3

Emergence and Spread of Infectious Diseases
Akio YAMADA
Department of Veterinary Science, National Institute of Infectious Diseases
1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japane-mail: yamada@nih.go.jp

Abstract
Most pathogens causing diseases in humans are derived from animals including both wildlife anddomestic animals, and the majority of emerging infectious diseases in particular have originated from wildlife. Since there are diverse species of animals yet unidentified globally, including viruses and bacteria, it
seems inevitable that emergence of new infectious diseases will continue if human activities that change ordestroy wildlife habitats are not stopped. It seems impossible, however, to stop such human activities, since
exploitation of resources is prerequisite to providing sufficient food, housing and clothing to the 6.7 billion
people living on the earth. Furthermore, international movement of wildlife also facilitates the emergence of
new infectious diseases. The only thing we can do to reduce the threat of emerging infectious diseases is todetect them and respond as quickly as possible so that we can prevent further spread of the diseases tohumans and establishment of the pathogens in human populations.
Key words: emerging infection, wildlife, zoonoses

1. Introduction
In 1995, the Centers for Disease Control and Prevention (CDC) started publishing a new scientific periodical,
Emerging Infectious Diseases, in response to increased
awareness of potential threats posed by emerging andre-emerging infections. Since then we have witnessed
the emergence of West Nile fever in North America,
Hendra and Nipah virus infections and severe acuterespiratory syndrome (SARS) in Southeast Asia,
monkeypox in the United States and so on. The H5N1
subtype of the influenza A virus now epizootic aroundthe world is regarded as a potential candidate for an
influenza virus which could cause a global pandemic. It
was previously shown that approximately three fourthsof emerging diseases were zoonotic (Taylor et al., 2001:
Woolhouse & Gowtage-Sequeria, 2005). In this review
article, therefore, I will provide an overview of theemergence and spread of new infectious diseases fromthe perspective of zoonoses.

2. Emerging Infectious Diseases
Diseases newly appearing or newly recognized,
diseases that are new to particular regions and alreadyknown diseases, the incidence of which has been
increasing recently, are regarded as emerging infectious
diseases. Nearly one infectious disease per eight months
has emerged since 1980 (Institute of Medicine, 2003).
The Institute of Medicine published reports in 1992 andGlobal Environmental Research
12: 3-7 (2008)
printed in Japan

2003 which pointed out thirteen key factors involved in
the emergence and spread of new infectious diseases(Institute of Medicine, 1992; Institute of Medicine,2003). Woolhouse and Gowtage-Sequeria (2005) ranked
these factors and the top ten are listed below.
Rank*
1
2
3
4
5
6
7
8
9
10

Factors
Changes in land use or agricultural practices
Changes in human demographics and society
Poor population health (e.g., HIV, malnutrition)
Hospitals and medical procedures
Pathogen evolution (e.g., antimicrobial drug
resistance, increased virulence)Contamination of food sources or water supplies
International travel
Failure of public health programs
International trade
Climate change* Ranked by the number of associated pathogen species(most to least).
From Woolhouse, M.E.J. and S. Gowtage-Sequeria (2005)

As is obvious from the list, the major drivers are
anthropogenic interventions in ecosystems. Humanactivities accelerate the emergence of infectious diseases.
To support the unprecedentedly increasing humanpopulation of the globe, it is inevitable that humans willcontinue to disturb ecosystems to obtain precious
resources through rain forest clearing, road and dam
building, agricultural irrigation and other activities.
©2008 AIRIES4

A. YAMADA

3. Most Emerging Diseases are Caused by
Zoonotic Pathogens
According to Woolhouse and Gowtage-Sequeria(2005), about 73% of emerging infectious diseases are
zoonoses―diseases or infections naturally transmissible
between vertebrate animals and humans (WHO/FAO,
1959). Moreover, even many diseases now considered
contagious only to humans are thought to be derived
from pathogens in animals domesticated several thousand years ago or from wild non-human primates (Wolfeet al., 2007). Human encroachment on the habitat ofwild animals harboring microbes will increase
opportunities for encounters between wild animals andhumans. If contact, whether direct or indirect, occurs
after the encounter, subsequent spillover of microbes
from animals to humans may follow. It is also possiblethat pathogens from wildlife might be transmitted tohumans via domestic animals. According to Taylor et al.
(2001), approximately 70% of zoonotic pathogens are
not transmitted among humans after successful spillover.
If the basic reproductive ratio (R0) of the pathogen is
greater than 1, the infection will continue to spread until
all susceptible individuals are dead or immune.
Pathogens showing R0 of greater than 1, therefore, havethe potential to emerge among the human population.
On the other hand pathogens with R0 of less than 1 will
not spread among humans. It is, however, possible that
pathogens with R0 of less than 1 could emerge if the
primary spillover from wild animals to humans occurs
very frequently. For instance more than ten million
people receive post-exposure prophylaxis against rabies
every year. Although rabies is not an emerging disease,
the rabies virus casts a great burden on humans eventhough the virus cannot spread from human to human.
Microbes perpetuating in their ecological niche will do
nothing to humans unless humans encroach on areas
where the microbes are lurking in natural reservoirs.

4. Several Examples of Recently Emerging
Infectious Diseases
Since this issue of the Global Environmental Research is devoted and confined to influenza and West
Nile fever, characteristics of some other zoonotic diseases which have recently emerged are discussed in thisarticle.
4.1 Nipah virus infection
In 1998, a previously unknown encephalitis struck
pig farmers in Malaysia (Chua et al., 1999). Since
respiratory and neurological disease in pigs preceded thehuman cases, over one million pigs were slaughtered tocontain the disease in humans. A virus resembling themeasles virus was isolated from a patient. It was foundthat the virus was closely related to but distinct from theHendra virus , which also emerged in 1994 in Australia(Murray et al., 1995). The new virus was named after
the place where the patient was found, Nipah. Together

with the Hendra virus, the Nipah virus was assigned to a
new genus Henipavirus. Epidemiological investigations
were conducted to look for the natural reservoir of the
Nipah virus and it was eventually found that fruit bats ofthe genus Pteropus were the natural reservoir of the
Nipah virus (Yob et al., 2001; Chua et al., 2002).
Habitat loss and hunting are believed to force those animals to approach areas where humans and domestic
animals live, resulting in cross-species transmission ofviruses from the bats to new hosts. Moreover, in
Bangladesh, infections were reported to have beencaused by consumption of fruit or palm sap contaminated with the saliva of infected bats (Luby et al., 2006).
Human-to-human infection was reported in Bangladesh,though apparently it occurred inefficiently. Although
there is no specific animal species that is responsible forthe emergence of new infectious diseases (Woolhouse &Gowtage-Sequeria, 2005), bats are receiving muchattention because they have been implicated as a causeof recent emergences of deadly pathogens (Wong et al.,2007) such as the Ebola virus, Marburg virus and severe
acute respiratory syndrome (SARS) corona virus.
4.2 Acquired immunodeficiency syndrome (AIDS)
If we stick to the definition of zoonoses proposed by
the World Health Organization (WHO), the humanimmunodeficiency virus (HIV) is not zoonotic, since thevirus can no longer spread to animals under natural
conditions. However, the evidence is accumulating thatHIV-1 was derived from the simian immunodeficiency
virus of chimpanzees in central Africa (Hahn et al.,
2000; Keele et al., 2006). Bush meat hunting and consequent exposure of people to the organs or blood of animals are thought to be the major drivers promoting aspillover of simian viruses to humans. Human behavior
such as intravenous drug injection and homosexuality
contributed to adaptation of the virus to human beingsand its establishment as a new human-specific pathogen.
According to UNAIDS, the Joint United Nations
Programme on HIV/AIDS, the estimated number ofpeople infected with HIV is more than 33 million,
whereas more than 2.5 million people are newly
infected and 2.1 million people die of AIDS every year
(UNAIDS, 2007). It would be therefore prudent to consider AIDS one of the most devastating zoonotic diseases in human history.
4.3 Ebola hemorrhagic fever
At this moment, there is an ongoing outbreak ofEbola hemorrhagic fever in Uganda. As of December 7,
2007, 93 people were suspected of being infected withthe virus, 22 of whom died. More than 300 people were
under observation (WHO, 2007). The Ebola virus
belongs to the family Filoviridae and was first identified
in 1976 (Johnson et al., 1977). The Ebola virus infects
not only humans but other non-human primates such as
chimpanzees and gorillas. Since non-human primates
are highly susceptible to the virus and die quickly after
infection, scientists believe that creatures other thanEmergence and Spread of Infectious Diseases

non-human primates might be the natural reservoir of
the Ebola virus. The subsequent search for the reservoir
animals has been hampered by the great diversity offauna and flora in African rain forests. Recent studies,
however, have suggested that three species of fruit bats
are potential hosts for the Ebola virus (Leroy et al.,2005). Non-human primates as well as forest duikers are
speculated to be incidental hosts from which the Ebola
virus is eventually transmitted to humans. Humans
become infected with Ebola virus by direct contact withdead animals. Hunting animals for bush meat, especiallyhunting weakened animals, may increase the potential
risk of acquiring the infection.
4.4 SARS
In 2003, a previously unknown virus was identifiedin patients suffering from severe pulmonary distress inHong Kong. The prominent feature of the virus causing
SARS was that it could be readily transmitted among
humans after its spillover to the human population. The
virus, SARS coronavirus (Drosten et al., 2003; Ksiazek
et al., 2003; Rota et al., 2003), was first thought to be
derived from Himalayan palm civets raised for sale inwet markets in the southern part of China (Peiris et al.,2004). Wet markets are notorious for the interminglingof diverse species of animals. Wet markets are also
implicated in the evolution of highly pathogenic avian
influenza viruses (HPAIV). Subsequent studies, however,showed that it was unlikely that palm civets were thenatural reservoir of the SARS coronavirus. Intensive
investigations revealed that many corona viruses ofdifferent lineages occur among different species of bats.
Furthermore, the presence of a coronavirus closely
related to the SARS coronavirus was discovered when
Chinese horseshoe bats were investigated (Li et al.,2005). It was thus speculated that a certain corona virus
harbored by an unidentified species of bat first gained
access to wildlife yet to be identified and then to otherspecies of wild animals, eventually reaching humans via
animals captured and sold at wet markets.
4.5 Monkeypox
The monkeypox virus was first isolated from captive
non-human primates but monkeys are not the natural
reservoir of this virus. Although monkeypox is zoonotic,
several cycles of transmission among humans are
known to have occurred. It is not well understood how
the virus is maintained in the environment, although thevirus is enzootic to geographically limited places like
West Africa and the Congo basin. However, in 2003, thevirus suddenly appeared in the United States. Seventy
two people who had been keeping prairie dogs as pets
were confirmed or suspected to be infected with thevirus. Epidemiological investigation conducted afterwards indicated that Gambian rats imported from Ghana
were the culprits (Regnery et al., 2007). It was thenrevealed that African dormice kept together with thoserats had been redirected to Japan. It was fortunate thatthe animals could be traced and recovered and that they5tested negative for the presence of monkeypox virus
infection.

5. Driving Forces of Emergence
As already discussed in the preceding sections, notonly spillover but also later spread of the infectious
agents among humans can be accelerated by biological,
environmental or sociological factors. Outbreaks of
Nipah and Hendra viruses were attributable to changes
in agricultural practices that resulted in close contact
between bats and domestic animals. Bushmeat hunting
was implicated in the emergence of AIDS and Ebola
hemorrhagic fever. In Central Africa, more than one
billion kilograms of wild animal meats are consumed
annually. The number of animals killed each year forfoods is estimated to be around 580 million in Central
Africa, whereas 6.4 to 15.8 million vertebrates are estimated to be consumed in the Amazon Basin every year
(Karesh et al., 2005; Fevre et al., 2006; Chomel et al.,2007). Furthermore, live animals, including wildlife aresold in wet markets in various geographic areas aroundthe globe, including the United States. Since different
species of animals intermingle within the premises, wetmarkets provide microbes great opportunities to find
new host species in which they can thrive. Wet markets
have played essential roles in the emergence of the
SARS coronavirus and HPAIV. In addition, international
trade in wildlife is estimated to bring six billion US
dollars to the industry. Introduction of the monkeypox
virus and possibly the West Nile virus was due to legal
as well as illegal importation of wildlife into the US. It
is estimated that more than 40,000 non-human primates,
four million live avian species, and 640,000 live reptiles
are traded every year. Humans are thus estimated to be
exposed to wildlife greater than several billion times ayear. Direct and indirect contact between humans andwildlife may increase the probability of spillover ofwildlife pathogens to humans. After spillover, humanbehavioral changes have accelerated the global spread of
AIDS and establishment of AIDS as a human-only
disease, whereas rapid movement of people contributed
to the worldwide spread of the SARS coronavirus.
International trade in live domestic animals likechickens and cows has promoted the dissemination of
HPAIV and bovine spongiform encephalopathy, respectively.

6. Detection and Response
The global human population is growing exponentially and is expected to reach seven billion in the year
2015, indicating that human encroachment into wildlife
habitats will never cease. The number of known species
is estimated to be no more than 12.8% of the total species that actually live on the earth. We have recognized
only 0.4 and 1% of bacteria and viruses (Watson et al.,1995), respectively, suggesting that human activities
such as further development of tropical rain forests will

6

A. YAMADA

result in encounters of humans with unknown species
harboring unknown microbes. It seems possible thathumans will experience quite a few infectious disease
emergences in the future. When domestic animals are
responsible for the emergence of new infectious diseases,
culling of animals is a prerequisite for prevention of the
spread of the disease. It is, however, impossible to take asimilar approach as far as wildlife is concerned.
Although at least 200 million domestic birds have diedor been culled to prevent the spread of HPAIV since2003, culling of wild birds, now thought to be partly
involved in dissemination of the virus, is not recommended by international organizations such as the WHO
and FAO. The most important measure to counteremerging infectious diseases is enhanced surveillancethat enables us to conduct early detection of clusters of
infected people as early as possible. Establishment ofsound response mechanisms is also important. The
International Health Regulations issued by the WHO in
2005 and enacted in 2007 are expected to enhance suchabilities globally. Furthermore expanded surveillancetargeting wildlife will be also needed to detect new
infectious diseases that may cause pandemics inhumans.

7. Conclusion
The explosion of the human population on the earth
makes it easier for microbes to find new hosts, whereby
some of them undergo evolutionary processes to adapt
to humans. Since human population growth shows nosigns of ceasing and since human activities disturbing
ecosystems will never end, it seems inevitable that
pathogens lurking in wildlife will emerge as humanpathogens in the near future. Detection of emerging
infectious diseases through vigilant surveillance andprompt response is mandatory to fight against thecontinuing threat of emerging infectious diseases.
References
Chua, K.B., K.J. Goh, K.T. Wong, A. Kamarulzaman, P.S. Tan,
T.G. Ksiazek, S.R. Zaki, G. Paul, S K. Lam and C.T. Tan (1999)
Fatal encephalitis due to Nipah virus among pig-farmers in
Malaysia. Lancet, 354:1256-1259.
Chua, K.B., C.L.Koh, P.S. Hooi, K.F. Wee, J.H. Khong, B.H.
Chua, Y.P. Chan, M.E. Lim and S.K. Lam (2002) Isolation of
Nipah virus from Malaysian Island flying-foxes. Microbes andInfection, 4:145-151
Chomel, B.B., A. Belotto and F.-X. Meslin (2007) Wildlife, exotic
pets and emerging zoonoses. Emerging Infectious Diseases,
13:6-11
Drosten, C., S. Günther, W. Preiser, S. van der Werf, H.R. Brodt,
S. Becker, H. Rabenau, M. Panning, L. Kolesnikova, R.A.
Fouchier, A. Berger, A.M. Burguière, J. Cinatl, M. Eickmann,
N. Escriou, K. Grywna, S. Kramme, J.C. Manuguerra, S.
Müller, V. Rickerts, M. Stürmer, S. Vieth, H.D. Klenk, A.D.
Osterhaus, H. Schmitz and H.W. Doerr (2003) Identification of
a novel coronavirus in patients with severe acute respiratory
syndrome. New England Journal of Medicine, 348:1967-1976.
Fevre, E.M., B.M. Bronsvoort, K.A. Hamilton and S. Cleaveland(2006) Animal movements and the spread of infectious diseases.
Trends in Microbiology, 14: 125-131.
Hahn, B.H., G.N. Shaw, K.M. De Cock and P.M. Sharp (2000)
AIDS as a zoonosis: Scientific and public health. Science,
287:607-614.
Institute of Medicine of the National Academy (1992) Emerging
Infections: Microbial Threats to Health in the United States.
The National Academy Press.
Institute of Medicine of the National Academy (2003) Microbial
Threats to Health: Emergence, Detection and Response. The
National Academy Press.
Johnson, K., P. Webb, J. Lange and F. Murphy (1977) Isolationand partial characterization of a new virus causing acutehemorrhagic fever in Zaire. Lancet, 309: 569-571.
Karesh, W.B., R.A. Cook, E.L. Bennett and J. Newcomb (2005)
Wildlife trade and global disease emergence. Emerging Infectious Diseases, 11:1000-1002.
Keele, B.F., F. Van Heuverswyn, Y. Li, E. Bailes, J. Takehisa, M.L.
Santiago, F. Bibollet-Ruche, Y. Chen, L.V. Wain, F. Liegeois, S.
Loul, E.M. Ngole, Y. Bienvenue, E. Delaporte, J.F. Brookfield,
P.M. Sharp, G.M. Shaw, M. Peeters and B.H. Hahn (2006)
Chimpanzee Reservoirs of Pandemic and Nonpandemic HIV-1.
Science, 313: 523-526.
Ksiazek, T.G., D. Erdman, C.S. Goldsmith, S.R. Zaki, T. Peret, S.
Emery, S. Tong, C. Urbani, J.A. Comer, W. Lim, P.E. Rollin,
S.F. Dowell, A.E. Ling, C.D. Humphrey, W.J. Shieh, J. Guarner,
C.D. Paddock, P. Rota, B. Fields, J. DeRisi, J.Y. Yang, N. Cox,
J.M. Hughes, J.W. LeDuc, W.J. Bellini and L.J. Anderson;
SARS Working Group (2003) A novel coronavirus associatedwith severe acute respiratory syndrome. New England Journalof Medicine, 348: 1953-1966.
Leroy, E.M., B. Kumulungui, X. Pourrut, P. Rouquet, A. Hassanin,
P. Yaba, A. Delicat, J.T. Paweska, J.P. Gonzalez and R.
Swanepoel (2005) Fruit bats as reservoirs of Ebola virus.
Nature, 438:575-576.
Li, W., Z. Shi, M. Yu, W. Ren, C. Smith, J.H. Epstein, H., Wang,
G. Crameri, Z. Hu, H. Zhang, J. Zhang, J. McEachern, H. Field,
P. Daszak, B.T. Eaton, S. Zhang and L.F. Wang (2005) Bats arenatural reservoirs of SARS-like coronaviruses. Science,
310:676-679.
Luby, S.P., M. Rahman, M.J. Hossain, L.S. Blum, M.M. Husain,
E. Gurley, R. Khan, B.N. Ahmed, S. Rahman, N. Nahar, E.
Kenah, J.A. Comer and T.G. Ksiazek (2006) Foodborne
transmission of Nipah virus, Bangladesh. Emerging Infectious
Diseases, 12: 1888-1894.
Murray, K., P. Selleck, P. Hooper, A. Hyatt, A. Gould, L. Gleeson,
H. Westbury, L. Hiley, L. Selvey, B. Rodwell and P. Ketterer(1995) A morbillivirus that caused fatal disease in horses andhumans. Science, 268:94-97.
Peiris, J.S.M., Y. Guen and K.Y. Yuen (2004) Severe acuterespiratory syndrome. Nature Medicine, 10:588-597.
Regnery, R.L. (2007) Poxviruses and the passive quest for novel
hosts. Current Topics in Microbiology and Immunology,
315:345-361.
Rota, P.A., M.S, Oberste, S.S. Monroe, W.A. Nix, R. Campagnoli,
J.P. Icenogle, S. Peñaranda, B. Bankamp, K. Maher, M.H. Chen,
S. Tong, A. Tamin, L. Lowe, M. Frace, J.L. DeRisi, O. Chen, D.
Wang, D.D. Erdman, T.C. Peret, C. Burns, T.G. Ksiazek, P.E.
Rollin, A. Sanchez, S. Liffick, B. Holloway, J. Limor, K.
McCaustland, M. Olsen-Rasmussen, R. Fouchier, S. Günther,
A.D. Osterhaus, C. Drosten, M.A. Pallansch, L.J. Anderson and
W.J. Bellini (2003) Characterization of a novel coronavirus
associated with severe acute respiratory syndrome. Science,
300:1394-1399.
Taylor, L.H., S.M. Latham and M.E.J. Woolhouse (2001) Risk
factors for human disease emergence. Philosophical Transactions of the Royal Society of London B: Biological Sciences,356:983-989.
UNAIDS (2007) AIDS epidemic update. Available at

Emergence and Spread of Infectious Diseases(http://data.unaids.org/pub/EPISlides/2007/2007_epiupdate_en.
pdf)
Watson, R.T., V.H. Heywood, I. Baste, B. Dias, R. Gamez, T.
Janetos, W. Reid and G. Ruark (eds.) (1995) Global
Biodiversity Assessment― Summary for Policy-Makers,
Cambridge University Press.
WHO/FAO (1959) Second Report of the Joint WHO/FAO Expert
Committee on Zoonoses. WHO Technical Report Series No.
169, World Health Organization, Geneva.
WHO (2007) Ebola hemorrhagic fever update. Available at(http://www.who.int/csr/don/2007_12_07/en/index.html)
Wong, S., S. Lau, P. Woo and K.-Y. Yuen (2007) Bats as acontinuing source of emerging infections in humans. Reviewsin Medical Virology, 17:67-91.
Wolfe, N.D., C.P. Dunavan and J. Diamond (2007) Origins ofmajor human infectious diseases. Nature, 447:279-283.
Woolhouse, M.E.J. and S. Gowtage-Sequeria (2005) Host range
and emerging and reemerging pathogens. Emerging Infectious
Diseases, 11:1842-1847.
Yob, J.M., H. Field, A.M. Rashdi, C. Morrissy, B. van der Heide,
P. Rota, A. bin Adzhar, J. White, P. Daniels, A. Jamaluddin and
T. Ksiazek (2001) Nipah virus infection in bats (order
Chiroptera) in peninsular Malaysia. Emerging Infectious
Diseases, 7:439-441.

7
Akio YAMADA

Akio YAMADA is Director of the Department of Veterinary Science, National
Institute of Infectious Diseases. He has
been studying various viruses including
mouse hepatitis virus, Rous sarcoma
virus, mumps virus, influenza virus, B
virus, rabies virus, West Nile virus, Nipah
virus and SARS coronavirus. He is now
also responsible for leading research on several bacteria, including
Bacillus anthracis, Francisella tularensis, and Brucella spp., in his
department. He is an enthusiastic bird watcher in his personal life.

(Received 31 January 2008, Accepted 27 June 2008)