Current challenges and possible solutions to improve access to care and treatment for hepatitis C infection in Vietnam: a systematic review.

BACKGROUND: Hepatitis C infection is a major public health concern in low- and middle-income countries where an estimated 71.1 million individuals are living with chronic infection. The World Health Organization (WHO) has recently released new guidance for hepatitis C virus (HCV) treatment programs, which include improving the access to new direct-acting antiviral agents. In Vietnam, a highly populated middle-income country, the seroprevalence of HCV infection is approximately 4% and multiple genotypes co-circulate in the general population. Here we review what is currently known regarding the epidemiology of HCV in Vietnam and outline options for reducing the significant burden of morbidity and mortality in our setting. METHODS: We performed a systematic review of the currently available literature to evaluate what has been achieved to date with efforts to control HCV infection in Vietnam. RESULTS: This search retrieved few publications specific to Vietnam indicating a significant gap in baseline epidemiological and public health data. Key knowledge gaps identified included an understanding of the prevalence in specific high-risk groups, characterization of circulating HCV genotypes in the population and likely response to treatment, and the extent to which HCV treatment is available, accessed and utilized. CONCLUSIONS: We conclude that there is an urgent need to perform up to date assessments of HCV disease burden in Vietnam, especially in high-risk groups, in whom incidence is high and cross infection with multiple genotypes is likely to be frequent. Coordinating renewed surveillance measures with forthcoming HCV treatment studies should initiate the traction required to achieve the WHO goal of eliminating HCV as a public health threat by 2030, at least in this region.

A Clinical and Epidemiological Investigation of the First Reported Human Infection With the Zoonotic Parasite Trypanosoma evansi in Southeast Asia.

BACKGROUND: Trypanosomais a genus of unicellular parasitic flagellate protozoa.Trypanosoma bruceispecies and Trypanosoma cruziare the major agents of human trypanosomiasis; other Trypanosomaspecies can cause human disease, but are rare. In March 2015, a 38-year-old woman presented to a healthcare facility in southern Vietnam with fever, headache, and arthralgia. Microscopic examination of blood revealed infection with Trypanosoma METHODS: Microscopic observation, polymerase chain reaction (PCR) amplification of blood samples, and serological testing were performed to identify the infecting species. The patient's blood was screened for the trypanocidal protein apolipoprotein L1 (APOL1), and a field investigation was performed to identify the zoonotic source. RESULTS: PCR amplification and serological testing identified the infecting species as Trypanosoma evansi.Despite relapsing 6 weeks after completing amphotericin B therapy, the patient made a complete recovery after 5 weeks of suramin. The patient was found to have 2 wild-type APOL1 alleles and a normal serum APOL1 concentration. After responsive animal sampling in the presumed location of exposure, cattle and/or buffalo were determined to be the most likely source of the infection, with 14 of 30 (47%) animal blood samples testing PCR positive forT. evansi. CONCLUSIONS: We report the first laboratory-confirmed case ofT. evansiin a previously healthy individual without APOL1 deficiency, potentially contracted via a wound while butchering raw beef, and successfully treated with suramin. A linked epidemiological investigation revealed widespread and previously unidentified burden ofT. evansiin local cattle, highlighting the need for surveillance of this infection in animals and the possibility of further human cases.

The Vietnam Initiative on Zoonotic Infections (VIZIONS): A Strategic Approach to Studying Emerging Zoonotic Infectious Diseases.

The effect of newly emerging or re-emerging infectious diseases of zoonotic origin in human populations can be potentially catastrophic, and large-scale investigations of such diseases are highly challenging. The monitoring of emergence events is subject to ascertainment bias, whether at the level of species discovery, emerging disease events, or disease outbreaks in human populations. Disease surveillance is generally performed post hoc, driven by a response to recent events and by the availability of detection and identification technologies. Additionally, the inventory of pathogens that exist in mammalian and other reservoirs is incomplete, and identifying those with the potential to cause disease in humans is rarely possible in advance. A major step in understanding the burden and diversity of zoonotic infections, the local behavioral and demographic risks of infection, and the risk of emergence of these pathogens in human populations is to establish surveillance networks in populations that maintain regular contact with diverse animal populations, and to simultaneously characterize pathogen diversity in human and animal populations. Vietnam has been an epicenter of disease emergence over the last decade, and practices at the human/animal interface may facilitate the likelihood of spillover of zoonotic pathogens into humans. To tackle the scientific issues surrounding the origins and emergence of zoonotic infections in Vietnam, we have established The Vietnam Initiative on Zoonotic Infections (VIZIONS). This countrywide project, in which several international institutions collaborate with Vietnamese organizations, is combining clinical data, epidemiology, high-throughput sequencing, and social sciences to address relevant one-health questions. Here, we describe the primary aims of the project, the infrastructure established to address our scientific questions, and the current status of the project. Our principal objective is to develop an integrated approach to the surveillance of pathogens circulating in both human and animal populations and assess how frequently they are exchanged. This infrastructure will facilitate systematic investigations of pathogen ecology and evolution, enhance understanding of viral cross-species transmission events, and identify relevant risk factors and drivers of zoonotic disease emergence.

The seed of the Amazonian fruit Couepia bracteosa exhibits higher scavenging capacity against ROS and RNS than its shell and pulp extracts.

Among the large number of scientifically unstudied fruits from the Amazonia biome, Couepia bracteosa acts as an interesting source of bioactive compounds, such as phenolic compounds and carotenoids, which may be used for protecting human health against oxidative damage. For the first time, the phenolic compounds and carotenoids in extracts obtained from the pulp, shell and seeds of C. bracteosa fruits are reported, as well as their in vitro scavenging capacities against some reactive oxygen species (ROS) and reactive nitrogen species (RNS). The shell extract presented the highest phenolic compound and carotenoid contents (5540 and 328 µg per g extract, dry basis, respectively), followed by the pulp and seed extracts. The major phenolic compound was acacetin sulphate (one methoxy and two OH groups) (62%) in the shells; however, only seeds presented apigenin sulphate (three OH groups), in which it was the major compound (44%). The high content of apigenin sulphate may explain why the seed extract had the highest scavenging efficiency against all tested ROS/RNS among the studied extracts. Regarding carotenoids, all-trans-neochrome (17%) and all-trans-ß-carotene (16%) were the major carotenoids in the pulp extracts, while all-trans-lutein (44%) was the most prevalent in the shell extracts and all-trans-α-carotene (32%) and all-trans-ß-carotene (29%) were the major ones in the seed extracts.

Stem bark and flower extracts of Vismia cauliflora are highly effective antioxidants to human blood cells by preventing oxidative burst in neutrophils and oxidative damage in erythrocytes.

CONTEXT: Vismia cauliflora A.C.Sm. [Hypericaceae (Clusiaceae)] is an Amazonian plant traditionally used by indigenous population to treat dermatosis and inflammatory processes of the skin. Previous research on V. cauliflora extracts suggests its potential to neutralize cellular oxidative damages related to the production of reactive oxygen and nitrogen species. OBJECTIVE: To determine the activity of stem bark and flower extracts of V. cauliflora on the modulation of oxidative burst in human neutrophils, as well as its potential to inhibit oxidative damage in human erythrocytes. MATERIALS AND METHODS: The modulation of neutrophil's oxidative burst by the ethanolic extracts (0.3-1000 µg/mL) was determined by the oxidation of specific probes by reactive species. Additionally, the potential of these extracts to inhibit oxidative damage in human erythrocytes was evaluated by monitoring its biomarkers of oxidative stress. RESULTS: Vismia cauliflora extracts presented remarkable capacity to prevent the oxidative burst in activated human neutrophils (IC50 < 15 µg/mL). However, the maximum percentage of inhibition achieved against hydrogen peroxide was 45%. Concerning the oxidative damage in human erythrocytes, the extracts were able to minimize the tert-butyl hydroperoxide-induced hemoglobin oxidation and lipid peroxidation in a very low concentration range (2.7-18 µg/mL). Furthermore, only stem bark extract (100 µg/mL) was able to inhibit the depletion of glutathione (13%). DISCUSSION AND CONCLUSION: These results reinforce the therapeutic potential of stem bark and flower extracts of V. cauliflora to heal topical skin disease, namely in the treatment of neutrophil-related dermatosis and skin conditions related to oxidative stress, including skin aging.

Bioactive compounds and scavenging capacity of extracts from different parts of Vismia cauliflora against reactive oxygen and nitrogen species.

CONTEXT: Vismia cauliflora A.C.Sm. [Hypericaceae (Clusiaceae)] is a plant from Amazonian forest. It is used by Amerindians to treat dermatosis and inflammatory processes in the skin and has been considered an interesting source of bioactive compounds. OBJECTIVE: We evaluated the scavenging capacity of extracts from V. cauliflora (leaf, branch, stem bark, flower, and whole fruit) against reactive oxygen (ROS) and nitrogen species (RNS), namely, superoxide radical ([Formula: see text]), hydrogen peroxide (H2O2), hypochlorous acid (HOCl), singlet oxygen ((1)O2), nitric oxide ((•)NO), and peroxynitrite (ONOO(-)). In addition, for the first time, the profile of phenolic compounds and carotenoids was determined. MATERIALS AND METHODS: The scavenging capacities of each extract were determined using specific probes (fluorescent, colorimetric, and chemiluminescent) to detect different reactive species ((1)O2, HOCl, H2O2, [Formula: see text], (•)NO, and ONOO(-)). The identification and the quantification of phenolic compounds and carotenoids were carried out by HPLC-DAD-ESI-MS/MS and HPLC-DAD, respectively. RESULTS: (-)-Epicatechin and proanthocyanidin dimers and trimer were the major phenolic compounds tentatively identified in leaf, branch, stem bark, and flower extracts, while dihydroxybenzoic acids were the major compounds in whole fruit extracts. All-trans-zeinoxanthin and all-trans-ß-carotene were the major carotenoids tentatively identified in leaf extracts. All extracts of V. cauliflora showed high efficiency against all tested ROS and RNS, although flower and stem bark extracts exhibited the most remarkable scavenging capacity, especially for (•)NO and ONOO(-). DISCUSSION AND CONCLUSION: Vismia cauliflora has great potential to be used in the development of phytopharmaceutical products due to its characteristic of being a promising source of bioactive compounds with high antioxidant properties.

Vismia cauliflora extracts: bioactive compounds and the in vitro scavenging capacity against reactive oxygen and nitrogen species.

Vismia cauliflora, a scientific unexploited plant from Amazonian forest, used by Amerindians to treat dermatosis and inflammatory processes in the skin may be considered an interesting source of bioactive compounds. Thus, we evaluated for the first time in literature, the scavenging capacity of five extracts of V. cauliflora (leaf, branch, stem bark, flower and whole fruit) against reactive oxygen and nitrogen species. In addition, the phenolic compounds and carotenoids were also identified and quantified (dry basis). In general, (-)-epicatechin and proanthocyanidin dimers and trimer were the major phenolic compounds identified in leaf, branch, stem bark and flower extracts, while dihydroxybenzoic in whole fruit extracts. The highest phenolic contents were found in stem bark extract (106mg/g extract), followed by leaf (103mg/g) and flower (85mg/g). Regarding carotenoids composition, leaf extract presented the highest contents (0.6mg/g extract) and the major compound tentatively identified was all-trans-zeinoxanthin, followed by all-trans--carotene. All V. cauliflora extracts showed high efficiency against superoxide anion radical, hypochlorous acid, singlet oxygen, nitric oxide and peroxynitrite; however, flower and stem bark exhibited the most remarkable scavenging capacity (IC50 from 0.9 to 11.5g/mL). Therefore, V. cauliflora has a great potential to be used in the development of phytopharmaceutical products due to its characteristic to be a promising source of bioactive compounds with antioxidant properties.

Stem bark and flower extracts of Vismia cauliflora: modulation of oxidative burst in human neutrophils' and inhibition of oxidative damage in human erythrocytes.

Vismia cauliflora is an Amazonian plant traditionally used to treat dermatosis and inflammatory processes of the skin by indigenous population. Our research group showed that stem bark and flower extracts of V. cauliflora are efficient in vitro scavengers of reactive oxygen and nitrogen species. In this study, we determined the activity of stem bark and flower extracts of V. cauliflora plant on the modulation of in vitro oxidative burst in human neutrophils and their potential to inhibit the oxidative damage in human erythrocytes. The oxidative burst in activated neutrophils were monitored by specific probes to detect the oxidizing effect of superoxide anion radical (MCLA), hydrogen peroxide (amplex red) and hypochlorous acid (APF), and both extracts were efficient to neutralize the oxidative burst (IC50 from 3 to 15µg/mL). These same extracts were also effective against oxidative damage in erythrocytes by inhibiting hemoglobin oxidation (IC50=18µg/mL) and lipid peroxidation (IC50=2.7 and 7.5µg/mL, flower and stem bark, respectively). In addition, stem bark extract (100µg/mL) inhibited the depletion of glutathione by 13%. These extracts have similar phenolic composition, but flower presents quercetin (14%) in its composition. Therefore, these results reinforce the potential therapeutic of stem bark and flower extracts of V. cauliflora to heal topical skin disease and requires further research targeted effectively to develop phytopharmaceutical drug based on this plant.

Hepatitis E virus in pork liver sausage, France.

We investigated viability of hepatitis E virus (HEV) identified in contaminated pork liver sausages obtained from France. HEV replication was demonstrated in 1 of 4 samples by using a 3-dimensional cell culture system. The risk for human infection with HEV by consumption of these sausages should be considered to be high.

Hepatitis E virus in pork food chain, United Kingdom, 2009-2010.

We investigated contamination by hepatitis E virus (HEV) in the pork production chain in the United Kingdom. We detected HEV in pig liver samples in a slaughterhouse, in surface samples from a processing plant, and in pork sausages and surface samples at point of sale. Our findings provide evidence for possible foodborne transmission of HEV during pork production.

Prevalence and transmission of hepatitis E virus in domestic swine populations in different European countries.

BACKGROUND: Hepatitis E virus (HEV) genotype 3 and 4 can cause liver disease in human and has its main reservoir in pigs. HEV investigations in pigs worldwide have been performed but there is still a lack of information on the infection dynamics in pig populations. FINDINGS: The HEV transmission dynamics in commercial pig farms in six different European countries was studied. The data collected show prevalence in weaners ranging from 8% to 30%. The average HEV prevalence in growers was between 20% and 44%. The fatteners prevalence ranged between 8% and 73%. Sows prevalence was similar in all countries. Boar faeces were tested for HEV only in Spain and Czech Republic, and the prevalence was 4.3% and 3.5% respectively. The collected data sets were analyzed using a recently developed model to estimate the transmission dynamics of HEV in the different countries confirming that HEV is endemic in pig farms. CONCLUSIONS: This study has been performed using similar detection methods (real time RT-PCR) for all samples and the same model (SIR model) to analyse the data. Furthermore, it describes HEV prevalence and within-herd transmission dynamics in European Countries (EU): Czech Republic, Italy, Portugal, Spain, The Netherlands and United Kingdom, confirming that HEV is circulating in pig farms from weaners to fatteners and that the reproductive number mathematical defined as R0 is in the same range for all countries studied.

Effect of amniotic membrane transplantation on corneal healing and proteoglycan expression in an experimental model of limbal deficiency in rabbits.

PURPOSE: Amniotic membrane transplantation (AMT) has been used as a graft or as a dressing in ocular surface reconstruction, facilitating epithelization, maintaining normal epithelial phenotype, and reducing inflammation, vascularization, and scarring. The corneal transparency is due, at least in part, to the arrangement in orthogonal lamellae of collagen fibrils, surrounded by proteoglycans (PGs). These PGs regulate fibrilogenesis, the matrix assembly, and ultimately the corneal transparency. The purpose of the present study was to investigate the effects of AMT upon the corneal PGs after severe limbal injury. METHODS: Experiments were performed on the right corneas of 22 New Zealand female albino rabbits, and their left corneas were used as matched controls. These animals were divided into 3 groups: G1 (n=10): total peritomy and keratolimbectomy, followed by application of 0.5 M NaOH; G2 (n=10): submitted to the same trauma as G1, and treated by AMT; G3: no trauma, only AMT (n=2). The right corneas of G2 and G3 were covered by DMSO4 cryopreserved human amniotic membrane, fixed by interrupted 9-0 mononylon sutures, with its stromal face toward the ocular surface. After 7 or 30 days, the corneas were removed and PGs were extracted. RESULTS: Normal corneas contained approximately 9 mg of PGs per gram of dry tissue. AMT on intact cornea (G3) did not cause any changes in the concentration of PGs. In contrast, injured corneas contained much less PGs, both on the seventh and on the 30th day posttrauma. The PG concentration was even lower in injured corneas treated by AMT. This decrease was due almost exclusively to dermatan sulfate PGs, and the structure of dermatan sulfate was also modified, indicating changes in the biosynthesis patterns. CONCLUSIONS: Although beneficial effects have been observed on clinical observation and concentration of soluble proteins after AMT, the normal PG composition of cornea was not attained, even 30 days postinjury, indicating that the normal ocular surface reconstruction, if possible, is a long-term process.

Proteoglycan synthesis by human corneal explants submitted to laser in situ keratomileusis (LASIK).

PURPOSE: To evaluate the acute effects of laser in situ keratomileusis (LASIK) upon the synthesis of proteoglycans (PGs) and collagen fibril organization in human corneal explants. METHODS: Human corneas that had been rejected for transplants were obtained at Banco de Olhos of Hospital São Paulo. For each eye pair, one cornea was submitted to refractive surgery, and the other was used as its matched control. After surgery, the corneas were excised from the eyes and immediately placed in a Ham F-12 nutrient mixture containing (35)S-sulfate for the metabolic labeling of PGs. After 24 h incubation, PGs were extracted and identified by a combination of agarose gel electrophoresis and enzymatic degradation with protease and specific glycosaminoglycan lyases. Histopathological and birefringence analysis were performed in fixed tissue slices. RESULTS: A marked decrease in (35)S-sulfate incorporation in PGs was observed in corneal explants that received LASIK, especially concerning dermatan sulfate-PGs, with keratan sulfate- and heparan sulfate-PG synthesis reduced to a lower degree. Only low molecular weight PGs were present in the corneas, both before and 24 h after LASIK. No sign of wound healing processes were observed, but a marked change in corneal birefringence was seen following LASIK treatment. CONCLUSIONS: Laser application led to decreased PG biosynthesis in human corneal explants, with marked changes in the collagen fibril organization, as revealed by changes in the tissue birefringence.

An improved methodology to produce Flavobacterium heparinum chondroitinases, important instruments for diagnosis of diseases.

Chondroitinases are very important tools for the identification and structural analysis of proteoglycans. Enzymic analysis with Flavobacterium heparinum chondroitinases has shown that chondroitin sulphate and dermatan sulphate structures are modified in many human diseases, suggesting a diagnostic value for these enzymes. Furthermore, it was recently shown that F. heparinum chondroitinases AC and B inhibit tumoural cell growth, invasion and angiogenesis. Due to the increasing importance of F. heparinum chondroitinases, we investigated optimized conditions for preparation and assay of chondroitinases AC, B and C. The Dimethylmethylene Blue assay was modified and fully developed to measure the chondroitinase activities of crude extracts of F. heparinum. This method estimates chondroitin sulphate or dermatan sulphate depolymerization upon the digestion of chondroitinase, and was compared with A (232), which measures the unsaturated products formed. Trypticase was the best culture medium, both for bacterial growth and enzyme induction. The chondroitinases were solubilized by ultrasound under conditions that do not completely disrupt the cells, suggesting that they are located at the periplasmic space. Maximum chondroitinase induction occurred in the presence of 0.2-1.0 g/l chondroitin sulphate. Chondroitin sulphate-degradation products were also inducers, but heparin and heparan sulphate were not. Chondroitinases AC, B and C were separated from each other by hydrophobic-interaction chromatography on Phenyl-Sepharose HP. When contaminant proteins were first removed from crude extract by Q-Sepharose, the chondroitinases could be purified to homogeneity in this phenyl-Sepharose chromatographic step.

A comparative analysis of structure and spatial distribution of decorin in human leiomyoma and normal myometrium.

Leiomyoma is a benign smooth muscle tumor of the uterus that affects many women in active reproductive life. It is composed by bundles of smooth muscle cells surrounded by extracellular matrix. We have recently shown that the glycosylation of extracellular matrix proteoglycans is modified in leiomyoma: increased amounts of galactosaminoglycans with structural modifications are present. The data here presented show that decorin is present in both normal myometrium and leiomyoma but tumoral decorin is glycosylated with longer galactosaminoglycan side chains. Furthermore, these chains contain a higher ratio D-glucuronate/L-iduronate, as compared to normal tissue. To determine if these changes in proteoglycan glycosylation correlates with modifications in the extracellular matrix organization, we compared the general structural architecture of leiomyoma to normal myometrium. By histochemical and immunofluorescence methods, we found a reorganization of muscle fibers and extracellular matrix, with changes in the distribution of glycoproteins, proteoglycans, and collagen. Thin reticular fibers, possibly composed by types I and III collagen, were replaced by thick fibers, possibly richer in type I collagen. Type I collagen colocalized with decorin both in leiomyoma and normal myometrium, in contrast to type IV collagen that did not. The relative amount of decorin was increased and the distribution of decorin and collagen was totally modified in the tumor, as compared to the normal myometrium. These findings reveal that not only decorin structure is modified in leiomyoma but also the tissue architecture changed, especially concerning extracellular matrix.