Obstructed ileocaecal tuberculosis with splenic tuberculosis and solid pseudopapillary tumour of tail of pancreas in an immunocompetent woman.

A 22-year-old young woman presented with fever, lower abdominal pain and vomiting for 20 days. She had persistent fever and abdominal pain. Fever panel was negative. Clinical features were suggestive of subacute small bowel obstruction. Contrast-enhanced CT abdomen showed thickening of distal ileum, ileocaecal junction and caecum with conglomerate necrotic nodal mass in the ileocolic mesentry along with a lesion in the tail of pancreas. Patient was discussed with multidisciplinary team and decided to undergo a single-stage procedure after adequate nutritional optimisation. During optimisation, she underwent acute obstruction and hence taken up for emergency laparotomy proceeded to right haemicolectomy with distal pancreatectomy and splenectomy 4 weeks after the time of admission. Histopathology showed ileocaecal tuberculosis and solid pseudopapillary tumour with margins free of tumour. Approach of obstructed ileocaecal tuberculosis in the setting of incidental diagnosis of solid pseudopapillary tumour of pancreas in a moribund patient was challenging.

Metastatic tubercular gummas and splenic tuberculoma secondary to tubercular lymphadenitis in an immunocompetent female.

Tubercular gummas and splenic tuberculomas are rare forms of extrapulmonary tuberculosis, usually occurring in immunocompromised individuals. We hereby report a rare combination of multiple tubercular gummas and splenic tuberculoma secondary to TB lymphadenitis in an immunocompetent individual. The patient responded to antitubercular therapy. Thus, in a developing country like ours, tuberculosis can present in a wide clinical spectrum even in an immunocompetent individual.

Diagnosing isolated hepatosplenic tuberculosis in an immunocompetent patient: a case report.

For many years, tuberculosis (TB) has been endemic in Pakistan; many rare and unusual presentations have been reported. There is a myriad of non-specific symptoms which always requires a high index of clinical suspicion for TB. World Health Organization data suggest that Pakistan ranks as the fifth highest country burdened with TB and has the fourth highest prevalence of multi-drug resistant TB globally. With an annual incidence of 277 cases per 100,000, the importance of early diagnosis and treatment is self-evident. We present a case where a strong suspicion of isolated hepatosplenic TB in an immunocompetent patient justified a directed approach.

Isolated splenic tuberculosis with subsequent paradoxical deterioration: a case report.

BACKGROUND: Isolated tuberculosis of the spleen has been described occasionally in literature, mostly in immunosuppressed individuals with various risk factors. Sequestration in the spleen makes such Mycobacterium tuberculosis infection difficult to diagnose. This report describes an extremely rare case of isolated splenic tuberculosis in an immunocompetent individual. CASE PRESENTATION: A 26 year old Kenyan male presented with pyrexia of unknown origin, with negative screening tests for bacterial, fungal and parasitic infections. Ziehl-Neelsen staining and GeneXpert tests were negative for M. tuberculosis. Diagnosis of isolated splenic tuberculosis was made on core biopsy of the spleen. The patient initially worsened upon treatment with antituberculous medication attributable to the 'Paradoxical Reaction' phenomenon, before making full recovery. CONCLUSIONS: This case highlights the need to continuously be on the lookout for tuberculosis especially in unusual presentations, including subsequent paradoxical reaction which may be encountered.

Genomic diversity in autopsy samples reveals within-host dissemination of HIV-associated Mycobacterium tuberculosis.

Mycobacterium tuberculosis remains a leading cause of death worldwide, especially among individuals infected with HIV. Whereas phylogenetic analysis has revealed M. tuberculosis spread throughout history and in local outbreaks, much less is understood about its dissemination within the body. Here we report genomic analysis of 2,693 samples collected post mortem from lung and extrapulmonary biopsies of 44 subjects in KwaZulu-Natal, South Africa, who received minimal antitubercular treatment and most of whom were HIV seropositive. We found that purifying selection occurred within individual patients, without the need for patient-to-patient transmission. Despite negative selection, mycobacteria diversified within individuals to form sublineages that co-existed for years. These sublineages, as well as distinct strains from mixed infections, were differentially distributed throughout the lung, suggesting temporary barriers to pathogen migration. As a consequence, samples taken from the upper airway often captured only a fraction of the population diversity, challenging current methods of outbreak tracing and resistance diagnostics. Phylogenetic analysis indicated that dissemination from the lungs to extrapulmonary sites was as frequent as between lung sites, supporting the idea of similar migration routes within and between organs, at least in subjects with HIV. Genomic diversity therefore provides a record of pathogen diversification and repeated dissemination across the body.

A Case of Splenic Tuberculosis Forming a Gastro-splenic Fistula.

We report a case of a 61-year-old man who presented with a cough and abdominal discomfort. CT scan of the chest showed two lesions across both lungs, and an abdominal CT scan revealed multiple hypodense lesions in the spleen with cystic lesions on the splenic hilum. Upper gastrointestinal tract endoscopy found creamy yellowish discharge through a fistula between the stomach and splenic hilum. Under fluoroscopic guidance, forceps was inserted into the fistula tract, and forcep biopsy was done. The pathology was consistent with tuberculosis, and a nine-month anti-tuberculosis medication regimen was started. Imaging performed three months after finishing medication indicated improvement of splenic lesions, and the gastro-splenic tract was sealed off. This case is a very rare clinical example of secondary splenic tuberculosis with a gastro-splenic fistula formation in an immunocompetent patient.

Pact with the devil: alemtuzumab therapy, immune suppression and infectious complications in chronic lymphocytic leukemia.

Infectious complications are an important cause of hospitalization in patients diagnosed with chronic lymphocytic leukemia. The pathogenesis of infection is complex, involving both disease-induced and treatment-related immune depression. During the last decade, the management of chronic lymphocytic leukemia (CLL) has been redefined by the approval of monoclonal antibody-based treatment, which resulted in improved therapeutic responses. Nonetheless, the profound lymphopenia induced by monoclonal agents was accompanied by increased incidence of infections caused by a new spectrum of opportunistic microorganisms. We report the case of a patient with hypercellular CLL who received Alemtuzumab as first line therapy and obtained a satisfactory therapeutic response, but developed subsequent atypical infectious complications.

[Abdominal tuberculosis: a retrospective series of 90 cases]. / Tuberculose abdominale : étude rétrospective de 90 cas.

PURPOSE: The aim of this study was to analyze the clinical, bacteriological, radiological and therapeutic features of abdominal tuberculosis in a series of 90 patients. METHODS: This was a retrospective and descriptive multicentre study of 90 cases of abdominal tuberculosis conducted from June 1997 to June 2008. Diagnosis of tuberculosis was based on bacteriologic evidence in 12 cases, histological evidence in 55 cases and on clinical and radiologic features with favorable outcomes under specific treatment in the 23 remaining cases. RESULTS: Thirty-one patients were male and 59 were female. The mean age of the patients was 41.5 years. Family history of tuberculosis was reported in three cases. Associated risk factors were: diabetes mellitus (five cases), ethylism (one case), post-hepatitis C cirrhosis (one case), systemic lupus erythematosus treated by corticosteroids (one case). Sites of involvement were: peritoneum (78 cases), liver (14 cases), gut (nine cases) and spleen (eight cases). Forty-eight patients (53,3%) had only an abdominal involvement, nine others patients (10%) had an abdominal involvement associated with intra-abdominal lymph nodes, 16 patients (17,8%) had a respiratory involvement (pulmonary, pleural and mediastinal lymph nodes), eight patients (8,8%) presented with an extra-abdominal and extra-respiratory involvement and 10 patients (11,1%) had respiratory and extra-respiratory disease associated with abdominal involvement. Among the 54 patients who underwent laparoscopy or laparotomy, diagnosis was evoked on macroscopic examination in 51. CONCLUSION: Laparoscopy and laparotomy are still helpful for the diagnosis of abdominal tuberculosis, especially in the presence of peritoneal involvement.

GLS/IL-12-modified Mycobacterium smegmatis as a novel anti-tuberculosis immunotherapeutic vaccine.

OBJECTIVE: To study the effects and mechanisms of recombinant Mycobacterium smegmatis (rMS) carrying pZM03 (a co-expression plasmid encoding human granulysin [GLS] and murine interleukin 12 [IL-12]) on murine M. tuberculosis infection. DESIGN: BALB/c mice infected with M. tuberculosis were treated with normal saline, M. smegmatis, pZM03 or rMS. The number of viable bacteria in the lungs and spleens were counted to observe the therapeutic effects. The levels of IL-12 and interferon-gamma (IFN-gamma) in serum, and IFN-gamma and tumour necrosis factor-alpha (TNF-alpha) released from spleen lymphocytes were detected to observe the T-helper 1 (Th1) response. Secretory IgA (SIgA) in bronchoalveolar lavage fluid was measured to observe the mucosal immunity. The lungs and spleens were prepared for pathological analysis. RESULTS: The rMS group showed a significantly reduced number of colony-forming units compared to the other groups. The expression of GLS in the tissue, and increased levels of IL-12, IFN-gamma, TNF-alpha and SIgA, were found in the rMS group. The pathological changes in the lungs of the rMS group were localised, while those in the control group were extensive. CONCLUSION: rMS had immunotherapeutic effects associated with a switch to the Th1 response and the antibacterial activity of GLS.

Sterilizing activity of R207910 (TMC207)-containing regimens in the murine model of tuberculosis.

RATIONALE: The diarylquinoline R207910 (TMC207) has potent bactericidal activity in a murine model of tuberculosis (TB), but its sterilizing activity has not been determined. OBJECTIVES: To evaluate the sterilizing activity of R207910-containing combinations in the murine model of TB. METHODS: Swiss mice were intravenously inoculated with 6 log(10) of Mycobacterium tuberculosis strain H37Rv, treated with R207910-containing regimens, and followed for 3 months to determine relapse rates (modified Cornell model). MEASUREMENTS AND MAIN RESULTS: Quantitative lung and spleen colony-forming unit counts and bacteriological relapse rates 3 months after the end of therapy were compared for the following regimens: 2, 3, or 4 months of R207910 (J) and pyrazinamide (Z) combined with rifampin (R) or isoniazid (H) or both and 3 or 4 months of a moxifloxacin (M)-containing regimen and 6 months of the standard WHO regimen RHZ. All J-treated mice were culture negative after 4 months of therapy. The relapse rate in the group treated with 4 months of JHRZ was similar to that of mice treated for 6 months with the RHZ regimen (6 vs. 17%; P = 0.54) and lower than that of RMZ (6 vs. 42%; P = 0,03), a moxifloxacin-containing regimen that was the most active in mice on once-daily basis. CONCLUSIONS: Four months of treatment with some J-containing regimens was as effective as the 6-month standard regimen and more effective than 4 months of treatment with M-containing regimens. Supplementation of standard regimen (RHZ) with J or substitution of J for H may shorten the treatment duration needed to cure TB in patients.

Post-exposure vaccination against Mycobacterium tuberculosis.

Enhancing immunity to tuberculosis in animal models after exposure to the infection has proved difficult. In this study we used a newly described flow cytometric technique to monitor changes in cell populations accumulating in the lungs of guinea pigs challenged by low-dose aerosol infection with Mycobacterium tuberculosis and vaccinated 10 days later. On day 40 after infection the fusion protein F36 and a pool of Ag85A and ESAT6 vaccines had significant effects on the bacterial load, showed increased expression of the activation marker CD45+ on CD4+ T cells, and reduced numbers of heterophils. Lung pathology and pathology scores were marginally improved in animals given these vaccines, but lymph node pathology was not influenced. Despite early effects no changes in long-term survival were seen. These results suggest that a single post-exposure vaccination can initially slow the disease process. However, this effect is transient, but this could be of use in an multidrug resistant/extremely drug resistant outbreak situation because it could potentially slow the infection long enough to complete drug susceptibility testing and initiate effective chemotherapy.

Splenic tuberculosis: a case report.

Splenic tuberculosis is an unusual clinical phenomenon, especially in immunocompetent hosts. It often demonstrates diagnostic complexity, which makes the identification of the agent difficult. We encountered the case of a middle-aged immunocompetent male who claimed to be suffering from pain in the left hypochondriac region without any indication of cough, hemoptysis, weight loss or fever. When physically examined, he had splenomegaly without any other clinical findings. This was further confirmed by imaging. A splenectomy was performed, and samples were taken for histopathological examination and microbiological analysis. Gross examination of the specimen showed multiple nodules coalescing to form a large yellowish-white mass of solid consistency. Histopathological examination showed large areas of caseation surrounded by multiple granulomas of epitheloid cells and Langhan's type giant cells throughout the splenic pulp. PCR verified the diagnosis of Mycobacterium tuberculosis infection. No primary focus of infection was detected in the lungs or any other organs.

Tubercular splenic abscess in an immunocompetent patient--a rare entity.

Tubercular splenic abscess is an uncommon entity. It has been reported in association with immunodeficiency states. Tubercular splenic abscess in an immunocompetent patient is extremely rare. A 24 year old female who had already received a complete course of anti-tubercular therapy (ATT) for pulmonary tuberculosis was diagnosed as having tubercular splenic abscess. She was successfully managed by performing splenectomy. Operative findings and histopathological examinations confirmed the diagnosis.

Superior virulence of Mycobacterium bovis over Mycobacterium tuberculosis (Mtb) for Mtb-resistant and Mtb-susceptible mice is manifest as an ability to cause extrapulmonary disease.

Mice of a Mycobacterium tuberculosis-resistant (BALB/c) and of a M. tuberculosis-susceptible (DBA/2) strain proved considerably more susceptible, and equally so, to infection with Mycobacterium bovis than with M. tuberculosis when infection was initiated via the iv route. Infection with M. tuberculosis was eventually controlled at an approximately stationary level in the lungs, livers, spleens and kidneys of BALB/c mice, and in all of these organs except the lungs in DBA/2 mice. M. tuberculosis-infected DBA/2 mice died with a much shorter median survival time (MST) than M. tuberculosis-infected BALB/c mice. By contrast, infection with M. bovis killed mice of both strains with the same and much shorter MST. Unexpectedly, M. bovis caused progressive infection and pathology in the livers of BALB/c mice, but not in this organ in DBA/2 mice. More importantly, this pathogen caused progressive infection and infection-induced pathology in the kidneys and adrenal glands of both strains of mice. It is proposed that disease of the adrenal glands might serve to explain why M. bovis caused mice of both strains to die with the same much shorter MST.

Miliary tuberculosis not affecting the lungs but complicated by acute respiratory distress syndrome.

A 61-year-old woman was admitted with fever and headache of 10-day duration. She was found to have anemia, jaundice, and signs of meningitis. The erythrocyte sedimentation rate was increased and the tuberculin skin test was positive. A provisional diagnosis of miliary tuberculosis was made and antituberculous therapy was started, although no miliary lesions were seen on chest radiography. However, her condition rapidly deteriorated with diffuse opacification of both lungs and she died on the 7th hospital day. Postmortem examination revealed miliary tuberculosis in several organs but not in the lungs with acute respiratory distress syndrome accounting for the lung pathology. It should be noted that on rare occasions the lungs may not be involved by miliary tuberculosis.