BABESIOOSI

Punkin/vertaimevien hyönteisten välityksellä voi saada useita erilaisia taudinaiheuttajia elimistöönsä.

Valvojat: Borrelioosiyhdistys, Bb, Jatta1001

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Liittynyt: Ke Tammi 21, 2009 14:16

BABESIOOSI

Viesti Kirjoittaja soijuv » To Syys 10, 2009 12:28

BABESIOOSI

Soile Juvonen TTT

Yleistä babesioosista:

Babesioosin voi saada punkkien välityksellä, mutta se voi tarttua myös verivalmisteista ja sen on ainakin kahdessa tutkimuksessa todettu tarttuneen raskauden aikana äidistä lapseen. Oireet alkavat yleensä 1 - 4 viikon kuluttua punkin puremasta tai 6 - 9 viikkoa infektoituneen verivalmisteen saannista.

Euroopassa babesioosia ihmisillä aiheuttaa kaksi alalajia (B. divergens ja bovis). Babesioosi on erityisen vakava sairaus sellaisilla henkilöillä, joilla on poistettu perna ja/tai heillä on jokin immuunipuutostauti. Ensimmäinen babesioositapaus ihmisessä on kirjattu vuodelta 1957. Jugoslavialainen nuori mies, jolle oli aiemmin tehty pernanpoisto, sairastui akuuttiin kuumesairauteen. Hänellä oli anemiaa ja verta virtsassa. Tauti johti lopulta kuolemaan.

Babesioosin oireet:

Oireet ilmenevät vähitellen; fatiikki, heikotus, kuumeilu, hikoilu, pahoinvointi, päänsärky, lihassärky, nivelsärky, yleinen kankeus, yskä, painonlasku, vatsakipu, ripuli, hengenahdistus, oksentelu, tumma virtsa, sivuääniä sydämestä, keltaisuus, outoja tuntemuksia päässä (Light-headedness), suurentunut maksa/perna.

Henkilöllä voi olla yhtä aikaa myös esim. borrelioosi, ehrlichioosi ja/tai bartonelloosi.

Hoito:

Hoito tulee aloittaa mahdollimman varhaisessa vaiheessa, jotta vältetään punasolujen hajoaminen ja munuaisten toiminnan heikkeneminen. Lääkitys on samantapainen kuin malarian hoidossa. Tässä artikkelissa suositellaan Kiniiniä suun kautta 650 mg 6 - 8 tunnin välein + iv klindamysiini 1200 - 2400 mg 6 - 8 tunnin välein 7 vuorokauden ajan. Vaihtoehtoisesti voidaan käyttää klindamysiiniä azithromysiinin ja doksisykliinin kanssa tai atovaquonen ja azithromysiinin kanssa.

Tapausselostus:

71-vuotiaalla miehellä todettiin yleistä heikkoutta, lämpöilyä, keltaisuutta, vilunväristyksiä. Ei ihomuutoksia.Verikokeista löytyi hepatiitti A IgG. Miehellä oli useita babesioosille tunnusomaisia oireita, mutta lääkäri ei tunnistanut niitä. Vasta laboratoriotyöntekijä huomasi näytteessä olevan jotakin outoa. Miehellä todettiin babesioosi ja borrelioosi. Mies oli sairaalassa kaksi viikkoa ja sai tänä aikana babesioosin hoitoon kiniiniä ja klindamysiiniä IV. Sairaalasta lähtiessä veriarvot olivat normalisoituneet.

Alkuperäinen teksti:



Coinfection With Babesia microti and Borrelia burgdorferi

Angela C. Kim, MD, North Shore University Hospital, Manhasset, NY; Marcia E.
Epstein, MD, North Shore University Hospital, Manhasset, NY and New York
University School of Medicine

Infect Med 18(5):271-276, 2001. © 2001 Cliggott Publishing, Division of SCP Communications

Abstract

A diagnosis of Lyme disease was made in a 71-year-old patient with fever, chills, and generalized weakness, but concurrent babesiosis was initially missed. A technician in the hematology laboratory noticed intraerythrocytic organisms initially thought to be Plasmodium, but close inspection of the blood smear and review of the patient's history pointed to infection with Babesia.

Introduction

Babesia species are intraerythrocytic protozoans that cause a spectrum of illness in humans, ranging from asymptomatic infection to cardiac, renal, pulmonary, and CNS complications to death.[1] Most manifestations are, however, subclinical.[2] Patients with babesiosis present with fever, chills, malaise, weakness, anorexia, hemolysis, and hemoglobinuria. Babesiais a zoonotic organism transmitted to humans by the arthropod vector Ixodes dammini. Other agents of tick-borne illness include Borrelia burgdorferi, Ehrlichia equi, and Ehrlichia chaffeensis. Cases of cotransmission have been described.[3-7]

Case Report

History

A previously healthy 71-year-old man was admitted to the hospital with fevers, chills, and generalized weakness. He had been in his usual state of health until 1 week before admission, at which time fatigue, anorexia, fevers, and chills developed. He visited his internist, who initiated an outpatient workup; however, the patient became more lethargic, and his family brought him to the emergency department.

The patient recalled having eaten shellfish approximately 8 to 10 days earlier without subsequent nausea, vomiting, diarrhea, or abdominal pain. He admitted to drinking 2 to 3 glasses of red wine daily. His travel history included the summer spent on the eastern end of Long Island, NY; he returned 2 weeks before admission. He had spent time gardening but was unaware of any tick bites. There was no history of recent blood transfusion, and he was a nonsmoker.

Physical and Laboratory Examination

The oral temperature was 37.3°C (99.1°F); pulse, 95 beats per minute and regular; respirations, 18 breaths per minute; and blood pressure, 103/57 mm Hg. The patient appeared noticeably jaundiced and had scleral icterus. No rashes were visible. Lungs, heart, abdomen, and extremities were normal. No hepatosplenomegaly was appreciated. Results of a guaiac test for occult blood in stool were negative. Blood chemistries and hematologic values are presented in Tables 1 and 2, respectively. Results of an ECG and chest radiographs were normal.

These initial findings were suggestive of alcoholic hepatitis, and supportive treatment was initiated.

Hospital Course

The abdominal sonogram revealed a normal liver, contracted callbladder, normal pancreas, normal kidneys, and splenomegaly (13.2 cm). Results of hepatitis serology were positive only for hepatitis A IgG. On hospital day 3, a peripheral blood smear showed greater than 50% intraerythrocytic inclusion bodies. The thin smear was consistent with babesiosis, as shown in the Figure.

Figure1. Intraerythrocytic trophozoites of Babesia microti.

Therapy was started with oral quinine and intravenous clindamycin, but the patient continued to do poorly, with persistently elevated levels on liver function tests and depressed platelet counts. Blood was sent for testing for both Lyme disease and Ehrlichia infection, and doxycycline was empirically added to the patient's regimen. On hospital day 5, the patient underwent exchange transfusion.

Lyme titers returned positive (IgG/IgM antibodies, 3.31 test units [TU]; [1.0 TU or greater is considered positive]) by traditional enzyme-linked immunosorbent assay and were confirmed by Western blot, while results of both indirect fluorescent antibody and polymerase chain reaction (PCR) tests for Ehrlichia were negative. The patient's parasitemia improved to less than 1% after exchange transfusion and was 0% on discharge on hospital day 14, at which time he had completed a 7-day course of treatment with quinine and clindamycin.

Just before discharge from the hospital, on day 13, tests revealed the following values: total bilirubin, 2.7 mg/dL; hemoglobin, 9.8 g/dL; hematocrit, 30.4%; blood urea nitrogen, 12 mg/dL; creatinine, 1 mg/dL; aspartate aminotransferase, 42 U/L; alanine aminotransferase, 67 U/L; and alkaline phosphatase, 175 U/L.

Discussion

This patient had many symptoms and signs of babesiosis, yet the admitting physician missed the diagnosis. The diagnosis of babesiosis was not considered until an astute technician in the hematology laboratory noticed intraerythrocytic organisms, thought initially to be malaria parasites. Close inspection of the smear in conjunction with the patient's clinical history suggested infection with Babesia.

Pathogen and Pathogenesis

Human babesiosis is a zoonosis caused by protozoa of the order Piroplasmida, the family Babesiidae, and the genus Babesia. There are more than 99 species of Babesia in the world that infect various hosts and are transmitted by multiple vectors. In 1957, the first reported case of babesiosis in humans was described in a splenectomized young Yugoslavian man in whom an acute febrile illness developed with hemoglobinuria, anemia, and ultimately death.[8] In humans, only a small percentage of species have been shown to cause illness. In Europe, the infectious agent is of bovine species (Babesia divergens and Babesia bovis), and in the United States, the patients are infected with the rodent species Babesia microti. In the western United States, a newly recognized species, WA-1, has been documented to cause clinical disease.[9,10] The parasites vary in length from 1 to 5 µm and may appear pear-shaped, oval, or round.

Transmission of B microti usually occurs via the tick vector I dammini. There are 3 stages of development (larva, nymph, and adult); each requires a blood meal in order to progress to the next stage. Both the larvae and nymphs are capable of infecting humans. The adult tick, which feeds primarily on the white-tailed deer, is also capable of transmitting infection to humans.[2]

On transmission from the salivary glands of the tick, merozoites will parasitize the erythrocytes, forming trophozoites. By way of synchronous, asexual budding or binary fission, each trophozoite then gives rise to 2 or 4 merozoites; the tetrad is classically referred to as the "Maltese cross."[11] There appears not to be an exoerythrocytic stage.

It has been suggested that erythrocytic invasion occurs via a complement-mediated pathway, resulting in red cell membrane abnormality with decreased deformability.[2,12,13] The change in lipid composition in the red blood cell membrane makes parasitized cells more cytoadherent to endothelial cells.[14] The ensuing hemolytic anemia is hypothesized to result from capillary sequestration.[13] Since the pathway of schizogony is asynchronous, the anemia is generally not a massive hemolysis, such as occurs in Plasmodium infection; in some cases, the anemia may be related to disseminated intravascular coagulation.[12]

Epidemiology

In the United States, the most common pathogen of babesiosis is B microti. The infection is endemic in coastal regions of the northeastern United States, such as Nantucket, Martha's Vineyard, and Cape Cod, Mass; Block Island, RI; and Shelter Island and eastern Long Island, NY.[2] Other areas include Connecticut, Wisconsin, and California.[15-17] Most cases occur during the spring and early summer. In an epidemiologic study of babesiosis in New York in 1992, 90% of 123 cases occurred during the months of June through August.[18]

Lyme disease is endemic in the same geographic locations, since the same vector transmits both diseases. As a result, much of the epidemiologic data we have for Lyme disease may potentially be applied to babesiosis. Both reservoir and vector (the white-tailed deer and the Ixodes tick, respectively) populate these locations. Patients infected with the WA-1 strain of Babesia have been from areas of Washington and northern California; however, neither the vector nor the host has yet been described.[9,10] Patients may also become infected by receiving blood products (erythrocytes, platelets) from infected donors with asymptomatic parasitemia.[19] In addition, cases of vertically transmitted Babesia have been described. In 2 cases, a history of tick bites was ascertained without ensuing smear evidence of parasitemia in the mothers, but there was serologic evidence of acute infection. Parasitemia developed in both infants.[20,21]

Clinical Features

Symptoms usually begin 1 to 4 weeks after a tick bite or 6 to 9 weeks
post-transfusion with infected blood products. The severity of signs and symptoms varies among infecting species. In Europe, both B divergens and B bovis cause fatal illness in asplenic patients. In the United States, B microti causes less severe disease in patients with an intact spleen, and the disease rarely results in death. The signs and symptoms are gradual in onset and include constitutional symptoms, anorexia, abdominal pain, and dark urine. The fever of babesiosis is not typically cyclical, as it is with malaria. Patients may or may not recall any tick bites, but most often, there is a history of outdoor activity or travel to an area where the disease is endemic.

Physical examination findings include fever, jaundice, hepatomegaly, and splenomegaly. Table 3 lists common manifesting symptoms and signs of babesiosis. Laboratory data suggest hemolytic anemia with decreased hematocrit, elevated total and direct bilirubin levels, elevated lactate dehydrogenase level, reticulocytosis, and elevated hepatic transaminase levels. Urinalysis reveals hemoglobinuria without red blood cells. The intensity of parasitemia can vary; the parasite may be undetectable, or its concentration can be greater than 85%.[22]

Prognostic Features

Risk factors for more severe outcome include male sex, alkaline phosphatase levels greater than 125 U/L, and white blood cell counts greater than 5 3 10[9]/L.[23] A history of splenec-tomy or functional asplenia and immunodeficiency (lymphoma or AIDS) are 2 other important risk factors that portend the development of clinically apparent disease or protracted illness. However, most patients with symptomatic babesiosis with a history of asplenia were infected with B divergens or the WA-1 strain. Patients infected with B microti are usually asymptomatic.

Diagnosis

The diagnosis of babesiosis may be based on Wright- or Giemsa-tained peripheral blood smears, immunofluorescent antibody tests, and/or PCR assay. Peripheral smear may reveal parasitized erythrocytes with organisms at various stages of development, consistent with the asynchronous replication of progeny. In cases of very low parasitemia, the smear may not demonstrate the intraerythrocytic parasites or the characteristic Maltese cross tetrads. Unlike in malaria, there are no schizonts or gametocytes. To avoid overlooking the correct diagnosis in the setting of a negative peripheral blood smear, suspicion should remain high and serologic studies and PCR should be pursued, especially if there is a history of travel to locations where the disease is endemic or of splenectomy with acute febrile illness and anemia. Serologically, a titer greater than 1:64 indicates a positive result or seropositivity, and a titer greater than 1:256 suggests an acute infection.[22] Quantification of the titer has not been shown to correlate with the severity of illness. PCR is a more sensitive test and may also be used to monitor progression or resolution of infection. In addition, PCR testing may detect persistent infection in patients with prolonged symptoms.[24,25]

Treatment

Treatment should be initiated early in symptomatic patients to avoid massive hemolysis with ensuing renal failure. Cases of subclinical infection need not be treated. Recommended treatment is with oral quinine, 650 mg every 6 to 8 hours, and with intravenous clindamycin, 1200 to 2400 mg every 6 to 8 hours, for 7 days. Side effects of quinine include hemolytic anemia (precaution should be taken in patients with glucose-6-phosphate dehydrogenase deficiency), thrombocytopenia, tinnitus, vertigo, hearing loss, lupus rash, gastric distress, and QT prolongation. This medication should not be administered to pregnant patients. In those who are unable to tolerate quinine, a combination of clindamycin with azithromycin and doxycycline has been used.[26] The combination of atovaquone and azithromycin has been shown to be an effective and better-tolerated alternative regimen.[27] In patients who are refractory to pharmacologic management, exchange transfusion with red blood cells has been shown to expedite recovery, probably secondary to diminishing the parasite load.[28]

Patients may remain parasitized despite adequate therapy with resolution of symptoms, with positive PCR test results raising the question of a possible exoerythrocytic stage.[25] Some patients may even require maintenance therapy to prevent recrudescence.

Cotransmission

It is important to keep in mind other tick-borne organisms that may be cotransmitted with Babesia, such as B burgdorferi (the agent of Lyme disease) and Ehrlichia species (the agent of human granulocytic ehrlichiosis).[3,5-7] Similar geographic and seasonal distribution as well as common vectors are likely responsible for this occurrence. An epidemiologic study of 136 cases of babesiosis showed that as many as 23% had concurrent Lyme disease based on clinical and serologic data.[14] In 2 separate studies, 10% of patients with Lyme disease were found to be coinfected with B microti on the basis of serologic and PCR test results.[6,7] In a study of 55 patients with confirmed Lyme infection, 2 patients had positive antibodies to Ehrlichia species.[6] Another study demonstrated cotransmission of both B microti and B burgdorferi in hamsters by disease-infected nymph forms of I dammini.[5] Taken together, these studies emphasize the need to consider coinfection with other tick-borne illnesses when the diagnosis of 1 is made.

Patients with Lyme disease present with fever, weakness, myalgias, arthralgias and, often, the characteristic rash, erythema migrans. Patients with ehrlichiosis often present with nonspecific febrile illness without rash. Laboratory data that suggest coinfection with Ehrlichia include leukopenia, thrombocytopenia, and elevation of liver enzyme levels.

Coinfection is thought to cause more severe illness than does disease with 1 organism alone.[4] The pathophysiologic explanation is yet to be described, although speculation suggests an immunosuppressive role of Babesia as a possibility.[6]

Drugs Mentioned in This Article
Atovaquone Mepron
Azithromycin Zithromax
Clindamycin Cleocin, Clindets
Doxycycline Vibramycin,
generic
Quinine Generic

Tables
Table 1. Blood chemistries

Value
Variable Normal range Day 1 Day 4
Alanine aminotransferase (U/L) 10 - 45 58 51
Albumin (g/dL) 3.3 - 5 2.4 2
Alkaline phosphatase (U/L) 39 - 128 198 183
Aspartate aminotransferase (U/L) 10 - 40 120 124
Creatinine (mg/dL) 0.7 - 1.3 1.6 1.2
Bilirubin, direct (mg/dL) 0 - 0.2 4.5 9.6
Bilirubin, total (mg/dL) 0.2 - 1.2 7.5 14
Lactate dehydrogenase (U/L) 50 - 242 -- 1332
Total protein (g/dL) 6.0 - 8.3 6.4 --
Urea nitrogen (mg/dL) 7 - 23 30 25

Table 2. Hematology values

Value
Variable Normal range Day 1 Day 4
White cell blood cells (3 109/L) 3.8 - 10.5 7.2
Hemoglobin (g/dL) 11.5 - 15.5 10.8
Hematocrit (%) 34.5 - 45 33.2
Platelets (3 109/L) 150 - 400 80
Differential (%)
Neutrophils 43 - 77 78 --
Bands 0 - 8 5 --
Lymphocytes 13 - 44 9 --
Reactive lymphocytes 1 --
Monocytes 2 - 14 -- --
Reticulocytes (%) 0.5 - 2.5 -- 4
Absolute reticulocytes (3 109/L) 25 - 125 -- 130
Prothrombin time (s) 10 - 14 Normal --
Partial thromboplastin time (s) 24 - 34.6 Normal --

Table 3. Common findings in babesiosis: Symptoms, signs, and history

Symptoms (%) Signs (%)
Fatigue, malaise, weakness (91.4)
Fever (90.6)
Rigors (76.7)
Diaphoresis (69.2)
Nausea/anorexia (57.3)
Headache (38.7)
Myalgia (33.6)
Cough (23.7)
Weight loss (20.5)
Arthralgias (17.1)
Abdominal pain (16.3)
Dyspnea (15.6)
Light-headedness (15.3)
Vomiting (14.1)
Dark urine (12.3)
Rash (11.7)
Diarrhea (9.6) Temperature > 38.5°C (101.3°F) (55.
Murmur (21.1)
Hepatomegaly (14.4)
Splenomegaly (10.
Jaundice (4.3)
History (%)
Chronic disease (51.
Tick bite (37.5)
Lyme disease (11.9)
Splenectomy (11.7)
Blood transfusion (2.2)
Adapted from White DJ et al. Arch Intern Med. Oct 26,
1998;158:2149-2154. Copyrighted 1998, American Medical Association.

References

1. Boustani MR, Lepore TJ, Gelfand JA, Lazarus DS. Acute respiratory
failure in patients treated for babesiosis. Am J Respir Crit Care Med.
1994;149:1689-1691.
2. Gelfand JA, Callahan MV. Babesiosis. Curr Clin Top Infect Dis.
1998;18:201-216.
3. Benach JL, Coleman JL, Habicht GS, et al. Serological evidence for
simultaneous occurrences of Lyme disease and babesiosis. J Infect Dis.
1984;152:473-477.
4. Marcus LC, Steere AC, Duray PH, et al. Fatal pancarditis in a patient
with coexistent Lyme disease and babesiosis: demonstration of spirochetes in