La tuberculosis zoonótica en la Argentina / Zoonotic tuberculosis in Argentina

Existen importantes logros en el control de la tuberculosis (TB) animal en la Argentina. Los porcentajes de bovinos con lesiones TB halladas en mataderos disminuyeron de 6.7% a 0.7% entre 1969 y 2011. En salud pública, el porcentaje promedio de TB por M. bovis sobre el total de los casos confirmados bacteriológicamente, fue en Santa Fe -provincia agro industrial- 2.3% en el período 1977-2001 y 1.6% entre 2002 y 2011. En Buenos Aires, en el Hospital Cetrángolo, ese porcentaje fue 0.34% (2001-2005) y 0.36% (2006-2011). En el Hospital Muñiz disminuyó de 1.75% en 1971 a 0.22% en 2006. La frecuencia de HIV entre los casos de M. bovis varió de 5.9% en Santa Fe a 11.1% y 20.5% respectivamente en los Hospitales Cetrángolo y Muñiz de Buenos Aires. En conjunto, la infección por M. bovis es más importante en las zonas rurales/ agro industriales, con un lento descenso, también observado en Buenos Aires. La coinfección por HIV es más frecuente en pacientes con M. bovis que en el conjunto de los casos de TB. Comparando la situación de la Argentina con la de EE.UU. y países de Europa y América Latina, se observa que las tendencias de la TB en el ganado, en humanos y la frecuencia relativa del M. bovis en salud pública, no siempre siguen una relación estrecha. Para avanzar hacia la meta común de erradicación de la TB, el empleo de estrategias adecuadas y el fortalecimiento de las medidas de control son fundamentales para ambos programas.(AU)

There are significant achievements in the control of animal tuberculosis (TB) in Argentina. The percentage of bovines with apparent TB lesions at the slaughterhouse inspection decreased from 6.7% to 0.6% between 1969 and 2011. On the other hand, the mean percentage of human TB cases due to M. bovis among all those bacteriologically confirmed, was in Santa Fe, an agro-industrial province, 2.3% in the period 1977-2001. It fell to 1.6% by 2011. In the Cetrángolo Hospital (Buenos Aires), it was 0.34% in the period 2001-2005, and 0.36% in 2006-2011. At the Muñiz Hospital, these percentages decreased from 1.75% in 1971 to 0.22% in 2006. Frequency of HIV infection among M. bovis cases varied from 5.9% in Santa Fe to 11.1% and 20.5% respectively, in Cetrángolo and Muñiz Hospitals (a reference institution for aids) in Buenos Aires. According to these data M. bovis infection predominates in agro- industrial/ rural areas, showing a slow decrease there as well as in Buenos Aires. Co-infection with HIV is more frequent among patients with M. bovis that in all cases of TB. The situation of M. bovis in Argentina is here compared with that in USA and in several European and Latin American countries. Trends followed by TB in cattle, in humans, and the percentages of M. bovis among them, are not always closely related. To move towards the common goal of eradicating TB, the employment of appropriate strategies and the strengthening of control measures are critical in both programs.(AU)

La tuberculosis zoonótica en la Argentina / Zoonotic tuberculosis in Argentina

Existen importantes logros en el control de la tuberculosis (TB) animal en la Argentina. Los porcentajes de bovinos con lesiones TB halladas en mataderos disminuyeron de 6.7% a 0.7% entre 1969 y 2011. En salud pública, el porcentaje promedio de TB por M. bovis sobre el total de los casos confirmados bacteriológicamente, fue en Santa Fe -provincia agro industrial- 2.3% en el período 1977-2001 y 1.6% entre 2002 y 2011. En Buenos Aires, en el Hospital Cetrángolo, ese porcentaje fue 0.34% (2001-2005) y 0.36% (2006-2011). En el Hospital Muñiz disminuyó de 1.75% en 1971 a 0.22% en 2006. La frecuencia de HIV entre los casos de M. bovis varió de 5.9% en Santa Fe a 11.1% y 20.5% respectivamente en los Hospitales Cetrángolo y Muñiz de Buenos Aires. En conjunto, la infección por M. bovis es más importante en las zonas rurales/ agro industriales, con un lento descenso, también observado en Buenos Aires. La coinfección por HIV es más frecuente en pacientes con M. bovis que en el conjunto de los casos de TB. Comparando la situación de la Argentina con la de EE.UU. y países de Europa y América Latina, se observa que las tendencias de la TB en el ganado, en humanos y la frecuencia relativa del M. bovis en salud pública, no siempre siguen una relación estrecha. Para avanzar hacia la meta común de erradicación de la TB, el empleo de estrategias adecuadas y el fortalecimiento de las medidas de control son fundamentales para ambos programas.

There are significant achievements in the control of animal tuberculosis (TB) in Argentina. The percentage of bovines with apparent TB lesions at the slaughterhouse inspection decreased from 6.7% to 0.6% between 1969 and 2011. On the other hand, the mean percentage of human TB cases due to M. bovis among all those bacteriologically confirmed, was in Santa Fe, an agro-industrial province, 2.3% in the period 1977-2001. It fell to 1.6% by 2011. In the Cetrángolo Hospital (Buenos Aires), it was 0.34% in the period 2001-2005, and 0.36% in 2006-2011. At the Muñiz Hospital, these percentages decreased from 1.75% in 1971 to 0.22% in 2006. Frequency of HIV infection among M. bovis cases varied from 5.9% in Santa Fe to 11.1% and 20.5% respectively, in Cetrángolo and Muñiz Hospitals (a reference institution for aids) in Buenos Aires. According to these data M. bovis infection predominates in agro- industrial/ rural areas, showing a slow decrease there as well as in Buenos Aires. Co-infection with HIV is more frequent among patients with M. bovis that in all cases of TB. The situation of M. bovis in Argentina is here compared with that in USA and in several European and Latin American countries. Trends followed by TB in cattle, in humans, and the percentages of M. bovis among them, are not always closely related. To move towards the common goal of eradicating TB, the employment of appropriate strategies and the strengthening of control measures are critical in both programs.

[Is the tuberculin skin test still suitable to diagnose tuberculosis infection ?]. / ¿Es suficiente la prueba tuberculínica para el diagnóstico de la infección tuberculosa ?

Tuberculosis (TB) infection is currently being diagnosed by the tuberculin skin test (TST) with PPD. Some Mycobacterium tuberculosis PPD components are present in BCG, which can be the cause of false positive TST results in BCG vaccinated persons. New IFN-g release assays (IGRAs) are based on the ex vivo release of IFN-g by peripheral blood cells in presence of M. tuberculosis antigens ESAT-6 and CFP-10, which should be absent in BCG. These assays consist in either quantifying released IFN-g or enumerating IFN-g producing cells. In principle, IGRAs should differentiate true TB infection from vaccination and results of several studies suggest that these assays display lower positivity than TST. Whether the lower positivity could be attributed to higher specificity or to lower sensitivity as compared with PPD is still unclear. BCG vaccination, if not recently applied, cannot be blamed for false positive TST reactions. Strong TST reactions (> or = 10 mm or > or =15 mm) are highly correlated with TB infection. In settings where TB continues being a serious health problem, cost-effectiveness evaluations would privilege TST under certain conditions: supply of quality-assured PPD reagent, standardized criteria for TST application, reading and interpretation, and regular availability in health centers countrywide. In view of current limitations in the supply of imported PPD in Argentina, its production/quality assurance should be considered a public health priority. Still, key questions remain to be addressed concerning the role of IGRAs and TST in predicting risk of TB disease, in other words, in identifying persons who will benefit most from chemoprophylaxis.

¿Es suficiente la prueba tuberculínica para el diagnóstico de la infección tuberculosa? / Is the tuberculin skin test still suitable to diagnose tuberculosis infection?

La infección tuberculosa (TB) se determina por la prueba tuberculínica (PTC) con PPD, un extracto de proteínas/péptidos de Mycobacterium tuberculosis, algunos compartidos con otras micobacterias como BCG, lo cual origina falsos resultados positivos en vacunados/no infectados. La nuevas pruebas ex vivo miden el interferón ? (IFN- ?) liberado en sangre, o la cantidad de células que lo producen, en presencia de los péptidos ESAT-6 y CFP-10 de M. tuberculosis. Como estos antígenos no existirían en BCG, las pruebas IFN-? diferenciarían infección TB de vacunación. Numerosos estudios han comparado estas pruebas con la PTC con resultados aún no concluyentes. Las pruebas IFN-? tendrían menor sensibilidad que la PTC, aunque su menor positividad en poblaciones vacunadas podría interpretarse como mayor especificidad. Por otra parte, la vacunación BCG, si no es reciente, no es causa de falsos positivos a la PTC: reacciones =10 mm o =15 mm indican infección TB con altísima probabilidad. Donde la incidencia de TB es mediana o alta, la PTC aventaja en costo-eficiencia a las pruebas IFN-?, siempre que se emplee PPD de calidad garantizada, disponible en todos los centros de salud del país, con aplicación, lectura e interpretación estandarizadas. Como existen en la Argentina problemas de abastecimiento de PPD importado, es preciso producirlo localmente y asegurar su control de calidad. También es necesaria la investigación aplicada al desarrollo de nuevos métodos y la evaluación de su capacidad de predecir la evolución de infección a TB activa, es decir, de identificar las personas que más se beneficiarían con quimioprofilaxis.

Tuberculosis (TB) infection is currently being diagnosed by the tuberculin skin test (TST) with PPD. Some Mycobacterium tuberculosis PPD components are present in BCG, which can be the cause of false positive TST results in BCG vaccinated persons. New IFN-? release assays (IGRAs) are based on the ex vivo release of IFN-? by peripheral blood cells in presence of M. tuberculosis antigens ESAT-6 and CFP-10, which should be absent in BCG. These assays consist in either quantifying released IFN-? or enumerating IFN-? producing cells. In principle, IGRAs should differentiate true TB infection from vaccination and results of several studies suggest that these assays display lower positivity than TST. Whether the lower positivity could be attributed to higher specificity or to lower sensitivity as compared with PPD is still unclear. BCG vaccination, if not recently applied, cannot be blamed for false positive TST reactions. Strong TST reactions (=10 mm or =15 mm) are highly correlated with TB infection. In settings where TB continues being a serious health problem, cost-effectiveness evaluations would privilege TST under certain conditions: supply of quality-assured PPD reagent, standardized criteria for TST application, reading and interpretation, and regular availability in health centers countrywide. In view of current limitations in the supply of imported PPD in Argentina, its production/quality assurance should be considered a public health priority. Still, key questions remain to be addressed concerning the role of IGRAs and TST in predicting risk of TB disease, in other words, in identifying persons who will benefit most from chemoprophylaxis.

Tuberculosis: a re-emerging disease in animals and humans.

Tuberculosis continues to be an important disease both in humans and animals. It causes morbidity, mortality and economic loss worldwide. The occurrence of Mycobacterium bovis disease in humans, domesticated and wild animals confirms the relevance of this zoonosis. M. bovis in humans continues to be reported in industrialised countries and in immigrants from regions of the world where tuberculosis in cattle is endemic. The real incidence of M. bovis in humans in developing countries continues to be roughly under-estimated due to the scarcity of appropriate laboratory facilities to isolate and to differentiate M. bovis strains. In Latin America, less than 1% of tuberculosis cases are reported as being due to M. bovis. However, the economic relevance that meat and dairy industries play in these countries stimulates the promotion of bovine tuberculosis eradication programmes. Human-to-human airborne transmission of M. bovis does occur and it may be important where human immunodeficiency virus (HIV) infection in humans is prevalent, M. bovis infection in cattle is enzootic and pasteurisation of dairy products is not routinely practised. Eradication of M. bovis in cattle and pasteurisation of dairy products are the cornerstones of prevention of human disease. Measures should be developed to identify and control M. bovis infection in wild animals as these may be important reservoirs of infection for domesticated food-producing animals. There is a need for medical and veterinary professionals to cooperate on disease outbreaks. The information presented herein strongly supports the 'One World/One Health/One Medicine' concept.

Human Mycobacterium bovis infection in ten Latin American countries.

The aim of this work was to obtain the best possible estimate of the relevance of bovine tuberculosis (BTB) in humans in Argentina, Brazil, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, Peru, Uruguay and Venezuela. Sources of information were a questionnaire filled by the participant laboratories, and a search of published literature (1970-2007). Only four of these countries reported bacteriologically confirmed cases of BTB in humans. Most of these were diagnosed in Argentina, where the mean percentage of Mycobacterium bovis cases in relation to those due to Mycobacterium tuberculosis (2000-2006) ranged from 0.34% to 1.0%, according to the region. A slowly decreasing trend was observed in non HIV as well as in HIV/AIDS patients in Buenos Aires. In most of these countries, the low coverage of culture methods, especially of those including pyruvate-containing media, appropriate to isolate M. bovis, contributes to an underestimate of the problem. It was confirmed that BTB in humans exists, even though its relevance seems to be low. Milk pasteurization, sanitary controls to dairy products, and meat inspection at slaughterhouses contribute to the protection of human health. However, occupational aerogenous exposure to TB cattle and their carcasses remains a source of infection in the region.

Susceptibility tests to second line drugs and re-treatment of tuberculosis revisiting early experiences.

The value of susceptibility tests in guiding antituberculous therapy with second-line drugs remains controversial. We reanalyzed three reports regarding the relationship between in vitro susceptibility of Mycobacterium tuberculosis and the clinical outcome of in-patients treated with these drugs at the Muñiz Hospital, Buenos Aires, during the sixties. These patients had been irregularly treated with a standard regimen consisting of isoniazid, streptomycin and PAS; they developed resistance to at least the first two drugs and persisted culture-positive. Susceptibility testing to ethionamide, cycloserine and kanamycin were performed by the proportion method on Löwenstein Jensen medium. Some level of resistance was detected among isolates from patients not previously treated with these drugs, that could be due to cross resistance with previously administered first line structural analogs. However, the studies evidenced significant association between resistance to ethionamide and cycloserine and prior treatment with these drugs. Increased resistance to all three drugs was detected within the first three months of treatment. In vitro resistance to ethionamide emerged earlier and was the most frequent followed by resistance to cycloserine and kanamycin. The low frequency of resistance to kanamycin could be related to the low dosage of this drug used at that time. Simultaneous resistance to the three agents, but not to two or one drug, appeared to be a marker of treatment failure. An apparent reversion of drug resistance was observed in near 6% of patients, for whom susceptibility tests were repeated on subsequent isolates, indicating this percentage of inconsistency in reproducibility of test results.

The importance of Mycobacterium bovis as a zoonosis.

Mycobacterium bovis and closely associated acid-fast bacilli cause disease in humans. Epidemiologic investigations reveal that the organism may be ingested or inhaled. Extra pulmonary lesions may occur associated to the consumption of infected milk, even though with the practice of boiling milk, and the growth of milk pasteurization plants all over the world, the digestive route of infection became less important. On the other hand, airborne infection continues to occur among meat industry and slaughterhouse workers, in regions where the infection is still prevalent in cattle. Evidence of person to person transmission is rare. Main causes of concern related to M. bovis in industrialized countries are: epizootics in domesticated and wild mammals and latent infection in immigrants. Although multidrug-resistant (MDR) strains of M. bovis have been identified, case reports reveal that anti-tuberculosis drugs routinely used to treat Mycobacterium tuberculosis-infected patients are effective when properly administered.

An update on bovine tuberculosis programmes in Latin American and Caribbean countries.

Of the approximately 374 million cattle in Latin America and the Caribbean, 70% are held in areas where rates of Mycobacterium bovis infection in cattle are higher than 1%. The remaining 30% are in countries where infection affects less than 1% of cattle, including 62 million in countries where bovine tuberculosis infection is virtually nil. Measures for controlling bovine tuberculosis are partially or extensively applied in most of the countries in the Region. These measures are based on test and slaughter, notification, post-mortem inspection and surveillance in slaughterhouses. A coordinated production, standardization and quality control of purified protein derivatives is urgently required for use in control and eradication campaigns in order to assure reliability of reagents and comparability of data on tuberculin testing within the Region. On the basis of information from Argentina, M. bovis is estimated to cause 2% of all human cases of tuberculosis in the Region. Slaughterhouse and dairy farms workers are most-frequently infected, with infection occurring via the respiratory tract. Various in vitro assays for the diagnosis of bovine tuberculosis have been developed and/or assessed in the Region, and DNA fingerprinting has been applied for a comprehensive understanding of the epidemiology of bovine tuberculosis at the local and regional level.

[Childhood tuberculosis and its diagnosis in Argentina]. / La tuberculosis infantil y su diagnóstico en la Argentina.

TB notification rate in infants and children 0-4 years was 24.3/100,000 in Argentina, in 2000, for a global incidence of 31.8/100,000. A 17% of all TB cases occurred in children (0-14 years), indicating a very active TB transmission. Usually TB is diagnosed when the disease is already advanced. Main criteria for the diagnosis are: a previous contact with an infectious TB patient, a positive PPD test result and clinical--radiological signs and symptoms. Bacteriology plays a limited role in diagnosis; gastric aspirate is the most often used specimen for bacteriological examination in children. Culture is performed on solid egg-media, but other more recently developed culture media systems are available in reference laboratories. Nucleic acid amplification assays are also used, but its systematic quality control is still lacking. Their results should be considered only as complementary. Strengthening of the laboratory network will contribute to increase diagnostic certainty of childhood TB, to improve reliability of cases reported, and to a better knowledge of the drug resistance profile. Early diagnosis of TB in children, by contacts investigation of infectious patients, followed by preventive chemotherapy or treatment when necessary, may revert the current epidemiological situation. TB meningitis in the 0-4 years group showed a significantly more pronounced decline than that of adults TB for the period 1980-2000, (only 10 meningitis cases were diagnosed in year 2000, 0.29/100,000), confirming the protection conferred by BCG vaccination when applied to newborns with a continuously high coverage.