Guido François

The seroepidemiology of herpes simplex virus type 1 and 2 in Europe

Objectives: To describe the seroepidemiology of herpes simplex virus (HSV) types 1 and 2 in the general populations of eight European countries to better understand recent reported changes in disease epidemiology. Methods: Belgium, Bulgaria, Czech Republic, England and Wales, Finland, Germany, Netherlands, and Slovenia conducted national cross sectional serological surveys for HSV-1 and HSV-2 between 1989 and 2000. Survey sizes ranged from 3000 to 7166 sera. External quality control was ensured through reference panel testing. Results: Large intercountry and intracountry differences in HSV-1 and HSV-2 seroprevalence were observed. Age standardised HSV-1 seroprevalence ranged from 52% in Finland, to 57% in the Netherlands, 67% in Belgium, 81% in Czech Republic, and 84% in Bulgaria. Age standardised (>12 years) HSV-2 seroprevalence ranged from 24% in Bulgaria, to 14% in Germany, 13% in Finland, 11% in Belgium, 9% in Netherlands, 6% in Czech Republic, and 4% in England and Wales. In all countries, probability of seropositivity for both infections increased with age. A large proportion of teenagers and young adults remain HSV-1 susceptible particularly in northern Europe. Women were significantly more likely to be HSV-2 seropositive in six of seven (p<0.05) countries and HSV-1 seropositive in four of seven (p<0.05) countries, particularly in northern Europe. No significant evidence of a protective role of HSV-1 for HSV-2 infection was found adjusting for age and sex (p<0.05). Conclusions: There is large variation in the seroepidemiology of HSV-1 and HSV-2 across Europe. The observation that a significant proportion of adolescents are now HSV-1 susceptible may have implications for transmission and clinical presentation of HSV-1 and HSV-2.

Hepatitis B virus and human immunodeficiency virus co-infection in sub-Saharan Africa: a call for further investigation.

Abstract: A growing body of evidence indicates that human immunodeficiency virus (HIV)‐positive individuals are more likely to be infected with hepatitis B virus (HBV) than HIV‐negative individuals, possibly as a result of shared risk factors. There is also evidence that HIV‐positive individuals who are subsequently infected with HBV are more likely to become HBV chronic carriers, have a high HBV replication rate, and remain hepatitis Be antigen positive for a much longer period. In addition, it is evident that immunosuppression brought about by HIV infection may cause reactivation or reinfection in those previously exposed to HBV. Furthermore, HIV infection exacerbates liver disease in HBV co‐infected individuals, and there is an even greater risk of liver disease when HIV and HBV co‐infected patients are treated with highly active anti‐retroviral therapy (HAART). Complicating matters further, there have been several reports linking HIV infection to ‘sero‐silent’ HBV infections, which presents serious problems for diagnosis, prevention, and control. In sub‐Saharan Africa, where both HIV and HBV are endemic, little is known about the burden of co‐infection and the interaction between these two viruses. This paper reviews studies that have investigated HIV and HBV co‐infection in sub‐Saharan Africa, against a backdrop of what is currently known about the interactions between these two viruses.

A randomised controlled trial with a diphtheria-tetanus-acellular pertussis (dTpa) vaccine in adults.

The aim of this assessor-blinded trial was to compare the immunogenicity and reactogenicity of a candidate diphtheria, tetanus toxoids and acellular pertussis vaccine with reduced antigen content for diphtheria and pertussis (dTpa) with a licensed reduced adult-type diphtheria-tetanus vaccine Td (reduced diphtheria content) and with an experimental candidate monovalent acellular pertussis vaccine with reduced antigen content (pa). The dTpa and pa vaccines had identical pertussis antigen content. A total of 299 healthy adults (> or =18 years, mean age: 30.1 years+/-10.7) were randomised into 3 groups to receive a single dose of one of the study vaccines. In all groups, clinically significant reactions (severe) were infrequent (0-6%) and no serious adverse events were reported during the study. The incidence of local and systemic reactions following the administration of dTpa was comparable to the Td vaccine group. Of the total study group, prior to vaccination 52. 3 and 93.2% of the subjects had anti-diphtheria and anti-tetanus antibody levels > or = 0.1 IU/ml, respectively; and 73.1, 98.2 and 74.5% of the subjects were seropositive for pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) antibodies, respectively. One month after vaccination, a similar percentage of subjects in the dTpa and Td groups had anti-diphtheria (88.4% vs 90. 1%) and anti-tetanus (100% vs 98.9%) antibody levels > or =0.1 IU/ml. Similar anti-FHA (100%) and anti-PRN (98.9%) vaccine response rates were seen in the dTpa and pa groups, while the anti-PT vaccine response rates were 96.8 and 100.0%, respectively. The dTpa vaccine is as well tolerated and immunogenic as the licensed Td vaccine, and additionally, can also boost antibodies against pertussis.

Vaccine Safety Controversies and the Future of Vaccination Programs

In the years following the hepatitis B vaccination/multiple sclerosis controversy, a number of new issues regarding vaccine safety have been raised, in some cases leading to more debate and confusion. Against this background, an international group of experts was convened to review the current points of view concerning the use of thimerosal as a preservative and its potential risks; the suggested link between thimerosal-containing vaccines and acute lymphoblastic leukemia; the alleged association between aluminum-containing vaccines/macrophagic myofasciitis and general systemic complaints; a possible link between vaccination and autoimmune pathology; and a hypothetical link between measles-mumps-rubella vaccination and autism. At present, there are no data to conclude that childhood vaccines, and in particular hepatitis B vaccine, pose a serious health risk or justify a change in current immunization practice. However, vaccine “scares” continue to have an international impact on immunization coverage. Creating a positive environment for immunization can be achieved by repositioning the value of vaccines and vaccination, supported by evidence-based information. The role of international organizations, the media, and the industry in the implementation of communication strategies was discussed and the impact of litigation issues on vaccination was evaluated. The Viral Hepatitis Prevention Board confirms its commitment to current recommendations for universal and risk group hepatitis B vaccination and further encourages the conduct of vaccine safety studies and the dissemination of their results.

Hepatitis B virus, hepatitis C virus and other blood-borne infections in healthcare workers: guidelines for prevention and management in industrialised countries

The Viral Hepatitis Prevention Board (VHPB) convened a meeting of international experts from the public and private sectors in order to review and evaluate the epidemiology of blood-borne infections in healthcare workers, to evaluate the transmission of hepatitis B and C viruses as an occupational risk, to discuss primary and secondary prevention measures and to review recommendations for infected healthcare workers and (para)medical students. This VHPB meeting outlined a number of recommendations for the prevention and control of viral hepatitis in the following domains: application of standard precautions, panels for counselling infected healthcare workers and patients, hepatitis B vaccination, restrictions on the practice of exposure-prone procedures by infected healthcare workers, ethical and legal issues, assessment of risk and costs, priority setting by individual countries and the role of the VHPB. Participants also identified a number of terms that need harmonisation or standardisation in order to facilitate communication between experts.

First synthesis of the antimalarial naphthylisoquinoline alkaloid dioncophylline C, and its unnatural anti-HIV dimer, jozimine C☆

Abstract The first total synthesis of dioncophylline C, a new antimalarial lead structure, is described. For the directed construction of the stereogenic biaryl axis, the ‘lactone methodology’ is applied, despite the lack of a ‘bridgehead oxygen’ function in the target molecule. Furthermore, the novel dimer of dioncophylline C, ‘jozimine C’, is prepared, by oxidative phenolic coupling of the protected natural monomer. Jozimine C displays good antimalarial activity (Plasmodium falciparum; IC50 = 0.445 μg/ml), and, in particular, represents the first unnatural dimer of a naphthylisoquinoline alkaloid with a high anti-HIV activity (HIV-1; EC50 = 27 μg/ml).

Activity of extracts and naphthylisoquinoline alkaloids from Triphyophyllum peltatum, Ancistrocladus abbreviatus and A. barteri against Plasmodium falciparum in vitro

Abstract Five extracts from the tropical plant species Triphyophyllum peltatum, Ancistrocladus abbreviatus and A. barteri, and six pure naphthylisoquinoline alkaloids derived from these species have been examined for their antiplasmodial activity. These species are well-known in the traditional medicine of West Africa and are used for the treatment of fevers, malaria and other diseases. The extracts and alkaloids were tested against the asexual erythrocytic stages of two strains of Plasmodium falciparum in vitro (K1/chloroquine-resistant and NF 54/64, clone A1A9/ chloroquine-sensitive). Incorporation of 3H-hypoxanthine was measured in the presence of the test substances after 42 hr of incubation at 37°. All extracts and three alkaloids displayed activity. The two most potent compounds were dioncopeltine A and dioncophylline B. Structure-activity considerations indicate two possible criteria for antiplasmodial activity: an R-configuration at C-3 associated with the absence of an oxygen substituent at C-6 and the absence of N-methylation.

Hepatitis B vaccination: how to reach risk groups

Current hepatitis B vaccination programmes targeting risk groups have met with little success in controlling HBV infection in the general population. Despite the long-standing existence of unambiguous recommendations for risk-group vaccination, hepatitis B vaccination coverage remains low in most risk groups in most high-income countries. This low coverage may be attributed to a lack of perceived risk of hepatitis B and the absence of appropriate health care programmes targeting hepatitis B monitoring and vaccination for certain risk groups, particularly sex workers, injecting drug users, and prisoners. The Viral Hepatitis Prevention Board (VHPB) recognises the importance of raising the awareness of health care providers, policymakers, and the general public, about hepatitis B as a risk to both the community in general and to specific groups considered at increased risk. The VHPB also recognises that new strategies will have to be developed and implemented.

Prevention of hepatitis C virus infection

In spite of advances made in our understanding of the biology of the hepatitis C virus (HCV), the epidemiology and natural history of HCV infection, and the treatment of chronic hepatitis C, the development and worldwide implementation of a comprehensive prevention and control strategy remains necessary. A World Health Organization informal consultation with the Viral Hepatitis Prevention Board was convened and met in Geneva, Switzerland, 13–14 May 2002, to review epidemiological and public health aspects of HCV infection, and the various prevention and control strategies that are currently in place. Based on the presentations and discussions, a number of specific recommendations were made, which should be considered in conjunction with previously published recommendations.

European survey of hepatitis B vaccination policies for healthcare workers

BACKGROUND The risk of transmission of hepatitis B virus (HBV) to healthcare workers (HCWs) is well known. Under current European Union (EU) legislation, all employers should perform a risk assessment to identify those exposed to HBV and offer vaccination. Immunization should happen early after the start of their career to avoid infection and development of carrier status. METHODS Cross-sectional survey of country representatives, to find out how policies are put into practice in European countries. RESULTS Answers were received from 17 countries, representing 89% of the population and 90% of HCWs in the EU-25. HBV vaccination was mandatory for medical, and nursing and other paramedical staff in five countries, and recommended in all other countries. It was mandatory for medical students and student nurses in five countries and recommended in nine other. Pre-vaccination serotesting was done in six countries. The vaccination schedule most often used was 0, 1, 6 months. Combined vaccine (hepatitis A virus /HBV) was used in 10 countries. Post-vaccination serotesting was done in 14 countries. Data on HBV vaccination coverage were available in 11 countries and published in five of them. Coverage was 85-93%. CONCLUSION These results show the variation as to how EU legislation is translated into practice in European countries. More consultation between key actors at EU level could help to optimize the way this matter is dealt with. A battery of measures and interventions-including introduction of immunization programmes against HBV infection and increasing immunization coverage in HCWs-can contribute to further reducing HBV transmission to HCWs.