the impact of the virus abated, epidemics have long-lasting economic ramifications: it has been estimated that the financial toll of this epidemic exceeded $1.6 billion, accelerating poverty, which, as estimated by one news organization, likely caused as many deaths as the outbreak itself.
Emergence of a Birth Defect Associated with Infection: Zika Virus in Brazil
As the Ebola outbreak was resolving in Africa in 2015, a new viral epidemic was beginning in South America. The first confirmed case of Zika virus infection in the Americas was reported in northeast Brazil in May 2015, although phylogenetic studies indicated that the virus had been introduced as early as 2013.
Zika virus is transmitted by mosquitos in temperate climates and causes a relatively mild disease in most cases: many adults seroconvert without ever knowing they were infected. However, during the 2015 outbreak it was rapidly appreciated that Zika virus infection of pregnant women can be associated with a terrifying new symptom in their newborns: small, misshapen heads (microcephaly) and severe developmental defects. As the virus spread throughout Brazil and beyond (Fig. 1.8), people in Mexico and North America quickly realized that the geographic range for the mosquito vector, Aedesaegypti, extended well into these areas. The rest of the Americas awaited the summer months braced for disaster, as mosquitos were predicted to carry Zika virus inexorably north. The outbreak coincided with the Summer Olympics in Rio de Janeiro, and prompted many enthusiastic supporters and athletes to stay home. For reasons still unclear, these fears did not materialize. By 2017, most of Latin America and the Caribbean had a massive decline in Zika virus infections. It has been suggested that the sharp reduction in cases is due, at least in part, to a phenomenon known as herd immunity (Chapter 7). Virus transmission between humans and mosquitos is greatly reduced in a population when enough people become immune to a virus, through vaccination or, as in the case of the Zika virus, natural immunity following infection.
Figure 1.8 Zika spread in Brazil. (A) In three short years, from 2014 to 2016, Zika virus moved progressively north and westward, spreading from the coastal region of Brazil to other countries in South America. (B) Decline of Zika virus cases since 2016. Adapted from Lowe R et al. 2018. Int J Environ Res Public Health 15:E96, under license CC BY 4.0.
Epidemiology
The stories above highlight some of the unique challenges, uncertainty, and urgency that face epidemiologists during an outbreak. The study of viruses can be likened to a set of con centric circles. The center comprises detailed analyses at the molecular level of the genome and the structures of viral particles and proteins that are crucial to understanding viral re production, and the biochemical consequences of interactions of viral and host cell proteins. How infection of individual cells affects the tissue in which the infected cells reside, and how that impacted tissue disturbs the biology of the host, de fine the landscape of the field of viral pathogenesis, in the next level (discussed in the following four chapters). But if a viral population is to survive, transmission must occur from an infected host to susceptible, uninfected ones. The study of infections of populations is the discipline of epidemiology, the cornerstone of public health research and response. Within this broad, outer circle, major areas of epidemiological research include outbreak investigation, disease transmission, surveillance, screening, biomonitoring, and public education.
An epidemiologist investigates outbreaks by undertaking careful data collection in the field (that is, where the infections occur) and performing statistical analyses. Questions often asked include “How might the symptoms observed in an infected individual implicate one mode of viral transmission over another?” or “Can a timeline be established to trace back the origins of an epidemic to a single event?” The goal is to learn more about the pathogen and how it caused the epidemic. Individual differences among prospective hosts, group dynamics and behaviors, geography, and climate all influence how efficiently a virus can establish infection within a population. Epidemiologists lack the luxury of performing controlled experiments, in which only one variable is manipulated. Instead, they must consider many parameters simultaneously to identify the source and transmission potential of a viral pathogen within a host community. Many of these variables are captured in various video games and mobile phone apps that simulate outbreaks (Box 1.4). In the next section, we identify some crucial terms and concepts used in this field. (For commentary and a personal account related to the topic, see the interview with Dr. Thomas London: http://bit.ly/Virology_London.)
Fundamental Concepts
Incidence versus Prevalence
Determining the number of infected individuals in a population is a primary goal of epidemiological studies. This information is required to establish both the incidence and the prevalence of infection. Incidence is defined as the number of new cases within a population in a specified period. Some epidemiologists use this term to determine the number of new cases in a community during a particular period, while others use incidence to indicate the number of new disease cases per unit of population per period. For example, the incidence of influenza can be stated as the number of reported cases in New York City per year or the number of new cases/1,000 people/year. Disease prevalence, on the other hand, is a measure of the number of infected individuals at one moment in time divided by an appropriate measure of the population. A highly infectious and lethal disease (such as the 1793 epidemic of yellow fever in Philadelphia) may have a high incidence but a low prevalence, because many of the infected individuals either died or cleared the infection. In contrast, a virus that can persist in a host for decades is likely to have high prevalence. An example of high prevalence is provided by hepatitis B virus; of the 300 million to 400 million people infected globally, one-third live in China, with 130 million carriers. For this reason, incidence is an in formative measure for acute or highly lethal infections, whereas prevalence is often used to describe long-lasting or persistent infections.
DISCUSSION
Video games model infectious-disease epidemics
The hugely popular online video game World of Warcraft became a model for the transmission of viral infections. In 2005, a dungeon was added to the fantasy world in which players could confront a powerful creature called Hakkar. In his death throes, Hakkar hit foes with “corrupted blood,” infected with a virus that killed the virtual player. The infection was meant to affect only those in the immediate vicinity of Hakkar’s corpse, but the virus spread as players and their virtual pets traveled to other cities in the game. Within hours after the software update, a full-blown virtual epidemic ensued as millions of characters became infected.
Although such games are meant only for entertainment, they do model disease spread in a mostly realistic manner. For example, as in real life, the spread of the virus in Hakkar’s blood depended on the ease of travel within the game, zoonotic transmission by pets, and transmission via asymptomatic carriers. Moreover, such games have a large number of participants, at one point more than 10 million for World of Warcraft, creating an excellent community for experimental study of infectious diseases. The players’ responses to dangerous situations approximated real-world reactions.
