The characteristics of epilepsy in a largely untreated population in rural Ecuador.

A house-to-house survey of epileptic seizures covering a population of 72,121 persons was carried out in a rural area of northern Ecuador. A cascade system of diagnosis was used to identify all cases of epileptic seizures in this population. 1029 cases were found, of whom 881 were considered to be definite cases and 148 were possible cases. Of the 1029 cases, 56% had active epilepsy. The lifetime prevalence rate was found to lie between 12.2 and 19.5/1000 and the prevalence of active cases between 6.7 and 8.0/1000. An annual incidence rate of between 122/100,000 and 190/100,000 was estimated. Seizure type was classified without EEG data and almost half of the cases had partial seizures. In 27% of cases an aetiology was proposed on clinical grounds. This is one of few reported studies of a population that has been largely unexposed to antiepileptic drugs, providing an opportunity to study the natural history of the untreated condition. It has been suggested that treatment in newly developing epilepsy will prevent its development to a chronic condition. Only 37% of the 1029 cases had ever received antiepileptic drugs, and only 12% of the cases were taking them at the time of the survey. Despite this, a high rate of inactivity was observed, with 44% of all cases free of seizures. Nearly two thirds of the inactive cases identified had never received treatment with antiepileptic drugs. In a subgroup of untreated cases with an active condition, treatment with antiepileptic drugs was initiated and was highly effective even in cases with a long previous history. Thus the findings from this study suggest that the development of epilepsy resistant to therapy is not always associated with a long duration of untreated epilepsy.

Antiepileptic drug treatment in a community health care setting in northern Ecuador: a prospective 12-month assessment.

The results of a prospective assessment of antiepileptic drug treatment carried out over a 12-month period, in the context of existing community health care in a rural area of a developing country (a highland region of northern Ecuador), are reported. A house to house survey defined all patients in the area with a history of epileptic seizures, and 192 patients with active epilepsy were recruited into the programme. These patients were randomised to treatment with carbamazepine or phenobarbital, and 139 completed the assessment. Treatment was carried out by health visitors and rural doctors, monitored by a team of neurologists, and standard treatment regimens were used. Treatment was effective in controlling seizures, 53% of the patients were rendered entirely seizure free in the second 6 months of therapy, and a further 14% had a 50% or more reduction in seizures. These results were similar to those reported in hospital based studies in developed countries. No significant differences were found between the efficacy and safety of phenobarbital or carbamazepine. Antiepileptic drug levels were monitored during the study, and ranges similar to those found in developed countries were recorded. Compliance was good. In view of the successful treatment in this community control programme, we would recommend that community programmes for the control of epilepsy in rural settings should be given a higher priority in the planning of health care provision than is commonly the case. Finally, the programme afforded the opportunity to study the efficacy of treatment in patients with chronic long-standing epilepsy, who had not been previously treated, and the results of this treatment were good.

Epileptic seizures in an Andean region of Ecuador. Incidence and prevalence and regional variation.

A large-scale neuro-epidemiological study was carried out in a population of 72,121 inhabitants of a region of Northern Ecuadorian Andean Sierra, to identify prevalence and incidence rates of epileptic seizures and to identify demographic and geographic variations in these rates. Calculations were made using three datasets. First, rates were calculated from all cases identified in the field (raw dataset); secondly, lower rates were calculated based on a further diagnostic and reclassification procedure (minimum estimated dataset); thirdly, higher rates were derived by calculating false negative rates from the screening procedures, and adding these to the cases actually identified (maximum estimated dataset). Lifetime point-prevalence rates between 12.2/1000 and 19.5/1000 were recorded (minimum and maximum estimated rates), and the prevalence of active epileptic seizures was between 6.7/1000 and 8.0/1000 (minimum estimated and raw datasets). Incidence rate ranging between 122/100,000/year and 190/100,000/year were found (minimum, estimated and raw datasets). A marked difference in prevalence rates was found in two subregions of the survey area, and also in urban and rural areas. The reasons for these differences were not identified.

Validation of a screening questionnaire for the detection of epileptic seizures in epidemiological studies.

A large-scale clinico-epidemiological study of epileptic seizures has been carried out in a highland area in northern Ecuador, South America. This paper describes the design and the two-staged validation procedures undertaken to authenticate the screening questionnaire, which was used to detect epileptic seizures in the community during this project. An initial questionnaire consisting of 20 questions was devised and then validated in a group of healthy subjects and a group of patients with known epileptic seizures. This questionnaire was found to have a sensitivity of 100% and a specificity of 50.8%. A cluster analysis of the responses rates was undertaken and a set of nine questions which presented a specificity of 92% and sensitivity of 98% were chosen to be used during the survey. The validation of this nine-question instrument was then undertaken by direct application to a general population of 72,121 persons. Positive, negative, false positive and false negative rates were derived. The screening instrument was found to have a sensitivity of 79.3%, a specificity of 92.9%, a positive predictive value of 18.3%, a negative predictive value of 99.6% and a Youden's index of 0.79. The methodology of the study and the instruments developed are recommended for future neuro-epidemiological work in epilepsy. The problems of validation are discussed, and previous epidemiological studies of epilepsy reviewed with special emphasis on the handling of questions of validation.

A large-scale study of epilepsy in Ecuador: methodological aspects.

The methodology is presented of a large-scale study of epilepsy carried out in a highland area in northern Ecuador, South America, covering a population of 72,121 people; The study was carried out in two phases, the first, a cross-sectional phase, consisted of a house-to-house survey of all persons in this population, screening for epileptic seizures using a specially designed questionnaire. Possible cases identified in screening were assessed in a cascade diagnostic procedure applied by general doctors and neurologists. Its objectives were: to establish a comprehensive epidemiological profile of epileptic seizures; to describe the clinical phenomenology of this condition in the community; to validate methods for diagnosis and classification of epileptic seizures by a non-specialised team; and to ascertain the community's knowledge, attitudes and practices regarding epilepsy. A sample was selected in this phase in order to study the social aspects of epilepsy in this community. The second phase, which was longitudinal, assessed the ability of non-specialist care in the treatment of epilepsy. It consisted of a prospective clinical trial of antiepileptic therapy in untreated patients using two standard anti-epileptic drugs. Patients were followed for 12 months by a multidisciplinary team consisting of a primary health worker, rural doctor, neurologist, anthropologist, and psychologist. Standardised, reproducible instruments and methods were used. This study was carried out through co-operation between the medical profession, political agencies and the pharmaceutical industry, at an international level. We consider this a model for further large-scale studies of this type.

Onchocercacidal effect of three drug regimens of amocarzine in 148 patients of two races and both sexes from Esmeraldas, Ecuador.

The objective of this multidisciplinary clinical investigation was to test whether amocarzine was absorbed effectively and safely in patients of two races and either sex infected with Onchocerca volvulus while living in the holoendemic area of Esmeraldas Province, Ecuador. The prerequisite for a systemic onchocercacidal effect is the regular absorption of orally administered amocarzine. Single dosing after overnight fasting proved to produce irregular absorption of amocarzine, although some microfilaricidal effect was achieved. A pilot study with repeated low dose and postprandial administration of amocarzine showed a regular and predictable absorption with acceptable tolerability and a microfilaricidal effect lasting up to one year post-therapy. Since amocarzine and its major N-oxide metabolite are coloured agents, urine colorimetry was used to assess the urinary excretion of the N-oxide qualitatively. For the postprandial drug regimens plasma concentrations of amocarzine and its metabolite were determined at two selected time points in patients of two races and either sex; the results showed no major differences. Excision of onchocercal nodules was performed four months post-therapy. The pooled results of the histologic analysis of 100 patients with the same drug regimen read under blinded condition showed that 65% of the adult female worms were dead, 20% necrobiotic and 15% alive. The male worms were fewer and mainly necrobiotic. Control worm populations in Esmeraldas without chemotherapy showed that on the average 81.5% were alive and 18.5% dead. Amocarzine was also microfilaricidal producing a reduction of skin dwelling microfilariae to about 10% of the initial value within the first week after start of therapy and lasting for half a year at a 20% level. The reduction of ocular microfilarial was slower and reached 35-40% after one year. The general tolerability was acceptable to good. Reversible dermal reactions were usually mild and peaked as a rash in 57% of the patients on day 6. No prohibitive ocular intolerance was observed. Mild and reversible dizziness peaked on day 4 in 74% of patients. A positive reversible Romberg sign was found in 12 patients on day 4. Amocarzine, the first oral micro- and macrofilaricidal agent administered as a low dose repeat regimen (3 mg/kg twice daily and postprandial for three consecutive days) can be recommended for oral onchocercacidal therapy in adult patients. Clinical trials in juveniles should be encouraged.

Concentrations of amocarzine in plasma of 71 Ecuadorian patients of two different races receiving 3 mg/kg b.i.d. and 5 mg/kg o.d. oral postprandial doses for 3 days.

The possible influence of sex, race and of postprandial administration conditions (either immediately after the end of meal or one hour later) on the plasma concentrations of amocarzine and its N-oxide metabolite, CGP 13 231, was investigated. 71 Ecuadorian patients (48 males and 23 females) of two different races (Indio and Negro) infected with Onchocerca volvulus participated in the study. The concentrations were measured on day 3 at times 3 and 6 h after postprandial administration in the morning of a treatment with either a dose of 5 mg/kg of amocarzine once daily (12 patients) or 3 mg/kg twice daily (59 patients) for 3 days. The concentrations of unchanged drug and of CGP 13 231 measured after the 5 mg/kg treatment were in the low range of those expected from dose proportionality by the comparison with the 3 mg/kg. After the 3 mg/kg dose, no significant difference in concentration of both compounds were detected between the male and female patients between Indio and Negro patients, between the administration immediately after food intake and one hour later. The only detected difference (P = 0.05) was that between Indio and Negro patients for the concentrations of CGP 13 231 at time 3 h. This difference was not confirmed at time 6 h. Therefore, the administration of amocarzine either immediately or one hour after food intake appeared to produce reproducible absorption conditions which were not influenced by sex and race.