Enteric diseases cause significant economic losses due to decreased weight gain, higher mortality, higher feed conversion, higher veterinary costs and medicine and a higher risk of contamination by poultry products in food production. The losses due to necrotic enteritis mainly occurring in broilers and fattening turkeys in intensive floor or free-range management are put at 2 billion US$ per year.

After the ban of antibiotic growth promoters, the relevance of this formerly well controllable disease reappeared and increased.

Necrotic enteritis is a disease of the gut
It is caused by specific gram-positive, anaerobic bacteria – Clostridium perfringens, mostly Type A. Clostridia are found in litter, faeces, soil, dust and in healthy animals’ guts. These spore forming bacteria are extremely resistant against environmental influences and can survive in soil, feed, and litter for several years and even reproduce.
Clostridium perfringens is a component of the normal gut flora. It occurs in a mixture of diverse strains in a concentration of up to 10⁵ CFU / g intestinal content. In animals suffering from necrotic enteritis particularly one strain of Clostridium perfringens is found in a much more higher concentration of 10⁶-10⁸ CFU / g.
Necrotic enteritis affects chickens and turkeys at the age of 2-16 weeks, proliferating at the age of 3-6 weeks. There is an acute clinical, and a subclinical form.
Birds suffering from the clinical form clearly show symptoms like a poor general state of health and diarrhoea. Mortality rates up to 50 % can occur. Subclinical necrotic enteritis cannot be diagnosed easily, as there are no clear symptoms. This form, however, stays within the flock and causes losses due to decreased growth.

Factors promoting an infection with necrotic enteritis should be avoided!
In general, factors have to be cited that create an intestinal environment favourable for the facultative anaerobic Clostridium perfringens or weaken the immune status of the host:

1. Feed:
   Here NSP’s have to be mentioned. Undigested NSP’s serve as substrate and some of them cause higher production of mucus also serving as substrate and providing ideal anaerobic conditions. Undigested proteins due to high contents in the diet also serve as substrates. Animal protein and fat are worse than vegetable variants and a homogeneous size of particles in the diet is better than an inhomogeneous mixture.
2. Stress
   Stresses such as feed change or high stocking density favour NE
3. Diseases
   Immunosuppressive diseases such as infective chicken anaemia, Gumboro or Marek’s decrease resistance against intestinal infections and facilitate their colonisation. Some pathogens exert pressure on the gut and prepare the way for clostridia. Here Cryptosporidia and salmonella have to be mentioned.

New approaches
Secondary plant compounds show good results against the two microorganisms just mentioned. In a trial conducted with free range broilers in France, a combination of a vaccination against coccidia and a mixture of secondary plant compounds (Activo liquid) resulted in a reduced occurrence of necrotic enteritis in the trial group compared to the control. Additionally due to an improved feed conversion, the margin per animal in the trial group was 5 Cent higher than in the control (1,44 € vs 1,39 €).
In an in vitro test, Activo liquid also showed bactericidal efficacy against field isolated Salmonella pulmorum and Salmonella gallinarum at a 2 % concentration.
The trials show that combined with a good feeding and stress management, secondary plant compounds, could be a good tool to eliminate predisposing factors for necrotic enteritis and could therefore help control this economically important disease.

Why should you read another story about phytogenics? Or, is it botanicals, spices, herbs, and extracts? No matter what we call them, scientists have named them “secondary plant compounds”, and if we are to follow the American tradition we can call them SPC. Then, here is the first interesting thing we can discuss about this plant-derived class of active compounds. They are “secondary” in nature, but not insignificant. They play no role in normal metabolism, but they help plants (and now animals) survive under adverse conditions. Perhaps, this is why some experts consider them as the next frontier in poultry nutrition. With poultry that are raised in less than ideal conditions, especially when we consider the movement towards antibiotic reduction (for growth promoting reasons, not complete removal of all medicines), we understand that such natural compounds can be of significant help.

As it happens, the majority of poultry specialists in Europe and increasingly in the Americas consider SPC as an almost-essential element in diets for broilers and layers (and turkeys, ducks, and all poultry for that matter) when birds are raised without antibiotics. Some go even further and use them along with antibiotics because, as we all know, antibiotics are never 100% efficient as bacteria sooner or later develop some form of resistance. Such resistance has not yet been observed with SPC. So if one is to use SPC in poultry feds, which ones to buy? A quick glance at the market will reveal more commercial products than can possibly be imagined. Some must be better than the rest, but how can we separate the wheat from the chaff? Price alone is not always a good indicator. A high quality product must be expensive – for there is no such thing as a free lunch – but all expensive products are not always of the highest possible quality!

There are three basic criteria, which we can mention briefly here:

1. SPC are volatile – at least most of them. As such, unprotected products will soon evaporate if left in the open air as it happens with feed prepared in commercial farms. So, some form of protecting SPC is essential.
2. SPC are innumerable – so finding the right mix for the job required is important. You cannot get the same results with any kind of mix. So, in designing an SPC mix, the manufacturer must declare and have knowledge of the target to be accomplished.
3. SPC are powerful – meaning you cannot just keep adding as much as possible. Here finding the exact dosage for the right purpose is a difficult balancing exercise. So, the right mix and the right dosage must be combined, otherwise animals will refuse the feed (worst case scenario) or just fail to benefit from SPC inclusion.

There is so much more to learn about this exciting class of compounds that can replace the growth promoting action of antibiotics that it is worth spending time learning more about them.

Due to incorrect therapeutic or preventive use of antibiotics in animal production as well as in human medicine, occurrence of antibiotic resistant pathogens has become a widespread problem. Enterobacteria in particular (e.g. Salmonella, Klebsiella, E. coli) possess a special mechanism of resistance. By producing special enzymes (ß-lactamases), they are able to withstand the attack of so-called ß-lactam antibiotics. The genes for this ability (resistance genes) can also be transferred to other bacteria resulting in a continuously increasing problem. Divers point mutations within the ß-lactamase genes lead to the occurrence of „Extended-Spectrum-Beta-Lactamases“ (ESBL), which are able to hydrolyse most of the ß-Lactam-antibiotics. AmpC Beta-Lactamases (AmpC) are enzymes, which express a resistance against penicillins, cephalosporins of the second and third generation as well as cephamycins.

What are ß-lactam antibiotics?
The group of ß-lactam antibiotics consists of penicillins, cephalosporins, monobactams and carbapenems. A characteristic of these antibiotics is the lactam ring (marked in orange):

Mode of action of ß-lactam antibiotic
If a bacterial cell is growing, the cell wall also has to grow. For this purpose, existing conjunctions are cracked and new components are inserted. ß-lactam-antibiotics disturb the process of cell wall construction by blocking an enzyme needed, the transpeptidase. If crosslinks necessary for the stability of the cell wall cannot be created, the bacteria cannot survive. Resistant bacteria, which are able to produce ß-lactamases, destroy the ß-lactam antibiotics and prevent their own destruction.

Secondary plant compounds
Secondary plant compounds and their components are able to prevent or slow down the growth of moulds, yeasts, viruses and bacteria. They attack at various sites, particularly the membrane and the cytoplasm. Sometimes they change the whole morphology of the cell. In the case of gram-negative bacteria, secondary plant compounds (hydrophobic) have to be mixed with an emulsifier so that they can pass the cell wall which is open only for small hydrophilic solutes. The modes of action of secondary plant compounds depend on their chemical composition. It also depends on whether single substances or blends (with possible positive or negative synergies) are used. It has been observed that extracts of spices have a lower antimicrobial efficacy than the entire spice.

The best explained mode of action is the one of thymol and carvacrol, the major components of the oils of thyme and oregano. They are able to incorporate into the bacterial membrane and to disrupt its integrity. This increases the permeability of the cell membrane for ions and other small molecules such as ATP leading to the decrease of the electrochemical gradient above the cell membrane and to the loss of energy equivalents of the cell.

Trial (Scotland)

Design
Two strains of ESBL-producing and AmpC respectively, isolated from the field, a non-resistant strain of E. coli as control. Suspensions of the strains with 1×10⁴ KBE/ml were incubated for 6-7 h at 37°C together with different concentrations of Activo Liquid or with cefotaxime, a cephalosporin. The suspensions were then put on LB-Agar plates and bacteria colonies were counted after a further 18-22h incubation at 37°C. Evaluation of the effects of Activo Liquid on ESBL-producing as well as on E. coli resistant for aminopenicillin and cephalosporin (AmpC)

Results
The antimicrobial efficacy of the blend of secondary plant compounds depended on concentration with bactericidal effect at higher concentrations and bacteriostatic at dilutions up to 0,1%. It is also possible that bacteria could develop a resistance to secondary plant compounds; the probability is however relatively low, due to the fact that essential oils contain hundreds of chemical components (more than antibiotics) making it difficult for bacteria to adapt.