Measuring Morbidity Associated with Urinary Schistosomiasis: Assessing Levels of Excreted Urine Albumin and Urinary Tract Pathologies

Background

Urinary schistosomiasis is responsible for a variety of debilitating conditions; foremost perhaps are urinary tract pathologies (UTPs). Although portable ultrasonography can be used to detect UTPs visually, there is still a need for rapid morbidity assessment (henceforth referred to as RaMA) tools that can be deployed in the field during implementation, monitoring and evaluation of control programmes. We therefore aimed to determine associations between excreted urine-albumin, as measured using a HemoCue photometer, and UTPs, as detected by ultrasonography, in children and adults from an urinary schistosomiasis endemic area in Zanzibar.

Methodology/Principal Findings

In a survey of 140 school-children of both sexes (aged 9 to 15 yr) and 47 adult males (≥16 yr) on the island of Unguja, the prevalence of egg-patent urinary schistosomiasis was 36.4% (CI₉₅ 28.5–45.0%) and 46.8% (CI₉₅ 32.1–61.9%) (P = 0.14), and that of UTPs was 39.4% (CI₉₅ 31.0–48.3%) and 64.4% (CI₉₅ 48.8–78.1%) (P = 0.006), respectively. In school-children, raised urine-albumin concentrations (>40 mg/L) were associated, albeit non-significantly, with prevalence of infection (OR = 3.1, P = 0.070), but more specifically and significantly with the prevalence of micro-haematuria (OR = 76.7, P<0.0001). In adults, elevated urine-albumin excretion was associated with UTPs, particularly lesions of the bladder wall (OR = 8.4, P = 0.013). Albuminuria showed promising diagnostic performance, especially in school-aged children with sensitivity of 63.3% and specificity of 83.1% at detecting lower UTPs, i.e. bladder-wall lesions (ultrasonography as ‘gold standard’).

Conclusion/Significance

This study indicates that albuminuria assays could be used as a RaMA tool for monitoring UTP prevalence during control programmes, as well as a tool for selecting those with more chronic bladder-wall lesions without resorting to ultrasonography.     

Urinary schistosomiasis in southern Ghana: 1. Prevalence and morbidity assessment in three (defined) rural areas drained by the Densu river

Epidemiological studies on urinary schistosomiasis were carried out in eight villages in the Ga and Akuapem South districts in Ghana. Single urine samples were collected from individuals aged 5 years and above between 10.00 and 14.00 h. The samples were examined for the presence of Schistosoma haematobium eggs using a filtration technique. Indirect morbidity was determined as the presence of microhaematuria and proteinuria using reagent strips, and macrohaematuria was recorded with the naked eye. Out of the study population of 3912 subjects, 2562 (65.5%) submitted urine samples. The prevalence of a Schistosoma haematobium infection ranged between 54.8 and 60.0%. Infection rates increased by age with a peak in the 10-19 years category, and decreased with increasing age. Disease prevalence was higher in males aged 15 years and above in Areas 2 (Ntoaso and Sansami Amanfro) and 3 (Dom Faase, Papase, Chento and Gidi Kope), whereas it was higher among males aged 10 years and above in Area 1 (Ayikai Doblo and Akramaman). The intensity of infection was highest among children aged 10-14 years in most of the villages. More than half of egg-positive children in this age group had a heavy infection (100 eggs and above in 10 ml of urine). Although both egg-positive and egg-negative individuals manifested variable degrees of macro- or micro-haematuria, microhaematuria was more prevalent among egg-positives (chi(2)=918.5, d.f.=1, P<0.01). The degree of microhaematuria and proteinuria were significantly associated with the intensity of the infection. These results indicate a high transmission of disease in the study area.     

Schistosoma haematobium infections in preschool children from two rural communities in Ijebu East, south-western Nigeria

There is an urgent need for information on schistosomiasis in preschool children, who are often excluded in mass treatment programmes. The prevalence and intensity of Schistosoma haematobium infection were determined in preschool children aged ≤ 6 years in two rural communities in Ijebu East, south-western Nigeria. Two urine samples each were collected from 83 preschool children from the two communities, tested for microhaematuria using reagent strips and then processed and examined with a microscope for S. haematobium eggs. Focus group discussions on perceptions of the disease and water contact practices were held in the communities with their guardians, caregivers and preschool children, using an interview guide. The prevalence of S. haematobium in the two communities was 14 (16.9%), with no significant differences (P = 0.661) in infection rate between boys (18.4%) and girls (14.7%). Both prevalence and intensity of infection did not increase significantly with age in both Korede and Obada community. However, there were significant differences in prevalence of infection between the two communities (P = 0.035). There was no association (P = 0.750) between intensity in boys (0.176 eggs/10 ml urine) and girls (0.110 eggs/10 ml urine). Focal group discussions with guardians and caregivers revealed that preschool children acquired infection early in their lives through exposure to infected stream water by their mothers, while the older children visit the stream for playing, bathing and swimming. It has therefore become imperative for preschool children to be included in the planning of schistosomiasis intervention programmes as a means of reducing transmission.     

Schistosoma haematobium Infection and CD4+ T-Cell Levels: A Cross-Sectional Study of Young South African Women

Schistosoma (S.) haematobium causes urogenital schistosomiasis and has been hypothesized to adversely impact HIV transmission and progression. On the other hand it has been hypothesized that HIV could influence the manifestations of schistosomiasis. In this cross-sectional study, we explored the association between urogenital S. haematobium infection and CD4 cell counts in 792 female high-school students from randomly selected schools in rural KwaZulu-Natal, South Africa. We also investigated the association between low CD4 cell counts in HIV positive women and the number of excreted schistosome eggs in urine. Sixteen percent were HIV positive and 31% had signs of urogenital schistosomiasis (as determined by genital sandy patches and / or abnormal blood vessels on ectocervix / vagina by colposcopy or presence of eggs in urine). After stratifying for HIV status, participants with and without urogenital schistosomiasis had similar CD4 cell counts. Furthermore, there was no significant difference in prevalence of urogenital schistosomiasis in HIV positive women with low and high CD4 cell counts. There was no significant difference in the number of eggs excreted in urine when comparing HIV positive and HIV negative women. Our findings indicate that urogenital schistosomiasis do not influence the number of circulating CD4 cells.     

Transmission of urinary schistosomiasis in Sukumaland, Tanzania. 1. Snail infection rates and incidence of infection in school children

Seasonal density fluctuations of Bulinus nasutus populations with accompanying Schistosoma haematobium infection rates in relation to rainfall and habitat water volumes were studied at Ukiriguru, Mwanza, Tanzania. Alongside the snail investigations, 50 school children initially negative for urinary schistosomiasis were examined regularly to determine seasonal incidence rates for the infection. Of the 17,646 B. nasutus collected in 2 years, 156 (0.88%) were found shedding cercariae. Snail populations fluctuated seasonally as influenced by rainfall through its effects on habitat water volume. Monthly snail infection rates ranged from 0.09% to 3.19% and were highest in February and March, at the time of the short dry period. Monthly incidence of S. haematobium in school children ranged between 2.6% and 12.5%, being highest in April and May. There was a significant linear association between monthly snail infection rates and S. haematobium incidence rates in school children (r2s = 0.65 in 1982/83; r2s = 0.87 in 1983/84) suggesting that the maximum transmission period for urinary schistosomiasis in the area occurs during the short dry period, sometime in February/March so that most of the infections in the community would be detected in April/May.     

Schistosomiasis in Cross River State, Nigeria: 1. Prevalence and intensity of infection in Adim, Akamkpa Local Government Area

Mid-stream urine was randomly collected from 248 subjects in Adim. Blood and protein concentrations were determined semi-quantitatively using Combi-7 reagent strips. The urine samples were then processed and any ova of Schistosoma haematobium present were counted per 10 ml urine. Fresh stool samples were also randomly collected, processed and examined for S. masoni and other helminthic ova. The prevalence of S. haematobium in the area was 43.5% and this was found to be age-related but not sex-related. Mean egg count was 137.2 per 10 ml urine. Intense haematuria of 250 ery/microliters and proteinuria of 500 mg/dl accompanied the high egg counts. The stool examination showed no cases of Manson's schistosomiasis but polyparasitism with other intestinal helminths was common particularly among children under 10 years old. This is the first report of urinary schistosomiasis in this area and the high prevalence rate is consistent with the rice farming occupation of the natives of the area. The sensitive nature and the case of application of the reagent strips in determining heavy infections by measuring haematuria and proteinuria is once again confirmed.     

Controlling Schistosomiasis: Significant Decrease of Anaemia Prevalence One Year after a Single Dose of Praziquantel in Nigerien Schoolchildren

Background

In the framework of the monitoring and evaluation of the Nigerien schistosomiasis and soil-transmitted helminth control programme, a follow-up of children took place in eight sentinel sites. The objective of the study was to assess the evolution of Schistosoma haematobium infection and anaemia in schoolchildren after a single administration of praziquantel (PZQ) and albendazole.

Methods/Principal Findings

Pre-treatment examination and follow-up at one year post-treatment of schoolchildren aged 7, 8, and 11 years, including interview, urine examination, ultrasound examination of the urinary tract, and measurement of haemoglobin. Before treatment, the overall prevalence of S. heamatobium infection was 75.4% of the 1,642 enrolled children, and 21.8% of children excreted more than 50 eggs/10 ml urine. Prevalence increased with age. The overall prevalence of anaemia (haemoglobin <11.5 g/dl) was 61.6%, decreasing significantly with increasing age. The mean haemoglobinemia was 11 g/dl. In bivariate analysis, anaemia was significantly more frequent in children infected with S. haematobium, although it was not correlated to the intensity of infection. Anaemia was also associated with micro-haematuria and to kidney distensions. In a sub-sample of 636 children tested for P. falciparum infection, anaemia was significantly more frequent in malaria-infected children. In multivariate analysis, significant predictors of anaemia were P. falciparum infection, kidney distension, and the village. One year after a single-dose praziquantel treatment (administered using the WHO PZQ dose pole) co-administered with albendazole (400 mg single dose) for de-worming, the prevalence of S. haematobium infection was 38%, while the prevalence of anaemia fell to 50.4%. The mean haemoglobinemia showed a statistically significant increase of 0.39 g/dl to reach 11.4 g/dl. Anaemia was no longer associated with S. haematobium or to P. falciparum infections, or to haematuria or ultrasound abnormalities of the urinary tract.

Conclusions

The high prevalence of anaemia in Nigerien children is clearly a result of many factors and not of schistosomiasis alone. Nevertheless, treatment of schistosomiasis and de-worming were followed by a partial, but significant, reduction of anaemia in schoolchildren, not explainable by any other obvious intervention.     

Genitourinary schistosomiasis among pre-primary schoolchildren in a rural community within the Cross River Basin, Nigeria

In Africa, most schistosomiasis control programmes defined the age 5-19 years as the target population for nationwide control through the school systems, excluding the under fives. A study was therefore undertaken to determine the prevalence and intensity of genitourinary schistosomiasis in children aged 0-5 years (pre-primary) in Adim, a rural and endemic community within the Cross River Basin, Nigeria. Of the 126 children examined, 25 (19.8%) were infected with Schistosoma haematobium, with no significant difference (P > 0.05) in infection rates between boys (21.1%) and girls (18.2%). Both prevalence and intensity of infection increased significantly (P 0.05) between intensity in boys (6.2 eggs/10 ml urine) and girls (5.6 eggs/10 ml urine). A total of 32.5 and 27.8% of the children had haematuria and proteinuria, respectively; it was not gender specific (P > 0.05). Six species of snail were encountered, with Bulinus globosus being the most abundant and widespread. The results of this study have shown that pre-primary schoolchildren are a source of transmission of schistosomiasis in endemic communities and should be integrated into any control intervention.     

Urinary fibrin-fibrinogen degradation products in nephrotic syndrome.

The urinary concentration of fibrin-fibrinogen degradation products (F.D.P.) was measured in 90 patients with proteinuria above 2 g/1 and correlated with proteinuria, differential protein clearances, serum urea and creatinine, and renal biopsy findings. There was a linear correlation (r equals 0-7; P less than 0-001) between the urinary F.D.P. excretion and the selectivity of the proteinuria such that patients with highly selective proteinuria excreted only small amounts of F.D.P. whereas those with non-selective proteinuria excreted much higher levels. There was a significant correlation between the urinary F.D.P. excretion and the urine:serum (U:S) ratio of IgG excretion but not with the U:S ratio or urinary excretion of albumin or transferrin. Sephadex G200 column chromatography of the concentrated urine in 26 cases showed that patients with highly selective proteinuria excreted predominantly F.D.P. of low molecular weight in the urine whereas those with non-selective proteinuria excreted mainly fibrinogen and products of high molecular weight. Hence the type and quantity of F.D.P. in the urine are determined primarily by the differential filtration of fibrinogen and the various degradation products from the plasma through the glomerular basement membrane, which in turn is determined by the "pore size" of the basement membrane. In clinical nephrology measurement of the urinary F.D.P. level provides a rapid and convenient means of estimating the differential protein clearance.     

Geographical distribution of schistosomiasis and soil-transmitted helminths among school children in informal settlements in Kisumu City, Western Kenya

This cross-sectional study determined the prevalence and distribution of schistosome and soil-transmitted helminth (STH) infections among 1,308 children aged 10-18 years in 34 primary schools in 8 informal urban settlements in Kisumu City, western Kenya. Stool samples were collected and examined for eggs of Schistosoma mansoni and STH (Hookworms, Ascaris lumbricoides and Trichuris trichiura) using the Kato-Katz technique. Haematuria was used as a proxy indicator of urinary schistosomiasis. Schools and water bodies were mapped using a geographical information system. Overall, 34% of children were infected with one or more helminth species whereas 16·2% of children were infected with one or more STH species. Schools in closest proximity to Lake Victoria and River Nyamasaria had the highest S. mansoni prevalence while schools with STH were more homogenously distributed. Mean school prevalence of S. mansoni infection was 21% (range=0-69·7%), S. haematobium 3·6% (range=0-12%), hookworms 6·1% (range=0-20%), A. lumbricoides 4·9% (range=0-18·4%), and T. trichiura 7·7% (range=0-18·6%). Helminth-related morbidities were not associated with infection. Our study demonstrates that schistosomiasis and STH are important health priorities among schools in informal settlements of Kisumu City, and highlights the need for routine deworming in similar settings.     

Effect of praziquantel on the immature stages of Schistosoma haematobium

Schistosoma mansoni is known to be refractory to praziquantel treatment in the pre-patent period of infection. Since Schistosoma haematobium has a much longer pre-patent period (10-12 weeks vs. 5-6 for the former species), we asked the question whether a correspondingly longer period of insusceptibility exists in urinary schistosomiasis. In hamsters treated at different times after infection, S. haematobium was partially refractory to praziquantel when treatment was given at week 5, but showed practically full sensitivity at 7-8 weeks and later times. Schistosoma haematobium worms obtained at different times after infection and exposed in vitro to praziquantel were refractory to low drug concentrations between 4 and 6 weeks, but were clearly affected at higher concentrations and at later time points. We conclude that S. haematobium does not have a praziquantel-insensitive window longer than in S. manson, in spite of its much longer maturation period. In addition, refractoriness of immature stages can be overcome at higher drug concentrations.     

The prevalence, intensity and clinical signs of urinary schistosomiasis in Imo state, Nigeria

Urine samples were assayed for urinary schistosomiasis in four local government areas (LGA) of Imo State, Nigeria between May 1998 and September 2000. A total of 3504 persons were sampled, with 880 (25.1%) being positive for urinary schistosomiasis, based on records of eggs of Schistosoma haematobium. The prevalence of S. haematobium infection differed in the various LGAs, with Oguta (38.9%) and Owerri-West (10.4%) showing the highest and the lowest values, respectively. Prevalence was higher in males (67.4%) than in females (32.6%) and in subjects 11-20 years of age (31.5%), while prevalence varied among different occupational groups, with farmers ranking the highest (41.6%). Visible haematuria was the predominant symptom (P<0.05). Of 880 persons positive for eggs of S. haematobium, 452 (51.4%) had visible haematuria, followed by suprapubic pains 214 (24.3%) and painful micturition 97 (11.0%). Although 367 (10. 5%) of the sampled subjects with eggs of S. haematobium showed no visible haematuria, 513 (14.6%) clearly demonstrated haematuria.     

Epidemiology of mixed Schistosoma mansoni and Schistosoma haematobium infections in northern Senegal

Due to the large overlap of Schistosoma mansoni- and Schistosoma haematobium-endemic regions in Africa, many people are at risk of co-infection, with potential adverse effects on schistosomiasis morbidity and control. Nonetheless, studies on the distribution and determinants of mixed Schistosoma infections have to date been rare. We conducted a cross-sectional survey in two communities in northern Senegal (n=857) to obtain further insight into the epidemiology of mixed infections and ectopic egg elimination. Overall prevalences of S. mansoni and S. haematobium infection were 61% and 50%, respectively, in these communities. Among infected subjects, 53% had mixed infections and 8% demonstrated ectopic egg elimination. Risk factors for mixed infection - i.e. gender, community of residence and age - were not different from what is generally seen in Schistosoma-endemic areas. Similar to overall S. mansoni and S. haematobium infections, age-related patterns of mixed infections showed the characteristic convex-shaped curve for schistosomiasis, with a rapid increase in children, a peak in adolescents and a decline in adults. Looking at the data in more detail however, the decline in overall S. haematobium infection prevalences and intensities appeared to be steeper than for S. mansoni, resulting in a decrease in mixed infections and a relative increase in single S. mansoni infections with age. Moreover, individuals with mixed infections had higher infection intensities of both S. mansoni and S. haematobium than those with single infections, especially those with ectopic egg elimination (P<0.05). High infection intensities in mixed infections, as well as age-related differences in infection patterns between S. mansoni and S. haematobium, may influence disease epidemiology and control considerably, and merit further studies into the underlying mechanisms of Schistosoma infections in co-endemic areas.     

Epidemiology of Schistosomiasis and Usefulness of Indirect Diagnostic Tests in School-Age Children in Cubal,Central Angola

Introduction

Schistosomiasis remains a public health major problem and little is known in many areas, mainly in Sub-Saharan Africa

Objectives

To assess the burden and risk factors of schistosomiasis and intestinal parasitic helminthes in the children of Cubal, Angola, and to compare different diagnostic approaches for urinary schistosomiasis under field conditions.

Methods

A cross-sectional study was conducted. Urine and faeces samples of school children were microscopically studied. A random sample of children was obtained from an alphabetically arranged list of children, taking one of two children. Urine dipstick, colorimetric test and macrohaematuria were considered as indirect diagnostic methods and compared to direct urine examination. Possible risk factors for the infection were sex, age, distance to the river and previous treatment with praziquantel; the assessment was performed using Chi-square test.

Results

A total of 785 (61.18%) children showed S. haematobium eggs in urine; children living within 500 meters from the river had a higher odds for infection: Odds ratio 1.97 (1.45–2.7 CI 95%); urine dipstick showed sensitivity of 96% and specificity of 61.3%, with a positive predictive value; colorimetric test showed sensitivity of 52.5%, specificity of 74.6% and a positive predictive value of 77%. Proteinuria was present in 653 (51.1%) children, being more frequent in children with S. haematobium in urine (75.2%); 32 of 191 stool samples (16%) showed the presence of other intestinal parasites and 8 (4%) for S. haematobium.

Conclusions

Prevalence of urinary schistosomiasis in our study area is much higher than the national average, considering it as a high-risk community. Proximity to a source of water was a risk factor for the infection. Indirect tests, as urine dipstick and colorimetric test, were useful tools for diagnosis, due to ease of use and low cost. Proteinuria was a common finding, probably showing an early structural damage due to schistosomiasis in this group of children.     

Endemicity, focality and seasonality of transmission of human schistosomiasis in Amagunze Village, eastern Nigeria

The pattern of transmission of human schistosomiasis was studied in Amagunze Village, eastern Nigeria, during 1986-1987. The prevalence of Schistosoma haematobium in 119 schoolboys aged 5-12 years was 79%. The geometric mean of intensity of infection was 49 eggs/10 ml urine and the frequency of visible haematuria was 25.2%. No S. mansoni infections were demonstrated. A marked seasonality in population density of Bulinus truncatus, B. forskalii and Biomphalaria pfeifferi was demonstrated with reduced densities during the late rainy and early dry seasons. Schistosoma sp. infected B. truncatus were found in the late dry and early rainy seasons in 2 out of 7 major human water contact sites studied. Seasonality and focality of transmission of S. haematobium and its high endemicity in the area were thus demonstrated.     

Single dose oral treatment in urinary schistosomiasis: a double blind trial.

A double blind trial of three oral preparations given in single doses for the treatment of Schistosoma haematobium infection was carried out in schoolchildren; selection was biased towards those who excreted large quantities of eggs. Praziquantel 40 mg/kg was the most effective drug giving a greater than 97% reduction in egg output six months after treatment; combined treatment with niridazole 25 mg/kg and metrifonate 10 mg/kg gave a reduction of greater than 92% and metrifonate 10 mg/kg alone a reduction of greater than 86%. Fewer children continued to have moderate to heavy infections (excretion greater than 124 ova/10 ml urine) six months after treatment with praziquantel (5%) and the combined regimen (7%) than with metrifonate (16%). Though our findings show that praziquantel appears to be the most effective and convenient drug available for individuals with S haematobium infection, the combined regimen is a cheaper alternative for treatment where cost is important and parasitological cure not an essential objective.     

Diagnostic Mr31/32,000 Schistosoma mansoni proteins (Sm31/32): reaction with sera from Sudanese patients infected with S. mansoni or S. haematobium

Sera of Sudanese patients with active infections of Schistosoma mansoni or S. haematobium were tested in immunoblots for their reactivity with Mr31/32,000 proteins of adult S. mansoni (Sm31/32). All sera from patients with intestinal (n = 123) and all but one from those with urinary schistosomiasis (n = 35) had antibodies against Sm31/32. These and additional data suggest that both specificity and sensitivity of Sm31/32 to detect schistosome infections are close to 100%. Antibodies against these proteins developed also in monkeys after experimental infection with S. haematobium. Sm31/32 antigens reacted in immunoblots as a doublet with most S. haematobium-patient sera and as a broad band with many S. mansoni-sera suggesting that at least two components are present in the molecular weight region of Mr31/32,000. The data demonstrate the potential use of Sm31/32 from adult worms to diagnose patients with intestinal or urinary schistosomiasis in endemic areas.     

Radioimmunological quantitation of urinary trypsin inhibitor

Using monospecific antibody to human urinary trypsin inhibitor, we developed a highly specific and sensitive radioimmunoassay (RIA) for measuring human urinary trypsin inhibitor. No cross-reactivity of the antibody with protein standard serum, which contained albumin, alpha 1-antitrypsin, haptoglobin, alpha 2-macroglobulin, transferrin, IgG and IgA, was observed. The sensitivity of the system was 10 ng of trypsin inhibitor per assay tube, and 5-10 microliters of urine was sufficient to determine the concentration of trypsin inhibitor in urine. The amounts excreted in the urine of 10 healthy men and 10 healthy women were 4.83 +/- 2.46 (mean +/- SD) and 3.86 +/- 1.35 mg/day, respectively. The correlation between estimates by RIA and those by enzymic assay was r = 0.96 (p less than 0.005). The method proposed here can be used to determine the concentration of urinary trypsin inhibitor in a small amount of biological fluids and cells.     

Comparison of biomarkers in workers exposed to 2,4,6-trinitrotoluene

2,4,6-Trinitrotoluene (TNT) is an important occupational and environmental pollutant. In TNT-exposed humans, notable toxic manifestations have included aplastic anaemia, toxic hepatitis, cataracts, hepatomegaly, and liver cancer. Therefore, methods were developed to biomonitor workers exposed to TNT. The workers were employed in a typical ammunition factory in China. The external dose (air levels and skin exposure), the internal dose (urinary metabolites), the biologically effective dose (haemoglobin adducts, urinary mutagenicity), biological effects (chromosomal aberrations and health effects), and individual susceptibility (genotypes of xenobiotic-metabolizing enzymes) were determined. Haemoglobin-adducts of TNT, 4-amino-2,6-dinitrotoluene (4ADNT) and 2-amino-4,6-dinitrotoluene (2ADNT), and the urinary metabolites of TNT, 4ADNT and 2ADNT, were found in all workers and in some controls. The levels of the haemoglobin-adducts or the urinary metabolites correlated weakly with the skin or air levels of TNT. The urinary mutagenicity determined in a subset of workers correlated strongly with the levels of 4ADNT and 2ADNT in urine. The haemoglobin-adducts correlated moderately with the urinary metabolites and with the urinary mutagenicity. The genotypes of glutathione S-transferases (GSTM1, GSTT1, GSTP1) and N-acetyltransferases (NAT1, NAT2) were determined. In general, the genotypes did not significantly influence the haemoglobin-adduct levels and the urine metabolite levels. However, TNT-exposed workers who carried the NAT1 rapid acetylator genotype showed an increase in urinary mutagenicity and chromosomal aberrations as compared with slow acetylators. The haemoglobin adduct 4ADNT was significantly associated with a risk of hepatomegaly, splenomegaly and cataract; urine metabolites and genotypes were not associated with health effects. These results indicate that a set of well-selected biomarkers may be more informative regarding exposure and effect than routinely performed chemical measurements of pollutants in the air or on the skin.     

Schistosoma japonicum: the pathology of experimental infection

The pathology of experimental schistosomiasis japonica is reviewed and compared with the pathology of schistosomiasis japonica in man and to some aspects of schistosomiasis mansoni and schistosomiasis haematobia in experimental animals. The induction of granulomas around Schistosoma japonicum eggs depends upon cell mediated immunity, as do the reactions to Schistosoma mansoni and Schistosoma haematobium eggs. However, the modulation of the reaction to S. japonicum eggs can be greatly influenced by antibody, while antibody has no effect on the granulomas around S. mansoni eggs. Adult worm pairs of S. japonicum tend to cluster in the mesenteric venules, and most eggs are laid in a few sites. This leads to large, focal intestinal lesions similar to the discrete lesions produced by S. haematobium in the intestine and urinary tract but in contrast to the widespread, diffuse lesions produced by S. mansoni. Comparison with S. japonicum infection in humans is limited chiefly by our scant knowledge of the pathology produced by S. japonicum in infected persons. Most such comparisons are, in any case, limited by the marked differences in the reactions of various experimental host species to the infection and by differences in the reaction of a given host species to different strains of the parasite.