Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 98(3): 311-318, April 2003 311 Coexistence of Antibodies to Tick-borne Agents of Babesiosis and Lyme Borreliosis in Patients from Cotia County, State of São Paulo, Brazil Natalino Hajime Yoshinari/+, Milena Garcia Abrão, Virginia Lúcia Nazário Bonoldi, Cleber Oliveira Soares*, Claudio Roberto Madruga*, Alessandra Scofield**, Carlos Luis Massard**, Adivaldo Henrique da Fonseca** Laboratório de Investigação em Reumatologia (LIM-17), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Arnaldo 455, 3º andar, 01246-903 São Paulo, SP, Brasil *Embrapa Gado de Corte, Campo Grande, MS, Brasil **Universidade Federal Rural do Rio de Janeiro, Seropédica, RJ, Brasil This paper reports a case of coinfection caused by pathogens of Lyme disease and babesiosis in brothers. This was the first case of borreliosis in Brazil, acquired in Cotia County, State of São Paulo, Brazil. Both children had tick bite history, presented erythema migrans, fever, arthralgia, mialgia, and developed positive serology (ELISA and Western-blotting) directed to Borrelia burgdorferi G 39/40 and Babesia bovis antigens, mainly of IgM class antibodies, suggestive of acute disease. Also, high frequencies of antibodies to B. bovis was observed in a group of 59 Brazilian patients with Lyme borreliosis (25.4%), when compared with that obtained in a normal control group (10.2%) (chi-square = 5.6; p < 0.05). Interestingly, both children presented the highest titers for IgM antibodies directed to both infective diseases, among all patients with Lyme borreliosis. Key words: lyme borreliosis - lyme disease - spirochetosis - borreliosis - babesiosis - coinfection - tick-borne disease - Brazil Babesiosis is a tick-borne disease distributed world- The first case of babesiosis in a healthy person, with wide, caused by hemoprotozoans of the genus Babesia, intact spleen, was reported in 1969 in a woman from Nan- which infects wild and domestic animals, promoting eco- tucket Island (Massachusetts, USA)(Wester et al. 1970), nomic losses due to mortality, weight loss in cattle popu- hospitalized with fever, headache and abdominal pain. lation, besides the costs involved in profilatic measures Blood smear analysis revealed numerous ring-like struc- and treatment. tures suggesting Plasmodium falciparum infection, and More than 70 species of babesias were described in the patient was treated with cloroquine. During the course animals: Babesia bovis, Babesia divergens and Babesia of the disease, diagnosis of babesiosis was established, bigemina in cattle; Babesia equi and Babesia caballi in the treatment with cloroquine was introduced, and longed horses; Babesia canis in dogs; Babesia microti in ro- for two months. Blood from patient was inoculated in sple- dents. Recently a new species very similar to B. microti nectomized rodent and monkey, with recovery of the etio- named Babesia WA-1 was described in USA (Quick et al. logical agent B. microti. 1993). The only case reported in Brazil (Alecrim et al. 1983) The parasite was first discovered by Babes (1888), was described from a patient from Tiuma, State of that reported intra-erytrocytic microorganisms in periph- Pernambuco, who was treated as having malaria, until eral blood of cattle suffering of fever and hemoglobinuria. the discovery of parasites identified as Babesia sp. Smith and Kilbourne (1983) identified the tick as transmit- Ixodid ticks (Healey et al. 1976, Piesman & Piesman ter of disease, and this description was the first case of 1980) are responsible vectors for protozoan transmission, protozoan transmission by arthropods. and belong to the genus Ixodes (B. microti, B. divergens), The first case of human babesiosis was discovered in Boophilus (B. bovis), Dermacentor (B. equi), Rhipi- Yugoslavia (Skrabalo & Deanovic 1957) in a 33 years old chephalus (B. equi, B. canis). farmer, splenectomized, who died eight days later with Humans are infected accidentally by tick bite or blood fever, anemia, jaundice and hemoglobinuria, and B. bovis transfusion. The microorganisms invade the erytrocytes was identified in the blood and cattle. The beggining of and present binary division, and differently from malaria, knowledge on human babesiosis was dramatic, since the parasite did not have sexual stage. three of four cases occurred in splenectomized patients Human babesiosis or piroplasmosis is a zoonosis as- followed by death. sociated with protozoa of the family Piroplasmorida in- cluding B. microti and recently described babesia like piroplasm named Babesia Wa-1 in the USA, and B. Financial support: Fundação de Amparo à Pesquisa do Estado divergens in Europe. A few cases in humans have been de São Paulo described in China, Egypt, Mexico, South Africa and Tai- +Corresponding author. Fax: +55-11-3066.7490. E-mail: wan (Gorenflot et al. 1998b). [email protected] The North American clinical manifestations of B. Received 7 June 2002 microti infection present incubation period that varies Accepted 10 January 2003 from one to four weeks, and first clinical manifestations 312 Antibodies to Tick-borne Agents • Natalino Hajime Yoshinari et al. include presence of fever, chills, myalgia, fatigue. Symp- motes systemic complications like cutaneous, rheumatic, toms may remain for weeks until the correct diagnosis is neurologic and cardiac symptoms. The etiological agent done, sometimes with spleen enlargement and anemia. The is different in Brazil, and not isolated yet (Abel et al. 2000). disease may be asymptomatic or course as prolonged se- The probable ticks transmitters of disease belong to the vere illness (Telford III et al. 1993). The clinical spectrum genus Ixodes and Amblyomma, the first implicated for associated with B. Wa-1 ranges from asymptomatic infec- keeping infection among wild animals, and the latter for tion or influenza-like illness to fulminant fatal disease promoting human disease (Barros-Battesti et al. 1995, (Persing et al. 1995). 2000). Due to etiological, clinical and laboratorial differ- Between 1982 and 1993, 139 patients were hospital- ences when compared with American and European pre- ized with babesiosis in the State of New York (White et sentations, the infection has been named Lyme disease al. 1998), nine patients died (6.5%), and the most common like illness in Brazil (Yoshinari et al 1999, 2000). symptoms were fever, myalgia, headache, fatigue, malaise, The aim of the present paper is to report the presence weakness, hemolytic anemia, jaundice, hemoglobinuria. of simultaneous infections caused by etiological agents Among these patients, 12% had had previous history of of Lyme disease like illness and babesiosis in two broth- Lyme disease, 12% had undergone splenectomy and 2% ers who acquired disease in Cotia county, State of São blood transfusion. Paulo, in 1992. Interestingly, they were the first cases of Osorno et al. (1976) performed an epidemiological borreliosis with cutaneous and systemic symptons, with survey at a risk area analysing 101 blood samples, and positive serology for B. burgdorferi G39/40 of American found antibodies to Babesia sp. in 38%, demonstrating origin. Clinical suspicion was done by Dr Marcelo that infection may be latent or asymptomatic. Mendonça when the boys were hospitalized at Instituto The European presentation of infection in most of de Infectologia Emílio Ribas, and the laboratorial confir- cases (76%) is caused by B. divergens, often it is a dra- mation performed at Laboratório de Investigação em matic medical emergency, with letality close to 50%, and it Reumatologia, Hospital das Clínicas, Faculdade de is clinically characterized by acute onset with appear- Medicina, Universidade de São Paulo (LIM-17). Serologic ance of high fever, chills, vomit, nausea, and important test for B. bovis was done only in 2000 at LIM-17, em- anemia, often followed by jaundice, hemolysis, hemoglo- ploying frozen sera kept at -70oC during eight years. binuria, renal failure, pulmonary edema and death. In gen- PATIENTS AND METHODS eral, human cases were reported in splenectomized per- sons (Loutan 1995). Babesiosis must also be considered Case 1 - EMDA, 10 years, male, white, resident in São as differential diagnosis of febrile process in HIV positive Paulo city. The boy started with fever 19 days before patients in endemic areas (Falagas & Klempner 1996). hospitalization, followed by cutaneous lesions on elbows First case of human babesiosis in Poland (Humiczewska and knees, with latter dissemination on trunk and mem- & Kuzna-Grygiel 1997) was diagnosed as imported from bers, associated with headache, anorexia, myalgia, nau- Brazil, and it was based on recovery of parasite after intra- sea, arthralgia of wrists. The skin lesions were multiple, peritoneal inoculation of patient’s blood in hamster, when expansive, and of different size, very suggestive of characteristic forms of babesia were identified. erythema migrans (EM). Diagnosis of human babesiosis includes history of The boy had visited an ownership of 125 hectares, visiting risk areas and development of clinical manifesta- named Transurb, located in Cotia, which is a region cov- tions as fever, hemolitic anemia with normal leucogram, ered with Atlantic Forest, 20 days before the beginning of slight elevation of transaminases and alkaline fosfatase symptons, and presented important epidemiological data enzymes (Telford III et al. 1993). like the history of contact with dog that died few days Laboratorial confirmation includes analysis of periph- latter, and many