Importancia diagnóstica de las infecciones extrapulmonares causadas por el género Mycobacterium / Diagnostic importance of extrapulmonary infections caused by the genus Mycobacterium

Introducción: el género Mycobacterium provoca infecciones pulmonares y extrapulmonares, dentro de estas últimas las localizaciones más frecuentes son; sistema nervioso linfático, central, circulatorio, genitourinario, gastrointestinal, tejido osteoarticular, y la piel. Objetivo: realizar las caracterizaciones etiológica de infecciones extra pulmonares producidas por el género Mycobacterium, destacar su importancia diagnóstica tanto en pacientes VIH- como VIH/sida. Métodos: se realiza un estudio descriptivo-prospectivo de corte transversal realizado de enero 2012 a mayo 2014. Durante este período se recibió un total de 825 muestras, 232 de pacientes VIH- y 593 de pacientes con VIH/sida. Las muestras que lo requerían se le aplicaron descontaminación cultivo, se utilizó el método de ácido sulfúrico al 4 por ciento, para el cultivo se usó el medio de Löwenstein-Jensen. Resultados: de las 825 muestras extra pulmonares en 29 (3,5 por ciento) se obtuvo cultivo positivo,14 (48,3 por ciento) con aislamiento de Mycobacterium tuberculosis (11 VIH+ y 3 VIH-), y 15 (51,7 por ciento) con aislamiento de otras especies micobacterianas (12 VIH+ y 3 VIH-), Mycobacterium avium-intracellulare, y Mycobacterium malmoense fueron las especies más aisladas. Conclusión: por todo lo anterior expuesto se recomienda mantener la vigilancia diagnóstica en este tipo de infección extra pulmonar, en especial en pacientes con sida, pues en muchos casos pueden tener fatales consecuencias por su diagnóstico tardío(AU)

Mycobacterial Pulmonary Infections in Patients with Idiopathic Pulmonary Fibrosis

Patients with idiopathic pulmonary fibrosis (IPF) have an increased risk for developing tuberculosis (TB). However, no studies have been reported regarding the development of nontuberculous mycobacterium (NTM) lung disease (NTMLD). We reviewed 795 patients with IPF from five university hospitals who were diagnosed by histological or radio-clinical criteria. In the 795 patients with IPF, pulmonary infections with mycobacterium tuberculosis (MTB) and NTM were found in 35 (4.4%) and 16 patients (2.0%), respectively, which was a higher frequency than that found in the general population. TB was more common in patients treated with immunosuppressants than in those who did not receive immunosuppressants (2.6% vs 1.4%, P = 0.12). Among the IPF patients who had mycobacterial infections,immunosuppressant users developed TB or NTMLD within 1 yr after treatment with immunosuppressants,while those occurred later than 2 yr after diagnosis of IPF in the subjects that did not receive immunosuppressants. Among 51 IPF patients who had mycobacterial infections, 9 (18%) died during follow-up. Of these, three died due to progression of pulmonary tuberculosis. TB and NTMLD is relatively common in patients with IPF in Korea and may be fatal in some groups. Careful evaluation of TB and NTMLD is necessary not only for immunosuppressant users, but also for nonusers with IPF.

Non tuberculous mycobacteria and toxoplasma co-infection of the central nervous system in a patient with AIDS

New-onset seizures are frequent manifestations in patients infected with Human Immunodeficiency Virus (HIV). We describe the clinical and radiological findings in an 25yr old AIDS patient presenting with new onset seizures as the primary manifestation of cerebral toxoplasmosis and Non Tuberculous Mycobacterial [NTM] co-infection. Cranial computed tomography showed a subtle ventricular dilatation whereas magnetic resonance imaging disclosed prominent temporal horn. Toxoplasma tachyzoites and rapidly growing mycobacteria were recovered from CSF. Seizures were complex partial in nature and refractory to antiepileptic therapy.

Mycobacterial infections in human immuno-deficiency virus seropositive patients: role of non-tuberculous mycobacteria.

BACKGROUND: There is high prevalence of tuberculosis in patients with HIV infection; hence the role of non-tuberculous mycobacteria (NTM) in HIV patients has always been undermined. NTM may be responsible for clinical disease in a substantial number of immuno-compromised HIV sero-positive individuals even in a country endemic for Mycobacterium tuberculosis (M. tuberculosis). The study was designed to look for the contribution of NTM to morbidity in HIV seropositive patients. MATERIAL AND METHODS: In a prospective study of ninety-four HIV seropositive individuals presenting with pulmonary or extra-pulmonary symptoms suggestive of mycobacterial infection, appropriate samples were collected and processed. Detailed clinical history was utilized to differentiate colonization or contamination by NTM from true lung disease. RESULTS: Fourteen samples grew mycobacterial species, 8(57.2%) being NTM. The distribution of NTM was--3 M. avium complex, 2 M. fortuitum, 2 M. vaccae, 1 M. phlei. 6 isolates were M. tuberculosis. CONCLUSION: NTM may be responsible for a significant proportion of mycobacterial infections in HIV seropositive individuals. Despite the high endemicity of tuberculosis in developing countries like India, the presence of NTM should be ruled out; especially in immuno-compromised HIV seropositive individuals before instituting anti-tubercular therapy empirically. In addition, non-response of NTM to ATT may be wrongly attributed to multi-drug resistant tuberculosis.

Chronic knee monoarthritis caused by Mycobacterium chelonae.

Extrapulmonary tuberculosis occurs in 20% of all patients with tuberculosis and tubercular arthritis occurs in 10% of those with extrapulmonary tuberculosis. Arthritis caused by Mycobacterium tuberculosis is not uncommon in India. However, arthritis caused by Mycobacterium chelonae has not been reported to the best of our knowledge. We report a patient with arthritis caused by Mycobacterium chelonae in whom the diagnosis was confirmed by smear and culture of acid-fast bacilli. Polymerase chain reaction of the synovial fluid using IS6110 was negative.

Asociación Micobacterias-VIH/SIDA en Pacientes Atendidos en un Hospital Universitario en Bogotá, Colombia / Mycobacteria-HIV/AIDS association in patients attending a teaching-hospital in Bogotá, Colombia

Objetivo El objetivo del presente estudio fue evaluar la frecuencia de infecciones micobacterianas en pacientes infectados por el VIH y su repercusión en la sobreviva de los pacientes a mediano plazo, además los factores clínicos y epidemiológicos asociados a la coinfección. Métodos La frecuencia de infección micobacteriana se determinó en una cohorte de 92 pacientes VIH positivos en el Hospital San Juan de Dios en Bogotá (Colombia), en 1996, mediante el empleo de métodos bacteriológicos estandarizados a partir de diferentes muestras clínicas. Los factores asociados con la enfermedad fueron medidos utilizando las razones de prevalencia RP IC= 95 por ciento y la regresión logística como método multivariado. La probabilidad de sobrevivir a tres meses fue evaluada usando las curvas de Kaplan Meir y se midieron los factores asociados con la sobrevida usando razones de tasas de incidencia y el modelo de Cox Resultados El 8 por ciento de los pacientes tenían tuberculosis y el 8,6 por ciento estaba infectado con micobacterias atípicas, siendo el complejo Mycobacterium avium (CMA), el más frecuente, seguido por M. fortuitum y M. chelonae. En un paciente se encontró M. tuberculosis y CMA y en otros dos se encontraron dos especies diferentes de micobacterias atípicas. Pacientes con tuberculosis, en estadios III y IV de enfermedad VIH tenían una sobreviva del 16 por ciento. Conclusiones La frecuencia de la asociación Tuberculosis/VIH-SIDA y Micobacteriosis/VIH-SIDA fue similar. La micobacteria atípica aislada con mayor frecuencia fue CMA. La sobrevida disminuyó en los pacientes con tuberculosis siendo menor si la cepa era multirresistente. El hallazgo clínico mas frecuentemente asociado a la tuberculosis fue la fiebre y la pérdida de peso se asoció a la presencia de micobacteriosis. La sangre fue la mejor muestra para el aislamiento de micobacterias.

Objective Evaluating the frequency of mycobacterium infection in an HIV-positive population and its influence on medium-term survival, along with clinical and epidemiological factors associated with co-infection. Methods Several clinical specimens were studied for mycobacteria in a sample of 92 HIV+ patients at the San Juan de Dios teaching-hospital in Bogota, Colombia, during 1996. Factors associated with infection were measured using a prevalence ratio (PR), CI=95 percent, and logistic regression was used in the multivariable models. The likelihood of survival for three months was measured using Kaplan-Meir curves and factors associated with survival were assessed using Rate ratios and Cox's model. Results Eight percent of the patients had tuberculosis and 6 percent of them were found to be infected with atypical mycobacterium. Mycobacterium avium complex (MAC) was the most frequent species, followed by M. fortuitum and M. chelonae. Mixed infections with M. tuberculosis and MAC were diagnosed in one patient and two different species of atypical mycobacterium were isolated in other two cases. Patients suffering from tuberculosis and stages III or IV HIV infection had a 16 percent survival rate. Conclusions Tuberculosis-HIV/AIDS frequency and atypical Mycobacterium-HIV/AIDS' association were very similar. The most frequently isolated atypical mycobacterium specie in this study was MAC. Survival rate was lower for patients infected by M. tuberculosis and even lower when a multi-resistant strain was involved. The most important clinical factor associated with M. tuberculosis was the presence of fever and loss of weight with mycobacterial infection. Blood provided the best samples for isolating mycobacteria.

Disseminated Bacille Calmette-Guérin disease as the initial presentation of X-linked severe combined immunodeficiency--a case report.

Bacille Calmette-Guerin (BCG) vaccination is used to prevent severe M. tuberculosis infection. It has been used in many countries for a long time. However, complications do occur, including localized abscesses, regional lymphadenitis and disseminated disease. The latter is often associated with underlying immunodeficiency. We report an 8-month-old male infant presenting with cough and fever who had had a generalized pigmented skin rash for one month. Skin biopsy revealed mycobacterial infection, but his response to treatment was poor and he had a persistent mild fever. Immunological studies revealed an IgG of 49 mg/dl, IgA 4 mg/dl, IgM 28 mg/dl, IgE < 1 mg/dl, CD3 1.1%, CD4 0.6%, CD8 0.6%, CD19 93.9%, CD57 1.1%, activated T cells 0.9%, and CH50 < 6.3%. These findings are compatible with the diagnosis of T(-)B(+)NK- severe combined immunodeficiency. Sequence analysis was performed and showed the presence of missense mutation in IL2Rgamma gene. An X-linked recessive inheritance pattern was proved by sequence analysis of his mother and grandmother. In order to identify the strain of the microorganism, we reviewed pathology of the skin biopsy which consisted of diffuse histiocytic infiltrate with poorly formed granulomas and no necrosis and used polymerase chain reaction (PCR) with the stain-positive clinical specimen and verify the organism found in the child's biopsy as M. bovis BCG strain. The diagnosis of disseminated BCG disease must be considered in any infant with cutaneous mycobacterial lesions, especially with atypical histologic findings. Such a patient's immunologic status should be evaluated and further family study is suggested. A high index of suspicion is needed to make a timely diagnosis, as early intervention with intensive treatment and bone marrow transplantation may be life-saving.

Mycobacterium fortuitum bacteraemia in an immunocompromised patient.

A case of Mycobacterium fortuitum bacteraemia in an immunocompromised patient confirmed by four positive serial blood cultures is reported here. The patient was a known case of acute lymphoblastic leukemia (ALL) on intensive chemotherapy. The source of bacteraemia was most probably a peripherally inserted vascular catheter. After initiation, of treatment with amikacin to which the strain was sensitive and clarithromycin and removal of the central line the patient's fever defervesced and repeat blood cultures were negative. This is the first time we have encountered an immunocompromised patient with M. fortuitum septicaemia in our hospital. The possibility of an infection with rapidly growing mycobacteria is important to consider when conventional organisms are not isolated in culture especially in the context of patients with malignancy.

Sweet's syndrome: a reaction to non-tuberculous mycobacterial infections.

Sweet's syndrome has been reported to be associated with many underlying conditions, such as non-tuberculous mycobacterial infections (NTMI). In the literature, only twelve patents with Sweet's syndrome in association with NTMI have been reported (most of the patients were from Thailand). Here, the authors report six more patients who developed Sweet's syndrome as a reaction to NTMI. Four patients had Mycobacterium chelonae/abscessus group infection; one patient had been infected with Mycobacterium avium complex first and became infected with M. chelonae/abscessus group 17 months later; and, the other one had Mycobacterium fortuitum infection. In each patient, the skin lesions of Sweet's syndrome relapsed many times while they still had NTMI, and these lesions usually responded well to short courses of systemic steroids without any deterioration of NTMI.

Hairy cell leukaemia with advanced treatment - a case report.

A case of hairy cell leukaemia (HCL), a rare leukaemia, is reported here. The patient was presented with high grade continuous fever with left upper abdominal discomfort for 6 days. He was moderately anaemic, had no peripheral lymphadenopathy with mild hepatosplenomegaly. He was anaemic (Hb-7.8 gm/dl), total leukocyte count was 20 x 109/L. Peripheral blood film showed lymphocytosis (92%) with neutropenia (8%) and absolute neutophil count (ANC) was 1 x 109/L. On review, 88% of the peripheral cells had peripheral hairy projections resembling hairy cell (HC). Bone marrow examination was consistent with HCL (morrow hairy cell = 52%) including marker studies. Tartrate resistant acid phosphatase test (TRAP) was also positive. He had opportunistic mycobecterial infection giving a positive bronchial lavage for acid fast bacilli. After controlling the infection he was advised a single dose chemotherapy of 2-chlorodeoxyadenosine (2-CDA). After that he was in partial remission and after 25 months clinical and pathological relapses occurred and a second dose of 2-CDA was given and the patient went into complete remission.

PCR diagnosis of tuberculosis--experience in India.

Rapid and accurate diagnosis of tuberculosis is the cornerstone of global tuberculosis control programmes. With increasing incidence of tuberculosis epidemics, the low sensitivity and the length of time taken by traditional diagnostic modalities have hampered the efforts to interrupt disease transmission. Introduction of Polymerase Chain Reaction has enhanced the diagnostic predictability of the disease especially in the extrapulmonary, paucibacillary samples. High specificity and sensitivity have been reported in different samples. The technique is capable of picking as few as ten to fifty tubercle bacilli. When PCR technique is performed under quality controlled conditions, false negatives (due to underfined polymerase inhibitors) and false positives (due to cross contamination during sample collection or in the laboratory) can easily by avoided. Samples from sites with a possible latent infection focus or DNA from dead bacilli may give a positive reaction. The use of PCR with traditional diagnostic tools along with clinical presentation can prove helpful in patients presenting with a diagnostic dilemma.

Tuberculosis in children--what has changed in last 20 years?

Several changes have been observed in the epidemiology, clinical manifestations, diagnostic modalities and treatment of tuberculosis. Emergence of HIV epidemic and drug resistance have posed significant challenges. With increase in number of diseased adults and spread of HIV infection, the infection rates in children are likely to increase. It is estimated that in developing countries the annual risk of tuberculosis infection in children is 2.5%. Nearly 8-20% of the deaths caused by tuberculosis occur in children. Lymph node tuberculosis has increased over last two decades. HIV infected children are at an increased risk of tuberculosis, particularly disseminated disease. In last two decades drug resistant tuberculosis has increased gradually. The rates of drug resistance to any drug varied from 20% to 80% in different geographic regions. Various diagnostic techniques such as improved culture techniques, serodiagnosis, and nucleic acid amplification have been developed and evaluated to improve diagnosis of childhood tuberculosis. Serodiagnosis is an attractive investigation but till date none of the tests have desirable sensitivity and specificity. Tests based on nucleic acid amplification are a promising advance. Relatively less experience in children, need for technical expertise and high cost are limiting factors for their use in children with tuberculosis. Short-course chemotherapy for childhood tuberculosis is well established. Treatment with intermittent regimens is comparable to daily regimens. Directly observed treatment strategy have shown encouraging result.

Improving bacteriological diagnosis of tuberculosis.

This review is to summarize recent developments in the field of mycobacteriology since the diagnosis of tuberculosis remains elusive in spite of our best efforts and great scientific advances. Progress has been made in further improving upon the age old, time tested traditional techniques like microscopy (Auramine-Rhodamine Fluorescent staining and peptide nucleic acids), culture and sensitivity techniques (solid, liquid, radiometric, and non-radiometric systems) that still remain as the gold standard for its diagnosis. Development of rapid methods [(high performance liquid chromatography, thin layer chromatography, RNA sequencing and polymerase chain reaction (PCR), nucleic acid sequence based amplification assay (NASBA), Transcription mediated assay (TMA) and Ligase chain reaction (LCR)] have paved the way for its rapid detection and treatment. It is interesting to see the role of molecular assays appearing more often in literature now. The molecular amplification systems (PCR, NASBA, TMA, LCR) besides identifying Mycobacterium tuberculosis (MTB) as well as non-tuberculous mycobacteria (NTM), directly from the sample can also identify Rifampin (rpoB gene)/Isoniazide (katG gene) resistant strain. Molecular assays have been found useful particularly in smear positive sputum with high sensitivity and specificity whereas variable sensitivity for sputum negative and extra pulmonary specimens has been observed. Representative specimen and its quality affect the performance of these assays. Emphasis should given to proper collection and transportation of the representative specimen for appropriate evaluation.

Radiological evaluation of bone changes in leprosy

A study involving 44 patients of leprosy was conducted in the Radiology Department, Combined Military Hospital, Rawalpindi in association with the Rawalpindi Leprosy Hospital. All patients had bone changes of either specific or non- specific type. Plain radiography was carried out with a view to evaluate its feasibility as a worthwhile source of supplementary data in planning strategy for treatment. The study group predominantly consisted of male patients between 51 and 60 years of age. Lepromatous leprosy accounted for 52% and borderline tuberculoid leprosy for 29% of the cases. The remaining belonged to either borderline lepromatous or indeterminate subtypes. Both specific and non-specific lesions were most commonly seen in lepromatous type, followed by border line type and were more frequent and marked in feet than in hands. Cortical thinning/irregularity was the most common specific bone change in 79% hands and 81% feet. On the other hand generalized osteoporosis was seen in 77% hands and 81% feet, making it the most commonly seen non-specific bone change

Bacillary angiomatosis and mycobacterium infection coexisting in a cutaneous lesion in a patient with AIDS.

Bacillary angiomatosis is a recently recognized bacterial infectious disease. It mainly affects patients with acquired immunodeficiency syndrome. The presence of coexistent infections of more than one pathologic process in skin lesions in patients with AIDS has been demonstrated. We report a patient with AIDS in whom both bacillary angiomatosis and mycobacterium infection were documented within the same cutaneous lesion.

The effect of thalidomide on BCG-induced granulomas in mice

Granuloma proliferation is the result of a series of complex biological events in wich a variety of cell types and cytokines are involved. Tumor necrosis factor alpha (TNF-Ó) plays a central role. In the present study, we investigated the effect of thalidomide (Ó-N-pthalimidoglutarimide), a sective inhibitor of TNF-Ó synthesis, on granuloma formation during BCG infection in Oncins France 1 (OF-1) mice. Subcutaneous injections of 30 mg/kg body weight of thalidomide daily for 14,21 or 28 days into the mice resulted in the reduction of the size and total number of liver granulomas. The most strikinf effect of thalidomide was observed after 28 days, when the total number of liver granulomas was reduced by as much as 40 percent (P<0.05). Serum TNF-Ó levels of thalidomide-treatment mice were significantly lower (85 percent) than control mice on day 14 and remained lower...

Abdominal mycobacterial infection in acquired immunodeficiency syndrome patients

The authors studied 12 patients with AIDS and abdominal mycobacteriosis hospitalized in the Hospital lpiranga (Sao Paulo, Brazil), from June 1989 to January 1992. Diagnosis was confirmed by the histopathological examination of organ specimens collected during laparotomy, which, in most cases, was carried out due to an emergency situation. Observations included perforation of the ileum, seropurulent fluid involved and bloked by viscera, epiploon, and fibrin. Hepatoesplenomegaly was present in all patients and generalized granulomatous peritonitis was observed in more than 50 percent. A patient died in the immediate post-op period, four after an average period of 55 days in the hospital. A patient evolved with stercoral fistula and asked to be discharged. Six patients were discharged after an average hospitalization period of 27 days. The authors stress that in developing regions where tuberculosis incidence is high, a patient with AIDS and a painful and irritative abdominal picture should always lead to the hypothesis of mycobacteriosis.