Successful control of onchocerciasis with community-based ivermectin distribution in the Rio Santiago focus in Ecuador.

Onchocerciasis is a major blinding disease in equatorial Africa and Central and South America. Ivermectin is a safe and effective drug in the treatment of this disease and now forms the basis of disease control in most endemic areas. We report the findings of long-term control of this infection in the Río Santiago focus in Ecuador, between January 1990 and December 1996, using a strategy of giving ivermectin treatments biannually in hyperendemic communities and annually in meso- and hypoendemic communities. Ivermectin was administered by local health workers from each community. A high level of compliance to ivermectin was achieved, with 81.9% to 98.0% of those eligible receiving the drug at each treatment instance. The impact of ivermectin therapy was monitored using a cohort of 120 randomly selected infected individuals from 8 hyperendemic communities. The geometric mean microfilarial density of this group declined from 19.3 to 0 mf/mg over the 84-month observation period. Ivermectin had a significant impact on anterior segment ocular disease, acute onchodermatitis and sowda. The rate of infection of blackflies declined from 1.1% in 1989-0.08% in 1996, which is below the vectorial capacity of the Simulium vector and, as no new nodules were detected after 1994 and no children under 5 became infected over the observation period, it is likely that the transmission of this infection was interrupted in the study area.

The pathogenesis of chorioretinal disease in onchocerciasis.

The pathogenesis of onchocercal chorioretinopathy is poorly understood. In this article, Philip Cooper, Ronald Guderian, Roberto Proaño and David Taylor discuss the important clinical, histological and epidemiological features of the resulting lesions that cause blindness, and review the numerous mechanisins that have been put forward to explain its pathogenesis. The pathogenesis of anterior segment disease, particulary sclerosing keratitis, has been reviewed in depth previously(1) and will not be discussed here.

Onchocerciasis in Ecuador: evolution of chorioretinopathy after amocarzine treatment.

AIMS: To investigate the impact of the macrofilaricidal drug, amocarzine, on the evolution of chorioretinopathy in onchocerciasis. METHODS: A prospective uncontrolled cohort study was performed using subjects infected with Onchocerca volvulus in a hyperendemic onchocerciasis focus in Esmeraldas Province in Ecuador. Study subjects were recruited into four cohorts in which ophthalmic and parasitological data were collected for 2, 3, 4, and 5 years respectively. RESULTS: Complete ophthalmic follow up was obtained for 294 individuals in the four cohorts. The incidence of retinal pigment epithelial atrophy tended to remain constant between cohorts while that of chorioretinal scarring with a greater observation period. The incidence rate of cases with new or extending chorioretinal lesions was greater with an increasing period of follow up. An association was seen between the cumulative microfilarial loads in the skin and the development of new chorioretinal lesions (p < 0.05). No relation was noted between cumulative microfilarial loads and the progression of existing disease. CONCLUSION: Amocarzine therapy did not prevent the natural evolution of chorioretinal disease. It was suggested that ocular microfilariae were necessary for the induction of chorioretinopathy in previously unaffected eyes and that extension of existing disease might also be related to the presence of ocular microfilariae or to other immunological mechanisms.

Onchocerciasis in Ecuador: changes in prevalence of ocular lesions in Onchocerca volvulus infected individuals over the period 1980-1990.

Trends in prevalence rates of onchocercal ocular lesions were examined over the period 1980 to 1990 using data from two cross-sectional surveys. There was evidence for increasing prevalence of anterior chamber microfilariae, iridocyclitis, optic atrophy, and chorioretinopathy. Large increases in prevalence, in particular, were seen for posterior segment lesions: optic atrophy increased from 2.7% to 6.4% and chorioretinopathy from 8.8% to 35.6%. Greatest increases in these lesions were seen in the Chachi which was attributed to the large increases in prevalence of microfilariae in the anterior chamber particularly in those aged 30 years or greater. The study findings suggest that ocular onchocerciasis is evolving in parallel with the well documented parasitological changes.

Absence of cellular responses to a putative autoantigen in onchocercal chorioretinopathy. Cellular autoimmunity in onchocercal chorioretinopathy.

PURPOSE: Onchocerciasis is a major cause of blindness in the developing world. An autoimmune pathogenesis for onchocercal chorioretinopathy was proposed after the identification of a recombinant Onchocerca volvulus antigen (designated Ov39) demonstrated immunologic crossreactivity with a component of the retinal pigment epithelium and other ocular tissues. The aim of this study was to determine whether patients with onchocercal chorioretinopathy have enhanced lymphoproliferative responses to Ov39 compared to those without chorioretinal disease. METHODS: Lymphocyte blastogenic assays were performed using peripheral blood mononuclear cells (PBMCs) from patients with and without evidence of chorioretinopathy. PBMCs were cultured with Ov39, and supernatant fluids from Ov39-stimulated PBMCs were used to determine levels of the cytokines, interferon-gamma, and interleukin-5. RESULTS: Lymphoproliferative responses to Ov39 were not enhanced in patients with onchocercal chorioretinopathy compared to those without clinical evidence of chorioretinal disease. CONCLUSIONS: A role for Ov39-specific cellular autoreactivity in the pathogenesis of onchocercal chorioretinopathy could not be demonstrated.

Onchocerciasis in Ecuador: ocular findings in Onchocerca volvulus infected individuals.

Little is known of the epidemiology and clinical picture of ocular onchocerciasis in South America. A survey of onchocercal eye disease was performed in the hyperendemic area of a rain forest focus of onchocerciasis in Esmeraldas Province in Ecuador. A total of 785 skin snip positive individuals from black and Chachi Amerindian communities were examined. The blindness rate attributable to onchocerciasis was 0.4%, and 8.2% were visually impaired. Onchocercal ocular lesions were seen in a high proportion of the study group: 33.6% had punctate keratitis, microfilariae in the anterior chamber and cornea were seen in 28.9% and 33.5% respectively, iridocyclitis was seen in 1.5%, optic atrophy in 5.1%, and chorioretinopathy in 28.0%. Sclerosing keratitis was not seen. The prevalence of all ocular lesions increased with age. Punctate keratitis was strongly associated with microfilarial counts in the cornea and chorioretinopathy was correlated with infection intensities in the cornea and anterior chamber. Chachi Amerindians had higher anterior chamber microfilarial counts and a greater prevalence of punctate keratitis than blacks though blacks had a greater prevalence of iridocyclitis and optic nerve disease. The pattern of ocular disease resembled rain forest onchocerciasis in west Africa with few severe ocular lesions in the anterior segment and all blinding lesions attributable to posterior segment disease.

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.

Onchocerciasis in Ecuador: infection in children in the Santiago Basin focus, province of Esmeraldas.

The prevalence of onchocerciasis infection in children aged 1-12 in the Santiago Basin focus, province of Esmeraldas, Ecuador, was determined to see if active transmission of the disease had occurred in the past 6 years. An infection rate of 45.0% was found. Compared to that found in 1980 (14.5%), the infection rate had increased by 210.1%. The increase was greater on the Rio Santiago (340.5%) than on the Rio Cayapas (195.5%). An increase of 286% was seen in the skin microfilarial density in the 1-4 year age group, with a 56.8% increase in the 5-12 year age group. The prevalence of infection in children aged 0-4 years (those born since the first enquiry in 1980) was 64.3%, with an average skin microfilarial density of 12.2 microfilariae (mf)/mg and with 20% presenting nodules, of which 92.1% occurred in the head region. Of the 34 children examined aged less than one year, 25 (73.5%) were positive for microfilariae with an average microfilarial skin density of 9.6 mf/mg. These data suggest that there is active transmission of the disease in the Santiago Basin onchocercal foci.

The reduction in microfilariae loads in the skin and eye after nodulectomy in Ecuadorian onchocerciasis.

This study is concerned with the relationship between palpable onchocercal nodules and Onchocerca volvulus microfilarial loads in the skin. The number of microfilariae in clinically normal skin decreases as the distance from the nodule increases. Surgical removal of nodules reduces the microfilarial loads in 40 of 46 patients studied over a period of five months, with an average reduction of 65.4% of the prenodulectomy microfilarial load at the iliac crest. Complete elimination of detectable parasites was seen in some patients. Five individuals had increased microfilarial loads, all of which had developed new palpable nodules. Also, nodulectomy had a significant effect on ocular tissue, reducing the levels of parasites in the cornea and anterior chamber in 10 of 15 patients observed with no new nodules developing during the observation period. Both dermal and ocular clinical manifestations of onchocerciasis were reduced in a proportion of the patients. These parasitological and clinical findings provide evidence that nodulectomy is a beneficial procedure to O. volvulus infected patients in Ecuador by reducing both microfilarial loads and the degree of pathology.

Onchocerciasis in Ecuador. III. Clinical manifestations of the disease in the province of Esmeraldas.

Considerable variation in the frequency of the clinical manifestations of onchocerciasis was seen in the individual endemic foci of the disease in province of Esmeraldas, Ecuador. In hypoendemic areas, 84.6% of all microfilaria-positive inhabitants were found to be free of any clinical manifestations of the disease, whereas in the hyperendemic area clinical manifestations were present in 57.9% of those infected. Ocular keratitis, macular papular rash of the skin and subcutaneous onchocercal nodules of varying frequency were the major clinical variants. Long-standing onchodermatitis and hypertrophy of the skin were rarely seen. Clinical evidence of prolonged ocular and skin invasion by microfilariae was seen only in the hyperendemic area. Of the 26.1% of the microfilaria-positive inhabitants who had onchocercal nodules, 91.7% lived in the hyperendemic area. 41.1% of all nodules occurred in the region of the iliac crest. Clinical conditions associated with high microfilarial density, i.e., elephantiasis of the legs and scrotum, lymphadenopathy, hanging groin, hydrocele and inguinal hernia were seen only in the hyperendemic area. The clinical features were similar to those seen in Africa, but the low incidence of the clinical presentation and severity of the disease suggested a recent infestation of the province.

Onchocerciasis in Ecuador, IV. Comparative studies of the disease relating to the Chachi and black populations in the province of Esmeraldas.

The frequency, intensity and clinical features of onchocerciasis in the two ethnic groups (Blacks and Chachilla--an indigenous tribe) in the endemic foci of the disease in Esmeraldas province (Ecuador) were evaluated. The incidence of infection and intensity of the disease seen in both groups were directly related to the frequency of man-vector contact and not to racial factors. Both groups showed the same rate of positivity in both the hyperendemic and hypoendemic areas. Males of both groups had a consistently higher positivity rate than did females. The Chachilla were found to have a higher mean microfilarial density than Blacks in both types of endemic areas. Certain clinical features of the disease analogous to those seen in the African form were present only in Blacks. No lymphatic involvement or hypertrophic scarring was seen in the Chachilla, suggesting that in the Blacks there may be a generaically related predisposition to lymphatic complications of microfilarial infections.

Onchocerciasis in Ecuador. I. Prevalence and distribution in the province of Esmeraldas.

In the province of Esmeraldas in Ecuador, 11 endemic foci of onchocerciasis were identified. The major focus, located on Rio Cayapas, consisted of 65 contiguous positive communities with an average infection rate of 51.1%. A distance-dependent characteristic of the onchocerciasis infection suggested that the transmission was centered principally in the areas near the head-waters of the river. This area, inhabited primarily by the indigenous tribe, Chachi, with an infection rate of 85%, was considered an area of hyperendemicity. Towards the river's mouth, where the majority of the inhabitants were Blacks, the rate of infection was 7%. The endemic focus located on Rio Santiago, populated entirely by Blacks and consisting of 17 contiguous positive communities, had an average infection rate of 18.8%. Again, the highest rate of infection, 33%, occurred in the upper reaches of the river. Resulting from the transient and migratory activity of some microfilariae-positive persons, 9 other isolated foci were found dispersed throughout the province. The infection rate of each focus was distinct, reflecting geographical location and ethnic composition. All foci other than the interior regions of Rio Cayapas were areas of hypoendemicity.

Onchocerciasis in Ecuador. II. Epidemiology of the endemic foci in the province of Esmeraldas.

The epidemiology of infection was studied in all endemic foci of onchocerciasis in the province of Esmeraldas in Ecuador. The incidence of infection and the density of microfilariae in the skin, both greater in males than females, increased with age, reaching highest levels at 40-45 years in males and at 60 years and older in females. In the hyperendemic area males and females had the same rate of infection, but the microfilarial density in males exceeded that in females. In the hypoendemic areas males had a higher infection rate than females, but females registered a higher density of microfilariae in the skin. The incidence and location of the onchocercal nodules correlated closely with the density of microfilariae. Adults, aged 50-54 had the highest prevalence of onchocercal nodules, which occurred primarily in the thorax and pelvic regions. Children aged 0-14 years showed a low prevalence of nodules, the head region being the primary site. Of the two diagnostic methods used to detect the presence of microfilariae, most of the diagnoses (85.6%) were made by skin biopsies as compared to those made by the Mazzotti test (14.4%).

Análisis dinámico y técnicas de reforzamiento en estructuras de infraestructura educativa

La infraestructura educativa en el Perú ha tenido importantes cambios en su concepción sismorresistente. La norma peruana de diseño sismorresistente NTE E.030 (1997) cataloga a los Centros Educativos como edificaciones esenciales, cuya función no debe interrumpirse inmediatamente después que ocurra un sismo. En el presente estudio, se muestra el análisis dinámico de un modelo pseudo-tridimensional de bloque cortante con diafragmas rígidos y otro modelo tridimensional considerando losas flexibles. Para verificar los periodos de la edificación, se ha recogido información in situ, mediante ensayos de microtrepidaciones. Las acciones correctivas en el proceso de reforzamiento, se orientan a independizar los dos módulos de la edificación existente he incluir elementos de muros de cortante para rigidizar la estructura en la dirección más débil. (AU)