Mathematical modelling of schistosomiasis japonica: comparison of control strategies in the People's Republic of China

We present the first mathematical model on the transmission dynamics of Schistosoma japonicum. The work extends Barbour's classic model of schistosome transmission. It allows for the mammalian host heterogeneity characteristic of the S. japonicum life cycle, and solves the problem of under-specification of Barbour's model by the use of Chinese data we are collecting on human-bovine transmission in the Poyang Lake area of Jiangxi Province in China. The model predicts that in the lake/marshland areas of the Yangtze River basin: (1) once-early mass chemotherapy of humans is little better than twice-yearly mass chemotherapy in reducing human prevalence. Depending on the heterogeneity of prevalence within the population, targeted treatment of high prevalence groups, with lower overall coverage, can be more effective than mass treatment with higher overall coverage. Treatment confers a short term benefit only, with prevalence rising to endemic levels once chemotherapy programs are stopped (2) depending on the relative contributions of bovines and humans, bovine treatment can benefit humans almost as much as human treatment. Like human treatment, bovine treatment confers a short-term benefit. A combination of human and bovine treatment will dramatically reduce human prevalence and maintains the reduction for a longer period of time than treatment of a single host, although human prevalence rises once treatment ceases; (3) assuming 75% coverage of bovines, a bovine vaccine which acts on worm fecundity must have about 75% efficacy to reduce the reproduction rate below one and ensure mid-term reduction and long-term elimination of the parasite. Such a vaccination program should be accompanied by an initial period of human treatment to instigate a short-term reduction in prevalence, following which the reduction is enhanced by vaccine effects; (4) if the bovine vaccine is only 45% efficacious (the level of current prototype vaccines) it will lower the endemic prevalence, but will not result in elimination. If it is accompanied by an initial period of human treatment and by a 45% improvement in human sanitation or a 30% reduction in contaminated water contact by humans, elimination is then possible. (C) 2002 Elsevier Science B.V. All rights reserved.

Current concepts - Schistosomiasis

In 1851, Theodor Bilharz described a parasitic infection (bilharzia) that would later be termed schistosomiasis. Currently, 200 million people in 74 countries have this disease; 120 million of them have symptoms, and 20 million have severe illness.1 Schistosomiasis is caused by parasitic trematode worms (schistosomes) that reside in the abdominal veins of their vertebrate definitive hosts. The life cycle of the schistosome is depicted in Figure 1. Schistosomiasis is 1 of the 10 tropical diseases especially targeted for control by the Special Program for Research and Training in Tropical Diseases of the United Nations Development Program, the World Bank, . . . [Full Text of this Article]

The epidemiology and control of schistosomiasis mansoni where Biomphalaria tenagophila is the snail host

The epidemiology and control of schistosomiasis mansoni in the Municipality of Pedro de Toledo (State of S. Paulo, Brazil) since 1980, has been studied. In 1980 the prevalence evaluated by stool exams (Kato-Katz method) was 22.8% and no statistical difference at 5.0% level was observed between rural and urban zones. The intensity of infection was low (58.5 eggs/g of faeces); the highest prevalence and intensity of infection rates were observed within the group of from 5 to 29 years of age, respectively. The transmission of schistosomiasis usually occurred during leisure time. The majority of the carriers of the parasite were asymptomatic. Of the B. tenagophila examined only 0.4% were found to be infected. The control programme has been intensified from 1981 on resulting in a sharp decrease in the prevalence from 22.8% in 1980 to 6% at the present time. This result shows that, in spite of the control programme there is a residual human prevalence. A beginning has been made on the investigation into the possible causes of this residual prevalence (6.0% was maintained through out 1987).

Epidemiology of malaria, schistosomiasis, geohelminths, anemia and malnutrition in the context of a demographic surveillance system in Northern Angola

Background: Malaria, schistosomiasis and geohelminth infection are linked to maternal and child morbidity and mortality in sub-Saharan Africa. Knowing the prevalence levels of these infections is vital to guide governments towards the implementation of successful and cost-effective disease control initiatives. Methodology/Principal Findings: A cross-sectional study of 1,237 preschool children (0–5 year olds), 1,142 school-aged children (6–15 year olds) and 960 women (.15 year olds) was conducted to understand the distribution of malnutrition, anemia, malaria, schistosomiasis (intestinal and urinary) and geohelminths in a north-western province of Angola. We used a recent demographic surveillance system (DSS) database to select and recruit suitable households. Malnutrition was common among children (23.3% under-weight, 9.9% wasting and 32.2% stunting), and anemia was found to be a severe public health problem (i.e., .40%). Malaria prevalence was highest among preschool children reaching 20.2%. Microhematuria prevalence levels reached 10.0% of preschool children, 16.6% of school-aged children and 21.7% of mothers. Geohelminth infections were common, affecting 22.3% of preschool children, 31.6% of school-aged children and 28.0% of mothers. Conclusions: Here we report prevalence levels of malaria, schistosomiasis and geohelminths; all endemic in this poorly described area where a DSS has been recently established. Furthermore we found evidence that the studied infections are associated with the observed levels of anemia and malnutrition, which can justify the implementation of integrated interventions for the control of these diseases and morbidities.

Association between Schistosomiasis mansoni and hepatitis C: systematic review

OBJECTIVE: To perform a systematic review of the prevalence of the HCV/ S. mansoni co-infection and associated factors in Schistosoma mansoni -infected populations. METHODS: The bibliographic search was carried out using the Medline, Lilacs, SciELO, Cochrane Library and Ibecs databases. The criteria for the studies' selection and the extraction data were based on systematic review methods. Forty five studies were found, with nine being excluded in a first screening. Thirteen articles were used for data extraction. RESULTS: The HCV infection rates in schistosomiasis populations range from 1% in Ethiopia to 50% in Egypt. Several studies had poorly defined methodologies, even in areas characterized by an association between hepatitis C and schistosomiasis, such as Brazil and Egypt, which meant conclusions were inconsistent. HCV infection rates in schistosomotic populations were heterogeneous and risk factors for acquiring the virus varied widely. CONCLUSIONS: Despite the limitations, this review may help to identify regions with higher rates of hepatitis C and schistosomiasis association. However, more studies are necessary for the development of public health policies on prevention and control of both diseases.

Assessment of oltipraz in schistosomiasis mansoni clinical trial

Seventy three children (6-15 years) and 75 adults (18-47 years) with active schistosomiasis mansoni were treated with oltipraz. All cases had at least 100 eggs per gram of feces as determined by the Kato-Katz technique. Children and adults were divided in two groups receiving respectively 25 or 30 mg/kg, as a single oral dose. Clinical examination, laboratories tests (haemogram, urinalysis, hepatic and kidney functions tests, glycemia, cholesterol, triglicerides, lipoprotein — HLD and LDL) and ECG were performed before, 3 or 7 days and 1 month after treatment. Parasitological control with 3 daily coprological examinations, was done on the 1st, 3rd j 6th month after drug administration. Giddiness, somnolence, headache, nausea, vomiting and abdominal distress were the most frequent side effects. Pain in the finger tips that need further investigations also occurred. No significant alteration in complementary tests were observed, whereas eosinophilia 1 month after treatment was detected, probably indicating worm death. The cure rate in children was 81.8% and 74.2% with 25 and 30 mg/kg respectively, and in adults 75.0% and 81.2% of the patients. No statistical significant difference was observed between cure rate and side effects at different dosages employed, neither between adults nor children. In all groups the percentage of egg reduction in feces in the non cured patients was higher than 96.0%. Further investigation with this new compound is necessary to accomplish the real value of oltipraz in the schistosomiasis chemotherapy.

A clinical epidemiologic study in a schistosomiasis mansoni endemic area (Tuparecê, Minas Gerais)

A population-based clinical epidemiologic study on schistosomiasis mansoni was carried out in Tuparecê, Minas Gerais. The patients were interviewed for symptoms, water contact, past history and examined for spleen and liver enlargement. From the 830 people registered in the census, 777 (93.6%) had their stools examined (Kato-Katz method) and 696 (83.9%) were clinically evaluated. The overall index of Schistosoma mansoni infection was 43.2%. Significant and increased infection risks could be detected in the young age group (2-14 years old) regarding occupation, time of residence in the area and frequency of water contact. Bloody stools were significantly more prevalent among positives, while diarrhea was significantly more prevalent among those negative. The area was shown to have a low morbidity as well as a low intensity of infection measured by the number of S. mansoni eggs per gram of feces. A close correlation was found between water contact pattern and the age prevalence curve. It has emphasized the importance of habits in determining prevalence rates, besides suggesting that schistosomiasis mansoni in the area is manifested as a light and somewhat harmless infection with little consequence for the population as a whole.

Evolution of schistosomiasis in an hyperendemic area of the Minas Gerais state: two cross-sectional studies

Two cross-sectional studies on schistosomiasis mansoni were done in Comercinho, Minas Gerais (Brazil), at an interval of 7 years. In 1974 and 1981 feces examinations (KATO-KATZ method) were done in 89 and 90% of the population (about 1,500 inhabitants) and clinical examinations were done in 78 and 92% of the patients who excreted Schistosoma mansoni eggs in the feces, respectively. The rate of infection by S. mansoni did not change (69.9% in 1974 and 70.4% in 1981), but the geometrical mean of eggs per gram of feces (431 ± 4 and 334 ± 4, respectively) and the rate of splenomegaly (11 and 7%, respectively) decreased significantly in 1981, when compared to 1974. This reduction was observed only in the central zones of the town (zones 1-2) where the rate of dwellings with piped water increased from 17 to 44%. In the surroundings (zones 3-4), where the proportion of houses with piped water did not change significantly between 1974 (10%) and 1981 (7%), the geometrical mean of S. mansoni eggs and the rate of splenomegaly did not change either.

Survey on the clinical trial results achieved in Brazil comparing praziquantel and oxamniquine in the treatment of mansoni schistosomiasis

A random, double-blind, parallel group clinical trial program was carried out to compare praziquantel, a recently developed anti-helmintic drug, and oxamniquine, an already established agent for treating mansoni schistosomiasis. Both drugs were administered orally as a single dose, on the average, praziquantel 55 mg/kg and oxamniquine 16 mg/kg BWT. The diagnosis and the parasitological follow-up lasting for a minimum of six months, were based on stool examinations according to Kato/Katz technique. A patient was considered cured if all results were negative and if he had performed at least three post-treatment controls, each one comprising three stool examinations. The finding of a single S. mansoni egg in any stool examination indicated, a therapeutical failure. A total of 267, cases were treated with praziquantel and 272 with oxamniquine. The two groups were homogeneous in regard to patients, age, clinical form of the disease, risk of reinfection and worm burden, relevant factors in the therapeutical response. The incidence and severity of untoward, effects were similar in both groups but abdominal distress and diarrhoea were more frequently reported under praziquantel and dizzines under oxamniquine (p < 0.05). In the former group a marked urticariform reaction was observed whereas in the latter one patient presented convulsion. The laboratory work-up. failed to disclose any significant alteration although the AST, ALT and y-GT mean values revealed a tendence to increase on the 7th day after oxamniquine intake. The overall parasitological cure rates were 75.5% (139/ 184) with praziquantel and 69.8% (134/192) with oxamniquine (p > 0.05). Amongst the noncured aptients a reduction of 88.6% and 74.6% in the mean number of eggs/g of feces Was seen following the treatment with praziquantel and oxamniquine, respectively (p < 0.05). In conclusion, in spite of their different chemical, pharmacological and toxicological profiles as well as mechanisms-of-action, inclusively praziquantel already had proved to be 100% active against S. mansoni strains resistant to oxamniquine, both drugs showed comparable tolerance and therapeutical efficacy.

Treatment of patients with Schistosomiasis mansoni: a double blind clinical trial comparing praziquantel with oxamniquine

A double-blind clinical trial involving 120 patients with chronic schistosomiasis was carried out to compare the tolerability and efficacy of praziquantel and oxamniquine. The patients were randomly allocated into two groups. One was treated with praziquantel, 55 mg/kg of body weight CBWT), and the other one with oxamniquine, 15mg/kg bwt, administered in a single oral dose. The diagnosis and the parasitological follow-up was based on stool examinations by quantitative Kato-Katz method and on rectal biopsies. Side-effects — mainly dizziness, sleepness, abdominal distress, headache, nausea and diarrhea — were observed in 87% of the cases. Their incidence, intensity and duration were similar for both drugs but abdominal pain was significantly more frequent after praziquantel intake and severe dizziness was more commonly reported after oxamniquine. A significant increase of alanine-aminotransferase and y-glutamyltransferase was found with the latter drug and of total bilirubin with the former one. A total of 48 patients treated with praziquantel and 46 with oxamniquine completed with negative findings the required three post-treatment parasitological controls — three slides of each stool sample on the first, third and sixth month. The achieved cure rates were 79.2% and 84.8%, respectively, a difference without statistical significance. The non-cured cases showed a mean reduction in the number of eggs per gram of feces of 93.5% after praziquantel and of 84.1% after oxamniquine. This diference also was not significant. Five patients retreated with praziquantel were cured but only one out of three treated a second time with oxamniquine. These findings show that both drugs — despite their different chemical structures, pharmacological properties and mechanisms-of-action — induce similar side-effects as well as a comparable therapeutical efficacy, in agreement with the results reported from analogous investigations.

Sensibility of different larval stages of Schistosoma mansoni to the Larvae Disappearing Reaction (LDR) in murine schistosomiasis

The delay produced by drug, in the process of cercaria-schistosomulum transformation, was used to verify the sensibility of different larval stages to the host cell immune responses, in vivo. The peritoneal cavity of mice, a model used for in vivo observations, was choiced for the experiments. As well characterized schistosomules, cercariae and larvae in the process of transformation were coated and arrested by host cells, and could not be recovered by simple saline washings. After 10-²M EDTA saline washings, they were released alive, with good vitality and movements. Thus, different kind of larvae in the process of adaptation of the cercaria to the host are strongly coated by immune cells, but these fail to kill the invading organisms, at least during a few hours after invasion.

Schistosomiasis mansoni: evidence for a milder response in germfree mice

Germfree (GF and conventional (CV) mice were infected intraperitoneally with GF cercariae of Schistosoma mansoni and kept for six weeks. Twenty four hours before killing, they were injected with [³H]-thymidine. Schistosoma worms, harvested after perfusion of portal system, were counted as well as eggs from liver and intestines. Liver was also used for DNA, protein, and collagen determinations. [³H] -Thymidine incorporation and collagen determinations were used to establish the indices given by the difference between their contents in infected and control animals and expressed per thousand eggs in liver. The recovery of worms in GF mice was around twice as much as in CV ones, and the total number of eggs was higher in the liver of GF animals. No hypertrophy of liver cells was observed by the ratio protein/DNA, but [³H]-thymidine incorporation into DNA was higher than in controls in both GF and CV infected animals. The [³H]-thymidine and collagen indices were lower in GF animals which indicate a more discrete cellular replication and smaller collagen content in relation to the number of eggs present in livers of these mice. It was concluded that the disease seems to be less severe in GF animals.

Therapeutical evaluation of different dose regimens of praziquantel in schistosomiasis mansoni, based on the quantitative oogram technique

A clinical trial involving 80 patients of both sexes, from ages 15 to 55, with chronic intestinal or hepatointestinal schistosomiasis mansoni, was carried out to evaluate the therapeutical efficacy of different dose regimens of praziquantel. The patients were randomly allocated into four groups with an equal number of cases and were then treated with one of the following dosages: 60 mg/kg for 1 day; 60 mg/kg daily for 2 days; 60 mg/kg daily for 3 days; and 30 mg/kg daily for 6 days. The assessment of parasitological cure was based on the quantitative oogram technique through rectal mucosa biopsies which were undertaken prior to, as well as, 1,2,4 and 6 months post-treatment. Concurrently, stool examinations according to the qualitative Hoffman, Pons & Janer (HPJ) and the quantitative Kato-Katz (K-K) methods were also performed. The best tolerability was observed with 30 mg/kg daily for 6 days whereas the highest incidence of side-effects (mainly dizziness and nausea) was found with 60 mg/kg daily for 3 days. No serious adverse drug reaction has occurred. The achieved cure rates were: 25% with 60 mg/kg for 1 day; 60% with 60 mg/kg daily for 2 days; 89.5% with 60 mg/kg daily for 3 days; and 90% with 30 mg/kg daily for 6 days. At the same time there has been a downfall of 64%, 73%, 87% and 84% respectively, in the median number of viable S. mansoni ova per gram of tissue. Thus, a very clear direct correlation between dose and effect could be seen. The corresponding cure rates according to stool examinations by HPJ were 39%, 80%, 100% and 95%; by K-K 89%, 100%, 100% and 100%. This discrepancy in results amongst the three parasitological methods is certainly due to their unequal accuracy. In fact, when the number of viable eggs per gram of tissue fell below 5,000 the difference in the percentage of false negative findings between HPJ (28%) and K-K (80%) became significative. When this number dropped to less than 2,000 the percentage of false negative results obtained with HPJ (49%) turned significant in relation to the oogram as well. In conclusion, it has been proven that praziquantel is a highly efficacious agent against S. mansoni infections. If administered at a total dose of 180 mg/kg divided into either 3 or 6 days, it yields a 90% cure rate. Possibly, one could reach 100% by increasing the total dose to 240 mg/kg. Furthermore, it was confirmed that the quantitative oogram technique is the most reliable parasitological method when evaluating the efficacy of new drugs in schistosomiasis mansoni.