Modeling outbreaks in Brazil

Our analysis showed that the occurrence of outbreaks of ORO, MAY, SLE and ROC is affected differently by environmental variables, although temperature seems to be strongly associated with all of them. Theses information is quite alarming, since the temporal analyses have shown that the average temperature of some Brazilian areas has been increasing over the decades (see Fig 4). This variable presents an important constraint on the extent of expansion of these diseases throughout the country, mainly because these changes are intimately linked to vector lifecycle development and associated with the virus itself [7,59]. In addition, the IPCC report [60] points out that heat waves are more prone to occur in the next years with more frequency and duration. Furthermore, events of extreme precipitation are also most likely to be more frequent and intense on the continental surfaces, in humid tropical regions such as the North of Brazil. Consequently, climate changes may directly interfere with the distribution of the diseases evaluated in this study, particularly ORO and MAY.

The increase in temperature may also change the distribution of virus vectors, because they may migrate to other areas where conditions are favorable for proliferation. In some cases, the elevation has an inverse effect on the temperature, because generally, higher altitudes correspond with lower temperatures; nevertheless, some vectors are adaptable. In Mexico, the vector Aedes aegypti for example, has been found at an elevation of 2,000 meters whereas previously, it was only found in places up to 1,000 meters high [61]. For ORO and MAY outbreaks specifically, one of the factors that seems to be more related is environmental change [59]. Following deforestation in the Amazon, and subsequently, the cocoa plantation and others cultivated in the region, the vectors found an ideal spot for reproduction in the cocoa shells, and, expanded their population, spreading the virus to humans along the Amazonian roads [62]. Therefore, ORO and MAY outbreaks appear to be the result of a strong relationship between the virus and its environment, with human activity (colonization, cocoa cultivation, and subsequent environmental changes) resulting in the proliferation of the Culicidae and Ceratopogonidae mosquito families, and subsequently increasing their human contact [59,62,63].

By analyzing the results of PCA, it was observed that diseases were grouped into three main clusters: SLE, ROC and ORO+MAY (see Fig 2). The relationship between ORO and MAY occurred because both diseases are influenced by similar climatic factors, such as seasonality of temperature. Both have high-risk areas in the Northern and Central regions of the country, where the Amazonian biome predominates [5]. Moreover, both diseases are related to wild vectors, such as Haemagogus mosquitoes for cases of MAY and C. paraensis (Ceratopogonidae) for ORO [7]. Furthermore, although restricted to the Amazon region, these diseases have the potential to spread throughout the country and around the world, since they affect birds that can move long distances by migration or by illegal wildlife trafficking, which is very common in this region.

In relation to ROC, the factors that were most related to high-risk areas were thermal amplitude and elevation. This is in accordance with the distribution of the Atlantic Forest biome, which covers a mountainous region that shelters the wild vectors, Aedes scapularis and Psorophora sp. mosquitoes. To the best of our knowledge, no reports have explained the emergence and sudden disappearance of ROC cases in the 1970s, but it is believed that this virus is remained in a cycle where birds, including some migratory species, are the reservoirs [12]. Furthermore, in 2004, antibodies were detected among birds in southern Brazil, and the ROC virus may be circulating in different Brazilian regions, which could represent a permanent threat of disease outbreaks [7,12].

Similarly, the SLE virus can also be found in migratory birds, and it is believed to be responsible for the spread of the virus throughout the Americas, as well as other encephalitis. However, there are biological and genetic differences between isolates from North and South America [64]. Despite the rare isolates of SLE in humans in Brazil, antibodies to this virus were found in approximately 5% of the populations of the Northern and Southeastern regions [21]. The present study revealed that the most important factors for SLE were annual RAIN and DTV, which can also affect the life cycle of the Culex vector. For example, greater rainfall results in increasing vegetation coverage, which is the primary food source of many vertebrates that are potential hosts for the mosquitoes. However, decreased precipitation can reduce vegetation and drive both the vertebrate hosts and the mosquitoes towards human settlements, which can increase vector-human contact [2,3,65].

By analyzing the distribution maps of the diseases generated by Maxent it was observed that the probable high-risk areas were much larger than those in which the cases were detected. For example, ROC cases were reported only in the Sao Paulo state, but it is possible that there are other areas suitable for other outbreaks, such as a small region observed between the Rondonia and the Mato Grosso states (see Fig 3). This discrepancy between the reported cases and the existing cases is due mainly to the similarity of the clinical symptoms among those arboviruses, leading to an underestimation of the occurrence of ORO, MAY, SLE and ROC in Brazil. This scenario is aggravated by the lack of accurate diagnostic methods that identify which virus is acting. In cases of acute febrile illness outbreaks of MAY, SLE and ORO, for example, the laboratory procedures for diagnosing suspected cases is indispensable because these pathogens cannot be differentiated from other viral diseases, such as dengue or chikungunya, and may remain unknown [7].

As Brazil has been facing a major dengue, zika and chikungunya epidemic in recent years [66], it is quite possible that other arboviruses with similar symptoms have been underreported or confused with dengue itself. Despite the knowledge of the significant occurrence of many arboviruses in the Amazon Region, like ORO and MAY, many cases remain undiagnosed, probably because of their clinical manifestations, being usually mild and self-limited; patients generally recover completely after a few days. However, more severe cases may remain undiagnosed, especially because of the long distances to health care facilities, transport difficulties of the sample and lack of laboratories capable of conducting diagnostic tests. With regard to ORO infections, the diagnosis can easily be confused with malaria, which is endemic in that region [11,12].

According to the predictive model HadGEM2-ES, high-risk areas for all diseases may change in the next decades. For MAY, for example, practically the whole country will have adequate climatic conditions for virus transmission (see Fig 5). In some cases, such as ORO, total areas of infection will decline, but those that remain, such as the Northwestern and Northeastern regions of the country will be at increased risk. For ROC, there will be an emergent high-risk area in the South of the country, while for SLE the southern areas will become less susceptible to outbreaks. This scenario can be more or less dramatic, and depends on the levels of greenhouse gas emissions. However, this difference in emission rates will most strongly affect ORO and MAY distribution, precisely because they occupy the Northern areas of Brazil and are more susceptible to temperature changes (see Fig 4). Climatic change also affect human activity and the migration of the people, as well as the redistribution of the vectors, and a more favorable environment for the propagation of arboviruses [59]. Therefore, future risk estimations should consider those factors. Nevertheless, despite all efforts and cumulated knowledge in the literature, it is still remains difficult to identify the main cause of an outbreak [67] and to determine the most efficient technique(s) for protecting humans from these viruses. However, our findings indicate that temperature-related variables appear to play a central role in the epidemiology of culicid-vectored arboviruses.