Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Onchocerca volvulus”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 955 records · Page 53Linked to original sources
PubMed1995

Human autoantibody to defensin: disease association with hyperreactive onchocerciasis (sowda).

Chronic hyperreactive onchodermatitis (sowda) is a severe form of onchocerciasis observed in a subset of individuals infected with the filarial nematode Onchocerca volvulus. SDS-PAGE and immunoblot analyses of O. volvulus adult worm extracts were used to characterize the antigens of the marked antibody response of sowda patients. One 2.5-kD antigen was recognized by sera from all 35(100%) sowda patients that were studied. In comparison, only 7 of 44 (16%) patients with generalized onchocerciasis and 11 of 21 (52%) of exposed individuals with no microfilariae in skin snips and no signs of disease showed reactivity to this antigen. Microfilaricidal treatment of sowda patients with improvement of the clinical status was associated with a decrease or disappearance of antibodies to the 2.5-kD antigen. Amino acid sequencing of the antigen indicated identity to human defensins 1-3 of neutrophils. Defensin was demonstrated by immunohistochemical staining in onchocercal nodules on the surface of adult filariae and in the surrounding tissue. A similar staining pattern was observed for other proteins present in neutrophils such as myeloperoxidase, elastase, and the L-1 protein complex (MRP 8/MRP 14), indicating that neutrophils, macrophages, and their proteins predominate in the environment adjacent to the worms. These results demonstrate an association between the presence of autoantibodies to defensins and an infectious disease of known etiology. The association with a particular form of onchocerciasis, sowda, suggests a link between formation of autoantibodies to defensin and enhanced immune reactivity towards the parasite.

Adolescent↗
PubMed2005

Status of forest onchocerciasis in the Lower Cross River basin, Nigeria: entomologic profile after five years of ivermectin intervention.

In the Lower Cross River basin in Nigeria, no pre-control entomologic profile of Onchocerca volvulus infection in the local Simulium damnosum population was available prior to the initiation of an ivermectin control program in 1995. A longitudinal entomologic study was therefore carried out over a 12-month period (January-December 2001) at the Agbokim waterfalls and Afi River, which are breeding sites of S. damnosum in the river basin. A total of 9,287 adult S. damnosum were caught on human bait; 9,048 (97.43%) were dissected, of which 313 (3.46%) were infected. Annual biting rates (ABRs) of 42,419 and 28,346 bites per persons per year were recorded at the Agbokim Waterfalls and Afi River, respectively. The annual transmission potential (ATP) was 419 infective larvae per person per year at the Agbokim Waterfalls and 427 at the Afi River. Monthly biting rate and monthly transmission potential varied significantly (P < 0.05) at the two sites. Transmission was highly seasonal from April to September, corresponding to the peak biting period of the vector. The high ATP and ABR values are a measure of the mesoendemicity of onchocerciasis in the river basin. There was a significant F(0).05 (1, 10) (P < 0.05) variation in the relative fly abundance from both sites. It was observed that human activities such as farming, fishing, timber cutting, and hunting are done in the early morning and late afternoon, which corresponds to the peak diurnal biting period of the vector. Changes in these practices and attitudes may markedly affect the disease intensity and transmission.

Animals↗
PubMed1996

In vivo molecular analysis of cytokines in a murine model of ocular onchocerciasis. I. Up-regulation of IL-4 and IL-5 mRNAs and not IL-2 and IFN gamma mRNAs in the cornea due to experimental interstitial keratitis.

Sclerosing keratitis is the major cause of blindness due to onchocerciasis which results from chronic infection with the filarial parasite Onchocerca volvulus. Using a murine model of onchocercal sclerosing keratitis, we have demonstrated previously that predominantly (> 85%) CD3 + /CD4+ T-cells as well as the IL-2 receptor bearing cells infiltrate into the cornea in vivo during development and progress of the disease. The identification of CD4+ subsets TH1 and TH2 based on the cytokine secretion patterns of murine T-lymphocytes has been useful for understanding the immune basis of resistance and pathogenesis in murine models of several parasitic diseases. The present investigation was carried out to demonstrate whether the local immune response at the corneal lesion due to onchocercal interstitial keratitis correlated with such distinct patterns of cytokine production. For that purpose, mRNA was extracted separately from corneas obtained from the diseased eyes and the normal eyes of A/J mice with onchocercal interstitial keratitis, reverse transcribed and amplified by the polymerase chain reaction with four different cytokine specific primers. In corneas obtained from the eyes affected with onchocercal interstitial keratitis, mRNAs coding for IL-4 and IL-5 were up-regulated compared to the normal eyes having no lesions from the same animals. However, the levels of mRNAs for IL-2 and IFN gamma were found to be the same in the diseased and normal eyes. Taken together, these data suggest that IL-4 and IL-5 producing TH2-lymphocytes are active at the corneal lesion due to onchocercal interstitial keratitis.

Animals↗
PubMed2003

Onchocerciasis among Ethiopian immigrants in Israel.

BACKGROUND: Onchocerciasis results from infestation by the nematode Onchocerca volvulus, and is characterized clinically by troublesome itching, skin lesions and eye manifestations. Since 1992, approximately 9,000 immigrants have arrived in Israel from the Kuwara province of northwest Ethiopia where the prevalence of onchocerciasis is particularly high. OBJECTIVES: To determine whether onchocerciasis is the cause of cutaneous and ocular symptoms among recent immigrants from the Kuwara province in Ethiopia. METHODS: We examined 1,200 recent immigrants from the Kuwara province residing at the Mevasseret Zion immigration center outside Jerusalem. Among them, patients with cutaneous signs suggestive of onchocerciasis underwent a skin-snip biopsy and a thorough eye examination. RESULTS: In the detailed skin examination performed in 83 patients, the most common skin finding was chronic papular onchodermatitis, found in more than 46 patients (55%); depigmentation and atrophy was found in 13 (15%) and 12 (14%), respectively. In 40 patients (48%), living microfilaria were detected in their skin snips. Of the 65 patients who underwent a through eye examination, 45 patients (66%) had ocular complaints. Corneal abnormalities were found in 55 of the 130 eyes (42%), active anterior segment intraocular inflammation and live microfilariae were found in 4 eyes (3%) and lens changes in 16 eyes (1%). Eleven eyes (9%) showed retinal or choroidal changes. CONCLUSIONS: Skin and eye manifestations associated with onchocerciasis are prevalent among symptomatic Ethiopians who immigrated to Israel from the Kuwara province.

Adolescent↗
PubMed1996

Dirofilaria immitis: ultrastructural localization, molecular characterization, and analysis of the expression of p27, a small heat shock protein homolog of nematodes.

A cDNA fragment encoding the complete coding region of a 27-kDa protein (p27) of Dirofilaria immitis was cloned. Antibody to the recombinant p27 bound to hypodermal tissues of third (L3) and fourth stage larvae (L4) of D. immitis and to both the hypodermis and the cuticle of L3s of Onchocerca volvulus, as visualized by immunoelectronmicroscopy. The deduced amino acid sequence of the central and C-terminal regions of p27 (amino acids S83 to H222) is 18-36% identical to members of the sHsp/alpha-crystallin family of proteins. The homologous region is thought to be responsible for the molecular chaperone activity of members of this family. The p27 cDNA does not encode a hydrophobic signal peptide. At least two homologous yet distinct p27 genes were identified in the D. immitis genome by Southern hybridization using the p27 cDNA as a probe. The p27 transcript was 0.9 kb in length on Northern blots. The expression of p27 in L3s of D. immitis was neither upregulated by heat shock (43 degrees C) nor by incubation at the physiologic temperature of 37 degrees C. Pulse-labeling experiments of both D. immitis and Brugia malayi L3s during the L3-L4 molt in vitro showed that synthesis of p27 is also not upregulated during this developmental phase. However, p27 is expressed constitutively throughout the D. immitis L3-L4 molt and therefore by both larval stages. In addition, both female and male adult worms of this species express p27 constitutively. P27, or an allomorph thereof, was detected in each of nine species representing four nematode superfamilies, thus indicating that this molecule is ubiquitous within the phylum Nematoda. In view of the hypodermal localization of p27, its constitutive expression, and its retention among nematodes, the function of this protein in essential housekeeping roles such as that of molecular chaperone during the molting process is discussed.

Amino Acid Sequence↗
PubMed1993

Regulation of IL-5 in onchocerciasis. A critical role for IL-2.

The cytokine profiles of PBMC obtained from individuals "immune" to Onchocerca volvulus infection were compared to those from infected individuals. The immune individuals had significantly higher levels of both IL-2 and IL-5 in response to parasite Ag than did those individuals with active infection (mean IL-2 = 1.3 and 0.138 U/ml, respectively; mean IL-5 = 973 and 147.4 pg/ml, respectively), and there was a direct correlation between the production of IL-2 and IL-5. To examine the mechanism underlying the possible association between these two cytokines in patients infected with onchocerciasis, reverse transcription followed by polymerase chain reaction was used to measure IL-5 mRNA. In response to rIL-2, IL-5 mRNA appeared as early as early as 3 h after stimulation of patient PBMC, reaching a peak at 24 h; further, this response was inhibited with neutralizing antibodies to IL-2. IL-2 was unable to induce mRNA expression for IL-4, IFN-gamma, IL-10, or granulocyte-macrophage-CSF. To assess whether IL-2 was specifically responsible for the up-regulation of Ag-induced IL-5 production in patients with onchocerciasis, IL-5 mRNA expression was measured in PBMC stimulated with parasite Ag. Up-regulation of IL-5 mRNA was seen in all patients (peaking at 72 h) in response to Ag stimulation and was found to be independent of proliferation to Ag; in addition, this up-regulation was specifically inhibited by neutralizing anti-IL-2 antibodies. Further, the primary source of IL-5 mRNA was determined to be CD4+ T cells. These findings suggest that IL-2 production is required to induce IL-5 and further implicates IL-5 as a possible mediator of protection in onchocerciasis.

Animals↗
PubMed1999

Population biology of human onchocerciasis.

Human onchocerciasis (river blindness) is the filarial infection caused by Onchocerca volvulus and transmitted among people through the bites of the Simulium vector. Some 86 million people around the world are at risk of acquiring the nematode, with 18 million people infected and 600,000 visually impaired, half of them partially or totally blind. 99% of cases occur in tropical Africa; scattered foci exist in Latin America. Until recently control programmes, in operation since 1975, have consisted of antivectorial measures. With the introduction of ivermectin in 1988, safe and effective chemotherapy is now available. With the original Onchocerciasis Control Programme of West Africa coming to an end, both the new African Programme for Onchocerciasis Control and the Onchocerciasis Elimination Programme for the Americas, rely heavily on ivermectin self-sustained mass delivery. In consequence, the need for understanding the processes regulating parasite abundance in human and simuliid populations is of utmost importance. We present a simple mathematical framework built around recent analyses of exposure- and density-dependent processes operating, respectively, within the human and vector hosts. An expression for the basic reproductive ratio, R0, is derived and related to the minimum vector density required for parasite persistence in localities of West Africa in general and northern Cameroon in particular. Model outputs suggest that constraints acting against parasite establishment in both humans and vectors are necessary to reproduce field observations, but those in humans may not fully protect against reinfection. Analyses of host age-profiles of infection prevalence, intensity, and aggregation for increasing levels of endemicity and intensity of transmission in the Vina valley of northern Cameroon are in agreement with these results and discussed in light of novel work on onchocerciasis immunology.

Adolescent↗
PubMed2004

An investigation of persistent microfilaridermias despite multiple treatments with ivermectin, in two onchocerciasis-endemic foci in Ghana.

If ivermectin-based programmes for the control of human onchocerciasis are to be successful, the drug must remain effective for as long as necessary. In an open, case-control study, an attempt was made to determine if the persistent, significant, Onchocerca volvulus microfilaridermias seen in some individuals who had received at least nine treatments with ivermectin were the result of the development of drug resistance in the parasite. Twenty-one of these 'sub-optimal' responders (cases) were matched, by age, weight, number of treatments, locality and skin microfilarial counts, with seven amicrofilaridermic responders and 14 ivermectin-naive subjects. The number of treatments taken, any potential drug interactions and significant underlying disease were determined from detailed clinical and laboratory studies. Each subject was treated with ivermectin during the study, so that plasma concentrations of the drug could be determined for 72 h from the time of dosage. The microfilarial and adult-worm responses to this treatment were assessed from skin microfilarial counts (obtained before the treatment and at days 8, 90 and 365 post-treatment), day-90 embryogrammes, and the results of fly-feeding experiments. Parasite-sensitivity criteria for various time-points were derived from earlier data on skin microfilaridermias and the effects of ivermectin on the adult worms. The results indicate that the significant microfilaridermias that persist despite multiple treatments with ivermectin are mainly attributable to the non-response of the adult female worms and not to inadequate drug exposure or other factors. The possibility that some adult female worms have developed resistance to ivermectin cannot be excluded. These results justify the routine monitoring of treatment efficacy in any ivermectin-based programme of disease control.

Adolescent↗
PubMed2000

Antigen-specific cellular hyporesponsiveness in a chronic human helminth infection is mediated by T(h)3/T(r)1-type cytokines IL-10 and transforming growth factor-beta but not by a T(h)1 to T(h)2 shift.

Exposure to infective larvae of the filarial nematode Onchocerca volvulus (Ov) either results in patent infection (microfilaridermia) or it leads to a status called putative immunity, characterized by resistance to infection. Similar to other chronic helminth infections, there is a T cell proliferative hyporesponsiveness to Ov antigen (OvAg) by peripheral blood mononuclear cells (PBMC) from individuals with patent infection, i.e. generalized onchocerciasis (GEO), compared to PBMC from putatively immune (PI) individuals. In this study, mechanisms mediating this cellular hyporesponsiveness in GEO were investigated: the low proliferative response in PBMC from GEO individuals was associated with a lack of IL-4 production and significantly lower production of IL-5 compared to those from PI individuals, arguing against a general shift towards a T(h)2 response being the cause of hyporesponsiveness. In contrast, IL-10 and transforming growth factor (TGF)-beta, two cytokines associated with a T(h)3 response, seemed to mediate hyporesponsiveness: PBMC from individuals with GEO produced significantly more IL-10, and T cell proliferative hyporesponsiveness in this group could be reversed by the addition of anti-IL-10 and anti-TGF-beta antibodies. Hyporesponsiveness was specific for OvAg and not observed upon stimulation with related nematode antigens, arguing for a T cell-mediated, Ov-specific down-regulation. Ov-specific T cells could be cloned from GEO PBMC which have a unique cytokine profile (no IL-2 but high IL-10 and/or TGF-beta production), similar to the T cell subsets known to suppress ongoing inflammation (T(h)3 and T(r)1), indicating that this cell type which has not been found so far in infectious diseases may be involved in maintaining Ov-specific hyporesponsiveness.

Animals↗
PubMedDate not supplied

Onchocerciasis in the Amazonian focus of southern Venezuela: altitude and blackfly species composition as predictors of endemicity to select communities for ivermectin control programmes.

In preparation for an ivermectin distribution programme, the prevalence and intensity of infection due to Onchocerca volvulus as well as the species composition and abundance of Simulium vectors were investigated in 22 Yanomami communities situated along 2 altitudinal transects in the southern Venezuelan onchocerciasis focus. These transects corresponded to the Ocamo-Putaco and Orinoco-Orinoquito river systems, covering a range of elevation between 50 m and 740 m above sea level (asl). A total of 831 people underwent parasitological examination in this survey and an additional 196 patients from a previous study, at an altitude of 950 m, were included in the analysis. A total of 92,659 man-biting blackflies were collected and identified to morphospecies. S. oyapockense s.l. was the predominant simuliid up to 150 m asl, whereas S. guianense s.l. and S. incrustatum s.l. prevailed above 150 m. Communities located below 150 m were found to range from hypo- to mesoendemic; all villages above 150 m proved to be hyperendemic (> 60% microfilarial prevalence) and mass ivermectin treatment should be implemented. Age above 10-14 years, altitude of the village and biting rate of S. guianense s.l. up to 200 m asl were found to be statistically significant independent predictors of infection by multivariate logistic regression using a spline model. There were no differences in infection status according to sex. Above 200 m, microfilarial rate and density remained approximately constant, prevalence averaging 79% regardless of blackfly abundance. For the implementation of ivermectin-based onchocerciasis control programmes in the Amazonian focus, altitude and species composition of the blackfly population might be adopted as useful indicators aiding selection of the most affected communities. However, below 200 m additional parasitological indicators may also be necessary. As a direct result of this study, regular mass-ivermectin delivery to meso- and hyperendemic communities is now in progress.

Adolescent↗
PubMed2000

Amazonian onchocerciasis: parasitological profiles by host-age, sex, and endemicity in southern Venezuela.

This paper describes, for the human onchocerciasis focus of southern Venezuela, the age profiles of Onchocerca volvulus microfilarial (mf) and nodule prevalence, mf intensity, and mf aggregation for the whole examined population (836 Yanomami people) living in 20 villages, and for these communities classified according to endemicity levels (hypoendemic: < or = 20 %; mesoendemic: 21-59 %; hyperendemic: < or = 60 % infected). Mf prevalence and intensity increased with age, particularly in the hyperendemic areas, and there were no marked differences between the sexes. The prevalence of nodules followed the same age pattern. Fifty percent mf prevalence was reached in the 15-19 year age-class when the population was taken as a whole; nearly in the 10 to 14-year-olds for the hyperendemic level, in those aged 20-29 years in mesoendemic areas, and not reached at all in hypoendemic villages. The degree of mf aggregation was measured by the k value of the negative binomial distribution and by the variance to mean ratio (VMR). The relationship between the standard deviation (S.D.) of mf counts and the mean mf density was also explored. These 3 indices (k, VMR, and S.D.) showed a tendency to increase with both mean mf load and host age. Since infection intensity and host age were themselves positively related, it was not possible to draw definite conclusions about age-specific changes of parasite aggregation. There was not a significant decrease of mf intensity after an earlier peak neither was there a shift towards younger ages of the maximum no. of mf/mg reached as the endemicity level increased. These results are discussed in relation to detection of density dependence in the human host, selection of an indicator age-group for rapid epidemiological assessment (REA) methods, and strategies of ivermectin distribution in the Amazonian focus. It is recommended that, for the Amazonian onchocerciasis focus, the indicator group for REA consists of all those aged 15 years and over.

Adolescent↗
PubMed1994

Density-dependent processes in the transmission of human onchocerciasis: intensity of microfilariae in the skin and their uptake by the simuliid host.

The transmission success of Onchocerca volvulus is thought to be influenced by a variety of regulatory or density-dependent processes that act at various points in the two-host life-cycle. This paper examines one component of the life-cycle, namely, the ingestion of microfilariae by the simuliid vector, to assess the relationship between intake of larvae and the density of parasites in the skin of the human host. Analysis is based on data from three areas in which onchocerciasis is endemic and includes published information as well as new data collected in field studies. The three areas are: Guatemala (Simulium ochraceum s.l.), West and Central Africa (savanna members of the S. damnosum complex), and South Venezuela (S. guianense). The data record experimental studies of parasite uptake by flies captured in the field and fed to repletion on locally infected subjects who harboured varying intensities of dermal microfilarial infection. Regression analyses of log transformed counts of parasite burdens ingested by the flies plotted against log transformed counts of microfilariae per mg of skin revealed little evidence for saturation in parasite uptake by the flies as the intensity in the human host increased. There was a positive and highly significant rank correlation between both variables for the three blackfly species. In an alternative analysis a model was fitted to data on prevalence of flies with ingested microfilariae (mff) versus dermal mean intensities. The model assumed an overdispersed distribution of the number of mff/fly and a given functional relationship between intake and skin load. The results of both approaches were consistent. It is concluded that parasite ingestion by the vector host is not strongly density dependent in the three geographical areas and ranges of dermal loads examined. It therefore appears that this transmission process is of reduced importance as a regulatory mechanism in the dynamics of parasite population growth.

Africa, Central↗
PubMed1996

Density-dependent processes in the transmission of human onchocerciasis: relationship between microfilarial intake and mortality of the simuliid vector.

In order to construct an analytical model of onchocerciasis transmission, it is necessary to elucidate the functional relationships of the various population rate processes taking place within the human and vector hosts. Two previous papers have explored the evidence for density-dependent regulation in relation to microfilarial intake by, and larval development within, the Simulium host. This paper investigates the survivorship of wild-caught blackfly samples fed on subjects with different intensities of Onchocerca volvulus microfilarial infection. Analyses were based on data for Guatemalan S. ochraceum s.l. (possessing a well-developed cibarial armature), West African S. damnosum s.l. (forest species), and South Venezuelan S. guianense (the latter two lacking a toothed cibarium). The mean survival times of samples of the 3 species, kept under laboratory conditions, decreased as parasite intake increased, the rate of mortality being dependent on the fly's age (measured as time post-feeding) and on the worm load acquired. An empirical, time-dependent hazard function was fitted to observed death rates/fly/day which rose very shortly after engorgement, declined subsequently, and rose again throughout the extrinsic incubation period of the parasite. The parameters of this hazard model were all positively correlated with the density of microfilariae in the bloodmeal. Expressions of survivorship and life-expectancy as explicit functions of time post-feeding and mean parasite intake were derived. The average expectation of life at engorgement for uninfected flies in the laboratory was estimated to be around 1 week for both, armed and unarmed blackflies. Residual life-expectancy decreased with time post-feeding and microfilarial load in both categories of vectors. This decline (resulting from age- and parasite-dependent mortality rates) was much more pronounced in those species lacking a toothed fore-gut. Whilst a fraction of heavily infected S. ochraceum was able to survive the latent period of the parasite, being therefore potentially capable of transmitting the infection, equivalent worm loads in S. guianense resulted in a drastic reduction of the expectation of infective life. These results provide additional evidence to support the hypothesis that, in the case of intrinsically susceptible vectors, unarmed simuliids are more efficient at low microfilarial loads, when the transmission rate from human to vector host is higher, and parasite-induced fly mortality is negligible. The opposite takes place in armed flies, which perform poorly at low parasite burdens and better at heavier loads, with little parasite-induced vector death.

Animals↗
PubMedDate not supplied

[The use of ivermectin in the control of onchocerciasis].

Onchocerciasis is an infection with the nematode Onchocerca volvulus. The main clinical symptoms are caused by the microfilariae. They include ocular lesions leading to blindness. Onchocerciasis is widely distributed in Africa from the Sahara to the southern tip, and is also found in some areas of South and Central America. Ivermectin was shown to be an effective treatment in the early 1980's, and is safe and better tolerated than diethylcarbamazine. We report the results of ivermectin treatment of onchocerciasis, and various features of the control obtained by large-scale ivermectin treatment programs. In large-scale programs, ivermectin (150 micrograms/kg) is administered once a year. This dose paralyses the microfilariae, such that they are carried away by the lymph to the lymph nodes where they are destroyed. This dose thereby reduces the load of microfilaria by 90%. The effects of a dose of ivermectin last about two or three years, and the lesions in the anterior segment of the eye can be cured or substantially reduced. Regular treatment prevents severe lesions of the posterior segment of the eye. The effects of repeated treatment on lesions of the retina are currently under investigation. Frequent doses of ivermectin prevent the development of embryo parasites in the females, and reduces the number of adults by attrition. Large-scale treatment programs reduce the transmission of the parasite by its vectors. There are several problems impeding large-scale treatment programs. Choosing patients for priority treatment requires expensive and sometimes aggressive methods of diagnosis. Thus new techniques for the identification of communities in which onchocerciasis is a serious public health problem are required. The choice of strategies for distribution, to optimize the cost, benefit ratio and feasibility, remain controversial. Wide distribution by mobile teams is effective, but expensive. Active distribution by trained community distributors is a cheaper potential alternative. Clinic-based or passive distribution requires the population to present to be able to obtain ivermectin. Thus, although cheap, this approach is generally poorly effective. A further complication is the clearly defined criteria on which these methods should be evaluated.

Africa↗
PubMed1997

Serious reactions after mass treatment of onchocerciasis with ivermectin in an area endemic for Loa loa infection.

BACKGROUND: In 1995, the World Bank launched an African Programme for Onchocerciasis Control to eliminate Onchocerca volvulus disease from 19 African countries by means of community-based ivermectin treatment (CBIT). Several cases of encephalopathy have been reported after ivermectin in people heavily infected with microfilariae of Loa loa (loiasis). We assessed the incidence of serious events in an area where onchocerciasis and loiasis are both endemic. METHODS: Ivermectin (at 150 micrograms/kg) was given to 17877 people living in the Lékié area of Cameroon. 50 microL samples of capillary blood were taken during the daytime before treatment from all adults (aged > or = 15 years), and the numbers of L loa and Mansonella perstans microfilariae in them were counted. Patients were monitored for 7 days after treatment. Adverse reactions were classified as mild, marked, or serious. Serious reactions were defined as those associated with a functional impairment that required at least a week of full-time assistance to undertake normal activities. We calculated the relative risk of developing marked or serious reactions for increasing L loa microfilarial loads. Risk factors for serious reactions were identified and assessed with a logistic regression model. FINDINGS: 20 patients (0-11%) developed serious reactions without neurological signs but associated with a functional impairment lasting more than a week. Two other patients were in coma for 2-3 days, associated with L loa microfilariae in cerebrospinal fluid. Occurrence of serious reactions was related to the intensity of pretreatment L loa microfilaraemia. The relative risk of developing marked or serious reactions was significantly higher when the L loa load exceeded 8000 microfilariae/mL; for serious reactions, the risk is very high (odds ratio > 1000) for loads above 50000 microfilariae/mL. INTERPRETATION: Epidemiological surveys aimed at assessing the intensity of infection with L loa microfilariae should be done before ivermectin is distributed for onchocerciasis control in areas where loiasis is endemic. In communities at risk, monitoring procedures should be established and adhered to during CBIT so that people developing serious reactions may receive appropriate treatment.

Adolescent↗
PubMed1996

Human onchocerciasis in Nigeria: isotypic responses and antigen recognition in individuals with defined cutaneous pathology.

Antigen (Ag)-specific isotype responses to Onchocerca volvulus Ag (OvAg) were assessed by enzyme-linked immunosorbent assay and immunoblot in 123 residents of a mesoendemic area in northern Nigeria and 16 Nigerians from a nonendemic area. Individuals from an endemic area were divided into six groups on the basis of cutaneous onchocercal pathology: acute papular onchodermatitis (APOD), chronic papular onchodermatitis (CPOD), lichenified onchodermatitis (LOD), atrophy (ATR), depigmentation (DPM) and normal skin, high microfilarial load (NSHMF). Immunoglobulin (Ig)G1-4 levels were all significantly associated with residence in an endemic area after controlling for age and sex (all P values = 0.0001). Both IgG1 and IgG3 were significantly associated with onchocercal clinical category after controlling for age, sex, and microfilarial load (P = 0.0031 and 0.0035, respectively). The IgG1 and IgG3 responses were both highest in LOD and lowest in NSHMF and ATR, respectively. A significant inverse association was found between IgG1 levels and microfilarial load after controlling for age, sex, and clinical category (P = 0.0061). On immunoblotting, 20 (44.4%) of 45 individual onchocerciasis sera contained IgG4 antibodies against a band of 29-31 kD, which was not recognized by pooled sera from individuals with other filarial infections. There was heterogeneity of antigen recognition within each of the onchocercal clinical groups, which together with the small numbers examined by immunoblotting, limits interpretation. Nevertheless, some differences in patterns of antigen recognition were found between the onchocercal groups. The LOD group demonstrated prominent immunoreactivity in IgG1 and IgG3 while a general paucity of low molecular weight reactivity was seen with NSHMF in IgG1-3 subclasses, but there was no specific banding pattern that differentiated NSHMF from those with pathology. Comparison of microfilariae-positive (mf+) and mf- individuals with onchocercal skin disease revealed significantly higher levels of all IgG subclasses and higher overall scores on semiquantitative assessment of immunoblots for IgG1, IgG2, and IgG4 for mf+ individuals. Differing isotypic responses may play a role in the pathogenesis of the clinical spectrum of cutaneous onchocerciasis.

Adolescent↗
PubMed2001

Neutrophil accumulation around Onchocerca worms and chemotaxis of neutrophils are dependent on Wolbachia endobacteria.

Unlike in many other helminth infections, neutrophilic granulocytes are major cellular components in the hosts immune response against filarial worms. The pathways that drive the immune response involving neutrophils are unclear. This study shows that Wolbachia endobacteria (detectable by polyclonal antibodies against endobacterial heat shock protein 60 and catalase and by polymerase chain reaction being sensitive to doxycycline treatment) are direct and indirect sources of signals accounting for neutrophil accumulation around adult Onchocerca volvulus filariae. Worm nodules from untreated onchocerciasis patients displayed a strong neutrophil infiltrate adjacent to the live adult worms. In contrast, in patients treated with doxycycline to eliminate the endobacteria from O. volvulus and to render the worms sterile, the neutrophil accumulation around live adult filariae was drastically reduced. Neutrophils were absent in worm nodules from the deer filaria Onchocerca flexuosa, a species which does not contain endobacteria. Extracts of O. volvulus extirpated from untreated patients showed neutrophil chemotactic activity and in addition, induced strong TNF-alpha and IL-8 production in human monocytes, in contrast to filarial extracts obtained after doxycycline treatment. Thus, neutrophil chemotaxis and activation are induced directly by endobacterial products and also indirectly via chemokine induction by monocytes. These results show that the neutrophil response is a characteristic of endobacteria-containing filariae.

Adult↗
PubMed1989

The further application of MTT-formazan colorimetry to studies on filarial worm viability.

Experiments have confirmed that MTT-formazan colorimetry in its simplest form (incubation of intact worms with MTT and direct visualisation of any formazan formed) can be readily applied to several species of filariae including Onchocerca volvulus. Data is presented which will assist the development of quantitative MTT reduction viability tests for a selection of the smaller filarial species. Assays of pieces of Onchocerca gutturosa and O. volvulus females have led us to tentatively conclude that the tips of filariae, particularly the anterior ends, may well be metabolically the most active part of the worm. Selective sampling of these regions for Onchocerca might therefore be a useful indicator for the viability of the parasite. An example of how MTT-formazan colorimetry has been applied to yield additional data to support motility observations on the in vitro survival of male O. gutturosa is also given. The in vitro timecourse of worm death caused by 10 microM CGP 20376 on Acanthocheilonema viteae females has been examined by MTT reduction and compared with 6 other non-subjective parameters. The results suggests that the parameters examined could be divided into two groups according to the time taken for CGP 20376 to cause 50% inhibition (t50) of the parameter. Fast response parameters had t50's between 1 and 6 h (motility indices, 14CO2 evolution, adenine uptake and leucine uptake), they are more sensitive measures of viability and indicate possible worm damage which may or may not be reversible. Slow response parameters had t50's between 34 and 48.5 h (lactate output, MTT reduction and adenine leakage), and are probably linked with severe degenerative changes and are indicative of worm death.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗