Sex ratio of Wuchereria bancrofti in surgical specimens from an endemic area of Brazil.

The sex ratio of adult Wuchereria bancrofti from 172 histologically diagnosed cases of lymphatic filariasis, all from an endemic area of Recife, in north-eastern Brazil, was investigated. Of 172 tissue specimens examined, 74 (43%) were lymph nodes and 98 (57%) lymphatic-vessel segments. The morphology of the worms was generally disrupted, in some cases to the point where the worms were almost completely absorbed by the granulomatous inflammatory response. Parasite gender was clearly determined in only 110 (64%) specimens, 61 (55.5 %) of which were lymph nodes and 49 (44.5%) lymphatic vessels. Eighty-seven (79.1%) of these tissue specimens contained only female worms, 17 (14.5%) both males and females, and six only males, giving an overall female:male 'specimen' ratio of 4.5:1. Of the 63 tissue specimens in which dead or degenerating worms were noted, 60 (92.2%) contained only females. All the female worms detected were gravid, regardless of whether male worms were present in the specimen. The implications of these findings for parasite dynamics, the pathogenesis of bancroftian filariasis and the interpretation of ultrasound images of living adult worms are discussed.

Bancroftian filariasis in children and adolescents: clinical-pathological observations in 22 cases from an endemic area.

In areas where bancroftian filariasis is endemic, the clinical manifestations of the disease, which are often very varied, appear most frequently during early adulthood or later. In consequence, very little attention, if any, has been given to the signs and symptoms of the disease in childhood. In an attempt to fill this gap, clinical and pathological observations were made, in Brazil, on 22 children (aged 2-15 years) who were infected with Wuchereria bancrofti. There was a predominance of lymph-node involvement. In all but three (14%) of the children (who had adult parasites in their intrascrotal lymphatic vessels), the adult worms were located in the afferent or efferent vessels of draining lymph nodes, predominantly in the inguinal region. None of the patients presented with distal lymphoedema, and the adenopathy was characterized by painless, localized, lymph-node enlargement, without signs of inflammation in the overlying skin. Histologically, the alterations in the lymphatic vessels and surrounding structures were similar to those described in adult patients, and depended essentially on adult-parasite viability. The localization of the adult worms in the paediatric cases was peculiar and distinct from that observed in adult patients, in whom the adult parasites are usually found in extra-nodal lymphatic vessels. In areas endemic for bancroftian filariasis, therefore, filarial infection should be considered as a possible cause of adenopathy. For the differential diagnosis of adenopathy in young patients from endemic areas, the authors recommend the use of ultrasound and other non-invasive diagnostic tools, as alternatives to excisional biopsies, which are often unnecessary in bancroftian filariasis.

Parkia pendula lectin as histochemistry marker for meningothelial tumour.

Lectins have been intensively used in histochemical techniques for cell surface characterization. These proteins are involved in several biological processes and their use as histochemical markers have been evaluated since they can indicate differences in cell surfaces. Parkia pendula lectin (PpeL) was evaluated as histochemical marker for meningothelial meningioma biopsies. Tissue slices were incubated with PpeL conjugated to horseradish peroxidase (PpeL-HRP) and Concanavalin A-HRP (ConA-HPR) and the binding visualized with diaminobenzidine and hydrogen peroxide. The lectin-tissue binding was inhibited with D-glucose. PpeL showed to be a useful tool for the characterization of meningothelial tumour and clinico-pathological diagnosis.

The histopathology of bancroftian filariasis revisited: the role of the adult worm in the lymphatic-vessel disease.

Although morphology is generally limited to static images, the histopathological features of bancroftian lymphatic disease are presented here in a way that is as dynamic as possible and closely associated with the clinical, ultrasonographic and surgical characteristics. The protean spectrum of alterations seen in the host's lymphatic vessels is discussed, and the changes caused by the live and dead worms are highlighted, as independent events. Evidence of a remodelling process, in which the lymphatic endothelial cells appear to have a key role, is provided for the first time. Despite many new pieces of information, there remain many 'blank pages' in the natural history of bancroftian filariasis.

Lymphatic filariasis in children: adenopathy and its evolution in two young girls.

Lymphatic filariasis is a widespread infectious disease of children in endemic areas, but little is known about the early lymphatic damage in children and its evolution, either with or without treatment. Two girls (ages 6 and 12 years) from a Wuchereria bancrofti endemic region of Brazil presented with chronic inguinal adenopathy. Neither had microfilaremia. By ultrasound both were shown to have living adult worms in their enlarged inguinal nodes and had occult local lymphatic damage (lymphangiectasis). One girl spontaneously developed acute adenitis in the affected node prior to any intervention; this adenitis resolved within 10 days and was associated with the progressive disappearance over 45-90 days of all local abnormalities detectable by ultrasound. In the other child, after treatment with a single dose of diethylcarbamazine (DEC), the same clinical picture of transient adenitis and resolving abnormalities (detectable by ultrasound) occurred. These findings demonstrated filariasis as the cause of adenopathy in children, and also both spontaneous and treatment-induced worm-death, with subsequent reversal of lymphatic abnormalities.

O sistema imune inato intestinal em pacientes com estrongiloidíase / The innate intestinal immune system in patients with strongyloidiasis

Foram estudados fragmentos da mucosa duodenal obtidos de nove pacientes apresentando sintomas leves de estrogiloidiase, nove com sintomas moderados, sete com sintomas graves e sete indivíduos aparentemente normais. A muramidase(lisozima) foi imunocitoquimicamente demonstrada em cortes contracorados pela técnica do PAS. Havia aparente aumento progressivo na secreçao de muramidase pela célula de Paneth aaacompanhado o agravamento dos sintomas, näo obstante o fato de que a sua populaçao permanecesse constante. Decréscimo progressivo no número de células caliciformes foi observado enquanto, concomitantemente, haavia aumento na populaçao de células intermediarias. Esses resultados foram interpretados como a indicaçao da participaçao do sistema imune inato intestinal no estabelecimento da interaçao Strongyloides stercoralis/hospedeiro, através do aumento da secreçao da enzima mucolítica muramidase

Pathogenesis of lymphatic disease in bancroftian filariasis: a clinical perspective.

The pathogenesis of lymphatic filariasis has been a matter of debate for many decades. Here, Gerusa Dreyer and colleagues propose a dynamic model of bancroftian filariasis, integrating clinical, parasitological, surgical, therapeutic, ultrasonographic and histopathological data. This model has profound implications for filariasis control programs and the management of the individual patient.

Bancroftian filariasis in a paediatric population: an ultrasonographic study.

Little is known about lymphatic filariasis or the anatomical location of adult Wuchereria bancrofti in children. Seventy-eight children from Greater Recife, 23 microfilaria-positive and 55 microfilaria-negative in approximately 60 microL blood, underwent ultrasound examinations of the major superficial lymphatic vessels of the limbs, scrotal area (boys), and breast area (girls). The characteristic movements of adult worms, known as the filaria dance sign (FDS), were detected in 11 (14.1%) children. In 9 boys, the FDS was detected in lymphatic vessels of the scrotal area (8, ages 14-16) and the inguinal cord (1, age 11). In girls, the FDS was detected in a crural lymphatic vessel and an axillary lymph node. FDS detection was more common in boys (P = 0.06), older children (P = 0.001), and children with microfilaraemia (P = 0.05). Diffuse lymphangiectasia was visualized in 4 boys (ages 14-16) and 2 children had clinical signs of filariasis. These ultrasonographic findings associate W. bancrofti with both infection and disease in children.

Survey for Trypanosoma cruzi infection in a municipality in northeast Brazil.

An epidemiological survey of Trypanosoma cruzi infection was carried out in Bodocó, located in the western part of the State of Pernambuco, Brazil. Two hundred and forty-one individuals were parasitologically and immunologically screened. Although hemoculture did not reveal the presence of parasites in the blood, the sera of 5 individuals were scored as positive by the indirect fluorescence antibody test and the enzyme-linked immunosorbent assay. Seropositivity in individuals above and below the age of 40 was 14.8 and 0.5%, respectively. These results indicate that recent infections with T. cruzi are rare in this area. However, since a T. cruzi-infected triatomid (Triatoma brasiliensis) was captured in a school classroom, this area must be considered endemic. When triatomid feces containing parasites were inoculated into a jird (mongolian gerbil), parasitemia appeared 10 days later. Immunohistochemical staining, using monoclonal antibody specific for T. cruzi, labeled organisms in jird tissues. These observations demonstrate that the jird is a suitable host for experimental T. cruzi infections and that monoclonal antibody is effective for detection of the parasite in host tissues.

Estudo Morfométrico da rede arteriolar miocárdica em indivíduos alcoolistas crônicos / Morphometric study of myocardic arteriolar net in chronic alcaholic patients

A patogênese da doença alcoolica cardíaca não é completamente conhecida. Segundo uma das hipóteses, as lesões miocárdicas resultariam de alterações na parede dos vasos. Para avaliar possíveis alterações vaculares parietais, foi realizado estudo morfométrico de arteíolas miocárdica em doze alcoolistas crônicos (nove homens e três mulheres, com idade variando de 24 a 45 anos) e em oito controles (três homens e cinco mulheres, com idade variando entre 20 e 39 anos). Cortes histólogicos de seções transversais, longitudinais e oblíquas da parede livre do ventrículo esuerdo foram analisados em sistema semi-automático de análise de imagem. Não se obseervaram diferenças estatisticamente significativas na espessura da parede articular entre os dois grupos. É possível, portanto, que alteraçõess vasculares, pelo nenos no que se refere a rede arteriolar miocárdica, não contribuam significativamente para a doença alcoólica cardíaca

Direct assessment in vivo of the efficacy of combined single-dose ivermectin and diethylcarbamazine against adult Wuchereria bancrofti.

When ivermectin and diethylcarbamazine (DEC) are given simultaneously in a single dose to persons with Wuchereria bancrofti infection, the resulting suppression of microfilaraemia is more profound and sustained than when either drug is given alone. To assess whether this effect is a result of enhanced macrofilaricidal efficacy, we used ultrasound to monitor the adult worms in the scrotal area of men with W. bancrofti microfilaraemia. Twenty-one men were treated simultaneously with DEC (6 mg/kg) and either 200 micrograms/kg or 400 micrograms/kg of ivermectin (11 and 10 men, respectively). Ten other men received a single 200 micrograms/kg dose of ivermectin followed 5 d later by a 6 mg/kg dose of DEC (sequential treatment). All men became amicrofilaraemic after treatment and all except one remained so for one year. Cessation of adult worm movement, indicative of death of all the adult worms in a given 'nest', was observed in none of 30 nests in men who received simultaneous treatment and in 3 of the 19 nests (16%) in the men who received sequential treatment (P = 0.05). Scrotal nodules were detected in 5 of 21 men (24%) who received simultaneous treatment and in 8 men (80%) who received sequential treatment (P < 0.01). Thus, co-administration of ivermectin with DEC seems to interfere with the macrofilaricidal action of DEC. These findings have implications both for treatment of the individual patient and for community-based drug distribution programmes designed to interrupt transmission of W. bancrofti.

Binding evaluation of Isoform 1 from Cratylia mollis lectin to human mammary tissues.

The phenomenon of altered carbohydrates in transformed cell surfaces has been studied through histochemical techniques using lectins. Specific binding patterns to normal and transformed mammary tissues were evaluated by Isoform 1 from Cratylia mollis lectin (Cra Iso 1). Protocols using a direct method, incubation of Cra Iso I conjugated to peroxidase (Cra Iso 1-Per) with mammary tissues, followed by diaminobenzidine and hydrogen peroxidase interaction, were performed. Neoplastic tissues, marked by Cra Iso 1, showed a higher intensity of staining than normal ones, in comparison with Canavalia ensiformis lectin, Concanavalin A (Con A), conjugated to peroxidase (Con A-Per). The assay with Cra Iso 1 also indicated a possible utilization of this lectin to characterize normal and transformed mammary cells.

Histological evidence for adulticidal effect of low doses of diethylcarbamazine in bancroftian filariasis.

The ability of diethylcarbamazine (DEC) to kill adult Wuchereria bancrofti worms was evaluated by examining lymphatic nodules formed after treatment with 4 different treatment schedules of 193 males living in the endemic area of Greater Recife, Brazil. Lymphatic nodules appeared in the spermatic cord or upper extremities in 43 of 138 microfilaraemic individuals, in 3 of 30 amicrofilaraemic patients with filarial disease manifestations, and in 1 of 25 asymptomatic amicrofilaraemic residents of the endemic area treated with DEC. Fourteen of these nodules were surgically removed 10-150 d after the start of treatment. Regardless of the DEC dosage and schedule used, all nodules contained damaged and degenerating adult worms. An exuberant granulomatous process with large numbers of eosinophils and progressive fibrosis gradually developed around the dead parasites. The mechanism(s) by which DEC killed adult W. bancrofti could not be determined.

Scanning electron microscopy of adult Wuchereria bancrofti (Nematoda: Filarioidea).

Despite the great importance of Wuchereria bancrofti in causing human lymphatic filariasis, only conventional morphological studies have been completed with adult forms of this filaria. No ultrastructural studies have been carried out, mainly due to the difficulty in obtaining viable parasites from human tissues and the lack of a suitable experimental model or in vitro cultivation. With the recent success in using ultrasound to localize adult worms in living tissues and their surgical recovery from human lymphatic vessels, we show in the present paper the first ultrastructural observations of this filarial form. The cuticle surface analyzed by scanning electron microscopy showed a transversal striated aspect with periodic annulations and many small protuberances irregularly distributed along the filaria. The adults present a specialized cephalic area, with the oral opening surrounded by a circular mouth, papillae, and amphidial opening. Other structures, for example the anal, vulvar, and cloacal opening and spicules, were also observed and are described herein.

Comparative efficacy of three different diethylcarbamazine regimens in lymphatic filariasis.

To assess the efficacy of diethylcarbamazine (DEC) in clearing Wuchereria bancrofti microfilariae (mf) from the circulation, we conducted a single blind hospital-based therapeutic trial of 3 DEC regimens. All patients were assessed by filtration of 1 mL of venous blood taken before and 1, 3, 6 and 12 months after DEC administration. The efficacy of a 12 d course of 6 mg/kg DEC once daily was identical to that of a similar course with 2 mg/kg given 3 times daily, indicating that split-dose treatment does not improve mf clearance over single daily drug administration. Microfilarial densities in patients treated only once with 6 mg/kg DEC remained significantly higher at 1, 3, and 6 months after treatment. However, all 3 treatment regimens proved equally effective in controlling microfilaraemia after 12 months, when 41, 42 and 40% of patients in the 3 treatment groups were amicrofilaraemic. These results suggest that a single DEC dose of 6 mg/kg administered annually or biannually may be a suitable regimen to control bancroftian filariasis in Recife, Brazil.

Esquistossomose murina esperimental: estudo imunohistoquímicos das células ganglionares mioentéricas / Experimental murine Schistosomiasis: an immunohistochemical study of the ganglionic myoenteric cells

Para estudar a influência do processo granulomatoso esquistossomóticosobre as células ganglionares mioentéricas, foram utilizados 30 camundongos albinos Swiss infectadoscom 50 cercárias da cepa SLM do S. mansoni.O grupo controle foi constituído por dez animais näo infectados. Após sessenta dias de infecçäo, cortes histológicos do intestino delgadocorados por hematoxilina-eosina e P.A.S. demonstraram granulomas periovulares em todas as camadas da parede intestinal. Através do método imunohistoquímico indireto, usando-se a enolase neurônio-específica como marcador, observou-se desorganizaçäo do plexo mioentêrico em áreas contendo granulomas. Além disso, ocorreu rarefaçäo das estaçöes ganglionares, com aparente destruiçäo de células neuronais. A possível contribuiçäo dessas alteraçöes para a sintomatologia da esquistossomose humana é avaliada

Live adult worms detected by ultrasonography in human Bancroftian filariasis.

Ultrasonographic examination of the scrotal area was performed in 14 asymptomatic individuals with bancroftian filariasis and microfilaremia. While in seven subjects (50%) the ultrasonographic findings were normal, lymphatic dilation and tortuosity were observed in the other seven. In these vessels, structures with peculiar aleatory movements (filaria dance sign) were detected. A segment of the lymphatic tract containing these mobile intraluminal structures that was resected surgically from the left spermatic cord of one individual confirmed that these structures were living Wuchereria bancrofti adult worms (two females and one male). Our study demonstrates for the first time the feasibility of using a low-cost, widely available, noninvasive technique (ultrasonography) to detect and monitor living adult worms and lymphatic dilation in patients with bancroftian filariasis.

Tolerance of diethylcarbamazine by microfilaraemic and amicrofilaraemic individuals in an endemic area of Bancroftian filariasis, Recife, Brazil.

To determine the tolerance to diethylcarbamazine (DEC) treatment of patients with Bancroftian filariasis, 193 individuals (138 asymptomatic microfilaraemic, 30 amicrofilaraemic diseased patients and 25 asymptomatic amicrofilaraemic endemic residents) were enrolled in a prospective trial with different dose schedules, in a hospital and outpatient clinic setting in Brazil. Systemic adverse reactions, localized adverse reactions, and side effects, related to microfilariae, adult worms and the drug itself, were evaluated. Systemic reactions occurred irrespective of the DEC dose and schedule in about 40% of the microfilariae carriers, but not in amicrofilaraemic diseased patients or residents; they usually consisted of microscopic haematuria, followed by fever and malaise. Localized reactions were manifested by the appearance of inflammatory reactions, mainly in the scrotal area. Nodules containing degenerating adult worms developed mainly in the scrotal lymphatics of microfilaraemic patients, diseased amicrofilaraemic patients, and residents. Drowsiness, which increased with higher doses of DEC, was the most common side effect in both microfilaraemic and amicrofilaraemic individuals, followed by nausea and gastric upset. The results indicate that the occurrence of systemic and local adverse reactions was unrelated to either the dose of DEC or the pretreatment microfilarial density. The severity of systemic reactions was proportional to the microfilarial density. Side effects were dependent on the drug dosage irrespective of infection status.

Bancroftian lymphadenopathy: absence of eosinophils in tissues despite peripheral blood hypereosinophilia.

We studied the association of eosinophils with Wuchereria bancrofti parasites in two children with biopsy-proven filarial lymphadenopathy and peripheral blood hypereosinophilia. In both cases, intact adult worms were present in lymph nodes but no inflammatory reaction was observed. The most remarkable histological feature in our patients was the absence of eosinophils in tissue sections in spite of persistently high numbers of eosinophils in peripheral blood. In the first case, treatment of intestinal parasites before lymph node excision promptly reduced eosinophil counts to normal levels even though levels of microfilaraemia remained virtually unchanged. In the second patient, hypereosinophilia persisted after lymph node resection but disappeared following curative treatment of intestinal helminths. These observations raise fundamental questions about the causal relationship and the role of eosinophils in lymphatic filariasis.