Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Patent
1999-01-27
2000-04-18
Mosher, Mary E.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
435 5, 435975, 536 2432, 536 2431, C12Q 168, C12Q 170
Patent
active
060513829
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to the detection of a nucleic acid of a host bitten by an arthropod and a nucleic acid of an arthropod-borne pathogen in the arthropod. Furthermore, this invention concerns a kit suitable for carrying out the detection.
There are a plurality of arthropods world-wide, which attack human or animal hosts by a prick or bite. These arthropods transmit a plurality of pathogens, e.g. viruses, bacteria, protozoa or worms. The most widely known pathogen transmitted by arthropods, particularly ticks, is Borrelia burgdorferi which causes Lyme disease. The connections and courses of the bite by an arthropod, particularly tick, are explained below by means of the Lyme disease.
Lyme disease is a disease which is transmitted by tick bite and occurs in wide regions of the Northern hemisphere. In Central Europe and North America, it is the most frequent arthropod-borne disease. The rate of attack by ticks bearing the Borrelia burgdorferi pathogen varies according to the region. The U.S. report attack rates of up to 55%, while values of attack are reported to be between 2.5% and 36% for Europe.
Lyme disease proceeds in stage-like fashion. A tick bite initially causes a local infection (stage I; erythema migrans) with an incubation period of several days to few weeks, pathogen generalization occurs in the further course (stage II; symptoms at the nervous system, heart or joints), and an organ manifestation is found after months or years (stage III, late stage; Lyme arthritis or acrodermatitis chronica atrophicans). Individual disease stages can also be omitted or spontaneous healing may occur.
All in all, both clinical and laboratory diagnostics of Lyme disease are difficult and in some clinical cases accompanied by great uncertainty. Since the direct detection of the pathogen in patients' materials is regarded as unreliable, serological methods are usually used in support of diagnosis. In early disease stages, however, the antibody titers found are frequently not increased even though an infection has taken place, so that serology is sometimes no reliable criterion here. In some cases, this applies even to neuroborreliosis which may show a dangerous clinical picture and whose limitation over neurological diseases having a different cause is of great importance.
The Lyme disease is treated in accordance with the level of knowledge from stage II of the disease by intravenous administration of antibiotics. Such an administration requires either daily visits or the patient's hospitalization. The costs for the administered antibiotics presently amount to about 2500.--to 5000.--German marks per treatment cycle alone. In some cases, very aggressive disease processes are observed, which require several treatment cycles thus causing very high treatment costs.
Statements on the infection risk after tick bite are scanty so far and have usually been determined without reference to the positivity or negativity of the tick. U.S. investigations assume that 1 to 3% of tick bites in endemic regions result in an infection with Borrelia burgdorferi. In this connection, Magid et al., N. Engl. J. Med. 327, (1992), 534-541, draw the conclusion by way of statistical cost-benefit analysis that in regions highly contaminated with ticks bearing Borrelia burgdorferi it would be useful to administer prophylactically antibiotics after every tick bite. In Germany, antibiotic prophylaxis after tick bite is rejected. It is recommended instead to start a treatment in well-calculated fashion only if symptoms of Lyme disease occur. This recommendation is accompanied by two essential drawbacks: (1) Individual stages of the disease (e.g. erythema migrans) may be omitted, and the disease can start with symptoms of stage II or III which are difficult to diagnose and whose treatment is expensive. (2) If there is a reliable possibility of evaluating the infection risk soon after a tick bite, it can hardly be justified under ethical aspects to expose patients to the risk of a disease and the accompanying ailments. In addition to these
REFERENCES:
Shott S.R.: "Diagnosis and management of Lyme Disease", Current Opinion In tolaryngology and Head and Neck Surgery, Bd. 3, Nr. 6, Dec. 1995, Seiten 379-382, XP002042421.
Peavey C.: "Transmission of Borellia Burgdorferi by Ixodes Pacificus" Journal of Parisitology, Bd. 81, Nr. 2, Apr. 1995, Seiten 175-8, XP002042422.
Schwartz J. et al., "Diagnosis of early Lyme disease by polymerase chain reaction amplification and culture of skin biopsies from Erythema Migrans lesions", J. Clin. Microbiol, BD. 30, Dec. 1992.
Kirstein et al, Applied and Environmental Microbiology 62:4060-4065, Nov. 1996.
Gokool et al, Med. Vet. Entomol 7:208-15, 1993, abstract only.
Maiwald Matthias
von Knebel-Doeberitz Magnus
Deutsches Krebsforschungszentrum Stiftung Des Offentlichen Recht
Mosher Mary E.
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