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PCV2 and reproduction failure in sows

Authors Vincent DEDET, DVM Auzalide Santé Animale, La Chouannière, Le Cannée 35380 Paimpont (France) [email protected]

François JOISEL, DVM, MSc MERIAL , 29, avenue Tony Garnier, BP 7123, 69348 Lyon Cedex 07 (France) [email protected]

Thaïs VILA, DVM MERIAL, 29, avenue Tony Garnier, BP 7123, 69348 Lyon Cedex 07 (France) [email protected]

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Summary Porcine Circovirus type 2 (PCV2) related diseases (PCVD) have been reported throughout the world, and reproductive failure can clearly be associated with PCV2 infection in sows. Following the guidelines set by evidence-based medicine, this bibliographic work highlights the PCV2-related reproductive failure, which has been described worldwide. It also draws attention to the increasing set of epidemiological studies, field trials and reports that show an association between the subclinical PCV2 infection of gilts and sows and their lifelong productivity.

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INTRODUCTION

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1. MATERIAL AND METHODS

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2. EXPERIMENTAL DATA

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2. 1. Trans-uterine inoculation of fetuses with PCV1

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2. 2. Trans-uterine inoculations of fetuses with PCV2

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2. 3. Oronasal inoculation of non-pregnant SPF gilts

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2. 4. Oronasal inoculations of pregnant sows with PCV2

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2. 5. Intra-uterine inoculation of PCV2-negative sows

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2. 6. Embryo exposure to PCV2

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3. EPIDEMIOLOGICAL DATA

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3. 1. Indirect proofs

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3. 2. Direct proofs 12 4. CLINICAL REPORTS

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4. 1. In cesarean derived-colostrum deprived (CDCD) piglets

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4. 2. In conventional farms

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5. ANECDOTAL REPORTS

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6. CONCLUSION

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REFERENCES

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Introduction Post-weaning Multisystemic Wasting Syndrome (PMWS) has emerged as a herd disease in Canada and in Europe in 1995/1996, and has been identified as linked to Porcine Circovirus type 2 (PCV2) infection in 1998. For the 10 following years, other PCV2-related diseases (PCVD) have been reported throughout the world. In a recent review about PCVD, reproductive failure is the last of the six items listed (Gillespie, 2007). It is described as including “abortions, stillbirths and foetal mummification”. The object of the present review is to screen the available published data in order to assess whether the mechanisms underlying this reproductive outcome of PCV2 infection are presently understood. We chose to follow the guidelines set by evidence-based medicine while performing this bibliographic work.

1. Material and methods The method used through the process of writing this review has followed the experience-based medicine1 recommendations regarding systematic reviews2. The question that guided our searching was structured according to the PICO method: Population, Indicator, Comparator, Outcome. This question was formulated as: “Can PCV2 infection be considered as a cause for reproductive failure in sows?”. Population considered were sow herds, or sow groups in experimental infection works (in some cases, the population considered were the fetuses/stillborn submitted to the diagnostic labs). Indicator was a reproductive failure (this inferred that the description of lesions such as myocardial necrosis in aborted foetuses/deadborn piglets was also an indicator of a reproductive failure). Comparator was taken either as the average reproductive performances of sow herds at regional/national levels, or as the “control” sows included in the case-control studies or in the experimental infection trials. Outcome is the presence of recent PCV2 infection in dams and/or the exclusive or nearly systematic presence of PCV2 in fetuses/stillborn piglets. The data that were consulted were:  The Pubmed database3, with the only key word “PCV2” in the first step of our search. This retrieved 320 references. It is to be noted that this search had not to be limited in time, since PCV2 has been first described in 1998, which is the year of publication of the oldest references retrieved by this search. It is to be noted that the Pubmed search with “PCV2 AND sows” only retrieved five references; which did not correspond to the amount of articles brought to our attention before beginning this extensive search. Consequently, each of the 320 abstracts available from the first search were read; those dealing with reproductive failure, experimental inoculation of sows and/or PCV2 lesions in aborted/stillborn piglets were selected for full article reading.  The table of contents of the proceedings of different Swine congresses (Leman Conference, ISU Swine disease Conference for Swine practitioners, George A. Young Swine Health and management Conference, IPVS and AASV) have also been screened, from 1996 to 2007. From 1996 to 1998, our screening was mostly focusing on reports of reproductive failure while from 1998 onwards, we focused on presentations dealing with PCV2.  We also consulted non-referenced journals with a peer-reviewed section, such as the Journal of Swine4 Health and Practice, the Pig Journal. Folia Veterinaria5 had a more erratic online presentation of its contents, none after 2003 being available online. Finally, two PhD thesis from Ghent University (Belgium) were available on the subject. Both were extensively read. In total, 59 references were found relevant to our question, and have been read in full. The reliability of the association between the presence of the agent (PCV2) and the occurrence of the outcome (reproductive failure) is here presented through the hierarchy retained in the evidence-based medicine approach: experimental studies with inoculation and re-isolation/sequencing of the agent come first. Case-control studies prevail on clinical reports. Finally, anecdotal reports are mentioned, although they should not be considered as providing conclusive answers to our question. 1 2 3 4 5

For more detailed information, see the UK Centre for evidence-based Medicine at http://www.cebm.net/?o=1016 See : “Teaching EBM with Learners' questions”, by Scott Richardson, on the same website (download section). http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed Journal of the American Association of Swine Veterinarians : www.aasv.org This Slovakian Journal has been presented to us by Dr G. Bilkei, which we acknowledge. More details are available on: http://www.uvm.sk/dept/journals/folia/contents.html

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2. Experimental data 2. 1. Trans-uterine inoculation of fetuses with PCV1 Late-term pregnant sows underwent laparotomy, the uterine horns were exposed to air and each fetus was injected through the uterine wall intramuscularly with PCV1 (Johnson et al, 1999). One of the sows died prior to farrowing. The remaining two sows farrowed as expected. One gave birth to nine liveborn pigs and one stillborn pig. The other sow gave birth to eight liveborn, one stillborn and five mummified fetuses. No gross lesions were observed in any of the animals that died or were euthanised. PCV1 was successfully isolated from some fetuses, all stillborn pigs and other piglets euthanised at birth. Prior to suckling colostrum, all piglets had anti-PCV1 antibodies. This demonstrates that PCV1 is capable of infecting and replicating in late-term fetuses. The presence of stillborn, weak-born and mummified fetuses “suggests that reproductive failure could result following foetal infection with PCV1”.

2. 2. Trans-uterine inoculations of fetuses with PCV2  Late-term pregnant sows underwent laparotomy, the uterine horns were exposed to air and each fetus was injected through the uterine wall intramuscularly with PCV2 (Johnson et al, 1999). One sow farrowed three stillborn, two partial mummies, five weakborn and two liveborn piglets. The other two sows farrowed 22 liveborn and two stillborn piglets. Piglets at farrowing of within their first week of age had relatively large lymph nodes. PCV2 was successfully isolated from the partial mummies, stillborn and weakborn piglets. The piglets that did not receive colostrum had antiPCV2 antibodies. This demonstrates that PCV2 is capable of infecting and replicating in late-term fetuses. The presence of stillborn, weak-born and mummified fetuses “suggests that reproductive failure could result following foetal infection with PCV2”. The absence of clinical disease after weaning suggests that the development of PMWS may not occur following congenital infection.  The Virology unit at Ghent Veterinary Faculty (Belgium) reproduced this work, with inoculation at different gestation stages for conventional (PCV2 seropositive) sows (Sanchez, 2003a). The PCV2 1121-isolate passaged in PK15 cells (4th passage) was used. In each gravid sow, two foetuses were inoculated via trans-uterine route, with 104.3 TCID50 PCV2. This procedure was applied for two sows at 57, 75 and 92 days of gestation. Twenty-one days after virus inoculation, sows were sacrificed, hysterectomies were performed and the fetuses were collected. As a positive control, day-old CDCD piglets received the same inoculum (intranasally and intratracheally) (Sanchez et al, 2003b). All inoculated fetuses provided a positive PCV2 isolation, but the heart was the only organ to be positive regardless of gestational age at inoculation. Viral antigens were localized in cardiomyocytes, hepatocytes and macrophages during foetal life and only in macrophages postnatally. Infected macrophages were observed in all types of tissues examined (heart, liver, lungs, spleen and inguinal lymph nodes) both in fetuses and in piglets. The absolute number of PCV2-positive cardiomyocytes was highest in 57-day fetuses and changed in decreasing order in 75- and 92-day fetuses (p