**1. Introduction**

[68] Zhu, Y. G., Li, H. M., & Zang, X. (1966). Pathology of attenuated Japanese encephali‐

tis virus. *Chin J Pathology*, 10, 113-6.

206 Encephalitis

Emergence and re-surgence of vector-borne diseases still constitute an important threat to human health in the 21st century, causing over a million death and considerable mortality and morbidity worldwide. Vector-borne diseases are linked to the environment by the ecol‐ ogy of the vectors and of their hosts, including humans. In the recent decades, climate change is a global phenomenon which has greatly influenced the emergence and resurgence of several infectious diseases such as malaria, dengue fever, plague, filariasis, trypanosomia‐ sis, leishmaniasis and arbo-viral diseases, particularly yellow fever. Indeed, arbo-viruses will represent a threat for the coming century too. The resource constrained developing countries are the foremost sufferer and the major victims of several vector-borne diseases [1], including yellow fever.

Yellow fever (YF) is one of the great infectious scourges of humankind. It is a zoonosis in‐ digenous to some tropical regions of South America and Africa which has caused numerous epidemics with high mortality rates throughout history [2]. Approximately 200,000 cases of YF occur annually, resulting in about 30 000 deaths; 90% of cases occur in Africa. Large epi‐ demics, with over 100,000 cases, have been recorded repeatedly in Sub-Saharan Africa, and multiple outbreaks have occurred in the Americas. The virus has never appeared in Asia or in the Indian subcontinent [3].

YFV is endemically transmitted in forests and savannas of South America and Africa, peri‐ odically emerging from enzootic cycles to cause epidemics of hemorrhagic fever [2],with re‐ ported fatality rates ranging from 20% to 80% due to two principal syndromes: YEL-AND (yellow-fever associated neurologic disease, which includes encephalitis, myelitis or myelo-

© 2013 Karunamoorthi; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

encephalitis [ADEM]), and YEL-AVD (yellow-fever associated viscerotropic disease, which usually involves multi-organ failure including liver, renal and circulatory failure) [4].

**2. Global public health impact**

competent vectors are present [10].

**3. A brief history of YF**

in the history of YF [18].

**4. Geographical distribution**

The virus is endemic in tropical areas of Africa and Latin America, with a combined popula‐ tion of over 900 million people [13]. During the past decade, official reports of YF incidence (50-120 cases a year from South America and 200–1200 cases a year from Africa) probably underestimate the true number of cases. Many cases of jaundice and fever (a surveillance definition of yellow fever) are not assessed, unexplained deaths go unreported, symptoms suggest alternative diagnoses, and, in some countries, surveillance systems for yellow fever are not in place [14]. The case-fatality rate ranges from 20% to 50% and is partly dependent on case recognition and testing practices [15,16]. The continued presence and epidemic po‐ tential of yellow fever virus make it a global health threat. The growth of international travel to endemic areas annually has increased the number of travelers potentially exposed to the virus and consequently it has increased the risk of introduction into other new areas where

Yellow Fever Encephalitis: An Emerging and Resurging Global Public Health Threat in a Changing Environment

http://dx.doi.org/10.5772/46041

209

The cause of YF was unknown, but it was thought to be contracted either by coming into contact with "effluvia" from those stricken by the disease or with fomites such as cloth‐ ing, sheets, and other articles that patients had used. Fear of contracting the contagion led people to shun their neighbours and friends and even to abandon loved ones. "It just tore society apart" [17]. Known today to be spread by infected mosquitoes, yellow fever was long believed to be a miasmatic disease originating from rotten vegetable matter and oth‐ er putrefying filth, and most believed the fever to be contagious. There were many de‐ bates regarding the agent that caused YF and Carlos Findlay was the first to suggest that mosquitoes transmitted the disease [8,9]. Text box 1 indicates some of the key milestones

The earliest description of yellow fever is found in a Mayan manuscript in 1648, but by ge‐ nome sequence analysis it appears that yellow fever virus evolved from other mosquitoborne viruses about 3000 years ago [19]. Yellow fever originated in Africa and in the 1500s yellow fever virus was probably introduced into the New World via ships carrying slaves from West Africa. Epidemics soon became common in the coastal communities of South and Central America and along the southern and eastern seaboard of North America as far north as Boston. Between 1668 and 1893, there were more than 135 epidemics in the USA [17]. Large epidemics occurred throughout the 18th and 19th centuries in the Caribbean islands,

YF is present in both the rural and urban tropical areas of 45 endemic countries in Africa and Latin America, with a potential combined population of over 900 million individuals

the United States, Africa, Europe, West Indies, and South America.

Although YF has undoubtedly been endemic in tropical Africa for thousands of years, it was only after the arrival of the European migrants in the New World at the end of the fifteenth century that this scourge emerged in the form of devastating epidemics. The term 'vomito‐ negro' was used in those days to describe clinical aspects of this pathological condition, be‐ cause death was frequently preceded by black vomit or by partially digested blood. Other terms used to designate yellow fever included 'Yellow Jack' and 'Safran scourge,' with refer‐ ence to the jaundice observed in many patients [5].

Griffin Hughes was the first to use the term "yellow fever" to describe the disease in his book in 1750 [6]. At different stages of human development, YF has caused untold hardship and indescribable misery among different populations in the Americas, Europe, and Africa. Hundreds of thousands of people have been affected by the disease throughout ages among which tens of thousands have died. YF brought economic disaster in its wake, constituting a stumbling block to development too [7].

YF is known for bringing on a characteristic yellow tinge to the eyes and skin, and for the terrible "black vomit" caused by bleeding into the stomach [8,9]. It was one of the most feared lethal diseases before the development of effective vaccine. Today the disease still af‐ fects as many as 200,000 persons annually in the tropical regions of Africa and South Ameri‐ ca, and poses a significant hazard to unvaccinated travellers to these areas [10]. Recent increases in the density and distribution of the urban mosquito vector, *Ae. aegypti*, as well as the rise in air travel has increased the risk of introduction and spread of yellow fever to North and Central America, the Caribbean and Asia [10].

In East Africa, yellow fever remains as a disease of increasing epidemic risk. The most recent yellow fever outbreak in the region was reported by the WHO in the late 2010 and included the first human cases reported in Uganda in almost 50 years [11]. Prior to this, outbreaks oc‐ curred in Sudan (2003 and 2005) and were the first reports of yellow fever from that country in approximately 50 years. These events were preceded by the first outbreak ever reported in Kenya (1992–1993), which were the first reported human cases in East Africa for close to 25 years [11].

Over the last 20 years the number of yellow fever epidemics has risen and more countries are reporting cases. Mosquito numbers and habitats are increasing. Nevertheless, in both Af‐ rica and the Americas, there is a large susceptible, unvaccinated population. Changes in the world's environment, such as deforestation and urbanization, have increased contact with the mosquito/virus. Widespread international travel plays an important role in spreading the disease. The priorities are vaccination of exposed populations, improved surveillance and epidemic preparedness [12]. During the 20th century yellow fever has reemerged as a cause of human suffering. The recent epidemics are clearly indicating the vulnerability and potentiality of the YF as a global public health threat in the changing environment. In this context, the present chapter becomes more significant and pertains.
