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Babesia Infections in Switzerland?

Infectious diseases — Official Swiss Federal Public Health Journal
January 12, 2000
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From 1998 to 1999 Babesia infections were diagnosed using fluorescence microscopic techniques and PCR in patients from the cantons of Freiburg and Bern with exposure to ticks and refractory and persistent Lyme Borreliosis. This raises the issue of newly occurring or newly observed infection with the protozoon Babesia microti that occurs in rodents and is transmitted by means of ticks.

Babesiosis is a protozoan disease similar to malaria transmitted by means of ticks. Various types of babesiosis have been known for a long time in veterinary medicine, in particular those caused by Babesia equi, B. canis, and B. rodhaini.

In Europe so far about 30 human diseases have been described, mostly due to the bovine parasite B. divergens. In 1995 Loutan (1) described a case imported into Switzerland. It concerned a splenectomised patient who had probably been infected in Wales. In splenectomised or immunosuppressed patients babesiosis is a life-threatening disease accompanied by high temperature, shivering, headache, extreme muscular pain, acute haemolysis, acute kidney failure and acute respiratory distress syndrome (ARDS). These patients, handled in intensive care units, are mostly treated intravenously with quinine and clindamycin.

In the USA B. microti, the type occurring in rodents, prevails. In human beings it usually causes mild symptoms such as attacks of fever, sweating episodes, myalgia, headache, changes of mood, slight anaemia, and hepatosplenomegaly. The course of the disease can also become life-threatening in splenectomised and immunosuppressed patients. In the USA B. microti is becoming increasingly significant as a co-infection with pathogens transmitted by ticks such as Borrelia and Ehrlichia. Severe courses have also been described in co-infections in patients who have not been splenectomised and are not immunosuppressed. The following appear to be risk factors: male gender, elderly age, high leukocyte count, and high alkaline phosphatase (2). Very little research has been carried out so far on interactions in co-infections. Cases of asymptomatic courses are known, and a paper on cases of acute severe babesiosis due to blood from a donor who was an asymptomatic carrier has been published recently (4).

Babesia infections are diagnosed microscopically (in blood smears, like malaria pathogens), serologically and, recently, with PCR.

The initial situation for the investigations described here consisted of patients with severe, unusually refractory Lyme-borreliosis for whom an additional infection transmitted by ticks was suspected. From November 1998 to April 1999 blood samples of 27 patients were analysed by the lGeneX Laboratory in Palo Alto, USA, for co-infection with Babesia, using indirect immunofluorescence (IFA), PCR, and fluorescence-in-situ hybridising (FISH) techniques. For the IFA, hamster erythrocytes infected with B. microti were used. The limit titre for IgG is 1:40 while for IgM it is 1:20. Cross-reactions with other infections are possible. 16S-similar small subunit B. microti rDNA was used as a primer for the PCR. For the FISH, B. microti-specific DNA sequences were applied on blood smears from the patients. Fluorescing merozoites or ring-form can then be detected by dark-field microscopy. A positive test is valid as definitive evidence of a babesia infection.

24 patients were sero-reactive (20 with IgG, 4 exclusively with IgM), 21 reacted positively to the PCR and/or FISH, 18 reacted positively to the FISH (18 for merozoites, patient number 14 also for ring forms), and 12 had a positive reaction to the PCR (9 [50 %] FISH-positive and 3 [33 %] FISH-negative). Nine patients were reactive to three tests (Table 1). The patients were aged between 5 and 71. 18 were female. Several of them had never left Switzerland or been outside Europe so far in their lives. All the patients had the typical symptoms of the milder Babesiosis microti, however none of them had severe haemolysis. Overlapping with symptoms of Lyme Borreliosis is of course possible. The collective was treated with a combination of Azithromycin and Atovaquone (3, 4). The two-year follow-up of clinical progress and laboratory parameters is in progress (5). The results of this investigation raise interesting questions, as indicated in the comment.

Table 1
Babesia infections in patients with protracted Lyme disease,
Switzerland, November 1998 to April 1999

Patient a Symptoms b Blood smear c PCR IFA 1
IgG titre-1
IgM
  T M D        
1 1941 f BE ++ + ++ Neg Pos

160

Pos
5 1948 m SO ++ ++ + Neg Pos Neg Pos
25 1964 f BE + + + Neg Pos Neg Pos
8 1962 f FR - + ++ Neg Neg Neg Pos
12 1946 f FR - + - Neg Neg 80 Pos
18 1942 f FR - ++ - Neg Neg 40 Pos
20 1967 m BE - + - Neg Neg 80 Pos
21 1961 f BE + + + Neg Neg 40 Pos
26 1961 m BE - - + Neg Neg Neg Neg
2 1940 m BE + + + Pos Pos 40 Neg
6 1965 f ZH ++ ++ - Pos Pos 80 Pos
9 1954 f FR ++ ++ ++ Pos Pos 40 Pos
14 1947 f FR + ++ ++ Pos (R) Pos 40 Pos
17 1943 f NE ++ ++ + Pos Pos 80 Pos
19 1954 f FR ++ ++ + Pos Pos 320 Neg
22 1970 f BE ++ - - Pos Pos 40 Pos
24 1942 m BE ++ + + Pos Pos Neg Neg
27 1942 m BE + + ++ Pos Pos 80 Neg
3 1943 f BE ++ + + Pos Neg Neg Neg
4 1971 m BE + + + Pos Neg 40 Pos
7 1950 f BE ++ + + Pos Neg 40 Pos
10 1928 m FR ++ ++ - Pos Neg 320 Pos
11 1954 f BE ++ ++ ++ Pos Neg 40 Pos
13 1994 f ZH - + ++ Pos Neg Neg Pos
15 1946 m FR ++ ++ + Pos Neg 320 Pos
16 1948 f BS ++ ++ + Pos Neg 40 Pos
23 1948 f BE + + ++ Pos Neg 80 Pos
  1. Number, year of birth, sex (f, m) and canton of residence (BE, BL, BS, FR, NE, SO, ZH).
  2. Symptoms due to which babesia was suspected (the typical symptoms for Lyme are not listed): T = hot stages/sweating episodes, M = headache/extreme myalgia, D = changeable moods/depression.
  3. FISH: fluorescence-in-situ hybridising with B. microti-specific DNA probes and dark-field microscopy. All FISH positive patients were found to have merozoites but only patient 14 also had ring forms (= R).

ACKNOWLEDGEMENTS

The Author thanks Dr. J. Burrascano Jr., New York, Dr. W. v. Lerber, Bern, the office staff, E. Czaja, B. Lottaz, M. Hildebrandt and her family, without whose support the study would not have been possible.

Author: Mrs. Laurence Meer-Scherrer, MD, Flamatt/Switzerland

References

1. Loutan L. La babesiose, une zoonose meconnue. J. Suisse Med 1995; 125; 886–889.
2. White DJ, Talerico J et al. Babesiosis in New York State. Arch Int Med 1998 158: 2149–2154.
3. Hughes WT, Oz HS. Successful prevention and treatment of babesiosis with atovaquone. J Inf Dis 1995; 172: 1042–1046.
4. Dobroszycki J, Herwaldt BL et al. A cluster of transfusion-associated babesiosis cases traced to a single asymptomatic donor. JAMA 1999; 281: 927–930.
5. Krause PJ, Spielmann A et al. Persistent parasitaemia after acute babesiosis. N Engl J Med 1998; 339: 160–165.

COMMENT by the FEDERAL HEALTH DEPARTMENT

The method of marked in-situ hybridising of blood smears suggests the presence of babesia infections. The possibility of mistaking them for other intra-erythrocytic pathogens (plasmodium, bartonella) does exist although it is not very likely due to the specificity of the probes used. Nevertheless, light-microscopic documentation, titres raised in paired serum tests, tests on animals and monitoring of the therapy would be desirable in order to confirm the diagnosis as well as determination of the species involved (6): B. divergens, B. microti or another of the over 70 types of babesia? It is also necessary to clarify the clinical status and possible clinical and immunological consequences of interaction with Borrelia burgdorferi s.l. (B. burgdorferi s.s., B. garinii, B. afzelii) (7).

In Switzerland babesia infections have been described in cattle, horses, dogs and rodents (8, 9).

If these findings are confirmed, they will be of significant interest, since they raise several questions, including the following: Is there another human tick-borne infection appearing in our country? How can such infections be diagnosed in Switzerland in the best possible way? Do they have any consequences for the blood donation service? What is the most suitable treatment? The investigation also shows that practising physicians can contribute considerably towards the early detection of newly occurring infections in Switzerland.

 

 

Department of Epidemiology and Infectious Diseases

BAG, Bulletin 52 / 1999
December 27th 1999
English Translation of a text published in Bull BAG 1999; 52 (December 27th) 978–979

References concerning the BAG comment

6. Persing DH, Herwaldt BL et al. Infection with a babesia-like organism in northern California. N Engl J Med 1995; 332: 298–303.
7. Krause PJ, Telford SR et al. Concurrent Lyme disease and babesiosis. Evidence for increased severity and duration of illness. JAMA 1996; 275: 1657–1660.
8. Gem L, Aeschlimmann A. Etude seroepidemiologique de 2 foyers a babesie de micromammiferes en Suisse. Schweiz Arch Tierheilkd 1986; 128: 587–600.
9. Deplazes P, Guscetti F, Wunderlin E, Bucklar H, Skaggs J, Wolfl K. Endoparasite infection in stray and abandoned dogs in southern Switzerland. Schweiz Arch Tierheilkd 1995; 137: 172–179.
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