DISENTANGLING THE WICKED PROBLEM OF ANTIBIOTIC RESISTANCE By SYLVIA ADHIAMBO

199 Pages·2017·1.25 MB·English

DISENTANGLING THE WICKED PROBLEM OF ANTIBIOTIC RESISTANCE

By

SYLVIA ADHIAMBO OMULO

A dissertation submitted in partial fulfillment of
the requirements for the degree of

DOCTOR OF PHILOSOPHY

WASHINGTON STATE UNIVERSITY
Paul G. Allen School for Global Animal Health

MAY 2017

© Copyright by SYLVIA ADHIAMBO OMULO, 2017
All Rights Reserved
© Copyright by SYLVIA ADHIAMBO OMULO, 2017
All Rights Reserved
To the Faculty of Washington State University:

The members of the Committee appointed to examine the dissertation of SYLVIA
ADHIAMBO OMULO find it satisfactory and recommend that it be accepted.

Douglas R. Call, Ph.D., Chair

Terrence F. McElwain, Ph.D.

M. Kariuki Njenga, Ph.D.

Margaret A. Davis, Ph.D.

Jennifer Zambriski, Ph.D.

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ACKNOWLEDGMENT
My journey to this end has been an excellent learning experience, largely attributed to the
immense mentorship I received from my advisor Prof. Call. When I joined the Call lab, I had no
previous background on antimicrobial resistance (AMR). This was not a deterrent for Prof. Call
(an AMR guru). He introduced me to his area of expertise by guiding me through a review of
various AMR literature, constantly keeping me abreast on the happenings in the field. Over time,
I learnt the ropes, identified an under-researched area (AMR in Africa) from which I curved my
dissertation topic. Perhaps one of the attributes I appreciated most in Prof. Call was his ability to
provide just the right amount of structure while also allowing me some level of independence.
This enabled me to not only develop confidence in my work but also be accountable for it. I also
appreciated that aside from his interest in my academics, he was constantly available to offer
personal personal help whenever I needed it. I am truly honored to have had him as an advisor.
I am also deeply grateful to the members of my PhD committee: Drs. Terry F. McElwain,
M. Kariuki Njenga, Margaret A. Davis and Jennifer Zambriski. They not only devoted their time
to read multiple iterations of my research proposal but also help me think more critically about
my work. Their contributions were instrumental in helping me successfully complete my
preliminary examination. I appreciate that they were always available for unscheduled walk-in
sessions to discuss academics or to just catch-up and moreso, that scheduling committee
meetings or gaining consensus on issues with them was always seamless – I have known many
students for whom these have been a challenge. Their cohesion and their diverse experiences
were extremely important in the development and smooth progression of my research work. I
remain overwhelmingly grateful to them; I could not have wished for a better committee
consistution.
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There have been numerous other players that have contributed to the studies described in
this dissertation. I would like to thank most specially the contributions of my study respondents
in Kibera. Their acceptance to participate in research studies, such as the ones described in this
dissertation, helps us to answer important scientific questions which may not be directly
beneficial to them at present but which shape our decisions for the better good of future
generations. I also acknowledge the dedication of various individuals who helped with or
facilitated various aspects of the field data collection, including A. Owuor, A. Ouma, D. Owiti,
D. Murunga, E. Olendi, G. Masyongo, G. Sitienei, G. Wanjau, L. Cosmas, L. Ochieng, M.
Omollo, P. Odawo, S. Muema and S. Owino. I thank the lab team in Kenya (D. Alando, G.
Kikwai, J. Obiya, K. Kipyegon, N. Wamola, R. Mugoh, V. Omballa, W. Gumbi) and in Pullman
(L. Orfe, O. Strom, M. Subbiah, J. Avillan) for their various roles during the preparatory stages
and over the course of my research. Special thanks to Prof. Samuel Kariuki and Dr. Robert
Onsare of the Center for Microbiology Research (CMR) at the Kenya Medical Research Institute
(KEMRI) for facilitiating local IRB approval and supporting my research work. I also thank
various staff and leadership within KEMRI and the Centers for Disease Control and Prevention
(CDC) – Kenya for providing resources and facilities for my field work.
I give special thanks to Drs. Svetlana Lockwood, Eric Lofgren and Todd Coffey who not
only helped me make sense of my research data, but through whom I learnt how to use different
data analysis tools. I also acknowledge with gratitude the help I received from Dr. Thumbi
Mwangi, who contributed to many aspects of my research, including proposal development,
designing the field survey tools, staff training, field supervision and data analysis.
The Paul G. Allen School for Global Animal Health, through its (past) leadership, Drs.
Guy Palmer and Terry McElwain, approved my acceptance in to the Immunology and Infectious
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Disease program, provided my research assistantship and funding for my research work. I remain
eternally indebted to the school and its leadership, and will endeavor to uphold the school’s
mission through my professional duties. I offer a big thank you to the administrative staff and
faculty within the Allen School and VMP.
I would not have made it this far without a strong support base. I would like to thank my
dearest friends, Azeza Falghoush and her lovely family, who opened the door to their home and
their hearts and gave me a home away from home. Many people have shown me kindness, love
and support at different stages of my Pullman journey, most notably Terry and Karen (my
American parents), Mr and Mrs. Njuguna (Seattle), Christine Odongo, my roommate of over two
years, and Shahriar Safaee, my all-time favorite roommate. To my friends, Zoe, Heba, Javier,
Julie, Winnie, Patience, Peter, Duncan and Cynthia, I value your friendship.
To the Omulo family (the late Joseph Omulo, Monica, Mary, Lucy, Kyle and Kayla) –
you make all this effort worth it. I appreciate you all more than you know.
Most importantly, I thank God, through whom all things are possible.

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DISENTANGLING THE WICKED PROBLEM OF ANTIBIOTIC RESISTANCE

Abstract

by Sylvia Adhiambo Omulo, Ph.D
Washington State University
May 2017

Chair: Douglas R. Call

Antimicrobial resistance (AMR) is currently an urgent public health concern worldwide. For
low-income regions such as sub-Saharan Africa, absence of surveillance data and systematic
investigations of risk factors prevents clear assessment of the impact that AMR has in these
communities. There is also no empirically-based guidance for intervention strategies. In chapter
one, we use PRISMA guidelines to review 116 journal articles from eastern Africa concerning
AMR in people and animals, with the aim of understanding the scale of the problem and
contributors to the problem. Over the last 40 years, AMR has reportedly increased, with
unregulated antibiotic use invoked to explain the high prevalence of AMR in the region.
Nevertheless, we note critical gaps: (i) consistent speculation about the risk factors for AMR
without critical examination; (ii) no standardized system of testing and reporting of AMR data;
and (iii) lack of community-based studies on AMR in people. Chapter two reports the outcome
of two cross-sectional surveys on antibiotic use in an informal settlement (slum) in Kenya.
Results from this survey show that residents generally have limited and inconsistent knowledge
of antibiotics, including a perceived effectiveness of antibiotics for colds and flu. Chapter three
explores how variation in lab resources and deviations from prescribed laboratory protocols
might impact estimates of AMR prevalence. For the set of factors investigated, i.e. culture
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conditions, sample storage, isolate selection and repeated re-isolation, we observe that subtle
variations are unlikely to significantly alter prevalence estimates. In chapter four, we use a
longitudinal study design to examine how sanitation and antibiotic use impact household- and
individual AMR loads in households living within an informal settlement in Kenya. While there
is a relationship between reported antibiotic use and resistance to sulfamethoxazole and
trimethoprim in children, most of the variance in the distribution of resistant bacteria is explained
by sanitation variables. We conclude that although it is possible to design educational
interventions based on our findings (chapter 2), such interventions are not likely to have a
significant impact on community-level AMR when sanitation challenges continue to impact
these communities (chapter 4).
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TABLE OF CONTENTS
Page
ACKNOWLEDGMENTS ............................................................................................................. iii
ABSTRACT ................................................................................................................................... vi
LIST OF TABLES ......................................................................................................................... xi
LIST OF FIGURES ..................................................................................................................... xiii
LIST OF ACRONYMS ................................................................................................................ xv

GENERAL INTRODUCTION ....................................................................................................... 1
1. REFERENCES ................................................................................................................... 4

CHAPTER ONE
1. ABSTRACT ........................................................................................................................ 7
2. INTRODUCTION .............................................................................................................. 9
3. METHODS ....................................................................................................................... 10
4. RESULTS ......................................................................................................................... 12
5. DISCUSSION ................................................................................................................... 15
6. CONCLUSION ................................................................................................................. 22
7. REFERENCES ................................................................................................................. 23
8. APPENDIX ....................................................................................................................... 47
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CHAPTER TWO
1. ABSTRACT ................................................................................................................ 52
2. INTRODUCTION ...................................................................................................... 53
3. METHODS ................................................................................................................. 54
4. RESULTS ................................................................................................................... 57
5. DISCUSSION ............................................................................................................. 61
6. CONCLUSION ........................................................................................................... 65
7. REFERENCES ........................................................................................................... 67

CHAPTER 3
1. ABSTRACT ................................................................................................................ 78
2. INTRODUCTION ...................................................................................................... 79
3. MATERIALS AND METHODS ................................................................................ 80
4. RESULTS ................................................................................................................... 84
5. DISCUSSION ............................................................................................................. 88
6. CONCLUSION ........................................................................................................... 91
7. REFERENCES ........................................................................................................... 92

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