Intestinal helminthiases and schistosomiasis among school children in an urban center and some rural communities in southwest Nigeria

Intestinal helminths and schistosomiasis among school children were investigated in an urban and some rural communities of Ogun State, southwest Nigeria. Fecal samples of 1,059 subjects (524 males, 535 females) aged 3-18 years were examined using direct smear and brine concentration methods between June 2005 and November 2006. The pooled prevalence of infection was 66.2%. Ascaris lumbricoides showed the highest prevalence (53.4%) (P < 0.001) followed by hookworms (17.8%), Trichuris trichiura (10.4%), Taenia sp. (9.6%), Schistosoma mansoni (2.3%), Strongyloides stercoralis (0.7%), Schistosoma haematobium (0.6%), and Enterobius vermicularis (0.3%). The prevalences of A. lumbricoides, hookworms, Taenia sp., S. mansoni, and S. stercoralis in the urban centre were similar (P > 0.05) to those in the rural communities. The fertile and infertile egg ratios of A. lumbricoides in the urban centre and the rural communities were 13: 1 and 3.7: 1, respectively. Each helminth had similar prevalences among both genders (P > 0.05). The prevalence of A. lumbricoides increased significantly with age (P < 0.001). The commonest double infections were Ascaris and hookworms, while the commonest triple infections were Ascaris, hookworms, and Trichuris. The study demonstrates the need for urgent intervention programmes against intestinal helminthiases and schistosomiasis in the study area.     

The effect of treatment on the age-antibody relationship in children infected with Schistosoma mansoni and Schistosoma haematobium

The effect of praziquantel treatment on the age-antibody relationship was studied in 174 children aged between 6 and 17 years from a schistosome endemic area in Zimbabwe. The children were co-infected with Schistosoma mansoni and S. haematobium with infection prevalences of 74% and 53% respectively. Antibody levels for the isotypes IgA, IgE, IgM, IgG1, IgG2, IgG3 and IgG4, directed against soluble egg antigen were measured using an indirect ELISA assay. Treatment resulted in a significant increase in levels of IgG2 and IgG3 while levels of IgA decreased significantly. In untreated children there were significant decreases in levels of IgG4. Treatment also resulted in significant alteration in the age-antibody profiles for the isotypes IgE, IgM, IgG1 and IgG2 in treated children but not in untreated children. The results are discussed in the context of factors believed to give rise to the age-antibody relationship; i.e. age-related exposure patterns, age-related development of acquired immunity, age-related hormonal changes and age-related changes in innate susceptibility to infection.     

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.     

Helminth communities of Nectomys squamipes naturally infected by the exotic trematode Schistosoma mansoni in southeastern Brazil

The water rat Nectomys squamipes is endemic in Brazil and found naturally infected with Schistosoma mansoni. Helminth communities, their prevalences, intensity of infection and abundance in N. squamipes in an endemic area of schistosomiasis in the state of Rio de Janeiro, Brazil were studied. Four species of nematodes (Physaloptera bispiculata, Syphacia venteli, Hassalstrongylus epsilon and Litomosoides chagasfilhoi) were recovered in 85.3%, two trematodes (Schistosoma mansoni and Echinostoma paraensei) in 38.8% and one cestode species (Raillietina sp.) in 1.7% of rats examined. Rats were infected with up to five helminth species each, and these were highly aggregated in distribution. For H. epsilon and S. venteli, intensities and abundances were higher in adult male and subadult female hosts, respectively. Hassaltrongylus epsilon, P. bispiculata, S. venteli and S. mansoni were classified as dominant species, L. chagasfilhoi and E. paraensei as co-dominant and Raillietina sp. as subordinated. No significant correlation was found in the intensity of infecton between each pair of helminth species. Schistosoma mansoni was not related to any other helminth species according to their infection rates, althougth S. mansoni was well established in the natural helminth comunity of the water rat.     

Schistosoma mansoni: control of hepatotoxicity and egg excretion by immune serum in infected immunosuppressed mice is schistosome species-specific, but not S. mansoni strain-specific.

Immunosuppressed mice infected with Schistosoma mansoni suffer from an acute hepatotoxicity reaction, and they fail to excrete as many parasite eggs as comparably infected immunologically intact control animals. The hepatotoxicity was shown here to be preventable, and egg excretion rates were enhanced, by transfer of serum from donors with chronic S. mansoni infections, but not by serum from donors with heterologous infections of Schistosoma haematobium, Schistosoma bovis, or Schistosoma japonicum. The effects of the transferred sera are considered to be due to specific antibody, but the possibility of cytokine involvement is discussed. A high degree of serological cross-reactivity was found between sera from mice infected with the different schistosome species and unfractionated egg homogenate (SEA) in ELISA. Cross-reactivity of the heterologous sera was, however, reduced against CEF6, a partially purified fraction of S. mansoni eggs that contains the putative hepatotoxin and has serodiagnostic potential. S. mansoni isolates from Puerto Rico, Brazil, Egypt, and Kenya shared similar characteristics with respect to the immune dependence of egg excretion and hepatotoxicity in immunosuppressed mice. The S. mansoni geographic isolates were also indistinguishable serologically, in terms of both the capacity of respective infection sera to neutralize hepatotoxicity and in their capacity to promote egg excretion of the other isolates in vivo. Complete immunological cross-reactivity of the geographically distinct isolates was also observed in ELISA with both CEF6 and SEA. Utilization of CEF6 for serodiagnosis of schistosomiasis mansoni is therefore unlikely to be restricted by geographical considerations.     

The influence of physical factors on the behaviour and infectivity of miracidia of Schistosoma mansoni and S. haematobium. II. Effect of light and depth

A striking difference was found in the responses of Schistosoma mansoni and S. haematobium miracidia to the intensity and direction of light and to gravity. S. mansoni miracidia were found to be positively phototactic and sensitive to small changes in light intensities. They were indifferent to gravity. S. haematobium miracidia however were negatively phototactic and unable to distinguish low light intensities from darkness. They showed a strong positive geotaxis. Both S. mansoni and S. haematobium miracidia could successfully find and infect snails to a depth of 2 metres of water: the significance of these findings in relation to transmission of schistosomiasis in the field is discussed.     

Mating interactions between Schistosoma haematobium and S. mansoni

Schistosoma haematobium and S. mansoni are two medically important schistosomes, commonly occurring sympatrically in Africa and so potentially able to infect the same human host. Experiments were designed to study the mating behaviour of these two species in mixed infections in hamsters. Analysis of the data obtained showed that both heterospecific and homospecific pairs readily form. No significant difference was seen between the two species in their ability in forming pairs, however, S. mansoni showed a greater homospecific mate preference. Analysis of the data using the Mantel-Haenszel test suggests that mating competition does occur between S. haematobium and S. mansoni, the former being the more dominant species. Both species appeared to be able to change mate, with S. haematobium showing a greater ability in taking S. mansoni females away from S. mansoni males when introduced into a pre-established S. mansoni infection highlighting the competitiveness of S. haematobium. The significance of the results is discussed in relation to the epidemiological consequences occurring in Senegal, and other areas where both species are sympatric.     

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.     

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.     

Studies on experimental mixed infections of Schistosoma mansoni and S. haematobium in hamsters

Golden hamsters were superinfected simultaneously with 100 Schistosoma haematobium cercariae, 1 and 3 weeks after initial infection with 100 S. mansoni cercariae. Results indicate that there was a higher degree of resistance to superinfection with S. haematobium at 1 week following initial infection with S. mansoni than that produced in the other two superinfections. This resistance was evidenced by a reduction in the number and size of worms of both species, decrease in S. haematobium egg extrusion per female and by a striking deviation in the egg distribution pattern of both species. Such an early host resistance was not recorded in previous works. Cross-mating was observed but no hybridization took place and the eggs produced were hatchable and typical of their species.     

Genetic diversity and recruitment pattern of Schistosoma mansoni in a Biomphalaria glabrata snail population: a field study using random-amplified polymorphic DNA markers.

Random-amplified polymorphic DNA markers have been used to assess the amount and the distribution of the genetic diversity of Schistosoma mansoni within a natural population of Biomphalaria glabrata at a transmission site of the murine schistosomiasis focus of Guadeloupe. Despite high infection rate and heavy schistosome load within the definitive hosts (Ratus rattus), prevalences within intermediate snails ranged from 0.2 to 4.8%. Whatever the transmission season may be (rainy vs. dry), most of the infected snails were spatially aggregated and 88.4% of them harbored a single parasite genotype indicative of a monomiracidial infection; 4.7% had dual sex infections and a parasite intensity not exceeding 3 miracidia per snail. A substantial resistance level toward the parasite and recruitment regulatory process within snails may explain in part the observed low parasite prevalences and intensities. Considering such a distribution pattern of larval S. mansoni genetic diversity among B. glabrata, mobility of the definitive hosts, or rapid turnover of infected snails, or both, are required to maintain genetic heterogeneity within adult schistosome populations.     

A Bayesian approach to estimate the age-specific prevalence of Schistosoma mansoni and implications for schistosomiasis control

Models that accurately estimate the age-specific infection prevalence of Schistosoma mansoni can be useful for schistosomiasis control programmes, particularly with regard to whether mass drug administration or selected treatment should be employed. We developed a Bayesian formulation of an immigration-death model that has been previously proposed, which used maximum likelihood inference for estimating the age-specific S. mansoni prevalence in a dataset from Egypt. For comparative purposes, we first applied the Bayesian formulation of the immigration-death model to the dataset from Egypt. We further analysed data obtained from a cross-sectional parasitological survey that determined the infection prevalence of S. mansoni among 447 individuals in a village in C?te d'Ivoire. Three consecutive stool samples were collected from each participant and analysed by the Kato-Katz technique. In the C?te d'Ivoire study, the observed S. mansoni infection prevalence was 41.6% and varied with age. The immigration-death model was able to correctly predict 50% of the observed age group-specific point prevalences. The model presented here can be utilized to estimate S. mansoni community infection prevalences, which in turn helps in the strategic planning of schistosomiasis control.     

Evidence for the segregation of a major gene in human susceptibility/resistance to infection by Schistosoma mansoni.

Severe clinical disease caused by the major human parasite Schistosoma mansoni is the consequence of high and prolonged infections. Epidemiological studies indicate that, for individuals having frequent contacts with cercaria-infested waters, both infection intensities and reinfection after treatment depend, in large part, on their intrinsic susceptibility/resistance to infection, suggesting the role of genetic factors in human resistance to S. mansoni. To investigate whether a major gene controls human susceptibility/resistance to infection by S. mansoni, segregation analysis of infection intensities, adjusted for the factors relevant in schistosomiasis (water contact, age, sex), was performed on 20 Brazilian pedigrees (269 individuals), using both the unified mixed model and the regressive model of analysis. The results are consistent with the hypothesis that there is a codominant major gene controlling human susceptibility/resistance to infection by S. mansoni. Parameter estimates indicate a frequency of .20-.25 for the deleterious allele; thus, about 5% of the population is predisposed to high infections, 60% is resistant, and 35% has an intermediate, although fairly good, level of resistance. These findings provide a genetic basis for earlier observations on the lower resistance and the predisposition to reinfection of certain individuals. In addition to the detection of a major gene effect, the data suggest that immunity to S. mansoni develops progressively during childhood to reach a maximum around the age of puberty. The implications of these results for the strategy to be used in endemic areas to reduce morbidity and to control parasite transmission are discussed.     

Study of the distribution pattern of Schistosoma haematobium egg antigens recognised by six different monoclonal antibodies in the parasite and the host

Recently a new panel of monoclonal antibodies was developed against soluble egg antigens in the hatching fluid of Schistosoma mansoni. These antibodies have been used to develop an improved ELISA for the detection of circulating soluble egg antigens in serum and urine that would have a higher sensitivity in the immunodiagnosis of S. mansoni infections. Although these antibodies showed no improvement in the immunodiagnosis of S. mansoni infections compared with egg antigen-based ELISAs already described (Nourel Din et al., 1994a), they may have a potential role in the identification of S. haematobium infections. This study has looked into the immunolocalisation of S. haematobium egg antigens in both the parasite and the host as recognised by four newly developed monoclonal antibodies (290-2D9-A, 290-2E6-A, 290-2H12-A and 290-4A8-A) and two already described antibodies (114-5B1-A and 114-4D12-A). The antibodies 114-5B1-A and 114-4D12-A appeared to have in S. haematobium eggs a similar staining pattern when compared to S. mansoni eggs. The antibodies prepared against the hatching fluid showed a characteristic signal, especially 290-2E6-A. These antibodies recognised a component originating from the lateral glands of the miracidium. In the host a similar immunohistochemical tissue localisation pattern (mainly phagocytising reticulo-endothelial cells) was seen as previously described for S. mansoni infected hamsters.     

Susceptibility of Iraqi fresh water snails to infection with Schistosoma haematobium and Schistosoma mansoni Egyptian strains

A great number of Egyptian workers and farmers are seeking settlement in Iraq and some of them proved to have either Schistosoma Haematobium (S.h.) or Schistosoma mansoni (S.m) or even mixed infection. Besides, there is the possibility that some of the Iraqi fresh water snails may prove to be susceptible to infection by one or both of the Schistosoma Egyptian strains. The present study deals with investigations on the susceptibility of Iraqi B. truncatus, Gyranaulus ehrenbergi, Physa c.f. fontinalis, Lymnea lagetis, Melanoides tuberculata and Melanopsis nodes by these parasites. Egyptian S. haematobium but not Egyptian S. mansoni infect Iraqi B. truncatus and both proved to be unable to infect any of the other snails included in the study. Yet, the number of cercariae shedded by B. truncatus snails infected with the Egyptian S. haematobium strain, was much less that the number of cercariae shedded by these snails when infected with the Iraqi S. Haematobium strain.     

Schistosoma mansoni, S. haematobium, and S. japonicum: identification of genus- and species-specific antigenic egg glycoproteins

Immunoreactive egg glycoproteins of Schistosoma mansoni, S. haematobium, and S. japonicum which are genus- and species-specific, or react with sera of patients infected with other parasites, have been identified. Egg proteins were labeled with Iodine-125, and the concanavalin A-binding glycoproteins were immunoprecipitated with sera of patients infected with one of four species of Schistosoma or Trichinella spiralis, Taenia solium, Echinococcus granulosus, Entamoeba histolytica, or Wuchereria bancrofti. These immunoprecipitates were analyzed by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Despite the strikingly different patterns of glycoproteins of the African species, the antibody immune responses of patients infected with S. mansoni and S. haematobium were found to be so similar that differentiation could not be established. In contrast, sera of patients infected with S. japonicum, S. mekongi, or parasites not of the genus Schistosoma, immunoprecipitated fewer of the major S. mansoni or S. haematobium glycoproteins. Likewise, antibody immune responses of patients infected with the Oriental schistosomes (S. japonicum and S. mekongi) could not be differentiated. Only a few quantitative differences were noted between our S. mansoni egg glycoprotein extract and a standardized soluble egg antigen extract. This study provides an explanation for the extensive cross-reactivity observed in diagnostic assays which utilize various fractions of schistosomal egg extracts as the antigen.     

Bladder Morbidity and Hepatic Fibrosis in Mixed Schistosoma haematobium and S. mansoni Infections: A Population-Wide Study in Northern Senegal

Background

The global distribution map of schistosomiasis shows a large overlap of Schistosoma haematobium- and S. mansoni-endemic areas in Africa. Yet, little is known about the consequences of mixed Schistosoma infections for the human host. A recent study in two neighboring co-endemic communities in Senegal indicated that infection intensities of both species were higher in mixed than in single infections. Here, we investigated the relationship between mixed Schistosoma infections and morbidity in the same population. So far, this has only been studied in children.

Methods

Schistosoma infection was assessed by microscopy. Schistosoma-specific morbidity was assessed by ultrasound according to WHO guidelines. Multivariable logistic regression models were used to identify independent risk factors for morbidity.

Principal Findings

Complete parasitological and morbidity data were obtained from 403 individuals. Schistosoma haematobium-specific bladder morbidity was observed in 83% and S. mansoni-specific hepatic fibrosis in 27% of the participants. Bladder morbidity was positively associated with S. haematobium infection intensity (OR = 1.9 (95% CI 1.3–2.9) for a 10-fold increase in intensity). Moreover, people with mixed infections tended to have less bladder morbidity than those with single S. haematobium infections (OR = 0.3 (95% CI 0.1–1.1)). This effect appeared to be related to ectopic S. mansoni egg elimination in urine. Hepatic fibrosis on the other hand was not related to S. mansoni infection intensity (OR = 0.9 (95% CI 0.6–1.3)), nor to mixed infections (OR = 1.0 (95% CI 0.7–1.7)).

Conclusions/Significance

This is the first population-wide study on the relationship between mixed Schistosoma infections and morbidity. Mixed infections did not increase the risk of S. mansoni-associated morbidity. They even tended to reduce the risk of S. haematobium-associated morbidity, suggesting a protective effect of S. mansoni infection on bladder morbidity. These unexpected results may have important consequences for schistosomiasis control in co-endemic areas and warrant further investigation.     

Schistosoma mansoni,S. haematobium,and S. japonicum: early events associated with penetration and migration of schistosomula through human skin

Migratory pattern of schistosomula of Schistosoma mansoni, S. haematobium, and S. japonicum through human skin were analyzed in skin organ cultures. These studies showed that the schistosomula of S. mansoni and S. haematobium has similar migratory patterns through human skin. During the first 24h after infection nearly 90% of S. mansoni and S. haematobium schistosomula were present only in the epidermis. Majority of the schistosomula were found in the dermis only after 48h and they appear to reach the dermal vessels around 72h after infection. Migratory pattern of S. japonicum on the other hand was significantly different from the other two species in that over 90% of the parasites had already reached the dermis within the first 24h and schistosomula were present in the dermal vessels within 2h after infection. Analysis of the cytokine pattern at 8h after infection by a macro gene array and RT-PCR analysis showed that out of 24 different cytokines analyzed only IL-1ra, IL-10, and TNF-alpha were increased in the human skin following infections with S. mansoni and S. haematobium, whereas, after infection with S. japonicum there was significant increases in IL-1beta, IL-1ra, IL-2, IL-6, IL-8, IL-10, IL-15, IL-18, and TNF-alpha. Immunohistochemical analysis of epidermal sheets showed focal accumulation of HLA-DR(+) cells in areas where schistosomula of S. mansoni had entered the human skin.     

Schistosome antigen gp50 is responsible for serological cross-reactivity with Trichinella spiralis.

The 50-kDa component (gp50) present in Schistosoma mansoni eggs and secretions of the various life stages of the parasite was recognized by experimentally infected mice and by humans with S. mansoni, Schistosoma haematobium, and Schistosoma japonicum infection. All sera reacting with crude S. mansoni-soluble egg antigens (SEA) also reacted strongly with gp50 in enzyme-linked immunosorbent assay. No reactivity against gp50 was seen with sera from individuals without schistosomiasis, with the exception of sera from patients with Trichinella spiralis infection. All of 10 sera from patients with trichinellosis also reacted with schistosomes by immunofluorescence essentially recognizing testes, ovaries, ootype epithelium and ducts of the reproductive system. Cross-reacting antigens were seen in T. spiralis hypodermis, stichocytes and possibly germinal primordia using anti-gp50 monoclonal antibodies and anti-gp50-positive schistosomiasis patient sera. The results suggest that the anti-gp50 antibody response constitutes a significant part of the anti-SEA antibody response in infected individuals and is a major reason for the previously recognized serological cross-reactivity between T. spiralis and schistosome species.     

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.