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P T Soboslay

Publications and source records attributed to P T Soboslay.

34 records · Page 2Linked to original sources
PubMed1997

The diverse expression of immunity in humans at distinct states of Onchocerca volvulus infection.

This study examined the development and persistence of immunity in humans presenting defined states of Onchocerca volvulus infection, i.e. in exposed endemic control individuals without microfilaridermia and clinical disease, in patients with patent or post-patent onchocerciasis, and in patients concurrently infected with Mansonella perstans. Onchocerca volvulus antigen (OvAg)-specific cellular reactivity was significantly diminished in microfilariae (mf)-positive patients, while the highest reactivity was measured in exposed but mf-negative endemic controls, those being free of any clinical signs of onchocercal disease. In patients who became post-patent, responses to OvAg were significantly augmented, but did not approach entirely the magnitude observed in endemic controls. In onchocerciasis patients with concurrent mansonelliasis, cellular unresponsiveness to OvAg persisted, even when mf of O. volvulus were eliminated permanently by repeated ivermectin therapy. Cells from mf-positive onchocerciasis patients produced significantly less interferon-gamma (IFN-gamma) (P < 0.01) and interleukin-5 (IL-5) (P < 0.05) in response to OvAg than those taken from endemic controls or post-patent individuals in whom IFN-gamma and IL-5 production was similarly high. In contrast, both OvAg-driven as well as spontaneous IL-10 secretion was higher in mf-positive patients than in endemic controls or post-patent cases. In all individuals examined, serological recognition of OvAg by immunoglobulins was dominated by IgG4; in mf-positive patients OvAg of 205,000-12,000 molecular weight (MW) were strongly bound. In post-patent individuals, and similarly in endemic controls. OvAg recognition by IgG4 varied from intense (with numerous antigens being recognized) to weak or absent antigen binding. Significantly elevated OvAg-specific IgG isotypes were measured in mf-positive onchocerciasis patients in comparison with endemic controls or post-patent individuals (with the exception of IgG3). IgG1, IgG2 and IgE were higher, but IgG4 was lower in endemic controls compared with post-patent onchocerciasis patients. The ratios of IgG4/IgG1 differed (P < 0.001) between endemic controls and mf-positive or post-patent onchocerciasis patients, with IgG4/IgG1 ratios of R < 3.0 being characteristic for endemic controls and post-patent O. volvulus infection. In conclusion, this cross-sectional immunoepidemiological investigation showed that distinct states of O. volvulus infection correlate with a particular cellular and humoral immune response. The mf-free condition appeared to be associated with a vigorous parasite-specific cellular reactivity and a particular cytokine production profile, while concurrent M. perstans infection depressed OvAg-specific cellular responsiveness. Antibody responses, in all likelihood, reflected the intensity and state of infection, and not the degree of acquired immunity protective against parasite aggregation.

Adolescent↗
PubMed1997

Antigenicity and specificity of very low molecular weight Onchocerca volvulus polypeptides in the range 2.2-12.5 kD.

Onchocerca volvulus polypeptides in the molecular mass range of 2.2 to 12.5 kD were separated by Tricine-SDS-PAGE and the serological recognition of these very low molecular weight antigens (VLMW-OvAg) was then investigated by immuno-blotting. Sera from 21 onchocerciasis patients as well as from 53 individuals with other filariases were used to determine the sensitivity and specificity of detection of individual VLMW-OvAg. In onchocerciasis patients, up to 16 VLMW-OvAg were recognized predominantly by IgG1 and IgG4, while only few antigens were recognized by IgG2 and IgG3. The antigen recognition pattern varied individually, but 4 VLMW-OvAg of 8.6, 6.2, 5.4, and 5.1 kD, respectively, were bound by IgG4 from more than 90% of the onchocerciasis patients. Six VLMW-OvAg of 7.3, 5.8, 5.4, 4.0, 3.8, and 3.6 kD were recognized exclusively by IgG1 from onchocerciasis patients. In amicrofilaraemic filariasis patients with lymphatic pathology, a strong reactivity of IgG3 to an OvAg of 2.2 kD was observed, indicating a possible contribution of this antigen to the pathogenesis. In the molecular mass range below 13 kD, no specific carbohydrate residues or phosphorylcholine-containing (PC) determinants could be identified by lectin-blotting or PC-specific immunoblotting, respectively. Two-dimensional separation and immunoblotting distinctly resolved more than 40 antigenic polypeptides, the majority focusing at acidic isoelectric points. In O. volvulus-infected chimpanzees the IgG1- and IgG4-reactivity against OvAg below 13 kD appeared concurrently with onset of patent infection. These data suggest that some of these VLMW-OvAg might be associated with the production and release of microfilariae from gravid female worms as well as be involved in immune-mediated pathogenesis during filarial infections.

Adolescent↗
PubMed1997

Subclass-specific serological reactivity and IgG4-specific antigen recognition in human echinococcosis.

Immunoglobulin (Ig) subclass-specific antibody responses and isotype-specific recognition of E. multilocularis (Em) and E. granulosus (Eg) antigens (Ag) were evaluated in both alveolar echinococcosis (AE) and cystic echinococcosis (CE). AE patients were divided into 3 groups by clinical and therapeutic criteria according to their actual state of infection, i.e. elimination of parasite, and regression or progression of disease, CE patients were either before or after surgery, of in continuous chemotherapy due to parasite persistence. Total IgE was highly elevated in progressive AE cases (7/11), but not in the cases with eliminated infection or regression. In AE patients with active disease, EmAg-specific IgE, total IgG, IgG1, IgG2 and IgG4 were particularly high. Similarly, in 9 of 30 CE patients, total IgE was raised above reference values, indicating progressive disease. CE patients" sera antibody cross-reacted with crude EmAg, and detectable Ig levels of the same isotype were also measured by ELISA. In both AE and CE, parasite-specific antigen recognition was dominated by IgG1 and IgG4. In AE patients with progressive disease, IgG4 distinctively recognized low molecular weight EmAg of Ar 26 kD, 18 kD, 16 kD and 12 kD. As prominent IgG4 and IgE responses develop with chronic helminth infections only, these serological parameters may indicate successful parasite infestation and severe outcome of disease. In summary, analyses of immunoglobulin isotype responses in AE patients by ELISA in combination with immunoblotting are a useful approach for post-treatment follow-up of patients at risk of developing recrudescent disease.

Adult↗
PubMed1996

Immunoregulation in onchocerciasis: predominance of Th1-type responsiveness to low molecular weight antigens of Onchocerca volvulus in exposed individuals without microfilaridermia and clinical disease.

Chronic and generalized onchocerciasis is associated with suppression of the parasite-specific cellular responsiveness, while exposed individuals without parasitological and clinical evidence of infection (endemic normals) display prominent cellular reactivity to Onchocerca volvulus antigens (OvAg). In order to identify those parasite antigens which may account for this differential cellular responsiveness, total adult worm-derived OvAg were fractionated by means of preparative SDS-PAGE and blot-elution into 22 antigen fractions of continuously decreasing molecular weight. Peripheral blood mononuclear cells (PBMC) from microfilariae (mf)-positive onchocerciasis patients (n = 18) proliferated weakly in response to all OvAg fractions. In contrast, in vitro reactivity of PBMC from endemic normals (n = 9) was depressed in response to OvAg of mol. wt 200-30 kD only, while antigens of mol. wt < 30 kD induced vigorous proliferation in these individuals compared with the microfilaridermic patients (P < 0.05). Highest proliferative reactivity of cells from endemic normals was observed in response to OvAg of mol. wt 15-11 kD. Furthermore, these low mol. wt antigen fractions induced substantial production of IL-2 and interferon-gamma (IFN-gamma) in PBMC from endemic normals, but not in those from onchocerciasis patients. Cells from individuals of both groups secreted similar amounts of IL-5 in response to all OvAg fractions, with highest production again being induced by low mol. wt OvAg. In contrast, PBMC from onchocerciasis patients clearly produced more IL-10 than did cells from endemic normals. This augmented IL-10 production by PBMC from mf-positive individuals was not only observed after stimulation with OvAg fractions, but was measured in unstimulated control cultures as well. IFN-gamma-specific mRNA in antigen-stimulated PBMC from endemic normals appeared to be more prominent than in cells from onchocerciasis patients. However, mRNA transcripts of IL-10 and IL-13 were clearly present in patients, but were absent or inconsistently observed in endemic normals. Our results suggest that vigorous Th1-type cellular responsiveness encountered in endemic normals is restricted to low mol. wt antigens of O. volvulus, while such reactivity will not be present in mf-positive individuals. Furthermore, spontaneous production of high levels of IL-10 in onchocerciasis patients is likely to suppress Th1-type immunity, and thus may favour manifestation of chronic onchocerciasis. These traits of cellular immunity may contribute to the differential outcome of O. volvulus infection, the manifestation of clinical disease, and may also regulate the build up of acquired immunity in humans.

Adolescent↗
PubMed1994

Ivermectin-facilitated immunity in onchocerciasis; activation of parasite-specific Th1-type responses with subclinical Onchocerca volvulus infection.

The present study examined the quantitative and qualitative changes registered in the parasite-specific antibody response, cellular reactivity and cytokine production profile in onchocerciasis patients repeatedly treated with ivermectin over a period of 8 years. The densities of Onchocerca volvulus microfilariae (mf) in treated patients remained significantly reduced, whereas the number of permanently amicrofilaridermic patients (subclinical infection) increased with repeated treatments. In vitro cellular responses to O. volvulus antigen (OvAg) were highest (P < 0.01) in untreated control individuals exposed to infection, but negative for mf of O. volvulus (endemic normals). Cellular reactivity in repeatedly treated patients was higher at 84 than at 36 months post initial treatment (p.i.t); furthermore, the proliferative responses to OvAg, mycobacterial purified protein derivative (PPD) and streptococcal SL-O were greater (P < 0.05) at 84 months p.i.t. in amicrofilaridermic than in microfilaria-positive onchocerciasis patients. In amicrofilaridermic patients such reactivity approached the magnitude observed in endemic normals. Peripheral blood mononuclear cells (PBMC) from patients and endemic normals produced equivalent amounts of IL-2, IL-4 and interferon-gamma (IFN-gamma) in response to mitogenic stimulation with phytohaemagglutinin (PHA); in response to OvAg, however, significantly more IL-2 and IFN-gamma were produced by PBMC from subclinical amicrofilaridermic patients or endemic normals than by mf-positive patients. OvAg-specific production of IL-4 by PBMC from treated patients was lower at 84 than at 36 months p.i.t. At three months p.i.t. the titres of circulating OvAg-specific IgG1-3 had increased (P < 0.05), but they then continuously declined with repeated treatments. Only IgG1 and IgG4 bound to OvAg of mol. wt 2-12 kD at 1 month p.i.t., while recognition of OvAg of mol. wt 10-200 kD by IgG1, IgG2 and IgG4 reached a maximum intensity at 3-6 months p.i.t., with the overall intensity of binding to OvAg gradually weakening thereafter. These results suggest that onchocerciasis-associated immunosuppression is reversible following ivermectin-induced permanent clearance of microfilariae from the skin; and that a vigorous parasite-specific cellular reactivity and a sustained production of IL-2 and IFN-gamma in amicrofilaridermic individuals may contribute to controlling O. volvulus infection.

Animals↗
PubMed1993

Characterization of a recombinant T cell and B cell reactive polypeptide of Onchocerca volvulus.

To identify potentially protective Ag of the filarial nematode Onchocerca volvulus on the molecular level we screened a cDNA library of O. volvulus with a human serum raised against radiation-attenuated infective larvae of O. volvulus. A cDNA clone of 218 bp (OvL3-1) was selected for further studies. It was expressed in Escherichia coli and affinity purified recombinant polypeptide was tested for its ability to stimulate in vitro PBMC from African onchocerciasis patients and PBMC from chimpanzees experimentally infected with O. volvulus. An enhanced cell proliferation by PBMC was observed in many patients after stimulation with the recombinant OvL3-1 polypeptide. In addition, some patients' PBMC responded to OvL3-1 stimulation with enhanced IL-2 production. Infected chimpanzees also showed an increase in T cell proliferation. Onchocerciasis patients had variable levels of specific antibodies directed to the recombinant polypeptide when sera were tested by ELISA. A mAb directed against the recombinant protein located the native target Ag in the muscles of the adult worm. The molecular mass of native OvL3-1 was found to be 50 kDa on immunoblots. Polymerase chain reaction analysis of RNA from different life stages of the parasite showed that OvL3-1 is transcribed in all parasite stages within the mammalian host. A homologous gene is also present in other filarial parasites. The protein corresponding to OvL3-1, therefore, represents an immunogen present during the whole life-span of the parasite, and because of its B and T cell stimulatory properties, it may be a candidate for a protective Ag in human filariasis.

Adult↗
PubMed1993

Experimental onchocerciasis in chimpanzees: cellular responses and antigen recognition after immunization and challenge with Onchocerca volvulus infective third-stage larvae.

Immunization of chimpanzees with radiation-attenuated infective 3rd-stage larvae (L3) of Onchocerca volvulus did not induce strong protective immunity against a subsequent challenge infection; only 1 out of 4 immunized animals remained non-patent (i.e. microfilariae-negative) after challenge, and may have been protected. However, during immunization and before challenge, a broad range of adult O. volvulus-derived antigens (OvAg) and also uterus-derived OvAg were recognized by circulating antibodies; moreover, the repertory of antigens recognized increased further in subsequently patent animals after challenge, particularly in the range of M(r) 12-42 kDa. In the immunized and non-patent chimpanzee, by contrast, serological recognition of uterus-derived OvAg with M(r) 14 kDa and 105 kDa disappeared by 19 months post-challenge (p.c.). During immunization, Acanthocheilonema viteae L3 antigens of M(r) 11-12 kDa were strongly recognized only by the non-patent animal, suggesting that recognition of these antigens may have supported resistance to the subsequent challenge infection. In immunized chimpanzees, a substantial increase in the cellular reactivity to OvAg was induced; this, however, declined by 19 months p.c. to levels similar to those seen prior to immunization. At that time, 3 out of 4 immunized animals were patently infected. The effect of exogenous cytokines on in vitro-reactivity of PBMC to OvAg was examined. Addition of exogenous IL-2 alone, IFN-gamma alone, and IFN-gamma in combination with IL-2, did not augment net cellular responses to OvAg by PBMC from infected and control chimpanzees. In the presence of IL-4 alone, IL-6 alone, IL-2 with IL-4, IL-2 with IL-4 and IFN-gamma, or IL-2 with IL-4 and IL-6, the net cellular reactivity to OvAg increased significantly in patent chimpanzees and reached levels similar to non-patent animals. Thus, non-patent chimpanzees maintain high cellular reactivity to OvAg and in vitro cellular unresponsiveness to OvAg on the part of patent chimpanzees is reversible after addition of several cytokines which act individually or synergistically.

Animals↗
PubMed1993

Onchocerca volvulus provides ligands for the stimulation of human gamma/delta T lymphocytes expressing V delta 1 chains.

Peripheral blood mononuclear cells (PBMC) from 8 onchocerciasis patients, treated or not with ivermectin, were analyzed for phenotypic cell surface markers. A significant increase (P < .05) in gamma/delta T cells expressing the V delta 1 chain compared with normal and endemic controls was detected in all patients. PBMC populations from onchocerciasis patients were not expanded after restimulation with Onchocerca volvulus antigens in vitro, but both V delta 1 and V delta 2 T cells from normal donors were increased significantly in response to O. volvulus and Mycobacterium tuberculosis (P < .05), respectively. Frozen sections of all 5 onchocerca nodules tested demonstrated an increased number of CD3+ cells in the vicinity of the adult worm, in all cases expressing the alpha/beta T cell receptor and in 2 patients also expressing the gamma/delta T cell receptor; 60% of T cells expressed the activation marker Ki67. These data suggest that O. volvulus provides ligands to V delta 1 T cells.

Adult↗
PubMed1992

Experimental onchocerciasis in chimpanzees. Antibody response and antigen recognition after primary infection with Onchocerca volvulus.

Nine of 18 chimpanzees inoculated with 250 infective third-stage larvae (L3) each developed patent (i.e., positive for microfilariae) Onchocerca volvulus infection. Four of 6 infected chimpanzees that received 200 micrograms/kg ivermectin at 28 days postinfection (pi) became patent, whereas, when ivermectin was given concurrently with L3 challenge only 1 of 6 infected animals developed patent infection. The antibody response to O. volvulus adult worm-derived antigens (OvAg) showed clear differences between patent and nonpatent chimpanzees. Three months pi, all sera detected several OvAg in the range of M(r) 35-120 k. Sera collected 6 mo pi from later patent animals recognized increasing numbers of OvAg, especially in the lower MW range of M(r) 13 to 33 k. Beginning 10 months pi Onchocerca-antigens of M(r) 21, 24, 26, and 28 k were detected only by patent chimpanzee's sera. The antibody response in nonpatent chimpanzees consistently recognized fewer OvAg, most of which were limited to the higher M(r) range (35-120 k). The reactivity of sera from infected chimpanzees to a low molecular weight fraction (LMW) of total OvAg doubled within 6 months pi, and increased continuously in patent animals from 13 until 30 months pi. Serological reactivity of nonpatent animals to LMW-OvAg remained low. The titers of circulating IgG directed against total OvAg increased in all infected chimpanzees, and continued to rise with patency. In nonpatent chimpanzees the antibody production gradually returned to preinfection values. Total and OvAg-specific IgE increased in patent and nonpatent chimpanzees. Also, during prepatency the granulocyte and antibody-mediated in vitro killing of microfilariae of O. volvulus increased in subsequently patent chimpanzees. The in vitro immobilization of L3 remained low.

Animals↗
PubMed1992

Ivermectin-facilitated immunity in onchocerciasis. Reversal of lymphocytopenia, cellular anergy and deficient cytokine production after single treatment.

A longitudinal investigation has been conducted into the cell-mediated immune responses of onchocerciasis patients after a single-dose treatment with ivermectin. Untreated patients tested for delayed cutaneous hypersensitivity (DCH) to seven recall antigens showed lower responses than infection-free control individuals (P less than 0.01), but 6 and 14 months after treatment DCH reactions increased to similar levels to those seen in the controls. The in vitro cellular reactivity to Onchocerca volvulus-derived antigen (OvAg) was reduced in untreated patients as compared with controls, and the lymphocyte blastogenic responses to OvAg and streptolysin-O clearly improved up to 14 months after treatment. Peripheral blood mononuclear cells (PBMC) from untreated patients produced IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6 in response to mitogenic stimulation with phytohaemagglutinin (PHA), only low levels of IL-1 beta, IL-2 and TNF-alpha in response to OvAg, but higher amounts of IL-4 and interferon-gamma (IFN-gamma) in response to OvAg than control individuals. After ivermectin treatment, the OvAg-induced production of IL-1 beta and TNF-alpha increased significantly 1 and 14 months after treatment. The PHA-induced production of IL-2 and IL-4 increased 1 month after treatment and remained significantly elevated until 14 months after treatment, whereas the OvAg-specific secretion of IL-2, IL-4 and IFN-gamma did not change after ivermectin treatment. Flow cytometric analysis of lymphocyte-subsets in the peripheral blood of untreated patients revealed a relative and absolute (P less than 0.01) diminution of CD4+ cells and a significantly smaller CD4+/CD8+ cell ratio as compared with controls. By 4 weeks after treatment and thereafter, CD4+ T cells increased relatively and absolutely (P less than 0.01); likewise there was an absolute increase in T-helper-inducer cells (CD4+CD45RO+) and a temporarily improved CD4+/CD8+ cell ratio (P = 0.001). The expression of the low-affinity receptor for IgE (CD23) on total lymphocytes decreased from 14% to 7% by 14 months after treatment. The CD8+ cells and CD3+TCR gamma delta + cells were higher in patients than in controls and both remained elevated until 14 months after treatment. These results suggest a distinctly improved cellular immunity in human onchocerciasis that was facilitated by ivermectin therapy.

Animals↗
PubMed1991

Experimental onchocerciasis in chimpanzees. Cell-mediated immune responses, and production and effects of IL-1 and IL-2 with Onchocerca volvulus infection.

Nine of eighteen chimpanzees inoculated with infective third-stage larvae of Onchocerca volvulus developed patent infection with microfilariae in skin biopsies. In all infected chimpanzees the in vitro cellular reactivity to O. volvulus adult worm-derived Ag (OvAg) increased significantly after exposure to third-stage larvae. However, during prepatency the in vitro cellular responses to OvAg decreased gradually in subsequently mf positive (patent) animals, and returned with patency to values not different to those before infection. In non-patent chimpanzees cellular responses remained significantly higher than before infection. Stimulation of PBMC in vitro with bacterial Ag and mitogen did not show any differences between the experimental groups through 20 months p.i. The addition of exogenous IL-2 did not restore the impaired responses of PBMC to OvAg in patent animals. Exogenous IL-2 elicited an additive increase of the cellular response to OvAg in nonpatent, and a mitogenic effect to OvAg in patent animals. Selective depletion of adherent, suppressor/cytotoxic (CD8+), NK cells (CD16+) and the use of autologous serum had no effect on antigenic and mitogenic cellular responsiveness. OvAg-induced IL-2 production decreased after patency, whereas, IL-1 production was significantly greater in both patent and nonpatent than in control chimpanzees. In summary, these data demonstrate that experimental O. volvulus infection in chimpanzees stimulated a substantial cell-mediated immune response. In patent chimpanzees an OvAg-specific cellular hyporesponsiveness occurred before onset of patency, possibly due to decreased IL-2 production and responsiveness.

Animals↗
PubMed1988

Isolation and characterization of expression cDNA clones encoding antigens of Onchocerca volvulus infective larvae.

The isolation of recombinant cDNA clones expressing antigens found in Onchocerca volvulus infective larvae is described. To isolate such clones, an expression cDNA library constructed from adult O. volvulus RNA was screened with antiserum raised against infective larvae. One clone, designated lambda RAL-1 was characterized further. The recombinant antigen produced by lambda RAL-1 stimulates proliferation of peripheral blood mononuclear cells from O. volvulus infected humans. Lambda RAL-1 is derived from a 1450 bases message that encodes a protein with an apparent molecular weight of 42,000 in adult O. volvulus. The inserted DNA of lambda RAL-1 contains an open reading frame of 1008 bp. The amino acid sequence predicted by this open reading frame contains three repeats of the sequence KKPEDWD. The identification of clones such as lambda RAL-1 will provide quantities of purified antigens sufficient to begin to study the immune response to and explore the development of immunity against the infectious form of the parasite.

Amino Acid Sequence↗
PubMed1988

Ivermectin prophylaxis against experimental Onchocerca volvulus infection in chimpanzees.

Ivermectin was tested for possible prophylactic action against the third and fourth larval stages (L3 and L4) of Onchocerca volvulus inoculated into chimpanzees. The infective larvae (L3) were obtained from laboratory-raised black flies. Eighteen chimpanzees were inoculated, each with approximately 250 L3. Six were treated with ivermectin (200 micrograms/kg) on the day of inoculation, 6 were treated with ivermectin on day 28, and 6 were not treated. Monthly skin snips were taken for the next 30 months to detect patent infection. One of the chimpanzees treated with ivermectin on the day of infection developed a patent infection as did 4 of the 6 treated at day 28 and 4 of the 6 control animals. The results suggest that ivermectin may have a partial in vivo effect against the L3 of O. volvulus but has no effect against later larval stages of the parasite.

Animals↗
PubMed1987

Ivermectin effect on microfilariae of Onchocerca volvulus after a single oral dose in humans.

Ivermectin is a broad spectrum anti-helminthic agent which is currently being tested for use in human onchocerciasis. Its activity is believed to result from its effect on GABA-mediated neurotransmission. We examined the effects of ivermectin on motility of microfilariae of O. volvulus following administration to humans. When ivermectin was given in dosages of 100, 150 and 200 mcg/kg on day 1 there was a clear reduction in motility of microfilariae obtained on day 3 when compared to microfilariae from the placebo group. The mean motility scores in microfilariae from ivermectin recipients were 3.1, 2.3, and 2.2 at 0, 12, and 24 hours of incubation compared to 3.3, 2.9, and 2.5, respectively, in microfilariae from placebo recipients (p less than 0.003, p less than 0.005, and p less than 0.012, respectively). Examination of the effect according to dose suggested a dose-response relationship. Microfilariae in the anterior chamber of the eye 2 days after a single oral dose of ivermectin showed abnormal and reduced winding and coiling. Microfilariae in 50% of ivermectin recipients showed abnormal motility compared to no such effects in subjects examined concurrently who received oral DEC, DEC lotion or placebo. These observations indicate that ivermectin has an effect on motility of microfilariae of O. volvulus following administration to humans.

Animals↗
PubMedDate not supplied

Efficacy of ivermectin in the treatment of concomitant Mansonella perstans infections in onchocerciasis patients.

As part of an ivermectin dose-ranging study of onchocerciasis patients in Togo, 55 onchocerciasis patients with concomitant mansonelliasis received single oral doses either of ivermectin (100 to 200 micrograms/kg body weight) or placebo. As expected, Onchocerca volvulus microfilariae in the skin were greatly reduced in number soon after drug treatment, but microfilariae of Mansonella perstans reacted differently. Microfilarial densities of M. perstans were assessed with a filtration technique both before, and 4 times after, treatment. In untreated patients microfilarial densities were stable until the end of the study at 6 months. In patients receiving ivermectin, microfilarial densities dropped on average to less than 60% of the pre-treatment level and remained there until the final post-treatment examination. This partial reduction was probably not caused by a microfilaricidal effect of ivermectin, but rather by an altered distribution of microfilariae in the peripheral blood and in a suspected microfilarial reservoir.

Animals↗