Babesia Infections
in Switzerland?
Mrs.
Laurence Meer-Scherrer, MD
Infectious diseases — Official Swiss Federal Public Health Journal
12 January 2000
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 |
- Number, year
of birth, sex (f, m) and canton of residence (BE, BL, BS, FR, NE,
SO, ZH).
- 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.
- 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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