Document Detail

Lessons from malaria control to help meet the rising challenge of dengue.
Jump to Full Text
MedLine Citation:
PMID:  23174383     Owner:  NLM     Status:  MEDLINE    
Achievements in malaria control could inform efforts to control the increasing global burden of dengue. Better methods for quantifying dengue endemicity-equivalent to parasite prevalence surveys and endemicity mapping used for malaria-would help target resources, monitor progress, and advocate for investment in dengue prevention. Success in controlling malaria has been attributed to widespread implementation of interventions with proven efficacy. An improved evidence base is needed for large-scale delivery of existing and novel interventions for vector control, alongside continued investment in dengue drug and vaccine development. Control of dengue is unlikely to be achieved without coordinated international financial and technical support for national programmes, which has proven effective in reducing the global burden of malaria.
Katherine L Anders; Simon I Hay
Related Documents :
24969643 - The effectiveness of bcg vaccination in preventing mycobacterium tuberculosis infection...
10931863 - A kinesin-related protein, krp(180), positions prometaphase spindle poles during early ...
16861643 - Immunogenicity of mycobacterium tuberculosis antigens in mycobacterium bovis bcg-vaccin...
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Lancet. Infectious diseases     Volume:  12     ISSN:  1474-4457     ISO Abbreviation:  Lancet Infect Dis     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-23     Completed Date:  2013-04-02     Revised Date:  2014-08-15    
Medline Journal Info:
Nlm Unique ID:  101130150     Medline TA:  Lancet Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  977-84     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Aedes / growth & development,  virology
Dengue / epidemiology,  prevention & control*,  transmission
Dengue Virus / isolation & purification*
Endemic Diseases
Insect Vectors / growth & development,  virology
Malaria / epidemiology,  prevention & control*,  transmission
Plasmodium / isolation & purification*
Grant Support
089276//Wellcome Trust; 095066//Wellcome Trust; //Wellcome Trust

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Lancet Infect Dis
Journal ID (iso-abbrev): Lancet Infect Dis
ISSN: 1473-3099
ISSN: 1474-4457
Publisher: Elsevier Science, The Lancet Pub. Group
Article Information
© 2012 Elsevier Ltd. All rights reserved.
pmc-release publication date: Month: 12 Year: 2012
Print publication date: Month: 12 Year: 2012
Volume: 12 Issue: 12
First Page: 977 Last Page: 984
PubMed Id: 23174383
ID: 3574272
Publisher Id: LANINF70246
DOI: 10.1016/S1473-3099(12)70246-3

Lessons from malaria control to help meet the rising challenge of dengue
Katherine L Andersabc* Email:
Simon I Hayde
aOxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam
bCentre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
cDepartment of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic, Australia
dSpatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, UK
eFogarty International Center, National Institutes of Health, Bethesda, MD, USA
*Correspondence to: Ms Katherine L Anders, OUCRU, Hospital for Tropical Diseases, 764 Vo Van Kiet, District 5, Ho Chi Minh City, Vietnam

Malaria's fall and dengue's rise

Malaria has been one of the major challenges to global health during the past century. In 1900, 58% of the world's land area was estimated to have sustained stable malaria transmission.1 More than a million deaths annually have been attributed to malaria throughout the latter half of the 20th century,2,3 most in children younger than 5 years, with countries of sub-Saharan Africa bearing the largest toll.4,5 However, mounting evidence suggests a decline in the global burden of malaria, a decrease that began in the mid 20th century in some regions but was most notable in parts of Africa over the past decade.1,2,6–8 This reduction has led to renewed focus among the malaria community on a goal of malaria elimination in many countries.9 While malaria has been in decline, the geographical range and disease burden of another tropical infectious disease has been on the rise.

Dengue has emerged as an increasing public health problem over the past 50 years, particularly in southeast Asia and Central and South America,10 with an unknown but possibly substantial level of transmission in Africa.11 Like malaria, dengue is a vector-borne disease of the tropics and is a major cause of morbidity in endemic areas, particularly in children and young adults;12 however, the scale of dengue morbidity and mortality is uncertain and thought to be less than that of malaria. Dengue is caused by four distinct but related viruses (serotypes DENV 1–4) that are transmitted among people by aedes mosquitoes. The disease burden and geographical range of dengue have expanded, from about 15 000 cases reported annually from fewer than ten countries during the 1960s to almost one million cases a year across more than 60 countries in 2000–2005.13 As a result, dengue has been identified as an important threat to global public health.10 In view of this rising challenge, could lessons learned from global efforts to control malaria help inform strategies to prevent and perhaps reverse the spread of dengue?

In this Personal View, we compare and contrast malaria and dengue with respect to epidemiology, current and future interventions available for prevention and control, and their prioritisation as global health issues, in terms of funding, capacity, and international collaborations. We also argue that improved data on the range and endemicity of dengue are a vital component of global prevention and control efforts.

Effect of vectors on epidemiology

The geographical ranges of both malaria and dengue are limited by the spatial extent of the competent vectors—particular species of anopheles and aedes mosquitoes, respectively. The bionomics of the vectors shapes the epidemiology of each disease. With a few exceptions, anopheles mosquitoes favour rural environments, mainly because of their larval habitat requirements.14–16 By contrast, the primary vector of dengue, Aedes aegypti, thrives in urban environments where abundant container breeding sites in and around human habitations allow immature vectors to develop and adults to feed and rest close to high densities of humans, their preferred host for blood meals.17

Although aedes mosquitoes have a restricted flight range of about 100 m in the field,18 passive transport of Ae aegypti by land and, in immature stages, by sea led to their re-establishment in countries of South and Central America, from which they had previously been eliminated in the mid 20th century,19 and dispersal throughout southeast Asia during and after World War 2.20 The geographical range of a secondary dengue vector, Aedes albopictus, has also expanded substantially over the past 30 years, but it is a less efficient vector and is not currently seen as a major contributor to or risk factor for increased dengue transmission.21

The growing mobility of viraemic people, both within endemic settings and into new regions by increased domestic and international travel and migration, has been key in driving the global expansion of dengue in recent decades.22 This movement has created conditions in which multiple virus serotypes cocirculate, leading to an increase in the risk of sequential infections and severe disease. By contrast, the ecological requirements of anopheles mosquitoes have not facilitated their dispersal,23 and the unprecedented urbanisation that has characterised the past century is associated with reduced risk of malaria transmission, at least in the African setting.4

Quantifying disease burden and distribution

The global burden of a disease is a function of both its geographical range and the intensity of transmission in affected areas. By both these measures, the global burden of malaria has unequivocally decreased over the past century,1 although this decline has not been consistent across all malaria-endemic countries.8 Serious efforts to define the geographical limits and intensity of malaria transmission go back to the mid 20th century,24–26 when global control and eradication efforts were gathering momentum. A renewed effort to quantify the magnitude and distribution of the burden of malaria has seen new epidemiological and cartographic techniques applied to multiple collated data sources to model the spatial extent of malaria transmission and so to estimate populations at risk of exposure.27–29 These calculations place 2·4 billion people living in 87 countries at risk of Plasmodium falciparum infection in 2007,27 resulting in around 450 million clinical cases of P falciparum malaria annually.29 The inclusion of uncertainty intervals around estimates has been a major step forward with these cartographic methods.30 For dengue, assessments of the spatial extent of transmission have been based largely on empirical data of reported dengue cases from endemic and epidemic settings, with models then fitted to correlate the observed distribution with environmental and climatic characteristics.31,32 WHO estimates that 50 million dengue virus infections occur every year across about 100 countries, representing a population at risk of 2·5 billion people,10 although this number could be an underestimate of the true burden.33 The most recent assessment of the global distribution of dengue identifies 128 countries with good evidence of transmission and puts almost four billion people at risk.11

The intensity of transmission of both malaria and dengue is spatially and temporally heterogeneous.34–37 The most commonly used measure of malaria endemicity is the parasite prevalence rate, which represents the proportion of a population with malaria parasites detectable in their blood.38 This measure has been used widely in malaria surveys throughout the past century and has been used to generate the first evidence-based global map of malaria endemicity in 2007, recently updated for 2010 (figure).39 Another key metric of malaria transmission risk is the entomological inoculation rate, which represents the rate at which people are bitten by infectious mosquitoes.40 The relationship between the entomological inoculation rate and the parasite prevalence rate is non-linear.41,42 Empirical measurements for the entomological inoculation rate have been gathered less routinely and consistently than for the parasite prevalence rate, making the former a less useful measure for global endemicity mapping.43 Consequently, the entomological inoculation rate and other important metrics for malaria have been inferred with modelled relationships44 between them and extensive maps of parasite rates.39

Epidemiological data on the global burden of dengue rely almost entirely on reports of clinically apparent disease, derived from national surveillance systems10,45–52 and, in a few cases, from prospective longitudinal studies.53,54 The figure shows a map of dengue risk that combines disease notification and outbreak data from international organisations, case reports on returning travellers, published scientific literature on dengue occurrence, and a biological model of environmental suitability.55 Serological data from longitudinal studies56–62 permit estimation of infection incidence in a population, including the ratio of symptomatic to inapparent infections. This type of study depends, however, on follow-up of cohorts, which needs far greater investment of time and money compared with cross-sectional surveys that are used to obtain estimates of the malaria parasite prevalence rate.

Traditional indicators of the abundance of aedes mosquitoes, based on immature vector stages (house index, container index, Breteau index), are collected routinely in many dengue-endemic countries, but their correlation with human infection and disease is poor.63,64 Counts of Ae aegypti pupae per person might correlate more closely with adult vector density and, therefore, potential for dengue transmission.36,65 Direct measurement of the density of adult Ae aegypti—with PCR to ascertain the proportion infected with dengue virus—would be most informative, but this approach is logistically and financially demanding to do on a sufficiently large scale in view of the difficulty in sampling adult vectors and the expected large variance in both adult numbers and prevalence of infection.36,66,67

For both malaria and dengue, the relationship between the risk of infection and the risk of disease is non-linear and depends on host immune status and age at infection.68–72 The most appropriate metric will be determined by its purpose. Clinical case numbers are relevant to the prediction of demand for diagnostic tests, health-care services, and treatments. WHO also defines laboratory-confirmed clinical dengue cases of any severity as the most appropriate endpoint for dengue vaccine trials.73 However, for describing transmission extent and intensity, especially when making comparisons between countries and over time, reliance on case-burden data is fraught with issues of inconsistent reporting patterns (both spatially and temporally), differences in clinical case definitions, over-reporting when laboratory testing is not routine, and under-reporting of patients who do not present to health services or who are managed as outpatients only.74,75 A measure of the incidence of infection, rather than disease, might also be an appropriate endpoint for trials of dengue vector-control interventions in the community; not only is active surveillance of clinical outcomes more resource-intensive than cross-sectional blood sampling but also a large (and variable) proportion of prevented infections are likely to be asymptomatic.76 Therefore, a smaller sample size will be needed to show an effect on infection rates, compared with a clinical effect of the same size, because of the higher overall event rate for infections versus clinical cases.

What alternative metric could be used to measure dengue endemicity, equivalent to the parasite rate for malaria? Virological markers of dengue—such as viraemia and presence of the NS1 antigen in blood—are short-lived compared with untreated malaria parasitaemia, disappearing about 1 week after onset of clinical symptoms.77 Furthermore, the magnitude and duration of viraemia varies with severity of disease, virus serotype, and host immune status.78–80 Cross-sectional age-stratified serological surveys of dengue-specific IgG can indicate the prevalence of past exposure to dengue virus but are confounded by antibodies directed against other flaviviruses, where these cocirculate. Cross-sectional seroprevalence surveys of dengue-specific IgM might indicate recent infection with dengue virus or other flaviviruses. Aside from potential low specificity, interpretation is complicated by the variable kinetics of the IgM response, most importantly, the difference between first and subsequent infections,81 making comparison of population-based IgM surveys between epidemiological settings difficult. Population-based surveys of dengue neutralising antibody, measured by the plaque reduction neutralisation test, would provide the most sensitive and specific information on virus transmission patterns, including serotype-specific data and multiple heterotypic exposures. However the plaque reduction neutralisation test is substantially more resource-intensive than standard IgM and IgG immunoassays. Finding the appropriate metric to measure the endemic level of dengue is a clear research priority.

Interventions for prevention and control

Success in controlling malaria over the past century has been attributed predominantly to widespread implementation of insecticide-treated bednets, household spraying of residual insecticides, and effective drugs to reduce mortality and interrupt transmission.6 The countries in which little progress has been made with malaria control are commonly those where political instability, war, or economic underdevelopment have hindered widespread implementation of these interventions.82

The situation with dengue is different; vector control is the only currently available approach for prevention and control and is pursued mainly through reduction of larval development sites, via environmental clean-up campaigns to dispose of discarded or unnecessary water containers, and prevention of mosquito access to breeding sites. Other methods include treatment of water-storage vessels with larvicide83 or predacious copepods84 to kill larval stages. The effectiveness of these interventions has been demonstrated at a local community level84–86 but rarely on a large scale or across diverse epidemiological settings (not since the Ae aegypti eradication campaign of the 1950s), with Singapore and Cuba perhaps the only exceptions.87–89 Success of such efforts depends on sustained community support and participation.90 However, even when mosquito populations have been reduced drastically, as in Singapore, cases of dengue still occur,91 with evidence of increasing risk of clinical disease associated with older age at first infection.72,92 Killing adult mosquitoes has a theoretically greater effect on transmission than does targeting larvae. Space-spraying of insecticide to kill adult vectors in and around households is popular because it represents a highly visible response to localised outbreaks of dengue, but a sustained effect on virus transmission has not been demonstrated.10,93

Indoor residual spraying of insecticide has a long history of use in malaria control, and its importance as a key intervention for interruption of malaria transmission has been reaffirmed by WHO.94 Many behavioural characteristics of anopheles vectors that make indoor residual spraying an effective malaria intervention, such as their anthropophagic biting preferences and tendency to rest and feed indoors,14–16 are common also to aedes dengue vectors. There is some evidence that high household coverage of indoor residual spraying in an outbreak setting could reduce dengue transmission.95 Use of this method to control yellow fever in the Americas in the mid 20th century had a concomitant and striking effect on dengue transmission, but there are very few reports of the application of indoor residual spraying specifically to control dengue.95–98 The preference of aedes vectors for daytime activity and feeding means that insecticide-treated bednets are ineffective for dengue control. Findings of several small trials99–101 of other insecticide-treated materials, such as curtains and water-jar covers, indicate a reduction in indices of household vectors, and larger trials are warranted to investigate effectiveness in a range of epidemiological settings.

Early diagnosis and treatment with effective drugs reduces morbidity and mortality from malaria. International guidelines recommend parasitological confirmation, when possible, of all suspected cases of malaria and prompt initiation of treatment to prevent progression to severe disease.102 Timeliness is also very important for effective clinical management of dengue; progression from an acute febrile phase to non-complicated recovery, or through a critical phase characterised by thrombocytopenia and capillary permeability with potential for haemorrhage and shock, takes place over 3–7 days.10

Unlike malaria, no specific treatment for dengue is available, and clinical management entails close haematological monitoring, fluid-replacement therapy as required, and recognition of warning signs of severe disease. Although serological, molecular, and rapid diagnostic tests for dengue are widely available, the expense, waiting time, and large case numbers mean that clinical management and case reporting in most endemic settings is based on clinical diagnosis alone. Increasing availability of rapid diagnostic tests could theoretically improve timeliness and accuracy of dengue diagnoses. However, studies of the effect of test results on clinical management and outcome of dengue cases, including cost-effectiveness studies, are needed to inform recommendations for widespread use. Demand for routine diagnostic testing for dengue could increase substantially if an antiviral drug were available.

Research efforts towards vaccines against malaria and dengue are similarly complicated by (among other challenges) the antigenic or serotypic variability of the organisms.103–105 A longlasting highly effective dengue vaccine should be much easier to develop than an equivalent malaria vaccine because of the relative antigenic complexity of the two pathogens and the longevity of immune responses to viral infections, compared with those to malaria parasites.106 However, developers of a dengue vaccine must contend with the theoretical risk of severe disease associated with sequential infection with a heterologous serotype and, thus, aim to develop a tetravalent vaccine.106 Candidate vaccines for malaria and dengue are in phase 3 field trials,107,108 but despite publication of promising clinical trial data for the leading malaria vaccine candidate,109 a substantial vaccine-mediated reduction in the global burden of either disease is not imminent. Thus, vector control, effective diagnosis, and clinical management remain the cornerstones of control for both diseases, for the foreseeable future.

The challenge now in malaria control is equitable and effective implementation of interventions that have proven efficacy. However, to tackle the increasing burden of dengue, well designed and controlled field trials are needed of both existing and novel vector-control interventions, linked to detailed epidemiological data, to improve the evidence base and inform local and national dengue-control strategies. Further challenges for evaluation of dengue interventions might include the effect of human movement on patterns of transmission, and the pronounced temporal and spatial heterogeneity in transmission, which will necessitate very large cluster-randomised study designs. These issues are also likely to be challenges for malaria control though the elimination or eradication phases.

Prioritisation and investment of funding and resources

Malaria control throughout the past century has been a combined effort of national, regional, and international programmes. The global malaria eradication programme launched in 1955 by WHO was the largest coordinated international public health campaign in history.110 With an intensive strategy of vector control using residual insecticides, combined with detection and treatment of cases, 22 countries in the Americas and 27 in Europe achieved malaria elimination between 1950 and 1978.111 Despite these successes, the goal of elimination was not met universally and was never proposed for sub-Saharan Africa; in 1969, WHO's strategy was revised to one of control.112

Efforts to control dengue also benefited from an elimination campaign in the mid 20th century; in 1947, the Pan-American Health Organization adopted a proposal by Brazil for a so-called hemispheric (pan-American) strategy to remove the Ae aegypti vector.113 Although the aim of this campaign was eradication of urban yellow fever, which shares the same vector as dengue, the successful elimination by 1967 of Ae aegypti from all countries of the Americas (except for the USA, Venezuela, and the Caribbean region)114 saw a substantial reduction in dengue morbidity across this region.115 Unfortunately, this campaign had the same outcome as the global malaria eradication programme, with a reversion to a strategy of control because of a combination of reduced political will, insufficient financing to sustain intensive control efforts, and increasing decentralisation of national public health authorities, among other factors.115,116 The Ae aegypti vector re-established itself in areas from which it had been eliminated, with a resultant rise in dengue epidemics in the Americas throughout the 1970s and 1980s. In southeast Asia, an elimination goal for dengue or its vector has never been proposed formally.117

Efforts to control malaria during the past 15 years have intensified after the development of international initiatives to coordinate and finance the scale-up of interventions, beginning with the Roll Back Malaria Partnership, launched in 1998, and the Global Fund for AIDS, Tuberculosis, and Malaria, founded in 2002. More recently, the Bill and Melinda Gates Foundation has allocated substantial funds to malaria control and eradication efforts. These initiatives recognise the need for external funding and support to malaria-endemic countries to achieve coverage of interventions at a level that will affect transmission and morbidity. An estimated US$9·9 billion was committed by international donor agencies for malaria control in endemic countries between 2002 and 2010.118 By contrast, vector-control interventions for dengue remain the financial and logistical responsibility of national control programmes in endemic countries, which are funded from national budgets with no substantial or sustained external sources of financing. Dengue is a high public health priority in endemic countries,119 but the main target of spending is responsive vector-control activities around reported cases, combined with passive case surveillance and some routine virus and vector surveillance. Budgets are usually insufficient to implement these actions fully, let alone to sustain breeding source reduction activities, larval control, and environmental management, which might be more effective120,121 but are highly resource-intensive.

It is difficult to see how the continuing geographical spread and increasing intensity of dengue transmission can begin to be reversed without support in coordination and financing from outside endemic countries. Support should include applied research to improve the evidence base for existing vector-control techniques, for novel interventions such as transfection of Wolbachia spp into Ae aegypti to suppress dengue transmission,122 and for strategic planning to implement and finance a future vaccine. Even when a dengue vaccine becomes a reality, external assistance for financing and implementation will be needed by some endemic countries, as will continued concerted efforts in vector control. Unlike malaria, which receded from southern Europe in the mid 20th century, aedes mosquitoes, and possibly dengue, could continue to expand into warmer areas of high-income countries, including Australia, the USA, and southern Europe.31,32 This possibility should provide any additional impetus needed for dengue to be viewed as more than a neglected tropical disease. The burden of morbidity, mortality, and economic loss attributable to dengue is not comparable with that caused by malaria. However, the coordinated initiatives for funding of regional and global collaborative research and control activities, which have proven effective to address the global burden of malaria,123 could also drive similar gains in dengue control.

Moving forward

Based on lessons learned from malaria control, we propose that development of better methods to quantify dengue endemicity and disease burden, permitting comparisons across countries and regions, is an essential step towards halting the current rise in disease range and intensity. We must be able to quantify these increases accurately so we can establish baselines against which future trends can be compared. Analysis of the clinical and demographic profile of acute cases can tell us much about local dengue transmission dynamics, but improved indices of transmission—including means of accounting for asymptomatic infections—that can be measured at a population level and within specific subgroups would provide a much more complete picture of local transmission patterns. This information can guide effective surveillance and implementation of interventions, including future vaccines. Use of serological markers of dengue infection in epidemiological studies has some limitations, but age-stratified serosurveys of neutralising antibodies against the virus probably represent the best equivalent to the malaria parasite prevalence survey for population-based estimates of the incidence of infection. Improved entomological measures of risk for dengue transmission, based on density of the adult vector and infection prevalence, could complement these estimates but might also be inferred, similar to malaria, from measurement of incidence in human populations.

Improved estimates of the dengue disease burden would inform economic analyses of vector-control activities and future vaccination strategies. Effective implementation of these interventions could be achievable within the national budgets of a few dengue endemic countries, but many national dengue control programmes would benefit from coordinated international funding to achieve adequate coverage, as has proven effective in malaria control. This fact reinforces the importance of developing improved indicators of local, regional, and global dengue endemicity and disease burden, to advocate for funding directed to areas of greatest need, to identify locations where interventions are most likely to succeed, and to monitor future progress of disease prevention efforts, including vaccines.

1. Gething PW,Smith DL,Patil AP,Tatem AJ,Snow RW,Hay SI. Climate change and the global malaria recessionNature465Year: 201034234520485434
2. Hay SI,Guerra CA,Tatem AJ,Noor AM,Snow RW. The global distribution and population at risk of malaria: past, present, and futureLancet Infect Dis4Year: 200432733615172341
3. Carter R,Mendis KN. Evolutionary and historical aspects of the burden of malariaClin Microbiol Rev15Year: 200256459412364370
4. Hay SI,Guerra CA,Tatem AJ,Atkinson PM,Snow RW. Urbanization, malaria transmission and disease burden in AfricaNat Rev Microbiol3Year: 2005819015608702
5. Snow RW,Omumbo JA. MalariaJamison DT,Feachem RG,Makgoba MWDisease and mortality in sub-Saharan Africa2nd edn.Year: 2006World BankWashington195213
6. O'Meara WP,Mangeni JN,Steketee R,Greenwood BM. Changes in the burden of malaria in sub-Saharan AfricaLancet Infect Dis10Year: 201054555520637696
7. Snow RW,Marsh K. Malaria in Africa: progress and prospects in the decade since the Abuja DeclarationLancet376Year: 201013713920417552
8. Murray CJL,Rosenfeld LC,Lim SS. Global malaria mortality between 1980 and 2010: a systematic analysisLancet379Year: 201241343122305225
9. Feachem RG,Phillips AA,Hwang J. Shrinking the malaria map: progress and prospectsLancet376Year: 20101566157821035842
10. WHODengue: guidelines for diagnosis, treatment, prevention and controlYear: 2009World Health OrganizationGeneva
11. Brady OJ,Gething PW,Bhatt S. Refining the global spatial limits of dengue virus transmission by evidence-based consensusPLoS Negl Trop Dis6Year: 2012e176022880140
12. Gubler DJ. Epidemic dengue/dengue hemorrhagic fever as a public health, social and economic problem in the 21st centuryTrends Microbiol10Year: 200210010311827812
13. Kroeger A,Nathan MB. Dengue: setting the global research agendaLancet368Year: 20062193219517189016
14. Sinka ME,Rubio-Palis Y,Manguin S. The dominant Anopheles vectors of human malaria in the Americas: occurrence data, distribution maps and bionomic précisParasit Vectors3Year: 20107220712879
15. Sinka ME,Bangs MJ,Manguin S. The dominant Anopheles vectors of human malaria in Africa, Europe and the Middle East: occurrence data, distribution maps and bionomic précisParasit Vectors3Year: 201011721129198
16. Sinka ME,Bangs MJ,Manguin S. The dominant Anopheles vectors of human malaria in the Asia-Pacific region: occurrence data, distribution maps and bionomic précisParasit Vectors4Year: 20118921612587
17. Scott TW,Chow E,Strickman D. Blood-feeding patterns of Aedes aegypti (Diptera: Culicidae) collected in a rural Thai villageJ Med Entomol30Year: 19939229278254642
18. Harrington LC,Scott TW,Lerdthusnee K. Dispersal of the dengue vector Aedes aegypti within and between rural communitiesAm J Trop Med Hyg72Year: 200520922015741559
19. Halstead SB. EpidemiologyHalstead SBDengueYear: 2008Imperial College PressLondon75122
20. Gubler DJ. Dengue and dengue hemorrhagic fever: its history and resurgence as a global public health problemGubler DJ,Kuno GDengue and dengue hemorrhagic feverYear: 1997CAB International PressWallingford122
21. Lambrechts L,Scott TW,Gubler DJ. Consequences of the expanding global distribution of Aedes albopictus for dengue virus transmissionPLoS Negl Trop Dis4Year: 2010e64620520794
22. Tatem AJ,Rogers DJ,Hay SI. Global transport networks and infectious disease spreadAdv Parasitol62Year: 200629334316647974
23. Tatem AJ,Rogers DJ,Hay SI. Estimating the malaria risk of African mosquito movement by air travelMalar J5Year: 20065716842613
24. Russell PF. The present status of malaria in the worldAm J Trop Med Hyg1Year: 195211112314903441
25. Russell PF. World-wide malaria distribution, prevalence, and controlAm J Trop Med Hyg5Year: 195693796513381870
26. Lysenko AJ,Semashko IN. Geography of malaria: a medical-geographic study of an ancient diseaseMedvedkov YVMedical geographyYear: 1968Academy of SciencesMoscow25146
27. Guerra CA,Gikandi PW,Tatem AJ. The limits and intensity of Plasmodium falciparum transmission: implications for malaria control and elimination worldwidePLoS Med5Year: 2008e3818303939
28. Hay SI,Guerra CA,Gething PW. A world malaria map: Plasmodium falciparum endemicity in 2007PLoS Med6Year: 2009e100004819323591
29. Hay SI,Okiro EA,Gething PW. Estimating the global clinical burden of Plasmodium falciparum malaria in 2007PLoS Med7Year: 2010e100029020563310
30. Patil AP,Gething PW,Piel FB,Hay SI. Bayesian geostatistics in health cartography: the perspective of malariaTrends Parasitol27Year: 201124625321420361
31. Hales S,de Wet N,Maindonald J,Woodward A. Potential effect of population and climate changes on global distribution of dengue fever: an empirical modelLancet360Year: 200283083412243917
32. Jetten TH,Focks DA. Potential changes in the distribution of dengue transmission under climate warmingAm J Trop Med Hyg57Year: 19972852979311638
33. Beatty ME, Letson W, Edgil DM, Margolis HS. Estimating the total world population at risk for locally acquired dengue infection. Presented at the 56th annual meeting of the American Society of Tropical Medicine and Hygiene; Philadelphia, PA, USA; Nov 4–8, 2007. Abstract 168.
34. Tran A,Deparis X,Dussart P. Dengue spatial and temporal patterns, French Guiana, 2001Emerg Infect Dis10Year: 200461562115200850
35. Thai KTD,Nagelkerke N,Phuong HL. Geographical heterogeneity of dengue transmission in two villages in southern VietnamEpidemiol Infect138Year: 201058559119653925
36. Mammen MP,Pimgate C,Koenraadt CJM. Spatial and temporal clustering of dengue virus transmission in Thai villagesPLoS Med5Year: 2008e20518986209
37. Bejon P,Williams TN,Liljander A. Stable and unstable malaria hotspots in longitudinal cohort studies in KenyaPLoS Med7Year: 2010e100030420625549
38. Hay SI,Smith DL,Snow RW. Measuring malaria endemicity from intense to interrupted transmissionLancet Infect Dis8Year: 200836937818387849
39. Gething PW,Patil AP,Smith DL. A new world malaria map: Plasmodium falciparum endemicity in 2010Malar J10Year: 201137822185615
40. Hay SI,Rogers DJ,Toomer JF,Snow RW. Annual Plasmodium falciparum entomological inoculation rates (EIR) across Africa: literature survey, Internet access and reviewTrans R Soc Trop Med Hyg94Year: 200011312710897348
41. Smith DL,McKenzie FE. Statics and dynamics of malaria infection in Anopheles mosquitoesMalar J3Year: 20041315180900
42. Smith DL,Dushoff J,Snow RW,Hay SI. The entomological inoculation rate and Plasmodium falciparum infection in African childrenNature438Year: 200549249516306991
43. Guerra CA,Hay SI,Lucioparedes LS. Assembling a global database of malaria parasite prevalence for the Malaria Atlas ProjectMalar J6Year: 20071717306022
44. Smith DL,Drakeley CJ,Chiyaka C,Hay SI. A quantitative analysis of transmission efficiency versus intensity for malariaNat Commun1Year: 201010821045826
45. Ha DQ. Dengue epidemic in southern Vietnam, 1998Emerg Infect Dis6Year: 200042242510905983
46. Beatty ME,Stone A,Fitzsimons DW. Best practices in dengue surveillance: a report from the Asia-Pacific and Americas dengue prevention boardsPLoS Negl Trop Dis4Year: 2010e89021103381
47. Guzmán MG,Kourí G. Dengue: an updateLancet Infect Dis2Year: 2002334211892494
48. Huy R,Buchy P,Conan A. National dengue surveillance in Cambodia 1980–2008: epidemiological and virological trends and the impact of vector controlBull World Health Organ88Year: 201065065720865069
49. Simmons CP,Farrar JJ. Changing patterns of dengue epidemiology and implications for clinical management and vaccinesPLoS Med6Year: 2009e100012919721698
50. Ooi E-E. Dengue in Southeast Asia: epidemiological characteristics and strategic challenges in disease preventionCad Saude Publica25Year: 2008S115S12419287856
51. San Martín JL,Brathwaite O,Zambrano B. The epidemiology of dengue in the Americas over the last three decades: a worrisome realityAm J Trop Med Hyg82Year: 201012813520065008
52. Suaya JA,Shepard DS,Beatty ME. Dengue: burden of disease and costs of illnessYear: 2007World Health OrganizationGeneva
53. Vong S,Khieu V,Glass O. Dengue incidence in urban and rural cambodia: results from population-based active fever surveillance, 2006–2008PLoS Negl Trop Dis4Year: 2010e90321152061
54. Schmidt W-P,Suzuki M,Dinh Thiem V. Population density, water supply, and the risk of dengue fever in Vietnam: cohort study and spatial analysisPLoS Med8Year: 2011e100108221918642
55. Simmons CP,Farrar JJ,van Nguyen VC,Wills B. DengueN Engl J Med366Year: 20121423143222494122
56. Balmaseda A,Standish K,Mercado JC. Trends in patterns of dengue transmission over 4 years in a pediatric cohort study in NicaraguaJ Infect Dis201Year: 201051419929380
57. Chau TNB,Hieu NT,Anders KL. Dengue virus infections and maternal antibody decay in a prospective birth cohort study of Vietnamese infantsJ Infect Dis200Year: 20091893190019911991
58. Burke DS,Nisalak A,Johnson DE,Scott RM. A prospective study of dengue infections in BangkokAm J Trop Med Hyg38Year: 19881721803341519
59. Anderson KB,Chunsuttiwat S,Nisalak A. Burden of symptomatic dengue infection in children at primary school in Thailand: a prospective studyLancet369Year: 20071452145917467515
60. Endy TP,Chunsuttiwat S,Nisalak A. Epidemiology of inapparent and symptomatic acute dengue virus infection: a prospective study of primary school children in Kamphaeng Phet, ThailandAm J Epidemiol156Year: 2002405112076887
61. Tien NTK,Luxemburger C,Toan NT. A prospective cohort study of dengue infection in schoolchildren in Long Xuyen, Viet NamTrans R Soc Trop Med Hyg104Year: 201059260020630553
62. Thai KTD,Nga TTT,Van Nam N. Incidence of primary dengue virus infections in Southern Vietnamese children and reactivity against other flavivirusesTrop Med Int Health12Year: 20071553155718076564
63. Honório NA,Nogueira RMR,Codeço CT. Spatial evaluation and modeling of Dengue seroprevalence and vector density in Rio de Janeiro, BrazilPLoS Negl Trop Dis3Year: 2009e54519901983
64. Scott TW,Morrison AC. Vector dynamics and transmission of dengue virus: implications for dengue surveillance and prevention strategiesCurr Top Microbiol Immunol338Year: 201011512819802582
65. Focks DA,Barrera R. Dengue transmission dynamics: assessment and implications for controlYear: 2007World Health OrganizationGeneva
66. Chow VT,Chan YC,Yong R. Monitoring of dengue viruses in field-caught Aedes aegypti and Aedes albopictus mosquitoes by a type-specific polymerase chain reaction and cycle sequencingAm J Trop Med Hyg58Year: 19985785869598444
67. Scott TW,Morrison AC,Lorenz LH. Longitudinal studies of Aedes aegypti (Diptera: Culicidae) in Thailand and Puerto Rico: population dynamicsJ Med Entomol37Year: 2000778815218910
68. Snow RW,Omumbo JA,Lowe B. Relation between severe malaria morbidity in children and level of Plasmodium falciparum transmission in AfricaLancet349Year: 1997165016549186382
69. Smith DL,Guerra CA,Snow RW,Hay SI. Standardizing estimates of the Plasmodium falciparum parasite rateMalar J6Year: 200713117894879
70. Hay SI,Okiro EA,Gething PW. Defining the relationship between Plasmodium falciparum parasite rate and clinical disease: statistical models for disease burden estimationMalar J8Year: 200918619656373
71. Guzmán MG,Kouri G,Bravo J,Valdes L,Vazquez S,Halstead SB. Effect of age on outcome of secondary dengue 2 infectionsInt J Infect Dis6Year: 200211812412121599
72. Egger JR,Coleman PG. Age and clinical dengue illnessEmerg Infect Dis13Year: 200792492517553238
73. WHOGuidelines for the clinical evaluation of dengue vaccines in endemic areasYear: 2008World Health OrganizationGeneva
74. Wichmann O,Yoon I-K,Vong S. Dengue in Thailand and Cambodia: an assessment of the degree of underrecognized disease burden based on reported casesPLoS Negl Trop Dis5Year: 2011e99621468308
75. Standish K,Kuan G,Avilés W,Balmaseda A,Harris E. High dengue case capture rate in four years of a cohort study in Nicaragua compared to national surveillance dataPLoS Negl Trop Dis4Year: 2010e63320300515
76. Endy TP,Anderson KB,Nisalak A. Determinants of inapparent and symptomatic dengue infection in a prospective study of primary school children in Kamphaeng Phet, ThailandPLoS Negl Trop Dis5Year: 2011e97521390158
77. Tricou V,Minh NN,Van TP. A randomized controlled trial of chloroquine for the treatment of dengue in Vietnamese adultsPLoS Negl Trop Dis4Year: 2010e78520706626
78. Duyen HTL,Ngoc TV,Ha DT. Kinetics of plasma viremia and soluble nonstructural protein 1 concentrations in dengue: differential effects according to serotype and immune statusJ Infect Dis203Year: 20111292130021335562
79. Nishiura H,Halstead SB. Natural history of dengue virus (DENV)-1 and DENV-4 infections: reanalysis of classic studiesJ Infect Dis195Year: 20071007101317330791
80. Vaughn DW,Green S,Kalayanarooj S. Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severityJ Infect Dis181Year: 20002910608744
81. Chanama S,Anantapreecha S,A-nuegoonpipat A,Sa-gnasang A,Kurane I,Sawanpanyalert P. Analysis of specific IgM responses in secondary dengue virus infections: levels and positive rates in comparison with primary infectionsJ Clin Virol31Year: 200418518915465410
82. Tatem AJ,Smith DL,Gething PW,Kabaria CW,Snow RW,Hay SI. Ranking of elimination feasibility between malaria-endemic countriesLancet376Year: 20101579159121035838
83. Suaya JA,Shepard DS,Chang M-S. Cost-effectiveness of annual targeted larviciding campaigns in Cambodia against the dengue vector Aedes aegyptiTrop Med Int Health12Year: 20071026103617875014
84. Vu SN,Nguyen TY,Tran VP. Elimination of dengue by community programs using Mesocyclops (Copepoda) against Aedes aegypti in central VietnamAm J Trop Med Hyg72Year: 2005677315728869
85. Vanlerberghe V,Toledo ME,Rodriguez M. Community involvement in dengue vector control: cluster randomised trialBMJ338Year: 2009b195919509031
86. Kittayapong P,Yoksan S,Chansang U,Chansang C,Bhumiratana A. Suppression of dengue transmission by application of integrated vector control strategies at sero-positive GIS-based fociAm J Trop Med Hyg78Year: 2008707618187787
87. Kourí G,Guzmán MG,Valdés L. Reemergence of dengue in Cuba: a 1997 epidemic in Santiago de CubaEmerg Infect Dis4Year: 199889929454563
88. Gubler DJ,Clark GG. Community involvement in the control of Aedes aegyptiActa Trop61Year: 19961691798740894
89. Toledo ME,Rodriguez A,Valdés L. Evidence on impact of community-based environmental management on dengue transmission in Santiago de CubaTrop Med Int Health16Year: 201174474721418448
90. Parks W,Lloyd L. Planning social mobilization and communication for dengue fever prevention and control: a step-by-step guideYear: 2004World Health OrganizationGeneva
91. Ooi E-E,Goh K-T,Gubler DJ. Dengue prevention and 35 years of vector control in SingaporeEmerg Infect Dis12Year: 200688789316707042
92. Egger JR. Reconstructing historical changes in the force of infection of dengue fever in Singapore: implications for surveillance and controlBull World Health Organ86Year: 200818719618368205
93. Esu E,Lenhart A,Smith L,Horstick O. Effectiveness of peridomestic space spraying with insecticide on dengue transmission; systematic reviewTrop Med Int Health15Year: 201061963120214764
94. WHOIndoor residual spraying: use of indoor residual spraying for scaling up global malaria control and eliminationYear: 2006World Health OrganizationGeneva
95. Vazquez-Prokopec GM,Kitron U,Montgomery B,Horne P,Ritchie SA. Quantifying the spatial dimension of dengue virus epidemic spread within a tropical urban environmentPLoS Negl Trop Dis4Year: 2010e92021200419
96. Ritchie SA,Hanna JN,Hills SL. Dengue control in North Queensland, Australia: case recognition and selective indoor residual sprayingAvailable at: 2002 (accessed Oct 2, 2012)..
97. Nathan MB,Giglioli ME. Eradication of Aedes aegypti on Cayman Brac and Little Cayman, West Indies, with Abate (Temephos) in 1970–1971Bull Pan Am Health Organ16Year: 198228396176286
98. Giglioli G. An investigation of the house-frequenting habits of mosquitoes of the British Guiana coastland in relation to the use of DDTAm J Trop Med Hyg28Year: 1948437018898698
99. Kroeger A,Lenhart A,Ochoa M. Effective control of dengue vectors with curtains and water container covers treated with insecticide in Mexico and Venezuela: cluster randomised trialsBMJ332Year: 20061247125216735334
100. Lenhart A,Orelus N,Maskill R,Alexander N,Streit T,McCall PJ. Insecticide-treated bednets to control dengue vectors: preliminary evidence from a controlled trial in HaitiTrop Med Int Health13Year: 2008566718291003
101. Seng CM,Setha T,Nealon J,Chantha N,Socheat D,Nathan MB. The effect of long-lasting insecticidal water container covers on field populations of Aedes aegypti (L) mosquitoes in CambodiaJ Vector Ecol33Year: 200833334119263854
102. WHOGuidelines for the treatment of malaria2nd edn.Year: 2010World Health OrganizationGeneva
103. Thomas SJ,Endy TP. Critical issues in dengue vaccine developmentCurr Opin Infect Dis24Year: 201144245021799408
104. Crompton PD,Pierce SK,Miller LH. Advances and challenges in malaria vaccine developmentJ Clin Invest120Year: 20104168417821123952
105. Webster DP,Farrar JJ,Rowland-Jones S. Progress towards a dengue vaccineLancet Infect Dis9Year: 200967868719850226
106. Whitehead SS,Blaney JE,Durbin AP,Murphy BR. Prospects for a dengue virus vaccineNat Rev Microbiol5Year: 200751852817558424
107. Leach A,Vekemans J,Lievens M. Design of a phase III multicenter trial to evaluate the efficacy of the RTS,S/AS01 malaria vaccine in children across diverse transmission settings in AfricaMalar J10Year: 201122421816029
108. Guy B,Barrere B,Malinowski C,Saville M,Teyssou R,Lang J. From research to phase III: preclinical, industrial and clinical development of the Sanofi Pasteur tetravalent dengue vaccineVaccine29Year: 20117229724121745521
109. The RTSS Clinical Trials PartnershipFirst results of phase 3 trial of RTS,S/AS01 malaria vaccine in African childrenN Engl J Med365Year: 201111321714642
110. Yekutiel P. The Global Malaria Eradication CampaignKlingberg MAEradication of infectious diseases: a critical studyYear: 1980KargerBasel3488
111. Wernsdorfer W,Hay SI,Shanks GD. Learning from historyFeachem RGA,Phillips AA,Targett GAShrinking the malaria map: a prospectus on malaria eliminationYear: 2009Malaria Elimination GroupSan Francisco95107
112. Nájera JA,González-Silva M,Alonso PL. Some lessons for the future from the Global Malaria Eradication Programme (1955–1969)PLoS Med8Year: 2011e100041221311585
113. Soper FL. The 1964 status of Aedes aegypti eradication and yellow fever in the AmericasAm J Trop Med Hyg14Year: 1965888891
114. Carmago S. History of Aedes aegypti eradication in the AmericasBull World Health Organ36Year: 19676026035299460
115. PAHOThe feasibility of eradicating Aedes aegypti in the AmericasRev Panam Salud Publica1Year: 199768729128110
116. Halstead SB. Successes and failures in dengue control: global experienceAvailable at: 2000 (accessed Oct 2, 2012)..
117. Soper FL. The prospects for Aedes aegypti eradication in Asia in the light of its eradication in BrazilBull World Health Organ36Year: 19676456475299470
118. Snow RW,Okiro EA,Gething PW,Atun R,Hay SI. Equity and adequacy of international donor assistance for global malaria control: an analysis of populations at risk and external funding commitmentsLancet376Year: 20101409141620889199
119. DeRoeck D,Deen J,Clemens JD. Policymakers' views on dengue fever/dengue haemorrhagic fever and the need for dengue vaccines in four southeast Asian countriesVaccine22Year: 200312112914604579
120. Morrison AC,Zielinski-Gutierrez E,Scott TW,Rosenberg R. Defining challenges and proposing solutions for control of the virus vector Aedes aegyptiPLoS Med5Year: 2008e6818351798
121. Eisen L,Beaty BJ,Morrison AC,Scott TW. Proactive vector control strategies and improved monitoring and evaluation practices for dengue preventionJ Med Entomol46Year: 20091245125519960667
122. Walker T,Johnson PH,Moreira LA. The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti populationsNature476Year: 201145045321866159
123. Snow RW,Guerra CA,Mutheu JJ,Hay SI. International funding for malaria control in relation to populations at risk of stable Plasmodium falciparum transmissionPLoS Med5Year: 2008e14218651785


KLA is supported by the Wellcome Trust and the Li Ka Shing Foundation. SIH is funded by a Senior Research Fellowship from the Wellcome Trust and is supported by the Li Ka Shing Foundation, the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. This research was also supported partly by the IDAMS Project (grant no 281803) within the 7th Framework Programme of the European Commission. The sponsors had no role in preparation of the manuscript or the decision to publish. We thank Cameron Simmons, Oliver Brady, Peter Gething, Thomas Scott, Philip McCall, and Jeremy Farrar for valuable comments and suggestions during the preparation of this manuscript; and Katherine Battle for proofreading.


SIH conceived of and contributed to writing of the paper. KLA wrote the paper.

Conflicts of interest

We declare that we have no conflicts of interest.

Article Categories:
  • Personal View

Previous Document:  Strategies to increase responsiveness to hepatitis B vaccination in adults with HIV-1.
Next Document:  Does the sickle cell trait (heterozygous carrier status) confer protection against malaria?