HBsAg loss after peginterferon-nucleotide combination treatment in chronic hepatitis B patients: 5 years of follow-up.

Combining peginterferon-alfa-2a (pegIFN) with a nucleotide analogue can result in higher rates of HBsAg loss than either therapy given alone. Here, we investigated the durability of the response to combination therapy in chronic hepatitis B (CHB) patients after 5 years of follow-up. In the initial study, 92 CHB patients (44 HBeAg-positive, 48 HBeAg-negative) with HBV DNA >100 000 c/mL (~20 000 IU/mL) and active hepatitis were treated for 48 weeks with pegIFN 180 µg/week and 10 mg adefovir dipivoxil daily. For the long-term follow-up (LTFU) study, patients were followed up for 5 years after the end of treatment. At year 5, 70 (32 HBeAg-positive, 38 HBeAg-negative) patients remained in the study. At year 5, 19% (6/32) of HBeAg-positive patients and 16% (6/38) of HBeAg-negative patients lost HBsAg, and no HBsAg seroreversion was observed. The 5-year cumulative Kaplan-Meier estimate for HBsAg loss was 17.2% for HBeAg-positive patients and 19.3% for HBeAg-negative patients. Fourteen of sixteen patients who lost HBsAg at any time point during follow-up developed anti-HBs antibodies (>10 IU/L). At year 5, in total 63% (20/32) of HBeAg-positive and 71% (27/38) of HBeAg-negative patients were retreated with nucleos(t)ide analogues during follow-up. The cumulative Kaplan-Meier estimate for retreatment was 60% of patients at year 5. At year 5 of follow-up, 18% of CHB patients treated with pegIFN/nucleotide analogue combination therapy had durable HBsAg loss and 88% of these had developed anti-HBs antibodies.

Soluble TLR2 and 4 concentrations in cerebrospinal fluid in HIV/SIV-related neuropathological conditions.

HIV in the central nervous system (CNS) mainly infects microglial cells which are known to express toll-like receptors (TLRs). This paper aimed to study the role of soluble TLR2 (sTLR2), sTLR4, and other inflammatory markers in cerebrospinal fluid (CSF) in HIV/Simian immunodeficiency virus (SIV)-related neurological sequelae. We determined sTLR2 and sTLR4 levels in CSF and serum/plasma of SIV-infected rhesus macaques with and without neurological sequelae, as well as in HIV-infected patients with and without cognitive impairments and Alzheimer's disease (AD) patients and matched controls. CSF cytokines and chemokines levels were analyzed in macaques as markers of neuroinflammation, while neopterin and S100B CSF concentrations were measured in HIV-infected patients as microglial and astrocyte marker, respectively. We found detectable levels of sTLR2 and sTLR4 in CSF of macaques and humans. Furthermore, CSF sTLR2 and sTLR4 concentrations were higher in SIV-infected macaques with neurological sequelae compared to those without neurological complications (p = 0.0003 and p = 0.0006, respectively). CSF IL-8 and monocyte chemoattractant protein-1 (MCP-1) levels were elevated in macaques with neurological sequelae, and a positive correlation was found between CSF levels of sTLR2/4 and IL-8 and MCP-1. Also in humans, elevated CSF sTLR4 levels were found in HIV-infected patients with cognitive impairments compared to HIV-infected patients with normal cognition (p = 0.019). Unlike CSF S100B levels, neopterin correlated positively with sTLR2 and sTLR4. No difference was found in plasma and CSF sTLR2 and sTLR4 levels between AD patients and control subjects (p = 0.26). In conclusion, CSF sTLR2 and sTLR4 may play a role in HIV/SIV-related neuroinflammation and subsequent neuropathology.

HLA-C and KIR combined genotype as new response marker for HBeAg-positive chronic hepatitis B patients treated with interferon-based combination therapy.

Current treatment for chronic hepatitis B infection (CHB) consists of interferon-based therapy. However, for unknown reasons, a large proportion of patients with CHB do not respond to this treatment. Hence, there is a pressing need to establish response markers to select patients who will benefit from therapy and to spare potential nonresponders from unnecessary side effects of antiviral therapy. Here, we assessed whether HLA-C and KIR genotypes were associated with treatment outcome for CHB. Twelve SNPs in or near the HLA-C gene were genotyped in 86 CHB patients (41 HBeAg positive; 45 HBeAg negative) treated with peginterferon alfa-2a + adefovir. Genotyping of killer immunoglobin-like receptors (KIRs) was performed by SSP-PCR. One SNP in HLA-C (rs2308557) was significantly associated with combined response in HBeAg-positive CHB patients (P = 0.003). This SNP is linked to the HLA-C group C1 or C2 classification, which controls KIR binding. The combination of KIR2DL1 with its ligand HLA-C2 was observed significantly more often in HBeAg-positive patients with a combined response (13/14) than in nonresponders (11/27, P = 0.001). Patients with the KIR2DL1/C2 genotype had significantly higher baseline ALT levels (136 vs 50 U/L, P = 0.002) than patients without this combination. Furthermore, KIR2DL1-C2 predicted response independent of HBV genotype and ALT at baseline. HLA-C and KIR genotype is strongly associated with response in HBeAg-positive CHB patients treated with interferon-based therapy. In combination with other known response markers, HLA-C/KIR genotype could enable the selection of patients more likely to respond to interferon-based therapy.

The diagnostic accuracy of serological tests for Lyme borreliosis in Europe: a systematic review and meta-analysis.

BACKGROUND: Interpretation of serological assays in Lyme borreliosis requires an understanding of the clinical indications and the limitations of the currently available tests. We therefore systematically reviewed the accuracy of serological tests for the diagnosis of Lyme borreliosis in Europe. METHODS: We searched EMBASE en MEDLINE and contacted experts. Studies evaluating the diagnostic accuracy of serological assays for Lyme borreliosis in Europe were eligible. Study selection and data-extraction were done by two authors independently. We assessed study quality using the QUADAS-2 checklist. We used a hierarchical summary ROC meta-regression method for the meta-analyses. Potential sources of heterogeneity were test-type, commercial or in-house, Ig-type, antigen type and study quality. These were added as covariates to the model, to assess their effect on test accuracy. RESULTS: Seventy-eight studies evaluating an Enzyme-Linked ImmunoSorbent assay (ELISA) or an immunoblot assay against a reference standard of clinical criteria were included. None of the studies had low risk of bias for all QUADAS-2 domains. Sensitivity was highly heterogeneous, with summary estimates: erythema migrans 50% (95% CI 40% to 61%); neuroborreliosis 77% (95% CI 67% to 85%); acrodermatitis chronica atrophicans 97% (95% CI 94% to 99%); unspecified Lyme borreliosis 73% (95% CI 53% to 87%). Specificity was around 95% in studies with healthy controls, but around 80% in cross-sectional studies. Two-tiered algorithms or antibody indices did not outperform single test approaches. CONCLUSIONS: The observed heterogeneity and risk of bias complicate the extrapolation of our results to clinical practice. The usefulness of the serological tests for Lyme disease depends on the pre-test probability and subsequent predictive values in the setting where the tests are being used. Future diagnostic accuracy studies should be prospectively planned cross-sectional studies, done in settings where the test will be used in practice.

Circulating galectin-3 in infections and non-infectious inflammatory diseases.

Recent studies point to a dual role for galectin-3 as both a circulating damage-associated molecular pattern and a cell membrane-associated pattern recognition receptor. The aim of this study was to assess the potential of circulating galectin-3 for discriminating between infections and non-infectious inflammatory disorders on the one hand, and between fungal and bacterial infections on the other. Galectin-3 and C-reactive protein (CRP) were measured in the plasma of 127 patients with either non-infectious inflammatory disorders (gout, autoinflammatory syndrome or pancreatitis) or an infection (viral lower respiratory tract infection, bacterial sepsis or candidaemia). Circulating galectin-3 concentrations were increased in patients with infections when compared with healthy volunteers or patients with non-infectious inflammatory diseases. At cut-off values with a specificity of 95%, the sensitivity of galectin-3 (>20.6 ng/ml) to discriminate between an infection and non-infectious inflammation was higher than that of CRP (>156 mg/l): 43% [95% confidence interval (CI) 33-53%] versus 27% (95% CI 19-37%), p = 0.03. After exclusion of patients with CRP <156 mg/l, galectin-3 concentration >20.6 ng/ml could identify 41 % (95% CI 29-53%) of the patients with an infection at the cost of one false-positive with non-infectious inflammation. Using this sequential approach, 57% of the patients with an infection could be selected. Galectin-3 concentrations were similar in patients with bacterial and Candida sepsis, while being lower in viral respiratory infections. Although galectin-3 does not discriminate between bacterial and Candida sepsis, the sequential use of CRP and galectin-3 in distinguishing infectious diseases from non-infectious inflammation may be superior to CRP alone.

Toll-like receptors and microbial exposure: gene-gene and gene-environment interaction in the development of atopy.

Environmental and genetic factors contribute to atopy development. High microbial exposure may confer a protective effect on atopy. Toll-like receptors (TLRs) bind microbial products and are important in activating the immune system. To assess whether interactions between microbial exposures and genes encoding TLRs (and related genes) result in atopy, genes, environmental factors and gene-environment interactions of 66 single-nucleotide polymorphisms (SNPs) of 12 genes (TLR 1-6, 9 and 10, CD14, MD2, lipopolysaccharide-binding protein (LBP) and Dectin-1), and six proxy parameters of microbial exposure (sibship size, pets (three different parameters), day-care and intrauterine and childhood tobacco smoke exposure) were analysed for association with atopic phenotypes in 3,062 Dutch children (the Allergenic study). The presence of two or more older siblings increased the risk of developing high total immunoglobulin (Ig)E levels at different ages. This risk increased further in children aged 1-2 yrs carrying the minor allele of TLR6 SNP rs1039559. Furthermore, novel two- and three-factor gene-gene and gene-environment interactions were found (e.g. between sibship size, day-care and LBP SNP rs2232596). Larger sibship size is associated with increased total IgE levels. Furthermore, complex two- and three-factor interactions exist between genes and the environment. The TLRs and related genes interact with proxy parameters of high microbial exposure in atopy development.

Interaction of T-cell and antigen presenting cell co-stimulatory genes in childhood IgE.

It is likely that multiple genes contribute to immunoglobulin (Ig)E production. Co-stimulatory molecules are crucial for the cross-talk between antigen presenting cells and T-lymphocytes which drives the IgE response. We evaluated gene-gene interactions of haplotype tagging polymorphisms in a pathway of 24 co-stimulatory genes in relation to serum IgE levels. We assessed this at ages 1-2 yrs and 6-8 yrs in 3,062 Dutch children from a pooled data set of three birth cohorts: PIAMA (Prevention and Incidence Asthma and Mite Allergy), PREVASC (Prevention of Asthma in Children) and KOALA (Child, parents and health: lifestyle and genetic constitution). Single- and multi-locus associations with serum IgE levels (3rd versus 1st tertile) were evaluated by Chi-squared tests and the multifactor dimensionality reduction (MDR) method in the following co-stimulatory genes: VTCN1, TNFRSF4, TNFRSF18, TNFRSF14, TNFSF18, TNFSF4, CD28, CTLA4, ICOS, PDCD1, BTLA, CD80, CD86, HLA-G, CD274, PDCD1LG2, CD276, LILRA4, LILRB1, LILRB2, LILRB4, CD40, ICOSLG, and CD40LG. We found multiple statistically significant single-locus ((S)) and multi-locus ((M)) associations for the genes VTCN1(SM), TNFSF18(SM), TNFSF4(S), CD28(S), CTLA4(M), ICOS(S), BTLA(M), CD80(M), CD86(SM), CD274(SM), PDCD1LG2(M), LILRA4(SM), LILRB4(M), and CD40(SM) with serum IgE. Two-locus interactions of CD86 with VTCN1 and CD274 with LILRA4 were confirmed by logistic regression. In conclusion, serum IgE levels are regulated by multiple gene-gene interaction effects in the co-stimulatory pathway. We suggest using research strategies that model multiple gene-gene interactions in genetic studies.

TLR-related pathway analysis: novel gene-gene interactions in the development of asthma and atopy.

BACKGROUND: The toll-like receptor (TLR)-related pathway is important in host defence and may be crucial in the development of asthma and atopy. Numerous studies have shown associations of TLR-related pathway genes with asthma and atopy phenotypes. So far it has not been investigated whether gene-gene interactions in this pathway contribute to atopy and asthma development. METHODS: One hundred and sixty-nine haplotype tagging single nucleotide polymorphisms (SNPs) of 29 genes (i.e. membrane and intracellular receptors, TLR4 or lipopolysaccharide-binding/facilitating proteins, adaptors, interleukin-1 receptor associated kinases, kinases, chaperone molecules, transcription factors and inhibitors) were analysed for single- and multilocus associations with atopy [total and specific immunglobulin E (IgE) at 1-2 and 6-8 years] and asthma (6-8 years). A total of 3062 Dutch children from the birth cohorts PIAMA, PREVASC and KOALA (Allergenic study) were investigated. Chi-squared test, logistic regression and the data mining approach multifactor dimensionality reduction method (MDR) were used in analysis. RESULTS: Several genes in the TLR-related pathway were associated with atopy and/or asthma [e.g. IL1RL1, BPI, NOD1, NOD2 and MAP3K7IP1]. Multiple, single associations were found with the phenotypes under study. MDR analysis showed novel, significant gene-gene interactions in association with atopy and asthma phenotypes (e.g. IL1RL1 and TLR4 with sIgE to indoor allergens and IRAK1, NOD1 and MAP3K7IP1 with asthma). Interestingly, gene-gene interactions were identified with SNPs that did not have an effect on their own. CONCLUSION: Our unbiased approach provided suggestive evidence for interaction between several TLR-related pathway genes important in atopy and/or asthma development and pointed to novel genes.

X-chromosome Forkhead Box P3 polymorphisms associate with atopy in girls in three Dutch birth cohorts.

BACKGROUND: The Forkhead Box P3 (FOXP3) gene, located on the X-chromosome, encodes a transcription factor that directs T cells toward a regulatory phenotype. Regulatory T cells may suppress development of atopy. We evaluated whether single-nucleotide polymorphisms (SNPs) of FOXP3 are associated with atopy development in childhood. METHODS: Seven SNPs in FOXP3 were genotyped in 3062 children (51% boys) participating in the Allergenic study, which consists of three Dutch birth cohorts (PIAMA, PREVASC and KOALA). Association of FOXP3 SNPs with total serum IgE and sensitisation (presence of specific serum IgE to egg, milk, and indoor, i.e. house-dust mite, cat, and/or dog allergens) was investigated at ages 1, 2, 4, and 8. Analysis of variance and logistic regression were performed, stratified for gender. RESULTS: Our most consistent finding was observed for sensitisation to egg and indoor allergens. In girls, five FOXP3 SNPs (rs5906761, rs2294021, rs2294019, rs6609857 and rs3761548) were significantly associated with sensitisation to egg at ages 1 and 2 and with sensitisation to indoor allergens at age 2 (P < 0.05), but not at 4 and 8, a finding that was observed across the three cohorts. Rs5906761 and rs2294021 were associated with remission of sensitisation to food allergens in boys, as tested in the PIAMA cohort. CONCLUSION: This is the first study showing across three cohorts that X-chromosomal FOXP3 genotypes may contribute to development of sensitisation against egg and indoor allergens in girls in early childhood. In addition, an association with remission of sensitisation to food allergens existed in boys only.

Early-life rotavirus and norovirus infections in relation to development of atopic manifestation in infants.

BACKGROUND: The increase in incidence of atopic diseases (ADs) in the developed world over the past decades has been associated with reduced exposure of childhood infections. OBJECTIVE: To investigate the relation between early intestinal viral infections in relation to the development of atopic symptoms (eczema, wheeze and atopic sensitization) in the first and second year(s) of life. METHODS: In the KOALA Birth Cohort Study, we assessed IgG seropositivity for rota- and norovirus (GGI.1 and GGII.4) at 1 year of age. This was related to allergic sensitization [specific immunoglobulin E (IgE)] at 1 and 2 years, and parent reported eczema and wheeze in the first 2 years, using logistic regression analysis adjusted for confounders. RESULTS: Rotavirus seropositivity (39%) was associated with an unexpected higher risk of recurrent wheeze in the first and second year of life [adjusted odds ratio (OR) 3.1 and 95% confidence intervals (CI) 1.1-9.1] and persistent and new recurrent wheeze (adjusted OR 2.7 and 95% CI 1.1-6.2). No further associations were found between intestinal viral seropositivity and atopic manifestations. CONCLUSION: Our data did not show a clear protection by enteric viral infections in young children on development of IgE response to allergens, but rotavirus infection in the first year was a risk factor for wheeze. However, this needs to be followed up to older ages in order to establish the true importance of intestinal viral infections and especially cumulative effects in AD aetiology. Exposure to rotavirus may offer a new and interesting focus on infant wheeze and later asthma development.

Occupational risk of human Cytomegalovirus and Parvovirus B19 infection in female day care personnel in the Netherlands; a study based on seroprevalence.

Cytomegalovirus (CMV) and Parvovirus B19 infections acquired during pregnancy may result in developmental disabilities of the foetus. This study evaluates the occupational risk of these infections in female day care personnel. IgG seroprevalence was determined in 310 Dutch day care workers and 158 nursing school students. CMV seroprevalence was age-related, starting at 21% in those <20 years and reaching 65% in those >35 years. Between the ages of 20 and 24 years the CMV prevalence was higher in day care personnel than in controls, 50% versus 31% (p = 0.03). In the first 2 years of employment the risk of attracting CMV was significantly increased (OR(adj) = 3.80; p < 0.001) and the occupational risk was also increased (OR(adj) 2.19; p < 0.001). Parvovirus seropositivity (71-77%) was not related to age or working at a day care centre. In conclusion, an occupational risk was observed for CMV, but not for Parvovirus infection in female day care personnel.

Interleukin 13, CD14, pet and tobacco smoke influence atopy in three Dutch cohorts: the allergenic study.

Studying gene-environment interactions may elucidate the complex origins of atopic diseases but requires large study populations. Pooling data from several cohort studies may help but may also obscure findings. Gene-environment interactions in atopy development were studied and the benefits of pooling data were evaluated. Haplotype-tagging polymorphisms in the genes interleukin (IL)13 and CD14 were genotyped in 3,062 children from the following birth cohorts: the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study; the Prevention of Asthma in Children (PREVASC) study; and the Child, Parent, Health, Focus on Lifestyle and Predisposition (KOALA) study, and tested for association with total and specific immunoglobulin (Ig)E and interaction with tobacco smoke and pet exposure at ages 1, 2, 4 and 8 yrs by analysis of variance, Chi-squared tests and regression analyses. At all ages, in IL13, minor alleles of rs1295685 and rs20541 were significantly associated with elevated IgE levels in pooled analyses. In CD14, the rs2569190-TT and rs2569191-CC genotypes associated with lower IgE and decreased risk of sensitisation at 4 and 8 yrs in children exposed to pets, with an opposite effect in nonexposed children. Findings for IL13 and CD14 were comparable in separate cohorts. The present study indicates that atopy is importantly influenced by interleukin 13 at age 1-8 yrs and by CD14 in interaction with pet exposure at ages 4 and 8 yrs. Additionally, pooled data improved effect estimates and genetic effects could be detected in interaction with important environmental factors.

A Dutch nationwide evaluation of serological assays for detection of Borrelia antibodies in clinically well-defined patients.

Numerous tests for the detection of antibodies against Borrelia burgdorferi are commercially available. Manufacturer-derived data invariably report a high sensitivity and specificity, but comparative studies demonstrate large differences in clinical practice, especially with regard to specificity. We retrospectively collected data from validation studies for B. burgdorferi antibody assays from 8 laboratories in the Netherlands. The total number of samples was 809. Samples were selected based on clinical and laboratory parameters. We included samples from patients with erythema migrans, acrodermatitis chronicum atrophicans, and neuroborreliosis; cross-reactivity controls; and healthy controls. Data are presented from 10 enzyme-linked immunosorbent assays and 5 immunoblots. For manifestations of B. burgdorferi infection with short disease duration, the positivity rate of the assays varied significantly. In patients with long disease duration, the positivity rate differed only marginally. In cross-reactivity controls, there was significant variation in the reactivity rate. The majority of false-positive reactions are of the IgM isotype.

Amyloid beta-42 (Aß-42), neprilysin and cytokine levels. A pilot study in patients with HIV related cognitive impairments.

HIV-associated dementia (HAD) is associated with amyloid-beta (Aß) deposition. This study measured CSF and plasma amyloid beta-42 (Aß-42), neprilysin (NEP) and cytokine levels in HIV-related cognitive impairments (HCI), HIV normal cognitive functioning (NF) and non-HIV controls. Our data showed a trend towards detectable plasma Aß-42 levels more frequently in HCI (67%), when compared to NF (29%) and controls (10%). We showed elevated IL-8 levels in CSF of HCI compared to NF, although not significant values. The data from this pilot study indicates that CSF IL-8 and plasma Aß-42 may be interesting biomarkers for the presence of HCI.

Morbidity due to heavy Schistosoma mansoni infections in a recently established focus in northern Senegal.

A study of morbidity due to Schistosoma mansoni infection was carried out in Ndombo, a recently established but intense focus in northern Senegal. A random population sample (n = 422) was examined by repeated egg counts, standardized interviews, and clinical examinations. Egg counts were positive in 91%, with more than 1,000 eggs per gram of feces in 41% of the subjects. Abdominal discomfort was reported by 60% of the subjects, diarrhea by 33%; 17% of the stools were liquid upon inspection. Hepatomegaly was mostly mild and found in 7% of the subjects, mainly in males less than 20 years of age. Splenomegaly was detected in only 0.5% of the people examined. There was no significant correlation between the frequency of complaints or symptoms and egg counts. The remarkably mild morbidity in spite of the intense level of many infections may be explained by the recent nature of the focus; more severe chronic morbidity may develop in the future.

Epidemiologic application of circulating antigen detection in a recent Schistosoma mansoni focus in northern Senegal.

Quantitative enzyme-linked immunosorbent assays (ELISAs) for the detection of circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) in serum and urine were applied as an epidemiologic tool in a recent, intense focus of Schistosoma mansoni in Senegal. Both CAA and CCA in serum and CCA in urine were found in 94%, 83%, and 95%, respectively, of the population, of which 91% were positive on stool examination. Circulating antigens were also detectable in sera and urines of most egg-negative individuals. The sensitivities of the urine CCA and serum CAA ELISA were substantially higher than that of a single egg count, and increased with egg output. The CAA and CCA levels correlated well with egg counts and with each other. The age-related evolution of antigen levels followed a similar pattern as egg counts, providing supplementary evidence for a genuine reduction of worm burdens in adults in spite of the supposed absence of acquired immunity in this recently exposed community. The antigen:egg ratios decreased in adults, suggesting lower worm fecundity in children. This would be compatible with a density-dependent reduction of fecundity, but not with anti-fecundity immunity in adults that perhaps has not yet developed in this new focus.

Efficacy and side effects of praziquantel in an epidemic focus of Schistosoma mansoni.

Schistosoma mansoni was first reported in the area of Richard Toll (Senegal) in 1988 and spread rapidly in the community, after a series of human-engineered ecologic changes. A random population sample (n = 422) from Ndombo, a village near Richard-Toll, was studied in 1991 by stool examination (four Kato slides from two stool samples) and antigen detection in urine and blood. Stool-positive individuals were treated with 40 mg/kg of praziquantel. A house-to-house interview regarding side effects was conducted 24 hr after treatment. Two hundred ninety-eight subjects were re-examined 10 days (antigen detection) and 12 weeks (egg counts, antigen detection) after treatment. Before treatment, positive egg counts were found in 91% of the subjects, with 41% excreting more than 1,000 eggs per gram (epg) of feces. Treatment of 352 individuals caused serious but transient side effects (colic, vomiting, urticaria, and edema), the frequency of which increased with increasing egg counts. The parasitologic cure rate 12 weeks after treatment was only 18%, the frequency of egg counts with more than 1,000 epg decreased to 5%, and the mean egg count of those remaining positive was reduced by 86%. Antigen detection in serum 10 days and 12 weeks after treatment remained positive in 90% of the subjects, although titers decreased sharply. The low cure rates may be due to intense transmission and/or undeveloped immune responses in this recently exposed population. However, reduced drug susceptibility of the parasite strain has now been confirmed in one local isolate.

Epidemiology of Schistosoma mansoni infection in a recently exposed community in northern Senegal.

The epidemiology of Schistosoma mansoni infection was investigated in Ndombo, a village in the epicenter of a very recent outbreak of schistosomiasis in northern Senegal. Repeated fecal egg counts and antigen detection in urine and serum were carried out in a random population sample (n = 422). Eggs were found in 91% of the subjects, with 41% excreting > 1,000 eggs per gram of feces (epg) (mean egg load of 646 epg). The prevalence was almost 100% in groups greater than five years of age. In spite of the supposed absence of acquired immunity, intensities of infection decreased strongly in adults. Antigen detection confirmed the high prevalence and intensity of infection and the age-related distribution of worm loads. The emergence of this new focus is probably due to the ecologic impact of newly built dams and the extension of irrigation projects in the Senegal basin.

Therapeutic evaluation of two different dose regimens of praziquantel in a recent Schistosoma mansoni focus in Northern Senegal.

A therapeutic trial, involving 130 Schistosoma mansoni-infected children, with no previous history of antischistosomal treatment, was carried out to evaluate the efficacy of two different dose regimens of praziquantel. The study was carried out because low cure rates were described in this recently established (1990) S. mansoni focus in northern Senegal, following treatment with a standard dosage of 40 mg/kg. The subjects were randomly allocated into two groups: one group (1) received 40 mg/kg in one oral dose, the other group (2) was treated with two oral doses of 30 mg/kg at a 6-hr interval. Parasitologic examination and circulating anodic antigen (CAA) detection were performed before, 10 days, three, six, and 21 weeks after chemotherapy. No significant differences in cure rates were found between the two groups. Six weeks after treatment, 34% and 44% of the individuals were found to be stool negative in group 1 and group 2, respectively. However, only 10-15% became completely negative according to the serum CAA antigen assay. Mean egg counts were reduced by 99% in both groups. Antigen detection confirmed the parasitologic results. Fewer side effects were observed in the group treated with 2 x 30 mg/kg, which may be explained by split dosage administration. Our study shows that the low cure rates observed in this area could not be improved by using a higher dosage of praziquantel.

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.