ORIGINAL ENGLISH UNEDITED E68515 WHO REGIONAL OFFICE FOR EUROPE REPORT ON A JOINT REVIEW OF TUBERCULOSIS IN UKRAINE Ministry of Health, Ukraine Research Institute for Pulmonology and Phthisiology, Ukraine Kiev City Tuberculosis Dispensary, Ukraine US Agency for International Development US Centers for Disease Control and Prevention International Federation of Red Cross and Red Crescent Societies Management Sciences for Health World Health Organization 6 15 December 1999 SCHERFIGSVEJ 8 DK 2100 COPENHAGEN Ø DENMARK TEL.: +45 39 17 17 17 TELEFAX: +45 39 17 18 18 TELEX: 12000 E-MAIL: POSTMASTER@WHO.DK WEB SITE: HTTP://WWW.WHO.DK 2000 EUROPEAN HEALTH21 TARGET 7
EUROPEAN HEALTH21 TARGET 7 REDUCING COMMUNICABLE DISEASES By the year 2020, the adverse health effects of communicable diseases should be substantially diminished through systematically applied programmes to eradicate, eliminate or control infectious diseases of public health importance (Adopted by the WHO Regional Committee for Europe at its forty-eighth session, Copenhagen, September 1998) ABSTRACT The tuberculosis (TB) epidemic in Ukraine has reached emergency proportions. Drugresistant TB is increasing rapidly. The economic decline following independence has led to increased poverty and difficulties in maintaining treatment services. There is also a growing epidemic of HIV. Against this background, the Government of Ukraine requested assistance from WHO, with a team of international and national experts, in conducting a review of the TB situation in December 1999. The team noted the clear commitment to the directly observed treatment, short course (DOTS) strategy (the WHO recommended TB control strategy) at every level in Ukraine, including in prisons. Successful implementation of this strategy will require radical changes to the financing of TB control services and to current policies for diagnosis, treatment and monitoring. The team recommended that a plan should be drawn up for nationwide coverage by DOTS by 2003, including the designation of pilot sites in Kiev city and Chernigev and Donetsk oblasts, the development of technical and operational guidelines based on the DOTS strategy, the identification of sources of funding, the appointment of a WHO medical officer to give technical assistance, the establishment of appropriate management personnel and systems, and the holding of a national TB drug resistance survey. Keywords TUBERCULOSIS prevention and control HEALTH SERVICES organization and administration FINANCING HEALTH HEALTH POLICY DRUG THERAPY PRISONS UKRAINE World Health Organization 2000 All rights in this document are reserved by the WHO Regional Office for Europe. The document may nevertheless be freely reviewed, abstracted, reproduced or translated into any other language (but not for sale or for use in conjunction with commercial purposes) provided that full acknowledgement is given to the source. For the use of the WHO emblem, permission must be sought from the WHO Regional Office. Any translation should include the words: The translator of this document is responsible for the accuracy of the translation. The Regional Office would appreciate receiving three copies of any translation. Any views expressed by named authors are solely the responsibility of those authors. This document was text processed in Health Documentation Services WHO Regional Office for Europe, Copenhagen
CONTENTS Summary...1 Introduction...1 Observations...1 Conclusions...3 Review methodology...3 Background information...5 Epidemiology of tuberculosis...6 HIV/AIDS...8 Anti-TB drug resistance...9 Structure of tuberculosis control services...9 Organization of health services...9 Coordination with other agencies...10 Health care financing and the economics of tuberculosis control...12 Health sector reform...13 Financial implications of DOTS...13 Policy and practice...14 Diagnosis and laboratory services...14 Treatment...16 Drug management...17 Information management...21 Training...23 Research...23 TB in prisons...25 Prison health infrastructure...25 Diagnosis and treatment...25 Logistics and information management...26 Prison reform...26 DOTS in prison...26 Annex 1 Programme and teams for field visits...28 Annex 2 Places visited and people met...29 Annex 3 Costs of TB services...33 Annex 4 Field visit report Donetsk...37 Annex 5 Field visit report Chernigev...46 Annex 6 Press release (in Russian)...50 Page
page 1 Summary Introduction The tuberculosis (TB) epidemic in Ukraine has reached emergency proportions. The number of cases of TB (all forms) reported annually has increased by 73% since 1990 from 32 to 55 per 100 000. Drug-resistant TB is also increasing rapidly: preliminary results indicate that half of all patients are resistant to at least one drug, and multidrug resistance (resistance to isoniazid and rifampicin) is present in 10 15% of new cases. This situation has been brought about by a combination of factors. Case notification rates fell until the late 1990s as a result of a comprehensive and effective (although inefficient) TB control system, which included active case-finding, prolonged hospitalization and regular use of preventive therapy and seasonal anti-relapse treatment. The economic decline that followed independence has led to increased poverty and difficulties in maintaining treatment services, although active case-finding and hospitalization have continued. In the health service, the combination of active case-finding, hospitalization, inadequate treatment, irregular drug supply and lack of direct observation of treatment has led directly to the epidemic of drug resistance. TB services are centralized to rayon (district) and oblast (region) dispensaries, which reduces access to care, results in late presentation with extensive disease, and contributes to the high default rate. The situation is potentially worsened by the growing epidemic of HIV. The number of HIV-positive people detected increased dramatically in 1995 and by 1997 had reached nearly 9000 a year. Over 1200 adults and 50 children have been diagnosed with AIDS and over 500 people have died; 30% of adults diagnosed with AIDS and 50% of adults who have died from AIDS had TB. Recognizing the urgency of this situation, the Government of Ukraine requested assistance from the World Health Organization (WHO) in conducting a review of the TB situation. The review took place from 6 to 15 December 1999, with a team of international and national experts, and included field visits to dispensaries and other health institutions in Donetsk and Chernigev oblasts and interviews with senior officials in government departments and international agencies in Kiev. Standardized data collection tools were used to assess the structure, process and outcome of TB control services in the institutions visited. Observations The review team members were impressed by the clear commitment to the directly observed treatment, short course (DOTS) strategy demonstrated at all levels and in different health service providers, including the Ministry of Health, academic institutions, Kiev City Administration and the State Department of Prisons. This is reflected in the desire to establish DOTS pilot projects rapidly in oblasts, Kiev City and prisons, and to include training on DOTS for medical students and in continuing medical education for doctors. However, successful implementation of DOTS will require radical changes to the financing of TB control services and to the current policies for diagnosis, treatment and monitoring. TB dispensaries at oblast and rayon levels provide most TB diagnostic and treatment services. Not all rayons have dispensaries. Some general hospitals also have TB departments. The budget for dispensaries comes from local oblast and rayon administrations and has declined in recent years,
page 2 resulting in delays in salary payments, shortages of drugs and laboratory supplies and inadequate maintenance of buildings and equipment. Active case-finding has continued despite severe resource constraints. Up to 50% of the adult population aged 15 years and over is examined annually by mass miniature radiography (fluorography), and children are tuberculin-tested twice a year up to the age of 17 years. TB is frequently diagnosed on the basis of X-ray alone, even without clinical signs and symptoms. Although laboratories are well staffed, their resources are limited, equipment is obsolete, there are shortages of reagents, and slides and culture tubes are often reused. There is no internal or external system for quality assurance. The quality of diagnosis is poor, resulting in high levels of over-diagnosis of TB, reflected in the low proportion of patients (35%) with bacteriologically proven pulmonary TB. Most patients diagnosed with TB are admitted to one of the 165 TB dispensaries at rayon and oblast level. Although there are specific guidelines for treatment, these are frequently not followed. In an assessment of 26 consecutive patients at one oblast, no two patients received the same treatment regimen, the regimens of 14 were changed within one month, and only 9 were treated for six months or more. Drug supplies are inadequate and many patients are required to buy their own medicines. This combination of non-standardized, irregular and inadequate treatment has led to the epidemic of drug-resistant TB which is now becoming apparent. The practice of hospitalizing asymptomatic patients with infectious cases means that some people who do not actually have TB on admission become infected and develop drug-resistant TB. Patients are frequently hospitalized for prolonged periods of one year or more. Many patients default from treatment and are not usually followed up. Treatment monitoring is primarily by sputum culture and X-ray. A patient is not declared cured until X-ray demonstrates closure of lung cavities. The drug management system is inefficient and fails to maintain a continuous supply of quality medicines. Drugs and supplies are purchased locally by oblasts and rayons from a list of approved drugs published by the Ministry of Health. However, drugs are approved by brand name and not by international non-proprietary name. Although the manufacturers prices for local drugs are generally lower than those for imported drugs, the mark-up taken by the chain of retailers between the manufacturer and dispensary means that the final prices paid by dispensaries are 2 3 times the international market prices. Financial disbursements and purchasing occurs monthly. Stock control is weak. Approximately 34% of the drug budget for Class A products is spent on anti-tuberculosis medicines, with most of the funds (48%) being used on medical supplies, including disinfectants. Drug shortages are common, with frequent and prolonged stock-outs of most drugs except isoniazid. Despite an extensive recording system, very little of the information collected is analysed and used for management purposes. Definitions for type of TB, case categorization and outcome of treatment are not compatible with international recommendations. There is no system of cohort reporting, and it is currently impossible to assess treatment outcomes systematically. About 30% of all TB patients are in prisons and remand prisons. There are 10 TB prison hospitals with 6000 beds and 12 000 patients. Approximately 1500 TB patients are treated in remand prisons. Prison TB control services are subject to similar resource constraints as those faced by public health services.
page 3 Conclusions The social, economic and epidemiological impact of TB in Ukraine is immense and is worsening as a result of resource constraints and inappropriate diagnosis and treatment practices. The rapid growth of the HIV epidemic threatens to exacerbate an already disastrous situation. It is imperative that immediate and effective action is taken to address the epidemic. Failure to do so will have profound consequences for Ukraine and neighbouring countries, as the epidemic of multidrugresistant TB and HIV will quickly accelerate beyond control. The Ministry of Health has an obligation to introduce radical changes in diagnostic, treatment and monitoring policies necessary to ensure that patients are cured of their disease and the transmission of TB is interrupted. This can be achieved by applying the DOTS strategy, which should be implemented in a series of pilot projects and then expanded as rapidly as possible to the rest of the country. International agencies have an obligation to support these efforts with technical and financial assistance, based on an action plan for DOTS implementation jointly developed with the Ministry of Health and other relevant national agencies, including the Kiev City Administration and State Department of Prisons. Recommendations The members of the review team recommend the following actions. Action Deadline By 1. Planning (a) Develop a detailed implementation plan for the introduction and expansion of DOTS to achieve nationwide coverage by the end of 2003 (b) Identify pilot sites for DOTS in Kiev City and Chernigev and Donetsk oblasts and TB prison hospitals in these oblasts 2. Policy (a) Develop technical and operational guidelines for TB control based on the DOTS strategy, including: diagnosis based on passive casefinding and sputum smear microscopy standardized regimens of short course chemotherapy, with direct observation of treatment (b) Abandon active case-finding by X-ray screening 31 January 2000 31 January 2000 31 March 2000 31 March 2000 Ministry of Health, Kiev City Administration, State Department of Prisons and WHO Ministry of Health, Research Institute for Pulmonology and Phthisiology and WHO Ministry of Health
page 4 3. Technical and financial assistance (a) Identify additional resources for the Ministry of Health, Kiev City Administration and the State Department of Prisons to facilitate the introduction of DOTS in pilot sites in 2000 and expansion from 2001 (b) Appoint a WHO medical officer with experience in DOTS to support the introduction and expansion of DOTS in Ukraine 4. Management (a) Identify a management team in the Ministry of Health with a full-time national TB programme manager (b) Establish a national TB drug management body to be responsible for central procurement of TB medicines, the TB drug management information system, and quality assurance (c) Adopt internationally recommended definitions, national TB programme indicators and a reporting system for TB control 29 February 2000 30 June 2000 31 January 2000 28 February 2000 31 March 2000 Ministry of Health, WHO, US Agency for International Development and other agencies Ministry of Health, WHO and US Agency for International Development Ministry of Health Ministry of Health Ministry of Health 5. Surveillance (a) Conduct a national survey of drug resistance in new and previously treated patients, in accordance with international guidelines 31 December 2000 Ministry of Health, WHO, US Centers for Disease Control and Prevention and Research Institute for Pulmonology and Phthisiology Review methodology In recognition of the fact that TB has reached epidemic proportions in the country, the Government of Ukraine has taken the first steps towards developing an effective response based on the directly observed treatment, short course (DOTS) strategy. The Ministry of Health has applied to the World Bank for a loan to fund TB and HIV control activities, and asked for the assistance of the World Health Organization (WHO) in conducting a comprehensive review of the TB situation in order to develop a plan for implementation of DOTS. The main objectives of the review were to: review the status of TB and TB control in Ukraine including: assessment of the level and trend of the burden of TB; current policy and practice for TB control, including diagnosis, treatment, logistics and monitoring; costings of current and proposed TB control activities; and trends in drug resistance; prepare a plan of action for DOTS implementation in public health services and prisons.
page 5 The review was carried out from 6 to 15 December 1999 by a team of international experts from WHO, the US Agency for International Development, the US Centers for Disease Control and Prevention, Management Sciences for Health and the International Federation of Red Cross and Red Crescent Societies, together with national experts from the Ministry of Health, the Research Institute for Pulmonology and Phthisiology, and Kiev City Tuberculosis Dispensary. The team visited dispensaries and other health institutions in Donetsk and Chernigev oblasts (regions) and interviewed senior officials in government departments and international agencies in Kiev (see Annexes 1 and 2 for the programme, participants, places visited and people met). The review teams used standardized data collection tools 1 to assess the structure, process and outcome of TB control services in the institutions visited. Background information Ukraine gained its independence from the former USSR on 1 December 1991. With a surface area of 603 700 km 2 it is the second largest country in Europe. It lies on the Black Sea and is bordered by Belarus, Poland, Slovakia, Hungary, Romania, the Republic of Moldova and the Russian Federation (Fig. 1). The total population is about 50 million, 68% of whom live in urban areas and 32% in rural areas (Table 1). The country is divided into 24 oblasts, an autonomous region (Crimea) and two municipalities with oblast status (Kiev City and Sevastopol). Oblasts are further subdivided into 488 rayons (districts). The economy has contracted since independence. In 1998 the gross national product per capita was US $850, declining on average by 9% a year between 1985 and 1995. The poorest 20% of the population share 4.3% of the national economy, and the richest 20% share 52.2%. 2 International loans of approximately US $3 billion are repayable in 2000, one third of which is owed to the International Monetary Fund and the World Bank. Fig. 1. Map of Ukraine 1 Kumaresan, J. et al. Guidelines for conducting a review of a national tuberculosis programme. Geneva, World Health Organization, 1998 (WHO/TB/98.240). 2 World Bank. World development report 1999/2000. Washington, World Bank, 1999.
page 6 Table 1. Development indicators Population 49 811 174 Population growth rate 0.62% Birth rate 9.54/1000 Death rate 16.38/1000 Life expectancy at birth All Males Females 65.91 60.23 71.87 Infant mortality rate 21.73/1000 Literacy 98% Source (1999 estimates): http://www.odci.gov/cia/publications/factbook/up.html. Epidemiology of tuberculosis The main source for epidemiological information are data on reported cases. There have been no recent studies of prevalence of infection or disease. The quality of routinely reported data is suspect, as there is probably a degree of under-reporting. In addition, definitions of type of TB are not directly comparable with international definitions. As in many of the newly independent states, TB has increased dramatically in Ukraine following independence from the former Soviet Union. In 1990, Ukraine reported its lowest number of TB cases: 16 465 for a case rate of 32.0 per 100 000 population. Since then morbidity has steadily risen each year to a high in 1998 of 27 763 cases and a case rate of 55.2, an increase of 72.5% since 1990. Case rates in the administrative regions range from 35.9 in Kiev to 72.9 in Zaporozhyeoblast (Table 2). Table 2. Number of tuberculosis cases and case notification rate (per 100 000 population), 1990 1998 Year Number of TB cases Case notification rate 1990 16 465 32.0 1991 16 713 32.0 1992 18 140 35.0 1993 19 964 38.2 1994 20 622 39.7 1995 21 459 41.6 1996 26 834 45.8 1997 27 204 49.1 1998 27 763 55.2 Cases of TB are diagnosed at a much more advanced stage of their disease in Ukraine than in other areas of the world. This is in part due to the general socioeconomic situation, which has resulted in a lower standard of living for the population, and in part to the inaccessibility of medical services for patients, especially in the rural areas. Overall, 75 80% of cases occur in the
page 7 group aged 20 59 years. The ratio of reported cases of TB in men to women is 7 : 1. The disease has risen by 141% in the urban population and 67.2% in the rural population. The situation in several oblasts is very similar (Table 3). For example, the case rate in Donetsk (the oblast with one of the greatest number of cases) reflects a similar increase. In 1998 there were 3453 cases, an increase of 15.3% on the 1997 total of 2994. The case rate also increased from 58.8 to 68.6 per 100 000 population. Kiev showed only a slight increase, of 1.1% from 933 cases in 1997 to 944 in 1998. The case rate in Kiev is one of the lowest in the country, 35.9 per 100 000. The Chernigev oblast was one of the few areas where there was a decrease from 726 to 706 cases (2.7%). Table 3. Tuberculosis cases and case notification rates (per 100 000 population) in selected oblasts, 1997 and 1998 1998 1997 Cases Case notification rate Cases Case notification rate Chernigev 706 53.9 726 54.8 Donetsk 3453 68.6 2994 58.8 Kiev 944 35.9 933 35.5 Tuberculosis is increasing in all age groups, for example in children it has risen by 115.2%. The occurrence of TB in children is considered a sentinel event, indicating that the disease is not under control within a jurisdiction. As a whole, there was a significant morbidity increase in this group of 12.9%. Of the three oblasts selected, only Chernigev showed an increase from 13 to 26 cases (Table 4). Kiev experienced the greatest decrease (63.4%), while Donetsk showed a decrease of 18.6%. Of the three oblasts, only Donetsk reported TB meningitis, with seven cases in 1998 more than double the number of cases reported the previous year. Table 4. Number of tuberculosis cases and case notification rate (per 100 000 population) in children in selected oblasts, 1997 and 1998 1998 1997 Cases Case notification rate Cases Case notification rate Chernigev 26 11.4 13 5.5 Donetsk 109 12.5 134 14.6 Kiev 30 6.6 82 17.3 Ukraine 954 9.9 845 8.5 Although TB death rates increased by 92.6% between 1990 and 1998, the number of deaths due to TB has declined during the past two years by 9.2% (Table 5). A total of 16.1% of TB patients die within one year of initial examination, further evidence of their late presentation for diagnosis. Each of the selected oblasts experienced decreases, from a low of 1.4% in Chernigev to a high of 26.8% in Kiev. Donetsk showed a 21.8% decrease in TB deaths.
page 8 Table 5. Number of tuberculosis deaths and deaths per 100 000 population in selected oblasts, 1997 and 1998 1998 1997 Deaths Deaths per 100 000 population Deaths Deaths per 100 000 population Chernigev 142 10.8 144 10.8 Donetsk 1137 22.5 1454 28.5 Kiev 169 6.5 231 8.9 Ukraine 7850 15.6 8651 17.1 HIV/AIDS The number of people infected with HIV has risen rapidly from 19 in 1990 to 8497 in 1998. Approximately 80% of these are injecting drug users. The number of AIDS cases reported to date is 1235 (58.4 per 100 000 population). The highest levels of infection are in Odessa, where the rate is 189 per 100 000 population, while the lowest rates are seen in the western part of the country. Some 30% of people with AIDS also have TB, but the number of TB cases with HIV infection is unknown. Prior to 1998, HIV testing was obligatory for people in a number of categories, including those with TB, but in that year a law was passed making HIV testing voluntary for all except blood donors. Since data on HIV began to be collected in Chernigev oblast, 215 people have been identified in this region with HIV infection (only 2 were identified up to 1996) (Table 6). Testing in Chernigev oblast has, however, declined in recent years largely because of the 1998 law making HIV testing voluntary. In 1997 a total of 34 347 HIV tests were done, 27 113 (78.9%) of them among blood donors. During the first 11 months of 1999 a total of 24 724 HIV tests were done, of which 22 537 (91.1%) were blood donors. Table 6. Number of HIV infections in Chernigev oblast, 1996 1999 Mode of transmission 1996 1997 1998 1999 a Totals Sexual contact 3 2 5 Blood transfusion 1 1 Injecting drug user 10 104 63 19 196 Maternal/child 2 1 3 Unknown 4 4 2 10 Totals 10 108 72 25 215 a First 11 months. Only two cases of AIDS have been identified in Chernigev oblast, one in 1998 and one in 1997. This is not believed to be an accurate representation of the true extent of the HIV infection problem in this area, as there is probably considerable under-reporting, of at least 30% of cases (Table 7).
page 9 Table 7. HIV infections in Chernigev oblast by age and sex, 1996 1999 Age group 1996 1997 1998 1999 Total Male Female Male Female Male Female Male Female 0 20 1 5 3 7 1 2 0 19 20 29 2 2 41 17 36 9 14 2 123 >30 1 4 11 31 14 5 6 1 73 Total 4 6 57 51 57 15 22 3 215 Anti-TB drug resistance There are no national data regarding drug resistance. According to information provided by the Research Institute of Pulmonology and Phthisiology, resistance is estimated to be present in approximately 5 7% of new cases and 28% of previously treated cases. Resistance to streptomycin is most common (60 70% of all resistance). Resistance to isoniazid is believed to be higher than for rifampicin. A sample of information reviewed during the visit to Chernigev revealed resistance to at least one drug in half the number reviewed (Table 8). Table 8. Percentage of drug resistance in new patients in two locations Resistance Chernigev (106 patients) % Mariupol (368 patients) % Isoniazid 15 42 Rifampicin 25 17 Streptomycin 46 35 Kanamycin 10 Ethambutol 3 6 Multidrug resistance 10 Any resistance 50 Structure of tuberculosis control services Organization of health services Operational policy formulation, coordination and administration of TB control is the responsibility of the Department of Socially Dangerous Diseases of the Ministry of Health. There is no national tuberculosis programme manager. Ukraine has a decentralized administrative system, and health is the responsibility of oblast and rayon administrations. Technical policy formulation has been provided by the Research Institute of Pulmonology and Phthisiology, which functions under the Academy of Medical Sciences. Technical policies for diagnosis and treatment of people with TB have been published but are not freely distributed and have to be purchased for 7 Hr (Gryvna) (US $1.3).
page 10 Table 9 shows the structure for the delivery of tuberculosis treatment services. These are mainly provided at the oblast and rayon level in specialized dispensaries providing inpatient and outpatient services. There are also several sanatoria for the rehabilitation of treated TB patients, mainly in the Crimea. Some large general hospitals also have TB departments. Table 9. Organizational structure for delivery of tuberculosis services Institution Function Research Institute for Pulmonology and Phthisiology Sanatorium oblast dispensary oblast hospital Rayon dispensary National referral centre for development of methodologies for TB diagnosis and treatment; research training of clinicians and laboratory personnel; surveillance monitoring and supervision; national reference laboratory; and referral centre for management of difficult TB cases. Rehabilitation of treated TB patients. 150 500 beds and several phthisiologists and other specialists. Provides diagnosis treatment and inpatient care. Maintains TB register for the region. Outpatient (polyclinic) and inpatient general health services for the oblast including all medical and surgical specialties. 75 150 beds and several phthisiologists and other specialists. Provides diagnosis treatment and inpatient care. Central I hospital Outpatient (polyclinic) and inpatient general health services for the rayon. 150 500 beds with several medical and surgical specialties, including pulmonology and phthisiology. CES department for public health functions. Peripheral health unit Feldsher post Serves several divisions of a rayon and is staffed by divisional doctors and feldshers. Feldsher is the most peripheral health worker. Provides basic curative services for the population of a division. Maintains list of people to be screened for TB. Performs tuberculin tests and BCG vaccinations. Provides anti-relapse treatment. The number of institutions providing TB services has contracted by 10 20% in recent years (Table 10). The number of phthisiologists has declined 25% since 1990 and their average age is now 67 years, indicating difficulties in recruiting doctors to this specialty. Table 10. Number of tuberculosis services in 1990 and 1998 Service 1990 1998 Dispensaries 185 165 TB beds 25 695 19 966 Sanatoria 136 98 Phthisiologists 3 734 2 729 Coordination with other agencies Several international agencies have expressed an interest in supporting TB control efforts in Ukraine. Effective utilization of the resources offered will require close coordination and assessment of the comparative strengths of each agency to determine the most appropriate inputs.
page 11 Relevant agencies include the following. National Agency of Ukraine for Development and European Integration The National Agency of Ukraine for Development and European Integration (http://www.naudei. kiev.ua/) has been appointed by the Government as international technical assistance coordinator, with responsibility for attracting and coordinating technical cooperation programmes and projects, including those of multilateral and bilateral agencies such as WHO and the World Bank. World Bank The Government has requested a loan from the World Bank to fund the development of TB and HIV prevention and control. The TB component will be used to expand the DOTS strategy. A preliminary mission (jointly with WHO) was held in September 1999 and will be followed up with further missions in 2000. If the loan is approved, it is likely to become available in 2001. World Health Organization WHO has provided technical support for the introduction of DOTS in Ukraine. A preliminary mission took place in July 1999 and was followed by a training course on DOTS for Kiev City, held in November 1999. TACIS TACIS (http://www.pharma-tacis.kiev.ua/) is a European Union project to encourage the transformation of the newly independent states and Mongolia to market economies and democratic societies. TACIS has several health projects in Ukraine, including one on assistance in restructuring the pharmaceutical industry in Ukraine contracted to CII, a German consultancy. This project aims to provide the population with higher quality and cheaper medicines, and will provide technical assistance to six private pharmaceutical companies (four involved in production and two in distribution). The project will help one of those companies to achieve good medical practice certification for a drug of clinical and public health importance. In view of the significance of the TB epidemic, rifampicin has been suggested as the pilot drug. TACIS will provide technical assistance and cooperate to identify potential investors and loans (e.g. the European Bank of Reconstruction and Development). Project staff believe that it will take approximately two years to achieve this. United States Agency for International Development The United States Agency for International Development (USAID) is firmly committed to supporting the implementation of effective TB prevention and control activities. A significant financial commitment has been allocated for this purpose. At present several possible activities are under consideration with an emphasis on capacity-building to ensure activities continue once funding ceased. International Federation of Red Cross and Red Crescent Societies The International Red Cross has recently launched a TB control programme for Belarus, the Republic of Moldova, the Russian Federation and Ukraine. The project will start shortly in Ukraine, in Kiev and the northern oblasts of Chernigev, Zitomin and Chergassy. The main activities focus on community support for TB control, with information, education and communication, training of health workers and patients, social support to patients and
page 12 identification of risk groups. There is at least one Red Cross visitor nurse in each rayon. These nurses could be involved in direct observation of treatment, counselling, education and referral. Project HOPE A small pilot project for DOTS was established in Odessa in 1998 by Project HOPE, with funding from the Canadian Government and the World Bank. Local difficulties resulted in fewer patients treated than expected. The project has concluded. Kuratorium Tuberkulose in Der Welte (Government of Bavaria) The Government of Bavaria has strong historical links with Ukraine and has provided extensive support to various development projects, including several in the health sector. In 1999, the Kuratorium Tuberkulose in Der Welte, a German nongovernmental organization based in Gauting, Munich, provided technical assistance (with financial support from the Government of Bavaria) to set up a modern mycobacterial laboratory in the Research Institute for Pulmonology and Phthisiology. The laboratory has been completed but is not yet operating. Health care financing and the economics of tuberculosis control Although health care is theoretically free, severe under-financing of health care services means that as much as 80% of health care expenditure is paid for by patients themselves. Owing to economic constraints, only about 40% of the requirement for the health services is budgeted, and usually less than half of the budget is actually financed. Revenue comes from two sources: state allocations and local tax revenues. It is not possible to determine the proportion of revenue for health coming from these two sources. Health services are the responsibility of the rayon and oblast, and are usually funded from the state allocation. Disbursements are monthly and must be spent that month. There are six main line items in the health budget: salaries, utilities, food for inpatients, drugs, consumables and maintenance. By law, salaries must be paid, and consume about 30% of the budget (76% in Donetsk oblast). Utilities consume about 50%, leaving 20% for drugs, etc. A doctor s salary is about 120 160 Hr a month, and a nurse s 80 100 Hr a month. Delays in salary payments are common. There is no single line item for TB in the national budget. Some programmes appear as a line item (e.g. the Expanded Programme on Immunization, Reproductive Health, HIV, Children of Ukraine, Blood Pressure Control and Health of the Elderly). However, there is no budget allocation to these line items. It is impossible to determine national expenditure on TB control accurately, as there is no central budget or accounting for it. Expenditure for TB control is financed from several sources: central allocation from Ministry of Health; central allocation from the Academy of Medical Sciences to the Research Institute for Pulmonology and Phthisiology; local allocations from oblasts and rayons to TB sanatoria and dispensaries; local allocations from oblasts and rayons to TB departments in general hospitals; central allocation for TB control from the State Department of Prisons.
page 13 The Ministry of Finance has estimated that national TB expenditure is 6000 7000 Hr (about US $1200) per TB bed per year (including salaries), giving a total expenditure of 160 180 million Hr (US $30 35 million). This is about 50% of the actual requirement as estimated by the Ministry of Finance. Data collected from Donetsk oblast during the review approximate to these figures. Of 45 000 hospital beds in the oblast, 3100 (8%) are for TB. The oblast health budget is allocated proportionately to the number of beds, so TB dispensaries receive 34 million Hr of the 345 million Hr allocated to the oblast. This is equivalent to 11 000 Hr per TB bed per year. In a joint planning exercise with the Ministry of Health and the Research Institute for Pulmonology and Phthisiology, the Ministry of Finance has estimated that it will require an additional 250 million Hr (US $50 million) to implement DOTS over the next five years, and has budgeted an additional 27.5 million Hr for the fiscal year 2000 (January December). In a separate exercise, a proposal for implementation of DOTS has been prepared by the Ministry of Health for submission to the World Bank. This envisages a total budget of US $124 million over a 10-year period. As expenditure on TB control mainly goes on infrastructure and staff costs, the largest proportion of incremental costs for DOTS will be for diagnostic equipment (e.g. microscopes), drugs and training. Most of these costs will accrue centrally, whereas cost savings will accrue locally in reduced infrastructure requirements. These savings are unlikely to become apparent quickly, as oblasts and rayons are not likely to be able to restructure their services immediately to accord with the reduced infrastructure and staffing needs of DOTS. Health sector reform Proposals for reform of the health sector have been prepared and are under discussion in the Ministry of Health. The main proposal is for revised health care financing, which will probably be based on an insurance system. The proportion of health care that will be financed by limited mandatory state health insurance has yet to be decided. Financial implications of DOTS The cost of DOTS will depend to a great extent on the policy decisions regarding diagnosis, treatment and hospitalization. The estimated costs for each option are given in Annex 3 and summarized in Table 11. These are not the total costs for DOTS, as they exclude training, supervision and equipment, but they can be used to indicate the comparative costs of different policy options in order to determine the most efficient and effective means of implementing DOTS in Ukraine. The minimum option is calculated for a basic programme. The optimum option is closest to the WHO recommended strategy for TB control in middle-income countries. The maximum option is calculated according to the old pre-independence system. The analysis shows that (a) the choice of diagnostic and hospitalization policies will have the greatest influence on overall costs, and (b) if the optimum policy is selected, the greatest costs will be for drugs and hospitalization. A more detailed costing exercise will be required as part of the plan for implementation of DOTS.
page 14 Table 11. Estimated costings of different DOTS policy options (US $) Component Minimum option Optimum option Maximum option Diagnosis 472 808 1 755 947 135 655 652 Treatment 2 086 996 9 804 943 13 533 011 Hospitalization direct indirect 3 626 582 2 333 965 10 054 652 6 470 887 231 583 191 149 040 325 Policy and practice Diagnosis and laboratory services The national TB programme is based on active case-finding involving routine fluorography (X-ray) for the general population. The fluorography method used for screening involves small films with much smaller resolution than standard chest X-rays. Additionally, some locations use fluoroscopy when they do not have film for fluorography. Fluorography screening is incorporated into a variety of health care systems, with the rate of screening varying by occupation, locality or access to the health care system. Segments of the population are defined as risk groups and screened more frequently, although the definitions for the risk groups include a large proportion of the population. Fluorography screening is funded through the general health care budget and does not depend on the TB programme funding. An estimated 50% of the population over 15 years of age are screened on an annual basis. In the Donetsk oblast, 0.88/1000 of those screened with fluorography had an abnormality indicating possible TB. In general, X-ray is considered the primary diagnostic test and in many cases it is the only diagnostic indicator used in defining a case of TB. In addition to TB suspects detected by fluorography and X-ray, symptomatic patients who present to feldshers, health stations, polyclinics and general hospitals are referred to the TB dispensaries. Additionally, all children aged under 14 years are screened by tuberculin skin test twice a year and adolescents aged 14 17 years are screened by tuberculin skin test and fluorography. Although fluorography is widely available in most health care settings, laboratory services for TB are primarily located in the TB dispensaries. The use of smears and/or culture examination of specimens to confirm the diagnosis varies from institution to institution. In general, the guidelines are followed, so that 3 6 sputum specimens are collected for initial diagnosis and additional specimens are collected monthly during treatment. The TB dispensaries carry out a significant number of both smears and cultures, and usually both a smear and culture are performed on every specimen received by these laboratories. There are exceptions, and some hospitals only perform microscopy and not culture on some or all specimens. Despite the large volume of smears and cultures, there were many indications that neither the smear nor culture results played a significant role in diagnosing TB or monitoring the effectiveness of therapy. For example, patients with repeated negative results from both smear and culture were often given a full course of treatment even if they had no symptoms of TB. In Donetsk in 1997 and 1998, only 25.6% and 24.5%, respectively, of new TB cases were smear-positive before treatment. A similar percentage was found by sampling patient results in Chernigev and Donetsk. In 1997, only 35% of new patients with active pulmonary TB had any positive smear or culture result despite having 7 10 specimens processed for smear and culture. The only evident role of smears
page 15 and cultures in patient management was as indicators for the need to extend or revise treatment in patients with persistent positive laboratory tests. Additionally, despite the frequent use of drug susceptibility testing, there was little indication that the results were used in modifying therapy. Drug susceptibility results were used in decisions about whether to perform surgery. There was no systematic collection of drug susceptibility testing results, and only one laboratory reviewed was aware of its rates of drug resistance. Each of the four TB dispensary laboratories outside Kiev was well staffed with 12 15 people, including 3 4 laboratory physicians. Equipment was obsolete and, in general, cultures were processed in areas with poor ventilation. There were shortages of reagents and slides, which are often of poor quality and reused. Monocular microscopes without internal light sources or mechanical stages were used in each facility. The magnification of the microscopes was lower (7X ocular with 90X objective = 630 magnification) than recommended, but staff appeared to be proficient in using them. The minimum number of microscopic fields that are examined before calling a smear negative for AFB varied from 15 to 200. The number of specimens examined by smear and culture varied by site but represented a sufficient volume to maintain proficiency. Cultures were performed using both Löwenstein Jensen and Finn II Medium. The culture medium was made on site from either basic ingredients or more expensive dehydrated medium. The identification of bacterial growth in culture as M. tuberculosis was based on macroscopic and microscopic appearance without the use of biochemical confirmation. Drug susceptibility testing was performed at all the laboratories performing culture, and were often carried out on any positive culture. Drug susceptibility testing was performed on Löwenstein Jensen media that incorporated drugs derived from tablets, capsules or intramuscular forms used for therapy, rather than drug reagents specifically made for drug susceptibility testing. The drugs tested included isoniazid, rifampicin, ethambutol, streptomycin, kanamycin and ethionamide. Although some quality control practices were observed, there was no systematic documentation of quality using either internal or external indicators. In general, the laboratory staff appeared competent and were proficient in using the resources available. The lack of any external quality control system to validate testing results for smear, culture or susceptibility testing prevents any evaluation of the accuracy of the testing methods. Testing methods were the same at the Research Institute for Pulmonology and Phthisiology and the Kiev City Central TB Dispensary. However, the Kiev laboratory had modern binocular microscopes and the Research Institute has a new modern laboratory that is not yet in service. This laboratory has the potential to serve as a national reference laboratory for providing reference testing services and external quality control for TB laboratories throughout the country. Recommendations 1. Abandon active case-finding by X-ray screening and emphasize passive screening of symptomatic patients with sputum smear microscopy. 2. Develop a system for the collection and transport of sputum from peripheral health institutions. 3. Develop and introduce systems for internal and external quality control, including national or regional programmes for external quality control for smear microscopy. 4. Identify the new laboratory at the Research Institute for Pulmonology and Phthisiology as the national reference laboratory for TB diagnostic services and external quality control. 5. Assess bacteriology cure rates (smear and culture) alongside X-ray information and adjust testing practices.
page 16 6. Provide appropriate equipment, supplies and training to support diagnosis with smear microscopy and continuing surveillance for drug resistance. 7. Introduce standard laboratory registers in the WHO format for patient monitoring and epidemiological analyses. Treatment Although technical policies for TB treatment have been developed by the Research Institute for Pulmonology and Phthisiology, they are rarely followed due to the frequent lack of drugs. There are no standardized treatment regimens. In an assessment of 26 consecutive patients at one oblast, no two patients received the same treatment regimen: the regimens of 14 patients were changed within 1 month, and only 9 were treated for 6 months or more. This situation, combined with frequent and prolonged shortages of medicines, has led to the epidemic of drug resistance. In general, all people with TB are hospitalized on diagnosis and kept as inpatients for most if not all their treatment course. Inpatient care usually lasts six to eight months or more but may be shortened depending upon the patient s progress. A form of directly observed therapy is being used, but to a very limited degree. However, because of the variations with regard to the regimen prescribed and the duration of therapy, it does not conform to WHO s recommendations. Patients are usually hospitalized and started on therapy with four or five drugs on admission. In addition to isoniazid, drug regimens may include rifampicin, pyrazinamide, ethambutol, streptomycin and/or kanamycin. Variations in the regimen may occur almost immediately due to the non-availability of anti-tuberculosis drugs in the oblast. Inpatient treatment may also include pathogenic treatment. The treatment usually lasts from nine to twelve months, or even longer, depending on the patient s progress. Following discharge from hospital, treatment is continued on an outpatient basis at the facility nearest the patient s home, depending on the resources available. Therapy is administered at the facility, so that the patient has to return to the facility for treatment on an intermittent basis. In those oblasts where directly observed therapy is used, it is primarily the patient s responsibility to return to clinic to continue his treatment. Some oblasts have visiting nurses who seek out patients who fail to return to the clinic. The team visited a rural rayon in the Chernigev oblast where directly observed treatment was being administered by a feldsher at an outlying health station. The patient came into the health station for his thrice weekly treatment; if he failed to come in the feldsher took his anti-tb medications out to him. There were no data to indicate the number of patients being treated in this way, but it is considered to be very small. Treatment is initiated within six days of admission as an inpatient. The treatment policy of the TB dispensary is to treat patients with at least four anti-tb drugs (isoniazid, rifampicin, pyrazinamide, streptomycin or ethambutol) for two months or until they convert their sputum. Once sputum conversion occurs, treatment is reduced to two drugs (isoniazid and rifampicin) for at least four months or until the closure of cavity is noted radiologically. Other drugs that may be used include kanamycin, ethionamide and ofloxacin. If the patient complains of a reaction to the medication, doctors will remove one drug at a time for several days to determine which one is causing the problem. In addition to anti-tb drugs, patients receive a variety of other treatments including hormones, vitamins, direct injection of anti-tb drugs into cavities, and inhalation of certain anti-tb drugs.
page 17 For cases of pulmonary TB, treatment is not terminated and the patient is not discharged until the cavity, if present, closes. If it does not close, the patient is evaluated for surgical intervention. Although monthly sputum samples are taken, monitoring is largely based on radiology. Doctors rely heavily on X-rays to evaluate progress. Bacteriology serves primarily as a support rather than a definitive indicator. During treatment, the administration of anti-tb drugs is stopped three days before the collection of a sputum sample. Private physicians are prohibited by law from treating TB. Anti-relapse/preventive treatment When the anti-tb treatment is completed, patients receive periodic treatment with two anti-tb drugs for two months at a time to prevent a relapse. Treatment includes isoniazid and rifampicin, if they are available. These treatments are given over approximately two years following discharge for the original diagnosis. Preventive therapy is given to a limited extent for high-risk patients, primarily those who have been identified as having a positive tuberculin skin test in one of several campaigns designed to screen high-risk populations. The definition of high risk covers a wide range of categories including contacts, children, and people in certain occupations, especially those who are in contact with the general public such as teachers. Recommendations 1. Introduce standardized regimens of short course chemotherapy, with direct observation of treatment. 2. Ensure that enough anti-tb drugs are available to enable treatment of cases for the entire course without any interruption. 3. Direct observation of treatment to be carried out by anyone willing, trained, responsible, acceptable to the patient and accountable to the TB control services. Visiting Red Cross nurses should play an important role in this observation. 4. Decentralize care of TB patients from the dispensaries to peripheral health facilities to improve access to diagnosis, care and observation of treatment. 5. Hospitalize infectious TB patients for a maximum of two months, i.e. during the intensive phase of TB treatment, unless the patient is in a bad condition or is infected by drugresistant TB. 6. Abandon tuberculin screening campaigns and limit skin testing to close contacts of newly diagnosed pulmonary cases. 7. Abandon the periodic anti-relapse treatment. 8. Limit preventive therapy to close contacts of infectious cases. Drug management TB hospitals and dispensaries are financed by oblast administrations and bear full responsibility for procurement of TB and other drugs along with medical, diagnostic and laboratory supplies. The budgets for the TB facilities largely depend on the economic wealth of the oblast and the