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Biomedical subjects

M L Eberhard

Publications and source records attributed to M L Eberhard.

At least 55 records · Page 3Linked to original sources
PubMed1996

Th1-like antifilarial immune responses predominate in antigen-negative persons.

To characterize immune responses associated with the putatively immune state in bancroftian filariasis (that is, both microfilaria and antigen free), humoral and cellular responses were compared among antigen- and microfilaria-negative, antigen-positive and microfilaria-negative, and microfilaria-positive individuals. Antifilarial isotype levels were measured by enzyme-linked immunosorbent assay. Peripheral blood mononuclear cell responses were measured by proliferation, by bioassay for interleukin-2 (IL-2) and IL-10, and by reverse transcription-PCR for IL-4, IL-5, and gamma interferon. The absence of circulating filarial antigen was associated with Th1-like responses, including significantly higher proliferative (P < 0.001) and IL-2 (P = 0.008) responses and a higher prevalence of gamma interferon (0.02 < P < 0.1) responses. Significantly elevated antifilarial immunoglobulin G4 (IgG4) levels (P = 0.0035) were associated with antigenemia, whereas microfilaremia was associated with significantly decreased antifilarial IgG2 levels (P = 0.0014). IL-4 mRNA levels were not significantly different among the three groups; however, there was a subpopulation of microfilaremic individuals who did not make detectable levels of IL-4 mRNA and who produced low antifilarial IgG4 levels compared with those of individuals who had detectable levels of IL-4 mRNA. IL-5 mRNA levels also were not significantly different among groups; however, more microfilaremic individuals produced IL-5 mRNA in response to adult filarial antigens, and total parasite-specific IL-4 and IL-5 mRNA levels were significantly correlated (P = 0.05). Although longitudinal data are not currently available, the elevated Th1-like responses in antigen- and microfilaria-negative individuals are consistent with the hypothesis that these responses contribute to protection in putatively immune individuals.

Adolescent↗
PubMed1996

A survey of knowledge, attitudes, and perceptions (KAPs) of lymphatic filariasis, elephantiasis, and hydrocele among residents in an endemic area in Haiti.

To assess knowledge, attitudes, and perceptions about bancroftian filariasis, 104 residents of an endemic area in Haiti were interviewed. Questions focused on 1) whether people understood the relationship between infection and disease, 2) recognition of the role that mosquitoes play in transmission, 3) perceived importance of hydrocele and elephantiasis in relation to other recognized diseases, and 4) the willingness of the community to participate in a control program. Fewer than 50% of residents had heard of filariasis and only 6% of those surveyed knew that it was transmitted by mosquitoes. In contrast, all persons knew of the clinical conditions of hydrocele and elephantiasis. Hydrocele was thought to be caused by trauma (60%) or trapped gas (30%); elephantiasis by walking bare foot on soil or water (37%) or by use of ceremonial powder that had been sprinkled on the ground (23%). Of 76 respondents, 53% and 38% thought that hydrocele could be treated through surgery or a drug, respectively, whereas 86 respondents, 85% and 15% believed that either surgery or a drug could be used to treat elephantiasis. In this context, persons were not referring to a specific drug; rather, they believed a drug existed (possibly in some other country) that could cure these conditions. Hydrocele and elephantiasis ranked second to acquired immunodeficiency syndrome as perceived health problems, most likely because residents believed treatment for conditions such as malaria, intestinal worms, anemia, and diarrhea was easily obtained. Responses were influenced by age, sex, and symptoms, but none of these effects were statistically significant except that persons with hydrocele or elephantiasis were more likely to have sought treatment than persons without these conditions (P = 0.0006). The survey results indicate that awareness of the causes of disease, the relationship between infection and disease, and goals of treatment must be heightened through community-based education campaigns to increase the possibility of acceptance and support of control programs.

Adolescent↗
PubMed1996

Respiratory symptoms and subcutaneous granuloma caused by mesocercariae: a case report.

A 38-year-old man with no history of pulmonary disease developed intermittent hives and bronchospasms shortly after returning from a hunting trip. Approximately one year later, examination of an excised subcutaneous nodule demonstrated infection with a mesocercaria (larval trematode). The morphology of the parasite was consistent with infection with a parasite of the Alaria spp. or Strigea spp. Eating undercooked wild goose meat during the hunting trip was the most likely source of infection. This appears to be the first report of human infection with mesocercariae acquired through the ingestion of wild goose meat.

Adult↗
PubMed1996

Immunopurification and measurement of IgE in serum samples from bancroftian filariasis patients.

Patent infection with Wuchereria bancrofti is associated with increased levels of filaria-specific IgG4 and IgE. In vitro quantification of filaria-specific IgE is hampered by its small proportion in serum relative to other isotypes and by potential competition with IgG4 for the same epitopes on parasite antigens. To determine if IgG4 or other isotypes inhibit the detection of parasite-specific IgE, total IgE was affinity purified prior to filaria-specific IgE enzyme-linked immunosorbent assay. Briefly, anti-human IgE mouse monoclonal antibody 6H10 was coupled to Affigel, and 50 microliters of patient serum was incubated on microcolumns for 16 hr. Total IgE was eluted with 25 mM triethylamine (pH 11.2) and levels of total and filaria-specific IgE and total IgG4 were assessed in the filtrates and eluates. Sera from 14 patients with W. bancrofti microfilaremia (Mf+) and 17 amicrofilaremic patients with chronic pathology (CP) were assayed. Filtrates and eluates were devoid of IgE and IgG4, respectively. The average yield of total IgE in the eluates was 70% (SEM = 6.5; range 21-100%) of that measured in the serum. Antifilarial IgE levels in column eluates were significantly higher in serum samples from CP patients than Mf+ patients. Antibody inhibition of IgE was assessed by comparing the levels of anti-filarial IgE detected in eluates and serum. Evidence for antibody-mediated inhibition of IgE detection was obtained with 2/2 samples from Indian tropical pulmonary eosinophilia patients, but only 2/14 and 4/17 Mf+ and CP patients, respectively.

Adult↗
PubMed1996

Pathology of acute fatal babesiosis in hamsters experimentally infected with the WA-1 strain of Babesia.

A strain of Babesia (strain WA-1), recently isolated from a human in Washington State, was found to be unusually virulent for hamsters; it caused acute infection and death in a large proportion of animals 5 to 7 days after inoculation. To assess the basic pathologic lesions associated with this infection, 30 male Syrian hamsters (Mesocricetus auratus) were inoculated intraperitoneally with the WA-1 strain. Twelve animals (40%) died within 5 to 6 days. The other 18 animals, all infected and clinically ill, were killed on the sixth or seventh day for biochemical study. All 12 animals that died from the infection showed high parasitemia, heavy intravascular hemolysis, and pronounced vascular stasis with red-cell sequestration in the spleen, liver, lungs, kidneys, and brain. Serologic study revealed severe anemia (mean hematocrit, 29) with hemolyzed serum and marked elevation of the serum transaminases. The mechanism of death was thought to be diffuse anoxic tissue damage secondary to vascular stasis, which led to multiorgan failure.

Acute Disease↗
PubMed1995

Onchocerca volvulus: parasitologic and serologic responses in experimentally infected chimpanzees and mangabey monkeys.

Six chimpanzees (Pan troglodytes) and six mangabey monkeys (Cercocebus atys) were inoculated with Onchocerca volvulus third-stage larvae (L3) of West African origin. Two chimpanzees each received 200, 300, or 400 L3, while three mangabeys each received either 50 or 250 L3. All six chimpanzees became microfilaria positive between 11 and 25 months postinoculation (PI), while two of the six mangabeys were skin-snip positive at 24 and 37 months PI, respectively. All chimpanzees developed antibodies to two native antigens of 14 and 22 kDa and to the recombinant antigens OV16, OC3.6, and OC9.3. Marked antibody responses were observed in the mangabey monkeys, and in general, the responses were similar to those observed in the chimpanzees. However, in the mangabeys, these responses did not generally manifest themselves until later in the infection. The results of this study suggest that in chimpanzees, the smallest inoculum used, 200 L3, was sufficient to initiate consistent infections that had parasitologic and immunologic parameters equivalent to animals inoculated with larger numbers of larvae. Similarly, inoculation of mangabey monkeys with small numbers of larvae appeared to be as likely to establish infection and induce immunologic responses as did inoculation of larger numbers of larvae. Microfilaria-positive chimpanzees and mangabey monkeys were examined by three conventional imaging techniques (X ray, ultrasound, and magnetic resonance imaging (MRI)), but no adult worms or nodules could be identified in any animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Clinical, parasitologic, and immunologic observations of patients with hydrocele and elephantiasis in an area with endemic lymphatic filariasis.

Hydrocele and elephantiasis, major clinical manifestations of bancroftian filariasis, are thought to share a common pathogenesis. The characteristics of 121 patients with hydrocele or elephantiasis in Leogane, Haiti, were compared: 39% of 57 men with hydrocele and 3% of 64 persons with lymphedema of the leg were microfilaria-positive (P < .001). Circulating filarial antigen, presumably from the adult worm, was detected in 15 (43%) microfilaria-negative men with hydrocele and 9 (15%) microfilaria-negative persons with leg edema (P = .004). Microfilaria-positive men had lower levels of filaria-specific IgG1 and hydroceles of significantly smaller volume and shorter duration than did microfilaria-negative men; hydrocele volume was inversely associated with microfilarial density (P = .001). In contrast, filarial antigen but not microfilariae was associated with filaria-specific IgG4 and decreased lymphocyte proliferation. Antigen status was not associated with severity of leg edema. In this filariasis-endemic area, men with hydrocele are more immunologically and parasitologically heterogeneous than are persons with elephantiasis.

Adolescent↗
PubMed1995

Reduced antifilarial IgG4 responsiveness in a subpopulation of microfilaremic persons.

Antifilarial IgG4 is a marker of active filarial infection; however, 10% of microfilaremic persons may have low levels of antifilarial IgG4. To gain insight into how persons with microfilaremia with low antifilarial IgG4 levels (< 10 micrograms/mL) differ from those with high levels (> 170 micrograms/mL), total IgG4 and IgE and filaria-specific IgE, IgG1, and IgG2 were measured by ELISA in serum samples collected from 85 microfilaremic Haitians. Persons with lower levels of antifilarial IgG4 had significantly lower total IgG4 and total IgE (P < .01), lower levels of antifilarial IgG1, IgG2, and IgE (P < .01, = .03, and < .01, respectively), and higher antigenemia and microfilaremia (P < .01) than did persons with higher levels of antifilarial IgG4. Increased antigen loads in microfilaremic persons may be associated with a down-regulation of antibody production, which extends to all isotypes.

Adolescent↗
PubMed1995

Acquisition and expression of humoral reactivity to antigens of infective stages of filarial larvae.

Measurement of anti-larval responses in filaria-exposed populations may shed light on the natural history of exposure to Wuchereria bancrofti. Using serum samples obtained by a cross-sectional survey of 172 individuals from two neighbourhoods in Leogane, Haiti, antibody responses directed against infective stage filarial larvae (L3) were assayed by enzyme-linked immunosorbent assay (ELISA), immunofluorescence (IFA), and immunoblot for the presence of anti-larval antibodies. ELISA results indicated that virtually all members of both neighbourhoods mounted an anti-larval antibody response within the first five years of life, suggesting that exposure to infection is universal. In a multiple linear regression analysis that modelled antibody levels as a function of age, gender, microfilaria status, and neighbourhood (as a proxy for transmission intensity), isotype-specific antibody levels were found to be significantly influenced by both age and neighbourhood. Antibodies directed against the surface of L3 also were age-dependent; the prevalence of IgG antibodies detected by IFA was significantly higher in children than in adults. The prevalence of antibody recognition of 16.7 and 72.3 kDa L3 antigens on immunoblots was significantly greater for serum samples from microfilaraemic than amicrofilaraemic persons. These results suggest that antibody responses to larval antigens are influenced to varying degrees by age, transmission intensity, and microfilaraemia status.

Adolescent↗
PubMed1995

Babesiosis in Wisconsin: a potentially fatal disease.

Babesiosis is emerging as an important tick-borne zoonosis in the United States. Most reported cases of this parasitic disease have been acquired in the Northeast. To date, only two clinical cases of Babesia microti infection acquired in the upper Midwest have been described. We report eight more cases. Most if not all of the 10 total cases probably were acquired in northwestern Wisconsin. Three cases (30% of 10) we now report were fatal and occurred in elderly patients (65-75 years old) who died after complicated hospital courses. One patient probably had had a latent Babesia infection that activated because of immunosuppression attributable to high-dose corticosteroid therapy and to splenic infarctions caused by cholesterol emboli. All three fatal cases were diagnosed incidentally and highlight the importance of considering the diagnosis of babesiosis in febrile patients who have been in babesiosis-endemic areas; examining their blood smears carefully; and treating promptly with clindamycin and quinine, and, if indicated, exchange transfusion. Medical personnel should be knowledgeable about this zoonosis, which is not limited to the northeastern United States, and is potentially serious, sometimes fatal.

Aged↗
PubMed1995

Survival and infectivity of Babesia in blood maintained at 25 C and 2-4 C.

Babesia microti-infected blood was stored at room temperature (approximately 25 C) or refrigerated (4 C) for 30 days. To assess viability of the parasites after storage at these 2 temperatures, a 0.25-ml aliquot was inoculated into each of 2 hamsters in 2 separate experiments at days 3, 7, 10, 14, 17, 21, 25, and 30. Blood films were prepared and examined weekly for the presence of parasites from all hamsters. Of hamsters inoculated with blood held at room temperature, only those inoculated at day 3 became positive, whereas 4/4 hamsters inoculated with refrigerated blood on day 17 became parasitemic and 1/4 hamsters inoculated with blood held for 21 days became parasitemic. These results indicate that under blood banking conditions, this intracellular protozoan parasite can remain infective and transfusion-acquired infection with this parasite could occur throughout most of the time that blood is normally stored.

Animals↗
PubMed1995

The role of tadpoles and frogs as paratenic hosts in the life cycle of Dracunculus insignis (Nematoda: Dracunculoidea).

The possibility exists that paratenic hosts play a role in the life cycle of various Dracunculus species. In the present study, we established that tadpoles of 2 genera of frogs (Xenopus and Rana) were capable of ingesting copepods infected with third-stage larvae (L3) of Dracunculus insignis. Once ingested, the L3s migrated from the gut to the somatic tissues of the tadpoles. In Xenopus, the dracunculid larvae persisted through the metamorphosis of the tadpoles into adult frogs. These observations confirm the concept that paratenic hosts, such as tadpoles or frogs, may be important means of transporting infective larvae of Dracunculus species up the food chain and facilitate transmission to the definitive hosts.

Animals↗
PubMed1994

Cultivation and phylogenetic characterization of a newly recognized human pathogenic protozoan.

An intraerythrocytic protozoan (WA1) recently isolated from a patient in Washington State was shown to be morphologically identical to Babesia microti but biologically and genetically distinct. Continuous growth of WA1 was established in stationary erythrocyte cultures. Hybridization of a chemiluminescent Babesia-specific DNA probe to Southern blots of restriction enzyme-digested genomic DNA showed that WA1 could be distinguished from other Babesia species that were antigenically cross-reactive (Babesia gibsoni and babesial parasites from desert bighorn sheep, Ovis canadensis nelsoni) or known to infect humans (B. microti, Babesia divergens, and Babesia equi), or both. A 1436-bp portion of the nuclear small subunit rRNA gene of WA1 was sequenced and analyzed. Genetic distance analysis showed that WA1 is most closely related to the canine pathogen B. gibsoni and lies within a phylogenetic cluster with Theileria species and B. equi. The methodology described will be useful for improved diagnosis and identification of human protozoal pathogens.

Animals↗
PubMed1994

Differential proliferative and interleukin-10 responses to fractionated filarial antigens: preferential recognition by patients with chronic lymphatic dysfunction.

To characterize filarial antigens that may be associated with the development of chronic lymphatic dysfunction in persons with lymphatic filariasis, T cell responsiveness to Brugia pahangi adult worm extracts and SDS-PAGE antigen fractions were examined among Haitians from an area in which Wuchereria bancrofti is endemic. Greater T cell proliferation and interleukin-10 (IL-10) production were observed in amicrofilaremic patients with hydrocele or elephantiasis than in amicrofilaremic or microfilaremic asymptomatic persons. Antigen fractions that stimulated the highest proliferative responses (in the 25-49 kDa range) and IL-10 production were not identical. Further separation of an immunodominant 30- to 38-kDa fraction by ion exchange high-pressure liquid chromatography identified several subfractions, including a 32-kDa protein band, that elicited T cell responses from patients with elephantiasis or hydrocele. By immunoblot, these patients also had markedly greater humoral reactivity to parasite antigens of approximately 52, 43, 32, and 30 kDa.

Adolescent↗
PubMed1994

Periorbital dirofilariasis.

A differential diagnosis of inflammatory periocular soft tissue masses includes sarcoidosis, ruptured dermoid cyst, infectious abscess, metastatic neoplastic disease, and idiopathic pseudotumor. The authors present the case of a 42-year-old woman with a periocular inflammatory mass caused by dirofilaria of a nematode classification as Dirofilaria tenuis. The extraction of the worm was curative and the patient has been symptom-free for the ensuing 12 months. This zoonotic infection, spread by mosquito vectors from animal hosts to humans, is rarely encountered in the United States as a cause of periorbital inflammation. A history of migratory swelling and residence in, or travel to, endemic areas (the southeastern United States) should suggest the possibility of Dirofilaria infection.

Adult↗
PubMed1994

Age-specific prevalence of antigenemia in a Wuchereria bancrofti-exposed population.

Antigen detection assays serve as a useful adjunct to blood examinations for studies of filariasis, in terms of the diagnostic and epidemiologic information provided. We examined the utility of the Og4C3 antigen detection enzyme-linked immunosorbent assay for field studies and analyzed the distribution of Wuchereria bancrofti antigenemia in a Haitian population. Using serum samples collected following venipuncture, antigenemia levels were correlated with microfilaremia (P < 0.001). The microfilariae had a pronounced nocturnal periodicity while the sensitivity of the antigen assay was the same whether serum samples were collected during the day or at night. To determine whether the Og4C3 assay could be used in conjunction with fingerprick blood examinations, nocturnal blood surveys were conducted. Of 419 persons surveyed, 207 (49.4%) were antigen-positive with the Og4C3 assay. Serum specimens from all 121 microfilaremic individuals were antigen positive (100% sensitivity). The age prevalence of antigenemia increased from 24.5% for 1-5-year-old children to 70% for persons greater than 50 years of age. These results demonstrate that the Og4C3 assay is a sensitive tool for the detection of infection and raise questions about the expression of protective immunity in populations exposed to infection.

Adolescent↗