Pulmonary tuberculosis in HIV infection in Tanzania. Clinical and immunological studies.

Contains fulltext : 30221_pulmtuinh.pdf (publisher's version ) (Open Access)RU Radboud Universiteit Nijmegen, 27 juni 2007Promotores : Dolmans, W.M.V., Shao, J.F. Co-promotor : Ven, A.J.A.M. van der233 p

Hepatosplenic shistosomiasis: a review.

Item does not contain fulltextBACKGROUND: Schistosomiasis is a granulomatous disease that is caused by infection with schistosomes. It is a major health threat in tropical and subtropical countries. Due to increased movement, all residents of the universe are at risk of contracting this infection. The infection goes through several stages, but the most life-threatening form and leading cause of mortality is hepatosplenic schistosomiasis (HSS). It is a chronic complication, which develops as a consequence of inflammatory response. This complication has not been adequately addressed or attended the and as a consequence most of patients presenting with this complication in our settings die. OBJECTIVES: To review literature on hepatosplenic schistosomiasis, to give the state-of-the-art management of HSS, to give our own experience on management of this complication and hence impart knowledge to medical personnel on HSS. DATA SOURCE: Literature is from Medline database and experience from gastroenterology clinics. Our own experience has been blended on top. STUDY SELECTION AND DATA EXTRACTION: We have selected material, which have been verified and can be applicable in resource poor-countries, where this problem is a major health threat. DATA SYNTHESIS: Based on published studies and meta-analyses and our own experience we have been able to draw conclusions on the current understanding of the subject. CONCLUSION: Hepatosplenic schistosomiasis is a deadly complication and occurs mainly in poor countries. Regular reviews and updates of our knowledge is important to enable stakeholders of health sector understand the problem and develop strategies on its management

Assessment of antibacterial sale by using the Anatomic Therapeutic Chemical classification and defined daily dose methodology in Moshi Municipality, Northern Tanzania.

Contains fulltext : 88335.pdf (publisher's version ) (Open Access

Pharmacokinetics of first-line tuberculosis drugs in tanzanian patients

Contains fulltext : 117415.pdf (publisher's version ) (Open Access)East Africa has a high tuberculosis (TB) incidence and mortality, yet there are very limited data on exposure to TB drugs in patients from this region. We therefore determined the pharmacokinetic characteristics of first-line TB drugs in Tanzanian patients using intensive pharmacokinetic sampling. In 20 adult TB patients, plasma concentrations were determined just before and at 1, 2, 3, 4, 6, 8, 10, and 24 h after observed drug intake with food to estimate the areas under the curve from 0 to 24 h (AUC0-24) and peak plasma concentrations (Cmax) of isoniazid, rifampin, pyrazinamide, and ethambutol. Acetylator status for isoniazid was assessed phenotypically using the isoniazid elimination half-life and the acetylisoniazid/isoniazid metabolic ratio at 3 h postdose. The geometric mean AUC0-24s were as follows: isoniazid, 11.0 h . mg/liter; rifampin, 39.9 h . mg/liter; pyrazinamide, 344 h . mg/liter; and ethambutol, 20.2 h . mg/liter. The Cmax was below the reference range for isoniazid in 10/19 patients and for rifampin in 7/20 patients. In none of the patients were the Cmaxs for pyrazinamide and ethambutol below the reference range. Elimination half-life and metabolic ratio of isoniazid gave discordant phenotyping results in only 2/19 patients. A substantial proportion of patients had an isoniazid and/or rifampin Cmax below the reference range. Intake of TB drugs with food may partly explain these low drug levels, but such a drug intake reflects common practice. The finding of low TB drug concentrations is concerning because low concentrations have been associated with worse treatment outcome in several other studies

Childhood tuberculosis in the Kilimanjaro region: lessons from and for the TB programme.

Contains fulltext : 87237.pdf (publisher's version ) (Closed access)OBJECTIVE: To determine the magnitude of childhood TB and treatment outcome in Kilimanjaro region. METHODS: Retrospective review of registration-based data on TB notifications in Kilimanjaro region for the period 2002-2006. RESULTS: Between 2002 and 2006, there were 1615 patients of childhood TB in Kilimanjaro region constituting 13% of total TB burden and the average case detection rate was 147/100 000 for urban and 41.8/100 000 for rural populations. Of them, 54.2% were men and 75.2% had pulmonary TB (PTB); 24.9% were tested for acid-fast bacilli (AFB) by Ziehl-Neelsen staining showing that 5.8% of all patients with TB were AFB smear positive. The remaining 94.2% were presumptively treated for TB. Treatment success rate was 79.9%, mortality 10.9% and default rate was 7%. Unfavourable outcome was more common among unconfirmed TB patients. HIV testing was very rare but increased after 2004 (<2% before 2005, 11-16% afterwards.) CONCLUSION: The rate of childhood TB in Kilimanjaro region is among the highest in the world. Microbiological diagnosis for TB and AFB smear positivity is very low. Treatment outcome in this region is poor. These findings argue for specific TB control strategies to be designed for children such as more AFB testing using new tools such as induced sputum and laryngeal swabs, active case finding, HIV testing of all suspected TB children, promoting and monitoring adherence. Regular epidemiological studies are also needed.1 mei 201

Light-emitting diode with various sputum smear preparation techniques to diagnose tuberculosis

Contains fulltext : 108513.pdf (publisher's version ) (Open Access)SETTING: Mawenzi Regional Hospital, northern Tanzania. OBJECTIVE: To determine the value of light-emitting diode (LED) microscopy in diagnosing tuberculosis (TB) on bleach-treated and direct sputum smears. DESIGN: Sputum samples were collected from patients suspected of pulmonary TB who presented consecutively at the laboratory for smear evaluation between December 2009 and February 2010. Four smears were prepared from each specimen: conventional Ziehl-Neelsen (ZN), direct auramine, bleach centrifugation and bleach short sedimentation auramine smears. A light microscope was used to examine ZN smears and an LED fluorescent microscope to examine auramine-stained smears. RESULTS: Of the 267 sputum samples examined, respectively 78 (29%), 62 (23%), 74 (28%) and 48 (18%) were acid-fast bacilli (AFB) positive by the bleach centrifugation, bleach short sedimentation, direct auramine and ZN methods. Bleach centrifugation identified 30 (11%) more positives than ZN microscopy (P < 0.001), but was not superior to the direct auramine method (P = 0.46), which yielded 26 (10%) more positives than ZN microscopy (P < 0.001). Fluorescent LED required a shorter smear reading time (1.5 min on average), while the light microscope took 4 min (P < 0.001). CONCLUSION: Fluorescent LED microscopy with direct smear preparation is rapid and effective. Further studies are needed to ascertain its performance under routine conditions

Pharmacological interactions between rifampicin and antiretroviral drugs: challenges and research priorities for resource-limited settings

Item does not contain fulltextCoadministration of antituberculosis and antiretroviral therapy is often inevitable in high-burden countries where tuberculosis (TB) is the most common opportunistic infection associated with HIV/AIDS. Concurrent use of rifampicin and many antiretroviral drugs is complicated by pharmacokinetic drug-drug interactions. Rifampicin is a very potent enzyme inducer, which can result in subtherapeutic antiretroviral drug concentrations. In addition, TB drugs and antiretroviral drugs have additive (pharmacodynamic) interactions as reflected in overlapping adverse effect profiles. This review provides an overview of the pharmacological interactions between rifampicin-based TB treatment and antiretroviral drugs in adults living in resource-limited settings. Major progress has been made to evaluate the interactions between TB drugs and antiretroviral therapy; however, burning questions remain concerning nevirapine and efavirenz effectiveness during rifampicin-based TB treatment, treatment options for TB-HIV-coinfected patients with nonnucleoside reverse transcriptase inhibitor resistance or intolerance, and exact treatment or dosing schedules for vulnerable patients including children and pregnant women. The current research priorities can be addressed by maximizing the use of already existing data, creating new data by conducting clinical trials and prospective observational studies and to engage a lobby to make currently unavailable drugs available to those most in need

Pharmacodynamic biomarkers for quantifying the mycobacterial effect of high doses of rifampin in patients with rifampin-susceptible pulmonary tuberculosis

BACKGROUND: Suboptimal drug exposure in patients with drug-susceptible tuberculosis (DS-TB) can drive treatment failure. Pharmacodynamics (PD) biomarkers such as the plasma TB drug-activity (TDA) assay may guide dose finding studies and predict microbiological outcomes differently than conventional indices. METHODS: A study was nested from phase 2b randomized double-blind controlled trial of Tanzanian patients who received a 600 mg, 900 mg, or 1200 mg with a standard dose for DS-TB. Serum at 6 weeks collected over 24-h at 2-h intervals was collected for rifampin area under the concentration-time curve relative to minimum inhibitory concentration (AUC(0-24)/MIC) or peak concentration and MIC (C(max)/MIC). TDA was the ratio of time-to-positive growth of the patient's Mycobacterium tuberculosis isolates with and without coculture of patient's plasma collected at C(max). Spearman's rank correlation (r) between PD parameters and culture convention on both liquid and solid culture media. RESULTS: Among 10 patients, 600 mg (3), 900 mg (3), and 1200 mg (4) of rifampin dosages. The mean ± standard deviation (SD) of AUC(0-24)/MIC for patients on 600 mg was 168 ± 159 mg·h/L, on 900 mg was 169 ± 166 mg·h/L, and on 1200 mg was 308 ± 238 mg·h/L. The mean-TDA (SD) was 2.56 (±0.75), 1.5 (±0.59), and 2.29 (±1.08) for patients on 600 mg, 900 mg, and 1200 mg rifampin doses, respectively. Higher TDA values correlated with faster time to culture convention on both liquid (r = -0.55, P = 0.099) and solid media (r = -0.65, P = 0.04). CONCLUSIONS: TDA and rifampin AUC(0-24)/MIC did not trend as expected with rifampin dose, but TDA better predicted the time to sputum culture conversion. TDA may provide additional discrimination in predicting treatment response for some regimens distinct from plasma exposure relative to MIC or mg/kg dose

An exploration of patient perceptions of adherence to tuberculosis treatment in Tanzania.

Item does not contain fulltextIn this study, we aimed to explore patient perceptions of adherence to tuberculosis (TB) treatment and construct a theoretical model of treatment adherence behavior. We conducted semistructured interviews with 11 adherent patients from Tanzania whom we recruited by purposive sampling. The interview data were analyzed by content analysis. We found that the patient's intention to adhere is the most important determinant of adherence behavior. This intention is preceded by the decision to seek biomedical health care, and based on knowledge and beliefs about TB treatment and the motivation to be cured. The intention to adhere helps patients to cope with perceived barriers to adherence, such as socioeconomic difficulties, and to create an adherence-enabling environment in which the presence of social support plays an important role. Our preliminary adherence behavior model should be validated in larger, nonadherent patient populations and evaluated for its applicability to the development of adherence-promoting strategies.1 juni 201