Mansoni Endemic Area Research Articles

Change in children's school behavior after mass administration of praziquantel for Schistosoma mansoni infection in endemic areas of western Kenya: A pilot study using the Behavioral Assessment System for Children (BASC-2).

BackgroundSchistosomiasis is a parasite-related chronic inflammatory condition that can cause anemia, decreased growth, liver abnormalities, and deficits in cognitive functioning among children.Methodology/Principal findingsThis study used the Behavior Assessment System for Children (BASC-2) to collect data on thirty-six 9–12 year old school-attending children’s behavioral profiles in an Schistosoma mansoni-endemic area of western Kenya, before and after treatment with praziquantel for S. mansoni infection. BASC-2 T scores were significantly reduced post-treatment (p < 0.05) for each of the ‘negative’ behavior categories including externalizing problems (hyperactivity, aggression, and conduct problems that are disruptive in nature), internalizing problems (anxiety, depression, somatization, atypicality, and withdrawal), school problems (academic difficulties, included attention problems and learning problems), and the composite behavioral symptoms index (BSI), signifying improved behavior. While the observed improvement in the ‘positive’ behavior category of adaptive skills (adaptability, functional communication, social skills, leadership, and study skills) was not statistically significant, there were significant improvements in two adaptive skills subcategories: social skills and study skills.Conclusion/SignificanceResults of this study suggest that children have better school-related behaviors without heavy S. mansoni infection, and that infected children’s behaviors, especially disruptive problem behaviors, improve significantly after praziquantel treatment.

Multiplex Serologic Assessment of Schistosomiasis in Western Kenya: Antibody Responses in Preschool Aged Children as a Measure of Reduced Transmission.

Currently, impact of schistosomiasis control programs in Schistosoma mansoni–endemic areas is monitored primarily by assessment of parasitologic indicators only. Our study was conducted to evaluate the use of antibody responses as a way to measure the impact of schistosomiasis control programs. A total of 3,612 serum samples collected at three time points from children 1–5 years of age were tested for antibody responses to two schistosome antigens (soluble egg antigen [SEA] and Sm25) by multiplex bead assay. The overall prevalence of antibody responses to SEA was high at baseline (50.0%). After one round of mass drug administration (MDA), there was minimal change in odds of SEA positivity (odds ratio [OR] = 1.02, confidence interval [CI] = 0.79–1.32, P = 0.89). However, after two rounds of treatment, there was a slight decrease in odds of SEA positivity (OR = 0.80, CI = 0.63–1.02, P = 0.08). In contrast to the SEA results, prevalence of antibody responses to Sm25 was lowest at baseline (14.1%) and higher in years 2 (19.8%) and 3 (18.4%). After one round of MDA, odds of Sm25 positivity increased significantly (OR = 1.51, CI = 1.14–2.02, P = 0.005) and remained significantly higher than baseline after two rounds of MDA (OR = 1.37, CI = 1.07–1.76, P = 0.01). There was a significant decrease in the proportion of 1-year-olds with positive SEA responses from 33.1% in year 1 to 13.2% in year 3 and a corresponding decrease in the odds (OR = 3.25, CI = 1.75–6.08, P < 0.001). These results provide preliminary evidence that schistosomiasis program impact can be monitored using serologic responses.

Association of Total Levels of Serum Antioxidants with Periportal Fibrosis and Intensity of Schistosoma mansoni Infections in Cheretee, North East Ethiopia

Schistosomiasis is only second to malaria in terms of public health importance among parasitic diseases. Hence morbidity and mortality associated with Schistosoma mansoni are mainly the result of periportal fibrosis of the liver. With the objective of evaluating the association of total serum antioxidants and intensity of S. mansoni infection a cross sectional study was conducted from February 2011 to June 2011 involving 414 individuals and 30 controls from S. mansoni non-endemic area. The study groups were selected using systematic random sampling technique and data were collected using a pre-tested clinical questionnaire, ulthersonographic examinations of the liver and serum ferric reducing antioxidant power (FRAP) assays. Prevalence of Schistosoma mansoni infection and periportal fibrosis in Cheretee was 36.72% and 9.42%, respectively. Prevalence of periportal fibrosis and intensity of infection had a sharp rise in the age group 11-20 years, reached its peak in the 21 to 30-year age group, and started to decline thereafter up to >40. Age, sex and intensity of infection were strongly associated with periportal fibrosis development (p<0.05). Mean total serum antioxidant concentrations were significantly lower in study subjects who were from S. mansoni endemic area (96.5 μM/L) compared with healthy participants from Addis Ababa (339.9 μM/L). However, mean total serum antioxidant concentration were not significantly different among PPF positive and negative individuals from S. mansoni endemic area. Finally, further studies are recommended on the cause of this low antioxidant concentration.

Sensitivity and specificity of multiple Kato-Katz thick smears and a circulating cathodic antigen test for Schistosoma mansoni diagnosis pre- and post-repeated-praziquantel treatment.

BackgroundTwo Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This ‘gold standard’ has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings.Method/Principle FindingsIn a high S. mansoni endemic area of Uganda, three days of consecutive stool samples were collected from primary school-aged children (six - 12 years) at five time-points in year one: baseline, one-week-post-, four-weeks-post-, six-months-post-, and six-months-one-week-post-praziquantel and three time-points in years two and three: pre-, one-week-post- and four-weeks-post-praziquantel-treatment/retreatment (n = 1065). Two Kato-Katzs were performed on each stool. In parallel, one urine sample was collected and a single POC-CCA evaluated per child at each time-point in year one (n = 367). At baseline, diagnosis by two Kato-Katzs (sensitivity = 98.6%) or one POC-CCA (sensitivity = 91.7%, specificity = 75.0%) accurately predicted S. mansoni infections. However, one year later, a minimum of three Kato-Katzs, and two years later, five Kato-Katzs were required for accurate diagnosis (sensitivity >90%) and drug-efficacy evaluation. The POC-CCA was as sensitive as six Kato-Katzs four-weeks-post and six-months-post-treatment, if trace readings were classified as positive.Conclusions/SignificanceSix Kato-Katzs (two/stool from three stools) and/or one POC-CCA are required for M&E or drug-efficacy studies. Although unable to measure egg reduction rates, one POC-CCA appears to be more sensitive than six Kato-Katzs at four-weeks-post-praziquantel (drug efficacy) and six-months-post-praziquantel (M&E).

Serological Screening of the Schistosoma mansoni Adult Worm Proteome

BackgroundNew interventions tools are a priority for schistosomiasis control and elimination, as the disease is still highly prevalent. The identification of proteins associated with active infection and protective immune response may constitute the basis for the development of a successful vaccine and could also indicate new diagnostic candidates. In this context, post-genomic technologies have been progressing, resulting in a more rational discovery of new biomarkers of resistance and antigens for diagnosis.Methodology/Principal FindingsTwo-dimensional electrophoresed Schistosoma mansoni adult worm protein extracts were probed with pooled sera of infected and non-infected (naturally resistant) individuals from a S. mansoni endemic area. A total of 47 different immunoreactive proteins were identified by mass spectrometry. Although the different pooled sera shared most of the immunoreactive protein spots, nine protein spots reacted exclusively with the serum pool of infected individuals, which correspond to annexin, major egg antigen, troponin T, filamin, disulphide-isomerase ER-60 precursor, actin and reticulocalbin. One protein spot, corresponding to eukaryotic translation elongation factor, reacted exclusively with the pooled sera of non-infected individuals living in the endemic area. Western blotting of two selected recombinant proteins, major egg antigen and hemoglobinase, showed a similar recognition pattern of that of the native protein.Concluding/SignificanceUsing a serological proteome analysis, a group of antigens related to the different infection status of the endemic area residents was identified and may be related to susceptibility or resistance to infection.

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

BackgroundThe 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 FindingsComplete 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/SignificanceThis 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.

Enhanced Protective Efficacy of a Chimeric Form of the Schistosomiasis Vaccine Antigen Sm-TSP-2

The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG1 and IgG3 from putatively resistant individuals resident in S. mansoni endemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to the immunogenic 5B region of the hookworm aspartic protease and vaccine antigen, Na-APR-1. Sm-TSP-2 formulated with alum/CpG showed significant reductions in adult worm and liver egg burdens in two separate murine schistosomiasis challenge studies. Sm-TSP-2/5B afforded significantly greater protection than Sm-TSP-2 alone when both antigens were formulated with alum/CpG. The enhanced protection obtained with the chimeric fusion protein was associated with increased production of anti-Sm-TSP-2 antibodies and IL-4, IL-10 and IFN-γ from spleen cells of vaccinated animals. Sera from 666 individuals from Brazil who were infected with S. mansoni were screened for potentially deleterious IgE responses to Sm-TSP-2. Anti-Sm-TSP-2 IgE to this protein was not detected (also shown previously for Na-APR-1), suggesting that the chimeric antigen Sm-TSP-2/5B could be used to safely and effectively vaccinate people in areas where schistosomes and hookworms are endemic.

Gastro-intestinal symptoms associated with intense Schistosoma mansoni infection affect class-attentiveness of schoolchildren in Ethiopia

Objective To assess effect of subtle morbidities related to schistosomiasis mansoni on class-attentiveness of schoolchildren. Methods A cross-sectional study was undertaken involving 568 schoolchildren (mean age 13.4 years; 333 from Schistosoma mansoni endemic villages (Sille and Worke-Mado) and 235 from the non-endemic town Sheno. A questionnaire on signs and symptoms of ill-health was administered to all study subjects. In addition, parasitological and nutritional anthropometric data were collected. All study subjects from S. mansoni endemic areas were treated with praziquantel and albendazol while children from the non-endemic town were only treated with albendazol. Findings Prevalence of S. mansoni infection was 95% in Sille and 90.6% in Worke-Mado. Overall, among schoolchildren from S. mansoni endemic areas, 36.3% were under-nourished; 66.4% reported easy fatigue/listlessness; 61.3% had abdominal cramps with bloody-mucoid stools, and 17.7% reported to have severe and frequent abdominal cramps which distracted their class-attentiveness. The latter two symptoms were significantly associated with intensity of S. mansoni infection. Among schoolchildren from the non-endemic town Sheno, only 8.9% were under-nourished, 20% reported infrequent abdominal cramps and none had symptoms that were severe enough to affect class-attentiveness. Conclusion Symptoms associated with intense S. mansoni infection may negatively affect class-attentiveness of schoolchildren which may have important implications on their overall educational achievements. Further detailed intervention-based prospective studies are recommended to validate these findings which, if confirmed, could further justify school-age targeted praziquantel-based control of schistosomiasis.

The effect of vaccinating &lt;i&gt;S. mansoni&lt;/i&gt;–infected BALB/c mice either before or after treatment

In Schistosoma mansoni endemic areas, there are people with ongoing S. mansoni infection, others have been infected and treated while others have never been infected. What would happen if these different groups of people were vaccinated against S. mansoni? BALB / c mice were divided into five groups: Infected-Treated-Vaccinated; Infected-Vaccinated-Treated; Vaccinated-Treated Control; Challenge Control and Untreated Challenge Control. Vaccination (500 20krad irradiated S. mansoni cercariae), Treatment (praziquantel), Infection and Challenge (150 S. mansoni cercariae) were carried out at specified times. Proliferation assay, Enzyme linked immunosorbent assay, gross pathology, histopathology and perfusion were performed. High protection levels were obtained in mice treated after vaccination: Vaccinated-Treated control, 96.5 %; Infected-Vaccinated-Treated, 68.9 %; and Infected-Treated-Vaccinated, 41 %. A good correlation was obtained between proliferative responses and protective levels, implying cellular involvement in protection. Although all protected animals had high IgG levels, there was no strong correlation between the two. Specificity rather than amounts of IgG, seem more important in protection. Praziquantel seemed to boost protective immunity when administered after vaccination. Granuloma development and modulation in the two test groups was similar. It seems better to vaccinate infected patients before treatment, the ideal situation being vaccinating people who have not encountered S. mansoni.

Ageing and Toll-like receptor expression by innate immune cells in chronic human schistosomiasis

There has been no systematic study of the immune response of individuals aged over 60 years living in Schistosomiasis mansoni-endemic areas, although senescence is reportedly associated with susceptibility to infection and progressive decline in immune function. We have shown previously, in two endemic areas in Minas Gerais, Brazil, that the frequency of individuals aged over 60 years with chronic schistosomiasis is no longer negligible. Moreover, several elderly individuals who have always lived in these endemic areas stay protected from infection. An important question for studies of ageing and disease control in developing countries is which differences in the immunological profile of these negatively tested (non-infected) individuals can account for their resistance to either infection or reinfection. We show, in the present study, that non-infected (negative) elderly individuals develop innate immune mechanisms of protection that replace the age-associated decline in T cell function. Non-infected elderly individuals from endemic areas of schistosome infection present an increase in the frequency of the natural killer (NK) CD56(low) subset of NK cells expressing Toll-like receptors (TLR)-1, -2, -3 and -4 as determined by flow cytometry analysis. In addition, the proportion of dendritic cells expressing TLR-1 is elevated as well as the frequency of monocytes expressing TLR-1 and -4. These results suggest that TLR expression by cells of the innate immune system may be related to the negative status of infection in some elderly individuals who are constantly exposed to S. mansoni. Developing mechanisms of protection from infection may represent a biomarker for healthy ageing in this population.

REDUCED SERUM CONCENTRATIONS OF RETINOL AND α-TOCOPHEROL AND HIGH CONCENTRATIONS OF HYDROPEROXIDES ARE ASSOCIATED WITH COMMUNITY LEVELS OF S. MANSONI INFECTION AND SCHISTOSOMAL PERIPORTAL FIBROSIS IN ETHIOPIAN SCHOOL CHILDREN

To study the relationship between micronutrient malnutrition and schistosomiasis mansoni, a cross-sectional study was undertaken involving 421 schoolchildren (mean age 12.6 years; 333 from schistosomiasis mansoni-endemic villages (Workemado and Sille) and 88 non-endemic controls from Sheno). Prevalence of schistosomiasis mansoni infection in Workemado and Sille was comparable (90.6% versus 95%, respectively), and prevalence of PPF in Workemado was significantly higher than in Sille (7.0% versus 0.6%, P < 0.001). Compared with non-endemic controls, serum retinol concentrations were significantly lower and hydroperoxides were significantly higher in subjects from schistosomiasis mansoni-endemic areas. Furthermore, serum alpha-tocopherol concentrations in subjects from an area with high prevalence of PPF were significantly reduced while the concentrations in subjects from an area with low prevalence of PPF were comparable to the levels found in non-endemic healthy controls. In conclusion, micronutrient malnutrition and oxidative stress are associated with Schistosoma mansoni infection and levels of schistosomal PPF.

The 434(G>C) polymorphism within the coding sequence of Eosinophil Cationic Protein (ECP) correlates with the natural course of Schistosoma mansoni infection

Schistosomiasis is a chronic parasitic infection with over 200 million people infected worldwide. In Schistosoma mansoni infections, parasite-derived eggs get trapped in the liver, causing the formation of granulomas, which may develop into periportal fibrosis and portal hypertension, and thus severe morbidity. Eosinophil cationic protein (ECP) is a secretory protein of eosinophil granulocytes that efficiently kills the larval stage of S. mansoni, but also affects fibroblast functions. We have investigated the prevalence of the ECP gene polymorphism 434(G>C) in two African populations, from an S. mansoni endemic area in Uganda (n=297) and from a non-endemic area in Sudan (n=78), and also compared these with a Swedish population (n=209). The genotype frequencies in the Ugandan population differed significantly from both the Sudanese and Swedish populations (P<0.001). In the Ugandan population there was a significant association between genotype and prevalence of infection (P=0.03), with lower prevalence in subjects with the GG genotype compared with GC (P=0.02) and CC (P=0.03). There was also a trend towards an association with periportal fibrosis (P=0.08) in the Ugandan population. This suggested association was confirmed when the predominant tribe (n=212) was analysed separately (P=0.004). Our results suggest that ECP may be an important protein, both in the immune response against S. mansoni and in the development of periportal fibrosis. The results also suggest genetic selection towards the ECP 434CC genotype in populations living in S. mansoni endemic areas.

Field-based evaluation of a reagent strip test for diagnosis of Schistosoma mansoni by detecting circulating cathodic antigen in urine before and after chemotherapy

The sensitivity of a reagent strip test for the diagnosis of schistosomiasis by detecting circulating cathodic antigen (CCA) in urine was evaluated under field conditions using 251 stool and urine samples collected from a Schistosoma mansoni-endemic area of Ethiopia. The specificity of the test was evaluated in an area where schistosomiasis is not endemic. Stool samples were examined microscopically using duplicate Kato slides and formol-ether concentration methods. The effectiveness of the test in monitoring efficacy was also evaluated following chemotherapy. The results revealed that detection of CCA in urine using the one-step reagent strip test was superior to the stool examination methods (P<0.05) in indicating the prevalence of the disease. Assuming the combination of parasitological test results as the gold standard, the sensitivity and specificity of the test were 82.1% and 75.9%, respectively. The results of egg counts suggested the potential use of urine CCA in indicating the intensity of infection as an alternative to parasitological methods. The sensitivity and specificity of the test were 75% and 73.7%, respectively, following chemotherapy. Diagnosis of S. mansoni infection in urine using reagent strips would provide information on the prevalence of the disease, although further study is needed to improve its sensitivity and specificity.

The effect of vaccinating &lt;i&gt;S. mansoni&lt;/i&gt;–infected BALB/c mice either before or after treatment

In Schistosoma mansoni endemic areas, there are people with ongoing S. mansoni infection, others have been infected and treated while others have never been infected. What would happen if these different groups of people were vaccinated against S. mansoni? BALB/c mice were divided into five groups: Infected-Treated-Vaccinated; Infected-Vaccinated-Treated; Vaccinated-Treated Control; Challenge Control and Untreated challenge Control. Vaccination (500 20krad irradiated S. mansoni cercariae), Treatment (praziquantel), Infection and Challenge (150 S. mansoni cercariae) were carried out at specified times. Proliferation assay, Enzyme linked immunosorbent assay, gross pathology, histopathology and perfusion were performed. High protection levels were obtained in mice treated after vaccination: Vaccinated-Treated control, 96.5%; Infected-Vaccinated-Treated, 68.9%; and Infected-Treated-Vaccinated, 41%. A good correlation was obtained between proliferative responses and protective levels, implying cellular involvement in protection. Although all protected animals had high IgG levels, there was no strong correlation between the two. Specificity rather than amounts of IgG, seem more important in protection. Praziquantel seemed to boost protective immunity when administered after vaccination. Granuloma development and modulation in the two test groups was similar. It seems better to vaccinate infected patients before treatment, the ideal situation being vaccinating people who have not encountered S. mansoni. African Journal of Health Sciences Vol. 12(3-4) 2005: 65-77

Enzyme-linked immunosorbent assay with worm vomit and cercarial secretions of Schistosoma mansoni to detect infections in an endemic focus of Burkina Faso

Cercariae and adult Schistosoma mansoni were used to prepare, respectively, cercarial secretions (CS) and worm vomit (WoV). These were used as antigens in an enzyme-linked immunosorbent assay (ELISA) to test the IgG-reactivity of sera obtained in an S. mansoni-endemic area of Burkina Faso. Among the egg-excreting individuals (n = 240), 94.6% reacted positively with WoV, but only 62.9% with CS, thus suggesting a high diagnostic sensitivity of WoV, but not of CS. Among those individuals without detectable eggs in two Kato-Katz thick smears from different stool specimens (n = 215), the respective percentages of positive IgG reactivity were 78.1% and 63.3%. These positive reactions in the absence of detectable eggs are interpreted in terms of limited sensitivity of parasitological stool examinations. Optical density values in ELISA with CS, but not with WoV, correlated negatively with age, which may reflect decreasing exposure to cercariae in older individuals.

Absence of cervical schistosomiasis among women from two areas of north–eastern Brazil with endemicSchistosoma mansoni

Genital manifestations in schistosomiasis haematobium are common and are associated with considerable morbidity. Although Schistosoma mansoni may also cause genital disease, the frequency of this complication is not known. Cervical biopsies (N=401) and Pap smears (N=981) were therefore collected from women living in two S. mansoni-endemic areas (in the states of Alagoas and Ceará, in north-eastern Brazil). The women were screened for the presence of sexually transmitted diseases and for the presence, in their cervical smears and/or biopsies, of S. mansoni eggs. Attempts at schistosomiasis control, which began in both study areas in 1977, have led to generally low intensities of infection (<30 eggs/g faeces in 99% of infections) and community prevalences of infection that range between 1% and 52%. As no schistosome ova were detected in any of the biopsies or smears, it appears that the risk, among women, of genital manifestations of S. mansoni infection is small in areas where the parasite load in the population is low (as the result of interventions to control intestinal schistosomiasis).

Serodiagnosis of Schistosoma mansoni infections in an endemic area of Burkina Faso: performance of several immunological tests with different parasite antigens

The performance of indirect haemagglutination assays (IHA), enzyme-linked immunosorbent assays (ELISA) and indirect immunofluorescent antibody tests (IFAT) were compared with 450 sera from a Schistosoma mansoni-endemic area in Burkina Faso. All participants in this survey provided at least one sample each of stool, urine and serum. From those with an egg-negative Kato–Katz thick smear, a second stool sample was examined. IHA was based on either extracts of adult S. mansoni worms (SmIHA) or S. japonicum egg antigen (SjIHA). For ELISA, three antigen preparations were used, namely: (i) soluble S. mansoni adult worm antigens (SWAP); (ii) soluble S. mansoni egg antigens (SEA); and (iii) a cationic exchange fraction of S. mansoni eggs (CEF6). IFAT was performed with S. mansoni male worm sections. Among the egg-excretors, the sensitivity of ELISA was high and egg antigens performed slightly better (SEA, 96%; CEF6, 97%) than worm antigen (94%). Sensitivity of IHA was satisfactory with homologous (Sm, >85%), but not heterologous (Sj, 56%) parasite antigen. In IFAT, the parenchyma-associated fluorescence showed high sensitivity (95%), but gut-associated fluorescence, which is known to be a sensitive diagnostic marker for schistosome-infected European travelers, was observed only in 76% of a sub-sample of 100 of the endemic sera. Among sera from egg-negative individuals, many gave positive reactions in several or all of the tests employed. These reactions (formally “false positive”) are considered to represent true infections, since chemotherapy had not yet been delivered to this population. For the purpose of further surveys in Burkina Faso or other resource-poor settings, we suggest IHA as an accurate diagnostic test and propose to further improve its performance by including egg rather than worm antigens.

Production of interferon-gamma by natural killer cells and aging in chronic human schistosomiasis.

BACKGROUND: Aging is associated with several alterations in the phenotype, repertoire and activation status of lymphocytes as well as in the cytokine profile produced by these cells. As a lifelong condition, chronic parasitic diseases such as human schistosomiasis overlaps with the aging process and no systematic study has yet addressed the changes in immune response during infection with Schistosoma mansoni in older individuals. AIM: Herein we study the influence of immunological alterations brought about by senescence in the course of schistosomiasis. MATERIALS AND METHODS: Individuals 10-95 years of age, from both sexes, from an endemic area for S. mansoni infection were matched by intensity of infection as measured by egg counts. We analyzed, as a parameter, cytokine expression by lymphocytes and natural killer cells after in vitro stimulation with soluble egg antigen and soluble worm antigen using flow cytometry. RESULTS: We demonstrated that the frequency of CD16+ interferon-gamma (IFN-gamma)+ natural killer cells in negative individuals over the age of 70 years is significantly higher than in positive individuals after in vitro stimulation with S. mansoni antigen extracts. The frequency of these cells is increased in all individuals over the age of 50 years and only declines in positive individuals after 70 years of age. Analysis of either CD4? or CD8? cells after antigen stimulation show no significant increase in frequency of IFN-gamma in negative or in positive individuals of this age group, suggesting that the effect on CD16+ cells is not T-cell dependent. CONCLUSION: Since production of IFN-gamma has been related to resistance to schistosome infection, our data suggest that age-associated changes in CD16+ cells may play a role in controlling infection intensity in the elderly in S. mansoni endemic areas of Brazil.

Cluster analysis of schistosome-specific antibody responses partitions the population into distinct epidemiological groups

Immuno-epidemiological studies in schistosomiasis continue to generate large amounts of immunology data, whose analysis requires sophisticated statistical approaches. Here cluster analysis, is used to explore the relationship between immune responses and observed epidemiological patterns of schistosome infection in two Zimbabwean communities. Analysis of cross-sectional antibody data (IgA, IgE, IgG1, IgG2, IgG3, IgG4 and IgM directed against Schistosoma haematobium soluble egg antigen (SEA)) showed that cluster analysis partitioned the data into distinct epidemiological groups based on all seven antibody isotypes (defined by age, infection intensity, treatment status and history of infection) confirming an already known partitioning based on IgA/IgG1 production. All treated participants (children) changed cluster membership following treatment from clusters where IgA was the predominant antibody to clusters where IgG1 predominated. There was a differential distribution of IgE and IgG4 between clusters consistent with the recently proposed balance between T-helper cells (Th) 1, Th2 and regulatory T cells. The analysis suggested that naturally acquired anti-schistosome responses associated with resistance to infection were different from drug-induced responses associated with resistance to re-infection. Furthermore, the analysis suggested that parasite-specific immune responses were dynamic. The analysis conducted on data from participants resident in the S. mansoni endemic area who were all children partitioned the data into two clusters, one with predominately pre-treatment data (cluster 1) and the other with post-treatment data (cluster 2). The antibody profiles of both clusters were most similar to the profile of people with a modified Th2 response. Following treatment 43% of the children in cluster 1 moved to cluster 2, which generally had higher levels of antibodies. A detailed study of factors determining which children moved between the clusters showed that it was mostly the older, infected children who moved to cluster 2. The results of the analysis are discussed in terms of current theories of the development of acquired immunity to schistosomiasis. The relative merits of cluster analysis as a statistical tool for analysing these data are also discussed.

Childhood stunting in Northeast Brazil: the role of Schistosoma mansoni infection and inadequate dietary intake.

To evaluate the relationship between stunting, Schistosoma mansoni infection and dietary intake in schoolchildren. This is a cross-sectional study. Two stool samples were obtained from each child and examined quantitatively for the presence of S. mansoni, Ascaris lumbricoides and Trichuris trichiuria eggs. Information on dietary intake, and demographic, biologic and socioeconomic variables was elicited during the in-home survey. Logistic regression was used to evaluate the association between stunting (height for age < -2s.d.), parasitic infection and food consumption. The study was carried out in the city of Nazaré, located in the Recôncavo region of the State of Bahia, Northeastern Brazil. The sample consisted of 461 children 7-14 y old, 228 boys and 233 girls, recruited from public schools. Of the children studied, 55.1% presented with S. mansoni infection and 22.1% were stunted. The median protein, lipid and carbohydrates intake were 47.8, 36.0 and 248.2 g/day, respectively. The median caloric consumption was 1527.0 kcal (6388.97 kJ/day). The analysis indicated that children heavily infected (> or = 400 eggs/g of stool) with S. mansoni had a 2.74-fold (95% CI: 1.32-5.67) higher risk of stunting than uninfected children, and those with inadequate intake of lipid (< 36 g/day) had a 1.83-fold (95% CI: 1.05-3.20) increased risk of stunting compared to those with adequate diets. Heavy S. mansoni infection and inadequate dietary intake of fat in schoolchildren play a significant and independent role in the development of stunting. This meaning that nutritional interventions in this age group in S. mansoni endemic areas must include the diagnosis and treatment of the infection associated with dietary measures. This study was supported by the Thrasher Foundation. Sandra Maria Conceição Pinheiro is a National Council on Technological Development Scholarship Awardee (CNPq), #302228/81-0.