[Clinical relevance of nontuberculous mycobacteria]. / Relevancia clínica de los aislamientos de micobacterias no tuberculosas.

BACKGROUND: The isolation of nontuberculous mycobacteria (NTM) has increased in recent years largely due to the use of liquid cultivation media. In many cases such isolations lack clinical relevance, which is why the evaluation of their meaning must be carried out on the basis of international clinical criteria. This article studies the impact of using the criteria that the American Thoracic Society (ATS) has established for differentiating an infection of NTM colonisation in respiratory samples. METHODS: Microbiological and clinical study of the patients with repeated isolations of NTM in respiratory samples registered in our laboratory between 2000 and 2004. RESULTS: One hundred and sixteen positive cultivations of NTM were obtained, repeatedly isolated in 46 episodes corresponding to 42 patients. Eleven different species were identified: M. xenopi (16 cases), M. avium (12), M. kansasii (7), M. fortuitum (5), M. malmoense (2) and, finally, 1 of each of the following: M. genavense, M. simiae, M. gordonae and M. lentiflavum. It was possible to study 36 patients, of whom 17 met the criteria of the ATS, and, out of these, only 12 received specific treatment. In those cases that did not meet the ATS criteria the isolations did not have any clinical repercussion. In both the treated and untreated groups a clearly differentiated evolution was not observed. CONCLUSIONS: Facing the difficulty of attributing an etiological role to an NTM of respiratory samples, it is necessary to follow international criteria such as those of the ATS before beginning a specific treatment in order to avoid the incorrect treatment of patients.

[Microbiology of tuberculosis]. / Microbiología de la tuberculosis.

For a century, the diagnosis of tuberculosis, based on bacilloscopy and the isolation and identification of Mycobacterium tuberculosis in cultures, has been slow and not very sensitive. This has made it necessary on occasions to initiate treatment with tuberculostatics in an empirical way. The routine incorporation of liquid mediums and molecular genetic techniques in the final decade of the XX century brought an important advance by clearly increasing the sensitivity, precision and rapidity of diagnosis. The present blossoming of molecular techniques is making possible a better understanding of the disease's epidemiology, the factors of virulence and the mechanisms of resistance, which in the near future will give rise to new strategies of prevention and for treating the disease.

[Study of the resistance of Mycobacterium tuberculosis to the principal tuberculostatics (Hospital of Navarra 1996-2003)]. / Estudio de la resistencia de Mycobacterium tuberculosis a los principales tuberculostáticos (Hospital de Navarra 1996-2003).

INTRODUCTION: The aim of this study was to evaluate the sensitivity to the principal tuberculostatics of the M. tuberculosis stocks isolated in our laboratory and to study the factors related to resistance. METHODS: Study of 475 stocks of M. tuberculosis corresponding to all cases diagnosed in the eight year period between 1996 and 2003. We employed the BACTEC 460TB system, together with Lowenstein solid medium, in the cultivation of the samples. The sensitivity studies were carried out using the BACTEC 460TB system. RESULTS AND CONCLUSIONS: Both the incidence and the number of cases of resistant tuberculosis showed oscillations over the eight years of the study. The fact that there is no homogeneous tendency makes it necessary to maintain active surveillance of this process. Global resistance to isoniacide was 8%, making it is convenient to carry out sensitivity studies in all the diagnosed cases. The cases of multiresistant tuberculosis (resistant to at least isoniacide and rifampicin), did not exceed 3%. The prognosis of the patients with resistant tuberculosis was bleak in cases of coinfection with HIV; however, when the immunological defences were conserved, and guidelines for treatment with active drugs were provided, the recovery of the majority of the patients was achieved. At present, sensitive and rapid procedures are available to us, making it recommendable to study the sensitivity of all the stocks of M. tuberculosis that are isolated; this is essential in the case of HIV positive or immigrant patients.

[Evaluation of the MTD-2 test for the direct detection of Mycobacterium tuberculosis in specimens]. / Valoración de la prueba de amplificación MTD-2 para la detección directa de Mycobacterium tuberculosis en la muestra.

BACKGROUND: To evaluate the utility of the Amplified Mycobacterium Tuberculosis Direct Test (MTD-2, Gen-Probe) in the microbiological diagnosis of tuberculosis. METHODS: We evaluated the results obtained in 146 specimens with the MTD-2 test, together with those of the culture and smears. The MTD-2 test was performed on all the smear positives specimens (n=47), on the smear-negative specimens, when the test was demanded (n=19), and in other smear-negative specimens previously selected, according to the clinical history of the patient (n=80). We considered real cases of tuberculosis, those that were culture positive for Mycobacterium tuberculosis and those that were specifically treated. RESULTS: The overall sensitivity, specificity, positive and negative predictive values for the MTD test were: 95, 76, 71, and 96%, for the culture; and 84, 100, 100 and 90% and 75, 94, 89 and 86% for the smears, respectively. In smear positive specimens, the test showed a great specificity, and differentiated M. tuberculosis from other mycobacteria. In the smear negatives, the sensitivity of the test was low and so was the positive predictive value, especially in series performed with a high work load. CONCLUSIONS: Data from our study show that the MTD-2 test is a reliable method for rapid diagnosis of tuberculosis in smear positive specimens. However, due to its low sensitivity and positive predictive value, it is not recommended in the routine diagnosis of tuberculosis. Also, for this reason, whenever a positive result is obtained with a smear negative specimen, the result needs to be confirmed with another specimen.

[Evolution of the epidemiological characteristics of tuberculosis in Navarra (1994-2003)]. / Evolución en las características epidemiológicas de la tuberculosis en Navarra (1994-2003).

AIM: To describe the changes in the incidence and the epidemiological profile of tuberculosis in Navarra. METHODS: The cases of tuberculosis in the 1994-2003 period were analysed. Cases reported to the system of obligatory notifiable diseases, completed with the microbiological diagnoses and the cases collected in other health registers. RESULTS: The incidence of tuberculosis fell from 21 per 100,000 inhabitants in the five-year period 1994-1998 to 16 per 100,000 in 1999-2003. In both periods the number of cases in men doubled that in women, and the maximum incidence occurred in the age groups from 25 to 44 and over 65 years of age. The diagnoses of tuberculosis in persons with HIV infection fell from 15.1% to 6.6% and those in immigrants rose from 2.2% to 21.3%. Somewhat over 3% of the cases had received prior anti-tuberculosis treatment and about 6% showed resistance to some medicine, without significant differences between periods. The proportion of potentially transmissible tuberculosis (73%) underwent no significant changes, nor did that of those with positive sputum bacilloscopy. The number of outbreaks (groupings of two or more cases) rose from 18 to 26 and the percentage of cases secondary to another recent case rose from 3.6% to 10.1% (p<0,001). In the 1999-2003 period, pulmonary localisation occurred in isolated form in 67.7% of the patients, and in combination with other localisations in another 5.1%. The isolated pleural form appeared in 9.9% and the meningeal form in 1.5%. CONCLUSION: There has been an advance in the control of tuberculosis although its incidence is still high with respect to other European countries. Control of imported cases is one of the challenges to be faced in coming years, without neglecting control measures in the autochthonous population.

[Changes in the diameter of the coronary arteries in heart transplant recipients with angiographically normal vessels during five years]. / Cambios de diámetro de las arterias coronarias en receptores de transplante cardíaco con vasos angiográficamente normales durante cinco años.

INTRODUCTION: Diffuse or focal coronary artery narrowing is a frequent complication of cardiac transplantation. Coronary enlargement has also been described although it is less known. To study the changes of the coronary arteries in transplant recipients, we have performed a quantitative study throughout 5 years. METHODS: Serial coronary angiography was performed annually in all survivors of heart transplant. Forty four patients with visually normal coronary arteries and at least 5 years of evolution were selected for this study. Quantitative measurements of the diameter of the coronary arteries were performed in each angiogram at different levels: proximal, medium and distal left anterior descending coronary artery; proximal and distal left circumflex; proximal, medium and distal right coronary artery. Changes in diameter were compared throughout the 5 years. RESULTS: In the entire group of patients there was a small increase in the diameter of each segment. Taking each patient separately, an enlargement of the diameter of the proximal descending coronary artery was seen in 17 cases; medium descending coronary artery in 13; distal descending coronary artery in 8; proximal left circumflex in 11; distal left circumflex in 14; proximal right coronary artery in 18; medium right coronary artery in 18 and distal right coronary artery in 15. In total, 114 of 352 coronary segments (32%) underwent dilatation. Only 6 patients failed to have dilatation of any segment. CONCLUSIONS: Enlargement of the coronary arterial diameter was seen in 32% of segments of the main coronary arteries in heart transplant recipients with angiographically normal coronary arteries during 5 years of evolution. This could be due to intimal thickening with overcompensation by an additional vessel enlargement with net lumen gain.

[Outbreak of multiresistant tuberculosis]. / Brote de tuberculosis multirresistente.

BASIS: Six cases of multiresistant tuberculosis diagnosed in the Hospital of Navarra in 1996 were studied. MATERIAL AND METHODS: Sensitivity tests were carried out using the BACTEC 460TB system against four main anti-tuberculosis medicines: Isoniazid, Streptomycin, Rifampizin and Ethambutol. "Fingerprinting" techniques by means of RFLP with IS 6110 were used in the epidemiological study. RESULTS: Four of the patients were also infected with HIV. All of them had a fatal short-term prognosis. These four showed resistance to the drugs under study; in three resistance was primary, and secondary in the fourth. The molecular study showed that three HIV+ patients had identical patterns of restriction fragment length polymorphism (RFLP). Two were brothers and nosocomial infection was demonstrated in the third. On the other hand, the RPLF pattern of these patients showed great similarity to that of one of the HIV- patients, which suggests a clone origin of the strains, no other epidemiological relationship being found. The RPLF pattern of the other HIV+ patient was identical to that of another of his strains, isolated 14 months before, with the first strain sensitive. The other two patients were HIV- women, and they evolved favourably. In one, who was diabetic, a multiresistant tuberculosis had been diagnosed 7 years before, remaining asymptomatic up until the present. The other involved a secondary resistance due to deficient treatment. CONCLUSIONS: The appearance of multiresistant tuberculosis is a very serious problem amongst HIV+ patients, especially at a time when their life expectancy has improved considerably due to the new therapies. In HIV- patients, multiresistant tuberculosis has a better prognosis. Typification by means of restriction fragment length polymorphism is very useful in clarifying the origin of the cases.

[Epidemiological surveillance of HIV/Aids infections in Navarra between 1985 and 2002]. / Vigilancia epidemiológica de las infecciones por el VIH/sida en Navarra entre 1985 y 2002.

In the year 1985, the first cases of Aids were diagnosed in Navarra. Since then and until December 2002, according to the notifications received, 2,329 persons with HIV have been counted, of whom 1,538 were from Navarra and 791 temporary residents in this autonomous community. In recent years, the incidence of new diagnoses of HIV infection and cases of Aids has shown a clear tendency to fall in Navarra. The decrease in cases has been very important amongst the users of intravenous drugs, while the cases amongst homo/bisexuals and cases related to heterosexual transmission have remained fairly stable. In the 1999-2002 period, the cases of infection through a sexual relationship have been more numerous than the cases registered in users of intravenous drugs. The proportion of cases in persons originating from countries with a high endemicity is increasing, coming to represent about 25% of the new cases of infection in the 2000-2002 period. The follow up of the 1,538 HIV patients of Navarra has shown that, at the end of 2002, death had occurred in 39.5% of cases, and it was possible to confirm that 55% were still alive. With regard to their relation to the health services, it has been found that of the 847 patients who are still living, the great majority (80%) are being attended to by the Infectious Services of the Hospital of Navarre and another 9.4% in the Internal Medicine Services of the Garcia Orcoyen and Reina Sofia Hospitals.

[Epidemiological surveillance of HIV/AIDS in Navarra]. / Vigilancia epidemiológica del VIH/SIDA en Navarra.

More than fifteen years have passed since the first cases of AIDS were diagnosed in Navarra in 1985. According to the notifications received from then until December 2001, 2,400 people have been counted with HIV infection, of whom approximately 700 have developed AIDS, and 565 have died of AIDS or other causes. The incidence of new infections by HIV, cases of AIDS and deaths related to the latter, have shown a clear tendency to decline in Navarra in recent years. The decrease in cases is very important amongst the users of intravenous drugs, while the cases amongst masculine homo/bisexuals and amongst persons infected following a heterosexual encounter have remained fairly stable. For the first time, starting in 1999, persons infected through a sexual encounter are higher than the users of parenteral drugs. There has been an increase in the proportion of cases of AIDS and infection in persons originating from countries where the disease is endemic, accounting for over 23% of new cases of infection in the years 2000 and 2001. The figures for Navarra also reflect the important reduction of cases of AIDS and AIDS-related deaths since the introduction of more efficient anti-retroviral treatments in 1996. The strategies for the detection of HIV infection in persons who have maintained risk practices is important if we consider that in the years 2000 and 2001, there was a simultaneous diagnosis of infection and disease in one in every five patients. This implies that these persons did not benefit from treatments in the same way as they would have if the diagnosis had been made earlier.

[Progress in the control of HIV infection and AIDS in Navarre, 1985-2003]. / Progresos en el control de la infección por el VIH y el sida en Navarra, 1985-2003.

The epidemiological situation of HIV infection and AIDS in Navarre in 2003 is reviewed. Up until December 2003, 1,610 HIV infections had been diagnosed in residents of Navarre, of whom 41% had died. The new diagnoses of HIV fell by some 81% between 1993 and 2003, a year in which 28 cases were diagnosed (4.8 per 100,000 inhabitants). The fall basically occurred in infections in injection drug users, since the cases due to sexual transmission had remained stable. Over half of the infections diagnosed in the period 2000-2003 (58%) were attributable to heterosexual transmission, 18% occurred in parenteral drug users and 12% in homosexual men. Thirty-three percent were persons originally from other countries. The incidence of AIDS fell from 75 cases in 1996 to 20 in 2003, and mortality from 65 to 8 cases, respectively. In the 2000-2003 period, the average annual incidence of AIDS was 4.2 per 100,000 inhabitants and the average annual rate of mortality was 1.6 per 100,000 inhabitants. At the end of 2003, there were 902 living persons with a diagnosis of HIV monitored by the health system (1.6 known infections per 1,000 inhabitants). In 2003, 65% of the youths aged between 15 and 29 referred to coital sexual relations, a higher percentage than in previous years, but their level of information on the prevention of AIDS was acceptable. It is necessary to insist on prevention and to adapt this to the new situation.

[Enteritis caused by Campylobacter fetus in Navarre]. / Enteritis por Campylobacter fetus en Navarra.

C. fetus ss jejuni was demonstrated in stool samples from 17 patients, among 605 studied, using the selective media of Skirrow. 13 of them were children, 11 two years' old or younger, and 4 were adult patients. The frequency of isolation of C. fetus ss jejuni in stool cultures has been greater than the isolation of Y. enterocolitica serotype 3, S. sonnei and E. coli, and has been only superated by the isolation of microorganisms belonging to the generus Salmonella.

[Disseminated Mycobacterium africanum infection]. / Infección diseminada por Mycobacterium africanum.

A case of disseminated Mycobacterium africanum infection in a 28 years old black male with no known causes of immunosuppression and resident in Spain 2 years prior to his symptomatology is described. In addition, the characteristics of Mycobacterium africanum and its capacity to produce pathology in man are discussed as is its proper treatment leading to satisfactory cure.

A large Legionnaires' disease outbreak in Pamplona, Spain: early detection, rapid control and no case fatality.

An outbreak of Legionnaire's disease was detected in Pamplona, Spain, on 1 June 2006. Patients with pneumonia were tested to detect Legionella pneumophila antigen in urine (Binax Now; Binax Inc., Scarborough, ME, USA), and all 146 confirmed cases were interviewed. The outbreak was related to district 2 (22 012 inhabitants), where 45% of the cases lived and 50% had visited; 5% lived in neighbouring districts. The highest incidence was found in the resident population of district 2 (3/1000 inhabitants), section 2 (14/1000). All 31 cooling towers of district 2 were analysed. L. pneumophila antigen (Binax Now) was detected in four towers, which were closed on 2 June. Only the strain isolated in a tower situated in section 2 of district 2 matched all five clinical isolates, as assessed by mAb and two genotyping methods, AFLP and PFGE. Eight days after closing the towers, new cases ceased appearing. Early detection and rapid coordinated medical and environmental actions permitted immediate control of the outbreak and probably contributed to the null case fatality.

Donepezil-tacrine hybrid related derivatives as new dual binding site inhibitors of AChE.

A new series of donepezil-tacrine hybrid related derivatives have been synthesised as dual acetylcholinesterase inhibitors that could bind simultaneously to the peripheral and catalytic sites of the enzyme. These new hybrids combined a tacrine, 6-chlorotacrine or acridine unit as catalytic binding site and indanone (the heterocycle present in donepezil) or phthalimide moiety as peripheral binding site of the enzyme, connected through a different linker tether length. One of the synthesised compounds emerged as a potent and selective AChE inhibitor, which is able to displace propidium in a competition assay. These results seem to confirm the ability of this inhibitor to bind simultaneously to both sites of the enzyme and make it a promising lead for developing disease-modifying drugs for the future treatment of Alzheimer's disease. To gain insight into the molecular determinants that modulate the inhibitory activity of these compounds, a molecular modelling study was performed to explore their binding to the enzyme.

[Cutaneous infections by Mycobacterium marinum. Description of 3 cases and review of the literature]. / Infecciones cutáneas por Mycobacterium marinum. Descripción de 3 casos y revisión de la bibliografía.

BACKGROUND: Human infection by Mycobacterium marinum is infrequent and is currently reported in association with the management of aquariums. The epidemiologic, clinical and microbiologic characteristics of three cases in our hospital are herein reported. METHODS: Three cases of cutaneous infection by M. marinum attended in our hospital from February 1993 to October 1994 are described. RESULTS: The three patients were related with the management of aquariums. In two cases the clinical presentation was of sporotricoid cutaneous dissemination, while the third patient presented a localized cutaneous form. The lesions were localized in the upper right extremity in the three cases. The delay in diagnosis was important in two of the cases. Cure, or improvement, were achieved in three cases with' treatment; one with cotrimoxazol, another with first line tuberculostatic drugs and another did not receive treatment. CONCLUSIONS: Human infection by M. marinum is currently described is association with the management of aquariums. The infection is usually cutaneous, alone or well disseminated, with invasion of deep tissue occasionally observed. The lesions are generally found on the upper extremities. Diagnostic delay is frequent. The most adequate treatment appears to be the combination of rifampicin plus etambutol or cotrimoxazol alone, with cases of spontaneous remission also being observed.

[Epidemiology of gastroenteritis by Salmonella (1983-1994)]. / Epidemiología de las gastroenteritis por Salmonella (1983-1994).

BACKGROUND: The incidence of Salmonella enteritidis infection has been study in order to determine their epidemic spread from 1983 to 1994, and the impact of the measures introduced to attempt its control. METHOD: Review of the stool cultures positives for enteric pathogens obtained in the Hospital de Navarra from 1983-1994. RESULTS: Looking at the isolation rates of the different enteric pathogens from 1983 to 1994, a sharp increase of S. enteritidis was recorded on 1985 as a consequence of several outbreaks associated with the consumption of mayonnaise elaborated with row eggs. From 409 strains of Salmonella isolated that year, 302 were serotype enteritidis, this means a 7.5 fold rise since the preceding year in which the prevailing serotype was S typhimurium. From 1985 through 1991 the incidence of S. enteritidis stand high, and pick again on 1990. Since then, a decline has been observed, and in 1994 the number of Salmonella cases recorded were about those on 1984, however, S. enteritidis is now the prevailing serotype. CONCLUSIONS: The egg-borne S. enteritidis epidemic emerged as a major public health problem in Navarra in 1995, associated to the consumption of home made mayonnaise. The measures introduced by local Public Health authorities to attempt control of non pasteurized mayonnaise were insufficient. Evidence from other places links human infections to vertical transmission from breeding flocks to layers. And makes of S. enteritidis infection an international challenge. The severity of the lived experience demands a time-temperature control of eggs in the interval from purchaser to consumer and a more generalized use of pasteurized egg products, no only in the industry but also in the household.

[Confirmation by molecular typing of cross-contamination in a mycobacteria laboratory]. / Confirmación mediante tipificación molecular de contaminaciones cruzadas en el laboratorio de micobacterias.

BACKGROUND: Detection of cross-contamination in the laboratory by restriction fragments length polymorphism (RFLP) analysis of Mycobacterium tuberculosis strains. MATERIAL AND METHODS: 224 strains isolated during a five years period were characterized by IS6110 fingerprinting performed (RFLP) by standardized protocols. RESULTS: Four groups of isolates with smear-negative specimens and low number of colony form its units were detected. They were processed in the same batch and day than other smear-positive specimens with identical RFLP patterns. Fifteen patients were involved and the review of four patients' charts showed that they did not have the typical manifestations of tuberculosis. CONCLUSIONS: When M. tuberculosis isolates were obtained from smear-negative specimens, the results of specimens processed in the same batch and the patients' charts should be reviewed. If with these data the possibility of cross-contamination is suspected, the isolates must be analyzed by molecular typing methods.

Rapid identification of Serratia marcescens by coagglutination.

All 20 O serotypes of Serratia marcescens produce a common, soluble antigen. Crude antigen was obtained by ammonium sulfate precipitation of spent growth medium, antiserum was produced in rabbits, and a coagglutination test for rapid identification of S. marcescens was developed. A total of 701 clinical isolates of gram-negative bacilli were examined, and a 100% correlation between biochemical identification of S. marcescens and identification by coagglutination was found.