Clinical and epidemiological aspects of a hepatitis E outbreak in Bangui, Central African Republic

<p>Abstract</p> <p>Background</p> <p>Outbreaks of hepatitis E frequently occur in tropical developing countries during the rainy season due to overflowing drains, short-circuiting of networks of clean water and use of contaminated water from wells. Hepatitis E virus (HEV) infections are usually accompanied by general symptoms of acute liver disease. This study was conducted to define the clinical and epidemiological aspects of the HEV outbreak that occurred in May 2004 in Bangui.</p> <p>Methods</p> <p>Blood samples were collected from 411 patients aged 1-87 years, most of whom presented with jaundice, asthenia or signs of uncomplicated malaria, for a transversal study from June 2004 to September 2005. Patients were recruited at 11 health care centres, including two referral hospitals, after they had given informed consent. The diagnosis of HEV was made with a commercial ELISA test to detect IgM and/or IgG antibodies. HEV RNA was amplified by RT-PCR to confirm the presence of the viral genome.</p> <p>Results</p> <p>The most frequent clinical signs found were jaundice (93.4%), vomiting (50.7%), hepatalgia (47.4%), hepatomegaly (30.9%) and asthenia (26.8%), which are the general clinical signs of hepatic disease. Acute hepatitis E was found in 213 patients (51.8%) who were positive for HEV IgM antibodies. The IgG anti-HEV seroprevalence during this outbreak was high (79.5%). The age group 18-34 years was more frequently infected (91.2%) than those aged 1-17 (78.0%) or over 34 (64.9%) (p < 10^-6). RT-PCR performed on 127 sera from the 213 IgM-HEV-positive patients was amplified, and the presence of the viral genome was found in 65 samples.</p> <p>Conclusion</p> <p>Although no specific clinical signs exist for hepatitis E infection, people presenting with jaundice, vomiting, hepatalgia, asthenia, hepatomegaly or distended abdomen with no signs of uncomplicated malaria in tropical developing countries should be sent to a laboratory for testing for hepatitis E.</p

The prevalence of HBV infection in the cohort of IDPs of war against terrorism in Malakand Division of Northern Pakistan

<p>Abstract</p> <p>Background</p> <p>Hepatitis B is an important public health problem in the Pakistani population and is the major cause of chronic hepatitis, cirrhosis, fibrosis and hepatocellular carcinoma. High prevalence of HBV infections has been observed especially in areas of low economic status. In spite of effective immunization programs, no significant change has been observed in the epidemiology of HBV in the rural areas of Pakistan (~67.5% of the total population) mainly due to lack of interest from government authorities and poor hygienic measures. The current study was aimed at estimating the prevalence and risk factors associated with HBV infection within internally displaced persons (IDPs) due to war against terrorism in the Malakand Division of Northern Pakistan.</p> <p>Methods</p> <p>Blood samples from 950 IDPs suspected with HBV infection (including both males and females) were collected and processed with commercial ELISA kits for HBsAg, Anti HBs, HBeAg, Anti HBe antibodies. The samples positive by ELISA were confirmed for HBV DNA by real-time PCR analysis.</p> <p>Results</p> <p>The overall prevalence of HBV observed was 21.05% of which 78.5% were males and 21.5% were females. Most confirmed HBV patients belong to the Malakand and Dir (lower) district. High-risk of infection was found in the older subjects 29.13% (46-60 years), while a lower incidence (11.97%) was observed in children aged <15 years. Lack of awareness, socioecomic conditions, sexual activities and sharing of razor blades, syringes and tattooing needles were the most common risk factors of HBV infection observed during the cohort of patients.</p> <p>Conclusion</p> <p>The present study, revealed for the first time a high degree of prevalence of HBV infection in rural areas of Northern Pakistan. The noticed prevalence is gender- and age-dependent that might be due to their high exposures to the common risk factors. To avoid the transmission of HBV infection proper awareness about the possible risk factors and extension of immunization to the rural areas are recommended.</p

Phosphodiesterase 3B Is Localized in Caveolae and Smooth ER in Mouse Hepatocytes and Is Important in the Regulation of Glucose and Lipid Metabolism

Cyclic nucleotide phosphodiesterases (PDEs) are important regulators of signal transduction processes mediated by cAMP and cGMP. One PDE family member, PDE3B, plays an important role in the regulation of a variety of metabolic processes such as lipolysis and insulin secretion. In this study, the cellular localization and the role of PDE3B in the regulation of triglyceride, cholesterol and glucose metabolism in hepatocytes were investigated. PDE3B was identified in caveolae, specific regions in the plasma membrane, and smooth endoplasmic reticulum. In caveolin-1 knock out mice, which lack caveolae, the amount of PDE3B protein and activity were reduced indicating a role of caveolin-1/caveolae in the stabilization of enzyme protein. Hepatocytes from PDE3B knock out mice displayed increased glucose, triglyceride and cholesterol levels, which was associated with increased expression of gluconeogenic and lipogenic genes/enzymes including, phosphoenolpyruvate carboxykinase, peroxisome proliferator-activated receptor γ, sterol regulatory element-binding protein 1c and hydroxyl-3-methylglutaryl coenzyme A reductase. In conclusion, hepatocyte PDE3B is localized in caveolae and smooth endoplasmic reticulum and plays important roles in the regulation of glucose, triglyceride and cholesterol metabolism. Dysregulation of PDE3B could have a role in the development of fatty liver, a condition highly relevant in the context of type 2 diabetes

Disease Progression in MRL/lpr Lupus-Prone Mice Is Reduced by NCS 613, a Specific Cyclic Nucleotide Phosphodiesterase Type 4 (PDE4) Inhibitor

Systemic lupus erythematosus is a polymorphic and multigenic inflammatory autoimmune disease. Cyclic AMP (cAMP) modulates inflammation and the inhibition of cyclic nucleotide phosphodiesterase type 4 (PDE4), which specifically hydrolyzes cAMP, inhibits TNFα secretion. This study was aimed at investigating the evolution of PDE activity and expression levels during the course of the disease in MRL/lpr lupus-prone mice, and to evaluate in these mice the biological and clinical effects of treatments with pentoxifylline, denbufylline and NCS 613 PDE inhibitors. This study reveals that compared to CBA/J control mice, kidney PDE4 activity of MRL/lpr mice increases with the disease progression. Furthermore, it showed that the most potent and selective PDE4 inhibitor NCS 613 is also the most effective molecule in decreasing proteinuria and increasing survival rate of MRL/lpr mice. NCS 613 is a potent inhibitor, which is more selective for the PDE4C subtype (IC50 = 1.4 nM) than the other subtypes (PDE4A, IC50 = 44 nM; PDE4B, IC50 = 48 nM; and PDE4D, IC50 = 14 nM). Interestingly, its affinity for the High Affinity Rolipram Binding Site is relatively low (Ki = 148 nM) in comparison to rolipram (Ki = 3 nM). Finally, as also observed using MRL/lpr peripheral blood lymphocytes (PBLs), NCS 613 inhibits basal and LPS-induced TNFα secretion from PBLs of lupus patients, suggesting a therapeutic potential of NCS 613 in systemic lupus. This study reveals that PDE4 represent a potential therapeutic target in lupus disease

A global research priority agenda to advance public health responses to fatty liver disease

Background & aims An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community. Methods Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy. Results The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of ‘agree’ responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement (‘agree’ + ‘somewhat agree’); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% ‘agree’), 13 priorities had 90% combined agreement. Conclusions Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community’s efforts to advance and accelerate responses to this widespread and fast-growing public health threat. Impact and implications An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat

A fatal case of acute hepatitis E among pregnant women, Central African Republic

Abstract Background Hepatitis E virus (HEV) is a major public health problem in developing countries. HEV infection in pregnant women is more common and more often fatal in the third trimester. The mortality rate due to HEV-induced hepatitis is as high as 15-20 per cent. The present study was designed to determine the potential factors responsible for high mortality rate among pregnant women. Findings Twenty one pregnant women attended the Maternity Center of Begoua in the Central African Republic during an outbreak of hepatitis E virus between July and October 2002 with symptoms of acute liver disease. Their mean gestational period was 29.9 (SD 8.3 weeks) and they were aged from 15 to 39 years old. The serology IgM showed that seven women (33%) had acute hepatitis E. Among them, one woman, aged 35 and her newborn died after an apparently normal preterm delivery. The 6 remaining young women, age 18 - 22, had preterm deliveries which included three live babies and three stillborn with one macerated. Conclusions These results suggest that maternal age, in addition to hormonal, immunological and environmental factors, may be a risk factor for fatal outcome.</p