A quantitative post mortem analysis of urinary schistosomiasis in Egypt. II. Evolution and epidemiology.

Further analysis of the data obtained from 190 unselected autopsies at the University of Cairo (Faculty of Medicine) hospitals reinforces our conclusion that a high prevalence of urinary schistosomiasis leads to infection intensity causing severe uropathy and mortality, both directly and by way of complications and sequelae. Based on histological study, two stages of urinary schistosomiasis must be considered in epidemiological work: "active disease", characterized by significant egg excretion; and "inactive disease", in which eggs are excreted rarely. The proportion between active and inactive cases is progressively reversed with advancing age, while mean tissue egg burdens rise, plateau, and ultimately decrease, most sharply beyond 50 years of age. A model of the progression of active disease has been derived from the relations of individual organ egg burdens to overall infection intensity, showing that both the onset and the termination of oviposition probably begin in the urinary bladder and spread centrifugally. Therefore, extravesical activity may persist longer than bladder activity. Severe uropathy and mortality occur at all stages of the disease and depend principally, but not exclusively, on egg burden, i.e., on infection intensity. Correlations of infection intensity with degree of uropathy show that severe disease is quantitatively separable from incidental disease by its tissue egg burdens and lesions. However, the factors determining death from urinary schistosomiasis are only partly understood. They include bilateral upper obstructive uropathy and, probably, focal egg concentrations leading to rapid obstruction, such as aberrantly high egg burdens in the left ureter relative to those in the bladder. Analysis of epidemiologically homogeneous population groups reveals close mutual relationships between the total frequency of infection (active plus inactive), the intensity of infection, and the frequency of severe uropathy. A statistical model predicts that any rise in frequency beyond a 30% threshold will result in a linear increase in the frequency of severe disease, whereas below that threshold the bulk of infections will be incidental. These insights, applicable only to pathological material, must be complemented by efforts to establish clinical and laboratory criteria defining the severity and stages of urinary schistosomiasis in living patients, and to examine their population dynamics, so that effects of therapeutic and preventive measures may be evalulated more precisely.

Schistosoma mansoni and S. haematobium infections in Egypt. IV. Hepatic lesions.

We performed 400 consecutive autopsies in Cairo, Egypt. The intensity of schistosome infection in these cases was measured by counting adult worms recovered by perfusion and dissection and by counting eggs in the tissues of infected cases. Symmers' clay pipestem fibrosis of the liver was clearly related to the presence and intensity of Schistosoma mansoni, but not S. haematobium, infection. Morphologic findings in cases with Symmers' fibrosis were comparable to those in Brazilian cases, and the intensity of S. mansoni infection associated with Symmers' fibrosis was similar in Brazil and Egypt. The fine bilharzial periportal fibrosis described by Hashem was not identified in our material, and Symmers' fibrosis was present in all cases of portal hypertension caused by schistosomiasis. Schistosome eggs were found concentrated in areas of portal fibrosis of cases with Symmers' fibrosis. In the absence of Symmers' fibrosis, eggs did not concentrate in large portal areas regardless of the intensity of infection or the presence of lesser degrees of portal fibrosis. We thus feel it unlikely that Symmers' fibrosis is formed by the fusion of fibrotic granulomas around the schistosome eggs.

Schistosoma mansoni and S. haematobium infections in Egypt. I. Evaluation of techniques for recovery of worms and eggs at necropsy.

Four hundred consecutive autopsy cases were examined in Cairo, Egypt. Sixty percent of cases had Schistosoma haematobium eggs in the tissues and 25% also were infected with S. mansoni. Only a quarter of S. haematobium infections were active, while nearly two-thirds of S. mansoni cases remained active. Adult S. haematobium and S. mansoni were effectively recovered from the mesenteric circulation by a combination of perfusion and dissection. Quantitative recovery from the genitourinary system was reasonably complete, although small numbers of worms were missed in the dissection of these organs.

Patterns of Schistosoma haematobium egg distribution in the human lower urinary tract. II. Obstructive uropathy.

In a series of 32 unselected consecutive autopsies of Egyptian male adults, we found a significant prevalence of schistosomal obstructive uropathy (SOU) and of precursor lesions of stenosis, fibrosis and induration of the ureters (62.5%). Lower urinary tracts with obstructive uropathy had a significantly higher total egg burden (TEB) than did lower urinary tracts with any other type of gross lesion (i.e., benign prostatic hypertrophy, other urethral outlet obstruction, or SOU precursor lesions). In turn, lower urinary tracts with any type of gross change had higher egg burdens than did tracts which appeared grossly normal. Lower urinary tracts with any type of gross lesion had significantly larger seminal vesicles than did tracts which were grossly normal. Moreover, relative weight of seminal vesicles could be correlated with the S. haematobium egg burdens in the seminal vesicles. In a series of lower urinary tracts taken from unselected consecutive American autopsies, seminal vesicle weight could be correlated with increase in prostatic weight in those tracts with prostatic hypertrophy; the same correlation could not be found in tracts without prostatic hypertrophy. Thus, seminal vesicle hypertrophy appears to correlate with obstructive uropathy in general, not solely obstructive uropathy of schistosomal origin. Digital evaluation of seminal vesicle size may be useful in the clinical evaluation of such patients.

Patterns of Schistosoma haematobium egg distribution in the human lower urinary tract. I. Noncancerous lower urinary tracts.

Schistosoma haematobium egg burdens (eggs/g of tissue) of 17 anatomic segments of lower urinary tracts from 32 unselected Egyptian autopsies have been determined by tissue digestion and replicate counts of aliquots of the digestate. There were three anatomic patterns of egg distribution in these lower urinary tracts: apical, basal and diffuse. Regression of egg burdens of each of the anatomic segments as the dependent variable against egg burdens of the entire lower urinary burden yielded a good fit for 15 of 17 of these segments. Statistical analyses revealed that many of these equations for discrete anatomic segments can be combined, generally giving one equation for anatomic regions which are in continuity, indicating that the female worm lives and oviposits in specified venous plexes. These equations also suggest that there are differences in the rates, duration and onset of egg accumulation which may be responsible for schistosomal obstructive uropathy as a cause of death in fairly young individuals.

Liver collagen-type characterization in human schistosomiasis. A histological, ultrastructural, and immunocytochemical correlation.

Liver biopsies of four patients with hepatosplenic schistosomiasis, two patients with schistosomiasis and chronic active hepatitis, two patients with chronic active hepatitis and four control patients with no clinical evidence of either disease, were examined by standard light microscopic techniques, electron microscopy and immunocytochemical staining for collagen type I, III and B. Pure schistosomiasis showed the classical "clay-pipe stem fibrosis" and granulomata composed of eosinophils, macrophages and lymphocytes. In that group, the hepatocellular damage was less conspicuous than in the groups with chronic hepatitis and was usually confined to the granulomatous or fibrotic areas. Destruction of the normal architecture and infiltration by macrophages and lymphocytes with severe damage of hepatocytes was found only in the cases of chronic active hepatitis, with or without associated schistosomiasis. Increased collagen deposits were demonstrated in all three groups. Types I, III and B were found in the enlarged portal triads and fibrotic septa. The intranodular or intralobular collagen stained negatively for type I and strongly positive for types III and B.

Patterns of Schistosoma haematobium egg distribution in the human lower urinary tract. III. Cancerous lower urinary tracts.

The distribution of S. haematobium eggs in urinary bladders containing tumors and removed at surgery has been studied; the majority of these tumors are well differentiated squamous cell carcinomas. The same three anatomic patterns of egg accumulation described in part I of this series (noncancerous lower urinary tracts) were found in these cancerous bladders, but, in addition, most of the tumors were surrounded by a collar of heavy S. haematobium egg deposition. The egg burdens in these collars were, on the average, twice the average egg burden in the remainder of the urinary bladder. These collars do not seem to be artifacts created by growth of the tumor and subsequent displacement of the adjacent normal tissue, creating a region of heavy egg concentrations; rather, these heavy S. haematobium egg concentrations seem to act as promoters of urothelial carcinogenesis.

Absence of schistosomal glomerulopathy in Schistosoma haematobium infection in man.

Kidneys were studied by light microscopy in 246 consecutive autopsies in Cairo, Egypt. Glomerulonephritis was not related to the presence or intensity of either S. haematobium or S. mansoni infection, and mesangial thickening and proliferation were also unrelated to schistosome infection. Acute and chronic pyelonephritis were also unrelated to the presence of schistosome infection.

Chronic hepatitis B antigenaemia in patients with hepatosplenic schistosomiasis.

Thirty-five male patients with decompensated hepatosplenic schistosomiasis were longitudinally studied and divided into 3 Groups; with hepatitis B surface antigen (HBsAg) or antibody (anti-HBs) and a control group negative to both. Patients with HBsAg were persistently carrying the antigen as estimated by radioimmunoassay (RIA) for up to 3 years and when compared with the other 2 groups, they had significantly higher serum glutamic transaminases, their liver biopsy showed more destructive liver cell lesions in the form of chronic active hepatitis or liver cirrhosis, they were refractory to diuretic treatment and had higher mortality rate (64% in 3 years compared to 22% and 33% in the other 2 groups). The majority of patients with dual infection are at greater risk in spreading hepatitis B as they proved to carry the 'e' antigen.

Liver collagen synthesis in schistosomiasis mansoni.

We determined collagen synthetic rates and utilization of key amino acid precursors of collagen in slices of wedge liver biopsy specimens obtained at required surgery from 9 patients with hepatosplenic schistosomiasis and from 4 control patients. The liver specimens from the patients with schistosomiasis showed advanced fibrosis, with histologic evidence of schistosomiasis alone in four, and both schistosomiasis and chronic active hepatitis in five cases. Liver slices were incubated with radioactive proline, arginine and glutamine, using quantitative assay conditions validated earlier for murine schistosomiasis. Collagen peptide synthesis in slices from all nine fibrotic liver specimens was 4- to 25-fold greater than normal and correlated positively with liver collagen content, which was 2- to 5-fold greater than normal. Free proline, an amino acid that may contribute to regulation of collagen peptide synthesis, was increased in six of the nine fibrotic liver specimens, and proline was actively formed from arginine in liver slices from all specimens. These measurements of the initial steps of collagen biosynthesis in fibrotic human liver are quantitatively similar to those previously made of the same processes in experimental animals.

Chronic hepatitis B in patients with schistosomiasis mansoni.

A village, 20 miles north of Cairo, with a census population of 2010, was surveyed in 1976 by the Center of Disease Control (CDC) and the Egyptian Ministry of Health for hepatitis B surface antigen (HBsAg). Ninety individuals (47 males and 43 females were positive for HBsAg (a prevalence rate of 4.5%). Forty-two of the 47 males were the subject of this study. They were admitted to the Naval Medical Research Unit Hospital 2 years later. They all had active Schistosoma mansoni infection. Nineteen of the 42 were carrying HBsAg and the remaining 23 were negative for hepatitis antigen at this time of investigation. Histological examination of percutaneous liver biopsies showed chronic-active hepatitis in five of 17 HBsAg carriers including two with additional cirrhosis. Two others with clinical evidence of cirrhosis could not safely have biopsies taken. Two of these 19 persons died and three became incapacitated over 2 years of further observation. Of the 23 individuals who had transient HBsAg in 1976 and equally heavy S. mansoni infection, evaluation in 1978 showed chronic active hepatitis in one, and at re-evaluation 2 years later, one had become unable to work but none had died. Ten other individuals (military recruits) from different villages of the Nile Valley who had no schistosomiasis but were carriers of HBsAg, were symptom free and liver biopsy showed chronic active hepatitis in one individual and no morbidity or mortality in 2 years. Morbidity of chronic hepatitis B infection in S. mansoni infected persons appears to be unusually severe compared with hepatitis B infection in other populations.

Clinical and immunological results of segmental splenectomy in schistosomiasis.

We evaluated segmental splenectomy in 51 patients who required splenectomy to relieve the symptoms of schistosomal splenomegaly, and compared their course with that of 44 patients who underwent total splenectomy in an unrandomized study. We describe a minor modification of our initial technique. Patients having segmental splenectomy had a similar postoperative course to those having total splenectomy. Conversion of a segmental to a total splenectomy was required in two cases due to technical faults. No regrowth of the spleen has occurred in up to 4 years of observation. We noted an increased percentage of T lymphocytes with an increased ratio of T helper to T suppressor cells in patients having segmental splenectomy. Our cumulative experience supports adoption and wider evaluation of segmental splenectomy in schistosomiasis.