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