**2. Entry and survival** *Coxiella burnetii* **in the cells**

*Coxiella burnetii* after the entry into the organism, is phagocytosed by macrophages. The entry of *Coxiella burnetii* into monocytes and macrophages is lakely to be critical for its adaptation to host cells and development of Q fever (Capo et al., 1999). The bacterial cells multiply in phagolyosome and next cells burst, spreading the pathogens throughout the body. In animals, they are mostly located in the lung, mammary gland, testis, lymph nodes, uterus and placenta. The disease process may be also extended to the liver and cardiovascular system. There are views that the animal can be infected lifelong but it takes place in a latent form. The amplification of larger number of bacteria and prevalence of typical symptoms of Q fever occurs during pregnancy or by the action of immunosuppressive agents. *Coxiella burntii* survives and divides in a phagolisosome (Fig.1). The small and large forms express different genes that permit the bacterium to survive in the acidified environment of phagolisosome (Arricau-Bouvery & Rodolaski, 2005).

Fig. 1. Life cycle of the bacteria (Arricau-Bouvery & Rodolakis, 2005) (1). Entry of the spore in the eukaryotic cell and acidification of the endosome of the phagosome. (2) Multiplication of small-cell variants (SCV) by transverse binary fission and differentiation to large-cell variants (LCV). (3) Fusion of the endosome with the lysosome, acidification of the phagolysosomal. (4) Multiplication of LCV by transverse binary fission, differentiation of LCV to SCV and development of the polar endospore in LCV. (5) Release of the spore and SCV out of the cell.

### **3. Epidemiology**

380 A Bird's-Eye View of Veterinary Medicine

preventing CR3 engagement. It is possible that *Coxiella burnetii* induced impairment of CR3

The heterogeneity among strains of *Coxiella burnetii* is low degree (Vodkin et al., 1986). However, when DNA from 38 *Coxiella burnetii* isolates was examined by using restriction fragment length polymorphism (RFLP) analysis, six genomic groups (I to VI) were detected (Hendrix et al., 1991). The genome size of *Coxiella burnetii* nine Mile strain amounts to 2.1 Mb. The size of genome is highly variable among different isolates and ranging from 1.5 to 2.4 Mb (Willems et al., 1998). Genomic groups (I, II and III) are associated with animal, tick or acute Q fever in human, whereas group IV and V are isolated from human Q fever endocarditis cases. Group VI isolates were obtained from feral rodents in dungway, and

*Coxiella burnetii* is the well-known causative agent of Q fever, but neglected as zoonosis. Q fever has spread worldwide both in humans and in animals (Kruszewska et al., 1996). C*oxiella burnetii* can infect many animal species including mammals, birds and arthropods such as ticks. Generally, Q fever is asymptomatic, but it can lead to abortions and stillbirths in mammals. In these animals, *Coxiella burnetii* can induce pneumonia as well as abortion, stillbirth and delivery of weak lambs, calves or kids, which are the most frequent clinical sings of the disease. *Coxiella burnetii* in humans causes highly variable clinical manifestations ranging from acute to fatal chronic infections. However, about 60% of the infections are asymptomatic seroconversions. Acute Q fever is mainly a flu-like disease, or atypical pneumonia or hepatitis. Q fever is essentially an airborne disease. The infections occur after inhalation of aerosols generated from infected placentas, body fluids or contaminated manure. Transmission of this pathogen is generally associated with abortion of domestic

Tetracyclines are the best for treating Q fever. Although, Q fever endocarditis has been treated by the use of the combination of doxycyline with chloroquinolone. The time of treatment is very long and it takes for 18 to 36 months in order to cure chronic Q fever

*Coxiella burnetii* after the entry into the organism, is phagocytosed by macrophages. The entry of *Coxiella burnetii* into monocytes and macrophages is lakely to be critical for its adaptation to host cells and development of Q fever (Capo et al., 1999). The bacterial cells multiply in phagolyosome and next cells burst, spreading the pathogens throughout the body. In animals, they are mostly located in the lung, mammary gland, testis, lymph nodes, uterus and placenta. The disease process may be also extended to the liver and cardiovascular system. There are views that the animal can be infected lifelong but it takes place in a latent form. The amplification of larger number of bacteria and prevalence of typical symptoms of Q fever occurs during pregnancy or by the action of immunosuppressive agents. *Coxiella burntii* survives and divides in a phagolisosome (Fig.1). The small and large forms express different genes that permit the bacterium to survive in

the acidified environment of phagolisosome (Arricau-Bouvery & Rodolaski, 2005).

function results from uncoupling αvβ3 integrin from IAP (Capo et al., 1999).

their pathogenicity is unknown (Maurin & Raoult, 1999).

ruminants, particularly sheep (Arricau-Bouvery & Rodolaski, 2005).

**2. Entry and survival** *Coxiella burnetii* **in the cells** 

(Maurin & Raoult, 1999).

#### **3.1 Zoonotic aspects**

In humans, Q fever occurs the most often in direct contact with infected animals in slaughterhouses, as well as fur and veterinarians. Infections from human to human are very rare, and may have place especially in hospitals where patients infect the others through sputum released during coughing. Sporadic human infections of Q fever occurred after contact with infected parturient women, via transplacental transmission resulting in congenital infections, during autopsies, intradermal inoculation or blood transfusion. It has been postulated that transmission of *Coxiella burnetii* among mammals occurs mainly via inhalation of infected dust and aerosols (Maurin & Raoult, 1999). It is very difficult to explain some cases of *Coxiella burnetii* infections. The literature dates showed that there is possibility of sexual transmission of Q fever among mammals. The studies showed that heifers infected intravaginally with a suspension of *Coxiella burnetii* shed bacteria in their urine few days later. Moreover studies on nine Polish patients, who were employed in Spain during sheep shearing season showed occurrence of antibodies to *Coxiella burnetii* antigens in their serum. The antibodies were detected also in their spouses but they did not occur in sera from the other family members. Moreover, scanning electron microscopy of

Epidemiology, Zoonotic Aspect and Current Epidemiological Situation of Q Fever in Poland 383

Bouvery & Rodolaski, 2005). Despite the isolation of *Coxiella burnetii* in the placenta and milk sick of mothers, children are born healthy (Lepe et al., 1999). Mortality in humans is relatively low at 1-2%, except for tropical countries where it amounts to up to 9% (Moquin et

Cattle, goats and sheep are considered the primary reservoirs that human contamination comes from. Epidemiological data indicated that dairy cows are more frequently chronically infected than sheep, and they are the most important source of human infections. The duration time of *Coxiella burnetii* excretion in infected animals depends on species and type

Ticks have been considered a reservoir and a vector of *Coxiella burnetii*. In the nature, there are about 40 species of ticks transmitting the infections including *Rihicephalus sanguineus*, *Amblyomma triuguattum* (Maurin & Raoult, 1999). The infection is transmitted from one stage to the next in the ticket cycle, and transovarian infection is observed. Ticks become infected after ingestion of infected mammal blood that in the time of the bacteremia. Microorganisms multiply mainly in the epithelial cells of the middle tick gut, then penetrate the intestinal wall, hemocytes and connective tissue of internal organs. Hence an infected tick is a carrier of the *Coxiella burnetii* for life, and its saliva may contain very high concentration of agent (108 – 1011) (Niemczuk, 2010). *Coxiella burnetii* in ticks, as in mammals, are in phase I and they are highly infectious. Morover, ticks are not considered essential in the natural cycle of *Coxiella burnetii* infections in livestock because animals can have many other opportunities to become infected. Ticks may play a significant role in the transmission of coxiellosi among the wild birds and vertebrates such as rodents and lagomorphs (Maurin & Raoult, 1999).

Cats and dogs may be reservoirs of *C. burnetii*. Dogs may be infected by tick bite, consumption of placentas or milk from infected ruminants, and the aerosol route. In the literature, the cases of Q fever human infections after contact with parturient cats are described in Nova Scotia (Kosatsky, 1984). Moreover, wild mammals, including horses, rabbits, swine, camels, water buffalo, rats and mice constitute the reservoirs of *Coxiella burnetii*. The serological studies of rats in the UK have shown anti-phase II antibody seroprevalences ranging from 7 to 53%

Birds, including pigeons, chickens, ducks, geese and turkeys can be infected with coxiellosis. Infected domestic poultry can be the sources of infections in human. People become infected by consumptions of raw eggs or inhalation of infected fomites (Maurin & Raoult, 1999).

According to world experts on counter-terrorism, the agent that causes Q fever, is considered as an effective component of biological weapon (Arricau & Rodolaski, 2005). It is a potential agent of bioterrorism because of its accessibility, low infection dose, resistance to environmental degradation, and aerosol route of transmission. The minimum number of pathogens is required for human infection is 1-10 microorganisms. According to WHO, 50 kilograms of powder containing *Coxiella burnetii* can cause the comparable number of cases to tularemia or anthrax (Spicer, 1994; Moquin 2002). Q fever, although not characterised by high mortality, is important in wartime because the disease is severe, and the patient requires long-term care. Furthermore, the high resistance of the bacteria to drying, moisture, high or low temperature, promotes long-term being in the air, on skin, wool and straw

of samples tested (Arricau-Bouvery N. & Rodolakis, 2005) (Tab. 1).

among wild brown rat populations (Webster et al., 1995).

al., 2002).

**3.2 Reservoirs** 

spermatozoa cells from patients with Q fever has revealed the presence of attached bacteria. (Kruszewska et al., 1993, 1996).

The incidence of Q fever in human occur very often during spring and early summer when it is warm, dry and windy because the environmental survival allows it to be transported by wind far away from its original source. Such environmental conditions in Jenna (German) in June 2005 caused that *Coxiella burnetii* - infected sheep, grazing and lambing on the meadow bordering a residential brought about infection in 331 human (Gildsdorf et al., 2007).

The source of human infections is often unknown, although sheep and goats are more frequently related to Q fever outbreaks in humans (Glisdorf et al., 2005). The largest Q fever outbreaks occurred in the Netherlands, involving 3,921 human cases in the years 2005-2009. The dairy goats and sheep were considered the source of the human Q fever outbreak. The disease was found in about 60 farms these animals (Roest et al., 2011).

The infection by ingestion (mainly drinking raw milk) is probably a minor factor of risk, and at present it constitutes even a point of controversy (Maurin & Raoult, 1999; Krumbiegel & Wiśniewski, 1996). Drinking contaminated milk has induced seroconversion in human volunteers but without clinical signs (Benson, 1963). However, some studies have reported clinical diseases linked to the ingestion of cheese (Hatchette et al, 2001; Fishbein & Raoult, 1992) but infection by inhaling contaminated dust or aerosols cannot be excluded. The serological and molecular studies performed in the herds, where antibodies were present in blood of lactating cows, showed that *Coxiella burnetii* DNA was detected in the milk (8.7%). The antibodies were detected only in the serum of 1 % of young cattle selected from these herds (Muskens, 2011).

*Coxiella burnetii* in humans causes highly variable clinical manifestations ranging from acute to fatal chronic infections. Initially, there is typically a noticeable slight increase in internal body temperature lasting for several days. In addition, eye inflammation is stated, as manifested by greater amounts of fluid seromucinous flowing from the conjunctiva sac and nose. These general symptoms do not give rise to suspicion of Q fever. Sometimes only the prevalence of many cases of people with the acute symptoms of flu can indicate the occurrence of the disease in animals. It comes more often to premature births and miscarriages. Swelling and local haemorrhages can be observed in the placenta of infected animals. The further course of disease depends on the degree of virulence of the agent and the immune status of animals. Acute form of Q fever is mainly a flu-like disease, atypical pneumonia or hepatitis. Atypical pneumonia is characterised by fever, headache and myalgia. Despite the prevalence of pneumonia, cough can be absent. The hepatitis could be asymptomatic, only with the raise of transaminase levels, or the infectious hepatitis - rarely with jaundice (Fournier et. al., 1998).

In about 5% of the cases, the disease may become chronic form and it can lead to the endocarditis, chronic fatigue syndrome or repeated abortions. Endocarditic is the most frequent. It represents 1.5 - 2.5% all human cases of endocarditis. Chronic fatigue syndrome is characterised by an inappropriate fatigue, myalgia, arthralagia, night sweats and changes in mood. This chronic forms occur very often in Australia (Arricau-Bouvery & Rodolaski, 2005). In pregnant women, *Coxiella burnetii* can cause placentitis leading to abortion, neonatal death, premature birth and low birth weight. The risk of chronic Q fever leading to repeating miscarriages, is very high when the infection occurs during pregnancy (ArricauBouvery & Rodolaski, 2005). Despite the isolation of *Coxiella burnetii* in the placenta and milk sick of mothers, children are born healthy (Lepe et al., 1999). Mortality in humans is relatively low at 1-2%, except for tropical countries where it amounts to up to 9% (Moquin et al., 2002).
