Diagnosis and management of infection caused by Chlamydia

a technology of chlamydia and chlamydia spores, applied in the direction of biocide, heterocyclic compound active ingredients, drug compositions, etc., can solve the problems of c. pneumoniae /i>infections may relapse, chlamydia is difficult to eradicate, etc., to prevent chlamydia from reactivation and the effect of preventing the reactivation of the pathogen

Inactive Publication Date: 2005-06-30
VANDERBILT UNIV
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  • Abstract
  • Description
  • Claims
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AI Technical Summary

Benefits of technology

[0008] The present invention provides a unique approach for the diagnosis and management of infection by Chlamydia species, particularly C. pneumoniae. The invention is based upon the discovery that a combination of agents directed toward many of the various stages of the chlamydial life cycle can successfully manage infection and ultimately prevent reinfection / reactivation of the pathogen. Accordingly, one embodiment of the invention pertains to methods of treating infection by a Chlamydia species, comprising administering to an individual in need thereof a combination of antichlamydial agents, comprising at least two agents, each of which is targeted against a different phase of the chlamydial life cycle. For example, the method can be carried out using agents chosen from among the following groups: a) at least one agent targeted against the elementary body phase of the chlamydial life cycle; b) at least one agent targeted against the replicating phase of the chlamydial life cycle; and c) at least one agent targeted against a cryptic phase of the chlamydial life cycle. The chlamydial pathogen can be eliminated more rapidly when a combination comprising agents targeted against each phase of the chlamydial life cycle is administered.
[0013] Detection of the presence of Chlamydia in a sample of biological material taken from an individual thought to be infected therewith is important in determining the course of therapy and the agents to be used. This can be achieved by detecting the presence of DNA encoding MOMP of Chlamydia or other chlamydial genes in the individual. In one aspect of the invention, diseases associated with Chlamydia infection, such as inflammatory diseases, autoimmune diseases and diseases in which the individual is immunocompromised, can be treated by managing (i.e., significantly reducing infection or eradicating) the Chlamydia infection using the novel approach described herein. Both clinical and serological improvements / resolutions in patient status have been demonstrated.
[0023] The invention also pertains to methods of maintaining a Chlamydia-free status in animals and cell lines which have been cleared of Chlamydia infection by the methods of this invention, or have never been infected, such as their Chlamydia-free offspring or progeny. Cells or animals can be maintained as Chlamydia-free by maintaining them on antibiotics and / or treating their nutrients and environment to ensure that they are Chlamydia-free. Particularly, a source of nutrients to be administered to Chlamydia-free cells or animals can be treated to inactivate or remove any chlamydial elementary bodies therefrom. This can be accomplished by exposing the nutrients to gamma irradiation for a period of time and level of exposure adequate to inactivate the elementary bodies. In addition to, or alternatively, a source of nutrients can be passed through a filtration system to physically remove the chlamydial elementary bodies therefrom. Optionally, the source of nutrients can be first treated with a disulfide reducing agent, such as dithiothreitol, before the filtration step is performed. The filter should be of adequate size such that objects larger than 0.5 microns are prevented from passing through.

Problems solved by technology

Once fully established, the Chlamydia are difficult to eradicate, with frequent relapse following antibiotic therapy.
Despite this demonstration of in vitro susceptibility, C. pneumoniae infections may relapse following antibiotic therapy with these agents.

Method used

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  • Diagnosis and management of infection caused by Chlamydia
  • Diagnosis and management of infection caused by Chlamydia
  • Diagnosis and management of infection caused by Chlamydia

Examples

Experimental program
Comparison scheme
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example 1

POLYMERASE CHAIN REACTION (PCR) FOR THE FULL LENGTH MOMP GENE OF C. PNEUMONIAE AND OTHER SPECIES OF CHLAMYDIA (DIAGNOSTIC)

[0200] a. Solution PCR

[0201] Serum, blood or tissue samples were pre-incubated in the presence of 10 μM dithiothreitol at room temperature for 2 hours to reduce the disulfide bonds and facilitate release of the outer shell of the elementary bodies. CSF and other body fluids are also suitable for use as described. Other suitable reducing agents for use in this step include, but are not limited to, succimer and glutathione (e.g., including, but not limited to, glutathione esters, other analogs and deriviatives). The failure to include a reducing agent initially may result in a negative PCR signal following the protease digestion step. Appropriate concentrations of these reducing agents can be readily determined by the skilled artisan without undue experimentation using the 10 μM concentration of dithiothreitol as a guideline. Alternatively, guanidine isothiocyana...

example 2

ENZYME LINKED IMMUNO SORBENT ASSAY (ELISA; DIAGNOSTIC)

[0206] a. Recombinant MOMP-Based ELISA

[0207] The full length MOMP gene of C. pneumoniae was directionally cloned into the pET expression plasmid at the NCOI and NOTI restriction sites using primers to introduce these unique restriction sites into the MOMP ends. Primer sequences are as follows:

CPOMPDNCO (Coding strand):(SEQ ID NO. 43)5′-AGCTTACCAT GGCTAAAAAA CTCTTAAAGT CGGCGTTATTATCCG-3′CPOMP_CNOT (complimentary strand):(SEQ ID NO. 44)5′-ATATGCGGCC GCTCATAGAA TCTGAACTGA CCAGATACG-3′

[0208] The construction of the MOMP insert into the pET expression vector (Novagen, Inc.) yields, on transformation of permissive E. coli, an amino terminal thioredoxin fusion domain, a polyhistidine for Ni+-affinity chromatography, a solubility sequence of approximately 5 kD, and an endopeptidase cleavage site which yields a full length MOMP with a modified amino terminal (as illustrated in FIG. 2) containing an alanine insert between the amino ter...

example 3

DETECTION ASSAY METHODS (DIAGNOSTIC)

[0212] a. Immunoglobulin (Ig) assay

[0213]C. pneumoniae EBs were grown in primary human umbilical vein endothelial cells (HuEVEC; early passage), HeLa 199, or a suitable alternative in the presence of 1 μg / ml cycloheximide at 35° C. under 5% CO2. Permissive cells were lysed by sonication at 3 days, thereby liberating EBs. The latter were harvested from infection flasks, sonicated, and cellular debris were removed after sonication by a low speed centrifugation (˜600×g) for 5 minutes. EBs were pelleted by high speed centrifugation (30,000×g) for 30 minutes at 4° C. The EB pellet was washed with PBS ×1 and was reconstituted in 2 ml PBS per four 25-cm2 culture flask and sonicated at maximum power for 20 seconds and a 0.5 cycle time using a Braun-Sonic U sonicator. EB protein concentration was determined by the Bradford method and the sonicated infectious EB suspension was rendered non-infectious by the addition of 37% formaldehyde to a final 10% form...

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Abstract

The present invention provides a method of treating coronary artery disease in a patient in need thereof by administering to the patient an antichlamydial amount of a rifamycin for a duration to treat said coronary artery disease.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation application of Ser. No. 10 / 100,759, filed Mar. 19, 2002, which is a continuation application of and claims priority to U.S. Ser. No. 09 / 073,661, filed May 6, 1998, which is a continuation-in-part of U.S. Ser. No. 09 / 025,521, filed Feb. 18, 1998, which is a continuation-in-part of U.S. Ser. No. 08 / 911,593, filed Aug. 14, 1997. U.S. Ser. No. 09 / 073,661 is also a continuation-in-part of U.S. Ser. No. 09 / 025,176 and U.S. Ser. No. 09 / 025,174, each filed Feb. 18, 1998, and claims benefit of U.S. Provisional Application Nos. 60 / 045,739, 60 / 045,779, 60 / 045,780, 60 / 045,784, 60 / 045,787, and 60 / 045,689, each filed May 6, 1997. Each of the foregoing applications is incorporated herein by reference.BACKGROUND OF THE INVENTION [0002]Chlamydiae are obligate intracellular microorganisms which parasitize eukaryotic cells and are ubiquitous throughout the animal kingdom. Members of the chlamydial genus are considered ba...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/455A61K45/06
CPCA61K31/192A61K31/455A61K31/496A61K31/573Y10S514/824A61K45/06A61K31/7052A61K2300/00
Inventor MITCHELL, WILLIAMSTRATTON, CHARLES
Owner VANDERBILT UNIV
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