Synopses Flea-borne Rickettsioses: Ecologic Considerations Abdu F. Azad, Suzana Radulovic, James A. Higgins, B. H. Noden, and Jill M. Troyer University of Maryland School of Medicine, Baltimore, Maryland, USA Ecologic and economic factors, as well as changes in human behavior, have resulted in the emergence of new and the reemergence of existing but forgotten infectious diseases during the past 20 years. Flea-borne disease organisms (e.g., Yersinia pestis, Rickettsia typhi, R. felis, and Bartonella henselae) are widely distributed throughout the world in endemic-disease foci, where components of the enzootic cycle are present. However, flea-borne diseases could reemerge in epidemic form because of changes in vector-host ecology due to environmental and human behavior modification. The changing ecology of murine typhus in southern California and Texas over the past 30 years is a good example of urban and suburban expansion affecting infectious disease outbreaks. In these areas, the classic rat-flea-rat cycle of R. typhi has been replaced by a peridomestic animal cycle involving, e.g., free-ranging cats, dogs, and opossums and their fleas. In addition to the vector-host components of the murine typhus cycle, we have uncovered a second typhuslike rickettsia, R. felis. This agent was identified from the blood of a hospitalized febrile patient and from opossums and their fleas. We reviewed the ecology of R. typhi and R. felis and present recent data relevant to the vector biology, immunology, and molecular characterization and phylogeny of flea-borne rickettsioses. A complex matrix of ecologic and economic and environmental modifications affecting factors and human behavior changes has resulted infectious disease outbreaks. In suburban areas, in the emergence of new infectious diseases vector fleas are most often associated with during the past 20 years. Ecologic changes lead to human habitation through their natural hosts, the emergence of both known and as yet unknown e.g., commensal rodents and peridomestic animals, pathogens circulating in the complex host and such as free-ranging cats and dogs, opossums, vector systems of undisturbed habitats. A drastic raccoons, and squirrels. Fleas commonly found increase of Rocky Mountain spotted fever in the on these animals are picked up by household pets late 1970s, Lyme disease in the early 1980s, and and brought into homes. These fleas, apart from ehrlichioses in the 1990s in the United States being a nuisance, may carry pathogenic orga- attests to the strong correlation of these diseases nisms of concern to human health. to human-made ecologic changes and further Of the 2,000 species and subspecies of fleas, illustrates the inability of existing monitoring only a handful serve as vectors of human systems to predict outbreaks and protect at-risk diseases. Several bacterial pathogens of public populations. Unmanaged growth and expansion health importance are maintained and trans- of the suburbs into undisturbed habitats have mitted by fleas, among them, Yersinia pestis, the generated ideal ecosystems for many displaced causative agent of plague (known in history as animals. The changing ecology of murine typhus black death). Flea-borne human pathogens are in southern California and Texas over the past 30 maintained in a zoonotic cycle involving mam- years is a good example of suburban expansion malian hosts and fleas. They seldom cause overt disease in their natural hosts but commonly result in clinical disease, e.g., plague, murine Address for correspondence: Abdu F. Azad, Department of Microbiology and Immunology, University of Maryland School typhus, and cat-scratch disease, in humans. The of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201 rapid spread of pathogens to human populations USA; fax: 410-706-0282; e-mail: [email protected]. is due to the frequent feeding behavior and Vol. 3, No. 3, July–September 1997 319 Emerging Infectious Diseases Synopses extraordinary mobility of fleas. Flea-borne diseases Rekindled interest in this disease is partially a are widely distributed throughout the world, in result of field data and epidemiologic surveys, the form of endemic foci, where components of the which have prompted a reconsideration of cycle are present; however, these diseases established components of the vector-reservoir become epidemic in human populations when cycle and their interaction with humans (5-7). infected mammalian hosts die and their fleas The classic cycle of R. typhi, the etiologic agent of leave in search of a bloodmeal. Of flea-borne murine typhus, involves rats (Rattus rattus and bacterial pathogens (e.g., Y. pestis, Rickettsia R. norvegicus) and the rat flea, Xensopsylla typhi, R. felis, and Bartonella henselae), the most cheopis (Figure 1). The flea has been considered studied and reviewed is Y. pestis. In this article, the main vector, and the disease is transmitted however, we want to examine the agents of flea- by flea bites or contact with rickettsia-containing borne rickettsioses, namely R. typhi and the feces and tissues during or after blood feeding. newly identified R. felis. Beginning with R. typhi Although the rat-flea-rat cycle is still the major ecology, we will review and discuss recent data route of human infection throughout the world, relevant to the ecology, vector biology, im- murine typhus exists in some endemic-disease munologic and molecular characterization, and foci where both rats and rat fleas are absent. phylogeny of the flea-borne rickettsiae. Reported cases of murine typhus in the United States are focused largely in central and Natural History of southcentral Texas and the Los Angeles and Flea-borne Rickettsioses Orange Counties in California; however, infected “Murine typhus is a good example of a disease rats and their fleas are hard to document in these whose importance is not adequately appreciated— areas (5-7). Thirty-three cases of locally acquired except by the patient, and, even today, in most murine typhus in Los Angeles County have been parts of the world, he will never know what ails him because the diagnosis will not be made” (1). Murine typhus is one of the most widely distributed arthropod-borne infections endemic in many coastal areas and ports through- out the world. It occurs in epidemics or with high prevalence; is often unrecog- nized and substantially underreported; and, although it can be clinically mild, it can also cause severe illness and death (2,3). The severity of murine typhus infection has been associated with old age, delayed diagnosis, hepatic and renal dysfunction, central nervous system abnormalities, and pulmonary compromise. Death occurs in up to 4% of hospitalized patients (3). Thousands of human cases were reported annually in the United States (1,2). Outbreaks have been reported in Australia and recently in China, Greece, Israel, Kuwait, and Thailand (1,2,4). Recent serosurveys have demonstrated high prevalence of anti-typhus group (TG) rickettsiae in Asia and southern Europe (4). Despite the current level of reported human cases in the United States of fewer than 100 per year, murine typhus has been the Figure 1. Urban and suburban life cycles of Rickettsia and subject of several recent studies (3,4). mammalian hosts. Emerging Infectious Diseases 320 Vol. 3, No. 3, July–September 1997 Synopses associated with seropositive domestic cats and within the Los Angeles murine typhus focus opossums (7). More than 16 (40%) of 38 opossums stimulated further interest (8,10). To understand and nine (90%) of 10 domestic cats collected from the potential role of the R. felis and nonrat hosts the case areas were seropositive for R. typhi in the biology of endemic typhus, we examined antibodies. No seropositive cats (n=21) or opos- the samples collected in southern Texas, a region sums (n=36) were found in the control areas. accounting for approximately one-third of the Although flea infection was not investigated, current reported murine typhus cases in the opossums were the most heavily infested with United States. Restriction digests of polymerase the cat flea, Ctencephalides felis (104.7/animal). chain reaction (PCR) products from 399 cat fleas C. felis was also the most prevalent flea species collected from nine opossums had an infection (97%) collected from opossums, cats, and dogs rate of 3.8% for R. felis and 0.8% for R. typhi. (but not rats) in southern Texas. Surveys in other Three of nine tested opossums were infected with areas of the country (7,8) had similar results, which R. felis (8,10). No R. typhi-infected rats (R. nor- further minimizes the role of rat fleas in the vegicus) or rat fleas (X. cheopis) were found in maintenance of endemic typhus within the United surveyed samples. The persistence of murine States. The maintenance of R. typhi in the cat flea/ typhus in both geographic foci appears to be better opossum cycle (Figure 1) is, therefore, of potential accounted for by infected cat fleas, opossums, and public health importance since C. felis is a wide- other nonrat hosts found near human populations spread pest that avidly bites humans (1,3,8-11). (Figure 1, Table 1). The presence of both R. typhi During the past 3 years, we have investigated and R. felis by PCR/restriction fragment length a new typhuslike rickettsia (initially designated polymorphism (RFLP) in opossums from murine as ELB and later named R. felis) identified in cat typhus foci in southern California and Texas thus fleas and opossums from California and Texas murine confirms the possible role of this marsupial in the typhus foci (8-12). Both R. typhi and R. felis were maintenance of murine typhus infection. However, found in fleas and in opossum tissues (8-11). our attempt to isolate either R. felis or R. typhi Additionally, a retrospective investigation of five from PCR-positive opossum blood or spleen murine typhus patients from Texas subse- collected in North Carolina, Texas, and California quently demonstrated that four patients were proved unsuccessful.