Peripartum dynamics of Coxiella burnetii infections in intensively managed dairy goats associated with a Q fever outbreak in Australia

Highlights

• First-time kidding does are highly susceptible to C. burnetii shed at kidding.

• Fomites from infected farms pose a low risk of C. burnetii transmission to negative farms.

• No milk production loss associated with acute C. burnetii infections was observed.

Abstract

Coxiella burnetii may cause reproduction disorders in pregnant animals but subclinical infection in other animals. Unrecognised disease may delay implementation of control interventions, resulting in transmission of infection to other livestock and to humans. Seroreactivity to C. burnetii phase-specific antigens, is routinely used to interpret the course of human Q fever. This approach could be similarly useful in identifying new and existing infections in livestock herds to help describe risk factors or production losses associated with the infections and the implementation of disease-control interventions. This study aimed to elucidate the dynamics of C. burnetii infections using seroreactivity to phase-specific antigens and to examine the impact of infection on milk yield in goats in an endemically-infected farm that was associated with a Q fever outbreak in Australia. Seroreactivity pre- and post-partum and milk yield were studied in 164 goats (86 nulliparous and 78 parous). Post-partum, the seroprevalence of antibodies to C. burnetti increased from 4.7% to 31.4% throughout goats’ first kiddings and from 47.4% to 55.1% in goats kidding for the second or greater time. Of 123 goats that were seronegative pre-partum, 26.8% seroconverted over the three-month peri-partum period, highlighting the importance of controlling infection throughout this time. The risk of seroconversion was comparable in first or later kidders, suggesting constant risk irrespective of parity. No loss in milk production associated with seroconversion to phase 2 was observed within the first nine weeks of lactation. However, seroconversion to only phase 1 was associated with extra 0.276 L of milk per day (95% Confidence Interval: 0.010, 0.543; P = 0.042), which warrants further investigation to ascertain whether or not the association is causal. Further studies on seroreactivity and milk production over longer periods are required, as milk production loss caused by C. burnetti may be an additional reason to control the disease in goat herds.

Introduction

Coxiella burnetii is the causative agent of Q fever, a zoonotic disease characterized by a flu-like illness in its acute form as well as cardiac malfunction and granulomatous hepatitis in its chronic form in humans (Arricau-Bouvery and Rodolakis, 2005). The bacterium mostly circulates sub-clinically in domestic animals and wildlife although infections in pregnant animals have been reported to result in abortions, still-births, weak offspring and neonatal death (Raoult et al., 2005, Sánchez et al., 2006). Early detection of C. burnetii outbreaks in ruminant herds has previously been hindered by the subclinical nature of C. burnetii infections in non-pregnant animals and the failure to routinely diagnose causes of abortions on farms (Rodolakis et al., 2007, Schimmer et al., 2009). During the 2007–2010 Q fever epidemic in the Netherlands, the link between infected farms and human cases became apparent after implementation of mandatory reporting of increased abortion rates on farms (Schimmer et al., 2009).

In ruminants, coxiellosis is thought to cause reproductive loss through inflammation of the placenta following massive replication of C. burnetii in the trophoblast cells (Sánchez et al., 2006); up to 90 fold within three days of infection (Amara et al., 2010). Thus C. burnetii infections in ruminants and other domestic animals consequently lead to environmental contamination during parturition or abortion when the placenta and birth fluids are shed. This is considered to be the primary source of human and domestic animal C. burnetii infections, with transmission mainly occurring through inhalation of C. burnetii-contaminated dust and fluid aerosols (Tigertt et al., 1961, Angelakis and Raoult, 2010).

Intensive ruminant farming, which often involves synchronisation of oestrus and thus parturition, may result in very high rates of both environmental contamination and transmission of infection to susceptible hosts, with bacterial shedding from numerous infected ruminants giving birth within narrow timeframes. Such an effect may explain why a number of previous outbreaks have been associated with intensive ruminant farms: over 4000 human cases of Q fever occurred in the Netherlands between 2007 and 2010, with increased risk of infection associated with living in close proximity to intensively-managed dairy goat herds (Delsing and Kullberg, 2008). Similarly, 147 human cases in the United Kingdom were associated with lambing ewes in the West Midlands in 1992 (Guigno et al., 1992, Smith et al., 1993), and 23% of the residents in a rural German town were considered to have contracted Q fever from a large sheep farm in 1996 (Lyytikäinen et al., 1998).

Testing for antibodies and C. burnetii DNA in bulk tank milk (BTM) has been widely used as a surveillance method (Muskens et al., 2011, Van den Brom et al., 2012). However, BTM testing does not describe infection dynamics within herds which is important for identifying infection risk factors (Guatteo et al., 2007). BTM monitoring of C. burnetii epidemiology also excludes non-lactating animals and may not detect the initial stages of an outbreak involving fewer animals, leading to falsely negative enzyme-linked immunosorbent assay (ELISA) or polymerase chain reaction (PCR) results (Guatteo et al., 2007). Thus, testing individual animals is required to comprehensively investigate exposure and transmission within herds.

Serological reaction to phase-specific antigens of C. burnetii is routinely used to diagnose and interpret the course of Q fever in humans but has not been widely used to study C. burnetii infection in domestic animals (Cutler et al., 2007, Böttcher et al., 2011). Recent infections may be identified by the presence of IgM antibodies to phase 2 C. burnetii surface glycoproteins, which appear within two weeks of infection, or through detecting seroconversion or a fourfold rise in titre of IgG antibodies to phase 2 C. burnetii antigens (Cutler et al., 2007, Rousset et al., 2007, Schimmer et al., 2009, Delsing et al., 2011). Conversely, IgG antibodies to phase 1 C. burnetii antigens appear much later in the course of infection—about 114 days after infection in humans—which indicates convalescence, recrudescence or chronic disease, and could also be a marker of constant antigenic stimulation (Powell and Stallman, 1962, Kimbrough et al., 1979, Peacock et al., 1979). The sequential production of antibodies to phase 2 and phase 1 antigens of C. burnetii was initially described in guinea pigs (Stoker and Fiset, 1956) and has recently been described in goats (Roest et al., 2013). Phase-specific serology may therefore be a valuable tool for studying the dynamics of infection within herds and for prompt detection of new infections.

Since antibodies are produced within a short timeframe of usually 2–3 weeks in newly infected animals (Roest et al., 2013), detecting antibodies is useful for timely diagnosis of new infections. In contrast, detectable C. burnetii DNA is usually only present in secretions or excreta during late pregnancy and after parturition following the massive replication of organisms in the placenta (Sánchez et al., 2006, Berri et al., 2007, Rodolakis et al., 2007). There seems to be no evidence of regular shedding of C. burnetii by infected ruminants outside the peri-parturient period (Woldehiwet, 2004).

Early detection and timely implementation of disease control interventions could reduce production losses attributed to C. burnetii infections in ruminant herds. These are mainly due to reproductive wastage following C. burnetii-induced abortions and perinatal deaths (Masala et al., 2004, López-Gatius et al., 2012). Economic losses due to the cost of interventions such as vaccination and cessation of breeding as well as the cost of treating human infections and weeks of lost work have also been previously described (Garner et al., 1997, Van Asseldonk et al., 2013). For example, in the Netherlands outbreak, the retention payoff index (value of future profitability foregone) was estimated to be €250 per goat for breeding prohibition and €300 per goat culled (Van Asseldonk et al., 2013).

There is limited information on direct production losses due to C. burnetii infection in livestock other than those arising from reproductive anomalies. However, one study reported a strong association between shedding of C. burnetii in milk and the occurrence of chronic mastitis in dairy cattle (Barlow et al., 2008). In this study, we aimed to describe the dynamics of C. burnetii infections and also to examine the impact of infection on milk production in goats on an intensively-managed goat enterprise associated with a Q fever outbreak in Australia, using phase-specific seroreactivity and milk yield.