Elsevier

The Lancet

Volume 350, Issue 9070, 5 July 1997, Pages 18-22
The Lancet

Articles
Serious reactions after mass treatment of onchocerciasis with ivermectin in an area endemic for Loa loa infection

https://doi.org/10.1016/S0140-6736(96)11094-1Get rights and content

Summary

Background

In 1995, the World Bank launched an African Programme for Onchocerciasis Control to eliminate Onchocerca volvulus disease from 19 African countries by means of community-based ivermectin treatment (CBIT). Several cases of encephalopathy have been reported after ivermectin in people heavily infected with microfilariae of Loa loa (loiasis). We assessed the incidence of serious events in an area where onchocerciasis and loiasis are both endemic.

Methods

Ivermectin (at 150 μg/kg) was given to 17 877 people living in the Lékié area of Cameroon. 50 μL samples of capillary blood were taken during the daytime before treatment from all adults (aged ≥15 years), and the numbers of L loa and Mansonella perstans microfilariae in them were counted. Patients were monitored for 7 days after treatment. Adverse reactions were classified as mild, marked, or serious. Serious reactions were defined as those associated with a functional impairment that required at least a week of full-time assistance to undertake normal activities. We calculated the relative risk of developing marked or serious reactions for increasing L loa microfilarial loads. Risk factors for serious reactions were identified and assessed with a logistic regression model.

Findings

20 patients (0·11%) developed serious reactions without neurological signs but associated with a functional impairment lasting more than a week. Two other patients were in coma for 2–3 days, associated with L loa microfilariae in cerebrospinal fluid. Occurrence of serious reactions was related to the intensity of pretreatment L loa microfilaraemia. The relative risk of developing marked or serious reactions was significantly higher when the L loa load exceeded 8000 microfilariae/mL; for serious reactions, the risk is very high (odds ratio >1000) for loads above 50 000 microfilariae/mL.

Interpretation

Epidemiological surveys aimed at assessing the intensity of infection with L loa microfilariae should be done before ivermectin is distributed for onchocerciasis control in areas where loiasis is endemic. In communities at risk, monitoring procedures should be established and adhered to during CBIT so that people developing serious reactions may receive appropriate treatment.

Introduction

Onchocerciasis is a major public-health and socio-economic problem in many rural areas of Africa. In the 19 endemic countries outside the area of the Onchocerciasis Control Progamme in West Africa (OCP), some 94·5 million people are exposed to the risk of infection with Onchocerca volvulus, and more than 15 million are infected.1 In parts of 12 of these countries, Loa loa infections are also endemic.

Ivermectin has proven to be a safe microfilaricide and microfilarial suppressant, suitable for the mass treatment and control of onchocerciasis;2, 3, 4, 5, 6 and the manufacturer, now provides the drug free of charge for the treatment and control of onchocerciasis in endemic countries. Mass ivermectin distribution programmes are now being implemented in most endemic countries. In December, 1995, the World Bank, in cooperation with WHO, the ministries of health of the participating countries, and several non-governmental development organisations, launched the African Programme for Onchocerciasis Control (APOC), which aims to develop self-sustaining, countrywide, community-based ivermectin treatment (CBIT) programmes in the 19 endemic African countries outside the OCP.7

APOC's strategy is to deliver ivermectin by community-based distributors supervised only by monitoring teams. In areas where loiasis is also endemic, some cases of encephalopathy have been recorded after treatment with ivermectin.8, 9, 10 These patients had very high L loa microfilaraemia and L loa microfilariae in cerebrospinal fluid (CSF), suggesting that ivermectin may occasionally provoke an L loa encephalopathy similar to that seen after treatment of loiasis with diethylcarbamazine.11

The aims of this study were to evaluate the incidence of serious reactions after treatment with ivermectin in an area of Cameroon where onchocerciasis and loiasis are both endemic, and to record the relation between serious reactions and the intensity of pretreatment L loa microfilaraemia.

Section snippets

Patients and methods

The study protocol, which was approved by the Ministry of Public Health of Cameroon and by WHO, involved 1-week follow-up of a cohort of people treated with ivermectin. The study was conducted in 106 villages of the Lékié Division (Central Province, Cameroon; figure 1), where 40–95% of the residents were infected with O volvulus, and 10–33% had L loa microfilaraemia (MB, unpublished data). The area was also endemic for the minimally pathogenic Mansonella perstans. The age and sex distribution

Results

17 877 people were treated; age and sex distributions were close to those of the total population, although there was a slight over-representation of children aged 10–14 years, and a slight under-representation of women aged 15–39 and of men aged 20–54. 6415 (35·9%) adults and 8261 children (46·2%) received their first filaricidal treatment; 2823 adults (15·8%) and 378 children (2·1%) had a history of previous filaricidal treatment (ie, either ivermectin or, for 154 of the adults,

Discussion

Ivermectin has proven to be a safe drug for onchocerciasis control, and can be delivered by small monitoring teams in most endemic areas. In 1995, more than 7 million people exposed to O volvulus were treated. Treated populations are well aware that reactions may occur, but the drug's popularity is high. However, the fall-off in attendance we noticed during the present study after the occurrence of several serious reactions suggests that such events might modify the target populations' attitude

References (21)

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