M. Rey 1 , O. Patey 2, F. Vincent-Ballereau 3
1 French league for the prevention of infectious diseases, Paris, France, 2 Villeneuve Saint-Georges Hospital , France, 3 School of pharmacy, Nantes, France
Since children have been vaccinated routinely, diphtheria has been eliminated in most European states and the recent occurrence of a large epidemic in the Newly Independent States (NIS) of the former USSR was unexpected. The resurgence of diphtheria in the NIS raises the following questions. Will the epidemic expand? How can it be controlled? Does it threaten other European countries? Are European countries sufficiently protected against a return of diphtheria?
Until the second world war, during which an upsurge of morbidity was observed, diphtheria was endemic in most countries, including countries in Europe. Children, particularly of preschool age, were the most commonly affected (1). At least 5% of people suffered any day from clinical diphtheria and among them 5% to 10% died, while the rest of the population was naturally immunised by asymptomatic infection. Industrialised countries introduced generalised vaccination of young children with diphtheria toxoid in the late 1940s or 1950s. Subsequently the incidence of diphtheria declined progressively, and even disappeared during the 1970s or 1980s. Infrequent and small outbreaks still occurred, as in Sweden in 1984-86. While the circulation of toxigenic strains ofCorynebacterium diphtheriae seemed to have been eliminated by the antitoxin, non-toxigenic strains continued to circulate, causing sporadic cases of septicaemia, endocarditis, arthritis, mainly in adults living in poor socioeconomic conditions (2). With widespread vaccination, a dramatic change was seen in the immunity of the general population in different industrialised countries. Serosurveys, however, showed a partial and progressive decline in adult immunity with age, attributable to the absence of recommended vaccine boosters and the lack of natural contacts with toxigenic C. diphtheriae (1,3,4). Women were generally found to be more susceptible than men, probably because men had been revaccinated during military service. Most children are now fully protected, provided that the majority of them are properly vaccinated, but about 50% of the European adult population is partly or totally susceptible to diphtheria.
In the USSR, the incidence of diphtheria declined dramatically after general vaccination of children was introduced but did not totally disappear, and was controlled at a low level in the 1970s (5). Its incidence began to increase slightly in the 1980s and has risen sharply since 1990, reaching 19 462 cases in 1993, and culminating in 1994 and 1995 with 47 808 and 50 412 cases, respectively. Case fatality rates have ranged from between 2% and 3% (Russia, Ukraine) to more than 20% (Georgia, Azerbaijan, Turkmenistan). Starting in Russia, mainly in Moscow and St Petersburg (where the attack rate exceeded 50 per 100 000 in 1993), the epidemic then spread to the Russian Federation, Ukraine, Belarus, Baltic Republics, Moldavia, Caucasian and Asiatic NIS. In 1995 the epidemic seemed to be stabilising in the European part of Russia and in the European NIS, following the implementation of a strengthened control programme, including vaccination, but continued to expand in Ukraine and in some Asiatic Republics. The epidemic was initially characterised by a shift in the age distribution of cases from children to adults: 60% to 80% of Russian or Ukrainian patients were over 15 years of age. On the other hand, children remain most affected in Asiatic republics. The biotype gravis has predominated. Several ribotypes were identified, but ribotypes 1-2 were commonest in the European part of the former USSR.
The resurgence of diphtheria in the NIS may be explained by (5,6):
(a) a decrease of vaccine coverage in young children, which fell to around 50% or less in some urban areas of Russia and in Ukraine. This was attributed to a loss of confidence in vaccines, which suffered some negative propaganda in the media, to an excessive number of contraindications and irregular supplies of vaccine; and to a lack of boosters in school age children and adults, which resulted in a very low protection rate in adults (less than 40% in individuals over 15 years of age in Moscow, according to serosurveys carried in 1994) ;
(b) the disorganisation of health services associated with political upheaval, resulting in a shortage of resources for the diagnosis and management of cases, and the prevention of secondary cases ; and
(c) large movements of the civil population, facilitating the spread of infection throughout the NIS, and high mobility of military personnel. On the other hand the vaccine potency was not implicated, as three doses were associated with a protective efficacy of 82% in Kiev and 96% in Moscow.
Several cases were imported from NIS into neighbouring European countries (Finland, Poland, Germany, Bulgaria, Norway) by travellers. Two cases were United States citizens staying or visiting Russia and Ukraine. In Turkey the incidence markedly increased in 1993-94, but subsequently fell to nearly zero.
Can diphtheria be reintroduced to well vaccinated European countries? Toxigenic strains of C. diphtheriae can have been imported by travellers from countries where infection is endemic. No secondary cases have yet been observed around the few imported cases in European countries. Another reassuring argument is that the health structures and resources of these countries should be able to face and rapidly control a threatened outbreak in susceptible groups or in the general population.
European countries which have eliminated diphtheria should improve their protection against the risk of reintroduction of respiratory diphtheria and strengthen control measures such as (6, 7):
(a) surveillance, clinical and biological: most physicians and biologists have never seen clinical diphtheria or isolated C. diphtheriae organism. They need education and awareness. The laboratory investigation of sore throats, particularly with a membranous appearance, should be emphasised. All isolated strains of C. diphtheriae should be sent to a national or regional reference laboratory for evaluation of toxin production and typing. Molecular typing, like ribotyping or pulse gel electrophoresis, has become essential to identify the source of the strains and to follow their movements throughout countries (4, 6) ;
(b) to restore and maintain the immune protection of adult population. In countries where the risk is higher, mass vaccination campaigns aimed at adult populations should be considered, as was carried out in Finland in 1993-94. In all countries, routine immunisation should be reinforced in adults. In order to attenuate the risk of clinical reactions after revaccination, a low dose of highly purified diphtheria toxoid combined with a full dose of tetanus toxoid (Td), should be used. Primary vaccination against diphtheria or a booster is already advised for travellers going to endemo-epidemic countries and could be recommended for some occupational groups at risk, including health care workers, teachers, and personnel who work with young children. Groups at high risk, such as alcohol and drug users, could also be targeted, but may be difficult to reach. A ten yearly booster of Td could be recommended for the general population, following the example of the United States; but the feasibility of this recommendation is questionable, and it has been suggested that monovalent tetanus toxoid should be replaced in general use by Td, whenever tetanus toxoid is indicated – e.g., after a wound.
The priority is to halt the current epidemic within the NIS. Concern extends beyond the NIS to the continent, if not the world. For their own safety, European countries have a vested interest to help NIS to control the epidemic. The WHO Regional Office for Europe (Copenhagen) played an important part (6) in coordinating international cooperation and planning control activities, such as (a) the large vaccination of the population at risk by mass campaigns (b) the proper management of diphtheria cases, including prompt recognition and confirmation by laboratory examination and their prompt treatment with antibiotics and antitoxin, (c) identification, chemoprophylaxis and surveillance of close contacts, and (d) strengthened epidemiological surveillance.
1. Galazka AM, Robertson S., Diphtheria: changing patterns in the developing world and the industrialized world. Eur J Epidemiol 1995; 11: 107-117
2. Groupe d’étude sur les infections à C. diphtheriae. Situation de C. diphtheriae en France (1987-95). Bulletin Epidemiologique Hebdomadaire 1996; 17: 78-79
3. Maple PA, Efstratiou A, George FC, Adrens NJ, Sesardic D. Diphtheria immunity in UK blood donors. Lancet 1995; 345: 963-65
4. Vincent-Ballereau F, Schrive I, Fisch A, Laurichesse H, Romasko C, Baron D, Dublanchet A, Deteix P, Rey M. Immunité antidiphtérique de la population française adulte, d’après une enquête sérologique multicentrique. Bulletin Epidemiologique Hebdomadaire 1995; 15: 65-66
5. Galazka AM, Robertson S, Oblapenko GP. Resurgence of diphtheria. Eur J Epidemiol 1995; 11: 95-105
6. Dittman S, Roure C. Plan of action for the prevention and control of diphtheria in the European Region of WHO (1994-1995) World Health Organisation, (Copenhaguen) 1994: 21 p
7. Popovic T, Wharton M, Wenger JD, McIntyre L, Wachsmuth IK. Are we ready for diphtheria? A report from the Diphtheria Diagnostic Workshop, Atlanta 11-12 July 1994. J Infect Dis 1995; 171: 765-7