Fleming Fund Stories by Global Health @ Mott MacDonald

Stories THE FLEMING FUND

Contents 4

William Olum

Jinja Hospital

Microbiology

MALDI-TOF

Eme Enkeng

Surveillance

Michael Omodo

William Olum

OUR AIMS

physicians, nurses, surgeons, administrators, pharmacists

William Olum

Encourage clinicians and farmers to use antibiotics better

– to review how drugs are used and prescribed. Their purpose is to reduce wastage, improve drug management

OUR ACTIVITIES

and supply, review trends in antibiotic resistance and

Develop AMR workforce technical capacity

improve hospital infection control.

A few months ago, William took the MTC group to a hospital in the north of the country so they could benchmark their own activities against another facility’s. “The goal was really to improve their understanding and highlight the MTC’s importance. Since that visit people have been really engaged,” he says. “We are also trying to get a small budget from the hospital for our committee to supply tea and snacks during our meetings. Small things like this really help pass the time and encourage attendance.”

Despite William’s tenacity and focus in improving antibiotic use in hospital he says regulations and government The pharmacy, covered in bright yellow paint, juts out

and control (or IPC) programme. “You can’t steward

intervention are vital to long-term success. “I’ve got a plan

towards the front of the Jinja hospital campus. Benches,

medicines well, without IPC,” he says.

for this hospital, but really we need government to control

covered by a zinc roof, shelter patients waiting to receive

access to antibiotics. If we don’t have a disciplined approach

their prescriptions. And two pharmacy officers peer out from

In a back room, behind his office full of cabinets and papers,

to antibiotic use and access as a country, much of the work

small windows at the building’s front, dispensing medicines

is a long thin room with what looks like a chemist’s bench.

we are doing here will not have an effect.”

to the waiting crowd.

This room, where William has been manufacturing alcoholbased hand sanitizer, has been the key to much of the

As a Fleming Fund Fellow, William has big aspirations to

William Olum’s office is at the back of the building. His desk

hospital’s success. In many public hospitals, water sources

improve the use antibiotics around the country. As part of

is covered with stacks of documents, pharmacy manuals

are not always reliable, resulting in abysmal hand-cleaning

the Fellowship, human and animal health professionals are

and a shiny new copy of the Ugandan AMR National Action

rates. However, by sourcing the raw ingredients to make

collaborating (many for the first time) to understand how

Plan. He says his passion for helping others comes from his

an alcohol-based hand rub locally, William has made Jinja’s

resistant bacteria move between animals and humans in

grandfather, a herbalist, who was revered in the community

hand-cleaning rates the best in the country, 51%. He and

Uganda. Over the next few months, William will be mentored

for his cures.

Sofia, who leads the bacteriology unit at the hospital’s

by an antimicrobial pharmacist, which he hopes will take his

medical laboratory, both agree that to save more lives,

initiatives in Jinja to a new level and help establish the type

William is the Head of Pharmacy at the hospital and was

these rates must improve. But supplying hand sanitizer is

of cooperation needed to help clinicians and farmers use

hand-picked by the Ministry of Health to manage the drug

only half the battle, they also have to change behaviour.

antibiotics better.

supply for Jinja. Before he arrived, there was rampant theft of pharmacy drugs and patients weren’t accessing critical

To that end, William has been breathing new life into Jinja’s

medicines. Since he’s been in post, he’s revolutionised the

Medicines and Therapeutics Committee (MTC). MTCs

pharmacy and has also initiated a full infection prevention

bring together practitioners from all parts of the hospital –

Fleming Fund Stories

Jinja Hospital

is done through disk diffusion, a method in which several wafers containing different drugs are placed onto a petri dish full of the bacteria. The dish is then incubated, to give time

“The drugs that are affordable are ineffective.”

OUR AIMS

for the antibiotic on the wafer to work and stop the growth

Equip countries to collect and use data on drug resistance

OUR ACTIVITIES Establish laboratory capacity and surveillance systems

of bacteria in its immediate area. If the antibiotic is effective, it will create a boundary around itself where no bacteria has been able to grow. The larger the circumference of the circle around the wafer, the more effective the antibiotic.

At this hospital, ineffective medicines are an everyday reality. “We don’t always set common antibiotics on the plate because we know they will come out resistant. For example, an antibiotic is resistant if the buffer around the wafer is 15mm, but here on this plate, the buffer is 6mm,” she said.

Many commonly used antibiotics are what clinicians refer to as “broad-spectrum”, meaning they treat a variety of She and her staff run through basic microbiology procedures

classifications of bacterial infections. Doctors frequently

past bright green tea plantations and lush forests, is Jinja.

on each sample including: culturing and incubating

prescribe these medications if their patient’s condition is

The city is most famous for being located at the source

the bacteria, conducting gram stains to determine the

quickly deteriorating or if they are unsure about the correct

of the Nile River, where a giant white cable-stayed bridge

classification of an organism, identifying the bacteria itself

treatment approach. Many of these drugs are on the WHO’s

connects the road from Kampala to the city.

(often through a series of biochemical tests) and testing the

List of Essential Medicines and can be purchased over the

bacteria’s susceptibility to a particular antibiotic (or its ability

counter in the low-income countries for just a few pence.

to be treated by a specific drug).

However, frequent and untargeted use creates resistance.

The local hospital is large. It has some 600 beds, several surgical theatres, a medical laboratory and a tuberculous isolation ward. Hundreds of patients and their families are

Microbiology is highly labour-intensive and for a laboratory

dotted throughout the campus. Relatives sit outside wards,

with only a few automated machines, even more so. The

bringing their family members food, clean water and items

sink in the corner is stained a deep purple from the gram-

like blankets and clothes from home.

stain testing and there are stacks of petri dishes in the incubator. The staff move from the sink to the microscope

The laboratory sits toward the back of the campus where

to an open bench where they plate bacteria onto an agar

crowds of people gather out front to await sample collections

before incubation – sterilising the tools on an open flame.

from the technicians. Inside the lab, Sofia Kasuswa, who heads up the bacteriology unit, has started her daily staff

Growing Resistance

meeting, where she and her team analyse samples and cultures from the day before.

Jinja Hospital

On the shores of Lake Victoria, three hours from Kampala

“Basically, all the samples we get are resistant to about four or five drugs – things like Ciprofloxacin, Cotrimoxazole, Ampicillin (used to treat variety of common infections). The drugs that are affordable are ineffective,” said Sofia. In some cases, the laboratory staff must plate 10-12 different drugs before finding one that is both affordable and effective. The staff say they’ve also found MRSA, better known as the ‘superbug’, in outpatients and in the community.

Evidence for a Healthier World

Testing whether an antibiotic is effective against an infection, (also known as antimicrobial susceptibility testing, or AST)

To curb the spread of resistance, more testing, more data and more awareness is needed, which is exactly what

Fleming Fund Stories

Jinja Hospital

the Fleming Fund supports. In any environment, it can be

too small for a full antibiogram, but on the whole, what we

government action in Uganda and across other countries is

difficult to encourage overstretched doctors to switch from

are seeing is that patient [infections] are resistant to broad

needed to ensure antibiotics are properly used.

syndromic treatment (based on symptoms) to ordering lab

spectrum antibiotics. If people don’t stop misusing these

tests before prescriptions are made. But in Jinja, an active

drugs and prescribing them only when needed, we will have

For Dr Asad and many of his patients in hospital, he knows

Medical Therapeutic Committee is hoping to change that.

nothing.”

without government intervention, his actions won’t lead to lasting change. He said, “One of our biggest challenges is

According to Sofia, a recent Global Point Prevalence Survey, (that analyses how and why medicines are prescribed in

In Jinja, Dr. Asad and his colleagues have adopted the WHO’s

that people can get antibiotics over the counter, without any

hospital) estimated that up to 77% of antimicrobial treatment

AWaRe framework, which instructs doctors to access, watch

prescription. There is also rampant drug misuse in small

in Uganda was based on empirical use - rather than

or reserve certain medicines to reduce broad-spectrum

local clinics. But what happens outside the hospital affects

laboratory testing. Jinja plans to reduce that number to 44%.

resistance. The hospital’s supply chain use the framework

us. If patients come in with resistant infections, it spills over.

and the resistance data to dictate their procurement lists-

We are a community; we all move in the same bus.”

“There are three things we need to do to bring that number

so the most effective and appropriate drugs reach patients.

down,” says Sofia. “Make sure doctors have the microbiology

Significant efforts have also been made to sensitise the

request forms near them, improve our turnaround time and

community to the dangers of antibiotic misuse and staff say

ensure that we provide doctors with preliminary laboratory

that patients are aware of the problem.

results so they can start treating patients right after a gram stain test.”

The final piece of the puzzle is ensuring that data from Jinja and other hospital laboratories reaches governments

In addition, their lab needs a steady supply of reagents and

for policy making. The Fleming Fund’s focus on building

equipment. “At one point we only had 20 glass plates in

national surveillance systems, by equipping countries

the lab, meaning our turnaround time was over three days

to coordinate data collection and analysis will help. But

and doctors stopped requesting testing,” said Sofia. Support from the Fleming Fund will help to change this - ensuring there is a steady supply of reagents, procuring essential lab equipment and exploring possible renovations to the building, like sealing off windows.

Critically, more testing means more data – vital to understanding the patterns of resistance in the local community and for building an antibiogram. Antibiograms are a summary of all the antimicrobial susceptibility testing (AST) results in a particular area or hospital. In short, they provide empirical evidence that helps doctors treat patients better and reveal resistance trends in the community.

Dr. Asad Muhinda, the head of the Medical Therapeutic Committee in Jinja said: “At the moment, our sample size is

Fleming Fund Stories

How does the laboratory process work?

Microbiology

Sample collection. There are several types of sample in

Antimicrobial Susceptibility Testing (AST). This test

human health, including blood, cerebrospinal fluid, stool,

determines which antibiotics are effective at fighting the

urine and genital samples. Each sample type requires a

identified bacteria and can take a further 12-36 hours, as

different type of process and preparation.

it requires additional bacterial incubation. AST can be done through disk diffusion, where paper discs containing different drugs are placed onto a petri dish inoculated with a single bacterial species. The dish is then incubated. If the antibiotic is effective, it will create a boundary around Gram Stain Test. Gram-stain testing differentiates

bacteria into two main categories based upon the contents of their cell wall, Gram-positive and Gramnegative. This is important because based on the type of bacteria, doctors can start to tailor treatment of patients based on the likely infection.

itself where no bacteria has been able to grow. Measuring the size of the area where bacteria canâ&#x20AC;&#x2122;t grow allows the laboratory staff to determine whether an antibiotic is likely to be effective for treating the patient. . Alternatively, AST can be completed through a machine which incubates the samples in plastic panels that include a series of preallocated drugs.

Incubation. Blood cultures are usually collected directly into a special culture bottle. Other samples must be plated out on to solid agar in a petri dish so that individual bacterial colonies can grow. This takes between 12-48 hours.

Microbiology is complex. Understanding the quagmire of information around how to test, when to test, how long to incubate samples and how to decide how to treat patients requires 4-8 years of advanced post-graduate study, which is beyond the scope of a two-page spread.

However, in bacteriology, there are a few key steps that most of the laboratory technicians will follow to test samples. The Fleming Fund supports laboratories and technicians to with equipment and training to ensure facilities can carry out these basic functions.

Separate colonies. Sometimes there are more than one bacteria type in a sample. If that is the case, the different colonies must be plated on to separate, fresh agar plates, so each can be identified independently.

Bacterial Identification. This can be done through a series of biochemical tests, or, in large, modern laboratories, by MALDI TOF mass spectrometry (more on that later).

Fleming Fund Stories

MALDI-TOF

Uganda’s national reference laboratory sits on a hill with a stunning view of green hills and the city in the distance. The building is clean and new, built a few years ago with support from the US Centers for Disease Control and Prevention.

OUR AIMS

The laboratory spans several floors and the bacteriology

Equip countries to collect and use data on drug resistance

unit is well equipped, except for the absence of a MALDI TOF mass spectrometer.

OUR ACTIVITIES Establish laboratory capacity and surveillance systems.

The acronym for MALDI-TOF is intimidating: it stands for matrix-assisted laser desorption/ionization-time of flight. But in short, it works by vaporising bacterial samples into small, charged particles that then “fly” into a vacuum tube. The speed at which the particles fly through the tube allows

MALDI-TOF

scientists to instantly identify the organism with high accuracy because every organism has its own “flight pattern”. To run the machine the laboratory staff pipe a microlitre (that’s onemillionth of a litre) onto a sterile metal plate which is loaded into the machine. They press a button and results pop up on a computer screen within a few minutes.

The

Fleming

Fund

providing

MALDI

TOF

mass

spectrometers in reference laboratories around the world, because they provide extra fast results (in two minutes rather than 18-48 hours), can test 96 samples at a time, and cost only 50 cents a test versus 5-10 USD for standard testing. They are also highly accurate and use far fewer chemicals and disposables.

For national surveillance systems to mature, laboratory results must be regularly quality assured for correctness. And because microbiology is a highly manual process, samples can easily become contaminated, skewing results. The MALDI-TOF will provide a national benchmark for laboratories. Hospitals can regularly quality assure their results at the national reference laboratory, which now has the equipment to ensure testing is accurate.

Fleming Fund Stories

My interest in AMR stems from personal experiences with ineffective drugs. I have seen the health of relatives significantly deteriorate because they could not get drugs effective against their ailment. The Fleming Fund is equipping me with the needed skills for AMR surveillance and data management to help inform policy in the right direction. Charles Emejuru, Nigeria Fellow

Eme Enkeng

different bacteria should be tested against different drugs,

many of her colleagues have high hopes for how she can

depending on their natural resistance.

use her new skills. “The Fellowship has given me a big sense of responsibility, because working at this reference

Intrinsic resistance means that bacteria are naturally

laboratory means we are affecting the whole population

resistant to certain antibiotics. This happens because

when we get it wrong. Doctors can injure patients when

some antibiotics target specific components of a bacteria’s

we make errors.”

structure. For example, bacteria that have no cell wall have intrinsic resistance to an antibiotic that destroys

In the coming months, Eme hopes the knowledge from

bacterial cell walls. “I’ve learned how to do antimicrobial

the Fellowship will help her support the laboratory to

susceptibility testing (AST) completely differently. Our visit

get accreditation and improve the quality management

to our Host Institution [academic mentor] blew our minds.

system, nationally and locally. “When we are up to

There is so much we need to correct,” said Eme.

standard, doctors and laboratories across the country will believe in us.”

She has also become acutely aware of her new position as a leader in the microbiology community in Nigeria. The level of training she has received is unique and

Nigeria’s public health reference laboratory sits just outside

Laboratory. Only the best scientists were chosen for the

the city centre in Abuja. That’s where Eme Enkeng, a medical

move, a decision aimed at improving the whole country’s

laboratory scientist for the Nigerian Centre of Disease

microbiology capacity.

Control, works. Growing up in Lagos, Eme was fascinated by biology, even as a child. “I love biology. I love the colours,

From the beginning, working in Abuja was a learning

the colour changes and seeing how bacteria grows over

experience, she learned new testing methods and

time. It was also always easy for me to understand.”

laboratory skills and was recently awarded a Fleming Fund Fellowship. The Fellowship programme provided her with

She went on to study medical bacteriology because it was

bespoke scientific and leadership training and expanded

a hands-on profession. She could read about a disease or

her perspective on microbiology.

pathogen and then go use a microscope and run tests on in the laboratory. “I prefer seeing, I prefer practical application

“The Fellowship programme has completely changed the

- bacteriology gave me that picture,” she said.

way I think on the job,” she said. In the past, she used to run a standard panel of susceptibility tests to determine whether

After working in Lagos for several years, her managers

a specific drug could be used to fight a particular organism.

saw potential in her and asked if she would move to Abuja,

But through the Fellowship, she has learned about the

Nigeria’s capital, to help set up a National Reference

intrinsic or natural resistance of certain bacteria, meaning

OUR AIMS Build partnerships across governments, sectors and organisations

OUR ACTIVITIES Build AMR workforce capacity

Surveillance

How do you set up an AMR surveillance system?

Surveillance

Get Governance in Order

Surveillance

Develop National Action Plan: Countries develop a

National Action Plan for AMR that outlines the objectives

committee is also formed that can spearhead discussions

systems

for

processing

Analyse and Use Data Locally: Testing results should be

samples, identifying the bacteria, performing antimicrobial

shared locally with clinicians to help them treat patients

susceptibility testing and sending data to the national

better and understand local resistance patterns.

national focal point for AMR, or government epidemiology

Analyse and Use Data Nationally: Results are shared

department).

with the national AMR Coordinating Committee and relevant technical working groups to compare patterns

Develop a Surveillance Strategy: The committee then

drafts a surveillance strategy for human, animal and environmental surveillance of AMR. Reference laboratories,

responsible for supporting surveillance site laboratories across the country, are selected for each sector.

Set up Surveillance Sites

Deliver Equipment & Training: Some surveillance sites

across human and animal health. Analysis should then be

and reference laboratories arenâ&#x20AC;&#x2122;t well-equipped and

provided to policy makers to guide national regulations

require renovations and/or new equipment. Staff must also

around antibiotics.

be trained to ensure they can perform core laboratory functions, including safe and reliable testing on specimens,

Report Internationally: Ideally, all data is also reported

identification

antimicrobial

to relevant international organisations (WHO, OIE) so that

susceptibility testing and collection of basic information of

patterns and trends can be analysed at the regional and

patients, animal herds or farms.

global level. For surveillance in humans, countries should

important

bacteria,

be participating in the WHO Global AMR Surveillance Choose Surveillance Sites: The national AMR committee selects surveillance sites which will collect and process samples and supporting information. For surveillance

Implement Protocols & Standard Procedures: Every

samples are collected as part of routine hospital care. AMR surveillance

responsible

data coordination body (often a technical working group,

and strategy for tackling drug resistance. A national AMR

in humans, these are usually government hospitals and

resistance

are

and take policy recommendations forward.

3 Antimicrobial

sites

involve

ongoing data collection and analysis of the type of bacteria, resistance patterns and use of antimicrobial drugs in humans and animals. Surveillance is important because understanding the patterns and trends of diseases is vital for guiding local treatment practices, monitoring and controlling outbreaks and for making public health policy.

System (GLASS).

laboratory must adhere to and implement biosafety & security guidelines, protocols for carrying out specific tests and general laboratory procedures for data storage, etc. These documents need to be written and implemented for

Surveillance in animals, is usually done on farms or food

each site.

production centres, like markets, abattoirs or processing

Gather & Use Data

plants and is managed by the national Veterinary Services, with the support from their network of laboratories.

Gather & Report Data: After protocols have been

established, bacteriology testing results from surveillance sites are entered into a national database, shared with the national data coordinating body (e.g. a technical working group, the national AMR focal point, or a government

Fully functioning systems should also share data with a

epidemiology unit.)

national coordinating centre so that a central body can develop a national picture of resistance. The Fleming Fund

This body compiles and analyses data to discover national

provides funds to countries to support each step of the

trends. Data should be shared and used locally, nationally

process.

and internationally.

Fleming Fund Stories

Michael Omodo

Michael Omodo OUR AIMS Build partnerships across governments, sectors and organisations

OUR ACTIVITIES Build AMR workforce capacity

decision in life there is always a driving factor behind that

and resistance (starting in chickens) and highlighting

choice,” he says, explaining that his uncle was the impetus

the importance of reducing drug misuse. Investments in

behind his study. “My uncle lives in our village and he owns

training and laboratory equipment will allow staff to gather

cattle, goats and chickens. The first time one of his animals

samples and analyse data, to develop a national picture of

fell sick, he consulted a veterinary doctor. They told him

drug resistance in chickens.

what to do and he bought the drugs. But the second time, because he thought he knew everything, he treated his

An automated susceptibility testing machine and a MALDI-

animals without consulting a veterinarian. A little while

TOF (an instrument that can identify bacteria within two

back I went to see him, and I saw him injecting his animals

minutes, rather than the normal 18-48-hour process) have

with stronger drugs – but they didn’t work, and he lost

been delivered and installed at the site. Michael says these

some of his animals. I told him I’d take samples for him

investments will make a huge difference and will give

and test them in the lab, and I found the pathogens in the

the laboratory and resulting surveillance data enormous

animals were resistant to the drugs.”

credibility. The challenge now, for both Michael and others in the laboratory, is to convince policy makers to turn their

Unfortunately, this is a common story for many farmers in

hard-earned evidence into action and enact regulations to

Uganda. According to the country’s situational analysis

curb misuse of antibiotics in farming.

on antibiotic resistance, antibiotics are frequently used as prophylaxis and as additives in animal feed. Tetracycline and penicillin are the most common antibiotics used,

Uganda’s National Animal Health Laboratory sits right next to Entebbe airport, facing Lake Victoria. Mango trees, wild

The Fellows, comprised of human and animal health

monkeys and the occasional bird are randomly peppered

specialists, are planning to gather some 9000 samples from

around the laboratory’s campus which is getting a huge

livestock and people across Uganda to demonstrate how

face-lift, thanks to investment from the Fleming Fund.

resistant bacteria transfers between humans and animals.

The buildings are being renovated, new state-of-the-art

The ultimate goal, he explains, is to ensure the data is of

equipment is being installed and some of the staff are

sufficient quality for policy making as it is only through

receiving on-going mentorship and training from global

regulation that the country can curb misuse of antibiotics

animal health experts as part of the Fleming Fund Fellowship

which leads to resistance.

programme. Throughout the world, a larger quantity of antibiotics is used In one of the rooms, Michael Omodo, is busy with a team

in animal rearing than in human health, which means curbing

of researchers preparing for an influx of samples from his

drug misuse and overuse in animals is critical to tackling

Fellowship project. Michael is a laboratory scientist with

resistance. For example, according to the UK’s AMR Review,

a background in animal health and has been working for

published in 2016, 70% of all antibiotics in the US are sold

the Ministry of Agriculture for nearly 10 years. He and his

for animal use.

colleagues from the Fellowship programme are being mentored by experts from the University of Edinburgh, in the

Michael’s interest in studying antibiotic resistance comes

UK and are starting work on their final collaborative project.

from direct experience of drug misuse in animals. “For every

but farmers rarely consult veterinary services and few laboratories are available to analyse samples from sick animals.

A lack of veterinarians and laboratory analysis services mean that AMR surveillance in animals is also rare. Across the country there is less investment in supporting animal health services than human health services. And surveillance efforts in animals are primarily targeted at zoonotic viruses or diseases which cause the most harm in animals. For example, foot and mouth disease in livestock, can cause lameness, a significant reduction in milk production and occasionally death in animals, but does not easily transfer to humans. In contrast, animals carrying E. coli bacteria may show no signs of illness, yet dairy and meat products, contaminated by faeces from that animal could cause sickness in humans. The Fleming Fund’s investment in Uganda aims to tackle those issues by boosting surveillance of antibiotic use

My passion for AMR arose when I lost my beloved father to multi-drug resistant tuberculosis. As a veterinarian and an epidemiologist with great passion for public health, I have always believed bridging gaps and understanding major health problems such as AMR is a task bothering the academia, public health institutions and the world at large. Oluwadamilola Abiodun-Adewusi, Nigeria Fellow