Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes. For some patients, dengue is a life-threatening illness. There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread. The contemporary worldwide distribution of the risk of dengue virus infection and its public health burden are poorly known. Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanization. Using cartographic approaches, we estimate there to be 390 million (95% credible interval 284-528) dengue infections per year, of which 96 million (67-136) manifest apparently (any level of disease severity). This infection total is more than three times the dengue burden estimate of the World Health Organization. Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help to guide improvements in disease control strategies using vaccine, drug and vector control methods, and in their economic evaluation.

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The global distribution and burden of dengue

As part of a World Health Organization-led effort to update the empirical evidence base for the leishmaniases, national experts provided leishmaniasis case data for the last 5 years and information regarding treatment and control in their respective countries and a comprehensive literature review was conducted covering publications on leishmaniasis in 98 regional level between 2007 and 2011. Two questionnaires regarding epidemiology and drug access were completed by experts and national program managers. Visceral and cutaneous leishmaniasis incidence ranges were estimated by country and epidemiological region based on reported incidence, underreporting rates if available, and the judgment of national and international experts. Based on these estimates, approximately 0.2 to 0.4 cases and 0.7 to 1.2 million VL and CL cases, respectively, occur each year. More than 90% of global VL cases occur in six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. Cutaneous leishmaniasis is more widely distributed, with about one-third of cases occurring in each of three epidemiological regions, the Americas, the Mediterranean basin, and western Asia from the Middle East to Central Asia. The ten countries with the highest estimated case counts, Afghanistan, Algeria, Colombia, Brazil, Iran, Syria, Ethiopia, North Sudan, Costa Rica and Peru, together account for 70 to 75% of global estimated CL incidence. Mortality data were extremely sparse and generally represent hospital-based deaths only. Using an overall case-fatality rate of 10%, we reach a tentative estimate of 20,000 to 40,000 leishmaniasis deaths per year. Although the information is very poor in a number of countries, this is the first in-depth exercise to better estimate the real impact of leishmaniasis. These data should help to define control strategies and reinforce leishmaniasis advocacy. Funding: The Spanish Agency for International Cooperation for Development (AECID) has provided generous support to the WHO Leishmaniasis program since 2005. This support permitted among many other activities regional meetings with the AFRO, EURO, PAHO and SEARO countries, and provided for short term contracts for IDV, MdB, MH and JS related to the preparation of the country profiles. Sanofi provided a grant for a regional meeting with the EMRO countries and various activities related to the control of cutaneous Leishmaniasis in the EMRO region. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: alvarj@who.int . These authors contributed equally to this work " For a full list of the members of the WHO Leishmaniasis Control Team please see the Acknowledgments section.

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Leishmaniasis Worldwide and Global Estimates of Its Incidence

https://biblio.ugent.be/publication/8617256/file/8617262.pdf

Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

Economic Control of Quality of Manufactured Product.

The Consolidated Standards of Reporting Trials (CONSORT) statement was developed to improve the reporting of randomised controlled trials. It was initially published in 1996 and focused on the reporting of parallel group randomised controlled trials. The statement was revised in 2001, with a further update in 2010. A separate CONSORT statement for the reporting of abstracts was published in 2008. In earlier papers we considered the implications of the 2001 version of the CONSORT statement for the reporting of cluster randomised trial. In this paper we provide updated and extended guidance, based on the 2010 version of the CONSORT statement and the 2008 CONSORT statement for the reporting of abstracts.

https://www.bmj.com/content/bmj/345/bmj.e5661.full.pdf

CONSORT statement: extension to cluster randomised trials

Dengue fever and dengue haemorrhagic fever are important arthropod-borne viral diseases. Each year, there are ∼50 million dengue infections and ∼500,000 individuals are hospitalized with dengue haemorrhagic fever, mainly in Southeast Asia, the Pacific and the Americas. Illness is produced by any of the four dengue virus serotypes. A global strategy aimed at increasing the capacity for surveillance and outbreak response, changing behaviours and reducing the disease burden using integrated vector management in conjunction with early and accurate diagnosis has been advocated. Antiviral drugs and vaccines that are currently under development could also make an important contribution to dengue control in the future.

Dengue: a continuing global threat

Anthropological and socio-medical health care research in developing countries.

Objectives To measure the impact on the dengue vector population (Aedes aegypti) and disease transmission of window curtains and water container covers treated with insecticide.

Design Cluster randomised controlled trial based on entomological surveys and, for Trujillo only, serological survey. In addition, each site had a non-randomised external control.

Setting 18 urban sectors in Veracruz (Mexico) and 18 in Trujillo (Venezuela).

Participants 4743 inhabitants (1095 houses) in Veracruz and 5306 inhabitants (1122 houses) in Trujillo.

Intervention Sectors were paired according to entomological indices, and one sector in each pair was randomly allocated to receive treatment. In Veracruz, the intervention comprised curtains treated with lambdacyhalothrin and water treatment with pyriproxyfen chips (an insect growth regulator). In Trujillo, the intervention comprised curtains treated with longlasting deltamethrin (PermaNet) plus water jar covers of the same material. Follow-up surveys were conducted at intervals, with the final survey after 12 months in Veracruz and nine months in Trujillo.

Main outcome measures Reduction in entomological indices, specifically the Breteau and house indices.

Results In both study sites, indices at the end of the trial were significantly lower than those at baseline, though with no significant differences between control and intervention arms. The mean Breteau index dropped from 60% (intervention clusters) and 113% (control) to 7% (intervention) and 12% (control) in Veracruz and from 38% to 11% (intervention) and from 34% to 17% (control) in Trujillo. The pupae per person and container indices showed similar patterns. In contrast, in nearby communities not in the trial the entomological indices followed the rainfall pattern. The intervention reduced mosquito populations in neighbouring control clusters (spill-over effect); and houses closer to treated houses were less likely to have infestations than those further away. This created a community effect whereby mosquito numbers were reduced throughout the study site. The observed effects were probably associated with the use of materials treated with insecticide at both sites because in Veracruz, people did not accept and use the pyriproxyfen chips.

Conclusion Window curtains and domestic water container covers treated with insecticide can reduce densities of dengue vectors to low levels and potentially affect dengue transmission.

https://www.bmj.com/content/bmj/332/7552/1247.full.pdf

Effective control of dengue vectors with curtains and water container covers treated with insecticide in Mexico and Venezuela: cluster randomised trials

Summary


Background 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.



Objectives  To analyse the experience of clinicians in using the dengue case classification and identify challenges in applying the criteria in routine clinical practice.



Method  Systematic literature review of post-1975 English-language publications on dengue classification.



Results  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.



Conclusion  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.




Donnees de base La classification actuelle de l'organisation Mondiale de la Sante (OMS) pour la dengue comprends deux entites: la fievre dengue et la fievre hemorragique dengue/syndrome de choque dengue; elle est largement basee sur des cas pediatriques du sud-est asiatique. La dengue s'est pourtant etendue a differentes zones tropicales et a des groupes plus âges. Des variations a la description originale des manifestations de la dengue sont couramment rapportees.



Objectifs Analyser les experiences des cliniciens dans la classification des cas de dengue et identifier les defis dans l'application des criteres en pratique clinique de routine



Methodes Revue systematique des publications anglaises depuis 1975 sur la classification de la dengue



Resultats 37 articles ont ete revus. Plusieurs etudes ont strictement applique tous les 4 criteres de l'OMS dans les cas de fievre hemorragique dengue. Cependant, la plupart des cliniciens ont rapporte des difficultes a rassembler tous les 4 criteres et ont alors utilise une classification modifiee. Le test positif du tourniquet representant le minimum requis pour une manifestation hemorragique ne distinguait pas entre fievre hemorragique dengue et fievre dengue. Dans les cas de fievre hemorragique dengue, de la thrombocytopenie etait observee chez 8,6 a 96% des cas, de l’ecoulement de plasma chez 6 a 95% des cas et des manifestations hemorragiques chez 22 a 93% des cas. La faible sensibilite de la classification de la fievre hemorragique de la dengue pourrait etre due au manque de repetition des tests ou d'examens physiques a des moments appropries, a l'instauration tres tot d'un traitement intraveineux des fluides et au manque de ressources adequates dans les situations d’epidemie et peut etre aussi a une superposition des manifestations cliniques dans differentes entites de dengue.



Conclusion Une etude multi centre prospective dans les regions endemiques de la dengue sur les groupes d’âge et le systeme des soins de sante est necessaire pour decrire les presentations cliniques de la dengue incluant de simples parametres de laboratoire afin de corriger et si necessaire de modifier la classification actuelle de la dengue.





Antecedentes La clasificacion actual de la Organizacion Mundial de la Salud (OMS) para el dengue incluye dos entidades diferentes: la fiebre del dengue (FD) y la fiebre hemorragica del dengue (FHD)/sindrome de shock por dengue (SSD). Esta clasificacion esta principalmente basada en casos pediatricos del sureste asiatico. El dengue se ha extendido a diferentes areas tropicales y a grupos con mayor edad. Las variaciones de la descripcion original de las manifestaciones del dengue se reportan en este articulo.



Objetivos Analizar la experiencia de los clinicos en el uso de la clasificacion del caso de dengue e identificar los retos en aplicar los criterios en una practica clinica de rutina.



Metodo Revision sistematica de publicaciones en ingles desde 1975 que tratasen el tema de la clasificacion del dengue.



Resultados Se revisaron 37 publicaciones. Algunos estudios aplicaban estrictamente los cuatro criterios de la OMS en casos de FHD; sin embargo, la mayoria de los clinicos reportaron dificultades para cumplir los cuatro criterios y utilizaron una clasificacion modificada. El test positivo del torniquete, que representa el requerimiento minimo para la manifestacion hemorragica no distinguio entre FHD y SSD. En los casos de FHD se observo trombocitopenia en un rango de 8.6% a 96%, fuga de plasma en 6% a 95% y manifestaciones hemorragicas en 22% a 93%. La baja sensibilidad en la clasificacion de FHD podria deberse a un fallo en la repeticion de las pruebas o examenes fisicos en el momento apropiado, a una terapia temprana de fluidos intravenosos y falta de recursos adecuados en una situacion epidemica y tal vez a un solapamiento considerable de manifestaciones clinicas en las diferentes entidades del dengue.



Conclusion Se requiere un estudio prospectivo, multicentrico que incluya todas las regiones endemicas para dengue, grupos de edad y sistemas sanitarios, que describa la presentacion clinica del dengue incluyendo parametros de laboratorio simples, con el fin de revisar y si fuese necesario modificar la clasificacion actual del dengue.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-3156.2006.01678.x

Classifying dengue: a review of the difficulties in using the WHO case classification for dengue haemorrhagic fever

Health interview surveys are carried out to gain knowledge of people's perceived morbidity, their use of different kinds of health services, and their perceived need for health care Many of such studies in less developed countries (LDCs) have failed to consider the methodological improvements which have been developed in health care research in recent years In the first part of this paper the research on methodological issues is summarized and the inherent problems in health interview surveys are stressed Some specific requirements for cross-cultural research are described The second part deals with health interview surveys carried out on a national, provincial and local level in LDCs Recommendations for a standardization of the methodology are given

Axel Kroeger

Papers

Dengue: a continuing global threat

Anthropological and socio-medical health care research in developing countries.

Effective control of dengue vectors with curtains and water container covers treated with insecticide in Mexico and Venezuela: cluster randomised trials

Classifying dengue: a review of the difficulties in using the WHO case classification for dengue haemorrhagic fever

Health Interview Surveys in Developing Countries: A Review of the Methods and Results