Q Fever in Bulgaria and Slovakia.

As a result of dramatic political and economic changes in the beginning of the 19 Q-fever epidemiology in Bulgaria has changed. The number of goats almost triple contact between goat owners (and their families) and goats, as well as goats and other animals, increased; consumption of raw goat milk and its products increase and goats replaced cattle and sheep as the main source of human Coxiella burne infections. Hundreds of overt, serologically confirmed human cases of acute Q [ILLEGIBLE TEXT] have occurred. Chronic forms of Q fever manifesting as endocarditis were also observed. In contrast, in Slovakia, Q fever does not pose a serious public health problem, and the chronic form of infection has not been found either in follow-ups Q-fever epidemic connected with goats imported from Bulgaria and other [ILLEGIBLE TEXT] fever outbreaks or in a serologic survey. Serologic diagnosis as well as control [ILLEGIBLE TEXT] prevention of Q fever are discussed.

Q fever, a widespread zoonosis recognized as a clinical entity in 1937 (1), is [ILLEGIBLE TEXT] obligate intracellular parasite, Coxiella burnetii. The disease is endemic [ILLEGIBLE TEXT] occurring in different geographic regions and climatic zones (2). New Zealand is the only large country without Q fever (3). The principal vectors of C. burnetii [ILLEGIBLE TEXT] which transmit the agent to wild animals (causing wildlife coxiellosis) or to [ILLEGIBLE TEXT] animals (creating the livestock reservoir of C. burnetii) (4). The most important [ILLEGIBLE TEXT] in nature are small wild rodents, but infection was also demonstrated in insectivo lagomorphs, carnivores, ungulates, ruminants, marsupials, monkeys, bats, birds, reptiles and fish (5,6). Infected domestic animals (cattle, sheep, and goats but [ILLEGIBLE TEXT] animals, especially cats), frequently with persistent and subclinical coxiellosis, [ILLEGIBLE TEXT] the main source of C. burnetii infection for humans, who become infected by [ILLEGIBLE TEXT] with these animals, by environmental contamination (from animal excrements), a (indirectly) through processing or consuming animal products. Human infection most often by the inhalation of contaminated aerosols but may also occur [ILLEGIBLE TEXT] digestive tract, through skin trauma, or by sexual contact. Mother-to-fetus [ILLEGIBLE TEXT] may also occur (7).

C. burnetii may cause acute and chronic forms of Q fever in humans, though in infection is asymptomatic and confirmed by serologic diagnosis only (8). The [ILLEGIBLE TEXT] Q fever manifests usually as a flulike illness or atypical pneumonia, but often it [ILLEGIBLE TEXT] protean character with a clinical picture resembling that of nearly any infectious (9). Whereas acute Q fever is usually self-limited, chronic Q fever is a serious an fatal illness with death rates exceeding 65% (10). Illness occurs months to years acute infection in 1% to 11% of patients and usually manifests as endocarditis. I of arterial aneurysm or prosthesis; bone infection; pseudotumor of the lung; [ILLEGIBLE TEXT] cutaneous, musculoskeletal, or renal involvement; and placentitis in pregnancy [ILLEGIBLE TEXT] miscarriage are also possible (11).

The first human cases of Q fever in Europe appeared in the Balkans during [ILLEGIBLE TEXT] when strange, febrile, influenzalike infections, named Balkangrippe, were [ILLEGIBLE TEXT] German troops (12,13). Similar infections occurred among allied troops during [ILLEGIBLE TEXT] in the Mediterranean area (14,15). In the 1940s, Q fever was recognized in Roma Greece (17), and Bulgaria (18). The Balkans thus became the territory in which could circulate in nature, be transmitted to humans, and be spread to other parts [ILLEGIBLE TEXT] for example, Q fever was probably introduced to Slovakia through infected [ILLEGIBLE TEXT] Romania (6).

Q Fever in Bulgaria

Though the first human Q-fever cases in Bulgaria were described as early as 194 thorough epidemiologic and epizootologic studies started later in connection [ILLEGIBLE TEXT] unification of land and livestock farms into state premises and agricultural [ILLEGIBLE TEXT] units. Concentration of domestic animals (especially cows and sheep) and [ILLEGIBLE TEXT] favoring circulation and maintenance of C, burnetii in nature (ticks, reservoir [ILLEGIBLE TEXT] turned the country into a huge natural focus of Q fever. The occurrence of C. [ILLEGIBLE TEXT] infection in different parts of the country was 6% to 100% in sheep, 5% to 31% [ILLEGIBLE TEXT] and 7% to 34% in goats (19), as confirmed serologically by complement fixation Infestation of ticks with C. burnetii reached 26% in southwest and 22% in [ILLEGIBLE TEXT] Bulgaria (20).

The situation changed dramatically in the 1990s as the large state premises and [ILLEGIBLE TEXT] farms collapsed and the number of cows and sheep decreased (e.g., sheep from 8 1990 to 3 million in 1997). As individual farmers started to raise goats for easily food, the number of goats increased from 430,000 in 1990 to more than 1 million Moreover, the proportion of sera containing antibodies to C. burnetii from [ILLEGIBLE TEXT] animals from five regions of Bulgaria in 1996 to 1997 also changed; more (90% samples from goats than from sheep (73% of 118) tested positive. At the same [ILLEGIBLE TEXT] rate of infestation of Dermacentor marginatus, Ixodes ricinus, and Rhipicephalu sanguineus with C. burnetii as demonstrated by the hemocyte test (21) was also (25 of 29 ticks tested were infected).

These changes also influenced the occurrence and seasonality of human Q-fever Bulgaria. Until 1990, more than 20 Q-fever outbreaks occurred in several region country, some with hundreds of patients (e.g., 725 cases near Knyezha from 198 [22] and as many as 630 cases in Pavlikeni in 1985 only). These Q-fever [ILLEGIBLE TEXT] farmers explain the sharp peak of Q fever incidence in 1985 (Figure 1). A sudden continual decrease thereafter could reflect a return to a nonepidemic situation; [ILLEGIBLE TEXT] increase in the 1990s was probably associated with an increase in the number of (Figure 1). Depicting the seasonality of the disease, the number of goats shifted [ILLEGIBLE TEXT] winter and spring months (December to May) with a peak in January in the 1980 and summer months (March to August) with a peak in May and June in the 1990

[Figure 1 ILLUSTRATION OMITTED]

2).

Several factors probably contributed to this shift. 1) A change in insemination [ILLEGIBLE TEXT] Until 1990, artificial insemination of ewes was carried out in early autumn, but [ILLEGIBLE TEXT] 1990s, this practice was abandoned. 2) Sheep deliver in January and February, [ILLEGIBLE TEXT] goats deliver in March and April. 3) Herds of cattle and flocks of sheep, though concentrated in larger numbers, were separated from most of the population and the source of C. burnetii infection usually among farmers and others exposed to and their products. 4) An increased number of goats have been kept in very close with goat owners and their family members. 5) Goats have been pastured daily ([ILLEGIBLE TEXT] March until October), so they cross the streets of villages and small towns twice Thus, at present in Bulgaria, goats (rather than sheep or cattle) seem to be an [ILLEGIBLE TEXT] source of C. burnetii infections for humans. Not only have great numbers of goat with their families been exposed to C. burnetii (when tending the goats or [ILLEGIBLE TEXT] unpasteurized milk products), but also occasional bystanders could contract C. [ILLEGIBLE TEXT] infection from exposure to the contaminated aerosols created from excrements of as they repeatedly passed through villages and small towns to their pastures or [ILLEGIBLE TEXT] exposure to infectious particles generated during parturition or abortion. For [ILLEGIBLE TEXT] fever outbreak in Val de Bagnes, Switzerland, which affected 415 persons, [ILLEGIBLE TEXT] weeks after 12 flocks of sheep descended from the Alpine pastures to the valley [ILLEGIBLE TEXT]

The largest Q-fever outbreak was registered in Panagyurische (central part of [ILLEGIBLE TEXT] Bulgaria) in the 1990s, after an influenza epidemic (end of 1992, beginning of 19 January to June 1993, a second epidemic wave with more than 2,000 cases of an flulike respiratory illness and bronchopneumonia occurred. Atypical pneumonia diagnosed in 589 cases by X-ray examination, and 254 patients were admitted to regional hospital. Q fever was confirmed serologically only at the end of the [ILLEGIBLE TEXT] more than 500 persons who recovered from Q-feverlike disease, 60% were serop several laboratories confirmed significant titers (from 80 to 640 in CF and microimmunoflourescence [MIF] tests) of antibodies to phase II C. burnetii. [ILLEGIBLE TEXT] of the patients and those with positive serologic tests were adults 20 to 59 years high positivity was also noticed in children [is less than] 6 years of age (19%) and in persons years of age (23%). Most of the patients were not employed in agriculture or the of animal products. Serologic examination of domestic animals by CF test gave [ILLEGIBLE TEXT] results for goats (26% of 969) and sheep (28% of 421). However, sheep did not [ILLEGIBLE TEXT] serve as a source of C. burnetii infection--they went to pastures far away from [ILLEGIBLE TEXT] from February to March. The highest number of human Q-fever cases was [ILLEGIBLE TEXT] April to June when goats delivered their kids and sporadic goat abortions [ILLEGIBLE TEXT]

A Q-fever outbreak occurred in Panagyurische again in April to June 1995 as [ILLEGIBLE TEXT] serologically in 78% of 89 patients admitted to the local hospital with [ILLEGIBLE TEXT] Acute Q fever was diagnosed in 28 (31%) on the basis of seroconversion or [ILLEGIBLE TEXT] antibody titers. The results indicate that Q fever appears to be endemic in the Panagyurische area (with seasonal spring occurrence) and goats are probably the source of human infection. Nevertheless, such a seasonal Q-fever occurrence has restricted to this area of Bulgaria (Table) but occurred in all the regions (Ichtima Pelin in the West, Stara Zagora in the South, Blagoyevgrad in the Southwest, [ILLEGIBLE TEXT] Northwest, and Varna in the Northeast) of the country in which it had been [ILLEGIBLE TEXT] 252 patients with bronchopneumonia and acute flulike symptoms, 66% (46%-10 antibodies to phase II C. burnetii detected by CF or microagglutination (MA) [ILLEGIBLE TEXT] Q fever was confirmed in 73 (29%) patients tested (13% to 60% in different [ILLEGIBLE TEXT] these regions, sheep, cattle, and goats have been raised not only in villages [ILLEGIBLE TEXT] above-mentioned towns, but also in their suburbs.

Table. Phase II-Coxiella burnetii antibodies in patients with bronchopneum acute respiratory symptoms, Bulgaria

                                             No. positive/
Town (region)              Testing period    No. tested(a)   %

Ichtiman (West)            April-June 1995       19/21        9
Elin-Pelin (West)          April 1995             9/9        10
Blagoyevgrad (Southwest)   March-June 1996       26/44        5
Blagoyevgrad (Southwest)   March-June 1997       24/30        8
Stara Zagora (South)       March-June 1997       24/52        4
Vraca (Northwest)          March-June 1997       37/6         6
Varna (Northeast)          Feb-March 1997        28/35        8
Total                                           167/252       6

(a) Sera from Ichtiman and Elin-Pelin were examined by complement fixation test, remaining sera microagglutination. All sera were from patients with bronchopneumonia, except those collected i which were from patients with acute respiratory flulike symptoms. Sera with titers [is greater than or equal to] 10 in either considered serologically positive. Acute Q-fever diagnosis was based on seroconversion or fourf antibody titers.

Similar results were observed when testing human sera from the serum bank. Of randomly chosen sera collected in nine localities (Gabrovo from the North, [ILLEGIBLE TEXT] Dobrich from the Northeast, Sofia from the West, Blagoyevgrad from the South Stara Zagora, Pazardzhik, Haskovo, and Sliven from the South of Bulgaria), 87 [ILLEGIBLE TEXT] reacted positively with phase II C. burnetii in MA or MIF tests. Serologic [ILLEGIBLE TEXT] from 6% in Sliven to 60% in Blagoyevgrad, except for Razgrad, where none [ILLEGIBLE TEXT] (however, only four sera were tested).

Chronic Q-fever cases manifesting as endocarditis were confirmed serologically titers from 640 to 1 mi of phase I- and phase II- C. burnetii immunoglobulin (Ig) antibodies in MIF, by demonstration of specific immunofluorescence in the [ILLEGIBLE TEXT] valves, and by C. burnetii isolation from the replaced prosthesis in three patients 1990 (23). Two additional cases of Q-fever endocarditis were diagnosed [ILLEGIBLE TEXT] MA and MIF tests from 1996 to 1997.

Antibodies to phase II C. burnetii by MA were found in 16 of 18 aborting [ILLEGIBLE TEXT] titers of 10 to 320, which indicates the possibility of acute Q-fever infection [ILLEGIBLE TEXT] pregnancy. In two cases, in paired sera collected in 23-day intervals, a shift from 160 to seronegativity (titer [is less than] 10) was observed. Even though abortion tissues [ILLEGIBLE TEXT] cultured or tested for C. burnetii, these findings deserve further study, since the [ILLEGIBLE TEXT] adverse effects of C. burnetii infection during pregnancy has also been suggested authors (24).

Q Fever in Slovakia

In Slovakia, Q fever has been known since 1954 when outbreaks occurred [ILLEGIBLE TEXT] agricultural workers who contracted the infection from sheep imported from [ILLEGIBLE TEXT] among workers of a textile plant who were exposed to contaminated imported [ILLEGIBLE TEXT] From that time until the 1980s, the waves of epizootics and small epidemics [ILLEGIBLE TEXT] factories processing cotton, wool, and hides from Mongolia and China, in a [ILLEGIBLE TEXT] with imported breeding rams from England, and in various agricultural premises connected with excursions of workers to cattle or sheep farms in which C. burnet infections could have occurred. Veterinary and serologically uncontrolled move cattle within the country also contributed to the establishment of domestic coxiel Some areas of the southern part of central Slovakia became a natural focus of Q [ILLEGIBLE TEXT] the D. marginatus tick as the main vector of C. burnetii (6).

Since the 1980s, only sporadic cases of Q fever have been reported from [ILLEGIBLE TEXT] the country, though almost 3% of approximately 7,000 ticks collected in all [ILLEGIBLE TEXT] Slovakia were found (by the hemocyte test) to harbor C. burnetii, and attempts to C. burnetii from pooled positive ticks resulted in the isolation of 10 virulent C. [ILLEGIBLE TEXT] strains from five ticks, mostly I. ricinus species (26). On the other hand, C. [ILLEGIBLE TEXT] isolated from cow milk were of lower virulence for guinea pigs and mice (Kovac submitted for publication). Circulation of such low virulent strains among [ILLEGIBLE TEXT] large-scale vaccination of cattle by inactivated phase I-C. burnetii corpuscular [ILLEGIBLE TEXT] subcutaneous dose consisting of 500 [micro]g of highly purified C. burnetii cells) [ILLEGIBLE TEXT] the 1970s and 1980s, together with improved veterinary control of domestic [ILLEGIBLE TEXT] transport within the country, could explain a decrease in the occurrence of [ILLEGIBLE TEXT] in Slovakia. This explanation is supported by results of a serologic survey (carrie 1989 to 1996) for Q-fever antibodies in groups of farmers or in patients with [ILLEGIBLE TEXT] burnetii infection. Of 21,197 human sera tested, 655 (3%) reacted with phase II-antigen in the CF test (until 1992) or (later on) in enzyme-linked immunosorbent (ELISA). Acute Q fever (as individual or clustered cases) was diagnosed in 23 [ILLEGIBLE TEXT] including 113 from the Q-fever epidemic discussed below, on the basis of [ILLEGIBLE TEXT] or IgM antibody detection. During the same period, phase-II C. burnetii [ILLEGIBLE TEXT] detected in 11% of cattle and in 3% each of sheep and goats.

Improved veterinary control of domestic animal transport within the country, [ILLEGIBLE TEXT] cannot exclude the possibility of introducing C. burnetii infection through [ILLEGIBLE TEXT] domestic animals or raw materials not tested properly. The use of CF, which is sensitive to Q-fever antibodies than other serologic tests (e.g., ELISA [27]), to [ILLEGIBLE TEXT] goats imported to Slovakia from Bulgaria is unsatisfactory, as confirmed in 1993 largest reported Q-fever epidemic in Slovakia (28). The epidemic started [ILLEGIBLE TEXT] the spring as an outbreak of respiratory infection in inhabitants of a village in [ILLEGIBLE TEXT] Slovakia. A total of 113 persons were affected from the beginning of March until as confirmed serologically (seroconversion, detection of IgM antibodies, and [ILLEGIBLE TEXT] antibody titers, respectively) by CF, MA, MIF, and ELISA. Of 42 patients [ILLEGIBLE TEXT] hospital, 33 had atypical pneumonia (diagnosed by X-ray examination), and 27 [ILLEGIBLE TEXT] involvement (diagnosed on the basis of the increased values of liver [ILLEGIBLE TEXT] many as 103 were male patients who used to visit the local pub, in which they [ILLEGIBLE TEXT] infection by the aerosol created from the heavily contaminated garments of boys aborting goats. C burnetii infection in incriminated goats was confirmed [ILLEGIBLE TEXT] of 216 goat sera tested were positive by ELISA) and by seroconversion in mice [ILLEGIBLE TEXT] with spleen, lung, and liver suspension from an aborted kid.

In contrast to the situation in Bulgaria, a 4-year follow-up of patients from this Q epidemic did not result in clinical or serologic confirmation of any chronic form disease (Kova ... ova et al., submitted for publication). In addition, evidence of [ILLEGIBLE TEXT] fever was obtained neither in the serologic survey carried out in Slovakia from 1 1996, nor in testing of more than 200 patients with chronic cardiovascular [ILLEGIBLE TEXT] them exposed to C. burnetii infection through their work). Similarly, observation patients from other Q-fever epidemics (including those with 98 cases in a cotton-plant in nearby Southern Moravia in 1980 [29]) was also negative. Whether this explained by C. burnetii strains of different virulence circulating in Bulgaria and respectively, remains to be seen, though in the latest Q-fever epidemic in West [ILLEGIBLE TEXT] Bulgarian C. burnetii strains were presumably involved. However, whereas C. [ILLEGIBLE TEXT] strains of tick and domestic animals origin isolated in Slovakia may differ, no [ILLEGIBLE TEXT] known on the virulence of Bulgarian strains. A total number of human C. [ILLEGIBLE TEXT] can also be important. Whereas in Bulgaria more than 1,000 patients were [ILLEGIBLE TEXT] Slovakia tens of human cases occurred, so the probability of developing the [ILLEGIBLE TEXT] of Q fever in Slovakia was lower. The small number of patients in Slovakia [ILLEGIBLE TEXT] explained by earlier diagnosis and proper antibiotic treatment at the early stage [ILLEGIBLE TEXT] The patients' history, e.g., previous rheumatic disease, should be also taken into consideration.

Lessons Learned from Q-Fever Outbreaks in Bulgaria and [ILLEGIBLE TEXT]

Epidemiologic and serologic investigations in Bulgaria and Slovakia indicate [ILLEGIBLE TEXT] increase in human Q fever in Bulgaria in the 1990s and Slovakia in 1993 was [ILLEGIBLE TEXT] with goats. The data on the propensity of goats to transmit C. burnetii to humans Greece, Cyprus, France, the United States, and even a trans-Pacific cargo ship [ILLEGIBLE TEXT] dairy goats, were summarized by Lang (4). More recently, a cluster of human [ILLEGIBLE TEXT] infections associated with exposure to vaccinated goats and their unpasteurized [ILLEGIBLE TEXT] was reported from France (30). Goats may pose a threat to human health as a [ILLEGIBLE TEXT] burnetii infection in every country in which they are raised extensively and are [ILLEGIBLE TEXT] contact with humans. However, Q fever can also be contracted from other source infection and has been, even in Bulgaria and Slovakia.

Reporting of Q fever in a given territory depends on the attention of public [ILLEGIBLE TEXT] authorities and the availability of diagnostic methods. Apart from C. burnetii [ILLEGIBLE TEXT] (mainly in cell cultures by a shell-vial method [31 ] or direct detection, preferably polymerase chain reaction [32]), these diagnostic methods are based mostly on [ILLEGIBLE TEXT] tests. Sensitivity of serologic tests for screening Q-fever antibodies increased [ILLEGIBLE TEXT] MA and from MIF to ELISA (27). The cut-off values for individual tests may [ILLEGIBLE TEXT] between laboratories and antigens used; for CF and MA tests, 1:8 and 1:16 [ILLEGIBLE TEXT] were acceptable (in Slovakia) and for either test 1:10 serum dilution was [ILLEGIBLE TEXT] Bulgaria). For a more sensitive MIF and ELISA allowing also detection of immunoglobulin classes, diagnostic titers were set at the phase-II IgG [is greater than or equal to] 200 and IgM [is greater than or equal to] 50 in MIF (33) and at [is greater than or equal to] 128 for the IgM and IgG phase-I responses, but [is greater than or equal to] the IgM and [is greater than or equal to] 1,024 for the IgG response to phase II C. burnetii in ELISA (34), respectively. Serologic diagnosis of acute Q fever relies on seroconversion from to positivity or at least fourfold rise of phase-II antibodies in paired (acute- and convalescent-phase) serum samples and demonstration of IgM antibody response titers (e.g., [is greater than or equal to] 128 in CF and 200 in MIF) of phase-II antibodies in a single serum For diagnosis of chronic Q fever, high titers (i.e., [is greater than or equal to] 200 in CF and [is greater than or equal to] 800 of in MI phase I antibodies, occurring rarely and in low titers in acute Q-fever cases, are [ILLEGIBLE TEXT] (9).

Q-fever control and prevention measures have been reviewed (35). Apart from [ILLEGIBLE TEXT] thorough control of imported domestic animals, raw materials, and movement of animals within a country, prevention measures should include adequate disinfect disposal of animal products of conception and strict hygienic measures in cattle, goat farms; plants processing products of these animals; boiling or pasteurization 62.8 [degrees] C for 30 minutes or at 71.7 [degrees] C for 15 seconds; and vaccination. At present, [ILLEGIBLE TEXT] of Q-fever vaccine are available for human use: a Formalin-inactivated whole-[ILLEGIBLE TEXT] C. burnetii vaccine used in Australia (36), a chloroform-methanol residue [ILLEGIBLE TEXT] I C burnetii recommended by American authors (37), and Q-fever [ILLEGIBLE TEXT] soluble subunit vaccine obtained by treatment with trichloroacetic acid of phase-developed and used in Romania (38) and the former Czechoslovakia (39). For [ILLEGIBLE TEXT] of domestic animals, corpuscular phase I (in Slovakia) or phase II (e.g., in [ILLEGIBLE TEXT] used. The fact that phase-II vaccine did not protect goats from shedding C. burne (30) confirmed that an effective Q-fever vaccine should consist of or be prepared phase-I C. burnetii (40). Efficient recombinant vaccines, however, should also be [ILLEGIBLE TEXT]

Mass vaccination of cattle in Slovakia in the 1970s, followed by selective [ILLEGIBLE TEXT] cattle in serologically positive herds and elimination of positive reactors in the [ILLEGIBLE TEXT] lessen not only distribution of C. burnetii among domestic animals, but also its transmission to humans. However, absence of vaccination of domestic animals [ILLEGIBLE TEXT] could contribute to the maintenance of C. burnetii and therefore to increased [ILLEGIBLE TEXT] human infection, though basic natural conditions for circulation of this agent in [ILLEGIBLE TEXT] country have been similar. Moreover, gradual changes in agriculture in Slovakia 1990s resulted in reduced numbers of cattle and sheep but not in the dramatic [ILLEGIBLE TEXT] goat numbers seen in Bulgaria after the collapse of state farms and cooperative [ILLEGIBLE TEXT] can conclude that in Bulgaria there is a permanent threat of more Q-fever [ILLEGIBLE TEXT] preventive measures, including improvement of veterinary services and [ILLEGIBLE TEXT] domestic animals, particularly goats, are established. In Slovakia, because of [ILLEGIBLE TEXT] veterinary control, and vaccination of domestic animals, the situation is much [ILLEGIBLE TEXT] however, attention should still be paid to avoid introduction of C. burnetii by [ILLEGIBLE TEXT] animals and raw materials and the possibility of coxiellosis outbreaks among [ILLEGIBLE TEXT] animals and consequently Q fever in humans.

[Figure 2 ILLUSTRATION OMITTED]

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This page last reviewed July 1, 1999

Emerging Infectious Diseases Journal National Center for Infectious Diseases Centers for Disease Control and Prevention

URL: http://www.cdc.gov/ncidod/eid/vol5no3/serbezov.htm

V. Serbezov,(*) J. Kazar,([dagger]) V. Novkirishki,(*) N. Gatcheva,(*) E. Kovacova,([double dagger]) and Voynova(*)

(*) National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria; ([dagger]) Institute Preventive and Clinical Medicine, Bratislava, Slovak Republic; and ([double dagger]) Institute of Slovak Academy of Sciences, Bratislava, Slovak Republic

Dr. Serbezov is consultant at the National Center of Infectious and Parasitic Diseases in [ILLEGIBLE TEXT]

Address for correspondence: Jan Kazar, Institute of Preventive and Clinical Medicine, Limbo 01 Bratislava, Slovak Republic; fax: [phone]; e-mail: [e-mail].