RESUMEN
Lethal disease in Schistosoma mansoni infections is mostly due to portal hypertension caused by hepatic periportal fibrosis. To evaluate the factors that may determine severe disease, livers and spleens were examined by ultrasound in a Sudanese population living in a village where S. mansoni is endemic. Early (FI), moderate (FII), or advanced (FIII) fibrosis was observed in 58%, 9%, and 3% of the population, respectively. Although FI affected 50%-70% of the children and adolescents, FII prevalence was low in subjects
Asunto(s)
Cirrosis Hepática/fisiopatología , Parasitosis Hepáticas/fisiopatología , Esquistosomiasis mansoni/genética , Esquistosomiasis mansoni/fisiopatología , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Progresión de la Enfermedad , Femenino , Predisposición Genética a la Enfermedad , Humanos , Cirrosis Hepática/epidemiología , Cirrosis Hepática/parasitología , Parasitosis Hepáticas/epidemiología , Parasitosis Hepáticas/parasitología , Masculino , Persona de Mediana Edad , Linaje , Vena Porta/patología , Prevalencia , Esquistosomiasis mansoni/complicaciones , Caracteres Sexuales , Bazo/irrigación sanguínea , Sudán/epidemiología , Venas/patologíaRESUMEN
Lethal disease due to hepatic periportal fibrosis occurs in 2%-10% of subjects infected by Schistosoma mansoni in endemic regions such as Sudan. It is unknown why few infected individuals present with severe disease, and inherited factors may play a role in fibrosis development. Schistosoma mansoni infection levels have been shown to be controlled by a locus that maps to chromosome 5q31-q33. To investigate the genetic control of severe hepatic fibrosis (assessed by ultrasound examination) causing portal hypertension, a segregation analysis was performed in 65 Sudanese pedigrees from the same village. Results provide evidence for a codominant major gene, with.16 as the estimated allele A frequency predisposing to advanced periportal fibrosis. For AA males, AA females, and Aa males a 50% penetrance is reached after, respectively, 9, 14, and 19 years of residency in the area, whereas for other subjects the penetrance remains <.02 after 20 years of exposure. Linkage analysis performed in four candidate regions shows that this major locus maps to chromosome 6q22-q23 and that it is closely linked (multipoint LOD score 3.12) to the IFN-gammaR1 gene encoding the receptor of the strongly antifibrogenic cytokine interferon-gamma. These results show that infection levels and advanced hepatic fibrosis in human schistosomiasis are controlled by distinct loci; they suggest that polymorphisms within the IFN-gammaR1 gene could determine severe hepatic disease due to S. mansoni infection and that the IFN-gammaR1 gene is a strong candidate for the control of abnormal fibrosis observed in other diseases.
Asunto(s)
Cirrosis Hepática/genética , Parasitosis Hepáticas/complicaciones , Escala de Lod , Receptores de Interferón/genética , Esquistosomiasis mansoni/complicaciones , Adolescente , Adulto , Niño , Cromosomas Humanos Par 6/genética , Femenino , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Humanos , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/parasitología , Parasitosis Hepáticas/genética , Parasitosis Hepáticas/parasitología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Linaje , Penetrancia , Esquistosomiasis mansoni/genética , Esquistosomiasis mansoni/parasitología , Factores Sexuales , Sudán , Factores de Tiempo , Ultrasonografía , Receptor de Interferón gammaRESUMEN
In order to compare clinical versus ultrasound based diagnosis of Schistosoma mansoni induced periportal fibrosis (pF) 536 infected Sudanese schoolchildren underwent clinical and sonographical examination. A liver exceeding 3 cm in sternal line and a palpable spleen were considered pathological. Ultrasound criteria for age dependent organometry of a Central European cohort were used as reference. Based on clinical criteria 190 children (35.4%) had hepatomegaly, whereas according to ultrasound results the rate was only 11.4%. Splenomegaly was detected in 77 cases (14.4%) by clinical means, but in 196 by ultrasound (36.6%). The sensitivity of clinical parameters as indication of pF was around 50%. Results for ultrasound detected organomegaly were only slightly better. It was concluded that assessment of liver and spleen sizes was of limited value as an indication for pF and that a considerable discrepancy existed between clinical and ultrasound based assessment of hepato- and splenomegaly.
Asunto(s)
Cirrosis Hepática/diagnóstico por imagen , Esquistosomiasis mansoni/complicaciones , Adolescente , Factores de Edad , Niño , Hepatomegalia , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Morbilidad , Prevalencia , Esplenomegalia , Sudán/epidemiología , UltrasonografíaRESUMEN
To improve diagnostic capabilities, an ultrasound unit was installed at a major hospital in Wad Medani, Sudan. During the implementation period (October 1986 to March 1987) of ultrasound service, 863 patients were examined cooperatively by Sudanese and German physicians. The service covered internal medicine (47.5%), obstetrics and gynecology (31.6%), surgery (12.5%), and pediatrics (8.4%). Pathologic findings were seen in 75% of the patients. In obstetrics, the rate of pathologic findings was 40%. Five hundred eighty-three pathologic findings were detected in organ systems that constituted the primary indication for ultrasonography (of a total of 1,009 indications). The clinical benefit of ultrasonography was evaluated in 289 randomly selected patients in a standardized questionnaire completed by the attending physicians. The final clinical diagnosis was established or substantially revised in 21.5% of the patients, based on the ultrasonographic report. The previously reported diagnosis was supported in 69.5% of the patients. Medical management was directly influenced in 26% of the patients. We conclude that the clinical benefit of ultrasonography at a district hospital in the tropics is substantial, providing cost-effective, immediate therapeutic benefits in 25% of the patients examined. The technique thereby contributes to better and more rational patient management in institutions with limited resources.
Asunto(s)
Hospitales de Enseñanza/métodos , Medicina Tropical , Ultrasonografía Prenatal , Ultrasonografía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Medicina Interna , Masculino , Persona de Mediana Edad , Servicio de Ginecología y Obstetricia en Hospital , Pediatría , Embarazo , Servicio de Cirugía en Hospital , Clima TropicalRESUMEN
In February 1987, 322 Sudanese school children were diagnosed for Schistosoma mansoni infection and treated randomly with praziquantel (either 20 mg/kg or 40 mg/kg body weight). A followup of these subjects was carried out in January 1989. This treatment resulted in a substantial reduction of egg output. Patients underwent complete abdominal ultrasonography and periportal fibrosis of the liver was graded into three degrees of severity. The proportion of patients with periportal fibrosis decreased from 36.6% in February 1987 to 21.7% in January 1989. At the time of followup, higher grades of periportal fibrosis (grades II and III) were encountered in only 4.3% and 0.3% of these patients, respectively, compared with 21.1% and 5.9%, respectively, before therapy. This was paralleled by a significant decrease in hepatomegaly from 10.9% to 7% of the patients. In contrast, the rate of splenomegaly showed a slight increase during the period of observation. The different dosage regimens of praziquantel did not result in a significantly different reversibility of periportal fibrosis or a decrease in egg excretion. The reversibility of specific liver lesions 23 months after antischistosomal therapy with praziquantel was substantial. The improvement was greater at 23 months than that obtained seven months after treatment.
Asunto(s)
Vena Porta/diagnóstico por imagen , Praziquantel/uso terapéutico , Esquistosomiasis mansoni/tratamiento farmacológico , Adolescente , Niño , Heces/parasitología , Fibrosis , Estudios de Seguimiento , Humanos , Hígado/diagnóstico por imagen , Morbilidad , Recuento de Huevos de Parásitos , Vena Porta/patología , Distribución Aleatoria , Esquistosomiasis mansoni/complicaciones , Esquistosomiasis mansoni/diagnóstico por imagen , Bazo/diagnóstico por imagen , Esplenomegalia , UltrasonografíaRESUMEN
Five hundred thirty six Sudanese schoolchildren with Schistosoma mansoni infection were treated at random with either 20 mg or 40 mg/kg praziquantel. Seven months later 420 children could be reinvestigated by ultrasonography. Reduction of egg excretion and reversibility of sonographically-proven periportal fibrosis (PF) was not significantly different in the two groups. Schistosoma mansoni-induced PF grade II decreased from 22.9% to 6.7% and grade III from 5.2% to 1.6%. An increased prevalence of PF grade I, from 10% to 29.8% of the investigated patients, was observed. This increase was caused partly by a downshifting of patients who had PF II (n = 45) and PF III (n = 8) before therapy, but also by patients who developed PF I in the seven months after therapy (n = 56). The overall percentage of patients with PF before and after treatment was 38.1%. Of 420 children, 17.4% increased in their PF grade, 55% remained at the same level and 27.6% improved. Children younger than 11 years of age had a higher rate of complete reversibility than older ones. The percentage of patients with hepatomegaly decreased significantly (11.6% to 6.9%; p = 0.001). The rate of splenomegaly remained unchanged. It was concluded that within seven months therapy with praziquantel resulted in a considerable qualitative improvement of PF in Sudanese schoolchildren with S. mansoni infection.
Asunto(s)
Cirrosis Hepática/tratamiento farmacológico , Praziquantel/uso terapéutico , Esquistosomiasis mansoni/tratamiento farmacológico , Niño , Hepatomegalia , Humanos , Hígado/diagnóstico por imagen , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/etiología , Recuento de Huevos de Parásitos , Distribución Aleatoria , Esquistosomiasis mansoni/complicaciones , Esquistosomiasis mansoni/diagnóstico por imagen , Esplenomegalia , Factores de Tiempo , UltrasonografíaRESUMEN
Morbidity of Schistosoma mansoni infection was assessed in 536 infected Sudanese schoolchildren using an ultrasonographical staging system for periportal fibrosis of the liver. S. mansoni ova excretion in stools was mild in 28%, moderate in 58%, and severe in 14% of the patients. Grade 1 periportal fibrosis was found in 10.3% grade 2 in 23.1%, and grade 3 in 4.7% of S. mansoni-infected children. Girls and boys were equally affected. The distribution of periportal fibrosis compared to the age of patients was homogenous. There was no significant difference of the rate of periportal fibrosis in the 3 groups of intensity of infection. However, in the 204 patients who showed periportal fibrosis, there was a strong relation between severity of ultrasonographically detectable fibrosis with intensity of egg excretion. In 332 children, of which 73 had a heavy infection, no signs of periportal fibrosis were detected. Sudanese children show a variable susceptibility towards the development of S. mansoni-induced periportal fibrosis. High risk patients can be detected at a childhood stage by measuring the intensity of infection and investigating the liver by ultrasound.