Elimination of Falciparum Malaria and Emergence of Severe Dengue: An Independent or Interdependent Phenomenon?

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.

Concurrent malaria and dengue fever in (sub-Saharan) Africa: a systematic review and meta-analysis

“…Our study also reported significantly higher odds of malaria infection among patients with malaria mono-infection than acute dengue virus co-infection. This could be due to the inter-species cross-protection of dengue virus infection against malaria [11]. Our finding does not corroborate the reports of Kotepui et al 2019 [47] and Kotepui et al 2020 [53].…”

“…This could be due to the inter-species cross-protection of dengue virus infection against malaria. 11 Our finding does not corroborate the reports of Kotepui et al 2019 53 and Kotepui et al 2020 59 . Kotepui et al 2019 showed significantly lower odds of co-infection while Kotepui et al 2020 reported no notable difference in co-infection due to acute dengue compared to malaria mono-infection.…”

“…9, 10 The two mosquito-borne diseases have an overlapping epidemic pattern in Africa. 11 Due to their similar clinical presentation, possible concurrent malaria-dengue fever is often neglected 12 and generally misdiagnosed as malaria only. 6, 13 Misdiagnosis is more probable during co-infection than mono-infection and this may result in slow identification of dengue fever outbreaks with potentially high morbidity and mortality.…”

“…Though malaria or dengue virus mono-infection can be severe, concomitant infections could be even more fatal [9, 10]. The two mosquito-borne diseases have an overlapping epidemic pattern in Africa [11]. Due to their similar clinical presentation, possible concurrent malaria-dengue fever is often neglected [12] and generally misdiagnosed as malaria only [6, 13].…”

Dengue serology in Indonesian COVID-19 patients: Coinfection or serological overlap?

“…Cross-reactivity of both dengue IgM and IgG, however, is known to exist with malaria and leptospirosis; there seems to be cross-reactivity with other flaviviruses as well, such as Zika and Japanese encephalitis [ [13] , [14] , [15] ]. The cross-reactivity with flaviviruses is expected as dengue virus and other flaviviruses share a large degree of structural and sequence homology; the same phenomenon occurring with malaria is speculated to result from the elicitation of cross-reactive antibodies or other immune responses that infer cross-protection, or at least partial cross-protection, against symptomatic and severe dengue [ 15 ].…”