Catching the Worm Early: An Atypical Case of Bancroftian Filarial Nephropathy.

Filarial glomerular disease has been attributed to circulating immune complex deposition. We report here a rare manifestation of filarial nephropathy with microfilariae documented in glomerular capillaries in addition to immune complex glomerulonephritis, thus suggesting that direct toxicity may also contribute to the pathogenesis of this entity.

Mesangial proliferative glomerulonephritis in murine malaria parasite, Plasmodium chabaudi AS, infected NC mice.

BACKGROUND: Malaria is an important tropical disease and has remained a serious health problem in many countries. One of the critical complications of malarial infection is renal injury, such as acute renal failure and chronic glomerulopathy. Few animal models of nephropathy related to malarial infection have been reported. Therefore, we developed and investigated a novel malarial nephropathy model in mice infected by murine malaria parasites. METHODS: NC mice and C57BL/6J mice were infected with Ttwo different murine malaria parasites, Plasmodium (P.) chabaudi AS and P. yoelii 17X. After the infection, renal pathology and blood and urinary biochemistry were analyzed. RESULTS: NC mice infected by the murine malaria parasite P. chabaudi AS, but not P. yoelii 17X, developed mesangial proliferative glomerulonephritis with endothelial damage, and decreased serum albumin concentration and increased proteinuria. These pathological changes were accompanied by deposition of immunoglobulin G and complement component 3, mainly in the mesangium until day 4 and in the mesangium and glomerular capillaries from day 8. On day 21, renal pathology developed to focal segmental sclerosis according to light microscopy. In C57BL/6J mice, renal injuries were not observed from either parasite infection. CONCLUSION: The clinical and pathological features of P. chabaudi AS infection in NC mice might be similar to quartan malarial nephropathy resulting from human malaria parasite P. malariae infection. The NC mouse model might therefore be useful in analyzing the underlying mechanisms and developing therapeutic approaches to malaria-related nephropathy.

Activation of autophagy and nucleotide-binding domain leucine-rich repeat-containing-like receptor family, pyrin domain-containing 3 inflammasome during Leishmania infantum-associated glomerulonephritis.

Chronic kidney disease is a major contributor to human and companion animal morbidity and mortality. Renal complications are sequelae of canine and human visceral leishmaniasis (VL). Despite the high incidence of infection-mediated glomerulonephritis, little is known about pathogenesis of VL-associated renal disease. Leishmania infantum-infected dogs are a naturally occurring model of VL-associated glomerulonephritis. Membranoproliferative glomerulonephritis type I [24 of 25 (96%)], with interstitial lymphoplasmacytic nephritis [23 of 25 (92%)], and glomerular and interstitial fibrosis [12 of 25 (48%)] were predominant lesions. An ultrastructural evaluation of glomeruli from animals with VL identified mesangial cell proliferation and interposition. Immunohistochemistry demonstrated significant Leishmania antigen, IgG, and C3b deposition in VL dog glomeruli. Asymptomatic and symptomatic dogs had increased glomerular nucleotide-binding domain leucine-rich repeat-containing-like receptor family, pyrin domain containing 3 and autophagosome-associated microtubule-associated protein 1 light chain 3 associated with glomerular lesion severity. Transcriptional analyses from symptomatic dogs confirmed induction of autophagy and inflammasome genes within glomeruli and tubules. On the basis of temporal VL staging, glomerulonephritis was initiated by IgG and complement deposition. This deposition preceded presence of nucleotide-binding domain leucine-rich repeat-containing-like receptor family, pyrin domain containing 3-associated inflammasomes and increased light chain 3 puncta indicative of autophagosomes in glomeruli from dogs with clinical VL and renal failure. These findings indicate potential roles for inflammasome complexes in glomerular damage during VL and autophagy in ensuing cellular responses.

Ultrastructural pathological changes in mice kidney caused by Plasmodium berghei infection.

Malaria, a common health problem in certain parts of the world, has a considerable morbidity and mortality. This work reports under electron microscopy studies serious ultrastructural kidney damage such as extensive cytoplasmic vacuolation, vesiculation and autophagic vacuoles in proximal tubular cells. A thickened endothelial wall on peritubular capillary, interdigitation disorganization and significant decrease of their number in some areas were detected. Swollen rough endoplasmic reticulum, swollen mitochondria, and parasitized erythrocytes were observed. Many epithelial cells exhibited cytoplasmic areas of autophagia and a myelin-like form. A tubular cell presented severe cytoarchitecture alterations. Abundant lipid droplets were noticed. Almost total loss of interdigitations, rough endoplasmic reticulum vesiculation, peritubular capillaries with endothelial cells thickened cytoplasm, papillary processes projected to the lumen, and an inflammatory infiltrate of macrophages were also observed. These ultrastructural kidney changes could cause, on the basis of their clinical and pathologic expressions, a fat accumulation, an acute temporary reversible glomerulonephritis, a chronic progressive irreversible glomerulonephritis, and an acute renal failure (ARF).

Kidney ultrastructural lesions in dogs experimentally infected with Dirofilaria immitis (Leidy, 1856).

Kidneys of 16 beagles with experimentally induced heartworm (Dirofilaria immitis) infections and 4 heartworm-nai;ve dogs were studied by light and electron microscopy. The infections were induced either by subcutaneous injection of infective larvae or by the transplantation of adult parasites, and infection periods varied from 111 to 818 days and 365 to 923 days, respectively. One control group of heartworm-naïve dogs and four groups of heartworm-infected dogs, which were divided according to the type and the length of infection, were used. In the infected dogs, thickening of the glomerular basement membrane (GBM), the presence of dense deposits in the GBM, and foot process effacement were the most frequent lesions observed. In some dogs, electron dense deposits were seen in the GBM and the mesangium and/or enlargement of the mesangial matrix could be characterized. The longer the infection period, the thicker the GBM and the more common the occurrence of foot process effacement. In general, these alterations were more evident in animals that had been infected for more than 1 year, had high microfilaremia, and had 14 or more parasites in the main pulmonary artery and its branches. The presence of dense deposits suggests that the pathogenesis of kidney disease in dirofilariasis is associated with deposits of immune complexes in the membrane. The finding of ultrastructural changes in dogs with early prepatent infections suggests that immature heartworms, as well as microfilariae and possibly adult worms, contribute to the glomerulonephropathy.

Schistosoma mansoni: kinetics of glomerulonephritis in Mongolian gerbils and its correlation with intensity and duration of infection.

The frequent occurrence of glomerular lesions in schistosomiasis patients has been reported, although appropriate animal models for the study of schistosomal glomerulonephritis have not been developed. To analyze the relationship between glomerulonephritis and Schistosoma mansoni infection, gerbils, Meriones unguiculatus, were infected with different number of cercariae and sacrificed at different weeks of post infection. Fifty cercariae were the optimum dose to produce the disease, glomerulonephritis, without early death of the animal. Infected gerbils showed heterogeneous types of glomerular lesions with increased serum creatinine level. Immune complex deposition was not detected at glomeruli of infected gerbils even by means of immunuofluorescence and also by transmission electron microscopy. However, infiltration of mononuclear cells in and around some of the altered glomeruli was observed. Immunohistochemical staining, using monoclonal antibody (HUSM-M.g. 15) specific to gerbil's T-cells, revealed significant infiltration of T-cells. These findings suggest that T-cells might be involved in the development of glomerulonephritis. Gerbil could be a useful model to clarify the role of T-cells in the development of glomerulonephritis of schistosomiasis.

Fine structure of Sarcocystis singaporensis merogony stages preceding sarcocyst formation in the rat.

The fine structure of merogony stages of Sarcocystis singaporensis (Zaman and Colley, 1975) is described from experimentally infected laboratory rats, 10 days after being fed sporocysts obtained from naturally infected Python reticulatus from Singapore. Infection was shown to consist exclusively of S. singaporensis. Parasites developed in the endothelial cells of the lungs, brain, kidney and heart. Infection comprised meronts prior to division, dividing and divided meronts, and dispersed merozoites. Undivided meronts developed deep pellicular invaginations and extensions of the nucleus toward the cell boundary, seemingly to sustain metabolic exchange. The course of merogonous development was the same in all organs. Hypertrophy of the endothelium induced by invading merozoites appeared to lead to obstruction of the capillary lumen.

Histological assessment of tissue repair after treatment of human schistosomiasis.

Schistosomiasis is one of the main health problems hindering socio-economic development in Egypt. It affects millions at an early age, diminishing productivity and exerting a significant socio-economic impact. Schistosomiasis endemicity in Egypt varies in different areas. Schistosoma mansoni, with a prevalence generally ranging between 20 to 40%, has replaced Schistosoma haematobium in the Nile Delta, and the latter is now localized to upper Egypt with low endemicity levels (5-10%). The pathology of schistosomiasis consists essentially of a series of chronic inflammatory lesions produced in and around blood vessels by eggs or their products and sometimes by dead adult worms. If the ova continued to be deposited in sufficient numbers and over several years, they would ultimately lead to progressive fibrosis of the portal tracts and urinary bladder, or may be carried in blood and become trapped in the lungs, gastro-intestinal and genital tracts with only occasional association with other organs. The etiology of human pipe-stem fibrosis is still not understood. The host immune response and frequency of exposure and the time of re-infection interval appear to be involved in the overall process of fibrosis. Additional factors are probably involved in the human disease as genetic host susceptibility, malnutrition, repeated infections and repeated treatment, mixed infections including hepatitis, tuberculosis and typhoid. Reversibility of the fibrosis might be related to the proportion of the collagen types present. Immuno-histopathological demonstration of various types of collagen confirms the importance of time for administration of the treatment and period of follow-up. According to previous studies, the timing for treatment affects the reversibility of liver fibrosis emphasizing the importance of early treatment of schistosomiasis to prevent complications.

Glomerular disease associated with Polysporoplasma sparis (Myxozoa) infections in cultured gilthead sea bream, Sparus aurata L. (Pisces: Teleostei).

Polysporoplasma sparis infection was studied in gilthead sea bream from different mariculture systems of the Spanish coasts. Culture conditions influenced the infection dynamics, as the parasite appeared only in semi-intensive cultures and was not found in intensive closed systems nor in open ones. No clear seasonal pattern was observed. No fish weighing less than 51 g was found parasitized in any group. A statistically significant dependence between infection prevalence and host weight was observed in some growing stocks. Light and transmission electron microscope observations revealed serious damage in the trunk kidney. Glomerular disease was provoked by the progressive occupation of the glomerular capillaries by P. sparis spores. Tubular epithelial cells were also affected. Inflammatory responses appeared towards the end of the infection, and consisted mainly of melanomacrophages and eosinophils. Rodlet cells were common close to infected capillaries and debris of rodlet sacs formed a belt encircling capillary vessels. Cytochemistry demonstrated the lipidic nature of these sacs and the glycogen and glycoprotein composition of the cytoplasmic granules of rodlet cells.

Ultrastructural alterations in glomerulophathy associated with hydatidosis in sheep

En el presente trabajo se investigaron las alteraciones ultraestructurales en el glomérulo renal de ovejas con hidatidosis. Utilizando microscopía electrónica de transmisión, fueron examinadas muestras renales de 39 ovejas, 34 de ellas con hidatidosis y 5 sin la parasitosis. Adicionalmente, fue realizado un estudio bioquímico a través de dosaje sérico de creatinina, úrea, proteínas totales y albumina. Las alteraciones ultraestructurales identificadas fueron la presencia de depósitos densos mesangiales, subendoteliales e intramembranosos; proliferación de células mesangiales con áreas de esclerosis segmentaria e interposición de células mesangiales con formación de neo-membrana. Durante el estudio bioquímico se observó un aumento significativo de proteínas totales séricas en el grupo experimental en relación con el de control. El estudio demostró que la glomerulonefritis asociada a hidatidosis en ovinos puede ser clasificada en 4 categorías: lesiones mínimas, glomerulonefritis mesangial, glomerulonefritis segmentaria y focal, y glomerulonefritis membranoproliferativa, siendo predominantemente proliferativa y mesangial

Secondary collapsing glomerulopathy associated with Loa loa filariasis.

This is the first case of nonprimary collapsing focal segmental glomerulosclerosis (FSGS) associated with Loa loa filariasis. Loa loa micofilariae were detected on a blood smear after a patient presented with nephrotic syndrome (NS), microhematuria, and renal failure. The renal biopsy showed a collapsing glomerulopathy variant of FSGS. Microfilariae also were identified in renal microvasculature, including the afferent arterioles and the glomerular and peritubular capillaries.

Immunoglobulin-A and the pathogenesis of schistosomal glomerulopathy.

Several observations suggest that the evolution of schistosomal glomerulopathy into clinically overt and progressive disease may involve pathogenetic mechanisms other than simple glomerular deposition of parasitic antigens. In a previous study, IgA was suggested to be a mediator of late glomerular lesions in this disease. This issue is further addressed in this work. The study includes 32 patients with hepatosplenic schistosomiasis, of whom 16 had overt glomerular involvement, along with four control groups: (a) 15 healthy volunteers; (b) 15 patients with simple intestinal mansoniasis; (c) 17 patients with non-schistosomal chronic liver disease; and (d) 21 subjects with primary nephrotic syndrome not associated with schistosomiasis. Routine assessment was done for all subjects including confirmatory tests for schistosomal infection, liver and renal function tests, hepatitis viral markers and abdominal ultrasonography. The total serum concentrations of IgG, IgM, IgA were measured, as well as their respective circulating immune complexes, rheumatoid factors, anti-gliadin- and anti-DNA-antibodies. Liver and renal biopsies were obtained from the relevant groups and studied by light microscopy. Renal biopsies were also examined by immunofluorescence. Patients with simple intestinal schistosomiasis had a significant increase in IgM antigliadin antibodies. Those complicated with hepatosplenic involvement also had a significant increase in the mean IgG anti-gliadin antibodies, IgG rheumatoid factor and IgM anti-DNA activity. Cases further complicated by overt glomerular disease showed a distinct IgA predominance, mainly expressed in the serum anti-gliadin antibody pool and anti-DNA activity. This profile was essentially similar to that observed in control cirrhotics. There was a significant increase in the frequency of IgA glomerular deposits in renal biopsies obtained from patients with overt schistosomal glomerulopathy, in contrast to control nephrotics. The deposits were mainly mesangial, but were also encountered in subendothelial, subepithelial and peritubular locations. Their frequency was significantly higher with more advanced lesions as seen by light microscopy. The relevance of these data is discussed, leading to the following conclusions: (a) serum IgA-anti-gliadin and -anti-DNA antibodies, and glomerular IgA deposits are markers of significant renal involvement in patients with hepatosplenic schistosomiasis. (b) IgA may be involved in the pathogenesis of advanced glomerular pathology when superimposed on parasite-induced lesions. (c) There is a significant increase in serum auto-reactivity in hepatosplenic schistosomiasis, which may also have pathogentic implications. (d) Increased production by the inflammatory bowel lesions, impaired clearance by the fibrotic livers and probable switching of immunoglobulin synthesis are suggested to explain the observed IgA predominance in those who develop renal complications.

O Projeto Queixadinha: a morbidade e o controle da esquistossomose em área endêmica no nordeste de Minas Gerais, Brasil / Queixadinha project: morbidity and control of schistosomiasis in an endemic area in the northeast of State of Minas Gerais, Brazil

In an endemic area for schistosomiasis in the northeast of the state of Minas Gerais in Brazil 516 individuals have been submitted to clinical and laboratory examination, ultrasonography of the abdomen and dopplerecocardiography in order to define the morbidity of schistosomiasis before and after treatment. A high prevalence of schistosomiasis (66.3 per cent) and of severe disease (9.5per cent with palpable spleens) were recorded. Ultrasonography classified liver periportal fibrosis as light (19.4 per cent), moderate (27.6 per cent) and intense (6.8 per cent), and 46.0 per cent presented no periportal fibrosis. Twenty one out of the 53 individuals (39.6 per cent) with palpable spleens did not present liver fibrosis on ultrasound. Periportal lymph nodes were described in 33.8 per cent of the population and anti-KLH antibodies were found in the serum of 40.7 per cent. Urinary alterations compatible with the glomerulopathy of schistosomiasis were observed in 4.5 per cent of the population, and 11.7 per cent of the individuals examined by dopplerecocardiography had pulmonary hypertension. Twelve months after treatment for schistosomiasis the prevalence of the disease dropped from 66.3 per cent to 25.0 per cent. In Queixadinha, a profile of the morbidity of schistosomiasis has just been established.

[The Queixadinha Project: morbidity and control of schistosomiasis in an endemic area in the northeast of Minas Gerais, Brazil]. / O Projeto Queixadinha: a morbidade e o controle da esquistossomose em área endêmica no nordeste de Minas Gerais, Brasil.

In an endemic area for schistosomiasis in the northeast of the state of Minas Gerais in Brazil 516 individuals have been submitted to clinical and laboratory examination, ultrasonography of the abdomen and dopplerecocardiography in order to define the morbidity of schistosomiasis before and after treatment. A high prevalence of schistosomiasis (66.3%) and of severe disease (9.5% with palpable spleens) were recorded. Ultrasonography classified liver periportal fibrosis as light (19.4%), moderate (27.6%) and intense (6.8%), and 46.0% presented no periportal fibrosis. Twenty one out of the 53 individuals (39.6%) with palpable spleens did not present liver fibrosis on ultrasound. Periportal lymph nodes were described in 33.8% of the population and anti-KLH antibodies were found in the serum of 40.7%. Urinary alterations compatible with the glomerulopathy of schistosomiasis were observed in 4.5% of the population, and 11.7% of the individuals examined by dopplerecocardiography had pulmonary hypertension. Twelve months after treatment for schistosomiasis the prevalence of the disease dropped from 66.3% to 25.0%. In Queixadinha, a profile of the morbidity of schistosomiasis has just been established.

Immune complex-mediated glomerulopathy in Barbus graellsi infected with Myxobolus spp.

Membranous glomerulonephritis caused in Barbus graellsi by myxosporidian infections have been studied by electron microscopy and immunoelectron microscopy techniques. This study indicates that Myxosporidian infection produces a chronic severe aggression. Spores reach the spleen, the kidney and the liver, where they are trapped and phagocyted by Melano Macrophage Centres. Consequently, the commencement of a immunological response to myxosporidian is evident. Our results show the presence of immunodeposits in the basement membrane of the glomeruli, suggesting that they might initiate glomerulonephritis. The lesion was markedly similar to immune complex-mediated glomerulonephritis disease in higher vertebrates.

Filarial nephritis: a cause of nephrotic syndrome.

A 26-year-old male presented with oedema, massive albuminuria and microscopic haematuria. Kidney biopsy revealed enlarged cellular glomeruli infiltrated by polymorphs and eosinophils with focal fibrin deposits along the basement membrane. Microfilariae were seen in the lumen of few glomerular capillaries. Antistreptolysin titre was negative. The absence of other aetiological factors and presence of microfilariae within glomeruli suggests that nephrotic syndrome may be due to a filarial nephritis.