Eurosurveillance - Volume 9, Issue 12, 01 December 2004

With the opening of the European Centre for Disease Prevention and Control (ECDC) in Stockholm in May, 2005 will be an important year for public health in Europe. The idea of a European CDC has been in the air for many years, following the successful and interesting results obtained by the United States CDC in Atlanta.

Nearly eight years after an outbreak of infectious syphilis was first reported in Bristol, England, successive outbreaks have occurred in most western European countries. In this issue of Eurosurveillance we take a look at the recent resurgence and evolution of infectious syphilis in seven European countries in order to critically review our understanding of its epidemiology, and to examine opportunities for directing interventions in the near future. The papers also provide some insight into the multilevel, multifactorial causation of syphilis epidemics, and how this may be changing over time in the presence of preventive interventions.

Over the past five years, a series of syphilis outbreaks mainly occurring among gay men have been observed in Europe. One of these outbreaks was reported in the city of Antwerp, Belgium, during the first quarter of 2001. This outbreak is still ongoing in 2004. Furthermore, active syphilis diagnoses reported by the Sentinel Laboratory Network rose by 89% in the country during the fourth quarter of 2003. An increase in Brussels was also observed during the same quarter (+300%; 24 cases reported). Overall, the sentinel network of clinicians reported that 93.4% of patients were male; among them, 79.9% were men having sex with men (MSM). The overall proportion of patients co-infected with HIV was 50.5% (MSM: 58.6%; male heterosexuals: 23.8%; females: 8.3%); 76.1% of co-infected patients were already aware of their HIV infection at the time they were diagnosed with syphilis.

This article describes syphilis trends, characteristics of patients from 2000 to 2003 in France and trends of the benzylpenicillin benzathine 2.4 million UI sales from 2001 to 2003. The ongoing surveillance system for syphilis case reporting since 2001 has been set up in volunteer settings, mostly public settings where STI treatment is offered. Clinical case reporting is complemented by sexual behavioural data based on a self-administered questionnaire. From 2000 to 2003, 1089 syphilis cases were reported in France, increasing from 37 cases in 2000 to 428 in 2003. Overall, 96% of syphilis cases were in men with a mean age of 36.5 years and 70% of whom were born in France. The proportion of syphilis cases with HIV co-infection decreased over time from 60% in 2000 to 33% in 2003. The most affected area by the syphilis epidemic is the Ile-de-France region, mainly the city of Paris. The greatest proportion of syphilis cases diagnosed in men who have sex with men (MSM) were in the Ile-de-France region, where they made up 87% of cases, compared with 75% in other regions. Among the patients who completed the self-administered questionnaire on sexual behaviour, 83% reported having casual sex partners in the 3 months prior to their syphilis diagnosis. Trends in the sales of benzylpenicillin benzathine 2.4 million UI in private pharmacies are similar to those observed in the surveillance system, and increased between 2001 and 2003. In conclusion, syphilis transmission is still ongoing in France in 2003 and the role of unprotected oral sex in the transmission of syphilis should be emphasised.

Recent surveillance reports from Europe and the United States show an increase in syphilis cases. Accurate epidemiological information about the distribution of syphilis is important for targeting screening and intervention programmes. The German syphilis notification system changed in 2001 from physician to laboratory-based reporting, which is complemented by a newly introduced sexually transmitted infection (STI) sentinel system. After reaching an all time low during the 1990s, syphilis notifications have increased significantly since 2001, coinciding with the introduction of the new reporting system. However, the increased reported incidence is reflecting a true rise in the number of cases and is not predominantly determined by more underreporting through the previous reporting system. The increase reflects syphilis outbreaks among men who have sex with men (MSM). The first of these outbreaks was observed in Hamburg in 1997. In 2003, incidence in men was ten times higher than in women. An estimated 75% of syphilis cases are currently diagnosed among MSM. A high proportion (according to sentinel data, up to 50%) of MSM diagnosed with syphilis are HIV positive. The continuously high number of syphilis cases diagnosed among heterosexuals in Germany in recent years compared with other western European countries may reflect the higher population movement between Germany and syphilis high incidence regions in south-east and eastern Europe.

In response to the increasing numbers of syphilis cases reported among men having sex with men (MSM) in Dublin, an Outbreak Control Team (OCT) was set up in late 2000. The outbreak peaked in 2001 and had largely ceased by late 2003. An enhanced syphilis surveillance system was introduced to capture data from January 2000. Between January 2000 and December 2003, 547 cases of infectious syphilis were notified in Ireland (415 were MSM). Four per cent of cases were diagnosed with HIV and 15.4% of cases were diagnosed with at least one other STI (excluding HIV) within the previous 3 months. The mean number of contacts reported by male cases in the 3 months prior to diagnosis was 4 (range 0-8) for bisexual contacts and 6 for homosexual contacts (range 1-90). Thirty one per cent of MSM reported having had recent unprotected oral sex and 15.9% of MSM reported having had recent unprotected anal sex. Sixteen per cent of cases reported having had sex abroad in the three months prior to diagnosis. The results suggest that risky sexual behaviour contributed to the onward transmission of infection in Dublin. The outbreak in Dublin could be seen as part of a European-wide outbreak of syphilis. The rates of co-infection with HIV and syphilis in Ireland are comparable with rates reported from other centres. There is a need to improve surveillance systems in order to allow real time evaluation of interventions and ongoing monitoring of infection trends.

Syphilis remains a public health problem in the Czech Republic and worldwide. The Czech Republic - until 1993 a part of Czechoslovakia - has a long tradition in public health activities, and STI surveillance is mainly focused on the infections traditionally called venereal diseases - syphilis, gonorrhoea, chancroid, and lymphogranuloma venereum. Campaigns from the early 1950s, were successful in controlling syphilis and gonorrhoea; and chancroid and lymphogranuloma venereum infections are extremely rare. In late 1980s, a low incidence of newly reported syphilis cases was achieved (100-200 cases annually), while around 6500 cases of gonorrhoea were recorded annually during the same period. Health care and prevention of STI diseases in the Czech Republic are based on close cooperation between clinical departments and laboratory and epidemiological services of Environmental Health Offices. Annual statistics showing data on reported cases of ’venereal diseases’, based on ICD-10 codes, are available from 1959. Separate statistical data on other STIs are not available, and aggregated numbers only for Chlamydia trachomatis infections have been presented annually since 2000. Following the political and social changes in the Czech community in 1989, a distinct increase of syphilis was recorded. Between 50% and 60% of notified cases were classified as late latent or of unknown duration. The continuing annual occurrence of congenital syphilis (7-18 cases per year) reported during the 1990s has also been a very serious phenomenon. Cases have been concentrated in large urban areas with a high level of commercial sex activity, and a high proportion of cases is also noted in refugees. While the annual incidence of gonorrhoea gradually decreased from 1994 to 2001 (from 28.5 to 8.9 per 100 000 population), the incidence of syphilis increased in this period from 3.6 to 9.6 per 100 000 population (the highest value was 13.4 in 2001) and in 2000, for the first time in many years, it exceeded the incidence of gonorrhoea.

The aim of this article is to describe trends in infectious syphilis in the UK, and specifically the epidemiology of the London syphilis outbreak, the largest in the UK to date. Analysis of routine surveillance data from genitourinary medicine (GUM) clinics was performed as well as data collection through enhanced surveillance systems. There have been substantial increases in diagnoses of infectious syphilis between 1998 and 2003, with a 25-fold increase seen in men who have sex with men (MSM) (from 43 to 1028 diagnoses); 6-fold (138 to 860) in heterosexual men and 3-fold (112 to 338) in women. The national rise in syphilis was driven by a series of local outbreaks, the first of which occurred in 1997. To date, 1910 cases have been reported in the London outbreak, first detected in April 2001. High rates of HIV co-infection were seen among MSM, with MSM likely to be of white ethnicity and born in the UK. In contrast, heterosexuals were more likely to be of black ethnicity and born outside the UK. Most syphilis infections were acquired in London. MSM bear the brunt of the national resurgence in infectious syphilis. Substantial rises in male heterosexual cases has resulted in a divergence between male heterosexual and female cases, which now requires further investigation.

Denmark is currently experiencing an outbreak of syphilis that began in 2003 and has continued in 2004. Data from the national surveillance system show that most cases are in men who have sex with men (MSM), and that a large proportion of these patients are also HIV positive. The proportion of known HIV positive cases in MSM notified with syphilis during the outbreak has, however, not been significantly different from previous years. The majority of cases were reported from Copenhagen municipality, and 70% of the cases were acquired domestically. The outbreak does not seem to be affecting the age group under 20 years. We speculate that most of the MSM found with both syphilis and HIV were already HIV positive when they acquired syphilis infection.

The deliberate release of anthrax in the United States shortly after the terrorist attacks of 11 September 2001 brought about a radical change in people’s perception of the risk of bioterrorism. These bioterrorist events, unlike others before, had a worldwide impact not only in respect of security and public health but also in other sectors. Governments and international entities with responsibilities related to maintenance of peace, security, safety and health protection reviewed urgently their political, economic, diplomatic, military and legal means to face up to such attacks and embarked upon major efforts to increase their preparedness.

The spore-forming Bacillus anthracis must be considered as one of the most serious potential biological weapons. The recent cases of anthrax caused by a deliberate release reported in 2001 in the United States point to the necessity of early recognition of this disease. Infection in humans most often involves the skin, and more rarely the lungs and the gastrointestinal tract. Inhalational anthrax is of particular interest for possible deliberate release: it is a life-threatening disease and early diagnosis and treatment can significantly decrease the mortality rate. Treatment consists of massive doses of antibiotics and supportive care. Isolation is not necessary. Antibiotics such as ciprofloxacin are recommended for post-exposure prophylaxis during 60 days.

Yersinia pestis appears to be a good candidate agent for a bioterrorist attack. The use of an aerosolised form of this agent could cause an explosive outbreak of primary plague pneumonia. The bacteria could be used also to infect the rodent population and then spread to humans. Most of the therapeutic guidelines suggest using gentamicin or streptomycin as first line therapy with ciprofloxacin as optional treatment. Persons who come in contact with patients with pneumonic plague should receive antibiotic prophylaxis with doxycycline or ciprofloxacin for 7 days. Prevention of human-to-human transmission via patients with plague pneumonia can be achieved by implementing standard isolation procedures until at least 4 days of antibiotic treatment have been administered. For the other clinical types of the disease, patients should be isolated for the first 48 hours after the initiation of treatment.

Smallpox is a viral infection caused by the variola virus. It was declared eradicated worldwide by the Word Health Organization in 1980 following a smallpox eradication campaign. Smallpox is seen as one of the viruses most likely to be used as a biological weapon. The variola virus exists legitimately in only two laboratories in the world. Any new case of smallpox would have to be the result of human accidental or deliberate release. The aerosol infectivity, high mortality, and stability of the variola virus make it a potential and dangerous threat in biological warfare. Early detection and diagnosis are important to limit the spread of the disease. Patients with smallpox must be isolated and managed, if possible, in a negative-pressure room until death or until all scabs have been shed. There is no established antiviral treatment for smallpox. The most effective prevention is vaccination before exposure.

Francisella tularensis is one of the most infectious pathogenic bacteria known, requiring inoculation or inhalation of as few as 10 organisms to initiate human infection. Inhalational tularaemia following intentional release of a virulent strain of F. tularensis would have great impact and cause high morbidity and mortality. Another route of contamination in a deliberate release could be contamination of water. Seven clinical forms, according to route of inoculation (skin, mucous membranes, gastrointestinal tract, eyes, respiratory tract), dose of the inoculum and virulence of the organism (types A or B) are identified. The pneumonic form of the disease is the most likely form of the disease should this bacterium be used as a bioterrorism agent. Streptomycin and gentamicin are currently considered the treatment of choice for tularemia. Quinolone is an effective alternative drug. No isolation measures for patients with pneumonia are necessary. Streptomycin, gentamicin, doxycycline or ciprofloxacin are recommended for post-exposure prophylaxis.

Haemorrhagic fever viruses (HFVs) are a diverse group of viruses that cause a clinical disease associated with fever and bleeding disorder. HFVs that are associated with a potential biological threat are Ebola and Marburg viruses (Filoviridae), Lassa fever and New World arenaviruses (Machupo, Junin, Guanarito and Sabia viruses) (Arenaviridae), Rift Valley fever (Bunyaviridae) and yellow fever, Omsk haemorrhagic fever, and Kyanasur Forest disease (Flaviviridae). In terms of biological warfare concerning dengue, Crimean-Congo haemorrhagic fever and Hantaviruses, there is not sufficient knowledge to include them as a major biological threat. Dengue virus is the only one of these that cannot be transmitted via aerosol. Crimean-Congo haemorrhagic fever and the agents of haemorrhagic fever with renal syndrome appear difficult to weaponise. Ribavirin is recommended for the treatment and the prophylaxis of the arenaviruses and the bunyaviruses, but is not effective for the other families. All patients must be isolated and receive intensive supportive therapy.

Botulism is a rare but serious paralytic illness caused by botulinum toxin, which is produced by the Clostridium botulinum. This toxin is the most poisonous substance known. It 100 000 times more toxic than sarin gas. Eating or breathing this toxin causes illness in humans. Four distinct clinical forms are described: foodborne, wound, infant and intestinal botulism. The fifth form, inhalational botulism, is caused by aerosolised botulinum toxin that could be used as a biological weapon. A deliberate release may also involve contamination of food or water supplies with toxin or C. botulinum bacteria. By inhalation, the dose that would kill 50% of exposed persons (LD50) is 0.003 microgrammes/kg of body weight. Patients with respiratory failure must be admitted to an intensive care unit and require long-term mechanical ventilation. Trivalent equine antitoxins (A,B,E) must be given to patients as soon as possible after clinical diagnosis. Heptavalent human antitoxins (A-G) are available in certain countries.

Interest in Brucella species as a biological weapon stems from the fact that airborne transmission of the agent is possible. It is highly contagious and enters through mucous membranes such as the conjunctiva, oropharynx, respiratory tract and skin abrasions. It has been estimated that 10-100 organisms only are sufficient to constitute an infectious aerosol dose for humans. Signs and symptoms are similar in patients whatever the route of transmission and are mostly non-specific. Symptoms of patients infected by aerosol are indistinguishable from those of patients infected by other routes. Regimens containing doxycycline plus streptomycin or doxycycline plus rifampin are effective for most forms of brucellosis. Isolation of patients is not necessary. Trimethoprim-sulfamethoxazole and fluoroquinolones also have good results against Brucella, but are associated with high relapse rates when used as monotherapy. The combination of ofloxacin plus rifampicin is associated with good results. Even if there is little evidence to support its utility for post-exposure prophylaxis, doxycycline plus rifampicin is recommended for 3 to 6 weeks.

Glanders and melioidosis are two infectious diseases that are caused by Burkholderia mallei and Burkholderia pseudomallei respectively. Infection may be acquired through direct skin contact with contaminated soil or water. Ingestion of such contaminated water or dust is another way of contamination. Glanders and melioidosis have both been studied for weaponisation in several countries in the past. They produce similar clinical syndromes. The symptoms depend upon the route of infection but one form of the disease may progress to another, or the disease might run a chronic relapsing course. Four clinical forms are generally described: localised infection, pulmonary infection, septicaemia and chronic suppurative infections of the skin. All treatment recommendations should be adapted according to the susceptibility reports from any isolates obtained. Post-exposure prophylaxis with trimethoprim-sulfamethoxazole is recommended in case of a biological attack. There is no vaccine available for humans.

Q fever is a zoonotic disease caused by Coxiella burnetii. Its interest as a potential biological weapon stems from the fact that an aerosol of very few organisms could infect humans. Another route of transmission of C. burnetii could be through adding it to the food supply. Nevertheless, C. burnetii is considered to be one of the less suitable candidate agents for use in a bioterrorist attack; the incubation is long, many infections are inapparent and the mortality is low. In the case of an intentional release of C. burnetii by a terrorist, clinical presentation would be similar to naturally occurring disease. It may be asymptomatic, acute, normally accompanied by pneumonia or hepatitis, or chronic, usually manifested as endocarditis. Most cases of acute Q fever are asymptomatic and resolve spontaneously without specific treatment. Nevertheless, treatment can shorten the duration of illness and decrease the risk of complications such as endocarditis. Post-exposure prophylaxis is recommended after the exposure in the case of a bioterrorist attack.

Most of the viruses involved in causing encephalitis are arthropod-borne viruses, with the exception of arenaviruses that are rodent-borne. Even if little information is available, there are indications that, most of these encephalitis-associated viruses could be used by aerosolisation during a bioterrorist attack. Viral transfer from blood to the CNS through the olfactory tract has been suggested. Another possible route of contamination is by vector-borne transmission such as infected mosquitoes or ticks. Alphaviruses are the most likely candidates for weaponisation. The clinical course of the diseases caused by these viruses is usually not specific, but differentiation is possible by using an adequate diagnostic tool. There is no effective drug therapy for the treatment of these diseases and treatment is mainly supportive, but vaccines protecting against some of these viruses do exist.