Candidate bacterial conditions.

Candidate bacterial conditions M.L. Cohen' This article provides background information on bacterial diseases and discusses those that are candidates for elimination or eradication. Only one disease, neonatal tetanus, is a strong candidate for elimination. Others. including Haemophilus influenzae b infection, leprosy. diphtheria. pertussis. tuberculosis, meningococcal disease, congenital syphilis, trachoma and syphilis are important causes of morbidity and mortality in industrialized and developing countnes. For all these diseases, eradication/elimination is not likely because of the characteristics of the disease and lmitations in the interventions. Background In 1900. infectious diseascs - especially bactenal diseases - were the leadinig cause of morbidity and mortalitv, and diseases sucih as tuberculosis and pneumococcal infection were called the "Captain of all these men of death". A series of factors tllat be- gan in the 16th and J7th centuries and extended irnto the 20th century greatly influenced the frequency o( infectious diseases. These factors included improve- ments in hygienc and sanitation, better housmg and nutrition, and safer food and water- the technologi- cal advances of the 20th century include use of vaccines and antibiotics. It is important to emphasize that. parLicuilaily foi bacteria] diseases. any reduc- tion in their trequencv is multi(actoilal and related to both specific and noDspcCific changes. For example, examination of the estimated aind reportcd mortality tor tuberculosis m England from 1700 to 1920 shoivs a peak around 1770 at a iate of 700 per 100000 - carnying a nearly 1% chance pei year of dying of tuberculosis. 1By 1920, the mortality rate had decreased to less than 50 per 100000. This decline preceded the introduction of BCG and anti- tuberculosis chemotherapy. Thus, factors such as improvements in nutrition, decreased crowding and better hygiene and sanitation were nmajor contribu- tors to the reduction in the incidcncc of tuberculosis. As we approach the 21st ceitury, bacterial diseases ancd infectious diseases in general are no longer the leading causes of death in the developed world. ex- cept for certain conditions (e.g. heart disease) which may hlave a significant infectious etiologv. as is cur- rently being discusscd. Globally. however, the per- spective is different. For example. in 1992. almost 20 million deathls were caused by infectious and para- sitic diseases. whiicJh WHO estiniates to ha\e bccn I Director, Division of Bacterial and MycoLic Diseases National Center for Infectious Diseases Centers for Disease Control and Prevention, Atlanta, GA 30333, USA the leading cause of deathi worldwide. Bacterial dis- case (e.g. tuberculosis aud othler iespiratory and diarrhocal diseases of bacterial etiology) accounted for more tbaln half of these deaths. Bacterial diseases are not static but include newly emerging dLseasCs. re-emerging diseases that were once thought Lo be conquercd. and diseases that showv changes of antimicrobial resistance. For example, in the last two decades. bacteria] diseases have been newly recognizcd. includincg Legionnaires' disease, toxic shock svndrome. Lynie disease. cam- pylobactenosis, Escherichia coli 0157: H7 intections. helicobacter infections associated with peptic ulcer disease, and Bartonella infections associated with cat scratclh disease. Cholera is an examnple of a ic- emerging disease in the Westerin hiemispherc which, since 199L has caused over a million cases and 10000 deaths. Other diseases, such as meningococcal intec- tions. Salmonella enierifidis ilnfcctions associated with) slheLleggs, foodboriie listeriosis. and tuberculo- sis have increased in frequency. in some instances in both the industrialized and developing world. Antimicrobial resistance, once thought to be prima- rily a problem o( hospital-acquired infections, is also a particular problem anmong comimunlt- acquired infectLon1s. In the hospital, there are strains of enterococci and tuberculosis that are essentialiy untrealable with antLimicrobials. and strains of Staphylococcius auoreuts that have become relalively rcsistant to vanconvcin - the last effective antimi- crobial for many, of these strains. In the community, drug-Tesistant infections witlh pneumococci. salmo- nella. slhigella. and gonococci liave become impor- tant public lhcalth problems. For example, strains of Shiigella dysente7rae IA in parts ot the developing world have become resistant to almost every oral antimicr-obial agent. Mlanv strains of multidrug- resistant pneumococci aie only susceptible to vaancomuvciin One final point involves tllc ofteni unexpected consequences of chlanges that either intentionally or unintentionally affect the frequency of bacterial dis- Bulletn of the World Health Organizatbon, 1998. 76 (SuopI 2): 6'-63 81 M.L. Cohen cases. In the latter part of the 19th century and into the 20th century, eflorts were made to improve hy- giene and sanitation in many parts of the developed world. In Germany, for example, with mcreases in the number of homes in Frankfurt-am-Main that were connected to sewvers and water mains, the death rate from typhoid fever rapidly decreased. However. an unexpected impact of such improvements in hy- giene and sanitation in the developed world resulted in postponement or prevention of the exposure of many parts of the population to poliomyelitis, creating a population susceptible to epidemics and paralytic cdsease at a later age. Thus, efforts to elimi- nate or eradicate one disease may have important implications for another. Candidate conditions Based on the responses trom the conference partici- pants to identify potential candidates lor elimination or cradication, only one bacterial disease- neonatal tetanus - was felt to be a strong candidate for elimination There was relatively little difference in support for other bacterial diseases, includmg HIaenophitus influenzae b uifection, leprosy. diph- thera, pertussis. tuberculosis, meningococcal dis- ease. congenital syphilis. trachoma. and syphilis. The low level for most bacterial diseases relates. in part, to various deficiencies in the criteria for elimination or eradication. For many of these dis- eases, there are either inadequate diagnostic meth- ods or inadequate interventions. or there are reservoirs that persist in the environmcnt or animal populations. Thus, for most bactenal diseases, eradi- cation is not ieasible and elimination is extremely complicated. Neonatal tetanus- the one potential candidate for elimination - is a devastating illness caused by infection with Clostrridin tetann. usually of the umbilical stump. The case-fatality ratio for this infection is greater than 80% and It ranks second only to measles as a cause of childhood mortality among the vaccine-preventable diseases that are mncluded in the Expanded Programme on Immuniza- tion. It is estimated that annually there are over 490000 deaths trom neonatal tetanus, accounting lor a global mortality rate of 6.5 per 1000 live births. Effective interventions include vaccination coverage with two doses of tetanus toxoid among women of childbearing age in high-risk areas. This approach. coupled with efforts to promote clean delivery and core care practices, as well as evaluation of the role of topical antimicrobial agents. provides a potential to eliminate this disease. Elimination goals have been set by WVHO and, between 1980 and 1995, the number of developing countries that eliminated nconatal tetanus increased from 38 to 97. Haemophtlus znfluenzae is also an important cause of global morbidity and mortality. causing meningitis. pneumonia, and septicaemia. In the USA, prior to the mtroduction of conjugate vaccines. an estimated 1 in 200 children were af- fected by age 5 years. At present. the estimates of the global burden of disease range from 380000 to 600000 deaths annuallv in children aged <5 years. The potential for eliinuation or eradication of this disease has been supported by the mtroduction of effective conjugate vaccines. These vaccines have lcd to a significant reduction in the incidence of invasive Haemnophilus influenizae type B disease in the devel- oped world (e.g. in the USA, >95% reduction). In additLion, in several industrialized countries. the vac- cine has led to significant reduction in the carriage rate of this organism. Even though these achieve- ments suggest that etfective use of the vaccine may lead to global eradication of related disease, several barriers persist. including its hlgh cost and the lack of data on both the effectiveness and the impact on carriage in developing countries compared with thc developed world. Leprosy (Hansen's disease) is an ancient prob- lem whose control has long been complicated by an incubation pernod that can range from 2 to 40 years. Although the disease appears to have low intectivitv, there remain questions about the occurrence of transmission. including the relative importance of person-lo-person and environmental transmission. The current prevalence ot the disease is greater than 1.1 million, a substantial decline trom the 10-12 million in recent years. None the less, 500000 new cases occur annually. predominantly in 55 countries throughout the world. Perhaps the greatest impacl on this diseasc has been the demonstrated effective- ness that rnultidrug therapy is curative. In contrast to the previous life-long therapy of patients infected with its causative agent, Mkycobacrerium leprae, multidrug regimens are curative within 6-12 months. Although. these regimens have raised optimism for elimination of leprosy, there arc. as with any chronic multidrug therapy. issues of compliance and microbial resistance. Diphtheria had been under good control m most developed countries until the early 1990s whenl it rcsurged, particularly in the Newly Independent States of the tormer Soviet Union. Although the specific explanation for this resurgence is unclear. contLnued circulation of toxigenic strains and waning immunity in adults have been postulated as possible explanations. Interventions include an inexpensive and safe toxoid and a pattern of seasonal transmis- WHO Bullelin OMS Vol 76, Suppl 2,199862 Candidate bacterial conditions sion that presents the opportunity for interruption of transmission. Pertussis is also an important cause of global morbidity and mnortality accounting annually for 39 million cases and 355000 deaths. Although intervention is part of routine infant immunization programmes, immunization does not prevent car- riage or circulation of the strain in the community and currcnt schedules do not provide immunization for adults. Thus, waning immunity in adults. continu- ing carriage, intection and disease limit the eflective- ness of interventions In addition. diagnostic tests are of limited effectiveness and the lack of surrogates for protection complicate the development of new vaccines. Congenital syphilis is another candLdate for elimination. There is an estimated 70% probability of transmission from an infectcd pregnant woman to the fetus. Over 900000 infected pregnancies occur globally each year, resulting in 360000 fetal or perinatal deatbs and the births of270000 infants with serious or permanenL impairment The intervention strategy involves tesling of all pregnant women for syphilis and the treatmenL of all positives with pcni- cillin. Penicillin remains an excellenl intervention tool since it is both inexpensive and the spirochacte has not developed resistance Most of the issues that could affect elimination of this disease are operational Conclusion Bacterial diseases remain an important cause of morbidity and mortality in both the developed and the developing world. The emergence ot new and re-emeroence of old bacterial diseases, and the de- velopment of antimicrobial resistance pose substan- tive challenges to public bcalth. For most bacterial diseases, eradication is not likely and any plans for elimination are complicated by the characteristics of the disease and limitations in intervention. WHO Buietin OMS. Vol 76, Suppl 2, 1998 63