Capacity building for international tuberculosis control through operations research training.

SETTING: In resource-poor countries, few tuberculosis (TB) program staff at the national, provincial, and even district levels have the basic analytical and epidemiological skills necessary for collecting and analyzing quality data pertaining to national TB control program (NTP) improvements. This includes setting program priorities, operations planning, and implementing and evaluating program activities. OBJECTIVES: To present a model course for building capacity in basic epidemiology and operations research (OR). DESIGN: A combination of didactic lectures and applied field exercises were used to achieve the main objectives of the 6-day OR course. These were to increase the understanding of quantitative and qualitative research concepts, study design, and analytic methods, and to increase awareness of how these methods apply to the epidemiology and control of TB; and to demonstrate the potential uses of OR in answering practical questions on NTP effectiveness. As a final outcome, course participants develop OR proposals that are funded and later implemented. RESULTS: Since 1997, this OR course has been conducted nine times in five countries; 149 key NTP and laboratory staff have been trained in OR methods, and 44 OR protocols have been completed or are underway. CONCLUSION: This low-cost model course can be adapted to a wide range of public health issues.

The validity of HIV testing using sputum from suspected tuberculosis patients, Botswana, 2001.

SETTING: The World Health Organization recommends that sentinel HIV surveillance be conducted on tuberculosis patients. However, serum HIV testing is complicated in the TB clinic context, and may not be acceptable to patients. DESIGN: To determine the utility of the OraQuick HIV-1/2 Assay for the detection of HIV antibodies in sputum, we consecutively enrolled adult in-patients in Botswana who had sputum sent for acid-fast bacilli testing and serum sent for HIV ELISA testing. OraQuick HIV-1/2 Assay was applied to gingival secretions according to manufacturer's guidelines, and was also dipped into sputum specimens. A subset of 60 sputum specimens was also serially tested up to 72 hours after collection. RESULTS: Of 377 patients, 84% were HIV-positive by serum ELISA. Compared with serum ELISA, the OraQuick HIV-1/2 Assay detected HIV in gingival secretions with 98.4% sensitivity and 98.3% specificity (95%CI 97-99 and 92-100, respectively), and 97.1% sensitivity and 98.3% specificity on initial sputum specimens (95%CI 95-99 and 92-100, respectively). OraQuick HIV-1/2 Assay performance on sputum declined slightly when tested up to 72 hours after collection. CONCLUSIONS: When applied to sputum specimens, the OraQuick HIV-1/2 Assay demonstrates sensitivity and specificity comparable to its intended application on gingival secretions. This novel testing method will be valuable in anonymous sentinel HIV surveillance surveys among tuberculosis patients.

Etiology of pulmonary infections in predominantly HIV-infected adults with suspected tuberculosis, Botswana.

SETTING: In countries with high HIV rates, diagnosis of lower respiratory disease etiology is both challenging and clinically important. OBJECTIVE: To determine the etiology of lower respiratory tract disease among persons with suspected tuberculosis (TB) and abnormal chest X-rays in a setting with very high HIV seroprevalence. DESIGN: Cross-sectional prevalence data from a prospective cohort of predominantly hospitalized adults with suspected TB in Botswana, January-December 1997. RESULTS: Of 229 patients, 86% were HIV-positive and 71% had a pathogen identified. TB was confirmed in 52%, 17% had acute mycoplasma pneumonia, 3% had Pneumocystis carinii, 27% grew a bacterial pathogen from sputum and 8% from blood. Ninety-four per cent of TB diagnoses were made through expectorated sputum and only 5% of TB cases were diagnosed by sputum induction alone. Polymerase chain reaction (PCR) for Mycobacterium tuberculosis had positive and negative predictive values of 94% and 59%, respectively. Male sex, cough < 2 weeks, and tuberculin skin test > or = 5 mm were independently associated with culture-positive TB among persons with negative acid-fast bacilli smears. Co-infection with two or more pathogens occurred in 25%. CONCLUSIONS: Mycoplasma pneumoniae infection was quite common despite clinical suspicion of TB, and sputum induction and PCR did not significantly improve our ability to diagnose TB, although clinical presentation had some predictive value.

Control of anti-tuberculosis drug resistance in Botswana.

SETTING: Botswana, where in 2000 the prevalence of human immunodeficiency virus (HIV) infection among adults was 38%, and the tuberculosis (TB) rate was 591/100,000. A 1995-1996 survey demonstrated low levels of anti-tuberculosis drug resistance. OBJECTIVE: Because TB drug resistance may increase rapidly in HIV-infected populations, a second survey was undertaken in 1999 to determine any increase in anti-tuberculosis drug resistance. DESIGN: Sputum specimens positive for acid-fast bacilli from patients without prior TB treatment (new patients), and all sputum specimens from patients reporting prior TB treatment (retreatment patients) were collected nationwide. Specimens were cultured for Mycobacterium tuberculosis and tested for resistance to isoniazid, rifampicin, ethambutol, and streptomycin. RESULTS: From January to May 1999, 783 patients were consecutively enrolled from all districts. Of these, 483 (61.7%) were male, the median age was 33 years, and 82% were new patients. Drug resistance occurred in 6.3% of new patients (95 % confidence interval [CI] 4.6-8.6) and 22.8% of retreatment patients (95% CI 16.5-30.1). Resistance to at least isoniazid and rifampicin was found in 0.5% of new (95% CI 0.1-1.3) and 9.0% of retreatment patients (95% CI 5.1-14.5). CONCLUSION: Anti-tuberculosis drug resistance remains relatively low in Botswana, probably as a result of a well-functioning TB program. Periodic surveys will be essential to adequately determine any significant trend.

Pathology and causes of death in a group of 128 predominantly HIV-positive patients in Botswana, 1997-1998.

BACKGROUND: Little is known about causes of death in countries of southern Africa seriously affected by the HIV/AIDS epidemic. METHODS: After obtaining informed consent, autopsies were performed on 128 mainly hospitalised adults in Francistown, Botswana, between July 1997 and June 1998. Criteria for case selection included those who died before a diagnosis could be established, those whose condition deteriorated unexpectedly during hospitalization, and those who had respiratory disease. This represented 14% of adult medical patients who died in hospital during the study period. RESULTS: Of the 128 patients, 104 (81%) were HIV-positive. Among HIV-positive patients, the most common pathologic findings were tuberculosis (TB) (40%), bacterial pneumonia (23%), Pneumocystis carinii pneumonia (11%), and Kaposi's sarcoma (11%); these conditions were the cause of death in 38%, 14%, 11%, and 6%, respectively. Of the 40 pulmonary TB cases, 90% also had disseminated extra-pulmonary TB. Chest radiology could not reliably distinguish the pathologies pre-mortem. CONCLUSIONS: TB was the leading cause of death in our series of HIV-positive adults in Botswana, selected towards those with chest disease; in most, it was widely disseminated. Bacterial pneumonia also played an important role in mortality. Pneumocystis carinii pneumonia was present, but relatively uncommon.

Occupational transmission of Mycobacterium tuberculosis to health care workers in a university hospital in Lima, Peru.

From November 1996 through March 1997, presumptive active pulmonary tuberculosis (TB) was detected in 44 health care workers (HCWs) at a university hospital in Lima, Peru. To further assess the magnitude of the outbreak and determine risk factors for occupational Mycobacterium tuberculosis transmission, we identified HCWs in whom active pulmonary TB was diagnosed from January 1994 through January 1998, calculated rates by year and hospital work area, and conducted a tuberculin skin test (TST) survey. Thirty-six HCWs had confirmed active pulmonary TB. The rate of TB was significantly higher among the 171 HCWs employed in the laboratory than among HCWs employed in all other areas. In multivariate analysis, the only independent risk factor for HCW M. tuberculosis infection in HWCs employed in the laboratory was the use of common staff areas. Very high rates of active pulmonary TB were detected among HCWs at this hospital, and occupational acquisition in the laboratory was associated with HCW-to-HCW transmission.

A case series: initial outcome of persons with multidrug-resistant tuberculosis after treatment with the WHO standard retreatment regimen in Ho Chi Minh City, Vietnam.

Few data address the outcomes of patients who have multidrug-resistant tuberculosis (MDR-TB), defined as resistance to at least isoniazid and rifampin, and who receive a standard World Health Organization (WHO) recommended retreatment regimen after relapse or failure with initial treatment. In this case series, we examined treatment outcomes of a convenience sample of 42 relapse or failure patients who had documented MDR-TB and who had received a standard WHO retreatment regimen (2SHRZE/1HRZE/5H3R3E3). One patient died of tuberculosis in the last month of treatment; the remaining 41 patients completed retreatment. Of the 42, 14 (33%) were sputum smear-negative on completion of therapy. The proportion of patients cured of MDR-TB with the WHO retreatment regimen was similar to historic outcomes when no chemotherapy for TB was given.

Substandard tuberculosis drugs on the global market and their simple detection.

SETTING: The prevalence of substandard anti-tuberculosis drugs is unknown. To maximize the effectiveness of tuberculosis (TB) control efforts, simple, inexpensive drug quality screening methods are needed. DESIGN: Isoniazid (INH) and rifampin (RMP) single- and fixed-dose combination (FDC) formulations were collected from selected TB programs and pharmacies in Colombia, Estonia, India, Latvia, Russia and Vietnam. Samples were screened using a recently developed thin-layer chromatography (TLC) kit. All abnormal samples and a 40% random sample of normal formulations were further analyzed using confirmatory techniques. Samples outside of 85% to 115% of stated content, and/or containing compounds other than the stated drug, were defined as being substandard. RESULTS: Overall, 10% (4/40) of all samples, including 13% (4/30) RMP samples, contained <85% of stated content. More FDCs (5/24, 21%) than single-drug samples (2/16, 13%) were substandard. A comparison of TLC with the confirmatory analysis for RMP analysis showed a sensitivity of 100% (4/4), a specificity of 92% (24/26), a positive predictive value (PPV) of 67% (4/6), and a negative predictive value (NPV) of 100% (24/24). An analysis of INH showed a specificity of 90% (9/10). However, sensitivity, PPV, and NVP could not be determined. CONCLUSION: A substantial number of anti-tuberculosis drugs from several countries, in particular FDCs, were found to be substandard. Such drugs may contribute to the creation of drug-resistant TB. TLC is an effective, convenient, and inexpensive method for the detection of substandard drugs.

Drug-resistant tuberculosis in foreign-born persons from Mexico, the Philippines, and Vietnam-United States, 1993-1997.

SETTING: Foreign-born persons in the United States represent a growing proportion of the nation's tuberculosis (TB) cases. OBJECTIVE: To characterize drug resistance patterns in foreign-born TB patients from the three most common birth countries. DESIGN: A descriptive analysis of national TB surveillance data for 1993-1997. TB case reports for foreign-born persons who were at least 15 years old and born either in Mexico (6221), the Philippines (3624), or Vietnam (3351) were included. RESULTS: Among those with no prior history of TB, the proportions with isoniazid-resistant TB and MDR-TB (resistance to at least isoniazid and rifampin) were 9.2% and 1.6% for persons from Mexico, 13.7% and 1.4% for those from the Philippines, and 17.8% and 1.4% for those from Vietnam. Levels of isoniazid resistance and MDR-TB did not change during the 5-year study period. Levels of isoniazid resistance decreased with older age for persons with no prior TB from all three countries; however, rates of MDR-TB did not vary with age. Persons with <1 year of residence in the US were more likely to have MDR-TB; however, duration of residence in the US was not associated with isoniazid resistance. CONCLUSION: Increased drug resistance in younger and more recent arrivals suggests that vigorous efforts to prevent further development of MDR-TB in the three countries are essential.

Molecular and conventional epidemiology of Mycobacterium tuberculosis in Botswana: a population-based prospective study of 301 pulmonary tuberculosis patients.

Little is known about patterns of tuberculosis (TB) transmission among populations in developing countries with high rates of TB and human immunodeficiency virus (HIV) infection. To examine patterns of TB transmission in such a setting, we performed a population-based DNA fingerprinting study among TB patients in Botswana. Between January 1997 and July 1998, TB patients from four communities in Botswana were interviewed and offered HIV testing. Their Mycobacterium tuberculosis isolates underwent DNA fingerprinting using IS6110 restriction fragment length polymorphism, and those with matching fingerprints were reinterviewed. DNA fingerprints with >5 bands were considered clustered if they were either identical or differed by at most one band, while DNA fingerprints with < or =5 bands were considered clustered only if they were identical. TB isolates of 125 (42%) of the 301 patients with completed interviews and DNA fingerprints fell into 20 different clusters of 2 to 16 patients. HIV status was not associated with clustering. Prior imprisonment was the only statistically significant risk factor for clustering (risk ratio, 1.5; 95% confidence interval, 1.1 to 2.0). In three communities where the majority of eligible patients were enrolled, 26 (11%) of 243 patients overall and 26 (25%) of 104 clustered patients shared both a DNA fingerprint and strong antecedent epidemiologic link. Most of the increasing TB burden in Botswana may be attributable to reactivation of latent infection, but steps should be taken to control ongoing transmission in congregate settings. DNA fingerprinting helps determine loci of TB transmission in the community.

Completeness and timeliness of treatment initiation after laboratory diagnosis of tuberculosis in Gaborone, Botswana.

SETTING: Gaborone, the capital of Botswana. OBJECTIVE: To determine the time from positive sputum smear microscopy for acid-fast bacilli (AFB) to initiation of therapy, and to identify risk factors for delays. DESIGN: Retrospective cohort study of medical records and surveillance data for patients with positive smear microscopy and newly diagnosed tuberculosis (TB) from January to May 1997. Treatment delay was defined as more than 2 weeks from the first positive sputum smear to the initiation of TB treatment. RESULTS: Of 127 patients identified, 15 (11.8%) had treatment delay, 13 (10.2%) had an incomplete workup (only one smear performed) and were not registered for TB treatment, and six (4.5%) had two or more positive smears but were not registered for TB treatment. Risk factors for treatment delay or non-registration included TB patients who had been diagnosed in a hospital outpatient setting vs. a clinic (RR 2.9, 95% CI 1.2-3.6, P = 0.02), or in a high volume vs. low volume clinic (RR 2.2, 95% CI 1.2-5.3, P = 0.01). CONCLUSION: More than a quarter of the smear-positive TB patients identified had treatment delay or no evidence of treatment initiation. Proper monitoring of laboratory sputum results and suspect TB patient registers could potentially reduce treatment delays and patient loss.

Clinical and programmatic mismanagement rather than community outbreak as the cause of chronic, drug-resistant tuberculosis in Buenaventura, Colombia, 1998.

SETTING: Buenaventura, Colombia. OBJECTIVE: To assess whether antituberculosis drug resistance was generated by poor management or community transmission. DESIGN: Treatment-failure and new tuberculosis (TB) patients identified between May 1997 and June 1998 were interviewed and their treatment histories reviewed. Bacteriologic testing, including drug susceptibility profiles (DSP) and DNA fingerprinting by restriction fragment length polymorphism (RFLP), was performed and human immunodeficiency virus (HIV) testing was offered. RESULTS: DSP and RFLP fingerprints were obtained for isolates from 34 of 64 treatment-failure patients; 25 (74%) were resistant to > or = one drug. Fifteen of the 25 patients consented to HIV testing; none were positive. An average of 2.8 major treatment errors per patient was identified. RFLP from the treatment-failure patients revealed 20 unique isolates and six clusters (isolates with identical RFLP); 4/6 clusters contained isolates with different DSP. Analysis of the RFLP from both treatment-failure and new patients revealed that 44/111 (40%) isolates formed 18 clusters. Four of 47 (9%) new patients had multidrug-resistant TB (MDR-TB). Eleven isolates belonged to the Beijing family, related to the MDR strain W. CONCLUSION: Drug resistance in Buenaventura results from both poor management and community transmission. Dependence on DSP to identify TB transmission is inadequate when programmatic mismanagement is common.

DNA fingerprinting of a national sample of Mycobacterium tuberculosis isolates, Botswana, 1995-1996.

DNA fingerprinting may be useful to elucidate tuberculosis (TB) transmission in community settings, but its utility is limited if only few fingerprint patterns are observed or band numbers are low. We performed DNA fingerprinting on a national, population-based sample of Mycobacterium tuberculosis isolates from Botswana. During 1995-1996, a random sample of 213 isolates, representing 5% of all smear-positive TB cases, underwent DNA fingerprinting using restriction fragment length polymorphism (RFLP) IS6110 analysis. Eighty-two (38%) of the 213 isolates belonged to one of 18 clusters, with 2-9 isolates/cluster. The median number of bands was 10 (range 1-19); 183 (86%) had six or more bands. Sixty-three (49%) of 128 patients tested were infected with the human immunodeficiency virus (HIV). The degree of RFLP pattern heterogeneity and high band number support the feasibility of a prospective DNA fingerprinting study in Botswana.

Tuberculin skin testing to assess the occupational risk of Mycobacterium tuberculosis infection among health care workers in Abidjan, Côte d'Ivoire.

SETTING: Tuberculin skin test (TST) survey of health care workers (HCWs) in selected clinical services in Abidjan, Côte d'Ivoire. OBJECTIVE: To assess whether HCWs in Abidjan are at increased risk for occupationally acquired Mycobacterium tuberculosis infection. DESIGN: From October 1996 to January 1997, consenting HCWs from four services where tuberculosis (TB) prevalence among patients was high and two services where it was low were evaluated with a questionnaire, TST (including evaluation of anergy) and chest radiograph. RESULTS: Of the 512 participants, 405 (79%) had a TST reaction of > or =10 mm, eight (2%) were anergic, five (1%) had a radiograph compatible with TB, and two had confirmed TB. Using a cut-off of 10 mm, we found a higher prevalence of TST positivity in services with high TB prevalence than in those with low TB prevalence (92% vs 72%; odds ratio [OR] 4.3; 95% confidence interval [CI] 2.3-8.0]) and among HCWs with direct (87%; OR 2.9; 95%CI 1.6-5.1) and indirect patient contact (80%, OR 1.7; 95%CI 1.0-2.3) than among those with minimal patient contact (69%). CONCLUSION: These findings indicate that TST positivity among HCWs is related to level of exposure to TB patients, and suggest that HCWs in Abidjan are at risk for the nosocomial transmission of TB.

Survey of drug resistance of Mycobacterium tuberculosis in 3 Mexican states, 1997.

BACKGROUND: Drug resistance threatens global tuberculosis (TB) control efforts. Population-based estimates of drug resistance are needed to develop strategies for controlling drug-resistant TB in Mexico. OBJECTIVE: To obtain population-based data on Mycobacterium tuberculosis drug resistance in Mexico. METHODS: To obtain drug resistance data, we conducted a population-based study of TB cases in the states of Baja California, Sinaloa, and Oaxaca, Mexico. We performed cultures and drug susceptibility testing on M tuberculosis isolates from patients with newly diagnosed, smear-positive TB from April 1 to October 31, 1997. RESULTS: Mycobacterium tuberculosis was isolated from 460 (75%) of the 614 patients. Levels of resistance in new and retreatment TB cases to 1 or more of the 3 current first-line drugs used in Mexico (isoniazid, rifampin, and pyrazinamide) were 12.9% and 50.5%, respectively; the corresponding levels of multi-drug-resistant TB were 2.4% and 22.4%. Retreatment cases were significantly more likely than new cases to have isolates resistant to 1 or more of the 3 first-line drugs (relative risk [RR], 3.9; 95% confidence interval [CI], 2.8-5.5), to have isoniazid resistance (RR, 3.6; 95% CI, 2.5-5.2), and to have multi-drug-resistant TB (RR, 9.4; 95% CI, 4.3-20.2). CONCLUSIONS: This population-based study of M tuberculosis demonstrates moderately high levels of drug resistance. Important issues to consider in the national strategy to prevent M tuberculosis resistance in Mexico include consideration of the most appropriate initial therapy in patients with TB, the treatment of patients with multiple drug resistance, and surveillance or periodic surveys of resistance among new TB patients to monitor drug resistance trends.

Tuberculosis among foreign-born persons in the United States, 1993-1998.

CONTEXT: Immigration is a major force sustaining the incidence of tuberculosis (TB) in the United States. OBJECTIVE: To describe trends and characteristics of foreign-born persons with TB and the implications for TB program planning and policy development. DESIGN, SETTING, AND SUBJECTS: Descriptive analysis of US TB surveillance data from case reports submitted from 1993 to 1998. MAIN OUTCOME MEASURE: Demographic and clinical characteristics of foreign-born persons with TB. RESULTS: The number of TB cases among foreign-born persons increased 2.6%, from 7402 in 1993 to 7591 in 1998, and the proportion of US cases that were foreign-born increased from 29.8% to 41.6%. During 1993-1998, the TB case rate was 32.9 per 100000 population in foreign-born persons compared with 5.8 per 100000 in US-born persons. Six states reported 73.4% of foreign-born cases (California, New York, Texas, Florida, New Jersey, and Illinois). Approximately two thirds of these cases were originally from Mexico, the Philippines, Vietnam, India, China, Haiti, and South Korea. Among those for whom date of US entry was known, 51.5% arrived 5 years or less prior to the diagnosis of TB. Most were male and aged 25 to 44 years. During 1993-1996, the proportion receiving some portion of treatment under directly observed therapy increased from 27.3% to 59.1% and approximately 70% completed therapy in 12 months. The rate of primary resistance to isoniazid was 11.6% and to both isoniazid and rifampin was 1.7%. Conclusions As the United States moves toward the goal of TB elimination, success will depend increasingly on reducing the impact of TB in foreign-born persons. Continued efforts to tailor local TB control strategies to the foreign-born community and commitment to the global TB battle are essential.

Knowledge, attitudes and beliefs regarding tuberculosis preventive therapy for HIV-infected persons, Botswana, 1999.

SETTING: Botswana, 1999. OBJECTIVE: To measure knowledge, attitudes and beliefs about tuberculosis (TB) preventive therapy (PT) for persons infected with the human immunodeficiency virus (HIV). DESIGN: A systematic sample of adult clinic attendees, using a standardised questionnaire. RESULTS: A total of 275 patients at 38 clinics in five districts were interviewed. The majority were female (65%) and unmarried (84%). Knowing someone with TB or AIDS was common (78% and 53%, respectively). Respondents perceived a relationship between TB and HIV (80%), and the majority were willing to undergo tuberculin skin testing (92%). Of those, most were willing to undergo evaluation for active TB (98%), and to take PT, although willingness to take PT declined with proposed duration (97% 6 months, 90% 1 year, 81% lifetime, P < 0.01). Previous HIV testing was reported by 13%; those who had not undergone testing reported that they would if doctors could improve the quality (95%) or duration (93%) of life of persons with AIDS. The majority favoured receiving HIV test results on the day they were tested (60%). CONCLUSIONS: Most clinic attendees in Botswana were willing to undergo HIV testing if it were beneficial to do so, such as by receiving PT. Pilot PT projects should be initiated. Voluntary HIV counselling and testing services should consider rapid HIV testing methods.

Detection of substandard fixed-dose combination tuberculosis drugs using thin-layer chromatography.

SETTING: A convenience sample of 13 fixed-dose combination (FDC) tuberculosis (TB) drugs from 'The Fixed Dose Combination Project' was analysed in laboratories at the University of Botswana and the US Food and Drug Administration (FDA). OBJECTIVE: To determine actual versus stated content of drugs in these FDCs. DESIGN: Chemical analysis was performed using thin-layer chromatography (TLC) as a screening method, and ultraviolet (UV) spectrophotometry or liquid chromatography (LC) as confirmation. FDCs with content outside of 85-115% of stated concentration were defined as substandard. RESULTS: All 13 FDCs contained the stated drugs. However, four (31%) were substandard, including two (15%) with low rifampicin content, one (8%) with excessive rifampicin, and one (8%) with excessive pyrazinamide. Both FDCs with low rifampicin contained four drugs and failed TLC screening. The FDC with excessive rifampicin was not detected by TLC screening. Using UV as the gold standard, the sensitivity of TLC for low rifampicin was 2/2 (100%), and the specificity was 9/10 (90%). CONCLUSION: This study found that 31% of the FDCs in 'The Fixed Dose Combination Project' had substandard content, irrespective of bioavailability. Low rifampicin content, which can be reliably detected by TLC screening, was identified in both four-drug FDC products and is particularly worrisome. TB drugs should be screened for quality using TLC to optimise treatment outcomes and to prevent increases in acquired drug resistance.

Tuberculosis prevention and control activities in the United States: an overview of the organization of tuberculosis services.

After a 20% increase in tuberculosis (TB) cases between 1986 and 1992, TB cases in the United States have declined from 1993 through 1997, an average of 5 to 7 per cent per year. In this paper, we review trends and the current epidemiology of TB in the US, present a brief history of TB control efforts in the country, and present the key strategies for TB control in the US. We describe the current organizational structure of TB services in the US, the role of the private sector in TB control, and how TB control is funded. Finally we discuss the mechanisms by which TB policy is developed. The US model represents a categorical disease program that combines a centralized role of the national government in development of policy, funding, and in the maintenance of national surveillance, and a decentralized role of state and local jurisdictions, which adapt and implement national guidelines and which are responsible for day-to-day program activities. Given the relative success of this combined approach, other countries facing the challenge of maintaining an effective TB control program in the face of increased decentralization of health services may find this description useful.