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PubMed1988

Loa loa - a neglected filaria.

There has been considerable research on the biochemistry and immunology of many human, veterinary and laboratory animal filariae, with a view to understanding pathogenic and protective immune mechanisms and developing ways to boost them(1-3). But, apart from a few isolated reports (eg. Refs 4,5), these aspects have been largely ignored for the human filarial parasite Loa loa. Obviously not all filariae can be studied in equal depth - almost 100 different life cycle patterns are documented(6) - but, as Margaret Pinder shows here, L. loa is an important human pathogen of considerable biological interest.

Journal Article↗
PubMed1987

The use of mebendazole in the treatment of filariases due to Loa loa and Mansonella perstans.

Patients harbouring Loa loa and/or Mansonella perstans infections, or presenting typical filarial symptomatology, were treated with mebendazole, a drug shown to be efficient in other parasitoses. Of the patients who took the drug during 21 days and provided regular blood samples, 84% showed a significant decrease in their L. loa microfilaraemia and 100% in their M. perstans microfilaraemia, with a concomitant improvement in the clinical manifestations and no side reaction to drug administration. Additionally, the long-lasting effect of the drug (up to day 200 in some cases) may suggest a positive action on the adult worm. Mebendazole may consequently be regarded as a safer alternative to diethylcarbamazine for the treatment of these two parasitoses.

Adolescent↗
PubMed1997

Experimental infection of a nonhuman primate with Loa loa induces transient strong immune activation followed by peripheral unresponsiveness of helper T cells.

Human infection with the parasite Loa loa is characterized by a good adaptation between the parasite and its host. One portion of the human population harbors only adult worms in subcutaneous tissues, whereas another portion also harbors the L1 microfilarial stage in peripheral circulation. This study was undertaken to understand the mechanisms by which the parasite evades or modulates host immunological attack. The cellular responses, based on T-cell proliferation, to the production of various cytokines (interleukin-2 [IL-2], gamma interferon [IFN-gamma], IL-4, and IL-5) and to expression of cytokine (IL-2, IFN-gamma, IL-4, IL-5, IL-10, and IL-12) mRNAs were investigated during the experimental infection with human parasite L. loa of a nonhuman primate which has been shown to display a spectrum of disease similar to that found in humans. Our results indicate that a T-cell unresponsiveness occurs when female worm products are released into the peripheral circulation, preceded by a transient period of strong T-cell proliferation, cytokine production, and cytokine mRNA expression. In the unresponsive state, only IL-10 mRNA is expressed, suggesting a role for IL-10 in down-regulation and maintenance of unresponsiveness. Taken together, these results indicate that both IL-10 production, which is known to inhibit B7 expression on monocytes, and the massive release of female products in the blood where T cells encounter antigens presented by nonactivated B lymphocytes, which lack costimulatory signals, should contribute to the inactivation of T cells.

Animals↗
PubMed1990

Comparison of thick blood smear and saponin haemolysis for the detection of Loa loa and Mansonella perstans infections.

In an endemic area, Loa loa and Mansonella perstans microfilariae were detected by the examination of 5 ml blood in respectively 7.4 and 26.2% of subjects who would have been erroneously considered amicrofilaraemic by the conventional method of two thick blood smears (40 microliters blood). Correction factors to be applied to the results obtained with thick blood films in order to approach the true parasitological prevalences were 1.5 for L. loa and 1.6 for M. perstans. In addition, the analysis of a large volume of blood provides a better estimation of microfilarial load of the parasitized population.

Animals↗
PubMed1994

Loa loa: immunological responses during experimental infections in mandrills (Mandrillus sphinx).

Six intact, adult mandrills (Mandrillus sphinx) were infected with human-derived, diurnal Loa loa infective larvae. Microfilaremia, hematological, and immunological parameters were followed for 2-4 years. A major aim was to investigate the relationship between specific humoral immunity to microfilariae and microfilaremia and also to assess whether infection led to generalized immune dysfunction. Microfilaremia was similar to previous studies for 4 mandrills, with a prepatent period of 153.5 +/- 10.1 days, a peak of 34-1,798 mf/ml around Day 200, followed by a decline to low, persistent microfilaremia. One mandrill (No. 20) had a longer prepatent period and very low, but persistent, levels of microfilaremia, and one (No. 19) had gradually increasing levels which remained > 10,000 mf/ml for 3 years. To assess generalized immune perturbations several parameters were studied. There was neither generalized leukocytosis nor relative or absolute eosinophila. Serum Ig concentrations were measured from 0-600 days postinfection by radial immunodiffusion using a rabbit anti-mandrill Ig serum, and these were remarkably stable. Proliferative responses of peripheral blood mononuclear cells from these infected mandrills and noninfected controls showed no significant differences in the magnitude of proliferation after stimulation with a range of doses of PHA, PWM, or Concanavalin A. Thus, no evidence of generalized immune dysfunction was found in the peripheral blood. Serum IgG levels to soluble mf antigens were estimated by an indirect ELISA and all animals had maximal levels around Week 22 postinfection, at the time of maximum microfilaremia, and these decreased over the next 2-3 years in all mandrills except No. 19, in which levels remained fairly constant. Serum IgG levels to adult worm antigens showed a similar pattern but were not, or were only slightly, diminished late in infection. Antibody to mf sheath antigens were detected by indirect immunofluorescence and agglutination of live mf. Antibody to sheath antigens were never detected in mandrill 19 but were present from Week 8 postinfection to 2-4 weeks before patency in all the others. Anti-sheath antibodies were not detected in serum at later time points, i.e., postpatency, in any mandrill, even at time points when microfilaremia was < 1 mf/ml. The anti-sheath antibody was IgM and no anti-sheath IgG was detected. Ig was detected on the surface of circulating mf in 1 mandrill (No. 20). The appearance of these antibodies prior to maturation of the adults indicates that certain L4 or immature adult antigens cross-react with the surface of mf.(ABSTRACT TRUNCATED AT 400 WORDS)

Agglutination Tests↗
PubMed2003

Epidemiology of concomitant infections due to Loa loa, Mansonella perstans, and Onchocerca volvulus in rain forest villages of Cameroon.

An epidemiological survey was conducted in 16 remote villages of the rain forest of southern Cameroon to ascertain the prevalence and intensity of three species of filariae: Loa loa, Onchocerca volvulus, and Mansonella perstans. We examined 1458 individuals for blood-dwelling microfilariae and 1255 of these were also for the presence of palpable nodules. All the villages surveyed were found highly endemic for onchocerciasis and mansonellosis with prevalence ranging from 28.44% to 87.17% for O. volvulus and 52.48% to 100% for M. perstans. The intensities of infection were also found high for M. perstans with arithmetic means of microfilaremia ranging from 280.94 to 4947.57 mf/ml. The loiasis prevalence was relatively low with value from 2.22% to 19.23%. Males were found more infected than females for the three species of filariae, and the prevalence and intensities of microfilaremia vary differently in males and females at different ages. The three species of filariae displayed different degrees of association in the inhabitants with a low prevalence of co-occurrence between L. loa/O. volvulus and between L. loa/M. perstans. In contrast, there was a high prevalence of co-occurrence between M. perstans and O. volvulus. The implications of the co-occurrence of the three species of filariae in the populations of these remote villages on the intervention programs based on mass treatment with mectizan are discussed.

Adolescent↗
PubMed1982

Survival of Loa loa following transplantation from drills (Mandrillus leucophaeus) into jirds (Meriones unguiculatus): parasitology and pathology.

Two drills infected with Loa loa maintained a microfilaraemia for four and a half years ranging from less than 1 mf/100 microliters to 1150 mf/100 microliters. No significant tissue reactions to the adult worms were seen at autopsy. Adult worms were transplanted into the peritoneal cavities of naive jirds when a persistent microfilaraemia first developed by 17 days. Retransplantation of adult worms into naive jirds produced a microfilaraemia and microfilariae in the peritoneal cavities of three out of five animals. These three animals were all negative for circulating parasites by eight and a half months. The tissue reactions to the worms in the jirds are described, including a granulomatous response surrounding adults and a myositis involving microfilariae.

Animals↗
PubMed1985

Loa loa: a simple method for isolation of microfilariae from blood with production of antigen in extraction medium.

A simple method for isolating Loa loa microfilariae from the blood of patients is described. This involves sedimentation on Ficoll followed by migration of the microfilariae into an extraction medium. During migration the microfilariae release antigen-rich excretory or secretory products. The procedure thus yields two products: pure microfilariae and large amounts of antigen in the extraction medium.

Antigens, Helminth↗
PubMedDate not supplied

Ecdysteroid-like compounds in the serum and urine of African patients infected with Loa loa and Mansonella perstans microfilariae.

Ecdysteroids are compounds related to 20-hydroxyecdysone, the insect moulting hormone. Surprisingly, they have been found in serum and urine of patients infected with helminths. In these cases, the substances are assumed to be produced by the parasites and, therefore, might be used as a marker of parasitic infection. Thus, we need to know exactly which species, at which developmental stage, can release ecdysteroids in such large quantities that they could be detected in the biological fluids of the host. Large-scale investigations must, accordingly, be devoted to the major species of helminths. In the present study, we examined 100 African patients with Loa loa and/or Mansonella perstans microfilaraemia. About 70 of them had high levels of ecdysteroid-like materials in serum or urine. In contrast, uninfected patients and European controls had much lower concentrations. However, the ecdysteroid titres did not reflect the concentration of microfilariae actually present in the blood, and some heavily infected patients were even negative. Nevertheless, the most important point was that high ecdysteroid levels in man were always associated with a pathological condition. The precise significance of the phenomenon should be determined.

Adult↗
PubMedDate not supplied

Chrysops silacea and C. dimidiata: fly densities and infection rates with Loa loa in the Chaillu mountains, Congo Republic.

The densities, infection rates with Loa loa, and parous rates of Chrysops silacea and C. dimidiata were studied in various ecological zones throughout the Chaillu mountains in the People's Republic of the Congo. In the rainy season, C. dimidiata was the major vector in the forest, whereas C. silacea was predominant in the cleared forest zones. Fly densities were higher in the forest (natural forest or palmgrove) than in the villages. Parous and infection rates varied according to the ecological zone. The infection rate of parous females was related to the microfilarial rate in the human population, indicating that the Chrysops populations were extremely stable in the rainy season.

Animals↗
PubMedDate not supplied

Reduced Loa loa microfilaria count ten to twelve months after a single dose of ivermectin.

The action of a single dose of ivermectin (200 micrograms/kg) on 71 Gabonese patients with Loa loa microfilariae in the peripheral blood, and living in areas highly endemic for loiasis, has been evaluated. Ten to 12 months after treatment, 43 patients (63%) had no circulating microfilaria and the geometric mean peripheral blood microfilaria count had decreased by 88.6% (P < 0.02). Thus, a single annual dose of ivermectin can markedly reduce loiasis transmission.

Adolescent↗
PubMed1984

Loa loa: the use of a blood cell separator to reduce microfilaraemia before specific chemotherapy.

Three years after returning to the U.K. a 58-year-old British engineer, who had worked in the Nigerian oilfields for 24 years, was found to have Loa loa. His midday microfilarial count ranged between 12 X 10(6) and 16 X 10(6) parasites per litre. Before starting treatment, I litre of leucocyte/platelet-rich plasma was removed by means of a blood cell separator. Six intermittent cycles of blood separation were performed during a single 4-h session around midday in order to coincide with the period of maximum microfilarial presence in the peripheral circulation. This resulted in a 50% reduction of the microfilaraemia. Where facilities for blood cell separation are available, this procedure, together with appropriate chemotherapy, should be particularly beneficial in the management of heavy filarial infections.

Blood↗
PubMed1997

T helper responsiveness in human Loa loa infection; defective specific proliferation and cytokine production by CD4+ T cells from microfilaraemic subjects compared with amicrofilaraemics.

The proliferation and cytokine profiles of peripheral blood mononuclear cells (PBMC) from microfilaraemic (Mf+) subjects infected by Loa loa in response to antigens of several parasitic stages were compared with those from amicrofilaraemic (Mf-) individuals. While a strong lymphoproliferative response and consistent levels of both Th1 (IL-2, interferon-gamma (IFN-gamma)) and Th2 (IL-4, IL-5) type cytokines were observed in response to adult worm (AW) and microfilariae (Mf) antigen in Mf- individuals, Mf+ subjects were characterized by a T cell unresponsiveness, including proliferation, cytokine production and IL-2 mRNA expression. Conversely, T cell responsiveness to mitogens and non-specific antigen were similar in the two endemic populations. Depletion of lymphocyte subpopulations indicated that T CD4+ were mainly involved in the specific cellular response. In contrast to other cytokines, IL-10 was produced in response to all parasitic stages, in both Mf+ and Mf- patients. Neutralization of IL-10 did not restore cytokine production in Mf+ patients, while B7 mRNA expression was similar between Mf+ and Mf- subjects in response to Mf antigen, suggesting that IL-10 was not the only factor responsible for T cell unresponsiveness. Mf+ patients have lower Mf antigen-specific IgG levels compared with Mf-, and there is a significant correlation between Mf antigen-specific antibodies and IL-5 responses. These findings suggest that Mf- status is correlated with T helper responsiveness, including proliferation and production of both Th1- and Th2-type cytokines, whereas Mf+ status is characterized by unresponsiveness of the same cell population, induced and/or maintained by microfilariae.

Animals↗
PubMed2003

Parasitological and immunological effects induced by immunization of Mandrillus sphinx against the human filarial Loa loa using infective stage larvae irradiated at 40 Krad.

Six mandrills were immunized with 150 Loa loa infective stage larvae (L3) irradiated with 40 Krad, and challenged with 100 L3, 60 days after initial vaccination. The parasitological outcome of this immunization was compared to results from six mandrills infected with normal L3. No clear association was seen between vaccination and microfilaremia until day 245 when a significant drop in the level of microfilaria occurred in vaccinated compared to infected animals (5 vs 10 mf/ml; p = 0.012). A one-year follow-up of the humoral immune response showed a strong adult, microfilariae (Mf) and L3 specific IgG response, with distinct profiles for each extract. In immunized animal a significant decrease in antibody level was systematically observed between days 90-145 for the anti-L3 and anti-adult IgG. However, in the same group anti-Mf antibody levels that peaked around 160-175 days post-challenge, were inversely correlated with the decrease in Mf density between day 200 and day 386. These results suggest that immunization with irradiated L3 using these specific conditions may affect the appearance of Mf.

Animals↗
PubMed1996

Detection of circulating antigens in Gabonese patients with Loa loa filariasis.

Circulating antigens were detected in sera of Gabonese patients with Loa loa filarial infection by co-electrosyneresis (Co-ES). The serum samples selected for this study were exposed to rabbit hyperimmune antifilarial antisera and human immune antisera: specific arcs were observed in 35/60 filarial patients, of whom 24/47 were microfilaraemic and 11/13 amicofilaraemic. The identity of rabbit hyperimmune antisera and loiasial immune sera was confirmed by the continuity of precipitation arcs. These preliminary studies were carried out to develop diagnostic tools for loiasis and to study the physiopathology of immune complexes.

Animals↗
PubMed1998

Monosymptomatic Loa loa infection.

We report the case of a 17-year-old student from Cameroon who presented an atypical, mono-symptomatic form of Loa loa infection, characterized only by rare subcutaneous movements of adult worms.

Adolescent↗
PubMed1979

Loaiasis (Loa loa) in an African student in Indiana.

Loaiasis was seen in an African student in Indiana, who had non-specific complaints, leukocyte count of 8,400/mm3, a 47% eosinophilia, and a high Loa loa microfilaremia. Successful treatment with diethylcarbamazine (Hetrazan) produced no allergic manifestations and no reactions to the adult parasites were evident.

Adult↗
PubMed1990

Transmission indices of Loa loa in the Chaillu Mountains, Congo.

A longitudinal entomological survey of the vectors of loiasis was conducted in the Missama area (Lekoumou region) in the Congo from September 1987 to August 1989. The principal catching site was a palm grove surrounded by forest 3 km from the village. Landing/biting densities of Chrysops were measured by standardized fly catches lasting 11 hr carried out twice a month. Vector landing densities were also assessed in the Bantu and Pygmy villages and in the fields. Populations of Chrysops from the palm grove were examined 6 times a month for infection with the infective stage of Loa loa. Chrysops silacea was the predominate vector except at the beginning of the rainy season, when C. dimidiata was the prevailing species. Chrysops were caught throughout rainy season, from October to June. The host-seeking activity of C. silacea was greatest in the middle of this season (February), but occurred sooner (October) for C. dimidiata. The following variables associated with transmission were calculated from our observations in the palm grove (the first figure corresponds to the first year of the study and the figure in parentheses corresponds to the second year). It was calculated that 2.658 (2.185) C. silacea and 1.412 (1.182) C. dimidiata could bite a person in the palm grove per year, including an average of 14.4 (12.7) infective C. silacea and 9.8 (7.2) infective C. dimidiata. The percentage of all dissected flies with third stage larvae in the head and the mean number of larvae in the head/infective fly were 0.57% and 10.1 +/- 6.8 for C. silacea and 0.66% and 11.2 +/- 6.5 for C. dimidiata, respectively. The estimated annual transmission potentials were 171.1 (102.9) for C. silacea and 116.1 (73.8) for C. dimidiata. In the palm grove, transmission was ensured by 2 effective vectors during the rainy season (October to May). Although the annual biting rate for both species was twice as low in the village as in the forest, our data suggest that effective transmission occurs there also.

Animals↗