How does clinical diagnosis of mycobacterial adenitis correlate with histological findings?

OBJECTIVE: To describe and compare histopathological findings with clinical criteria in diagnosis of TB adenitis. METHODS: Lymph node biopsies were obtained from 213 patients. Specimens were processed for culture and histopathologic examination, using standard methods. One hundred blocks with good preservation of tissue morphology were selected for detailed histological examination. RESULTS: About 75% of 213 patients had granulomas. In the remaining 25%, neither histopathological nor microbiological evidence of mycobacterial disease was found. Of 100 blocks selected for detailed examination, 79 blocks had granulomatous changes. The granulomas were well organised in 24%, mixed in 33%, and poorly organised in 43%. Langhans giant cells and acid-fast bacilli were observed in 88.6% and 21.5% of the 79 blocks, respectively. Cultured specimens were positive in about 10% of 79 biopsy specimens. CONCLUSIONS: Histological evidence of mycobacterial disease was only found in three quarters of patients that were clinically diagnosed and started on empirical treatment for tuberculous adenitis. Neither histological nor mycobacteriological evidence was found in a quarter of the patients who were already on treatment for TB, basing on clinical criteria. These findings call for new research on simple diagnostic tools for patients who seek care for s ymptoms of extra-pulmonary TB.

Patient knowledge, practices and challenges to health care system in early diagnosis of mycobacterial adenitis.

OBJECTIVE: To assess diagnostic delay, knowledge and practices related to tuberculosis among patients with mycobacterial adenitis. DESIGN: A cross sectional study involving comparison analysis of high-risk groups. SETTING: Seven hospitals in rural and semi-rural districts of Arusha. SUBJECTS: Four hundred and twenty six clinically diagnosed adenitis patients. INTERVENTIONS: Biopsy specimens were processed for culture, histology, and sera for HIV testing. A questionnaire was used to assess knowledge, practice, and diagnostic time. MAIN OUTCOME MEASURES: Tribal comparisons were made using proportions and means. RESULTS: About 90% (387/423) of patients first visited medical facilities within a mean time of 10.1(SD, 15.7) weeks after becoming aware of their illness, and a diagnosis was made at a mean of 27 (SD, 25) weeks. Non-Iraqw patients, especially the Datoga, practised drinking raw milk (35.2% 43/122), eating raw animal products (18.8% 24/128) and living in houses with poor ventilation (33.6% 44/131), more than Iraqw patients. Of the investigations done, 14.5% (60/415) were culture positive, 11.3% (16/142) were HIV positive, and 73.6% (128/174) had histological features consistent with tuberculosis. The knowledge of TB spread by air droplets was poorer in Iraqw (74.1%, 203/274) than in non-lraqw (61.1%, 77/126) patients. About 35.0% (45/129) of non-lraqw and 27.3% (79/289) of Iraqw patients were not aware that TB could be transmitted from animals to humans. CONCLUSIONS: The health system diagnostic delay is about twice the patient delay. The knowledge and practices related to both human and bovine TB transmission were poor in all patients, especially in the patients from nomadic tribes.

99mTc sestamibi scintimammography in the diagnosis of palpable breast masses.

The aim of this prospective study was to evaluate the diagnostic performance of 99mTc sestamibi scintimammography in a region with a low incidence of breast cancer (East, central and West Africa) and to verify the clinical usefulness of this technique in identifying benign breast diseases. Thirty-eight women (age range 22-38 years) with palpable breast masses (n =38) and inconclusive mammograms were included. Prone scintimammography was performed 10 min and 60-90 min in all patients after injection using an isotime acquisition of 10 min. A positive scan for breast cancer was defined as tracer uptake on the 10 min image and retention of activity on the 60-90 min image. A negative scan was defined as uptake on the 10 min image and complete washout of activity on the 60-90 min image. All patients subsequently underwent excisional biopsy of the breast masses and histological confirmation of the pathology. The results of scintimammography and histopathology were in agreement in all patients, revealing 36 benign lesions and two malignant lesions. Histopathologically, the lesions were fibroadenomas (27), fibrocystic disease (five), abscesses (four) and invasive intraductal carcinoma (two). It is concluded that, in regions with high incidence of benign breast diseases in young women, 99mTc sestamibi scintimammography can be used to rapidly characterize benign and malignant breast masses and thereby give priority to the management of those with a serious condition.

Evaluation of risk factors for Alzheimer's disease in elderly east Africans.

A number of biological risk factors have been implicated for Alzheimer's disease (AD). The investigation of prevalence rates of AD in crosscultural populations has much potential in validating these factors. We previously assessed brain amyloid beta (A beta) protein deposition and other lesions associated with AD as possible markers for preclinical AD in elderly nondemented East Africans. In further analysis, we demonstrate that 17-19% of elderly East African subjects without clinical neurological disease exhibited neocortical A beta deposits and minimal neurofibrillary changes at necropsy that was qualitatively and quantitatively similar to that in an age-matched elderly control sample from Cleveland, OH. A beta deposits varied from numerous diffuse to highly localized neuritic plaques and were predominantly reactive for the longer A beta 42 species. In parallel studies, we evaluated another recently implicated factor in AD, the apolipoprotein E genotype. We found relatively high frequencies of the apolipoprotein E-epsilon 4 allele in elderly nondemented East Africans. The frequencies were comparable to those in other African populations but higher than in subjects from developed countries. Our limited study suggests that elderly East Africans acquire cerebral lesions found in AD subjects but the apolipoprotein E-epsilon 4 allele may not be a highly specific factor for the disease among East Africans.

Cerebral amyloid beta protein deposits and other Alzheimer lesions in non-demented elderly east Africans.

There is little knowledge of the existence of Alzheimer disease (AD) or Alzheimer type of dementia in indigenous populations of developing countries. In an effort to evaluate this, we assessed the deposition of amyloid beta (A beta) protein and other lesions associated with AD in brains of elderly East Africans. Brain tissues were examined from 32 subjects, aged 45 to 83 years with no apparent neurological disease, who came to autopsy at two medical Institutions in Nairobi and Dar es Salaam. An age-matched sample from subjects who had died from similar causes in Cleveland was assessed in parallel. Of the 20 samples from Nairobi, 3 (15%) brains exhibited neocortical A beta deposits that varied from numerous diffuse to highly localized compact or neuritic plaques, many of which were also thioflavin S positive. Two of the cases had profound A beta deposition in the prefrontal and temporal cortices and one of these also exhibited moderate to severe cerebral amyloid angiopathy. Similarly, 2 of the 12 samples from Dar es Salaam exhibited diffuse and compact A beta deposits that were also predominantly reactive for the longer A beta 42 species compared to A beta 40. We also noted that A beta plaques were variably immunoreactive for amyloid associated proteins, apolipoprotein E, serum amyloid P and complement C3. Tau protein reactive neurofibrillary tangles (NFT) were also evident in the hippocampus of 4 subjects. By comparison, 4 (20%) of the 20 samples from randomly selected autopsies performed in Cleveland showed A beta deposits within diffuse and compact parenchymal plaques and the vasculature. These observations suggest A beta deposition and some NFT in brains of non-demented East Africans are qualitatively and quantitatively similar to that in age-matched elderly controls from Cleveland. While our small scale study does not document similar prevalence rates of preclinical AD, it suggests that elderly East Africans are unlikely to escape AD as it is known in developed countries.

Clinical features of HIV seropositive and HIV seronegative patients with tuberculous lymphadenitis in Dar es Salaam.

SETTING: The medical wards of a referral hospital in Dar es Salaam, Tanzania. OBJECTIVE: To investigate the impact of HIV infection on clinical features in tuberculous lymphadenitis. DESIGN: A prospective clinical study of HIV seropositive and HIV seronegative patients with lymphadenopathy. RESULTS: Of 128 patients with peripheral lymphadenopathy, 24 had no tuberculosis (TB) and in 10 patients TB was found only in other organs. The remaining 94 patients, of whom 76% were HIV seropositive, formed our study population. TB lymphadenitis was considered proven in 89 and probable in 5 patients. Disseminated TB (both TB adenitis and TB in other organs) was diagnosed more often in HIV seropositive than in HIV seronegative patients (52% versus 26%, P < 0.03). 59% of the 71 HIV-infected patients compared to only 4% of the 23 patients without HIV infection were over 30 years of age (P < 0.02). The following clinical features were significantly associated with HIV infection: dyspnoea, respiratory rate > 20/min, low motility score (bedridden), neurological abnormalities, hepatomegaly, splenomegaly, lymph node size < 2.5 cm, negative PPD skin test, lymphopenia (< 1000/cm3) and presence of pleural fluid. CONCLUSION: Co-infection with HIV influences several clinical and laboratory features in patients with tuberculous lymphadenitis.

Clinical features of HIV-seropositive and HIV-seronegative patients with tuberculous pleural effusion in Dar es Salaam, Tanzania.

In a prospective study, we investigated whether human immunodeficiency virus (HIV) infection alters the clinical presentation in patients with tuberculous pleuritis. One hundred twelve of 118 patients who presented with pleural effusion suffered from tuberculosis (TB); 65 patients (58%) were HIV seropositive. Evidence of disseminated TB was found more often in HIV-positive than in HIV-negative patients (30.8% vs 10.6%, p < 0.02). Dyspnea, fever, night sweat, fatigue, and diarrhea, severe tachypnea, hepatomegaly, splenomegaly, and lymphadenopathy were significantly more common in HIV-infected than in HIV-negative patients with TB. The same applied to a negative Mantoux reaction, lower hemoglobin, higher beta 2-microglobulin values, and in pleural fluid, lower albumin and higher gamma-globulin levels. Among HIV-infected patients, PPD skin test anergy was significantly associated with relative low albumin and gamma-globulin levels of pleural fluid. However, the radiographic features did not differ with respect to HIV status; they were predominantly those of primary pleuritis (78% in each group). We conclude that coexisting HIV infection affects clinical and laboratory features, but not the radiographic presentation of patients with TB pleuritis in Tanzania.

Influence of HIV status on pathological changes in tuberculous pleuritis.

SETTING: The AIDS epidemic has been associated with an increase in the incidence of tuberculosis, pulmonary or extrapulmonary. OBJECTIVE: To compare morphological changes in tuberculous pleurisy, and response to therapy in HIV-positive and-negative patients. DESIGN: 57 consecutive patients admitted between January and August 1991 with tuberculous pleurisy who were biopsy proven were studied. 36 were HIV-positive and 21 were HIV-negative. RESULTS: 3 types of morphological changes were observed: reactive, hyporeactive and non-reactive. Hypo- and non-reactive patterns were found in 14 of 36 HIV-positive patients but in only 2 of 21 HIV-negative patients (P < 0.02). In the HIV-positive group, 10 of the 14 with hypo- or non-reactive patterns had other HIV-related complications, compared to 6 of 22 with reactive patterns (P < 0.01). When HIV-positive patients' response to therapy was investigated, 2 of 5 patients with hypo- and non-reactive patterns improved compared to all 13 with reactive patterns (P < 0.05). CONCLUSION: A hypo- or non-reactive tissue reaction in HIV-positive patients with tuberculous pleuritis seems to indicate a less favourable prognosis.

Diagnosis of tuberculous lymphadenitis in an area of HIV infection and limited diagnostic facilities.

In order to evaluate procedures leading to the diagnosis of tuberculous lymphadenitis, a prospective clinical study was carried out of patients with lymphadenopathy admitted to the medical wards of a referral hospital in Tanzania. The yield of diagnostic procedures (direct auramine/Ziehl-Neelsen (ZN) stained smears, Löwenstein-Jensen (LJ) cultures, cytology and histological examinations of fine needle aspirations (FNA) and biopsy material of lymph nodes, respectively, was compared. We also tried to identify clinical diagnostic markers. One hundred and twenty-eight (99 HIV-seropositive) patients were included. In 89 (67 HIV-positive) patients TB lymphadenitis could be proven. Histology and LJ culture of a lymph node biopsy had the highest diagnostic yield, 85% and 88% respectively, followed by detection of acid-fast bacilli (AFB) in biopsy smear (53%) and in fine-needle aspirations (35%). The diagnostic yield of the several procedures was not affected by associated HIV infection. Macroscopic caseation was 100% predictive for TB with a sensitivity of 69%. Firm and matted lymph nodes, ESR > 100 mm/hr, a positive PPD skin test and pleural opacity on a chest x-ray proved to be independent predictors for TB. Retrospective testing of a stepwise diagnostic approach based on direct smears of FNA, macroscopic visible caseation and direct smear of biopsy tissue, suggests that in 93% of the patients a definite diagnosis of TB lymphadenitis could have been made. Our data suggest that in HIV/TB epidemic areas most of the cases of TB lymphadenitis can be diagnosed correctly by simple and cheap methods which are generally available at district hospitals. Our findings need further prospective validation, however.

PIP: In order to evaluate procedures leading to the diagnosis of tuberculous lymphadenitis, a prospective clinical study was carried out on patients with lymphadenopathy admitted to four medical wards of the Muhibili Medical Center, Dar es Salaam, Tanzania, from January to August 1991. The yield of diagnostic procedures (direct auramine/Ziehl-Neelsen stained smears, Lowenstein-Jensen [LJ] cultures, cytology and histological examinations of fine needle aspirations [FNA], and biopsy material of lymph nodes) was compared. Clinical diagnostic markers were also identified. 128 (99 HIV-seropositive) patients with a mean age of 30 years were included. 41% were male. In 89 (67 HIV-positive) patients, TB lymphadenitis could be demonstrated. 46 (30 HIV-positive) had TB lymphadenitis only and 43 (37 HIV-positive) had disseminated TB. In 10 patients TB was found in specimens other than the lymph node, making the total of TB patients 99. Histology and LJ culture of lymph node biopsy had the highest diagnostic yield, 85% and 88%, respectively, followed by detection of acid-fast bacilli in biopsy smears (53%) and in FNAs (35%). The diagnostic yield of the procedures was not affected by associated HIV infection. Macroscopic caseation was 100% predictive of TB with a sensitivity of 69%. Multivariate logistic regression analysis demonstrated four independent predictors of TB: 1) firm and matted lymph nodes (odds ratio [OR] 11.8); 2) erythrocyte sedimentation rate (ESR) 100 mm/hr (OR 4.6); 3) a positive purified protein derivative (PPD) skin test (OR 10.2); and 4) pleural opacity on a chest X-ray (OR 9.5). Retrospective testing of a stepwise diagnostic approach based on direct smears of FNA, macroscopic visible caseation, and direct smears of biopsy tissue suggests that in 93% of the patients a definite diagnosis of TB lymphadenitis could have been made. These data suggest that in HIV/TB epidemic areas most of the cases of TB lymphadenitis can be diagnosed correctly by simple and cheap methods which are generally available at district hospitals.

Diagnosis of tuberculosis in patients with pleural effusion in an area of HIV infection and limited diagnostic facilities.

In a prospective study of 118 patients with pleural effusion, tuberculosis (TB) was diagnosed in 112. In 84 patients the diagnosis of TB was made by detection of acid-fast bacilli by stain (auramine, Ziehl-Neelsen) or by culture of mycobacteria (Löwenstein-Jensen medium) in pleural fluid or pleural tissue (obtained by closed biopsy) or by the presence of caseating granulomas in histological sections. In 28 patients the diagnosis of TB was considered probable, based on good response to anti-tuberculous therapy. The highest diagnostic yield was obtained by histology (85%), followed by culture of pleural biopsy (37%) and pleural fluid culture (36%). Pulmonary tuberculosis was found in 8 patients and dissemination of TB to other sites in 25 patients of whom 20 were HIV positive. By logistic regression analysis we identified 2 independent diagnostic markers for TB pleuritis: pleural fluid protein > 50 g/l (Odds ratio 12.1, 95% confidence interval (CI): 1.1-128.3) and adenosine deaminase of > 10 U/l (Odds ratio 11.08, 95% CI: 1.3-96.4). We conclude that conventional facilities of a referral hospital are sufficient to diagnose tuberculous pleuritis as well as disseminated tuberculosis irrespective of HIV infection. However, for regions with overstretched health services and high prevalences of tuberculous pleurisy in patients with pleural effusion we suggest a simplified diagnostic approach based on exclusion of other causes of pleural effusion by simple means and use of these diagnostic markers.

PIP: In a prospective study of 118 patients with pleural effusion admitted to four medical wards in Muhimbili Medical Center between January and August 1991, Dar es Salaam, Tanzania, tuberculosis (TB) was diagnosed in 112. In 84 patients the diagnosis of TB was made by detection of acid-fast bacilli by stain (auramine, Ziehl-Neelsen) or by culture of mycobacteria (Lowenstein-Jensen medium) in pleural fluid or pleural tissue obtained by closed biopsy or by the presence of caseating granulomas in histological sections. In 28 patients the diagnosis of TB was considered probable, based on good response to anti-tuberculous therapy. In the remaining 6 non-TB patients adenocarcinoma (1), bacterial infection (2), and aspecific inflammation (3) were diagnosed. 58% of the TB and 3 of the non-TB patients were infected with HIV. The diagnostic procedures were evaluated in 75 patients. The highest diagnostic yield was obtained by histology (85%), followed by culture of pleural biopsy (37%), and pleural fluid culture (36%). Pulmonary tuberculosis was found in 8 (4 HIV-positive) patients and dissemination of TB to other sites in 25 patients, of whom 20 were HIV-positive. By logistic regression analysis, two independent diagnostic markers for TB pleuritis were identified: pleural fluid protein 50 g/l (odds ratio [OR] 12.1) and pleural fluid adenosine deaminase level of 10 U/l (OR 11.08). The sensitivity of these two diagnostic tests was 82% and 97.3%, and the specificity was 83.6% and 50%, respectively. TB was the underlying cause in nearly all patients who presented with pleural effusion (94.9%). TB was confirmed in 75% of these using the referral hospital. Conventional facilities of a referral hospital are sufficient to diagnose tuberculous pleuritis as well as disseminated tuberculosis irrespective of HIV infection. However, in regions with overburdened health facilities and high prevalence of tuberculous pleurisy in patients with pleural effusion, a simplified diagnostic approach is suggested based on exclusion of other causes of pleural effusion by simple use of these diagnostic markers.

Chylopericardium and chylothorax, resulting from a catheter to the left subclavian vein: an autopsy report.

A 47-year-old woman with long-standing myelofibrosis and thrombocytosis whose spleen was removed 9 days prior to death, died of a heart tamponade. Subsequent autopsy revealed the development of chylothorax and chylopericardium due to the existence of a thrombus obstructing the ostium of the left thoracic duct, as a consequence of the particular location of a central venous catheter in the left subclavian vein in the proximity of the confluence of the left thoracic duct in the afore-mentioned vein.