Tuberculosis meningitis in Hong Kong: experience in a regional hospital

Tuberculous meningitis (TBM) remains common in Hong Kong. From January 1996 to June 1997, 11 adult patients with TBM presented to Queen Mary Hospital, a regional hospital in Hong Kong. The annual incidence of TBM was estimated at 1.8 per 100,000 population. Nine patients were local Chinese, and only one patient had the acquired immune-deficiency syndrome (AIDS). In contrast to the classical presentation as a chronic indolent disease, our patients presented acutely: the mean duration from onset of symptoms to presentation was 4.8 days (range 0-10). The most common presenting symptoms were headache (64%), fever (46%), or both (36%), with focal deficits occurring in 64% of patients. Cerebrospinal fluid (CSF) culture and polymerase chain reaction (PCR) were positive in 30% and 29% of cases. Mean CSF cell count, protein and glucose levels were 340 x 10(6)/L, 267 mg/dL, and 2.3 mmol/L, respectively. Extra-neural tuberculosis occurred in 46% of cases. All patients survived and responded to treatment. Drug-induced hepatotoxicity was common; 64% of patients developed biochemical hepatitis.     

Evaluation of detection of M. tuberculosis in clinical specimens of tuberculosis by DNA amplification

The sensitivity of detection of M. tuberculosis genomic DNA were 1pg or 10-100 bacterial cell by PCR. Only M. tuberculosis, M. bovis and BCG were positive with 165 b.p band, but all other 14 mycobacterium and 10 bacteria of non-mycobacterial tested, were negative. Of 75 sputum specimens of pulmonary tuberculosis, the positive rate of PCR were 53.3%, culture method showed only 21.3%, fast-acid staining were 25.3%. 17 non-tuberculosis lung disease were negative in three methods. Of 58 tuberculosis meningitis, the positive rate of PCR, the fast-acid staining and culture in cerebrospinal fluid were 51.7%, 8.6%, 1.7% respectively. 30 non-tuberculosis meningitis were negative in three methods. The results showed that DNA amplification is a superior method with high degree of sensitivity and specificity for rapid diagnosis of pulmonary tuberculosis and tuberculosis meningitis.     

Salmonella meningitis: clinical experience of third-generation cephalosporins

Fifteen paediatric patients with Salmonella meningitis were retrospectively reviewed. Presenting symptoms and signs included fever, vomiting, seizures, poor activity, diarrhoea and bulging anterior fontanelle in most patients. Seven out of eight patients with prolonged fever for > 10 days had neurologic sequelae; therefore, prolonged fever is a significant prognostic factor of a poor outcome (p < 0.005). All 15 patients had a brain ultrasound or computed tomography in the acute stage and 11 patients had abnormal findings. The 14 surviving patients were treated with a third-generation cephalosporin for at least 3 weeks. Seven patients (47%) made complete recoveries; two of them were treated solely with a third-generation cephalosporin. Only one mortality (6%) occurred and there were no relapses. In conclusion, high frequencies of prolonged fever, neuroimaging abnormalities and neurologic sequelae were seen in patients with Salmonella meningitis treated with third-generation cephalosporins.     

Tuberculous meningitis: a 30-year review

Tuberculous meningitis remains an important illness that can be difficult to diagnose in a timely fashion and carries significant morbidity. We present a retrospective review of the cases of tuberculous meningitis diagnosed and treated at a single institution. Fifty-eight cases were identified and stratified according to stage of disease at presentation. Four patients (7%) died; three (5%) developed severe neurological sequelae. Poor outcomes were largely confined to cases presenting in an advanced stage and at the extremes of age. Corticosteroids were administered to 56 patients and may have contributed to the comparatively good outcome in these cases.     

Tuberculous meningitis. A case with severe ocular complications

Tuberculosis in the world is the mean cause of death from single infectious agent. It is reported increase not only in underdeveloped countries but in developed too. Tuberculosis meningitis is a very serious form of tuberculosis. Outcome in tuberculosis meningitis is associated with the stage of the disease at presentation. When the child at presentation is extremely ill with coma the completely recovery is seen only in about 20% of cases. In our case patient had severe ocular complications: optochiasmatic tuberculomas. It is difficult recognize the two forms of tuberculomas intra- and perichiasmatic even with RNM. The good response at intrathecal therapy with recovery of the visus proves the perichiamsatic localitation of tuberculomas.     

Mutation of cis-proline 207 in mitochondrial creatine kinase to alanine leads to increased acid stability

SETTING: Hamad General Hospital, the tertiary health centre for Doha, Qatar. OBJECTIVE: The purpose of the study was to define and correlate the role of radiology with clinical and pathological findings in abdominal tuberculosis. MATERIAL AND METHODS: A total of 59 patients (47 males and 12 females) diagnosed bacteriologically and/ or histologically for abdominal tuberculosis were radiologically assessed. Evaluation was based on the analysis of plain abdominal radiographs, gastro-intestinal contrast studies (barium meal follow through and barium enema), ultrasonography and computed tomography. RESULTS: Plain abdominal radiographs performed in 38 patients were positive in 19 cases (50%). Gastrointestinal contrast examinations were positive in 27 out of 34 cases (80%). Ultrasound examinations were abnormal in 25 out of 31 cases (81%), while computed tomography, performed in 24 patients, revealed abnormal findings in 19 cases (80%). Combined radiographic and imaging procedures revealed peritoneal involvement (ascites) in 16 patients (27%), bowel involvement in 36 (61%), mass lesion in 11 (19%), lymphadenopathy in 13 (22%) and organ involvement in 13 (22%). CONCLUSION: There was no single radiological method that provided all necessary information suggestive of abdominal tuberculosis. Although unequivocal diagnosis of abdominal tuberculosis can only be made by culture and histological findings, combined computed tomography and ultrasound findings were the most important imaging tools in the diagnostic process for abdominal tuberculosis, while contrast studies helped to assess the extent of bowel disease, hence influencing decisions concerning surgery.     

Patients with malignant meningitis presenting with neuropsychiatric manifestations

BACKGROUND: Malignant meningitis is often thought of as a late event in the course of cancer. At one time, it was thought to be rare, but it has been recognized more frequently in recent times. Clinical suspicion of malignant meningitis is prompted by neurologic symptoms and signs in patients at risk for this oncologic complication. Neuropsychiatric symptoms previously were not considered as presenting symptoms of malignant meningitis. METHODS: Three patients with cancer with no neurologic symptoms were examined for malignant meningitis based on neuropsychiatric symptoms. Cerebrospinal fluid was examined for malignant cells to confirm the diagnosis of malignant meningitis. RESULTS: The clinical presentation of malignant meningitis for three patients was neuropsychiatric. None of the patients had delirium during their initial presentation. CONCLUSIONS: It is important that clinicians recognize that psychiatric symptoms without neurologic findings may indicate malignant meningitis and that malignant meningitis needs to be included in the differential diagnosis of neuropsychiatric disorders in patients with cancer.     

Granulomatous hepatitis in three children due to cat-scratch disease without peripheral adenopathy. An unrecognized cause of fever of unknown origin

OBJECTIVE: To report the clinical experience of three patients with fever of unknown origin ultimately diagnosed as having cat-scratch granulomatous hepatitis in the absence of peripheral adenopathy. DESIGN: Case-control study. SETTING: Referral center at university-based referral practice. PATIENTS: Three children with fever of unknown origin. Follow-up following presentation was 6 months for each patient. MEASUREMENT AND RESULTS: All three patients with fever of unknown origin were diagnosed radiographically to have multiple hepatic defects. The defects were shown histologically to be granulomatous. Two of the three patients had Warthin-Starry staining bacilli in the granulomas consistent with a diagnosis of Afipia felis. All three had positive cat-scratch skin test results. CONCLUSIONS: Cat-scratch disease in the absence of peripheral adenopathy is a heretofore unrecognized cause of fever of undetermined origin and may account for a small, but significant, percentage of children presenting with it.     

Risk factors for pulmonary tuberculosis in bone marrow transplant recipients

Little is known about the profile of infection with Mycobacterium tuberculosis in bone marrow transplant (BMT) recipients. Of five BMT series with a total of more than 5,000 patients, only 10 cases of M. tuberculosis infection were described, with an overall incidence of 0.19%. We have conducted a prospective evaluation of 183 consecutive BMT recipients, and 10 patients were found to develop pulmonary tuberculosis post-BMT, yielding an incidence of 5.5%. We described the clinical features of these 10 patients, and analyzed the risk factors for development of tuberculosis using age- and sex-matched case control subjects who did not develop the disease. The median age of the 10 patients who developed tuberculosis was 29 yr (range, 17 to 40 yr). The median time for onset of symptoms was 150 d (range, 23 to 550 d), mainly presenting with fever and cough, with infiltrates on chest radiograph. Respiratory tract specimens, mostly sputum, yielded positive smears for acid-fast bacilli in three and positive M. tuberculosis culture in eight, whereas lung tissue histology was the first diagnostic test in two patients. Treatment with standard antituberculosis drugs for a longer duration was highly effective, with no excessive side effects. Risk factors identified for development of tuberculosis included allogeneic BMT (p < 0.05, relative risk [RR] = 23.7), total body irradiation (p < 0. 05, RR = 4.9), and chronic graft-versus-host disease (GVHD) (p < 0. 05, RR = 3.6). It is postulated that chronic GVHD predisposed to development of tuberculosis mainly via disruption of host reconstitution of immune defenses against M. tuberculosis.     

Bone marrow biopsy in the diagnosis of fever of unknown origin in patients with acquired immunodeficiency syndrome

BACKGROUND: Fever is commonly observed in patients with human immunodeficiency virus (HIV) disease and frequently eludes diagnosis. The role of bone marrow biopsy in the diagnosis of fever of unknown origin in patients infected with HIV remains controversial. PATIENTS AND METHODS: One hundred twenty-three consecutive patients with 137 episodes of fever lasting 10 or more days without diagnosis after 1 week of hospitalization were evaluated by bone marrow biopsy. RESULTS: Overall, a specific diagnosis was achieved in 52 episodes by means of culture and histopathological examination (diagnostic yield, 37.9%). Three types of disease were found: mycobacterial infections (n = 36, 69% of documented episodes), including 18 patients with disseminated tuberculosis and 14 with Mycobacterium avium-intracellulare complex infections; non-Hodgkin lymphomas (n = 12, 23%); and visceral leishmaniasis (n = 4, 8%). Although bone marrow cultures were more sensitive than microscopic examination with special stains for the diagnosis of mycobacterial infections, the pathological examination of bone marrow led to a more rapid diagnosis of disease. In addition, the histopathological examination of bone marrow alone led to the diagnosis of a specific condition in 43 episodes (31.3% of all episodes). CONCLUSIONS: Bone marrow biopsy is a useful procedure for the diagnosis of fever in patients with advanced HIV disease, particularly in areas where tuberculosis and leishmaniasis are prevalent. Involvement of the marrow may be the first indication of the existence of extranodal non-Hodgkin lymphoma. For Mycobacterium avium-intracellulare complex infection, blood cultures were more sensitive than bone marrow biopsy.     

Influence of picrotoxin and strychnine on the spectral sensitivity of the turtle ERG b- and d-waves: II. Light adaptation

Clinical and laboratory features of acute meningococcal meningitis according to age were studied in 255 patients. Whereas males accounted for three out of five patients aged 0-4 years, females accounted for three out of four patients older than 50 years of age. All patients had clinical signs of nuchal rigidity and fever. Patients older than 30 years of age had less frequent petechiae (62%) than younger patients (81%). Furthermore, elderly patients above 50 years of age were prone to an obtunded mental state and a prolonged disease course with fever. Without relation to age, 2/3 had purulent meningitis and 2/3 had marked peripheral leucocytosis (> 15 x 10(9) cells/l); 90% of patients had at least one of these findings. The cellular inflammatory response in peripheral blood indicated a bacterial aetiology in > 95% of the cases. More than 80% of children and adults had abnormal CSF biochemical findings, but the level of protein and the glucose ratio (CSF/serum) were positively and negatively correlated to increasing age of the patient, respectively: thus, in children these biochemical markers may be unreliable in the differentiation between a bacterial and non-bacterial aetiology. Thrombocytopenia (< 100.000 x 10(9)/I) was not associated with age, though the lowest platelet count was found in elderly patients. The case fatality rate was 7.5%, but neither age, sex nor sign of septicaemia was associated with fatality. Thrombocytopenia, a lowered coagulation index (< 0.5, factors II, VII, X), a moderate anaemia (haemoglobin < 11 g/dl), an obtunded mental state and a history of convulsions were poor prognostic factors; only anaemia was independently correlated to fatality so this should be considered as an important prognostic marker in the acute phase of meningococcal meningitis.     

Neurological complications caused by cytomegalovirus in patients with AIDS

In patients with HIV infection, disease due to CMV depends on reactivation of the virus. Such reactivation usually occurs at an advanced stage of the disease, when there is severe immunodepression and the CD4+ leukocyte count is < 100/ml. CMV infection is seen clinically as three syndromes: 1) encephalitis with or without associated meningitis and/or ventriculitis. 2) polyradiculomyelitis affecting the lumbosacral roots, and 3) multifocal senso-motor neuropathy. Diagnosis depends on showing the virus to be present in the CSF, by detecting the early CMV antigen or by conventional culture. There are marked differences between encephalitis, polyradiculomyelitis and multifocal neuropathy in the rentability of viral culture. Whilst in encephalitis CMV culture is negative in most patients, in polyradiculomyelitis the sensitivity of viral culture may be 50-60% and in multifocal neuropathy 15%. The treatment indicated is with ganciclovir or foscarnet. Results depend on the type of neurological disease, degree of involvement when treatment is started and an history of extracerebral CMV infection previously treated with these drugs.     

Evaluation of the erythrocyte sedimentation rate in children presenting with limp, fever, or abdominal pain

An erythrocyte sedimentation rate (ESR) is commonly ordered as part of the evaluation of patients with nonspecific but potentially serious symptoms. To investigate the performance of ESR in this setting, we used a computerized database and medical chart review to identify children (n=299) with ESR done for a previously undiagnosed condition. Medical records were reviewed to determine symptoms at presentation, referral status, and subsequent diagnoses, which were classified as serious (n=93) or benign (n=206). We found that serious underlying disease was about 7 times as likely in patients with ESR>50 mm/hr (57/102) than in patients with ESR<20 mm/hr (7/89). Although the prevalence of serious disease was higher among referral patients, the likelihood ratios were similar for referral and primary-care patients. An erythrocyte sedimentation rate greater than 50 mm/hr was most informative in patients presenting with limp (likelihood ratio [LR] =8.2) and abdominal pain (LR=6.0) and least informative in patients presenting with fever (LR=2.5). On the other hand, an ESR<20 mm/hr is reassuring in patients presenting with fever (LR=0) or limp (LR=0.3), but not in patients presenting with abdominal pain (LR=0.8). An ESR between 20 and 50 mm/hr (23% of the patients) provided little information (LR 1.2-1.5) in each of the three groups. These results suggest that the ESR often provides useful information about the likelihood of serious illness among children presenting with worrisome but nonspecific symptoms, in particular in patients presenting with limp.     

Murine typhus presenting as subacute meningoencephalitis

Murine typhus is a febrile systemic illness, presenting with headache and undulating fever. Neurological involvement is considered a rare complication. During 1994 and 1995, 34 patients admitted to our hospital were diagnosed as having murine typhus. Five of these patients presented with a syndrome of subacute "aseptic" meningitis or meningoencephalitis. Three had bilateral papilloedema and 2 had focal neurological signs. None had a rash or other systemic findings suggestive of rickettsial disease. The diagnosis was based on serum and cerebrospinal fluid serology and on prompt response to doxycycline therapy. These cases suggest that neurological involvement in murine typhus is more common than previously suspected and that murine typhus should be included in the differential diagnosis of subacute meningitis in endemic areas.     

Incidence and clinical features of splenic abscesses, with special reference to tuberculous etiology in a general hospital

BACKGROUND: The aim of this revision is to know the incidence of splenic abscess (SA) in our hospital, its etiology, with special reference to tuberculosis, and clinical characteristics. PATIENTS AND METHODS: Abdominal CT-scan performed during the period 1987-1997, with the diagnosis of splenic abscess were reviewed. Etiologic diagnosis standed on blood or sputum cultures, PAAF and/or histologic study of lymph nodes. RESULTS: Seventeen cases of SA were obtained, 12 males and 5 females. Limits of age: 13 and 77 years. The causal microorganisms were: M. tuberculosis (7), Mycobacterium aviumintracellulare (1), S. aureus (2), S. anginosus (1), S. milleri (1), E. coli (1), C. albicans (1), T. biguelle (1) and polymicrobian flora (1). One case was of unknown etiology. Underlying illnesses were: AIDS (7), malignant neoplasms (3), diabetes (2), endocarditis (2), Sj?gren syndrome (1) and complications of abdominal surgery (2). Clinical presentation in nontuberculous splenic abscess was fever and upper-left abdominal pain. Predominant symptoms in tuberculous splenic abscess were fever and weight loss. Blood cultures were positive in 80% of non tuberculous splenic abscess. Specific treatment for tuberculosis improved all patients with tuberculous splenic abscess, without needing surgery or corticosteroids. CONCLUSIONS: From the total of splenic abscess, 41.1% were tuberculous, six with AIDS and one with Sj?gren syndrome. Diabetes and malignant neoplasms were the commonest underlying illnesses in the non-tuberculous. In these, clinical presentation consisted in fever and upper-left abdominal pain. In patients with tuberculous splenic abscess, the main complaint was weight loss. A prompt treatment is generally succesful.     

Rapid diagnosis of tuberculous meningitis by polymerase chain reaction assay of cerebrospinal fluid

A polymerase chain reaction (PCR) method for the rapid diagnosis of tuberculous meningitis (TBM) was used to study prospectively 47 cerebrospinal fluid (CSF) samples from 45 patients. Twenty CSF samples were from patients with clinically suspected TBM and another 27 samples came from patients without clinically suspected TBM. Mycobacterial DNA was detected in 15 CSF samples (14 from patients with clinically suspected TBM and 1 from a patient not suspected of having TBM). Of the PCR-positive samples, 4 were also positive for mycobacterial culture. However, 32 PCR-negative samples were all culture-negative. All samples were negative for the acid-fast bacillus by direct smear. The single PCR-positive patient in the clinically unsuspected TBM group was initially diagnosed as suffering from aseptic meningitis on the basis of his clinical features. The mycobacterial culture of his CSF specimen was also positive and a revised diagnosis of an aseptic type of TBM was made. The estimations of specificity and sensitivity in this study were 100% and 70% respectively. The results showed that using a PCR to detect mycobacterial DNA in CSF for the early diagnosis of TBM is not only a rapid but also an accurate method.     

Primary giant granulomatous basal meningitis: an unusual presentation of tuberculosis

A case of granulomatous tuberculous meningitis in a 3-year-old child without any known primary disease in any other organ is presented. Tuberculous meningitis is an uncommon presentation of tuberculosis and is characterized by diffuse or circumscribed granulomatous involvement of the meninges, particularly at the base of the brain. Early diagnosis and treatment are essential to prevent the worst events it can bring and to improve the chances of survival. Diagnosis remains difficult because of the lack of reliable clinical diagnostic criteria.     

Rapid diagnosis of Mycobacterium tuberculosis bacteremia by PCR

A method based on DNA amplification and hybridization has been used for the rapid detection of Mycobacterium tuberculosis in blood samples from 38 hospitalized patients (15 human immunodeficiency virus [HIV] positive and 23 HIV negative) in whom localized or disseminated forms of tuberculosis were suspected. In 32 of these patients, the diagnosis of tuberculosis was eventually confirmed by conventional bacteriological or histological procedures. M. tuberculosis DNA was detected with the PCR technique in the peripheral blood mononuclear cells from 9 of 11 (82%) HIV-infected patients and in 7 of 21 (33%) HIV-negative patients (P < 0.01), while M. tuberculosis blood cultures were positive in 1 of 8 (12.5%) and 1 of 18 (5.5%) patients, respectively. PCR was positive in all cases with disseminated disease in both HIV-negative and HIV-positive patients and also in the HIV-positive patients with extrapulmonary tuberculosis. Seven samples from patients with documented illness other than tuberculosis and 12 specimens from healthy volunteers, including seven volunteers with a recent positive purified protein derivative test, were used as controls and had a negative PCR. These results suggest that detection of M. tuberculosis DNA in peripheral blood mononuclear cells may be a useful tool for rapid diagnosis of disseminated and extrapulmonary forms of tuberculosis, especially in an HIV-positive population.     

Role of antigen specific circulating immune complexes in diagnosis of tuberculosis

SETTING: Tuberculosis is a public health problem worldwide. Early accurate diagnosis in patients with active disease is essential to reduce morbidity and mortality. Conventional methods for detection of Mycobacterium tuberculosis have given disappointing results. OBJECTIVE: To evaluate the utility of detection of M. tuberculosis antigen in circulating immune complexes (CIC) for the diagnosis of tuberculosis. METHOD: Eighty-four clinically diagnosed cases of mainly extra-pulmonary tuberculosis, 85 patients with diseases other than tuberculosis and 30 healthy controls, were evaluated for the presence of antigen of M. tuberculosis in CIC in serum using sandwich enzyme linked immunosorbent assay (ELISA). RESULTS: In total, 22 out of 84 cases were positive for culture on Lowenstein Jensen medium; 76.5% (n = 65) of the clinically diagnosed patients (including 20 culture-positive cases) were found to be positive by ELISA. The difference in mean absorbance values of ELISA in cases of tuberculosis was significantly higher than in controls. The sensitivity of ELISA was 90.9% and the specificity was 93.04%. CONCLUSION: Detection of M. tuberculosis antigen in CIC by ELISA has potential as a useful diagnostic tool for the rapid diagnosis of tuberculosis, especially extra-pulmonary forms where results of conventional methods of diagnosis are disappointing.