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At least 469 records · Page 26Linked to original sources
PubMed2000

The role of nitric oxide in the innate resistance to microfilariae of Litomosoides sigmodontis in mice.

Nitric oxide (NO) has been shown to be an important effector mechanism in the defence against various pathogens, including filariae. The production of NO, as well as H2O2, is induced by the Th1 cytokine IFN-gamma. Therefore, the microfilariae (mf) of filarial nematodes, which are known to elicit the release of IFN-gamma, may be a target of NO release. In this study, we found that mf of the filarial species Litomosoides sigmodontis were resistant to the attack of H2O2, but vulnerable to NO exposure in vitro by a chemical NO donor, as well as activated macrophages. Adult worms were considerably less affected by exposure to NO. In-vivo production of NO following injection of mf, in this and previous studies, suggested a central role in the defence to filariae. However, neither pharmaceutical inhibition of nitric oxide synthesis, nor genetic knockout of the gene for inducible nitric oxide synthase (iNOS), abrogated resistance to circulating mf in mice. Interestingly, however, iNOS-KO mice showed higher interleukin (IL)-2 responses and lower IL-10 production, compared to their wild-type counterparts. In conclusion, despite its effectiveness in vitro and the observed production of NO by ex vivo cells following infection, nitric oxide seems not to be an important factor in elimination of mf of L. sigmodontis in vivo. However, it may have a regulatory role in the immune response.

Animals↗
PubMed2002

Interferon-gamma and nitric oxide production are not required for the immune-mediated clearance of Brugia malayi microfilariae in mice.

Previous research has shown that Brugia malayi microfilariae (Mf) primarily induce type 1 cytokine production, and that in-vitro nitric oxide (NO) can mediate Mf killing. This study addresses the role of interferon (IFN)-gamma-mediated immune responses in the clearance of Mf from fast-clearing (CBA/Ca) and slow-clearing (C57Bl/6) mouse strains. Analysis of spleen cell cytokine production at early timepoints p.i. showed that Mf-induced IFN-gamma and nitrite (NO-) levels were significantly greater in CBA/Ca mice than C57Bl/6 mice. However, in-vivo neutralization of IFN-gamma or inhibition of NO- production in CBA/Ca mice did not alter Mf survival kinetics. Similarly, the rate of Mf clearance in both C57Bl/6 mice lacking the IFN-gamma gene and (C57Bl/6 x 129) mice deficient in the receptor for IFN-gamma was similar to that of wild-type animals. Furthermore, the dramatic abrogation of NO- production in IFN-gammaR-/- mice suggests that Mf clearance in slow-clearing mouse strains is also independent of NO- production. Thus, in both rapid-clearing and slow-clearing mouse strains, IFN-gamma-mediated mechanisms are not a requirement for Mf clearance from the bloodstream.

Animals↗
PubMed1996

Vaccination generates serum-mediated protection against Onchocerca lienalis microfilariae in the mouse.

Mice vaccinated with an aqueous extract of Onchocerca lienalis microfilariae (mf) plus adjuvant exhibited 51% protection against challenge with live mf. Protection was ablated by prior treatment of the extract with heat or proteinase K, indicating the involvement of proteinaceous epitope(s). A 54% level of protection was conferred on naive mice by passive transfer of serum from vaccinated donors, suggesting that host resistance was principally mediated by humoral components of the immune response. In contrast, the protection induced by sensitization of mice with living mf is transferable with cells, but not serum. Western blot data reveal different antigen recognition profiles for serum antibodies from these two groups of mice. These results indicate that vaccination and infection activate distinct protective mechanisms against Onchocerca mf in the mouse.

Animals↗
PubMed2002

Treatment of Brugia timori and Wuchereria bancrofti infections in Indonesia using DEC or a combination of DEC and albendazole: adverse reactions and short-term effects on microfilariae.

Filariasis caused by Brugia timori and Wuchereria bancrofti is an important public health problem on Alor island, East Nusa Tenggara, Indonesia. To implement a control programme, adverse reactions and short-term effects on the microfilaria (mf) density were studied following a divided dose of diethylcarbamazine (DEC, 6 mg/kg body weight - 100 mg on day 1 and the rest on day 3) or a single dose of DEC (6 mg/kg body weight on day 3) and albendazole (Alb, 400 mg). In order to define the most appropriate regimen, 30 persons infected with B. timori were treated in the hospital and results were compared with those obtained from the treatment of 27 persons infected with W. bancrofti. Adverse reactions consisted of systemic reactions such as fever, headache, myalgia, itching and local reactions such as adenolymphangitis. Fever experienced by a number of patients in both treatment groups generally occurred 12-24 h after drug administration and lasted up to 2 days. Adenolymphangitis tended to occur later and was resolved within 4 days. The number of W. bancrofti patients suffering from adverse reactions was lower and the reactions were milder than those of the B. timori patients. There was no difference in adverse reactions between DEC alone and DEC-Alb treatment for either infection. The geometric mean mf count decreased on day 7 in the B. timori infected patients from 234 mf/ml in the DEC group and from 257 mf/ml in the DEC-Alb group to 7 and 8 mf/ml, respectively. The mf densities of the W. bancrofti infected patients decreased on day 7 from 214 mf/ml in the DEC group and from 559 mf/ml in the DEC-Alb group to 15 and 14 mf/ml, respectively. Our data indicate that the microfilaricidal effect of the drugs is achieved more rapidly for B. timori, which is associated with more adverse reactions than W. bancrofti. In addition, 111 B. timori infected persons were treated in the community with DEC-Alb in one selected village. The adverse reactions and the reduction of mf density was similar to the findings of the hospital-based study. In this group, there was a strong correlation of mf density with the frequency and severity of adverse reactions. The addition of Alb resulted in no additional adverse reactions compared with DEC treatment alone and can also be used for the treatment of B. timori infection. In Indonesia, where the prevalence of intestinal helminths is high, the use of a combination of DEC and Alb to control lymphatic filariasis may also have impact on the control of intestinal helminths.

Adolescent↗
PubMed2004

Comparative methodology for the detection and differentiation of circulating microfilariae of Dirofilaria immitis in the dog.

The sensitivities of the Knott's test (four 20-microl sediment aliquots), quantitative buffy coat capillary tube method (QBC tube, 111 microl of whole blood) and direct blood smear (DBS, 20 microl of whole blood) were evaluated for the detection of microfilaraemia in dogs. Undiluted whole blood samples taken from 70 Dirofilaria immitis antigen-positive dogs and 10 serially diluted microfilaraemic blood samples at concentrations of 400, 200, 100, 50, 25 and 12 microfilariae (mff) ml(-1) were examined. For filarial speciation, the buffy coat of QBC tubes was mixed with one drop of methylene blue-formalin solution and examined as a direct smear. In 52/70 microfilaraemic blood samples, the number of mff ranged from 12 to 321987 ml(-1) (median: 3199 ml(-1)). The diagnostic sensitivity of the Knott's test, QBC tube method and DBS in undiluted blood samples attained the 100%, 98% and 92.3% levels, respectively. Eighteen dogs tested amicrofilaraemic by all three methods. At concentrations of 400 mff ml(-1), a 100% sensitivity was found by all three methods, while at 200 mff ml(-1) the Knott's test, QBC tube and DBS were 100%, 100% and 90% sensitive, respectively. The relevant figures at 100 mff ml(-1) were 100%, 100% and 80%, at 50 mff ml(-1) 100%, 100% and 50%, at 25 mff ml(-1) 100%, 100% and 10% and at 12 mff ml(-1) 80%, 50% and 10%. At 50 and 25 mff ml(-1), the DBS was less sensitive compared to the other two methods, while at 12 mff ml(-1), only to the Knott's test. A significant correlation was found between the QBC tube method and Knott's test regarding mff speciation. Therefore, the QBC method may be considered a reliable alternative to the Knott's test for both the detection and speciation of mff in the dog.

Animals↗
PubMed1976

Diagnosis of Wuchereria bancrofti filariasis by immunofluorescence using microfilariae as antigen.

A new technique for the diagnosis of wuchereriasis is described. Microfilariae treated with proteolytic enzyme were used as antigen for the immunofluorescent reaction. The specificity of the reaction is demonstrated in sera from persons who have a microfilariaemia, individuals with clinical symptoms of the disease but no microfilariaemia, those who have no clinical symptoms, but harbour other parasites, and in persons living in France, where the Wuchereria bancrofti filariasis is absent.

Antigens↗
PubMed1991

The development of Onchocerca dukei and O. ochengi microfilariae to infective-stage larvae in Simulium damnosum s.l. and in members of the S. medusaeforme group, following intra-thoracic injection.

Neonate Simulium females from an endemic area of human and bovine onchocerciasis in North-Cameroon were injected in one set of experiments with microfilariae (mff) of Onchocerca dukei and in another with mff of O. ochengi. Onchocerca dukei was found to develop to infective third-stage larvae in Simulium flies: 148 third-stage larvae (28.1% of injected mff) were recovered in S. hargreavesi, seven (10.4% of injected mff) in S. vorax, and 12 (1.3%) in S. damnosum s.l. Onchocerca ochengi mff developed in S. hargreavesi at a rate of 17.3% and in S. damnosum s.l. at 16.1%, yielding a total of 77 and 32 third-stage larvae respectively. Onchocerca dukei infective larvae had a mean length of 717.3 microns and a mean maximum diameter of 17.5 microns, and were slightly shorter and conspicuously thinner than those of O. ochengi (748.3 microns x 20.4 microns). All larval stages of O. dukei typically had an attenuated anterior end. The implications of these findings for the epidemiology of human onchocerciasis are discussed.

Animals↗
PubMed2002

Onchocerca volvulus microfilariae avoid complement attack by direct binding of factor H.

The filarial parasite Onchocerca volvulus is the causative agent of river blindness. The adult worms produce microfilariae (mf), which are responsible for the disease pathogenesis; mf activate the complement system, but the activation stops before the formation of terminal complement complexes. Because of the arrest of complement activation, this study analyzed binding of the main alternative pathway regulator, factor H (fH), to the mf. The mf bound fH after incubation in nonimmune human serum or with purified radiolabeled fH. In the presence of factor I, mf-bound fH promoted the cleavage of complement 3 molecule b (C3b) to iC3b. An analysis with recombinant constructs of fH showed that the C-terminal short consensus repeats (SCRs) 8-20 of fH bound to mf, whereas the N-terminal SCRs 1-7 containing the complement-regulatory domains in SCRs 1-5 did not. Thus, mf of the nematode O. volvulus may evade human complement by binding fH and by promoting inactivation of C3b into iC3b.

Animals↗
PubMed2003

Immune responses directed against microfilariae correlate with severity of clinical onchodermatitis and treatment history.

The induction of pathological changes in Onchocerca volvulus infections is directly related to the presence of the microfilarial stage of this filarial nematode. Patients with either of the 2 major forms of the clinical disease (i.e., asymptomatic/mild [n=12] and severe [n=16] dermatopathology) were studied. The cellular immune responses (cell proliferation) of those with severe disease were stronger (stimulation index [SI], 12.3+/-1.9) than those with mild dermatopathological effects (SI, 2.9+/-0.6) or control patients (SI, 4.5+/-0.4). Cytoadherence antibody responses were greatest (grade 4) in the clinically severe group and only weak (grades < or = 1) in the mild group or the control patients. Ivermectin treatment was followed by an increase in immune responsiveness in those with initially poor responses. Thus, the degree of dermatopathological effect is related to the host's immune response against microfilariae, and ivermectin augments such responses.

Animals↗
PubMed2004

Assessing density dependence in the transmission of lymphatic filariasis: uptake and development of Wuchereria bancrofti microfilariae in the vector mosquitoes.

Understanding density dependence in the transmission of lymphatic filariasis is essential for assessing the prospects of elimination. This study seeks to quantify the relationship between microfilaria (Mf) density in human blood and the number of third stage (L3) larvae developing in the mosquito vectors Aedes polynesiensis Marks and Culex quinquefasciatus Say (Diptera: Culicidae) after blood-feeding. Two types of curves are fitted to previously published data. Fitting a linearized power curve through the data allows for correction for measurement error in human Mf counts. Ignoring measurement error leads to overestimation of the strength of density dependence; the degree of overestimation depends on the accuracy of measurement of Mf density. For use in mathematical models of transmission of lymphatic filariasis, a hyperbolic saturating function is preferable. This curve explicitly estimates the Mf uptake and development at lowest Mf densities and the average maximum number of L3 that can develop in mosquitoes. This maximum was estimated at 23 and 4 for Ae. polynesiensis and Cx. quinquefasciatus, respectively.

Aedes↗
PubMed1991

Development of Onchocerca volvulus microfilariae injected into Simulium species from Cameroon.

Microfilariae (mff) of the savanna and forest strains of Onchocerca volvulus (Leuckart) were injected intrathoracically into adult females of Simulium damnosum Theobald sensu stricto, S.sirbanum Vajime & Dunbar, S.squamosum Enderlein and S.mengense Vajime & Dunbar. Nine days post infection (pi) 27-29% of the savanna mff and 31-38% of the forest strain had developed to third-stage larvae (L3), irrespective of the fly species, size or injection dose (5, 10 or 15 mff). Savanna flies supported the development of forest O.volvulus better than forest flies, in contrast to the results after per os infections. Therefore, in these four species of the S.damnosum complex from Cameroon, the peritrophic membrane is considered to be the main factor limiting the success rate of microfilarial development following the ingestion of blood infections, while the fly's haemolymph and intracellular environment play minor roles.

Animals↗
PubMed1986

In vitro antibody-mediated macrophage activity on Breinlia macropi microfilariae. I. Adherence and cytotoxicity.

Intense adherence accompanied by cytotoxicity, which initially occurred at 4 h of interaction was observed when the microfilariae of Breinlia macropi were introduced to cultures of quokka peritoneal macrophages previously sensitized in 20% immune serum. No significant difference in the adherence or cytotoxic effects was observed among macrophages from normal, microfilaraemic and amicrofilaraemic quokkas. However, the serum component mediating these effects was found only in microfilaraemic and seropositive amicrofilaraemic quokkas. This mediator was heat-labile and its mediation of the adherence and cytotoxic effects was independent of complement. Because of its apparent dissociation from IgG and its heat lability, the possibility that the mediator resides in the previously-described reaginic antibody of the quokkas was discussed.

Adhesiveness↗
PubMed1988

Parasite-specific immune responses to Onchocerca lienalis microfilariae in normal and immunodeficient mice.

The model of Onchocerca lienalis microfilariae (mf) in CBA mice has been employed to examine the immunological mechanisms underlying the destruction of skin-dwelling mf in onchocerciasis. Comparative studies among immunologically intact (CBA/H) or deficient (CBA/N, T-cell-deprived) syngeneic animals demonstrated that levels of mf of a primary infection were reduced most rapidly in fully immunocompetent mice. Significant reductions in recoveries of a secondary infection were evident in CBA/H (80%) and CBA/N (44%) mice, but not in T-cell-deprived animals. The establishment of primary and secondary infections was apparently not influenced by complement, as judged by C3 depletion with Cobra Venom Factor. Eosinophilia was demonstrated to varying degrees in all infected animals; similar levels occurred in CBA/H and CBA/N mice which were greatly elevated after mf challenge. In contrast, the eosinophil response of T-cell-deprived mice was weak and not potentiated during secondary infection. Type I immediate hypersensitivity responses to soluble mf antigen (mf-Ag) were mounted by all groups, but significantly less strongly in T-cell-deprived mice. Type IV delayed responses were generally weak, although CBA/N mice reacted strongly in the early phase of primary infections. During the first 2 weeks of infection CBA/H and T-cell-deprived mice mounted rapid IgM responses to mf-Ag. Subsequently, levels of IgG2a, IgG2b and IgG1 increased in all mice. There was a potentiated IgG2a, IgG2b and IgG1 response in all groups following challenge, with levels of IgG1 highest in CBA/H mice. IgE responses were also detected by passive cutaneous anaphylaxis during primary and secondary infections. Peak levels of parasite-specific antibodies coincided with the timing of mf clearance.

Animals↗
PubMed1991

Eosinophil-larval-interaction in onchocerciasis: heterogeneity of in vitro adherence of eosinophils to infective third and fourth stage larvae and microfilariae of Onchocerca volvulus.

Adherence of eosinophilic granulocytes from patients with onchocerciasis to microfilariae (Mf), third (L3) and fourth (L4) stage larvae of Onchocerca volvulus was studied in vitro. Native and heat-inactivated sera from patients with onchocerciasis (OS), from endemic controls without signs of the disease (ECS), from healthy Caucasians (NS) or foetal calf serum (FCS) served as sources for adherence mediating factors. In FCS-supplemented medium eosinophils did not adhere to any larvae. None of the sera mediated the adherence of eosinophils to L4. Eosinophils adhered to L3 in the presence of OS, ECS and NS, whereas OS exclusively mediated adherence to Mf. Reduced adherence rates of eosinophils to L3 occurred in heat-inactivated or zymosan-activated OS, ECS or CS. Eosinophils bound to the L3 cuticle of moulting stage but not to the newly exposed L4 cuticle. A single adherent layer of effector cells was found around cast L3 cuticle, multiple layers were found around intact L3 leading to subsequent paralysis of the larvae and to an amplification of the toxic effector potential by homotypic intereosinophilic adhesion. Our experiments document heterogeneity of in vitro effector cell adherence to the three larval stages of O. volvulus and indicate that complement-dependent as well as independent mechanisms are operative in eosinophil-larval-interaction. The results emphasize the importance of the invading infective larval stages of O. volvulus as possible targets for vaccine production.

Animals↗
PubMed1984

Enhanced arboviral transmission by mosquitoes that concurrently ingested microfilariae.

Infection, dissemination, and transmission of an arbovirus in mosquitoes are enhanced by concurrent ingestion of microfilariae. Ingestion of Rift Valley fever virus alone infected only 64 percent of female Aedes taeniorhynchus. Of these, only 5 percent of refeeding mosquitoes actually transmitted virus. In contrast, ingestion of the same amount of virus from concurrently microfilaremic (Brugia malayi) gerbils resulted in 88 percent infection and 31 percent transmission. Enhanced transmission of virus may be attributed to increased transit of virus across the midgut wall. Endemic filariasis may promote arbovirus transmission in nature.

Aedes↗
PubMed2002

Nitric oxide limits the expansion of antigen-specific T cells in mice infected with the microfilariae of Brugia pahangi.

Infection of BALB/c mice with the microfilariae (Mf) of the filarial nematode Brugia pahangi results in an antigen-specific proliferative defect that is induced by high levels of NO. Using carboxyfluorescein diacetate succinimydl ester and cell surface labeling, it was possible to identify a population of antigen-specific T cells from Mf-infected BALB/c mice that expressed particularly high levels of CD4 (CD4(hi)). These cells proliferated in culture only when inducible NO synthase was inhibited and accounted for almost all of the antigen-specific proliferative response under those conditions. CD4(hi) cells also expressed high levels of CD44, consistent with their status as activated T cells. A similar population of CD4(hi) cells was observed in cultures from Mf-infected gamma interferon receptor knockout (IFN-gammaR(-/-)) mice. Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling staining revealed that the CD4(+) T cells from Mf-infected wild-type mice were preferentially susceptible to apoptosis compared to CD4(+) T cells from IFN-gammaR(-/-) mice. These studies suggest that the expansion of antigen-specific T cells in Mf-infected mice is limited by NO.

Animals↗