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HIV-associated tuberculosis in developing countries: clinical features, diagnosis, and treatment.

This article reviews the clinical aspects and diagnosis of HIV-associated tuberculosis in developing countries, and summarizes WHO's recommendations for treatment. According to WHO estimates (early 1992) over 4 million persons worldwide have been infected with HIV and tuberculosis; 95% of them are in the developing countries. Clinical features of HIV-associated pulmonary tuberculosis in adults are frequently atypical, particularly in the late stage of HIV infection, with non-cavitary disease, lower lobe infiltrates, hilar lymphadenopathy and pleural effusion. More typical post-primary tuberculosis with upper lobe infiltrates and cavitations is seen in the earlier stages of HIV infection. Extrapulmonary tuberculosis is reported more frequently, despite the difficulties in diagnosing it. WHO's recent guidelines recommend 6-month short-course chemotherapy with isoniazid, rifampicin, pyrazinamide and ethambutol for patients with HIV-associated tuberculosis. The older 12-month regimen without rifampicin is much less effective. Streptomycin should not be used, because of the risk of transmitting blood-borne pathogens through contaminated needles. Thioacetazone should be abandoned, because of severe adverse reactions observed among HIV-infected patients. The roles of preventive chemotherapy and BCG vaccination for prevention of tuberculosis are also briefly discussed.

Adolescent

Tuberculosis in Tanzania: a national sampling survey of drug resistance and other factors.

This survey was conducted in 1969/70 in a random sample of 15 of the 61 administrative districts in Tanzania. It included clinics with a long established tuberculosis service (A group), those with a tuberculons service of recent inception (B group) and those with no specialised tuberculosis service (C group), and 3 additional centres of special interest. The aim was to obtain, for tuberculous patients newly registered for treatment during a specified 6-month period, information on: a) the proportions of patients with pulmonary and/or extra-pulmonary tuberculosis; b) the history of previous chemotherapy with antituberculosis drugs: c) the prevalence of bacteriologically-positive pulmonary tuberculosis; d) the prevalence of initial and acquired resistance to the standard antituberculosis drugs; e) the radiographic extent and type of disease and of cavitation. Of 1884 patients in the random sample, 87.4 per cent had pulmonary tuberculosis only, 2.5 per cent had pulmonary and extra-pulmonary tuberculosis and 10.1 per cent had extra-pulmonary tuberculosis only. Although there were differences in the proportions with extra-pulmonary disease in individual districts in each group there were no important differences in the average levels for the A, B and C groups. Of 256 extra-pulmonary tuberculous lesions in 237 patients, 58 per cent were lymph node, 26 per cent bone and joint and 12 per cent pleural, pericardial or peritoneal. Of 1694 patients with pulmonary tuberculosis with or without extra-pulmonary tuberculosis, 96.3 per cent gave no history of previous chemotherapy and 3.6 per cent a definite history. A sputum specimen from each of 1338 patients with pulmonary tuberculosis was examined by direct smear; 675 (50 per cent) were positive as were 694 (55 per cent) of 1257 cultures. For the patients with no history of previous chemotherapy the positivity rates were 59 per cent on smear and 66 per cent on culture for the A group, 53 per cent and 57 per cent for the B group and 35 per cent and 38 per cent for the C group. Of 636 patients with no history of previous chemotherapy and sensitivity test results, 9 per cent had a strain resistant to isoniazid and/or streptomycin. The total prevalence of resistance to isoniazid was 6 per cent and to streptomycin 4 per cent. Of 1278 patients aged 5 or more with a postero-anterior chest radiography available and a diagnosis of intra-thoracic tuberculosis in Tanzania, 86 per cent were reported at an independent assessment in London as having a lung lesion. Among the 1171 patients of all ages reported as having a lung lesion, gross extensive or moderate disease was present in 73 per cent of the radiographs and cavitation in 66 per cent. The type of radiographic disease was assessed as acute in 36 per cent, mixed-acute in 40 per cent, mixed in 19 per cent and chronic in 5 per cent. There was no evidence of associations between drug resistance and the extent or type of disease of presence of cavitation...

Adolescent

Microbiology of cutaneous tuberculosis.

Detailed bacteriological characteristics including drug sensitivity of 12 mycobacteria isolated from 51 cases of different types of cutaneous tuberculosis were studied; no mycobacterium could be isolated from remaining 39 cases. Nine were identified as M. tuberculosis and 3 as 'anonymous' mycobacteria. Acquired resistance to one or more than one drug (streptomycin, isoniazid, PAS and thiacetazone) was observed in 3 out of 9 strains of M. tuberculosis. All the 'anonymous' strains were resistant to all the drugs except ethionamide and ethambutol.

Aminosalicylic Acids

Initial resistance of Mycobacterium tuberculosis in Northern Nigeria.

Of 61 isolates of Mycobacterium tuberculosis form patients in northernn Nigeria denying any previous treatment for tuberculosis 7 (11.5 per cent) yielded resistant cultures. Four (6.6 per cent) were resistant to isoniazid, 2 (3.3 per cent) to PAS (1 also to thiacetazone), and 1 (1.6 per cent) to streptomycin. No mycobacteria other than M. tuberculosis were isolated from these patients. These results suggest that the level of initial drug resistance in northernn Nigeria may be lower than that found in other African countries.

Aminosalicylic Acids

A system for the examination of tubercle bacilli and other mycobacteria.

Methods are described for the examination of mycobacteria cultured from clinical specimens. In the "screening" procedure used for new isolates tubercle bacilli are non-pigmented, do not grow at 25 degrees C and are sensitive to p-nitrobenzoic acid as well as normally to anti-tuberculosis drugs. Classification is extended when necessary by the use of four tests--temperature requirements, pigmentation, oxygen preference and Tween hydrolysis. These define 15 species or groups meeting the needs of clinical bacteriology. Drug-sensitivity tests are described which relate the end-points of titrations to the modal response of normal wild strains of M. tuberculosis. They are used not only as a guide to chemotherapy but also to support and amplify classification.

Aminosalicylic Acid

Tuberculosis in Tanzania: a follow-up of a national sampling survey of drug resistance and other factors.

A total of 1873 patients admitted to a random sampling survey in 15 of the 61 administrative districts in Tanzania in 1969 has been followed up at 1 year or later. The random sample included districts with a long-established tuberculosis service (A districts), those with a service of recent inception (B districts), and those with no specialized tuberculosis service (C districts). The main follow-up concerns 1607 patients with pulmonary tuberculosis of whom 693 had a positive culture at the initial survey, 557 a negative culture and 357 had not produced a specimen. At 1 year or later 12% of the 1607 patients were lost from observation, 10% were alive but with no specimen or no result, 60% were culture-negative, 5% were culture-positive, and 12% were known to be dead. The proportion of patients known to be dead was similar in the 3 types of service, but the proportion lost from observation was highest in the B districts, 24% compared with 7% in the A and 10% in the C districts. Most of the losses occurred early, 73% within the first 3 months. Of the 693 patients with positive culture initially 9% were culture-positive at 1 year, as were 1% of the 557 culture-negative initially. The estimated proportion culture-negative at 1 year for the patients culture-positive initially was highest in the A districts, 78%, and very similar in the B and C districts, 66% and 67%, respectively. The policies of therapy were studied in 1459 patients; 86% were treated in hospital initially for a mean duration of 63 days. The standard regimen of streptomycin, thiacetazone and isoniazid was prescribed in 78% of the patients initially, the proportions being 93% in the A, 48% in the B and 81% in the C districts. The proportion of patients who received or collected supplies of medicament for the full 12 months was only 35%, the proportions being 40% in the A, 20% in the B and 39% in the C districts.

Adolescent

Primary and secondary resistance of mycobacterium tuberculosis in Eastern Botswana.

Of 51 patients in Eastern Botswana who denied previous anti-tuberculosis treatment, 6 (11.8 %) were excreting tubercle bacilli resistant to one of the first-line drugs in regular use: 4 patients (7.8 %) showed resistance to isoniazid, 2 (3.9 %) to thiacetazone and none to streptomycin. Of 44 patients known to have been on previous anti-tuberculosis treatment, 31 (70.5 %) were found to show resistance to one or more of the first line drugs: 31 (70.5 %) to isoniazid, 12 (27.2 %) to streptomycin and 11 (25.9 %) to thiacetazone. No appreciable resistance was found to second line drugs. These resistance patterns, which correspond quite well with other published results from Africa, are related to the overall problem in Botswana, namely the failure of a high proportion of patients, to complete a full course of first line treatment.

Antitubercular Agents

Cross-sectional survey of HIV infection among patients with tuberculosis in Nairobi, Kenya.

Evidence from many countries suggests an association of human immunodeficiency virus (HIV) infection and tuberculosis of major public health significance. In order to begin assessing the impact of HIV on tuberculosis in Kenya, we have determined the HIV-1 seroprevalence among tuberculosis patients and compared the clinical characteristics of tuberculosis in HIV-positive and HIV-negative patients in two cross-sectional studies at the Infectious Disease Hospital (IDH) and the Ngaira Avenue Chest Clinic (NACC), Nairobi, Kenya. The diagnosis in 92% of all patients with pulmonary tuberculosis was confirmed by culture. The remainder were diagnosed on histological, clinical or radiological grounds. HIV seroprevalence among tuberculosis patients at IDH was 26.5% (52/196) compared to 9.2% (18/195) at NACC (P less than 0.001). There was no association between numbers of streptomycin injections in the previous 5 years and HIV infection. Positive sputum smear rates in HIV-positive patients were slightly lower than in HIV-negative patients at both study sites (71% vs 83% at IDH and 73% vs 82% at NACC) but the difference was not significant. Only Mycobacterium tuberculosis was isolated. Miliary disease was not associated with HIV infection. Persistent diarrhoea, oral candidiasis, generalized itchy rash, herpes zoster and generalized lymphadenopathy were all associated with HIV infection, but 46% (95% CI:38-54%) of all HIV-positive patients had none of the clinical features listed in the WHO Clinical Criteria for the Diagnosis of AIDS, apart from fever, cough and weight loss. Stevens-Johnson Syndrome was reported in 7/52 (13%) patients with HIV infection, and in 4/144 (3%) patients without (RR 4.85, 95% CI: 1.45-15.88).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The influence of HIV status on single and multiple drug reactions to antituberculous therapy in Africa.

OBJECTIVE: To document the influence of HIV status on drug reactions occurring in patients on antituberculous therapy in Harare, Zimbabwe. DESIGN: Retrospective cohort study. SETTING: City of Harare Tuberculosis Unit. PATIENTS: Records of 906 patients with tuberculosis, of whom 162 reacted to antituberculous therapy, were analysed. RESULTS: Reactions to antituberculous drugs were more frequent in HIV-positive (98 out of 363) than in HIV-negative (64 out of 543; P less than 0.0001) patients. The most common drug reaction was cutaneous hypersensitivity, occurring in 139 patients, 89 (64%) of whom were HIV-positive. Thiacetazone was implicated in 115 (82.7%) of the 139 cutaneous reactions and streptomycin in 10 (7.2%). Almost all cutaneous reactions occurred within 8 weeks of beginning treatment. Severe cutaneous reactions occurred more often in HIV-positive patients (P less than 0.001) and the only two deaths occurred in this group. Reactions to multiple drugs occurred in 18 HIV-positive and three HIV-negative patients (P = 0.017). CONCLUSIONS: The use of thiacetazone and streptomycin in antituberculous drug regimens should be reassessed in those countries where coinfection with HIV and tuberculosis is common.

Adult

The correlation of bacteriophage types of Mycobacterium tuberculosis with guinea-pig virulence and in vitro-indicators of virulence.

Among 58 isoniazid-sensitive strains of Mycobacterium tuberculosis from India, Burma and East Africa, 23 were of phage type A, 31 of type I (intermediate), 4 of type B and none of type C. Type I strains differed from type A strains in being attenuated in the guinea-pig, susceptible to H2O2, sensitive to thiophen-2-carboxylic acid hydrazide and resistant to thiacetazone and p-aminosalicylic acid; the content of strongly acidic lipids and of sulphatide lipids was low and the attenuation indicator lipid was present. The pattern of results with the type B strains did not correspond to the patterns for types A or I. Strains of type I appear to be a distinct group within the species M. tuberculosis.

Aminosalicylic Acid