[Emerging Infectious Diseases]
[Volume 4 No. 2 / April - June 1998]

Perspectives

Wild Primate Populations in Emerging Infectious Disease Research:  The
Missing Link?

Nathan D. Wolfe,* Ananias A. Escalante, William B. Karesh, Annelisa
Kilbourn, Andrew Spielman,* and Altaf A. Lal
*Harvard School of Public Health, Boston, Massachusetts, USA; Centers for
Disease Control and Prevention, U.S. Public Health Service, Chamblee,
Georgia, USA; Wildlife Health Sciences, Wildlife Conservation Society,
Bronx, New York, USA.
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           Wild primate populations, an unexplored source of
           information regarding emerging infectious disease,
           may hold valuable clues to the origins and evolution
           of some important pathogens. Primates can act as
           reservoirs for human pathogens. As members of
           biologically diverse habitats, they serve as
           sentinels for surveillance of emerging pathogens and
           provide models for basic research on natural
           transmission dynamics. Since emerging infectious
           diseases also pose serious threats to endangered and
           threatened primate species, studies of these diseases
           in primate populations can benefit conservation
           efforts and may provide the missing link between
           laboratory studies and the well-recognized needs of
           early disease detection, identification, and
           surveillance.

Infectious diseases respect no species or geographic boundaries. For a
parasite, closely related hosts offer new environments in which infection,
maintenance, replication, and transmission remain possible. The anthropoid
primates (which include humans) and to a lesser degree simian primates
share broadly similar physiologic and genetic characteristics and thus
susceptibility to many viruses, bacteria, fungi, protozoa, helminths, and
ectoparasites (1) that have the potential to cross primate-species
boundaries (2).

Similarities in pathogen susceptibility have made nonhuman primates ideal
laboratory models. During the 20th century, laboratory research on captive
primates has elucidated the life cycle and pathogenesis of many infectious
agents and facilitated drug and vaccine development. Nevertheless, the
ecology of infectious agents found in wild populations of primates has only
recently been addressed. Just as captive primates have proved invaluable
for research at the level of the organism, wild populations can provide the
opportunity to study infectious disease phenomena at the population and
ecosystem levels. Research at these levels addresses such pressing
questions as the origin(s) of pathogens, determinants of pathogen
emergence, and factors influencing maintenance of pathogens in animal
reservoirs.

During the past two decades unknown human diseases, including AIDS, Ebola
fever, hantavirus infection, and dengue hemorrhagic fever, have emerged
from enzootic foci. The emergence of these and other diseases has been
linked to the interface of tropical forest communities with high levels of
biodiversity and agricultural communities with relative genetic homogeneity
and high population densities of humans, domestic animals, and crops. This
interface poses a high risk for the emergence of novel disease (3-5).

Since most nonhuman primates live in tropical forest habitats, most
interactions between humans and wild nonhuman primates occur in this
high-risk interface, which has recently increased because of expanded
ecotourism and forest encroachment. These interactions can lead to pathogen
exchange through various routes of transmission (Table). Arthropod vectors,
shared water, and hunting of wild animals have facilitated pathogen
exchange and may have played an important role in pathogen transfers since
ancient times. In the recent past, laboratory research has led to
accidental human exposure to such agents as primate malaria parasites (12)
and a simian immunodeficiency virus (SIV) (16). The potential for exchange
through xenotransplantation has been discussed (17), and infection from
vaccine contaminated with SV40, a primate papovavirus, led to the exposure
of millions of persons in the 1950s (15). Conversely, pathogen transmission
from humans to nonhuman primates places both captive and wild animals at
serious risk for diseases such as measles and tuberculosis (TB), which are
deadly in many nonhuman primate species. In general, as levels of
interaction increase, so does pathogen exchange, resulting in further risks
to both humans and nonhuman primates.

The need for improved surveillance and basic research on emerging
infectious disease is well documented (3,18-20). Wild primates can serve as
sentinels by signaling which pathogens pose a risk for humans in the
immediate area (21) as well as in distant countries (5). Here, we describe
potential benefits of incorporating wild populations into emerging
infectious disease research.

Pathogen Origins

Nonhuman primates are infected with the closest relatives of important
human pathogens. The construction of molecular phylogenies has played an
important role in studying the evolution and classification of many
pathogens. While trees that result from these analyses must be interpreted
with care, they can provide valuable information on the history of
pathogens. Furthermore, the selection of genes that are evolving at the
appropriate rate should allow phylogenetic analyses to assess both ancient
and more recent epidemic origins (22).

Human herpes simplex virus infection is common in nonhuman primates and may
reflect contact with humans. A study of viral infection in nonhuman
primates found that chimpanzees and gorillas were seropositive to human
herpes simplex virus-1 and -2 strains, but orangutans and gibbons were not
(23).

Research on SIV phylogeny (24,25) has shown that HIV-1 and HIV-2 are each
more closely related to primate pathogens than they are to one another.
HIV-1 is in a group with SIV(sub CPZ) (26), a chimpanzee (Pan troglodytes) virus,
while HIV-2 falls within a clade consisting of West African primate viruses
(Figure 1; 24). In fact, Mindell (27) has argued that HIVs and SIVs should
be referred to as `primate immunodeficiency viruses' to more accurately
reflect their heritage. Preliminary evidence suggests that the origins of
global T-cell lymphotropic virus-1 subtype diversity may be analogous,
leading Liu et al. (28) to propose that HTLV-I subtypes emerged from three
separate nonhuman primate reservoirs.

Table. Routes of pathogen exchange between human and nonhuman primates
--------------------------------------------------------------------------
						   Direction of 
Route of exchange  	Pathogen       exchange  Evidence(sup a)  Reference
--------------------------------------------------------------------------
                                        Nonhuman
                                        primate to
Animal bite        	Herpes B        human           E        	 6(sup b)
                                        Nonhuman
                                        primate to
                        Monkeypox       human           E            7
                                        Human to
                                        nonhuman
Fecal-oral         	Poliovirus      primate         L           2(sup b)
                                        Chimpanzee
                                        to
                        Poliovirus      chimpanzee      E            8
                                        Nonhuman
Hunting, food prep                 	    primate to
& eating           	Ebola           human           E            9
                        Mycobacterium   Among
Nasal secretions   	leprae          primates       P, L     	10(sup b)
                                        Human to
                                        nonhuman
Respiratory droplet	Tuberculosis    primate         L       	11(sup b)
                                        Both
Vector-borne       	Malaria         directions     L,E       	12(sup b)
                                        Both
                        Filaria         directions     L,E       	 8(sup b)
                                        Human to
                                        nonhuman
Water-mediated     	Dracunculiasis  primate         L        	 13
                                        Nonhuman
                                        primate to
                        Schistosomiasis human           E        	 14
                                        Nonhuman
                                        primate to
Xenotransplantation	SV40            human        E(sup c)     15(sup b)  
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(sup a)L = laboratory; E = epidemiologic; P = evidence that parasites
live naturally in multiple primate hosts.
(sup b)Evidence reviewed.
(sup c)The only current evidence for xenotransplantation includes SV40
spread through vaccine production.

This pattern is not unique to viruses, as demonstrated through decades of
research on primate malarias. More than 26 species of Plasmodia infect
primates (12,29). Both morphologic and molecular analyses show human and
nonhuman primate malarias interdigitating on phylogenetic trees (Figure 2;
30,33). Preliminary evidence suggests that this group of parasites has a
range of coevolutionary scenarios, including the speciation of P. vivax and
related parasites in Asian primates, the recent exchange of parasites
between humans and New World monkeys (30), and perhaps an ancient exchange
of a falciparum-like parasite from a bird or lizard to an African hominoid
(31,34,35). Further analyses are likely to lead to surprises. For example,
recent research has shown that the diversity of human P. vivax (previously
considered to be a single species) also includes a P. vivax-like parasite,
a widespread pathogen, which is most closely related to P. simiovale, a
primate malaria of Asian macaques (Macaca sp.) (30,36).

					[fig 1]
            Figure 1. Relationships among primate and human
            lentiviruses: Phylogeny of primate lentiviruses
            based on the gag gene obtained by (25). The names
            of the strains are indicated in parentheses. Hosts
            are indicated on trees. The description of the
            lentivirus strains is provided in (25).

A major limitation of these studies is that they rely on very small numbers
of nonhuman primate isolates only two SIV(sub cpz) isolates for the HIV-1 clade,
a single P. simiovale isolate for malaria phylogeny. In addition, very few
data are available on the distribution of these pathogens in wild
populations; more data on the distribution and extent of shared pathogens
should provide clues to origins (37), thereby pointing to general
conditions that may contribute to disease emergence.

Molecular phylogenies can also play a direct role in the control of
pathogens, for example, in charting their antigenic diversity, a task
necessary for vaccine design (38). Because nonhuman primate pathogens are
often evolutionary outgroups, vaccines that are targeted at antigens shared
by human and nonhuman pathogens should provide more universal coverage.
Molecular phylogenies can also assist in determining the rate of evolution
of vaccine candidate antigens. Because low rates of mutation often indicate
selective constraint, this technique may point to candidate antigens that
cannot easily mutate to evade vaccine-induced antibodies. Similar analyses
identifying highly constrained gene products or metabolic pathways as
targets for drug development may contribute to slowing the emergence of
drug resistance.

Reservoirs

The study of pathogen transmission has been encumbered by the use of
inappropriate terminology. Such terms as "primary hosts," "reservoir
hosts," "carriers," "arthroponoses," "xenonoses," and "zoonoses" pose
premature assumptions and belie aspects of the origins and natural
transmission cycles of pathogens. The factors that determine pathogen
viability within a vertebrate host may correspond only roughly, or not at
all, to species boundaries. Primate pathogens do not adhere to the
faithfully maintained sanctity of the distinction between humans and
nonhumans.

                         [fig 2]
          Figure 2. Relationships between primate and human
          parasites: Malaria phylogeny based on the
          circumsporozoite protein gene. The alignment does not
          include the central repeat region. P. falciparum (Pfa),
          P. vivax (Pvi), and P. malariae (Pma) are from humans;
          P. cynomolgi (Pcy), P. simiovale (Pso), and P. knowlesi
          (Pkn) are from macaques; P. simium (Psi) and P.
          brasilianum (Pbr) are from New World monkeys; P.
          reichenowi (Pre) is from chimpanzees; P. gallinacium
          (Pga) is from birds; and P. berghei (Pbe) and P. yoelii
          (Pyo) are from rodents. The numbers in the names
          indicate different isolates as described in (30). The
          sequence of P. gallinacium was reported by (31). The
          numbers on the branches are bootstrap % based on 500
          pseudoreplications. The tree was estimated by the
          neighbor-joining method with the Tajima and Nei
          distance (32).

The misconception of an evolutionary trend toward increasing host
specificity (39) has contributed to the belief that pathogen exchange
should be rare. An apparently restricted host range, however, may be the
product of specific ecologic conditions and not of an intrinsic
characteristic of the pathogen. In many cases, ecologic changes can broaden
the host range of a pathogen. For example, the filarid worm Loa loa remains
outside human populations, primarily because of vector behavior (40);
changes in ecology, such as the availability of a novel host, can change
vector behavior and expand the pathogen's host range. Similar phenomena may
have played a role in the emergence of a range of flaviviruses (e.g.,
yellow fever, dengue, and Japanese encephalitis) from primarily
forest-dwelling nonhuman primate cycles. For these flaviviruses, primate
populations may also continue to play a role by introducing novel genetic
variants, which, at least in the case of dengue, may be involved in
pathogenesis.

Another misconception is that primate populations are too sparse to
maintain human pathogens. A number of variables influence whether or not a
pathogen is maintained in a given population. The capacity for latency, for
example, may decrease the host population size necessary to maintain
pathogens. This characteristic has evolved independently in pathogens as
diverse as herpesviruses and Plasmodium and may help explain sustained
transmission in hosts with low population density. Orangutans (Pongo
pygmaeus), for example, are thought to act as hosts to two distinct
Plasmodium species (41), despite an estimated population size of two per
km2. While molecular phylogenies have not yet been used to verify that
these parasites are unique, the presence of a dormant hypnozoite stage
might allow for sustained transmission even at this extreme. Where human
and nonhuman hosts overlap, both must be factored into epidemiologic
models. Small populations of nonimmune humans alone may not be capable of
maintaining a pathogen, but when nearby nonhuman hosts are considered, a
critical population size may be reached.

Surveys to assess pathogen prevalence among nonhumans can play an important
role in control strategies. Eradication programs must consider animal
reservoirs; even if complete human coverage is achieved, long-term
reemergence from animal reservoirs can undo the best eradication efforts.
For example, it is not known if poliovirus infections can be maintained in
nonhuman primate populations. Seroprevalence surveys conducted before and
after eradication may prove invaluable.

Accidental exposure to infected laboratory workers has led to poliovirus
infections of chimpanzees and gorillas since the 1940s (1). Poliovirus can
infect not only our closest living relatives, chimpanzees, gorillas
(Gorilla gorilla), and orangutans (Pongo pygmaeus) (2), but also more
distantly related anthropoids like the colobus monkeys (e.g., Colobus
abyssinicus kikuyuensis [=guereza]) (42). Antibodies and shed virus have
also been found in recently imported animals (8), and some chimpanzees may
act as symptomless carriers (2). Long-term research by Jane Goodall on wild
Tanzanian chimpanzees documented the potential for transmission of
poliovirus (or a similar virus) in free-ranging chimpanzee populations
(43). Since no samples were collected, it is impossible to determine if the
epidemic described by Goodall was part of a natural chimpanzee cycle or the
result of introduction from local human populations or researchers. As
poliovirus eradication efforts intensify, it may be useful to monitor virus
prevalence in humans living near primate habitats.

Control efforts that rely on antimicrobial drugs must also take into
account the potential for nonhuman primate reservoirs. Despite
demonstrations that mass administration of diethylcarbamazine citrate
successfully controlled Brugia malayi (a filarid worm), Mak et al. found a
high prevalence of B. malayi after a large-scale administration of
chemotherapy (44). Research showed that even though periodic prevalence of
B. malayi decreased, subperiodic prevalence remained high. The maintenance
of subperiodic B. malayi was eventually attributed to mosquitoes infected
by leaf monkeys (Presbytis obscura). In this particular free-ranging
primate host, approximately 83% of the monkeys were infected (44).

Nonhuman "reservoirs" may also confer potential benefits. It is at least
theoretically possible that nonhuman primate populations may provide a
barrier to the spread of drug-resistant pathogens; while these pathogens
benefit from resistance in environments where drug pressure exists, drug
resistance can be costly, and resistant pathogens may not compete
effectively against susceptible `wild-type' pathogens in the absence of
drug pressure. As drug-free populations, reservoirs may provide havens for
susceptible pathogens, thereby decreasing the rate at which drug-resistant
genes spread and increasing the rate at which susceptibility may return
after drug pressure ends. This hypothesis may help explain why the rates of
drug-resistant gram-negative enteric bacteria of wild baboons (Papio
cynocephalus) living with limited human contact are significantly lower
than those of baboons living with human contact (45).

Sentinel Surveillance

In tropical lowland forests, which contain the greatest biodiversity of
terrestrial habitats (46), exist rarely seen or unknown pathogens with the
potential to enter human populations. These pathogens may affect residents
of and visitors to forested regions (21) and act as the source of
introduction of infectious agents to distant susceptible populations (47).
Increasing human contact with forested systems almost certainly leads to a
corresponding increase in the emergence of infections in the human
population. Nevertheless, predicting which pathogens humans may encounter
and be susceptible to remains a methodologic challenge.

Surveillance methods for predicting emerging pathogens include surveillance
of vectors or forest-dwelling human populations and wildlife epidemiology
(epidemiologic study of infections in wild populations) (48). These
approaches have limitations. While vector sampling may prove the easiest
method for widespread surveillance, the pathogens identified from vectors
may be difficult or impossible to culture. Even when successful, vector
sampling is likely to identify a range of pathogens, only some of which may
infect humans. Studies of human populations, while providing valuable
information, are limited to regions in which forest-dwelling human
populations exist.

Epidemiologic research among free-ranging primate populations has the
potential to predict which pathogens might enter human populations as
contact with forested regions increases. In addition to their physiologic
similarities to humans, primates have other characteristics that contribute
to their accumulation of infectious agents. Primates live primarily in
forested environments (49); in general, they have large bodies and live in
large groups-characteristics that may attract vectors (50). Furthermore,
dependence on fruit, a characteristic of most primates, requires mobility
(both terrestrially and arboreally), a trait that may increase exposure to
pathogens (51,52).

Despite the lack of organized attempts to document the distribution of
pathogens in wild populations, recognized "die-offs" in wild primate
populations have played an important role in identifying novel pathogens.
In 1956, for example, a novel flavivirus was identified through the
investigation of large-scale deaths of bonnet macaques (Macaca radiata) and
hanuman langurs (Presbytis entellus) in the Kyanasur Forest of India
(Seymour, 1981, cited in [2]) caused by Kyanasur Forest virus. More
recently, in 1995, deaths in a chimpanzee population studied by Christoph
Boesch in the Ti Forest, Cte d'Ivoire, and a single human case following
a necropsy led to the identification of a novel strain of Ebola virus
(9,53). The single human case in the Swiss researcher foreshadowed the
localized mini-outbreak of Ebola hemorrhagic fever in Mayibout, a village
in the northeast of Gabon in January 1996. The Gabon epidemic was linked to
the handling, preparation, and consumption of a chimpanzee that had been
found dead; 29 of 37 identified cases involved exposure to the dead
chimpanzee (54). Close monitoring of such populations, as is being
conducted in the Ti Forest, has the potential to identify emergence-linked
behavior, such as the consumption of specific plants or insects, which may
lead to the still elusive reservoir of Ebola virus. Considering the
exceptionally small percentage of wild primate populations under long-term
study, these examples represent only the tip of the iceberg. More
systematic monitoring of wild primate populations will likely provide a
substantial payoff in our understanding, identification, and possible
control of novel pathogens, both for humans and endangered primates.

Surveillance for certain types of human-nonhuman primate contact may be
particularly useful. Hunting, which involves tracking, capturing, handling,
transporting, preparing, and consuming meat, may play a particularly
important role in pathogen exchange. In addition to the recent evidence of
hunting-mediated Ebola transmission, the hunting of a red colobus (Colobus
pennanti oustaleti [=badius]) has been implicated in a localized epidemic
of monkeypox, an orthopoxvirus similar to smallpox, which continued for
four generations of human-to-human contact (55). Another example is the
increased risk for feline plague among cats that hunt rodents (7).
Necropsies share many characteristics with hunting and are appropriately
considered a high-risk activity.

Bites from wild primates may also play a role in the transmission of
certain pathogens. For example, chimpanzee-to-human transmission of
monkeypox occurred when a wild chimpanzee bit a 2-year-old girl (6).
Further sampling demonstrated high prevalence in forest squirrel
populations (up to 49% among Funisciurus lemniscatus) (56), underlining the
need for comprehensive studies before determining the ultimate source and
reservoir of pathogens. Bites and scratches have transmitted pathogens to
laboratory workers. The transmission of B-virus, a herpesvirus infecting
rhesus macaques (Macaca mulatta), has caused death in 18 of 24 known human
cases (57). Surveillance and education in human populations that hunt
nonhuman primates, as well as follow-up of reported primate bites in
nonlaboratory settings, may be indicated.

Ecologic and Social Factors Involved in Natural Transmission

The potential for disease emergence and reemergence depends on the
interaction of complex social, ecologic, and genetic factors at the host,
vector, and pathogen levels (58). Because wild populations of primates
display diverse social behavior and live in a range of ecologic
environments, they exemplify natural transmission. Furthermore, monitoring
pathogens in wild primate populations does not involve the treatment or
behavior change interventions that monitoring pathogens in humans requires.
Exceptions include the increasingly common need for wildlife medicine to
maintain the health of endangered species and decrease the impact of
pathogens from humans and domestic animals on free-ranging animals (59).
Nevertheless, for many pathogens, basic epidemiologic research, and not
treatment, remains the primary goal of wildlife medicine (59).

Studies of wild populations can highlight factors associated with the
pathogen exchange across species boundaries. Some parasites, for example,
the chewing licepocket gopher system, complete their entire life cycle on
a single host. This high level of host specificity may contribute to the
close cospeciation between pocket gophers and their respective lice; the
phylogenetic trees of host and parasite are nearly mirror images (60).
Nevertheless, such host-specific parasites may be the exception rather than
the rule. Many intestinal parasites, for example, seem to be generalists.
One epidemiologic study of wild primates in the Kibale Forest National
Park, Uganda, evaluated the role of primate distribution on the
distribution of intestinal amoebas (61); the park contains a number of
spatially separate primate groups, each of which consists of multiple
primate species. Most variation in amoeba prevalence was explained by group
membership, and little was explained by species, which suggests that these
parasites treated the primate groups as biologic islands (62), spreading
easily among diverse members of the same island but rarely spreading to new
islands.

Long-term behavioral research combined with occasional pathogen sampling
may provide valuable data. Long-term research on the SIVs of East African
primates, for example, has provided evidence for a recent cross-species
transmission of SIV between baboons and African grivet monkeys
(Cercopithecus aethiops aethiops) (62). This research has documented the
incidence of SIV(sub agm) among Ethiopian grivet monkeys for more than 20 years
(63). By examining prevalence in age groups over time, this research
demonstrated the minimal impact of SIV(sub agm) on the survival of grivets, the
predominance of sexual transmission, and the lack of maternal transmission.

An ecologic approach to pathogen transmission can benefit our understanding
of emerging diseases. By determining how humans become a part of the life
cycle of pathogens rather than how pathogens enter human populations, we
can better understand the factors associated with emergence and improve the
quality of public health responses. How humans become part of the life
cycle of pathogens depends on human migrations, environmental changes, and
cultural and social factors, in the context of evolutionary history of the
pathogens, vectors, and hosts, which make up an infectious system. Ecologic
and evolutionary studies of wild animals in general, and primate
populations in particular, can address questions arising from these complex
interactions.

The Future

Traditionally, the study of wild populations of primates has been the
domain of primatologists and wildlife veterinarians, who have worked to
overcome logistic difficulties in the field, develop methods, and address
ethical issues. Opportunities exist for collaborative work on infectious
disease; the benefits of such efforts are considerable. The translocation
of animals from vulnerable forest fragments to forest reserves, an
increasingly common conservation effort, is an opportunity for pathogen
sampling. Other possibilities are provided by collaboration with long-term
behavioral research on free-ranging animals. While behavioral research
sites may only provide fecal and urine samples, the study of intestinal
parasites is often possible; recent advances in urinalysis demonstrate that
urine may be a source of both antigen and antibody from systemic
infections, such as malaria (64). The distribution of appropriate necropsy
protocols and sample collection kits would improve data collection and
decrease risks associated with necropsies. Urgently needed are strategies
for noninvasive remote diagnosis. For example, combined with sensitive
molecular diagnostics, a remote tissue-biopsy dart system (65) may have
potential for obtaining epidemiologic samples.

Efforts to preserve endangered primates and monitor disease emergence have
some common objectives. Pathogen exchange is a two-way street, and exposure
to human pathogens poses a serious threat to endangered animals (11). While
the main focus of this article has been risk to humans, nonhuman primates
are frequently more threatened by microorganisms indigenous to humans than
vice versa (2). TB, which is often fatal to nonhuman primates, represents a
serious threat to laboratory primate communities, which commonly are
infected by humans and can occasionally reinfect laboratory workers (66).
TB is prevalent in wild populations, as demonstrated by the presence in
wild olive baboons (Papio cynocephalus) of Mycobacterium bovis infection,
an infection that most likely originated from cattle (67).

Both hunting and forest encroachment threaten endangered primates and
increase the possibility of human and nonhuman infectious disease
emergence. Research on the pathogens of primates and humans on forest
boundaries helps assess risks to wild primates and to humans. In addition
to their value in the study of infectious disease and human evolution, many
primates are valuable natural resources in their home countries. The
veterinary expertise and wildlife management skills of conservation
organizations can both supplement the basic pathogen research and control
work of the public health community and benefit from it.

The examination of pathogen exchange in regions of host overlap may
identify social factors that influence pathogen emergence. Data on forest
use by human communities surrounding forest reserves and levels of
crop-raiding by nonhuman primates have been collected as part of ongoing
conservation projects. A comparison of these data with human and nonhuman
primate pathogen prevalence may provide a measure of forest-oriented
behavioral risks. Further research comparing infection rates among hunters
and nonhunters could confirm the findings and determine the role of
behavioral control measures to decrease risk.

Much remains to be done. Recent evidence has suggested that some wild
primates self-medicate with plants in their environment (68). An
understanding of the underlying wildlife epidemiology, therefore, combined
with long-term dietary data and analysis of plant chemistry, may lead to
new chemotherapeutic drugs (69). In addition, research on the dynamics of
primate pathogens in their natural hosts may elucidate novel host
resistance mechanisms. In particular, evidence of impaired host survival
and reproduction, as well as long-term host-parasite association, may point
to hosts that are likely to have evolved genetically mediated resistance.
Such resistance mechanisms in humans (70) have begun to play an
increasingly important role in vaccine and drug development (71,72). While
the findings from captive primate studies have played an important role in
medicine in the 20th century, this period has also been marked by a notable
absence of research on the basic ecology of disease systems. Perhaps by
learning from primates in their natural environments we may better prepare
ourselves for the disease threats to humans and wildlife populations in the
coming century.

Acknowledgments

We thank Adria Tassy Prosser and Daniel G. Colley for valuable suggestions
and Mary Bartlett for editorial assistance. Nathan Wolfe is supported by a
Taplin Graduate Fellowship and a National Science Foundation-Predoctoral
Fellowship. Ananias A. Escalante is supported by the ASM/NCID Postdoctoral
Research Associates Program.

Nathan Wolfe is a doctoral candidate in the Department of Immunology and
Infectious Disease at the Harvard School of Public Health. Mr. Wolfe has
conducted research on self-medicating behavior among chimpanzees and
mountain gorillas in Uganda and is collaborating with Drs. Altaf Lal and
Ananias Escalante on malaria evolution research.

Address for correspondence: Altaf A. Lal, Centers for Disease Control and
Prevention, Mail Stop F12, 4770 Buford Hwy, Chamblee, Georgia 30341, USA;
fax: 770-488-4454; e-mail: aal1@cdc.gov.

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Emerging Infectious Diseases
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Centers for Disease Control and Prevention
Atlanta, GA

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