Table 2 Summary of studies on phage therapy in bacterial infections in poultry
From: Bacteriophage therapy to combat bacterial infections in poultry
Animals | Objective | Challenge | Phage application | Observations | Reference |
|---|---|---|---|---|---|
One-day-old chickens | Reduce contamination of poultry products by food-borne pathogens; reduce morbidity, disease severity and mortality | Oral inoculation with 100 μl fresh S. Enteritidis PT4 culture at 108 CFU/bird | Single oral application of phage cocktail (CNPSA1, CNPSA3 and CNPSA4) at 1011 PFU | 1. A single dose of a bacteriophage suspension with a high titre was highly effective in reducing the population of pathogenic bacteria in the digestive tract. 2. Reduction of 3.5 orders of magnitude in colony-forming units of S. Enteritidis PT4 per gram of caecal content | Fiorentin et al. 2005 |
6-week-old chickens | Reduce morbidity, disease severity and mortality | Oral challenge with S. Gallinarum at 5 × 108 CFU/mL | Bacteriophage CJø01 as feed additive at 106 PFU/kg | 1. Treatment using bacteriophages as a feed additive for chickens having contact with infected individuals led to a mortality rate of only 5%, as compared to 30% in the group that did not receive phage therapy | Lim et al. 2011 |
One-day-old chickens | Reduce morbidity, disease severity and mortality | Challenge with S. Enteritidis by oral gavage (0.25 mL) at 9 × 103 CFU/chick | Cocktails of 4 different bacteriophages obtained from commercial broiler houses (CB4∅) and 45 bacteriophages from a municipal wastewater treatment plant (WT45∅), administered by oral application at 108 PFU/chick | 1. Bacteriophages as cocktail in oral administration to prevent colonization by S. Enteritidis strains in poultry were only effective for a short time (24–48 h) with no long-term protective effect | Andreatti Filho et al. 2007 |
36-day-old chickens | Reduce morbidity, disease severity and mortality | Challenge with 1 ml of an 8.0-log 10 CFU/ml−1 suspension of S. Enteritidis | Bacteriophage 151 against S. Enteritidis, bacteriophage 25 against S. Hadar, bacteriophage 10 against S. Typhimurium. Bacteriophage suspensions administered by oral gavage at 109 PFU/ml and 1011 PFU/ml) | 1. Significant reduction in the concentration of two of three serovars (S. Enteritidis, Typhimurium) by 2–4 log units after administration of a bacteriophage suspension with a density of 1011 PFU | Atterbury et al. 2007 |
33-day-old quails | Efficiency of bacteriophage administration in prophylactic and therapeutic contexts | Oral challenge with 100 ml of S. Enteritidis at 1.2 × 109 CFU/mL | Single Salmonella-lysing phage (PSE) at 109 PFU/ml in 100 μl aliquot by oral gavage for 2 days | 1. 100% efficacy in eliminating S. Enteritidis strains from the tonsils, 6 h after application of bacteriophage suspension 2. PSE phage was more effective when administered prophylactically prior to S. Enteritidis infection than as a treatment for established S. Enteritidis infections. | Ahmadi et al. 2016 |
One-day-old chickens | Reduce morbidity, disease severity and mortality | Oral challenge with 0.5 ml of a suspension of S.Typhimurium at 2.4 × 105 CFU/mL or 7.9 × 105 CFU/mL | Bacteriophage cocktail (S2a, S9, S11), at an oral dosage of 106 PFU/bird on days 4–6 and 8–10 of age | 1. 10-fold reduction in bacteria in chicken ileum, caeca, liver and spleen 2. Synergistic antibacterial effect of oral commercial probiotic preparation applied together with a bacteriophage cocktail | Toro et al. 2005 |
One-day-old chickens | Reduce morbidity, disease severity and mortality | Oral challenge with 2.95 × 105 CFU/mL S. Enteritidis | Cocktail of 3 phages by aerosol spray at 108 PFU/ml/dose for each phage at 6 days of age (two daily doses) and probiotics administered at 1 day of age by coarse spray | 1. Effective method for reducing S. Enteritidis colonization in intestinal chickens, leading to complete elimination of deaths in broiler chickens caused by infection with S. Enteritidis | Borie et al. 2009 |
One-day-old chickens | Reduce morbidity, disease severity and mortality | Oral challenge with S. Enteritidis at 5 × 108 CFU/mL | Bacteriophage CJ07 as a feed additive at three concentrations (105, 107 and 109 PFU/g) for 21 days after challenge with S. Enteritidis | 1. Highest doses of bacteriophage significantly inhibited the replication of pathogens in the digestive tract of the chickens. 2. The efficacy of phage therapy should be maximized by the use of a high titre of bacteriophage to reduce Salmonella colonization by passive inundation. | Lim et al. 2012 |
3-day-old birds 7-day-old birds | Reduce morbidity, disease severity and mortality | E. coli by injection of 104 CFU/mL into the thoracic air sac at 7, 8, or 10 days of age | Bacteriophages SPR02 applied directly to air sac in a range of titres from 108 to 103 PFU Bacteriophage suspension applied to drinking water (103 or 104 PFU/ml) | 1. Reduced mortality rates to 5% and 25% and 100% depending on the titre of bacteriophage suspensions 2. Reduced mortality rates to 5 and 25% depending on the titre of bacteriophage suspensions | Huff et al. 2002 |
3-week-old chickens | Reduce morbidity, disease severity and mortality | E. coli O1:K1 or O2:K1 106 CFU/mL by intramuscular inoculation | Bacteriophage R intramuscularly (108 PFU and 106 PFU) | 1. Good protection against morbidity and mortality following intracranial/intramuscular inoculation with E. coli 2. The phage was able to multiply in the blood. | Barrow et al. 1998 |
3-day-old birds | Reduce morbidity, disease severity and mortality | E. coli 6 × 104 CFU/mL by injection into the thoracic air sac | Bacteriophage suspension via aerosol spray (108 PFU/ mL, 104 PFU/mL) | 1. Significantly reduced mortality (100%) and morbidity (35%) depending on the titre of bacteriophage | Huff et al. 2009 |
10-day-old birds | Reduce morbidity, disease severity and mortality | Injection of 104 CFU/mL of E. coli into the thoracic air sac | Bacteriophage cocktail (108 PFU/mL DAF6, 109 PFU/mL SPR02) in aerosol spray Bacteriophage cocktail (109 PFU/mL DAF6, 108 PFU/mL SPR02) - intramuscular application | 1. Decrease in mortality ranging from 20% to 27% in comparison with untreated chickens immediately after challenge 2. Significantly reduced mortality independent of time when bacteriophage cocktail was used | Huff et al. 2003 |
7-day-old birds | Reduce morbidity, disease severity and mortality | Injection of 104 CFU/mL of E. coli into the thoracic air sac. | 2 different bacteriophages DAF6 and SPR02 (109 PFU/ml) in intramuscular dosage administered immediately after E. coli challenge with enrofloxacin administered with drinking water | 1. Significantly decreased mortality to 15% in comparison with untreated birds challenged with E. coli (68%) 2. Synergistic additive effect of protection in chickens after use of bacteriophage and enrofloxacin together | Huff et al. 2004 |
10-week-old chickens | Reduce morbidity, isease severity and mortality | 0.2 ml of a 3 h E.coli (APEC H839E) culture at 5.0 × 108 CFU/mL by injection into the left air sac | Bacteriophage cocktail (phi F78E, F258E and F61E) at two different titres: 107 and 109 PFU/ml) applied in aerosol spray and drinking water in a single application | 1. High titre of bacteriophage decreased mortality and morbidity by 25% and 43%, respectively. 2. Effect in prophylactic context depended on titre. 3. Synergistic protective effect after aerosol spraying of housing systems together with administration of bacteriophages per os | Oliveira et al. 2010 |
Three-week-old chickens | Reduce morbidity, disease severity and mortality | 0.5 mL E. coli culture containing 4.5 × 108 CFU/mL or 5.5 × 108 CFU/mL/bird | Bacteriophage preparation applied to litter at titre 108 PFU/ml - 200 ml sprayed on surface of 3.9 m2 pens after E. coli challenge | 1. Mortality was significantly reduced by spraying bacteriophage on the litter. 2. Reduction in shedding of E. coli among poultry flocks | El-Gohary et al. 2014 |
10-day-old chickens, 32-day old chickens | Reduce contamination of poultry products by food-borne pathogens and efficiency of bacteriophage administration in prophylactic and therapeutic contexts | Oral dose of 1 × 105 CFU/g C. jejuni | Bacteriophage 71 in a range of titres (from 109 to 1010 PFU) applied in oral gavage for 10 days; on day 10 oral C. jejuni challenge of 105 CFU (prophylactic context) Oral dose of 105 CFU C. jejuni on day 10, followed by inoculation with phage strain 71 (from 109 to 1010 PFU) for 6 days starting 5 days after Campylobacter administration (therapeutic context) First oral dose of 105 CFU C. jejuni followed by inoculation with phage strain 71 (from 1010 to 1011PFU) and phage 69 (from 109 to 1010PFU) for 4 days | 1. Inhibited C. jejuni in 10-day-old chicks and adult birds, first by 2 and then by 1 log unit in broiler caeca. 2. Phage treatment prior to bacterial challenge does not prevent but could delay bacterial colonization. 3. Bacteriophage cocktail used in adult birds resulted in a significant decrease in Campylobacter colonization. | Wagenaar et al. 2005 |
25-day-old chickens | Reduce contamination of poultry products by food-borne pathogens | C. jejuni HPC5 log10 2.7 to 7.8 CFU/g by oral gavage (n = four birds per dosage) | Bacteriophage cocktail (CP34 or CP8 from 107 to 109 PFU), application by oral gavage | 1. Short-lived reduction in the number of bacteria in the intestines of infected birds, ranging from 0.5 to 5 log units | Loc-Carrillo et al. 2005 |
Reduce contamination of poultry products by food-borne pathogens | Challenge with C. jejuni HPC5 or C. coli OR12 8 log10 CFU/mL by oral gavage | Bacteriophage CP220 at titres of 107 and 109PFU/ml, application for 5 days | 1. Reduction in C. jejuni bacteria after administration of a bacteriophage suspension with a density of 109 PFU 2. Significant decrease in the number of birds infected C. coli following administration of a bacteriophage suspension with a density of 109 PFU | El-Shibiny et al. 2009 | |
31-day-old chickens | Reduce contamination of poultry products by food-borne pathogens | C. jejuni 2140 CD1 at titre of 2.2 and 1.1, and 5.8 × 106 CFU/g by oral gavage and in feed | Bacteriophage cocktail (phiCcoIBB35, phiCcoIBB37, phiCcoIBB12) at 107 PFU in feed gavage and 106 PFU oral dosage | 1. Reduction in titre of both C. coli and C. jejuni in faeces by approximately 2 log units after oral gavage and in feed administration. 2. 30-fold reduction in the incidence of campylobacteriosis associated with consumption of chicken | Carvalho et al. 2010 |
One-day-old chickens | Reduce morbidity, disease severity and mortality | C. perfringens CP-6 strain 108 CFU/ml at 1.0 ml/bird by oral gavage | Bacteriophage cocktail (CPAS-7, CPAS-12, CPAS-15, CPAS-16, and CPLV-42 at titres of 105 PFU/ml) with feed or water or oral gavage and spray application | 1. Significantly reduced mortality of C. perfringens-challenged birds by 92%. 2. Weight gain and feed conversion ratios were significantly better in C. perfringens-challenged chickens treated with the bacteriophage cocktail. | Miller et al. 2010 |