• Spirochetes in the blood of patients with relapsing fever - a disease c

    From georgia@21:1/5 to All on Sat Oct 10 13:14:58 2015
    author: Patricia Coyle
    title: "Neurological Complications of LymeDisease
    "Lyme disease shares properties with other spirochetal infections
    (syphilis, leptospirosis, and relapsing fever) that cause neurological
    disease. Awareness of these similarities is helpful to predict disease features. Spirochetes first infect locally at their skin or mucous
    membrane entry site. Subsequently there is early spirochetemia with wide
    organ dissemination. Ultimately there is chronic infection of organs, with periods of clinical disease activity separated by periods of remission.
    The clinical disease syndromes of these spirochetal infections are protean."

    source: Journal of the American Academy of Dermatology
    Volume 23 Number 2 part 1 August 1990
    author: Donald C. Abele, MD, Kenya H. Anders, MD
    title: Continuing Medical Education
    The many phases and faces of borreliosis I. Lyme disease
    "...Because members of the Borrelia genus share common antigens with each other and the treponemes, cross-reacting antibodies can occur with these other spirochetal infections, particularly relapsing fever, yaws, pinta, leptospirosis, and all stages of syphilis. (223) ...."
    223. Magnarelli LA, Anderson, Johnson, Cross reactivity in serological test for Lyme disease and other spirochetal infections J Infect Dis 1987;156:183-8

    source: Medicine
    volume 48, No. 2
    1969 by Williams and Wilkens Co.
    title: Relapsing fever -A Clinical and Microbiological Review
    from The Department of Internal Medicine, The University of Texas Southwestern Medical School at Dallas,
    Dallas, Texas
    authors: Paul M. Southern, Jr., M.D., and Jay P. Sanford M.D.

    "..............Otto Obermeier, working in Berlin in 1868, was the first to discover spirochetes in the blood of relapsing fever patients, and was responsible for much of the early knowledge of the disorder (107). His work was confirmed by Munch at Odessa, who in 1874 innoculated himself with blood from a relapsing fever patient, and subsequently acquired the disease. These observations were further confirmed by Motschutkoffsky in 1876, when he proved infectivity of the organisms by innoculating healthy subjects with blood from relapsing fever patients.(98,99,120)
    Munch was also among the first to suggest the possibility of a vector aand investigated the possible role of bedbugs and fleas (99). In 1891, Flugge proposed that the human body louse might act as a vector, a conclusion also reached by Mackie in India in 1907 (23, 120, 134). This was later confirmed by innoculation of monkeys with crushed lice taken from patients with relapsing fever (120, 134) . In 1904, Ross and Milne, in Uganda, showed that "human tick disease" described by Livingston in 1857 (considered by natives to be tick-transmitted) was caused by a spirochete that invaded the bloodstream. (23, 114). A number of observers in Central Africa studied and described this entitiy near that time. Among them were Button and Todd who reported the mechanism of infection in the tick Ornithoforos moubata and the transovarial passage of spirochetes to succeeding generations of ticks (50, 105, 120, 134, 139). During the latter half of the 19th and the first quarter of the 20th centuries, numerous reports describing relapsing fever came from India, China, Indochina, the middle East, the U.S.S.R., and many sections of Africa (23, 105, 120) .
    "In 1927, Nicolle and Anderson (102) advanced the interesting and popular hypothesis that relapsing fever spirochetes originated as parasites of small mammals, became adapted to human beings via ticks and finally acquired the ability to survive in and be transmitted by lice. This chain of events was, according to their hypothesis, responsible for the spread from Africa into Europe.
    "Relapsinging fever was FIRST RECOGNIZED in North America in PHILADELPHIA in 1844. It was allegedly imported in immigrants from Liverpool, thus was considered IDENTICAL to the European Disease (31, 99, 120). During the next 25 years several other epidemics occurred in New York and Philadelphia among immigrants of various European origins (23, 120). In 1874 an epidemic was observed among Chinese laborers in California (23, 97). Since that time the disease has occured in Cental and South America, The Carribbean, MANY PARTS of the United States, Canada and Mexico (8, 9, 23, 30, 72, 82, 94, 99, 101, 108, 128, 132, 138). In 1906 several groups of investigators studying the spirochete of American relasing fever concluded it was different from those in Europe, Africa, and Asia (104, 105). Thus, the name Spirochaeta (NOW BORRELIA) novyi was given to the American strain. Subsequently other names have been used describing spirochetes isolated in various parts of the United States (vide infra) (99, 139).

    II. Etiology

    A. General Incidence and Predisposing Causes

    Relapsing fever occurs throughout most of the world, with the possible exception of Australia, New Zealand, and parts of the Southwest Pacific (56). It occurs in epidemic (usually louse-borne ), endemic and sporadic (tick-borne) fashion. ........

    B. Causative Organism

    1. "Confusion exists with regard to exact classification of relpasing fever
    spirochetes." (remember-B. burgdogferi has not yet been discovered)"Although most authhorities agree that they belong in in the order
    Spirochaetales Buchanan, 1918, certain morphologic , immunologic, pathophysiologic are reminiscent of protozoans, particulary trypanosomes." (flagy is used for protozoal infections) " Other sources of confusion relate to many different generic designations ......the 7th edition of Bergey's Manual of Determinative Bacteriology classifies borelliae in the order of Spirochetales Buchanan 1918, family Treponemataceae Robinson 1948, genus
    BORRELIA Swellengrebel, 1907, along with the genera Treponema (syphilis) and Leptospira. the major differentiatiing point between borrelia and the other two genera is tha Borrelia stain easily with ordinary aniline dyes...."

    "....Many species of argasid ticks belonging to the genus Ornithodoros are important as vectors of relapsing fever borreliae. A complete discussion of this group of ticks is beyond the scope of this communication; however, the more important species are listed .......Orthiodoros mobata, the principle vector of B. duttoni in Africa, was the first and most extensively studied tick of the group. Experience with O. moubata
    has added immeasurably to present concepts of the epidemiology and pathogenesis of relapsing fever, as well as to the useful taxonomy of BORRELIAE. ...........Transovarial passage of B. duttoni by O. moubata has been repeatedly confirmed. thus, although filial infection rates vary widely, it is obvious that this is a major mechanism in the continued propagation of relapsing spirochetes (18). The same general scheme is applicable to other ornithodoros ticks and the borreliae which they harbor and transmit. Though natural habitats, feeding characteristics and mammalian hosts of ornithodoros ticks vary around the globe, the pattern is similar and allows understanding of important epidemiologic concepts
    .
    6.Biochemistry

    Advancement of knowledge regarding metabolism in borreliae has been slow owing largely to inability to cultivate organisms effectively. Studies of the chemical composition of B. novyi have been performed by McKee and Geiman (96). They also performed glycolytic studies which suggested utilization of glucose, with about 10 % completely oxidized to carbon dioxide and water, and about 65% accumulated as lactate. Only a minute amount of oxygen was utilized, but
    oxygen was not toxic to the organisms (61)..................

    8. Cultivation

    a. in vitro.......A phenomenon they termed 'periodicity' was observed in culture tubes examined daily for the presence of spirochetes. This cyclic appearance and disappearance of organisms was felt by these workers to be an innate property of borreliae, perhaps related to te relapse phenomenon. Organisms appear to survive in these 'cultivation' media over wide temperature ranges (0-45 dgrees C.) under aerobic conditions (10, 20, 133, 141).............
    .............
    c. Preservation in Arthropods and Vertebrates.
    "The long lived natural vectors of tick-borne relapsing fever spirochetes are ideal for maintaining organisms in the laboratory for extended periods. Several species of ornithodoros ticks have been utilized for this purpose. Survival of BORRELIAE in ticks without loss of infectivity has been reported for periods up to 12 years (3, 56).
    "The propensity of certain rodents to develop latent brain infection has led to utilization of this model to preserve borreliae in the laboratory........
    iii. Epidemiology

    A. Geographic Distribution

    "Relapsing fever is virtually GLOBAL in distribution, ....

    B. Louse-Borne variety

    "The louse borne form of relaspsing fever, generally considered to be caused by B. recurrentis. is usually seen in epidemics..........[very interesting considering the outbreaks of treatment resisitant lice being reposrted in the US]

    C. Tick-Borne Variety

    "The occurrence of endemic, tick-borne relaspsing fever depends upon the exposure of susceptible humans to the arthropod vector of relapsing fever spiochetes in the specific geographic locality in question,...In mountainous areas of Western United States, where O. hermsii is the prinicipal vector, human disease is seen almost exclusively in the summer months when rodents carrying ticks come out of hibernation and people visit in larger numbers. (5, 143) In other locations the ticks live mainly in caves. This is particularly true in the Middle East, Mexico, Texas and adjacent parts of Southwetern United States . Infections in these locations are also more prevalent in warmer months (5, 7, 144).............

    IV. Immunology

    A. The Relapse Phenomen

    "One of the most interesting features of relapsing fever is the phenomenon of the relapse. the ability of borreliae to undergo antigenic variation in an infected host is truly remarkable. Many studies have been performed in attempts to elucidate this phenomenon. Only a few will be mentioned here..........

    C. Interference

    The phenomenon of an infectious agent interfering with the ability of another t infect the same host has received modest attention with regard to relapsing fever spirochetes. Various borreliae have been noted not to have any perceptible influence on laboratory animals infected with leptospira, Coxsackie B. viruses, Spirillum minus or Coxiella burnetii (56). simultaneous outbreaks of relapsing fever and typhus have occured on several occasions, but it is difficult to make an accurate assesssment of the effects of either one on the other, either in humans or in lice. .........

    V. Clinical Manifestations
    Although there are at times variations in the clinical syndrome of relapsing fever based upon whether infection is tick-borne or louse-borne.....we will consider that all syndromes are somewhat similar. Tables 3 and 4 contain clinical data gathered from a review of many reported series of cases of relapsing fever (based on 1,105 cases of tick-borne and 2,073 cases of louse-borne relapsing fever).
    .............
    2. Mode of Onset
    Characteristically the onset of illness is abrupt, with sudden appearance of fever...shaking chills, severe headache....There is rarely any significant prodomal [the initial stage of a disease-Taber's] illness during the incubation period. Early, there is frequently severe pain in muscles, bones and joints of the extremities, lumbar region and neck. Nausea and vomiting are common. Extreme muscular weakness, preventing walking, may be seen soon after onset. Striking mental lethargy is common. Headache is usually intense and may be retrobulbar [behind the eyeball-Taber's] or occipital [concerning the back part of the head-Taber's]. Eye pain is also a frequent complaint, at times associated with a burning sensation and photophobia. Early the skin is hot and dry.....diffuse or upper abdominal pain and occasionally retrosternal [behind the sternum] chest pain occurs.........Cough is an early symptom in some instances. Rarely dyspnea [Air hunger, resulting in labored breathing...sometimes accompanied by pain-Taber's] and cyanosis are early manifestations. Severe respiratory symptoms early in the disease are more common in infants and young children................

    C. Clinical course

    During the ilness other clinical manifestations may also be observed......Fever is most often remittent, occasionally intermittent and rarely continuous. Peak temperatures are usually lower during relapses than during the intial febrile attack. Epistaxis [nosebleed] is common. Conjunctivitis, iritis and irdocyclitis may also occur. Herpes labialis is relatively common. Some individuals report a persistent, penetrating feeling of coldness, with or without shaking chills or shivering.......Robinson (112) described frequent tongue syptoms, with pain in the tongue being common to all stages. These included brown-stained tongue, (similar to typhus), later atrophy (much like pernicious anemia), and occasionally multiple ulcerations which tended to heal spontaneoulsy within two weeks.....Cough or other respiratory symptoms may occur in 16 to 34 % of patients, a few of whom appear to develop pneumonia or severe bronchitis. Otitis media [ middle ear infection ] is seen on rare occasions. Joint pains occur in some individuals and joint effusions have been reported....Hemotypsis [cough up blood] and hematuria [blood in urine] may occur, usually as a manifestation of multiple mucous memebrane hemorrhages. A skin rash is observed in up to 28% of cases. It may take one of several forms:1) small violet-red petechiae ( the size of rose spots), .....2) purely petechiae; 3) papules [a small, elavated area on the skin, solid and circumscribed, a pimple....] 4) circular, sharply demarcated, 18 to 24 mm rose red spots, not elavated, blanching on pressure (similar to erythema multiforme); 5) macules [discolored spot or patch of skin, neither elevated nor depressed, of various colors, sizes and shapes....] The rash may be generalized or localized, and tends to occur after the primary attack has abated ..............
    Other less common features include marked anorexia to the extent of striking weight loss and cachexia [wasting] in a few severly ill patients, nausea, vomiting, diarrhea, urinary frequency and burning (with normal urinalyses), loin pain radiating to the groin or scrotum, edema, chest pain, and meningismus. Acute thyroiditis, parotitis and acute nephritis have also been reported.
    A few clinical reports emphasize occurrence of atypical syndromes(22, 100, 145)....................
    A feeling of profound weakness is typical. this may also be associated with pronounced mental depression which may be prolonged into subsequent convalescence. Frequent headache, backache, asthenia [lack or loss of strength] and inability to work for weeks or months after the final crisis in some individuals....In a smal number of patients the interval following the initial crisis is characterized by low-grade fever and symptoms similar to but less intense than those experienced before the crisis.

    D. Complication

    Occasionally clinical features are severe and prolonged , leading to residual functional and/or anatomical derangements which may persisit for months or life............. ..Neurological complications indicative of central nervous system involvement are a feature in up to 30 % of cases in some series. These include signs and symptoms of meningitis with or without abnormal cerebrospinal fluid, coma, isolated cranial nerve lesions (V N., VI N., VII N., VIII N.; unilateral or bilateral), hemiplegia, monoparesis (arm or leg), cervical neuritis, Jacksonian epilepsy, paresthesias and neuralgic pains (usually of cranial nerve distribution), flaccid paralysis of the lower extremities simulating poliomyelitis, pupillary abnormalities and isolated pathologica reflexes (unilateral Babinski's sign). In addition severe incapacitating psychic depression and asthenia may persisit for months...women who develop relapsing fever during pregnancy have a high incidence of abortion..................The case history illustrated in Figure 1 is that of a 14 year old boy who developed relapsing fever after visiting a cave in Denton County, TEXAS, a cave known to harbor ticks infected with borreliae for MANY YEARS (63). .........Latent brain
    infection has been a feature in many surviving animals (1, 126). Involvement of the eye, with spirochetes in the cornea and anterior chamber, has been described by .....No direct information has thus far been reported to show that phagocytosis contributes in any way to resistance against borrelia (126, 129).........Routine laboratory procedures are of little benefit except for excluding other conditions.......Robinson(112) reported the occurence of valvular
    endocarditis as being common during an epidemic of louse-borne relapsing fever in Ethiopia. No other pathologic description was given, but heart murmurs and heart failure were said to be present in many patients....
    Differential diagnosis willl necessarily vary according to geographic location, season of the year and recent activities of the individual patient. In some tropical regions one must consider malaria, yellow fever, chikungunya, O'nyong-nyong and some forms of trypanosomiasis. In other areas dengue, scrub typhus, leptospirosis,....and plague must be excluded.......In parts of the United States early relapsing fever must be differentiated from Q fever, Rocky Mountain spotted fever, and Colorado tick fever. Meningoccemia, enteric [pertaining to the small intestine-Taber's] fever syndromes, influenza and sepsis (particularly in infants) must also be considered.......
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