Ivermectin and human onchocerciasis. A study of 234 onchocerciasis patients in the Republic of Mali

In a double blind study Ivermectin has been compared to a placebo in 234 male and female with onchocerciasis who had more than 20 microfilariae per milligram of skin and moderate ocular involvement. Patient was randomized to receive a simple oral dose of Ivermectin 100, 150 and 200 micrograms/kg or placebo. The following was 12 months. The decrease of microfilarodermia since to the 3rd day was from 72.8 to 79.3% of initial rate. At six months it was more than 91% and more than 87% in 12 months. Ocular microfilariae, initially between 12 and 23 stay lower than 2 at 12 months. Punctuated keratitis disappear and did not recidive still 6 months in patients with persistent microfilariae. Ivermectin produce only few side effects. Negative waves have been observed on ECG but without any clinical signs. The Power efficient dose seen to be 100 micrograms/kg.     

A study in the Ivory Coast (1985-1987) of the efficacy and tolerance of ivermectin (Mectizan) in human onchocerciasis. II. Evaluation in the light of mass campaigns on the effect of yearly or half-yearly administration of single oral doses of 100, 150 or 200 mcg/kg

One hundred and twenty patients out of 220 in a previous study were retreated after 6 months or one year with doses of 100, 150 or 200 mcg/kg of ivermectin. The tolerance was excellent due probably to the small number of skin microfilariae obtained with the first treatment. The annual treatment with 150 to 200 mcg/kg, better than with 100 mcg/kg, keeps for the year following the second treatment the microfilariae number between 6 and 11% of the initial level. The half-yearly administration keeps it between 1 and 7% and especially 94 to 100% of these retreated patients have a level of microfilariae less than 5 mf/mg. The results obtained with the half-yearly treatment show a considerable reduction of the number of microfilariae in the anterior chamber of the eye and the percentage of positive patients. Ivermectin is a very efficient microfilaricidal drug for the treatment of onchocerciasis and the prevention of ocular complications. Its rational use in mass campaigns should reduce, if not interrupt, the transmission of this parasitic disease.     

A study in the Ivory Coast (1985-1987) of the efficacy and tolerance of ivermectin (Mectizan) in human onchocerciasis. III. The tolerance and efficacy of a single oral dose of 150 mcg/kg in children

One hundred and three male and female children of 6 to 14 years old with onchocerciasis, having or not ocular involvement and a mean skin microfilariae level of 36.1 mf/mg, received, in October 1986, a single oral dose of 150 mcg/kg ivermectin and controlled at day 4, 3 months, 6 months and 12 months post treatment. After the last control they were retreated with the same dose. The skin microfilariae count fell down to 94% of the initial level at day 4 and to 99% at 3 months. At 6 months the microfilariae count was 2% of the initial level and 5% at 12 months. The percentage of patients having microfilariae in the anterior chamber of the eye which was 33% before treatment fell down to 6% at 12 months. The percentage of patients having microfilariae in the cornea was 39% before treatment and 18% at 12 months. In the cornea and anterior chamber there was a very reduced number of microfilariae still present. 65% of the children had lesions of keratitis before treatment and 34% two months later. Adverse effects (fever, headache, pruritus, oedemas, myalgias, arthralgias) occurred in 64% of children after the first treatment and 50% after the second. They were of weak or moderate intensity and receded rapidly after administration of aspirin and/or anti-histaminic. The administration of ivermectin is an efficient and well tolerated drug in children above 5 years old.     

Chemokines in onchocerciasis patients after a single dose of ivermectin

Ivermectin treatment will effectively diminish microfilariae (Mf) of Onchocerca volvulus in the skin of patients, but therapy is associated with adverse host inflammatory responses. To investigate the association of proinflammatory chemokines with the intensity of infection and clinical adverse reactions, chemokine serum levels were measured in patients following ivermectin treatment (100 microg/kg, 150 microg/kg or 200 microg/kg) or placebo. The density of O. volvulus Mf per mg skin decreased by 85%, 97%, 97% and 90% at day 3, at month 3, month 6 and at 1 year post-ivermectin. The cutaneous T cell-attracting chemokine (CTACK/CCL27) was found highly elevated in onchocerciasis patients compared to infection-free European controls (P = 0.0004) and it did not change following ivermectin or placebo to 1 year post-therapy. The chemokine RANTES/CCL5 (regulated on activated and normally T cell-expressed) was similarly high in onchocerciasis patients and infection-free European controls; the RANTES/CCL5 levels did not change following treatment until 6 months post-therapy but were slightly elevated at 1 year post-therapy (P < 0.02). In contrast, the Th2-type chemoattractants, thymus and activation regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22), were activated at 3 days post-ivermectin (P < 0.0001) to return to pretreatment or lower levels thereafter. The Th1-type chemoattractants, macrophage inflammatory protein (MIP)-1alpha/CCL3 and MIP-1beta/CCL4 were low before ivermectin treatment, but following clearance of microfilariae of O. volvulus their levels increased from 6 months post-therapy onwards (for both at 12 months post-therapy, P < 0.0001). The adverse reaction scores (RS) in treated patients increased significantly on day 3 (P < 0.02) while it remained unchanged in those who received placebo (P = 0.22); RS interacted with the microfilarial density (P = 0.01), but not with the dose of ivermectin or with the serum levels of MIP-1alpha/CCL3, MIP-1beta/CCL4, TARC/CCL17, MDC/CCL22 and CTACK/CCL27. Our observations suggest that following ivermectin, macrophages as well as memory Th2-type lymphocytes and B cells, attracted and activated by MDC/CCL22, TARC/CCL17 and CTACK/CCL27, may contribute to dermal immune responses and O. volvulus Mf killing and clearance. The transient changes of TARC/CCL17 and MDC/CCL22 were not associated with clinical adverse responses, and the later rise of MIP-1alpha/CCL3 and MIP-1beta/CCL4 showed a reactivation of Type 1 immune responses associated with persistent low levels of O. volvulus microfilariae and an expiring O. volvulus infection.     

Comparison of ivermectin and diethylcarbamazine in the treatment of onchocerciasis

We compared ivermectin with diethylcarbamazine for the treatment of onchocerciasis in a double-blind, placebo-controlled trial. Thirty men with moderate to heavy infection and ocular involvement were randomly assigned to receive ivermectin in a single oral dose (200 micrograms per kilogram of body weight), diethylcarbamazine daily for eight days, or placebo. Diethylcarbamazine caused a significantly more severe systemic reaction than ivermectin (P less than 0.001), whereas the reaction to ivermectin did not differ from the reaction to placebo. Diethylcarbamazine markedly increased the number of punctate opacities in the eye (P less than 0.001), as well as the number of dead and living microfilariae in the cornea over the first week of therapy. Ivermectin had no such effect. Both ivermectin and diethylcarbamazine promptly reduced skin microfilaria counts, but only in the ivermectin group did counts remain significantly lower (P less than 0.005) than in the placebo group at the end of six months of observation. Analysis of adult worms isolated from nodules obtained two months after the start of therapy showed no effect of either drug on viability. Ivermectin appears to be a better tolerated, safer, and more effective microfilaricidal agent than diethylcarbamazine for the treatment of onchocerciasis.     

Treatment of human onchocerciasis with ivermectin

Twenty immigrants from Mali and West Senegal were treated in Paris. Onchocerciasis was diagnosed by six skin snips using a Holth punch. Ivermectine was given in a single oral dose: ten patients were given 50 mcg/kg, three were given 75 mcg/kg and seven received 100 mcg/kg. No patients had ocular symptoms. The results were as follows: Pruritus disappeared rapidly in 9 out of 11 patients who itched before treatment. The microfilarial load decreased rapidly, especially in cases treated with 75 mcg/kg and 100 mcg/kg as all patients tested on day 60 were negative. Clinical signs of the Mazzotti reaction and ocular reactions were not observed following the treatment. Pruritus was briefly aggravated in only two patients. No cardiovascular, hematological, hepatic or renal toxicity was noted.     

Wolbachia endobacteria depletion by doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis: a randomized placebo-controlled study

In a randomized, placebo-controlled trial in Ghana, 67 onchocerciasis patients received 200-mg/day doxycycline for 4-6 weeks, followed by ivermectin (IVM) after 6 months. After 6-27 months, efficacy was evaluated by onchocercoma histology, PCR and microfilariae determination. Administration of doxycycline resulted in endobacteria depletion and female worm sterilization. The 6-week treatment was macrofilaricidal, with >60% of the female worms found dead, despite the presence of new, Wolbachia-containing worms acquired after the administration of doxycycline. Doxycycline may be developed as second-line drug for onchocerciasis, to be administered in areas without transmission, in foci with IVM resistance and in areas with Loa co-infections.     

Ivermectin in human onchocerciasis: a clinical-pathological study of skin lesions before and three days after treatment.

Findings are presented from an histological study of 360 skin-snips (from iliac crests, calves, ankles) taken from 30 Ivory Coast onchocerciasis patients before and three days after an oral dose of ivermectin (200 micrograms/kg). This dose causes a nearly complete disappearance of the intralymphatic microfilariae and, surprisingly, of the "extra-vascular" ones. That shows the difficulty to localize the microfilariae on histological sections; these microfilariae are in fact inside the lymphatic pre-capillaries. There was no intensification of acute skin lesions after the treatment, thus showing that, contrary to diethylcarbamazine (DEC), ivermectin does not induce an exit of microfilariae into the extralymphatic connective tissue. Under the influence of ivermectin, paralyzed microfilariae may be carried passively towards the deep sub-cutaneous lymphatics, and then destroyed inside the regional lymph nodes, without producing major changes in the skin.     

A study of ivermectin in the treatment of lymphatic filariasis due to Wuchereria bancrofti var. pacifica in French Polynesia

Forty carriers of 20 or more W. bancrofti var. pacifica per ml were blind administered ivermectin at 50, 100, 150 or 200 mcg/kg doses. The rate of successful treatment was 100% with the 4 dosages. The percentage cure rate and the decrease percentage in the microfilarial count were significantly higher in persons treated with 100, 150 and 200 mcg/kg than in persons treated with 50 mcg/kg. Frequency and intensity of side-reactions were similar to those observed during treatment with DEC; they were more frequent and severe in persons with greatest microfilaremia but did not depend on the dosage. Ivermectin in 100 mcg/kg single-dose, administered once a year, is the best candidate to replace DEC in mass treatments.     

Management in Senegal of the 1st efficacy and tolerability studies of ivermectin (MK 933) in human onchocerciasis

In 1981, 32 adult Senegalese males infected with Onchocerca volvulus but without ocular involvement were treated by groups of 8 with single oral dosages of 5, 10, 30 or 50 micrograms/kg of ivermectin . As soon as the second day after treatment, we observed a marked decrease of the dermal microfilaremic charge after a posology of 30 micrograms/kg. However the decrease is most important in the group subjected to 50 micrograms/kg and 75% of them had no more microfilariae in the dermis 28 days following treatment.     

Doxycycline as a novel strategy against bancroftian filariasis—depletion of<Emphasis Type="Italic"> Wolbachia</Emphasis> endosymbionts from<Emphasis Type="Italic"> Wuchereria bancrofti</Emphasis> and stop of microfilaria production

Chemotherapy of onchocerciasis by doxycycline, which targets symbiotic Wolbachia endobacteria, has been shown to result in a long-term sterility of adult female worms and corresponding absence of microfilariae. It represents an additional chemotherapeutic approach. The aim of this study was to determine whether a similar regimen would also show efficacy against Wuchereria bancrofti. Ghanaian individuals ( n=93) with lymphatic filariasis and a minimum microfilaremia of 40 microfilariae/ml were included in a treatment study consisting of four arms: (1) doxycycline 200 mg/day for 6 weeks; (2) doxycycline as in (1), followed by a single dose of ivermectin after 4 months; (3) ivermectin only; or (4) no treatment during observation period of 1 year (ivermectin at the end of the study). Doxycycline treatment resulted in a 96% loss of Wolbachia, as determined by real time PCR from microfilariae. After 12 months, doxycycline had led to a 99% reduction of microfilaremia when given alone, and to a complete amicrofilaremia together with ivermectin. In contrast, after ivermectin treatment alone a significant presence of microfilariae remained (9% compared to pretreatment), as known from other studies. This study shows that doxycycline is also effective in depleting Wolbachia from W. bancrofti. It is likely that the mechanism of doxycycline is similar to that in other filarial species, i.e., a predominant blockade of embryogenesis, leading to a decline of microfilariae according to their half-life. This could render doxycycline treatment an additional tool for the treatment of microfilaria-associated diseases in bancroftian filariasis, such as tropical pulmonary eosinophilia and microfiluria.     

The murid filaria Monanema martini: a model for onchocerciasis. Part I. Description of lesions.

A study of the anatomo-pathological lesions induced by Monanema martini, a filaria with skin-dwelling microfilariae, was performed using 65 Lemniscomys striatus fixed from 30 minutes to 36 months after inoculation of the infective larvae, 5 Arvicanthis niloticus and 3 Meriones unguiculatus fixed during the patent phase, and controls. Attempts at quantification of lesions in L. striatus was made. Approximately 20% of L. striatus had microfilariae in the eyeballs, and many more presented ocular lesions. The delay of the patent period seems to have more effects on the gravity of lesions than repeated inoculations. The location of the lesions and parasites presuppose that microfilariae enter the eyeball through the lymphatic capillaries of the irido-corneal angles. Cutaneous lesions were often severe: there is a parallel between the importance of lesions and the abundance of microfilariae. Larvae are responsible for damage to various structures of the lymphatic system (thrombo-lymphangitis, acute or granulomatous lymphadenitis...) into which they migrate, explaining the mechanism of elephantiasis. These rodent lesions appear similar to those observed in human onchocerciasis and lymphatic filariasis. Whatever the M. martini stage and the organ examined, major lesions belonged to the inflammatory process. Various types of inflammatory reaction (acute, subacute, or chronic inflammation, scarring sclerosis etc.) can co-exist within a single tissue area. The accidental escape of a microfilaria from a lymphatic capillary into the connective tissue (including the corneal stroma) induces an inflammatory reaction. Thus M. martini, as human Onchocerca species, causes a chronic disease, associating recent lesions to old ones.     

Tolerance of ivermectin treatment of rural communities infected by savannah onchocerciasis in Mali]

In an open clinical trial in phase IV, 856 onchocerciasis infected subjects received 150 micrograms/kg of ivermectin in May 1987. While 607 were included as witness. This cohort was revisited 7 and 12 months after. In June 1988, the same treatment was administrated to the previously treated subjects, and the witnesses received their first ivermectin' dose. The clinical tolerance of the treatment appears good and, even improved during the second dose one year after. Among the subjects treated in May 1987, 15.2% of them showed secondary reactions mostly discrete or moderate, precocious and quickly reversible after a second dose. Only 8 of them were incommodated in their daily occupations. A second treatment of these same subjects one year later, caused reactions of feeble intensity 3.7% only. The research of intolerance risk factors, incriminated the high density of microfilaremia. This incite to be careful in mass treatment of hyperendemic area.     

Wolbachia-induced neutrophil activation in a mouse model of ocular onchocerciasis (river blindness)

Endosymbiotic Wolbachia bacteria are abundant in the filarial nematodes that cause onchocerciasis (river blindness), including the larvae (microfilariae) that migrate into the cornea. Using a mouse model of ocular onchocerciasis, we recently demonstrated that it is these endosymbiotic bacteria rather than the nematodes per se that induce neutrophil infiltration to the corneal stroma and loss of corneal clarity (Saint Andre et al., Science 295:1892-1895, 2002). To better understand the role of Wolbachia organisms in the pathogenesis of this disease, we examined the fate of these bacteria in the cornea by immunoelectron microscopy. Microfilariae harboring Wolbachia organisms were injected into mouse corneas, and bacteria were detected with antibody to Wolbachia surface protein. Within 18 h of injection, neutrophils completely surrounded the nematodes and were in close proximity to Wolbachia organisms. Wolbachia surface protein labeling was also prominent in neutrophil phagosomes, indicating neutrophil ingestion of Wolbachia organisms. Furthermore, the presence of numerous electron-dense granules around the phagosomes indicated that neutrophils were activated. To determine if Wolbachia organisms directly activate neutrophils, peritoneal neutrophils were incubated with either parasite extracts containing Wolbachia organisms, parasite extracts depleted of Wolbachia organisms (by antibiotic treatment of worms), or Wolbachia organisms isolated from filarial nematodes. After 18 h of incubation, we found that isolated Wolbachia organisms stimulated production of tumor necrosis factor alpha and CXC chemokines macrophage inflammatory protein 2 and KC by neutrophils in a dose-dependent manner. Similarly, these cytokines were induced by filarial extracts containing Wolbachia organisms but not by Wolbachia-depleted extracts. Taken together, these findings indicate that neutrophil activation is an important mechanism by which Wolbachia organisms contribute to the pathogenesis of ocular onchocerciasis.     

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-γ) in response to mitogenic stimulation with phytohaemagglutinin (PHA); in response to OvAg, however, significantly more IL-2 and IFN-γ 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-γ in amicrofilaridermic individuals may contribute to controlling O. volvulus infection.     

Immunopathology of ocular onchocerciasis. I. Inflammatory cells infiltrating the anterior segment.

Ocular tissue (conjunctiva and iris) was obtained from 12 adult African men with active ocular onchocerciasis and from nine age-matched persons from the same endemic region but without onchocercal infection. These tissues were examined immunohistologically and two major findings were noted. First, mild-to-moderate chronic inflammatory cellular infiltration was present in the conjunctiva of the onchocerciasis patients. T lymphocytes (CD3+) were the major inflammatory cells, and the T suppressor/cytotoxic (CD8+) subset was significantly increased in the ocular onchocerciasis patients (P less than 0.03). Second, in the onchocerciasis patients, non-lymphoid cells of the conjunctiva and iris, such as vascular endothelium, pericytes and fibroblasts were in an activated state, as shown by increased expression of Class II MHC antigens (P less than 0.02, conjunctiva; P less than 0.05, iris). These concomitant findings of lymphocyte infiltration and resident cell activation indicate a dynamic state of localized host responsiveness presumably to the microfilarial parasites and their products in the anterior segments of the eyes of patients with ocular onchocerciasis.     

Effects of 6-week azithromycin treatment on the <Emphasis Type="Italic">Wolbachia</Emphasis> endobacteria of <Emphasis Type="Italic">Onchocerca volvulus</Emphasis>

The effects of azithromycin treatment on the presence of Wolbachia endobacteria and on the embryogenesis and microfilariae production of Onchocerca volvulus were studied. In 2002, in an endemic area in Ghana, 37 onchocerciasis patients were treated for 6 weeks with azithromycin: 23 patients received 250 mg every day, and 14 took 1,200 mg once a week. After 6 and/or 12 months, all palpable worm nodules were extirpated from 31 treated and nine additional untreated patients, and the presence of Wolbachia and embryogenesis were assessed by immunohistology. In nodules taken 6 months after treatment with either dose and 12 months after 1,200 mg/week, the Wolbachia loads of the worms were not different from those of untreated worms. However, 12 months after the 250-mg/day azithromycin regimen, significantly less female worms (65% compared to 92% untreated ones) presented many Wolbachia, although the reduction was less pronounced than observed in other studies after treatment with doxycycline. Embryogenesis and microfilariae production were not reduced. It is concluded that azithromycin administered alone for 6 weeks at 250 mg/day or 1,200 mg/week is not suitable for treatment of human onchocerciasis. But daily azithromycin should be studied in combination with other drugs and with other doses.     

Can the thyrotropin (TSH) suppressive dose of L-thyroxine (T4) be individually predicted in athyroid patients?

TSH-suppressive doses of L-thyroxine (T4) are needed in the treatment of athyreotic cancer patients in order to prevent metastases. We were interested to know whether the TSH-suppressive dose can be predicted on a body weight-or body surface basis in athyreotic individuals, which might save them the control TRH-test. 92 athyreotic patients (22 men, 70 females; age 25-81, mean 50.4 yrs; body weight ranging from 48-114 kg, mean 73), who have been operated for differentiated thyroid cancer and who have had at least one treatment ablative doses of 131-I, were investigated. After 4 weeks without thyroid hormone supplementation (checked by TSH serum concentration above 20 microU/ml) patients were set on 150 mcg of L-T4/day. TSH serum concentration before and 20' after 200 mcg of TRH were measured by the ultrasensitive TSH kit of Behringwerke. Total and free T4 as well as total T3 were also measured by radioimmunoassay kits. TRH tests were performed 6 weeks after start of treatment in 51 patients and 8 or more weeks respectively in 41 patients. Only the inclusion of the influence of age (multiple correlation) yielded a significant positive correlation between basal TSH and L-T4 dose/body weight.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interleukin-12 modulates T-cell responses to microfilariae but fails to abrogate interleukin-5-dependent immunity in a mouse model of onchocerciasis

Infection of mice with microfilariae of Onchocerca lienalis induces high levels of protective immunity to reinfection, which is dependent on interleukin (IL)-5 but not IL-4. Here, we have investigated the effect of exogenous IL-12 administration during either the priming or effector phases of the immune response. When administered during priming, IL-12 induced down-regulation of parasite-specific serum immunoglobulin (Ig)E and up-regulation of IgG2a. Antigen-specific IL-4 responses were strongly suppressed, whilst blood eosinophil levels were partially reduced. When administered during a challenge infection, IL-12 did not significantly influence the balance of antibody isotypes, but partially reduced eosinophil production. Antigen-specific IL-4 responses were again completely ablated. Unusually, interferon-gamma (IFN-gamma) responses were not significantly affected following IL-12 administration, either during priming or after challenge infections. Moreover, despite a fall in antigen-specific IL-5 production, the expression of IL-5-dependent immunity, as determined by reduction in worm recoveries, was fully maintained. These data demonstrate that parasite-induced IL-4 can be abrogated without affecting protective immunity to Onchocerca microfilariae in mice. In view of the established role of IL-4 in pathogenesis, this may have important implications for the development of immunoprophylaxis aimed at microfilariae and the alleviation of pathology in onchocerciasis.     

Efficacy of 2- and 4-week rifampicin treatment on the <Emphasis Type="Italic">Wolbachia</Emphasis> of <Emphasis Type="Italic">Onchocerca volvulus</Emphasis>

The microfilaricidal and temporarily sterilizing drug ivermectin is used for mass treatment of filarial infections. Filariae containing Wolbachia endobacteria can also be treated by the antibiotic doxycycline. The loss of Wolbachia results in sterilization of Onchocerca volvulus and macrofilaricidal effects. Besides doxycycline, other antibiotics may be effective in depleting Wolbachia. A preliminary study on the effects of rifampicin on the endobacteria, embryogenesis and microfilariae production of O. volvulus was carried out in the year 2000 in Ghana. Twenty-six onchocerciasis patients were treated for 2 or 4 weeks with 10 mg/kg/day rifampicin. From 17 treated and nine untreated patients, all palpable nodules were extirpated 1 or 18 months after the start of the study and examined for Wolbachia and embryogenesis using immunohistology. One and 18 months after rifampicin treatment, the proportion of Wolbachia-positive worms was significantly reduced compared to the untreated group. In patients treated 4 weeks with rifampicin, only 21% and 18% of living female filariae contained Wolbachia after 1 and 18 months, respectively, compared to 92% in the untreated patients. The reduction of Wolbachia after 2 weeks rifampicin was less but also significant. Embryogenesis and microfilariae production were reduced after 4 weeks rifampicin treatment, rendering rifampicin an antibiotic with anti-wolbachial efficacy in human onchocerciasis. This treatment is less efficient than treatment with 6 weeks doxycycline, but might be an alternative for cases that cannot be treated with doxycycline, e.g. children, or might be further developed for combination therapy.