Diphtheria.

Diphtheria* 1. Brief description of the condition/disease Before thic development of a vaccine. diphtheria was a major cause of morbidity and mortality among cbil- dren in lemperate climates. espccially in crowded urban areas. evcn after the introduction of ani anti- toxin in the 1890s reduced thc mortality for severe cases Crom 25-50% to 5-10%. DiphLteria is caused by toxigenic strains of Corynebacteriwim diphtlieriae: these strains carry a phage coding lor the toxin and are transmitted Irom hunman to human primarily by infected secretions from the respiratory tract and skin lesions Absorp- tion of the toxin causes severe tissue damage locally in the respiratory tract. heart and peripheiat nerves, resulting in fatalities due to obstruction ot the air- way, myocalditis, and diffuse polyneuntis 2. Current global burden and rating within the overall burden of disease Almost complete elimination of diplitheria has been noted in developed countries atter childhood vacci- nation coverage against diphthleria reached 70-80%. Many European countries have not reported cases in more than a decade: almost all tlhe rare cases in otlhers are lnked to known importation. In the USA during 1980-95, only 41 cases were reported. and all excepl one of the culture-provsenl cases since 1990 were linkcd to known importation Low ilncidence and lack of epidemics persist in these countries de- spite the gradual accumulation of largc numbers of adults who are susceptible because of wanino vaccine-induced immunity. Many developing countries do not have reliable incidence data on diphtheria because of the need for laboratory diagnosis and good sunreillance systems. However, the disease burden appears mucb smaller for diplhtheria than lor measles or dcarrhoeal disease Cases reported from developing counlLnes have de- creased dramatically as coverage with three doses of DPT (DPT3) increased (from 46% in 1985 to 79% in 1992), accounting for most of the global decrease during the 1970s and 1980s (77040 cases in 1974 and 23557 in 1988). Contnbuted by Charles Vitek and Jay Wenger Centers for Dis- ease Control and Prevention Atlanta. GA USA. However. during the 1990s. diphtheria has resurged in both developed aiid developing coun- tries where it had been well conLtrolled An epidemic that began in 1990 in. the Newly Independent States (NIS) of the Former USSR caused almost 150000 reported cascs and 5000 cleaths by the end of 1996. Before aggressive vaccination campaigns during the epidemic. coverage of DPT3 was <80% among in- fants and <25% (or recelpt of a booster dose among adults. Overall, most reported cases and fatalities occuired in adults. Control has been achieved in mosL NTS by achieving unprecedented levels of adult immunization in addition to intensilying childhood immunization. Developing countries, such as Ecua- dor (approximately 400 cases in 1993-94) and Algeria (approximately 1000 cases in 1992-96), have also reported outbreaks after periods of good control folloving implementation of childhood im- muniization programnmes. Circulation of toxigenic strains of C. tdiplhtlheriae persists in parts of both developed and developing countries where diphthena is not being reportcd. For exanmple. a focus of toxigenic C. cliphlt1eriae was found in South Dakota in 1996 withl imiolecular analy- sis of strains suggCsti6g local persistence since the 1970s: and a recent serological study in rural Kenya showed hiolh diphtheria immunity among unvac- cinated persons. suggzesting continued circulation. 3. Feasibility (biological) of eliminationleradication Eradication is not currentlv feasible because prelinii- nary evidencc suggests that circulation of toxigcilc C diphtlreiiae mighlt persist. even in populations with fairly hiah childhlood immulunization coverage, and mLglht be difficult to detect: and sustainable res- ervoirs foi the toxin gene might exist in iionhuman mammals. Future feasibility depends on understand- ing prevention ot continiued cilculation and evidence that circulation ot the toxin gene in the animal reser- voirs is not sustained indefinitely Four facLors favour eradication: humans are the only known sustained reservoii: an incxpensive and sate toxoid vaccine exists: high coverage with this vaccinie appears to reduce circulation of toxigenic strains of C. diphdtreiriae in the human population and to prcvent disease; and seasonality exists for both respiratory anid cuLaneous diplitheria, making transmission of toxigeniic sttains morc vulnerable to inLerrupLtoii. Bulletin of Ui6 World Health Organizabon, 1998, 76 (Suppi 2) 129-130 129 Diphtheria Seven factors could hinder eradication: the phage carrying the toxin gene can occasionally be found in nondiphtheria Corytebacternm species infecting animals (this may represent an ineradi- cable reservoir tor reintroduction of toxin gene into non-toxigenic C diphtheriae strains): infection with a toxigenic strain can either be direct or zn situ by a phage carrying the toxin gene, infecting a commensal non-toxigenic C. diphthenrae strain: an asvmptomatic carrier state exists, even among immune persons, and circulation appears to be able to continue under some settings. even in populations Nvith fairly high childhood immunization rates; immumty to diphthe- ria is not life-long (a minimumn of three doses is required for etfective primary immunization, and pe- nodic booster doscs are required throughout adult life to maintain protective titres - in addition, im- mune persons are not distinguishable from suscepti- ble persons except by serological or Schlck testing: in countries with low incidence, both the clinician and the laboratory can easily miss the diagnosis ot diphtheria, and empirncal antibiotic treatment can prcvent recovery of the organism; limited epide- miological, clmical, and laboratory expertise is avail- able on diphtheria; and political will may be lacking because the discase burden is low in developed coun- tries and is perceived to be relatively low in develop- ing countries. could require some level of coverage of the adult population (as suggested by the recent epidemic m the NIS). For eradication. high coverage and high socio- economic standards in many temperate-zone countries appear to have interrupted circulation of toxigenic C. diphtheriae. It is unclear whether this strategy is applicable to developing countries, espe- cially those with lower socioeconomic conditions. 6. Research needs For elination, knowledge is needed of the level of vaccine-induced Immunity among both children and adults which is sufficient to prevent circulation of toxigenic strains in the population and to provide herd immunity in both developed and developing countnes. In addition, knowledge is needed of the epidemiological effect of widespread vaccination in developing countries. For eradication, knowledge Is needed about whether carriage of the toxin gene among zoonotic Corynebacteriuim strains is stable enough to make eradication impossible and the tactors that allow persistent circulation of toxigcnic strains despite fairly higlh levels of childhood vaccination. 7. Status of elimination/eradication 4. Estimated costs and benefits of efforts to date e 1 n1111ha lniJGrauInutUi i Near eliminiation could be achieved with full imple- mentation of EPI. Benefits of diphtheria elimination are difficult to estimate in the absence of good data on disease burden in many developing countries. Developed countries would have fewer imported cases. The benefits of full implementation of EPI would extend to the other childhood diseases. Be- cause an etlective strategy for eradication is un- known. costs have not yet been calculated 5. Key strategies to accomplish the objectives For climination, implcmentation of the EPI pro- gramme (>90% coverage with DPT3), coupled with childhood boosters, might allow near elimination of tlie disease. Maintenance of the disease-frec state Implementation of EPI has achieved remarkable progress in decreasing the burden of disease in coun- tries where reliable data are collected. 8. Principal challenges to elimination/eradication The principal challenges to elimination are lack of adequate data about the schedule of childhood and adult boostcrs which can prevent the disease reli- ably. and ditficulties in global implementation ot EPI and the necessary booster schedules. The principal challenges to eradication are lack of data that toxigenic C. diphtheriae can be eradi- cated with the current vaccine under the present socioeconomic conditions in which much ol the global population lives. and lack of consensus that diphtheria is an important problem globally. 0WHO Bulletin OMS Vol 76, Suppl 2 1998130