003.
Geneva, Switzerland, WHO, 2003. vii, 22 p. (VAB/VIR/2003.03)Dr M.P. Kieny introduced the Steering Committee (SC) meeting by stating that the objectives for the meeting are to evaluate progress in the following areas (1) dengue vaccines that are in early stages of development and pre-clinical evaluation, (2) research related to the assessment of efficacy and immunogenicity of JE vaccines and (3) vaccines and vaccination against other flaviviruses. The anticipated outcomes are to define research priority for further WHO activity, and recommend new research projects for support in 2003-4. No progress in clinical trials of dengue vaccines was included in the agenda of the 2003 SC meeting. It is based on the fact that WHO/IVR has established the Task Force for clinical trials of dengue vaccine and this Group is responsible for scientific advice on the next steps of clinical trials paying special attention to the vaccine safety. The previous TF meeting was held in November 2002 in Denver. The next one will be convened in December 2003 probably in conjunction with the annual meeting of the ASTMH. WHO decided to extend the area of the SC research by including some other flaviviruses vaccines of high priority for developing countries. The SC will consider yellow fever, West Nile and tick-borne encephalitis vaccines as potential components of the future SC activity. (excerpt)
Initiative for Vaccine Research. Task Force on Clinical Trials of Dengue Vaccines, 14 November 2002.
Geneva, Switzerland, WHO, 2002. 12 p. (VAB/IVR/VIR2002.03.1)The second meeting of the WHO Task Force on Clinical Trials of Dengue Vaccines was held on 14 November 2002 in Denver, Colorado, USA. The Task Force was established to accelerate the development, evaluation, and introduction of urgently needed dengue vaccine candidates. The main objective of the Task Force is to continue to analyze results on safety, immunogenicity, and efficacy of currently available vaccine candidates in clinical trials and to provide scientific advice on the next steps to be taken, giving special attention to vaccine safety. The meeting reviewed the progress in clinical trials of four live attenuated vaccine candidates. The task force recommended specific activities in support of future development and clinical studies and identified the role of WHO in this process. The meeting was co-sponsored by the Pediatric Dengue Vaccine Initiative. (excerpt)
Clinical diagnosis and assessment of severity of confirmed dengue infections in Vietnamese children: is the World Health Organization classification system helpful?
American Journal of Tropical Medicine and Hygiene. 2004; 70(2):172-179.Classification of dengue using the current World Health Organization (WHO) system is not straightforward. In a large prospective study of pediatric dengue, no clinical or basic laboratory parameters clearly differentiated between children with and without dengue, although petechiae and hepatomegaly were independently associated with the diagnosis. Among the 712 dengue-infected children there was considerable overlap in the major clinical features. Mucosal bleeding was observed with equal frequency in those with dengue fever and dengue hemorrhagic fever (DHF), and petechiae, thrombocytopenia, and the tourniquet test differentiated poorly between the two diagnostic categories. Fifty-seven (18%) of 310 with shock did not fulfill all four criteria considered necessary for a diagnosis of DHF by the WHO, but use of the WHO provisional classification scheme resulted in considerable over-inflation of the DHF figures. If two separate entities truly exist rather than a continuous spectrum of disease, it is essential that some measure of capillary leak is included in any classification system, with less emphasis on bleeding and a specific platelet count. (author's)
TDR News. 2002 Jun; (68):14.This article presents the three main requests put forth in the Resolution on dengue fever and dengue hemorrhagic fever prevention and control passed by the 55th World Health Assembly in Geneva.
Evaluation of the World Health Organization standard tourniquet test and a modified tourniquet test in the diagnosis of dengue infection in Viet Nam.
Tropical Medicine and International Health. 2002 Feb; 7(2):125-32.A positive tourniquet test is one of several clinical parameters considered by the WHO to be important in the diagnosis of dengue hemorrhagic fever, but no formal evaluation of the test has been undertaken. As many doctors remain unconvinced of its usefulness, this study was designed to assess the diagnostic utility of both the standard test and a commonly employed modified test. A prospective evaluation of the standard sphygmomanometer cuff tourniquet test, compared with a simple elastic cuff tourniquet test, was carried out in 1136 children with suspected dengue infection admitted to a provincial pediatric hospital in southern Vietnam. There was good agreement between independent observers for both techniques, but the sphygmomanometer method resulted in consistently greater numbers of petechiae. This standard method had a sensitivity of 41.6% for dengue infection, with a specificity of 94.4%, positive predictive value of 98.3% and negative predictive value of 17.3%. The test differentiated poorly between dengue hemorrhagic lever (45% positive) and dengue lever (38% positive). The simple elastic tourniquet was less sensitive than the sphygmomanometer cuff, but at a threshold of 10 petechiae (compared with the WHO recommendation of 20) per 2.5 sq. cm the sensitivity for the elastic tourniquet rose to 45% (specificity 85%). Other evidence of bleeding was frequently present and the tourniquet test provided additional information to aid diagnosis in only 5% of cases. The conventional tourniquet test adds little to the diagnosis of dengue in hospitalized children. The simple, cheap elastic tourniquet may be useful in diagnosing dengue infection in busy rural health stations in dengue endemic areas of the tropics. A positive test should prompt close observation or early hospital referral, but a negative test does not exclude dengue infection. (author's)
Lancet. 2000 Jul 29; 356(9227):409.In Dhaka, Bangladesh, it has been recorded that hundreds of people are infected by dengue (a mosquito-borne viral infection), and there have been at least 12 dengue-related deaths. Those who have died include a dentist, an orthopedic surgeon, a hospital auxiliary, and a number of patients coming to the hospitals everyday. Such an outbreak is attributed to unchecked growth in the urban population, poor household water storage, and inadequate solid waste disposal services. Dengue fever has also hit the cities of Chittagong, Faridpur and Sylhet. Despite the enormity of the outbreak, the government insists that the situation is not that serious and that there is no reason to panic. However, Bangladesh has made an emergency appeal to the WHO to help control the country's increase in dengue fever.
Dengue: an evaluation of dengue severity in French Polynesia based on an analysis of 403 laboratory-confirmed cases.
Tropical Medicine and International Health. 1999 Nov; 4(11):765-73.WHO has published a regularly updated guide to improve the diagnosis and management of severe dengue cases by determining the severity using the prognostic criteria, evaluating the impact and improving the control of the disease. This retrospective study aimed to assess the validity of the WHO classification through the analysis of 403 laboratory-confirmed cases in French Polynesia, Tahiti between August 1989 and March 1997. According to standard WHO criteria, 337 cases were considered dengue fever (DF) and 64 were dengue hemorrhagic fever (DHF). About 10 fatal cases were recorded, 6 of which were DF and 4 DHF. As an alternative, a correspondence analysis procedure was used to define dengue severity based on basic clinical and biological criteria for which a severity score was assigned, and then 50 most severe cases from the analysis were selected. Of the latter, 17 patients had been classified as DF and 33 as DHF by the WHO criteria. From this analysis, hemorrhages and decreased platelet counts associated with hepatic disorders were the main criteria associated with the severe dengue cases. This study confirmed that WHO classification does not accurately account for the severity of dengue. Hepatic failure causing plasma leakage, a pathophysiologic hallmark of DHF, should be considered because this is one of the pathogenic mechanisms to the severity of dengue.
TDR NEWS. 1999 Aug; (Spec No):5.This article reports the outcome of the informal consultation of the WHO in-house expert scientists on the proposed inclusion of dengue and tuberculosis in the Training in Tropical Diseases (TDR) portfolio to be reviewed during the 22nd session of the Joint Coordinating Board. The purpose of the meeting was to identify research gaps, pinpoint research needed, and proposed a potential agenda for TDR activities regarding dengue and dengue hemorrhagic fever (DHF). During the meeting, WHO staff presented an analysis of the global situation for dengue and an outline of WHO activities in dengue control and vaccine development. Three discussion groups proposed a list of priority subjects where TDR could initiate activities: 1) in social, economic and behavioral research; 2) in vector research; 3) in diagnosis; 4) in pathophysiology; and 5) in vaccine discovery and development. At present, the only method for controlling or preventing dengue and DHF rely on controlling the mosquito vector. Therefore, developing appropriate and efficient vector control methods, improving laboratory diagnosis and case management of patients, and developing an effective vaccine were the primary objectives of research and capability strengthening.
Lancet. 1998 Sep 12; 352(9131):889.Last week, the Delhi High Court, during its own suo moto motion against the Municipal Corporation of Delhi and the Central government, chastised the government of India and the government of the Delhi state for ignoring warnings concerning dengue. These warnings were given by the World Health Organization (WHO) and experts at the meeting in Pune in 1994. The Court also chastised the government's criminal negligence which caused hundreds of deaths from the disease in 1996. The Court was alerted by mass media reports of the government's failure to deal with the spreading epidemic in the second half of 1996. 10,252 patients were admitted to hospitals in Delhi; 423 patients died. Hospitals were ill equipped, and blood banks were disorganized. There were no dengue control initiatives until 1997, when they were instituted by court order. The 10 major Delhi hospitals are now required to be fully equipped for any dengue outbreak, and the Central and Delhi governments have been ordered to prepare dengue control programs at the national and state levels. Justices Bhandari and Kumar stated that the respondents must adhere to any further suggestions or warnings by WHO, and that a similar blunder must not be repeated.
Management of dengue epidemic. Report of a technical meeting, SEARO, New Delhi, 28-30 November 1996.
New Delhi, India, WHO, Regional Office for South-East Asia, 1997 May. , 38 p. (SEA/DEN/1; SEA/VBC/55)In 1993, the World Health Organization (WHO) passed a resolution urging Member States to strengthen their local and national programs for the control of dengue fever (DEN) and dengue hemorrhagic fever (DHF) and to develop and implement cost-effective control strategies for achieving an interruption of transmission. This was followed, in 1995, by development of a global strategy for vector control of DEN/DHF. However, a 1996 outbreak of DHF in India and Sri Lanka highlighted the deficient preparedness of countries both for case management and quick interruption of transmission. This document summarizes the proceedings of a technical meeting held in New Delhi, India, in 1996 to enhance the capacity for more coordinated, timely action to arrest the build-up of future epidemics in South East Asia. Topics covered are the magnitude of the DEN/DHF problem in South East Asia, risk factors, administrative arrangements and requirements for intersectoral collaboration and logistic support, the role and functions of public information and community, medical and laboratory services and standard case management of DEN/DHF during epidemics. vector control, post-DHF epidemic management, prospects of dengue prevention and control, and recommendations. WHO's Regional Office for South East Asia will assist this effort by collecting regional epidemiologic data, developing manuals and guidelines on disease management and control, arranging intercountry workshops, developing standard training modules to boost capacity building, designating additional WHO collaborating centers, standardizing existing rapid diagnostic test kits, and conducting an inventory of dengue viruses.