Table 1 In vivo studies from the scientific literature performed on young calves to assess the impact of virus/bacteria coinfection on BRD

Collier et al. [115]

BoHV-1

3 days

M. haemolytica

Coinfected group: longer duration of illness

3

Hamdy et al. [15]

BPIV-3

6 h

P. multocida/M. haemolytica

BPIV-3 group: no respiratory disease, transient leukopenia Coinfected group: severe respiratory disease and pneumonic lesions

3

The animals were stressed, which could be a confounding factor

Saunders et al. [92] Trial 7

BPIV-3 (Intratracheal, 5 mL of 10⁶ TCID₅₀/mL)

30 days

P. multocida/M. haemolytica (Intratracheal, 10 mL of 10⁹ CFU/mL)

BPIV-3 group: slight febrile response and leukopenia, nasal discharge and cough Exposure to M. haemolytica and P. multocida one month later did not provoke illness

2

Small number of animals (2), lack of mono-infected controls

Saunders et al. [92] Trial 8

BPIV-3 (Intratracheal, 5 mL of 10⁶ TCID₅₀/mL)

Simultaneous

P. multocida/M. haemolytica (Intratracheal, 10 mL of 10⁹ CFU/mL)

BPIV-3 group: nasal discharge until day 3 Coinfected group: 40 °C fever and increased nasal discharge until day 11

3

Small number of animals (2), lack of non-infected controls

Baldwin et al. [116]

BPIV-3

M. haemolytica

Coinfected group: more severe respiratory symptoms upon subsequent exposure to M. haemolytica

3

Collier et al. [117]

BoHV-1 (Intratracheal)

30 days

M. haemolytica (Aerosol)

Coinfected group: bronchopneumonia leading to the death of one calf

4

Jericho et al. [118]

BoHV-1 (Aerosol, 10⁶ to 10¹⁰ TCID₅₀/mL)

3 to 4 days

M. haemolytica (Aerosol, 5.5 × 10⁵–1.8 × 10¹⁰ CFU/mL)

Coinfected group: signs of bronchopneumonia ~ 4 days after virus exposure M. haemolytica group: no clinical signs

3

Viral and bacterial shedding were determined only after exposure; unclear number of animal/group

*Al-Darraji et al. [120, 124, 165, 166]

BRSV (Transtracheal, 20 mL of 2.9 × 10⁴ PFU/mL)

3 and 5 days

M. haemolytica biotype A serotype 1 (Transtracheal, 5 mL of 3 × 10⁷ CFU/mL)

M. haemolytica group: reduced physical activity BRSV group: inactivity, fever Coinfected group: inactivity, dry and intermittent cough, fever, increased respiratory rate, dyspnoea, anorexia, signs more pronounced in 5 day delayed group, loss of condition until the end of the experiment

4

Yates et al. [119]

BoHV-1 (Aerosol, 10⁷ PFU)

4, 10, 20 and 30 days

M. haemolytica biotype A serotype 1 (Aerosol, 10⁶ PFU)

Coinfected group: higher fever, lung and pharyngeal lesions more severe in animals with a 4-day delay

3

Lack of control groups (non-infected, mono-infected)

Carrière et al. [120]

BPIV-3 (Aerosol, 100 mL of 5 × 10⁴ TCID₅₀)

4 and 7 days

M. haemolytica biotype A serotype 1 (Aerosol, 100 mL of 10¹² CFU)

All groups (BPIV-3, M. haemolytica and coinfected): no difference in terms of lung lesions, increase in rectal temperature and respiratory rate

2

*Trigo et al. [124]

BRSV (Aerosol)

0, 3 and 6 days

M. haemolytica (Intranasal)

Virus or bacteria alone groups: mild clinical response BRSV + M. haemolytica superinfected group: increased pulmonary lesions; mono-infected groups: no observed lesions Coinfected group: higher rectal temperature compared to M. haemolytica group

3

Potgieter et al. [121]

BVDV (Endobronchial inoculation)

5 days

M. haemolytica (Endobronnchial inoculation)

BVDV group: fever, nasal discharge, cough M. haemolytica group: mild signs Coinfected group: severe fibrinopurulent bronchopneumonia and pleuritis

3

Potgieter et al. [129]

BRSV (Endobronchial inoculation, 10⁸ TCID₅₀)

8 days

H. somni (Endobronchial inoculation, 10⁷-10⁹CFU)

BRSV group: no signs H. somni group: mild signs (fever, occasional cough and depression) Coinfected group 10⁹ CFU: severe clinical signs (mortality, diffused pneumonic lesions); 10⁷ CFU: mild clinical signs, less extended lung lesions

4

*Sharma et al. [125]

BRSV (Intranasal)

6 days

M. haemolytica biotype A serotype 1 (Intranasal and intratracheal, 5 mL of 9 × 10⁷ CFU/mL)

Coinfected group: increased disease score, higher fever and higher mortality than both mono-infected groups

4

BRSV dose is not reported

Gånheim et al. [122]

BVDV (Intranasal, 2 mL of 10⁶ TCID₅₀/mL)

5 days

M. haemolytica (Intranasal, 10 mL of 5 × 10⁷ CFU/mL)

Mono-infected groups: a few calves had fever and depression Coinfected group: all animals had fever and mild to severe depression, one calf did not recover, slower bacterial clearance, duration of elevated APPs lasted longer in coinfected group than BVDV but similar in Mannheimia group

4

Gershwin et al. [128]

BRSV (Aerosol, 5 mL of 10⁶ TCID₅₀)

6 days

H. somni (Intratracheal, (10 mL of 10⁸ CFU)

BRSV group: no lung lesions H. somni group: limited lung lesions Coinfected group: higher magnitude and duration of clinical signs, isolation of H. somni in lungs, extended lung lesions

3

Pathogen replication profile in animals is missing

Prysliak et al. [126]

BVDV (Intranasal aerosol⁷, 4 mL of 10 PFU/mL)

4 days

M. bovis (Intratracheal, 4 mL of 1.5 × 10¹⁰ CFU)

BVDV group: no lung lesions nor clinical signs, rectal temperature spike at 8 dpi Coinfected group: no lung lesions nor clinical signs

2

Prysliak et al. [126]

BoHV-1 (Intranasal aerosol, 4 mL of 10⁵ TCID₅₀/mL)

4 days

M. bovis (Intratracheal, 4 mL of 1.5 × 10¹⁰ CFU)

Coinfected group: higher weight loss and rectal temperature, higher rate of M. bovis isolation from blood of coinfected animals, more extensive lung lesions and shorter survival terms

4

Lack of BoHV-1 mono-infected group

Zhang et al. [130]

IDV (Intranasal, 10 mL of 10⁷ TCID₅₀/mL)

5 days

M. haemolytica biotype A serotype 1 (Intratracheal, 30 mL of 10⁹ CFU)

Coinfected group: decreased clinical score compared to Mannheimia group, retarded viral shedding compared to IDV group; Mannheimia group: slightly increased lung lesions

2

Lion et al. [131]

IDV (Nebulization, 10 mL of IDV 10⁷ TCID₅₀/mL)

Simultaneous

M. bovis (Nebulization, 10¹⁰ CFU)

All infected groups: clinical signs present Coinfected group: earlier appearance and increased severity of clinical signs, gross lung lesions at 6 dpi

3