The Impact of Schistosoma japonicum Infection and Treatment on Ultrasound-Detectable Morbidity: A Five-Year Cohort Study in Southwest China

Schistosomiasis is a water-borne parasite that infects approximately 200 million people worldwide. Schistosoma japonicum, found in Asia, causes disease by releasing eggs in the liver, leading to fibrosis, anemia, and, in children, impaired growth. Ultrasound can assess liver pathology from schistosomiasis; however more information is needed to evaluate the relevance of standard ultrasound measures. We followed 578 people for up to five years, testing for schistosomiasis infection and conducting ultrasound examinations to assess the relationship between infection and seven ultrasound measures and to evaluate the impact of treatment with anti-schistosomiasis chemotherapy (praziquantel) on morbidity. All infections were promptly treated. Fibrosis of the liver parenchyma, pathology unique to S. japonicum, was associated with schistosomiasis infection, and was most advanced in people with high worm burdens. Liver fibrosis declined significantly following treatment, but reversal of severe liver fibrosis was rare. Other ultrasound measures were not consistently related to schistosomiasis infection or treatment. These findings suggest parenchymal fibrosis can be used to measure morbidity attributable to S. japonicum and evaluate the impact of disease control efforts. Because reversal of severe fibrosis was limited, disease control efforts will be most effective if they can not only treat existing infections but also prevent new infections

A cross-sectional study of the prevalence of intensity of infection with Schistosoma japonicum in 50 irrigated and rain-fed villages in Samar Province, the Philippines

BACKGROUND: Few studies have described heterogeneity in Schistosoma japonicum infection intensity, and none were done in Philippines. The purpose of this report is to describe the village-to-village variation in the prevalence of two levels of infection intensity across 50 villages of Samar Province, the Philippines. METHODS: This cross-sectional study was conducted in 25 rain-fed and 25 irrigated villages endemic for S. japonicum between August 2003 and November 2004. Villages were selected based on irrigation and farming criteria. A maximum of 35 eligible households were selected per village. Each participant was asked to provide stool samples on three consecutive days. All those who provided at least one stool sample were included in the analysis. A Bayesian three category outcome hierarchical cumulative logit regression model with adjustment for age, sex, occupation and measurement error of the Kato-Katz technique was used for analysis. RESULTS: A total of 1427 households and 6917 individuals agreed to participate in the study. A total of 5624 (81.3%) participants provided at least one stool sample. The prevalences of those lightly and at least moderately infected varied from 0% (95% Bayesian credible interval (BCI): 0%–3.1%) to 45.2% (95% BCI: 36.5%–53.9%) and 0% to 23.0% (95% BCI: 16.4%–31.2%) from village-to-village, respectively. Using the 0–7 year old group as a reference category, the highest odds ratio (OR) among males and females were that of being aged 17–40-year old (OR = 8.76; 95% BCI: 6.03–12.47) and 11–16-year old (OR = 8.59; 95% BCI: 4.74–14.28), respectively. People who did not work on a rice farm had a lower prevalence of infection than those working full time on a rice farm. The OR for irrigated villages compared to rain-fed villages was 1.41 (95% BCI: 0.50–3.21). DISCUSSION: We found very important village-to-village variation in prevalence of infection intensity. This variation is probably due to village-level variables other than that explained by a crude classification of villages into the irrigated and non-irrigated categories. We are planning to capture this spatial heterogeneity by updating our initial transmission dynamics model with the data reported here combined with 1-year post-treatment follow-up of study participants

Adolescent Binge Drinking Leads to Changes in Alcohol Drinking, Anxiety, and Amygdalar Corticotropin Releasing Factor Cells in Adulthood in Male Rats

Heavy episodic drinking early in adolescence is associated with increased risk of addiction and other stress-related disorders later in life. This suggests that adolescent alcohol abuse is an early marker of innate vulnerability and/or binge exposure impacts the developing brain to increase vulnerability to these disorders in adulthood. Animal models are ideal for clarifying the relationship between adolescent and adult alcohol abuse, but we show that methods of involuntary alcohol exposure are not effective. We describe an operant model that uses multiple bouts of intermittent access to sweetened alcohol to elicit voluntary binge alcohol drinking early in adolescence (∼postnatal days 28–42) in genetically heterogeneous male Wistar rats. We next examined the effects of adolescent binge drinking on alcohol drinking and anxiety-like behavior in dependent and non-dependent adult rats, and counted corticotropin-releasing factor (CRF) cell in the lateral portion of the central amygdala (CeA), a region that contributes to regulation of anxiety- and alcohol-related behaviors. Adolescent binge drinking did not alter alcohol drinking under baseline drinking conditions in adulthood. However, alcohol-dependent and non-dependent adult rats with a history of adolescent alcohol binge drinking did exhibit increased alcohol drinking when access to alcohol was intermittent. Adult rats that binged alcohol during adolescence exhibited increased exploration on the open arms of the elevated plus maze (possibly indicating either decreased anxiety or increased impulsivity), an effect that was reversed by a history of alcohol dependence during adulthood. Finally, CRF cell counts were reduced in the lateral CeA of rats with adolescent alcohol binge history, suggesting semi-permanent changes in the limbic stress peptide system with this treatment. These data suggest that voluntary binge drinking during early adolescence produces long-lasting neural and behavioral effects with implications for anxiety and alcohol use disorders

Global Distribution of Outbreaks of Water-Associated Infectious Diseases

Water is essential for maintaining life on Earth but can also serve as a media for many pathogenic organisms, causing a high disease burden globally. However, how the global distribution of water-associated infectious pathogens/diseases looks like and how such distribution is related to possible social and environmental factors remain largely unknown. In this study, we compiled a database on distribution, biology, and epidemiology of water-associated infectious diseases and collected data on population density, annual accumulated temperature, surface water areas, average annual precipitation, and per capita GDP at the global scale. From the database we extracted reported outbreak events from 1991 to 2008 and developed models to explore the association between the distribution of these outbreaks and social and environmental factors. A total of1,428 outbreaks had been reported and this number only reflected ‘the tip of the iceberg’ of the much bigger problem. We found that the outbreaks of water-associated infectious diseases are significantly correlated with social and environmental factors and that all regions are affected disproportionately by different categories of diseases. Relative risk maps are generated to show ‘hotspots’ of risks for different diseases. Despite certain limitations, the findings may be instrumental for future studies and prioritizing health resources

Controlling Viral Immuno-Inflammatory Lesions by Modulating Aryl Hydrocarbon Receptor Signaling

Ocular herpes simplex virus infection can cause a blinding CD4+ T cell orchestrated immuno-inflammatory lesion in the cornea called Stromal Keratitis (SK). A key to controlling the severity of SK lesions is to suppress the activity of T cells that orchestrate lesions and enhance the representation of regulatory cells that inhibit effector cell function. In this report we show that a single administration of TCDD (2, 3, 7, 8- Tetrachlorodibenzo-p-dioxin), a non-physiological ligand for the AhR receptor, was an effective means of reducing the severity of SK lesions. It acted by causing apoptosis of Foxp3- CD4+ T cells but had no effect on Foxp3+ CD4+ Tregs. TCDD also decreased the proliferation of Foxp3- CD4+ T cells. The consequence was an increase in the ratio of Tregs to T effectors which likely accounted for the reduced inflammatory responses. In addition, in vitro studies revealed that TCDD addition to anti-CD3/CD28 stimulated naïve CD4+ T cells caused a significant induction of Tregs, but inhibited the differentiation of Th1 and Th17 cells. Since a single TCDD administration given after the disease process had been initiated generated long lasting anti-inflammatory effects, the approach holds promise as a therapeutic means of controlling virus induced inflammatory lesions

The Role of Natural Killer (NK) Cells and NK Cell Receptor Polymorphisms in the Assessment of HIV-1 Neutralization

The importance of innate immune cells in HIV-1 pathogenesis and protection has been highlighted by the role of natural killer (NK) cells in the containment of viral replication. Use of peripheral blood mononuclear cells (PBMC) in immunologic studies provides both HIV-1 target cells (ie. CD4+ T cells), as well as anti-HIV-1 effector cells, such as NK cells. In this study, NK and other immune cell populations were analyzed in HIV-negative donor PBMC for an impact on the anti-HIV activity of polyclonal and monoclonal antibodies. NK cell percentages were significantly higher in donor PBMC that supported lower levels of viral replication. While the percentage of NK cells was not directly associated with neutralization titers, NK cell-depletion significantly diminished the antiviral antibody activity by up to three logs, and polymorphisms in NK killer immunoglobulin receptor (KIR) and FcγRIIIa alleles appear to be associated with this affect. These findings demonstrate that NK cells and NK cell receptor polymorphisms may influence assessment of traditional HIV-1 neutralization in a platform where antibody is continuously present. This format appears to simultaneously assess conventional entry inhibition (neutralization) and non-neutralizing antibody-dependent HIV inhibition, which may provide the opportunity to delineate the dominant antibody function(s) in polyclonal vaccine responses

Effects of the social environment during adolescence on the development of social behaviour, hormones and morphology in male zebra finches (Taeniopygia guttata)

Abstract Background Individual differences in behaviour are widespread in the animal kingdom and often influenced by the size or composition of the social group during early development. In many vertebrates the effects of social interactions early in life on adult behaviour are mediated by changes in maturation and physiology. Specifically, increases in androgens and glucocorticoids in response to social stimulation seem to play a prominent role in shaping behaviour during development. In addition to the prenatal and early postnatal phase, adolescence has more recently been identified as an important period during which adult behaviour and physiology are shaped by the social environment, which so far has been studied mostly in mammals. We raised zebra finches ( Taeniopygia guttata ) under three environmental conditions differing in social complexity during adolescence\ua0-\ua0juvenile pairs, juvenile groups, and mixed-age groups - and studied males\u2019 behavioural, endocrine, and morphological maturation, and later their adult behaviour. Results As expected, group-housed males exhibited higher frequencies of social interactions. Group housing also enhanced song during adolescence, plumage development, and the frequency and intensity of adult courtship and aggression. Some traits, however, were affected more in juvenile groups and others in mixed-age groups. Furthermore, a testosterone peak during late adolescence was suppressed in groups with adults. In contrast, corticosterone concentrations did not differ between rearing environments. Unexpectedly, adult courtship in a test situation was lowest in pair-reared males and aggression depended upon the treatment of the opponent with highest rates shown by group-reared males towards pair-reared males. This contrasts with previous findings, possibly due to differences in photoperiod and the acoustic environment. Conclusion Our results support the idea that effects of the adolescent social environment on adult behaviour in vertebrates are mediated by changes in social interactions affecting behavioural and morphological maturation. We found no evidence that long-lasting differences in behaviour reflect testosterone or corticosterone levels during adolescence, although differences between juvenile and mixed-age groups suggest that testosterone and song behaviour during late adolescence may be associated

The epidemiology of bacterial vaginosis in relation to sexual behaviour

<p>Abstract</p> <p>Background</p> <p>Bacterial vaginosis (BV) has been most consistently linked to sexual behaviour, and the epidemiological profile of BV mirrors that of established sexually transmitted infections (STIs). It remains a matter of debate however whether BV pathogenesis does actually involve sexual transmission of pathogenic micro-organisms from men to women. We therefore made a critical appraisal of the literature on BV in relation to sexual behaviour.</p> <p>Discussion</p> <p><it>G. vaginalis </it>carriage and BV occurs rarely with children, but has been observed among adolescent, even sexually non-experienced girls, contradicting that sexual transmission is a necessary prerequisite to disease acquisition. <it>G. vaginalis </it>carriage is enhanced by penetrative sexual contact but also by non-penetrative digito-genital contact and oral sex, again indicating that sex <it>per se</it>, but not necessarily coital transmission is involved. Several observations also point at female-to-male rather than at male-to-female transmission of <it>G. vaginalis</it>, presumably explaining the high concordance rates of <it>G. vaginalis </it>carriage among couples. Male antibiotic treatment has not been found to protect against BV, condom use is slightly protective, whereas male circumcision might protect against BV. BV is also common among women-who-have-sex-with-women and this relates at least in part to non-coital sexual behaviours. Though male-to-female transmission cannot be ruled out, overall there is little evidence that BV acts as an STD. Rather, we suggest BV may be considered a sexually enhanced disease (SED), with frequency of intercourse being a critical factor. This may relate to two distinct pathogenetic mechanisms: (1) in case of unprotected intercourse alkalinisation of the vaginal niche enhances a shift from lactobacilli-dominated microflora to a BV-like type of microflora and (2) in case of unprotected and protected intercourse mechanical transfer of perineal enteric bacteria is enhanced by coitus. A similar mechanism of mechanical transfer may explain the consistent link between non-coital sexual acts and BV. Similar observations supporting the SED pathogenetic model have been made for vaginal candidiasis and for urinary tract infection.</p> <p>Summary</p> <p>Though male-to-female transmission cannot be ruled out, overall there is incomplete evidence that BV acts as an STI. We believe however that BV may be considered a <it>sexually enhanced disease</it>, with frequency of intercourse being a critical factor.</p

ICAR: endoscopic skull‐base surgery

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