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A placebo-controlled double-blind trial for the treatment of bancroftian filariasis with ivermectin or diethylcarbamazine.

Therapeutic efficacy and clinical side-effects of ivermectin (single dose of 100 micrograms/kg) and diethylcarbamazine (DEC) (3 mg/kg for one day, then 6 mg/kg daily for 12 d) were evaluated for microfilaricidal effect in Bancroftian filariasis. Seventy-one microfilaraemic consenting adult male patients (greater than or equal to 100 microfilariae (mf)/ml) were randomly assigned to receive ivermectin, DEC or placebo and kept in hospital for 15 d. Those receiving placebo were treated with ivermectin on day 9. Ivermectin (19 'double-blinded' and 22 'unblinded' patients) caused an abrupt reduction in mf count to 1.5% of the pre-treatment level 12 h after drug administration and to 0.06% on day 14, with recrudescence to 1.8% after one month and to 9.2% after 3 months. DEC (30 patients) caused a gradual drop in mf count to 1.1% of the pre-treatment level on day 14, which increased to 2.4% after one and 3 months. The total scores of side-effects were 77 (1%), 305 (2.1%) and 311.5 (3.0%) for placebo, ivermectin and DEC respectively; the differences between DEC or ivermectin and placebo were statistically significant. Ivermectin produced lower side-reaction scores than DEC and the differences were highly significant at the 95% confidence level. Side-effects were mainly headache and body aches in the ivermectin patients, which appeared as early as 4 h after drug administration, resolved within 36 to 48 hours, and were significantly related to mf densities. Side-effects in DEC patients were mainly testicular and epididymal pain and swelling, unrelated to mf densities, which began at day 2 and continued to day 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Adverse reactions to ivermectin treatment for onchocerciasis. Results of a placebo-controlled, double-blind trial in Malawi.

A three-year placebo-controlled, double-blind trial involving 7148 persons was conducted to determine adverse reactions to ivermectin given annually for treatment of onchocerciasis by mass distribution. Musculoskeletal pains, oedema of the face or extremities, itching and papular rash were statistically associated with ivermectin treatment in the first year. In the second year of treatment these reactions were less frequently reported, although still more prevalent in ivermectin recipients. During the third year of treatment all persons received ivermectin. Persons who had missed ivermectin treatment in the second year did not have significantly more adverse reactions after treatment in the third year. Those who had received placebo during the first 2 years reported some adverse reactions more frequently following ivermectin than did those who had received ivermectin from the beginning of the study. Oedema was the adverse reaction of greatest concern to patients and this involved the face most commonly. A single episode of bullous skin lesions developed in 5 persons who had received ivermectin. These lesions did not reoccur with subsequent treatment. No episode of hypotension after treatment was observed.

Adolescent↗

Efficacy of topically applied ivermectin against Boophilus microplus (Canestrini, 1887) in cattle.

Systemic efficacy of ivermectin applied topically was evaluated against the cattle tick, Boophilus microplus. Twenty cattle with induced infestations were randomly allocated to five groups of equal size based on the numbers of engorged female ticks which fell through the slatted floor of individual pens during the 3 days prior to treatments. Control cattle were non-medicated. Cattle in three groups were given ivermectin at 200, 500 or 1000 mcg kg-1 in a topical formulation applied along the backline from the withers to the rump; cattle in the fifth group were given ivermectin in an injectable formulation subcutaneously at 200 mcg kg-1. Individual 24-h tick collections were made three times weekly for 5 weeks after treatment. Engorged female B. microplus were incubated to determine effects on reproduction. Based on the numbers of engorged female B. microplus collected following treatments, overall efficacy of ivermectin applied topically at 200, 500 and 1000 mcg kg-1 was 50, 85 and 91%, respectively, whereas ivermectin given at 200 mcg kg-1 subcutaneously was 80% effective. The index of reproduction for ivermectin given topically was reduced by 84, 94 and 95%, respectively, and that for ivermectin subcutaneously was 94%. No significant differences (P greater than 0.05) were found for these variables between ivermectin given topically at 500 or 1000 mcg kg-1 versus 200 mcg kg-1 given subcutaneously.

Administration, Topical↗

Effect of ivermectin on feeding by Haemonchus contortus in vivo.

While several in vitro studies have shown that the anthelmintic ivermectin inhibits feeding by parasites, the relevance of this putative site of action in vivo has not been demonstrated. For this study, techniques to measure feeding by Haemonchus contortus in vivo relied on the blood feeding characteristics of the worm, and utilised tritiated inulin administered to sheep intravenously and subsequently measured in worms recovered from abomasa. Nematodes recovered from sheep treated with ivermectin 4 h prior to the [3H]inulin administration showed equivalent feeding levels (over a 1 h period) to those recovered from sheep not treated with ivermectin. In addition, there was no difference in the radioactivity in nematodes of an ivermectin-susceptible and an ivermectin-resistant isolate recovered from individual sheep with concurrent infections after a dose with ivermectin. Ivermectin, therefore, had no effect on feeding by H. contortus in vivo under these experimental conditions. The results are discussed in relation to the dynamics of the expulsion of H. contortus from sheep following ivermectin treatment.

Abomasum↗

Prolonged clearance of microfilaraemia in patients with bancroftian filariasis after multiple high doses of ivermectin or diethylcarbamazine.

In a double-blind trial on 37 asymptomatic microfilaraemic subjects (minimum 400 microfilariae [mf] per mL) with Wuchereria bancrofti infection, the safety, tolerability and macrofilaricidal efficacy of 12 fortnightly doses of ivermectin, 400 micrograms/kg (ivermectin group), was compared with 12 fortnightly doses of diethylcarbamazine (DEC), 10 mg/kg (DEC group), over a period of 129 weeks after treatment. A control group (LDIC group) was treated with low dose ivermectin to clear microfilaraemia, for ethical reasons. Both ivermectin and DEC in high multiple doses were well tolerated and clinically safe. Macrofilaricidal efficacy was assessed by prolonged clearance of microfilaraemia, appearance of local lesions, and reduction of circulating W. bancrofti adult antigen detected by an antigen capture enzyme-linked immunoassay based on the monoclonal antibody AD12. Mf counts fell more rapidly after ivermectin than after DEC, but low residual mf levels were equivalent in these groups after week 4. Conversely, filarial antigen levels fell more rapidly after DEC than after ivermectin, but low residual antigen levels in these groups were statistically equivalent at all times beyond 12 weeks. Mild, self-limited systemic reactions to therapy were observed in all 3 treatment groups. Local reactions, such as development of scrotal nodules, were observed in several subjects in the DEC and ivermectin groups. These results suggested that high dose ivermectin and DEC both had significant macrofilaricidal activity against W. bancrofti, but neither of these intensive therapeutic regimens consistently produced complete cures. Thus, new drugs or dosing schedules are needed to achieve the goal of killing all filarial parasites in the majority of patients.

Animals↗

[Systemic adverse reactions with ivermectin treatment of scabies].

BACKGROUND: Scabies is a common parasitic infestation and is very difficult to eradicate from institutions. Ivermectin is used extensively thanks to its efficacy and ease of use through oral administration; it was approved for the treatment of scabies in humans in 2001 in France. Most of the adverse effects noted with this drug have been seen during treatment of onchocerciasis and other filarial disease, but they are rare in the treatment of scabies. We report side effects with ivermectin in two elderly patients with scabies. CASES REPORT: A 72-year-old man was referred for scabies and was treated with benzyl benzoate (Ascabiol) and ivermectin (200 microg/kg) in a single dose. Two days later, the patient presented abdominal pain and nausea. Laboratory tests revealed cytolysis tests for other causes of hepatitis were negative. Within two weeks, liver function had returned to normal. Hepatitis due to ivermectin was diagnosed. An 86-year-old woman hospitalised for scabies was treated with benzyl benzoate and a single dose of ivermectin (200 microg/kg). She developed sinus tachycardia and asthma 3 days later. Screening for embolic, cardiac and infectious origins was found. Toxicity of ivermectin was suspected. DISCUSSION: Since the introduction of ivermectin for the treatment of scabies, reports of adverse events are rare although this drug can cause cardiac dysfunction and liver disease in other indications. In our cases, the causal relationship with ivermectin is probable and care must be taken, particularly in the elderly, the population in which this drug is probably most widely prescribed.

Aged↗

Treatment and prophylaxis of psoroptic mange (sheep scab) using an ivermectin intraruminal controlled-release bolus for sheep.

In an experiment to determine the therapeutic efficacy of an ivermectin intraruminal controlled-release (CR) bolus, 14 mixed breed sheep of one lot were infested with Psoroptes ovis and subsequently divided into two groups of seven. In one of these groups each sheep received one ivermectin CR bolus appropriate to its weight, the other group remained as an untreated control. All mites were eliminated from the group receiving the bolus while the control group remained infested, the disease progressed, and all but one sheep required treatment for psoroptic mange before the end of the experimental period. A second lot of 14 sheep, free from P. ovis, were divided equally into two groups to determine the prophylactic efficacy of the ivermectin CR bolus. In one group, each sheep was given an ivermectin CR bolus according to body weight and the sheep in the other group received no medication and served as untreated controls. Twenty-one days later two sheep infested with psoroptic mange were introduced into each of the groups. These donor sheep were removed 10 days later. The group treated with the ivermectin CR bolus remained mange-free and did not harbour any mites. All of the sheep in the control group developed psoroptic mange and required treatment to control the infestation at the end of the experimental period. Sheep that received the ivermectin CR bolus had greater mean weight gains than the control groups in these experiments. The ivermectin CR bolus releases a minimum dose of 20 microg ivermectin kg/day for 100 days: this prolonged activity should prove a valuable asset for the treatment and control of psoroptic mange in sheep.

Animals↗

On the distribution of a fluorescent ivermectin probe (4" 5,7 dimethyl-bodipy proprionylivermectin) in Ascaris membranes.

The distribution of the fluorescent ivermectin derivative (4" 5,7 dimethyl bodipy proprionylivermectin, referred to here as bodipy ivermectin) was studied in muscle vesicle membranes from the parasite Ascaris suum. Incubation in bodipy ivermectin, at concentrations greater than 1 ng/ml, produced a dose-dependent fluorescence in the vesicles. The level of fluorescence was not depressed (but increased) by prior incubation with 1 microM unlabelled ivermectin. This observation suggested that most of the bodipy ivermectin was free in the lipid phase of the membrane and not associated with a receptor. The trypan blue quenching technique showed that the bodipy ivermectin did not cross the membrane bilayer but remained in the outer monolayer. Lateral mobility of the probe in the membrane was studied using the fluorescence recovery after photobleaching (FRAP) technique. The lateral diffusion coefficient (DL) was 14.0 x 10(-10) cm2/s which was nearly three times faster than the lipid probe octadecanoyl-aminofluorescein in membranes from the same preparations; only 46% of the probe was mobile, showing that within a 1.2 microns radius the distribution of the bodipy ivermectin in the membrane was not homogeneous. These observations are used to suggest that: the site of action of ivermectin is located in the outer monolayer of the membrane (possibly on the Cl- channel); and that the speed of onset of action in isolated membrane preparations may be limited by diffusion in the membrane.

Animals↗

L-glutamate binding sites of parasitic nematodes: an association with ivermectin resistance?

Nematode membrane preparations contain high amounts of low-affinity specific L-glutamate binding sites. The numbers of these sites were increased in 2 isolates, one field-derived and the other laboratory-derived, of ivermectin-resistant Haemonchus contortus and a field isolate of ivermectin-resistant Telodorsagia circumcincta, when compared to control, drug-sensitive isolates. Specific [3H]ivermectin binding to these membrane preparations showed no differences between ivermectin-sensitive and resistant isolates and the number of ivermectin binding sites was approximately 100-fold less than the number of L-glutamate binding sites. Kinetic analysis of L-glutamate binding suggested the presence of at least 2 classes of binding site. L-Glutamate binding was blocked by ibotenic acid, kynurenic acid and beta-hydroxyaspartate, but not by ivermectin, argiopine, kainate, quisqualate or NMDA. Competition assays with ibotenic acid suggested that there were 2 distinct populations of glutamate binding sites and that the site with the lower affinity for ibotenate was upregulated in the ivermectin-resistant nematodes. In the field isolate of resistant H. contortus we found no coding changes in the cDNAs encoding glutamate-gated chloride channel subunits HG2, HG3 and HG4, nor were any changes in channel expression detected using subunit-specific antibodies. The low-affinity binding site is unlikely to be associated with the ivermectin receptor in these nematodes.

Animals↗

Ivermectin and nodulisporic acid receptors in Drosophila melanogaster contain both gamma-aminobutyric acid-gated Rdl and glutamate-gated GluCl alpha chloride channel subunits.

35S-labeled derivatives of the insecticides nodulisporic acid and ivermectin were synthesized and demonstrated to bind with high affinity to a population of receptors in Drosophila head membranes that were previously shown to be associated with a glutamate-gated chloride channel. Nodulisporic acid binding was modeled as binding to a single population of receptors. Ivermectin binding was composed of at least two kinetically distinct receptor populations, only one of which was associated with nodulisporic acid binding. The binding of these two ligands was modulated by glutamate, ivermectin, and antagonists of invertebrate gamma-aminobutyric acid (GABA)ergic receptors. Because solubilized nodulisporic acid and ivermectin receptors comigrated as 230-kDa complexes by gel filtration, antisera specific for both the Drosophila glutamate-gated chloride channel subunit GluCl alpha (DmGluCl alpha) and the GABA-gated chloride channel subunit Rdl (DmRdl) proteins were generated and used to examine the possible coassembly of these two subunits within a single receptor complex. DmGluCl alpha antibodies immunoprecipitated all of the ivermectin and nodulisporic acid receptors solubilized by detergent from Drosophila head membranes. DmRdl antibodies also immunoprecipitated all solubilized nodulisporic receptors, but only approximately 70% of the ivermectin receptors. These data suggest that both DmGluCl alpha and DmRdl are components of nodulisporic acid and ivermectin receptors, and that there also exists a distinct class of ivermectin receptors that contains the DmGluCl alpha subunit but not the DmRdl subunit. This co-association of DmGluCl alpha and DmRdl represents the first biochemical and immunological evidence of coassembly of subunits from two different subclasses of ligand-gated ion channel subunits.

Animals↗

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.

Adult↗

The treatment of scabies with ivermectin.

BACKGROUND: Ivermectin is an anthelmintic agent that has been a safe, effective treatment for onchocerciasis (river blindness) when given in a single oral dose of 150 to 200 micrograms per kilogram of body weight. Anecdotal reports of improvement in patients who suffered from infestation with the mite Sarcoptes scabiei suggest that the ectoparasitic disease scabies might be treated with ivermectin. METHODS: We conducted an open-label study in which ivermectin was administered in a single oral dose of 200 micrograms per kilogram to 11 otherwise healthy patients with scabies and to 11 patients with scabies who were also infected with the human immunodeficiency virus (HIV), 7 of whom had the acquired immunodeficiency syndrome. All patients received a full physical and dermatologic examination; scrapings from the skin of all patients tested positive for scabies. Patients were reexamined two and four weeks after treatment, when the scrapings for scabies were repeated. The patients used no other scabicides during the 30 days before ivermectin treatment or during the 4-week study period. RESULTS: None of the 11 otherwise healthy patients had evidence of scabies four weeks after a single dose of ivermectin. Of the 11 HIV-infected patients, 2 had < or = 10 scabies lesions before treatment, 3 had 11 to 49 lesions, 4 had > or = 50 lesions, and 2 had heavily crusted skin lesions. In eight of the patients the scabies was cured after a single dose of ivermectin. Two patients received a second dose two weeks after the first. Ten of the 11 patients with HIV infection (91 percent) had no evidence of scabies four weeks after their first treatment with ivermectin. CONCLUSIONS: The anthelmintic agent ivermectin, given in a single oral dose, is an effective treatment for scabies in otherwise healthy patients and in many patients with HIV infection.

Acquired Immunodeficiency Syndrome↗

The safety and efficacy of amocarzine in African onchocerciasis and the influence of ivermectin on the clinical and parasitological response to treatment.

The hundred men from a forest area of Ghana, without vector control or ivermectin distribution, were randomized to receive a single dose of ivermectin (150 micrograms/kg body weight) on day 1 followed by amocarzine (3 mg/kg twice daily after meals) on days 8, 9 and 10 (34 patients), the ivermectin alone (33 patients) or the amocarzine alone (33 patients). Detailed clinical and laboratory examinations were made before, during and after drug administration. On day 120, all palpable nodules were excised, fixed, sectioned, stained and examined by two blinded observers and the results compared with those for nodules from untreated controls. Mazzotti-type reactions, such as itching, rash, peripheral sensory phenomena and swellings, were more severe or frequent with amocarzine than ivermectin. Pretreatment with ivermectin markedly suppressed these reactions to amocarzine but did not affect other manifestations such as dizziness and gaze-evoked nystagmus. Ocular effects were minor in all groups. Ivermectin produced minor macrofilaricidal effects on the adult male worms, marked degeneration of intra-uterine embryos, and potent microfilaricidal effects and suppressed skin microfilariae. Amocarzine did not affect the male worms or the intra-uterine embryos, was a less potent microfilaricide and did not suppress skin microfilariae. The efficacy of ivermectin plus amocarzine was similar to that of ivermectin alone. The present results do not support the findings from the Americas and show that amocarzine has no role in the treatment of onchocerciasis in Africa.

Adolescent↗

First documentation of in vivo and in vitro ivermectin resistance in Sarcoptes scabiei.

Ivermectin is increasingly being used to treat scabies, especially crusted (Norwegian) scabies. However, treatment failures, recrudescence, and reinfection can occur, even after multiple doses. Ivermectin resistance has been documented for some intestinal helminths in animals with intensive ivermectin exposure. Ivermectin resistance has also been induced in arthropods in laboratory experiments but, to date, has not been documented among arthropods in nature. We report clinical and in vitro evidence of ivermectin resistance in 2 patients with multiple recurrences of crusted scabies who had previously received 30 and 58 doses of ivermectin over 4 and 4.5 years, respectively. As predicted, ivermectin resistance in scabies mites can develop after intensive ivermectin use.

Adult↗

Maintaining compliance to ivermectin in communities in two West African countries.

We have investigated various aspects related to managing wide-scale ivermectin distribution schemes within randomized controlled trials in communities where onchocerciasis is endemic. Multiple logistic regression analysis of determinants of compliance to five doses of ivermectin in 589 people in Sierra Leone showed independent significant associations with leopard skin depigmentation, the severity of side effects of treatment, fulfilling the exclusion criteria for treatment, and long-term residence in the community. These results are useful for tailoring health promotion messages in Sierra Leone, but the associations may differ in other West African societies. In Nigeria 1847 people were interviewed about various subjective responses, including itching. None of these showed clear improvement after three years of ivermectin treatment. Positive comments about treatment were generally non-specific and similar in the placebo and ivermectin groups. Negative comments were usually related to adverse reactions, especially itching and rash, and were more common after ivermectin. The lack of any benefit attributable to ivermectin that is discernible to its recipients may make it difficult to maintain the high compliance rates needed for long periods if mass dosing programmes are to have a lasting impact on onchocerciasis. In addition, no consistent effects of ivermectin were found by measuring visual acuity, height, weight or haematocrit in comparison with placebo. This may indicate that evidence of clinical impact is very slow to develop and is hard to measure using simple objective methods after only three doses of treatment. At present it seems that parasitological, entomological and detailed ophthalmological or dermatological methods are required to demonstrate the impact of ivermectin treatment in the medium-term.

Adolescent↗

Oral ivermectin treatment in two cases of scabies: effective in crusted scabies induced by corticosteroid but ineffective in nail scabies.

We report two cases of scabies treated with oral ivermectin (200 micro g/kg). Case 1, a 72-year-old man, developed crusted scabies with the use of oral corticosteroids due to a misdiagnosis by an earlier physician. The patient was successfully treated with two doses of oral ivermectin at a 7 day interval with concomitant topical use of crotamiton and keratolytic agents. However, the nail scabies in this patient failed to respond to these treatments. Live mites were detected from all his toenails two weeks after the second dose of ivermectin. A complete cure of the nail scabies was achieved by occlusive dressing of 1% gamma-BHC on all toenails for one month. Case 2, a 52-year-old woman, had been treated with oral corticosteroid for mesangial nephritis. She developed common scabies, but a topical scabicide, crotamiton, was not effective. Two weeks after treatment with a single dose of oral ivermectin, eggs were still detected from a burrow on her trunk. Her treatment was completed after a further two doses of oral ivermectin were administered at 7 day intervals. In both patients, the administration of oral ivermectin did not induce any clinical or laboratory side effects. Oral ivermectin is effective for crusted scabies, but not effective for nail scabies. Two doses of oral ivermectin, administered with a one-week interval, is an appropriate treatment regimen.

Administration, Cutaneous↗

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.

Adolescent↗

The impact of ivermectin treatment alone and when in parallel with Simulium neavei elimination on onchocerciasis in Uganda.

The study was conducted in August 2002 in Kigoyera parish in Kyenjojo district, where ivermectin treatment had been the strategy to control onchocerciasis since 1991 and was later supplemented with Simulium neavei control in 1995 and subsequent elimination; and in July 2003 in Kicece parish in Kamwenge district, where ivermectin treatment alone had been the strategy used to control onchocerciasis since 1991. Our objective was to examine and compare the impact of ivermectin treatment alone and when in parallel with S. neavei elimination on nodule and microfilariae carrier rates and on onchocercal dermatitis to provide baseline data that could be used to monitor the trends of microfilariae carrier rates for decision-making on when to discontinue ivermectin treatment. The combined interventions had significantly reduced onchocercal dermatitis from 34% pre-control to 2.9% (P < 0.001), microfilariae carrier rate from 88 to 7.5% (P < 0.001) and nodule prevalence from 49 to 19.2% (P < 0.001). Ivermectin treatment alone had also reduced onchocercal dermatitis prevalence from 34.2% pre-control to 9.5% (P < 0.001), the microfilariae carrier rate from 78 to 27.8% (P < 0.001) and nodule prevalence from 49.1 to 14.2% (P < 0.001). None of the children under 10 years were nodule or microfilariae carriers in both study areas. Histological examination of eight nodules extirpated from patients in Kigoyera identified five male and 12 female adult worms that were all old and alive. Five live and one dead female worms and one live male worm were identified from nodules extirpated from patients in Kicece. There was no female worm with embryogenesis from the nodules obtained from Kigoyera while two female worms from five nodules obtained from Kicece still showed a few embryos. Two female worms in each of the study area had sperms in uteri indicating that male worms were still active. Ivermectin treatment in parallel with vector elimination had a greater impact on onchocercal dermatitis and microfilariae carrier rates than ivermectin treatment alone. It would be worthwhile considering supplementation of ivermectin treatment with vector elimination in all isolated foci with S. neavei transmission to hasten the elimination of onchocerciasis as a public health and socio-economic problem in those foci.

Adolescent↗