Biomedical subjects

G Dreyer

Publications and source records attributed to G Dreyer.

At least 37 records · Page 2Linked to original sources

PubMed1996

Studies on the periodicity and intravascular distribution of Wuchereria bancrofti microfilariae in paired samples of capillary and venous blood from Recife, Brazil.

We examined the periodicity and intravascular distribution of Wuchereria bancrofti microfilariae (mf) and determined the effect of these parasite properties on the accuracy of blood filming and filtration methods for diagnosis of bancroftian filariasis in the endemic area of Recife, Brazil. Microfilariae in both venous and capillary blood exhibited a nocturnal periodicity pattern with a relatively high amplitude. Overall, capillary blood contained approximately 1.25 times the number of mf present at the same time in the same volume of venous blood. However, the ratio of mf present in capillary and venous blood varied over a 24-hour period, so that the fewest mf were present in the capillary bed of the skin at the time when biting activity of the local Culex vector is the lowest. Twenty or 60 microliters blood films did not reliably detect carriers with fewer than 100 or 60 mf/ml venous blood, respectively, and were thus inadequate for the identification of low density mf carriers. In contrast, all carriers with > 1 mf/20 or 60 microliters blood smear at night could be identified during daytime hours by filtration of 1 micromilligram venous blood.

Animals↗

PubMed1996

Evaluation of the Og4C3 ELISA in Wuchereria bancrofti infection: infected persons with undetectable or ultra-low microfilarial densities.

The recently developed Og4C3 ELISA, which detects circulating Wuchereria bancrofti antigen, appears promising for use in epidemiological surveys, but its sensitivity is unknown in persons with ultra-low microfilarial densities. We used the Og4C3 to test the sera of 282 persons who were microfilaria-positive in 1-16 ml of blood, 18 persons who were microfilaria-negative but who had ultrasonographic or biopsy evidence of adult W. bancrofti infection, and 63 lifelong residents of a non-endemic area of Brazil. A total of 276 (97.9%) persons with detectable microfilaraemia tested positive (optical density > 0.033). At microfilarial densities of < 1, 1-30, and > 30 microfilariae per ml of blood, the sensitivity of the Og4C3 was 72.2, 97.6 and 100%, respectively (chi 2-test for trend, P < 10(-6)). The assay was positive in 66.7% of amicrofilaraemic persons with evidence of adult worm infection and in one (1.6%) of 63 residents of the non-endemic area (specificity, 98.4%). Our findings support the increasingly widespread use of the Og4C3 for field investigations and epidemiological assessments. However, the sensitivity of the assay may be low in persons who are microfilaria-negative or with densities of < 1 microfilaria per ml.

Adolescent↗

PubMed1996

Patterns of detection of Strongyloides stercoralis in stool specimens: implications for diagnosis and clinical trials.

Reported efficacies of drugs used to treat Strongyloides stercoralis infection vary widely. Because diagnostic methods are insensitive, therapeutic trials generally require multiple negative posttreatment stool specimens as evidence of drug efficacy. However, only a single positive stool specimen is usually required for study enrollment. To determine the reproducibility of detection of S. stercoralis larvae in the stool, 108 asymptomatic infected men submitted 25 g of fresh stool once a week for eight consecutive weeks for examination by the Baermann technique. During the 8-week study, 239 (27.7%) of 864 stool specimens were positive for S. stercoralis. Rates of detection of larvae in the stool specimens ranged from eight of eight specimens in 3 (2.8%) men to none of eight specimens in 36 (33.3%) men. Of 43 men for whom S. stercoralis was detected in at least two of the first four stool specimens, only 1 (2.3%) man tested negative on all of the next four specimens. In comparison, of 29 men who had detectable larvae in only one of the first four specimens, 22 (75.9%) tested negative on all of the next four samples. Thus, if these 29 men had been enrolled in a therapeutic trial between the first and second sets of four specimens, the efficacy of a drug with no activity against this parasite would have been estimated to be 76%. These data suggest that patterns of S. stercoralis detection vary widely among infected persons and that intermittent larval shedding can lead to inflated estimates of drug efficacy. Before a patient is entered in a clinical trial of drug efficacy, four consecutive stool specimens should be examined for S. stercoralis; only persons with two or more positive specimens should be enrolled.

Adolescent↗

PubMed1996

Detection of living adult Wuchereria bancrofti in a patient with tropical pulmonary eosinophilia.

Tropical pulmonary eosinophilia (TPE) is a relatively unusual and diagnostically challenging manifestation of infection with Wuchereria bancrofti. The pathogenesis of TPE remains unclear, although immune hyperresponsiveness to the microfilarial stage of the parasite is thought to play an essential role. Microfilariae are almost never detected in the peripheral blood of persons with TPE and living adult worms have not been reported. Thus, no parasitologic marker has existed with which to assess the effectiveness of antifilarial treatment. In 1986, a 74-year old man from Olinda, Pernambuco, Brazil, developed classic signs and symptoms of filarial TPE. Within 48 h after beginning treatment with diethylcarbamazine (DEC), the drug of choice for TPE, his symptoms dramatically improved. He remained symptom-free until June 1994, when he again developed signs and symptoms of TPE. To visualize the adult worm and monitor the macrofilaricidal effectiveness of DEC treatment, ultrasound examinations of the scrotal area were performed before, during, and for 6 months after treatment. These examinations revealed diffuse dilatation of the lymphatic vessels of the spermatic cord and movements characteristic of living adult W. bancrofti known as the "filaria dance sign". Although the patient responded clinically to treatment, no change was noted in the filaria dance sign throughout the observation period. Visualization of adult W. bancrofti by ultrasound can be used to monitor the parasitologic effectiveness of treatment for TPE and to explore the relationship between death of the adult worm and recurrence of symptoms.

Aged↗

PubMed1995

Characterization of the metabolites of the peptidomimetic human immunodeficiency virus type 1 protease inhibitor SK&F 107461 in rats using liquid chromatography/mass spectrometry.

The metabolic fate of SK&F 107461 [Cbz-Ala-Ala-Phe psi [CHOHCH2] Gly-Val-Val-OMe], a potent and specific inhibitor of the protease encoded by human immunodeficiency virus type 1, in male Sprague-Dawley rats is described. SK&F 107461 is a hexapeptide analog containing a hydroxyethylene linkage in place of one of the peptide bonds, and in which the amino terminus is blocked with a carbobenzyloxy group and the carboxy terminus is modified to a methyl ester. The major metabolites of SK&F 107461 found in bile and urine after intravenous administration of 3H-labeled compound were characterized by LC/MS using either thermospray or continuous flow/FAB models of ionization. Approximately 80% of the administered radioactivity was recovered in the bile of bile duct-exteriorized rats following an intravenous dose. Radiochromatographic profiling indicated that SK&F 107461 was subject to extensive biotransformation. Structures were determined for three major biliary and five major urinary metabolites. Two of the major circulating plasma metabolites observed after intravenous bolus administration had similar retention times to metabolites that were observed in both bile and urine. A pathway for the biotransformation of SK&F 107461 in the rat is proposed. The parent molecule underwent two primary modes of metabolism. Hydrolysis of the carboxy-terminal ester or hydrolysis of the Ala-Ala peptide bond near the amino terminus were the primary metabolic events. All of the other metabolites characterized can be accounted for by exopeptidase activity subsequent to one or both of these primary events. There were no major metabolites observed resulting from anything other than hydrolysis of the ester or peptide bonds in the parent molecule.

Amino Acid Sequence↗

PubMed1995

Differential recognition of microfilarial chitinase, a transmission-blocking vaccine candidate antigen, by sera from patients with Brugian and Bancroftian filariasis.

We examined the reactivity of human sera with recombinant microfilarial chitinase and with the antigenic determinant on the native parasite molecule identified by monoclonal antibody (MAb) MF1. In Brugian filariasis, the MF1 epitope is preferentially recognized by residents of endemic areas who remain amicrofilaremic and asymptomatic despite lifelong exposure to filarial worms. Reactivity with filarial chitinase and its MF1 epitope inversely correlates with microfilaremia levels in Bancroftian filariasis and is associated with a prolonged amicrofilaremic state following a single course of treatment with diethylcarbamazine. Chitinase does not appear to be a target of human antibodies that promote the adherence of cells to microfilariae, even though MAb MF1 itself promotes antibody-dependent, cell-mediated cytotoxic (ADCC) reactions that kill microfilariae in vitro. Such ADCC reactions are most often mediated by sera from amicrofilaremic patients with chronic elephantiasis that contain low or undetectable levels of IgG antibodies to chitinase. In contrast, antibodies to the MF1 epitope on this microfilarial stage-specific antigen are mostly present in amicrofilaremic donors without clinical lymphatic disease. These observations indicate that antibodies to the MF1 epitope of microfilarial chitinase reflect some degree of immune resistance to microfilaremia in a subgroup of patients with asymptomatic lymphatic filariasis. The amicrofilaremic state of individuals with chronic lymphatic disease appears to be mediated by reactivity to a different parasite antigen(s).

Adult↗

PubMed1995

Scanning electron microscopy of adult Wuchereria bancrofti (Nematoda: Filarioidea).

Despite the great importance of Wuchereria bancrofti in causing human lymphatic filariasis, only conventional morphological studies have been completed with adult forms of this filaria. No ultrastructural studies have been carried out, mainly due to the difficulty in obtaining viable parasites from human tissues and the lack of a suitable experimental model or in vitro cultivation. With the recent success in using ultrasound to localize adult worms in living tissues and their surgical recovery from human lymphatic vessels, we show in the present paper the first ultrastructural observations of this filarial form. The cuticle surface analyzed by scanning electron microscopy showed a transversal striated aspect with periodic annulations and many small protuberances irregularly distributed along the filaria. The adults present a specialized cephalic area, with the oral opening surrounded by a circular mouth, papillae, and amphidial opening. Other structures, for example the anal, vulvar, and cloacal opening and spicules, were also observed and are described herein.

Animals↗

PubMed1994

Ivermectin treatment of bancroftian filariasis in Recife, Brazil.

To determine the effectiveness of single oral dosages of ivermectin ranging between 20 and 200 micrograms/kg and to make detailed observations of both the kinetics of parasite killing and the adverse reactions induced by treatment, the present double-blind study on ivermectin treatment of lymphatic filariasis caused by Wuchereria bancrofti was undertaken with 43 microfilaremic patients in Recife, Brazil. Follow-up at one year indicated equivalent efficacy for the 20-, 100-, and 200-micrograms/kg drug dosages in reducing microfilaremia to geometric means of 13-25% of pretreatment levels. Adverse clinical reactions (predominantly fever, headache, weakness, and myalgia) occurred to some degree in almost all patients but generally lasted only 24-48 hr and were easily managed symptomatically. Adverse reactions were significantly milder in those receiving the lowest (20 micrograms/kg) ivermectin dose, and they were significantly correlated with individuals' pretreatment microfilaremia levels in all groups. Posttreatment eosinophilia was a regular feature of the response to treatment, with the magnitude and kinetics also proportional to pretreatment microfilarial levels. Transient pulmonary function abnormalities (16 of 42, 38%), liver enzyme elevations (10 of 43, 23%), and hematuria (9 of 42, 22%) developed posttreatment, but all cleared without significant complications. The results indicate that W. bancrofti from Brazil is similar to strains of the parasites studied elsewhere in susceptibility to ivermectin, that the drug's systemic adverse reactions are essentially those resulting from parasite clearance, and that the intensity of these reactions can be significantly reduced by using the low (20 micrograms/kg) dose of ivermectin. This detailed dose-finding study provides information necessary for developing optimal regimens to treat bancroftian filariasis with ivermectin either alone or in combination with other medications.

Adult↗

PubMed1994

Evaluation of a recombinant parasite antigen for the diagnosis of lymphatic filariasis.

We evaluated the usefulness of a recombinant parasite antigen (recSXP1) for the serologic diagnosis of lymphatic filariasis. A large proportion of sera from microfilaremic donors living in five different endemic countries (356 of 446 [80%]) contained IgG antibodies to recSXP1, as do sera from approximately 33% of amicrofilaremic patients with acute filarial disease and/or indirect evidence of active filarial infection. Exposure to filarial worms per se does not appear sufficient to elicit an anti-SXP1 antibody response. Thus, this serologic test identifies a large proportion of persons with active lymphatic filariasis among residents of endemic areas.

Animals↗

PubMed1994

Live adult worms detected by ultrasonography in human Bancroftian filariasis.

Ultrasonographic examination of the scrotal area was performed in 14 asymptomatic individuals with bancroftian filariasis and microfilaremia. While in seven subjects (50%) the ultrasonographic findings were normal, lymphatic dilation and tortuosity were observed in the other seven. In these vessels, structures with peculiar aleatory movements (filaria dance sign) were detected. A segment of the lymphatic tract containing these mobile intraluminal structures that was resected surgically from the left spermatic cord of one individual confirmed that these structures were living Wuchereria bancrofti adult worms (two females and one male). Our study demonstrates for the first time the feasibility of using a low-cost, widely available, noninvasive technique (ultrasonography) to detect and monitor living adult worms and lymphatic dilation in patients with bancroftian filariasis.

Adolescent↗

PubMed1994

Bancroftian lymphadenopathy: absence of eosinophils in tissues despite peripheral blood hypereosinophilia.

We studied the association of eosinophils with Wuchereria bancrofti parasites in two children with biopsy-proven filarial lymphadenopathy and peripheral blood hypereosinophilia. In both cases, intact adult worms were present in lymph nodes but no inflammatory reaction was observed. The most remarkable histological feature in our patients was the absence of eosinophils in tissue sections in spite of persistently high numbers of eosinophils in peripheral blood. In the first case, treatment of intestinal parasites before lymph node excision promptly reduced eosinophil counts to normal levels even though levels of microfilaraemia remained virtually unchanged. In the second patient, hypereosinophilia persisted after lymph node resection but disappeared following curative treatment of intestinal helminths. These observations raise fundamental questions about the causal relationship and the role of eosinophils in lymphatic filariasis.

Adolescent↗

PubMed1993

Wuchereria bancrofti: freeze-fracture study of the epicuticle of microfilariae.

The freeze-fracture technique was used to analyze the surface of microfilariae of Wuchereria bancrofti. The examination of thin sections showed that the epicuticle is formed by two closely apposed membrane-like structures, appearing as hepta-laminated structures. Freeze-fracture replicas revealed the presence of two fracture faces. The outer one is smooth but presents rosette-like structures. The inner face, which is in contact with the hypodermal cells, presents a large number of particles.

Animals↗

PubMed1993

A study of placentas from Wuchereria bancrofti microfilaraemic and amicrofilaraemic mothers.

The prevalence of transplacental transfer of microfilariae and structural lesions in the placentas of amicrofilaraemic (n = 10) and Wuchereria bancrofti microfilaraemic (n = 10) pregnant women from the prenatal care unit of the Hospital das Clinicas, Recife, Brazil, was investigated. Study participants were selected by filtration (3 microns/13 mm) of nocturnal (2300-0100 h) venous blood. A detailed histopathological examination was performed to detect abnormalities in the placenta, the cord and the foetal membranes. Both study groups had similar obstetric profiles. Parasitaemia was present during labour in nine of ten microfilaraemic women, but no microfilariae were found by filtration of 5-10 ml cord blood. No macroscopic abnormalities were seen in placentas from microfilaraemic mothers; two placentas from the amicrofilaraemic cases contained, respectively, infarcted areas and cysts at the cut surface. Microscopy failed to detect microfilariae in the intervillous spaces, chorionic and decidual vessels, or the umbilical cord. Thus, transplacental transfer of Wuchereria bancrofti microfilariae seems to be a rare phenomenon, and microfilaraemia does not appear to be a risk factor for placental pathology.

Animals↗

PubMed1993

Immunocytochemical localization of surface and intracellular antigens recognized by human sera in microfilariae of Wuchereria bancrofti.

Sera from patients with various clinical pictures of lymphatic filariasis, including tropical pulmonary eosinophilia (TPE), were used for the localization of surface and intracellular antigens in microfilariae of Wuchereria bancrofti embedded in Lowicryl K4M. Very few or no antigenic sites were located on the outer face of the sheath. The most inner layer, as well as the space between the cuticle and the sheath, was intensely labeled. Sera from TPE patients intensely labeled the cuticle and the cytoplasm of muscle cells.

Animals↗

PubMed1992

Renal abnormalities in microfilaremic patients with Bancroftian filariasis.

To determine the frequency of renal abnormalities occurring with Bancroftian filarial infections and to assess the effects of treatment on such abnormalities, we initiated a prospective, hospital-based study of 20 microfilaremic and five amicrofilaremic patients with Wuchereria bancrofti infections. Thorough clinical evaluations and detailed renal assessments were made prior to treatment and at multiple time points for 60 days following a standard twelve-day course of treatment with diethylcarbamazine (DEC). There were two important findings. First, even prior to DEC treatment, almost half of the microfilaremic patients had hematuria and/or proteinuria. Second, treatment with DEC induced these same abnormalities in almost all of the remaining microfilaremic patients. However, this DEC-induced hematuria and/or proteinuria was transient, and the long-term response to DEC in all of the microfilaremic patients was resolution of the abnormal renal findings during the two-month followup period. In the amicrofilaremic study patients, no hematuria or proteinuria was detected before, during, or after treatment with DEC.

Adolescent↗

PubMed1992

Bancroftian lymphangitis in northeastern Brazil: a histopathological study of 17 cases.

The histological features in 17 patients (3 males and 14 females) with bancroftian lymphangitis, apparently not associated with lymphadenitis, are described. Degenerative alteration in the worms and a severe inflammatory process were observed in the great majority of the cases. The patterns of tissue reaction varied, including exudative, infiltrative and granulomatous lesions. Eosinophils were present, usually in great numbers. Thirteen out of 14 female subjects showed involvement of the breast lymphatics, and in two of these cases microfilariae were found in addition to adult worms. The breast parenchyma was in general spared. In men, lymphatics of the epididymis were affected; in one case, the patient was submitted for surgical castration for prostatic cancer and intact filarial worms without tissue reaction were incidentally detected in peritesticular lymphatics.

Adolescent↗

PubMed1992

Wuchereria bancrofti microfilarial density of autochthonous cases and natural Culex infectivity rates in northeast Brazil.

Autochthonous Wuchereria bancrofti microfilaraemic cases from three neighbouring cities of Northeast Brazil (Recife, Jaboatao and Olinda) were selected from thick smear or filtration positive individuals and classified by their microfilarial (mf) densities through polycarbonate membrane blood filtration. Individuals were subdivided into two groups: autochthonous cases without any previous specific drug administrations (group A) and those with one or more previous DEC treatments (group B). In Recife, unlike Jaboatao and Olinda (P less than 0.05), the majority of autochthonous cases were over 20 years old and no microfilaraemics were found under the age of 10. The majority of cases in Recife had lower levels of mf density (66.6%), while in Jaboatao and Olinda higher mf carriers (65.6%) prevailed when group A (n = 141) individuals were rearranged in mf density above and below 500 mf ml-1 (P less than 0.01). All subjects in group B (n = 110) had less than 501 mf ml-1 and the great majority less than 100 mf ml-1, but a significant difference (P less than 0.05) between Recife and the two other cities was observed. Captured mosquitoes in Recife, Jaboatao and Olinda totalled 7856, 8010 and 8003 respectively. The infectivity rate found in Recife (0.61%) was significantly lower than in Jaboatao (1.21%) and Olinda (1.31%) (P less than 0.001). The authors discuss the possible influences of previous disease control programmes (medicated salt and individual treatments) applied only to the city of Recife in relation to the outcome of this investigation.

Animals↗

PubMed1991

Bancroftian lymphadenopathy: a histopathologic study of fifty-eight cases from northeastern Brazil.

Histologic study of Bancroftian lymphadenopathy in 58 patients originating from an endemic area revealed a wide range of tissue reactions to the filarial worms. In seven patients (12.0%), no attendant inflammation or parasite damage was observed. A mild-to-intense nongranulomatous chronic lymphangitis was found in 12 patients (20.7%). Granulomatous reactions with variable composition were the most common pattern observed (37 patients, 63.8%); fibrotic lesions containing calcified worms were present in 13 of these patients. Epithelioid granulomas without worms, associated either with granulomatous reactions to the worms (seven patients) or nongranulomatous lymphangitis (two patients), were also detected. Lymphoid hyperplasia and lymphatic dilation were constant, and eosinophil infiltration was usually remarkable. These findings were compared with those reported from nonendemic populations and emphasize the parallelism between the pathologic findings and the immune responsiveness reported in such patients.

Adolescent↗