The global hepatitis delta virus (HDV) epidemic: what gaps to address in order to mount a public health response?

BACKGROUND: Co-infection between hepatitis B virus (HBV) and hepatitis delta virus (HDV) causes the severest chronic hepatitis and is associated with a high risk of cirrhosis and hepatocellular carcinoma (HCC). The Global Health Sector Strategy on Viral Hepatitis called for the elimination of hepatitis (- 65% mortality and - 90% incidence) by 2030. Our aims were to summarize key points of knowledge and to identify the gaps that need to be addressed to mount a public health response to HDV. METHODS: We performed a current literature review in terms of epidemiology by WHO regions, genotypes distribution and their pathogenicity, factors associated with HDV infection, mortality due to HDV infection, testing strategies and treatment. RESULTS: Prevalence of infection and genotypes are heterogeneous distributed, with highest prevalence in foci around the Mediterranean, in the Middle East, and in Central, Northern Asia and Eastern Asia. Persons who inject drugs (PWID) and migrants from highly endemic areas are highly affected. While antibody detection tests are available, HDV RNA tests of current infection are not standardized nor widely available. The few therapeutic options, including lofartinib, are not widely available; however several new and promising agents have entered clinical trials. CONCLUSION: HDV infection is an poorly known cause of chronic liver disease. To mount a public health response, we need a better description of the HDV epidemic, standardized testing strategies and better treatment options.

Global progress on the elimination of viral hepatitis as a major public health threat: An analysis of WHO Member State responses 2017.

In 2016, the World Health Assembly passed a resolution to eliminate viral hepatitis as a public health threat by 2030. We aimed to examine the status of the global viral hepatitis response. METHODS: In 2017, the World Health Organization (WHO) asked the Ministries of Health in all 194 Member States to complete a Country Profile on Viral Hepatitis policy uptake indicators, covering national plans/funding, engagement of civil society, testing guidance, access to treatment, and strategic information. RESULTS: Of 194 Member States, 135 (70%) responded, accounting for 87% of the global population infected with hepatitis B virus (HBV) and/or C virus (HCV). Of those responding, 84 (62%) had developed a national plan, of which, 49 (58%) had dedicated funding, and 62 (46%) had engaged with civil society; those engaged with civil society were more likely to have a funded plan than others (52% vs. 23%, p = 0.001). Guidance on testing pregnant women (for HBV) and people who inject drugs (for HCV) was available in 70% and 46% of Member States, respectively; 59% and 38% of Member States reported universal access to optimal therapies for HBV and HCV, respectively. CONCLUSIONS: Most people living with hepatitis B and C reside in a country with a national hepatitis strategy. Governments who engaged with civil society were more advanced in their response. Member States need to finance these national strategies and ensure that those affected have access to hepatitis services as part of efforts to achieve universal health coverage. LAY SUMMARY: The World Health Organization's goal to eliminate viral hepatitis as a public health threat by 2030 requires global action. Our results indicate that progress is being made by countries to scale-up national planning efforts; however, our results also highlight important gaps in current policies.

Viral Hepatitis Strategic Information to Achieve Elimination by 2030: Key Elements for HIV Program Managers.

Evidence documenting the global burden of disease from viral hepatitis was essential for the World Health Assembly to endorse the first Global Health Sector Strategy (GHSS) on viral hepatitis in May 2016. The GHSS on viral hepatitis proposes to eliminate viral hepatitis as a public health threat by 2030. The GHSS on viral hepatitis is in line with targets for HIV infection and tuberculosis as part of the Sustainable Development Goals. As coordination between hepatitis and HIV programs aims to optimize the use of resources, guidance is also needed to align the strategic information components of the 2 programs. The World Health Organization monitoring and evaluation framework for viral hepatitis B and C follows an approach similar to the one of HIV, including components on the following: (1) context (prevalence of infection), (2) input, (3) output and outcome, including the cascade of prevention and treatment, and (4) impact (incidence and mortality). Data systems that are needed to inform this framework include (1) surveillance for acute hepatitis, chronic infections, and sequelae and (2) program data documenting prevention and treatment, which for the latter includes a database of patients. Overall, the commonalities between HIV and hepatitis at the strategic, policy, technical, and implementation levels justify coordination, strategic linkage, or integration, depending on the type of HIV and viral hepatitis epidemics. Strategic information is a critical area of this alignment under the principle of what gets measured gets done. It is facilitated because the monitoring and evaluation frameworks for HIV and viral hepatitis were constructed using a similar approach. However, for areas where elimination of viral hepatitis requires data that cannot be collected through the HIV program, collaborations are needed with immunization, communicable disease control, tuberculosis, and hepatology centers to ensure collection of information for the remaining indicators.

Assessment of the viral hepatitis response in Kyrgyzstan: 11–15 July 2016: mission report

The WHO Regional Office for Europe conducted an assessment mission in Kyrgyzstan over a period of four days, with the aim to make a short review of hepatitis related surveillance, national policies and services. The result of this short review would inform the Ministry of Health and WHO identify specific areas for further technical cooperation. The report does not claim to be a comprehensive assessment of all aspects related to viral hepatitis prevention and control but it could best be used to start a dialogue between WHO and the MOH for further technical support in the priority areas identified.

Challenges and priorities in the management of HIV/HBV and HIV/HCV coinfection in resource-limited settings.

Liver disease due to chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is now emerging as an increasing cause of morbidity and mortality in human immunodeficiency virus- (HIV-) infected persons in resource-limited settings (RLS). Existing management guidelines have generally focused on care in tertiary level facilities in developed countries. Less than half of low-income countries have guidance, and in those that do, there are important omissions or disparities in recommendations. There are multiple challenges to delivery of effective hepatitis care in RLS, but the most important remains the limited access to antiviral drugs and diagnostic tests. In 2010, the World Health Assembly adopted a resolution calling for a comprehensive approach for the prevention, control, and management of viral hepatitis. We describe activities at the World Health Organization (WHO) in three key areas: the establishment of a global hepatitis Program and interim strategy; steps toward the development of global guidance on management of coinfection for RLS; and the WHO prequalification program of HBV and HCV diagnostic assays. We highlight key research gaps and the importance of applying the lessons learned from the public health scale-up of ART to hepatitis care.

Systematic review of economic evaluations of preparedness strategies and interventions against influenza pandemics.

BACKGROUND: Although public health guidelines have implications for resource allocation, these issues were not explicitly considered in previous WHO pandemic preparedness and response guidance. In order to ensure a thorough and informed revision of this guidance following the H1N1 2009 pandemic, a systematic review of published and unpublished economic evaluations of preparedness strategies and interventions against influenza pandemics was conducted. METHODS: The search was performed in September 2011 using 10 electronic databases, 2 internet search engines, reference list screening, cited reference searching, and direct communication with relevant authors. Full and partial economic evaluations considering both costs and outcomes were included. Conversely, reviews, editorials, and studies on economic impact or complications were excluded. Studies were selected by 2 independent reviewers. RESULTS: 44 studies were included. Although most complied with the cost effectiveness guidelines, the quality of evidence was limited. However, the data sources used were of higher quality in economic evaluations conducted after the 2009 H1N1 pandemic. Vaccination and drug regimens were varied. Pharmaceutical plus non-pharmaceutical interventions are relatively cost effective in comparison to vaccines and/or antivirals alone. Pharmaceutical interventions vary from cost saving to high cost effectiveness ratios. According to ceiling thresholds (Gross National Income per capita), the reduction of non-essential contacts and the use of pharmaceutical prophylaxis plus the closure of schools are amongst the cost effective strategies for all countries. However, quarantine for household contacts is not cost effective even for low and middle income countries. CONCLUSION: The available evidence is generally inconclusive regarding the cost effectiveness of preparedness strategies and interventions against influenza pandemics. Studies on their effectiveness and cost effectiveness should be readily implemented in forthcoming events that also involve the developing world. Guidelines for assessing the impact of disease and interventions should be drawn up to facilitate these studies.

The attitude of elderly lay people towards the symptoms of dementia.

OBJECTIVES: To assess the attitude of elderly lay people towards the concept and symptoms of dementia. METHODS: A population-based, cross-sectional study of 859 residents without dementia, aged 70 years or older, living in an urban area in Istanbul. Nine questions with yes/no responses were designed to investigate the attitudes of the responders to the concept of dementia and symptoms related to particular aspects of dementia. The chi(2)-test was used to test for differences between proportions of respondents in different age, sex and education groups. RESULTS: Dementia was considered as normal by the majority of respondents and age and education did not influence this attitude. Women were significantly less inclined to consider dementia and its associated problems as normal. CONCLUSION: The concept of dementia is generally not considered as a medical problem by the elderly Turkish population, independent of age and education. These results are important in guiding policy makers and shaping awareness raising campaigns of local Alzheimer's Associations.

Unrecognized depression in community-dwelling elderly persons in Istanbul.

OBJECTIVE: Depression, one of the most prevalent psychiatric disorders, causes disability and reduces quality of life. Rates of clinical depression in community samples of older adults range between 1-16%. Most studies of old age depression have been conducted in developed countries. The present study was conducted to determine the prevalence of depressive disorders among Turkish elderly in an urban community. METHOD: This study was carried out in the Kadiköy district of Istanbul. The sample for the cross-sectional part of the study was 1067 individuals age 70 or older, randomly selected from population registries. Geriatric Depression Scale (GDS), Mini-mental State Examination (MMSE) scores and demographic data were obtained by face-to-face home interviews. The data were analyzed using regression analysis for each variable. RESULTS: The study group consisted of 623 (61%) females and 395 (39%) males. The mean age was 74.8 years, with 63% of subjects aged 70-74, 29% between 75-84 years old and 8% aged 85 and above. Sixteen percent (n = 163) of the total group scored 14 or higher on the GDS. Only 9% of the depressed group were on antidepressant medication. Logistic regression analysis indicated that significant predictors for higher scores GDS scores were: illiteracy, aged 75-79 yrs, female sex and having 4 or more children. CONCLUSION: Depression is a common but unrecognized and thus untreated problem among the elderly population in Turkey. While gender and age are unmodifiable, education level and multiparity can be altered. Education of caregivers and medical staff about old age depression may increase its rate of detection and facilitate improved treatment.

Risk factors for Alzheimer disease: a population-based case-control study in Istanbul, Turkey.

The objective is to study risk factors for Alzheimer disease (AD) in Istanbul, Turkey. This is a population-based case-control study. We screened people over age 70 in the community for cognitive impairment. The screen positives and a proportion of screen negatives underwent neurologic examination in the second phase. Cases were 57 "probable" AD patients and controls were 127 cognitively normal individuals identified by neurologic examination. Odds ratios (OR) were calculated using multivariate logistic regression analysis. Having a university/college degree had a protective effect on AD risk (OR = 0.10, 95% confidence interval [CI] = 0.02-0.50). Exposure to occupational electromagnetic field had an OR of 4.02 (95% CI = 1.02-15.78). Use of electricity for residential heating also showed elevated risk (OR = 2.77, 95% CI = 1.12-6.85). Our results suggest that having a higher education is protective from AD and that electromagnetic field exposure at work or at home is a significant risk factor.

Helicobacter pylori infection in Turkish preschool and school children: role of socioeconomic factors and breast feeding.

It has been shown that Helicobacter pylori (H. pylori) infection is rare among children in developed countries. In Turkey, the prevalence of H. pylori infection among adults is about 80-85%, which is close to the ratios reported in developing countries. There is limited knowledge, however, on the prevalence, determinants and associations of this infection, such as short stature, familial history of dyspepsia and abdominal pain, in children. The aims of this study were to estimate the prevalence, determinants and associations of H. pylori infection in a group of healthy school children using 13C-urea breath test (13C-UBT). The study subjects were selected from a kindergarten and an elementary school. The H. pylori status was determined by 13C-UBT. Standard questionnaires ascertaining sociodemographic data were completed for each child by questioning the mothers. Three hundred twenty-seven children aged 3-12 years participated in the study. Overall, 162 children (49.5%) were infected with H. pylori, and the prevalence increased with age: 18.2% under 4 years, 41% at 4-6 years, 48.6% at 6-8 years, 50% at 8-10 years, and 63% at 11-12 years of age. No association was determined between H. pylori infection and height and weight percentiles, history of abdominal pain or family history of dyspepsia in the study group. Investigation of the prevalence of H. pylori infection in our study group in relation to socioeconomic data in a logistic regression model revealed that low income, high household density of children, use of stove for heating, and no breast feeding were important risk factors for H. pylori infection. This study was done in a group of healthy Turkish children to estimate the age-related prevalence of H. pylori infection and to determine the factors predisposing to H. pylori infection during childhood. It was found that 1/5 of healthy Turkish children were infected with H. pylori before four years of age, and that every one child out of two under 11 years of age was infected with H. pylori. Low socioeconomic status, poor household living conditions and no breast feeding were determined as independent risk factors of H. pylori infection.

Looking for Our Ten Years Results for Coronary Heart Disease and Ischemic Stroke Group for the Standpoint of Haemostasis.

To evaluate the role the coagulation and fibrinolysis abnormalities in the pathogenesis of ischemic stroke of undetermined etiology, we assayed plasma concentration of fibrinopeptide-A and thrombin-antithrombin III complex, both sensitive markers for thrombin activation and fibrin formation, and D-dimer, a marker of plasmin activity and fibrinolysis. Hemostatic markers were measured in 32 patients with acute stroke and 20 patients with chronic stroke, and compared with 21 normal subjects. Fibrinopeptid-A and thrombin-antithrombin III complex levels were not elevated significantly, whereas the D-dimer level was markedly raised in acute (p<< 0.001) and chronic (p< 0.05) phases of ischemic stroke in comparison with the control group. Prolonged elevation of D-dimer concentration suggests that hemostatic abnormalities have a primary role in the pathogenesis of ischemic stroke. The measurement of D-dimer concentration may help to better decide the indications for therapy of the patients with ischemic stroke of undetermined etiology.