Background & aims Several animal studies have emphasized the role of gut microbiota in non-alcoholic fatty liver disease (NAFLD). However, data about gut dysbiosis in human NAFLD remains scarce in the literature, especially studies including the whole spectrum of NAFLD lesions. We aimed to evaluate the association between gut dysbiosis and severe NAFLD lesions, i.e. non-alcoholic steatohepatitis (NASH) and fibrosis, in a well-characterized population of adult NAFLD. Methods 57 patients with biopsy-proven NAFLD were enrolled. The taxonomic composition of gut microbiota was determined using 16S ribosomal RNA gene sequencing of stool samples. Results 30 patients had F0/1 fibrosis stage at liver biopsy (10 with NASH), and 27 patients had significant F≥2 fibrosis (25 with NASH). Bacteroides abundance was significantly increased in NASH and F≥2 patients, whereas Prevotella abundance was decreased. Ruminococcus abundance was significantly higher in F≥2 patients. By multivariate analysis, Bacteroides abundance was independently associated with NASH and Ruminococcus with F≥2 fibrosis. Stratification according to the abundance of these 2 bacteria generated 3 patient subgroups with increasing severity of NAFLD lesions. Based on imputed metagenomic profiles, KEGG pathways significantly related to NASH and fibrosis F≥2 were mostly related to carbohydrate, lipid, and amino acid metabolism. Conclusion NAFLD severity associates with gut dysbiosis and a shift in metabolic function of the gut microbiota. We identified Bacteroides as independently associated with NASH and Ruminococcus with significant fibrosis. Thus, gut microbiota analysis adds information to classical predictors of NAFLD severity and suggests novel metabolic targets for pre/probiotics therapies.

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BackgroundWell-functioning surveillance systems are crucial for effective disease control programs. The Integrated Disease Surveillance and Response (IDSR) strategy was developed and adopted in 1998 for Africa as a comprehensive public health approach and subsequently, Ghana adopted the IDSR technical guidelines in 2002. Since 2012, the IDSR data is reported through the new District Health Information Management System II (DHIMS2) network. The objective was to evaluate the Integrated Disease Surveillance and Response (IDSR) system in northern Ghana.MethodsThis was an observational study using mixed methods. Weekly and monthly IDSR data on selected infectious diseases were downloaded and analyzed for 2011, 2012 and 2013 (the years before, of and after DHIMS2 implementation) from the DHIMS2 databank for the Upper East Region (UER) and for two districts of UER. In addition, key informant interviews were conducted among local and regional health officers on the functioning of the IDSR.ResultsClinically diagnosed malaria was the most prevalent disease in UER, with an annual incidence rate close to 1. Around 500 suspected HIV/AIDS cases were reported each year. The highest incidence of cholera and meningitis was reported in 2012 (257 and 392 cases respectively). Three suspected cases of polio and one suspected case of guinea worm were reported in 2013. None of the polio and guinea worm cases and only a fraction of the reported cases of the other diseases were confirmed. A major observation was the large and inconclusive difference in reported cases when comparing weekly and monthly reports. This can be explained by the different reporting practice for the sub-systems. Other challenges were low priority for surveillance, ill-equipped laboratories, rare supervision and missing feedback.ConclusionsThe DHIMS2 has improved the availability of IDSR reports, but the quality of data reported is not sufficient. Particularly the inconsistencies between weekly and monthly data need to be addressed. Moreover, support for and communication within the IDSR system is inadequate and calls for attention.

Since 1999 a lineage of the pathogen Cryptococcus gattii has been infecting humans and other animals in Canada and the Pacific Northwest of the USA. It is now the largest outbreak of a life-threatening fungal infection in a healthy population in recorded history. The high virulence of outbreak strains is closely linked to the ability of the pathogen to undergo rapid mitochondrial tubularisation and proliferation following engulfment by host phagocytes. Most outbreaks spread by geographic expansion across suitable niches, but it is known that genetic re-assortment and hybridisation can also lead to rapid range and host expansion. In the context of C. gattii, however, the likelihood of virulence traits associated with the outbreak lineages spreading to other lineages via genetic exchange is currently unknown. Here we address this question by conducting outgroup crosses between distantly related C. gattii lineages (VGII and VGIII) and ingroup crosses between isolates from the same molecular type (VGII). Systematic phenotypic characterisation shows that virulence traits are transmitted to outgroups infrequently, but readily inherited during ingroup crosses. In addition, we observed higher levels of biparental (as opposed to uniparental) mitochondrial inheritance during VGII ingroup sexual mating in this species and provide evidence for mitochondrial recombination following mating. Taken together, our data suggest that hypervirulence can spread among the C. gattii lineages VGII and VGIII, potentially creating novel hypervirulent genotypes, and that current models of uniparental mitochondrial inheritance in the Cryptococcus genus may not be universal.

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Enteroendocrine cells (EECs) are specialized sensory cells in the intestinal epithelium that sense and transduce nutrient information. Consumption of dietary fat contributes to metabolic disorders, but EEC adaptations to high fat feeding were unknown. Here, we established a new experimental system to directly investigate EEC activity in vivo using a zebrafish reporter of EEC calcium signaling. Our results reveal that high fat feeding alters EEC morphology and converts them into a nutrient insensitive state that is coupled to endoplasmic reticulum (ER) stress. We called this novel adaptation 'EEC silencing'. Gnotobiotic studies revealed that germ-free zebrafish are resistant to high fat diet induced EEC silencing. High fat feeding altered gut microbiota composition including enrichment of Acinetobacter bacteria, and we identified an Acinetobacter strain sufficient to induce EEC silencing. These results establish a new mechanism by which dietary fat and gut microbiota modulate EEC nutrient sensing and signaling.

Significant numbers of perch, Perca fluviatilis, raised on a pilot fish farm in Switzerland presented focal skin lesions on the lateral sides and fin rot. Mortality rates reached levels of up to 1% of the total fish on the farm per day. Virtually pure cultures of Aeromonas sobria were isolated from the liver, kidney, spleen and skin lesions of affected fish. Aeromonas sobria isolated from the farmed perch had a haemolytic effect on sheep and trout erythrocytes, autoaggregated, was cytotoxic for cultured fish cells and possessed genes involved in type III protein secretion. Experimental infection of naive perch with a single colony isolate of A. sobria from an affected farm fish resulted in the development of clinical signs identical to those seen on the farm. The results indicate that A. sobria can act as a primary pathogen of perch.

BackgroundThis study aimed to explore factors shaping the decision to undergo Human Immunodeficiency Virus (HIV) testing among men in rural Burkina Faso.MethodsThe study took place in 2009 in the Nouna Health District and adopted a triangulation mixed methods design. The quantitative component relied on data collected through a structured survey on a representative sample of 1130 households. The qualitative component relied on 38 in-depth interviews, with men purposely selected to represent variation in testing decision, age, and place of residence. A two-part model was conducted, with two distinct outcome variables, i.e. “being offered an HIV test” and “having done an HIV test”. The qualitative data analysis relied on inductive coding conducted by three independent analysts.ResultOf the 937 men, 357 had been offered an HIV test and 97 had taken the test. Younger age, household wealth, living in a village under demographic surveillance, and knowing that HIV testing is available at primary health facilities were all positively associated with the probability of being offered an HIV test. Household wealth and literacy were found to be positively associated, and distance was found to be negatively associated with the probability of having taken an HIV test. Qualitative findings indicated that the limited uptake of HIV testing was linked to poor knowledge on service availability and to low risk perceptions.ConclusionWith only 10% of the total sample ever having tested for HIV, our study confirmed that male HIV testing remains unacceptably low in Sub-Saharan Africa. This results from a combination of health system factors, indicating general barriers to access, and motivational factors, such as one’s own knowledge of service availability and risk perceptions. Our findings suggested that using antenatal care and curative services as the exclusive entry points into HIV testing may not be sufficient to reach large portions of the male population. Thus, additional strategies are urgently needed to increase service uptake.