Mary Jande

4??-Hydroxycholesterol is a new endogenous CYP3A marker: relationship to CYP3A5 genotype, quinine 3-hydroxylation and sex in Koreans, Swedes and Tanzanians

Objectives To study the potential endogenous marker of CYP3A activity, 4&bgr;-hydroxycholesterol, and its relation to sex and the CYP3A5 geno/haplotypes and compare with CYP3A4/5 catalyzed 3-hydroxylation of quinine in the three major races. Methods The plasma concentration of 4&bgr;-hydroxycholesterol was measured in healthy Tanzanians (n=138), Swedes (n=161) and Koreans (n=149) by gas chromatography–mass spectrometry. The metabolic ratio of quinine/3-hydroxyquinine in plasma 16-h post dose was determined by high performance liquid chromatography, previously reported in Tanzanians and Swedes, and now also in Koreans. The participants were genotyped for relevant alleles of CYP3A5. Results The mean plasma concentrations of 4&bgr;-hydroxycholesterol in Koreans, Swedes and Tanzanians were 29.3, 26.8 and 21.9 ng/ml, respectively (P<0.01 between all three populations). Within all three populations there were significant differences in 4&bgr;-hydroxycholesterol levels between the CYP3A5 genotypes. Women had higher concentrations than men, but the difference was only significant in Tanzanians (P<0.001) and Koreans (P<0.00001). The quinine/3-hydroxyquinine metabolic ratio was significantly different in all three populations with the highest CYP3A activity in Koreans and the lowest in Tanzanians. Korean women had a lower metabolic ratio than men (P<0.00001). Significant correlations between 4&bgr;-hydroxycholesterol and quinine 3-hydroxylation were found in Tanzanians and Koreans. Conclusion Clear differences in the activity of both CYP3A4 and CYP3A5 were shown in the three major human races. Both 4&bgr;-hydroxycholesterol and quinine/3-hydroxyquinine metabolic ratio showed a higher CYP3A activity in women than in men. The results give strong evidence that the plasma concentration of 4&bgr;-hydroxycholesterol may be used as an endogenous marker of CYP3A activity (CYP3A4+5).

Decreased capacity for debrisoquine metabolism among black Tanzanians: analyses of the CYP2D6 genotype and phenotype.

The cytochrome P450 2D6 (CYP2D6) genotypes and phenotypes of 106 unrelated, healthy black Tanzanians of Bantu origin were investigated. The results revealed a population with a generally decreased capacity to metabolize the CYP2D6 substrate debrisoquine with 59% of the Tanzanian extensive metabolisers having debrisoquine metabolic ratios (MRs) > 1 versus 20% in Caucasians. This decrease in metabolic capacity was not fully explained by the partially or fully detrimental CYP2D6 gene mutations analysed for in this study. As many as 7% poor metabolizers of debrisoquine were identified but none was homozygous for defective CYP2D6 alleles. The majority among the group of poor metabolizers had relatively low metabolic ratios. The mutational profile indicated a closer association of the Tanzanian CYP2D locus to that of Zimbabweans rather than to that of Ethiopians. The defective alleles CYP2D6*3, *4, *5 and *6 were found at low frequencies (0%, 1%, 6%, 0%, respectively), whereas the CYP2D6*17 allele causing an enzyme with altered specificity was common (allele frequency = 17%). It is concluded that the CYP2D6 genotype in the Tanzanian Bantu population is different from that of other African populations examined to date and that further studies are required to explain the generally lower capacity to metabolize CYP2D6 substrates.

The prevalence of substance use among psychiatric patients: the case study of Bugando Medical centre, Mwanza (northern Tanzania).

ABSTRACT World Health Organization (2004) documented that substance use or abuse and mental disorders are important causes of disease burden accounting for 8.8% and 16.6% of the total burden of disease in low income and lower middle-income countries, respectively. Alcohol use/abuse disorders alone contribute to 0.6%–2.6% of the total burden of disease in these countries. This cross-sectional descriptive study recruited 184 psychiatric patients seen at Bugando Medical centre and assessed them for substance involvement using the WHO Alcohol, Smoking and Substance Involvement Screening Test. The most frequently used substances among respondents were alcohol (59.3%), tobacco (38.6%), and cannabis (29.3%), while heroin and cocaine were least used (2.1% and 1.6%, respectively). Statistical significant difference existed between substance use and participants: level of education, formal employment, marital status, gender, family history of mental illness, and family history of substance use. About a third attributed their involvement into substance exclusively to peer pressure, 8.7 to both peer pressure and curiosity while 7.1% exclusively to curiosity. This result represents one of the most important risks to mental health, and is a leading factor that causes high rates of admission or reason to be seen by a psychiatrist, this cannot be ignored when managing psychiatric disorders and therefore calls for routing screening for substance involvement among clients seeking psychiatric treatment. It also calls for appropriate standard operation policy procedures that can be operationlized as a matter of clinical practice by mental health workers in their routine medical practice.

Outcome of the second Medicines Utilisation Research in Africa Group meeting to promote sustainable and appropriate medicine use in Africa

ABSTRACT The second Medicines Utilization Research in Africa (MURIA) group workshop and symposium again brought researchers together from across Africa to improve their knowledge of drug utilization (DU) methodologies and exchange ideas to further progress DU research in Africa. This built on extensive activities from the first conference including workshops and multiple publications. Anti-infectives were again the principal theme for the 2016 symposium following the workshops. This included presentations regarding strategies to improve antibiotic utilization among African countries, such as point-prevalence studies, as well as potential ways to reduce self-purchasing of antibiotics. There were also presentations on antiretrovirals including renal function and the impact of policy changes. Concerns with adherence in chronic treatments as well as drug-drug interactions and their implications were also discussed. The deliberations resulted in a number of agreed activities including joint publications before the next MURIA conference in Namibia in 2017.

Prescription patterns and adequacy of blood pressure control among adult hypertensive patients in Kenya; findings and implications

ABSTRACT Background: Hypertension is a major cause of global morbidity and mortality, with high prevalence rates in Africa including Kenya. Consequently, it is imperative to understand current treatment approaches and their effectiveness in practice. Currently, there is paucity of such data in Kenya, which is a concern. The aim is to describe prescribing patterns and adequacy of blood pressure (BP) control in adult hypertensive patients to guide future practice. Method: Retrospective study of patients attending a sub-county outpatient clinic combined with qualitative interviews. Results: 247 hypertensive patients, predominantly female, mean age 55.8 years on antihypertensive therapy for 1–5 years, were analyzed. ACEIs and thiazide diuretics were the most commonly prescribed drugs, mainly as combination therapy. Treatment typically complied with guidelines, mainly for stage 2 hypertension (75%). BP control was observed in 46% of patients, with a significant reduction in mean systolic (155 to 144 mmHg) and diastolic (91 to 83 mmHg) BP (P < 0.001). Patients on ≥2 antihypertensive drugs were more likely to have uncontrolled BP (OR:1.9, p = 0.021). Conclusion: Encouragingly good adherence to guidelines was helped by training. Poor blood pressure control in the majority needs to be addressed. Additional training of prescribers and follow-up of measures to improve BP control will be introduced and followed up.

Microbial contamination of traditional liquid herbal medicinal products marketed in Mwanza city: magnitude and risk factors

Introduction The use of the traditional herbal medicinal products (THMPs) has been increasing worldwide due to the readily availability of raw materials and low cost compared to the synthetic industrial preparations. With this trend in mind, the safety and quality of THMPs need to be addressed so as to protect the community. The present study evaluated the magnitude and risk factors associated with microbial contamination of liquid THMPs marketed in Mwanza. Methods A cross-sectional study was conducted in Mwanza city involving 59 participants from whom 109 liquid THMPs were collected and processed following the standard operating procedures. The data were analyzed using STATA software version 11. Results The median age (interquartile range) of participants was 35 (27-43) years, with males accounting for 36 (61%). Of 109 liquid THMPs collected, 89 (81.7%) were found to be contaminated; with predominant fecal coliforms being Klebsiella spp and Enterobacter spp. fortunately, no pathogenic bacteria like Salmonella spp and Shigella spp were isolated. There was a significant association of liquid THMPs contamination with low education level (p< 0.001), lack of formal training on THMPs (p = 0.023), lack of registration with the Ministry of Health (p = 0.001), lack of packaging of products (p < 0.001) and use of unboiled solvents during preparation of THMPs (p < 0.001). Conclusion There is high contamination rate of liquid THMPs in Mwanza City which is attributable to individuals and system-centered factors. Urgent measures to provide education to individuals involved in THMPs as well as setting up policies and regulations to reinforce THMPs safety is needed.

Public Awareness and Identification of Counterfeit Drugs in Tanzania: A View on Antimalarial Drugs

Background. The illicit trade in counterfeit antimalarial drugs is a major setback to the fight against malaria. Information on public awareness and ability to identify counterfeit drugs is scanty. Aim. Therefore, the present study aimed at assessing public awareness and the ability to identify counterfeit antimalarial drugs based on simple observations such as appearance of the drugs, packaging, labelling, and leaflets. Methodology. A cross-sectional study was conducted using interviewer administered structured questionnaire and a checklist. Respondents were required to spot the difference between genuine and counterfeit antimalarial drugs given to them. Data was analysed using SPSS version 20. Results. The majority of respondents, 163 (55.6%), were able to distinguish between genuine and counterfeit antimalarial drugs. Respondents with knowledge on health effects of counterfeit drugs were more likely to identify genuine and counterfeit drugs than their counterparts (; OR = 2.95; 95% CI: 1.47–5.65). The majority of respondents, 190 (64.8%), perceived the presence of counterfeit drugs to be a big problem to the community. Conclusions. A substantial proportion of respondents were able to distinguish between genuine and counterfeit antimalarial drugs. Public empowerment in identifying counterfeit drugs by simple observations is a major step towards discouraging the market of counterfeit drugs.