Atorvastatin improves sputum conversion and chest X-ray severity score.

BACKGROUND: We report the results of a phase IIB study investigating the safety and effectiveness of atorvastatin use with standard anti-TB drugs.METHODS: In this multicentre, open-labelled study, we recruited treatment-naÏve patients with uncomplicated pulmonary TB aged at least 18 years. Participants were randomly assigned to standard-of-care or standard-of-care plus oral dose of atorvastatin (40 mg) daily for 2 months. Primary end points were safety measured by the number of participants with severe adverse events and effectiveness measured by the number of participants with negative sputum culture. Secondary endpoint was chest X-ray (CXR) severity score.RESULTS: Of the 185 participants screened, 150 were enrolled and equally assigned to the standard-of-care and atorvastatin groups. Adverse event severity was similar in the two groups. There was increased frequency of muscle pain in the trial group (12/75, 16% vs. 4/75, 5%). For efficacy analysis, respectively 64 (97%) and 57 (85.1%) patients in the trial and control groups had culture-negative results (P = 0.02) and experienced a reduction in CXR severity score of respectively 37% and 22%, with a mean difference of 1.4-4.9%.CONCLUSION: Atorvastatin is safe and associated with improved microbiological and radiological outcomes in TB.

ADVERSE EVENTS TO FIRST LINE ANTI-TUBERCULOSIS DRUGS IN PATIENTS CO-INFECTED WITH HIV AND TUBERCULOSIS.

BACKGROUND: The combination and use of multiple drugs in the treatment of tuberculosis (TB) predispose to adverse drug events and reactions. This study evaluated the incidence, frequency, and severity of adverse events to first line anti-tuberculosis (anti-TB) drugs in patients with TB and co-infections with Human Immunodeficiency Virus (HIV). OBJECTIVE: The objective of this study was to determine the effects of HIV status on the risk of developing adverse events to first line anti-TB therapy. METHOD: The study was carried out between 2006 and 2007 when TB therapy was administered without concomitant anti-retroviral therapy. Patients with TB presenting at the chest clinic of a tertiary hospital were sequentially enrolled. Those with TB alone were allocated to the first group while those with TB-HIV infection were allocated to a second group. A checklist of adverse events to the drugs was used to screen for adverse drug events and reactions during the period of anti-TB therapy. Adverse drug events were graded as serious and others (mild-moderate). RESULTS: One hundred and three patients completed the study. Thirty one (30.1%) of the patients had TB-HIV co-infection. Majority (70.4%) of the events were detected during the first week of therapy, 92% of these events were mild-moderate. Eight (25.5%) of those with TB-HIV co-infection had serious adverse events. All the serious events occurred in the TB-HIV group. Independent factors for occurrence of ADEs include HIV status, increasing age, and female gender. CONCLUSION: The rate of adverse drug events among patients on first line antituberculosis treatment was higher in HIV co-infected patients.

Resistance to first-line tuberculosis drugs in three cities of Nigeria.

OBJECTIVES: To determine the levels of resistance to first-line tuberculosis drugs in three cities in three geopolitical zones in Nigeria. METHODS: A total of 527 smear-positive sputum samples from Abuja, Ibadan and Nnewi were cultured on BACTEC- MGIT 960. Drug susceptibility tests (DST) for streptomycin, isoniazid, rifampicin and ethambutol were performed on 428 culture-positive samples on BACTEC-MGIT960. RESULTS: Eight per cent of the specimens cultured were multi-drug-resistant Mycobacterium tuberculosis (MDR-TB) with varying levels of resistance to individual and multiple first-line drugs. MDR was strongly associated with previous treatment: 5% of new and 19% of previously treated patients had MDR-TB (OR 4.1 (95% CI 1.9-8.8), P = 0.001) and with young adult age: 63% of patients with and 38% without MDR-TB were 25-34 years old (P = 0.01). HIV status was documented in 71%. There was no association between MDR-TB and HIV coinfection (P = 0.9) and gender (P > 0.2 for both). CONCLUSIONS: MDR-TB is an emerging problem in Nigeria. Developing good quality drug susceptibility test facilities, routine monitoring of drug susceptibility and improved health systems for the delivery of and adherence to first- and second-line treatment are imperative to solve this problem.

Pattern of presentation of tuberculosis and the hospital prevalence of tuberculosis and HIVco-infection in University College Hospital, Ibadan: a review of five years (1998 - 2002).

A 5-year review (1998-2002) was done at the pulmonary unit of the University College Hospital (UCH), Ibadan, Nigeria to determine the pattern of presentation of tuberculosis (TB) and the prevalence of TB and human Immunodefiency virus (HIV) co-infection. A total of one thousand patients were managed for TB but 777 confirmed as having TB had their case files analysed. There were 418 males and 359 females giving a male to female ratio of 1.16:1.00. Pulmonary tuberculosis (PTB) accounted for 78.6% of the patients seen over the period, followed by tuberculosis meningitis 7.8% then TB spine 6.8% and that of the lymph node 4.1%. The other types of TB (Abdomen, pericardial and miliary) accounted for less than 3%. The highest number of cases of tuberculosis (27.8%) was in the 20-29 age group for both male and female followed by those less than 40 years (26.0%). Less than 20% (18.3%) were 40 years old and above. The number of TB cases decreased sharply from a total of 188 in the year 2000 to 89 in 2002. The decrease in number was most likely due to the fact that directly observed therapy short course (DOTS) are now available at other centres within the city and its environs. Only 180 out of the 640 cases of TB were confirmed as HIV positive giving a seroprevalence rate of 28.12%. The annual distribution of TB/HIV co-infection showed a rising trend from 26 cases in 1998 to 42 cases in 2002.

A single blinded randomised trial to compare the efficacy and safety of once daily budesonide (400microg) administered by turbuhaler with beclomethasone dipropionate (400microg) given twice daily through a metered-dose inhaler in patients with mild to moderate asthma.

The study compared clinical efficacy and safety of beclomethasone dipropionate (BDP) given at a dose of 400microg in the mornings and evenings and delivered via pressurised metered dose inhaler (pMDI) with budesonide given via a dry-powder, inspiratory flow driven device at a daily dose of 400microg in the evening. The study was conducted as a week screening. 8-week open comparative clinical trial. At the commencement of the therapy, the baseline characteristics of the patients randomised into the two drug groups were comparable. Efficacy was assessed by changes in symptoms, number of times beta2-agonist was used and results of pulmonary function tests (PEF and FEV1) while safety was assessed by adverse event experiences. At the end of the study, 24 patients (12 in each group) were evaluated. Both drugs were effective in reducing asthma symptoms and frequency of beta2-agonist usage, as well as improving the lung function tests (FEV1 and PEF). However, budesonide given via Turbuhaler provided better effects in all parameters. The drugs were well tolerated and no adverse event was noticed in any of the patients. We therefore concluded that budesonide Turbuhaler administered once daily at a dose of 400microg is more efficacious than beclomethasone 400microg twice daily administered via pressurized metered dose inhaler.

Evaluation of modified short course chemotherapy in active pulmonary tuberculosis patients with human immunodeficiency virus infection in University College Hospital, Ibadan, Nigeria--a preliminary report.

Over the period, 1st October 1999 to 30th April 2002 a clinical trial of the modified short-course chemotherapy (SCC) in newly diagnosed cases of pulmonary tuberculosis with human immunodeficiency virus (HIV) infection in Ibadan, Nigeria was carried out. The modified SCC used was adopted by World Health Organisation (WHO)/International Union against Tuberculosis and Lung Diseases (IUALTD) for developing countries and also by the Nigerian National Tuberculosis and Leprosy Control Programmed (NTLCP). The regimen used consisted of ethambutol (E), isoniazid (H), rifampicin (R) and pyrazinamide (Z) in the intensive phase of 2 months. The continuation phase was 6 months of ethambutol (E) and isoniazid(H), i.e. 2EHRZ/6EH. Sputum conversion was 90% at the second month of treatment and there was no bacteriological relapse after 18 months of follow-up. Side effects were few and consisted mainly of acne vulgaris in 20 (22.5%) of 89 patients during the continuation phase. It is concluded that this modified 8-month chemotherapy regimen adopted by NTLCP is efficacious in treatment of smear positive pulmonary tuberculosis (PTB) patients with background HIV infection.

The clinical efficacy of fluticasone propionate (Fluvent) compared with beclomethasone dipropionates (Becotide) in patients with mild to moderate brochial asthma at the University College Hospital, Ibadan, Nigeria.

This open, randomized trial was conducted at the Medical Out patient Department of University College Hospital, Nigeria to compare the clinical efficacy of Beclomethasome dipropionate (Becotide) with Fluticasone propionate (Fluvent) in patients with mild to moderate bronchial asthma. The study was performed as a week screening, 8-weeks open comparative clinical trial involving Fluticasone propionate (Fluvent) at a daily dose of 22 microg and Beclomethasone Dipropionate (Becotide) at a dose of 400 microg daily delivered through pressurized metered-dose inhaler (pMDI). The main objective of this study is to assess the efficacy of Fluvent in patients with mild to moderate asthma compared to Becotide. At the second visit (end of 1 week), 10 patients were given either Becotide of Fluvent but all were maintained on as needed beta2agonist (Salbutamol inhaler) therapy throughout the study. Efficacy was assessed by changes in symptoms, number of times beta2-agonist was used and results of pulmonary function tests (PEFR and FEV1) while safety was assessed by adverse event experiences. The baseline characteristics of the patients randomized into the two drug groups were comparable and of no statistical significance. The changes in the pulmonary function tests as well as the reduction in the asthma symptoms suggest a statistically significant improvement in the asthma status of the patients. However, these changes were more rapid among the patients using Fluvent. Also, there was higher percentage decline in the episodes of asthma symptoms either in the morning, day or night in the Fluvent group than Becotide group. The drugs were well tolerated and no adverse event was noticed on any of the patients. We therefore concluded that Fluvent would be more efficacious than Becotide in the treatment of Asthma.