Abstract
The global malaria burden, including falciparum malaria, has been reduced by 50% since 2000, though less so in Sub-Saharan Africa. Regional malaria elimination campaigns beginning in the 1940s, up-scaled in the 1950s, succeeded in the 1970s in eliminating malaria from Europe, North America, the Caribbean (except Haiti), and parts of Asia and South- and Central America. Dengue has grown dramatically throughout the pantropical regions since the 1950s, first in Southeast Asia in the form of large-scale epidemics including severe dengue, though mostly sparing Sub-Saharan Africa. Globally, the WHO estimates 50 million dengue infections every year, while others estimate almost 400 million infections, including 100 million clinical cases. Curiously, despite wide geographic overlap between malaria and dengue-endemic areas, published reports of co-infections have been scarce until recently. Superimposed acute dengue infection might be expected to result in more severe combined disease because both pathogens can induce shock and hemorrhage. However, a recent review found no reports on more severe morbidity or higher mortality associated with co-infections. Cases of severe dual infections have almost exclusively been reported from South America, and predominantly in persons infected by Plasmodium vivax. We hypothesize that malaria infection may partially protect against dengue – in particular falciparum malaria against severe dengue – and that this inter-species cross-protection may explain the near absence of severe dengue from the Sub-Saharan region and parts of South Asia until recently. We speculate that malaria infection elicits cross-reactive antibodies or other immune responses that infer cross-protection, or at least partial cross-protection, against symptomatic and severe dengue. Plasmodia have been shown to give rise to polyclonal B-cell activation and to heterophilic antibodies, while some anti-dengue IgM tests have high degree of cross-reactivity with sera from malaria patients. In the following, the historical evolution of falciparum malaria and dengue is briefly reviewed, and we explore early evidence of subclinical dengue in high-transmission malaria areas as well as conflicting reports on severity of co-morbidity. We also discuss examples of other interspecies interactions.
Highlights
We hypothesize that malaria infection may partially protect against dengue – in particular falciparum malaria against severe dengue – and that this inter-species cross-protection may explain the near absence of severe dengue from the Sub-Saharan region and parts of South Asia until recently
We conclude that at the population level the evidence of interaction between dengue and malaria is perhaps already there: when comparing time trends in the two diseases at continent level, a suggestive pattern emerges
We have discussed the striking coincidence of the emergence of dengue in recent years (Figure 1D), with the reduction in incidence of malaria (Figure 1B), suggesting that declining malaria exposure due to successful control programs or other environmental factors may have inadvertently led to the cessation of protection against clinically apparent and severe dengue infections, especially in Sub-Saharan Africa
Summary
PRESENT AND PAST PREVALENCE OF MALARIA, DENGUE, AND POPULATION-LEVEL PROTECTION AGAINST EACH DISEASE. Plasmodium falciparum malaria parasites probably emerged as a human pathogen from its enzootic origin in West Africa about 5,000–10,000 years ago (Carter and Mendis, 2002) This coincides with the point in time when humans began living in large agricultural communities, and when African Anopheles mosquitoes adapted to the novel agrarian environment breeding in man-made water collections and feeding almost exclusively on humans. These show consistent dispersal of each serotype from South Asia over Southeast Asia to the Pacific and the Americas, with relatively few reported occurrences in sub-Saharan Africa, tribal areas of Papua NewGuinea, North-East India and inner parts of South America This recently intensified transmission and spread of the DENVs is largely attributed to massive urbanization and globalized travel and trade that characterize the latter half of the 20th century. Public health efforts currently focus on environmental management for elimination of vector breeding sites and on various insecticide applications targeting either larvae or adult stages in the peri-domestic environment (Chu et al, 2013)
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