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

Perspectives

Rickettsial Pathogens and Their Arthropod Vectors

Abdu F. Azad* and Charles B. Beard
*University of Maryland School of Medicine, Baltimore, Maryland, USA; and
Centers for Disease Control and Prevention, Atlanta, Georgia, USA

---------------------------------------------------------------------------
      Rickettsial diseases, important causes of illness and death
      worldwide, exist primarily in endemic and enzootic foci that
      occasionally give rise to sporadic or seasonal outbreaks.
      Rickettsial pathogens are highly specialized for obligate
      intracellular survival in both the vertebrate host and the
      invertebrate vector. While studies often focus primarily on the
      vertebrate host, the arthropod vector is often more important
      in the natural maintenance of the pathogen. Consequently,
      coevolution of rickettsiae with arthropods is responsible for
      many features of the host-pathogen relationship that are unique
      among arthropod-borne diseases, including efficient pathogen
      replication, long-term maintenance of infection, and
      transstadial and transovarial transmission. This article
      examines the common features of the host-pathogen relationship
      and of the arthropod vectors of the typhus and spotted fever
      group rickettsiae.

Rickettsial diseases, widely distributed throughout the world in endemic
foci with sporadic and often seasonal outbreaks, from time to time have
reemerged in epidemic form in human populations. Throughout history,
epidemics of louse-borne typhus have caused more deaths than all the wars
combined (1). The ongoing outbreak of this disease in refugee camps in
Burundi involving more than 30,000 human cases is a reminder that
rickettsial diseases can reemerge in epidemic form as a result of the
catastrophic breakdown of social conditions (2). In addition to explosive
epidemics, sporadic but limited outbreaks of louse-borne typhus and other
rickettsial diseases have been reported throughout the world. In the United
States, a drastic increase of murine typhus in the 1940s, Rocky Mountain
spotted fever (RMSF) in the late 1970s, and the human ehrlichioses in the
1990s attests to the potential emergence of these infections in populations
at risk (3).

The rickettsiae's obligate intracellular existence in both mammalian and
arthropod hosts serves as an excellent model for the study of complex
host-parasite interactions. Rickettsial associations with obligate
blood-sucking arthropods represent the highly adapted end-product of eons
of biologic evolution. The ecologic separation and reduced selective
pressure due to these associations may explain rickettsial genetic
conservation. Their intimate relationships with vector hosts (Table 1) are
characterized by efficient multiplication, long-term maintenance,
transstadial and transovarial transmission, and extensive geographic and
ecologic distribution. Although rickettsiae have a symbiotic relationship
with their arthropod hosts, in some instances, they act as true
parasites-for example, members of the Wolbachia and Orientia tsutsugamushi
alter reproduction and manipulate cellular processes in their arthropod
hosts (4), and the agent of epidemic typhus, Rickettsia prowazekii, kills
its vector, the human body louse (5).

Although rickettsiae are maintained in nature through arthropod vectors,
they frequently infect vertebrates, which in turn allow new lines of
vectors to acquire infection from the rickettsemic hosts. The involvement
of vertebrates, including humans, in the rickettsial cycle is variable and
in some cases complicated (Figure). With the exception of epidemic typhus,
humans are not essential in the rickettsial cycle. Humans acquire
rickettsial infection from the infected vectors. While tick-borne
rickettsiae are transmitted to humans by tick salivary secretions, flea-
and louse-borne rickettsiae are transmitted to humans through contamination
of broken skin and mucosal surfaces by infected vector feces.

Table 1. Epidemiologic features of the pathogenic rickettsiae(sup a)
--------------------------------------------------------------------------------

Rickettsia                        Natural cycle(sup b)     Geographic
species             Disease       Vectors      Hosts      distribution
--------------------------------------------------------------------------------
Typhus group:
Rickettsia    Epidemic typhus     Human     Humans       Worldwide
prowazekii                        body lice
              Recrudescent typhus None      Humans       Worldwide
                                  Lice,     Flying       Eastern USA
                                  fleas     squirrels
R. typhi      Murine typhus       Fleas     Rodents      Worldwide
                                  Fleas     Opossums     USA
R. felis      Murine typhuslike   Fleas     Opossums     USA
Spotted Fever group:
R. rickettsii Rocky Mountain      Ticks     Small        North & South
              spotted fever                 mammals,     America
                                            dogs,
                                            rabbits,
                                            birds
R. conorii    Boutonneuse fever   Ticks     Rodents,     Africa,
                                            dogs         Southern
                                                         Europe, India
R. sibirica   North Asia tick     Ticks     Rodents      Eurasia, Asia
              typhus
R. japonica   Japanese spotted    Ticks     Rodents,     Japan
              fever                         dogs
R. australis  Queensland tick     Ticks     Rodents      Australia
              typhus
R. akari      Rickettsialpox      Mites     House mice,  Worldwide
                                            rats
Ehrlichioses group:
Ehrlichia     Human monocytic     Ticks     Humans, deer USA, Europe
chaffeensis   ehrlichiosis
Ehrlichia Sp  Human granulocytic  Ticks     Humans,      USA, Europe
              ehrlichiosis                  deer,
                                            rodents
Others:
Coxiella      Q fever             Ticks     Small        Worldwide
burnetii                                    mammals,
                                            sheep,
                                            goats,
                                            cattle, dogs
Orientia      Scrub typhus        Mites     Rodents      Asia, Indian
tsutsugamushi                                            subcontinent,
                                                         Australia
--------------------------------------------------------------------------------
(sup a)Not listed are R. helvetica, R. honei, and R. slovaca (6).
*sup b)Evidence for arthropod serving as a vector or vertebrate serving as a host is based on the rickettsial isolation from field-collected specimens,
experimental studies, and indirect evidence for rickettsial presence or
exposure to rickettsiae (hemolymph test and serosurveys).

Although rickettsiae have common      
features with their vertebrate and    
invertebrate hosts, they differ       [fig]
considerably in terms of arthropod    Figure. Composite diagram of the
vectors, geographic distribution, and life cycle of Rocky Mountain spotted
virulence (Table 1). In this article, fever, rickettsialpox, and murine
we focus on the members of the typhus typhus. A. Life cycle of Rickettsia
group (TG) and spotted fever group    rickettsii in its tick and mammalian
(SFG) rickettsiae to construct a      hosts (7); B. Rickettsia akari life
conceptual framework of the natural   cycle; and C. Rickettsia typhi life
history of human rickettsioses and    cycle.
evaluate feeding behavior of the
vectors with regard to rickettsial
maintenance and transmission.

Tick-borne Rickettsial Pathogens

The development and extensive use of the hemolymph test (which has been
fundamental to tick and rickettsial surveys), improved isolation methods,
and the application of molecular techniques have helped identify 14 valid,
relatively distinct SFG rickettsiae (Tables 1, 2). Except for mite-borne R.
akari, all SFG rickettsiae are transmitted by ixodid ticks (Tables 1, 2).
In addition to R. rickettsii, the etiologic agent of RMSF, eight other
tick-borne rickettsial species are human pathogens (Table 1; 6). The
remaining SFG rickettsiae are isolated only from ticks and have low or no
pathogenicity to humans or certain laboratory animals (7). However, some of
these rickettsiae could be etiologic agents of as-yet-undiscovered, less
severe rickettsioses.

Distribution of SFG rickettsiae is limited to that of their tick vectors.
In the United States, a high prevalence of SFG species in ticks cannot be
explained without the extensive contributions of transovarial transmission.
The transovarial and transstadial passage of SFG rickettsiae within tick
vectors in nature ensures rickettsial survival without requiring the
complexity inherent in an obligate multihost reservoir system. Although
many genera and species of ixodid ticks are naturally infected with
rickettsiae, Dermacentor andersoni and D. variabilis are the major vectors
of R. rickettsii. SFG infection rates vary considerably by state. For
example, the infection rate for adult D. variabilis collected from
vegetation and mammalian hosts was 2% to 9% in Connecticut, 5% in New York,
6% in Kentucky-Tennessee and Maryland, 8.8% in Arkansas, and 10% in Alabama
(5,8,9). Rickettsia and tick surveys indicate that R. rickettsii is less
prevalent in vector ticks than some other SFG rickettsiae. In most cases,
the SFG-positive ticks, including D. andersoni and D. variabilis, are
infected with nonpathogenic rickettsiae rather than with R. rickettsii
(Table 2). The low prevalence of R. rickettsii in SFG-positive ticks is
intriguing. Interspecific competition among ticks may result in stable
maintenance of SFG rickettsiae through transovarial transmission and may
cause the gradual replacement of R. rickettsii in the tick population. Very
little is known about the process of interspecific competition between
prokaryotic microorganisms in ticks. Burgdorfer et al. (10) reported that
D. andersoni from the east side of Bitterroot Valley in western Montana
contained a nonpathogenic SFG-rickettsia, which they named East Side agent.
East Side agent has recently been described as a new species, R. peacockii
(11). This rickettsia is rarely present in tick hemolymph and is readily
missed by the standard hemolymph test. The rickettsiae are confined
primarily to the tick posterior diverticulae of the midgut, the small
intestine, and most importantly, the ovaries. R. peacockii is maintained in
the tick population through transovarial transmission, and the infected
ticks were shown to be refractory to ovarian infection with R. rickettsii.
However, these ticks acquired experimental infection with R. rickettsii and
transmitted rickettsiae horizontally (10,11). Thus, ticks constitutively
infected with R. peacockii and infected experimentally with R. rickettsii
were unable to transmit R. rickettsii to their progeny. In effect,
infection of D. andersoni with R. peacockii blocked the subsequent ability
of the ticks to transmit R. rickettsii transovarially (10,11). The
phenomenon of transovarial interference provided an explanation for the
curious long-standing disease focus in Bitterroot Valley. Most cases of
RMSF have occurred among residents on the west side of the valley where D.
andersoni were abundant; on the east side, D. andersoni were also abundant
and were reported to feed on residents, yet few (if any) locally acquired
cases of RMSF occurred there (8,10). In the presence of R. peacockii, R.
rickettsii could not be maintained transovarially-it could only be
transmitted horizontally, and thus long-term maintenance could not be
sustained. Transovarial interference by tick-associated symbionts such as
R. peacockii is unlikely to be confined only to D. andersoni ticks on the
east side of Bitterroot Valley, Montana. Burgdorfer et al. (10) stated that
transovarial interference of R. rickettsii in D. andersoni ticks may be
mediated by other nonpathogenic SFG rickettsiae-R. montana and R.
rhiphicephali. Tick surveys for SFG rickettsiae generally report finding R.
rickettsii only in a minority of ticks with rickettsiae (Table 3). Most
infected ticks harbor nonpathogenic species. Thus, transovarial
interference may have epidemiologic significance: it may explain why ticks
collected from various geographic regions are not infected with two or more
species of SFG rickettsiae.

Table 2. Epidemiologic characteristics of the North American tick-borne
rickettsia(sup a)
---------------------------------------------------------------------------
                                                Natural cycle
Rickettsia                         ----------------------------------------
species           Disease          Vectors                   Hosts
---------------------------------------------------------------------------
Rickettsia        Rocky Mountain   Dermacentor, Amblyomma,   Small mammals,
rickettsii        spotted fever    Rhipicephalus,            dogs, rabbits,
                                   Haemaphysalis             birds
R. akari          Rickettsialpox   Liponyssoides             House mice,
                                                             rats
R. amblyommii                      R. amblyommii A.          Small mammals
                                   americanum Small mammals
R. bellii                          D. andersoni, D.          Rodents, dogs
                                   variabilis,
                                   D. occidentalis, D.
                                   albopictus,
                                   H. leporispalustris
R. canada                          Haemaphysalis             Rabbits,
                                                             hares, birds
R. montana                         D. andersoni, D.          Rodents, dogs
                                   variabilis
R. parkeri                         A. americanum, A.         Domestic
                                   maculatum                 animals,
                                                             birds, rodents
R. peacockii                       D. andersoni              Rodents, deer
R. rhipicephali                    R. sanguineus, D.         Small mammals
                                   andersoni,
                                   D. variabilis, D.
                                   occidentalis
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(sup a)Excluding four as yet undescribed species of SFG rickettsiae (WB-8-2,
364-D, Tillamook, and the D. parumapertus agent).



Table 3. Species composition of tick-borne rickettsiae isolated from
hemolymph-positive Dermacentor ticks(sup a)

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            California     Montana       Ohio      Long Island   Maryland
         D.occidentalis D.andersoni  D.variabilis D.variabilis D.variabilis 
Rickettsial (No.            (No.        (No.      (No.            (No.
 sp         isolates)      isolates)    isolates) isolates)       isolates) 
---------------------------------------------------------------------------
R. rickettsii 0 (0)         9 (10)     18 (4)      0 (0)         8 (2)
R.
rhipicephali  96 (79)       44 (47)    0 (0)       0 (0)         0 (0)
R. montana    -             7 (8)      59 (13)     100 (100)     0 (0)
Other 
SFG(sup b)    -             -          5 (1)(sup c) -           88 (23)(sup d)
R. bellii     4 (3)         39 (41)    18 (4)      0 (0)         4 (1)
Total number
isolates      82            106        22          100          26
---------------------------------------------------------------------------
(sup a)Shows a compilation of various statewide surveys, comparing the species
composition of SFG rickettsiae in Dermacentor spp. ticks that tested
positive by immunofluorescence assay.
(sup b)SFG, spotted fever group.
(sup c)R. amblyommii.
(sup d)Mouse anti-sera made against Maryland isolates reacted with WB-8-2
(unnamed SFG rickettsiae).

The tick-rickettsia interrelationships are complex, and the mechanisms used
by rickettsiae to survive in unfed overwintering ticks or during molting
are poorly understood. How changes (e.g., before and after blood meal) in
tick gut physiology influence rickettsial growth, cell division, and
differential expression of rickettsial surface protein is not well
understood. Although experiments (8,10) have deciphered the phenomenon of
reactivation of rickettsial virulence after infected ticks take a blood
meal, the underlying molecular events have yet to be elucidated. Other
aspects of rickettsia-tick interactions need to be studied. For example,
after feeding, a tick larva enters a quiescent period before emerging as a
questing nymph the following year. How rickettsiae survive within the tick
during this quiescent period and regain infectivity during the nymphal
feeding is poorly understood. Although the precise mechanisms of
rickettsial reactivation are not known, temperature shift and blood intake
are believed to reactivate rickettsiae. As in the Borrelia
burgdorferi-Ixodes scapularis model, transmission of rickettsiae probably
cannot occur until after 24 hours of tick attachment, which allows time for
rickettsial growth.

Insect-Borne Rickettsial Pathogens

Unlike SFG, TG rickettsiae are associated with insects (Table 1). Their
association with blood-sucking insects such as human body lice (Pediculus
humanus) and fleas (Xenopsylla cheopis and other rodent fleas [13-15])
provides rickettsiae the potential to spread rapidly among susceptible
populations. Both fleas and human body lice, intermittent feeders, are
capable of multiple feeding and thus of transmitting rickettsiae to several
hosts. Outbreaks of epidemic typhus thereby can result from rapid
transmission of R. prowazekii from human to human by infected lice. Unlike
ticks that transmit SFG rickettsiae, lice infected with R. prowazekii die
within 2 weeks after imbibing infected blood. R. typhi, the etiologic agent
of murine typhus, does not shorten the life span of fleas (15). Although R.
typhi and R. felis are maintained transovarially in fleas (15-18), there is
no evidence that R. prowazekii is maintained in human body lice vertically.
Since lice die of R. prowazekii infection, the role of the reservoir in
maintaining the rickettsiae in nature becomes essential. R. prowazekii
sequesters in its human host; persistence of rickettsiae occurs despite the
strong, long-lasting immunity after infection with R. prowazekii. Patients
with recrudescent typhus (Brill-Zinsser disease) serve as potential
reservoirs capable of infecting lice. Although a search for a zoonotic
cycle of R. prowazekii in areas with louse-borne typhus epidemics (e.g.,
Ethiopia and Burundi) proved to be unsuccessful, flying squirrels
(Glaucomys volans) in the eastern United States are naturally infected with
this organism. Flying squirrel ectoparasites (lice and fleas) were
implicated in the transmission of R. prowazekii between the squirrels and
from squirrels to humans (5). Although the distribution of G. volans
extends to the entire eastern United States as well as to isolated areas of
Mexico and Guatemala, the search for an extrareservoir of R. prowazekii was
not pursued further. Consequently, the importance of the R. prowazekii and
squirrel system remains unclear. In the absence of a zoonotic cycle,
conditions such as widespread lice infestations, active human infection,
reactivation of latent infection in patients with recrudescent typhus could
easily ignite a resurgence of louse-borne typhus. Louse-borne typhus
continues to occur in epidemics following the breakdown of social,
economic, or political systems, as exemplified by recent outbreaks in
Burundi and remote parts of South America. Therefore, active surveillance
to monitor louse-borne typhus and prevent its spread is indicated.

In contrast to louse-borne typhus, murine typhus is prevalent throughout
the world and accounts for widespread illness in areas infested with many
rats and fleas. Murine typhus occurs in epidemics or has a high prevalence,
is often unrecognized and substantially underreported, and although it may
be clinically mild, can cause severe and even fatal cases (19). Thousands
of human cases used to occur annually in the United States (13,14).
Outbreaks have been reported in Australia and recently in China, Kuwait,
and Thailand (13,15). The classic cycle of R. typhi involves rats (Rattus
rattus and R. norvegicus) and primarily the rat flea, X. cheopis (13,14).
X. cheopis is the main vector, and transmission is affected by contact with
rickettsia-containing flea feces or tissue during or after blood feeding.
Reported cases of murine typhus in the United States are from south and
central Texas and the Los Angeles and Orange County area of California
(21-25). However, most of the cases are attributed to opossum-cat flea
cycles. Both opossums and domestic cats collected from the case areas were
seropositive for R. typhi antibodies. The cat flea, Ctencephalides felis,
which is a competent vector of murine typhus, is the most prevalent flea
species (97%) collected from opossums, cats, and dogs in southern Texas; no
fleas were recovered from rats in this area. In addition to R. typhi, R.
felis was also found in opossums and their fleas (15). This finding,
consistent with surveys in other areas of the country (14,20), further
documents the reduced role of rat and X. cheopis in the maintenance of
murine typhus within endemic-disease areas of the United States. The
maintenance of R. typhi in the cat flea and opossum cycle is therefore of
potential public health importance since C. felis is a prevalent and
widespread pest that avidly bites humans (12,15).

In many parts of the world, murine typhus infection is intimately
associated with introduced commensal rodents (R. rattus, R. norvegicus, and
Mus musculus) and their ectoparasites, particularly fleas. Although R.
typhi have been isolated from other commensal rodents and even shrews, they
do not seem to play a role in the transmission of murine typhus to humans
(13,14). In Rangoon (Myanmar), of four species of murines and one shrew
commonly found in buildings, 7% (M. musculus) to 30% (R. rattus) and 38%
(Bandicota bengalensis) of those tested were seropositive to R. typhi. In
contrast, 62% of R. rattus collected from buildings in Addis Ababa
(Ethiopia) and 49% of those collected in Sarawak (Nepal) were seropositive
for murine typhus (Azad et al., unpub. data). Infection rates in X. cheopis
fleas collected from rats were 7% to 18%. While infection rates vary
considerably among indoor rats and their fleas, murine typhus infection
seems clearly associated with indoor rat populations throughout the world.
However, in the absence of indoor rats, murine typhus infection is
maintained in suburban and rural cycles when native animals seek shelter in
human habitations where food and hospitable environments are plentiful.

Pathogen-Arthropod Interaction

The process of displacement of pathogenic rickettsiae with nonpathogenic
endosymbionts in ticks through transovarial interference is of potential
epidemiologic importance. The displacement might occur only if transovarial
maintenance of pathogenic rickettsiae harms the host or the maintenance of
nonpathogenic organisms confers important advantages to the tick progeny.
Burgdorfer et al. (10), in experimental studies with the D. andersoni-R.
rickettsii model, observed that maintenance of this pathogen in ticks over
several generations resulted in unusually high death rates among engorged
females and reduced numbers and fertility of deposited eggs. If tick
infection with pathogenic rickettsiae in nature adversely affected egg
maturation, oviposition, and embryogenesis, the balance would favor a tick
population infected with the nonpathogenic rickettsiae, and over time such
tick populations would displace those infected with R. rickettsii. Also,
ticks infected experimentally with R. montana and R. rhipicephali could not
maintain R. rickettsii through transovarial transmission, which suggests an
interference phenomenon. Such a precedent exists-several tick species carry
nonpathogenic rickettsiae (e.g., D. andersoni in east side Bitterroot
Valley of western Montana, A. americanum in Maryland) frequently
encountered in tick samples from different parts of the United States
(8,9).

Recent work in our laboratory with TG rickettsiae suggests that
interspecific competition between closely related rickettsiae may control
rickettsial establishment in arthropods. Studies have identified both R.
typhi and R. felis in opossums and in their cat fleas in endemic-disease
regions in Texas and California (21-25). However, infection with both
rickettsiae has not been observed in individual fleas (20-24). The
intermittent feeding behavior of cat fleas associates them with various
hosts, which increases the likelihood of infection with more than one
pathogenic organism. Cat fleas constitutively infected with R. felis and
experimentally infected with R. typhi contained both rickettsial species.
While the R. felis infection rate in the infected flea population was 86%
to 94%, prevalence of dually infected fleas was 13% and 26% (25). While no
other relationships involving multiple bacterial infections in arthropods
have been studied as thoroughly, the results from the few available studies
show that dual infections in arthropod vectors are rare (e.g., human
granulocytic ehrlichia was recently identified in 2.2% and 4% of I.
scapularis ticks coinfected with B. burgdorferi) (26).

Whether infection with nonpathogenic rickettsiae presents an advantage to
the tick population is difficult to ascertain because of lack of
experimental data. There is no experimental evidence for
rickettsial-induced postzygotic reproductive incompatibility,
parthenogenesis, and feminization of genetic males as observed for members
of the genus Wolbachia (4,27). Although a rickettsial relative is
associated with male killing in the ladybird beetle (27), we do not know
whether any nonpathogenic members of the SFG rickettsiae can induce
reproductive incompatibility or sex distortion in ticks. A compilation of
data from various laboratories that maintain cat flea colonies indicate
that after several generations R. felis infection in fleas approaches 100%
(28). Whether the high infection rate is the result of selection through
reproductive incompatibility remains to be elucidated. Flea samples from
opossums, cats, and dogs in different parts of the United States were
infected with R. felis. Since it is maintained transovarially, R. felis
could be used as a marker to follow changes in the infection rates over
time.

Several questions remain: 1) why does infection with nonpathogenic
rickettsiae prevent establishment of virulent species in the ovaries of
infected ticks; 2) what are the molecular bases for transovarial
interference; 3) are nonpathogenic rickettsiae selected favorably by their
arthropod hosts through reproductive incompatibility; and 4) why are
nonpathogenic rickettsiae found more often in ticks than a virulent
species.

Summary and Conclusions

Ixodid ticks, fleas, and lice are temporary obligate ectoparasites often
found on the same vertebrate hosts. They differ substantially with respect
to feeding behavior and digestion of blood meals (30), which can affect
rickettsiae transmission from vector to vertebrate hosts. While all stages
of ticks and lice are blood feeders, only adult fleas take blood from the
host. Fleas and lice feed intermittently and digest blood meals rapidly,
while ixodid ticks feed for several days and digest meals very slowly
(29,30). SFG rickettsiae are associated with ixodid ticks, while TG
rickettsiae are transmitted by fleas and lice. Efficient transovarial and
transstadial transmission of rickettsiae in ticks ensures rickettsial
survival while maintaining the genetic integrity of the SFG rickettsiae.
This mechanism also allows ticks to serve as reservoir host for SFG
rickettsiae. The SFG rickettsiae are transmitted by tick bites, whereas TG
rickettsiae are deposited with insect feces at the bite site. At each life
stage (larva, nymph, and adult), ticks feed only once; if undisturbed, they
transmit rickettsiae to a single host, whereas repeated feedings allow
fleas and lice to infect several hosts. Thus, vector feeding behavior
accounts for the observed differences in disease epidemiology and natural
history between tick- and insect-borne rickettsioses. Despite their strong
similarities, SFG and TG rickettsiae have major differences in terms of
growth, entry, and exit from host cells. Rickettsial characteristics
related to vector compatibility were discussed in a recent publication by
Hackstadt (31).

The molecular aspects of rickettsia-vector interactions are not well
understood largely because only a few laboratories have addressed the
mechanisms by which arthropods and rickettsiae interact. These
intracellular organisms have long been associated with arthropods, and yet
we know very little about their relationship with arthropod vectors.

This work was supported by grants R37 AI 17828 and R01 AI 43006 from the
National Institutes of Health.

Dr. Abdu Azad is professor of microbiology and immunology, University of
Maryland School of Medicine, Baltimore. His laboratory research focuses on
host parasite interactions with particular interest in the molecular
aspects of rickettsial pathogenesis.

Dr. Charles Ben Beard is research entomologist and chief, Vector Biology
Activity, Entomology Branch, Division of Parasitic Diseases, NCID, CDC.
Research in his laboratory focuses on the molecular biology of insect
disease vectors and the molecular epidemiology of opportunistic infections
in persons with AIDS.

Address for correspondence: Abdu F. Azad, Department of Microbiology and
Immunology, University of Maryland School of Medicine, 655 W. Baltimore
Street, Baltimore, MD 21201 USA; fax: 410-706-0282; e-mail:
aazad@umaryland.edu.

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

URL: http://www.cdc.gov/ncidod/EID/vol4no2/azad.htm

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