Mini Review
Zoonotic babesiosis: Overview of the disease and novel aspects of pathogen identity

https://doi.org/10.1016/j.ttbdis.2009.11.003Get rights and content

Abstract

Babesiosis is a zoonosis caused by tick-transmitted intraerythrocytic protozoa of the Phylum Apicomplexa. The disease mostly occurs in the USA, but cases have also been reported in several European countries, in Egypt, India, Japan, Korea, Taiwan, and South Africa. The main pathological event is lysis of erythrocytes resulting in haemolytic anaemia, which in severe cases may lead to organ failure and death, particularly in immunocompromised patients. The 2 groups of parasites involved, Babesia microti-like and Babesia sensu stricto (s.s.) species, differ in their life cycle characteristics and susceptibility to antibabesial drugs. Molecular taxonomy is now making a major contribution to the identification of novel pathogens within both groups. Effective treatment of severe cases was initially hampered by the lack of specific antibabesial drugs for human use, but increased use of supportive measures and of the recently developed antimalarial, atovaquone, particularly in combination with azithromycin, has improved the prospects for management of acute disease especially when caused by Babesia s.s. species. Prevention should be based primarily on increasing the awareness of physicians and the public to the risks, but infection from blood transfusions is particularly difficult to prevent. Expanding deer populations, resulting in wider distribution and greater abundance of ticks, heightened medical awareness, and growing numbers of immunocompromised patients are likely to result in a continuing rise of reported cases.

Introduction

Although best known as an animal disease, human babesiosis is attracting increased attention as a worldwide emerging zoonosis. More than 30 cases, most likely caused by the cattle parasite Babesia divergens or by closely related species, have been reported in Europe (Yugoslavia [modern Croatia], France, Great Britain, Ireland, Portugal, Spain, Sweden, Switzerland), almost all in splenectomised patients, often with additional immunocompromising conditions, and usually characterised by acute fulminant infections (Zintl et al., 2003). Recently a related though quite distinct babesia, B. venatorum (EU1), was incriminated in similar, though generally milder cases in Austria, Italy, and Germany (Herwaldt et al., 2003a; Häselbarth et al., 2007). In the USA, B. divergens-like parasites have caused acute disease in 3 asplenic patients (Herwaldt et al., 1996, Herwaldt et al., 2004; Beattie et al., 2002).

A much more common form of babesiosis in the USA is caused by B. microti, a natural parasite of microtine rodents. Several hundred cases have been reported on the eastern seaboard and upper mid-west in both spleen-intact and asplenic patients. This disease usually occurs as relatively mild infections, except in immunocompromised or elderly patients. Many cases have been reported from New England and more recently from Wisconsin and Minnesota (Gray and Weiss, 2008). In Washington State and California, at least 9 cases of another form of babesiosis have occurred in spleen-intact and asplenic patients, caused by parasites (WA1 et seq. and CA1 et seq., respectively) that are morphologically similar to B. microti but taxonomically distinct (Kjemtrup and Conrad, 2000). Some of these isolates have been characterised and named B. duncani (Conrad et al., 2006).

Isolated cases of human babesiosis caused by B. microti-like parasites have been reported in Germany, Japan, and Taiwan (reviewed by Hunfeld et al., 2008), and uncharacterized babesias have also been detected in patients from South Africa, Brazil, India, and Egypt (Bush et al., 1990; Humiczewska and Kuźna-Grygiel, 1997; Marathe et al., 2005; El-Bahnasawy and Morsy, 2008). Kim et al. (2007) reported that a parasite in a Korean case involving a splenectomised woman is unrelated to any of the previously recorded zoonotic species.

The different forms of human babesiosis reported so far are summarised in Table 1.

Section snippets

Clinical features

In heavy infections, particularly those caused by B. divergens-like parasites occurring in immunocompromised patients, acute illness appears suddenly, usually with haemoglobinuria as a presenting symptom. The clinical presentation also includes persistent non-periodic high fever (40–41 °C), shaking chills, intense sweats, headaches, myalgia, and lumbar and abdominal pain. Jaundice may develop as a result of the high level of haemolysis; vomiting and diarrhoea may be present, and the toxins and

Pathogen identity

Traditionally, babesias have been divided into ‘large’ and ‘small’ forms such as B. bigemina and B. microti, respectively (Fig. 1). The large babesias, also referred to as Babesia sensu stricto (s.s.), can be further differentiated from small babesias by their relative susceptibility to antibabesial drugs (Gray and Pudney, 1999) and by details of their life cycles, particularly the presence of transovarial transmission (Uilenberg, 2006). Transovarial transmission appears to be absent in small

Life cycles

Babesia spp. multiply in erythrocytes by asynchronous binary fission, resulting in considerable pleomorphism (Fig. 2). This replication eventually gives rise to gametocytes that are ingested by the vector tick. Conjugation of gametocytes occurs in the tick gut followed by multiplication by multiple fission and migration to various tissues including the salivary glands. Further development occurs in the salivary glands before transmission. In Babesia s.s. species, the ovaries are also invaded,

Epidemiology

The reported incidence of approximately 40 human cases due to B. divergens and related parasites in Europe (Vannier and Krause, 2009) is surprisingly low in view of the widespread distribution of infected ticks, cattle (and deer), and the size of the population at risk. Although most cases have occurred in splenectomised individuals, other as yet unidentified risk factors may be involved, since splenectomy is not a particularly rare procedure. The case fatality rate, although very high

Diagnosis, treatment, and prevention

Preliminary diagnosis of Babesia spp. infection can be made from indicative clinical features, especially in acute cases in which haemoglobinuria is evident. However, in chronic and subacute B. microti infections, clinical presentations may be further complicated by coinfection with other human pathogens such as Borrelia burgdorferi s.l. and Anaplasma phagocytophilum both of which are transmitted by the vectors of babesiosis (Swanson et al., 2006). Definitive diagnosis can be made by detection

Conclusion

Reports of human babesiosis cases will probably occur more frequently in the future as a result of increased medical and public awareness, and the rising numbers of immunocompromised patients. Advances in molecular taxonomy have helped to detect new pathogens and to elucidate some aspects of their ecology. However, for other species there is still no information on the identity of vertebrate reservoirs or tick vectors. Educating the public on infection risk and personal protection measures, and

Acknowledgments

We are grateful to Bernard Kaye (University College Dublin, Ireland) for invaluable assistance with the figures, and to Pat Conrad (University of California, Davis, CA, USA), Pat Holman (Texas A&M University, TX, USA), Jung-Yeon Kim (National Institute of Health, Seoul, Korea), Anne Kjemtrup (California Dept. of Health Services, Sacramento, CA, USA), and Sam Telford (Tufts University, North Grafton, MA, USA) for photographs or blood smears of parasites. We are also grateful to the anonymous

References (70)

  • A.S. Olmeda et al.

    A subtropical case of human babesiosis

    Acta Trop

    (1997)
  • N. Schmid et al.

    Babesia divergens-like organisms from free-ranging chamois (Rupicapra r. rupicapra) and roe deer (Capreolus c. capreolus) are distinct from B. divergens of cattle origin – an epidemiological and molecular genetic investigation

    Vet. Parasitol.

    (2008)
  • E. Sinski et al.

    Babesia microti: prevalence in wild rodents and Ixodes ricinus ticks from the Mazury Lakes District of north-eastern Poland

    Int. J. Med. Microbiol.

    (2006)
  • G. Uilenberg

    Babesia – a historical overview

    Vet. Parasitol.

    (2006)
  • D. Zwart et al.

    Babesiosis: non-specific resistance, immunological factors and pathogenesis

    Adv. Parasitol.

    (1979)
  • J.F. Beattie et al.

    Acute babesiosis caused by Babesia divergens in a resident of Kentucky

    N. Engl. J. Med.

    (2002)
  • K.J. Bown et al.

    Relative importance of Ixodes ricinus and Ixodes trianguliceps as vectors for Anaplasma phagocytophilum and Babesia microti in field vole (Microtus agrestis) populations

    Appl. Environ. Microbiol.

    (2008)
  • S. Bonnet et al.

    Babesia sp. EU1 from roe deer and transmission within Ixodes ricinus

    Emerg. Infect. Dis.

    (2007)
  • J.B. Bush et al.

    A preliminary report of two cases in southern Africa

    S. Afr. Med. J.

    (1990)
  • S. Centeno-Lima et al.

    A fatal case of human babesiosis in Portugal: molecular and phylogenetic analysis

    Trop. Med. Int. Health.

    (2003)
  • I.A. Clark et al.

    Do babesiosis and malaria share a common disease process?

    Ann. Trop. Med. Parasitol.

    (1998)
  • A.J. de Vos et al.

    Babesia

  • D. Duh et al.

    Cervids as babesiae hosts, Slovenia

    Emerg. Infect. Dis.

    (2005)
  • M.M. El-Bahnasawy et al.

    Egyptian human babesiosis and general review

    J. Egypt. Soc. Parasitol.

    (2008)
  • M.R. Filstein et al.

    Serosurvey for human babesiosis in New York

    J. Infect. Dis.

    (1980)
  • C.L. Fritz et al.

    Seroepidemiology of emerging tickborne infectious diseases in a Northern California community

    J. Infect. Dis.

    (1997)
  • H.K. Goethert et al.

    What is Babesia microti?

    Parasitol

    (2003)
  • J.S. Gray et al.

    Activity of atovaquone against Babesia microti in the Mongolian gerbil, Meriones unguiculatus

    J. Parasitol.

    (1999)
  • J. Gray et al.

    Transmission studies of Babesia microti in Ixodes ricinus ticks and gerbils

    J. Clin. Microbiol.

    (2002)
  • J.S. Gray et al.

    Babesia microti

  • Gubernot, D.M., Nakhasi, H.L., Mied, P.A., Asher, D.M., Epstein, J.S., Kumar, S., 2009. Transfusion-transmitted...
  • J.C. Hatcher et al.

    Severe babesiosis in Long Island: review of 34 cases and their complications

    Clin. Infect. Dis.

    (2001)
  • B. Herwaldt et al.

    A fatal case of babesiosis in Missouri: identification of another piroplasm that infects humans

    Ann. Intern. Med.

    (1996)
  • B.L. Herwaldt et al.

    Molecular characterization of a non-Babesia divergens organism causing zoonotic babesiosis in Europe

    Emerg. Infect. Dis.

    (2003)
  • B.L. Herwaldt et al.

    Endemic babesiosis in another eastern state: New Jersey

    Emerg. Infect. Dis.

    (2003)
  • Cited by (217)

    • Human Babesiosis

      2022, Infectious Disease Clinics of North America
    View all citing articles on Scopus
    View full text