Tuberculosis in Low Endemic countries
An International Seminar on "Prevention, Treatment and Research"
This seminar was held in Tokyo on 17-18 March 1997 and was attended by more than 400 health staff; doctors, public health nurses and others mainly from public health centres at the front line of tuberculosis control in Japan. The main purpose was to learn from experiences in tuberculosis control in other developed countries where the incidence of TB is already low, and to apply this knowledge to the current and to the future situation in Japan. Speakers were invited from Europe and the USA, as well as from Japan. The main points are summarized below.
"Tuberculosis control programme in low prevalence setting" by Dr. J.F. Broekmans, Director of Royal Netherlands Tuberculosis Association:
In a low prevalence situation, physicians lose TB contact experience. The general public also becomes ignorant of the disease. Politicians do not care about the disease.
In the Netherlands, the TB control budget is decentralized. Yet the public health people are still responsible for TB control and must maintain the programme for the foreseeable future until TB is eliminated. Thus, the central task is to concentrate experts and assure quality of service in municipal public health centres where preventive and curative services are available. Collaboration between chest physicians and public health centre staff doctors and public health nurses is important. Most treatment in the Netherlands is self-dministered . But some high risk groups such and homeless people require a DOTS system. Health staff must continue to work to attract the interest of the public and to maintain the necessary authority to secure funds for the programme through objective evaluation and advocacy.
"BCG Vaccination in Low Prevalence Countries" by Dr. Eero Tala, Department of Diseases of the Chest, Turku University, FinlandEven in controlled clinical trials the effectiveness of BCG has varied from 80 per cent to nil. However, the prevailing consensus continues to be that BCG vaccination at birth gives good protection against serious and often fatal forms of childhood tuberculosis.
Consequently, in high prevalence areas of tuberculosis, mass BCG vaccination programmes are indicated , although they have a low epidemiological impact.
In industrialized countries, criteria have recently been adopted to permit cessation of mass BCG vaccination, and the BCG vaccination programmes are being phased out. Only people at high risk are given BCG. At present, evidence is accumulating which demonstrates that tuberculin skin sensitivity and protective immunity are different concepts, and that environmental Mycobacterium interfere with BCG and that BCG revaccination(s) have limited value.
Criteria for and against BCG must be evaluated and decisions made at the local level. Although the current freeze-dried BCG vaccine is an improvement over the previous liquid preparations, a far more effective new tuberculosis vaccine than the existing BCG is needed if the global tuberculosis situation is to be improved by vaccination.
"New Drugs for the Treatment and Prevention of Tuberculosis" by Dr. Richard J. O'Brien, Chief, research and Evaluation Branch, Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, USA
Need for New Drugs: In tuberculosis control, there are three reasons for needing new drugs (1) to improve current treatment by providing for regimens and treatment schemes which improve compliance, (2) to improve the treatment of drug resistant cases, and (3) to provide for better chemoprophylaxis.
Drugs Related to Existing Anti-Tuberoulosis Drugs : Rifabutin, rifapentin and KRM-1648 all have a Ionger half-life and greater in vitro activity against M. tuberculosis than rifampin does. Rifabutin is approved for tuberculosis treatment in a number of countries and is being evaluated in an international trial for tuberculosis preventive therapy in HIV-infected persons. Experimental studies have suggested that, in combination with isoniazid, a 3-month regimen with weekly administration of rifapentin would be highly effective. It is suggested that KRM-1648, a long-acting rifamycin, might shorten current treatment regimens.
Broad-Spectrum Antibiotics with Anti-Mycobacterial Activity : The quinolone antibiotics such as ofloxacin, ciprofloxacin, sparfloxacin and levofloxacin are under clinical trials. Macrolide derivatives, clarithromycin and azithromycin have been approved for prophylaxis against MAC in HIV-infection. However, no macrolide antibiotics with significant activity against M. tuberculosis have been identified.
Conclusion : Without a significant change in the present environment, progress in new drug development for tuberculosis may continue to be slow. lnnovative collaborative relationships. between the public sector and individual companies, as well as provision of public funding, are required to stimulate greater private sector interest in tuberculosis.
"Epidemiological Issue in Tuberculosis in Low Incidence Countries and Challenges for a Research Agenda" by Dr. Hans L. Rieder, Chief, Tuberculosis Division of the International Union Against Tuberculosis and Lung Disease, Paris, France.
The present trend of the median age of tuberculosis patients shifting progressively to higher ages reflects that the risk of infection has been declining rapidly, sparing younger cohorts from ever becoming infected. As tuberculosis recedes, outbreaks surrounding index cases become increasingly identifiable. Furthermore, differences in disease risk between different population segments become increasingly apparent and allow more targeted interventions.
Incident rate of infection with the human immunodeficiency virus (HIV) has remained low in the general population of most industrialized countries, but is high in certain segments of the population, particularly among injecting drug users. Thus, groups at a particular risk of HIV infection can generally be identified.
Research Priorities : If all strains isolated in a society are made available for typing by Restriction Fragment Length Polymorphism (RFLP) techniques, relatedness studies can help to determine the basic reproduction ratio, i.e., the ratio between an index case and the number of secondary cases. If this ratio exceeds 1 , an epidemic ensues; if it is less than 1 , the epidemic is regarded as in decline, since each case produces less than one secondary case. Such attempts are already being made in the Netherlands and allow a much better appreciation of the dynamics of tuberculosis transmission and epidemiology.
The genome project, i.e., the complete mapping of the entire genome of Mycobacterium tuberculosis is well under the and way expected to be completed by the end of the year. Knowledge of the genome will open numerous avenues for improved diagnosis, for intervention strategies, and for the understanding of virulence. In addition to the above international guest speakers, seven national experts gave lectures on current issues in chemotherapy, BCG, chemprophylaxis, contact screening, patient follow-up, tuberculosis control in urban areas, and HIV/TB.