appendix 1 o short list of bocterio 1 Bacterium Disease2 Remarks Phage therapy Page Acinetobader Opportunistic Primarily infects patients - 26,47 baumannii infections (lung) with weakened immunity. Mortality 25-50 per cent (pneumonia). Bacillus anthracis Anthrax (various One of the most important A phage enzyme that dissolves 245 forms: skin, lung) bacteria used in germ anthrax bacteria in a highly specific "'-> VI warfare (used in the anthrax manner has proved effective in "'-> attacks in the US after Sept. animal experiments (see Chap. 7, 11, 2001 ). Pulmonary note 34). anthrax has a high mortality. Bordetel/a Whooping Primarily infects children. - 163 pertussis cough A safe and effective vaccination is available. Campylobacter Diarrhoea, Transmitted primarily Dutch researchers are working on 223,224-5 spp.3 enteritis through undercooked reducing the bacterial load in chicken. Campylobacter-infected chickens by using phage therapy.4 Clostridium Opportunistic Can colonize the alimentary In animal experiments C. difficile 159 difficile infections canal of patients who have intestinal infections have been (gastrointestinal) been treated with cured with phages (see Chapter 5, antibiotics. -- note 91). Bacterium Disease2 Remarks Phage therapy Page Clostridium spp. 3 Gas gangrene Severe infection of wounds In the Soviet Union during the 153 by anaerobic bacteria; Second World War. frequent infection during war in earlier times. Corynebacterium Diphtheria Childhood disease. A safe - 52, 198 diphtheriae and effective vaccination is available. Escherichia coli Gastrointestinal Normal inhabitant of the In the early phase of phage therapy. 43, 71, 92, infections, human intestine, infects Practised today in Russia and 166, 168, urinary tract patients with weakened Georgia, clinical studies in 198, 223-5, infections, immunity. E. coli that are Bangladesh soon (see Chapter 7). 226, 230, I pathogenic for equipped with additional Veterinary experiments with cows 236, 241 i animals or toxic or virulence genes also and chickens in the UK, the US and humans infect healthy humans. Canada (see Chapter 7, notes 11, depending on Particularly virulent strains 15 and 16). thestrain like 0157:H7 made the headlines as the culprit behind 'hamburger disease'. Haemophilus Meningitis, Primarily infects children in a - 25 influenzae among other whole number of organs. (different types) diseases There is a vaccination for H. influenzae type b (Hib). Klebsiella Opportunistic Primarily infects patients In Georgia. 25,45, 215 pneumoniae infections (lung) with weakened immunity. Mortality 25-50 per cent (pneumonia). Often tv antibiotics. V1 resistant to w N VI Bacterium Disease2 Remarks Phage therapy Page ~ Listeria Listeriosis Infection through In Switzerland and the US, experi- 224,232 monocytogenes contaminated dairy ments are being conducted with a products and vegetables. phage enzyme that dissolves listeria Insidious because the in a highly specific manner in order bacteria can also multiply in to keep cheese rinds free of the the refrigerator. bacteria (see Chapter 7, note 32). Mycobacterium Tuberculosis Increasing rapidly in African At least two scientists are doing 15 tuberculosis (various forms: countries and Russia, among research to develop phage therapy. M. bovis tuberculosis of others. The mycobacteria hide in the 52 M. africanum the lung is most Multi-drug resistant (MDR) interior of human cells, making it 115 frequent) tuberculosis drastically extremely difficult for phages to increases the cost of target them (see Chapter 4, treatment. note 23). Neisseria Gonorrhoea - - 16, 19 gonorrhoeae (clap) Proteus spp. 3 Opportunistic Primarily infects patients In Georgia. 166, 168, infections (lung, with weakened immunity. 200,206 among others) Mortality 25-50 per cent (pneumonia). Pseudomonas Wound infection Primarily infects patients In Georgia and Russia (burns). 26, 166, 195, aeruginosa (burns), with weakened immunity. 200,204, pulmonary Frequent cause of death in 212,215, infection in the the case of severe burns and 249 case of cystic cystic fibrosis. fibrosis Bacterium Disease2 Remarks Phage therapy Page Salmonella Primarily Primarily transmitted by A company in the US is developing 39, 214, 223, enteritidis/ gastroenteritis chicken and eggs. methods that use phages to reduce 231 typhimurium Multi-resistant strains like the Salmonella load of fattening DT1 04 exist. hens. s. typhi Typhoid fever In the US and Canada in the 1940s. 70, 92, 101, 113,229 S. paratyphi Paratyphoid fever In Germany in the 1940s 92, 107 (Behringwerke). S. gallinarum Fowl typhoid Aviary disease. F. d'Herelle performed experiments 60 in the 1920s. Serratia Opportunistic Primarily infects patients - 174 marcescens infections with weakened immunity. Mortality 25-50 per cent (pneumonia). Often resistant to antibiotics. Shigella spp. 3 Bacterial A whole series of species In the 1920s, 30s and 40s 48, 71, 73, dysentery (colitis (S. dysenteriae, S. sonnei, throughout the world; afterwards in 75, 92, 105, with diarrhoea) S. flexneri, etc.) exist that are the Soviet Union; today in Georgia 150, 156, virulent to different extents. and Russia. 162,248 There is also a type of dysentery that is caused by amoebas. - N V1 V1 2 Page Bacterium Disease Remarks Phage therapy N V1 Staphylococcus Wide range of One of the most important In the 1920s, 30s and 40s in many Entire Chaps 0\ aureus types of infection, germs transmitted in countries; afterwards in the Soviet 1 and 2, 69, including sepsis, hospitals (referred to as Union; today in Georgia, Poland 74, 92, 100, abscesses, nosocomial infections). and Russia, intensive research in the 104,117, furuncles, Frequently multi-resistant. US and India. 161,168, carbuncles, 169,200, osteomyelitis 207, 214, 218 Streptococcus Wide range of - Two phage enzymes that 20,200 spp.3 types of infection specifically dissolve S. pneumoniae S. pneumoniae Pneumonia A vaccination is available. and S. pyogenes respectively are 244 (pneumococci) effective in animal experiments (see S. pyogenes Strep throat Chapter 7, note 32). 244 Enterococcus Opportunistic One of the most important Entire Chap. spp.3 infections germs transmitted in 2, 219 hospitals. Frequently multi- resistant. Vibrio cholerae Cholera Many multi-resistant variants In the 1920s, 30s and 40s in many 82, 1 02, 129 I occur primarily in Africa and countries, primarily in India and in India. the Soviet Union; afterwards experiments in the Soviet Union, I WHO-sponsored experiments in Pakistan well into the 1960s.5 Xanthomonas Various infections - A phage preparation for X. 233 campestris from plants campestris infections in tomatoes is available for purchase in the US. Yersinia pestis Plague - In the 1930s. 79, 102 (pneumonic and bubonic) -- appendix 2 the odvontoges ond disadvantages of phage therapy Advantage Remarks Page 1 Phages are very specific and do As a result, there are no 159 not harm the useful bacteria that side effects like diarrhoea or live in and on the body. secondary infections such as those that occur in treatment with antibiotics. See disadvantage 2. 2 Due to their specificity, phages do 159 not cause a selection of resistances in the useful bacteria that live in and on the body. 3 We are constantly ingesting Because they are harmless, 54, phages. In general, they are phages can be used for 123, harmless to human beings. When combating harmful 221, well-purified phages are used, few bacteria in fattening 223 side effects have been described animals and food. See for all types of administration. disadvantage 8. 4 Phages are an 'intelligent' drug. See disadvantage 5. 111 They multiply at the site of the infection until there are no more bacteria. Then they are excreted. 5 Bacteria that have become Bacteria that have become 73, resistant to a certain type of phage resistant to a certain 162 continue to be destroyed by other antibiotic often become types. resistant to other drugs more easily. 6 Phages are found throughout If each newly isolated 162, nature. This means that it is easy phage requires approval, 250 to find new phages when bacteria this procedure could become resistant to them. become too expensive. 257 258 appendix 2 Advantage Remarks Page 7 Evolution drives the rapid The development of a new 162 emergence of new phages that antibiotic for resistant can destroy bacteria that have bacteria takes several years. become resistant. This means that there should be an 'inexhaustible' supply. 8 Some resistant bacteria that have Antibiotic-resistant bacteria 228 been selected during treatment are generally not less with phages are less virulent and virulent. can be fought by the immune system. 9 Phages are also active against 196, bacteria that have become 208 resistant to antibiotics. 10 Phages can be genetically 241 modified in order to make up for some of their disadvantages. 11 Individual components of phages 242 (e.g. lysins) can also be used as antibiotic substances. So far resistances have not occurred despite comprehensive testing. Disadvantage Remarks Page 1 There are no Numerous animal experiments 209,212, internationally demonstrate the efficacy against 215,219, recognized studies that different infections. The first 226,237 prove the efficacy of studies on humans are phages in humans. underway. 2 The great specificity of For good results, the efficacy of 99, 168, phages is a disadvantage phages against the infecting 211 when the exact species bacteria should be tested prior of infecting bacteria is to application in the lab. For this unknown or if there is a reason, phages are less suitable multiple infection. for acute cases. Mixtures consisting of several phages can fight mixed infections. 3 Bacteria can also become See advantages 5, 6, 7 and 8. 73, 162, resistant to phages. 228 appendix 2 259 Disadvantage Remarks Page 4 Bacteria have a type of The efficacy of phages needs to 99, 'immune system' that be tested in the lab prior to use in 121 destroys the hereditary treatment. material of some penetrating phages. Only suitable phages can conquer this 'immune system'. 5 In comparison to chemical So far there have been too few 73, molecules, phages are pharmacological studies that have 92, relatively large.