Bilharzia induced pathologies and techniques of detection in Uganda: a review.

BACKGROUND: Schistosoma S. mansoni was observed and reported in Uganda in 1902. Schistosoma S. mansoni is widely distributed in Uganda along permanent water bodies. OBJECTIVE: To review the literature on previous techniques and conventional ones used for the assessment and comparison of morbidity due to schistosomiasis in Uganda. DESIGN: Retrospective study. SETTING: Gulu University, Faculty of Medicine, Department of Microbiology and Immunology. RESULTS: Since its first detection in 1902 Schistosomiasis mansoni and later Schistosomiasis haematobium in Uganda, morbidity assessment was based on physical examination and intensity of eggs excretion. The first field study in Uganda of schistosomiasis pathologies using ultrasound was that conducted in West Nile in Obongi, Rhino Camp and Pundu in 1991 and reviewed in 1992. These armless and none invasive method of pathologies detection has the advantage of repeatability. It showed that after treatment there was reversibility of pathological conditions introduced by the parasites in the hosts. CONCLUSION: Schistosomiasis mansoni pathologies as detected by the none invasive ultrasound findings compared well with those of the more risky invasive liver biopsy. The detection of pathologies by clinical examination was less sensitive. Pathological lesions due to S. haematobium correlated with abnormalities of the urinary tract and intensity of eggs in urine.

The effect of metrifonate in mixed Schistosoma haematobium and Schistosoma mansoni infections in humans.

In order to examine the effect of metrifonate, 156 patients with mixed Schistosoma haematobium and mansoni infection were randomly divided into three groups and treated with metrifonate (twice 10 mg/kg body weight), oxamniquine (60 mg/kg) and praziquantel (40 mg/kg), respectively. The output of S. haematobium and S. mansoni ova were quantitatively assessed in urine and stool. Application of metrifonate resulted in a similar reduction of S. haematobium and S. mansoni eggs in the urine, whereas no effect on egg excretion was observed in the stool irrespective of the parasite species. In contrast, oxamniquine influenced the output of S. mansoni ova in stool and urine, but showed no effect on S. haematobium egg excretion. praziquantel was equally effective against both parasite species. The chemotherapeutic effects were not of transient nature since the number of ova of both parasite species remained unchanged five months after treatment. The results clearly indicate that metrifonate acted exclusively on adult worms located in the perivesical plexus irrespective of the parasite species.

Daily urinary protein loss in Schistosoma haematobium infection.

Proteinuria was studied in 128 children aged 6 to 18 years with Schistosoma haematobium infection in the People's Republic of Congo. Urinary protein concentration in spontaneously voided midday urine of patients with greater than 100 ova/10 ml was significantly higher than in 24-hr urine specimens. Median daily urinary protein loss in patients with moderate intensity of infection (100-350 ova/10 ml) was 300 mg and 584 mg/1.73 m2 body surface in heavily infected patients (greater than 350 ova/10 ml). A significant correlation existed between egg excretion at noon and protein concentration in spontaneous urine samples as well as daily urinary protein loss (r = 0.76 and r = 0.68, respectively). Heavily infected patients had a daily protein loss of up to 3.3 g/1.73 m2, total serum protein and albumin concentration, however, were within normal limits. This may indicate adaptive mechanisms in patients with urinary schistosomiasis and high proteinuria which maintain a balanced serum protein concentration.

Ultrasonographic assessment of Schistosoma mansoni and S haematobium morbidity in Zimbabwean schoolchildren.

Ultrasound examinations for Schistosoma haematobium - and S. mansoni-related morbidity were done in 174 schoolchildren from a subsistence farming community in southern Zimbabwe. The examinations were done according to the standardized protocol elaborated by the Cairo Working Group (the Cairo classification) and the Managil classification. Forty-six percent of the children had grade I periportal thickening (PPT) on ultrasound according to the Cairo classification, but none had grade II or higher. The significance of grade I PPT in the Cairo classification is questionable, since there were no differences between those without and those with grade I PPT with respect to intensity of S. mansoni infection or liver size. The prevalence of grade I PPT according to the Managil classification was 10%, and no association between the two classifications was seen. In multiple regression analysis, S. mansoni egg output was found to be a significant predictor of liver size, when controlling for height and sex. An interaction between S. haematobium and S. mansoni infection is suggested because the positive relationship between S. mansoni and liver size was seen in the presence but not in the absence of S. haematobium infection.

Efficacy of metrifonate in urinary schistosomiasis: comparison of reduction of Schistosoma haematobium and S. mansoni eggs.

Patients with schistosomiasis mansoni and schistosomiasis haematobium from the Gezira area of the Sudan were investigated for the simultaneous presence of Schistosoma mansoni and S. haematobium eggs in urine. Before treatment, 28 or 34 mixed-infection patients constantly excreted eggs of S. mansoni in the urine; however, the concentration was only 1.7% that of S. haematobium eggs. Patients were given two doses of metrifonate (10 mg/kg body weight) 2 weeks apart in order to compare the effect of the organophosphorous compound on the two parasite species. Each dose of metrifonate was followed by a significant decrease in egg output in urine (P less than 0.01). The egg reduction was similar for both parasite species, and was almost 99% after the second treatment. Before treatment was started, a positive correlation existed between the numbers of S. haematobium and S. mansoni eggs excreted in urine (r = 0.75, P less than 0.001), and this correlation did not change after the first or the second dose of metrifonate. After treatment, in 6 of 37 patients S. haematobium eggs and in 8 of 28 patients S. mansoni eggs were not, or were only slightly, reduced. When chemotherapeutic failure of metrifonate against S. haematobium or S. mansoni occurred, it was quantitatively similar for both parasite species.

Toxoplasma gondii antibodies in pregnant women and their newborns in Dar es Salaam, Tanzania.

The sera of 849 Tanzanian pregnant women were tested at delivery for Toxoplasma gondii antibodies with the Sabin-Feldman dye test (DT) and an immunosorbent agglutination assay. A total of 296 (35%) of these women had DT titers greater than 1:4. The percentage of women with dye test titers greater than 1:4 was 34-37% regardless of the individual ages. The rate of positivity for human immunodeficiency virus 1/2 (HIV-1/2) using Western blotting was 11.5%. There was no relationship between prevalence of a positive DT result and HIV infection nor between the intensity of the DT result and HIV infection. Sixty-four parturients had a DT titer of 1:1,000 or more. From 57 newborns of these mothers, cord sera were available and were screened by the DT and the immunosorbent agglutination assay. Seven of these were found to be positive for IgM and/or IgA antibodies. It was concluded that the rate of serologic evidence for prenatal Toxoplasma infection in cord blood samples in the present study of Tanzanian pregnant women was approximately 0.8%.

Evidence for a long-term effect of a single dose of praziquantel on Schistosoma mansoni-induced hepatosplenic lesions in northern Uganda.

Treatment with praziquantel reduces the prevalence and intensity of Schistosoma mansoni infection. However, reversibility of periportal fibrosis of the liver, which potentially leads to fatal complications, is not unequivocally substantiated. In the Nile District of Uganda, 460 patients were parasitologically (Kato-Katz method) and ultrasonographically examined during October 1991, October 1992, and May 1994. Treatment with praziquantel at a dosage of 40 mg per kilogram of body weight was given in October 1991 and October 1992 to 460 individuals (group A). Another 192 patients were seen during the baseline study in October 1991 and missed the follow-up in October 1992 but took part in the second follow-up in May 1994. Thus, they received praziquantel only once in October 1991 (group B) and had an interval of 2.7 years until the next investigation in May 1994. Periportal thickening (PT) of the liver was assessed by ultrasound at each time point. Praziquantel therapy reduced the prevalence of S. mansoni in group A from 84% in 1991 to 31% in 1992 and 30% in 1994. The respective intensities of infection (geometric means of egg output) were 81 eggs per gram (epg) of stool in 1991, 31 epg in 1992, and 30 epg in 1994. Periportal thickening was found in 46% of patients in 1991, 32% of patients in 1992, and 35% of patients in 1994. Reversibility of PT was influenced by age (markedly lower reversibility in individuals older than 30 years) and sex (women and girls responded less favorably than did men and boys). Surprisingly, no significant difference was detected between group A and group B with respect to reversibility of PT The outcome between the 2 groups did not differ significantly. This may indicate that a single dose of praziquantel (as given to group B) may have a longer lasting effect than previously thought, that is, more than 2.5 years.

Hepatosplenic morbidity in schistosomiasis japonica: evaluation with Doppler sonography.

In Southeast Asia, schistosomiasis japonica is an important cause of hepatic fibrosis and gastrointestinal hemorrhage. Reliable methods to investigate portal hypertension (PHT) clinically and epidemiologically on community level are lacking. Doppler sonography is an established tool for investigating PHT in hospital settings. In Leyte, The Philippines, 137 individuals underwent color Doppler sonography, stool examination, and serology for hepatitis B and C, liver cell injury and cholestasis. A total of 85% of the study population had been infected with Schistosoma japonicum. Sonographically, periportal liver fibrosis was seen in 25% and reticular echogenicities (network pattern) in 44%. Portal blood flow was decreased or portosystemic collaterals were present in 10% (adults throughout) and correlated with periportal fibrosis, but not with network lesions. Chronic viral hepatitis was rare. Thus, hepatic lesions are frequent in adults but not in children in areas endemic for S. japonicum. Periportal liver fibrosis indicates a risk of PHT, and network pattern fibrosis apparently does not. Doppler sonography is suitable for research under tropical field conditions.

The public health significance of urinary schistosomiasis as a cause of morbidity in two districts in Mali.

Schistosoma haematobium-related morbidity was studied in the perennial irrigation area of Office du Niger and the small reservoirs area of Plateau Dogon in Mali. Questionnaire, clinical, parasitologic, and ultrasound examination data were collected from 1,041 individuals at the baseline survey in 1991; 705 were re-examined one year after treatment. At baseline, the overall prevalence of S. haematobium infection was 55.2%; half of those infected had no clinical symptoms and 30% had pathologic lesions. Both infection and morbidity were more frequent in children than in adults, with a peak prevalence at 7-14 years of age. The rates of lesions were more than twice as high in those heavily infected as in lightly infected individuals. Reagent strip testing for microhematuria was more sensitive in detecting individuals with pathologic lesions than in detecting individuals with infection. One year after treatment with praziquantel, more than 80% of the urinary tract lesions had cleared. It is concluded that S. haematobium-related morbidity is frequent in Mali, but passive case detection for treatment would not cover a great deal of early stages of the disease; active intervention using reagent strip testing for microhematuria at the most peripheral levels would be an efficient system for morbidity control and monitoring of control operations.

Intraobserver and interobserver variation of ultrasound diagnosis of Oesophagostomum bifurcum colon lesions.

Infection by the nematode Oesophagostomum bifurcum is focally distributed in Africa and causes a syndrome of abdominal pain, obstruction, or abdominal mass because of its predilection for invasion of colonic mucosa. To determine the reliability of ultrasound for the detection of colon pathology induced by this parasite, three studies to assess the intraobserver and interobserver variation of the technique were performed. In an area of northern Ghana endemic for O. bifurcum, 181 people from a low-prevalence village and 62 people from a high-prevalence village were examined twice by the same observer, and 111 people were independently examined by two observers in a moderately endemic village. The kappa statistics for the prevalence observations in the three studies were 0.82, 0.87, and 0.81, respectively, and kappa values for the intensity observations were 0.66, 0.63, and 0.71, respectively. The upper 95% confidence intervals of the average absolute difference in nodule size measurements in Study 1 and Study 3 were 3.6 and 4.5 mm, respectively. Therefore, ultrasound is useful in the diagnosis and management of O. bifurcum colon infection.

Organometric investigations of the spleen and liver by ultrasound in Schistosoma mansoni endemic and nonendemic villages in Senegal.

With the intention of ultrasonographically assessing hepatosplenic morbidity in Schistosoma mansoni infection and of validating the grading system applied (Cairo classification), 191 subjects in a schistosomiasis endemic village and 247 controls from a nonendemic village in northern Senegal underwent sonographic examination of the liver and spleen. Measurements of the diameters of the peripheral periportal vein branches, the main portal vein stem, liver size (left lobe and right lobe), and spleen length in the endemic village were compared with those in the nonendemic village to evaluate the much discussed influence of S. mansoni infection on those variables. To subtract this presumed influence from reference values for the named variables, they are given as measured in the nonendemic village, stratified by body weight, enabling future investigators on schistosomiasis-induced morbidity to refer to these reference values. The 95th percentile regarding peripheral periportal vein branch diameter in the control groups was exceeded in 24% of the subjects in the endemic group. It was exceeded by 6% for the main portal vein stem diameter, 13% for the left liver lobe, 12% for the right liver lobe, and 14% for the spleen length. According to the Cairo classification, 97% of the endemic population and 81% of the controls had periportal thickening of the liver, mostly grade I. We conclude that 1) hepatic morbidity in the S. mansoni endemic area was low, despite strikingly high intensities of infection; 2) the Cairo classification in its present form overestimates periportal thickening, especially in the case of mild morbidity; and 3) body height-dependent reference values, obtained from endemic controls, must be applied for organometric parameters.

Ultrasonography in a Senegalese community recently exposed to Schistosoma mansoni infection.

Inhabitants of Ndombo (n = 614), a village in an area recently infected with Schistosoma mansoni in Northern Senegal, were examined clinically, parasitologically, and ultrasonographically to investigate the presence and degree of S. mansoni-related hepatosplenic morbidity after a few years of exposure to schistosomal infection of regional canals. Despite previous praziquantel treatment of 56% of the inhabitants prior to our investigation, the prevalence of S. mansoni infection in 1993 was 90%, and 42% of the villagers excreted more than 1,000 eggs per gram of stool. Previously untreated individuals were found to have significantly higher egg counts than treated ones. Despite the high intensities of infection, ultrasonographically detected severe periportal thickening of the liver was infrequent. Grading according to body length-dependent normal values of cross-section diameter of peripheral portal vein branches of a European control group correlated with intensities of infection. Of the total group of patients, 30% (n = 182) had more severe thickening of portal vein branch diameters above the 97th percentile and 70% of these had a splenomegaly. The highest egg counts and the most frequent development of periportal thickening were found in 11-20 year-old individuals. Periportal thickening was less frequent in praziquantel-treated adolescents than in untreated ones. This suggests that early antischistosomal medication may be useful to limit schistosomiasis-induced hepatic morbidity especially in children, even though reinfection seems inevitable.

Simultaneous use of a sensitive filtration technique and reagent strips in urinary schistosomiasis.

A sensitive filtration technique and polyvalent urine analysis reagent strips were used simultaneously in patients with urinary schistosomiasis in order to detect pathological conditions other than haematuria and proteinuria. A significant correlation was found between haematuria, proteinuria, leucocyturia and intensity of infection as measured by egg excretion in urine. The best correlation between the reagent strip findings and intensity of infection was obtained when the three parameters were combined. After treatment with metrifonate the reduction of egg excretion was paralleled by the normalization of the reagent strip findings. Analysis of day-to-day variation demonstrated a similar low variation of the filtration technique and the reagent strip findings. Specificity of urine analysis of reagent strips was tested in two age-matched control groups. Although the study was designed only as a pilot study, the results suggests that polyvalent reagent strips may be a useful tool for diagnosis of heavily infected patients under field conditions, as they permit rapid and easy identification of subjects with high egg counts.

Morbidity of schistosomiasis mansoni in the highlands of Madagascar and comparison of current sonographical classification systems.

To study the morbidity of schistosomiasis mansoni in the highlands of Madagascar, a cross-sectional study examined the extent to which liver fibrosis occurred in a rural community. The Managil and the Cairo classification systems were used. A second purpose was to investigate the effect of the measurements of 2 different branches of the portal vein (either segmental or sub-segmental branches) on the resulting staging of morbidity using the Cairo classification system. In a rice farmer village, 656 inhabitants (95% of the total population) were parasitologically examined; 561 patients underwent sonographic work-up based on the Managil scoring system, and in 307 randomized patients the outer to outer diameters of both the segmental and the sub-segmental branches of the portal vein were measured and scored by the Cairo classification system. Overall prevalence of schistosomiasis mansoni in the study area in 1994 was 68.3%. Upon sonographic examination and scoring by the Managil system 23.4% of the population showed liver changes (Managil degree I/II/III, 20%/2.5%/0.9%). Measuring the sub-segmental branches only and scoring by the Cairo classification, 19% of the study population were found to have liver changes, none with severe fibrosis. By contrast, 82% were found to have liver changes (Cairo degree 1/2/3, 70%/11%/2%) when the segmental branches were measured. The diameters of the sub-segmental branches were about two-thirds of those of the segmental branches. Both the Cairo- and the Managil-examination protocols have pitfalls. Using the Cairo classification, a considerable systematic error in classifying morbidity is created by measuring different branches of the portal vein.

Clinical experience with metrifonate. Review with emphasis on its use in endemic areas.

Metrifonate is an excellent drug for the treatment of urinary schistosomiasis in areas with S. haematobium monoinfection. Toxicity apparently is negligible. Side effects due to the inhibition of acetylcholinesterase are usually scarce, light and transient in nature. At the recommended dosage of 3 times 10 mg/kg the chemotherapeutic potential of metrifonate to cure can be expected to range between 60 and 90%. Each dose of metrifonate reduces egg excretion by almost 90%. Treatment with metrifonate clearly reverses lower and upper renal tract pathology. An intermittent course of metrifonate may be administered by minimally trained health personnel. When appropriately timed with regards to local transmission dynamics the minimal requirement to achieve 99% reduction of egg excretion may be as low as three or four doses spaced over a period of two years.

Diagnostic value of connective tissue metabolites in Schistosoma mansoni related liver disease.

Reliable non-invasive markers of hepatosplenic involvement in schistosomiasis are needed for determination of morbidity levels in endemic populations and for diagnosis and follow-up of affected individuals. Serum levels of connective tissue metabolites have been investigated as fibrosis markers in various hepatic disorders, but their accuracy in the detection of hepatosplenic schistosomiasis under endemic conditions has not been fully elucidated. 206 adult inhabitants of a Tanzanian village highly endemic for schistosomiasis mansoni (prevalence 88%) underwent clinical, parasitological and sonographic work-up; sera were tested for aminoterminal procollagen III-peptide (PIIIP), carboxyterminal procollagen IV peptide (NC1) and laminin. Connective tissue marker levels did not correlate with the presence or intensity of infection. NC1 levels were significantly correlated with periportal liver fibrosis (P < 0.001), splenomegaly (P < 0.002), portal vein dilatation (P < 0.004) and the presence of portosystemic collaterals (P < 0.001); for PIIIP and laminin, none of the respective relationships was significant. Due to wide overlap of NC1 levels between individuals with normal sonography findings and those with advanced periportal fibrosis and portal hypertension, the sensitivity and positive predictive value of this markers to detect these individuals were low (< 40%), although specificity and overall accuracy in the given setting were good (80-90%). It is concluded that PIIIP and laminin are not useful as diagnostic serum markers of hepatosplenic schistosomiasis at the community level; NC1 was significantly related to various indices of hepatosplenic involvement, but its low sensitivity precludes its use as a screening tool under endemic conditions.

Evaluation of ultrasonographic staging systems for the assessment of Schistosoma mansoni induced hepatic involvement.

For the sonographic assessment and grading of hepatosplenic morbidity induced by Schistosoma mansoni infection, several quantitative and qualitative classification systems have been used. In an attempt to evaluate two staging systems, a study was performed as part of a schistosomiasis research and control programme in Richard Toll, Senegal. A total of 700 residents of the township N'diangué were parasitologically, clinically and sonographically examined in July 1993. Two ultrasound observers (M.D. and E.D.) applied the Cairo and the Managil classification (E.D. only) for the grading of periportal thickening of the liver. In spite of high prevalence and intensity of infection, severe hepatic morbidity was rare. According to the Cairo classification, there was a high percentage of subjects with grade I periportal thickening, with considerable inter-observer variability. In the Cairo classification, which is based on the diameter of peripheral portal vein branches, firm cut-offs are used, independent of body height. We show the relationship between body height and portal vein diameters and recommend the use of body height-dependent reference values to avoid falsely high percentages of periportal thickening, especially in children. To minimize inter-observer variability, a clarification of existing instructions for taking measurements for grading is suggested. These suggestions have been considered during the follow-up expert meeting on the Cairo classification in Niamey under the auspices of the World Health Organization in October 1996.

Integrated control trial of schistosomiasis at Nakiwogo fishing village near Entebbe, Uganda.

Using the Kato Katz technique, 600 people living in Nakiwogo fishing village at Lake Victoria, Uganda, were examined for Schistosoma mansoni infection. The total population of this village was estimated between 1,000 and 1,500 mainly consisting of migrants from western Uganda. Of the 600 individuals in the study group, 328 people (54.7%) were found to be infected with S. mansoni. The geometric mean egg count was 422 eggs per gramme of stool. A survey of the snail intermediate hosts for S. mansoni and S. haematobium at Nakiwogo was carried out. The collected snails were tested for cercariae shedding. A significant decrease in the number of Biomphalaria choanomphala and Biomphalaria pfeifferi (52%) which both still shed cercariae and Bulinus tropicus (52.5%) could be observed. There was a lower none-significant decrease of 13.3% of the Bulinus globosus population. With a combined approach including community participation in control measures in the form of health education, sanitation, environmental management and chemotherapy, the prevalence of S. mansoni infection was reduced from 54.7% to 14.6% in the period of one year.

Cost saving with ultrasonography in a developing country district hospital.

OBJECTIVE: To estimate the potential monetary reduction induced by the introduction of an ultrasound unit in a major district hospital in a developing country. DESIGN: Propective study. SUBJECTS: Patients referred with abnominal diseases and pregnancy. SETTING: Wad Medani Teaching Hospital, Central Sudan. RESULTS: Local specialists referring the patients stated that an estimated 792 radiologic procedures would have been carried out to obtain the same amount of information as achieved by ultrasound. Such procedures budgeted approximately 8100 US dollars, in terms of equipment, material and personnel by 1987 rates. Such savings have benefited all departments of the hospital. CONCLUSION: The authors consider this as evidence for the fact that despite its initial high investment (15,000 US dollars), availability of ultrasound virtually reduced expenditure on other radiological diagnostic procedures. This is of special benefit for the limited budgets of hospitals in non-industrialised countries.

Schistosomiasis in childhood.

Schistosomiasis is a parasitic disease of the tropics which is estimated to affect up to 300 million people worldwide. In endemic areas the childhood age group has the highest prevalence and intensity of infection. There are several distinct species of schistosomes. The principal organ system involved in Schistosoma haematobium infection is the urinary tract since parasite eggs penetrate the bladder and are excreted in the urine. Hematuria, proteinuria, leukocyturia and symptoms like dysuria or nocturia are the most common clinical presentations. Heavily infected patients show obstructive uropathy of different severity which may lead to renal failure. Intestinal schistosomiasis is caused by Schistosoma mansoni infection. Initial symptoms can be diarrhea and blood-tinged stool. Chronic infection is characterized by fibrotic involvement of the liver and consecutive portal hypertension. The diagnosis of schistosomiasis depends on the demonstration of schistosome eggs in human excreta or biopsy material. Imported cases of schistosomiasis to Europe show an increasing tendency due to expanding international travel. Furthermore imported cases are usually not diagnosed until years after the patients have left an endemic area. The treatment of choice is a single dose of praziquantel 40 m/kg bodyweight resulting in cure rates of around 90% and considerable reversibility of pathological abnormalities due to schistosome infections.