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Biomedical subjects

M L Eberhard

Publications and source records attributed to M L Eberhard.

At least 73 records · Page 4Linked to original sources

Dirofilariasis in Kuwait: first report of human infection due to Dirofilaria repens in the Arabian Gulf.

Zoonotic dirofilariasis has been reported sporadically from many areas of the world but thus far, there are no such reports from the Arabian Peninsula. We present the first report of human dirofilariasis from this region in the Middle East and discuss the significance of the finding. A fixed, elongated mass in the abdominal wall of a 50-year-old Kuwaiti man was excised and a worm was identified in an abscess in tissue sections. The location of the nodule in subcutaneous tissue, the diameter of the worm in section, the multilayered cuticle with fine longitudinal ridges on the external layer, prominent internal cuticular ridges, and abundant somatic muscles suggested the diagnosis of the worm as Dirofilaria (Nochetiella) repens, a natural parasite of dogs and cats in Asia, Africa, and Europe.

Abdominal Muscles↗

Babesiosis in Washington State: a new species of Babesia?

OBJECTIVE: To characterize the etiologic agent (WA1) of the first reported case of babesiosis acquired in Washington State. DESIGN: Case report, and serologic, molecular, and epizootiologic studies. SETTING: South-central Washington State. PATIENT: A 41-year-old immunocompetent man with an intact spleen who developed a moderately severe case of babesiosis. MEASUREMENTS: Serum specimens from the patient were assayed by indirect immunofluorescent antibody (IFA) testing for reactivity with seven Babesia species and with WA1, which was propagated in hamsters inoculated with his blood. A Babesia-specific, ribosomal-DNA (rDNA) probe was hybridized to Southern blots of restriction-endonuclease-digested preparations of DNA from WA1, Babesia microti, and Babesia gibsoni. Serum specimens from 83 family members and neighbors were assayed for IFA reactivity with WA1 and B. microti. Small mammals and ticks were examined for Babesia infection. RESULTS: The patient's serum had very strong IFA reactivity with WA1, strong reactivity with B. gibsoni (which infects dogs), but only weak reactivity with B. microti. DNA hybridization patterns with the rDNA probe clearly differentiated WA1 from B. gibsoni and B. microti. Four of the patient's neighbors had IFA titers to WA1 of 256. The tick vector and animal reservoir of WA1 have not yet been identified, despite trapping 83 mammals and collecting 235 ticks. CONCLUSIONS: WA1 is morphologically indistinguishable but antigenically and genotypically distinct from B. microti. Some patients elsewhere who were assumed to have been infected with B. microti may have been infected with WA1. Improved serodiagnostic and molecular techniques are needed for characterizing Babesia species and elucidating the epidemiology of babesiosis, an emergent zoonosis.

Adolescent↗

Maternal filarial infection - a persistent risk factor for microfilaremia in offspring?

The observation that children born to mothers that are infected with Wuchereria bancrofti ore more susceptible to filarial infection than those born to uninfected mothers, raises many questions, particularly regarding immune mechanisms. In this article, Allen Hightower, Patrick Lommie and Mark Eberhard discuss these issues and their implications for the epidemiology of filarial infection.

Journal Article↗

Strianema venezuelensis gen. et sp. n. (Filarioidea: Onchocercidae) from Venezuelan armadillos (Dasypus spp.).

A new filaria, Strianema venezuelensis gen. et sp. n., is described from armadillos in Venezuela. The adults inhabit the subcutaneous tissues and the microfilariae are found in the skin and occasionally the blood. The adults, which are of small size (males 9.6 to 13.8 mm in length by 57 to 63 microns in diameter, females 18.3 to 26.3 mm in length by 95 to 120 microns in diameter), have a distinctly striated cuticle. This filaria resembles most closely the genus Cercopithifilaria, from which it can be distinguished by the absence of a buccal capsule or pre-esophageal ring, and 11 to 13 pair of caudal papillae, three or four pair of which are separated as a group anterior to the cloaca. The species, S. venezuelensis, can be distinguished from the three other species of filariae described from armadillos by the undivided esophagus, number and distribution of caudal papillae in the male, size and shape of the spicules, and the distinctive microfilaria. The microfilaria, which averages 280 microns in length, has a unique, slender, almost filamentous tail.

Animals↗

Heterogeneity in filarial-specific immune responsiveness among patients with lymphatic obstruction.

The relationship between chronic obstructive disease and antifilarial immune responsiveness was studied in the Haitian community of Leogane, where Wuchereria bancrofti is endemic. Differences in sex ratios and in the prevalence of microfilaremia were observed between patients with hydrocele and those with lymphedema or elephantiasis of the lower limb. Only 2 of 84 patients with limb involvement (74 women, 10 men) were microfilaremic compared with 25 of 42 men with hydrocele. Microfilaria-positive men with hydrocele had significantly lower IgG2 and proliferative responses to filarial antigen than did amicrofilaremic men with hydrocele or individuals with lymphedema or elephantiasis. Parasite-specific cellular responses of amicrofilaremic individuals with obstructive disease were greater, although not significantly so, than those of amicrofilaremic asymptomatic members of the community. These results are compatible with the hypothesis that development of obstructive disease of the lymphatics has an immune component in amicrofilaremic persons.

Adolescent↗

Zoonotic Brugia infection in western Michigan.

A case of zoonotic lymphatic filariasis is reported from a resident of Michigan. Numerous sections of a small, nongravid female worm, measuring approximately 65 microns in diameter, were identified in histological preparations of an excised inguinal lymph node. Based on its location, small size, thin cuticle, small number of muscle cells, and paired uterine tubes, the worm was identified as a Brugia species, undoubtedly of zoonotic origin from the local animal population. The pathological response of the host to the parasite was one of hyperplastic lymph nodes with a focal granulomatous reaction. This is the first such case to be reported from Michigan and further expands the geographical range of states in which zoonotic Brugia infection have been reported.

Adult↗

Preliminary evaluation of recombinant Onchocerca volvulus antigens for serodiagnosis of onchocerciasis.

Serodiagnostic assays for onchocerciasis based on native antigens are hampered by the scarcity of antigen, and they suffer from poor specificity. The present study was designed to evaluate the diagnostic utility of recently described recombinant Onchocerca volvulus antigens OC 3.6 and OC 9.3 in enzyme immunoassays. The recombinant proteins were expressed as glutathione S-transferase fusions and were tested in several enzyme immunoassay formats to measure immunoglobulin G (IgG) and IgG4 antibodies with sera from patients with onchocerciasis in Nigeria and with various types of control sera. The best results were obtained by measuring IgG4 antibodies to the fusion proteins. Forty of 42 (95%) serum specimens from patients with onchocerciasis were reactive with OC 3.6; the reactivity with OC 9.3 was 81%. Results obtained with sera from experimentally infected chimpanzees suggest that OC 3.6 might be especially useful for detecting prepatent infections in humans, while OC 9.3 mainly detects mature, patent infections. Sera from individuals in Nigeria and the United States residing in areas nonendemic for onchocerciasis were uniformly nonreactive with these antigens in IgG and IgG4 assays, as were sera from patients with bancroftian filariasis, brugian filariasis, loiasis, ascariasis, schistomiasis, and dracunculiasis. These results suggest that enzyme immunoassays based on the recombinant antigens OC 3.6 and OC 9.3 are useful for the diagnosis of onchocerciasis.

Animals↗

Comparative efficacy of clearing-dose and single high-dose ivermectin and diethylcarbamazine against Wuchereria bancrofti microfilaremia.

To compare the efficacy and tolerability of various combinations of low- and high-dose ivermectin and diethylcarbamazine (DEC), 59 persons with Wuchereria bancrofti microfilaremia were enrolled in a double-blinded six-arm clinical trial in Leogane, Haiti. On day 1, study participants were treated with low clearing doses of ivermectin, DEC, or placebo; on day 5 they received 200-400 micrograms/kg of ivermectin or 6 mg/kg of DEC. Adverse reactions, which were generally mild, occurred more frequently with ivermectin than with DEC. One year after treatment, the geometric mean microfilarial density returned to 0.9% of pretreatment levels for persons who received a total of 420 micrograms/kg of ivermectin. This rate was significantly lower than 5.6% for persons who were treated with 220 micrograms/kg of ivermectin (P = 0.02) and 9.3% for those receiving 6 or 7 mg/kg of DEC (P = 0.006). Persons treated with a clearing dose of ivermectin followed by 6 mg/kg of DEC also had low microfilarial densities (1.7% of pretreatment levels), suggesting an additive or synergistic effect of the two drugs. The addition of a clearing dose neither reduced the severity of adverse reactions nor improved the efficacy of high-dose ivermectin. Community-based intervention trials are now warranted to determine the feasibility and effectiveness of mass chemotherapy with single high-dose ivermectin for the prevention and control of lymphatic filariasis.

Adolescent↗

Trypanosomes and microfilariae in feral owl and squirrel monkeys maintained in research colonies.

A group of 358 owl and squirrel monkeys imported from Colombia, Peru, and Bolivia for the U.S. Agency for International Development Malaria Vaccine Development Program was examined for trypanosomes and microfilariae. Trypanosoma rangeli, isolated by hemoculture from Aotus nancymai, Saimiri b. boliviensis, and S. b. peruviensis, accounted for 76.6% of all trypanosome infections. Trypanosoma cruzi was isolated from 25 of 194 S. b. boliviensis, including two mixed infections with T. rangeli. Identifications of trypanosomes were confirmed by blinded tests with a panel of five rRNA probes on a subsample of cultures identified morphologically. Although no trypanosomes were isolated from Aotus vociferans or A. lemurinus griseimembra, positive serologic responses to T. cruzi were observed by indirect immunofluorescence assay in all species of monkeys examined and ranged from 42.1% among S. b. peruviensis to 92.3% among A. vociferans. Among T. rangeli-infected monkeys, 43.7% were seronegative for T. cruzi. No microfilariae were found in S. b. boliviensis or A. l. griseimembra. Mansonella barbascalensis and Dipetalonema caudispina were observed in A. vociferans, M. panamensis in A. nancymai, and M. saimiri and D. caudispina in S. b. peruviensis. Such naturally occurring infections in imported animal models are potential sources of accidental transmission to animal handlers and uninfected laboratory animals and can introduce confounding variables into otherwise well-planned and well-executed studies.

Animals↗

Survival and development of larval Onchocerca volvulus in diffusion chambers implanted in primate and rodent hosts.

Third-stage larvae (L3) of Onchocerca volvulus were implanted in diffusion chambers in chimpanzees, mangabey monkeys, rhesus monkeys, squirrel monkeys, and inbred strains of mice, jirds, and rats for 3-63 days. At different times during the experimental period, larvae were recovered and assessed for their viability and development. Survival and growth rates were equal regardless of whether the implanted larvae were fresh or cryopreserved. Survival and growth rates of the larvae did not differ among the primate and rodent hosts tested, with the exception of squirrel monkeys and rats, which were resistant to infection. Molting from L3 to fourth-stage larvae began on day 3 and continued through day 14 in the primates and rodents. The primate and rodent models developed in the present study will be useful for the study of the immunology and chemotherapy of onchocerciasis.

Animals↗

Transplacental transmission of Wuchereria bancrofti in Haitian women.

To document the occurrence of transplacental transmission of microfilariae and to determine how frequently it occurred, umbilical cord blood samples and placental tissues were collected from 22 microfilaria-positive women in an area with endemic Wuchereria bancrofti. Microfilaria (mf) counts in the women ranged from 1 to 3,820 mf/ml. Microfilariae were detected in 2 placenta samples and a single cord blood sample. The positive cord blood sample and 1 of the positive placenta samples came from the same woman; no microfilariae were found in a finger prick sample taken from the infant 3 wk after delivery. Our results suggest that microfilariae cross the placenta in less than 10% of pregnancies of microfilaria-positive mothers. Furthermore, the microfilaria count of the mother does not seem to influence directly whether microfilariae are present in the placental blood pool. Although actual transfer of microfilariae to the fetus may occur infrequently, exposure to parasite antigens occurs with much greater frequency. The effect of in utero exposure to either microfilariae or parasite antigens may render newborns tolerant and explain why children born to infected mothers are almost 3 times more likely to become infected than are children born to uninfected women.

Animals↗

Mansonella ozzardi: the course of patency in experimentally-infected patas monkeys.

Twenty-five of 30 patas monkeys (Erythrocebus patas) inoculated with varying numbers (35 to 135) of third-stage larvae of Mansonella ozzardi developed patent infections in an average of 163 days. There was no correlation between the size of the inoculum and the length of the prepatent period. Ten of the monkeys were monitored thereafter by regular blood examination for extended periods of time in order to characterize the onset, course and duration of patency. Typically, with the onset of patency, microfilaremias increased steadily, peaking at about 20 weeks and then decreased slowly stabilizing at low levels for up to 48 weeks. Thereafter microfilariae disappeared from the blood and occasionally reappeared in scanty numbers. Laparotomies and followup studies indicated that the spleen was involved in the suppression of peripheral microfilaremia as had been observed earlier in patas monkeys infected with Loa loa. In ten monkeys splenectomized after the initial "wave" of microfilaremia, it was observed that (a) 30% of the animals remained amicrofilaremic, (b) another 30% reestablished patent infections but microfilaremias were lower than presplenectomy levels, and (c) in the remaining 40%, levels of microfilaremia equaled or exceeded pre-splenectomy levels. Patent infections persisted for up to 212 weeks. One monkey splenectomized prior to inoculation with 87 larvae developed a patent infection with microfilaremia which persisted for 156 weeks. Three monkeys with low and high levels of microfilaremia bled at four hour intervals over a 28 hour period showed no evidence of periodicity in the microfilaria.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Kinetics of circulating human IgG4 after diethylcarbamazine and ivermectin treatment of bancroftian filariasis.

Patent filarial infections are associated with elevated levels of parasite-specific IgG4. This study investigated the shifts of filarial-specific human IgG and IgG4 antibodies after diethylcarbamazine and ivermectin treatment of bancroftian filariasis. Thirty adult Haitians were treated first with a 1-mg clearing dose of ivermectin and then with either one or two 200-micrograms/kg doses of ivermectin or with 12 daily 6-mg/kg doses of diethylcarbamazine. Posttreatment levels of antifilarial IgG4 were dependent on both treatment group and time of follow-up. IgG4 increased markedly to a maximum by day 30 in all treatment groups and then began to decrease; the greatest decrease was among diethylcarbamazine-treated patients. Posttreatment microfilaremia was inversely correlated with the decrease in IgG4; thus, shifts in IgG4 were associated with treatment response for all groups. Antifilarial IgG levels were not correlated with drug treatment and did not change to the same degree as did IgG4 responses.

Animals↗

Alterations in filarial antigen-specific immunologic reactivity following treatment with ivermectin and diethylcarbamazine.

The presence of circulating microfilariae has been associated with alterations in B and T cell functions. In this study, we compared the influence of diethylcarbamazine (DEC) and ivermectin on filarial antigen-specific immune responses in a Haitian population. Both drugs were effective at reducing microfilaremia levels to less than 10% of pretreatment levels for up to one year. This reduction in microfilaremia was associated with two phases of altered cellular responsiveness monitored with in vitro assays. Five days post-treatment, cellular proliferation in response to both filarial and nonfilarial antigens was significantly increased, as was the background response in the absence of any antigen. At both nine months and one year post-treatment, the filarial antigen-specific reactivity of both DEC- and ivermectin-treated patients was significantly increased over baseline levels. No differences were observed between the two treatment groups in terms of humoral or cellular reactivity to filarial antigens, despite evidence suggesting a role for DEC in adult worm killing. These results provide additional evidence that microfilariae modulate antifilarial immune reactivity.

Animals↗

Albendazole in the treatment of onchocerciasis: double-blind clinical trial in Venezuela.

A double-blind clinical trial was conducted in Monagas State, Venezuela to assess the tolerance and efficacy of albendazole in the therapy of Onchocerca volvulus infection. Forty-nine patients (26 treated and 23 controls) received a 10-day course of albendazole (400 mg/day) or a placebo. Consistent with the excellent tolerance observed, albendazole did not kill microfilariae. However, analysis of changes in microfilarial densities (mf/mg of skin) over one year showed that albendazole was active against O. volvulus, presumably by interfering with embryogenesis. The nature, degree, and duration of this effect remain to be determined.

Adolescent↗

Identification of surrogate rodent hosts for larval Onchocerca lienalis and induction of protective immunity in a model system.

The objectives of this project were to screen a variety of inbred rodent species and strains to determine their usefulness as surrogate hosts for the study of the early larval development of Onchocerca lienalis and then to use a selected model to study the induction of protective immunity. In the primary screen, 6 strains of mice, 5 strains of rats, jirds, and multimammate rats were tested. Animals were infected with fresh O. lienalis by subcutaneous implantation of third-stage larvae (L3) contained in diffusion chambers covered with 5.0-microns pore-size membranes. After 7 days the chambers were recovered, and larval viability and growth were assessed. Approximately one-half of inoculated larvae were recovered alive regardless of the host tested. Larvae were implanted in CBA/J and DBA/2J mice in chambers covered with membranes that prevented host cells from entering; survival and growth rates of the larvae were not altered by the absence of cells from the chambers. Cryopreserved larvae were implanted in chambers with 5.0-microns pore-size membranes in CBA/J and DBA/2J mice and Wistar Furth rats for 3-28 days. No statistically significant difference was seen in the larval recoveries on days 3-28 in all 3 hosts. Statistically significant increases in length were seen in the 3 strains from day 3 to day 14, after which growth appeared to cease. Molting from L3 to fourth-stage larvae was observed in all 3 hosts beginning on day 3, with most larvae completing the molt by day 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Guatemalan human onchocerciasis. I. Systematic analysis of patient populations, nodular antigens, and specific isotypic reactions.

The population from five Guatemalan plantations in areas endemic for onchocerciasis was surveyed, and 1032 individuals were recruited to participate in our study. From physical examination, past clinical history (5 to 8 yr), laboratory evidence and sample availability, a group of 778 long term residents with confirmed disease status were selected for detailed examination. We were able to identify 268 long term residents of endemic areas who had never been infected, 44 of these are from hyper- and mesoendemic areas. The 44 uninfected individuals from the hyper- and mesoendemic areas, because of their considerable exposure to this disease, were classified as "putatively immune." Intact nodules containing adult worms of Onchocerca volvulus were homogenized in the presence of protease inhibitors and fractionated into particulate and aqueous isotonic soluble antigens. Systematic analysis of these Ag fractions showed considerable amounts of Ig, presumably associated with Ag in the form of immune complexes. Individual specific antibody reactions from all 778 patients to nodule Ag were examined. Reactions to O. volvulus antigens by antibodies from patients with confirmed parasitic infections were almost exclusively restricted to IgG1 and IgG4 isotypes. Antigenic activity appeared to be primarily associated with low molecular mass (14 to 29 kDa) components. Some competitive blocking of antibody activities of other isotypes by IgG1 was observed, most notable was that of IgG3 and IgA. IgG4 and IgM activities were not significantly blocked.

Adolescent↗