Profiles of patients on warfarin anticoagulation therapy in a leading tertiary referral hospital in Kenya; findings and implications for Kenya.

Background: Patients' profiles affect the outcome with warfarin; however, this data, and its implications, is scarce in resource-poor countries without access to pharmacogenetics or regular INR testing.Objectives: To characterize the profiles of patients on long-term warfarin therapy and subsequently use these to guide future anticoagulation management.Methods: Cross-sectional study among 180 adult patients receiving warfarin therapy in at a leading referral hospital in Kenya. Sociodemographic characteristics were obtained through face-to-face interviews. Details of warfarin therapy, concomitant medication and comorbidities were retrieved from medical records. Associations between patients' profiles and the clinical indications of anticoagulation were computed at p ≤ 0.05.Results: Warfarin maintenance dose was 6.17 (±2.75) mg per day. Venous thromboembolism (56.6%) amongst obese patients (p = 0.0019) and cardioembolic events (48.3%) among males (p = 0.0316) aged ≤50 years (p = 0.0436) whose body mass indices were ≤ 25 (p < 0.0001) were the most common indications. Two-fifths and 45.0% of the patients had at least one other disease and concomitant medications.Conclusions: Long term warfarin therapy among Kenyans is mainly for overweight or lean middle-aged individuals suffering from venous or cardioembolic diseases. Studies should correlate patients' profiles with warfarin response to guide future management.

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 [ß = -1.24; 95% CI (-2.253, -0.226)], absence of pain [ß=0.413; 95% CI (0.152, 0.674)] and patient stated inability to cope with HIV [ß = -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.

Selected ethno-medicinal plants from Kenya with in vitro activity against major African livestock pathogens belonging to the "Mycoplasma mycoides cluster".

ETHNOPHARMOCOLOGICAL RELEVANCE: Members of 'Mycoplasma mycoides cluster' are important ruminant pathogens in Africa. Diseases caused by these Mycoplasma negatively affect the agricultural sector especially in developing countries through losses in livestock productivity, mortality and international trade restrictions. There is therefore urgent need to develop antimicrobials from alternative sources such as medicinal plants to curb these diseases. In Kenya, smallholder farmers belonging to the Maasai, Kuria and Luo rely on traditional Kenyan herbals to treat respiratory symptoms in ruminants. In the current study extracts from some of these plants were tested against the growth of members of Mycoplasma mycoides cluster. AIM: This study aimed at identifying plants that exhibit antimycoplasmal activities using an ethnobotanical approach. MATERIALS AND METHODS: Kenyan farmers of Maasai, Luo and Kuria ethnic groups were interviewed for plant remedies given to livestock with respiratory syndromes. The plant materials were thereafter collected and crude extracts prepared using a mixture of 50% of methanol (MeOH) in dichloromethane (CH2Cl2), neat methanol (MeOH), ethanol (EtOH) and water to yield four crude extracts per plant part. The extracts were tested in vitro against five strains of Mycoplasma mycoides subsp. capri, five strains of Mycoplasma mycoides subsp. mycoides and one strain of Mycoplasma capricolum subsp capricolum using broth micro-dilution assays with an initial concentration of 1mg/ml. Minimum inhibitory concentration (MIC) of the most active extracts were determined by serial dilution. RESULTS: Extracts from five plants namely: Solanum aculeastrum, Albizia coriaria, Ekebergia capensis, Piliostigma thonningii and Euclea divinorum exhibited the highest activities against the Mycoplasma strains tested. Mycoplasma mycoides subsp. mycoides were more susceptible to these extracts than Mycoplasma mycoides subsp. capri and Mycoplasma capricolum susp. capricolum. The activities of the crude extracts varied with the solvent used for extraction. The MICs mean values of the active extracts varied from 0.02 to 0.6mg/ml. CONCLUSIONS: The results suggested that these plants could potentially contain antimicrobial compounds that might be useful for the treatment of respiratory diseases in ruminants. Future work should focus on the isolation and identification of the active compounds from the plant extracts that showed interesting activities and evaluation of their antimicrobial and cytotoxic potential.

Building capacity in implementation science research training at the University of Nairobi.

BACKGROUND: Health care systems in sub-Saharan Africa, and globally, grapple with the problem of closing the gap between evidence-based health interventions and actual practice in health service settings. It is essential for health care systems, especially in low-resource settings, to increase capacity to implement evidence-based practices, by training professionals in implementation science. With support from the Medical Education Partnership Initiative, the University of Nairobi has developed a training program to build local capacity for implementation science. METHODS: This paper describes how the University of Nairobi leveraged resources from the Medical Education Partnership to develop an institutional program that provides training and mentoring in implementation science, builds relationships between researchers and implementers, and identifies local research priorities for implementation science. RESULTS: The curriculum content includes core material in implementation science theory, methods, and experiences. The program adopts a team mentoring and supervision approach, in which fellows are matched with mentors at the University of Nairobi and partnering institutions: University of Washington, Seattle, and University of Maryland, Baltimore. A survey of program participants showed a high degree satisfaction with most aspects of the program, including the content, duration, and attachment sites. A key strength of the fellowship program is the partnership approach, which leverages innovative use of information technology to offer diverse perspectives, and a team model for mentorship and supervision. CONCLUSIONS: As health care systems and training institutions seek new approaches to increase capacity in implementation science, the University of Nairobi Implementation Science Fellowship program can be a model for health educators and administrators who wish to develop their program and curricula.

Directed evolution of the alpha-L-fucosidase from Thermotoga maritima into an alpha-L-transfucosidase.

The alpha-L-fucosidase from Thermotoga maritima (Tm alpha fuc) was converted into alpha-L-transfucosidase variants by directed evolution. The wild-type enzyme catalyzes oligosaccharide synthesis by transfer of a fucosyl residue from a pNP-fucoside donor to pNP-fucoside (self-condensation) with alpha-(1-->3) regioselectivity or pNP-galactoside (transglycosylation) with alpha-(1-->2) regioselectivity at low yields (7%). The wild-type enzyme was submitted to one cycle of mutagenesis, followed by rational recombination of the selected mutations, which allowed identification of variants with improved transferase activity. The transferase and hydrolytic kinetics of all the mutants were assessed by NMR methods and capillary electrophoresis. It was shown that the best mutant exhibited a dramatic 32-fold increase in the transferase/hydrolytic kinetic ratio, while keeping 60% of the overall wild-type enzyme activity. Accordingly, the maximum yield of a specific transglycosylation product [pNP-Gal-alpha-(1-->2)-Fuc] reached more than 60% compared to 7% with WT enzyme at equimolar and low concentrations of donor and acceptor (10 mM). Such an improvement was obtained with only three mutations (T264A, Y267F, L322P), which were all located in the second amino acid shell of the fucosidase active site. Molecular modeling suggested that some of these mutations (T264A, Y267F) cause a reorientation of the amino acids that are in direct contact with the substrates, resulting in a better docking energy. Such mutants with high transglycosidase activity may constitute novel enzymatic tools for the synthesis of fucooligosaccharides.