Revisiting the role of environmental and climate factors on the epidemiology of Kawasaki disease

Abstract

Can environmental factors, such as air-transported preformed toxins, be of key relevance to the health outcomes of poorly understood human ailments (e.g., rheumatic diseases such as vasculitides, some inflammatory diseases, or even severe childhood acquired heart diseases)? Can the physical, chemical, or biological features of air masses be linked to the emergence of diseases such as Kawasaki disease (KD), Henoch-Schönlein purpura, Takayasu's aortitis, and ANCA-associated vasculitis? These diseases surprisingly share some common epidemiological features. For example, they tend to appear as clusters of cases grouped geographically and temporarily progress in nonrandom sequences that repeat every year in a similar way. They also show concurrent trend changes within regions in countries and among different world regions. In this paper, we revisit transdisciplinary research on the role of environmental and climate factors in the epidemiology of KD as a paradigmatic example of this group of diseases. Early-warning systems based on environmental alerts, if successful, could be implemented as a way to better inform patients who are predisposed to, or at risk for, developing KD. Further research on the etiology of KD could facilitate the development of vaccines and specific medical therapies.

Environmental epidemiology of Kawasaki disease: Linking disease etiology, pathogenesis and global distribution

“…Importantly, our data and proposed framework support the novel paradigm proposed by Rodo et al . [ 24 ], whereby the trigger for KD is not an infectious agent but another environmental trigger, potentially a fungal toxin. The different elements of this framework are supported by the data presented herein, but will also be contextualized in the current knowledge base available on the topic of KD.…”

“…In this proposed framework, environmental factors would influence, over time, the susceptibility of children to develop KD when encountering the disease trigger, but these factors would not directly act as the trigger. The mechanism for modulation could be either an immunological process, such as maturation, an alteration in the microbiome or both [ 24 ]. Based on this study, we have identified 4 potential modulating factors: early development of the immune system, habitual exposure to environmental allergens, temporal exposure to biological atmospheric particles, and temporal experience of a stimulatory or co-stimulatory event, potentially of infectious origin.…”

“…Temporal clustering of cases in geographically unrelated areas is not consistent with person-to-person area, which would be typical of an infectious process [ 37 ]. No infectious agent is known to have a global distribution pattern similar to KD [ 24 , 42 ], and there is no consistency in the type of infectious disease reported to co-occur with KD. These inconsistencies have led many to conclude that multiple infectious agents could trigger KD [ 36 , 39 , 41 , 42 ].…”

On the interpretation of the atmospheric mechanism transporting the environmental trigger of Kawasaki Disease

“…Finally, Rodó et al [4] pointed to possible microbial antigens or toxins in aerosol particles as a possible trigger for KD, which are capable of eliciting an idiosyncratic immune response in susceptible children. This pathway, though not proved, would be consistent with an agricultural source, a short incubation time and synchronized outbreaks [5].…”

Human health in the face of climate change

“…Effects on noncommunicable diseases, such as allergies, cancer, and respiratory and cardiovascular diseases, in highly populated urban areas are other foci of interest. Along these lines, contributions about air pollution, dust, and human health were reviewed during the meeting by J. Centeno, and in this monograph also by Rodó et al . An emerging domain of research was introduced encompassing the effects on the air we breathe of the interaction with the altered environment in cities and rural landscapes in a changing climate.…”