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Potential zoonoses among bank voles.

Definition:

A Zoonose can be defined to be a so-called "etiological agent" which is present in the host organism and can be transferred to humans and by that cause sickness. An etiological agent can be anything but usually that implies some kind of bacteria, virus, parasite or even prion. "Etiology" is the study of the reasons, (causality) to a disease [sometimes spelled "aetiology"]. The problem with zoonotic diseases is that the etiological agents are present in the host organism in the wild where it does not makes the host sick (the host is typically a so-called   "a -symptomatic" carrier of the disease and this host organism is then considered a "reservoir" for this agent. That implies that the disease can "jump" from the wild organism to humans again and again which can be illustrated by the regular epidemic sweeps of influenza.

Wild living Bank voles can be infected with several suspected etiological agents of which the following can be mentioned.

Puumalavirus

Genus: Hantavirus. Family: Bunyaviridae. This virus can lead to the disease Nephropatia Epidemica (NE) in Scandinavia which is a milder form of Hemorrhagic fever with renal syndrome (HFRS). Mostly the patients have an un-dramatic course of the sickness starting with acute symptoms of fever; pain in the back and/or head and/or stomach; polyuria, proteinuria (proteins and/or blood in urine meaning more or less degree of kidney failure) and increased levels of serum creatinine. Settergren (1991 describes these symptoms using other references and mention that the average time for hospitalization was 8 days (Sweden); 17 days (Finland) and 22 days (Norway). The prognosis is good; seven months after having left the hospital all 66 patients in a Swedish study was cured. The mortality from this sickness was 0.2% in a Finnish study (1300 cases of NE) which is considerably less than seen in the Korean variant of NE (Korean Hemorrhagic Fever - KHF) where it is estimated roughly 5-10% dies as a result of chock, haemorrhages in the brain/intestines and kidney failure.

The Puumala virus is capable of infecting via inhalations of vaporized faeces/urine and there is a connection between occupation/geographical situation and the risk of getting into contact with Hantavirus. Brummer-Korvenkontio et al., (1980) were the first which convincingly isolated the etiological agent behind NE and Sommer et al., (1985) were, already at that time, suggesting that bank voles played an important role as a source for human NE and formed an important reservoir for the virus in Norway. Still, it is far from all sero-positive bank voles that are actually infected: Alexeyev et al., (1998) found in a study covering 299 bank voles from an area with a prevalence of Puumala virus that 42 was sero-positive for antibodies against Puumala. Only among 11 voles were there traces of virus RNA or virus-antigen. Out of the remaining 257 sero-negative bank voles only two turned out to harbour virus-antigen. According to Niklasson & LeDuc (1987) it seems like the southern borderline of Swedish human NE cases correspond fairly accurate with the southern borderline of Puumala-infected Swedish bank voles and that line is around a bio-geographical line (Limes norrlandicus) separating the northern boreal zone from the southern nemoral zone.

Ahlm et al. (1998) describes in a study how they measured antibodies against Puumala among a sample of 910 farmers and 663 non-farmers from various locations in Sweden. 12.9% of the farmers living north of the 59 th latitude showed anti-Puumala (6.8% among non-farmers) where anti-Puumala south of this latitude only was measurable in two out of 459 persons in total. The authors concluded that it was only in the mid- to north of Sweden that people had a significant risk of being infected with Puumala, a result in line with Niklasson & Leduc (1987).

The incidence in the most heavily infected areas was 23.5: 100.000 inhabitants (Vasterbotton County, Sweden) where the incidence in Sweden (total) is 1.3: 100.000. The southernmost cases were to be found near the 59 th latitude and the male/female ratio was 2.7 (Settergren et al., 1988) In the European part of Russia (Bashkirtostan) a similar pattern emerged with 10% of the female's sero-positive against Puumala (15% of the males). The incidence of human NE here were a bit higher (50: 100.000 inhabitants) and the same was the case for the male/female ratio (4.6) (Niklasson et al., 1993).

The incidences of Hantavirus among Danish rodents were studied in a design covering Funen (or "Fyen" - the middle island of Denmark) and Jutland (the peninsular mainland of Denmark). The majority of human NE cases in Denmark has been from Funen (only a few from Jutland) and among 310 sampled rodents in total, 11 sero-positive were found, all from Funen (Sironen et al., 2002). I don't know whether Hantavirus is observed among rodents from Zealand (The largest of the Islands in Denmark), but I would be surprised if such studies were not already being undertaken, meaning the results would probably start to be published within a couple of years.

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Ljunganvirus

Ljunganvirus is according to Samsioe et al., (2006) a virus which is closest related to Parechovirus but related too to Cardiovirus - a group of Picornavirus. This recently described virus (Niklasson et al., 1999) is according to patent number EP0941240 (in EU. In USA the patent number is 7.101.554) a suspected as an etiological agent behind various diseases among humans. The following is from the abstract of this patent:

"[snip].. Further aspects of the invention comprise...[snip]... use of the picornaviruses in medicaments, particularly for the treatment or prevention of Myocarditis, Cardiomyopathia, Guillain Barre Syndrome, and Diabetes Mellitus, Multiple Sclerosis, Chronic Fatique Syndrome, Myasthenia Gravis, Amyothrophic Lateral Sclerosis, Dermatomyositis, Polymyositis, Spontaneous Abortion, and Sudden Infant Death Syndrome, and methods of treatment of diseases caused by the picornaviruses."

Ljungan virus and the effect on humans:

A connection between exposure to Ljunganvirus and subsequent diseases in humans is until now of a more indicative nature. Both Niklasson et al., (2003a) and patent number EP0941240 in EU (7.101.554 in USA) describes the results of a comparing serological analysis performed on two groups of children. One (n= 53) had just been diagnosed as type 1 diabetics and the other (n= 17) was healthy controls at approximately the same age (samples taken between 1992-95). It turned out that the diabetics had significant more antibodies against ljunganvirus than the healthy children (p< 0.009). Niklasson et al., (2003a) further describes the results of a similar study on 239 newly diagnosed type 1 diabetic children and 37 healthy young adults (age not specified - samples taken between 1995-2000). A significant reverse proportionality was seen between the age of the children at diagnose and the level of antibodies against Ljunganvirus (Spearman: r= -0.151; p< 0.01). In his present patent application from 2003 (WO2004073710), Niklasson provide the results of several tests for the presence of Ljunganvirus in patients which either suffered, or died, of a number of different diseases. To this day it has not been possible for me to identify a scientific paper which mentions the same results which is the reason I mention them with the explicit reservation that these results to my knowledge has not been subject to a "peer review" nor is publicly available except in this patent application. The results is seen in Table 1 below.

Table 1 extracted from the pending patent application "Treatment of diseases caused by Ljungan virus by using Pleconaril" af Bo Niklasson (2003)

Ljungan virus and the effect on animals:

Samsioe et al., (2006) describes in their study of pregnant CD-1 lab mice the consequences of infecting the pregnant mice with Ljungan virus early in the pregnancy. The mice were additionally stressed by being weighed four times during the pregnancy and exposed to a Glucose Tolerance Test (GTT) late in the pregnancy. Of the seven infected mice, six gave birth to stillborn pups where the seven non-infected did much better (only one stillbirth; p= 0.029). In another experiment six pregnant females were infected and killed just before giving birth with the purpose of checking for embryo resorbtion; four showed evidence for such resorbtions. Among four females in total, which were not infected, none showed signs of embryo resorbtion (data not statistical significant). This experiment is by the way not directly comparable to the first since these mice were stressed by being weighed eight times during the pregnancy as opposed to the four weightings which were used in the first experiment. A third experiment seemed to suggest that the combination of stress and infection resulted in more still-births (5/8) than infection alone or stress alone (1/7 in both cases). Only by using a statistical trick was it possible to make data significant (one-sided p-value = 0.032). Samsoie et al. furthermore examined all pregnant females for antibodies against Ljunganvirus and all were sero-positive, while none of the non-infected mice were. The result was interpreted as a lack of viral transfer between the [presumably adjacent - not clarified in paper] cages. A great number of the stillbirths exhibited serious malformations. Finally, an experiment with adult offspring from infected vs. non-infected females showed that the time between formation of breeding pairs and subsequent births were related to the infection-background of the male and female in a pair (p= 0.014). Those pairs where both the male and the female had a non-infected mother were the fastest to give birth (35.8 days) where breedings where a male from an infected mother were put together with a female from a non-infected mother were the slowest (39.5 days; pair wise comparing: p= 0.009).

Niklasson et al., (2006b) had previously demonstrated that male offspring from CD-1 females which had been exposed to Ljunganvirus either on pregnancy day 4, 8, 12 or 17 could develop a type 2 diabetes-like disease at the age of 11 weeks provided they after weaning had been exposed to social stress by being kept in cages with three other males. Furthermore it seemed that early exposure to Ljunganvirus during pregnancy had an effect on the three variables used in the design (bodyweight, epididymal fat layer and glucose tolerance; p<= 0.003) and a clear trend was seen, indicating that the earlier the infection had been performed, the more powerful the effect (Spearman: p< 0.001). A test for antibodies against GAD65 (increased levels are a typical indicator of type 1 diabetes) proved to be negative. Contrary to the CD-1 mouse, bank voles do develop antibodies against GAD65 and the research behind the discovery of bank voles as a potential new animal model for type 1 diabetes can be seen here.

Niklasson et al., (2007) demonstrated in their research-letter that 16 BB-rats from a colony in Sweden along with 10 BB-rats from a colony in USA all tested positive for Ljungan virus in several organs. The infection in pancreas was limited to the beta-cells which produces insulin. However, it is noteworthy that the same publication in addition showed that 10 regular Wista rats and five Sprague-Dawley rats (all from Sweden) also was tested positive for Ljungan virus. As noted by the authors, this result would be "indicating that the virus may be found in several, possibly all, strains of rats".

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Borreliose and TBE (tick borne encephalitis)

Wildcaught bank voles can carry ticks (Ixodes ricinus) which in turn can be infected with a bacteria (Borrelia burgdorferi - a spirochete) which finally can cause the disease borreliose and TBE (tick borne encephalitis) if transferred to humans. Bank voles is one of many hosts for the tick and intimate handling with hundreds of bank voles carry therefore a certain risk of acquiring one of these, at worst, extremely annoying infections.

Pawelczyk et al., (2004) studied bank voles (C. glareolus; n= 112) and the Yellow-necked mouse (Apodemus flavicollis; n= 84) in North-East of Poland from May-October for occurrence of the adult tick; it's larvae and the bacteria B. burgdorferi sensu lato. In short the authors found that the number of bank voles was highest in the autumn (October) where the infestations were most intense in the beginning of the year and thereafter decreased. 87% of the voles were parasitized by either larvae (80%) or nymphs (7%) of the tick. The researchers used two methods to detect for the bacteria in the ticks and both methods (Polymerase Chain Reaction (PCR) and indirect immunoflourescense assey (IFA)) showed that the larvae's were infected with B. burgdorferi. According to the IFA, the infection rate increased from May till October (12.5% - 15.6%) in concordance to the PCR method, which too showed an increase (4% - 8%). Tissue samples from the ears showed that 2.5% of the bank voles were positive for B. borrelia DNA, meaning they were infected by this bacteria.

However, in reality I doubt a vole keeper will be at a particular risk of getting borrelia. Any ticks present will probably stay attached on the vole or, in case of a vole dying in its cage, stay in the bedding, which most likely will be discharged soon after the dead vole is found.

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Various other infections.

Fernie & Healing (1976) established that English Bank voles was infected with Campylobacter - a type of bacteria which can cause cows to become sterile; provoke sheep to miscarriage and make pigs dysenteric. Kaplan et al., (1980) examined English voles (C. glareolus) and the Skomer vole (C. glareolus skomerensis and discovered antibodies against Ectromelia (Mouse pox) virus; Louping ill virus; Reovirus III; Lymphocytic choriomeningitis virus and Encephalomyocarditis virus. The vast majority of the antibodies were against Pneumonia Virus of Mice and Sendai virus.

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Last revised the 3. June 2007