Biomedical subjects

P J Krause

Publications and source records attributed to P J Krause.

At least 19 recordsLinked to original sources

PubMed2001

Coinfecting deer-associated zoonoses: Lyme disease, babesiosis, and ehrlichiosis.

The heightened worldwide recognition of the health burden of tickborne infection derives largely from the increasing incidence of Lyme disease, human babesiosis, and human granulocytic ehrlichiosis, both individually and in concert. Because these infections share the same rodent reservoir and tick vector hosts, they can be cotransmitted to human hosts. Indeed, human coinfections involving various combinations of these pathogens are common, and some tend to be particularly severe. Diagnostic procedures and clinical management of the resulting disease syndrome is rendered complex by the diversity of pathogens involved and by the unusual diversity and duration of symptoms.

Animals↗

PubMed2001

Lactobacillus acidophilus sepsis in a neonate.

Lactobacillus species are non-spore-forming, anaerobic, gram-positive rods that cause disease in immunocompromised adults. Few cases have been described in children. We present the case of a 2-month-old infant who apparently developed Lactobacillus acidophilus sepsis from an infected central venous catheter. Physicians should be aware that although Lactobacillus species rarely cause disease in children, they should be considered a possible pathogen when isolated from the blood of a newborn infant.

Adult↗

PubMed2001

Diagnosis of babesiosis using an immunoblot serologic test.

Although the current indirect immunofluorescent assay (IFA) diagnostic antibody test for human babesiosis is sensitive and specific, an immunoblot antibody test may be easier to standardize and to perform. Our objective, therefore, was to determine the efficacy of and develop interpretive criteria for an immunoblot antibody test for diagnosing acute human babesiosis using a Babesia microti whole-cell lysate as the antigen. We compared the reactivity of sera to a B. microti immunoblot assay in 24 human subjects experiencing symptoms and expressing laboratory evidence of babesiosis, 28 subjects who experienced Lyme disease, 12 subjects who experienced human granulocytic ehrlichiosis, and 51 subjects who reported no history of any of these diseases and whose sera did not react against B. microti antigen in an IFA test. Immunoblot strips were impregnated with proteins derived from the GI strain of B. microti that had been electrophoresed in an acrylamide sodium dodecyl sulfate gel, followed by electroblotting onto nitrocellulose membranes. The sera of all subjects who experienced babesiosis reacted against the B. microti antigen in the IFA and against at least one of nine immunoblot protein bands specific to B. microti. In contrast, none of the sera from people who appeared not to have experienced this infection reacted against the B. microti antigen in the IFA (compared to 4% in the immunoblot assay). When two reactive bands were considered as definitive, immunoblot test sensitivity was 96%, while specificity was 99% and predictive positivity and predictive negativity were 96 and 99%, respectively. Our B. microti immunoblot procedure shows promise as a sensitive, specific, and reproducible assay for routine clinical diagnosis of acute babesiosis.

Antibodies, Protozoan↗

PubMed2001

Safety and immunogenicity of a recombinant Borrelia burgdorferi outer surface protein A vaccine against lyme disease in healthy children and adolescents: a randomized controlled trial.

OBJECTIVE: A recombinant lipoprotein outer surface protein A (OspA) Lyme disease (LD) vaccine (LYMErix) has been shown to be safe and effective in preventing LD in adults and in adolescents 15 years of age and older. Children are at risk for developing LD. This clinical study was conducted to address the safety and immunogenicity of LD vaccine in children 4 to 18 years of age. METHODS: A randomized, placebo-controlled clinical trial was conducted at 17 investigational sites in Lyme-endemic areas in the United States. Immunogenicity data from this study also were compared with data obtained from the adult efficacy study. A total of 4090 healthy children and adolescents (age range: 4-18; mean age: 10.4 years) were randomized; 4087 were vaccinated, and a subset of 301 children participated in the immunogenicity analysis. Children were randomized to receive either 30 microgram of LD vaccine (N = 3063) or placebo (N = 1024) on a 0, 1, 12-month schedule. Safety assessments evaluated both solicited (local: redness, swelling, and pain; general: fever, headache, fatigue, arthralgia, and rash) and unsolicited adverse events. Serum specimens were collected at month 0 or month 2, and months 6, 12, and 13. RESULTS: Solicited reactogenicity data revealed a higher incidence of local injection site reactions and general symptoms (fever, headache, fatigue, and arthralgia) in vaccine than placebo recipients. The majority of events were limited in duration (mean: 2-3 days) and were mild to moderate in severity. The total IgG anti-OspA geometric mean titer (GMT) in the pediatric vaccine recipients at month 13 was as good as and statistically higher than the GMT in the adult cohort at month 13 (27 485 enzyme-linked immunosorbent assay units [EL.U]/mL vs 8216 EL.U /mL). All of the pediatric vaccine recipients attained a level of antibody concentration >/=1400 EL.U/mL (proposed seroprotective level) compared with 90% of adults attaining levels >/=1400 EL.U/mL in the efficacy trial. CONCLUSIONS: LD vaccine administered on a 0, 1, 12-month schedule generally is well tolerated and immunogenic in children 4 to 18 years of age. The safety profile consists of mild to moderate local injection site reactions and flu-like symptoms of limited duration and did not worsen with subsequent injections. IgG GMT at month 13 was threefold higher than the month 13 GMT obtained in the adult efficacy study. This higher immune response in children should provide protection against LD.

Adolescent↗

PubMed2001

Evaluation of a two-test serodiagnostic method for community assessment of Lyme disease in an endemic area.

Epidemiological methods are needed to evaluate community exposure to Borrelia burgdorferi, the causative agent of Lyme disease (LD). For LD serodiagnosis, the Centers for Disease Control and Prevention (CDC) recommends a 2-test approach that involves enzyme immunoassay (EIA) testing and Western immunoblotting (WB) of EIA-equivocal and EIA-positive specimens. The specificity of this approach was evaluated among residents of a LD-endemic community and was compared with WB alone and with a simplified 2-test approach (WB of equivocal EIA only). Participants reporting no previous diagnosis of LD were recruited during a community-wide serosurvey on Block Island, Rhode Island. Of 80 eligible participants, 20 had received LD vaccine. Seven (35%) of 20 vaccinees and 22 (37%) of 60 nonvaccinees reported nonspecific symptoms compatible with LD in the previous year. In this highly LD-endemic community, the overall specificity of the CDC-recommended approach was highest (100%), followed by WB alone (98.7%), then the simplified approach (95%).

Blotting, Western↗

PubMed2000

Atovaquone and azithromycin for the treatment of babesiosis.

BACKGROUND: Babesiosis is a tick-borne, malaria-like illness known to be enzootic in southern New England. A course of clindamycin and quinine is the standard treatment, but this regimen frequently causes adverse reactions and occasionally fails. A promising alternative treatment is atovaquone plus azithromycin. METHODS: We conducted a prospective, nonblinded, randomized trial of the two regimens in 58 subjects with non-life-threatening babesiosis on Nantucket, on Block Island, and in southern Connecticut. The subjects were assigned to receive either atovaquone (750 mg every 12 hours) and azithromycin (500 mg on day 1 and 250 mg per day thereafter) for seven days (40 subjects) or clindamycin (600 mg every 8 hours) and quinine (650 mg every 8 hours) for seven days (18 subjects). RESULTS: Adverse effects were reported by 15 percent of the subjects who received atovaquone and azithromycin, as compared with 72 percent of those who received clindamycin and quinine (P<0.001). The most common adverse effects with atovaquone and azithromycin were diarrhea and rash (each in 8 percent of the subjects); with clindamycin and quinine the most common adverse effects were tinnitus (39 percent), diarrhea (33 percent), and decreased hearing (28 percent). Symptoms had resolved three months after the start of therapy in 65 percent of those who received atovaquone and azithromycin and 73 percent of those who received clindamycin and quinine (P=0.66), and after six months no patient in either group had symptoms. Three months after the completion of the assigned regimen, no parasites could be seen on microscopy, and no Babesia microti DNA was detected in the blood of any subject. CONCLUSIONS: For the treatment of babesiosis, a regimen of atovaquone and azithromycin is as effective as a regimen of clindamycin and quinine and is associated with fewer adverse reactions.

Adult↗

PubMed2000

Babesiosis in a renal transplant recipient acquired through blood transfusion.

BACKGROUND: The success of organ-replacement therapies has resulted in a population of chronically immunosuppressed but active people who experience increased vulnerability to tick-borne zoonoses. Several of these infections may be life threatening. Human babesiosis is an emerging zoonosis that is transmitted by the same tick that transmits Lyme disease and human granulocytic ehrlichiosis. METHODS: We briefly review these zoonoses and present a case of a renal transplant recipient who survived infection by Babesia microti contracted through blood transfusion. RESULTS: A recipient of a living-related renal transplant developed acute postoperative hemolytic anemia. The etiology of this anemia was diagnosed by peripheral red blood cell smear as Babesia microti. The patient was managed by a reduction in transplant immunosuppressive therapy and administration of clindamycin and quinine antimicrobials. CONCLUSIONS: Transplant patients may contract babesiosis after tick exposure and/or via blood transfusion. The diagnosis of babesiosis may be confused with malaria and should be included in the differential diagnosis of posttransplant hemolytic-uremic syndrome in organ transplant patients.

Acute Disease↗

PubMed2000

Babesiosis.

Babesiosis is an emerging, tick-transmitted, zoonotic disease caused by hematotropic parasites of the genus Babesia. Babesial parasites (and those of the closely related genus Theileria) are some of the most ubiquitous and widespread blood parasites in the world, second only to the trypanosomes, and consequently have considerable worldwide economic, medical, and veterinary impact. The parasites are intraerythrocytic and are commonly called piroplasms due to the pear-shaped forms found within infected red blood cells. The piroplasms are transmitted by ixodid ticks and are capable of infecting a wide variety of vertebrate hosts which are competent in maintaining the transmission cycle. Studies involving animal hosts other than humans have contributed significantly to our understanding of the disease process, including possible pathogenic mechanisms of the parasite and immunological responses of the host. To date, there are several species of Babesia that can infect humans, Babesia microti being the most prevalent. Infections with Babesia species generally follow regional distributions; cases in the United States are caused primarily by B. microti, whereas cases in Europe are usually caused by Babesia divergens. The spectrum of disease manifestation is broad, ranging from a silent infection to a fulminant, malaria-like disease, resulting in severe hemolysis and occasionally in death. Recent advances have resulted in the development of several diagnostic tests which have increased the level of sensitivity in detection, thereby facilitating diagnosis, expediting appropriate patient management, and resulting in a more accurate epidemiological description.

Animals↗

PubMed2000

Serological expression cloning of novel immunoreactive antigens of Babesia microti.

Increased recognition of the prevalence of human babesiosis in the United States, together with rising concern about the potential for transmission of this infection by blood transfusion, has provided motivation to develop definitive serologic and molecular tests for the causative agent, Babesia microti. To develop more sensitive and specific assays for B. microti, we screened a genomic expression library with patient serum pools. This screening resulted in the identification of three classes of novel genes and an additional two novel, unrelated genes, which together encode a total of 17 unique B. microti antigens. The first class (BMN1-2 family) of genes encodes seven closely related antigens with a degenerate six-amino-acid repeat that shows limited homology to Plasmodium sp. merozoite and sporozoite surface antigens. A second class (BMN1-8 family) of genes encodes six related antigens, and the third class (BMN1-17 family) of genes encodes two related antigens. The two remaining genes code for novel and unrelated sequences. Among the three classes of antigens and remaining novel sequences, five were chosen to code for the most immunodominant antigens (BMN1-2, -9, -15, and -17 and MN-10). Western blot analysis with the resulting recombinant proteins indicated that these antigens were targets of humoral immune responses during B. microti infection in humans.

Amino Acid Sequence↗

PubMed2000

A polymorphic multigene family encoding an immunodominant protein from Babesia microti.

Human babesiosis in the United States is caused predominantly by Babesia microti, a tick-transmitted blood parasite. Improved testing methods for the detection of infection with this parasite are needed, since asymptomatic B. microti infection represents a potential threat to the blood supply in areas where B. microti is endemic. We performed immunoscreening of an expression library of genomic DNA from a human isolate of B. microti (strain MN1). Among 17 unique immunoreactive clones, we identified 9 which represent a related family of genes with little sequence homology to other known sequences but with an architecture resembling that of several surface proteins of Plasmodium. Within this family, a tandem array of a degenerate six-amino-acid repeat (SEAGGP, SEAGWP, SGTGWP, SGTVGP) was found in various lengths between relatively well conserved segments at the N and C termini. In order to examine within-clone variation, we developed a PCR protocol for direct recovery of a specific bmn1-6 homologue directly from 30 human blood isolates, 4 corresponding hamster isolates, and 5 geographically corresponding Peromyscus leucopus (white-footed mouse) isolates. Isolates from the hamsters had the same sequences as those found in the corresponding human blood, suggesting that genetic variation of bmn1-6 does not occur during passage. However, clones from different patients were often substantially different from each other with regard to the number and location of the degenerate repeats within the bmn1-6 homologue. Moreover, we found that strains that were closely related geographically were also closely related at the sequence level; nine patients, all from Nantucket Island, Mass., harbored clones that were indistinguishable from each other but that were distinct from those found in other northeastern or upper midwestern strains. We conclude that considerable genetic and antigenic diversity exists among isolates of B. microti from the United States and that geographic clustering of subtypes may exist. The nature of the bmn1-6 gene family suggests a mechanism of antigenic variation in B. microti that may occur by recombination, differential expression, or a combination of both mechanisms.

Amino Acid Sequence↗

PubMed1999

Evaluation of two-test serodiagnostic method for early Lyme disease in clinical practice.

The Centers for Disease Control and Prevention (CDC) recommend a two-test approach for the serodiagnosis of Lyme disease (LD), with EIA testing followed by Western immunoblotting (WB) of EIA-equivocal and -positive specimens. This approach was compared with a simplified two-test approach (WB of EIA equivocals only) and WB alone for early LD. Case-patients with erythema migrans (EM) rash >/=5 cm were recruited from three primary-care practices in LD-endemic areas to provide acute- (S1) and convalescent-phase serum specimens (S2). The simplified approach had the highest sensitivity when either S1 or S2 samples were tested, nearly doubling when S2 were tested, while decreasing slightly for the other two approaches. Accordingly, the simplified approach had the lowest negative likelihood ratio for either S1 or S2. For early LD with EM, the simplified approach performed well and was less costly than the other testing approaches since less WB is required.

Adolescent↗

PubMed1999

Southern extension of the range of human babesiosis in the eastern United States.

We sought evidence of babesiosis in three residents of New Jersey who were suspected of local acquisition of Babesia microti infection. We tested serial blood samples from these residents for B. microti antibodies and amplifiable DNA by using immunofluorescent antibody and PCR techniques. All three residents experienced symptoms suggestive of acute babesiosis. The sera of each of the patients reacted against babesial antigen at a titer fourfold or higher in sequentially collected blood samples. PCR-amplifiable DNA, characteristic of B. microti, was detected in their blood. These data suggest that human B. microti infections were acquired recently in New Jersey, extending the range of this piroplasmosis in the northeastern United States.

Adult↗

PubMed1998

Persistent parasitemia after acute babesiosis.

BACKGROUND: Babesiosis, a zoonosis caused by the protozoan Babesia microti, is usually not treated when the symptoms are mild, because the parasitemia appears to be transient. However, the microscopical methods used to diagnose this infection are insensitive, and few infected people have been followed longitudinally. We compared the duration of parasitemia in people who had received specific antibabesial therapy with that in silently infected people who had not been treated. METHODS: Forty-six babesia-infected subjects were identified from 1991 through 1996 in a prospective, community-based study designed to detect episodes of illness and of seroconversion among the residents of southeastern Connecticut and Block Island, Rhode Island. Subjects with acute babesial illness were monitored every 3 months for up to 27 months by means of thin blood smears, Bab. microti polymerase-chain-reaction assays, serologic tests, and questionnaires. RESULTS: Babesial DNA persisted in the blood for a mean of 82 days in 24 infected subjects without specific symptoms who received no specific therapy. Babesial DNA persisted for 16 days in 22 acutely ill subjects who received clindamycin and quinine therapy (P=0.03), of whom 9 had side effects from the treatment. Among the subjects who did not receive specific therapy, symptoms of babesiosis persisted for a mean of 114 days in five subjects with babesial DNA present for 3 or more months and for only 15 days in seven others in whom the DNA was detectable for less than 3 months (P<0.05); one subject had recrudescent disease after two years. CONCLUSIONS: When left untreated, silent babesial infection may persist for months or even years. Although treatment with clindamycin and quinine reduces the duration of parasitemia, infection may still persist and recrudesce and side effects are common. Improved treatments are needed.

Animals↗

PubMed1996

Concurrent Lyme disease and babesiosis. Evidence for increased severity and duration of illness.

OBJECTIVE: To determine whether patients coinfected with Lyme disease and babesiosis in sites where both diseases are zoonotic experience a greater number of symptoms for a longer period of time than those with either infection alone. DESIGN: Community-based, yearly serosurvey and clinic-based cohort study. SETTING: Island community in Rhode Island and 2 Connecticut medical clinics from 1990 to 1994. STUDY PARTICIPANTS: Long-term residents of the island community and patients seeking treatment at the clinics. MAIN OUTCOME MEASURES: Seroreactivity to the agents of Lyme disease and babesiosis and number and duration of symptoms. RESULTS: Of 1156 serosurvey subjects, 97 (8.4%) were seroreactive against Lyme disease spirochete antigen, of whom 14 (14%) also were seroreactive against babesial antigen. Of 240 patients diagnosed with Lyme disease, 26 (11%) were coinfected with babesiosis. Coinfected patients experienced fatigue (P = .002), headache (P < .001), sweats (P < .001), chills (P = .03), anorexia (P = .04), emotional lability (P = .02), nausea (P = .004), conjunctivitis (P = .04), and splenomegaly (P = .01) more frequently than those with Lyme disease alone. Thirteen (50%) of 26 coinfected patients were symptomatic for 3 months or longer compared with 7 (4%) of the 184 patients with Lyme disease alone from whom follow-up data were available (P < .001). Patients coinfected with Lyme disease experienced more symptoms and a more persistent episode of illness than did those (n = 10) experiencing babesial infection alone. Circulating spirochetal DNA was detected more than 3 times as often in coinfected patients as in those with Lyme disease alone (P = .06). CONCLUSIONS: Approximately 10% of patients with Lyme disease in southern New England are coinfected with babesiosis in sites where both diseases are zoonotic. The number of symptoms and duration of illness in patients with concurrent Lyme disease and babesiosis are greater than in patients with either infection alone. In areas where both Lyme disease and babesiosis have been reported, the possibility of concomitant babesial infection should be considered when moderate to severe Lyme disease has been diagnosed.

Adolescent↗

PubMed1996

Comparison of PCR with blood smear and inoculation of small animals for diagnosis of Babesia microti parasitemia.

The specific diagnosis of babesiosis, which is caused by the piroplasm Babesia microti, is made by microscopic identification of the organism in Giemsa-stained thin blood smears, detection of babesial antibody in acute-and convalescent-phase sera, or identification of the organism following the injection of patient blood into laboratory animals. Although rapid diagnosis can be made with thin blood smears, parasites are often not visualized early in the course of infection. PCR is a new, rapid diagnostic technique for the detection of Babesia spp. that has not yet been systematically evaluated. We conducted a blinded study of the sensitivity, specificity, and reproducibility of the PCR-based test with patients with babesiosis and a group of asymptomatic subjects residing in a region in southern New England where babesiosis is enzootic. Among 19 patients with recent babesial illness, we found that PCR was as sensitive and specific as the use of Giemsa-stained blood smears and inoculation of hamsters. Among asymptomatic subjects, the PCR result was positive for 3 persons with recent babesial infection and was negative for 41 persons without previous babesial infection. We conclude that the B. microti PCR procedure is sufficiently sensitive, specific, and reproducible for use in the diagnosis of acute babesiosis.

Animals↗

PubMed1996

Efficacy of immunoglobulin M serodiagnostic test for rapid diagnosis of acute babesiosis.

To evaluate the efficacy of an immunoglobulin M indirect immunofluorescent-antibody procedure for diagnosing acute babesiosis, we tested patients with acute babesiosis from a site in New England where the disease is enzootic. The sensitivity of the test was 91%, the specificity was 99%, the positive predictive value was 86%, and the negative predictive value was 99%. This B. microti immunoglobulin M indirect immunofluorescent-antibody procedure is sufficiently sensitive, specific, and reproducible for use in the routine clinical diagnosis of acute babesiosis.

Acute Disease↗

PubMed1995

Infection with a babesia-like organism in northern California.

BACKGROUND: Human babesiosis is a tick-transmitted zoonosis associated with two protozoa of the family Piroplasmorida: Babesia microti (in the United States) and B. divergens (in Europe). Recently, infection with an unusual babesia-like piroplasm (designated WA1) was described in a patient from Washington State. We studied four patients in California who were identified as being infected with a similar protozoal parasite. All four patients had undergone splenectomy, three because of trauma and one because of Hodgkin's disease. Two of the patients had complicated courses, and one died. METHODS: Piroplasm-specific nuclear small-subunit ribosomal DNA was recovered from the blood of the four patients by amplification with the polymerase chain reaction. The genetic sequences were compared with those of other known piroplasm species. Indirect immunofluorescent-antibody testing of serum from the four patients and from other potentially exposed persons was performed with WA1 and babesia antigens. RESULTS: Genetic sequence analysis showed that the organisms from all four patients were nearly identical. Phylogenic analysis showed that this strain is more closely related to a known canine pathogen (B. gibsoni) and to theileria species than to some members of the genus babesia. Serum from three of the patients was reactive to WA1 but not to B. microti antigen. Serologic testing showed WA1-antibody seroprevalence rates of 16 percent (8 of 51 persons at risk) and 3.5 percent (4 of 115) in two geographically distinct areas of northern California. CONCLUSIONS: A newly identified babesia-like organism causes infections in humans in the western United States. The clinical spectrum associated with infection with this protozoan ranges from asymptomatic infection or influenza-like illness to fulminant, fatal disease.

Adult↗

PubMed1995

Acyclovir-induced neutropenia in an infant with herpes simplex encephalitis: case report.

A newborn infant whose condition was diagnosed as herpes simplex encephalitis and who had subsequent recurrences of skin disease had repeated episodes of neutropenia while receiving therapy with intravenous (30 mg/[kg.d]) or oral (30 mg/]kg.d]) acyclovir. The neutropenia did not recur when the dosage of oral acyclovir was reduced to 10 mg/(kg.d). This case represents the first well-documented report of acyclovir-induced neutropenia.

Acyclovir↗