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Fleas and flea-borne diseases

Open ArchivePublished:March 02, 2010DOI:https://doi.org/10.1016/j.ijid.2009.11.011

      Summary

      Flea-borne infections are emerging or re-emerging throughout the world, and their incidence is on the rise. Furthermore, their distribution and that of their vectors is shifting and expanding. This publication reviews general flea biology and the distribution of the flea-borne diseases of public health importance throughout the world, their principal flea vectors, and the extent of their public health burden. Such an overall review is necessary to understand the importance of this group of infections and the resources that must be allocated to their control by public health authorities to ensure their timely diagnosis and treatment.

      Keywords

      Introduction

      The past decades have seen a dramatic change in the geographic and host ranges of many vector-borne pathogens, and their diseases. This process is often driven by climate change and the destruction of wild habitats. Fleas, as hosts for a wide range of largely understudied pathogens (except Yersinia pestis), are no exception, and flea-borne diseases may re-emerge in epidemic form. Examples of this are the changing ecology of murine typhus,
      • Azad A.F.
      • Radulovic S.
      • Higgins J.A.
      • Noden B.H.
      • Troyer J.M.
      Flea-borne rickettsioses: ecologic considerations.
      the finding of Rickettsia spp in new hosts,
      • Bechah Y.
      • Capo C.
      • Mege J.L.
      • Raoult D.
      Rickettsial diseases: from Rickettsia–arthropod relationships to pathophysiology and animal models.
      and the finding of fleas on new hosts or in geographical areas previously unreported in the literature.
      • de Carvalho R.W.
      • Serra-Freire N.M.
      • Linardi P.M.
      • de Almeida A.B.
      • da Costa J.N.
      Small rodents fleas from the bubonic plague focus located in the Serra dos Órgãos mountain range, State of Rio de Janeiro, Brazil.
      Therefore, it is timely to provide a concise review of flea biology, synanthropic fleas, and flea-borne diseases, presenting updated evidence on their evolutionary history, emergence, and re-emergence.

      Fleas and their biology

      Fleas (Insecta, Siphonaptera) are small, laterally flattened, wingless, and highly specialized insects. Fleas are of great importance as vectors of pathogens in many parts of the world. Both adult males and females are obligate hematophagous ectoparasites of mammals and birds. About 2574 species belonging to 16 families and 238 genera have been described, but only a minority is synanthropic, that is they live in close association with humans (Table 1).
      • Lewis R.E.
      Resume of the Siphonaptera (Insecta) of the World.
      • Lewis R.E.
      Notes on the geographical distribution and host preferences in the order Siphonaptera. Part 8. New taxa described between 1984 and 1990, with a current classification of the order.
      Table 1Siphonaptera families (from Lewis 1999, 1993
      • Lewis R.E.
      Resume of the Siphonaptera (Insecta) of the World.
      ,
      • Lewis R.E.
      Notes on the geographical distribution and host preferences in the order Siphonaptera. Part 8. New taxa described between 1984 and 1990, with a current classification of the order.
      )
      FamilyDistribution (region)GeneraSpeciesMajor host
      AncistropsyllidaeOriental13Ungulates
      CeratophyllidaeCosmopolitan but predominantly Holarctic44403Primarily rodents, occasionally viverrids, mustelids, birds, and a single species on an insectivore (Siberian mole)
      ChimaeropsyllidaeEthiopian826Rodents, insectivores, elephant shrews
      CoptopsyllidaePalearctic119Rodents (gerbils and their allies)
      CtenophthalmidaePrimarily Holarctic, some in southern hemisphere42548Rodents, occasionally pikas, insectivores (shrews and moles), marsupials, and a single species on mustelids
      HystrichopsyllidaeNearctic, Palearctic, Neotropical, Australian636Rodents, insectivores
      IschnopsyllidaeCosmopolitan20122Bats
      LeptopsyllidaePalearctic, Nearctic, Oriental, a few species in Australian or Ethiopian regions (Madagascar)29230Rodents, lagomorphs (hares, rabbits, pikas), insectivores, and rarely elephant shrews and foxes
      MalacopsyllidaeNeotropical22Edentales (armadillos)
      Pulicidae (includes tungid flea)Cosmopolitan27182Very broad host range, including carnivores, ungulates, bats, edentales (armadillos), and occasionally birds (Cariama spp).
      PygiopsyllidaeEthiopian, Oriental Australian, and one Neotropical genus37166Rodents, marsupials, insectivores, and occasionally monotremes, birds, or tree shrews
      RhopalopsyllidaeNeotropical, southern Nearctic, Oceanic10122Primarily rodents, some on oceanic seabirds
      StephanocircidaePrimarily Neotropical, two Australian species951Rodents, a few species on marsupials
      VermipsyllidaeHolarctic339Carnivores and ungulates
      XiphiopsyllidaeEthiopian18Rodents

      Morphology

      Adult fleas are strongly sclerotized, and ca. 2–10 mm in length. They have thin, flattened bodies and backward-directed spines on their legs and bodies that facilitate forward movement through fur, hair, or feathers and prevent them from being easily dislodged (Figure 1). Compound eyes are absent. Antennae are short, situated in lateral grooves, and are erectable in males, allowing the support of the female during copulation. Fleas have three thoracic segments, each sustaining a pair of legs. They have strongly developed hind legs that permit them to jump up to 150 times their own body length.
      • Guiguen C.
      • Beaucournu J.C.
      Présence de Pulex irritans (Siphonaptera) au Burundi, région à risque pesteux.
      • Beaucournu J.C.
      • Launay F.
      Les puces (Siphonaptera) de France et du bassin méditerranéen occidental.
      This behavior is possible due to resilin, an elastomeric protein, which is compressed during the flexion of the coxa in the metathorax, and then rapidly relaxed. Larval morphology is inconspicuous, and newly hatched flea larvae are slender, white, segmented, and worm-like. They are sparsely covered with short hairs and are 1–2 mm in length (first instar) or 4–5 mm length (second instar). Some have an egg-tooth, which is used to cut their way out of the egg.
      • Rothschild M.
      Recent advances in our knowledge of the order Siphonaptera.
      Flea eggs are pearly white, oval with rounded ends, and approximately 0.5 mm long.
      • Beaucournu J.C.
      • Launay F.
      Les puces (Siphonaptera) de France et du bassin méditerranéen occidental.
      Figure thumbnail gr1
      Figure 1Morphology of the cat flea Ctenocephalides felis; male (top) and female (bottom).

      Life cycle

      As holometabolous insects, fleas complete a cycle from egg to adult through several larval stages and a pupal stage. The completion of the entire life cycle from egg to adult emergence varies significantly among species, and details are mostly known from synanthropic flea species. Xenopsylla cheopis for instance takes between nine and 15 days for its full development, but may take much longer depending on conditions.
      • Marshall A.
      Ecology of ectoparasitic insects.

      Egg

      Once on a host, adult fleas take a blood meal and mate. Generally, a blood meal is required to complete ovary development in female fleas.
      • Vashenok V.S.
      Fleas: vectors of pathogens causing diseases in humans and animals (In Russian).
      The female then begins laying eggs in the fur or the surroundings of the host. Thus, flea eggs may be deposited in all those places to which domestic animals have access. Female life time fecundity varies among species, and depending on ecological parameters. Some species only produce a low number of eggs (e.g., X. cheopis (rat flea)), whereas others are rather prolific (e.g., Tunga penetrans (chigoe flea)).
      • Samarina G.P.
      • Alekseev A.N.
      • Shiranovich P.I.
      A study of fecundity of rat fleas (Xenopsylla cheopis Rothschild and Ceratophyllus fasciatus Bosc) when fed on different host species.
      • Barnes A.M.
      • Radovsky F.J.
      A new Tunga (Siphonaptera) from the Nearctic region with description of all stages.
      • Silverman J.
      • Rust M.K.
      Extended longevity of the pre-emerged adult cat flea (Siphonaptera: Pulicidae) and factors stimulating emergence from the pupal cocoon.
      Eggs may hatch in one to 10 days, depending on temperature and humidity.
      • Rothschild M.
      Recent advances in our knowledge of the order Siphonaptera.
      Due to their spherical or oval shape, they roll into cracks and crevices on the floor or in or near nests and bedding.

      Larvae

      Larvae lack legs or eyes or other conspicuous morphological characteristics, but possess biting mouthparts. They pass through three stages (instars) of varying duration, depending on the availability of food, relative humidity, and other environmental factors.
      • Silverman J.
      • Rust M.K.
      Extended longevity of the pre-emerged adult cat flea (Siphonaptera: Pulicidae) and factors stimulating emergence from the pupal cocoon.
      Larvae are free moving and survive by feeding on organic debris found in their environment. Some are also known to feed on flea feces, which may be essential for successful development.
      • Rothschild M.
      Recent advances in our knowledge of the order Siphonaptera.
      Since larvae are negatively phototactic (avoid light) and positively geotropic (prefer to move downward as a response to gravity),
      • Sgonina K.
      Die Reizphysiologie des Igelflohs (Archeopsylla erinacei Bouché) und seiner Larve.
      they are found deep in carpet fibers, mattresses or couch stuffing materials, and organic debris (branches, leaves, etc.). They accumulate in areas where the animal spends a great amount of time (e.g., pet resting areas).

      Pupae

      The ovoid, whitish, and loosely spun pupal cocoon is sticky, and quickly becomes coated with debris, which helps to camouflage it. Some fleas may spin multiple cocoons (e.g. Xenopsylla sp).
      • Krasnov B.R.
      Functional and evolutionary ecology of fleas: a model for ecological parasitology.
      If the pre-emerged adult does not receive the proper stimulus to emerge, it can remain dormant in the cocoon for several weeks and in rare conditions as long as one year, until a suitable host arrives (diapause).
      • Silverman J.
      • Rust M.K.
      Extended longevity of the pre-emerged adult cat flea (Siphonaptera: Pulicidae) and factors stimulating emergence from the pupal cocoon.
      This stage can extend the lifespan of the flea, and is troublesome from a control standpoint. Other fleas may not require any stimulus for emergence.
      • Tipton V.J.
      • Mendez E.
      The fleas (Siphonaptera) of Panama.

      Adult (imago)

      Once the flea emerges from the cocoon, it immediately seeks a host to find a blood meal. Depending on species, adult fleas may prefer the hosts habitat (‘nest’ fleas), or the host itself (‘body’ fleas). Newly emerged fleas are attracted by various stimuli produced by these hosts. The known cues to host-finding in fleas are body heat, movement, and exhaled carbon dioxide.
      • Krasnov B.R.
      Functional and evolutionary ecology of fleas: a model for ecological parasitology.
      If the flea does not find a host, it can survive for some time, depending on species, humidity, and temperature.
      • Krasnov B.R.
      Functional and evolutionary ecology of fleas: a model for ecological parasitology.
      Once fed, fleas usually survive less time if subsequently starved, than an unfed flea. Adults make up only about 5% of a flea population.
      • Rothschild M.
      Recent advances in our knowledge of the order Siphonaptera.
      • Silverman J.
      • Rust M.K.
      Extended longevity of the pre-emerged adult cat flea (Siphonaptera: Pulicidae) and factors stimulating emergence from the pupal cocoon.
      • Tipton V.J.
      • Mendez E.
      The fleas (Siphonaptera) of Panama.
      • Silverman J.
      • Rust M.K.
      • Rajerson D.K.
      Influence of temperature and humidity on survival and development of the cat flea, Ctenocephalides felis (Siphonaptera: Pulicidae).

      Taxonomy, phylogeny, and evolution

      The majority of characteristics used for the morphological identification of flea species are based on the shape and structure of their extraordinarily complex genitalia, and the presence and distribution of setae, spines, and ctenidia on the body.
      • Dunnet G.M.
      • Mardon D.K.
      Siphonaptera, the insects of Australia: a textbook for students and research workers.
      • Whiting M.F.
      Mecoptera is paraphyletic: multiple genes and phylogeny of Mecoptera and Siphonaptera.
      Identification requires an extensive knowledge of flea morphology. New molecular data have explored phylogenetic relationships at the ordinal, familial, and generic level. Whiting and colleagues showed that the order Siphonaptera is monophyletic, and most closely related to Boreidae (snow fleas, Mecoptera).
      • Whiting M.F.
      Mecoptera is paraphyletic: multiple genes and phylogeny of Mecoptera and Siphonaptera.
      Their recent analyses based on four genes show that many extant families are paraphyletic and thus warrant a reorganization of taxonomy.
      • Whiting M.F.
      • Whiting A.S.
      • Hastriter M.W.
      • Dittmar de la Cruz K.
      A molecular phylogeny of fleas (Insecta: Siphonaptera): origins and host associations.
      In the context of flea host specificity and fleas as vectors, taxonomy and phylogenies play important roles as scaffolding for further knowledge acquirement regarding vector–flea and flea–host co-evolutionary patterns. Furthermore, better resolved scenarios of flea evolution allow for a deeper understanding of adaptation to certain ecological parameters, which may ultimately affect vector efficiency, and thus influence the rate of human infection.

      Host specificity

      Host specificity is important from the standpoint of transmission of disease agents. In general, hosts that are taxonomically related or are similar in their ecologies are likely to share flea species, and thus have the potential of hosting similar pathogens. Fleas are rarely specific at the host species level, but some clades of fleas associate with a particular host group at higher ordinal levels. Generally, mammals that have vast home ranges and do not inhabit dens for rearing their young, almost always lack fleas of their own, whereas hosts (mammals or birds) with dens or nests exhibit a more specific flea fauna. Recent studies
      • Whiting M.F.
      • Whiting A.S.
      • Hastriter M.W.
      • Dittmar de la Cruz K.
      A molecular phylogeny of fleas (Insecta: Siphonaptera): origins and host associations.
      have shown that fleas likely emerged with mammals and speciated with rodents, which still have the most speciose extant fauna (74%). Only 8% of fleas are known from insectivores, 5% each from marsupials and bats, whereas 6% of the total diversity is ornithophilic (Figure 2).
      Figure thumbnail gr2b
      Figure 2Phylogenetic relationships among fleas based upon four molecular loci. This topology has host association data mapped on the topology, as described in Vashenok
      • Vashenok V.S.
      Fleas: vectors of pathogens causing diseases in humans and animals (In Russian).
      .

      Fleas as vectors

      Fleas are mainly vessel feeders, thus damaging blood vessels directly. Another, more concerning effect of this dietary preference is that fleas themselves are hosts to pathogens, and thus provide a natural avenue for pathogen dispersal. The two commonly known ways of pathogen transmission by fleas are by oral route through regurgitation of blood meals, or by fecal route, by contaminated fecal pellets. Specific examples of this will be given in the following sections.

      Important synanthropic fleas

      There is no flea specific to humans, and only a fraction of all fleas come into contact with humans on a regular basis. Many fleas, however, associate with domesticated animals, and may thus have an economic, rather than direct effect on humans and their health. Although Pulex irritans is frequently called the human flea, recent works in Africa have described an abundance of human-associated fleas (P. irritans, Ctenocephalides felis, and X. cheopis) in human dwellings in plague-endemic regions of Africa.
      • Laudisoit A.
      • Leirs H.
      • Makundi R.H.
      • Van Dongen S.
      • Davis S.
      • Neerinckx S.
      • et al.
      Plague and the human flea, Tanzania.
      • Eisen R.J.
      • Borchert J.N.
      • Holmes J.L.
      • Amatre G.
      • Van Wyk K.
      • Enscore R.E.
      • et al.
      Early-phase transmission of Yersinia pestis by cat fleas (Ctenocephalides felis) and their potential role as vectors in a plague-endemic region of Uganda.
      Brief descriptions of the most common synanthropic species are provided in the following text.

      Pulex irritans (human flea)

      This flea has a nearly cosmopolitan distribution. It is mistakenly called the human flea, because it attacks a wide variety of mammals, including guinea pigs, domestic dogs,
      • Garcia M.J.
      • Calvette C.
      • Estrada R.
      • Castillo J.A.
      • Perbanez M.A.
      • Lucientes J.
      Fleas parasitizing domestic dogs in Spain.
      cats,
      • Millan J.
      • Ruiz-Fons F.
      • Marquez F.J.
      • Viota M.
      • Lopez-Bao J.V.
      • Paz Martin-Mateo M.
      Ectoparasites of the endangered Iberian lynx (Lynx paradinus) and sympatric wild and domestic carnivores in Spain.
      rats,
      • He J.H.
      • Liang Y.
      • Zhang H.Y.
      A study on the transmission of plague through seven kinds of fleas in rat type and wild rodent type foci in Yunnan.
      and goats.
      • Christodoulopoulos G.
      • Theodoropoulos G.
      • Kominakis A.
      • Theis J.H.
      Biological, seasonal and environmental factors associated with Pulex irritans infestation of dairy goats in Greece.
      Infestations can reach tremendous levels, particularly when farmers share their dwellings with their livestock, or hold these animals in corrals or buildings adjacent to their homes.

      Ctenocephalides felis felis (cat flea) and Ctenocephalides canis (dog flea)

      The cat flea is extremely common on cats and dogs in many temperate and tropical regions, but it also infests opossums,
      • Pung O.J.
      • Durden L.A.
      • Banks C.W.
      • Jones D.N.
      Ectoparasites of opossums and raccoons in Southeastern Georgia.
      raccoons,
      • Pung O.J.
      • Durden L.A.
      • Banks C.W.
      • Jones D.N.
      Ectoparasites of opossums and raccoons in Southeastern Georgia.
      and rats.
      • Loftis A.D.
      • Reeves W.K.
      • Szumlas D.E.
      • Abbassy M.M.
      • Helmy I.M.
      • Moriarity J.R.
      • et al.
      Surveillance of Egyptian fleas for agents of public health significance: Anaplasma, Bartonella, Coxiella, Ehrlichia, Rickettsia, and Yersinia pestis.
      It represents the great majority of fleas in human homes. The dog flea is closely related to the cat flea and is very similar to it in appearance and biology. Despite its name it is actually less common on dogs than cat fleas.

      Xenopsylla cheopis (oriental rat flea)

      Various species of Xenopsylla are found throughout Africa and central and southern Asia, coinciding with the distribution of gerbils or rats. X. cheopis is common in many tropical and warm temperate environments around the world, although it probably arose in north-eastern Africa. This flea is the primary vector of Y. pestis – the agent of plague,
      • Bitam I.
      • Baziz B.
      • Rolain J.M.
      • Belkaid M.
      • Raoult D.
      Zoonotic focus of Plague, Algeria.
      and is involved in the transmission of murine (endemic) typhus
      • Brouqui P.
      • Raoult D.
      Arthropod-borne diseases in homeless.
      and parasitic helminths.
      • Bordes F.
      • Blumstein D.T.
      • Morand S.
      Rodent sociality and parasite diversity.
      Recently, Bartonella spp have also been detected.
      • Reeves W.K.
      • Rogers T.E.
      • Durden L.A.
      • Dasch G.A.
      Association of Bartonella with the fleas (Siphonaptera) of rodents and bats using molecular techniques.

      Nosopsyllus fasciatus (northern rat flea)

      The northern rat flea is common on commensal rats in temperate regions, especially Rattus norvegicus.
      • Schwan T.G.
      • Thompson D.
      • Nelson B.C.
      Fleas on roof rats in six areas of Los Angeles County, California: their potential role in the transmission of plague and murine typhus to humans.
      It spends more time in the host's nest than the oriental rat flea (X. cheopis) and is very likely to occur on rats with underground burrows. N. fasciatus occasionally infests other mammals, including mice,
      • Iakunin B.M.
      • Kunitskaia N.T.
      Experimental interspecific hybridization in fleas of the genus Nosopsyllus (Siphonaptera; Ceratophyllidae).
      voles,
      • Gomez M.S.
      • Fernandez-Salvador R.
      • Garcia R.
      First report of Siphonaptera infesting (Microtus) cabrerae (Rodentia - Muridae - Avicolinae) in Cuenca, Spain and notes about the morphologic viability of Ctenophthalmus (Ctenophthalmus) apetus personatus (Insecta -Siphonaptera - Ctenophtalmidae).
      ground squirrels, carnivores,
      • Visser M.
      • Rehbein S.
      • Wiedemann C.
      Species of fleas (Siphonaptera) infesting pets and hedgehogs in Germany.
      and occasionally humans.
      • Iakunin B.M.
      • Kunitskaia N.T.
      Experimental interspecific hybridization in fleas of the genus Nosopsyllus (Siphonaptera; Ceratophyllidae).
      Although considered to be a relatively poor vector of plague,
      • Schwan T.G.
      • Thompson D.
      • Nelson B.C.
      Fleas on roof rats in six areas of Los Angeles County, California: their potential role in the transmission of plague and murine typhus to humans.
      it has been implicated in the maintenance and transmission of Salmonella enteriditis,
      • Eskey C.R.
      • Prince F.M.
      • Fuller F.B.
      Transmission of Salmonella enteritidis by the rat fleas Xenopsylla cheopis and Nosopsyllus fasciatus.
      Francisella tularensis,
      • Olsufiev N.G.
      Taxonomy, microbiology, and laboratory diagnostics of the tularemia pathogen (In Russian).
      and Trypanosoma lewisi,
      • Molyneux D.H.
      The attachment of Trypanosoma lewisi in the rectum of its vector flea Nosopsyllus fasciatus.
      a blood protozoan of rats.

      Echidnophaga gallinacea (sticktight flea)

      This small, angular-headed species is widely distributed in tropical and semitropical environments.
      • Boughton R.K.
      • Atwell J.W.
      • Schoech S.J.
      An introduced generalist parasite, the sticktight flea (Echidnophaga gallinacea), and its pathology in the threatened Florida scrub-jay (Aphelocoma coerulescens).
      It belongs to a group of fleas called sticktights, because of the females’ habit of using their serrated mouthparts to anchor themselves to their hosts. They then begin feeding while waiting for a male to copulate. Once a female begins feeding, she remains attached for many days. Eggs are deposited in the host's nest or in the ulcers caused by heavy infestations of these fleas. These fleas are by no means restricted to fowl, and also infest a wide variety of mammals, including dogs,
      • Garcia M.J.
      • Calvette C.
      • Estrada R.
      • Castillo J.A.
      • Perbanez M.A.
      • Lucientes J.
      Fleas parasitizing domestic dogs in Spain.
      cats,
      • Akucewich L.H.
      • Philman K.
      • Clark A.
      • Gillespie J.
      • Kunkle G.
      • Nickin C.F.
      • et al.
      Prevalence of ectoparasites in a population of feral cats from north central Florida during the summer.
      rabbits,
      • Pfaffenberger G.S.
      • Valencia V.B.
      Ectoparasites of sympatric cottontails (Sylvilagus audubonii Nelson) and jack rabbits (Lepus californicus Mearns) from the high plains of eastern New Mexico.
      rodents,
      • Loftis A.D.
      • Reeves W.K.
      • Szumlas D.E.
      • Abbassy M.M.
      • Helmy I.M.
      • Moriarity J.R.
      • et al.
      Surveillance of Egyptian fleas for agents of public health significance: Anaplasma, Bartonella, Coxiella, Ehrlichia, Rickettsia, and Yersinia pestis.
      and birds.
      • Boughton R.K.
      • Atwell J.W.
      • Schoech S.J.
      An introduced generalist parasite, the sticktight flea (Echidnophaga gallinacea), and its pathology in the threatened Florida scrub-jay (Aphelocoma coerulescens).

      Tunga penetrans (sand flea, jigger, chigoe)

      T. penetrans is a small flea, and exhibits the unique traits of female neosomy, tachygenesis, and burrowing. Neosomy is radical intrastadial metamorphosis, characterized by cuticular growth in unsclerotized parts of the abdomen, without correlated molting. In endemic areas, fleas inhabit sandy beaches and soil, and it is commonly found in human dwellings.
      • Bruce C.O.
      • Knigin T.D.
      • Yolles S.F.
      A discussion of chigoe (Tunga penetrans) based on experiences in British Guiana.
      • Darmstadt G.L.
      • Francis J.S.
      Tungiasis in a young child adopted from South America.
      • Feldmeier H.
      • Eisele M.
      • Sabóia-Moura R.C.
      • Heukelbach J.
      Severe tungiasis in underprivileged communities: case series from Brazil.
      The primary hosts are cows,
      • Heukelbach J.
      • Costa A.M.
      • Wilcke T.
      • Mencke N.
      • Feldmeier H.
      The animal reservoir of Tunga penetrans in severely affected communities of northeast Brazil.
      pigs,
      • Ugbomoiko U.S.
      • Ariza L.
      • Ofoezie I.E.
      • Heukelbach J.
      Risk factors for tungiasis in Nigeria: identification of targets for effective intervention.
      and dogs,
      • Pigler D.
      • Schwalfenberg S.
      • Heukelbach J.
      • Witt L.
      • Mehlhorn H.
      • Mencke N.
      • et al.
      Investigations on the biology, epidemiology, pathology, and control of Tunga penetrans in Brazil: VII. The importance of reservoirs for human infestation.
      but may also be humans.
      • Pigler D.
      • Schwalfenberg S.
      • Heukelbach J.
      • Witt L.
      • Mehlhorn H.
      • Mencke N.
      • et al.
      Investigations on the biology, epidemiology, pathology, and control of Tunga penetrans in Brazil: VII. The importance of reservoirs for human infestation.
      Due to its poor jumping ability, the most common location for bites is the foot. The female flea first burrows its head into the skin until reaching the dermis with its capillary supply. In this position the flea feeds on blood and breathes air through the last pair of its abdominal stomata.
      • Darmstadt G.L.
      • Francis J.S.
      Tungiasis in a young child adopted from South America.
      The volume of the fertilized sand flea increases by a factor of approximately 2000, reaching the size of a pea.
      • Feldmeier H.
      • Eisele M.
      • Sabóia-Moura R.C.
      • Heukelbach J.
      Severe tungiasis in underprivileged communities: case series from Brazil.
      It remains as a ‘foreign body’ in the skin for a period of up to three weeks, during which time it matures, releases eggs, and eventually dies.

      Flea-borne diseases

      Despite continued efforts, we still lack much knowledge regarding the vector function of wild fleas, thus potentially missing an important piece of information. The most severe infection spread by fleas is plague, caused by Y. pestis.
      • Stenseth N.C.
      • Atshabar B.B.
      • Begon M.
      • Belmain S.R.
      • Bertherat E.
      • Carniel E.
      • et al.
      Plague: past, present, and future.
      Fleas are also known as vectors of murine typhus (endemic typhus, Rickettsia typhi), and play a role in the transmission of rural epidemic typhus (Rickettsia prowazekii) in the USA.

      World Health Organization. Geographical distribution of arthropod-borne diseases and their principal vectors. Report No. WHO/VBC/89.967. Geneva; WHO; 1989.

      In recent years, the flea-borne spotted fever agent Rickettsia felis has emerged and can be found throughout the world.
      • Pérez-Osorio C.E.
      • Zavala-Velázquez J.E.
      • Arias León J.J.
      • Zavala-Castro J.E.
      Rickettsia felis as emergent global threat for humans.
      Fleas have also been proven to harbor and sometimes transmit Bartonella spp, including Bartonella henselae, the agent of cat-scratch disease (CSD).
      • Chomel B.B.
      • Boulouis H.J.
      • Maruyama S.
      • Breitschwerdt E.B.
      Bartonella spp in pets and effect on human health.
      • Billeter S.A.
      • Levy M.G.
      • Chomel B.B.
      • Breitschwerdt E.B.
      Vector transmission of Bartonella species with emphasis on the potential for tick transmission.
      Additionally, fleas are hosting helminths: Dipylidium caninum and Hymenolepis diminuta, respectively parasites of carnivores and rats.
      • Duchemin J.B.
      • Fournier P.E.
      • Parola P.
      Les puces et les maladies transmises à l’homme.
      Finally, in tropical areas, tungiasis caused by T. penetrans is a human disease directly linked to the parasitism of humans by fleas.
      • Reiss F.
      Tungiasis in New York City.
      However, to many of the general population, the insidious attacks by fleas on people and domestic animals causing irritation, blood loss, and severe discomfort are equally important as disease threat.

      Flea bites

      The skin reaction to bites is of the delayed type. The lesion initially is a punctuate hemorrhagic area representing the site of probing by the insect. Lesions may occur in clusters, as the flea explores the skin surface, frequently re-probing. There is usually formation of a wheal around each bite, reaching its peak in 5 to 30 min. Pruritus (itching) is almost always present. In most cases there is a transition to a hardened papillar lesion within 12–24 h. In sensitized individuals the reaction appears faster, persisting for a week or more. The intense itching is often the reason people consult a physician rather than come to a clinic.
      • Feingold B.F.
      • Benjamini E.
      Allergy to flea bites.

      Tungiasis (Tunga penetrans)

      Infestation with this flea is usually limited to the feet, in the periungual region, but penetration can occur in any part of the body.
      • Reiss F.
      Tungiasis in New York City.
      • Goldman L.
      Tungiasis in travelers from tropical Africa.
      • Bezerra S.M.
      • Tungiasis
      an unusual case of severe infestation.
      • Gordon R.M.
      The jigger flea.
      Within 24 h after penetration by the female flea, the site becomes irritated and painful. Erythema and edema develop around the lesion. The female needs eight to 12 days to reach maturity. During this process, its abdomen enlarges considerably and eventually reaches a diameter of 1 cm containing up to 200 ova.
      • Geigy R.
      • Herbig A.
      Die Hypertrophie der Organe beim Weibchen von Tunga penetrans.
      • Zalar G.L.
      • Walther R.R.
      Infestation by Tunga penetrans.
      • Tonge B.L.
      Tetanus from chigger flea sores.
      The inevitable pruritus causes the host to scratch the lesion, which in turn helps to expel the eggs. Fleas can live in their host for several weeks.
      • Zalar G.L.
      • Walther R.R.
      Infestation by Tunga penetrans.
      After all eggs have been released, the flea dies.
      • Zalar G.L.
      • Walther R.R.
      Infestation by Tunga penetrans.
      Thereafter, the lesion desiccates in situ and eventually the remains of the ectoparasite are expelled. A small scar is left which, if it is limited to the epidermis, disappears over time. Without appropriate treatment however, secondary infections are common.
      • Bezerra S.M.
      • Tungiasis
      an unusual case of severe infestation.
      • Tonge B.L.
      Tetanus from chigger flea sores.
      Various pathogenic bacteria have been isolated from tungiasis lesions: Clostridium tetani,
      • Chadee D.D.
      Distribution patterns of Tunga penetrans within a community in Trinidad, West Indies.
      Streptococcus pyogenes, pathogenic Staphylococcus aureus, Klebsiella aerogenes, Enterobacter agglomerans, Escherichia coli and other Enterobacteriaceae. In areas with low vaccination coverage, tetanus is a common complication in children,
      • Obengui P.
      La tungiose et le tétanos au CHU de Brazzaville.
      • Mashek H.
      • Licznerski B.
      • Pincus S.
      Tungiasis in New York.
      and immediate vaccination for patients is recommended. Sepsis, lymphedema, gangrene, and loss of toenails have been described.
      • Reiss F.
      Tungiasis in New York City.
      • Obengui P.
      La tungiose et le tétanos au CHU de Brazzaville.
      • Burke W.A.
      • Jones B.E.
      • Park H.K.
      • Finley J.L.
      Imported tungiasis.
      Severe infestation with hundreds of jigger fleas can produce honeycomb-like lesions.
      • Gordon R.M.
      The jigger flea.
      The diagnosis of tungiasis is usually made by macroscopic inspection, where the embedded gravid female abdomen can be seen as a white patch with a black dot in its center. Frequently, a few eggs stick to the skin near the lesion, a finding that is pathognomonic for the infection.
      The differential diagnosis of tungiasis includes myiasis, verruca vulgaris, ingrown toe nail, acute paronychia, mycotic granuloma, malignant melanoma, and arthropod bites.
      • Muehlen M.
      • Heukelbach J.
      • Wilcke T.
      • Winter B.
      • Mehlhorn H.
      • Feldmeier H.
      Investigations on the biology, epidemiology, pathology and control of Tunga penetrans in Brazil. II. Prevalence, parasite load and topographic distribution of lesions in the population of a traditional fishing village.
      The first line of therapy is the mechanical extraction of the flea from the infected host. Removal is not always easy and may be painful for the patient. It can be accomplished using a sterile needle after cleaning the area with an antiseptic solution. This should be followed by irrigation with sterile saline and application of a topical antibiotic. The procedure bears the risk of bursting the flea, and inevitably leading to an exaggeration of the inflammatory response. An alternative is the enucleation of the cavity by curettage or punch biopsy.
      • Burke W.A.
      • Jones B.E.
      • Park H.K.
      • Finley J.L.
      Imported tungiasis.
      Oral antibiotics may be indicated if a secondary infection develops. Prognosis is excellent as long as proper sterile methods are followed during extraction.
      Although the treatment of infested lesions with topical ivermectin or metrifonate has appeared significantly more effective than placebo on the seventh day of therapy, all drugs in this study failed to kill the ectoparasite in the early phase of its penetration.
      • Clyti E.
      • Couppie P.
      • Deligny C.
      • Jouary T.
      • Sainte-Marie D.
      • Pradinaud R.
      Effectiveness of 20% salicylated vaseline in the treatment of profuse tungiasis. Report of 8 cases in French Guiana.
      Other therapeutic agents reported in the literature include topical chlorophenotane, clofenotane, 4% formaldehyde solution, chloroform, turpentine and 20% salicylated vaseline,
      • Muehlen M.
      • Heukelbach J.
      • Wilcke T.
      • Winter B.
      • Mehlhorn H.
      • Feldmeier H.
      Investigations on the biology, epidemiology, pathology and control of Tunga penetrans in Brazil. II. Prevalence, parasite load and topographic distribution of lesions in the population of a traditional fishing village.
      and oral thiabendazole.

      Plague

      Plague, caused by Y. pestis is a zoonotic disease primarily affecting rodents, but that can affect human beings. Small outbreaks continue to occur throughout the world; around 2000 cases are reported annually.
      • Gage K.L.
      • Kosoy M.Y.
      Natural history of plague: perspectives from more than a century of research.
      Plague has recently been recognized as a re-emerging disease and remains a serious problem for international public health, especially in Africa.
      • Stenseth N.C.
      • Atshabar B.B.
      • Begon M.
      • Belmain S.R.
      • Bertherat E.
      • Carniel E.
      • et al.
      Plague: past, present, and future.
      • Neerinckx S.B.
      • Peterson A.T.
      • Gulinck H.
      • Deckers J.
      • Leirs H.
      Geographic distribution and ecological niche of plague in sub-Saharan Africa.
      • Bertherat E.
      • Bekhoucha S.
      • Chougrani S.
      • Razik F.
      • Duchemin J.B.
      • Houti L.
      • et al.
      Plague reappearance in Algeria after 50 years, 2003.
      If used by the aerosol route of exposure as a bioterrorism agent, it could cause mass casualties.
      • Gage K.L.
      • Kosoy M.Y.
      Natural history of plague: perspectives from more than a century of research.
      Y. pestis has been the cause of three recorded pandemics.
      • Drancourt M.
      • Roux V.
      • Dang L.V.
      • Tran-Hung L.
      • Castex D.
      • Chenal-Francisque V.
      • et al.
      Genotyping, Orientalis-like Yersinia pestis, and plague pandemics.
      • Achtman M.
      • Zurth K.
      • Morelli G.
      • Torrea G.
      • Guiyoule A.
      • Carniel E.
      Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis.
      • Raoult D.
      • Aboudharam G.
      • Crubezy E.
      • Larrouy G.
      • Ludes B.
      • Drancourt M.
      Molecular identification by ‘suicide PCR’ of Yersinia pestis as the agent of the Medieval Black Death.
      • Zietz B.P.
      • Dunkelberg H.
      The history of the plague and the research on the causative agent Yersinia pestis.

      Pollitzer R. Plague. WHO monograph series No. 22. Geneva: World Health Organization; 1954.

      At present, its circulation has been detected within populations of more than 200 species of wild rodents inhabiting natural plague foci on all continents, except for Europe, Australia, and Antarctica (Figure 3). The persistence of zoonotic foci is worrying, since persons living in these areas remain in close contact with rodents and fleas.
      Figure thumbnail gr3
      Figure 3Geographical location of the plague worldwide, 1989–2003 (Source World Health Organization).
      Morbidity in humans is noted, as a rule, when rodent epizootics are spreading, and is a consequence of mainly flea bites, but also direct contact with infected animal tissues, the consumption of insufficiently cooked meat products, or the inhalation of aerosolized respiratory excreta of animals or patients with the pneumonic form of infection.
      • Gage K.L.
      • Kosoy M.Y.
      Natural history of plague: perspectives from more than a century of research.
      • Anisimov A.P.
      • Lindler L.E.
      • Pier G.B.
      Intraspecific diversity of Yersinia pestis.
      • Brubaker R.R.
      Factors promoting acute and chronic diseases caused by yersiniae.
      • Prentice M.B.
      Rahalison L. Plague.
      • Lewis R.E.
      Resume of the Siphonaptera (Insecta) of the World.
      • Lewis R.E.
      Notes on the geographical distribution and host preferences in the order Siphonaptera. Part 8. New taxa described between 1984 and 1990, with a current classification of the order.
      While only a small number (over 31) of these are proven vectors of plague, any flea species may be biologically capable of transmission under the appropriate conditions.
      • Perry R.D.
      • Fetherston J.D.
      Yersinia pestis—etiologic agent of plague.
      Important flea vectors include X. cheopis (nearly worldwide in moderate climates), Xenopsylla brasiliensis (Africa, India, and South America), Xenopsylla astia (Indonesia and Southeast Asia), Xenopsylla vexabilis (Pacific islands), and N. fasciatus (nearly worldwide in cool, temperate climates). Oropsylla montanus is the most important flea vector in the USA.
      • Gage K.L.
      • Lance S.E.
      • Dennis D.T.
      • Montenieri J.A.
      Human plague in the United States: a review of cases from 1988-1992 with comments on the likelihood of increased plague activity.
      In the former USSR, Ctenophilus tesquorum, Oropsylla silantiewi, Rhadinopsylla ventricosa, as well as species of Xenopsylla, Nosopsyllus, Neopsylla, and Citellophilus, are considered important plague vectors.
      • Velimirovic B.
      Plague and glasnost. First information about human cases in the USSR in 1989 and 1990.
      The human fleas (P. irritans) may play an important role in spreading plague by human-to-human transmission.
      • Stenseth N.C.
      • Atshabar B.B.
      • Begon M.
      • Belmain S.R.
      • Bertherat E.
      • Carniel E.
      • et al.
      Plague: past, present, and future.
      In northwest Uganda, which has had recent plague outbreaks, cat fleas (C. felis) have been reported as the most common fleas in the home environment, which is suspected to be a major exposure site for human plague in this country. In the past, C. felis has been viewed as only a nuisance biting insect because limited laboratory studies have suggested that it is incapable of transmitting Y. pestis or is an inefficient vector.
      • Eisen R.J.
      • Borchert J.N.
      • Holmes J.L.
      • Amatre G.
      • Van Wyk K.
      • Enscore R.E.
      • et al.
      Early-phase transmission of Yersinia pestis by cat fleas (Ctenocephalides felis) and their potential role as vectors in a plague-endemic region of Uganda.
      While infection can occur by direct contact or ingestion, these routes do not normally play a role in the maintenance of Y. pestis in animal reservoirs. Fleas acquire Y. pestis from an infected blood meal. Infection in the flea is restricted to the alimentary canal, and is not transmitted transovarially. Consequently, maintenance of plague in nature is entirely dependent upon cyclic transmission between fleas and mammals.
      • Stenseth N.C.
      • Atshabar B.B.
      • Begon M.
      • Belmain S.R.
      • Bertherat E.
      • Carniel E.
      • et al.
      Plague: past, present, and future.
      Plague can have several clinical manifestations; bubonic plague is the most common. Other manifestations include septicemic plague without bubo, pneumonic plague (primary or secondary to bacteremia), meningitis, and pharyngitis.
      • Prentice M.B.
      Rahalison L. Plague.
      Following an incubation period of two to five days, plague has a sudden onset of fever, chills, headache, malaise, myalgia, and nausea. Pneumonic plague is rapidly fatal if untreated. For further details we refer the reader to a major review on plague.
      • Prentice M.B.
      Rahalison L. Plague.
      All patients suspected of having bubonic plague should be placed in isolation until two days after starting antibiotic treatment to prevent the potential spread of the disease should the patient develop secondary plague pneumonia.
      • Prentice M.B.
      Rahalison L. Plague.
      • Inglesby T.V.
      • Dennis D.T.
      • Henderson D.A.
      • Bartlett J.G.
      • Ascher M.S.
      • Eitzen E.
      • et al.
      Plague as biological weapon: medical and public health management. Working Group on Civilian Biodefense.
      The antibiotics and regimes used to treat Y. pestis infections and as prophylactic measures have been recently reviewed
      • Perry R.D.
      • Fetherston J.D.
      Yersinia pestis—etiologic agent of plague.
      .

      Rickettsial diseases

      Rickettsia are obligate intracellular Gram-negative bacteria associated with arthropods including ticks, mites, body lice, and fleas.
      • Raoult D.
      • Roux V.
      Rickettsioses as paradigms of new or emerging infectious diseases.

      Murine typhus (Rickettsia typhi)

      Murine typhus is a worldwide zoonosis, and also known as flea-borne, rat, urban and endemic typhus.
      • Traub R.
      • Wisseman C.L.
      • Farhang-Azad A.
      The ecology of murine typhus—a critical review.
      The etiologic agent, R. typhi (formerly Rickettsia mooseri) is transferred from a rodent reservoir by an arthropod (often X. cheopis) to humans.
      • Traub R.
      • Wisseman C.L.
      • Farhang-Azad A.
      The ecology of murine typhus—a critical review.
      Many recent reports stress this as a re-emerging disease, which spreads through travelers returning from endemic regions.
      • Letaief A.O.
      • Yacoub S.
      • Tissot-Dupont H.
      • Le Cam C.
      • Ghachem L.
      • Letaief J.
      • et al.
      Seroepidemiological survey of rickettsial infections among blood donors in central Tunisia.
      R. typhi infects endothelial cells in mammalian hosts and mid-gut epithelial cells in the flea host. It is passed in the flea's feces, and transmission to humans is by fecal contamination.
      • Azad A.F.
      • Radulovic S.
      • Higgins J.A.
      • Noden B.H.
      • Troyer J.M.
      Flea-borne rickettsioses: ecologic considerations.
      The complete genome of R. typhi was reported in 2004.
      • McLeod M.P.
      • Qin X.
      • Karpathy S.E.
      • Gioia J.
      • Highlander S.K.
      • Fox G.E.
      • et al.
      Complete genome sequence of Rickettsia typhi and comparison with sequences of other rickettsiae.
      Incubation periods range from six to 14 days. Many of its symptoms are shared with other infectious diseases, and thus cases may be overlooked without a laboratory confirmed diagnosis. The most common clinical manifestations are high fever, severe headache, chills, myalgia, weakness, and nausea.
      • Dumler J.S.
      • Taylor J.P.
      • Walker D.H.
      Clinical and laboratory features of murine typhus in South Texas, 1980 through 1987.
      The pathognomonic rash is described as macular (49%), maculopapular (29%), papular (14%), petechial (6%), and morbiliform (3%), usually centrally distributed on the trunk, but also found on the extremities.
      • Betz T.G.
      • Rawlings J.A.
      • Taylor J.P.
      • Davis B.L.
      Endemic typhus in Texas.
      Physicians practicing in or near R. typhi-endemic areas need to consider murine typhus in the differential diagnosis of a febrile illness without a clear source of infection.
      Patients respond rapidly to treatment with tetracycline, doxycycline, or fluoroquinolone. Untreated patients show signs for two to three weeks and a significant number are hospitalized, with up to 10% requiring intensive care.
      • Civen R.
      • Ngo V.
      Murine typhus: an unrecognized suburban vectorborne disease.

      Flea-borne spotted fever (Rickettsia felis)

      This emerging rickettsiosis is caused by a member of the spotted fever group of Rickettsia spp. It was probably first detected in cat fleas, C. felis, in 1918, but is in fact hosted by a variety of fleas.
      • Pérez-Osorio C.E.
      • Zavala-Velázquez J.E.
      • Arias León J.J.
      • Zavala-Castro J.E.
      Rickettsia felis as emergent global threat for humans.
      Although few confirmed human cases have been described, this infection occurs worldwide; the geographical distribution is summarized in Figure 4. There is controversy regarding the culture of R. felis; the first isolate grown at 37 °C has been lost
      • Radulovic S.
      • Higgins J.A.
      • Jaworski D.C.
      • Dasch G.A.
      • Azad A.F.
      Isolation, cultivation, and partial characterization of the ELB agent associated with cat fleas.
      and the conditions of culture did not allow the reproduction of this work. R. felis has been propagated reproducibly only at temperatures below 35 °C.
      • Znazen A.
      • Raoult D.
      Flea-borne spotted fever.
      The genome of R. felis has been sequenced and comprises one or two plasmids.
      • Fournier P.E.
      • Belghazi L.
      • Robert C.
      • Elkarkouri K.
      • Richards A.L.
      • Greub G.
      • et al.
      Variations of plasmid content in Rickettsia felis.
      • Ogata H.
      • Renesto P.
      • Audic S.
      • Robert C.
      • Blanc G.
      • Fournier P.E.
      • et al.
      The genome sequence of Rickettsia felis identifies the first putative conjugative plasmid in an obligate intracellular parasite.
      More cases have been described in hot countries. Infected people may develop severe clinical signs, commonly involving fever, headache, and rash. Other signs include marked fatigue, myalgia, photophobia, conjunctivitis, abdominal pain, vomiting, and diarrhea, as well as solitary, black crusted skin lesions, muscle pain, local lymphadenopathy (in some cases), and a characteristic inoculation eschar at the site of the flea bite.
      • Pérez-Osorio C.E.
      • Zavala-Velázquez J.E.
      • Arias León J.J.
      • Zavala-Castro J.E.
      Rickettsia felis as emergent global threat for humans.
      • Znazen A.
      • Raoult D.
      Flea-borne spotted fever.
      Thus it may be misdiagnosed as the similar tick-borne rickettsiosis.
      Figure thumbnail gr4
      Figure 4Geographical distribution of Rickettsia felis detected in fleas, and reported cases of flea spotted fever rickettsioses.
      Patients have been successfully treated with doxycycline.
      • Richter J.
      • Fournier P.E.
      • Petridou J.
      • Häussinger D.
      • Raoult D.
      Rickettsia felis infection acquired in Europe and documented by polymerase chain reaction.
      In vitro studies have shown R. felis is sensitive to doxycycline, rifampin, thiamphenicol, and fluoroquinolones.
      • Rolain J.M.
      • Maurin M.
      • Vestris G.
      • Raoult D.
      In vitro susceptibilities of 27 rickettsiae to 13 antimicrobials.

      Bartonelloses

      The genus Bartonella contains aerobic, fastidious, Gram-negative bacilli (Proteobacteria, alpha-2 subgroup).
      • Chomel B.B.
      • Boulouis H.J.
      • Maruyama S.
      • Breitschwerdt E.B.
      Bartonella sp in pets and effect on human health.
      Currently, 23 Bartonella species are recognized and associated with mammalian hosts, and 11 species have been implicated in human disease.
      • Moriarty R.A.
      • Margileth A.M.
      Cat scratch disease.
      The role of fleas as competent vectors of Bartonella spp has been poorly studied. Current known records are summarized in Table 2, and pathogens are introduced in the following text.
      Table 2Bartonella species detected in fleas worldwide
      FleaBartonellaDisease in humansKnown geographical distribution region of Bartonella [Ref.]
      Ctenocephalides felisB. henselae, B. clarridgeiae, B. quintana, B. koehleraeCSD, BA, BAC, ENDFrance
      • Rolain J.M.
      • Franc M.
      • Davoust B.
      • Raoult D.
      Molecular detection of Bartonella quintana, B. koehlerae, B. henselae, B. clarridgeiae, Rickettsia felis, and Wolbachia pipientis in cat fleas, France.
      , Japan, New Zealand, Thailand, UK, USA
      Ctenocephalides canisB. henselaeCSD, BAJapan
      Pulex irritans /Pulex simulansB. quintana, Bartonella spBAC, ENDGabon, Peru
      • Rolain J.M.
      • Bourry O.
      • Davoust B.
      • Raoult D.
      First molecular detection of Bartonella quintana in Pulex irritans fleas from Cercopithecus cephus monkey in Gabon.
      Xenopsylla cheopisB. elizabethae, B. tribocorumENDAlgeria, Egypt
      • Loftis A.D.
      • Reeves W.K.
      • Szumlas D.E.
      • Abbassy M.M.
      • Helmy I.M.
      • Moriarity J.R.
      • et al.
      Surveillance of Egyptian fleas for agents of public health significance: Anaplasma, Bartonella, Coxiella, Ehrlichia, Rickettsia, and Yersinia pestis.
      Leptopsylla segnisBartonella sp, B. elizabethaeENDAlgeria, Egypt
      • Loftis A.D.
      • Reeves W.K.
      • Szumlas D.E.
      • Abbassy M.M.
      • Helmy I.M.
      • Moriarity J.R.
      • et al.
      Surveillance of Egyptian fleas for agents of public health significance: Anaplasma, Bartonella, Coxiella, Ehrlichia, Rickettsia, and Yersinia pestis.
      Nosopsyllus fasciatusBartonella spUnknownThailand
      Oropsylla hirsutaBartonella spUnknownUSA (Colorado)
      Archeopsylla erinaceiB. clarridgeiae, B. elizabethaeENDAlgeria unpublished data
      Pulex spB. rochalimaePeru
      Ornithophaga spBartonella sp, B. elizabethaeENDPortugal
      Stenoponia tripectinataBartonella spENDPortugal
      Ctenophthalmus nobilisB. taylorii, B. grahamiiENDEngland
      Ctenophthalmus lushniensisB. clarridgeiaeENDChina
      CSD, cat scratch diseases; BA, bacillary angiomatosis; BAC, bacteremia; END, endocarditis.

      Bartonella henselae

      This pathogen is associated with the extremely common, worldwide zoonotic CSD. Transmission mainly occurs directly by a cat scratch and possibly via a cat bite or possibly the cat flea, C. felis.
      The initial lesion consists of a papule, pustule, or vesicle that develops at one week, and enlarged lymph nodes at two to three weeks, after a cat bite or scratch, usually on the arm.
      • Fournier P.E.
      • Lelievre H.
      • Eykyn S.J.
      • Mainardi J.L.
      • Marrie T.J.
      • Bruneel F.
      • et al.
      Epidemiologic and clinical characteristics of Bartonella quintana and Bartonella henselae endocarditis: a study of 48 patients.
      Although the initial lesion heals uneventfully, regional lymphadenopathy (pathognomonic) develops one week later and persists for two weeks to three months before resolving spontaneously.
      In 75% of patients the adenopathy occurs with mild systemic symptoms including fever, malaise, fatigue, headache, anorexia, weight loss, and emesis that usually resolves within two weeks. Enlarged lymph nodes can be tender, and up to 20% of these nodes suppurate. Most cases are self-limiting with the adenopathy resolving spontaneously in two to four months. In immunocompromised patients (e.g., the HIV-positive), bacillary angiomatosis may occur. This is a potentially fatal pseudoneoplasic vascular proliferative disease that might mimic Kaposi sarcoma. Additionally, it may cause an acute onset of febrile illness in HIV-positive patients, with arthralgia, myalgia, headaches, and lymphadenopathy or hepatosplenic involvement.
      • Maurin M.
      • Birtles R.
      • Raoult D.
      Current knowledge of Bartonella species.
      Endocarditis due to B. henselae occurs most often in patients with pre-existing valvulopathies who have contact with cats and their fleas.
      • Ives T.J.
      • Marston E.L.
      • Regnery R.L.
      • Butts J.D.
      In vitro susceptibilities of Bartonella and Rickettsia spp to fluoroquinolone antibiotics as determined by immunofluorescent antibody analysis of infected Vero cell monolayers.
      The mortality rate is high (25%) and most patients require valve replacement surgery.
      In vitro, B. henselae is susceptible to most antibiotics, although only aminoglycosides are bactericidal.
      • Margileth A.M.
      Antibiotic therapy for cat scratch disease: clinical study of therapeutic outcome in 268 patients and a review of the literature.
      Most cases of CSD, however, respond very poorly to antimicrobial therapy and the disease generally resolves spontaneously within four months.
      • Koehler J.
      • Relman D.
      Bartonella species.
      There is an unresolved debate as to whether patients with complicated CSD benefit from antibiotics,
      • Plettenberg A.
      • Lorenzen T.
      • Burtsche B.T.
      • Rasokat H.
      • Kaliebe T.
      • Albrecht H.
      • et al.
      Bacillary angiomatosis in HIV-infected patients—an epidemiological and clinical study.
      although most HIV-positive patients respond well.
      • Plettenberg A.
      • Lorenzen T.
      • Burtsche B.T.
      • Rasokat H.
      • Kaliebe T.
      • Albrecht H.
      • et al.
      Bacillary angiomatosis in HIV-infected patients—an epidemiological and clinical study.
      In patients with suppurative lymph nodes, needle aspiration is an appropriate treatment.

      Bartonella quintana

      These infections have recently re-emerged, predominantly among the homeless populations in cities in both Europe and the USA.
      • Foucault C.
      • Barrau K.
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      The pathogen has been detected in cat fleas
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      and in P. irritans,
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      although its main vector is the body louse. B. quintana has been identified in the dental pulp of domestic cats.
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      After the louse bite or after scratching and inoculating louse feces, the incubation period varies between 15 and 25 days.
      Asymptomatic infections to severe illness have been reported, but the classical clinical symptoms correspond to an acute febrile illness, often accompanied by severe headache and pain in the long bones of the legs. Although trench fever may result in prolonged disability, no fatalities have been recorded. In a few cases, the illness becomes chronic with nervous manifestations, fever, anemia, weight loss, and also causes bacillary angiomatosis.
      Bacteremia and endocarditis should be suspected in homeless, chronic alcoholic patients with culture-negative endocarditis, as well as in patients regularly exposed to flea bites.
      • Brouqui P.
      • Raoult D.
      Arthropod-borne diseases in homeless.
      Effective antibiotic therapy for suspected trench fever should include an aminoglycoside (gentamicin) for at least 14 days, in association with ceftriaxone and/or doxycycline for six weeks.

      General prevention of flea-borne infections

      Flea control is typically undertaken for two reasons, first to reduce the risks of disease transmission and second to address a pest problem or economic losses associated with parasitization of domestic animals by fleas. The strategies used for each situation are often different, and the best results are achieved when the biology and behavior of the host are taken into account.
      • Gage K.L.
      • Burkot T.R.
      • Eisen R.J.
      • Hayes E.B.
      Climate and vectorborne diseases.
      Typically, flea control involves using insecticidal dusts to treat runways, burrows, and pet bedding. In emergencies, liquid spray formulations of insecticides can be applied to runways and burrow entrances. Flea eggs can be reduced by regular vacuuming of carpets and pet bedding areas. Contact with vectors can be minimized by eliminating rodents in the household. In the case of domestic animal or pet infestations, veterinary advice should be sought.
      • Rust M.K.
      Advances in the control of Ctenocephalides felis (cat flea) on cats and dogs.

      Conclusions

      Flea-borne organisms are widely distributed throughout the world in endemic disease foci, where components of the enzootic cycle are present. However, flea-borne diseases could re-emerge in epidemic form because of changes in vector–host ecology due to environmental and human behavior modifications. While local environmental changes are frequent, global climate change may influence parameters of flea development, distribution, and disease transmission on a much larger scale. For many fleas, temperature and humidity are crucial for development and survival. The warmer temperatures predicted through most climate change scenarios could lead to an increased expansion of flea vectors into the northern hemispheres.
      • Gage K.L.
      • Burkot T.R.
      • Eisen R.J.
      • Hayes E.B.
      Climate and vectorborne diseases.
      Furthermore, our myopic concentration on synanthropic vectors often leads us to forget about the vast number of flea species associated with wild animals. Climate change, and our continued encroachment on natural areas, may provide new lines of transmission for a largely unknown pathogen population of wild fleas.
      The incidence of flea-borne diseases and tick-borne diseases in the world is much greater than is generally recognized by physicians and health authorities. As a result, diagnosis and treatment are often delayed by health care professionals who are unaware of the presence of these infections and thus do not take them into consideration when attempting to determine the cause of a patient's illness. In the absence of major and dramatic outbreaks, health authorities often fail to allocate adequate funding to the surveillance and control of this group of diseases. It is important that those engaged in all aspects of public health surveillance are aware of the distribution and epidemiology of this group of diseases and are able to prepare for their control when necessary.

      Acknowledgements

      This study was supported by the French Centre National de la Recherche Scientifique (CNRS).
      Conflict of interest: No conflict of interest to declare.

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