Unmasking the hidden tuberculosis mortality burden in a large post mortem study in Maputo Central Hospital, Mozambique.

Sensitive tools are needed to accurately establish the diagnosis of tuberculosis (TB) at death, especially in low-income countries. The objective of this study was to evaluate the burden of TB in a series of patients who died in a tertiary referral hospital in sub-Saharan Africa using an in-house real time PCR (TB-PCR) and the Xpert MTB/RIF Ultra (Xpert Ultra) assay.Complete diagnostic autopsies were performed in a series of 223 deaths (56.5% being HIV-positive), including 54 children, 57 maternal deaths and 112 other adults occurring at the Maputo Central Hospital, Mozambique. TB-PCR was performed in all lung, cerebrospinal fluid and central nervous system samples in HIV-positive patients. All samples positive for TB-PCR or showing histological findings suggestive of TB were analysed with the Xpert Ultra assay.TB was identified as the cause of death in 31 patients: three out of 54 (6%) children, five out of 57 (9%)maternal deaths and 23 out of 112 (21%) other adults. The sensitivity of the main clinical diagnosis to detect TB as the cause of death was 19.4% (95% CI 7.5-37.5) and the specificity was 97.4% (94.0-99.1) compared to autopsy findings. Concomitant TB (TB disease in a patient dying of other causes) was found in 31 additional cases. Xpert Ultra helped to identify 15 cases of concomitant TB. In 18 patients, Mycobacterium tuberculosis DNA was identified by TB-PCR and Xpert Ultra in the absence of histological TB lesions. Overall, 62 (27.8%) cases had TB disease at death and 80 (35.9%) had TB findings.The use of highly sensitive, easy to perform molecular tests in complete diagnostic autopsies may contribute to identifying TB cases at death that would have otherwise been missed. Routine use of these tools in certain diagnostic algorithms for hospitalised patients needs to be considered. Clinical diagnosis showed poor sensitivity for the diagnosis of TB at death.

Changes in tuberculosis in human immunodeficiency virus infected patients in a Spanish tertiary hospital (1995-2013).

OBJECTIVE: Although the incidence of human immunodeficiency virus (HIV)-associated tuberculosis (TB) has decreased, changes in other characteristics of the disease are largely unknown. To describe the trends in TB in patients infected with HIV from 1995 to 2013. METHODS: We review all cases of TB in a tertiary hospital in Madrid, Spain. RESULTS: Among 1,284 patients diagnosed of TB, 298 (23%) were coinfected with HIV. The prevalence of HIV infection during the period of study has decreased from 40% to 14% (p for the trend < 0.001). Clinical presentation has also changed. Although pulmonary and extrapulmonary TB has remained unchanged, miliary presentation has significantly decreased (from 36% to 22%, p = 0.005). The 4-drug regimen was the preferable scheme, with higher implementation at the end of the study period (82% from 1995-1999 to 95% in 2010-2013, p = 0.43). Factors such as treatment failure (OR: 11.7; CI 95%: 3.12-44.1) and miliary form (OR: 2.8; CI 95%; 1.09-7.3) were independently associated with TB related mortality, while the longer duration of treatment was as a protective factor (OR 0.7; CI 95%: 0.6-0.8). CONCLUSIONS: HIV has decreased very significantly as a risk factor for the development of TB. Despite improvement in the treatment of both TB and HIV, and in overall mortality, deaths attributable to the disease in this population remain high mostly in miliary and relapsing forms.

Fatal Disseminated Tuberculosis during Treatment with Ruxolitinib Plus Prednisolone in a Patient with Primary Myelofibrosis: A Case Report and Review of the Literature.

A 73-year-old man with primary myelofibrosis (PMF) was being treated with hydroxyurea, which was changed to ruxolitinib treatment because of worsening constitutional symptoms. Although ruxolitinib rapidly induced relief, he developed a high-grade fever. A comprehensive fever work-up found no apparent cause of the fever, except for PMF. Therefore, we increased the dose of ruxolitinib and added prednisolone, which was gradually withdrawn with resolution of the fever. However, the patient subsequently developed disseminated tuberculosis and died eight months after initiation of ruxolitinib. Our case highlights the importance of assessing and monitoring the immune status of patients receiving ruxolitinib.

Fatal Unusual Miliary Tuberculosis in which a Patient Developed Acute Respiratory Distress Syndrome Induced by Infliximab: An Autopsy Case Report.

Anti-tumor necrosis factor α (anti-TNFα) agents increase the risk of tuberculosis (TB), but cases are rarely fatal. This report concerns a patient who was undergoing treatment with infliximab and presented with acute respiratory distress syndrome due to miliary TB without a miliary shadow. The findings of a pathological autopsy revealed innumerable granulomas in the organs, and the miliary nodules in the lung consisted of more unstructured granulomas. Anti-TNFα agents are unusual in the presentation of TB. It is important, particularly for patients receiving anti-TNFα agents, to constantly consider the possibility of TB and to prepare for appropriate management.

Complications of miliary tuberculosis: low mortality and predictive biomarkers from a UK cohort.

BACKGROUND: Untreated, miliary tuberculosis (TB) has a mortality approaching 100%. As it is uncommon there is little specific data to guide its management. We report detailed data from a UK cohort of patients with miliary tuberculosis and the associations and predictive ability of admission blood tests with clinical outcomes. METHODS: Routinely collected demographic, clinical, blood, imaging, histopathological and microbiological data were assessed for all patients with miliary TB identified from the London TB register from 2008 to 2012 from Northwest London Hospitals NHS Trust. Multivariable logistic regression was used to assess factors independently associated with the need for critical care intervention. Receiver operator characteristics (ROC) were calculated to assess the discriminatory ability of admission blood tests to predict clinical outcomes. RESULTS: Fifty-two patients were identified with miliary tuberculosis, of whom 29% had confirmed central nervous system (CNS) involvement. Magnetic resonance imaging (MRI) was more sensitive than computed tomography (CT) or lumbar puncture for detecting CNS disease. Severe complications were frequent, with 15% requiring critical care intervention with mechanical ventilation. This was independently associated with admission hyponatraemia and elevated alanine aminotransferase (ALT). Having an admission sodium ≥125 mmol/L and an ALT <180 IU/L had 82% sensitivity and 100% specificity for predicting a favourable outcome with an area under the ROC curve (AUC) of 0.91. Despite the frequency of severe complications, one-year mortality was low at 2%. CONCLUSIONS: Although severe complications of miliary tuberculosis were frequent, mortality was low with timely access to critical care intervention, anti-tuberculous therapy and possibly corticosteroid use. Clinical outcomes could accurately be predicted using routinely collected biochemistry data.

Clinically unrecognized miliary tuberculosis: an autopsy study.

BACKGROUND: Miliary tuberculosis (TB) usually presents with atypical clinical manifestations; thus it is often recognized only at autopsy. OBJECTIVES: Our objectives were to study the frequency of MT diagnosed at autopsy and determine clinical diagnoses that masked TB, as well as causes of death and comorbidities. DESIGN: Retrospective study of all autopsies performed between 2008 and 2014. SETTING: Institute of Pathology, Belgrade, Serbia. SUBJECTS AND METHODS: in subjects where autopsy showed the presence of MT that was not recognized clinically, we recorded the clinical diagnoses (presumed causes of death) as reported in autopsy request forms, as well as actual cause of death and comorbidities as determined at autopsy. MAIN OUTCOME MEASURES: Clinically unrecognized MT. RESULTS: The total number of autopsies in this period was 6206. thirty-five individuals showed clinically unrecognized MT (0.56% of all autopsies, age: 62.2 [17.2] years, M:F=2:3). Common clinical diagnoses masking pulmonary MT were exacerbation of COPD (25%) and pulmonary thromboembolism (25%), with common radiological presentation of diffuse pulmonary infiltrates (56.3%). Dominant clinical diagnoses in patients with generalized MT were adult respiratory distress syndrome, sepsis, gastrointestinal bleeding and meningoencephalitis. Disseminated MT was often associated with secondary anemia or thrombocytopenia (15.8%) and recent surgery (15.8%). Frequent comorbidities included chronic renal failure and malignancies, whereas MT was a dominant cause of death. CONCLUSION: Greater awareness of MT is needed to improve recognition in clinical settings. In particular, MT should be considered in patients with atypical clinical presentation and diffuse pulmonary infiltrates on chest X-ray, particularly if they have chronic renal failure, malignancy, hematological disorders or a history of recent surgery. LIMITATIONS: None.

Acute respiratory distress syndrome in disseminated tuberculosis: an uncommon association.

OBJECTIVE: To analyse clinicopathological features of acute respiratory distress syndrome (ARDS) in disseminated tuberculosis (TB) at autopsy. METHODS: A retrospective analysis of an autopsy database of disseminated TB from 1990 to 2010 was conducted. ARDS cases were assessed for histological changes of diffuse alveolar damage (DAD) and other pathological pulmonary features. RESULTS: Disseminated TB was diagnosed in 196 cases. The clinical diagnosis of disseminated TB was made in 67% of cases. Of the 196 cases, 10 met the clinical criteria for ARDS, 60% of whom showed histological evidence of DAD. One case of DAD was diagnosed on histology alone. DAD was thus found in 7/196 cases of disseminated TB. Other pulmonary changes included necrotising granulomas (n = 10), tuberculous bronchopneumonia (n = 4), tuberculous vasculitis (n = 3), infarction (n = 1) and aspergilloma (n = 1). Histopathological diagnosis other than DAD was found in 4/10 cases and disseminated TB was presumed clinically in only 4/10 cases of ARDS. CONCLUSION: Disseminated TB may be clinically missed and diagnosed only post mortem. Disseminated TB is a relatively uncommon cause of ARDS; however, it should always be presumed clinically as it is a potentially treatable cause. DAD is a rare histological feature of disseminated TB and there may not always be a clinicopathological correlation between ARDS and DAD.

Extrapulmonary tuberculosis: 7 year-experience of a tertiary center in Istanbul.

BACKGROUND: Although a decreasing trend of tuberculosis (TB) was reported in Turkey, higher proportion of extrapulmonary tuberculosis (EPT) was revealed. MATERIAL AND METHODS: In this retrospective study, clinical and laboratory data of 141 EPT patients were evaluated for a seven-year period by using descriptive statistics, and parametric and non-parametric tests where appropriate. RESULTS: The most frequent types of EPT were meningeal TB (23%) and TB lymphadenitis (21%), respectively. Other types of EPT were skeletal, miliary, peritoneal, abscess, genitourinarial, cutaneous and gastrointestinal involvement which ranged between 18% and 1%. Mean age was 42 and female/male ratio was almost equal. All patients were born in Turkey. Although all of them were permanent residents of Istanbul, 73% of the patients came from East and Southeast Region of Turkey. For the patients, being older than 40 years old (p<0.01), having miliary TB (p<0.05) and high CRP levels (p<0.05) were found to be associated with mortality. CONCLUSIONS: EPT still remains as a significant morbidity and mortality reason in lower income populations and developing countries. In our study, although all patients were residents of Istanbul approximately two thirds of them have migrated from East and Southeast parts of the country. The relatively high prevalence of tuberculosis cases in Istanbul may be due to the permanent migration from other parts of the country. Early diagnosis and initiation of appropriate treatment are the keys for reducing morbidity and mortality in patients with EPT, particularly in the cases of older ages.

Muerte por tuberculosis milliar / Death from miliary tuberculosis

Se describe el caso clínico de un anciano, en estado senil y desnutrido, quien presentaba síndrome febril prolongado, por lo que fue ingresado en el Hospital Clinicoquirúrgico Docente Dr Ambrosio Grillo Portuondo de Santiago de Cuba, pero al efectuar los exámenes complementarios no se obtuvo un diagnóstico definitivo. Posteriormente tuvo descompensación cardiovascular y fue trasladado a la Unidad de Terapia Intensiva, donde se le realizó urgentemente una radiografía de tórax, la cual mostró lesiones características de tuberculosis milliar. En consecuencia, se interconsultó con especialistas de neumología y se decidió iniciar el tratamiento con drogas antituberculosas; sin embargo, el paciente falleció un día después de comenzada la terapia. La necropsia mostró una granulomatosis crónica inespecífica, cuyo resultado solo se confirmó 2 meses más tarde, cuando el cultivo de las secreciones bronquiales fue positivo (codificación 7) de Mycobacterium tuberculosis(AU)

A case report of an elderly man in senile and malnourished state was described, who had prolonged febrile syndrome and was admitted to Dr Ambrosio Grillo Portuondo Clinical and Surgical Teaching Hospital of Santiago de Cuba, but a definitive diagnosis could not be obtained with complementary tests. Later he had cardiovascular decompensation and was transferred to the Intensive Care Unit, where he underwent an emergent chest radiograph, which showed characteristic lesions of miliary tuberculosis. Consequently, pulmonary specialists were consulted and it was decided to start treatment with antitubercular drugs; however, the patient died a day after the beginning of therapy. The autopsy showed a nonspecific chronic granulomatosis, which results were only confirmed 2 months later, when the culture of bronchial secretions was positive (coding 7) for Mycobacterium tuberculosis(AU)

[Death due to tuberculosis requiring treatment or an accompanying disease? A contribution to the lethality and mortality of tuberculosis in Germany]. / Tod an behandlungsbedürftiger Tuberkulose oder an Begleitkrankheiten? Ein Beitrag zur Letalität und Mortalität der Tuberkulose in Deutschland.

BACKGROUND: Tuberculosis (TB) is a curable disease. Nevertheless, patients in Germany also die of TB. Although mortality is decreasing, there are indications for an increase in lethality. This observation provided the impetus for a detailed analysis that sought to investigate the validity of the statistics on deaths caused by TB. METHOD: The study population consists of the 926 fatal cases that were classified either as "death from TB" or as "death due to other causes" out of the 6044 TB patients in the DZK study. For the analysis, health authorities were asked to provide additional information and such documents as the death certificate, the autopsy protocol and the final medical report. In 778 cases, there was at least one additional piece of information available. Three teams of two experts each conducted independent evaluations of the documents. RESULTS: Based on the findings of the experts, every second death caused by TB in 1997 and 1998 was not recorded correctly during the post-mortem examination. Every third TB death was not diagnosed during the patient's lifetime. Patients who died due to TB were, on average, older and more likely to be born in Germany. This indicates that age-related comorbidity among the native German population plays a relevant role. Yet, the unicausal death registration did not acknowledge comorbidity as a contributing factor to the fatal outcome. Pulmonary TB with positive microscopy and culture, miliary TB and meningeal TB were more common among the deaths due to TB than among the general study population, and led more often to a fatal outcome than other organ manifestations. However, the two groups did not differ with regard to multi-drug resistant TB. Alcohol abuse was a leading risk factor for death caused by TB in patients under 65 years. Patient's delay ranged from six to 34 days, and doctor's delay from eight to 46 days. For example, alcohol abusers, on average, visited a physician much later, but were diagnosed more rapidly after the first visit than patients who were not alcohol-dependent. A period of 32 - 200 days elapsed between diagnosis and death caused by TB. CONCLUSIONS: The post-mortem examination often missed TB as the cause of death. Many native German TB patients showed age-related comorbidity. Pulmonary TB with positive microscopy, miliary TB and meningeal TB led more often to a fatal outcome than other organ manifestations. Alcohol abuse was a leading risk factor for TB deaths in patients younger the 65 years. The average period between the onset of symptoms and the diagnosis was significantly longer than the one month generally considered acceptable. The experts could not confirm an increase in lethality for the period under investigation.

Acute respiratory distress syndrome caused by miliary tuberculosis: a multicentre survey in South Korea.

BACKGROUND: Miliary tuberculosis (TB) is an unusual cause of acute respiratory distress syndrome (ARDS). OBJECTIVE: To evaluate the clinical characteristics and outcomes of patients with ARDS caused by miliary TB admitted to the intensive care unit (ICU). DESIGN: A total of 67 patients were enrolled during the period 1999-2008. RESULTS: The median age of the patients was 56 years (range 17-81), 19 (28.4%) were aged >71 years, and 38 (56.7%) were male. All-cause mortality in the ICU and hospital were respectively 58.2% and 61.2%. Of the total number of enrolled patients, 49 (73.1%) were prescribed anti-tuberculosis medication within 3 days of hospital admission. On the day of ARDS diagnosis (10.0 ± 3.7 vs. 7.4 ± 3.5, P = 0.005), non-survivors had a significantly higher Sequential Organ Failure Assessment (SOFA) score than survivors. Multivariate analysis showed that SOFA score on the day of ARDS diagnosis was a significant predictor of survival (OR 0.809, 95%CI 0.691-0.946, P = 0.008). It was difficult to determine the efficacy of systemic corticosteroids on patient survival. CONCLUSION: ARDS caused by miliary TB was associated with a high in-hospital mortality rate, with SOFA score on the day of ARDS diagnosis being a valuable prognostic indicator.

[Miliary tuberculosis: a report of 49 cases]. / Miliaire tuberculeuse: à propos de 49 cas.

INTRODUCTION: Miliary tuberculosis is a severe, acute form of tuberculosis due to lymphohaematogenous dissemination of tubercle bacilli from a focal lesion. PATIENTS AND METHODS: A prospective study of was undertaken at the Pneumology Clinic of the National University Hospital Centre (CHUN) of Fann, over a period of 30 months (January 2007-June 2009), in order to assess the epidemiological, clinical, paraclinical and evolutionary aspects of miliary tuberculosis. RESULTS: Miliary tuberculosis accounted for 3.8% (n=49) of all diagnosed cases of tuberculosis. The sex-ratio was 1.7. The average age of patients was 37.5 years with a range of 15 to 70 years. The typical radiological appearances were present in 88% of cases whereas only 10% were positive on direct smear. HIV serology was positive in 29%. In the hospital environment, the mortality was 12.2%. CONCLUSION: Miliary tuberculosis is a severe form of the disease. The prognosis depends on early diagnosis and treatment.

Miliary tuberculosis in human immunodeficiency virus infected patients not on antiretroviral therapy: clinical profile and response to shortcourse chemotherapy.

BACKGROUND: An increase in tuberculosis (TB) incidence has been associated with human immunodeficiency virus (HIV). AIMS: To describe the clinical characteristics and treatment outcome of patients with HIV and miliary TB treated with short-course intermittent chemotherapy in the absence of access to highly active antiretroviral therapy (HAART). SETTINGS AND DESIGN: Prospective study of HIV infected adults referred to a TB clinic between July 1999 and July 2004. MATERIALS AND METHODS: On diagnosis of miliary TB, patients were treated with a standard regimen of two months of isoniazid, rifampicin, ethambutol and pyrazinamide followed by four months of isoniazid and rifampicin (2EHRZ 3 /4RH 3 ) thrice weekly and followed up for 24 months. Patients were reviewed clinically every month and two sputa were collected. Chest radiographs and blood investigations were done at two months, end of treatment and every six months thereafter. RESULTS: Of 498 patients with HIV and tuberculosis, 31 (6%) were diagnosed as miliary tuberculosis. At diagnosis, sputum smear was positive for acid-fast bacilli (AFB) in 14 patients (45%) and Mycobacterium tuberculosis was isolated in 21 (68%). The mean CD4 cell count was 129 +/- 125 cells/mm3 . Twenty-five patients were declared cured at the end of treatment (81%) while one (3%) died and five (16%) failed. The recurrence rate was 19.4/100 person-years and the median survival was 17 months (95% CI 14 to 20). None of the patients received antiretroviral therapy. CONCLUSIONS: Miliary TB tends to occur among HIV infected patients with severe immunosuppression. Though the initial response to short-course chemotherapy was encouraging, a high recurrence rate and mortality was observed indicating poor prognosis in HIV.

[Evaluation of accuracy of clinical diagnosis of TB by annual autopsy report].

PURPOSE: To investigate the accuracy of clinical diagnosis of TB in Japan in recent years and to compare them with previous studies. METHOD: Data (sex, age, clinical diagnosis, pathological diagnosis as cause of death) on deceased cases clinically or pathologically diagnosed ante mortem as having tuberculosis was collected from annual reports of the pathological autopsy cases in 1984, 1989, 1994, and 1999-2004. Information on TB death from population statistics in those 9 years also was collected and compared with data of autopsied cases. RESULT: Autopsy rate in these years was stably around 10 %. Comparison of gender ratio and mean age between the two surveys showed similar numbers. During 1999-2004, 1725 death cases were diagnosed as TB clinically or pathologically. Number of pathologically proven pulmonary TB cases was 429 and that of miliary TB was 283. 55.7% of pulmonary tuberculosis and only 21.9% of miliary tuberculosis were correctly diagnosed before death. Out of 156 cases clinically diagnosed as non-TB diseases but proven as TB pathologically, 30.8% of clinical diagnosis was pneumonia and/or bronchitis, followed by diagnoses of interstitial pneumonia, respiratory failure, pneumoconiosis and lung cancer. However, the main clinical diagnoses of 175 miss-diagnosed miliary TB cases were diseases other than pulmonary diseases such as renal failure, malignant diseases and sepsis. CONCLUSION: In order to reduce undiagnosed pulmonary TB cases and to prevent nosocomial TB infection, differential diagnosis among pneumonia and/or bronchitis cases should be done. In case of miliary TB, not only pneumonia but also diseases other than pulmonary diseases such as renal failure, malignant diseases and sepsis should be included in the list differential diagnosis.

Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness.

BACKGROUND: BCG vaccine has shown consistently high efficacy against childhood tuberculous meningitis and miliary tuberculosis, but variable efficacy against adult pulmonary tuberculosis and other mycobacterial diseases. We assess and compare the costs and effects of BCG as an intervention against severe childhood tuberculosis in different regions of the world. METHODS: We calculated the number of tuberculous meningitis and miliary tuberculosis cases that have been and will be prevented in all children born in 2002, by combining estimates of the annual risk of tuberculosis infection, the proportion of infections that lead to either of these diseases in unvaccinated children, the number of children vaccinated, and BCG efficacy. FINDINGS: We estimated that the 100.5 million BCG vaccinations given to infants in 2002 will have prevented 29,729 cases of tuberculous meningitis (5th-95th centiles, 24,063-36,192) in children during their first 5 years of life, or one case for every 3435 vaccinations (2771-4177), and 11,486 cases of miliary tuberculosis (7304-16,280), or one case for every 9314 vaccinations (6172-13,729). The numbers of cases prevented would be highest in South East Asia (46%), sub-Saharan Africa (27%), the western Pacific region (15%), and where the risk of tuberculosis infection and vaccine coverage are also highest. At US2-3 dollars per dose, BCG vaccination costs US206 dollars (150-272) per year of healthy life gained. INTERPRETATION: BCG vaccination is a highly cost-effective intervention against severe childhood tuberculosis; it should be retained in high-incidence countries as a strategy to supplement the chemotherapy of active tuberculosis.

Non-tuberculous mycobacteria disease as a cause of hospitalization in HIV-infected subjects.

OBJECTIVES: The present study characterized and determined the prevalence of mycobacterial diseases (tuberculosis (TB) and non-tuberculous mycobacteria (NTM)) as a cause of hospitalization among HIV-infected subjects consecutively admitted to a large metropolitan hospital during 2001/2002. METHODS: Hospital discharge diagnoses were established for 521 HIV-positive patients. RESULTS: Respiratory disease accounted for 49% of the admissions. Community acquired pneumonia (CAP) was the main cause of respiratory disease (52%) followed by Pneumocystis carinii (PCP, 24%), non-tuberculous mycobacteria (NTM, 11%) and Mycobacterium tuberculosis (TB, 9%). Mycobacterium tuberculosis disease was established using bacteriological, clinical and radiographic criteria. NTM disease was defined following the American Thoracic Society criteria. NTM was disseminated in the majority of cases (19 Mycobacterium avium complex (MAC), one Mycobacterium kansasii). Nine patients had respiratory disease (seven MAC, one Mycobacterium fortuitum, one Mycobacterium kansasii) and one had gastrointestinal disease caused by MAC. Mortality was 10% for NTM disseminated cases; none of the TB patients died over the course of the study. The length of hospitalization for NTM patients was longer (15+/-13 days) than for other respiratory cases (10+/-10, p=0.04). CONCLUSIONS: NTM disease along with its related mortality is a significant pathology as a cause of hospitalization among HIV-infected individuals.

Clinical characteristics of 110 miliary tuberculosis patients from a low HIV prevalence country.

SETTING: A university teaching hospital in Karachi, Pakistan. OBJECTIVE: To define the clinical characteristics and outcome of miliary tuberculosis (TB) patients from a low human immunodeficiency virus (HIV) prevalence country. DESIGN: Review of adult miliary TB patients admitted between 1994 and 2001. Clinical characteristics of those dying from miliary TB were compared with those of the survivors. RESULTS: Most of the 110 cases reviewed were middle aged or elderly, with a female preponderance. An underlying medical condition was present in 47%. Presenting symptoms were of several weeks' duration, and mostly constitutional (fever and weight loss). Common laboratory findings included anaemia (62%), lymphopaenia (71%), hyponatraemia (74%), elevated serum alkaline phosphatase (57%) and hypoalbuminaemia (92%). Typical miliary pattern was observed in 77% of radiographs. Sputum smear and culture were positive in respectively 36% and 52% of those tested. Biopsy was performed in selected patients. Mean hospital stay was 8.8 days, and mortality was 30%. Those who died were significantly older than survivors and had a more fulminant course. Presence of altered mental status, lung crackles, leucocytosis, thrombocytopaenia and the need for ventilation were associated with increased mortality. CONCLUSION: Miliary TB carries a high mortality. It should be considered in patients who present with prolonged systemic symptoms. A positive TB culture or biopsy is needed to establish a diagnosis.

[A clinical study of miliary tuberculosis].

Eighteen patients with miliary tuberculosis (MTB) were admitted to our hospital from 1994 to 2003. The mean age of the patients was 63.9 years (range 19-92). Past history of tuberculosis was recognized in one case. Six cases suffered from another underlying diseases, and 3 of them had been treated with corticosteroids. Smear, PCR and culture of sputum were positive for mycobacterium tuberculosis in 61%, 79% and 94% of cases, respectively. Chest computed tomography revealed diffuse micronodular shadow and diffuse infiltration in 100% and 22% of cases, respectively. The laboratory findings of 18 patients with MTB were compared with 240 patients with non-MTB who were admitted to our hospital from 1999 to 2001. Body mass index, serum total protein, albumin and peripheral blood lymphocyte count were significantly lower in MTB patients than in non-MTB patients. Five patients died during admission, 3 of them died of MTB and 2 of them died of cardiac disease. In the 3 died patients due to MTB, 2 of them had been treated with corticosteroids for fever, 2 of them had acute respiratory distress syndrome and 3 of them had disseminated intravascular coagulation. Serum total protein, albumin and platelet count were lower in the died patients due to MTB than in the living patients.

Overt and cryptic miliary tuberculosis misdiagnosed until autopsy.

Autopsy confirmed deaths due to miliary tuberculosis in Finland were analysed in order to improve the diagnosis of the disease. Tuberculosis deaths from mortality statistics were examined in order to identify miliary tuberculosis deaths, and the medical records of the autopsied cases were studied. The deceased were divided into 2 groups, 'overt' disease and 'cryptic' disease, on the basis of chest X-ray findings. There were 114 overt (mean age 79 y) and 140 cryptic (mean age 78 y) miliary tuberculosis cases. The majority of patients in both groups were females. There was no difference between the groups in history of previous tuberculosis, in predisposing factors or in symptoms. Suspicion of tuberculosis was recorded before death in 86% in overt form and in 53% in cryptic form. In overt disease 50% of the patients received chemotherapy, but in cryptic form only a quarter were treated. In one third of cases autopsy had been carried out without suspicion of tuberculosis. Suspicion of tuberculosis had arisen too seldom, especially in the cryptic group. On the other hand, those suspected to have tuberculosis were not promptly treated with the appropriate chemotherapy. Absence of suspicion and delayed diagnosis mean increased risk in health care and at autopsy.