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Biomedical subjects

D A Denham

Publications and source records attributed to D A Denham.

At least 73 records · Page 4Linked to original sources

The filaricidal activity of some derivatives of N-[2-(4-thiazolyl)benzimidazol-5-yl]benzamide against Brugia pahangi adults.

A series of analogues of N-[2-(4-thiazolyl)benzamidazol-5-yl]benzamide with halogen substituents on the benzamide ring was tested for activity against adult Brugia pahangi in the peritoneal cavities of jirds. None of the chloro, bromo or iodo analogues was active at 5 x 100 mg/kg by subcutaneous injection. The 2-fluoro, 3-fluoro and 4-fluoro analogues showed greater activity than the parent compound and the 2,5-difluoro analogue had the same activity as the parent. The 3-fluoro, 4-fluoro and 2,5-difluoro analogues were not active in cats treated per os with 5 x 50 mg/kg.

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Detection of antibodies in Brugia pahangi-infected cats by counter immunoelectrophoresis, indirect fluorescent antibody test and enzyme-linked immunosorbent assay.

In cats infected with Brugia pahangi, antibodies first appeared against the larvae (L3), then against the adults (L5) and the microfilariae (mf). Homologous antigens were better than antigens prepared from heterologous species (Dirofilaria immitis, Dipetalonema viteae, Litomosoides carinii and Onchocerca gutturosa) in detecting antibodies to B. pahangi in the infected cats by indirect fluorescent antibody test (IFAT). Metabolic products of L5, but not L3 or mf, of B. pahangi were antigenic and were used in the enzyme-linked immunosorbent assay (ELISA) for detection of antibodies. Using various homologous antigens, IFAT was found to be more sensitive than counter immunoelectrophoresis and ELISA in the detection of antibodies in the infected cats. The best antigen was cryosections of L3, with a positivity rate of 81%. However, using L3, L5 and mf antigens in IFAT, a total positivity of 97% was obtained.

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Survival of Loa loa following transplantation from drills (Mandrillus leucophaeus) into jirds (Meriones unguiculatus): parasitology and pathology.

Two drills infected with Loa loa maintained a microfilaraemia for four and a half years ranging from less than 1 mf/100 microliters to 1150 mf/100 microliters. No significant tissue reactions to the adult worms were seen at autopsy. Adult worms were transplanted into the peritoneal cavities of naive jirds when a persistent microfilaraemia first developed by 17 days. Retransplantation of adult worms into naive jirds produced a microfilaraemia and microfilariae in the peritoneal cavities of three out of five animals. These three animals were all negative for circulating parasites by eight and a half months. The tissue reactions to the worms in the jirds are described, including a granulomatous response surrounding adults and a myositis involving microfilariae.

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The infectivity of microfilariae of Brugia pahangi of different ages to Aedes aegypti.

By transferring microfilariae of Brugia pahangi which had been born over a 24-hour period in the peritoneal cavities of jirds (Meriones unguiculatus) to the blood circulation of other jirds, infections of known age were tested for their ability to develop into third-stage larvae (L3) in mosquitoes Aedes aegypti. Microfilariae less than three days old were not able to develop to L3. Microfilariae which had been in circulation for three days to six months were capable of developing if ingested.

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The number and distribution of Brugia pahangi in cats at different times after a primary infection.

The number of larvae and adults of Brugia pahangi and their distribution throughout the lymphatics and extra-lymphatic tissue were studied in cats infected by subcutaneous injection of larvae into their hind feet. For the first 20 days approximately 55% of the inoculum is recovered as living worms. After 25 days the recovery falls by a half. It is suggested that this loss of worms may be due to either the developing immunological response or the moult from the 4th to the 5th stage. Larvae penetrate the lymphatics rapidly (50% within 3 h) and migrate to the popliteal lymph node after about 20 days they migrate back down into the afferent lymphatic.

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Detection of filarial antibodies in Malayan and Bancroftian filariasis by the indirect fluorescent antibody test, using different filarial antigens.

Indirect fluorescent antibody tests (IFAT) using Wuchereria bancrofti infective larvae as antigen had the highest positivity rates in detecting Malayan and Bancroftian filariasis as compared to IFAT using antigens prepared from 5 other animal filarial species, Brugia pahangi, Dirofilaria immitis, Dipetalonema viteae, Litomosoides carinii and Onchocerca gutturosa. This study also recommends the use of human filarioids as the source of antigen in serological tests. However, before B. malayi and especially W. bancrofti can be easily available from the common laboratory animals. B. pahangi seems to be a suitable source of antigen for use in serological tests for human lymphatic filariasis.

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The effects of some avermectins on the growth of Brugia pahangi.

The effects of 10 different avermectins upon the development of Brugia pahangi in jirds was studied. Three of these were shown to inhibit the development of the worm to the adult form but this appeared to be at least partially reversible. The females were more severely affected than males. The commercially available compound ivermectin had no effect under these conditions.

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The effect of Trichinella spiralis on the rate of clearance of 51Cr-labelled sheep red blood cells and 125I-polyvinyl pyrrolidone from the bloodstream of mice.

Mice infected for one to eight weeks with Trichinella spiralis cleared either 51Cr-labelled sheep red blood cells (SRBC) or 125I-polyvinyl pyrrolidone (PVP) given intravenously. PVP was cleared more rapidly from the blood of mice infected for one week than from uninfected mice with older infections which behaved in a similar manner to the controls. SRBC were consistently cleared faster from the blood of mice infected for one week than from normal mice. If the infections were older than this a more rapid clearance was also demonstrated as long as the infections were reasonably heavy.

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Serum-mediated adherence of feline granulocytes to microfilariae of Brugia pahangi in vitro: variations with parasite maturation.

Feline eosinophils and neutrophils readily adhered in vitro to the sheaths of microfilariae of Brugia pahangi in the presence of suitable serum. Both cell types flattened along the surface of the parasite undergoing cytoplasmic changes which included degranulation. Adherence was dependent on properties of both the serum and the history of the microfilaria used. Two types of serum factor were found to mediate adherence. Heat labile factors were present in sera from infected and uninfected cats as well as in sera from other species. They were removed by preincubation of sera with zymosan suggesting that complement components were involved. This suggestion was supported by the demonstration of C3 on the surface of microfilariae participating in adherence reactions. A heat stable factor, present in the serum of less than 10% of infected cats, also mediated adherence. This factor was demonstrated to be IgG by immunoadsorption and immunofluorescence. The ability of the microfilariae to participate in the adherence reaction mediated by complement factor varied with maturation of the parasite. Microfilariae obtained directly from the uteri of adult worms, or produced in vitro, did not possess the ability to participate in adherence. Young blood microfilariae (i.e. taken from the blood of cats recently patent) were similar to the in vitro produced parasites; however, the majority of blood microfilariae from infections of greater than three weeks patency participated in this form of adherence. No difference between blood and uterine/in vitro microfilariae was seen in adherence reactions mediated by heat stable antibody.

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Successful development of Brugia pahangi in T-cell deprived CBA mice.

CBA mice were thymectomized and treated with anti-thymocyte serum. Seven such mice were given 90--100 infective larvae of Brugia pahangi each by intraperitoneal (ip) injection and 5 given 99-100 larvae each by subcutaneous (sc) injection. From 62 days after infection 6 of 7 mice infected ip had microfilariae in their peritoneal cavities. Only one mouse infected by sc injection showed microfilariae in peripheral blood and this not until 98 days. At autopsy 5-45 adult worms were recovered from the ip infected mice. Only 2 od the 5 sc infected mice had adults and these only 3 each. No microfilariae or adult worms were detected in similarly infected unthymectomized CBA mice.

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Detection of circulating antigens and immune complexes in feline and human lymphatic filariasis.

Circulating worm antigens were detected in 61% to 81% of sera from Brugia pahangi -infected cats and in 0-93% of sera from humans with malayan of bancroftian filariasis by counter immunoelectrophoresis and a double antibody sandwich enzyme-linked immunosorbent assay, using rabbit antisera to B. pahangi adult worms. In some situations, both antigen tests were as sensitive as antibody tests. However, ELISA was likely to be affected by the presence of antiglobulins, such as rheumatoid factor, in the test sera. Only 10% to 22% of B. pahangi-infected cats (treated with drugs or not) had circulating immune complexes by the conglutinin-binding assay and no sera were positive by C1q-BA. A significantly higher percentage (56%) of B. malayi clinical sera was positive for immune complexes by either C1q- or conglutinin- binding assays as compared to other groups of B. malayi and Wuchereria bancrofti sera (6% to 14%).

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