Human tuberculosis caused by Mycobacterium bovis in the United States, Latin America and the Caribbean.

Human tuberculosis (TB) caused by Mycobacterium bovis appears to be rare in most of the region of the Americas, although some localities have reported an unusually high prevalence of M. bovis among human TB cases (e.g., San Diego, CA, USA; parts of Mexico). As surveillance data are lacking in many countries, there is substantial uncertainty regarding actual incidence. M. bovis is most often not identified, as the diagnosis of TB is made by smear microscopy alone or using egg-containing culture media lacking pyruvate. Where human M. bovis cases have been studied in the region, they appear to be associated with ingestion of unpasteurized dairy products, or with airborne acquired infection in animal keepers and meat industry workers from countries where bovine TB remains a problem. Human-to-human transmission of M. bovis does occur, but appears to account for a very small proportion of cases. Efforts to eradicate M. bovis in humans in the Americas should therefore be directed at eradicating the disease in cattle, increasing pasteurization of dairy products and providing education about the dangers of consuming unpasteurized dairy products.

AIDS pacient's long-term battle with multiply recurrent tuberculosis: reinfection or reactivation?

The advent of Mycobacterium tuberculosis strain genotyping has allowed differentiation between disease relapse and exogenous re-infection. We report here a remarkable case of multiply recurrent tuberculosis in a patient living with HIV. Between 1995 and 2009, a young HIV-infected intravenous drug user, who was reluctant to comply with anti-retroviral treatment, underwent at least five tuberculosis episodes caused by three distinct M. tuberculosis strains sharply differentiated by drug susceptibility profile, genotype and infectious source. Eventually, the patient died during a relapse of tuberculosis due to a notorious multidrug-resistant outbreak-strain, which infected him during a prolonged hospitalization in the epicentre of such outbreak. Whether recurrent tuberculosis is due to a new infection or to reactivation of a previous one is a century-long controversial question. In our patient, both conditions alternated throughout his 15 years of living with HIV. Cases such as this might not be exceptional in certain underprivileged suburban areas of Argentina and should raise concern over three pending issues in tuberculosis control policies, namely secondary preventing therapy, institutional infection control and patient follow-up throughout the health network system.

[Resistance and multiresistance to antitubercular drugs in Argentina and in other Latin American countries]. / La resistencia y multirresistencia a los medicamentos antituberculosos en la Argentina y en otros países de América Latina.

Resistance of Mycobacterium tuberculosis to both isoniazid (INH) and rifampicin (RPM), the most important antituberculosis drugs, with or without simultaneous resistance to other drugs, is known as multidrug resistance (MDR). It is the main obstacle to attain the cure of patients by the specific treatment, and a threat to the tuberculosis control. Between 1994 and 1997, several Latin American countries undertook countrywide surveys or surveillance programs to determine their primary and acquired drug resistance prevalence rates. These studies followed the WHO/International Union Against Tuberculosis and Lung Diseases (IUATLD) guidelines. Percentages of not previously treated patients with tuberculosis due to MDR strains ranged from null or very small (Uruguay, Cuba, Chile) to 4% or higher (Dominican Republic, Argentina). In Argentina, a remarkable correlation between MDR tuberculosis, AIDS and the assistance in urban reference hospitals for infections diseases was observed. Coincidentally with the survey, nosocomial spread of HIV-related MDR tuberculosis occurred in two of these hospitals situated in Buenos Aires and Rosario. But, at the same time, an alarming emergence of MDR was evidenced among non HIV-infected patients with history of previous antituberculosis treatment. Directly observed treatment (DOT) should be increasingly applied, and drug supply guaranteed. Treatment as well as microscopy services for diagnosis and follow up of patients, should be decentralized from the big specialized hospitals in urban areas to the peripheral health centers, in order to make easier for the patients to attend regularly and receive their medications. These strategies will contribute to increase cure rates and to reduce the tuberculosis transmission.

Zoonotic tuberculosis due to Mycobacterium bovis in developing countries.

The World Health Organization (WHO) estimates that human tuberculosis (TB) incidence and deaths for 1990 to 1999 will be 88 million and 30 million, respectively, with most cases in developing countries. Zoonotic TB (caused by Mycobacterium bovis) is present in animals in most developing countries where surveillance and control activities are often inadequate or unavailable; therefore, many epidemiologic and public health aspects of infection remain largely unknown. We review available information on zoonotic TB in developing countries, analyze risk factors that may play a role in the disease, review recent WHO activities, and recommend actions to assess the magnitude of the problem and control the disease in humans and animals.

Nosocomial spread of human immunodeficiency virus-related multidrug-resistant tuberculosis in Buenos Aires.

A steep upsurge of human immunodeficiency virus (HIV)-associated multidrug-resistant tuberculosis (MDR-TB) was recently observed at a referral treatment center in Buenos Aires City. Between January 1994 and June 1995, TB isolates resistant to at least five drugs were recovered from 101 of 272 HIV-infected inpatients. Highly resistant isolates from 77 patients underwent restriction fragment length polymorphism study with IS6110. After cross-contamination was eliminated, a single TB strain was found to have caused disease in 68 patients with a history of on-site exposure. The frequency of smear-positive pulmonary disease was higher among these patients than among non-MDR-TB HIV-infected patients (50/68 vs. 60/148, P < .001), and the 1-year survival was dramatically reduced (5/68 vs. 92/148). The strain involved in the outbreak was traced back to patients hospitalized in 1992. Institutional infection control policies were and may still be inadequate to contain the spread of TB among immunodepressed subjects, as is the case in other large urban hospitals in Argentina.

Multidrug resistant tuberculosis outbreak in Buenos Aires. DNA fingerprinting analysis of isolates.

In order to determine the possible relationship among HIV patients coinfected with multidrug resistant tuberculosis strains who had been receiving clinical assistance in our Hospital, clinical and epidemiological information from 28 patients was collected. DNA fingerprinting by restriction fragment length polymorphism (RFLP) pattern was performed on the mycobacterial isolates from these patients, using the restriction enzyme Pvull and IS 6110 as genetic marker. A unique RFLP pattern was found in 10 isolates from 10 different patients who had a disease caused by a single strain. Our findings confirm RFLP as a reliable and useful tool to analyze TB transmission.

Bovine tuberculosis in Latin America and the Caribbean: current status, control and eradication programs.

Out of the approximately 300 million head which constitute the bovine population in Latin America and the Caribbean, 80 million are found in countries where rates of Mycobacterium bovis infection are very low or nil. The remaining 220 million are found in countries with either a moderate to high prevalence or where no recent information is available. Argentina and Brazil, both have huge cattle populations with estimated prevalences higher than 1%, and together may harbour 3.5 million infected cattle. Information on the impact of M. bovis on human health in the Region is scarce and does not include data on infection of children. In Argentina, human tuberculosis of bovine origin was found to be mainly an occupational disease, transmitted by aerosol. Control or eradication has been achieved in several countries in the Region by use of the tuberculin test followed by sacrifice of reactors. In countries such as Cuba, where the prevalence is already very low, area tuberculin testing is being replaced by slaughter surveillance and epidemiological trace-back. Other countries, where the prevalence is high (e.g. Chile, Paraguay, Peru and Argentina), promote regional campaigns based on the decision and active participation of cattle farmers. Recent diagnostic developments based on the in vitro measurement of humoral and cellular immune responses could be an aid in control and eradication campaigns, provided their usefulness is demonstrated in field trials. In heavily infected areas complementary or alternative strategies should also be proposed, aiming at lowering the prevalence rates prior to the application of the test and slaughter method.

Drug-resistant tuberculosis: laboratory issues. World Health Organization recommendations.

There is a suggestion that drug resistance rates decreased in developing countries over the period 1962-85, while recent data suggest that resistance may be increasing. The initial decrease in resistance appears to be associated with well-functioning National Tuberculosis Control Programmes (NTP), while the recently observed increase may be due either to understaffed, resource-poor programmes or to the effect of the HIV epidemic, or to both. It is possible that the HIV epidemic may overwhelm the NTP, resulting in decreased programme efficiency and ultimately increased drug resistance. Resistance surveillance appears to be a good measure of programme efficiency. For research purposes, primary drug resistance surveys should be done on a sample of relevant patients which includes and distinguishes between HIV-positive and HIV-negative patients. At this time, there is not enough information to warrant a recommendation regarding HIV testing of TB patients for surveillance purposes. In order for resistance surveys to be relevant from the public health perspective, one must know the proportion of patients presenting for treatment having previously received treatment. The meaningful denominator for drug resistance surveys from the programme evaluation perspective should be the number of patients presenting for treatment. For initial drug resistance surveys the measurement should be the number of people never having received prior TB treatment with resistant bacilli, divided by the number of new patients presenting for treatment. For acquired resistance, one should look at all patients who begin treatment with susceptible bacilli who become resistant 6 months later.