Miliary tuberculosis: clinical manifestations, diagnosis and outcome in 38 adults

OBJECTIVE: The aim of the study was to determine the clinical, radiographic and laboratory characteristics, diagnostic methods, and prognostic variables in patients with miliary tuberculosis (TB). METHODOLOGY: The records of 38 patients (15 male, 23 female; mean age 41 years, range 16-76 years) with miliary TB from 1978 to 1998 were analyzed. Patients were evaluated also as to whether they presented with a fever of unknown origin (FUO). Criteria for the diagnosis of miliary TB were (i) miliary pattern on chest X-ray or (ii) biopsy or autopsy evidence of miliary organ involvement. Paraffin-embedded tissues with granulomata (n = 15) were re-evaluated for the presence of Mycobacterium tuberculosis DNA by polymerase chain reaction (PCR). RESULTS: Predisposing conditions were present in 24% of the patients. The findings were fever, weakness, night sweats, anorexia/weight loss (100% for each), hepatomegaly (37%), splenomegaly (32%), choroidal tubercles (13%), neck stiffness (11%), altered mental status (8%), anaemia (76%), leukopenia (26%), thrombocytopenia (16%), lymphopenia (76%), pancytopenia (8%) and hypertransaminasemia (55%). Eighteen patients (47%) met the criteria for a FUO. Miliary infiltrates were found on chest X-rays of 32 of 38 cases (84%). In six cases without miliary infiltrates, the diagnosis was made by laparotomy in four cases, and autopsy in two cases. Tuberculin skin test was positive in 32% of cases. Acid-fast bacilli were demonstrated in 37% (16/43), and cultures for M. tuberculosis were positive in 90% (9/10) of tested specimens (predominantly sputum and bronchial lavage). Granulomas were found in 85% (11/13) of lung, 100% (15/15) of liver, and 56% (9/16) of bone marrow tissue specimens. Acid-fast bacilli staining was negative in all (0/21), while PCR was positive in 47% (7/15) of specimens with granulomata. Mortality was 18%. Stepwise logistic regression identified male sex (P = 0.005), non-typical miliary pattern (P = 0.015), altered mental status (P = 0.002) and failure to treat for TB (P = 0.00001) as independent predictors of mortality. CONCLUSIONS: Miliary infiltrates on chest X-ray or FUO should raise the possibility of miliary TB. Therapy should be administered urgently to prevent an otherwise fatal outcome.     

HIV-1 co-infection in children hospitalised with tuberculosis in South Africa.

SETTING: Hospitals associated with the Department of Paediatrics at the University of the Witwatersrand, Johannesburg, South Africa. OBJECTIVES: To define the prevalence of human immunodeficiency virus (HIV) co-infection and differences in clinical presentation between HIV-infected and non-infected hospitalised children with tuberculosis. DESIGN: Children were prospectively enrolled between August 1996 and January 1997. RESULTS: Of 161 children enrolled, 42% were HIV-infected, including 67/137 with pulmonary tuberculosis (PTB) and 1/24 with extra-pulmonary disease (EPTB). Positive microscopy or bacteriology did not differ by HIV status for children with either PTB or EPTB. Although age did not differ between HIV-infected and non-infected children with PTB, non-HIV-infected children with EPTB were significantly older than those with PTB only (median age 32 months vs 14.5 months, P = 0.004). Chronic weight loss, malnutrition and the absence of BCG scarring were more common in HIV-infected children with PTB. HIV-infected children were also more likely to show cavitation (P = 0.001) and miliary TB (P = 0.01) on chest X-ray. Reactivity to tuberculin (> or = 5 mm and > or = 10 mm in HIV-infected and non-infected children, respectively) was significantly lower in HIV-infected children, as were CD4+ lymphocyte levels. The mortality rate during the study was 13.4% in HIV-infected children compared with 1.5% in non-HIV-infected children (P = 0.03). CONCLUSIONS: There is a high prevalence of HIV co-infection in children with TB. Progressive PTB and death are more common in HIV-infected children. Tuberculin skin testing is of limited use in screening for TB in HIV-infected children even when using a cut-point of > or = 5 mm.     

Diagnostic utility of cerebrospinal fluid studies in patients with clinically suspected tuberculous meningitis.

OBJECTIVE: To compare yields of cerebrospinal fluid (CSF) studies in the diagnosis of tuberculosis meningitis (TBM). DESIGN: Prospective laboratory study, Kenyatta National Hospital, Kenya. STUDY POPULATION: Consecutive patients with 1) headache, neck stiffness and altered consciousness for more than 14 days, 2) above features plus evidence of tuberculosis elsewhere in the body, and 3) on standard antimeningitic drugs for one week without response, were included. Those with contraindications to lumbar puncture, confirmed causes of meningitis (except TB) and on anti-tuberculosis treatment were excluded. METHODS: CSF cell counts, glucose and protein were assayed. CSF was stained on ZN, cultured on LJ and BACTEC and subjected to PCR and LCR for Mycobacterium tuberculosis DNA sequences. Positive tests for M. tuberculosis were classified as definite and the rest as probable TBM. RESULTS: Fifty-eight patients with a mean age of 33.0 years were recruited. Mean CSF cell count was 71/microl and CSF lymphocyte count up 67%. Mean CFS protein and glucose were 2.10 g/l and 2.05 mmol/l, respectively. BACTEC was positive in 20 cases, LJ 12, LCR eight, and PCR and ZN one each. Twenty-six patients had definite and 32 probable TBM. Patients with definite TBM had significantly higher CSF protein, lower CSF glucose, higher CSF cell count and lower CSF lymphocytes. CONCLUSION: TBM can be confirmed in half of clinically suspected cases. More sensitive tests for confirmation of TBM are required.     

Clinical and radiologic characteristics of radiologically missed miliary tuberculosis

While chest CT provides important clue for diagnosis of miliary tuberculosis (TB), patients are occasionally missed on initial CT, which might delay the diagnosis. This study was to evaluate the clinical and radiological characteristics of radiologically missed miliary TB.Total 117 adult patients with microbiologically confirmed miliary TB in an intermediate TB-burden country were included. ‘Missed miliary TB’ were defined as the case in which miliary TB was not mentioned as a differential diagnosis in the initial CT reading. Clinical characteristics and radiologic findings including the predominant nodule size, demarcation of miliary nodules and disease extent on CT were retrospectively evaluated. Findings were compared between the missed and non-missed miliary TB groups. Multivariable analyses were performed to determine independent risk factors of missed miliary TB.Of 117 patients with miliary TB, 13 (11.1%) were classified as missed miliary TB; these patients were significantly older than those with non-missed miliary TB (median age, 71 vs 57 years, P = .024). There was a significant diagnostic delay in the missed miliary TB group (P < .001). On chest CT, patients with missed miliary TB had a higher prevalence of ill-defined nodules (84.6% vs 14.4%; P < .001), miliary nodule less than 2 mm showing granular appearance (69.2% vs 12.5%; P < .001), and subtle disease extent (less than 25% of whole lung field, 46.2% vs 8.7%; P < .001). Multivariable analysis revealed that only CT findings including ill-defined nodule (Odd ratios [OR], 15.64; P = .002) and miliary nodule less than 2 mm (OR, 10.08; P = .007) were independently associated with missed miliary TB.Approximately 10% of miliary TB could be missed on initial chest CT, resulting in a delayed diagnosis and treatment. Caution is required in patients with less typical CT findings showing ill-defined miliary nodules less than 2 mm showing granular appearance and follow-up CT might have a benefit.     

Pleural tuberculosis in Harare, Zimbabwe: the relationship between human immunodeficiency virus, CD4 lymphocyte count, granuloma formation and disseminated disease

objective   To elucidate the relationship between HIV, CD4¹ count and pleural TB. method   In a prospective study, 94 patients presenting at two large Harare hospitals with clinically suspected pleural TB were enrolled over a 10-month period. All underwent standardized evaluation, closed pleural aspiration and biopsy. Patients receiving directly observed anti-TB therapy were followed-up. results   Pleural TB was diagnosed in 90 individuals (median age 33 years; range 18-65; 64 males); the seroprevalence of HIV was 85%. HIV-positive patients were older than HIV-negative individuals (median age 33 vs 23 years, P = 0.013) and had a significantly lower median CD4¹ count (191 vs 1106 × 10⁶/l respectively, P = 0.004). A CD4¹ count of <200 × 10⁶/l was associated with a length of illness >30 days (65% vs 37%; P = 0.05), a positive pleural fluid smear (37% vs 0%; P = 0.0006) and a positive pleural biopsy Ziehl-Neelsen stain (35% vs 7%; P = 0.021). However, a relationship between CD4¹ count and either pleural granuloma formation or radiological evidence of disseminated disease was not observed. conclusion   In sub-Saharan Africa, TB pleural effusions have become associated with older age, a chronic onset, and an increased mycobacterial load. These data emphasize the complex relationship between pleural TB, HIV infection and a low CD4¹ count.     

TB PCR in the early diagnosis of tuberculous meningitis: evaluation of the Roche semi-automated COBAS Amplicor MTB test with reference to the manual Amplicor MTB PCR test. .

SETTING: Cecilia Makiwane Hospital, Mdantsane, Eastern Cape, Republic of South Africa. OBJECTIVE: To assess the role of the semi-automated Roche COBAS AMPLICOR(TM)Mycobacterium tuberculosis PCR test in the diagnosis of tuberculous meningitis (TBM). DESIGN: Eighty-three specimens of cerebrospinal fluid (CSF) were collected prospectively from 69 patients with suspected TBM. The COBAS AMPLICOR TB PCR test was compared with the manual AMPLICOR(TM)TB PCR test, clinical and cerebrospinal fluid (CSF) findings, direct ZN smear and radiometric TB culture. RESULTS: CSF from 7/40 (17.5%) patients treated for TBM were positive by TB COBAS AMPLICOR(TM). The sensitivity of the test was not significantly different (p=0.375) from the manual TB AMPLICOR(TM)PCR test. The comparative sensitivities of the TB COBAS AMPLICOR(TM)PCR and the manual AMPLICOR PCR for detecting cases of definite and probable TBM from CSF collected within 9 days of commencing antituberculosis treatment were 40% and 60% respectively. All 29 patients not treated for TBM were negative by COBAS AMPLICOR(TM), giving a specificity of 100%. CONCLUSION: The COBAS AMPLICOR(TM)TB PCR test is a rapid and highly specific diagnostic test for TBM. However, there was a non-significant trend favouring slightly greater sensitivity using the manual AMPLICOR(TM)TB PCR test.     

Tuberculous pleurisy as a manifestation of primary and reactivation disease in a region with a high prevalence of tuberculosis.

SETTING: A teaching hospital in Malaysia. OBJECTIVE: To review the demographic and clinical features of patients with pleural tuberculosis (TB). DESIGN: Retrospective chart and chest radiograph review. RESULTS: The chest radiograph of 54 (61.4%) of a total of 88 patients with pleural TB did not show any lung infiltrate (considered a manifestation of primary TB), while that of 32 (36.3%) patients showed infiltrates in the upper lobes or superior segment of the lower lobes, or the presence of parenchymal scarring in the upper lobes (typical of reactivation TB). Additionally, the chest radiograph of two (2.3%) patients showed miliary mottling (also classified as having primary TB). The mean age of patients with primary versus reactivation tuberculous pleurisy was 36.3 (+/-14.8) years and 44.6 (+/-19.3) years, respectively (P = 0.041). The median duration of symptoms before presentation was 14 days and 60 days in patients with primary and reactivation disease, respectively (P = 0.001). CONCLUSION: In Malaysia, where the prevalence of TB is high, tuberculous pleurisy is more commonly a manifestation of primary rather than reactivation disease. Patients with primary TB pleurisy are younger and have a shorter duration of symptoms than those with reactivation TB pleurisy.     

222例儿童结核性脑膜炎的临床特征及其预后影响因素分析

目的 探讨分析儿童结核性脑膜炎(tuberculous meningitis, TBM)的临床特征及其预后影响因素。方法 参照TBM诊断标准纳入2015年1月至2019年1月重庆医科大学附属儿童医院收治的222例TBM患儿,通过单因素和多因素logistic回归分析,评估患儿临床各种指标及因素对预后转归(治疗后6个月)的影响。结果 222例患儿中,129例(58.11%)患儿预后良好,93例预后差,其中7例死亡。男童117例(52.70%),中位年龄6岁,其中<5岁者107例(48.20%);108例(48.65%)有与结核病患者的密切接触史;110例(49.55%)确诊时长>21 d;137例(61.71%)患儿存在营养不良;205例(92.34%)结核病灶累及2个及以上部位或脏器,并以并发肺结核最常见[200例(90.09%)];病情分期(按照GCS评分)为Ⅱ期和Ⅲ期的患儿有144例(64.87%)。多因素logistic回归分析显示,脑脊液葡萄糖及氯化物含量高是患者预后良好的保护因素[OR(95%CI)=0.444(0.257~0.769);OR(95%CI)=0.914(0.854~0.980)],两者含量越高预后不良的发生率越低;而意识改变、性格改变、脑积液和梗阻性脑积液的高发生率则是患者发生不良预后的危险因素[OR(95%CI)=6.969(2.283~21.277);OR(95%CI)=2.531(1.105~5.796);OR(95%CI)=3.429(1.546~7.604);OR(95%CI)=10.233(1.059~98.886)]。结论 TBM患儿预后差的发生率和死亡率均较高,积极寻找结核病密切接触史和其他脏器结核感染证据有助于TBM的早期诊断,改善患儿营养不良、降低脑积液的发生率则有助于改善TBM患儿的预后转归。     

The radiographic appearance of tuberculosis in patients with the acquired immune deficiency syndrome (AIDS) and pre-AIDS

We reviewed the medical records and chest radiographs of 23 adult patients with culture-proved tuberculosis and verified acquired immune deficiency syndrome. Seventeen patients, including 8 with disseminated tuberculosis, had positive sputum or bronchial washing cultures for Mycobacterium tuberculosis. Their initial pretreatment radiographs revealed hilar and/or mediastinal adenopathy in 10 patients (59%), localized pulmonary infiltrates limited to the middle or lower lung fields in 5 patients (29%), localized pulmonary infiltrates involving an upper lobe in 3 patients (18%), diffuse miliary or interstitial infiltrates in 3 patients (18%), no pulmonary infiltrates in 6 patients (35%), and no abnormalities in 2 patients (12%). Pulmonary cavitation was not seen. Only 1 patient (6%) had a chest radiograph typical of adult onset reactivation tuberculosis (i.e., localized pulmonary infiltrate involving the upper lung fields without hilar or mediastinal adenopathy). Six patients (35%) had pulmonary infiltrates that may have been caused by concomitant nontuberculous infection. Six patients had positive cultures for M. tuberculosis from extrapulmonary sites only. Three (50%) of these patients had hilar and/or mediastinal adenopathy. None of them had pulmonary infiltrates on their initial chest radiograph.     

The current situation and treatment of childhood tuberculosis]

We performed a retrospective analysis of 394 patients who were treated for active tuberculosis (TB) at our hospital from 1976 to 1997. The diagnosis criteria for establishing TB were history of direct contact with TB patients, tuberculin skin test reactivity, positive bacteriology and radiographic findings compatible with TB. There were 192 males and 202 females (age range 1 month to 18 years of age, mean 6.3 years of age). Fifty-four percent of the cases were under 5 years of age. Primary pulmonary TB was presented in 200, post primary pulmonary TB in 97, pleural effusion in 53, endbronchial TB in 4, TB meningitis (TBM) in 28, miliary TB in 28 and other extra-pulmonary TB in 31. A history of contact with the patients was obtained in 72.8% of cases. Two hundred and thirty (58.4%) had received BCG, 134 (34%) no BCG, 30 (7.6%) were unclear. Especially, under 5 years of age, only 29 (13.6%) had received BCG. TBM is not disappeared in Japan and there were 28 cases with TBM. Fifteen patients out of them recovered completely, 8 patients recovered with severe neurological sequelae which included mental retardation, motor weakness, seizures and hydrocephalus and 5 patients died. Twenty-six had no BCG. Particularly in 1990s, we had experienced 4 dead TBM cases, 1 multi-drug resistant (MDR) TBM case and 1 TBM case due to nosocomial infection. Children with TBM should received 12-month regimen using initial daily treatment with isoniazid, rifampin, pyrazinamide, and streptmycin, followed by isoniazid and rifampin administered daily. Pulmonary TB in children is successfully treated with 6-month standard chemotherapy using isoniazid, rifampin, and pyrazinamide daily for 2 months, followed by isoniazid and rifampin daily for 4 months. In order to promote TB control and eliminate childhood TB, especially in infants, the following is necessary; 1) early detection and treatment of adult TB patients, source of infection, 2) prompt and appropriate contact examination and chemoprophylaxis, 3) BCG vaccination during early infancy, 4) protection from MDR TB are most important in Japan.     

Bone and joint tuberculosis concurrent with tuberculosis of other organs

OBJECTIVES: To study the characteristics of bone or joint tuberculosis (TB) accompanied by TB in other organs (especially the lung), and to study patients' and doctors' delay in detecting bone or joint TB. SUBJECTS AND METHODS: A retrospective study was conducted on 33 patients with bone or joint TB concurrent with TB of other organs, especially the lung, who were admitted to our hospital between 1981 and 2005. The patients were divided into the following three groups according to the organ of concurrent TB : (1) miliary TB group (N = 10), (2) pulmonary TB group (N = 19), and (3) other TB site group (N = 4). The relationship between bone/joint TB and TB of other organs was studied by comparing the three groups with respect to the time of appearance of musculo-skeletal symptoms or signs such as swelling and pain and that of symptoms or signs originating from other organs, such as cough, sputum, miliary pattern on chest radiograph and superficial lymph node swelling. RESULTS: The mean age (SD) of patients was 50.5 (18.9) yr, and the male to female ratio was 23 : 10. Among 33 patients, bone TB (including 18 spinal TB) was detected in 24 patients, joint TB in 14, and abscess in 3 (concurrent lesions in some patients). The mean intervals from onset of symptoms to consultation (patients' delay), from consultation to diagnosis (doctors' delay) and from symptom onset to diagnosis (total delay) were 5.5 (13.9), 3.4 (5.2) and 8.9 (13.9) months, respectively. (1) Bone/joint TB concurrent with miliary TB (N = 10) In 8 patients with mean age of 61.0 (17.4) yr, musculo-skeletal symptoms/signs preceded respiratory symptoms or appearance of miliary pattern on chest radiograph by 7.8 (7.2) (range; 1-24) months. The patients', doctors' and total delays were 0.4 (0.5), 7.3 (7.8), and 7.7 (7.6) months, respectively. In most cases, bone/joint TB was diagnosed after the onset of miliary pattern on chest radiograph. In one patient with simultaneous onset of musculo-skeletal and respiratory symptoms/signs (age 21 yr), the interval of total delay was 1 month, and in one patient with musculoskeletal symptoms which appeared six months later than respiratory symptoms (age 28 yr), the interval of total delay was 2 months. (2) Bone/joint TB concurrent with active pulmonary TB (N = 19). In this group, the mean age was 52.2 (17.1) yr, and males were predominant (M/F = 15/4). Active pulmonary TB was diagnosed by positive sputum culture in 13 patients, by positive sputum smear or PCR results in 4 patients, and by the clinical course in 2 patients. Ten patients (53%) had a previous TB history. Cavitary lesion was observed in 15 patients, and the upper lobes were predominantly involved on chest radiograph in 19 patients, indicating that the pulmonary TB was probably post-primary (reactivation) in all patients. In 9 patients with mean age of 49.7 (15.7) yr, musculo-skeletal symptoms/signs preceded respiratory symptoms by 14.1 (14.0) (range; 4-48) months. The patients', doctors' and total delays were 13.3 (17.8), 3.8 (6.6), and 17.1 (16.1) months, respectively. On the other hand, in 10 patients with mean age of 54.5 (18.7) yr, musculo-skeletal symptoms/signs and respiratory symptoms/signs appeared simultaneously, and the total delay was 2.7 (1.9) months. Twelve of 19 patients (63%) had complications such as diabetes mellitus, steroid use, and liver diseases. In cases with miliary or pulmonary tuberculosis, the total delay in diagnosis (Y) correlates positively with the time lag from onset of musculo-skeletal symptoms to respiratory symptoms/signs (X), and the regression line (Y = 0.94X + 2.3, r = 0.98, p < 0.001) was almost linear (Y = X), indicating that the diagnosis of bone/joint TB was made just after the diagnosis of miliary or pulmonary TB. (3) Bone/joint TB concurrent with TB of other sites (N = 4) In 2 female cases (21 and 28 yrs) with cervical lymph node TB, musculo-skeletal symptoms/signs and cervical lymph node swelling appeared simultaneously. In a 54-yr male patient, musculo-skeletal symptoms/signs appeared 5 years after appearance of testicular enlargement, and testicular TB was diagnosed by biopsy simultaneously. In a 33 year-old male patient, musculo-skeletal symptoms/signs appeared 7 months after the drainage of pleural and pericardial effusions (TB was not diagnosed initially), and then the diagnosis of bone/joint, pleural, and pericardial tuberculosis was made for the first time. CONCLUSIONS: In middle-aged or elderly patients with active bone/joint TB, miliary TB is sometimes caused by bacillemia originating from the infected bone/joint lesions. In cases with bone/joint TB and concurrent pulmonary TB, bone/joint TB and pulmonary TB are probably reactivated independently as a result of decreased systemic immunocompetence.     

Chest X-ray findings in relation to gender and symptoms: a study of patients with smear positive tuberculosis in Vietnam

The aim of the study was to analyse chest X-ray (CXR) findings among men and women with smear positive pulmonary tuberculosis (TB). All new cases of smear positive pulmonary TB diagnosed during 6 months in 23 districts in Vietnam were included in a cross-sectional study. 366 cases fulfilled the inclusion criteria. Pleuritis was demonstrated in 17% of the men's CXR versus 3% of the women's, p = 0.002. A miliary pattern was seen in 11% of the men's CXR versus 3% of the women's, p = 0.04. Hilar adenopathy was common and equally distributed among men and women (65% vs 61%). Dyspnoea was common among patients with pleuritis (67%) and a miliary pattern (65%). The radiological findings were more advanced in men than women, despite a similar time from symptom onset to diagnosis. The primary manifestations of TB found among men were unexpected in this setting with an HIV prevalence <0.1% at the time. The association with other risk factors for TB in men needs further investigation. The less advanced CXR findings in women may correspond to a slower rate of progression to smear positive disease, which would have implications for the possibilities of women to obtain a timely TB diagnosis.     

Analysis of clinical features and influencing factors of prognosis in 222 children with tuberculous meningitis

目的 探讨分析儿童结核性脑膜炎(tuberculous meningitis, TBM)的临床特征及其预后影响因素。方法 参照TBM诊断标准纳入2015年1月至2019年1月重庆医科大学附属儿童医院收治的222例TBM患儿,通过单因素和多因素logistic回归分析,评估患儿临床各种指标及因素对预后转归(治疗后6个月)的影响。结果 222例患儿中,129例(58.11%)患儿预后良好,93例预后差,其中7例死亡。男童117例(52.70%),中位年龄6岁,其中<5岁者107例(48.20%);108例(48.65%)有与结核病患者的密切接触史;110例(49.55%)确诊时长>21 d;137例(61.71%)患儿存在营养不良;205例(92.34%)结核病灶累及2个及以上部位或脏器,并以并发肺结核最常见[200例(90.09%)];病情分期(按照GCS评分)为Ⅱ期和Ⅲ期的患儿有144例(64.87%)。多因素logistic回归分析显示,脑脊液葡萄糖及氯化物含量高是患者预后良好的保护因素[OR(95%CI)=0.444(0.257~0.769);OR(95%CI)=0.914(0.854~0.980)],两者含量越高预后不良的发生率越低;而意识改变、性格改变、脑积液和梗阻性脑积液的高发生率则是患者发生不良预后的危险因素[OR(95%CI)=6.969(2.283~21.277);OR(95%CI)=2.531(1.105~5.796);OR(95%CI)=3.429(1.546~7.604);OR(95%CI)=10.233(1.059~98.886)]。结论 TBM患儿预后差的发生率和死亡率均较高,积极寻找结核病密切接触史和其他脏器结核感染证据有助于TBM的早期诊断,改善患儿营养不良、降低脑积液的发生率则有助于改善TBM患儿的预后转归。     

Expansile pneumonia in children caused by Mycobacterium tuberculosis: clinical, radiological, and bronchoscopic appearances

A cohort of 24 children with expansile pneumonia caused by Mycobacterium tuberculosis is described in mostly HIV-noninfected children (n = 22). The children presented with nonresolving pneumonia and a swinging fever (83%). On chest radiography, they had dense opacification with bulging fissures mainly in the upper lobes (75%). On computed tomography, the lobes are consolidated, with areas of liquefacation. Other features visible are enlarged mediastinal lymph adenopathy with ring enhancement (100%), cavities (63%), and tracheal compression (71%). On bronchoscopy, bronchi were obstructed by more than 75% in 20 (83%) of cases. Lymph gland enucleation was required in 42% of cases. Phrenic nerve palsy was present in 3 children, of whom 2 underwent diaphragmatic plication. The children received standard antituberculous therapy, to which prednisone (2 mg/kg/day) was added for 1 month. The mortality was 4% after 6 months of therapy.     

结核性脑膜炎评分系统对儿童结核性脑膜炎的诊断价值

目的 评价结核性脑膜炎(TBM)评分系统对儿童TBM与病毒性脑炎进行鉴别的价值。方法 回顾性分析2010年1月1日至2017年12月31日天津市儿童医院呼吸科收住院的确诊及临床诊断TBM的患儿102例(TBM组),以及同期病毒性脑炎患儿125例(病毒性脑炎组)。TBM评分系统采用包括临床表现、脑脊液检测结果、影像学表现、肺结核或肺外结核的其他表现进行综合评分来诊断TBM(分值越高,越支持TBM诊断;评分≥12分可以临床诊断TBM)。采用病例对照研究的方法,比较该评分系统诊断TBM的敏感度及特异度;同时比较该评分系统与结核菌素皮肤试验(TST)、γ干扰素释放试验(IGRA)及脑脊液病原学检测敏感度的差异。结果 TBM组患儿中,16例(15.69%,16/102)脑脊液病原学检测阳性,确诊为TBM患儿;其余86例(84.31%,86/102)TBM患儿经评分系统评估,分值为(13.25±2.22)分,明显高于病毒性脑炎组患儿的评分[(3.79±2.48)分],差异有统计学意义(t=29.97,P<0.001)。86例患儿中,76例患儿TBM评分≥12分,判断为临床诊断TBM患儿;TBM诊断的敏感度为90.20%(92/102),特异度为100.00%(102/102)。脑脊液病原学检查中,抗酸杆菌染色的敏感度为15.69%(16/102),结核分枝杆菌培养的敏感度为10.78%(11/102),DNA检测的敏感度为16.47%(14/85),均明显低于TBM评分系统(χ ²值分别为113.65、128.66、100.64,P值均<0.001)。免疫学检查方法中,TST的敏感度为50.00%(51/102),特异度为99.20%(124/125);IGRA的敏感度为72.55%(74/102),特异度为99.20%(124/125);敏感度均明显低于TBM评分系统(χ ²值分别为39.31、10.48,P值均<0.001)。 结论 TBM评分系统对TBM诊断价值较好,其敏感度明显高于脑脊液抗酸染色、脑脊液结核分枝杆菌培养、脑脊液DNA检测、TST及IGRA等检测方法。     

Adenosine deaminase from the cerebrospinal fluid for the diagnosis of tuberculous meningitis: A meta-analysis

Objective

To comprehensively evaluate the diagnostic efficacy of adenosine deaminase in cerebrospinal fluid (CSF) for tuberculous meningitis (TBM), and the potential influence of patients' age groups and cutoffs of measured adenosine deaminase.

Methods

Systematic review and meta-analysis of relevant studies retrieved from PubMed, Embase, and Web of Science databases. Pooled sensitivity and specificity were calculated with a random-effect model.

Results

Overall, 43 studies with 1653 patients with TBM and 3417 controls without were included. Pooled results showed that adenosine deaminase in CSF is associated with satisfactory diagnostic efficacy for TBM, with a pooled sensitivity of 0.86 (95% confidence interval [CI]: 0.82–0.90), specificity of 0.89 (95% CI: 0.86–0.91), positive likelihood ratio of 7.70 (95% CI: 6.16–9.63), and negative likelihood ratio of 0.15 (95% CI: 0.12–0.20). The pooled receiver operating characteristic (AUC) was 0.94 (95% CI: 0.91–0.96), suggesting good performance. Subgroup analyses showed good diagnostic efficacies of adenosine deaminase in CSF for both adults (AUC 0.95) and children (AUC 0.96) with TBM. AUCs indicating the diagnostic accuracies of adenosine deaminase in CSF for TBM were 0.93 for studies with cutoffs <10 U/L and and 0.94 for a cutoff =10 U/L, but only 0.90 for studies with cutoffs >10 U/L.

Conclusions

Measuring adenosine deaminase of CSF shows satisfactory diagnostic efficacy for TBM in children and adults, particularly if using a cutoff ≤10 U/L.     

Suppression of cerebrospinal fluid HIV burden in antiretroviral naive patients on a potent four-drug antiretroviral regimen

OBJECTIVE: To determine the longitudinal response of HIV in the cerebrospinal fluid (CSF) to highly active antiretroviral therapy (HAART) and to investigate the levels of indinavir penetrating into the CSF. DESIGN: Open study of HIV-infected subjects naive to therapy with protease inhibitors. SETTING: Tertiary care referral center. SUBJECTS: Twenty-five participants were begun on indinavir, nevirapine, zidovudine, and lamivudine. INTERVENTIONS: Lumbar punctures were performed prior to therapy and 2 and 6 months after beginning therapy. Plasma and CSF were assayed for routine cell counts, chemistries, HIV load and indinavir levels. RESULTS: Twenty-two subjects had CSF HIV RNA level data available at all three time points, three others at baseline and 2 months. At month 2 of therapy, nine of 25 (36%) subjects had CSF HIV RNA levels > 50 HIV RNA copies/ml. By 6 months, all 22 subjects had CSF HIV RNA levels < 50 HIV RNA copies/ml. CSF white blood cell counts fell from a baseline mean of 5.3 x 10(6)/l to 1.9 x 10(6)/l (P = 0.013) at 6 months. Plasma indinavir levels declined rapidly while CSF levels remained stable throughout the 8-h dosing interval. The median CSF indinavir level was 71 ng/ml, approximating the upper limit of the 95% inhibitory concentration for indinavir against HIV-1. CONCLUSIONS: CSF HIV RNA levels cannot be expected to fall below 50 HIV RNA copies/ml even after 2 months of therapy on HAART. Prolonged therapy may be required to suppress HIV levels within the central nervous system.     

Clinical and radiographic features of pulmonary tuberculosis in non-AIDS immunocompromised patients.

SETTING: Department of Chest Diseases, Istanbul Faculty of Medicine, Istanbul University. OBJECTIVE: To determine the clinical and radiographic presentation of pulmonary tuberculosis in non-AIDS immunocompromised patients (ICP). DESIGN: A retrospective review of medical records of 143 patients (63 immunocompromised patients and 80 immunocompetent patients) with pulmonary tuberculosis from 1992 to 2001. RESULTS: In ICPs, fever was more frequently observed (84.1% vs. 40%, P = 0.0000002), tuberculosis was more frequently disseminated (23.8 vs. 3.8%, P = 0.0008), and lung infiltrations were more often lobar or segmental consolidation (20.6% vs. 0%, P = 0.00007) and miliary lesions (17.5 vs. 3.8%, P = 0.014) than in the control patients. Hilar and/or mediastinal adenopathy was also more frequently documented in ICPs (14.3% vs. 2.5%, P = 0.01). CONCLUSION: Fever, atypical chest radiograph and disseminated disease are common findings of pulmonary tuberculosis in ICPs.     

Glycaemic control and familial factors determine hyperlipidaemia in early childhood diabetes. Oxford Regional Prospective Study of Childhood Diabetes.

AIMS: To determine whether abnormal lipid levels in children with Type 1 diabetes mellitus are the result of poor metabolic control or may in part be determined by genetic factors. METHODS: Non-fasting lipid levels were measured in 141 children with Type 1 diabetes (age range 7.7-19 years) 3 years after diagnosis, and in 192 of their parents. Glycosylated haemoglobin and the urinary albumin-creatinine ratio (three urine samples) were estimated in each child annually. RESULTS: The children had a mean total cholesterol of 4.46 +/- 1.25 mmol/l (+/- SD) and a median triacylglycerol of 1.18 mmol/l (range 0.32-4.7). A total of 15.3% of the population had a total cholesterol > 5.2 mmol/l and 17.9% had a triacylglycerol > 1.7 mmol/l; in 5.6% both total cholesterol and triacylglycerol were greater than these cut-off points. Total cholesterol, triacylglycerol and very low density lipoprotein-cholesterol were significantly correlated to glycaemic control. However, total cholesterol was also significantly related to parental total cholesterol either as analysed separately or as mean parental total cholesterol (r = 0.37, P = 0.0001). In stepwise multiple regression analysis both mean parental total cholesterol (P = 0.001) and HbA1c (P = 0.015) were significant determinants of the child's total cholesterol. The children studied were being followed prospectively for the development of microalbuminuria and there was a weak association across tertiles of total cholesterol, linking higher levels to the development of microalbuminuria (P < 0.05). CONCLUSIONS: We conclude that both glycaemic control and familial factors may be important determinants of lipid levels in young people with diabetes. Both may contribute to the subsequent risk of cardiovascular disease and possibly the development of incipient diabetic nephropathy.