Jorge L. Benach

A Focus of Rocky Mountain Spotted Fever within New York City

In the spring and summer of 1987, four persons acquired Rocky Mountain spotted fever within New York City, an area in which the disease had not previously been known to be endemic. Three of the four patients were residents of the Soundview area of the Bronx. All diagnoses were confirmed by indirect fluorescent-antibody tests. Environmental investigation revealed that the tick vector for Rickettsia rickettsii, Dermacentor variabilis, was present in a local park. Of the 66 specimens of D. variabilis collected, 5 (8 percent) were positive for rickettsiae from the spotted fever group. Of an additional 96 specimens of D. variabilis, 5 (5 percent) were found positive for rickettsiae by a more specific monoclonal antibody assay. Eight additional New York City parks in all five boroughs were searched for ticks. D. variabilis was found in only one other park; of the 147 ticks collected there, none were positive for rickettsiae. These findings emphasize the focal nature of Rocky Mountain spotted fever and the need to consider that disease in the differential diagnosis of any obscure acute febrile illness, even in the absence of a history of travel to known endemic areas.

Occupational Risk of Lyme Disease in Endemic Areas of New York State

Although Lyme disease (LD) is the most common tick-borne disease in the United States, little is known about the frequency of and risk factors for infection with Borrelia burgdorferi in occupational groups. In 1986, we recruited primarily outdoor workers from six employee groups in southeastern New York where LD is endemic. Of 414 participants who completed questionnaires and had blood samples tested for antibodies against B. burgdorferi by ELISA and Western immunoblot, 27 (6.5%) were seropositive, but only 14 of the 27 reported previous symptoms of LD. Persons who spent more than 30 hours per week outdoors during leisure were 2.5 times more likely to be seropositive than those who did not (p = .02). Those with a history of outdoor employment were twice as likely to be seropositive as those without such a history, although this finding was not statistically significant (p = .70). However, the seroprevalence rate for the employees was 5.9 times higher than the rate for a comparison group of anonymous blood donors from the same region of New York (p less than .001). These results suggest that there was a relatively high rate of seropositivity for the employee groups and that infection was frequently asymptomatic and associated with outdoor exposure.

Borrelia burgdorferi and other related spirochetes bind to galactocerebroside

Spirochetes are agents of neurologic disease that may utilize specific neural cell surface molecules for adhesion. Borrelia burgdorferi, the etiologic agent of Lyme disease, bound to galactocerebroside (GalCer) in numbers that were two- to threefold greater than to ceramide and glucocerebroside, and four- to fivefold greater than to sphingosine, psychosine, sulfatide, cholesterol, and three membrane phospholipids. The adherence was greater to GalCer and ceramide with a higher content of a-hydroxyl fatty acids. Treponema phagedenis Reiter and Borrelia hermsii also bound to GalCer. The binding of B burgdorferi to GalCer was inhibited in a concentration-dependent manner by rabbit polyclonal and murine monoclonal antibodies to this glycosphingolipid component of myelin. The monoclonal antibody to GalCer also inhibited adhesion of the organisms to Schwann cells. Neither free D or L monosaccharides nor the lectin peanut agglutinin inhibited binding. Since B burgdorferi and other spirochetes cause neurologic disease, these results suggest a role for GalCer as a binding site in both the central and peripheral nervous systems.

Lyme disease in childhood: clinical and epidemiologic features of ninety cases.

In 1982 and 1983 practicing pediatricians in a Lyme disease-endemic county, reported 90 cases of Lyme disease among children 19 years of age and younger (median age, 9 years). Three-fourths of the children had initial symptom onset in the summer months, with peak incidence in July. Infection occurred twice as often in boys than in girls, and tick bites were recalled by less than half (49%) of the children or parents. Erythema chronicum migrans was present in two-thirds (67%) of the cases with median onset 7 days after a definite tick bite. Arthritis or arthralgia occurred in 59% and neurologic symptoms, especially seventh nerve palsy, occurred in 14%. Asymmetric involvement of a few large joints, especially the knee, was most commonly reported for those with joint involvement. Antibiotics were prescribed for 79% of the children, three-fourths of whom were treated with oral penicillin. Initial diagnosis of Lyme disease is usually made on clinical grounds alone because serologic tests are often negative. Serologic tests for antibody to Borre-lia burgdorferi were more often positive in cases with neurological or joint involvement, in addition to erythema chronicums migrans (80%), than in cases presenting with erythema chronicums migrans only.

Isolation of the outer envelope from Borrelia burgdorferi

Borrelia burgdorferi consists of an inner protoplasmic cylinder, containing the genome and cytoplasmic elements, surrounded by a number of axial filaments, all completely encased within a multiple-layered outer envelope structure (OE). In this study, a sodium dodecyl sulfate-mediated technique was used to isolate the OE from Borrelia burgdorferi in an attempt to better understand this structure in terms of its antigenic reactivity to Lyme disease patient sera. Electron microscopic evidence suggested that the OE product was relatively free of other spirochete cellular components. SDS-PAGE analysis indicated that the electrophoretic pattern of the OE was consistent with that of the remaining protoplasmic cylinder (PC) and whole spirochete controls. Antigenic determinants in the OE were recognized by sera from Lyme disease patients in Western blots. Chemical analysis of the OE revealed a composition of 45.90% protein, 50.75% lipid and 3.33% carbohydrate. The OE comprised 16.5% by lyophilized dry weight of the whole spirochete. Antigenic determinants located within or associated with this structure are likely to play a significant role in the development of immunity in the infected host.

Clinical and geographic characteristics of Lyme disease in New York.

The clinical and geographic characteristics of 679 patients who met the clinical definition of Lyme disease and who had antibody titers of greater than or equal to 1: 128 to Borrelia burgdorferi for a two year period, 1983-1984, are described. Males outnumbered females 60% to 40% for the two year period and nearly half of all cases were children and young adults nineteen years old or younger. Forty percent of the patients reported single or multiple tick bites prior to the onset of illness and tick bites were clustered in the summer months. Skin lesions (ECM) were reported in 63% of all the patients. Joint involvement as the only manifestation of Lyme disease was reported in 21% and 22% of all the patients in 1983 and 1984 respectively. A 2: 1 ratio of males to females was noted on this subgroup and 63% of these were 19 years old or less. Onset of joint manifestations were most frequent in the last three months of the year. Neurological manifestations were noted in 20% of the patients with facial palsy being the most frequent. Twenty nine patients had neurological disorders as the only manifestation of Lyme disease. Cardiovascular symptoms were reported in 26 patients (4%). The secondary manifestations of Lyme disease were of summer and early fall onset. Lyme disease in New York is restricted to suburbs north of New York City in Westchester County, and in suburbs to the east of New York City in Suffolk County, Long Island. Incidence for the two year period can range from 0.01 cases per 1000 in some communities to 28 cases per 1000 in highly endemic areas.

An IgE response to spirochete antigen in patients with lyme disease

Most but not all Lyme disease patients produce specific IgE antibodies to Borrelia burgdorferi. Development of IgE antibodies paralleled that of other immunologic classes and appeared to be directed against a polypeptide with a molecular weight of 41,000. Total serum IgE levels in Lyme disease patients were usually within the normal range in all stages of the disease. However, highly elevated total serum IgE in certain patients were not correlated to any particular disease stage nor to specific antibody titers. Spirochetes and spirochetal sonicates in high concentration induced release of histamine from basophils derived from both patients and controls. At lower antigen concentrations, histamine release could be induced only from basophils derived from patients. Synovial fluids from patients with Lyme arthritis contained IgE but only negligible amounts of histamine.

The significance of controls in Lyme arthritis of children

In order to better define the specificity of Lyme disease (LD) seropositivity and seronegativity during a study of Lyme arthritis in a pediatric rheumatology population, three groups of controls are in the process of being developed. Children with other rheumatic disorders. Siblings and parents of children with Lyme arthritis. Individuals with intense environmental exposure to LD. Sera from each have been tested for antibody to Borrelia burgdorferi (Bb), by indirect immunofluorescence assay (IFA), enzyme linked immunosorbent assay (ELISA), or both. Of the 57 children with rheumatic disorders of whom 25 had JRA, 4 (7%) reached a border zone, non-specific level of 1:64 by IFA, and 53 sera were non-reactive. 7 household relatives of LD cases had non-reactive sera. The 42 intensely Bb-exposed individuals all had non-reactive sera. The fact that none of the 106 controls attained a clinically significant level of antibody is a general indication of the specificity of the serologic tests. The use of selected control groups such as these might potentially solve the ambiguities in clinical-laboratory correlations in Lyme arthritis.