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PubMed2004

Cutaneous onchocercoma.

Onchocerciasis is a common, chronic multisystem disease with dermatologic, ocular, and systemic manifestations. Although the disease is endemic in Africa, Latin America, and Yemen, imported cases have been described in the United States. The causative organism, Onchocerca volvulus, is transmitted by the bite of a black fly of the genus Simulium. There are a number of cutaneous manifestations of the disease, including onchocercomas, which are subcutaneous bundles of worms. The antiparasitic agent ivermectin is the drug of choice for both prophylaxis and treatment of active disease.

Adult↗

PubMed2005

Associations between filarial and gastrointestinal nematodes.

The possibility that positive or negative associations occur between the filarial nematode Onchocerca volvulus and the gastrointestinal nematodes Ascaris lumbricoides and Trichuris trichiura was investigated in 205 children attending three schools in central Cameroon. Despite the closeness of their locations, marked differences between the schools were detected with respect to the number of species carried, the prevalence of O. volvulus and T. trichiura and the interaction between the prevalence of these two species. The number of species carried and these same prevalences varied significantly across the narrow age range of the study group. In addition, we observed an interaction between the prevalences of O. volvulus and A. lumbricoides that was dependent upon school but independent of host age and sex. Quantitative analyses revealed that the abundances of O. volvulus, A. lumbricoides and T. trichiura were affected by both school and age whereas host sex was significant only for O. volvulus. Finally, we observed significant positive interactions between the intensities of A. lumbricoides and T. trichiura and between O. volvulus and T. trichiura, that were school, age and sex independent. Our data suggest that associations do occur between filarial and gastrointestinal nematodes and that certain individuals are prone to multiple and high-level infections.

Age Distribution↗

PubMed1992

Hydrolytic activity of an onchocercoma.

The onchocercoma or nodule produced by the nematode Onchocerca volvulus (Filarioidea) in the skin of patients suffering from onchocerciasis has not been examined by histochemical techniques. In this work we have used histochemical techniques to evaluate 5 hydrolytic enzymes, namely phosphatases, esterases and beta-glucuronidase. The results show increased enzymatic activity at the sites of major metabolic activity and within reactive cells including macrophages (mc) and giant cells (gc) of the onchocercoma.

Animals↗

PubMed1998

Tropomyosin implicated in host protective responses to microfilariae in onchocerciasis.

A cDNA from adult female Onchocerca volvulus encoding the C-terminal portion of a tropomyosin isoform (termed MOv-14) has been shown previously to confer protective immunity in rodent models of onchocerciasis. The full-length sequence (designated Ov-tmy-1) obtained by PCR amplification, codes for a protein of 33 kDa and shares 91% identity with tropomyosins from other nematodes, falling to 57% identity with human alpha-tropomyosin. Ov-TMY-1 migrates with an apparent molecular mass of 42 kDa on SDS/PAGE and is present in all life-cycle stages, as determined by immunoblotting. Immunogold electron microscopy identified antigenic sites within muscle blocks and the cuticle of microfilariae and infective larvae. Anti-MOv14 antibodies were abundant in mice exhibiting serum-transferable protection against microfilariae conferred by vaccination with a PBS-soluble parasite extract. In contrast, little or no MOv14-specific antibody was present in mice inoculated with live microfilariae, in which resistance is mediated by antibody-independent mechanisms. In human infections, there was an inverse correlation between anti-tropomyosin IgG levels and densities of microfilariae in the skin. Seropositivity varied with the relative endemicity of infection. An immunodominant B cell epitope within Ov-TMY-1 (AQLLAEEADRKYD) was mapped to the N terminus of the MOv14 protein by using sera from protectively vaccinated mice. Intriguingly, the sequence coincides with an IgE-binding epitope within shrimp tropomyosin, believed to be responsible for hypersensitivity in individuals exhibiting allergy to shellfish. IgG and IgE antibodies reacting with the O. volvulus epitope were detected in human infections. It is concluded that antibody responses to tropomyosin may be important in limiting microfilarial densities in a proportion of individuals with onchocerciasis and have the potential to mediate hypersensitivity reactions to dead microfilariae, raising the possibility of a link with the immunopathology of infection.

Adult↗

PubMed2006

Ivermectin: uses and impact 20 years on.

PURPOSE OF REVIEW: Ivermectin was first discovered and used in veterinary medicine over 20 years ago. This review highlights some of the recent published research from 2005 through June 2006 on the use of ivermectin in both helminth and arthropod infection. RECENT FINDINGS: In recent years, several published studies have detailed the expanding role for ivermectin in multiple endo and ectoparasitic infections, including scabies, pediculosis, soil transmitted helminths, gnathostomiasis and myiasis. In addition, there is increasing experience with parenteral ivermectin for the treatment of disseminated strongyloidiasis. The success of ivermectin in reducing Onchocerca volvulus and Wuchereria bancrofti transmission through universal treatment in disease control programs continues to be well documented, but recent epidemiologic data describe suboptimal response to ivermectin by O. volvulus in a minority of individuals, the molecular markers for which are currently under investigation. SUMMARY: Over 20 years of research and clinical use have advanced ivermectin from its beginnings as a veterinary anthelmintic to its significant role in several successful disease control programs. Nevertheless, further research is needed to understand the basis for suboptimal response and to better define optimal drug regimens for varying diseases.

Animals↗

PubMed2003

Multicentre laboratory evaluation of Brugia Rapid dipstick test for detection of brugian filariasis.

A multicentre evaluation of the Brugia Rapid dipstick test was performed using 1263 serum samples in four international laboratories, i.e. T.D. Medical College (TDMC, India), National Institutes of Health (NIH, USA), Swiss Tropical Institute (STI, Switzerland) and Leiden University Medical Centre (LUMC, Netherlands). In comparison with microscopy, the dipstick demonstrated sensitivities of 97.2% (70 of 72) at TDMC, 91.6% (175 of 191) at LUMC and 100% (six of six) at STI. Sera of chronic patients showed a positivity rate of 11.3% (19 of 168) and 61.2% (71of 116) at TDMC and LUMC, respectively. All 266 sera of non-endemic normals from STI, NIH and LUMC tested negative with the dipstick. At LUMC, sera of 'endemic normals' (amicrofilaraemics with no clinical disease) from an area with approximately 35% microfilaria positivity showed 60.8% positive results (31 of 51), thus demonstrating the likelihood of many cryptic infections occurring in this population. Specificities of the test with Onchocerca volvulus sera were 98.8% (80 of 81) and 100% (10 of 10) at the NIH and STI, respectively; while specificity with Loa loa sera at the NIH was 84.6% (44 of 52). At the STI, the dipstick test also demonstrated 100% specificity when tested with 75 sera from various protozoan and helminthic infections.

Animals↗

PubMed1997

Research notes from the Onchocerciasis Chemotherapy Research Centre, Ghana.

Brief notes are given on drugs which have been tested at the Onchocerciasis Chemotherapy Research Centre at Tamale and Hohoe and found to have activity against Onchocerca volvulus. Ivermectin in single doses as high as 800 micrograms/kg was found to be no more effective than the standard dose of 150 micrograms/kg. The benzimidazole carbamates, mebendazole and albendazole, differ in their effects on O. volvulus. The former has microfilaricidal effects and is toxic to developing embryos surrounded by an egg shell but not the stretched microfilariae. Albendazole has no microfilaricidal activity but is toxic to all intra-uterine stages. The reasons for these differences are unclear. Early studies with amocarzine are described; the maximum tolerable dose is 20 mg/kg and the predominant activity, against the microfilariae, is marked only at doses greater than 12 mg/kg. None of the drugs tested has macrofilaricidal activity.

Albendazole↗

PubMed2001

Immunisation of mice with fractions derived from the intestines of Dirofilaria immitis.

Antigens that are not normally seen by the host but that are nevertheless, accessible to host immune effector molecules and cells such as the native endoantigens associated with the intestinal epithelium of haematophagous tissue-dwelling parasites, could be potentially useful vaccine antigens. In this study, intestines were dissected from adult Dirofilaria immitis, homogenised, and a 105,000 x g pellet obtained and extracted with Triton X-100. The soluble 105,000 x g supernatant from this extract induced partial protection (51%) against a challenge infection of third stage larvae (L3) implanted in micropore chambers. Sera from mice immunised with this soluble detergent extract reacted with proteins ranging in size from 38 to 130 kDa. Immunolocalisation studies indicated the mouse sera reacted primarily to the lumenal surface of the intestines of adult D. immitis, though reactivity to the lateral nerve/epithelial chords, hypodermis and reproductive tracts was also noted, indicating the presence of shared antigens. Tissues of L3s were also recognised by the immunised mouse sera. These mouse sera did not react to a dog blood fraction prepared identically to the D. immitis fraction. Only those sera from D. immitis-infected dogs with heavy or long-term infections were reactive to a single 42 kDa protein. After 24 h incubation in fluorescein isothiocyanate-conjugated serum the intestinal tract of Onchocerca volvulus and D. immitis L3 and L4 fluoresced, indicating the serum had been ingested. These data suggest that filarial gut-associated antigens (apart from the single 42 kDa antigen) are not seen by normally infected hosts, that they can be accessible to antibodies and that they can induce an immune response which is partially protective.

Animals↗

PubMed1994

Pathogenesis of onchocercal dermatitis: possible role of parasite proteases and autoantibodies to extracellular matrix proteins.

We examined the immunogenicity of various connective tissue proteins in patients with chronic onchocercal dermatitis and the effect of filarial proteases on this host-parasite interaction. Sera from patients with onchocerciasis reacted strongly with cuticular collagens from filarial parasites and with mammalian laminin. Some sera also contained antibodies to elastin and collagen type IV, but none reacted with collagen types I-III or fibronectin. This pattern of reactivity was characteristic for onchocerciasis: sera from patients with mansonellosis reacted strongly with collagen type IV but only weakly with laminin. Reactivity with mammalian laminin or collagen could not be absorbed with cuticular proteins from filarial worms and vice versa. Digestion fragments of laminin treated with filarial proteases retain antigenic determinants recognized by sera from patients with onchocerciasis. In contrast, proteases from Onchocerca volvulus adults and microfilariae drastically decreased the reactivity of the same sera with collagen type IV. These results indicate that filarial proteases may contribute to the pathogenesis of chronic onchocercal dermatitis, directly, by enzymatically destroying connective tissue of the skin, and indirectly, by triggering autoimmune responses to self-determinants on connective tissue proteins that are normally hidden within the supramolecular structure of the extracellular matrix complex.

Animals↗

PubMed1999

Structural studies of N-glycans of filarial parasites. Conservation of phosphorylcholine-substituted glycans among species and discovery of novel chito-oligomers.

N-Type glycans containing phosphorylcholine (PC-glycans), unusual structures found in the important human pathogens filarial nematodes, represent a novel target for chemotherapy. Previous work in our laboratories produced compositional information on the PC-glycan of ES-62, a secreted protein of the rodent parasite Acanthocheilonema viteae. In particular, we established using fast atom bombardment mass spectrometry (MS) analysis that PC was attached to a glycan with a trimannosyl core, with and without core fucosylation, carrying between one and four additional N-acetylglucosamine residues. In the present study, we demonstrate that this structure is conserved among filarial nematodes, including the parasite of humans, Onchocerca volvulus, for which new drugs are most urgently sought. Furthermore, by employing a variety of procedures, including collision-activated dissociation MS-MS analysis and matrix-assisted laser desorption MS analysis, we reveal that surprisingly, filarial nematodes also contain N-linked glycans, the antennae of which are composed of chito-oligomers. To our knowledge, this is the first report of such structures in a eukaryotic glycoprotein.

Animals↗

PubMed2000

Longitudinal studies of skin microfilaria and antibody conversion rates in children living in an endemic focus of onchocerciasis in Nigeria.

We monitored skin microfilarial conversion and antibody (serum) conversion rates to Onchocerca volvulus recombinant antigens (OC3.6 and OC9.3) over a 2-year period, in a cohort of 208 children aged 9-11 years and living in a mesoendemic focus of savannah-type onchocerciasis in Nigeria in order to detect prepatent onchocerciasis in children. Between time point A and time point B (9 months apart) the seroconversion rate was 19.4 per cent, and between time points B and C (15 months apart), a further 31.4 per cent of seronegative children had seroconverted. However, only a third of the seroconverted children became microfilaria-positive. From the time-lag between antibody conversion and skin snip conversion, we estimated that a 9-12 month interval was required for the detection of O. volvulus microfilariae following infection with viable third stage larva (L3s). The predictive value of antibody detection as a measure of skin microfilarial conversion was >90 per cent when the optical density (OD) at 490 nm was >0.80. We therefore propose a strategy for monitoring changes in transmission of onchocerciasis following vector control or chemotherapy through an evaluation of annual antibody seroconversion rates in a standardized sentinel population of children.

Animals↗

PubMed1994

Community treatment with ivermectin for onchocerciasis in the east Usambara mountains.

Ivermectin 150mcg/kg was given orally to 743 patients with positive skin snips for Onchocerca volvulus and to 697 residents in two villages in the Usambara mountains. 620 villagers attended for a second dose. On direct questioning, 98.7% patients with +ve skin snips and 91.8% villagers given mass chemotherapy admitted to adverse reactions. After a second dose, 16.6% had mild reactions. No serious problems were encountered. 167 of 170 repeat skin snips were negative. Repeated administration of ivermectin is well tolerated and offers a chance of reducing the burden of onchocerciasis in the Usambara mountains.

Adolescent↗

PubMedDate not supplied

Onchocerciasis and reproductive health in Ecuador.

A retrospective study was performed comparing the number of spontaneous abortions in a hyperendemic area for onchocerciasis in Ecuador before and after invermectin treatment with that of a comparable non-endemic area. The frequency of spontaneous abortions was associated with a change in the community microfilarial load, suggesting that there may be a relationship between spontaneous abortions and infection with Onchocerca volvulus. In the endemic area, a significantly greater rate of spontaneous abortions was seen in the period before ivermectin distribution compared to that after the start of ivermectin treatments every 6 months. In the non-endemic area, no change in the rate of spontaneous abortions was seen over the same time period. In addition to the well-documented improvements in skin and ocular disease, ivermectin may also improve the reproductive health of endemic populations.

Abortion, Spontaneous↗

PubMed1995

Salivary apyrase in New World blackflies (Diptera: Simuliidae) and its relationship to onchocerciasis vector status.

Salivary gland apyrase is believed to be critical to blood-feeding in arthropod vectors. This enzyme was measured in six New World blackflies representing three taxonomic pairs of non-vectors and vectors of Onchocerca volvulus. In Simulium (Psilopelmia) ochraceum, a highly anthropophilic vector in Mexico and Guatemala, apyrase exhibited maximum activity between pH 8.0 and 9.0, mean 39.8 +/- 4.7 milliUnits/pair of gland equivalents (mU), and was enhanced when ATP was used as a substrate. In the zoophilic non-vector Simulium (Psilopelmia) bivittatum maximum activity was significantly less (5.1 +/- 0.7 mU) under all conditions examined. Preference for ADP or ATP as substrate was a function of the pH of the reaction for this species. Apyrase activity in Simulium (Simulium) metallicum Bellardi (29.5 +/- 11.5 mU), a zoophilic secondary vector in Mexico and Guatemala, resembled that of S. (Ps.) ochraceum (24.8 +/- 13.7 mU at pH 8.5) with ADP as substrate, but showed reduced activity with ATP. Both these Central American vectors had higher apyrase activity than found in Simulium (Notolepria) exiguum, a vector of O. volvulus in Ecuador and Colombia. However, maximum apyrase activity, measured at pH 8.0 with ADP as substrate, was greater in S. (N.) exiguum (10.9 +/- 0.6 mU) than in Simulium (Notolepria) gonzalezi (5.9 +/- 1.9 mU), a non-vector species widespread in Central America. Therefore, for the consubgeneric species pairs examined, a positive association was detected between higher concentrations of apyrase activity and their vector status for O.volvulus.

Adenosine Diphosphate↗

PubMedDate not supplied

Onchocerciasis-associated limb swelling in a traveler returning from Cameroon.

Travelers to West Central Africa are at risk for infection with Onchocerca volvulus. We describe the case of an adventurous traveler who became infected with O volvulus after a 10-day stay in rural Cameroon. Two years after his return, he was diagnosed with a 3-month history of limb swelling with pruritus and fixed edema of the right arm. He was successfully treated by a single dose of ivermectin, with an additional treatment with doxycycline. The patient was followed-up during 1 year after therapy without relapse. Such travelers experiencing unusual dermatitis syndromes should prompt evaluation for onchocerciasis.

Animals↗

PubMed1993

Cross-reactive antigens in the pathogenesis of onchocerciasis.

The ocular disease associated with infection with Onchocerca volvulus is unique in that there is a wealth of epidemiological evidence to support the casual nature of the association but there is little known about the pathogenic mechanisms involved. We have identified a 44,000 M(r) component of ocular tissues that shows immunological cross-reactivity with an O. volvulus antigen. This immunological cross-reactivity between parasite and a component of host tissues may underlie the development of ocular disease in onchocerciasis. Preliminary experiments indicate that it is possible to initiate ocular disease in susceptible rats using the recombinant parasite antigen. This should allow the development of a laboratory model of ocular onchocerciasis and further our understanding of the mechanisms by which an infective organism can produce an auto-immune-like disease in the host.

Animals↗

PubMed2006

High infection rates at low transmission potentials in West African onchocerciasis.

Onchocerciasis has been successfully controlled for many years in endemic countries but more than 120 million people are still at risk. Factors which stabilise the persistence of the parasite in the population must be studied to minimise the future risk of re-infection. Among these factors, the relationship between the annual transmission potential and the parasite establishment rate is a main determinant which has to date not been quantified. Using entomological information and palpation data collected by the Onchocerciasis Control Programme in West Africa prior to the initiation of control activities, we derive annual transmission potential-dependent estimates of the parasite establishment rate from statistical analyses and computer simulations. Even at very low transmission intensities, the filarial parasite Onchocerca volvulus can efficiently establish in the human population, originating from an infection process which is strongly limited with respect to the annual transmission potential. Implementing the estimates into a simplified transmission model predicts that the critical annual biting rate, below which transmission is not possible, is much lower than previously assumed. We conclude that under the current strategy of mass distribution of microfilaricides without additional measures of vector control, the risk of re-infection is higher than previously assumed.

Africa, Western↗

PubMed2005

Cytotaxonomic description of Simulium kaffaense, a new member of the S. damnosum complex (Diptera: Simuliidae) from south-western Ethiopia.

Although Ethiopia is one of the countries worst affected by human onchocerciasis, the exact taxonomic identity of the blackflies acting as the main vectors in the endemic areas has never been determined. A cytotaxonomic analysis of Simulium damnosum s.l. collected from three endemic sites in south-western Ethiopia has now revealed the existence of the 'Kisiwani' form (a non-anthropophilic cytoform that is common in East Africa) and a newly recognized species, Simulium kaffaense. Simulium kaffaense sp. nov. is differentiated from other members of the S. damnosum complex by six fixed inversions and dozens of 'new' floating inversions. The rearing of egg batches from some of the biting adult females, to larvae or adults, indicated that the human-biting blackflies were all S. kaffaense. As S. kaffaense is not only highly anthropophilic but also, apparently, the only anthropophilic member of the S. damnosum complex present, it is likely to be the main (if not the only) vector of Onchocerca volvulus in the study area. The presence of inversion 1S-1 and a complex inversion possibly involving 1L-3 indicates that S. kaffaense either belongs or is close to the 'Nile' phylogenetic group of S. damnosum s. l. The karyotype frequencies of the inversions in the collections from the three study sites indicate that at least two forms of S. kaffaense, here designated 'Bebeka' and 'Jimma', were caught. The taxonomy and medical importance of S. kaffaense are discussed.

Animals↗