103 research outputs found
Tuberculosis in Sudan: a study of Mycobacterium tuberculosis strain genotype and susceptibility to anti-tuberculosis drugs.
No full textBACKGROUND: Sudan is a large country with a diverse population and history of civil conflict. Poverty levels are high with a gross national income per capita of less than two thousand dollars. The country has a high burden of tuberculosis (TB) with an estimated 50,000 incident cases during 2009, when the estimated prevalence was 209 cases per 100,000 of the population. Few studies have been undertaken on TB in Sudan and the prevalence of drug resistant disease is not known. METHODS: In this study Mycobacterium tuberculosis isolates from 235 patients attending three treatment centers in Sudan were screened for susceptibility to isoniazid, rifampicin, ethambutol and streptomycin by the proportion method on Lowenstein Jensen media. 232 isolates were also genotyped by spoligotyping. Demographic details of patients were recorded using a structured questionnaire. Statistical analyses were conducted to examine the associations between drug resistance with risk ratios computed for a set of risk factors (gender, age, case status--new or relapse, geographic origin of the patient, spoligotype, number of people per room, marital status and type of housing). RESULTS: Multi drug-resistant tuberculosis (MDR-TB), being resistance to at least rifampicin and isoniazid, was found in 5% (95% CI: 2,8) of new cases and 24% (95% CI: 14,34) of previously treated patients. Drug resistance was associated with previous treatment with risk ratios of 3.51 (95% CI: 2.69-4.60; p < 0.001) for resistance to any drug and 5.23 (95% CI: 2.30-11.90; p < 0.001) for MDR-TB. Resistance was also associated with the geographic region of origin of the patient, being most frequently observed in patients from the Northern region and least in the Eastern region with risk ratios of 7.43 (95%CI:3.42,16.18; p: < 0.001) and 14.09 (95%CI:1.80,110.53; p:0.026) for resistance to any drug and MDR-TB. The major genotype observed was of the Central Asia spoligotype family (CAS1_Delhi), representing 49% of the 232 isolates examined. CONCLUSIONS: We conclude that emergence of drug resistant tuberculosis has the potential to be a serious public health problem in Sudan and that strengthened tuberculosis control and improved monitoring of therapy is needed. Further surveillance is required to fully ascertain the extent of the problem
Long-term dominance of Mycobacterium tuberculosis Uganda family in peri-urban Kampala-Uganda is not associated with cavitary disease
No full textPrevious studies have shown that Mycobacterium tuberculosis (MTB) Uganda family, a sub-lineage of the MTB Lineage 4, is the main cause of tuberculosis (TB) in Uganda. Using a well characterized patient population, this study sought to determine whether there are clinical and patient characteristics associated with the success of the MTB Uganda family in Kampala.; A total of 1,746 MTB clinical isolates collected from1992-2009 in a household contact study were genotyped. Genotyping was performed using Single Nucleotide Polymorphic (SNP) markers specific for the MTB Uganda family, other Lineage 4 strains, and Lineage 3, respectively. Out of 1,746 isolates, 1,213 were from patients with detailed clinical data. These data were used to seek associations between MTB lineage/sub-lineage and patient phenotypes.; Three MTB lineages were found to dominate the MTB population in Kampala during the last two decades. Overall, MTB Uganda accounted for 63% (1,092/1,746) of all cases, followed by other Lineage 4 strains accounting for 22% (394/1,746), and Lineage 3 for 11% (187/1,746) of cases, respectively. Seventy-three (4 %) strains remained unclassified. Our longitudinal data showed that MTB Uganda family occurred at the highest frequency during the whole study period, followed by other Lineage 4 strains and Lineage 3. To explore whether the long-term success of MTB Uganda family was due to increased virulence, we used cavitary disease as a proxy, as this form of TB is the most transmissible. Multivariate analysis revealed that even though cavitary disease was associated with known risk factors such as smoking (adjusted odds ratio (aOR) 4.8, 95% confidence interval (CI) 3.33-6.84) and low income (aOR 2.1, 95% CI 1.47-3.01), no association was found between MTB lineage and cavitary TB.; The MTB Uganda family has been dominating in Kampala for the last 18 years, but this long-term success is not due to increased virulence as defined by cavitary disease
A pre–post intervention study of pulmonary rehabilitation for adults with post-tuberculosis lung disease in Uganda
No full textRupert Jones,1 Bruce J Kirenga,2 Wincelsas Katagira,2 Sally J Singh,3 Jill Pooler,4 Alphonse Okwera,2 Richard Kasiita,5 Doyo G Enki,6 Siobhan Creanor,6 Andy Barton4 1Population Studies and Clinical Trials, Peninsula Schools of Medicine and Dentistry, Plymouth University, Plymouth, UK; 2Population Studies and Clinical Trials, Makerere Lung Institute, Makerere University College of Health Sciences, Mulago Hospital, Kampala, Uganda; 3Cardio-Respiratory Directorate, University Hospitals of Leicester NHS Trust, Leicester, 4Population Studies and Clinical Trials, Peninsula Schools of Medicine and Dentistry, Plymouth University, Plymouth, UK; 5Department of Physiotherapy, Mulago Hospital, Kampala, Uganda; 6Medical Statistics, Peninsula Schools of Medicine and Dentistry, Plymouth University, Plymouth, UK Setting: The study was conducted at Mulago Hospital, Kampala, Uganda.Objective: As chronic respiratory disease (CRD) is a huge, growing burden in Africa, with few available treatments, we aimed to design and evaluate a culturally appropriate pulmonary rehabilitation (PR) program in Uganda for people with post-tuberculosis lung disorder (p-TBLD).Design: In a pre–post intervention study, a 6-week, twice-weekly PR program was designed for people with p-TBLD. Outcome measures included recruitment, retention, the Clinical COPD Questionnaire (CCQ), tests of exercise capacity, and biometrics. Given this was a developmental study, no formal statistical significance testing was undertaken.Results: In all, 34 participants started PR and 29 (85%) completed all data collection. The mean age of the 29 participants was 45 years, and 52% were female. The mean (95% confidence interval) CCQ score at baseline was 1.8 (1.5, 2.0), at the end of PR was 1.0 (0.8, 1.2), and at 6 weeks after the end of PR was 0.8 (0.7, 1.0). The Incremental Shuttle Walking Test (ISWT) was 299 m (268.5, 329.4) at baseline, 377 (339.6, 413.8) at the end of PR, and 374 (334.2, 413.5) at 6 weeks after the end of PR. Improvements were seen in measures of chest pain; 13/29 (45%) participants reported chest pain at baseline but only 7/29 (24%) at the end of PR, and in those with persistent pain, the mean pain scores decreased. Mild hemoptysis was reported in 4/29 (17%) participants at baseline and in 2/29 (7%) at the end of PR.Conclusion: PR for people with p-TBLD in Uganda was feasible and associated with clinically important improvements in quality of life, exercise capacity, and respiratory outcomes. PR uses local resources, requires little investment, and offers a new, sustainable therapy for p-TBLD in resource-limited settings. With the rising global burden of CRD, further studies are needed to assess the value of PR in p-TBLD and other prevalent forms of CRD. Keywords: tuberculosis, exercise training, self-management, nonpharmacological intervention 
Treatment outcomes of new tuberculosis patients hospitalized in Kampala, Uganda: a prospective cohort study.
No full textBACKGROUND: In most resource limited settings, new tuberculosis (TB) patients are usually treated as outpatients. We sought to investigate the reasons for hospitalisation and the predictors of poor treatment outcomes and mortality in a cohort of hospitalized new TB patients in Kampala, Uganda. METHODS AND FINDINGS: Ninety-six new TB patients hospitalised between 2003 and 2006 were enrolled and followed for two years. Thirty two were HIV-uninfected and 64 were HIV-infected. Among the HIV-uninfected, the commonest reasons for hospitalization were low Karnofsky score (47%) and need for diagnostic evaluation (25%). HIV-infected patients were commonly hospitalized due to low Karnofsky score (72%), concurrent illness (16%) and diagnostic evaluation (14%). Eleven HIV uninfected patients died (mortality rate 19.7 per 100 person-years) while 41 deaths occurred among the HIV-infected patients (mortality rate 46.9 per 100 person years). In all patients an unsuccessful treatment outcome (treatment failure, death during the treatment period or an unknown outcome) was associated with duration of TB symptoms, with the odds of an unsuccessful outcome decreasing with increasing duration. Among HIV-infected patients, an unsuccessful treatment outcome was also associated with male sex (P = 0.004) and age (P = 0.034). Low Karnofsky score (aHR = 8.93, 95% CI 1.88 - 42.40, P = 0.001) was the only factor significantly associated with mortality among the HIV-uninfected. Mortality among the HIV-infected was associated with the composite variable of CD4 and ART use, with patients with baseline CD4 below 200 cells/µL who were not on ART at a greater risk of death than those who were on ART, and low Karnofsky score (aHR = 2.02, 95% CI 1.02 - 4.01, P = 0.045). CONCLUSION: Poor health status is a common cause of hospitalisation for new TB patients. Mortality in this study was very high and associated with advanced HIV Disease and no use of ART
Evaluation of giant african pouched rats for detection of pulmonary tuberculosis in patients from a high-endemic setting
No full textThis study established evidence about the diagnostic performance of trained giant African pouched rats for detecting Mycobacterium tuberculosis in sputum of well-characterised patients with presumptive tuberculosis (TB) in a high-burden setting.; The TB detection rats were evaluated using sputum samples of patients with presumptive TB enrolled in two prospective cohort studies in Bagamoyo, Tanzania. The patients were characterised by sputum smear microscopy and culture, including subsequent antigen or molecular confirmation of Mycobacterium tuberculosis, and by clinical data at enrolment and for at least 5-months of follow-up to determine the reference standard. Seven trained giant African pouched rats were used for the detection of TB in the sputum samples after shipment to the APOPO project in Morogoro, Tanzania.; Of 469 eligible patients, 109 (23.2%) were culture-positive for Mycobacterium tuberculosis and 128 (27.3%) were non-TB controls with sustained recovery after 5 months without anti-TB treatment. The HIV prevalence was 46%. The area under the receiver operating characteristic curve of the seven rats for the detection of culture-positive pulmonary tuberculosis was 0.72 (95% CI 0.66-0.78). An optimal threshold could be defined at ≥2 indications by rats in either sample with a corresponding sensitivity of 56.9% (95% CI 47.0-66.3), specificity of 80.5% (95% CI 72.5-86.9), positive and negative predictive value of 71.3% (95% CI 60.6-80.5) and 68.7% (95% CI 60.6-76.0), and an accuracy for TB diagnosis of 69.6%. The diagnostic performance was negatively influenced by low burden of bacilli, and independent of the HIV status.; Giant African pouched rats have potential for detection of tuberculosis in sputum samples. However, the diagnostic performance characteristics of TB detection rats do not currently meet the requirements for high-priority, rapid sputum-based TB diagnostics as defined by the World Health Organization
Diagnosis, treatment and immunopathogenesis of the HIV-associated tuberculosis immune reconstitution inflammatory syndrome
No full textThe paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of antiretroviral therapy (ART) among patients who start ART while on treatment for tuberculosis (TB). The condition manifests with new, worsening or recurrent inflammatory features of TB due to immunopathology attendant on rapidly recovering immune function
Impact of Human Immunodeficiency Virus Infection on the Outcome of Treatment and Survival of Tuberculosis Patients in Mwanza, Tanzania.
No full textLittle is known about the outcome of tuberculosis (TB) treatment and subsequent survival of human immunodeficiency virus (HIV) infected patients treated under routine programme conditions in a developing country. We followed a cohort of HIV-positive and HIV-negative tuberculosis patients during therapy and assessed their vital and tuberculosis status 3 years after completion of treatment in Mwanza, Tanzania. Newly diagnosed and relapse tuberculosis cases consecutively registered over a 6-month period were enrolled into an epidemiological study of TB/HIV. Treatment outcome was based on information in tuberculosis treatment registers. Patients surviving treatment were assessed 3 years later by personal interview. Cause of death was determined by verbal autopsy. Of 561 patients enrolled into the study, 505 patients alive at completion of treatment were eligible for assessment at 3 years. Except for mortality, HIV infection was not statistically associated with differing treatment outcomes. At time of follow-up, the overall mortality was 19% and was associated with HIV infection (hazard ratio [hr] 3.7, 95% confidence interval [CI] 2.6-5.2) and age 35 years and over (hr 1.5, 95% CI 1.02-2.1), but not with type of tuberculosis, gender, or initial drug resistance. By life table analysis, probability of survival at 4 years was 35% for HIV-positive patients compared to 90% for HIV-negative patients. Although no relapse cases were diagnosed, verbal autopsy suggested equivalent low rates of relapse in both groups. These results demonstrate the effectiveness of the current approach to the treatment of tuberculosis patients regardless of HIV status. However, HIV-related mortality remains high both during and following completion of treatment, and further studies are needed to determine if this mortality might be reduced by simple interventions which are feasible in developing countries.\u
Importance of Ethnicity, CYP2B6 and ABCB1 Genotype for Efavirenz Pharmacokinetics and Treatment Outcomes: A Parallel-group Prospective Cohort Study in two sub-Saharan Africa Populations.
No full textWe evaluated the importance of ethnicity and pharmacogenetic variations in determining efavirenz pharmacokinetics, auto-induction and immunological outcomes in two African populations. ART naïve HIV patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively enrolled in parallel to start efavirenz based HAART. CD4+ cell counts were determined at baseline, 12, 24 and 48 weeks. Plasma and intracellular efavirenz and 8-hydroxyefvairenz concentrations were determined at week 4 and 16. Genotyping for common functional CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 variant alleles were done. Patient country, CYP2B6*6 and ABCB1 c.4036A>G (rs3842A>G) genotype were significant predictors of plasma and intracellular efavirenz concentration. CYP2B6*6 and ABCB1 c.4036A>G (rs3842) genotype were significantly associated with higher plasma efavirenz concentration and their allele frequencies were significantly higher in Tanzanians than Ethiopians. Tanzanians displayed significantly higher efavirenz plasma concentration at week 4 (p<0.0002) and week 16 (p = 0.006) compared to Ethiopians. Efavirenz plasma concentrations remained significantly higher in Tanzanians even after controlling for the effect of CYP2B6*6 and ABCB1 c.4036A>G genotype. Within country analyses indicated a significant decrease in the mean plasma efavirenz concentration by week 16 compared to week 4 in Tanzanians (p = 0.006), whereas no significant differences in plasma concentration over time was observed in Ethiopians (p = 0.84). Intracellular efavirenz concentration and patient country were significant predictors of CD4 gain during HAART. We report substantial differences in efavirenz pharmacokinetics, extent of auto-induction and immunologic recovery between Ethiopian and Tanzanian HIV patients, partly but not solely, due to pharmacogenetic variations. The observed inter-ethnic variations in efavirenz plasma exposure may possibly result in varying clinical treatment outcome or adverse event profiles between populations
Pharmacogenetic aspects of HIV/AIDS, tuberculosis and malaria : emphasis on Ugandan population
No full textInfectious diseases such as HIV, tuberculosis and malaria are endemic in Africa and often require concomitant treatments that may result into subsequent drug–drug interactions. Inter-individual variability in the pharmacokinetics and pharmacodynamics of drugs used in infectious diseases, as a result of genetic polymorphism, has been reported. Pharmacogenetics of HIV, TB and malaria treatments is inadequately described in the African population. This thesis describes the pharmacogenetic aspects of HIV, TB and malaria treatment focusing on the Ugandan population.Studies were conducted among Ugandan adult healthy volunteers (n=161) and HIV patients (n = 263), some of whom were co-infected with TB. Healthy volunteers were examined for the effect of sex and different single nucleotide polymorphisms (SNPs) in ABCB1, CYP2B6 and CYP3A5 genes on single dose pharmacokinetics of efavirenz (n=30) and quinine (n=20). Patients were examined for effects of rifampicin and CYP2B6 (*6 &*11), CYP3A5 (*3,*5 & *7) and ABCB1 (c.3435C>T & c.4036A>G) on enzyme induction, efavirenz clearance and efavirenz related CNS toxicities.Apparent efavirenz oral clearance in subjects homozygous to CYP2B6*6 and *11 was 21 and 20% lower than extensive metabolizers respectively, while efavirenz relative bioavailability was 26% higher in subjects homozygous for ABCB1 (rs3842). A two-fold increase in apparent peripheral volume of distribution was associated with female sex. Comparisons of efavirenz pharmacokinetics between HIV and healthy volunteers revealed 30% decrease in its bioavailability with HIV/AIDS disease. Long term enzyme induction during efavirenz treatment was greater without rifampicin than during rifampicin co-treatment and it was majorly driven by CYP2B6 polymorphism rather than rifampicin treatment. Rifampicin co-treatment influenced neither efavirenz plasma concentrations nor incidence of efavirenz CNS toxicities (p = 0.8). Additionally, efavirenz plasma concentration dependent CNS side effects are common in HIV/AIDs patients.Thirty and thirteen fold variations in plasma quinine concentrations and quinine-to-3-hydroxyquinine metabolic ratio respectively, were observed. Plasma quinine concentration was significantly influenced by ABCB1 haplotype, CYP3A5 genotype / haplotype as well as sex.CYP2B6 is the major predictor of efavirenz pharmacokinetics and pharmacodynamics with or without rifampicin co-treatment. CYP3A5 influences quinine but not efavirenz disposition while ABCB1 plays a role in disposition of both drugs. Pharmacogenetics rather than rifampicin co-treatment may determine efavirenz treatment outcomes in TB co-infected HIV patients treated with efavirenz and rifampicin based regimens.List of scientific papersI. Mukonzo JK, Röshammar D, Waako P, Andersson M, Fukasawa T, Milani L, Svensson JO, Ogwal-Okeng J, Gustafsson LL, Aklillu E. A novel polymorphism in ABCB1 gene, CYP2B6*6 and sex predict single-dose efavirenz population pharmacokinetics in Ugandans. Br J Clin Pharmacol. 2009;68:690-99. https://doi.org/10.1111/j.1365-2125.2009.03516.x II. Mukonzo JK, Waako P, Ogwal-Okeng J, Gustafsson LL, Aklillu E. Genetic variations in ABCB1 and CYP3A5 as well as sex influence quinine disposition among Ugandans. Ther Drug Monit. 2010;32:346-52. https://doi.org/10.1097/FTD.0b013e3181da79d6 III. Mukonzo JK, Nanzigu S, Rekić D, Waako P, Röshammar D, Ashton M, Ogwal-Okeng J, Gustafsson LL, Aklillu E. HIV/AIDS patients display lower efavirenz relative bioavailability than healthy subjects. Clin Pharmacokinet. 2011; 50: 531-40. https://doi.org/10.2165/11592660-000000000-00000 IV. Mukonzo JK, Nanzigu S, Ma Q, Waako P, Ogwal-Okeng J, Morse G, Gustafsson LL, Aklillu E. CYP2B6 genetype but not rifampicin co-administration explains variability in long term efavirenz clearance and plasma exposure among HIV patients in Uganda. [Submitted]V. Mukonzo JK, Okwera P , Nakasujja N, Luzze H, Sebuwufu D, Waako P, Ogwal-Okeng J, Gustafsson LL, Aklillu E. Rifampicin co-treatment exhibits no effect on efavirenz central nervous system toxicity among HIV-1 infected Ugandans. [Manuscript]</p
Angle-specific eccentric hamstring fatigue after simulated soccer
No full textPurpose:To evaluate the effect of simulated soccer on the hamstrings eccentric torque-angle profile and angle of peak torque (APTeccH), and on the hamstrings:quadriceps torque ratio at specific joint angles (ASHecc:Qcon).Methods:The authors assessed dominant-limb isokinetic concentric and eccentric knee flexion and concentric knee extension at 120°/s in 9 semiprofessional male soccer players immediately before and after they completed the Loughborough Intermittent Shuttle Test (LIST).Results:The LIST resulted in significant decreases in eccentric hamstrings torque at 60°, 50°, and 10° and a significant (21.8%) decrease in ASHecc:Qcon at 10° (P < .05). APTeccH increased from 7.1° ± 1.0° to 18.8° ± 4.2° (P < .05). Eccentric hamstrings peak torque significantly declined from 185.1 ± 70.4 N·m pre-LIST to 150.9 ± 58.5 N·m post-LIST (P = .002), but there were no significant changes in hamstrings or quadriceps concentric peak torque (P = .312, .169, respectively).Conclusions:Simulated soccer results in a selective loss of eccentric hamstrings torque and hamstrings-to-quadriceps muscle balance at an extended joint position and a shift in the eccentric hamstrings APT to a shorter length, changes that could increase vulnerability to hamstrings injury. These findings suggest that injury-risk screening could be improved by evaluating the eccentric hamstrings torque-angle profile and hamstrings strength-endurance and that the development of hamstrings fatigue resistance and long-length eccentric strength may reduce injury incidence
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