Report of the Workgroup on Bacterial Diseases.

Report of the Workgroup on Bacterial Diseases A.R. Hinman1 Introduction The Workgroup felt that 14 factors should be con- sidered w%hcn discussing the potential feasibility of elimination or eradication of any disease These par- tially overlap but further expand on the seven issues named in the "Framework for considerng candidate conditions." The list comprises the following: dis- ease burden: existence of an effective intervention; surveillance/diagnosis mechanism: commonality of delbvery; cost-effectiveness: demonstrated effective- ness ot the programme; contribution to overall infra- structure; existence of a delivery infrastructure; barriers; roles of technology; existence of nonhuman hosts; time trame: significance of imported cases: and strategies to be followed. The results of the pre-Conferencc survey were discussed. The top 10 conditions identified in the survey, in rank order, were as foUlows: neonatal tetanus; Haemophilus influenzae type b ([I-b) infec- tion; leprosy: diphthena; pertussis: tuberculosis (TB); meningococcal disease: congenital syphilis: trachoma: and syphilis. None of these conditions was considered eradicable in the imediate future. al- though several were thought to be candidates for national or regional elimination. Several conditions brought up in the survey were deemed important but not currently amenable to elimination or eradication. Consequently. they were not considered turther. For diphtheria arnd pertussis, it was felt there was an incompletc under- standing of the epidemiology of the disease and transmission as well as inadequate surveillance systems. Additionally. there was uncertainty as to whether the available interventions could achieve elimination. Meningococcal disease is an important condition tor which effective interventions are under development and, in a fcw years, it may well be a candidate for elimnination. Thc same can be said for pneumococcal disease, which was not mcluded in the top 10m the survey but is very importaiit because of its high incidence. Regional elimination of typhold may be feasible but has not been demonstrated. For each of these conditions. improved control is botl feasible anld necessarv. The Task Force for Child Survival and Development One Copenhill, Atlanta, GA 30307, USA. Subgroups were formed to discuss neoniatal tetanus, Hib, TB (aud leprosy). and syphilis (both acquired and congenital. with some consideration of chancroid). and trachoma. In the discussions, a con- tinuum of levels of disease incidence was considered, ranging trom the situation in which disease occurs uncontrolled to a level of control which, with addi- tional effort. becomes "very good control". The tran- sition from very good control to elimination is likely. to require considerable additional effort, in terms of both programne interventions and surveillance. Elimination is a stage which will take major effort to maintain, which will be more difficult the more com- mon the disease is in other parts of the world and the more transmissible it is. In general. elimination should be viewed as a stepping stone to eradication and considered senously only when eventual eradi- cation seems possible. Neonatal tetanus This is a significant problem. with an estimated 490 000 deaths per year (a global rate of 6.5 per WOOO live births). Actions taken to reduce the occurrence of neoniatal tetanus would have other positive mi- pacts on health and health carc systems, including decreased neonatal mortality and naternal mortality (from other conditions as well as maternal tetanus). Eradication is clearly not feasible, given the ubiqui- tous distribution of ClostridiuLm lean spores in the soil. Using the strictest definition. elimination also cannot be guaranteed, although radically improved control is possible and should be a high pnority. The W1HO eliination' goal of an incidence of <I per 1000 live births in everv distLrct iS attainable. Achievement of this goal will require fuller imple- mentation of a three-pronged strategy: vaccination of women of childbearing age. clean delivery, and application of topical antimicrobials to the um- b1lLcal stump. The last-mentioned component is niot being sufficicntly emphasized at present. Because ot the combined nature of the strategies, very close collaboration between the Expanded Programme on Immunization (EPI) and Maternal and Child Health (MCH) programmes wll be needed to achieve the goal Since eradication is nol feasiblc and interven- tionis will need to be continued indefinitely, vertical approaches are insufficient; nieonatal tetanus control efforts will need to be integrated into developing Bulletin of the World health Organizaton. 1998, 76 (Suppi 2) 85-88 85 A.R. Hinman comprehensive care systems. Substantial research needs remain, from ongoing monitoring of immunity levels in girls attaining childbearing age to develop- ment of more effective (possibly single-dose) vaccines. Haemophilus influenzae type b (Hib) infection In most parts of the world, the burden of Hib infection has been documented and is of comparable severity. However. in some Western Pacific coun- tries (e.g. China. Republic of Korea. Japan) the severity of this burden is not yet clear. Current estimates are that there are 380000-600000 deaths per year globally among under-5-year-olds as a re- sult of Hib infections. Although case management is an important strategy to reduce mortality, it does not have a significant impact on transmission; consequently. the primarv intervention is vaccination. Results from introduction of HILb vaccine have been dramatic in both industrialized and developing countries. The (unexpected) impact of Hib vaccine in reducing carriers of Hib has raised possibilities of elimination/eradication which were previously not considered. In the USA, United Kingdom, and several other industrialized countries. Hib infections have virtually disappeared (>95% reductLon) within 4-7 years after introduction of universal vaccination of infants/young children. The disease appears to have been eliminated in Iceland and Fin- land. In both Chile and the Gambia dramatic results have been seen. and in the latter country there was also a nearly 25% reduction in the incidence of lobar pneumonia among young children following intro- duction of vaccination. Whether this finding will be replicated in other countries is currently under study. A major barrier to the wider use of Bib vac- cine is its current price: at more than US$ 1 per dose, it may not be cost-effective for introduction in developing countries. Fortunately, it appears that the different formulations of Hib vaccine are inter- changeable in terms of safety and efficacy. Important research questions include better estimation of the disease burden (especially in south-east Asia), the need to document changes in carner rates before and after introduction of vaccine, and the impact of infant vaccination on the reservoir of Hib in older age groups. If the disease burden is such as to justify global use of the vaccines and if vaccina- tion has an impact on carrier rates in adults, eradication might be feasible in the relatively near future. Tuberculosis Tuberculosis (TB) is currently the leading infectious cause of death in the world, with 2-3 million deaths each year. A three-pronged strategy has been adopted for control of this disease, including case management, vaccination, and preventive therapy. Case management is currently the essential activity of TB control, and the highest priority is given to providing a short course (3-6 months) of directly observed therapy (DOTS) to infectious cases (those wvith tubercle bacilli demonstrated on microscopic examination of the sputum), with guaranteed supply of drugs. This strategy has been shown to result in high cure rates and is feasible. even m developing countries. BCG vaccination in infancy prevents a substantial proportion of disseminated tuberculosis in childrcn (e.g. TB meningitis), but has little impact on TB transmission or incidence in adults. Preven- tive therapy. administered to persons who are in- fected with TB (i.e. tuberculin-positive) but who have not developed disease, is highly effective in preventing development of the disease and is an im- portant strategy to be introduced once a sufficiently hlgh proportion of diagnosed (i.e. infectious) cases are being effcctively treated. The unfortunate interaction between tuberculo- sis and HIV infection (in wbich each exacerbates the other) means that the TB problem will deteriorate further in countries which now suffer most from either TB or HIV (e.g. in sub-Saharan Africa and south-east Asia). In addition. multidrug-resistant TB is an increasing problem in many areas, including the Newly Independent States of the Soviet Union and the Russian Federation. Research needs includc development of a more effective vaccine, improve- ments in preventive therapy. better understanding of latent infections and the existence of a possible animal reservoir. and demonstration that elimina- tion is feasible in a defined geographical area. The US "elimination" target of an incidence of <1 case per million population does not meet the Dahlem criteria. Improvements in TB control depend on (and contribute to) general health infrastructure. A long-term (>70 years) goal of elimination/eradica- tion may help retain focus on thcse eftorts. Leprosy There are approximately 500000 new cases of lep- rosy each year. occurringm geographically restricted areas; 90% of all cases occur in 15 countries. Current interventions focus on finding cases of leprosy and administering directly observed multidrug therapy for 6-24 monlths (depending on the type of leprosy) WHO Bullehn OMS Vol 76, Suppl 2,199886 Report of the Workgroup on Bacterial Diseases and on the use of BCG vaccine. An "elimination" goal has been established. with the target being an incidence of <1 case per 10000 population. Neither elimination (using Dahlem definitions) nor eradica- tion is feasible, although there are important oppor- tunities for improved control. Some of the barriers to improved control include insufficient knowledge of lbe epidemiology. pathogenesis, and transmission of leprosy (including carriage and incubation period) and the difficulty in growing thc organism in the laboratory. Syphilis Approximately 1 mtllion pregnancies each year are complicated by syphilis. EliminatLon of congenital syphilis in some geographical areas was considered feasible. but not eradication - more because oC weaknesses in the healtli care delivery system than because of faults with the intervention. The same strategies used to attain control and very good con- trol over congenital syphilis should also be adequate to achieve elimination. but with a considerably higher cost. These strategies are as followvs: to exam- me pregnant women at their first prenatal visit, per- form an on-site diagnostic test, treat those who are positive and their partners, and take a systematic approach to reduce adult syphilis through diagnosis and treatment of cases of genital ulcer disease. The antenatal care infrastructure necessary tor pre- ventioin of congenital syphilis is the same as that necessary for prevention of other pennatal condi- tions such as neonatal telanus and iron deficiency anaemia. Improvemnents to the infrastructure will benefit reproductive health services for women overall. Elimination cannot be acbieved stnctly througl approaclhes to pregnant women. but also requircs activities to prevent and control acquired syphilis in adults. Syndromic approaches to management of genital ulcer disease (pnmnarily syphilis and chancroid) can also have a significant impact on de- creasing the transmission of HIV. A goal of "elimi- nation" from the Region of the Americas. which does not meet the Dalilem definiition has been estab- lished by the Pan American Health Organization. True elimination in the Americas was felt feasible in the next 5-10 years. Elimination of adult syphilis was not considered programmatically feasible at prcsent, although substantial improvements in surveillance and control are both feasible and necessary It is possible that mass therapy in high prevalence areas could be quite effective i unprovmg control. as it was wth yaws. Research needs include development of less invasive diagnostic techniques. effective single-dose oral therapies and vaccines. as well as operational research. Althoughl elinmnation of chancroid might be biologically feasible, it does not seem programmati- cally attainable at present. Factors favourng the po- tential for elimination include availabilitv of effective oral therapy: clinically apparent. sympto- matic disease; a relatively short period of transmissi- bility; and a high concentration of disease in core transmission groups. Pilot efforts to eliminate chancroid could be undertaken as part of the genital ulcer disease component of congenital syphilis elimination. Trachoma Trachoma is the leading preventable cause of blind- ness worldwide. with an estinmated 5.9 million per- sons blind or at immediate risk becausc of tnchiasis. Trachoma accounts for nearly one-sixth of the global burden of blindness: women are affected dis- proportionately. Genital strains of Chlan2ydia trachornatis do not infect the eye. Effective interven- tions have been demonstrated in developLng coun- tries to have a major impact on blindness due to trachoma using the "SAFE' strategy - Surgery to correct lid deformity and prevent blindness, Anti- biotics for acute infections and community control, Facial hygiene, and Environmental change. includ- ing improved access to water and sanitation, and health education. An "elimination" target of 2020 has been estab- lished by an intemational alliance but does not meet the Dablem definition. Elimination of blindness due to trachoma is considered feasible: eradication of trachomna is not. Research needs include validation of rapid community assessment techniques, identifi- cation of barriers to the arceptance of the preventive surgical procedure, operational research on the effectiveness of annual treatment cycles, and cost- benefit and cost-effectiveness studies. Conclusions and recommendation * Each of the above conditions has a significant disease burden. most notablv in developing countries. * Each of these conditions has an effective interven- tton with at least some existing infrastructure to deliver it. but many of the interventions are not optimal. * Each condition is poorly controlled globally. WHO Bullebn OMS. Vol 76, Suppl 2, 1996 87 A.R. Hinman * Each condition has surveillance techniques available. although they may not be in place in all areas. * None of these conditions is a candidate for eradi- cation in the next 10-15 years with current inter- ventions. Hib infection and congenital syphilis are currently candidates for regional (but not global) elimination. The long-term vision for Hib infec- tion and tuberculosis is eradication (for TB, this would require decades); for congenital syphilis and trachoma the long-term vision is regional cimination. * Effective control or elimination of most of these conditions requires a combination of strategies, rather than a single strategy such as vaccination. * Iinproved control or elimination of each of the conditions is closely related to existing health care delivery systems, rather than a vertical approach. However, it is important that health workers be identified and made responsible for achieving the goals. even though they have many other responsi- blhties (the concept of "designated" but not "dedicated" personnel). a Public education and social mobilization are im- portant factors in improved control or elimination! eradication for each of these conditions. * Behavioural modification is an important factor for the control of most of these conditions. v There are many research needs for each of the conditions which must be addressed before eradi- cation could be attempted. These range from the need for improved understanding of the epidemiology of disease to developing improved interventions and improved strategies to delivcr interventions. * Elimination is expensive, both in the extra effort needed to achieve zero incidence and in the sur- veillance system needed to document zero inci- dence. * Unless elimination is a step on the road to eradica- tion, very good control may be a more appropriate goal This would potentially allow broader use of the additional resources which may be required for elimination. * Public health institutions have been imprecise in their use of the term "elimination", often using it to indicate very good control (e.g. "elimination as a public health problem"). Several incidence goals have been set and labelled as elimination goals which do not meet the definitions agreed at the Dahlem Workshop. Efforts should be made to use this term precisely. None the less, it is important to set specific targets for control activities ("control with a goal"), which could encompass some of the targets currently labelled as "elimination" (e.g. global goal for neonatal tetanus, U S. goal for tuberculosis). Given all these tactors, the Workgroup re- commends that, while actively pursuing the researchl needed to improve our understanding of these dis- eases and our interventions for dealing with them, the global community should take aggressive action to improve global control of neonatal tetanus, Hoemophiluis inflienzae type b infection, tuberculo- sis. leprosy, congenital syphilis, and trachoma. Acknowledgements Thanks are due to Helen Makela and Sunadi Gunawan (Co-Chairs), and to Ken Castro, Joe Cook, Lyn Finelli, Dace Madore and Rebecca Prevots (subgroup rapporteurs) for their special contnbution to this report WHO Bulletin OMS Vol 76 Suppl 2 1996so