The collective burden of childhood dementia: a scoping review.

Childhood dementia is a devastating and under-recognized group of disorders with a high level of unmet need. Typically monogenic in origin, this collective of individual neurodegenerative conditions are defined by a progressive impairment of neurocognitive function, presenting in childhood and adolescence. This scoping review aims to clarify definitions and conceptual boundaries of childhood dementia and quantify the collective disease burden. A literature review identified conditions that met the case definition. An expert clinical working group reviewed and ratified inclusion. Epidemiological data were extracted from published literature and collective burden modelled. One hundred and seventy genetic childhood dementia disorders were identified. Of these, 25 were analysed separately as treatable conditions. Collectively, currently untreatable childhood dementia was estimated to have an incidence of 34.5 per 100 000 (1 in 2900 births), median life expectancy of 9 years and prevalence of 5.3 per 100 000 persons. The estimated number of premature deaths per year is similar to childhood cancer (0-14 years) and approximately 70% of those deaths will be prior to adulthood. An additional 49.8 per 100 000 births are attributable to treatable conditions that would cause childhood dementia if not diagnosed early and stringently treated. A relational database of the childhood dementia disorders has been created and will be continually updated as new disorders are identified (https://knowledgebase.childhooddementia.org/). We present the first comprehensive overview of monogenic childhood dementia conditions and their collective epidemiology. Unifying these conditions, with consistent language and definitions, reinforces motivation to advance therapeutic development and health service supports for this significantly disadvantaged group of children and their families.

Identification of miR-93 as a suitable miR for normalizing miRNA in plasma of tuberculosis patients.

Tuberculosis (TB) remains a major public health issue. New tests to aid diagnoses and monitor the response to therapy are urgently required. There is growing interest in the use of microRNA (miRNA) profiles as diagnostic, prognostic or predictive markers in a range of clinical and infectious diseases, including Mycobacterium tuberculosis infection, however, challenges exist to accurately normalise miRNA levels in cohorts. This study examined the appropriateness of 12 miRs and RNU6B to normalise circulating plasma miRNA levels in individuals with active TB from 2 different geographical and ethnic regions. Twelve miRs (let-7, miR-16, miR-22, miR-26, miR-93, miR-103, miR-191, miR-192, miR-221, miR-423, miR-425 and miR-451) and RNU6B were selected based on their reported production by lung cells, expression in blood and previous use as a reference miRNA. Expression levels were analysed in the plasma of newly diagnosed TB patients from Australia and China compared with individuals with latent TB infection and healthy volunteers. Analysis with both geNorm and NormFinder software identified miR-93 as the most suitable reference miR in both cohorts, either when analysed separately or collectively. Interestingly, there were large variations in the expression levels of some miRs, in particular miR-192 and let-7, between the two cohorts, independent of disease status. These data identify miR-93 is a suitable reference miR for normalizing miRNA levels in TB patients, and highlight how environmental, and possibly ethnic, factors influence miRNA expression levels, demonstrating the necessity of assessing the suitability of reference miRs within the study population.

Transcriptional profiling of chronic clinical hepatic schistosomiasis japonica indicates reduced metabolism and immune responses.

Schistosomiasis is a significant cause of human morbidity and mortality. We performed a genome-wide transcriptional survey of liver biopsies obtained from Chinese patients with chronic schistosomiasis only, or chronic schistosomiasis with a current or past history of viral hepatitis B. Both disease groups were compared with patients with no prior history or indicators of any liver disease. Analysis showed in the main, downregulation in gene expression, particularly those involved in signal transduction via EIF2 signalling and mTOR signalling, as were genes associated with cellular remodelling. Focusing on immune associated pathways, genes were generally downregulated. However, a set of three genes associated with granulocytes, MMP7, CLDN7, CXCL6 were upregulated. Differential gene profiles unique to schistosomiasis included the gene Granulin which was decreased despite being generally considered a marker for liver disease, and IGBP2 which is associated with increased liver size, and was the most upregulated gene in schistosomiasis only patients, all of which presented with hepatomegaly. The unique features of gene expression, in conjunction with previous reports in the murine model of the cellular composition of granulomas, granuloma formation and recovery, provide an increased understanding of the molecular immunopathology and general physiological processes underlying hepatic schistosomiasis.

Evaluation of the tuberculosis programme in Ningxia Hui Autonomous region, the People's Republic of China: a retrospective case study.

BACKGROUND: Tuberculosis is a devastating disease due to its rapid transmission and high rate of mortality. Ningxia Hui Autonomous Region (NHAR), located in the North-west, is one of the poorest provinces in China and national surveys have shown TB has been hyper endemic in NHAR for several decades. As no active surveys had been undertaken since the initiation of the DOTS control program across all of NHAR. METHODS: A retrospective study was undertaken of all clinical records of TB patients registered from January 2005 to September 2009. Poisson regression was performed to investigate the change in incidence over time and accounted for age, sex and county. Length of time on treatment, disease severity and patient delay were assessed by county. RESULTS: More than 30% of patients had been on treatment for over 12 months and 10% for over 3 years, reflecting drug-resistance or failure of DOTS. More than 93% of patients had grade III disease at time of diagnosis and >15% of patients had severe disease grade IV-V in some NHAR counties. Further, 8.8% of patients were not diagnosed for over 6 months from the onset of symptoms; this was as high as 20% in some counties. The reported incidence of TB is most likely grossly underestimated and the data indicate TB is a major public health concern in NHAR. CONCLUSIONS: It is clear that active surveillance is necessary to determine the full extent of the burden of TB in NHAR. New control and treatment strategies for TB are required that increase awareness in the health-care system and at the individual and community level.

High sensitivity and specificity of a 5-analyte protein and microRNA biosignature for identification of active tuberculosis.

OBJECTIVES: Non-sputum-based tests to accurately identify active tuberculosis (TB) disease and monitor response to therapy are urgently needed. This study examined the biomarker capacity of a panel of plasma proteins alone, and in conjunction with a previously identified miRNA signature, to identify active TB disease. METHODS: The expression of nine proteins (IP-10, MCP-1, sTNFR1, RANTES, VEGF, IL-6, IL-10, TNF and Eotaxin) was measured in the plasma of 100 control subjects and 100 TB patients, at diagnosis (treatment naïve) and over the course of treatment (1-, 2- and 6-month intervals). The diagnostic performance of the nine proteins alone, and with the miRNA, was assessed. RESULTS: Six proteins were significantly up-regulated in the plasma of TB patients at diagnosis compared to controls. Receiver operator characteristic curve analysis demonstrated that IP-10 with an AUC = 0.874, sensitivity of 75% and specificity of 87% was the best single biomarker candidate to distinguish TB patients from controls. IP-10 and IL-6 levels fell significantly within one month of commencing treatment and may have potential as indicators of a positive response to therapy. The combined protein and miRNA panel gave an AUC of 1.00. A smaller panel of only five analytes (IP-10, miR-29a, miR-146a, miR-99b and miR-221) showed an AUC = 0.995, sensitivity of 96% and specificity of 97%. CONCLUSIONS: A novel combination of miRNA and proteins significantly improves the sensitivity and specificity as a biosignature over single biomarker candidates and may be useful for the development of a non-sputum test to aid the diagnosis of active TB disease.

sTNFR-II and sICAM-1 are associated with acute disease and hepatic inflammation in schistosomiasis japonica.

Soluble intracellular adhesive molecule 1 (sICAM-1) and tumour necrosis factor receptors I (TNFR-1) and II (TNFR-II) have been shown to be associated with numerous liver disorders. Shedding of these membrane proteins can be triggered by the Th1 cytokines, TNF-alpha and IFN-gamma, which are associated with susceptibility or resistance to hepatic schistosomiasis, respectively. Further, TNF-alpha receptors and sICAM-1 have been implicated in periportal fibrosis in advanced human schistosomiasis mansoni and correlate with schistosome granuloma formation in the murine model. We measured serum levels of sICAM-1, TNFR-I and TNFR-II in Chinese patients with different clinically defined stages of schistosomiasis japonica and controls; these included 35 patients with acute schistosomiasis, 45 patients with chronic schistosome infections, 34 advanced patients with evidence of severe morbidity and 20 patients with no known history of exposure to infection. Markedly elevated levels of soluble TNFRs (sTNFRs) and sICAM-1 were observed in the acute and advanced patients compared with the chronic and control groups. Mean sTNFR-II levels were significantly higher in acute patients compared with advanced (P<0.00001) and chronic patients (P<0.00001) and showed the strongest association of the markers with acute disease (odds ratio (OR)=1.099). sTNFR-II and sICAM-1 levels both correlated with infection intensity and there were significant positive correlations observed between eosinophil count and infection intensity (P=0.0072) and sICAM-1 (P=0.0014). Although there were significantly higher levels of antigen-specific IgG4 and total IgG in infected individuals compared with controls, none correlated with infection intensity. Further, no differences in IgG4 and total IgG levels were observed between the acute and chronic groups. The results suggest sTNFRs and sICAM-1 are associated with liver inflammation and disease progression. Measurement of sTNFR-II and sICAM-1 levels in serum could serve as additional markers for the diagnosis of acute stage disease and the monitoring of hepatic inflammation in human schistosomiasis japonica.

A randomized, double-blind, placebo-controlled trial of safety and efficacy of combined praziquantel and artemether treatment for acute schistosomiasis japonica in China.

OBJECTIVE: To evaluate the safety and efficacy of combining artemether (AM) and praziquantel (PZQ) in different regimens for treating acute schistosomiasis japonica. METHODS: We undertook a randomized, double-blind, placebo-controlled trial within four specialized schistosomiasis hospitals in the Dongting Lake region, Hunan province, China, between May 2003 and December 2005. Study participants were randomized into one of four treatment regimes: group A received 60 mg/kg PZQ + 6 mg/kg AM; group B received 60 mg/kg PZQ + AM placebo; group C received 120 mg/kg PZQ + 6 mg/kg AM; and group D received 120 mg/kg PZQ + AM placebo. All participants were followed up over a 45-day period. The primary endpoint of the trial was human infection status (determined by positive stool examination). Secondary endpoints involved clinical observations and blood biochemistry, including monitoring haemoglobin and alanine aminotransferase levels over time. FINDINGS: Treatment efficacies of the four different treatment regimens were 98.0%, 96.4%, 97.7% and 95.7% for group A, B, C, and D respectively (P > 0.05). The group B had a greater treatment efficacy (96.4%) than the group D (95.7%) (P > 0.05). Group A treatment was better for clearance of fever (P < 0.05) and resulted in a shorter hospitalization time (P < 0.05). CONCLUSION: This is the first report of a randomized, double-blind, placebo-controlled trial for evaluating combined chemotherapy with AM and two different dosages (60 mg/kg and 120 mg/kg) of PZQ in the treatment of acute schistosomiasis japonica in China. The combination of AM and PZQ chemotherapy did not improve treatment efficacy compared with PZQ alone. PZQ given as a dosage of 60 mg/kg (1 day, 3 x 20 mg/kg doses at 4-5 hour intervals) may be as effective as a dosage of 120 mg/kg (6 days, 20 mg/kg for each day split into 3 doses at 4-5 hour intervals).

Identification of a plasma microRNA profile in untreated pulmonary tuberculosis patients that is modulated by anti-mycobacterial therapy.

OBJECTIVE: microRNA expression profiles are of interest as a biomarker of tuberculosis (TB). How anti-TB therapy effects miRNA profiles is unknown and was examined. METHODS: We identified 87 plasma miRNAs that were significantly modified in an exploratory group of 19 Chinese pulmonary TB (PTB) patients compared to 14 healthy controls. We selected 10 of these miRNAs for analysis in a cohort of 100 PTB patients prior to, and at one, two and six months during treatment. RESULTS: Five miRNAs were differentially expressed in PTB patients compared to controls at diagnosis; miRs -29a and -99b were up-regulated, whilst miRs -21, -146a and -652 were down-regulated. A combination of 5 miRNA distinguished TB from healthy controls with a sensitivity of 94%, a specificity of 88%, and an AUC of 0.976. Within one month of treatment, significant changes in miRs -29a, -99b, -26a and 146a levels occurred in successfully treated patients, although not all miRNAs returned to baseline by treatment completion. CONCLUSION: A 5-miRNA signature shows potential for development as a novel biomarker for TB disease with potential to predict response to treatment. The failure of all miRNA to return to baseline levels may reflect ongoing remodelling in the lung parenchyma that continues after completion of anti-TB therapy.

A proline deletion in IFNAR1 impairs IFN-signaling and underlies increased resistance to tuberculosis in humans.

Type I interferons (IFN), best known for their anti-viral functions, have been shown to impair host resistance to intracellular bacteria in mice. However, the precise role of type I IFN signaling in bacterial infection in humans is unclear. Here, we show that genetic variation in the human IFNAR1 gene is associated with decreased susceptibility to tuberculosis and an increased risk of viral hepatitis in Chinese populations. Receptor mutagenesis and cell signaling studies establish that the IFNAR1 mutation corresponding to a proline deletion in the hinge region of the membrane-proximal domain of IFNAR1 decreases the binding affinity of IFNAR1 to IFN-ß, impeding type I IFN signaling. Our findings suggest that IFNAR1 signaling underlies an increased risk of tuberculosis in humans and reveals a function for the IFNAR1 inter-domain region in cytokine-cytokine receptor interaction and signal transduction.

Familial aggregation of human susceptibility to co- and multiple helminth infections in a population from the Poyang Lake region, China.

Human helminthiases are common in China, especially in rural areas where sanitation conditions are poor. Co- and multiple infections with helminths are strikingly frequent. A cross-sectional parasitological and questionnaire survey was carried out in a population of 3205 individuals belonging to 498 families from five villages in the Poyang Lake region, Jiangxi Province, China, to assess their helminth infection status and to collect information on risk factors for infection. The prevalences for Ascaris lumbricoides, Schistosoma japonicum and Trichuris trichiura were 30.9%, 15.7% and 47%, respectively. Hookworm infection prevalence was low (0.7%). A significant association was observed between A. lumbricoides and T. trichiura infection, and also between S. japonicum and T. trichiura infection. Variance components analysis was undertaken to investigate the aggregation of S. japonicum and the soil-transmitted helminths, A. lumbricoides and T. trichiura. While A. lumbricoides was found to aggregate only at a household level, T. trichiura was shown to cluster predominantly in families. Both genetic and household effects were found to be important in determining the risk of infection with S. japonicum. Variance components analysis for A. lumbricoides/T. trichiura co-infections indicated a significant domestic environmental effect, attributable for 32.7% of the co-infection risk. Aggregation of S. japonicum/T. trichiura co-infection was also observed at a household level. The risk of infection with multiple helminth species, although mainly environmentally influenced, was also shown to have significant involvement of genetic and household components. The results of this study indicate that a shared household is a major contributing risk factor for helminth co-infections and emphasises the need for increased standards of sanitation and hygiene to prevent parasite transmission. Further, the results suggest that susceptibility to one helminth infection is not completely independent of another, and that there exist common genetic factors underlying infection with multiple helminth species.

Familial aggregation of human infection with Schistosoma japonicum in the Poyang Lake region, China.

Despite the success of extensive control measures that have been implemented in China for over 50 years, the number of individuals infected with Schistosoma japonicum remains high in the existing endemic areas. A variance components analysis was undertaken to estimate the heritable and environmental components that contribute to S. japonicum infection in the Poyang Lake region of Jiangxi Province, PR China. The total target population was 3148 from four separate administrative villages. Two thousand seven hundred and five of these comprised 400 families ranging in size from 3 to 188. After adjustments were made for gender, water contact and past history of having had schistosomiasis, the heritable component was estimated to account for as much as 58% of the phenotype variation under the polygenic model. Household was not shown to be an important environmental factor. Incorporating village effects indicated that the results were valid for the total population. We conclude that genetic heritability in this region is high and plays an important role in determining risk of infection with S. japonicum.

CD4+ T-cell counts, CD4+/CD8+ T-cell count ratios, and antibody levels in migrant fishermen infected with Schistosoma japonicum in the Dongting Lake, China.

In this study, CD4(+) and CD8(+) T cells and antibody levels were measured in 94 migrant fishermen infected with Schistosoma japonicum from Dongting Lake, China. Prevalence among these fishermen was high (63.8%), with a mean infection intensity of 61.4 +/- 3.8 epg, and included a high proportion of individuals (39.4%) with substantial parenchymal fibrosis (stages > or = 2/3). The CD4(+)/CD8(+) ratio in men (1.34 +/- 0.11) was significantly lower than that of women (1.58 +/- 0.15). CD4(+) T cells and the ratio of CD4(+)/CD8(+) were significantly decreased both in subjects infected with S. japonicum and those with parenchymal fibrosis. However, levels of total IgA, IgM, and anti-schistosome egg antigen IgG correlated positively with infection intensity and pathologic lesion number. These results suggest an imbalance between cell-mediated and humoral immunity in these fishermen, the precise cause of which remains undetermined.

Unique family clustering of human echinococcosis cases in a chinese community.

We have identified a significant focus and unusual clustering of human cases of cystic echinococcosis (CE) and alveolar echinococcosis (AE) in the village of Nanwan, Xiji County, Ningxia Hui Autonomous Region, in one of the most highly endemic areas for both diseases in China. The village, a Chinese Hui Islamic community, is composed of 167 members of four extended families. A total of 28 people died (12 of echinococcosis) since the village was first settled in the 1950s. Despite similar life patterns, the number of AE and CE cases occurring in each family was different. Overall, the prevalences of AE and CE were 9% (20 cases) and 5.9% (13 cases), with a combined prevalence of 14.9%. In contrast to CE, a comparison of the prevalence of AE indicated significant differences between the four family clusters. Although suggestive that host genotype might play a role in susceptibility to AE, this hypothesis requires further investigation.

Applications and outcomes of periodic epidemiological surveys for schistosomiasis and related economic evaluation in the People's Republic of China.

The great success in schistosomiasis control in China is attributable to a range of factors. Periodic epidemiological surveys (PES) used for monitoring and adapting control interventions over time are an integral feature of the national schistosomiasis control programme. PES have enabled the dynamic trends of schistosomiasis epidemics to be closely pursued and have assisted in analysing subtle changes in endemicity. The results can be summarised mathematically allowing the variation in efficacy of control measures to be readily determined and enabling control strategies to be adjusted and updated. PES have been used in both cross-sectional and longitudinal pilot studies selected by appropriate sampling methods. In the early 1990s, when the World Bank Loan Project for schistosomiasis control commenced, economic evaluations were initiated in parallel. Cost-effectiveness analysis became a necessary tool to identify the most financially feasible yet effective options among a range of alternative control strategies. There was, however, a lack of standardised approaches rendering study comparisons across sites difficult. The global burden of disease study established the disability adjusted life year (DALY) as a measure of population health, combining in a single indicator years lost from premature death and years of life lived with disability. However, a recent meta-analysis reveals that the burden of schistosomiasis is underestimated, and hence, needs to be revised. It is envisaged that after the revision of DALYs lost due to schistosomiasis japonica, they will become an essential measure in future schistosomiasis control assessments in China and in other schistosome-endemic areas of the world.

A double-blind field trial on the effects of artemether on Schistosoma japonicum infection in a highly endemic focus in southern China.

To further strengthen the evidence-base of artemether for the control of schistosomiasis japonica, a randomised controlled trial was carried out in the Poyang Lake region, a highly endemic area in southern China. A total of 783 individuals, aged 6-60 years, were enrolled. They were first given a single oral dose of praziquantel (50 mg/kg). Then, they were randomly assigned oral artemether (6 mg/kg) or placebo, administered once every 2 weeks for 9-11 doses, covering the entire transmission season for Schistosoma japonicum in 2004. Stool examination 1 month after the final dosing revealed eggs of S. japonicum in 3/373 (0.8%) of the artemether recipients and 56/361 (15.0%) in placebo recipients (chi2=53.69, P<0.001). Compared to the baseline, the geometric mean intensity of S. japonicum infection had decreased by 96.1% in the artemether group, and increased by 50.8% in the placebo group. No acute cases of schistosomiasis japonica were observed in the artemether group, whereas three such cases were reported from the placebo group. Compliance with regard to multi-doses of artemether and placebo was 84.9, and 77.9%, respectively. This study confirms that repeated oral artemether produces no drug-related adverse effects, significantly reduces incidence and intensity of patent S. japonicum infection and results in high compliance. Hence it can be used as an additional tool for the control of schistosomiasis japonica in the lake regions of China.

Rare variants in MYD88, IRAK4 and IKBKG and susceptibility to invasive pneumococcal disease: a population-based case-control study.

Although rare variants within the Toll-like receptor signalling pathway genes have been found to underlie human primary immunodeficiencies associated with selective predisposition to invasive pneumococcal disease (IPD), the contribution of variants in these genes to IPD susceptibility at the population level remains unknown. Complete re-sequencing of IRAK4, MYD88 and IKBKG genes was undertaken in 164 IPD cases from the UK and 164 geographically-matched population-based controls. 233 single-nucleotide variants (SNVs) were identified, of which ten were in coding regions. Four rare coding variants were predicted to be deleterious, two variants in MYD88 and two in IRAK4. The predicted deleterious variants in MYD88 were observed as two heterozygote cases but not seen in controls. Frequencies of predicted deleterious IRAK4 SNVs were the same in cases and controls. Our findings suggest that rare, functional variants in MYD88, IRAK4 or IKBKG do not significantly contribute to IPD susceptibility in adults at the population level.

Polymorphisms of SP110 are associated with both pulmonary and extra-pulmonary tuberculosis among the Vietnamese.

BACKGROUND: Tuberculosis (TB) is an infectious disease that remains a major cause of morbidity and mortality worldwide, yet the reasons why only 10% of people infected with Mycobacterium tuberculosis go on to develop clinical disease are poorly understood. Genetically determined variation in the host immune response is one factor influencing the response to M. tuberculosis. SP110 is an interferon-responsive nuclear body protein with critical roles in cell cycling, apoptosis and immunity to infection. However association studies of the gene with clinical TB in different populations have produced conflicting results. METHODS: To examine the importance of the SP110 gene in immunity to TB in the Vietnamese we conducted a case-control genetic association study of 24 SP110 variants, in 663 patients with microbiologically proven TB and 566 unaffected control subjects from three tertiary hospitals in northern Vietnam. RESULTS: Five SNPs within SP110 were associated with all forms of TB, including four SNPs at the C terminus (rs10208770, rs10498244, rs16826860, rs11678451) under a dominant model and one SNP under a recessive model, rs7601176. Two of these SNPs were associated with pulmonary TB (rs10208770 and rs16826860) and one with extra-pulmonary TB (rs10498244). CONCLUSION: SP110 variants were associated with increased susceptibility to both pulmonary and extra-pulmonary TB in the Vietnamese. Genetic variants in SP110 may influence macrophage signaling responses and apoptosis during M. tuberculosis infection, however further research is required to establish the mechanism by which SP110 influences immunity to tuberculosis infection.

Immunogenetics of human echinococcosis.

Susceptibility and resistance to human Echinococcus infection and disease, although poorly understood, appear to reflect a complex interaction of parasite and host immunological and genetic factors. Disease stage, progression, and prognosis following treatment appear to be strongly influenced by cytokine and antibody profiles, and more recent evidence has suggested an important role of dendritic cells (DCs) and T regulatory cells (Tregs) in immunomodulation. Microarrays have supported these findings, highlighting both known and novel pathways involved in chronic murine disease. Genetic studies to date have been few and with limited success. Advanced genomic approaches, such as genome-wide association studies (GWAS), may provide further insight to identify the relevant pathways involved, thereby facilitating a new approach for the development of new clinical therapies.

Diagnostic value of non-invasive bio-markers for stage-specific diagnosis of hepatic fibrosis in patients with advanced schistosomiasis japonica.

Hepatic fibrosis caused by schistosome infection can be fatal. Its management depends on the degree of fibrosis present. To assess the diagnostic value of bio-markers in patients with advanced schistosomiasis japonica at different stages of disease progression, 84 advanced schistosomiasis japonica patients and nine controls were recruited in The People's Republic of China. Fibrosis was histologically assessed in wedge liver biopsies using the Chinese criteria for fibrosis (F) Stages. Seven selected hepatic fibrosis bio-markers were assessed and compared between the groups. The method of area under receiver operating characteristic curves (AUROCs) was used as a measurement of diagnostic efficacy. Our results showed that routine laboratory test results were normal for the controls but were significantly elevated or decreased in patients with fibrosis. While serum hyaluronic acid (HA) and matrix metalloproteinase (TIMP)-1 levels were shown to be elevated in patient groups compared with controls, the levels of platelet derived growth factor (PDGF)-BB were markedly lower. To distinguish F≥2 from no fibrosis or mild fibrosis, HA gave a high AUROC of 0.938 (95% confidence interval (CI), 0.886-0.990). Combining the aspartate aminotransferase (AST) to platelet ratio index (APRI) and HA/100 showed an AUROC of 0.958 (95% CI, 0.914-1.000). APRI in combination with TIMP-1/100 provided an AUROC of 0.873 (95% CI, 0.805-0.942) for the diagnosis of fibrosis stages greater than 2. We conclude that AST and APRI levels were reliable and sensitive markers for differentiating significant hepatic fibrosis in patients with advanced schistosomiasis japonica. HA and TIMP-1 show potential as additional markers for the diagnosis of fibrosis and cirrhosis in advanced schistosomiasis patients.

Human cases of simultaneous echinococcosis and tuberculosis - significance and extent in China.

During analysis of retrospective community survey data, we identified two patients from Xiji County, south Ningxia Hui Autonomous Region with simultaneous echinococcosis and tuberculosis (TB), representing the first such reports for China. As the echinococcosis chronicity increased, the immune profile in both subjects changed from a Th1 to Th2 response, as shown by a TB skin test, originally positive, becoming negative. Such an elevated Th2 immune profile, with subsequent suppression of the Th1 immune response, is a common feature of chronic helminth infections. Given the difficulties in definitive diagnosis, and the potential increased susceptibility for TB infection in patients with advanced echinococcosis, we suggest that combined TB/echinococcosis surveys be undertaken in this area in the future. This would allow early diagnosis of both TB and echinococcosis cases with better prognosis for effective and sustainable treatment outcomes, ultimately reducing associated morbidity and mortality, and also the overall financial costs to the individual and the public health care system in this under developed part of China.