Health And Vectors In Ecology-traducido

Ecologic Studies of Rodent Reservoirs:

Their Relevance for Human Health

James N. Mills and James E. Childs

Centers for Disease Control and Prevention, Atlanta, Georgia, USA

Address for correspondence: James N. Mills, Centers for

Disease Control and Prevention, 1600 Clifton Road, Mail Stop

G14, Atlanta, GA 30333, USA; fax: 404-639-4436; e-mail:

jum0@cdc.gov.

Within the past few years, the number of “new” human diseases associated with

small-mammal reservoirs has increased dramatically, stimulating renewed interest in

reservoir ecology research. A consistent, integrative approach to such research allows

direct comparisons between studies, contributes to the efficient use of resources and

data, and increases investigator safety. We outline steps directed toward understanding

vertebrate host ecology as it relates to human disease and illustrate the relevance of

each step by using examples from studies of hosts associated with rodent-borne

hemorrhagic fever viruses.

The practical importance of understanding

host and vector ecology has been recognized at

least since the early 1900s. Knowledge of the

container-breeding habits of Aedes aegypti

enabled early successes in the control of yellow

fever virus transmission and, ultimately, the

completion of the Panama Canal in 1914 (1).

Diverse applications of vector/reservoir ecologybased

measures to prevent zoonotic disease

include the prediction of Lyme disease risk by

monitoring acorn mast production and its impact

on the vertebrate hosts of the tick vectors (2),

control of vector populations for Borrelia

burgdorferi and Yersinia pestis through the

application of acaricides and insecticides to

rodents and deer at feeding stations (3,4),

dissemination of bait containing vaccines to

control rabies in foxes (5), and use of satellite

imagery to predict the activity of Rift Valley

fever in East Africa (6,7).

The rodent-borne hemorrhagic fevers, among

the most dramatic of recently emerging

infectious diseases, are caused by two distinct

groups of negative-stranded RNA viruses: the

arenaviruses (family Arenaviridae) and the

hantaviruses (genus Hantavirus, family

Bunyaviridae). With few exceptions, each virus

in these two groups is primarily associated with

a single species of rodent host of the family

Muridae. In the specific host, the virus

establishes a prolonged infection, which rarely

causes disease in the animal. The infected host

sheds virus into the environment (in urine, feces,

and saliva) for extended periods (8-10). These

characteristics are key to the transmission of the

viruses to humans (by the inhalation of

aerosolized virus) and to other rodents (by

horizontal and sometimes vertical mechanisms).

Arenaviruses cause the South American

hemorrhagic fevers, which produce hundreds of

cases annually, with a case-fatality ratio as high

as 33%. The best studied of these agents is Junín

virus, which is carried by the corn mouse

(Calomys musculinus) and causes Argentine

hemorrhagic fever (AHF). AHF was first

recognized in 1955 on the central pampas of

Argentina (11), where before the deployment of a

new vaccine in 1992, hundreds of cases occurred

each year. Although arenaviral diseases of

humans (other than lymphocytic choriomeningitis

associated with the introduced Old World

rodent Mus musculus) have not been recognized

in North America, Tamiami virus has been

recognized in association with cotton rats

(Sigmodon hispidus) since 1969 (12), and

Whitewater Arroyo virus was identified from

wood rats (Neotoma species) in the southwestern

United States in 1995 (13). The potential of

Whitewater Arroyo virus for causing human

disease is under investigation.

Hantaviruses cause hundreds of thousands

of cases of hemorrhagic fever with renal

syndrome (HFRS) in Europe and Asia each year.

Hantaviral disease was thought to be rare or

Ecologic Studies of Rodent Reservoirs:

Their Relevance for Human Health

James N. Mills and James E. Childs

Centers for Disease Control and Prevention, Atlanta, Georgia, USA

Address for correspondence: James N. Mills, Centers for

Disease Control and Prevention, 1600 Clifton Road, Mail Stop

G14, Atlanta, GA 30333, USA; fax: 404-639-4436; e-mail:

jum0@cdc.gov.

Within the past few years, the number of “new” human diseases associated with

small-mammal reservoirs has increased dramatically, stimulating renewed interest in

reservoir ecology research. A consistent, integrative approach to such research allows

direct comparisons between studies, contributes to the efficient use of resources and

data, and increases investigator safety. We outline steps directed toward understanding

vertebrate host ecology as it relates to human disease and illustrate the relevance of

each step by using examples from studies of hosts associated with rodent-borne

hemorrhagic fever viruses.

Emerging Infectious Diseases 530 Vol. 4, No. 4, October–December 1998

Perspectives

absent in the United States, although three cases

of mild HFRS associated with rat-borne Seoul

virus had been described (14). In 1993, the

discovery of hantavirus pulmonary syndrome

(HPS), which rapidly kills approximately half of

those infected, surprised public health officials

and virologists in the United States. The

causative agent, Sin Nombre virus (SNV), is

hosted by the deer mouse, Peromyscus

maniculatus, and the disease syndrome markedly

differs from HFRS. Since 1993, at least 20

additional hantaviruses have been isolated from

rodents throughout the Americas; about half are

known human pathogens (Figure 1).

Recognition of new rodent-borne diseases

has renewed interest in reservoir host ecology in

the United States, and recognition of HPS in

South America has prompted field studies in

Paraguay, Argentina, Chile, and Brazil. In 1997,

representatives from 13 American countries,

meeting in Lima, identified surveillance in

humans and rodents as a priority for combating

emerging hantaviral disease. Reservoir studies

are being designed and conducted in many parts

of the world by mammalogists, ecologists, and

vector-control personnel. However, sanitarians

and others with no specific training in such areas

are being asked to conduct reservoir studies in

the course of investigating disease outbreaks.

Rarely are these professionals trained in the safe

handling of animals potentially infected with

viruses capable of causing fatal disease.

To promote discussion of study design, data

collection, and appropriate and safe methods for

reservoir studies, we review prior efforts and

lessons learned. Although specific examples are

restricted to the rodent-borne hemorrhagic fever

viruses, many of the generalizations can be

applied to other pathogens maintained by smallmammal

reservoirs.

An Outline for Reservoir Studies

Assuming that the primary reservoir host

has already been implicated, the following

consecutive but overlapping steps can promote

an understanding of rodent reservoir ecology

as it relates to human disease: 1) determination

of the geographic distribution of the host;

2) determination of the geographic range of the

pathogen within the host range; 3) determination

of the regional distribution of the host and

pathogen among the distinct biomes or habitat

types; 4) determination of the relative prevalence

of infection among demographic subpopulations

of the host (e.g., males versus females and

adults versus juveniles); 5) elucidation of the

temporal and fine-scale spatial patterns of hostpathogen

dynamics through prospective, longitudinal

studies; and 6) development of an integrative

time- and place-specific predictive model.

Examples from studies of hantaviruses and

arenaviruses illustrate how each step is relevant

to human health.

Geographic Distribution of the Host

The geographic distribution of the host(s)

defines the maximum area in which the disease

can be endemic. For most small-mammal species

in North America, these distributions are known

relatively precisely (15). For example, the deer

mouse is one of the best-studied small-mammal

species in the world, and its distribution

throughout North America is well defined

(Figure 2). Fewer data are available on the

distribution of Central and South American

species. The range of the cotton rat, S. hispidus,

which is the reservoir of both Black Creek Canal

virus (a hantavirus that causes HPS) and

Tamiami virus (an arenavirus not associated

with human disease) is well defined in the

United States. However,

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