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Setting: The Komfo Anokye Teaching Hospital, Kumasi, Ghana, West Africa., Objective: To evaluate simple and commonly used parameters of the acute-phase response as correlates of successful resolution of smear-positive pulmonary tuberculosis (PTB) during drug treatment., Design: Serum C-reactive protein (CRP) concentration, erythrocyte sedimentation rate (ESR), body weight, and blood haemoglobin were measured in human immunodeficiency virus (HIV) negative Ghanaian patients with PTB (n = 15) and in age- and sex-matched healthy controls (n = 15). These parameters were subsequently measured in patients after 1, 2 and 3 months of antituberculosis treatment. Serum concentrations of soluble interleukin-2-receptor-alpha (sCD25) were also measured as a comparative index of resolution of the systemic inflammatory process., Results: Anti-tuberculosis treatment resulted in sputum smear conversion in all 15 patients. After one month of treatment, reductions in serum CRP concentration (>20%) and increases in haemoglobin concentration (>0.4 g/dl) occurred in the majority of patients and correlated with steep reductions in serum levels of sCD25. In contrast, weight loss and elevated ESR were slower to resolve, and were insensitive early markers of response to treatment., Conclusion: A fall in serum CRP and a rise in blood haemoglobin are correlates of the initial response to drug treatment of PTB. These parameters may assist in the evaluation of empiric trials of treatment in microbiologically unconfirmed cases of suspected PTB.

Objective: To determine the impact of treatment of tuberculosis on plasma HIV-1 load in African subjects and to correlate viral load with response to treatment and changes in immune activation., Design: Clinical and microbiological responses, immune activation parameters and plasma HIV-1 load were determined in 20 patients with pulmonary tuberculosis and HIV-1 coinfection in Ghana, West Africa during the first 3 months of anti-tuberculosis treatment., Methods: Plasma HIV-1 load and markers of immune activation were determined by commercially available assays. Human leukocyte antigen (HLA)-DR incorporation into the HIV-1 envelope was measured by using an immunomagnetic capture technique., Results: Treatment of tuberculosis resulted in significant improvements in weight and haemoglobin, a high sputum smear conversion rate and marked reductions in mean plasma tumour necrosis factor (TNF) receptor-1, interleukin-6 and C-reactive protein. Furthermore, incorporation of host HLA-DR into the HIV-1 envelope decreased; this also suggested a reduction in immune activation of the cells supporting viral replication. However, of importance with regard to AIDS pathogenesis, neither mean plasma TNF-alpha nor HIV-1 load decreased significantly., Conclusions: The failure of HIV-1 plasma load to decline significantly during the initial months of anti-tuberculosis treatment is associated with high, sustained systemic levels of TNF-alpha. The dissociation between the sustained levels of plasma TNF-alpha and the major reductions in other, diverse immune activation parameters may represent dysregulation of cytokine production in these African patients.

Antituberculosis treatment containing thiacetazone is associated with a high incidence of life-threatening cutaneous drug reactions in patients infected with the human immunodeficiency virus (HIV). In order to develop a local policy concerning the use of this drug, a study was undertaken to determine the incidence of such reactions in a total of 1063 Ghanaian adult patients treated for pulmonary tuberculosis (PTB) with thiacetazone-containing regimens. The incidence was retrospectively determined in 3 different treatment groups, comparing: (A) unselected use of thiacetazone; (B) exclusion of thiacetazone from all patients with positive HIV serology; (C) selective exclusion of thiacetazone from patients with clinical criteria suggesting HIV infection plus education of health workers and patients. Of the 408 patients in group A receiving thiacetazone, 9 (2.2%) developed life-threatening cutaneous reactions and 7 of these were HIV-positive. Overall, 6.8% of HIV-positive patients compared to 0.65% of HIV-negative patients developed severe reactions (P < 0.01; relative risk = 10.5). Six of the 9 patients with reactions died. All 379 patients in group B were screened for HIV antibodies and positive cases (23%) received a regimen in which thiacetazone was substituted by ethambutol. In contrast to Group A, only one HIV-negative patient (0.26%) developed a severe cutaneous reaction (P = 0.02). Among 276 patients in group C, thiacetazone was substituted with ethambutol only in those with clinical evidence of HIV infection (8%) and staff and patients were educated about early recognition of the side-effect. With this policy, these were no admissions with severe cutaneous reactions compared to 2.2% of those in group A (P = 0.01). In conclusion, a policy of selective use of thiacetazone in the treatment of PTB based on clinical criteria combined with patient and staff education was found to be a practical and cost-effective strategy combating severe cutaneous reactions to thiacetazone.

Setting: Department of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana, West Africa., Objective: To determine the factors affecting the delay from the onset of symptoms of pulmonary tuberculosis until the initiation of treatment., Design: A retrospective questionnaire survey of 100 adults with newly diagnosed smear-positive pulmonary tuberculosis., Results: The median total delay in diagnosis was 4 months (mean = 7.7), and total delay exceeded 6 months in 44% of patients. Total delay was strongly associated with rural residence (P = 0.001). The median doctor delay from the first consultation until diagnosis was double the median patient delay in initial presentation (8 weeks versus 4 weeks). Doctor delay was significantly increased in females, rural patients, and among those needing hospital admission. Increased doctor delay was strongly correlated with rates of failure to perform sputum microscopy (r = 0.99), low rates of diagnosis, and was seen particularly among private practitioners and rural government institutions., Conclusion: Delays in the diagnosis of pulmonary tuberculosis are prolonged in Kumasi, Ghana, with a frequently lengthy doctor delay. The new National Tuberculosis Programme is decentralising the diagnosis and management of tuberculosis, with the introduction of widely available sputum microscopy and rigorous training of health personnel. This should help to reduce doctor delay and thereby improve tuberculosis control.

Unlabelled: We evaluated 'Mycodot', a commercially marketed immunodiagnostic test for tuberculosis which detects antibodies to lipoarabinomannan antigen. Serum was tested from 52 patients with newly diagnosed smear-positive pulmonary tuberculosis, of whom 20 were HIV-positive and 32 HIV-negative. Control sera were taken from 40 patients of whom 20 had acute non-tuberculous lobar pneumonia and 20 patients had no respiratory disease. The test was found to have a very high specificity of 97.5% (95% CI:92.5-100%). However, the sensitivity in HIV-negative patients was 56% (95% CI:39-73%), and was substantially lower at 25% (95% CI:6-44%) in HIV-positive patients., In Conclusion: 'Mycodot' was found to be a highly specific and easily performed assay. However, the poor sensitivity, especially in HIV-infected patients, renders it unlikely to be useful either as a primary or adjunctive diagnostic test for tuberculosis, particularly in countries with a high prevalence of HIV. A larger trial of this assay in Ghana was not deemed necessary.