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Biomedical subjects

M Pinder

Publications and source records attributed to M Pinder.

At least 73 records · Page 4Linked to original sources
PubMed1993

Tolerance and efficacy of single high-dose ivermectin for the treatment of loiasis.

A study was carried out in southeastern Gabon to evaluate the tolerance and efficacy of single high doses of ivermectin in 31 Loa loa-infected subjects with low-to-moderate parasitemia (7-7,700 microfilaria/ml). The first group of 16 subjects received 300 micrograms/kg of ivermectin and, seven days later, a second group of 15 received 400 micrograms/kg. Complete clinical and biological monitoring was carried out during the first 10 days post-treatment and again after one and three months. All subjects continued with their usual activities during the study. The clinical tolerance of treatment was very good, and except in one case, only mild adverse reactions were observed, with pruritus being the most common symptom. There were no significant changes in blood or urine function test results or in hematologic results, except for a pronounced eosinophil reaction. The 400 micrograms/kg dose of ivermectin equaled or surpassed in tolerance that of 300 micrograms/kg dose. After treatment, L. loa microfilaremia decreased rapidly to less than 9% of the pretreatment value by day 10. This decrease was enhanced with the 400 micrograms/kg dose, although differences between the two groups diminished slightly with time. At 100 days post-treatment, the microfilaremia was still at less than 10% of the initial values in the two groups, which may indicate an effect of ivermectin on the adult worms.

Adult↗
PubMed1992

Antibody-dependent cell-mediated immune reactions to Loa loa microfilariae in amicrofilaraemic subjects.

Antibody-mediated mechanisms that could be important in controlling microfilaraemia in Loa loa infected amicrofilaraemic adults (mf-ve) were studied. These subjects were selected as having a verified ocular passage of an adult L. loa but being amicrofilaraemic and without recent diethylcarbamazine treatment. Sera from 37 mf-ve subjects were compared to 14 sera from heavily (greater than 4000 mf/ml) infected subjects (mf+ve) and 9 sera from Caucasian control subjects for their reactions with L. loa mf (mf). Many mf-ve sera (22/37) were strongly positive in immunofluorescence (IFAT) on living mf. Mf+ve sera were negative, or only weakly positive, and Caucasian sera were negative. Clinical signs were not significantly different between IFAT reactive and non-reactive mf-ve subjects. Approximately half of the IFAT positive, mf-ve sera were also able to agglutinate mf; no other sera were active in this test. Titres ranged from log2 3-6 and in most cases, 9/11, the agglutination reaction was mercaptoethanol-sensitive. Antibody-dependent cellular adherence was studied using mf and leukocytes from uninfected donors. Using cryopreserved mf many heat-inactivated mf-ve sera gave strong reactions with obvious adherence by 4 h and few motile mf remained by 16 h but when fresh mf were employed these reactions were weak. However, addition of complement to many (10/11) mf-ve sera considerably enhanced adherence to fresh mf. The effect of various treatments on the complement source indicated a role for both the classical and alternative pathways. The cells attached to mf were mainly neutrophils (83%) with some eosinophils (15%) and few mononuclear cells (2%). The common occurrence of antibodies able to mediate complement-dependent adherence of polymorphonuclear leukocytes to L. loa mf in the sera of mf-ve subjects may indicate that such a mechanism is important in controlling microfilaraemia in vivo.

Adult↗
PubMed1992

Specific and sensitive IgG4 immunodiagnosis of onchocerciasis with a recombinant 33 kD Onchocerca volvulus protein (Ov33).

The full length cDNA of the immunodominant Ov33 protein of Onchocerca volvulus was expressed in E. coli using various vector constructs. Expression was best with the vectors pGEX2T and pCG808fx, yielding fusion protein Ov33-GST and Ov33-MBP, respectively. Purified fusion protein Ov33-GST and O. volvulus antigen extracts (OvAg) were used to compare antibody responses (IgM and IgG-subclasses) of patients infected with O. volvulus, Brugia malayi, Wuchereria bancrofti, Mansonella perstans/Loa loa and of Sudanese control sera. Sera of all groups contained IgM reacting with Ov33-GST and with OvAg. There was no IgG1 response to Ov33-GST. IgG1 responses to OvAg were only detected in filariasis sera. IgG2 and IgG3 responses were not detectable or marginal in all groups. The IgG4 reaction of onchocerciasis patients to Ov33-GST and to OvAg was high, whereas few other filariasis sera contained IgG4 antibodies to Ov33-GST and to OvAg. A serodiagnostic test for onchocerciasis based on detection of IgG4 to Ov33-GST had a sensitivity of 93.3% and a specificity of 96%. An epitope common to Ov33 and to the homologous proteins of other filarial species was demonstrated with a monoclonal antibody. Purified Ov33-MBP fusion protein was used to follow the development of the antibody response of four chimpanzees experimentally infected with O. volvulus. The data indicates that antibodies to Ov33 are induced by developing worms and later parasite stages.

Animals↗
PubMed1991

The improvement of maintenance conditions for wild-caught Chrysops silacea and the production of infective larvae of Loa loa.

Previous reports have shown that Chyrsops silacea survive poorly in captivity. Only 5% survive for more than 12 days, which is the time required for Loa loa microfilariae to develop into infective larvae. Improved maintenance conditions for C. silacea for the production of infective larvae were studied. Wild-caught female C. silacea were allowed to feed to repletion on mandrills, (Mandrillus sphinx), which were microfilaremic with human L. loa or on uninfected laboratory rats. Under optimal conditions 30-50% of flies engorged. The survival rates of fed and unfed flies were compared under a variety of conditions. Survival rates varied considerably under the various maintenance conditions. Ingestion of either rat or mandrill blood made no significant difference to fly survival. Optimal conditions were found to be as follows: one to two flies per sterilized jar with damp sand, constant access to sterilized 10% sucrose, a temperature of 23-29 degrees C and 84-98% relative humidity. Under these conditions 42% of the flies survived until day 12, when maximal numbers of infective larvae were present in the head.

Animals↗
PubMed1990

Macaca fascicularis, a nonpermissive host for the human filarial parasite Loa loa.

The ability of the filarial nematode Loa loa to infect 2 species of primates was studied. The primate species selected were closely related to species known to be susceptible. A mandrill (Mandrillus sphinx) and 6 cynomolgus monkeys (Macaca fascularis) were infected by subcutaneous injection of third-stage larvae of human L. loa from Gabon. The mandrill developed microfilaremia with an estimated prepatent period of 147 days, but microfilariae were not detected in any of the cynomolgus monkeys. Thus, mandrills appear permissive to human L. loa, whereas cynomolgus monkeys are not. Serum antibody responses were examined on western blots of adult L. loa antigens. Preinfection sera from all animals gave no reactions, but, after infection, sera from cynomolgus monkeys reacted more intensely and with more antigens than mandrill sera. Antibodies were still detectable in cynomolgus monkeys 15 mo postinfection. These reactions were compared with those found using human infection sera. Reactions with the cynomolgus monkey sera resembled those found with resistant endemic and amicrofilaremic human sera.

Animals↗
PubMed1989

Differential recognition of Loa loa antigens by sera of human subjects from a loiasis endemic zone.

Somatic antigens of Loa loa adult worms with molecular weights of 15-180 kDa were identified by Western blot analysis using sera from 3 categories of parasitologically and clinically defined subjects from a loiasis endemic zone. Sera of occult, amicrofilaremic (OL), and 'resistant' individuals with no clinical signs of infection (R) reacted with an antigen of 160 kDa; sera of highly microfilaremic individuals (ML) did not. ML sera strongly reacted with an antigen of 18 kDa which was recognized only weakly or not at all by OL and R sera. At higher dilutions, OL sera only reacted with antigens at 23 and 160 kDa and ML sera reacted with antigens at 18 and 23 kDa, whereas R sera reacted with antigens at 23, 42, 54, 70, 100, and 160 kDa. These data suggested that R sera contained a higher concentration of antibodies which reacted with denatured, nitrocellulose-bound antigens. The IgG4 isotype predominated for all groups of sera, while IgG3 antibody responses were observed only with R sera. IgG1 antibodies were seen in all groups but reacted with fewer antigens than IgG4 antibodies, and no IgG2 antibody responses were detected. Sera against Brugia malayi, Wuchereria bancrofti, Onchocerca volvulus, and Dirofilaria immitis cross-reacted with somatic antigens greater than 70 kDa, whereas none reacted with Loa loa antigens less than 23 kDa.

Animals↗
PubMed1988

Identification of a surface antigen on Loa loa microfilariae the recognition of which correlates with the amicrofilaremic state in man.

Filarial infections induce a spectrum of disease in their natural hosts, and by correlating immunity found in individuals with their disease pattern, one may delineate non-pathogenic, protective mechanisms. Loa loa is causal of mild to moderate pathology, and it is unique among the human filaria in that adult worms are occasionally visible during subconjunctival migration. To study immune mechanisms controlling microfilaremia, sera from 15 subjects with amicrofilaremic occult loiasis (OL) were compared with sera from 10 subjects with microfilaremic loiasis (ML) microfilaremia, (greater than 4000/ml) for their reactions with living microfilariae (mf). An IFA was first used to detect antibodies able to bind to the surface of living L. loa mf. ML subjects either did not react (7/10) or reacted only very weakly (3/10). Highly reactive sera were found only in OL subjects; 7/15 gave very bright fluorescence, 5/15 gave moderate reactions, and 3/15 were negative. Most of these antibodies were of the IgG class. Sera from all subjects were also reacted with living mf in an antibody-dependent cellular adherence test using normal leukocytes. Sera that were strongly positive in IFA showed strong adherence and IFA-negative sera were non-reactive. To identify the Ag involved, mf were surface iodinated, detergent-extracted Ag were immunoprecipitated, and Mr was determined on SDS-PAGE. Several OL sera, all highly reactive in the above tests, precipitated a 23-kDa molecule with which all ML sea failed to react. Sera from a mandrill experimentally infected with L. loa also precipitated the 23-kDa Ag when taken post-patency. In conclusion, it appears that certain people who control L. loa microfilaremia have high levels of IgG antibodies that bind to a surface Ag of 23 kDa and are able to mediate cellular adherence.

Adhesiveness↗
PubMed1988

Immune responses of trypanoresistant and trypanosusceptible cattle after cyclic infection with Trypanosoma congolense.

To study the mechanisms by which certain West African taurine cattle are able to resist trypanosomiasis, the disease course and several immune parameters were examined in eleven Baoulé and five Zebu cattle after infection with tsetse-transmitted T. congolense (clone 1180 of stock Serengeti/71/STIB/212). All animals showed a similar onset of parasitemia but subsequently a continuum of disease was observed ranging from four Baoulé which were mildly susceptible (controlled parasitemia by week 10 post-infection and had little anemia) to two Baoulé and two Zebu which were highly susceptible (unable to control parasitemia, severe anemia leading to death or drug treatment in extremis). The remaining five Baoulé and three Zebu showed intermediate susceptibility. Although the most resistant animals were of the Baoulé breed, there was a spectrum of susceptibility which crossed the two breeds. Neutralizing antibody to metacyclic trypanosome antigens was detectable by day 18 in four of the mildly susceptible and three of the highly susceptible individuals but such antibodies were delayed in the remaining one severely susceptible animal. Neutralizing antibodies to antigenic variants of the first peak of blood trypanosomes were of significantly higher titre and appeared earlier in the four mildly susceptible as opposed to the highly susceptible animals. No differences in lymphocyte in vitro mitogen responses were observed in these animals except shortly before death in those severely affected. In vitro lymphocyte responses to allogeneic cells did appear to correlate with disease severity, in that animals with mild disease showed little immunosuppression of this response whilst in severely affected individuals the response was almost ablated.

Animals↗
PubMed1988

Biochemical and immunochemical characterization of surface and excretory-secretory antigens of Loa loa microfilariae.

Detergent solubilized extracts of 125Iodogen surface-labelled Loa loa microfilariae revealed a relatively simple profile of two strongly labelled molecules of 23 and 67 kDa for blood microfilariae and several strongly labelled molecules of 23, 40, 42-67 kDa for in vitro born microfilariae. In addition, there were other weakly labelled molecules which were resolved after prolonged autoradiographic exposure. Surface molecules of 28, 29, and 33 kDa were unique to blood microfilariae, a 14.4 kDa molecule was unique to in vitro born microfilariae and molecules of 23, 40, and 75-84 kDa were common to both forms of microfilariae. The profile of excretory-secretory products consisted of molecules of 14.4-198 kDa. Human albumin was a predominant component of surface molecules and excretory-secretory products from blood microfilariae. Immunoprecipitation with occult and microfilaremic loaiasis sera demonstrated that the 23 kDa surface molecule and excretory-secretory products of 14.4 and 33 kDa were only recognized by occult loaiasis sera whereas surface molecules of 40 and 75-84 kDa and excretory-secretory products of 28 and 67 kDa were recognised by both sera. Studies with heterologous sera demonstrated that with the exception of the 75-84 kDa antigens, all the L. loa microfilarial surface antigens contained epitopes which were restricted to filarial parasites. Further studies revealed that the 23 kDa antigen was a protein which contained neither asparagine-N-linked oligosaccharides nor interchain disulfide-linkages.

Animals↗
PubMed1988

The identification and partial characterization of an immunodominant 29-31 kilodalton surface antigen expressed by adult worms of the human filaria Loa loa.

Detergent solubilized extracts of 125Iodogen surface labelled adult Loa loa revealed a relatively simple profile consisting of a strongly labelled molecule at 29-31 kDa and weakly labelled molecules at 14.5, 17, 21, 23, 34, 58, and 86 kDa. Residents of a L. loa endemic zone were assessed clinically and parasitologically and classified as microfilaremic, amicrofilaremic with documented ocular passage of adult worms, or 'resistant' subjects without any signs of infection. Sera from these subjects were used to identify L. loa adult surface antigens. All 'resistant' sera immunoprecipitated the 29-31 kDa antigen although some were more strongly reactive than others. The amicrofilaremic sera strongly immunoprecipitated the 29-31 kDa antigen, whereas microfilaremic sera reacted weakly or not at all with this antigen. Longer exposures of immunoprecipitates of strongly reactive sera revealed the recognition of additional antigens of 86, 44, 34, 23, 21, 17 and 14.5 kDa. Studies with heterologous sera demonstrated that these antigens contain cross-reactive epitopes which are restricted to filarial parasites. Biochemical characterization of the predominant 29-31 kDa antigen showed that it bound concanavalin A, was sensitive to proteases, and its antigenicity was resistant to heat but sensitive to periodate and endo-beta-N-acetylglucosaminidase H. These observations suggest that it is a glycoprotein containing mannose and N-acetylglucosamine residues and that the carbohydrate moiety is important for antibody binding. The importance of the 29-31 kDa glycoprotein in the immunobiology of loaiasis is suggested by the finding that resistant and infected amicrofilaremic individuals have strongly reactive IgG antibodies to this antigen.

Animals↗
PubMed1988

Loa loa - a neglected filaria.

There has been considerable research on the biochemistry and immunology of many human, veterinary and laboratory animal filariae, with a view to understanding pathogenic and protective immune mechanisms and developing ways to boost them(1-3). But, apart from a few isolated reports (eg. Refs 4,5), these aspects have been largely ignored for the human filarial parasite Loa loa. Obviously not all filariae can be studied in equal depth - almost 100 different life cycle patterns are documented(6) - but, as Margaret Pinder shows here, L. loa is an important human pathogen of considerable biological interest.

Journal Article↗
PubMed1987

Trypanosoma congolense: lack of correlation between the resistance of cattle subjected to experimental cyclic infection or to field challenge.

Twelve male cattle of the Baoulé breed were exposed to natural trypanosome challenge in an area of high Glossina density, to characterize them as trypanoresistant or trypanosensitive. Weekly blood samples were taken for the determination of parasitemia and packed cell volume, as a measure of anemia. Seven Zebu cattle were also exposed to challenge at the same time. The Zebu proved to be trypanosensitive with high parasitemia, pronounced anemia and died or were drug treated in extremis. Five Baoulé were as sensitive as the Zebu while 7 others were trypanoresistant since they showed little or no patent parasitemia, only mild transient anemia and survived in good condition. The 12 Baoulé were allowed to recover from challenge in the field and along with 7 Zebu were subjected to experimental fly challenge in fly-proof accommodation. Glossina morsitans submorsitans infected with a clone of Trypanosoma congolense derived from the stock Serengeti/71/STIB/212 were allowed to engorge on the shaven flanks of tranquilized animals. All animals showed persistent parasitemia for at least 7 weeks, including all the Baoulé resistant to natural challenge. Two Baoulé, one resistant and one sensitive to natural challenge, and 4/7 Zebu appeared unable to control parasitemia, had severe anemia, and were drug treated in extremis. The remaining Baoulé, 6 resistant and 4 sensitive, appeared to be undergoing spontaneous cure by Week 9-10, as did 3/7 Zebu. In Zebu, anemia was as pronounced as under natural challenge. Three resistant Baoulé maintained packed cell volume above 30 as under field challenge but the others showed marked anemia. On the contrary, 4 sensitive Baoulé showed only slight anemia after artificial fly challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The role of antibody in natural resistance to African trypanosomiasis.

The nature and usefulness of trypanoresistance in West African Baoule cattle was studied by exposing animals in areas of high Glossina density. Under such conditions, Zebu and some Baoule died soon with high parasitaemia while resistant Baoule showed little patent parasitemia, almost no anaemia and thrived. Subsequently the role that specific antibody may play in such trypanoresistance was analyzed. In the first instance we examined protective antibody titres during T. congolense infection of inbred mice strains, comparing results obtained in trypanosome-mouse combinations where the host controls parasitemia and survives with those obtained when the host fails to control parasitemia and dies. We then attempted to extend these observations to cattle by following the disease course and appearance of neutralizing antibodies in animals of known sensitivity to natural Glossina challenges, following artificial challenge with T. congolense infected Glossina.

Animals↗
PubMed1987

The virulence of Trypanosoma congolense can be determined by the antibody response of inbred strains of mice.

Three inbred strains of mice, BALB/c, C57Bl/6 and CBA/J were infected with three clones of Trypanosoma congolense, DIND/3.1, SAM/28.1 and KAR/57.1, which were obtained from three different stocks. DIND/3.1 was of high virulence for BALB/c and CBA/J but of negligible virulence for C57Bl/6. SAM/28.1 was of high virulence and KAR/57.1 of negligible virulence for the three strains of mice. In each case, high virulence was correlated with a late, transient and low titre protective antibody response measured by complement mediated lysis of live organisms. Negligible virulence was correlated with an early, high titre protective antibody response. Suppression of the antibody response by sub-lethal irradiation or cyclophosphamide treatment of the host turned a trypanosome infection of negligible virulence into one of high virulence. In mice with mixed infections it was shown that highly virulent trypanosomes did not influence the course of infection and antibody response to trypanosomes of negligible virulence and vice-versa. The relationship of total antigen mass to the kinetics of the antibody response suggests that 1000- to 10,000-fold less antigen is required in good responder than in bad responder mice to trigger the immune response. Thus the virulence of T. congolense can be determined by the antibody response of inbred strains of mice. The specificity and dose dependency of this antibody response seem to implicate the involvement of Ir genes.

Animals↗