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The impact of digital technologies on point-of-care
diagnostics in resource-limited settings
Natasha Gous, Debrah I. Boeras, Ben Cheng, Jeff Takle, Brad Cunningham &
Rosanna W. Peeling
To cite this article: Natasha Gous, Debrah I. Boeras, Ben Cheng, Jeff Takle, Brad
Cunningham & Rosanna W. Peeling (2018): The impact of digital technologies on point-of-
care diagnostics in resource-limited settings, Expert Review of Molecular Diagnostics, DOI:
10.1080/14737159.2018.1460205
To link to this article: https://doi.org/10.1080/14737159.2018.1460205
Published online: 10 Apr 2018.
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2. REVIEW
The impact of digital technologies on point-of-care diagnostics in resource-limited
settings
Natasha Gousa
, Debrah I. Boerasb,c
, Ben Chengc
, Jeff Takled
, Brad Cunninghama
and Rosanna W. Peelinge
a
Global Health Department, SystemOne LLC, Johannesburg, South Africa; b
Global Health Impact Group, Atlanta, GA, USA; c
International Diagnostics
Centre, London, UK; d
Global Health Department, SystemOne LLC, Springfield, MA, USA; e
Department of Clinical Research, London School of
Hygiene and Tropical Medicine, London, UK
ABSTRACT
Introduction: Simple, rapid tests that can be used at the point-of-care (POC) can improve access to
diagnostic services and overall patient management in resource-limited settings where laboratory
infrastructure is limited. Implementation of POC tests places tremendous strain on already fragile health
systems as the demand for training, supply management and quality assurance are amplified. Digital
health has a major role to play in ensuring effective delivery and management of POC testing services.
Area covered: The ability to digitise laboratory and POC platforms, including lateral flow rapid
diagnostic test results, can standardize the interpretation of results and allows data to be linked to
proficiency testing to ensure testing quality, reducing interpretation and transcription errors. Remote
monitoring of POC instrument functionality and utilization through connectivity, allows programs to
optimize instrument placement, algorithm adoption and supply management. Alerts can be built into
the system to raise alarm at unusual trends such as outbreaks.
Expert commentary: Digital technology has had a powerful impact on POC testing in resource limited
settings. Technology, markets, and medical devices have matured to enable connected diagnostics to
become a useful tool for epidemiology, patient care and tracking, research, and antimicrobial resistance
and outbreak surveillance. However, to unlock this potential, digital tools must first add value at the
point of patient care. The global health community need to propose models for protecting intellectual
property to foster innovation and for safeguarding data confidentiality.
ARTICLE HISTORY
Received 27 November 2017
Accepted 29 March 2018
KEYWORDS
Digital technology;
connected diagnostic
system; health system
strengthening; quality
assurance; data governance
1. Introduction
Infectious diseases impose a huge burden in the developing
world. Every year, millions of people worldwide die from infec-
tious diseases such as human immunodeficiency virus (HIV),
tuberculosis (TB), malaria, pneumonia, and diarrhoea [1].
Diagnostics play a critical role in clinical decision-making and
disease control and prevention. Sensitive and specific laboratory-
based diagnostic assays are commercially available for the detec-
tion of most infectious diseases of public health importance, but
they are costly and often not accessible to patients in the devel-
oping world where laboratory services are often limited.
Laboratory networks in resource-limited settings (RLS) may
struggle with sustaining the basics needed to support centra-
lized testing, and infrastructure for surveillance of infectious
pathogens, and outbreak detection and response, is often
lacking.
Point-of-care (POC) testing (POCT) refers to testing that can
be performed at the site of patient care and can improve
access to diagnostic services, turnaround time for results,
and overall patient management. The development and
deployment of simple, rapid tests and devices that can be
used at the POC to screen for HIV, diagnose TB, and guide
malaria treatment has led to significant reductions in
morbidity and mortality in the developing world where access
to laboratory services is limited. However, despite its many
benefits, a number of challenges exist, mostly related to the
quality of tests and of decentralized testing, the management
and oversight of POC programs, and the high cost and utiliza-
tion of POCT services [2,3].
The Joint United Nations Programme of HIV/AIDS (UNAIDS)
have a set of ambitious targets for HIV known as the 90-90-90
targets, calling on countries to ensure 90% of infected indivi-
duals know their HIV status, 90% of those known to be
infected are on antiretroviral treatment (ART), and 90% of
those on treatment are virally suppressed by 2020 [4].
Attainment of these 90-90-90 targets depends on increasing
access to POC tests for marginalized and hard-to-reach popu-
lations, POC molecular assays for early infant diagnosis (EID),
and HIV viral load (VL) monitoring. Similarly, the global com-
mitment to eliminate mother-to-child transmission of HIV and
syphilis requires ensuring access to POC tests for screening
pregnant women at every antenatal clinic [4]. In 2015, coun-
tries committed to a Sustainable Development Agenda with
17 Sustainable Development Goals (SDGs) calling for the
United Nations and its partners to build a better world with
no one left behind [5]. The efforts toward Universal Health
CONTACT Rosanna W. Peeling Rosanna.peeling@lshtm.ac.uk Department of Clinical Research, London School of Hygiene and Tropical Medicine, Keppel
Street, London, UK
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, 2018
https://doi.org/10.1080/14737159.2018.1460205
© 2018 Informa UK Limited, trading as Taylor & Francis Group

3. Care coverage to achieve the SDGs will need to be under-
pinned by affordable and accessible POC tests.
The WHO End TB Strategy, that aims to bring the global
TB epidemic to an end by 2035, is the first to acknowledge
the role of digital health in ensuring more effective and
efficient service delivery and ultimately achieving global
health targets [6]. Digital health refers to the convergence
of information technology, digital media, and mobile
devices with health care and is enabling patients and
health-care providers easier access to data and health
information in order to improve quality and outcomes [7].
Various digital technologies, including but not limited to,
connected diagnostics devices, decision support systems,
mobile health Applications (Apps), connected biometric
sensors, and electronic health records [8], are able to gen-
erate and transmit electronic data (whether it be wirelessly
or by wired connection) to the Internet to digitally report
results in real time and hold great promise to improve the
efficiency of the health-care system.
With the increasing demand for POC diagnostics, the con-
vergence of digital technologies with a range of POC plat-
forms that vary from simple rapid diagnostic tests (RDTs) in
lateral flow formats to POC molecular devices is transforming
patient care and disease surveillance in RLS beyond that of
data transmission. This review presents the potential impact
and benefits of digitizing POC diagnostics in RLS by discussing
the role of digital technologies in improving linkage to care
and data collection, optimizing placement and usage within
the health-care system, facilitating outbreak control and
remote program management, addressing quality concerns,
and improving overall return of investment for programs and
funders. The review also highlights the importance of data
governance frameworks for effective data management
when considering digital technologies.
2. Digitizing POCT programs
2.1. Application to rapid diagnostic testing
RDTs are a double-edged sword. While RDTs can greatly
improve access to testing services, the implementation of
RDT programs places tremendous strain on already fragile
health systems as the demand for training, supply chain man-
agement, and quality assurance are amplified. RDT results
have to be read visually and this subjective interpretation
can result in reader variation in interpretation of results.
New innovations and strategies to digitize RDT result inter-
pretation using optical readers and mobile phones may
improve the interpretation and allow result data to be trans-
mitted in an electronic format. FIONET (Fio Corporation,
Toronto, Canada), as an example, combines a device-based
RDT reader, termed Deki, with a configurable cloud informa-
tion system to ensure that program managers can remotely
monitor field activities and performance. This system has been
deployed in Ghana to collect data on malaria RDTs as well as
microscopy results for quality and comprehensive reporting
[9]. The Deki Reader provides guidance on the testing process
and objectively interprets RDT results based on line intensity
thus reducing or eliminating common processing errors and
improving diagnostic accuracy. In Cameroon, the Deki Reader
is showing potential for strengthening their RDT malaria pro-
gram and initial trials demonstrated >98% agreement with
visual result interpretation of malaria RDTs [10].
Similarly, for HIV, RDTs are the critical entry point for the
HIV treatment and care cascade and the cornerstone of
national reporting on country epidemiological and surveil-
lance data. However, although the HIV RDT is one of the
easiest and least expensive tests to perform, it has been
shown to pose great challenges with regards to ensuring
compliance to the testing algorithm, external quality con-
trol, and accuracy of reading the visual result [11–13].
Various mobile applications have been developed, or are
in development, for application to HIV RDT programs in RLS
to improve the overall quality and reliability of results
(Table 1) [14]. One such platform, developed by Global
Solutions for Infectious Diseases, is an App-based reader
that was piloted in Zimbabwe for HIV and malaria test
result interpretation and real-time reporting [15]. By
uploading test result images through the App, the central
laboratory is able to monitor nurses test administration and
quickly identify issues related to result reporting and data
collection.
Electronic self-testing instruments for sexually transmitted
infections (STI) are also in development [16]. The UK Clinical
Research Collaboration Translational Infection Research
Initiative Consortium is supporting research to reduce burden
of STI (current test for chlamydia) by developing rapid POC
tests that can work with a noninvasive, easyto-use sample
collection device (p-stick) – 4 mL urine, vaginal swab for
Table 1. Examples of automated RDT readers either commercially available or in
the developmental pipeline.
Reader Reader format Data format
Deki Reader (Fio
Corporation,
Toronto, Canada)
Commercially available,
universal device-based
reader that can
interpret commercially
available RDTs
Results can be
automatically
transmitted to
FIONET cloud
database via 3G or
Wi-Fi
Infectious Disease
Reader (iStoc,
Koulukatu, Finland)
Commercially available,
universal reader
consists of software
that runs on standard
smartphone or iPad
Results can be sent to a
Immediate
Diagnostics and
Analytics (IDA) cloud-
based server
Holomic LLC (Holomic,
Los Angeles, CA,
USA)
Commercially available,
universal reader that
consists of an
attachment that clips
onto a mobile phone
An application on
phone transmits data
to a central server
and can interface
with Holomics Cloud
mReader
(MobileAssay™,
Denver, CO, USA)
Commercially available,
universal reader that
consists of software
that runs on a standard
smartphone or iPad
device
Results can be uploaded
via Wi-Fi or cellular
network to Mobile
Assay cloud server
Global Solutions for
Infectious Diseases
system (University of
Washington, Dimagi,
Boston, MA, USA)
Universal reader consists
of software that runs
on standard
smartphone or iPad.
SIM card can be used to
store and transmit
results
NovarumDx (BBI
Solutions and
Albagaia, Scotland
and Wales, UK)
Commercially available,
customizable software
that runs on a
smartphone device
Results can be
transmitted to a BBI
server
RDTs: rapid diagnostic tests.
2 N. GOUS ET AL.

4. females with a time to result of 30 min. Patients are then
linked to an electronic pathway for treatment and contract
tracing without having to see a doctor.
In general, automated RDT readers, through their ability to
capture, digitize, and transmit RDT results, will have a critical role
to play in not only strengthening data collection and manage-
ment for RDT programs but also improve the overall quality of
POC RDT testing and surveillance efforts [14]. Thus, it seems that
investments in digital technologies to enhance visual readings of
lateral flow assays and improve result reporting could provide
huge returns on investment for RDT programs.
2.2. Application to POC molecular diagnostic platforms
Underneath a medical instrument’s diagnostic result is a rich
set of sub-result data (‘deep instrument data’) that are still
largely untapped as a resource. Pathogen or human genetic
profiles, thermal temperatures, cycle threshold (Ct) values, and
similar data are merged, analyzed, and distilled into a ‘Positive’
or ‘Negative’ result in many instruments and this is typically
where the health-care system steps in to take action. But those
genetics, temperatures, curves, and values indicate clusters of
genetic mutations when matched to age, sex, or prior treat-
ment history; or over time can indicate an emerging resistance
to antibiotics in a rural province; or when married to treat-
ments and outcome monitoring, hold the potential for perso-
nalized medicine. Accessing this data was impossible before as
the data were either entirely inaccessible or manually imprac-
tical to record, e.g. thousands of interim measurements that
compile a curve.
However, through emerging digital technologies in the new
generation of POC molecular devices (most have inbuilt con-
nectivity capabilities), the ability to natively collect electronic
diagnostic and deep instrument data is now possible. Programs
with connected diagnostic platforms are able to remotely col-
lect data coming from both decentralized POC technologies
and readers in near real time. These data can potentially be
merged through a middleware solution and linked to Ministries
of Health (MoH) and used to provide critical information on
testing coverage, disease trends, epidemiological surveillance,
supply chain management, and quality monitoring of the tests
and testing process (Table 2) across national programs, as well
as international systems thus increasing the efficiency of health-
care systems and improving patient outcomes.
In RLS, these advances can also form the basis of early warning
systems to optimize control and elimination interventions
through building in automated alerts to raise alarms for outliers
and erroneous results and to monitor the performance of
instruments.
With Global Positioning System data transmission capabil-
ities, diagnostic data can be linked to geographical locations
to report national and global testing trends to central data-
bases to optimize programs, report on outbreaks, inform dis-
ease control strategies, and monitor progress towards
elimination. Geographic Information Systems (GIS) are also
being used to map existing laboratory networks, collect infor-
mation on testing volumes and needs, in order to appropri-
ately place POC instruments within the network, and improve
the overall health system. Such systems can also be used for
tracking progress towards elimination of diseases.
3. The impact of digital technologies on POCT
programs
3.1. Rapid return of diagnostic results and linkage to
care
Reduced time to diagnosis and rapid treatment initiation have
been shown to improve TB patient outcomes and reduce
transmission rates [17]. However, one of the weaknesses of
many health systems is that they are oftentimes not equipped
to support rapid diagnostic systems, such as the GeneXpert,
with prompt return of patient results and thus end up negat-
ing the impact of the technology [18,19]. This is especially
pertinent with many countries opting for centralized
GeneXpert testing. Although laboratory turnaround times are
short, the return of paper-based results back to referring
clinics has been reported to delay patient initiation onto
treatment [20]. Even though POCT is designed to provide
rapid return of results during the patient visit, a few studies
have shown that in reality, same-day results are not always
possible due to device throughput, logistics, and clinical work-
flows [21,22].
Thus, one of the most compelling arguments for digital
technologies is the capability to return diagnostic test results
to the health-care provider or even the patient, in real-time,
via short message service (SMS) or e-mail notifications to link
them to care. An exciting application of this is in HIV RDT self-
testing programs. The standard algorithm for HIV diagnosis is
Table 2. Summary of the potential impact of digitizing data on POC
technologies.
Parameters Local impact Health system impact
Rapid return of
diagnostic
results
Reducing time for
management of patients
Increasing health systems
efficiency
Improving data
quality/
reliability
Reducing transcription
errors
Monitoring POC
instrument
placement and
utilization
Reduce stock outs by
optimizing instrument
placement and supply
management
Quality assurance Improving diagnostic
accuracy by linking
proficiency results to
testing centers allows for
corrective action and
remedial training
Improving patient
outcomes
Monitoring
adherence to
diagnostic
algorithms
Improving the correct use
of diagnostics to guide
patient management
Alerts for unusual
trends
Faster recognition of
emerging or reemerging
health security issues
Allowing timely
surveillance and alerts
for outbreaks and
antimicrobial resistance
POC instrument
operation
Alerts for instrument errors Facilitates innovation;
improving return on
investment on POC
instruments
Alerts for instrument
breakdown
Reminders for
maintenance and
warranty
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS 3

5. two sequential RDTs; one for screening and one for confirma-
tion. For HIV self-testing, the same algorithm applies but, in
this case, the person self-tests in private and needs to be
linked to care for their confirmatory testing. New digital inno-
vations, such as the HIVSmart! App developed by McGill
University, allow persons to download an open-source App
on their mobile phone, which provides guidance on testing
and result interpretation, educational information and
attempts to link positive patients to health-care facilities to
ensure confirmatory testing [23].
In Nigeria, the GxAlert connectivity platform by SystemOne
(Boston, MA, USA) is being used to reduce the turnaround
time for reporting of GeneXpert multidrug resistant (MDR)-TB
results, whether they initiate from centralized or POC sites, to
the TB government supervisor, state program manager, and
national program enrolment officer [24,25]. Since implementa-
tion of the GxAlert system for real-time reporting of drug
resistant-TB results via SMS alerts, the proportion of patients
initiated onto treatment has significantly increased from 20%
in 2014 to 85% in 2015 [11].
A further concern with POCT is that results are often not
captured electronically, and once the patient leaves the health
facility, are no longer available for reporting, statistical analy-
sis, monitoring, and billing purposes [26]. Traditionally, POC
results are manually captured in paper registers that may or
may not be transcribed into the laboratory information system
(LIS) or electronic medical record (EMR). The advantage of a
connected POC device is that results will automatically be
incorporated into the LIS or EMR to ensure better manage-
ment, faster response, automated billing, and inclusion of data
for reporting.
3.2. Improved data quality
To ensure the appropriate planning, monitoring, and resource
allocation to meet global HIV and TB diagnostic and treatment
goals, the need for collection of data representative of the
populations being served, as well as geographic locations of
services being offered, is imperative to understanding pro-
gram performance and future planning needs [27]. It is
worth noting, however, that nationwide EMR or nationwide
LIS are generally not present in the developing world and
continue to have little penetration. Lacking a nationwide
underpinning of these systems, which typically capture demo-
graphic patient data, treatment history, and other important
metadata about a patient or diagnosis, emerging connectivity
solutions are filling those gaps by making modest adjustments
to which data are collected at the diagnostic instrument itself.
By prompting the capture of additional information alongside
the diagnostic test result, for example, indicators such as
gender, age, HIV/TB status, previous treatment history, and
referring facility, programmatic reporting is enriched and
allows monitoring of which populations are being reached
and those that are missed. As an example, the National TB
program in the Philippines is capturing very granular data
alongside their GeneXpert TB results such as gender, age,
specimen, and facility details, etc. and in doing so, is collecting
a rich data set to improve on their programmatic reporting.
Capture of this information is facilitated through GxConnect
(SystemOne), a small piece of software installed on the
GeneXpert instrument which is able to collect these custom
fields together with the TB result, transmit it to the in-county
server and then displays all data on the GxAlert dashboard.
Program managers can remotely monitor what populations
are being tested and where, identify gaps, determine if inter-
ventions are working and further intervention needs.
3.3. Optimizing POC technology placement and remote
oversight
Countries often struggle with the optimal placement of POC
instruments. When the decision to adopt a new digital tech-
nology is made, it is important to understand the necessary
infrastructure and systems needed to maintain these new
technologies and ensure optimal usage. Most POC devices
for CD4 enumeration, as an example, have inherent connec-
tivity capabilities but countries have lacked the necessary
resources to support the information technology and trouble-
shooting, such as lack of data plans and skilled human
resources. This resulted in inappropriate placement of devices,
inoperative devices, and fragmented laboratory networks. In
South Africa, the National Health Laboratory Service gathered
electronic data on CD4 testing volumes, instrument place-
ment, and GIS-mapped clinical locations to develop a tiered
CD4 testing model, incorporating both centralized and POCT
[28]. Through this model, they have successfully managed to
improve not only the turnaround times for CD4 service deliv-
ery but also have the potential to save in HIV programmatic
costs.
The ‘optimal’ pace for adding new instruments into a
country should be a balance between the need to increase
catchment, the speed with which underlying demand genera-
tion strategies are employed (e.g. clinical sensitization and
specimen referral), and the rate at which the population of
instruments’ utilization rate climbs.
Lack of reporting on commodity consumption can also
result in major stock outs and delays in issuing of new stock,
leading to instrument downtimes, as was experienced in
Kenya during the rollout of the Pima™ CD4 (Alere
Technologies, GmbH) and BD FACSPresto™ CD4 devices (BD
Biosciences) [29]. Test purchasing and consumption rate can
also be tracked in real time against purchases using connec-
tivity software if procurement data are captured and can help
avoid interruptions in service delivery and wastage of
resources [27].
For example, by analyzing the average useful life left in
Xpert® MTB/RIF cartridges at the time they are consumed, the
government can extrapolate whether they are purchasing fre-
quently enough or receiving stock with sufficient lifespan
remaining to prevent expired cartridges. Ideally, one would
want to see smaller more frequent procurements to ensure
fewer stock outs (Figure 1).
Similarly, the monitoring of instruments or modules on a
monthly basis quickly allows central program managers to
identify if a diagnostic instrument is out of service and prompt
appropriate action (Figure 2). Interruptions in diagnostic test-
ing may be due to several possible causes, including
4 N. GOUS ET AL.

6. instrument failures, laptop/computer issues, or test/consum-
able stock-outs, absence of testing personnel, and each will
display a different pattern of interruption. If diagnostic
instruments are connected, these patterns can be identified
and rectified [30]. This would allow automated notifications to
the in-country service provider to fast track and improve
Figure 1. Cartridge useful life left. Red bars indicate Xpert cartridge stock with less than 2 months to expiry. Green bars indicate stock with more than 6 months
expiry. By monitoring useful life, test purchasing practices can be better informed. (a) When smaller, more frequent purchases are made, stock is less likely to expire
before use, but this will have supply chain and logistical implications. (b) Larger, less frequent purchases may result in stock expiring before it can be used. Full color
available online.
Figure 2. Monitoring of instrument down-time: Stoppages in testing can easily be identified and prompt investigation as to possible causes.
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS 5

7. service and maintenance and facilitate backup plans such as
reallocation of samples to other laboratories for testing.
3.4. Quality assurance
Ensuring the accuracy of diagnostic testing improves patient
outcomes. The quality of tests and testing can be monitored
through the use of external quality assessment (EQA) or
Proficiency Testing (PT). EQA for POCT is often difficult due
to a range of factors including the cadre of staff performing
the EQA (non-laboratory or non-technical), difficulty in ensur-
ing compliance with EQA schedules and protocols, obtaining
EQA results back in a timely manner, and reporting back to
POC sites [31]. Connectivity solutions that can link EQA/PT
results to POCT sites would allow assessment of adequacy of
training, need for corrective action and/or remedial training,
and should be seen as a complementary approach to EQA
[32,33]. This is especially important in POC sites with high staff
turnovers.
The benefit of having connected POC devices was demon-
strated in Zimbabwe for managing their CD4 EQA program.
Usually, the Pima CD4 EQA program is a time-intensive pro-
cess requiring sample shipping to remote sites, testing and
reporting back to the central facility, a process which can take
up to 12 weeks [33]. In 2015, an automated EQA program was
piloted with Oneworld Accuracy, whereby an application pro-
gram interface for their informatics system, OASYS (Oneworld
Accuracy System), was developed to automatically query Alere
Data Point every hour for any new data that had been identi-
fied as an EQA sample. This automated system resulted in a
significant reduction in time to reporting, with Oneworld
Accuracy receiving EQA results within 60 min of the test
being performed on the PIMA [33].
Monitoring of device errors is also an important way to
monitor the quality of POCT programs. As with laboratory test-
ing, errors can occur during any stage of the POCT process and
much focus has been applied to the analytical and post-analy-
tical phases. Connected POC devices allow remote monitoring
of test failures or unsuccessful tests (operator and instrument
errors, no or invalid results). Instrument failure rates can vary
significantly within countries, across instruments, regions, or
time. Given the ability to have all unsuccessful test data auto-
matically reporting to a server allows central monitoring of
distribution, frequency, and trends. These data can be visua-
lized down to a peripheral site-level and on a per user basis,
without ever having to travel to those sites and without the
missing or erroneous data typical of paper-based self-reporting.
General patterns exist in terms of expected errors, what per-
centages to anticipate, and what remediation might be most
effective. Figure 3 illustrates how monitoring of error rates by
testing sites over a specific period of time can facilitate rapid
identification of problem sites and (automatically) trigger an
investigation into potential causes [34].
This process can serve to proactively alert National
Reference Laboratories (NRLs), quality assurance teams, and
partners when an instrument is ‘out of the norm.’ The cate-
gorization of errors according to their cause (instrument, user,
assay) is also an important activity for NRLs to facilitate rapid
response and implement corrective actions.
3.5. Monitoring adherence to diagnostic testing
algorithms
Through a connectivity system, a health-care system can moni-
tor the adoption of new algorithms and report on the interven-
tion to determine if it is being implemented appropriately,
Figure 3. Bar chart showing the diagnostic instrument error rates for 16 laboratories over a specific time period. Red bars show laboratories with higher than the
average national error rate of 6.3% (grey line), whilst green bars depict laboratories performing below the acceptable benchmark of 5% (green dashed line). Full
color available online.
6 N. GOUS ET AL.

8. whether it is cost-effective, and what other factors are needed
for implementation to be successful [35]. Connectivity can also
inform scalability and adoption of a diagnostic program by
providing information on adherence and/or any deviations at
a country, regional, or site level [36]. The Global Laboratory
Initiative has stated that the GeneXpert TB diagnostic algorithm
should be dictated by the epidemiological disease profile of the
country [37]; however, a few studies in Africa have shown poor
adherence to TB diagnostic algorithms [38–40].
Figure 4. Example of how a connectivity solution can facilitate monitoring of a new diagnostic algorithm adopted within a given country. One would expect to see
variability in certain indicators, in this case TB positivity rates, at programme adoption (2013) due to unfamiliarity and novelty of the diagnostic algorithm. However,
as the programme evolves and compliance with the algorithm is achieved, the TB positivity pattern should become more uniform and meet expected rates (2016).
Figure 5. Identifying outliers. Scatter plots can be used to identify whether indicators such as TB and Rifampicin resistance fall within expected rates for given
countries/regions/laboratories.
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS 7

9. To illustrate, Figure 4 shows the adoption of the GeneXpert
MTB/RIF® assay as the national first-line TB diagnostic in a new
setting. Connectivity was instrumental for monitoring specific
indicators. For example, connectivity monitored if the pre-
sumed TB or MDR-TB prevalence is within the range expected
[41] given the new intervention, and hence if the country
algorithm is being followed.
By delving deeper and observing data on a per-facility
basis, one can quickly identify outliers or particular testing
sites that are not following the diagnostic process appropri-
ately, i.e. if their rates of disease do not fall within expected
ranges (Figure 5). For example, if an instrument or site is
focused on screening all prisoners for TB regardless of whether
they are symptomatic or not, one would expect that site to
have very low TB positivity rates. In contrast, sites attached to
MDR treatment wards or in-country algorithms using the
GeneXpert primarily for rifampicin resistance confirmation
would display very high TB positivity and rifampicin resistance
rates several times higher than the average. Rates falling out-
side of expected ranges could therefore prompt further inves-
tigation. Ideally, if all instruments in all countries were
reporting to a connected diagnostic solution, the algorithm
could be much more precise, country-specific, and evolving as
the situation evolves. This is the focus of some connectivity
software platforms like GxAlert™ that are not only connecting
the GeneXpert for TB diagnosis, but also the GenoScan for
Line Probe Assay (Hain LifeScience, GmbH) drug resistance
testing and MGIT liquid culture system (Becton Dickinson) for
monitoring response to treatment. Under a Challenge TB pro-
ject in Mozambique, the integration of all three TB diagnostics
within the algorithm will allow the treatment cascade across
instruments to be looked at in more detail and provide a
unified view of drug resistance by tracking patients using a
connected diagnostics patient ID solution.
3.6. Harnessing the power of digital technologies for
global health security
Outbreak response and real-time disease surveillance are an
urgent global health priority. The Ebola crisis of 2014–2016 is
just one example of a global health crisis that served to demon-
strate the importance of integrating digital technologies with
the new generation of POC molecular tests that are highly
sensitive and specific. During the outbreak, GeneXpert devices
located in mobile laboratories in Guinea and Sierra Leone were
interfaced to GxAlert. This enabled automatic, real-time report-
ing of positively identified cases directly to the laboratory
directors via SMS and e-mail alerts giving key decision-makers
accurate, reliable, and timely information, improving the time
to coordinate a response. Similarly, digitized data from antimi-
crobial resistance (AMR) surveillance testing within a connected
national surveillance system would allow real-time monitoring
of the impact of antibiotic stewardship strategies and contin-
uous improvement and optimization.
Another benefit of these digital tools is the ability for a
country to set outbreak algorithms to automatically trigger
based on statistical anomalies in disease data [42] or too
many diagnostic results falling outside of preset criteria.
Responding immediately – literally within seconds of a
confirmed diagnosis – helps the health-care system respond
faster and interrupt person-to-person transmission. Tracing of
infected contacts and containment of infected persons
becomes exponentially more difficult and expensive with
each passing day and the ability to have a latent early warning
system running in the background can save valuable days that
can be used to address the outbreak at 0 instead of Patient 231.
In Nigeria, a mobile App, dashboard, and GIS mapping tool
have been used to speed up the timeliness of reporting and
communication for new Ebola case detection and response
[43]. Since implementation of this system, improvement has
been seen in reporting of daily follow-ups of contacts, turn-
around time between identification of symptomatic contacts
and evacuation, and reporting of laboratory results.
Furthermore, although many information systems exist today
to monitor infectious disease outbreaks, they rely on manually
reported information and, as the prior Ebola, H1N1, SARS, and
various other outbreaks repeatedly demonstrate, the decision to
declare an outbreak has been constrained; either the data was
not of sufficient quality to merit a political response sooner, or
the data was ‘shaped’ prior to public release in order to minimize
the political or economic penalty for being ‘an Ebola country’
[44]. Connected diagnostics equip all stakeholders with the
same, unadulterated set of information against which to coordi-
nate and take action; namely the actual phenomenon of an
outbreak as it happens, rather than personal reporting and
interpretation of the outbreak after it happens.
Connected diagnostic systems can also improve a county’s
ability to monitor disease trends and inform intervention
needs. In South Africa, the GeneXpert Xpert MTB/RIF national
testing footprint is connected to the in-country LIS, allowing
diagnostic and operational data to be collected centrally. The
National TB program is using this data, specifically the Ct
values, as an audit indicator for program and laboratory per-
formance as well as identifying variability in bacterial burden
and clusters of drug resistance [45]. Not only does this allow
the program to monitor and improve on algorithm adherence
but also improves upon molecular surveillance. Similarly, a
spatial decision support system is being used in the South
West Pacific to automatically locate and map the distribution
of confirmed malaria cases in order to rapidly identify hotspots
for transmission and guide response efforts [46].
3.7. Improving return of investment of a diagnostic
instrument
The benefits of a connected diagnostic platform also become
apparent in the ability to inform programmatic implementa-
tion of new diagnostic purchases. Typically, POC programs and
diagnostic networks, in general, have been plagued by over-
capacity and underutilization of instruments [47]. Between
2011 and 2013, a survey of HIV VL, EID, and CD4 instrument
availability and utilization was conducted in 127 WHO coun-
tries [48]. Major gaps were found; underutilization of VL and
CD4 instrumentation was widespread, with only 13.7% utiliza-
tion of CD4 capacity and 36.5% utilization of VL capacity being
reported in 2013 [48].
8 N. GOUS ET AL.

10. The ability to monitor utilization rates in real-time can pro-
vide important insights into appropriate purchasing models for
instruments and consumables, as well as identify where alter-
native investments into infrastructure or specimen transport
may be more pertinent. In general, utilization rates will differ
by country but tend to cluster into three distinct categories: (1)
countries accelerating instrument utilization, (2) countries that
have hit a ceiling in instrument utilization, and (3) countries that
are lagging or declining in instrument utilization (Figure 6).
A country showing an upward trend in utilization may indi-
cate that new instruments introduced into this system are
being adopted more quickly and effectively due to leveraging
of the existing infrastructure; countries with declining utiliza-
tion rates may be suggestive that too many instruments are
being purchased too quickly for appropriate absorption into
the health-care system. In this case, it may be prudent to
channel investments into improving and strengthening under-
lying demand such as improving specimen referral and trans-
port systems or clinical sensitization programs.
Over the last 60 years, rapid advances in portable commu-
nications devices such as the smart phone have improved the
speed, efficiency and cost of data acquisition, processing and
storage. Mobile phones are now in widespread use, even in the
hardest to reach areas. Smartphone-based devices with the
ability to power and interpret serological assays in microfluidic
formats have been developed and are in clinical trials [49,50].
Smartphone-based molecular assays are now under develop-
ment. Test results can be displayed on the smartphone as well
as transmitted to a central database. These are suitable for self-
use or by health providers in a facility or in a community setting.
Testing using these smartphone-based diagnostic devices will
complement laboratory-based diagnostic testing system, espe-
cially for outbreak investigations.
4. Data governance
Any private or public legal entity processing or storing perso-
nal information needs to do so in an appropriate manner to
protect the right to privacy of the individuals [51]. Diagnostic
and patient identifiable information falls under this category,
and as such, a burden of responsibility is placed on protecting
this information. The South African Protection of Personal
Information (POPI) Act [52] provides (in part) some clarity:
To promote the protection of personal information processed by
public and private bodies; to introduce certain conditions so as to
establish minimum requirements for the processing of personal
information.
As present, in all industries influenced by continuous advances
in information technology, the regulatory and legislative fra-
mework which governs the process will always lag behind the
current state of technology. Legislation simply cannot be
updated at the same rate as technology progresses; and this
is a common threat across many industries.
The major governance frameworks which influence the con-
nected diagnostics industry are General Data Protection
Regulation (GDPR) [53], Data Protection Act [54], POPI [52], and
the Privacy Shield [55]. All four of these frameworks span from a
similar purpose and reflect minor differences in the nuances
around the terminology and processes, with the same goal in
Figure 6. Illustrative example of trends in diagnostic instrument utilization for the GeneXpert. The bar chart plots the average number of tests performed (Y axis) per
instrument per month (X axis). A theoretical maximum utilization of 200 tests is used as the benchmark for a four module GeneXpert instrument. The blue line plot
depicts the overall trend in instrument utilization as a percentage (alternative Y axis).
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS 9

11. mind. These policies/acts should not be viewed as mechanisms
to thwart or prevent the sharing of diagnostic data. These poli-
cies should be regarded as processes which promote the sharing
of diagnostic data and information by appropriate means.
Although these legislative processes are well established in
the developed world, they are generally absent in the devel-
oping world, and are not likely to find widespread adoption
within the next 5 years. The inherent risk in the lack of legal
requirement to ensure appropriate mechanisms for storing,
processing, and sharing health-care information is that devel-
oped systems may abuse this process. Due diligence should
still be conducted to meet international security standards and
the responsible and appropriate protection of this information
is still required. Failing to do so will likely result in the abuse of
this information; or inappropriate dissemination of personal
information; data breaches and further reputational and trust
violations can stunt the growth of this industry.
A number of international companies and organizations
such as mSTAR, Foundation for Innovative New Diagnostics,
SystemOne, London School of Hygiene and Tropical Medicine
are all working to promote the establishment of best practice
for connected diagnostic systems to ensure adequate protec-
tion which promotes the sharing of information to a new
ecosystem being established to process and consume data
which the ultimate goal of improving patient treatment and
ultimately, patient outcomes.
4.1. Data ownership
The legislation referenced above deals with the storage and
processing of personal and special personal information and
the necessary requirements to do so appropriately. The legis-
lation, however, does not delineate data ownership [56]. The
entity which owns the data is not necessarily obvious and if
often a contentious topic in the developing world due to the
nature of the industry and the dynamics of funding agencies,
implementing partners, technology providers, and MoH.
As an example, a funding agency funds the implementa-
tion of a third-party contracted solution, via an implementing
partner, to be utilized by the MoH to interface a number of
diagnostic instruments. Under this arrangement, at least four
different groups would like to have access to various sets of
data for different activities, and the right to access this data is
determined by the Data Controller using GDPR/POPI parlance
[54]. The Data Controller determines the reasons for collection
and processing of the data and is legally liable to ensure the
protection of this data – but the Data Controller is not neces-
sarily the owner of the data.
For the industry of connected diagnostics, the most appro-
priate assignment would be the entity responsible for the
treatment of the patient owns the data. If more than one
entity is involved, a joint responsibility model is inherent
with both entities responsible for the protection and proces-
sing of this information and a written agreement outlining
such is required under POPI and the GDPR binding these
entities. This assignment of ownership of connected diagnos-
tic information to the MoH (or branch thereof) is fair since (a)
they are responsible for the care of the patient; and (b) if ever
a data breach was identified, the MoH would likely be the
liable entity incurring legal damages over the implementing
partners, third-party providers, or global funders.
4.2. Data glossary/data dictionary
Diagnostic device makers, especially smaller firms, have a
singular focus to innovate and invent faster, more sensitive,
and cheaper means to provide a diagnosis. However, a nota-
ble gap in the development process is the lack of a standard
set of information, data, or reportable fields which should be
included as part of the diagnostic result. The state of technol-
ogy has progressed well beyond the need for a diagnostic
device to simply produce a result and an entire ecosystem has
been created (the connected diagnostics industry) processing
the metadata reported with the test result.
The metadata which accompanies a test result is able to
provide and inform a wealth of activities which allow MoH’s
and organizations the ability to
● Ensure the quality and accuracy of a reported result (first
and foremost)
● Track inventory and consumable expiration
● Monitor the quality of consumable lots and inform man-
ufacturing requirements
● Analyze the difference in testing quality at high- vs. low-
infrastructure facilities
● Inform supply chain and sample logistics
● Identify potential specimen contamination
● Proactively monitor and predict instrument failures, cali-
bration, and maintenance requirements.
● Monitor instrument utilization and uptime
. . . among many others. Providing a standardized list of
requirements for these reportable fields for new devices
would significantly improve the remote monitoring and
reporting capabilities present in the industry.
Similarly, MoHs are discovering the richness of reporting
and analysis which additional patient demographic informa-
tion (age, gender, region, etc.) can provide national programs
and imposing additional requirements on new devices to be
flexible enough to support this kind of information.
5. Conclusion
Health systems need to evolve to take advantage of this
convergence of POC and digital technologies [57, 58]. New
technologies and devices should, by default, utilize open inter-
face and standards to provide digital output as well any
necessary metadata required for quality control verification
and analysis. Commonly used open-interface formats such as
HL-7, ASTM, and the POC-1A/2A standards are appropriate for
these devices. In the future, laboratories need to take on a
novel role as the central command of a digitized diagnostic
system that extends beyond laboratories across all POCT sites,
assuring quality, supply chain, providing training and monitor-
ing patient outcomes [59]. The connected diagnostic system is
critical in providing data for disease surveillance to inform
disease control strategies, and outbreak investigations and in
combating AMR.
10 N. GOUS ET AL.

12. 6. Expert commentary
Technology, markets, and medical devices have matured to
enable connected diagnostics as a tool for epidemiology,
patient care and tracking, research, outbreak control, and
AMR surveillance. However, to unlock this potential, digital
tools must first add value at the point of the phenomenon, i.e.
in a clinical context at the point of patient care. This value could
be realized through assisting in automatic referrals for follow-
up care, connecting a patient to nearby treatment centers,
automatic ordering of drugs, or decision support for the
health-care worker. These types of value-added activities
encourage adoption of the technologies and, as a by-product,
create comprehensive aggregate disease intelligence. Never
before have millions of patient diagnoses been accumulated
without data loss or integrity issues, geo-located to create real-
time heat maps to track disease outbreaks while also triggering
automated alerts to the relevant first responders, surrounding
nations, national policy makers, and international organizations
all automatically. This ability to add value at all levels of the
health system simultaneously from a single data source is one
of the most promising innovations in health-care.
7. Five-year view
The future of disease intelligence will rely on latent outbreak
algorithms assisting difficult political decisions that a country
must make and allow these decisions to be made as early as
possible for the right action to be taken. A faster, smarter
response leads to earlier quarantine and a dramatic reduction
in the cost of each outbreak as well as impact on morbidity
and mortality [57]. Outbreaks cannot be prevented, but pan-
demics can be prevented by establishing stronger disease
surveillance and intelligence networks.
Device makers are, understandably, deeply concerned about
the unforeseen exposure of their deep instrument data and the
potential for exposing proprietary data and their intellectual prop-
erty to competitors. Some companies such as Thermo Fisher are
capitalizing on this de-identified research data for their own
instruments and are exposing it safely and in a controlled manner
through their ‘Thermo Fisher Cloud’ for analytics in hopes of
inspiring the next generation of research. Other device makers
have responded by attempting to close off access to their deep
instrument data, choosing protection over innovation.
Careful, thoughtful business models are possible to safely
harness this untapped potential in ways that can fundamen-
tally transform the role connected diagnostics play in the very
near future. It is the role of the global health community to
communicate their strong desire for these innovations and to
propose safe models that protect device makers’ intellectual
property while ushering in personalized medicine 10 years
faster into the market. Together, global health partners,
MoH, and device manufacturers can bring the potential of
connected diagnostic systems to fruition.
Key issues
● Simple, rapid tests that can be used at the point-of-care
(POC) can improve access to diagnostic services and overall
patient management. However, ensuring quality of tests
and of decentralized testing, supply chain management,
increasing training needs, reporting and monitoring patient
outcomes put tremendous stresses on fragile health sys-
tems in resource-limited settings
● A connected diagnostic system has positive impact at both
local level and for the entire health system. The rapid return
of result can reduce delay in appropriate management of
patients, including initiating treatment
● Digitising diagnostic results and utilizing data connectivity
capacity to transmit diagnostic results from POC instru-
ments, linked to quality assurance and supply chain sys-
tems can facilitate health system strengthening and
improve patient outcomes.
● Data privacy, confidentiality and security issues will become
more complex as health data sources become more diverse,
including those from mobile phone-based devices
● Digital technology has had a powerful impact on POC test-
ing in resource limited settings. However, there are con-
cerns about data governance and intellectual property. It is
the role of the global health community to communicate
their strong desire for these innovations and to propose
models that protect device makers’ intellectual property
and safeguard data confidentiality.
Funding
R Peeling would like to acknowledge funding from the UK Engineering
and Physical Sciences Research Council, grant EP/K031953/1.
Declaration of interest
Authors N Gous, J Takle and B Cunningham are all either employees,
shareholders or both, of SystemOne LLC, a connected diagnostics com-
pany currently operating in the industry. The authors have no other
relevant affiliations or financial involvement with any organization or
entity with a financial interest in or financial conflict with the subject
matter or materials discussed in the manuscript apart from those dis-
closed. Peer reviewers on this manuscript have no relevant financial or
other relationships to disclose.
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