Yellow fever outbreak in Brazil: the puzzle of rapid viral spread and challenges for immunisation

Abstract

We discuss the complex eco-social factors involved in the puzzle of the unexpected rapid viral spread in the ongoing Brazilian yellow fever (YF) outbreak, which has increased the reurbanisation risk of a disease without urban cases in Brazil since 1942. Indeed, this rapid spatial viral dissemination to the Southeast and South regions, now circulating in the Atlantic Forest fragments close to peri-urban areas of the main Brazilian megalopolises (São Paulo and Rio de Janeiro) has led to an exponential increase in the number of yellow fever cases. In less than 18 months, 1,833 confirmed cases and 578 deaths were recorded most of them reported in the Southeast region (99,9%). Large epizooties in monkeys and other non-human primates (NHPs) were communicated in the country with 732 YF virus (YFV) laboratory confirmed events only in the 2017/2018 monitoring period. We also discuss the peculiarities and similarities of the current outbreak when compared with previous great epidemics, examining several hypotheses to explain the recent unexpected acceleration of epizootic waves in the sylvatic cycle of the YFV together with the role of human, NHPs and mosquito mobility with respect to viral spread. We conclude that the most feasible hypothesis to explain this rapidity would be related to human behavior combined with ecological changes that promoted a significant increase in mosquito and NHP densities and their contacts with humans. We emphasize the urgent need for an adequate response to this outbreak such as extending immunisation coverage to the whole Brazilian population and developing novel strategies for immunisation of NHPs confined in selected reserve areas and zoos. Finally, we stress the urgent need to improve the quality of response in order to prevent future outbreaks and a catastrophic reurbanisation of the disease in Brazil and other South American countries. Continuous monitoring of YFV receptivity and vulnerability conditions with effective control of the urban vector Aedes aegypti and significant investments in YF vaccine production capacity and research and development for reduction of adverse effects are of the highest priority.

The Impact and Control of Emerging and Re-Emerging Viral Diseases in the Environment: An African Perspective

“…In the warm, humid savanna regions of Africa, tree-hole-breeding Aedes mosquitoes reach very high densities and are implicated in the endemic and epidemic transmission of viruses from monkeys to humans. Aedes aegypti, a domestic mosquito species that breeds in human-made containers, transmits the yellow fever virus among humans in cities (Possas et al 2018). The virus is maintained over the dry season by vertical transmission in mosquitoes.…”

A model for yellow fever with migration

“…This case is the most important one, since it implies that YF could be introduced from the forest to the urban areas. The basic reproduction numbers satisfy R s 0 > 1 and R u 0 < 1, and Equations (4), (5), (6) have an equilibriumP w = (s w ,ζ w ,̄w,s m ,ζ m ,s u ,ζ u ,̄u) withs…”

“…It is worth to mention that the largest outbreak of YF in Brazil in the last years, with more than 2000 confirmed cases and 676 deaths from December 2016 to March 2018, was originated in nonhuman primates according to genetic and poblational studies . Analysis of YF cases combined with genomes generated locally revealed an early phase of sylvatic transmission and posterior spatial expansion toward areas free of YF, followed by a rise in viral transmission to humans in urban areas in late 2016.…”

Inactivation of yellow fever virus with amotosalen and ultraviolet A light pathogen‐reduction technology

“…Sylvatic yellow fever (YF) cycles propagate the virus among monkeys with occasional transmission to humans, and are responsible for the majority of the human cases reported to the World Health Organization (WHO) . The risk for explosive urban YFV cycles becomes a concern when sylvatic YFV outbreaks occur near densely populated areas infested by Aedes aegypti . In such areas, YF control can be obtained through mosquito control and through human immunization.…”

“…While no antiviral therapy exists to treat YF disease, an efficient live attenuated YFV vaccine strain 17D (YFV‐17D), developed in 1937, is being used for routine immunization in endemic areas and for travelers to endemic areas . Reactive massive vaccine campaigns have been used to prevent urban YF cycles during the most recent 2015 Angola and 2016 to 2018 Brazil outbreaks . YFV‐17D live attenuated vaccine is associated with serious adverse events, such as vaccine‐associated neurotropic or viscerotropic diseases, reported at a rate of 0.3‐3.2 cases/100,000 doses with increasing risk factors in immunocompromised patients …”