Q Fever
an emerging disease RAPHAﾃ記 GUATTEO
Q Fever, an emerging disease
Experimental infection Until today, only one experimental infection has been conducted in cattle at the French National Institute for Agricultural Research (INRA) in Tours (France). This study was carried out among 12 heifers aged between 8 and 11 months in 1973 (Plommet et al., 1973). The inoculation of Coxiella burnetii was made by intradermal injection. Then, heifers were followed during 18 months. Two phases –acute and chronic– were observed during the evolution of the infection (table 1). In goats, experimental infections were conducted, especially to assess the efficacy of a vaccine against Coxiella burnetii infection to prevent clinical signs, the goats being a more relevant model due to the high expected number of abortions in case of Coxiella burnetii infection in comparison with sheep and cattle, where abortions are scarcest events. Within a recent study (Arricau-Bouvery et al., 2005) at 84 days of gestation, 12 goats were subcutaneously challenged with 104 bacteria of Coxiella burnetii strain CbC1. In addition, 27 goats were not challenged. The result in terms of occurrence of clinical signs is displayed in table 2. Four criteria were used to assess the consequences of the challenge on pregnancy in the 2 groups: mean duration of gestation (in days), percentage of abortions, percentage of placenta with detection of Coxiella at parturition and percentage of infected fœtuses.
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5. CLINICAL ASPECTS OF Q FEVER
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Q Fever, an emerging disease
Table 1. Evolution of infection in heifers between 8 and 11 months of age after experimental inoculation of Coxiella burnetii (Plommet et al., 1973).
Phases
Acute phase (first 24-48 hours post-inoculation)
Clinical signs and lesions
• Severe hyperthermia • Clear cut and rapid pneumonia
Number of cases/ animals 12/12 12/12
Spontaneous clinical “recovery” observed during the 7 following days
• Histological examination: myocardial Chronic phase
and pulmonary lesions (lesions which are also found in humans with chronic disease) • Reproductive disorders: 2 out of 11 heifers aborted and 3 did not get pregnant afterwards • Anorexia during the 6 first days postinoculation but growth was not altered
Abortions: 2/11 Infertility: 3/11
Table 2. Occurrence of abortions following inoculation of Coxiella burnetii in goats (ArricauBouvery et al., 2005).
Number of goats Duration of gestation (days) Abortion (%) Number of kids per goat Percentage of goats with contaminated placenta (%)
not challenged
challenged
27
12
150 (±1.8)
141 (±8)
15
75
1.9 (±0.88)
1.75 (±0.87)
ND
100
All together, these results confirm Coxiella burnetii as an abortifacient agent.
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5. CLINICAL ASPECTS OF Q FEVER
Natural infection Clinical manifestations of Coxiella burnetii infection Clinical manifestations of Q fever are less referenced in ruminants than in humans. In fact, infection due to Coxiella burnetii appears often to be subclinical (Aitken, 1989; Maurin and Raoult, 1999; Rodolakis, 2009). The most common clinical signs observed are related to reproductive disorders (Lang, 1990; Arricau-Bouvery and Rodolakis, 2005; Wouda and Dercksen, 2007): ◗ Abortions (fig. 1). ◗ Stillbirths. ◗ Birth of weak offspring. Q fever seems also associated with endometritis and retained placentas (Arricau-Bouvery and Rodolakis, 2005). However, it is still unknown if this relation is due to the bacterium itself or it is the abortion which predisposes to retained placentas which, in turn, predisposes to metritis. Thus, Q fever should be included in infertility differential diagnoses (EFSA, 2010).
Figure 1. Aborted calf with no external alterations.
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Q Fever, an emerging disease
Other manifestations are also attributed to Q fever. Martinov et al. (1989) report that experimentally infected ewes suffered from fever or respiratory disorders. These signs have been observed during the acute phase of the disease and followed by reproductive disorders (stillbirths, birth of non-viable lambs). In goats, Q fever would be also responsible for pneumonia (Berri et al., 2007). Coxiella burnetii has been sometimes blamed for inducing subclinical mastitis (Barlow et al., 2008) and clinical mastitis (To et al., 1998) in dairy cattle. However, these studies cannot differentiate between Coxiella as the trigger for mastitis and the simple detection of Coxiella shedding in cattle with high concentrations of somatic cells in milk.
1 Up to date, it has been clearly shown: ◗ The role of Coxiella in abortions.
2 Up to date, it is strongly suspected, but not definitively confirmed: ◗ The role of Coxiella in reproductive disorders (infertility, metritis, retained placentas) and even in cases of stillbirths (particularly in cases of premature calvings).
3 Further research may be required to determine: ◗ If Coxiella burnetii is involved in respiratory disorders. ◗ If Coxiella burnetii is involved in subclinical mastitis.
Abortions associated with Coxiella burnetii Abortions due to Coxiella burnetii are more frequent in ewes and goats than in cattle (Parisi et al., 2006; Berri et al., 2007). Apart from a supposed higher susceptibility to the infection in goats, seasonal management of reproduction in small ruminants and births in confined spaces (in comparison with the extended period of calving in cows) is a plausible element that might explain the outbreak of abortions observed (Arricau-Bouvery et al., 2005). In a study carried out in the North of Spain, Coxiella burnetii had been detected in 9 % of sheep flocks where abortions occurred (Oporto et al., 2006). Similarly, in Sardinia (Italy), the bacterium has been isolated in 11 % of analysed abortions (Masala et al., 2007). 74
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5. CLINICAL ASPECTS OF Q FEVER
Q fever is often considered as the first or second cause for infectious abortions in cattle (together with neosporosis), in goats (together with toxoplasmosis) and in sheep (together with chlamydiosis). A recent study conducted in the West of France has analysed 846 cattle abortions with PCR test using vaginal swab samples. Among these abortions, 166 (i.e. 19.6 %) were PCR positive for Coxiella burnetii detection (Guatteo, personal communication). The number of abortions due to Coxiella burnetii within the herd is highly variable. In goats, it can reach up to 90 % of females in the flock (Palmer et al., 1983). In both species, after the first week post abortion, the shedding of Coxiella burnetii rapidly decreases (table 3 and table 4). Apparently, any clinical sign can be observed before the onset of an abortion due to the infection with Coxiella burnetii. Abortions appear to be more frequent in the last third of gestation (Zeman et al., 1989; Arricau-Bouvery and Rodolakis, 2005) as bacteria are more easily detected in placentas of cows who have aborted in the last third of pregnancy (Bildfell et al., 2000). However, the fact is that abortions are also more easily detected and, consequently, investigated during this period. The same applies to goats (Moeller et al., 2001). Abortions occur in the first parturition after the infection with Coxiella burnetii. It seems that females who have already aborted once do not abort again in subsequent gestations (Babudieri, 1959; Lang, 1990; Berri et al., 2007). In other study of Berri et al. (2002), no abortion was observed in the second or third gestation after an abortion outbreak within a same flock of infected ewes. Moreover, newborn lambs were healthy at birth. On the contrary, it appears that goats can abort, in rare cases, in two consecutive gestations. Thus, in a flock of sixty goats and after a Q fever outbreak, two goats gave birth to dead kids in two consecutive gestations and another one aborted twice (Berri et al., 2007). This information is not available for cattle, as cows who have aborted are frequently culled by cow farmers.
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Q Fever, an emerging disease
Table 3. Shedding kinetics of Coxiella (detected using PCR test applied on vaginal mucus) after abortions (n = 12 Coxiella-inoculated goats, Arricau-Bouvery et al., 2005).
Days after parturition
Weeks after parturition
0
1
2
3
1
2
3
4
5
6
7
8
+ + + + + + + + + + + +
+ + + + + + + + + + + +
+ + + + + + + + + + + +
+ + + + + + + + + + + +
+ + + + + + + + + + + +
+ + + + + + + + + + +
+ + + + + + + +
+ + + + -
+ + -
-
-
-
-
-
Table 4. Shedding kinetics of Coxiella (detected using PCR test applied on vaginal mucus) after abortions (n = 24 cows naturally infected) (Guatteo et al., 2011).
Cow 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
D0
D14
D21
D28
+ + + -
+ + + + -
PCR results + + + + + + + + + + + + + + + + + + + + + + + +
+ + + + + + + + -
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5. CLINICAL ASPECTS OF Q FEVER
Placenta lesions in abortions ◗ Lesions observed in abortions due to Coxiella burnetii are not specific (fig. 2) (Arricau-Bouvery, 2005). ◗ These lesions often appear as placentitis associated with necrosis (Bildfell et al., 2000; Sánchez et al., 2006; Moore et al., 1991; Van Moll et al., 1993). ◗ Usually, fœtuses look normal (Arricau-Bouvery, 2005). ◗ In goat fœtuses, hepatitis, nephritis and bronchopneumonia have been sometimes observed (Moeller, 2001; Moore et al., 1991). ◗ In cattle fœtuses, bronchopneumonia lesions have also been reported (Bildfell et al., 2000). ◗ In cattle, placenta inflammation is rarely observed when an infection exists but do not end up in abortion. This suggests the infection is often subclinical (Hansen et al., 2011). ◗ In case of cattle abortion, placenta lesions are apparent, being sometimes moderated (Muskens et al., 2012).
Figure 2. A proper collection and submission of bovine abortion samples can help the clinician in his diagnosis. 77
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