Margaret Oluka

Establishment of a biobank and pharmacogenetics database of African populations

Pharmacogenetics and genomics research has experienced great advances over the past decade as witnessed by the completion of the human genome in 2003 (www.genome.gov/HGP). The field has been driven by the belief that understanding the human genome, that of pathogens, and interindividual genetic variability would result in radical advances in medicine. Anticipated measurable end points include increased targets for which drug discovery campaigns could be initiated, increased understanding of human susceptibility to disease and variability in drug response hence development of diagnostic tools to realize individualized treatment where drugs would be given to patients in whom they are predicted to work and at doses predicted to be safe.1 Toward the realization of this biomedical paradigm, Biobanking and Pharmacogenetics Databasing have become well established in developed countries (www.biobanks.se, www.icelandbio.com, www.ukbiobank.ac.uk). Little has, however, been done in developing countries.2 Starting with a workshop organized by the African Institute of Biomedical Science and Technology (www.aibst.com) in 2003 on Pharmacogenetics of Drug Metabolism in Nairobi, Kenya, a number of African scientists initiated a consortium for the biobanking and pharmacogenetics databasing of African populations. We here report the results of the first phase of this initiative that has seen research groups from five different African countries with collaborative support from leading experts in Europe and America establish a biobank of blood and DNA from nine ethnic groups from across the African continent. The biobank of anonymous samples has been used to establish baseline frequency distribution of SNPs of genes important in drug metabolism, hence the initiation of a pharmacogenetics database (http://www.aibst.com/biobank.html).

Outcome of the first Medicines Utilization Research in Africa group meeting to promote sustainable and rational medicine use in Africa

The first Medicines Utilization Research in Africa group workshop and symposium brought researchers together from across Africa to improve their knowledge on drug utilization methodologies as well as exchange ideas. As a result, progress was made on drug utilization research and formulating future strategies to enhance the rational use of medicines in Africa. Anti-infectives were the principal theme for the 1-day symposium following the workshops. This included presentations on the inappropriate use of antibiotics as well as ways to address this. Concerns with adverse drug reactions and adherence to anti-retroviral medicines were also discussed, with poor adherence remaining a challenge. There were also concerns with the underutilization of generics. These discussions resulted in a number of agreed activities before the next conference in 2016.

Initiatives across countries to reduce antibiotic utilization and resistance patterns: impact and implications

Introduction: Greater accessibility to antibiotics has resulted in their excessive use, leading to increasing antimicrobial resistance (AMR) and strains on healthcare systems, with only a limited number of patients in ambulatory care treated according to guidelines. High rates of AMR are now seen across countries and continents, resulting in AMR becoming one of the most critical issues facing healthcare systems. It is estimated that AMR could potentially cause over 10 million deaths per year by 2050 unless addressed, resulting in appreciable economic consequences. There are also concerns with under-treatment especially if patients are forced to fund more expensive antibiotics as a result of AMR to first-line antibiotics and do not have available funds. Overprescribing of antibiotics is not helped by patient pressure even when physicians are aware of the issues. There is also extensive dispensing of antibiotics without a prescription, although this is now being addressed in some countries. Aim: Review interventions that have been instigated across continents and countries to reduce inappropriate antibiotic prescribing and dispensing, and associated AMR, to provide future guidance. Method: Narrative case history approach. Findings: A number of successful activities have been instigated to reduce inappropriate prescribing and dispensing of antibiotics across sectors. These include the instigation of quality indicators, suggested activities of pharmacists as well as single and multiple interventions among all key stakeholder groups. Multiple interlinking strategies are typically needed to enhance appropriate antibiotic prescribing and dispensing. The impact of ongoing activities need to be continually analysed to provide future direction if AMR rates, and their impact on subsequent morbidity, mortality and costs, are to be reduced.

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.

Impact of First Line Antiretroviral Therapy on Clinical Outcomes Among HIV-1 Infected Adults Attending One of the Largest HIV Care and Treatment Program in Nairobi Kenya

Objective: This study evaluated the immunologic (CD4 cell count), virological (HIV RNA viral load), hepatic (alanine and aspartate aminotransferase - ALT and AST), renal (creatinine) and hematological (hemoglobin -HB, White Blood Cell - WBC, Lymphocytes - LYM and platelets - PLT) response to a six months ART treatment among HIV participants in Nairobi Kenya. Methods: Blood samples were obtained from 599 consenting HIV infected participants receiving HIV treatment in Nairobi. CD4 cell counts were measured using flow cytometer and viral load determined using real-time polymerase chain reaction. The blood hematology, liver and kidney function tests were also measured. One-way ANOVA and Linear regression analysis were conducted. Results: The median age at ART initiation was 41 years (IQR 35-47 years). The majority of participants (60.3%) were female and 56.1% started on regimens with 2 NRTIs and efavirenz based NNRTI. About 40% of the participants were failing treatment 6 month post ART initiation. The CD4 count significantly increased at the 6-month post ART initiation (301.7 ± 199.4 to 329.4 ± 305.8; P 5 times the upper limit of normal - ULN) and renal abnormalities (elevated serum creatinine levels) were all high at month 6 compared to baseline; ALT (2.5 to 10.5%), AST (5.3 to 23.4%) and creatinine (63.4 to 68.84%). Fewer participants at month 6 had anemia (29.4% verses 56.4%), leucopenia (42.4% vs. 46.9%) and thrombocytopenia (6.5% vs. 84.1%) compared to baseline. In multivariable models, baseline levels of this parameter, ART regimen and duration with HIV at ART initiation were the most important determinant of month 6 levels. Conclusion: These data demonstrate sustained immunologic/virologic response to ART among participants remaining on therapy. Anemia, leucopenia and thrombocytopenia were minimized with marginal hepatotoxicity and renal impairment seen. Interventions leading to earlier HIV diagnosis and initiation of ART could substantially improve patient outcomes in Kenya.

Dispensing of antimicrobials in Kenya: A cross-sectional pilot study and its implications

Objective: The objective of this study was to evaluate the extent of self-medication of antibiotics and dispensing practices in Kenya. Methods: A cross-sectional study was carried out at three selected pharmacies in Nairobi (Kenya), between January and March 2017, targeting principally antibiotic prescriptions for systemic use issued and dispensed as well as antibiotics sold over-the-counter without a prescription. The quality of antibiotics prescribed and dispensed was assessed against key WHO and other criteria. Benchmarking was used to assess the quality of antibiotics prescribed as there are no predetermined levels, just guidance and the rationale. Key indicators included: utilization of penicillins, percentage utilization of third-and fourth-generation of cephalosporins versus first and second generation, utilization of macrolides including lincosamides and utilization of quinolones as a percent of total systemic antibiotic use. Findings: There was a low level of dispensing of antibiotics without a prescription with over 90% (94.1%) of antibiotics dispensed with a valid prescription. The most common antibiotics dispensed were the penicillins at just over 50% of all antibiotics, the cephalosporins at over 12% (12.6%) and the fluoroquinolones at just under 12% (11.7%). There were concerns with high use of third and fourth generation cephalosporins versus first- and second-generation as well as co-amoxiclav versus other penicillins. Conclusion: Low levels of self-medication of antibiotics and high adherence to quality standards for dispensing are encouraging and provide direction to other countries. Educational initiatives are needed though to address high levels of co-amoxiclav prescribing.

Point prevalence survey of antibiotic use and resistance at a referral hospital in Kenya: findings and implications

ABSTRACT Background and aims: A substantial amount of antibiotic use in hospitals may be inappropriate, potentially leading to the development and spread of antibiotic resistance, adverse effects, mortality and increased hospital costs. The objective was to assess current patterns of antibiotic use in a leading referral hospital in Western Kenya. This would lead to the identification of opportunities for quality improvement in this hospital and others across Kenya. Methodology: A point prevalence survey was carried out with data abstracted principally from patient medical records supplemented by interviews from physicians when needed. The pattern of antibiotic use was analyzed by descriptive methods. Differences in antibiotic use and indications between the selected wards were compared using the Chi-square test or Fisher’s exact tests. Results: Among the patients surveyed, 67.7% were on antibiotics. The most common classes of antibiotics prescribed were third generation cephalosporins (55%), imidazole derivatives like metronidazole (41.8%) and broad spectrum penicillins (41.8%). The most common indication for antibiotic use was medical prophylaxis (29%), with local guidelines advocating antibiotic prophylaxis in mothers after delivery of their child as well as in neonates with birth asphyxia and low weight at birth. Dosing of antibiotics was seen as generally optimal when assessed against current recommendations. Conclusion: Whilst the dosing of antibiotics seemed adequate, there was high use of antibiotics in this hospital. This needs to be urgently reviewed with currently appreciable empiric antibiotic use. Programmes are being instigated to address these concerns. This includes developing antibiotic guidelines and formularies especially for empiric use as well as implementing antimicrobial stewardship activities.

Comparison of zidovudine and tenofovir based regimens with regard to health-related quality of life and prevalence of symptoms in HIV patients in a Kenyan referral hospital

Aim: Zidovudine and tenofovir form the backbone of antiretroviral therapy in Kenya. However, their side-effects may affect the quality of life (QoL) of patients. The aim was to compare the health-related quality of life (HRQoL) of adult patients on tenofovir versus zidovudine based regimens in a referral hospital in Kenya to provide future guidance. Methods: A comparative cross sectional study among 501 adult out-patients on either tenofovir or zidovudine was undertaken in Kenyatta National Hospital between 2015 and 2016. The Medical Outcome Study HIV Health Survey (MOS-HIV) was administered along with other key aspects of treatment. Linear regression analysis was performed to identify determinants of HRQoL. Results: Patients on zidovudine had a higher Physical Health Summary Score (PHSS) and Mental Health Summary Score (MHSS) compared to those on tenofovir. The presence of any symptom of the disease and a stated inability to cope were negatively associated with PHSS, whilst having a regular source of income improved PHSS. Being on tenofovir, symptom of illness [β = -1.24; 95% CI (-2.253, -0.226)], absence of pain [β=0.413; 95% CI (0.152, 0.674)] and patient stated inability to cope with HIV [β = -1.029; 95% CI (-1.441, -0.617)] affected the MHSS. Patients on tenofovir and second line regimens had more signs and symptoms of illness. Conclusion: Participants on zidovudine based regimens showed a better performance across all aspects of HRQoL. These are considerations for the future.

VP25 African Countries Are Working Together To Enhance Medicine Use

Growing burden of infectious and NCDs across Africa, e.g. 70% of world’s HIV patients live in sub-Sahara Africa and 30 to 45% of adults have hypertension. This requires groups to collaborate. This is happening, e.g. SAHTAS, PharfA and MURIA. MURIA is researching antibiotic use, adherence to medicines and strengthening DTCs. This should continue to optimise medicine use and scarce resources. The socioeconomic burden of diseases is increasing in Africa. For instance in 2011, 70% of the world’s HIV population resided in sub-Sahara Africa. There are also growing rates of AMR, which necessitates newer more expensive antibiotics adding to costs. There is also a growing burden of NCDs, 3 out of 4 patients with hypertension currently live in LMICs, with prevalence rates up to 30% to 45% among adults in Africa. Alongside this, up to 70% of total healthcare expenditure is spent on medicines in LMICs; much of this out-of-pocket. Consequently, an urgent need to strengthen collaborative research to improve medicine use. Summary of groups working together in Africa including the Medicines Utilisation Research in Africa (MURIA) group. African Strategies for Health identifies and advocates best practices, as well as works with others to develop sustainable solutions. Pharmacology for Africa (PharfA) organises and promotes pharmacology on the African continent, including research in clinical pharmacology, alongside the IUPHAR sub-division. ISPOR Africa co-ordinates activities from the different African country chapters. SAHTAS is a scientific and professional society for all those who produce, use, or encounter HTA in Southern Africa, and WHO International and Regional groups are improving antibiotic drug utilisation capabilities in Africa. The MURIA group was established in 2015 [1]. Ongoing collaborative research includes (i) initiatives to optimise antibiotic use; (ii) methods to enhance adherence to anti-infective prescribing guidance, (iii) approaches to improve adherence to HIV and NCDs; (iv) researching current anti-hypertensive and anti-diabetes medicines utilisation patterns and knowledge; (v) approaches to enhance DTC activities, and (vi) strengthening medicine utilisation capabilities [2,3]. These activities have already strengthened research ties across Africa. A number of groups are already working across Africa to enhance appropriate medicine use, and should continue. Ongoing MURIA activities include antibiotic point-prevalence studies, ongoing research into infectious diseases, NCDs and DTCs including adherence as well as the third workshop and symposium in Namibia in 2017.