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Biomedical subjects

C D Mackenzie

Publications and source records attributed to C D Mackenzie.

At least 37 records · Page 2Linked to original sources
PubMed1989

Onchodermatitis--correlation between skin disease and parasitic load in an endemic focus in Ecuador.

Onchocerciasis is a chronic parasitic infection in which infiltration of the skin by microfilariae has been associated with a number of different pathological changes. This survey compared the prevalence of different forms of skin disease in two villages, one of which was located within the endemic zone for onchocerciasis (Zapallo Grande), in a lowland rain forest area of western Ecuador. The commonest skin diseases in both villages were scabies, pyoderma and pityriasis versicolor. In addition changes closely correlated with the presence of microfilariae in skin snips were found in Zapallo Grande--such as atrophic gluteal changes, and acute and chronic papular dermatitis. The only other skin disease associated with onchocerciasis was widespread tinea corporis due to T. rubrum. The Amerindians in the endemic onchocerciasis area were more likely than Negroes to have generalized atrophic changes of the skin, whereas in the latter group significant numbers of individuals had no obvious skin lesions but large numbers of microfilariae were detected in skin snips. Acute papular dermatitis was common in both groups and in biopsied lesions microfilariae could usually be identified within the epidermis or close to the dermo-epidermal junction. One patient had developed severe reactive onchodermatitis (Sowda). Swabs taken from onchocercal skin lesions showed no evidence of skin surface carriage of Staphylococcus aureus. Changes classically associated with onchocerciasis such as pretibial hypopigmentation (leopard skin) and hanging groin were notably absent in this population.

Adolescent↗
PubMed1989

Identification of Mycobacterium leprae antigens in tissues of leprosy patients using monoclonal antibodies.

Five monoclonal antibodies (MAbs) directed against antigens of Mycobacterium leprae were tested for their ability to bind to components of tissue sections prepared from biopsies taken from patients with various forms of leprosy. Immunoperoxidase was the most successful marker system used, although immunofluorescence and alkaline phosphatase were also successful in certain cases. Positivity was high with all five antibodies successfully staining those sections containing a bacterial index of 3+ or more; sections with 0 bacterial counts also had areas staining positively with two of the MAbs. The positive staining in the tissues was confined to areas infiltrated by inflammatory cells; however it was not identifiable as being associated with individual bacteria. These findings suggest that immunostaining with specific monoclonal antibodies can help to identify leprosy in diagnostic samples in which acid-fast bacilli are not identifiable by standard histochemical means. Immunohistochemical techniques are likely to be valuable in studies of the distribution of M. leprae antigens and their association with individual tissue elements.

Adolescent↗
PubMed1989

Rapid recovery of lung histology correlates with clearance of influenza virus by specific CD8+ cytotoxic T cells.

Previous studies have shown that influenza nucleoprotein (NP)-specific cytotoxic T-cell clones do not prevent influenza infection of mice but lead to a more rapid viral clearance and recovery of the host. Here we examine the histology of the lung to see if viral clearance by cytotoxic T cells (Tc) correlates with recovery of pulmonary pathology or if it is in any way deleterious. Intransasal (i.n.) A/X31 virus infection of BALB/c mice produces lung tissue changes lasting 8-10 days in BALB/c mice, with the most severe abnormalities appearing between Days 4 and 6 (e.g. loss of epithelium, airway obliteration, peribronchiolar and perivascular cell accumulation). The transfer of Tc clone T9/13 into i.n.-infected BALB/c mice induces a transient enhanced loss of epithelium on Day 4, while by Day 6 epithelial abnormalities are much reduced in the lung compared to control infected mice. This correlates with a significant reduction in lung virus titres by Day 6; by Day 8 virus is cleared in Tc recipients and lung histology is normal. Another Tc clone (T5/5) with greater cytolytic activity resulted in significant recovery of the lung tissues by Day 4. Tc clones also resulted in enhanced perivascular infiltration of cells and variation in the infiltrating cell type. Quantification in our system required careful attention to the level of the airway assessed. These histological findings showing an enhanced tissue recovery support the previous assessment of reduced lung viral levels following the transfer of Tc cells, and show that a transient increase in lung pathology can occur.

Animals↗
PubMed1988

Moulting and exsheathment of the infective larvae of Onchocerca lienalis (Filarioidea) in vitro.

Fourth-stage larvae (L4) of the cattle filarial parasite Onchocerca lienalis were produced from third stage forms (L3) and maintained in vitro using a variety of culture media and feeder cell layers. Up to 50% of the L3 larvae moulted to the fourth stage in the presence of two jird (Meriones unguiculatus) cell lines, a monkey kidney cell line and also with Vero cells. Moulting took place 2-5 days after of the initiation of the cultures: These L4 parasites could be maintained in a healthy condition for up to 88 days, although no significant increases in size of these larvae were observed during the culture period. The medium giving the most promising results, both in terms of moulting and survival, was 199 supplemented with heat inactivated foetal bovine serum (20%) and glucose (2 mg/ml). The feeder layer cells could be replaced by fresh jird red blood cells. Moulting of parasites occurred in medium alone but the viability was reduced under these conditions.

Animals↗
PubMed1988

Experimental dermatophytosis in mice: correlation between light and electron microscopic changes in primary, secondary and chronic infections.

The histopathological and electron microscopic features of experimental dermatophytosis due to Trichophyton quinckeanum in Balb/c mice have been studied in animals with primary, secondary and chronic infections. Infected animals all showed pathological changes with adherence of microconidia to keratinocytes within 4 h of infection. Other features were the early infiltration of neutrophils, the formation of a mycelial mass (scutulum) in the epidermis, and epidermal oedema. Increased thickness of the epidermis was measured within 3 days of infection, although this was mainly due to oedema. The main differences seen in secondary infections were the paucity of fungal elements, even after 24 h, a sustained increase in epidermal thickness, and the dense dermal infiltrate of mononuclear cells. Chronically infected animals showed similar changes to those at the peak of a primary infection, but in addition there were large numbers of mast cells in the dermis. Cells carrying Ia markers were identified in the epidermis (Langerhans cells) and the dermis (macrophages) in all infections and their distribution did not appear to change. Although recovery from infection has been correlated previously with T lymphocyte mediated responses an increase in the number of cell layers of the epidermis and a dense infiltrate of neutrophils at the zone of infection were both seen within 2 days of infection. It is suggested that neutrophil killing of fungi and increased epidermal proliferation, not dependent on T cell activation, may also be implicated in host defence against dermatophytes.

Animals↗
PubMed1988

The effect of diethylcarbamazine on the in vitro serum-mediated adherence of feline granulocytes to microfilariae of Brugia pahangi.

The effect of the antifilarial drug diethylcarbamazine (DEC) on immunologically mediated destruction of the microfilariae (mf) of Brugia pahangi in vitro is addressed by studying the drug's influence on the granulocyte adherence to the surface of mf and the subsequent death of these parasites. DEC enhanced the adherence of cat blood-derived granulocytes to the surface of mf through the meditation of cuticle direct antibodies but not that mediated by complement alone; the parasites became immobilized and degenerated subsequent to cell adherence. The rate of cell adherence in the antibody-containing cultures was enhanced by DEC. As previously reported, this drug had no direct effect on the viability of the parasites. Preincubation of the cells in DEC had a greater effect on cell adherence than did preincubating the parasites in the drug, thus supporting the contention that this antifilarial compound may act on host components. Further investigation of this possibility may contribute significantly to a more complete understanding of why DEC can cause severe side reactions in filariae infected patients.

Animals↗
PubMed1988

Onchocerciasis in Ecuador: recent observations in the province of Esmeraldas.

To evaluate the transmission of onchocerciasis that had occurred in the past 6 years in the province of Esmeraldas, in 1986 the onchocercal focus was re-examined using the same methodology as in the original survey of 1980. An increased prevalence of infection of 73.9% was noted, with an increase of 73.0% found in the principal focus, the Santiago Basin, and a 76.7% increase in the satellite foci. In the principle focus, a higher increase was noted on the Rio Santiago (88.8%) than on the Rio Cayapas (68.6%), while an increase of only 39.7% was seen on the Rio Onzoles. Geographical extension of both the onchocercal focus and its respective hyperendemic areas were found on the Rio Cayapas and Rio Santiago. A higher increased prevalence of infection was found in the children (210.0%) than in the adults (29.5%). In the satellite foci, the Rio Canande showed the higher increase of infection (146.4%), with an increase of 61.3% seen in adults and 1409.1% in children. Active transmission of the disease exists in all onchocercal foci, each with its distinct and varying intensity.

Adult↗
PubMed1987

Cell adherence to microfilariae of Onchocerca volvulus: a comparative study.

The conditions were examined for in vitro antibody-mediated adherence of granulocytes to microfilariae of Onchocera volvulus and Dirofilaria immitis. Reactivity in human sera from patients in endemic foci in Sudan was specific for O. volvulus and no reactions were observed with heterologous Onchocerca species or with Mansonella perstans. Microfilariae from skin, nodules or adult female worms were satisfactory targets for cell adherence, and the cells involved were almost exclusively eosinophils. The reaction was inhibited by indomethacin but not by nordihydroguaiaretic acid, an inhibitor of leukotriene production. Agents that slowed or stopped microfilarial motility (e.g. nifedipine, lidocaine, chloroquine) inhibited the reaction, probably by reducing target/cell contact. Ivermectin did not enhance the reaction, and in the absence of cells exerted only slight effects on the movement of microfilariae at higher concentrations (greater than 10 micrograms/ml). Antibody activity was labile, and did not persist well through freeze-thaw cycles. Some differences between homologous and heterologous mixtures (microfilariae/cells/serum) were seen but they could not be resolved satisfactorily. There were no apparent geographical differences between microfilariae from different foci in Sudan. In the D. immitis system neutrophils were the dominant cell type adhering to microfilariae, and the activity was stable to storage and freeze-thaw. No enhancement was detectable with diethylcarbamazine. Antibody activity was absorbable with microfilarial antigens and was reduced by agents that inhibited microfilarial motility. In dogs, adherence-mediating antibody was seen only in amicrofilaraemic animals with occult infection, and in only a minority of these sera. In humans the relationship to clinical findings was less clear, but patients with punctate keratitis were the most likely to have positive serum and were the most reactive in the assay. This system may therefore offer some insights into disease mechanisms in vivo, and its molecular mechanisms deserve further characterization.

Animals↗
PubMed1987

Clinical responses in human onchocerciasis: parasitological and immunological implications.

Onchocerciasis can cause severe dermal and ocular disease due, it is thought, to the events surrounding the destruction of the microfilarial stage. The evolution of papular pruritic dermatitis and punctate keratitis is clearly related to the killing of microfilariae. Other more chronic changes such as dermal and epidermal atrophy are probably due to repeated episodes of microfilarial killing. It is common to find that not all patients are, at any one time, mounting clinically obvious destructive host responses against the microfilariae, and such individuals can carry very high loads of parasites without any apparent adverse effects. The immunological basis of the differences between these types of patients forms one of the most important questions in the pathogenesis of onchocerciasis today. Various explanations are now emerging. These include immunosuppressive factors and variation in the form of Onchocerca volvulus antigens presented to the host. Clinical presentations of this disease appear to reflect variations in host responses and can be used to provide information concerning the protective immune responses an individual can mount against this parasite.

Animals↗
PubMed1987

A histocytochemical study of the macrophages present in tissue responses to adult Onchocerca volvulus.

Immunocytochemical and histochemical properties of macrophages present in the subcutaneous chronic inflammatory responses surrounding adult Onchocerca volvulus (nodules) in human tissues were examined. Macrophages with strong non-specific esterase (NSE) and acid phosphatase (AcPase) activities but weak adenosine triphosphatase (ATPase) activity and HLA-DR expression (NSE+++, AcPase+++, ATPase-/+, HLA-DR-/+) were present in the centre of nodules. Many of the cells adhering to the surface of worms were NSE+++, AcPase+++, ATPase-, HLA-DR+++. The inner zone of the fibrous capsule of nodules contained macrophages with the profile NSE+++, AcPase-, ATPase-/+, HLA-DR-/+. A fourth type, NSE+++, AcPase-/+, ATPase-/+, HLA-DR+++, was located in the outer zone of the capsule, frequently within perivascular accumulations of macrophages, lymphocytes and plasma cells. Active fibroblasts were identified at the inner edge of the fibrous capsule by alkaline phosphatase staining. A feature of all nodules examined was the presence of lipid-filled macrophages, demonstrated by Oil Red O stain; these cells were usually situated in zones adjacent to the centre of nodules, and were of the NSE++, AcPase++, ATPase-/+, HLA-DR-/+ type. Lipid accumulation was not found to be related to the clinical status of the patients studied. The origin and functional significance of this lipid is unknown.

HLA-DR Antigens↗
PubMed1987

Associations between clinical disease, circulating antibodies and C1q-binding immune complexes in human onchocerciasis.

Onchocerciasis is a disease where often there are high levels of serum antibodies and high parasitic loads. The role of immune complexes in the development of the disease is investigated here by studying non-specific and Onchocerca volvulus specific immune complex levels, as well as the antibody concentrations, in the sera of 372 people living in either Southern (199) or Northern (173) Sudan; sera from Sudanese individuals (31) and Caucasians (21) living outside the onchocerciasis endemic area were also tested. The levels of non-specific immune complexes (NS-IC) in these sera were measured by a solid phase radio-immunoassay and those of O. volvulus-specific immune complexes (OV-IC) by an assay measuring antibody-excess complexes using C1q-coated plates. The concentrations of O. volvulus IgG antibodies were measured by ELISA. Immune complex and antibody levels of the serum donors were compared with regard to their clinical status due to onchocerciasis. These clinical changes were classified according to onchocercal lesions related to either the active destruction of microfilariae (acute changes), or the long term tissue alterations (chronic changes). Data was analysed using the Odds Ratio method. A negative association between microfilarial load and immune complex level was found, with the higher levels of OV-IC present in patients with the lower levels of dermal microfilariae (i.e., less than 10 mf/mg). Significant associations between immune complex levels and the severity of onchocercal disease were also found. Levels of OV-IC specific immune complexes were higher in infected individuals carrying dermal onchocercal lesions than in those without such clinical changes; there was no apparent relationship between these levels and the presence of ocular lesions. OV-IC levels varied considerably within each age group and from age to age. A weak positive association was detected between microfilarial load and parasite-specific IgG antibody concentration in the sera. On average younger individuals (less than 25 years) had the higher antibody levels with a gradual reduction in mean concentrations with age. The significance of these serological findings in terms of the pathogenesis of onchocerciasis is discussed.

Age Factors↗
PubMed1987

Onchocerciasis in southwestern Sudan: parasitological and clinical characteristics.

Parasitological and clinical observations were made on residents of Pongo Nuer, a village in the province of Bahr El Ghazal, southwestern Sudan. Of 202 skin biopsies, 189 (94%) were positive for microfilariae of Onchocerca volvulus. Nodules were most common around the pelvic girdle and rare on the limbs or head. Microfilarial intensities, ranging up to 1,094 mf/mg of skin, were highest at the iliac crest and shoulder; they increased rapidly in childhood but then appeared to reach a plateau maintained through adult life. Nodule presence and number, especially at multiple sites, was significantly related to skin microfilarial intensity. Dermal manifestations of O. volvulus infection were widespread and severe, ranging from acute maculopapular eruptions to chronic, diffuse, and degenerative changes, even in young adults. However, high skin microfilarial intensities were found in asymptomatic individuals; conversely, lowest intensities were in those with severest maculopapular lesions, suggesting that host response was a major determinant of disease outcome. Microfilariae were detected in the cornea or anterior chamber of the eyes of one third of those examined in all age groups, but lesions of the posterior segment, including optic neuritis, chorioretinitis, and pigmentary abnormalities, were considered responsible for visual deficits in the population sample. Some pathologic changes in the anterior segment attributable to microfilariae were more common in the young than in adults but there was no preponderance of sclerosing keratitis in adults, contrary to expectations in hyperexposed individuals in a Sudan savannah zone. The best correlate of the presence of microfilariae in the eye was the intensity of infection in shoulder skin snips. Little value could be derived from data on outer canthus samples, either in terms of severity of ocular infection or disease. Microfilaremia was common (76%) but in only one case was attributed to O. volvulus; the remainder were due to Mansonella perstans.

Adolescent↗
PubMed1987

Lectin binding to the developing forms of Onchocerca gutturosa microfilariae.

Uterine and skin derived forms of microfilariae (mf) and earlier developing stages of the cattle filarial nematode Onchocerca gutturosa were examined for the lectin binding properties of their external surfaces (ie. egg shell and microfilarial cuticle). Both the uterine and skin derived forms of mf failed to bind any of the lectins tested. Incubation in known microfilaricides did not promote any binding of lectins to these parasites. Peanut agglutinin (PNA) was the only lectin found to bind specifically to earlier developing stages (i.e. the shells of freshly obtained eggs). Diethylcarbamazine (DEC) did not alter the binding pattern from that observed in untreated eggs. Ivermectin eliminated PNA binding but increased Ricinus communis lectin (RCA-1) positivity. Trypsin, collagenase and protease enzymes all affected the binding; chitinase however did not have any effect. These results support the concept that the eggshells of filariae can interact with the host defence responses.

Animals↗
PubMed1987

Secondary amyloidosis in normal and immunocompromised mice infected with Schistosoma japonicum.

Secondary amyloidosis developed in various tissues of immunologically intact and T-cell deprived CBA mice infected with Schistosoma japonicum as indicated by histological, histochemical and immunofluorescence techniques. Mice deprived of T-cells were most susceptible both in terms of the timing of the onset of amyloidosis, first noted 6 weeks post-infection, and in terms of the incidence, reaching 100% 12 weeks post-infection. Amyloidosis developed later in the infection in immunologically intact mice, the incidence was lower and there was less extensive replacement of normal tissue compared with that seen in T-cell deprived mice. Amyloid-related changes were most noticeable in the spleen where there was replacement of both follicular and non-follicular tissue. In the liver, amyloid deposits caused hepatocellular atrophic changes and in the kidney, glomerular and interstitial deposits were observed. The relationships between immunological reactivity and amyloidosis during schistosome infection is discussed.

Amyloidosis↗
PubMed1987

The reduction in microfilariae loads in the skin and eye after nodulectomy in Ecuadorian onchocerciasis.

This study is concerned with the relationship between palpable onchocercal nodules and Onchocerca volvulus microfilarial loads in the skin. The number of microfilariae in clinically normal skin decreases as the distance from the nodule increases. Surgical removal of nodules reduces the microfilarial loads in 40 of 46 patients studied over a period of five months, with an average reduction of 65.4% of the prenodulectomy microfilarial load at the iliac crest. Complete elimination of detectable parasites was seen in some patients. Five individuals had increased microfilarial loads, all of which had developed new palpable nodules. Also, nodulectomy had a significant effect on ocular tissue, reducing the levels of parasites in the cornea and anterior chamber in 10 of 15 patients observed with no new nodules developing during the observation period. Both dermal and ocular clinical manifestations of onchocerciasis were reduced in a proportion of the patients. These parasitological and clinical findings provide evidence that nodulectomy is a beneficial procedure to O. volvulus infected patients in Ecuador by reducing both microfilarial loads and the degree of pathology.

Animals↗
PubMed1987

Onchocerciasis in Ecuador: absence of microfilaraemia.

Blood samples from 497 people positive for onchocerciasis in the hyperendemic onchocercal focus in Ecuador were analysed for the presence of microfilaraemia using the Knott technique. No evidence of Onchocerca volvulus microfilaraemia was found, nor that of any other microfilaria.

Adult↗