Tackling antimicrobial resistance across sub-Saharan Africa: current challenges and implications for the future.

INTRODUCTION: Antimicrobial resistance (AMR) is a concern as this increases morbidity, mortality, and costs, with sub-Saharan Africa having the highest rates globally. Concerns with rising AMR have resulted in international, Pan-African, and country activities including the development of national action plans (NAPs). However, there is variable implementation across Africa with key challenges persisting. AREAS COVERED: Consequently, there is an urgent need to document current NAP activities and challenges across sub-Saharan Africa to provide future guidance. This builds on a narrative review of the literature. EXPERT OPINION: All surveyed sub-Saharan African countries have developed their NAPs; however, there is variable implementation. Countries including Botswana and Namibia are yet to officially launch their NAPs with Eswatini only recently launching its NAP. Cameroon is further ahead with its NAP than these countries; though there are concerns with implementation. South Africa appears to have made the greatest strides with implementing its NAP including regular monitoring of activities and instigation of antimicrobial stewardship programs. Key challenges remain across Africa. These include available personnel, expertise, capacity, and resources to undertake agreed NAP activities including active surveillance, lack of focal points to drive NAPs, and competing demands and priorities including among donors. These challenges are being addressed, with further co-ordinated efforts needed to reduce AMR.

Point-prevalence survey of antibiotic use at three public referral hospitals in Kenya.

Antimicrobial stewardship encourages appropriate antibiotic use, the specific activities of which will vary by institutional context. We investigated regional variation in antibiotic use by surveying three regional public hospitals in Kenya. Hospital-level data for antimicrobial stewardship activities, infection prevention and control, and laboratory diagnostic capacities were collected from hospital administrators, heads of infection prevention and control units, and laboratory directors, respectively. Patient-level antibiotic use data were abstracted from medical records using a modified World Health Organization point-prevalence survey form. Altogether, 1,071 consenting patients were surveyed at Kenyatta National Hospital (KNH, n = 579), Coast Provincial General Hospital (CPGH, n = 229) and Moi Teaching and Referral Hospital (MTRH, n = 263). The majority (67%, 722/1071) were ≥18 years and 53% (563/1071) were female. Forty-six percent (46%, 489/1071) were receiving at least one antibiotic. Antibiotic use was higher among children <5 years (70%, 150/224) than among other age groups (40%, 339/847; P < 0.001). Critical care (82%, 14/17 patients) and pediatric wards (59%, 155/265) had the highest proportion of antibiotic users. Amoxicillin/clavulanate was the most frequently used antibiotic at KNH (17%, 64/383 antibiotic doses), and ceftriaxone was most used at CPGH (29%, 55/189) and MTRH (31%, 57/184). Forty-three percent (326/756) of all antibiotic prescriptions had at least one missed dose recorded. Forty-six percent (204/489) of patients on antibiotics had a specific infectious disease diagnosis, of which 18% (37/204) had soft-tissue infections, 17% (35/204) had clinical sepsis, 15% (31/204) had pneumonia, 13% (27/204) had central nervous system infections and 10% (20/204) had obstetric or gynecological infections. Of these, 27% (56/204) had bacterial culture tests ordered, with culture results available for 68% (38/56) of tests. Missed antibiotic doses, low use of specimen cultures to guide therapy, high rates of antibiotic use, particularly in the pediatric and surgical population, and preference for broad-spectrum antibiotics suggest antibiotic use in these tertiary care hospitals is not optimal. Antimicrobial stewardship programs, policies, and guidelines should be tailored to address these areas.

HIV-1 Integrase Inhibitory Effects of Major Compounds Present in CareVid™: An Anti-HIV Multi-Herbal Remedy.

In our continued study on the anti-HIV activity of compounds present in CareVidTM, we report the HIV-1 integrase ((HIV-1 IN) inhibitory effects of pellitorine (1), oleuropein (2), magnoflorine (3), crotepoxide (4), ent-kaurane-16ß,17-diol (5), crotocorylifuran (6), lupeol (7), betulin (8), and ellagic acid (9) in an in vitro enzyme assay, and in an in silico study. Ellagic acid, pellitorine, lupeol, and betulin showed an in vitro percentage inhibition against HIV-1 IN of 21.1%, 19.0%, 18.5%, and 16.8%, respectively, at a standard concentration of 25 µg/mL. However, from a pharmacokinetic perspective, ellagic acid has poor bioavailability, due to rapid elimination in metabolism in the gut microbiome. It was postulated that known gut catabolites of ellagic acid, urolithin A (10) and urolithin B (11) could be more promising candidates in exploring the anti-HIV activity of ellagic acid-rich medicinal species consumed orally. On the contrary, urolithin A and urolithin B demonstrated lower activity with comparison to ellagic acid. The binding affinity of compounds 1-9, urolithin A, and urolithin B against the catalytic domain of HIV-1 IN was also explored by in silico methods. Docking studies showed oleuropein as the best candidate, with a predicted energy of binding of ΔG -5.81 kcal/mol, while ellagic acid showed moderate predicted inhibition (ΔG -4.38 kcal/mol) caused by the interaction between the carbonyl and the key Mg2+ ion in the active site.

Challenges and Innovations Brought about by the COVID-19 Pandemic Regarding Medical and Pharmacy Education Especially in Africa and Implications for the Future.

BACKGROUND: Multiple measures introduced early to restrict COVID-19 have dramatically impacted the teaching of medical and pharmacy students, exacerbated by the lack of infrastructure and experience with e-learning at the start of the pandemic. In addition, the costs and reliability of the Internet across Africa pose challenges alongside undertaking clinical teaching and practical programmes. Consequently, there is a need to understand the many challenges and how these were addressed, given increasingly complex patients, to provide future direction. METHOD: An exploratory study was conducted among senior-level medical and pharmacy educators across Africa, addressing four key questions, including the challenges resulting from the pandemic and how these were dealt with. RESULTS: Staff and student members faced multiple challenges initially, including adapting to online learning. In addition, concerns with the lack of equipment (especially among disadvantaged students), the costs of Internet bundles, and how to conduct practicals and clinical teaching. Multiple activities were undertaken to address these challenges. These included training sessions, developing innovative approaches to teaching, and seeking ways to reduce Internet costs. Robust approaches to practicals, clinical teaching, and assessments have been developed. CONCLUSIONS: Appreciable difficulties to teaching arising from the pandemic are being addressed across Africa. Research is ongoing to improve education and assessments.

HIV-1 Reverse Transcriptase Inhibition by Major Compounds in a Kenyan Multi-Herbal Composition (CareVid™): In Vitro and In Silico Contrast.

CareVid is a multi-herbal product used in southwest Kenya as an immune booster and health tonic and has been anecdotally described as improving the condition of HIV-positive patients. The product is made up of roots, barks and whole plant of 14 African medicinal plants: Acacia nilotica (L.) Willd. ex Delile (currently, Vachelia nilotica (L.) P.J.H Hurter & Mabb.), Adenia gummifera (Harv.) Harms, Anthocleista grandiflora Gilg, Asparagus africanus Lam., Bersama abyssinica Fresen., Clematis hirsuta Guill. & Perr., Croton macrostachyus Hochst. ex Delile, Clutia robusta Pax (accepted as Clutia kilimandscharica Engl.), Dovyalis abyssinica (A. Rich.) Warb, Ekebergia capensis Sparm., Periploca linearifolia Quart.-Dill. & A. Rich., Plantago palmata Hook.f., Prunus africana Hook.f. Kalkman and Rhamnus prinoides L'Her. The objective of this study was to determine the major chemical constituents of CareVid solvent extracts and screen them for in vitro and in silico activity against the HIV-1 reverse transcriptase enzyme. To achieve this, CareVid was separately extracted using CH2Cl2, MeOH, 80% EtOH in H2O, cold H2O, hot H2O and acidified H2O (pH 1.5-3.5). The extracts were analysed using HPLC-MS equipped with UV diode array detection. HIV-1 reverse transcriptase inhibition was performed in vitro and compared to in silico HIV-1 reverse transcriptase inhibition, with the latter carried out using MOE software, placing the docking on the hydrophobic pocket in the subdomain of p66, the NNRTI pocket. The MeOH and 80% EtOH extracts showed strong in vitro HIV-1 reverse transcriptase inhibition, with an EC50 of 7 µg·mL-1. The major components were identified as sucrose, citric acid, ellagic acid, catechin 3-hexoside, epicatechin 3-hexoside, procyanidin B, hesperetin O-rutinoside, pellitorine, mangiferin, isomangiferin, 4-O-coumaroulquinic acid, ellagic acid, ellagic acid O-pentoside, crotepoxide, oleuropein, magnoflorine, tremulacin and an isomer of dammarane tetrol. Ellagic acid and procyanidin B inhibited the HIV-1 reverse transcription process at 15 and 3.2 µg/mL-1, respectively. Docking studies did not agree with in vitro results because the best scoring ligand was crotepoxide (ΔG = -8.55 kcal/mol), followed by magnoflorine (ΔG = -8.39 kcal/mol). This study showed that CareVid has contrasting in vitro and in silico activity against HIV-1 reverse transcriptase. However, the strongest in vitro inhibitors were ellagic acid and procyanidin B.

Comparative Assessment of the Pharmacovigilance Systems within the Neglected Tropical Diseases Programs in East Africa-Ethiopia, Kenya, Rwanda, and Tanzania.

Monitoring the safety of medicines used in public health programs (PHPs), including the neglected tropical diseases (NTD) program, is a WHO recommendation, and requires a well-established and robust pharmacovigilance system. The objective of this study was to assess the pharmacovigilance systems within the NTD programs in Ethiopia, Kenya, Rwanda, and Tanzania. The East African Community Harmonized Pharmacovigilance Indicators tool for PHPs was used to interview the staff of the national NTD programs. Data on four components, (i) systems, structures, and stakeholder coordination; (ii) data management and signal generation; (iii) risk assessment and evaluation; and (iv) risk management and communication, were collected and analyzed. The NTD programs in the four countries had a strategic master plan, with pharmacovigilance components and mechanisms to disseminate pharmacovigilance information. However, zero individual case safety reports were received in the last 12 months (2017/2018). There was either limited or no collaboration between the NTD programs and their respective national pharmacovigilance centers. None of the NTD programs had a specific budget for pharmacovigilance. The NTD program in all four countries had some safety monitoring elements. However, key elements, such as the reporting of adverse events, collaboration with national pharmacovigilance centers, and budget for pharmacovigilance activity, were limited/missing.

Response to the Novel Corona Virus (COVID-19) Pandemic Across Africa: Successes, Challenges, and Implications for the Future.

BACKGROUND: The COVID-19 pandemic has already claimed considerable lives. There are major concerns in Africa due to existing high prevalence rates for both infectious and non-infectious diseases and limited resources in terms of personnel, beds and equipment. Alongside this, concerns that lockdown and other measures will have on prevention and management of other infectious diseases and non-communicable diseases (NCDs). NCDs are an increasing issue with rising morbidity and mortality rates. The World Health Organization (WHO) warns that a lack of nets and treatment could result in up to 18 million additional cases of malaria and up to 30,000 additional deaths in sub-Saharan Africa. OBJECTIVE: Document current prevalence and mortality rates from COVID-19 alongside economic and other measures to reduce its spread and impact across Africa. In addition, suggested ways forward among all key stakeholder groups. OUR APPROACH: Contextualise the findings from a wide range of publications including internet-based publications coupled with input from senior-level personnel. ONGOING ACTIVITIES: Prevalence and mortality rates are currently lower in Africa than among several Western countries and the USA. This could be due to a number of factors including early instigation of lockdown and border closures, the younger age of the population, lack of robust reporting systems and as yet unidentified genetic and other factors. Innovation is accelerating to address concerns with available equipment. There are ongoing steps to address the level of misinformation and its consequences including fines. There are also ongoing initiatives across Africa to start addressing the unintended consequences of COVID-19 activities including lockdown measures and their impact on NCDs including the likely rise in mental health disorders, exacerbated by increasing stigma associated with COVID-19. Strategies include extending prescription lengths, telemedicine and encouraging vaccination. However, these need to be accelerated to prevent increased morbidity and mortality. CONCLUSION: There are multiple activities across Africa to reduce the spread of COVID-19 and address misinformation, which can have catastrophic consequences, assisted by the WHO and others, which appear to be working in a number of countries. Research is ongoing to clarify the unintended consequences given ongoing concerns to guide future activities. Countries are learning from each other.

Review of Ongoing Activities and Challenges to Improve the Care of Patients With Type 2 Diabetes Across Africa and the Implications for the Future.

BACKGROUND: There has been an appreciable increase in the number of people in Africa with metabolic syndrome and Type 2 diabetes (T2DM) in recent years as a result of a number of factors. Factors include lifestyle changes, urbanisation, and the growing consumption of processed foods coupled with increasing levels of obesity. Currently there are 19 million adults in Africa with diabetes, mainly T2DM (95%), estimated to grow to 47 million people by 2045 unless controlled. This has a considerable impact on morbidity, mortality and costs in the region. There are a number of issues to address to reduce the impact of T2DM including improving detection rates and current access to services alongside addressing issues of adherence to prescribed medicines. There are also high rates of co-morbidities with infectious diseases such as HIV and tuberculosis in patients in Africa with T2DM that require attention. OBJECTIVE: Document ongoing activities across Africa to improve the care of patients with T2DM especially around issues of identification, access, and adherence to changing lifestyles and prescribed medicines. In addition, discussing potential ways forward to improve the care of patients with T2DM based on ongoing activities and experiences including addressing key issues associated with co-morbidities with infectious diseases. OUR APPROACH: Contextualise the findings from a wide range of publications including internet based publications of national approaches coupled with input from senior level government, academic and other professionals from across Africa to provide future guidance. ONGOING ACTIVITIES: A number of African countries are actively instigating programmes to improve the care of patients with T2DM starting with improved diagnosis. This recognises the growing burden of non-communicable diseases across Africa, which has been neglected in the past. Planned activities include programmes to improve detection rates and address key issues with diet and lifestyle changes, alongside improving monitoring of care and activities to enhance adherence to prescribed medicines. In addition, addressing potential complexities involving diabetes patients with infectious disease co-morbidities. It is too early to fully assess the impact of such activities. CONCLUSION: There are a number of ongoing activities across Africa to improve the management of patients with diabetes including co-morbidities. However, more needs to be done considering the high and growing burden of T2DM in Africa. Ongoing research will help further benefit resource allocation and subsequent care.

Ongoing and planned activities to improve the management of patients with Type 1 diabetes across Africa; implications for the future.

BACKGROUND: Currently about 19 million people in Africa are known to be living with diabetes, mainly Type 2 diabetes (T2DM) (95%), estimated to grow to 47 million people by 2045. However, there are concerns with early diagnosis of patients with Type 1 diabetes (T1DM) as often patients present late with complications. There are also challenges with access and affordability of insulin, monitoring equipment and test strips with typically high patient co-payments, which can be catastrophic for families. These challenges negatively impact on the quality of care of patients with T1DM increasing morbidity and mortality. There are also issues of patient education and psychosocial support adversely affecting patients' quality of life. These challenges need to be debated and potential future activities discussed to improve the future care of patients with T1DM across Africa. METHODOLOGY: Documentation of the current situation across Africa for patients with T1DM including the epidemiology, economics, and available treatments within public healthcare systems as well as ongoing activities to improve their future care. Subsequently, provide guidance to all key stakeholder groups going forward utilizing input from senior-level government, academic and other professionals from across Africa. RESULTS: Whilst prevalence rates for T1DM are considerably lower than T2DM, there are concerns with late diagnosis as well as the routine provision of insulin and monitoring equipment across Africa. High patient co-payments exacerbate the situation. However, there are ongoing developments to address the multiple challenges including the instigation of universal health care and partnerships with non-governmental organizations, patient organizations, and pharmaceutical companies. Their impact though remains to be seen. In the meantime, a range of activities has been documented for all key stakeholder groups to improve future care. CONCLUSION: There are concerns with the management of patients with T1DM across Africa. A number of activities has been suggested to address this and will be monitored.

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.

Comparative Assessment of the National Pharmacovigilance Systems in East Africa: Ethiopia, Kenya, Rwanda and Tanzania.

INTRODUCTION: The increased access to medicinal products in Africa is not well-matched with the pharmacovigilance capacity to monitor drug safety. The objective of this study was to assess the functionality and identify the strengths and limitations of the national pharmacovigilance systems in Ethiopia, Kenya, Rwanda, and Tanzania, and compare these systems. METHODS: Legal and statutory documents governing the pharmacovigilance systems of each participating country were examined by assessors prior to on-site review. The staff of the pharmacovigilance unit of the National Medicines Regulatory Authorities (NMRAs) were interviewed using the East African Community Harmonized Pharmacovigilance Indicators tool, supplemented with indicators from the World Health Organization (WHO) Global Benchmarking Tool. Responses were recorded, and data were analyzed. RESULTS: The pharmacovigilance systems were supported by law and regulations in line with international standards. Standard operating procedures for receiving, processing, and communicating suspected adverse event reports were in place, but reporting of suspected medicine-related harm from stakeholders was inadequate in all countries. The number of Individual Case Safety Reports (ICSRs) received by NMRAs in Kenya, Ethiopia, and Tanzania (mainland) were 35.0, 6.7, and 4.1 per million inhabitants, respectively, in the last calendar year. At the time of assessment, Rwanda did not have an operational system. Overall, ≤ 1% of the total number of health facilities per country submitted ICSRs. Only Kenya and Tanzania had a designated budget for pharmacovigilance activities and an electronic ICSR reporting system. The national pharmacovigilance systems in all four countries did not have access to data on drug utilization. CONCLUSIONS: The national pharmacovigilance systems in the four East African countries have policy and legal frameworks defined by law and regulation to conduct pharmacovigilance activities. However, the four national pharmacovigilance systems are at different levels of capacity and performance with respect to conducting pharmacovigilance activities. Targeted interventions are needed to strengthen the pharmacovigilance systems to enable evidence-based decision making for patient safety.

Rapid Assessment of the Potential Paucity and Price Increases for Suggested Medicines and Protection Equipment for COVID-19 Across Developing Countries With a Particular Focus on Africa and the Implications.

Background: Countries across Africa and Asia have introduced a variety of measures to prevent and treat COVID-19 with medicines and personal protective equipment (PPE). However, there has been considerable controversy surrounding some treatments including hydroxychloroquine where the initial hype and misinformation led to shortages, price rises and suicides. Price rises and shortages were also seen for PPE. Such activities can have catastrophic consequences especially in countries with high co-payment levels. Consequently, there is a need to investigate this further. Objective: Assess changes in utilisation, prices, and shortages of pertinent medicines and PPE among African and Asian countries since the start of pandemic. Our approach: Data gathering among community pharmacists to assess changes in patterns from the beginning of March until principally the end of May 2020. In addition, suggestions on ways to reduce misinformation. Results: One hundred and thirty one pharmacists took part building on the earlier studies across Asia. There were increases in the utilisation of principally antimalarials (hydroxychloroquine) and antibiotics (azithromycin) especially in Nigeria and Ghana. There were limited changes in Namibia and Vietnam reflecting current initiatives to reduce inappropriate prescribing and dispensing of antimicrobials. Encouragingly, there was increased use of vitamins/immune boosters and PPE across the countries where documented. In addition, generally limited change in the utilisation of herbal medicines. However, shortages have resulted in appreciable price increases in some countries although moderated in others through government initiatives. Suggestions in Namibia going forward included better planning and educating patients. Conclusion: Encouraging to see increases in the utilisation of vitamins/immune boosters and PPE. However, concerns with increased utilisation of antimicrobials needs addressing alongside misinformation, unintended consequences from the pandemic and any appreciable price rises. Community pharmacists and patient organisations can play key roles in providing evidence-based advice, helping moderate prices through improved stock management, and helping address unintended consequences of the pandemic.

Proactive risk assessment of vincristine use process in a teaching and referral hospital in Kenya and the implications.

INTRODUCTION: The chemotherapy use process is potentially risky for cancer patients. Vincristine, a "High Alert" medicine, has been associated with fatal but preventable medication errors. Consequently, there is a need to improve the use of vincristine especially in lower- and middle-income countries where there are constraints with resources and often a lack of trained personnel to administer cancer medicines. However, where there is a rising prevalence of cancer cases. These concerns can be addressed by performing proactive risk assessments using Healthcare Failure Mode Effect Analysis (HFMEA) and implementing the findings. METHODS: A multidisciplinary health team driven by pharmacists identified and evaluated potential failure modes based on a vincristine use process flow diagram using a hazard scoring matrix in a leading referral hospital in Kenya. RESULTS: The processes evaluated were: prescribing, preparation and dispensing, transportation and storage, administration and monitoring of the use of vincristine. Seventy-seven failure modes were identified over the three-month study period, of which 25 were classified as high risk. Thirteen were adequately covered by existing control measures while 12 including one combined mode required new strategies. Two of the failure modes were single-point weaknesses. Recommendations were subsequently made for improving the administration of vincristine. CONCLUSIONS: HFMEA is a useful tool to identify improvements to medication safety and reduction of patient harm. The HFMEA process brings together the multidisciplinary team involved in patient care in actively identifying potential failure modes and owning the recommendations made, which are now being actively followed up in this hospital. Pharmacists are a key part of this process.

The international partner universities of East African health professional programmes: why do they do it and what do they value?

BACKGROUND: Globalization and funding imperatives drive many universities to internationalize through global health programmes. University-based global health researchers, advocates and programmes often stress the importance of addressing health inequity through partnerships. However, empirical exploration of perspectives on why universities engage in these partnerships and the benefits of them is limited. OBJECTIVE: To analyse who in international partner universities initiated the partnerships with four East African universities, why the partnerships were initiated, and what the international partners value about the partnerships. METHODS: Fifty-nine key informants from 26 international universities partnering with four East African universities in medicine, nursing and/or public health participated in individual in-depth interviews. Transcripts were analysed thematically. We then applied Burton Clark's framework of "entrepreneurial" universities characterized by an "academic heartland", "expanded development periphery", "managerial core" and "expanded funding base", developed to examine how European universities respond to the forces of globalization, to interpret the data through a global health lens. RESULTS: Partnerships that were of interest to universities' "academic heartland" - research and education - were of greatest interest to many international partners, especially research intensive universities. Some universities established and placed coordination of their global health activities within units consistent with an expanded development periphery. These units were sometimes useful for helping to establish and support global health partnerships. Success in developing and sustaining the global health partnerships required some degree of support from a strengthened steering or managerial core. Diversified funding in the form of third-stream funding, was found to be essential to sustain partnerships. Social responsibility was also identified as a key ethos required to unite the multiple elements in some universities and sustain global health partnerships. CONCLUSION: Universities are complex entities. Various elements determine why a specific university entered a specific international partnership and what benefits it accrues. Ultimately, integration of the various elements is required to grow and sustain partnerships potentially through embracing social responsibility as a common value.

What Makes International Global Health University Partnerships Higher-Value? An Examination of Partnership Types and Activities Favoured at Four East African Universities.

BACKGROUND: There are many interuniversity global health partnerships with African universities. Representatives of these partnerships often claim partnership success in published works, yet critical, contextualized, and comparative assessments of international, cross-border partnerships are few. OBJECTIVE: The objectives of this paper are to describe partnerships characterized as higher-value for building the capacity of four East African universities and identify why they are considered so by these universities. METHODS: Forty-two senior representatives of four universities in East Africa described the value of their partnerships. A rating system was developed to classify the value of the 125 international partnerships they identified, as the perceived value of some partnerships varied significantly between representatives within the same university. An additional 88 respondents from the four universities and 59 respondents from 25 of the international partner universities provided further perspectives on the partnerships identified. All interviews were transcribed and analysed in relation to the classification and emergent themes. FINDINGS: Thirty-one (25%) of the partnerships were perceived as higher-value, 41 (33%) medium-value, and 53 (42%) lower-value for building the capacity of the four focus universities. Thirteen (42%) of the higher-value partnerships were over 20 years old, while 8 (26%) were between 3 and 5 years old. New international partners were able to leapfrog some of the development phases of partnerships by coordinating with existing international partners and/or by building on the activities of or filling gaps in older partnerships. Higher-valued partnerships supported PhD obtainment, the development of new programmes and pedagogies, international trainee learning experiences, and infrastructure development. The financial and prestige value of partnerships were important but did not supersede other factors such as fit with strategic needs, the development of enduring results, dependability and reciprocity. Support of research or service delivery were also considered valuable but, unless education components were also included, the results were deemed unlikely to last. CONCLUSION: International partnerships prioritizing the needs of the focus university, supporting it in increasing its long-term capacity and best ensuring that capacity benefits realized favour the focus university are valued most. How best to achieve this so all partners still benefit sufficiently requires further exploration.

Mapping International University Partnerships Identified by East African Universities as Strengthening Their Medicine, Nursing, and Public Health Programs.

BACKGROUND: International university partnerships are recommended for increasing the capacity of sub-Saharan African universities. Many publications describe individual partnerships and projects, and tools are available for guiding collaborations, but systematic mappings of the basic, common characteristics of partnerships are scarce. OBJECTIVE: To document and categorize the international interuniversity partnerships deemed significant to building the capacity of medicine, nursing, and public health programs of 4 East African universities. METHODS: Two universities in Kenya and 2 in Tanzania were purposefully selected. Key informant interviews, conducted with 42 senior representatives of the 4 universities, identified partnerships they considered significant for increasing the capacity of their institutions' medicine, nursing, and public health programs in education, research, or service. Interviews were transcribed and analyzed. Partners were classified by country of origin and corresponding international groupings, duration, programs, and academic health science components. FINDINGS: One hundred twenty-nine university-to-university partnerships from 23 countries were identified. Each university reported between 25 and 36 international university partners. Seventy-four percent of partnerships were with universities in high-income countries, 15% in low- and middle-income countries, and 11% with consortia. Seventy percent included medicine, 37% nursing, and 45% public health; 15% included all 3 programs. Ninety-two percent included an education component, 47% research, and 24% service; 12% included all 3 components. CONCLUSIONS: This study confirms the rapid growth of interuniversity cross-border health partnerships this century. It also finds, however, that there is a pool of established international partnerships from numerous countries at each university. Most partnerships that seek to strengthen universities in East Africa should likely ensure they have a significant education component. Universities should make more systematic information about past and existing partnerships available publicly.

Pharmacological evidence for the folk use of Nefang: antipyretic, anti-inflammatory and antinociceptive activities of its constituent plants.

BACKGROUND: Nefang is a polyherbal anti-malarial composed of Mangifera indica ( MiB and MiL; bark and leaf), Psidium guajava ( Pg ), Carica papaya ( Cp ), Cymbopogon citratus ( Cc ), Citrus sinensis ( Cs ) and Ocimum gratissimum ( Og ) (leaves). Previous studies have demonstrated its in vitro and in vivo antiplasmodial activities, antioxidant properties and safety profile. This study aimed at evaluating the antipyretic, anti-inflammatory and antinociceptive activities of the constituent plants of Nefang which are relevant to the symptomatic treatment of malaria fever. METHODS: Antipyretic activities were determined by the D-Amphetamine induced pyrexia and Brewer's Yeast induced hyperpyrexia methods. Anti-inflammatory activities were investigated using the carrageenan-induced rat paw edema method. Antinociceptive activities were determined by mechanical nociception in the tail pressure and thermal nociception in the radiant heat tail flick and hot plate methods. Data was analysed using the one way ANOVA followed by Neuman-Keuls multiple comparison test. RESULTS: Best percentage inhibition of induced pyrexia (amphetamine/brewer's yeast; p < 0.05) was exhibited by Cc (95/97) followed by Og (85/94), MiL (90/89), MiB (88/84) and Cs (82/89). Cc and Og exhibited comparable activities to paracetamol (100/95). Anti-inflammatory studies revealed paw edema inhibition (%) as follows (p < 0.05): Indomethacin (47), MiL (40), Cp (30), MiB (28) and Og (22), suggesting best activity by MiL. Antinociceptive studies revealed significant (p < 0.01) pain inhibition (%) as follows: Paracetamol (97), Og (113), MiL (108), Pg (84) and MiB (88). Og and MiL exhibited the best activities. CONCLUSION: The results obtained suggest that the constituent plants possess biologically active compounds with antipyretic, anti-inflammatory and antinociceptive activities. These activities are essential in the symptomatic treatment of malaria fever, thereby justifying the folk use of Nefang. This would be useful in its subsequent development for clinical application.

Cytochrome P450 2B6 genetic variants are associated with plasma nevirapine levels and clinical response in HIV-1 infected Kenyan women: a prospective cohort study.

BACKGROUND: Polymorphisms in cytochrome P450 2B6 (CYP2B6) affect the steady state plasma concentration of nevirapine. CYP2B6 516G>T and 983T>C are common in African populations, but data on their influence on plasma nevirapine concentration and clinical response in African women are limited. We investigated the impact of CYP 516G>T and 983T>C on plasma nevirapine concentration and clinical outcomes in a prospective cohort study of HIV-infected Kenyan women. METHODS: Study subjects were 66 HIV-1-seropositive women taking nevirapine-based antiretroviral therapy. Plasma collected at week 12 was analyzed for nevirapine concentration by high performance liquid chromatography. Baseline samples were genotyped for CYP2B6 516G>T and 983T>C single nucleotide polymorphisms by real-time polymerase chain reaction. CD4 cell count, plasma viral load, and genotypic drug resistance in plasma and genital secretions were assessed at baseline and during follow up. We evaluated the effect of each genotype on plasma nevirapine concentration at week 12 and on change in CD4 cell count at months 3, 6 and 12. Associations between plasma nevirapine concentration and clinical outcomes were analyzed by logistic or linear regression. RESULTS: Women with CYP2B6 516TT genotype (n=9) had higher mean nevirapine plasma levels (14.33 µg/mL) compared to those with heterozygous 516GT (9.18 µg/mL; n=25) and wild- type 516GG (7.95 µg/mL; n=32) genotypes (P=0.01). Women heterozygous for the CYP2B6 983TC genotype (n=13) had higher mean nevirapine plasma levels (12.94 µg/mL), compared to women with the homozygous 983TT (8.35 µg/mL; n=53) genotype (P=0.007). In Generalized Estimating Equation analysis, plasma nevirapine levels predicted greater change in CD4 cell count after ART initiation (adjusted beta 119.4 cells/µL, 95% CI, 27.3-211.5 cells/µL, P=0.01). The CYP2B6 983TT genotype also predicted greater change in CD4 cell count (adjusted beta 68.6 cells/µL, 95% CI, 3.9-133.4 cells/µL, P=0.04). We found no associations between CYP2B6 genotypes and virologic response or toxicity. CONCLUSIONS: CYP2B6 516G>T and CYP2B6 983T>C genotypes were strongly associated with plasma nevirapine concentration, which predicted immunologic response in women on nevirapine-based antiretroviral therapy. These data support continued work on the potential utility of human genetic testing to inform nevirapine dosage optimization for individual patients.

Management of Type 2 Diabetes Mellitus by Traditional Medicine Practitioners in Kenya--Key Informant Interviews.

INTRODUCTION: Worldwide, plant based medicines are increasing in popularity due to perceptions of safety and efficacy. Herbalists in Kenya are widely consulted for the management of many diseases including Type 2 Diabetes Mellitus (T2DM). This study investigated the level of knowledge of the herbalists in management of T2DM. METHODS: Purposive sampling was used to identify 4 herbalists working in the urban areas who actively manage T2DM. Key informant interviews were used to gather data about the management of T2DM. It was analyzed using a content thematic approach. RESULTS: Diverse management methods which included both pharmacological and non- pharmacological were noted. Glycemic control was assessed with the help of a glucometer. In addition, presenting signs and symptoms were key in diagnosing T2DM. The herbalists used various herbs, minerals and animals as medicinal sources. The drugs were dispensed as decoctions with excipients being added appropriately. Adverse effects were recorded. The herbalists acknowledged that patients use both herbal and allopathic medicine together. A level of record keeping was observed but patient follow-up was poor. The cost of the herbal drugs was perceived to be excessive. CONCLUSION: Some similarities exist in the management of T2DM between allopathic and traditional medicine practitioners. Training of herbalists is required to improve the quality of care given to patients.

Anti-malarial activity of a polyherbal product (Nefang) during early and established Plasmodium infection in rodent models.

BACKGROUND: The emerging resistance of Plasmodium species to currently available anti-malarials remains a public health concern, hence the need for new effective, safe and affordable drugs. Natural products remain a reliable source of drugs. Nefang is a polyherbal anti-malarial of the Cameroonian folklore medicine with demonstrated in vitro antiplasmodial and antioxidant activities. It is composed of Mangifera indica (bark and leaf), Psidium guajava, Carica papaya, Cymbopogon citratus, Citrus sinensis, Ocimum gratissimum (leaves). This study aimed at investigating the suppressive, prophylactic and curative activities of Nefang in Plasmodium infected rodent models. METHODS: Systemic acute oral toxicity of Nefang aqueous and ethanol extracts was assessed in mice up to a dose of 5,000 mgkg(-1) body weight. BALB/c mice and Wistar rats were inoculated with Plasmodium chabaudi chabaudi and Plasmodium berghei, respectively, and treated with Nefang, the Mangifera indica bark/Psidium guajava combination and a Psidium guajava leaf aqueous extracts (75, 150, 300 and 600 mgkg(-1) bwt). Their schizonticidal activity was then evaluated using the Peter's 4-day suppressive test). The prophylactic and curative (Rane's Test) activity of Nefang was also evaluated by determining the parasitaemia, survival time, body weight and temperature in pre-treated rodents. RESULTS: Acute oral toxicity of the extract did not cause any observed adverse effects. Percent suppressions of parasitaemia at 600 mgkg(-1) bwt were as follows (P. berghei/P. chabaudi): Nefang - 82.9/86.3, Mangifera indica bark/Psidium guajava leaf combination extract - 79.5/81.2 and Psidium guajava leaf - 58.9/67.4. Nefang exhibited a prophylactic activity of 79.5% and its chemotherapeutic effects ranged from 61.2 - 86.1% with maximum effect observed at the highest experimental dose. CONCLUSION: These results indicate that Nefang has excellent in vivo anti-malarial activities against P. berghei and P. chabaudi, upholding earlier in vitro antiplasmodial activities against multi-drug resistant P. falciparum parasites as well as its traditional use. Hence, Nefang represents a promising source of new anti-malarial agents.