Publications

2021
Atkinson EG, Dalvie S, Pichkar Y, Kalungi A, Majara L, Stevenson A, Abebe T, Akena D, Alemayehu M, Ashaba FK, Atwoli L, Baker M, Chibnik LB, Creanza N, Daly MJ, Fekadu A, Gelaye B, Gichuru S, Injera WE, James R, Kariuki SM, Kigen G, Koen N, Koenen KC, Koenig Z, Kwobah E, Kyebuzibwa J, Musinguzi H, Mwema RM, Neale BM, Newman CP, Newton CRJC, Ongeri L, Ramachandran S, Ramesar R, Shiferaw W, Stein DJ, Stroud RE, Teferra S, Zingela Z, Martin AR,, R.K. Genetic structure correlates with ethnolinguistic diversity in eastern and southern Africa [Internet]. bioRxiv 2021; WebsiteAbstract
African populations are the most diverse in the world yet are sorely underrepresented in medical genetics research. Here, we examine the structure of African populations using genetic and comprehensive multigenerational ethnolinguistic data from the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) consisting of 900 individuals from Ethiopia, Kenya, South Africa, and Uganda. We find that self-reported language classifications meaningfully tag underlying genetic variation that would be missed with consideration of geography alone, highlighting the importance of culture in shaping genetic diversity. Leveraging our uniquely rich multi-generational ethnolinguistic metadata, we track language transmission through the pedigree, observing the disappearance of several languages in our cohort as well as notable shifts in frequency over three generations. We further find significantly higher language transmission rates for matrilineal groups as compared to patrilineal. We highlight both the diversity of variation within the African continent, as well as how within-Africa variation can be informative for broader variant interpretation; many variants appearing rare elsewhere are common in parts of Africa. The work presented here improves the understanding of the spectrum of genetic variation in African populations and highlights the enormous and complex genetic and ethnolinguistic diversity within Africa.Competing Interest StatementA.R.M. has consulted for 23andMe and Illumina and received speaker fees from Genentech, Pfizer, and Illumina. B.M.N. is a member of the Deep Genomics Scientific Advisory Board. He also serves as a consultant for the Camp4 Therapeutics Corporation, Takeda Pharmaceutical and Biogen. M.J.D. is a founder of Maze Therapeutics. The remaining authors declare no competing interests.
Martin AR, Atkinson EG, Chapman SB, Stevenson A, Stroud RE, Abebe T, Akena D, Alemayehu M, Ashaba FK, Atwoli L, Bowers T, Chibnik LB, Daly MJ, DeSmet T, Dodge S, Fekadu A, Ferriera S, Gelaye B, Gichuru S, Injera WE, James R, Kariuki SM, Kigen G, Koenen KC, Kwobah E, Kyebuzibwa J, Majara L, Musinguzi H, Mwema RM, Neale BM, Newman CP, Newton CRJC, Pickrell JK, Ramesar R, Shiferaw W, Stein DJ, Teferra S, van der Merwe C, Zingela Z. Low-coverage sequencing cost-effectively detects known and novel variation in underrepresented populations. The American Journal of Human GeneticsThe American Journal of Human Genetics 2021;108:656-668.Abstract
Summary Genetic studies in underrepresented populations identify disproportionate numbers of novel associations. However, most genetic studies use genotyping arrays and sequenced reference panels that best capture variation most common in European ancestry populations. To compare data generation strategies best suited for underrepresented populations, we sequenced the whole genomes of 91 individuals to high coverage as part of the Neuropsychiatric Genetics of African Population-Psychosis (NeuroGAP-Psychosis) study with participants from Ethiopia, Kenya, South Africa, and Uganda. We used a downsampling approach to evaluate the quality of two cost-effective data generation strategies, GWAS arrays versus low-coverage sequencing, by calculating the concordance of imputed variants from these technologies with those from deep whole-genome sequencing data. We show that low-coverage sequencing at a depth of ≥4× captures variants of all frequencies more accurately than all commonly used GWAS arrays investigated and at a comparable cost. Lower depths of sequencing (0.5–1×) performed comparably to commonly used low-density GWAS arrays. Low-coverage sequencing is also sensitive to novel variation; 4× sequencing detects 45% of singletons and 95% of common variants identified in high-coverage African whole genomes. Low-coverage sequencing approaches surmount the problems induced by the ascertainment of common genotyping arrays, effectively identify novel variation particularly in underrepresented populations, and present opportunities to enhance variant discovery at a cost similar to traditional approaches.
Abrha S, Christenson JK, McEwen J, Tesfaye W, Vaz Nery S, Chang AY, Spelman T, Kosari S, Kigen G, Carroll S, Heukelbach J, Feldmeier H, Bartholomaeus A, Daniel M, Peterson GM, Thomas J. Treatment of tungiasis using a tea tree oil-based gel formulation: protocol for a randomised controlled proof-of-principle trial [Internet]. BMJ Open 2021;11(7):e047380. WebsiteAbstract

Introduction Tungiasis (sand flea disease or jigger infestation) is a neglected tropical disease caused by penetration of female sand fleas, Tunga penetrans, in the skin. The disease inflicts immense pain and suffering on millions of people, particularly children, in Latin America, the Caribbean and sub-Saharan Africa. Currently, there is no standard treatment for tungiasis, and a simple, safe and effective tungiasis treatment option is required. Tea tree oil (TTO) has long been used as a parasiticidal agent against ectoparasites such as headlice, mites and fleas with proven safety and efficacy data. However, current data are insufficient to warrant a recommendation for its use in tungiasis. This trial aims to generate these data by comparing the safety and efficacy of a 5% (v/w) TTO proprietary gel formulation with 0.05% (w/v) potassium permanganate (KMnO4) solution for tungiasis treatment.Methods and analysis This trial is a randomised controlled trial (RCT) in primary schools (n=8) in South-Western Kenya. The study will include school children (n=88) aged 6–15 years with a confirmed diagnosis of tungiasis. The participants will be randomised in a 1:1 ratio to receive a 3-day two times a day treatment of either 5% TTO gel or 0.05% KMnO4 solution. Two viable embedded sandflea lesions per participant will be targeted and the viability of these lesions will be followed throughout the study using a digital handheld microscope. The primary outcome is the proportion of observed viable embedded sand fleas that have lost viability (non-viable lesions) by day 10 (9 days after first treatment). Secondary outcomes include improvement in acute tungiasis morbidities assessed using a validated severity score for tungiasis, safety assessed through adverse events and product acceptability assessed by interviewing the participants to rate the treatment in terms of effectiveness, side effects, convenience, suitability and overall satisfaction.Ethics and dissemination The trial protocol has been reviewed and approved by the University of Canberra Human Research Ethics Committee (HREC-2019-2114). The findings of the study will be presented at scientific conferences and published in a peer-reviewed journal.Trial registration numbers Australian New Zealand Clinical Trials Registry (ACTRN12619001610123); PACTR202003651095100 and U1111-1243-2294.

2020
Karwa R, Miller ML, Schellhase E, Tran D, Manji I, Njuguna B, Fletcher S, Kanyi J, Maina M, Jakait B, Kigen G, Kipyegon V, Aruasa W, Crowe S, Pastakia SD. Evaluating the impact of a 15-year academic partnership to promote sustainable engagement, education, and scholarship in global health [Internet]. JACCP: JOURNAL OF THE AMERICAN COLLEGE OF CLINICAL PHARMACY 2020;3:885-896. WebsiteAbstract
Abstract Introduction In 2003, Purdue University College of Pharmacy (PUCOP) in West Lafayette, Indiana, began the Purdue Kenya Partnership (PKP) in collaboration with the Academic Model Providing Access to Healthcare, Moi University, and Moi Teaching and Referral Hospital, in Eldoret, Kenya. PUCOP's involvement utilized a tripartite approach of engagement, education, and scholarship to provide and expand sustainable access to high quality care. Objective This paper discusses outcomes and impacts of this academic partnership. Methods Purdue Kenya Partnership's progress in achieving its stated mission was evaluated using an outcome-approach logic model. This model highlighted inputs, activities, and results which encompassed outputs, outcomes, and impact. A comprehensive set of ratios were calculated to quantify annual change in PKP investments against estimated metrics for engagement, education, and scholarship. These metrics were weighted by involvement level and pharmacist effort in various clinical domains. Descriptive statistics were completed that identified cumulative and totals per year for each collected data type of data collected. Results Purdue Kenya Partnership implementation utilized initial inputs of human resources, financial capital, and strategic partnerships. These inputs supported pharmacy involvement in 16 distinct care programs in both inpatient and outpatient settings which supported the care of 457 833 individual patients and grown a clinical pharmacy staff from 0 to 22 practicing clinical pharmacists. Five unique educational programs have been established which have graduated 457 trainees. Purdue Kenya Partnership has generated over \$6.2 million in grant funding and disseminated 302 peer reviewed manuscripts, posters, and oral presentations combined. Ratios describing trends in engagement, education, and scholarship as a result of using the locally focused PKP approach highlight higher initial costs compared with much lower costs per outcome several years into the partnership. Conclusion The PKP's global health approach of prioritizing the population's care needs (“leading with care”) has enabled the development of sustainable engagement, education, and scholarship infrastructure with significant gains in all three domains.
Martin AR, Atkinson EG, Chapman SB, Stevenson A, Stroud RE, Abebe T, Akena D, Alemayehu M, Ashaba FK, Atwoli L, Bowers T, Chibnik LB, Daly MJ, DeSmet T, Dodge S, Fekadu A, Ferriera S, Gelaye B, Gichuru S, Injera WE, James R, Kariuki SM, Kigen G, Koenen KC, Kwobah E, Kyebuzibwa J, Majara L, Musinguzi H, Mwema RM, Neale BM, Newman CP, Newton CRJC, Pickrell JK, Ramesar R, Shiferaw W, Stein DJ, Teferra S, van der Merwe C, Zingela Z,, R.K. Low-coverage sequencing cost-effectively detects known and novel variation in underrepresented populations [Internet]. bioRxiv 2020; WebsiteAbstract
Background Genetic studies of biomedical phenotypes in underrepresented populations identify disproportionate numbers of novel associations. However, current genomics infrastructure–including most genotyping arrays and sequenced reference panels–best serves populations of European descent. A critical step for facilitating genetic studies in underrepresented populations is to ensure that genetic technologies accurately capture variation in all populations. Here, we quantify the accuracy of low-coverage sequencing in diverse African populations.Results We sequenced the whole genomes of 91 individuals to high-coverage (>=20X) from the Neuropsychiatric Genetics of African Population-Psychosis (NeuroGAP-Psychosis) study, in which participants were recruited from Ethiopia, Kenya, South Africa, and Uganda. We empirically tested two data generation strategies, GWAS arrays versus low-coverage sequencing, by calculating the concordance of imputed variants from these technologies with those from deep whole genome sequencing data. We show that low-coverage sequencing at a depth of >=4X captures variants of all frequencies more accurately than all commonly used GWAS arrays investigated and at a comparable cost. Lower depths of sequencing (0.5-1X) performed comparable to commonly used low-density GWAS arrays. Low-coverage sequencing is also sensitive to novel variation, with 4X sequencing detecting 45% of singletons and 95% of common variants identified in high-coverage African whole genomes.Conclusion These results indicate that low-coverage sequencing approaches surmount the problems induced by the ascertainment of common genotyping arrays, including those that capture variation most common in Europeans and Africans. Low-coverage sequencing effectively identifies novel variation (particularly in underrepresented populations), and presents opportunities to enhance variant discovery at a similar cost to traditional approaches.Competing Interest StatementA.R.M. serves as a consultant for 23andMe and is a member of the Precise.ly Scientific Advisory Board. B.M.N. is a member of the Deep Genomics Scientific Advisory Board. He also serves as a consultant for the Camp4 Therapeutics Corporation, Takeda Pharmaceutical and Biogen. M.J.D. is a founder of Maze Therapeutics. J.K.P. is an employee of Gencove, Inc. The remaining authors declare no competing interests. D.J.S. has received research grants and/or consultancy honoraria from Lundbeck and Sun.
2019
Kigen G, Kamuren Z, Njiru E, Wanjohi B, Kipkore W. Ethnomedical Survey of the Plants Used by Traditional Healers in Narok County, Kenya [Internet]. Evidence-Based Complementary and Alternative Medicine 2019;2019 DOIAbstract

Most of the plants used by herbalists amongst the various Kenyan communities have not been documented despite their widespread use. The purpose of this research was to document the medicinal plants used by the herbalists from the Maasai, a community that still relies on herbal medicine to a large extent for the provision of medical services. Semistructured interviews, direct observations, group discussions, and in-depth interviews were used to collect information from the traditional healers. A total of 47 plant species belonging to 31 families were identified. They were used in the treatment of 33 medical and 4 veterinary conditions.

2018
2017
Karwa R, Tran DN, Maina M, Njuguna B, Manji I, Wasike P, Tonui E, Kigen G, Pastakia SD. Addressing the 3A’s (Availability, Accountability, Adherence) of Supply Chain Systems in Western Kenya [Internet]. In: Mobilizing Chemistry Expertise To Solve Humanitarian Problems Volume 1. American Chemical Society; 2017 p. 129-157. WebsiteAbstract

The right to access essential medicines and medical technologies is crucial to attain the highest-quality health care for all citizens of the world. Unfortunately, in many low- and middle-income countries (LMICs) around the world, patients’ ability to access quality essential medicines still remains a critical challenge. Barriers that impact the quality of essential medicines from chronic communicable and chronic non-communicable diseases lie within three specific areas (3A’s): availability, accountability, and adherence. First, unnecessarily complex supply chain management, poor operational procedures, and inadequate financing for health lead to low availability of medicines. Second, corruption contributes to falsified and substandard medicines and low accountability of the supply chain to the patients who rely on it. Lastly, poor patient adherence to medicines is affected by low health literacy, lack of communication between providers and patients, and social stigma of diseases. Based on our on-the-ground experiences working in western Kenya, we propose solutions that target each of these challenges to improve access and quality of medicines. Through this chapter, we hope to compel chemists to apply and focus their efforts to create transformative chemical techniques with the potential to significantly improve quality of medicines, to improve patient outcomes, and to alter the delivery of care to patients all over the world.

2016
2015

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