- Email: [email protected]
Unrecognised Mycobacterium tuberculosis
Sir—Clifford McDonald and colleagues1 try to make a case for expanding the repertoire of the microbiology laboratory in lessdeveloped countries to include the routine detection of mycobacteraemia. They argue that early recognition of patients with active tuberculosis is crucial in hospital settings to limit nosocomial transmission of Myco bacterium tuberculosis. Resources for carrying out simple tests such as chest radiographs and sputum smears are limited in many less-developed countries. Mycobacteraemia is a key event in the pathogenesis of tuberculosis, and clinicians frequently do not suspect underlying mycobacteraemia and do not request blood cultures. I disagree strongly with this viewpoint. I believe their argument is seriously flawed, and that their results misrepresent the real situation. Malawi is one of the poorest countries in the world, but despite a lack of resources it has a strong, countrywide, and well-run National Tuberculosis Control programme. Several other countries in southern Africa also receive technical support from the International Union against Tuberculosis and Lung disease and WHO. In these countries, sputumsmear examination is the cheapest and most efficient way of screening for tuberculosis. All district and mission hospitals in Malawi can perform smear microscopy, and several health centres also offer this service. In 1998, 88 254 patient with suspected tuberculosis submitted sputum for smear testings in 44 Malawian hospital laboratories (data from National Tuberculosis Control Programme). Chest radiography facilities are also available at these hospitals. There may well be operational problems from time to time, but to suggest that resources for carrying out these investigations is limited is not correct. McDonald and colleagues state that half the patients with M tuberculosis bacteraemia had unrecognised active disease. Their definition of unrecognised disease was an adult patient who had neither an abnormal chest radiograph nor a positive sputum smear on or before the day of admission. In a similar general hospital in Blantyre, Malawi, 578 (42%) of 1365 patients diagnosed as having smear-positive pulmonary tuberculosis were admitted for investigation of tuberculosis—none of these patients had sputum smears or chest radiographs done until after they had been admitted.2 If febrile, these patients would have fulfilled McDonald and colleagues’ definition of unrecognised
142
active disease. Most smear-positive pulmonary tuberculosis patients have chronic cough, fever, and weight loss. All clinicians in Malawi are taught that these symptoms suggest pulmonary tuberculosis and are an indication that sputum specimens should be collected for smear microscopy. Many of McDonald and colleagues’ patients should therefore have been diagnosed with suspected pulmonary tuberculosis, if they had been properly assessed. McDonald and colleagues’ study has limited value for those of us working in tuberculosis control in countries like Malawi. A more useful study would have been to assess the frequency of bacteraemia in patients presenting with fever, no features of pulmonary tuberculosis, negative sputum smears, and normal chest radiographs, in whom there has been no response to anti-malarial treatment and broadspectrum antibiotics. In the era of HIV infection and AIDS this is a common and taxing clinical problem in sub-Saharan Africa, and to have information on the extent of mycobacteraemia and the value of a trial of anti-tuberculosis treatment in these patients would be extremely useful. The Department of Medicine at the medical school in Blantyre has just such a proposal. Sadly the US$50 000 needed to fund this study cannot be found. A D Harries National Tuberculosis Control Programme, PO Box 30042, Lilongwe, Malawi (e-mail: [email protected]) 1
McDonald LC, Archibald LK, Rheanpumikankit S, et al. Unrecognised Mycobacterium tuberculosis bacteraemia among hospital inpatients in less developed countries. Lancet 1999; 354: 1159–63. 2 Harries AD, Kamenya A, Namarika D, et al. Delays in diagnosis and treatment of smearpositive tuberculosis and the incidence of tuberculosis in hospital nurses in Blantyre, Malawi. Trans R Soc Trop Med Hyg 1997; 91: 15–17.
Authors’ reply Sir—Our study was limited to determining the prevalence of M tuberculosis infection in the bloodstream (mycobacteraemia) in febrile patients and the frequency of unrecognised active pulmonary tuberculosis in these patients. We highlighted the occurrence of occult mycobacteraemia and the risk of nosocomial transmission of tuberculosis in less-developed countries with high rates of tuberculosis and HIV-1 co-infection. Christopher Hudson, Nicola Hargreaves and their colleagues and A D Harries disagree with our definition of unrecognised active disease. Harries refers to a Blantyre
hospital in which 42% of patients with smear-positive tuberculosis were diagnosed. 1 But, he fails to mention the long delays from admission to diagnosis and subsequent treatment, and the high annual rates (14%) of active tuberculosis among nurses that suggested nosocomial transmission was a substantial problem. Since we defined unrecognised active disease from the perspective of early detection as a prevention measure for nosocomial tuberculosis (rather than case finding), we believe our definition was most appropriate. Furthermore, your correspondents have misconstrued our conclusions and recommendations. Our results emphasise the need for sputum smears or chest radiography in adults in developing countries with chronic fever, chronic cough, weight loss, or oral thrush, on or before hospital admission. Among such patients in our study, only 24% (14 of 59) admitted to the Malawi hospital versus 84% (106 of 126) admitted to the Thai hospital had a sputum smear or chest radiograph on or before the day of admission. Harries suggests that there are no important barriers to obtaining these tests in Malawi. However, in his own survey, only 15% of Blantyre outpatients with cough who should have had sputum microscopy had records of the test being done. 2 In our suggestion that the Malawi hospital had limited resources, we did not distinguish between limitation of management resources (ie, operational problems) and lack of equipment or supplies. Until radiography and sputum smears are available on admission for at least 90% of high-risk patients, routine tuberculosis blood cultures would seem inappropriate. Nonetheless, in some settings, blood cultures could be considered for patients with negative sputum smears and non-diagnostic radiographs, or to answer questions of clinical or publichealth importance. Hargreaves and colleagues express concern about only patients with chronic cough. However, 56% of patients with mycobacteraemia in our study had chronic cough and 18% had neither acute nor chronic cough. Moreover, in Tanzania, 38% (23 of 60) of inpatients with mycobacteraemia had neither symptoms nor signs to suggest underlying tuberculosis.3 These cases should be detected as early as possible before nosocomial transmission occurs. Hudson and colleagues suggest that needle aspiration of lymph nodes should suffice. However, only 60% (20 of 34) of patients with mycobacteraemia in our study had
THE LANCET • Vol 355 • January 8, 2000
142
active disease. Most smear-positive pulmonary tuberculosis patients have chronic cough, fever, and weight loss. All clinicians in Malawi are taught that these symptoms suggest pulmonary tuberculosis and are an indication that sputum specimens should be collected for smear microscopy. Many of McDonald and colleagues’ patients should therefore have been diagnosed with suspected pulmonary tuberculosis, if they had been properly assessed. McDonald and colleagues’ study has limited value for those of us working in tuberculosis control in countries like Malawi. A more useful study would have been to assess the frequency of bacteraemia in patients presenting with fever, no features of pulmonary tuberculosis, negative sputum smears, and normal chest radiographs, in whom there has been no response to anti-malarial treatment and broadspectrum antibiotics. In the era of HIV infection and AIDS this is a common and taxing clinical problem in sub-Saharan Africa, and to have information on the extent of mycobacteraemia and the value of a trial of anti-tuberculosis treatment in these patients would be extremely useful. The Department of Medicine at the medical school in Blantyre has just such a proposal. Sadly the US$50 000 needed to fund this study cannot be found. A D Harries National Tuberculosis Control Programme, PO Box 30042, Lilongwe, Malawi (e-mail: [email protected]) 1
McDonald LC, Archibald LK, Rheanpumikankit S, et al. Unrecognised Mycobacterium tuberculosis bacteraemia among hospital inpatients in less developed countries. Lancet 1999; 354: 1159–63. 2 Harries AD, Kamenya A, Namarika D, et al. Delays in diagnosis and treatment of smearpositive tuberculosis and the incidence of tuberculosis in hospital nurses in Blantyre, Malawi. Trans R Soc Trop Med Hyg 1997; 91: 15–17.
Authors’ reply Sir—Our study was limited to determining the prevalence of M tuberculosis infection in the bloodstream (mycobacteraemia) in febrile patients and the frequency of unrecognised active pulmonary tuberculosis in these patients. We highlighted the occurrence of occult mycobacteraemia and the risk of nosocomial transmission of tuberculosis in less-developed countries with high rates of tuberculosis and HIV-1 co-infection. Christopher Hudson, Nicola Hargreaves and their colleagues and A D Harries disagree with our definition of unrecognised active disease. Harries refers to a Blantyre
hospital in which 42% of patients with smear-positive tuberculosis were diagnosed. 1 But, he fails to mention the long delays from admission to diagnosis and subsequent treatment, and the high annual rates (14%) of active tuberculosis among nurses that suggested nosocomial transmission was a substantial problem. Since we defined unrecognised active disease from the perspective of early detection as a prevention measure for nosocomial tuberculosis (rather than case finding), we believe our definition was most appropriate. Furthermore, your correspondents have misconstrued our conclusions and recommendations. Our results emphasise the need for sputum smears or chest radiography in adults in developing countries with chronic fever, chronic cough, weight loss, or oral thrush, on or before hospital admission. Among such patients in our study, only 24% (14 of 59) admitted to the Malawi hospital versus 84% (106 of 126) admitted to the Thai hospital had a sputum smear or chest radiograph on or before the day of admission. Harries suggests that there are no important barriers to obtaining these tests in Malawi. However, in his own survey, only 15% of Blantyre outpatients with cough who should have had sputum microscopy had records of the test being done. 2 In our suggestion that the Malawi hospital had limited resources, we did not distinguish between limitation of management resources (ie, operational problems) and lack of equipment or supplies. Until radiography and sputum smears are available on admission for at least 90% of high-risk patients, routine tuberculosis blood cultures would seem inappropriate. Nonetheless, in some settings, blood cultures could be considered for patients with negative sputum smears and non-diagnostic radiographs, or to answer questions of clinical or publichealth importance. Hargreaves and colleagues express concern about only patients with chronic cough. However, 56% of patients with mycobacteraemia in our study had chronic cough and 18% had neither acute nor chronic cough. Moreover, in Tanzania, 38% (23 of 60) of inpatients with mycobacteraemia had neither symptoms nor signs to suggest underlying tuberculosis.3 These cases should be detected as early as possible before nosocomial transmission occurs. Hudson and colleagues suggest that needle aspiration of lymph nodes should suffice. However, only 60% (20 of 34) of patients with mycobacteraemia in our study had
THE LANCET • Vol 355 • January 8, 2000