Natural Distribution of the Ixodes dammini spirochete.

Spirochetes believed to be the cause of Lyme disease were isolated from white-footed mice and white-tailed deer, the preferred natural hosts of Ixodes dammini, the tick vector. Evidence suggests that deer act as a reservoir of the disease and provide an overwintering mechanism for both spirochetes and adult ticks. Some tick larvae may acquire the spirochete by transovarial passage and the nymphal stage may transmit the disease to humans.

Amblyomma americanum: a potential vector of Lyme disease in New Jersey.

Amblyomma americanum is a likely secondary vector of Lyme disease in New Jersey. Ticks of this species were removed from the site of the characteristic skin lesion known as erythema chronicum migrans on two patients with the disease, and the Lyme disease spirochete was isolated from nymphs and adults of this species. That A. americanum is a potential vector is supported by its similarities to Ixodes dammini, the known tick vector, in seasonal distribution and host utilization. The extensive range of A. americanum may have great implications for potential Lyme disease transmission outside known endemic areas.

Genetic diversity of ospC in a local population of Borrelia burgdorferi sensu stricto.

The outer surface protein, OspC, is highly variable in Borrelia burgdorferi sensu stricto, the agent of Lyme disease. We have shown that even within a single population OspC is highly variable. The variation of ospA and ospC in the 40 infected deer ticks collected from a single site on Shelter Island, New York, was determined using PCR-SSCP. There is very strong apparent linkage disequilibrium between ospA and ospC alleles, even though they are located on separate plasmids. Thirteen discernible SSCP mobility classes for ospC were identified and the DNA sequence for each was determined. These sequences, combined with 40 GenBank sequences, allow us to define 19 major ospC groups. Sequences within a major ospC group are, on average, <1% different from each other, while sequences between major ospC groups are, on average, approximately 20% different. The tick sample contains 11 major ospC groups, GenBank contains 16 groups, with 8 groups found in both samples. Thus, the ospC variation within a local population is almost as great as the variation of a similar-sized sample of the entire species. The Ewens-Watterson-Slatkin test of allele frequency showed significant deviation from the neutral expectation, indicating balancing selection for these major ospC groups. The variation represented by major ospC groups needs to be considered if the OspC protein is to be used as a serodiagnostic antigen or a vaccine.

Human and rodent hantavirus infection in New York State: public health significance of an emerging infectious disease.

BACKGROUND: A case of hantavirus pulmonary syndrome with possible exposure in New York and/or Rhode Island was confirmed in February 1994. OBJECTIVE: To conduct four studies to determine the historical and geographic distribution of human and small-mammal infection with hantaviruses in New York State. METHODS: Enzyme-linked immunosorbent assays were performed on serum samples obtained from 130 humans during a 1978 babesiosis survey, 907 small mammals collected in New York State since 1984, 12 rodents collected in 1994 near the residences of the patients with hantavirus pulmonary syndrome, and 76 New York patients with acute respiratory distress syndrome-like illness (as suspected cases of hantavirus pulmonary syndrome). RESULTS: None of the human serum samples from the 1978 serosurvey showed evidence of hantavirus exposure by enzyme-linked immunosorbent assay. Statewide historical serum samples from white-footed mice showed evidence of Sin Nombre virus infection in 12.0% (97/809) and Seoul-like virus infection in 9.6% (78/809). Site-specific seropositivity rates were as high as 48.5% with Sin Nombre virus during 1 year (1984). Two of 12 mice captured near the residences of a human patient were positive for Sin Nombre virus by enzyme-linked immunosorbent assay, yet were negative for viral RNA by polymerase chain reaction. None of the patients with suspected hantavirus pulmonary syndrome was serologically reactive for Sin Nombre virus. CONCLUSIONS: We provide serologic evidence of small-mammal infection with hantaviruses in New York State as long ago as 1984. Human cases of hantavirus pulmonary syndrome are rare in New York, and data indicate that transmission to humans is probably infrequent. A unique set of host, agent, and environmental factors may be necessary to cause hantavirus pulmonary syndrome in humans.

Dose-escalation, phase I/II study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS.

OBJECTIVE: To assess the safety, tolerance and activity of increasing doses of azithromycin in combination with pyrimethamine for the treatment of toxoplasmic encephalitis (TE) in patients with AIDS. DESIGN: A phase I/II dose-escalation study of oral azithromycin in combination with pyrimethamine. SETTING: Eight clinical sites in the United States. PATIENTS: Forty-two adult HIV-infected patients with confirmed or presumed acute TE. METHODS: Patients were enrolled into three successive cohorts receiving azithromycin 900, 1200 and 1500 mg a day with pyrimethamine as induction therapy. The induction period was 6 weeks followed by 24 weeks of maintenance therapy. MAIN OUTCOME MEASURES: Patient response was evaluated clinically and radiologically. RESULTS: Of the 30 evaluable patients, 20 (67%) responded to therapy during the induction period. Ten experienced disease progression. Of the 15 patients who received maintenance therapy, seven (47%) relapsed. Six patients discontinued treatment during the induction period as a result of reversible toxicities. Treatment-terminating adverse events occurred most frequently among the patients receiving the 1500 mg dose. CONCLUSION: The combination of azithromycin (900-1200 mg a day) and pyrimethamine may be useful as an alternative therapy for TE among patients intolerant of sulfonamides and clindamycin, but maintenance therapy with this combination was associated with a high relapse rate. The combination was safe, but low-grade adverse events were common.

Vector tick populations and Lyme disease. A summary of control strategies.

Although many aspects of Lyme disease have been intensely studied for over a decade, little research has been directed toward control of the principal tick vector, Ixodes dammini. Ecological and epidemiological investigations have provided not only an ample understanding of tick biology and behavior, they have also identified the types of areas at risk for disease transmission. The advantages and limitations of previous attempts to control I. dammini by host reduction, habitat modification, and acaricide applications have been discussed in relation to overall control strategies for high-risk areas, and an integrated approach to control proposed.

Host responses to Borrelia burgdorferi in dogs and horses.

By using paired sera the IgM and IgG host responses were analyzed in dogs with ELISA and Western blot techniques. Antibodies in clinical seropositive dogs bound to 4-25 IgM and up to 40 or more IgG antigenic determinants. Early IgM response to the 41-kDa flagellin persisted for at least 9 months and involved as many as seven other peptides. IgG response expanded later in the disease and involved more immunogens than are currently recognized in late human disease. A percentage of asymptomatic dogs that later developed clinical symptoms were seropositive. Immunoblot studies suggested that B. burgdorferi is persistent in both asymptomatic and weakly reactive animals and if untreated could lead to disease expression. Clinical seropositive, asymptomatic seronegative, and experimentally infected horses were similarly studied. In experimentally inoculated animals IgG antibodies were initially bound to flagellin and later to the 34- and 31-kDa polypeptides, even though ELISA values were considered only slightly reactive.

Epidemiologic studies of Lyme disease in horses and their public health significance.

A serologic survey of horses in the New Jersey-Pennsylvania area demonstrated that about 10% (6.2-14.2%) have significant levels of serum antibody to Borrelia burgdorferi. However, in a highly endemic area of central New Jersey, up to 60% of the mares and yearlings samples on one farm were seropositive. In 1983, sera from this same farm exhibited only 12% positives in mares and 35% positives in yearlings. Longitudinal studies of paired sera obtained from individual yearlings over a 6-month period in 1985 showed that 34% of them declined during the period. A new clinical syndrome associated with this farm has been observed in 1985-87. In 1985 only an edema of the legs and a dermatitis were noted, in 19.2% of the foals. There was a clustering of cases on one site, where one peer group of foals was sequestered after weaning, which suggested a point source of infection other than arthropods. In 1986, 14.6% of the foals were affected, four of them with arthritis, two of which resisted antibiotic treatment for over several months' time. Experimental infection of a pony with triturated B. burgdorferi infected tick material indicated low specific antibody levels starting about the ninth day that continued for a 3-week period. When this animal was challenged 6 months later with primary B. burgdorferi cultures, a rapid and significant booster effect was evidenced within 4 days.

Toxoplasmosis in individuals with AIDS.

Toxoplasmosis remains an important complication of AIDS. Recent advances in both diagnosis and treatment have decreased the immediate mortality. New innovations in prophylaxis will ultimately decrease incidence of this disease.

Biopsy of canine ear tissue for detection of Borrelia burgdorferi following Ixodes dammini feeding.

A punch biopsy method was developed to detect and cultivate Borrelia burgdorferi from canine ear tissue. The biopsy procedure was sensitive in that spirochetes were detected in 100% of the dogs upon which infected ticks had fed. B. burgdorferi could be cultured as early as 6 days after tick feeding at which time the organisms could not be concurrently recovered from peripheral blood. The ear punch biopsy provides a reliable method for sampling live canines and should prove useful for detecting early B. burgdorferi infection and for monitoring duration of non-disseminated infection. Additionally, the procedure will aid in the development of an animal model for evaluation of preventive and therapeutic treatment modalities.

Effectiveness of selected granular acaricide formulations in suppressing populations of Ixodes dammini (Acari: Ixodidae): short-term control of nymphs and larvae.

Applications of selected granular acaricide formulations to the shrub layer of forested habitats during the peak activity periods of Ixodes dammini Spielman, Clifford, Piesman & Corwin nymphs and larvae significantly reduced the abundance of these stages on Peromyscus leucopus. The granules effectively penetrated growing vegetation and suppressed populations of subadult ticks questing in the leaf litter. The use of granular acaricide formulations provides the only documented method of control of free-living I. dammini nymphs and larvae in dense vegetation. As such, this technique will serve as a major component of any integrated control program against this vector tick species.

Increased population densities of Amblyomma americanum (Acari: Ixodidae) on Long Island, New York.

Lone star ticks, Amblyomma americanum comprised a significantly greater proportion of total ticks flagged on eastern Long Island and Fire Island, New York, in 1986 and 1990 than in samples reported by other authors from the 1940s (when A. americanum was not collected by flagging or from hosts) and the 1970s. Therefore, population densities of A. americanum apparently have increased in recent years on southeastern Long Island, where this species now is distributed widely.

Seroprevalence of antibodies to Borrelia burgdorferi in a population of horses in central Texas.

Four hundred sixty-nine serum samples were obtained from horses admitted to the internal medicine service of the Texas Veterinary Medical Center between Jan 1 and Dec 31, 1990. Serum samples were tested by ELISA for antibody to Borrelia burgdorferi. Of these 469 samples, 1 (0.2%) was repeatedly seropositive for the organism by ELISA. Confirmatory testing by protein immunoblot was negative. The observed seroprevalence was 0%; the upper bound of the 95% confidence interval was 0.6%. These findings indicate the evidence of infection with B burgdorferi is presently uncommon in horses in central Texas.

The prevalence and significance of Borrelia burgdorferi in the urine of feral reservoir hosts.

Live Borrelia burgdorferi were isolated from the blood and/or urine of white-footed mice (Peromyscus leucopus) collected on Shelter Island, New York, in 1984 and 1985. Prevalence of spirochetes in urine was consistently higher than in blood or both fluids simultaneously. Spirochetes remained viable for 18-24 hours in urine and were maintained in culture for one week. Mice removed from the field were spirocheturic for at least 13 months. One spirocheturic mouse developed spirochetemia one month after field removal indicating the pathogen can return to the peripheral circulation. Twenty-one kidneys from 22 mice had spirochetes in the interstitial areas and bridging the tubules. A positive correlation between Babesia microti infection and spirocheturia was seen. Although the mechanism of entry into the urine is unknown, B. microti infection may increase glomerular permeability. Babesia induced hematuria may provide possible nutrients to maintain spirochetes. Urine may provide a method for contact non-tick transmission of B. burgdorferi in natural rodent populations particularly during periods of nesting and/or breeding.

Toxoplasma pneumonia.

Toxoplasma gondii, an obligate intracellular parasite, is the causal agent of significant morbidity and mortality worldwide. In the presence of a normal immune response, the pathogen becomes latent and the immunocompetent host remains chronically infected throughout life, often without clinical disease. In the case of the patient with the acquired immunodeficiency syndrome (AIDS) or other defects in cell-mediated immunity, the infection reactivates and is most often manifest as toxoplasmic encephalitis. Toxoplasmic pneumonitis follows the same pathogenetic mechanism, but occurs less frequently than either toxoplasmic encephalitis or other opportunistic pneumonias, such as a Pneumocystis carinii pneumonia (PCP). During the past decade the incidence of toxoplasma pneumonia has increased in immunocompromised patients and as a result, it has become essential that clinicians include this infectious agent in the diagnostic testing and differential diagnostic of pneumonia in T gondii seropositive patients. Most patients present with clinical and radiographic findings suggestive of PCP. The onset of disease tends to be more rapid, however. Diagnosis is based upon a high degree of clinical suspicion and demonstration of T gondii in bronchioalveolar lavage fluid and/or lung biopsy specimens. Effective therapy, pyrimethamine and sulfadiazine or trisulfapyrimidine with folinic acid, is available if initiated promptly.

Adult Ixodes dammini on rabbits: a hypothesis for the development and transmission of Borrelia burgdorferi.

A histological study of unfed Ixodes dammini adults has shown that the Lyme disease spirochete can be found in the midgut diverticula of these ticks and is presumably carried over from the nymphal stage. Sequential histology of the early stages of ticks feeding on a rabbit showed that spirochetes began to divide and were located in close proximity or attached to the epithelial cells of the diverticulae. Evidence for division was obtained by the higher number of spirochetes per tick after a three-day feeding period than in the unfed females. Although the mechanism is unclear, some spirochetes become systemic by the fifth day of feeding and can be detected in low numbers in other tick organs. Spirochetes were also noted in the feeding cavities created by I. dammini in the dermis after five days of attachment. Spirochetes were not detected in salivary glands or in the feces of I. dammini during the feeding period.

Lyme disease: a proposed ecological index to assess areas of risk in the northeastern United States.

BACKGROUND: Recent public awareness has resulted in a demand for information about ways to reduce the risk of acquiring Lyme disease. METHODS: Twenty-two school properties and recreational areas within a Lyme disease endemic area of central Monmouth County, New Jersey were evaluated for risk of transmission using an ecological index on the suitability, amount, and access to Ixodes dammini habitat by target human populations and the abundance of infected adult ticks. RESULTS: The characterization of tick habitat accurately predicted the elimination of 11 sites from concern. Of the remaining 11 sites, six were classified high risk and five as moderate risk. On-site tick surveys identified infected I. dammini adults at only four sites (three risk; one moderate risk). CONCLUSIONS: These results indicate that the use of selected ecological parameters provides a cost-effective method to rapidly identify areas at risk for Lyme disease transmission.