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Purulent Infections of Neonates and Prevention with Bacteriophages

#G-1242


Purulent Infections of Neonates and Prevention with Bacteriophages

Tech Area / Field

  • MED-DIS/Disease Surveillance/Medicine
  • BIO-MIB/Microbiology/Biotechnology

Status
3 Approved without Funding

Registration date
17.02.2005

Leading Institute
Georgian Academy of Sciences / Institute of Bacteriophage, Microbiology and Virology, Georgia, Tbilisi

Collaborators

  • University of Florida / College of Medicine, USA, FL, Gainesville

Project summary

Within the last five years, because of the socio-economic conditions in the Republic of Georgia, the health indices have decreased significantly – the mortality rate now exceeds the birth rate. Since 1990, the morbidity of children who survived the first days of life has increased 3-fold; the number of traditional diseases in young children has increased and the course of the diseases has been aggravated. In many regions, a significant increase of infectious-inflammatory pathologies of newborns has been recorded. In addition, there is an increasing rate of intra-uterine infection, eliciting even more concern. To improve the health of the children and lessen the mortality rate, both important state problems, requires, first of all, a complex investigation of intrauterine and newborn diseases.

While infections of the uterus or fetus can result in stillbirth, infections are also one of the leading causes of neonatal morbidity and mortality. Almost any microbe can cause a neonatal infection, but the leading causes (up to 50% of cases) are the pyogenic cocci, Staphylococci and Streptococci. Another 36% are caused by the gramnegative microflora – Klebsilla, E.coli, and Pseudomonas. Lately, some changes have been noted in the causes of these infections; there has been an increase of conditionally pathogenic (opportunistic) infections, especially gram-negative, and the gravity of the diseases has increased. So called “hospital strains”. which are characterized by multiple antibiotic resistances and plasmid determined virulence factors have become common. Development of hospital strains occurs in clinics because of the sometimes irrational use of antibiotics.

In addition, rapid spread of multiply antibiotic-resistant bacteria has decreased the effectiveness of these drugs for the treatment of infectious diseases.Mainly because of the spread of multiply resistant organisms, scientists have tried to develop alternative therapies for both treatment and prophylaxis. These therapies should be, of course, safe and effective. One such extremely safe and highly effective therapy is therapy with bacteriophages. Implementation of the Bacteriophages seams to be most promising, because they display high specific of action against the specific infectious agents only.

For a number of years, the G. Eliava Institute of Bacteriophage, Microbiology and Virology, Georgian Academy of Sciences, supervised by Academician T. Chanishvili, has been a leading institution, which is occupied by theoretical and applied problems relating to bacteriophage, and to the development of phage preparations for prophylactic, treatment, and diagnosis of bacterial infections.

In the Laboratory-Center of Investigation, Storage, Standartization and Deposition of Bacteriophages and Bacteriophage Preparations, under the supervision of Dr. M. Darsavelidze, a number of technologies have been developed for the production of medicinal-prophylactic polyvalent preparations against enteric and pyogenic infections. A rich collection of pathogenic and opportunistic bacterial strains and their respective phages has been compiled. The success of the laboratory is indicated by the fact that in their collection they have many phages against Y. enterocolitica, E. coli, Pseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus epidermidis, Salmonella sp., and Streptococcus pyogenes. The laboratory would now like to turn its attention to the problem of material fetal and newborn health.

The aim of our work is to determine the causes of neonatal infections, to select phages active against the antibiotic and phage resistant, and to construct a highly specific medicinal-prophylactic bacteriophage preparation. Realization of this goal requires the following:

  1. Epidemiology of neonatal infections in different maternity homes of Georgia. Bacteria causing these infections will be isolated and their genus and species determined. The incidence of opportunistic and pathogenic microbes will be determined.
  2. Identification of the most prevalent microflora of the genetic tract in pregnant women. Swabs will be taken from the vaginas of pregnant women and the bacteria therein isolated and their genus and species determined.
  3. Determination of particular properties of the isolated bacteria, (Staphylococcus, Pseudomonadaceae, Klebsiella) morphological, biochemical, and serological typing will be done. In addition the antibiotic sensitivity and the phage specificity of the isolated organisms will be determined.
  4. Isolation of new phages against the antibiotic and phage resistant microbial species (Staphylococcus, Pseudomonadaceae, Klebsiella) Most of these will be isolated from sewage or other environmental material by techniques of enrichment followed by plaque isolation and growth.
  5. Determination of the biological properties of isolated phage clones – morphology, activity, serology of the virion, interaction with their respective hosts, lytic spectrum and influences of physical and chemical factors. We will also determine the frequency of mutation of the bacterial host from phage sensitivity to phage resistance.
  6. Investigation of molecular properties of the phages.
  7. Creation of a collection of pathogenic and opportunistic microbes and their phages. The phages chosen will be highly active and in concentrated and purified preparations.
  8. Selection of the tutor-strains and specific phages for creation of mother-races.
  9. Development of techniques for obtaining polyvalent bacteriophages.
  10. Testing the phage in a neonatal rat model. This will be done using a artificially reared rat pup model. In this model the rat pups are fed via a gastrostomy. Five-day old rat pups are given an inhalation anaesthetic. Percutaneous gastrostomy tubes constructed from polyethylene tubing are inserted into the pups and the pups allowed to recover from anaesthesia. The pups are then fed rodent milk substitute on a cycled hourly basis. The gastrostomy tube can also be used to infect the pups with specific bacteria. Phage can be administered either through the tube or injected. Analyses will include body weights, intestinal, lung, liver and brain gross histology, intestinal tissue cytokines, and myeloperoxidase activities in the liver, brain and lung in non-infected, infected and not treated and phage treated pups. These experiments will be done at the University of Florida, Gainesville, Florida, with bacteria and phage isolated at the G. Eliava Institute.

Successful realization of the problem will result the creation of collection of new pathogenic strains (Staphylococcus, Pseudomonas, Klebsiella) and respective phages that can be tested in the rat pup or other models, development of a technology for production of polyvalent bacteriophage with an aim of further production of medicinal-prophylactic preparations against neonatal infections.

Joint realization of the Project by Georgian and American scientists, using the latest methods, will contribute largely to the development of Georgian science and economics, it will help young scientists and students in further increasing their scientific potential. The results to be obtained within the Project will discussed on a regular basis by Georgian and American scientists.

The collaborators agree to co-operate in scientific-research activities envisaged by the Project, exchange information in the process of its implementation, discuss report materials and in case of necessity provide consultations, discuss the results at conferences, visit the participants of the Project and invite them as will.

The following methods of research will be used in the realization of Project; determination of morpho-cultural traits of bacterial strains; selection of virulent phages and determination of their morphology with the aid of electron microscopy, obtaining and purifications of bacteriophages by the method of ultrafiltration, ultracentrifugation in different gradients, etc.; study of the phage propagation cycle; influence of physical-chemical factors on the validity of phages, obtaining of anti-phage searum in rabbits, research of serologic characteristics of phages under the neutralization method; determination of the scope, specific effect of phages on homo- and heterological strains; cross phage-resistance and stability of lysis.


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