Improvement in severe onchocercal skin disease after a single dose of ivermectin.

PURPOSE: Skin disease is the most common clinically important manifestation of onchocerciasis. Ivermectin, a newly available drug, is well tolerated and effective in Onchocerca volvulus infection. However, little information is available regarding its effect on onchocercal skin disease. The purpose of this study was to examine, in patients with well-characterized onchodermatitis, the effect of a single dose of ivermectin. SUBJECTS AND METHODS: Twenty-one persons with severe onchodermatitis were followed over a 6-month period. In order to evaluate the effect of ivermectin on their skin lesions, photographic transparencies were made before treatment and at 3 and 6 months after treatment. These were then evaluated in a blinded fashion. RESULTS: Following a single dose of 150 micrograms/kg, there was a significant improvement in dermatitis in the first 3 months after treatment. All 14 persons with the worst skin disease showed improvement. The drug had no demonstrable effect on depigmented lesions over the period of observation. Treatment was well tolerated. CONCLUSION: Single-dose ivermectin shows promise as the first acceptable treatment for severe onchocercal dermatitis.

A comparison of 6-, 12-, and 24-monthly dosing with ivermectin for treatment of onchocerciasis.

This study was designed to examine the optimal dose and interval of administration of ivermectin, the now-accepted drug of choice for onchocerciasis. Two hundred Liberians with Onchocerca volvulus infection received 100, 150, or 200 micrograms/kg ivermectin or placebo and were followed for 36 months. The reaction after the second dose of ivermectin was significantly less than after the initial dose, although it was still significant in the 200-micrograms/kg group. The skin microfilaria counts in the group treated 6-monthly with 150 micrograms/kg was significantly less than in the group treated yearly (12 and 24 months after initial therapy). Prevalence of microfilariae in the anterior chamber and punctate corneal opacities decreased progressively in all groups over 3 years. There appears to be a slight advantage, in terms of antiparasitic effect over the first 2 years, of therapy given 6-monthly compared with yearly.

Safety of and compliance with community-based ivermectin therapy.

In a study of the safety, acceptability, and efficacy of ivermectin for community-based mass treatment of onchocerciasis, the drug was issued twice, one year apart, to the population of a rubber plantation (14,000 people) in Liberia, where over 80% of the adults have Onchocerca volvulus infection. The plantation microfilarial load in a sample of adults was reduced by 86% 6 months after initial treatment and by 78% after 1 year. Compliance was 97% with each round of treatment. After the initial treatment of 7699 people, 101 (1.3%) had moderate adverse reactions. After re-treatment only 37 (0.5%) people had moderate adverse reactions. No ivermectin-related death or severe adverse reactions occurred. The data show that community-based treatment with ivermectin is well accepted and effective in reducing microfilarial loads. Ivermectin is likely to provide the first realistic means of chemotherapy-based control of onchocerciasis on a mass scale.

A prospective study in high risk subjects of electrocardiographic changes with ivermectin.

Thirty-two elderly Liberian men, mean age 61 years, were treated with ivermectin and serial electrocardiograms (EKG's) were performed. Twenty of the 32 (62.5%) had baseline EKG abnormalities including poor R wave progression, 1 degrees AV block, non-specific intraventricular conduction abnormalities, left anterior hemiblock, supraventricular premature beats, left axis deviation, and early repolarization. Twelve lead EKG's were done twice daily, pretreatment and on five occasions post-treatment. No significant changes and no new abnormalities were observed. This study fails to demonstrate any significant cardiac effect of ivermectin.

Application of the verbal autopsy during a clinical trial.

During a community-based treatment trial of onchocerciasis with ivermectin, verbal autopsies were employed as one method to assess the safety of the drug. The verbal autopsy questionnaire was designed to determine causes of death and mortality differentials in the treated population. During the 8 months of surveillance here reported, 25 individuals died, yet only 9 of these deaths were certified. Seven of the deaths occurred to individuals who had been treated with ivermectin and the majority of the deaths occurred to children under 5, who were excluded from treatment. The verbal autopsy method was evaluated and validated by comparing the verbal autopsy diagnosis of cause of death to death certificate diagnosis, when available. In addition, verbal autopsies were retrospectively performed for all deaths which had occurred at the hospital during the 6 months preceding the start of the study, if these deaths were traceable to households in the surveillance population. We found that in 80% of the adult deaths, the verbal autopsy and death certificate diagnoses of underlying cause of death agreed. The verbal autopsy was less accurate in diagnosing child deaths which we attribute to the design of the verbal autopsy (being to detect potential drug related deaths in adults) and to the delay between death and interview. We conclude that verbal autopsies are an important addition to surveillance systems in remote areas where the absence or inadequacy of health information systems does not allow a thorough follow-up of all subjects in drug studies.

Ivermectin treatment of patients with severe ocular onchocerciasis.

The treatment of onchocerciasis with diethylcarbamazine and suramin is associated with an exacerbation of ocular disease. This occurs more frequently in patients with severe onchocercal ocular disease. We assessed ocular changes following ivermectin treatment in 39 patients with severe ocular onchocerciasis. Patients were treated with 100, 150, or 200 micrograms/kg of ivermectin at either 1 or 2 year intervals and followed for 3 years. There was no evidence for an acute exacerbation of either anterior or posterior segment eye disease, and there was a marked improvement in ocular status in the group as a whole. There was a significant decrease in onchocercal involvement which was maintained for at least 3 years. Annual treatment with ivermectin can be used safely in patients with severe ocular disease and is beneficial over a prolonged period of time.

Community-based treatment of onchocerciasis with ivermectin: acceptability and early adverse reactions.

A study of community-based treatment of onchocerciasis with ivermectin was undertaken in a rain forest area of Liberia to investigate the possible occurrence of serious adverse effects. The total population was 13,704, the microfilarial load was 5.35 mf/mg skin, and the prevalence of Onchocerca volvulus infection was 50% at 9 years of age and over 80% among those aged 15 years and older. Certain groups (like pregnant women and young children) were excluded from treatment. Out of the 7956 people eligible for treatment, 7699 (97%) accepted the ivermectin. Data on possible adverse reactions were collected by four different methods, including systematic house-by-house follow-up visits three days after treatment, biweekly population surveillance, and monitoring of both mobile clinic records and hospital records. No severe adverse reactions were noted, and no deaths could be related to ivermectin treatment; only 1.3% of the persons treated had a moderate adverse reaction of the Mazzotti type, presumably related to the killing of microfilariae. The study showed good acceptance by the population, and that mass treatment campaigns with ivermectin are feasible.

Community-based treatment of onchocersiasis with ivermectin: acceptability and early adverse reactions

A study of community-based treatment of onchocerciasis with invermectin was undertaken in a rain forest area of Liberia to investigate the possible occurrence of serious adverse effects. The total population was 13,704, the microfilarial load was 5.35 mf/mg skin, and the prevalence of Onchocerca volvulus infection was 50 percent at 9 years of age and over 80 percent among those aged 15 years and older. Certain groups (like pregnant women and young children) were excluded from treatment

Out of the 7,956 people eligible for treatment, 7,699 (97 percent) accepted the ivermectin. Data on possible adverse reactions were collected by four different methods, including systematic house-by-house follow-up vistis three days after treatment, biweekly population surveillance, and monitoring of both mobile clinic records and hospital records. No severe adverse reactions were noted, and no deaths could be related to ivermectin treatment; only 1.3 percent of the persons treated had a moderate adverse reaction of the Mazzotti type, presumably related to the killing of microfilariae. The study showed good acceptance by the population, and that mass treatment campaigns with invermectin are feasible(AU)