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PubMed1998

Molecular and immunodiagnosis of human filarial nematode infections.

The filarial nematodes Wuchereria bancrofti, Brugia malayi and Onchocerca volvulus represent major public health problems in the Tropics. Effective diagnosis of infection with these parasites is required both for administration of drugs to infected individuals and for monitoring of control programs. However parasitological diagnosis is associated with a number of problems including frequently inadequate sensitivity, long pre-patency of infection and inconvenience for patients. For these reasons there has been considerable effort expended in developing other forms of diagnosis, in particular immunoassays for measuring antibody and circulating parasite antigen as well as molecular-biology-based assays for detecting parasite DNA. This article reviews the progress and achievements obtained to date. The latter include the development of ELISAs employing recombinant antigen for detection of antibody to O. volvulus which have both high sensitivity and specificity, the commercial availability of immunoassays to measure circulating antigen in W. bancrofti infection and the generation of specific DNA-based detection systems for all three parasites.

Animals↗

PubMed2000

A comparison of newer tests for the diagnosis of onchocerciasis.

Samples of human serum, skin and urine, collected in Cameroon, were used to assess the value of some newer methods for the diagnosis of onchocerciasis. Parasite DNA was detected in skin snips and urine by PCR, and parasite antigen was detected in serum and urine by immunoblotting. Serum concentrations of IgG4 antibodies reacting with recombinant Onchocerca volvulus antigens (OC3.6 and OC9.3) were also measured, using an ELISA. The PCR-based tests of skin snips and the serological tests for antigen and antibody tests showed higher sensitivities (90%-100%) than the urine PCR (14%) or the urine antigen test (68%). Although antibody detection is much easier to perform than tests based on PCR or antigen detection, the latter have an advantage in that they are only positive in people with current infections. Thus, antibody testing may be more useful for screening populations for infection or exposure to O. volvulus, whereas PCR and antigen testing are potentially more useful for diagnosis of infections in individuals and for monitoring the success of therapy.

Adolescent↗

PubMed2000

The cytotaxonomy of Simulium damnosum s.l. (Diptera: Simuliidae) from the Thyolo onchocerciasis focus in Malawi and description of a new member of the complex.

Larvae of the Simulium damnosum complex were collected in southern Malawi, in particular from the Thyolo onchocerciasis focus. Cytological identifications revealed the occurrence of S. (Edwardsellum) thyolense sp.nov., S. kilibanum Gouteux, 'Ketaketa', a new cytoform tentatively designated 'Mwamphanzi', and two unassigned specimens. Simulium thyolense sp.nov. is presumably the major vector of Onchocerca volvulus in the area, but it remains possible that the other cytospecies are secondary vectors. Simulium thyolense sp.nov. is most appropriately classified near the 'Sanje' subcomplex, whereas 'Mwamphanzi' and the unassigned specimens are members of the 'Ketaketa' subcomplex.

Animals↗

PubMed2006

Recent updates on onchocerciasis: diagnosis and treatment.

Recent progress in onchocerciasis research has led to improved understanding of the immunopathology of Onchocerca volvulus, as well as improvements in diagnosis and treatment of this morbid disease. This article reviews the recent literature, highlighting breakthroughs in sensitive means of antigen testing and an unusual new approach to therapy that targets an endosymbiotic bacterium required for filarial worm fecundity.

Animals↗

PubMedDate not supplied

Onchocerciasis-associated morbidity: hypothesis.

Tissue concentrations of vitamin A in Onchocerca volvulus are about 8 times higher than those of the host. About 100,000 microfilariae (mf) die every day in heavily infected persons. Onchocerciasis-associated morbidity may be due in part to the release of retinoids from dying mf and their gradual accumulation to toxic concentrations in affected tissues.

Animals↗

PubMed1992

Albendazole in the treatment of onchocerciasis: double-blind clinical trial in Venezuela.

A double-blind clinical trial was conducted in Monagas State, Venezuela to assess the tolerance and efficacy of albendazole in the therapy of Onchocerca volvulus infection. Forty-nine patients (26 treated and 23 controls) received a 10-day course of albendazole (400 mg/day) or a placebo. Consistent with the excellent tolerance observed, albendazole did not kill microfilariae. However, analysis of changes in microfilarial densities (mf/mg of skin) over one year showed that albendazole was active against O. volvulus, presumably by interfering with embryogenesis. The nature, degree, and duration of this effect remain to be determined.

Adolescent↗

PubMed1994

Identification and characterisation of a novel repetitive antigen from Onchocerca spp.

A novel repetitive antigen from the cattle parasite Onchocerca gibsoni was shown to be recognised by sera from humans infected with Onchocerca volvulus, Wuchereria bancroftii or Brugia malayi. The O. gibsoni protein was produced in a recombinant form, and antibodies raised to this protein used to screen cDNA libraries for O. volvulus. A series of clones were isolated which encoded repetitive regions very similar to those in O. gibsoni, but interspersed between these were longer repeating units which we have not so far found in O. gibsoni. The repetitive antigen was shown to be of high molecular weight and present only in the insoluble (membrane) fraction of O. gibsoni microfilariae. Immunofluorescence techniques demonstrated that the antigen was associated both with muscle and with specific membrane layers, including a peripheral layer which corresponds to either the outer hypodermis or an inner region of the cuticle in adult female O. gibsoni. In many respects, the proteins encoded by the O. gibsoni and O. volvulus cDNA clones resembled repetitive antigens from several distantly related eukaryotic parasites, and a possible common role in immune evasion is discussed.

Amino Acid Sequence↗

PubMed2000

Endosymbiotic bacteria in worms as targets for a novel chemotherapy in filariasis.

Endosymbiotic bacteria living in plasmodia or worm parasites are required for the homoeostasis of their host and should be excellent targets for chemotherapy of certain parasitic diseases. We show that targeting of Wolbachia spp bacteria in Onchocerca volvulus filariae by doxycycline leads to sterility of adult worms to an extent not seen with drugs used against onchocerciasis, a leading cause of blindness in African countries.

Adolescent↗

PubMed1957

Factors in the pathogenesis of ocular onchocerciasis.

This article briefly reviews the history and distribution of Onchocerca volvulus, and the disease for which it is responsible. The importance is stressed of ophthalmic examination, as opposed to clinical inspection, in determining the incidence of onchocerciasis in a region, such as the Sudan, where eye diseases are common. A description of the ocular manifestations of the infection is given, and their etiology is discussed.

Animals↗

PubMed2002

Immunity to Onchocerca spp. in animal hosts.

This review summarizes research using Onchocerca spp. in chimpanzees, cattle and mice to gain insight into the protective immune response to the filarial worm Onchocerca volvulus in humans. In addition, Acanthocheilonema viteae has been evaluated as a surrogate filarial worm for studying immunity to the infection. Immune mechanisms controlling these infections are described and initial success using recombinant antigen vaccines in these models is reviewed.

Animals↗

PubMed1992

Filariasis in Gongola State Nigeria. I: Clinical and parasitological studies in Mutum-Biyu District.

A total of 2,552 persons living in 9 villages along the Benue river valley, Mutum Biyu district of Gongola State, Nigeria were examined between October and December 1989 for filariasis. It is the first time a filariasis survey will be carried out in this state. 276 (10.8%) had Wuchereria bancrofti, 50 (2.0%) had Loa loa, 281 (11.0%) were positive for Mansonella perstans while 12 (0.5%) were positive for Onchocerca volvulus. Villages located near the Benue river had higher prevalence rates than those further away. Dermatitis and hydrocoele were common and clinical manifestations were associated with parasite types. Clinical symptoms without microfilaremia and microfilaremia without clinical symptoms were also observed.

Adolescent↗

PubMed1995

cis-splicing and polyadenylation of actin RNA can precede 5' trans-splicing in nematodes.

In nematodes many precursor RNAs undergo both cis-splicing (intron removal) and trans-splicing (spliced leader addition) via molecular mechanisms thought to be very similar. We examined the temporal order of trans- and cis-splicing by analyzing cDNAs of partially processed transcripts from an actin gene of the parasitic nematode, Onchocerca volvulus, which has five short introns. We found that in this model gene system trans-splicing can follow cis-splicing and polyadenylation, and we obtained no evidence for alternative pathways of splicing. This result is in contrast to the tubulin genes of African trypanosomes where trans-splicing precedes polyadenylation (1).

Actins↗

PubMed1998

Current status of onchocerciasis in Colombia.

To assess the current epidemiologic status of onchocerciasis in Colombia two surveys were undertaken in 1995 in a suspected new focus on the border between Colombia and Ecuador and in the known focus located on the Micay River. No new focus was found along the Colombia-Ecuador border. In the known focus, communities along the upper Micay River and its tributaries were surveyed; 655 adults underwent physical examinations and skin biopsies. Infected individuals were found almost exclusively in the community of Naiciona, where prevalence of infection was 40% (36 of 91). Polymerase chain reaction detection of onchocercal DNA in skin snips correlated with the skin-snip biopsy results. The prevalence of punctate keratitis, the only ocular manifestation found, was 33%. A rapid entomologic assessment demonstrated Simulium exiguum infected with Onchocerca volvulus. This is the first finding in Colombia of naturally infected black flies and confirms S. exiguum as a vector species. These data will be used for implementing a control program using periodic ivermectin distribution.

Adolescent↗

PubMed1995

Effect of repeated treatments with ivermectin on the incidence of onchocerciasis in northern Cameroon.

Mass treatments with ivermectin have been undertaken each year since 1987 in an area hyperendemic for onchocerciasis in northern Cameroon. The impact of these successive treatments on the incidence of infection in humans was evaluated by comparing the prevalence of skin microfilariae (PMF) and the mean microfilarial skin densities (MFD) observed in 1987 and 1992 in 5-7-year-old children who had never taken the drug but who were members of the treated communities. In 1992, the PMF and the MFD in children in this age group who never received ivermectin were reduced by 55% and 77%, respectively, in comparison with the values observed in 1987, before the first treatment round. These results reflect a pronounced reduction in the intensity of the transmission of Onchocerca volvulus in the treatment zone. The influence of the ivermectin treatment coverage in the human population, as well as the vectorial capacity and the dispersal of the vector blackflies, on the transmission of onchocerciasis is discussed.

Adolescent↗

PubMed2002

Comparison between the skin snip test and simple dot blot assay as potential rapid assessment tools for Onchocerciasis in the postcontrol era in Ghana.

Successful control of onchocerciasis through mass distribution of ivermectin needs to be coupled with reliable, sensitive, specific, yet affordable diagnostic methods to monitor and ensure the efficacy of such measures. The effort put into the development of diagnostic methods for onchocerciasis that can substitute for or work in combination with the present "gold standard," the skin snip test, has resulted in the discovery of a number of immunogenic proteins with potential use as diagnostic tools in the postcontrol era. Most of these proteins have now been produced through recombinant DNA techniques. However, when costs are not a trivial issue, none of them have yet found their way into the areas where the disease still exists. In the present study, we have evaluated the performance of a simple dot blot assay which uses a mixture of native proteins designated PakF as a serious contender in the quest for a less invasive and more sensitive method to detect Onchocerca volvulus infection in areas with diverse endemicities. Our results indicate that the assay we propose is more sensitive than the skin snip test and shows high specificity, both characteristics required for a suitable tool for the monitoring of onchocerciasis in the postcontrol era.

Animals↗

PubMed1992

Identification of circulating parasite acetylcholinesterase in human and rodent filariasis.

In the present study, the enzyme acetylcholinesterase (AChE) from filarial parasites was identified in sera from humans infected with Onchocerca volvulus as well as in Mastomys natalensis infected with Brugia pahangi. The enzyme was present in immune complexes precipitated with cold 4% polyethylene glycol. The infected sera showed 3-4 times more AChE activity than did normal sera, and enzyme activity could be demonstrated in 5% polyacrylamide gels by specific staining. The enzyme from infected serum showed 3 times more activity when acetylthiocholine was used as the substrate as compared with butyrylthiocholine, whereas the enzyme activity present in normal serum was low and did not show this substrate specificity. Immunoprecipitation assays confirmed the presence of anti-AChE antibodies in the infected serum. The enzyme was further analysed by enzyme-linked immunosorbent assay and immunoblotting with rabbit antibodies to B. malayi AChE. Immunoblotting of the B. pahangi-infected serum revealed two closely located bands at about 200 kDa and one 95-kDa band, whereas in O. volvulus-infected serum, only one specific band was observed at about 200 kDa. The identification of parasite AChE may be particularly useful for diagnosis of the disease or for the study of the involvement of this enzyme in the host-parasite relationship.

Acetylcholinesterase↗

PubMed1993

A sensitive serodiagnostic test for onchocerciasis using a cocktail of recombinant antigens.

A specific serodiagnostic test for onchocerciasis has been a priority objective of the World Health Organization. Fragments of cDNA encoding Onchocerca volvulus antigens selected on the basis of their specificity for this parasite were subcloned into a protein purification and expression system. No individual recombinant antigen showed a high sensitivity in an enzyme-linked immunosorbent assay because of heterogeneity in the response of O. volvulus-infected individuals. However, a cocktail of three recombinant proteins showed 96% sensitivity with 100% specificity, compared with 99% sensitivity and only 59% specificity against a crude O. volvulus extract. The sensitivity of detection of individual antigens varied between sera taken from individuals from different geographic areas infected with O. volvulus, but when used as a cocktail, all but one of the microfilaria-positive individuals from all the geographic areas studied were detected. Recombinant probes provide a practical basis for specific diagnostic tests for helminth infections.

Africa↗

PubMed1997

[Apropos of 5 new cases of onchocerciasis edema].

We report 5 cases of onchocerciasis presenting as limb's swelling collected in the tropical disease unit of a parisian hospital between 1982 and 1993. They are 5 men which have lived between 3 weeks and 4 years in forested areas of Cameroon in four cases and Côte d'Ivoire in one case. The incubation period varied from 5 months to 2 years. The limb oedema was always located to one arm. It was associated with a blood eosinophilia above 2000/mm3 in 4 of 5 patients. The skin detection of microfilaria of Onchocerca volvulus was positive in every case. The serodiagnostic tests were negative for indirect immunoflurescent assay and immunoelectrophoresis with exception of one patient. These patients were cured with ivermectine and/or diethylcarbamazine. In addition, 26 other cases described in the literature are discussed.

Animals↗