Comparative Study of Commercially Available Typhoid Point of Care Tests to Benchmark Current and Emerging Tools
Conditions: Typhoid Fever
Sponsor: Kenya Medical Research Institute

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Comparative study of commercially available typhoid point of care tests to 
benchmark current and emerging tools 
 
 
Short title: 
Commercial Typhoid tests validation 
 
Principal Investigator 
Dr. Robert S. Onsare1 
Co-Investigators 
Elizabeth Ndegwa2 
Prof. Sam Kariuki1 
 
Collaborators 
Sabine Dittrich3 
 
Institutional Affiliations 
1Centre for Microbiology Research (CMR), KEMRI, PO Box 54840-00200, Nairobi, Kenya 
2Centre for Respiratory Diseases Research (CRDR), KEMRI, PO Box 54840-00200, Nairobi, 
Kenya 
3Foundation for Innovative New Diagnostics (FIND), 
Campus Biotech,  
Chemin des Mines 9,  
1202 Geneva, Switzerland 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
List of Abbreviations and Acronyms ....................................................................................... 3 
ABSTRACT ……………………………………………………….………………………....4 
LAY SUMMARY.....................................................................................................................4 
INTRODUCTION/ BACKGROUND....................................................................................5 
PROBLEM STATEMENT……………….…………………………………….……………5 
JUSTIFICATION FOR THE STUDY.................................................................................. 6 
TRIAL OBJECTIVES AND ENDPOINT.............................................................................7 
DESIGN AND METHODOLOGY.........................................................................................7 
Study site….………………………………………………………………………………….. 7 
Study design...............................................................................................................................8 
Trial participants.........................................................................................................................8 
Inclusion criteria ........................................................................................................................8 
Exclusion criteria........................................................................................................................8 
Screen failures ...........................................................................................................................9 
Participant Discontinuation/Withdrawal....................................................................................9 
Sample Size ...............................................................................................................................9 
TRIAL PROCEDURES………….........................................................................................10 
Specimen Collection, Handling, Transport and Storage......................................................... 10 
Study workflow....................................................................................................................... 11 
Investigational products ..........................................................................................................12 
DATA MANAGEMENT...................................................................................................... 14 
Data handling and record keeping .......................................................................................... 14 
Source data and source documents.......................................................................................... 14 
Data management ................................................................................................................... 15 
Statistical Analysis.................................................................................................................. 15 
QUALITY MANAGEMENT............................................................................................... 18 
Quality control (monitoring) ….............................................................................................. 18 
Quality Assurance (auditing)................................................................................................... 18 
Trial site closure...................................................................................................................... 18 
DURATION OF THE PROJECT ....................................................................................... 19 
ETHICAL CONSIDERATIONS ........................................................................................ 19 
Regulatory and Ethics approval ............................................................................................. 19 
Informed consent process ........................................................................................................20 
Benefit/Risk Assessment……………………………………………………………………..21 
Data protection........................................................................................................................ 21 
EXPECTED APPLICATION OF RESULTS…………………………………………….22 
REFERENCES ..................................................................................................................... 24 
BUDGET SUMMARY ......................................................................................................... 25 
Budget Justification ................................................................................................................ 25 
APPENDIX 1……………………………………………………………………………......27 
APPENDIX 2………………………………………………………………………………..40 
 
 
 
 

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List of Abbreviations and Acronyms 
Abbreviation/acronym 
Meaning 
CRF 
Case Report Form 
EDC 
Electronic Data Capture 
EDL 
Essential Diagnostic List 
FIND 
Foundation for Innovative New Diagnostics 
GCLP 
Good Clinical Laboratory Practice 
GCP 
Good Clinical Practice 
IAF 
Informed Assent Form 
ICF 
Informed Consent Form 
ICH 
International Council on Harmonisation 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
ISF 
Investigator Site File 
IVD 
In vitro Diagnostic 
LMIC 
Low and Middle Income Countries 
PCR 
Polymerase Chain reaction 
PI 
Principal Investigator 
RDT 
Rapid Diagnostic Test 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SOP 
Standard Operating Procedure 
WHO 
World Health Organisation 
 
 
 
 
 
 
 
 
 

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ABSTRACT  
 
Typhoid fever is an enteric bacterial infection caused by Salmonella enterica serovar Typhi 
(Salmonella Typhi; S. Typhi). It is an important infectious disease in low- and middle-income 
countries with over 10.9 million new cases worldwide and 116.8 thousand death in 2017. 
South Asia and Sub Saharan Africa are the most affected areas of the world. Typhoid fever is 
common in areas with inadequate sanitation and hyegine. In routine practice, diagnosis of 
typhoid fever is rarely confirmed as diagnostic tests are unavailable or have limited 
diagnostic accuracy. Blood culture is the commonest reference standard test but has a lower 
sensitivity. Alternatives to those methods exist but their performance is poor. The Widal test 
is still used but as it is based on cross-reactive antigens, it lacks sensitivity and specificity. 
Clinician often use rapid diagnostic tests to diagnose typhoid. A number of typhoid fever 
RDTs are commercially available but performance data are not available or not consistent 
from a study to another. This prospective, multicentre, cross-sectional study will be carried 
out in 3 hospitals of Nairobi, Kenya. 2000 clinically suspected typhoid cases will be enrolled 
in this study, blood culture as well as serum for RDT will be received. All typhoid positive 
and equal typhoid negative serum will be tested for investigational RDTs.  
This collaborative study between KEMRI and FIND will systematically compare different 
point of care typhoid tests currently available in the market against the same set of reference 
standard.The knowledge gained from this trial may benefit health providers’ by providing 
information on diagnostic accuracy of current typhoid test and to decide on utility of these 
commercial tests. The result obtained from this trial will also be made available to help 
inform Ministry of Health in Kenya and the WHO Essential Diagnostic list (EDL) and 
stakeholder decision making more broadly. 
 
 
 
LAY SUMMARY 
Typhoid fever bacterial disease caused by Salmonella Typhi. It is one of the most common 
serious bacterial diseases in the developing world, with an estimated 10.9 million people 
contracting the disease worldwide and 116.8 thousand people dying of the disease in 2017. 
Culture method using blood and bone marrow samples are considered as the benchmark for 
teting for typhoid disease. Those methods are however time consuming, requires drawing 
blood from the body, and requires adequate infrastructure and trained staff that are not 
available in most of areas where the disease is very common locally. There are other methods 

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but their performance is poor. The Widal test is a cheap test that is widely used despite its 
high rate of giving test results which wrongly indicates that typhoid is present. Rapid 
Diagnostic tests (RDTs) have been developed and are available in the market but their 
performance data are not available or not consistent from one study to another. Therefore, 
this study will aim to perform a direct comparison of typhoid tests currently in the market to 
help inform the Ministry of Health in Kenya and the WHO Essential Diagnostic list (EDL) 
and stakeholder decision making more broadly. 
 
INTRODUCTION/BACKGROUND 
Typhoid is an enteric disease caused by the bacterium Salmonella Typhi; it is estimated that 
11 to 20 million people contract typhoid each year and 128 000 to 161 000 die from the 
disease; children under 5 are at higher risk of contracting the disease (1). 
Typhoid endemic areas are located mainly in South Asia and Sub-Saharan Africa and is 
transmitted through contaminated water and food (2). The disease is treatable with a specific 
regimen of antibiotics, however antimicrobial resistance has been reported in several 
countries, particularly in Pakistan (3). Several vaccines have been developed but their uptake 
has been low, partly due to limited information on the exact burden of the disease in endemic 
countries. 
The symptoms of typhoid are similar to other undifferentiated febrile illnesses and typhoid 
can be mistaken with vector borne febrile illnesses such as scrub typhus (4). 
Blood and bone marrow cultures are considered the gold standard for the diagnosis of 
typhoid. Those methods require specific infrastructure and skilled staff that are not always 
available in LMICs and are not adequate for rapid patient management. In addition, although 
very specific, blood culture sensitivity is impacted by misuse of antibiotics that lower the 
bacterial load to undetectable levels in patients’ blood (5). 
PCR assay for diagnosis of typhoid fever has been used in many studies. Lower concentration 
for bacterial load in peripheral blood in typhoid fever results in lower sensitivity of PCR (6). 
Currently there is no validated PCR test in common use, only in-house system which are 
open to differing interpretation and none would meet the rigors of quality control. (7) 
As a consequence, alternatives to blood culture have been used in LMIC. The Widal test is 
the most used test despite a low performance (sensitivity range: 57-34%; specificity range: 
43-83 %;(4) reported in several studies. Other options in typhoid diagnosis are rapid 
diagnostic tests; among them, three tests (Typhidot, Tubex and Test‐it™ Typhoid IgM) have 
been evaluated in several studies. It has been reported a variability of tests performance in 
different studies and according to the geographical regions (6). Variability in the test 
performance reported so far in the literature has hampered WHO to recommend any of these 

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rapid tests in the EDL. FIND in collaboration with international typhoid experts developed a 
target product profile outlining the ideal characteristics of point of care tests. As part of this 
activity it became apparent that no quality data are available that systematically compare all 
available commercially point of care tests against the same set of reference standards used in 
multiple populations (e.g. Africa vs Asia). These lack of benchmarking data significantly 
impedes health providers’ ability to decide on the utility of commercial tests in different 
settings, ultimately restricting use and access. Further the lack of well characterized samples 
reduces the ability for targeted innovation in the typhoid space.  
 
PROBLEM STATEMENT 
Differentiating typhoid infection from other cause of fever in endemic areas is a diagnostic 
challenge. Although commercial point of care rapid diagnostic tests for enteric fever are 
available as alternatives to the current reference standard test of blood or bone marrow 
culture or to the widely used Widal test, their diagnostic accuracy is unclear. 
 
JUSTIFICATION FOR THE STUDY 
The gold standard test to confirm typhoid fever is through isolating Salmonella Typhi from 
blood or bone marrow culture. However, this method takes several days to get the test result. 
In addition, due to misuse of antibiotics and the biology of the pathogens that renders the 
bacterial load difficult to detect in blood, the blood culture method may give a false negative 
test result even though the person has typhoid fever. Besides, the blood culture also requires 
adequate infrastructure and trained manpower that are not easily available in most of endemic 
areas such as Kenya (5).  
A cost-effective alternative to the culture method using blood /bone marrow sample is Widal 
test which is widely being used in endemic areas. However, published reports show that 
Widal test has low sensitivity and specificity (10). Other alternatives are Rapd Diagnostic 
Tests (RDTs) which are easy to use and deliver quick results. There are number of 
commercially available RDTs for typhoid fever but their performance data are not available 
or not consistent from a study to another (7). Foundation for Innovative New Diagnostics 
(FIND) in collaboration with international typhoid experts developed a target product profile 
outlining the ideal characteristics of point of care tests. As part of this activity it became 
apparent that no quality data are available that systematically compare all available 
commercially point of care tests against the same set of reference standards used in multiple 
populations (e.g. Africa vs Asia). This lack of benchmarking data significantly impedes 
health provider’s ability to decide on the utility of commercial tests in different settings, 
ultimately restricting use and access. Furthermore, the lack of well characterized samples 
reduces the ability for targeted innovation in the typhoid space. A second gap that was 

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identified was the lack of a simple well-performing gold standard suggesting latent class 
modelling as a solution used for other pathogens with an imperfect gold standard (8). 
Therefore, this study will aim to perform a head to head comparison of typhoid tests currently 
available in the market in two different and geographically distant countries and 
simultaneously develop a sample set that can be used in future evaluations of emerging 
technologies and/or to support innovative test development. The knowledge gained from this 
trial may benefit society by providing information on diagnostic accuracy of currently 
available point of care typhoid tests. Further the data obtained in this trial will be made 
available to WHO to support the EDL and stakeholder decision making more broadly. 
 
TRIAL OBJECTIVES AND ENDPOINTS 
General Objective 
      To compare commercially available typhoid point of care tests (RDTs) against a defined 
reference standard of blood culture and simultaneously develop a sample set to evaluate 
emerging technologies and/or to support innovation test development. 
 
Primary Objective 
1.1. 
To evaluate different RDTs that are commercially available internationally for 
detecting antigens or antibodies to Salmonella Typhi and use Blood culture as standard 
for comparison. 
1.2. 
Establish a biorepository of well characterized specimen collection that can be used to 
evaluate emerging tests. 
Secondary Objectives 
2.1 Evaluation of operational characteristics (invalid and indeterminate rates) of Typhoid 
RDTs 
Primary Endpoint: 
1.1 Point estimates of sensitivity and specificity for each test, with 95% confidence interval, 
using blood culture as reference standard.\ 
1.2 Establishment of a biorepository of well characterized specimen collection at the site 
available for future assessments of emerging technologies  
 

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Secondary Endpoints: 
2.1 Estimates of operational characteristics of different RDTs based on quantitative 
assessment including invalid and indeterminate rates 

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DESIGNS AND METHODOLOGY 
Trial Site 
The study will take place in three hospitals in Nairobi County, found in Sub-Saharan Africa 
(Kenya). The three hospitals in Nairobi are Mbagathi County Hospital, Mbagathi Road; 
Medical Missionaries of Mary, Reuben Centre Hospital in Mukuru Slum, Embakasi and City 
Council Clinic in Mukuru Slum, Embakasi. 
Justification for selectig the the three study hospitals: Mbagathi County Hospital, Mbagathi 
Road draws majority of its patients from Kibera informal settlement (slum), an area with high 
burden of bacterial infections due to poor sanitation and limited resources. Kibera is a large, 
densely populated (77,000 persons/km2) urban settlement situated within Nairobi, a city with 
>4 million inhabitants. It is characterized by poor sanitation evidenced by excreta and 
garbage in footpaths and open sewers. Water supply in Kibera is largely unregulated and food 
vendors trade outdoors under minimal hygiene standards (Njuguna, 2013). 
Medical Missionaries of Mary, Reuben Centre Hospital and City Council Clinic are located 
with andserves Mukuru informal settlement (slum) population. Maukuru slum also suffers 
from high bacterial disease burden due to poor sanitation and limited resources. Mukuru slum 
(20 km East of Nairobi) is home to a population of over 150,000 in an area approximately 
2km2(population density, 75,000/km2) [Kenya Population Census, 2010] living in congested 
housing and under poor sanitary conditions. The majority of the populations work in nearby 
industrial areas. 
 
Study Design 
 
This is a prospective multicentre diagnostic accuracy study using collected blood and/or 
serum samples that will be conducted in three hospitals at Nairobi, Kenya. Participants will 
be recruited when they present to three hospitals where the study will take place. Clinical 
officers appointed in the 3 hospitals will collect blood samples from individuals older than 
eight years presenting with fever because most documented typhoid fever cases involve 
school-aged children and young adults.  The samples will be transported in cold chain to the 
Centre for Microbiology Research (CMR), KEMRI laboratories where they will be processed 
using blood culture. Once culture results are available, investigational RDTs will be 
performed on all blood culture positive and equal culture of negative serum. 
 

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Trial Population 
The trial population will be composed of adults and children suspected of typhoid between 8-
65 years of age because most documented typhoid fever cases involve school-aged children 
and young adults. Participants will be recruited in 3 hospitals in Nairobi, Kenya. 
Inclusion Criteria 
 
Participants are eligible to be included in the Trial only if all of the following inclusion 
criteria apply:  
- 
Individuals aged 8 years of age to 65 years of age 
- 
History of fever or axillary temperature of >37.50Cfor at least 3 consecutive days 
within the last 7 days prior to enrolment 
- 
Clinical suspicion of enteric fever 
- 
One of the following scenarios: 
• Presents to outpatient department or Emergency Department 
• Admitted to hospital within last 12 hours 
- 
Able and willing to provide informed consent (and assent when required) 
 
Exclusion Criteria 
 
Participants are excluded from the Trial if any of the following exclusion criteria apply:  
- 
Unwillingness to participate in the study 
- 
Inability to provide the required volume of blood 
- 
Unwillingness to provide blood 
- 
Known non-infectious / Non typhoid Infectious causes of fever or other alternate 
diagnosis of fever 
 
Screen Failures  
 
Screen failures are defined as participants who consent to participate in the clinical trial but 
are not subsequently entered in the trial. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Studies (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information including demography, 
and screen failure details (i.e. eligibility criteria, participation refusal, site operational 

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issues/facilities issues, other) will be recorded in a dedicated Screening Log. Moreover, 
individuals who are considered screen failures may not be rescreened.   
 
Participant Discontinuation/Withdrawal from the Trial  
 
A participant may withdraw voluntarily from trial participation at any time without any 
impact on their care or treatment.  
A participant may be withdrawn at any time at the discretion of the investigator for safety, 
behavioural, compliance, or administrative reasons. 
If the participant withdraws consent for disclosure of future information, the study may retain 
and continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the trial, he/she may request destruction of any samples taken 
and not tested 
The investigator must document the withdrawal of participant and the reason for withdrawal 
using a Note to File (attached to the Informed Consent Form in the participant’s file at the 
site) 
 
Sample Size 
 
The reported values for prevalence of Salmonella Typhi positive patients in Kenya is 5% 
(Data from personal communication with Prof. Sam Kariuki Co-PI). The reported values of 
sensitivity and specificity of diagnostic tests are generally low, (Review article on typhoid 
RDTs summarizes TUBEX test from IDL Biotech has sensitivity of 78% and specificity of 
87%, TestTM It from LifeAssay has sensitivity of 69% and specificity of 90%, Typhidot from 
Reszon Diagnostic has sensitivity of 78% and specificity of 77%.(9) Similarly reported 
sensitivity and specificity of SD Bioline Salmonella Typhi IgG/IgM from Abbot and Typhoid 
IgG/IgM Combo rapid test from CTK Biotech are 69%/76% and 40-79%/68-79% 
respectively (15)).  For the purpose of determining the sample size, sensitivity and specificity 
were both assumed to be 50%, which corresponds to the scenario that requires the highest 
number of samples to estimate sensitivity and specificity. Based on this hypothesis, and on 
the feasibility of recruitment at the sites of enrolment, it was decided to set the sample size in 
order to recruit at least 100 culture positive and culture negative samples in Kenya. These 
sample sizes will allow to estimate the sensitivity of the test with 80% power to detect a 95% 
confidence interval of width of +/- 14% in Kenya (11). Based on the prevalence mentioned 
above, this number of positive samples requires the enrolment of at least 2,000 participants in 
Kenya (at a prevalence of 5%). From a similar study carried out by an MSc student in our lab 
that we supervised (Performance of tubex® tf IGM antibody test against culture in typhoid 
fever detection in Nairobi county, MSc Thesis by Walter Kipngetich Lelei, JKUAT, 2019), the 
average number of patients presenting with febrile illnesses at Mbagathi County Hospital was 
20 per day, using this as a basis and considering their relatively smaller sizes, we estimate 
that for Medical Missionaries of Mary, Reuben Centre Hospital and City Council Clinic, we 
will have 10 and 5 patients presenting per day in Medical Missionaries of Mary, Reuben 
Centre Hospital and City Council Clinic respectively. We plan to sample for only 3 days in a 
week (Mon-Wed) due to the observed trend of high patient inflow on these days from Walter 

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Lelei’s MSc work (total 35 patients per day, 420 per month). This works out to a minimum of 
2,520 which is above the sample size of 2,000 participants that we are targeting. 
TRIAL PROCEDURES 
Trial procedures are summarized in Study flow in Figure 1. Protocol waivers or exemptions 
are not allowed. 
Adherence to the trial design requirements, including those specified in the study flow 
(Figure 1) is essential and required for trial conduct. 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. All enrolled participants will be registered on an enrolment 
form. 
Procedures conducted as part of the participant’s routine clinical management and obtained 
before signing of the Informed Consent Form (ICF) and Informed Assent Form (IAF) may be 
utilized for screening or baseline purposes provided the procedures met the protocol-specified 
criteria. 
 
Specimen Collection, Handling, Transport and Storage 
 
Procedures for specimen collection, handling, transport, and storage will be described in 
detail in the Trial Manual provided by FIND to the site. Blood will be collected by 
venepuncture following national guidelines on drawing blood. The maximum amount of 
blood collected from each participant in the trial, including any extra assessments that may be 
required, will not exceed 14 mL. Repeat may be taken at the time of enrolment for safety 
reasons or for technical issues with the samples. Blood will be handled as follows: 
Table 1: Amount of blood to be collected 
Samples For 
Amount of sample in adults 
(>14 years) 
(14ml- 10+4ml) 
Amount of sample in children 
(8-14 years) 
 (7ml-3.5+3.5 ml) 
Blood Culture 
1 x 10 ml whole blood 
1 x 3.5 ml whole blood 
Serum 
1 X 4 ml whole blood 
1 X 3 ml whole blood 
 
Study workflow  
 

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The study flow is shown in Figure 1.  
Figure 1: Study flow  
 
Consenting patients will be enrolled in the study based on eligibility criteria. Blood will then 
be obtained from the patients by venepuncture method. The blood samples will be collected 
in blood culture bottles and in serum tubes. The volume of blood from the patient will follow 
the guidelines in Table 1. After collection at study hospitals, samples will be transported to 
the CMR, KEMRI laboratories in cold boxes every day and will be processed within 24 hours 
maximum. Samples will be stored at 4°C at CMR laboratories until further processing.  
All samples preparations (blood culture and serum preparation) will be conducted in parallel. 
Blood culture will be done using an automated blood culture system (BD BACTEC 9050). 
BACTEC vials will be processed as per manufacturer's instructions. Bottles will be incubated 
until signal-positive or till the end of day 5, whichever is earlier. When positive signal is 

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observed, bottles are unloaded from instrument and Gram's stain and cultures and 
biochemical tests to identify Salmonella Typhi will be performed using standard 
microbiological procedures. Patients will be classified as typhoid or non-typhoid cases 
according to the blood culture results. However, since the results of the blood culture may 
take several days to be available, serum will be separated from all whole blood samples and 
will be aliquoted. It is expected that at least 100 blood culture positive and 100 blood culture 
negative samples will be tested with index tests and will be kept for long term storage. 
Testing with the index tests will be performed in batch at the end of each month while the 
remaining volumes of the selected sera will be kept at -80°C. Depending on the initial volume 
that will differ between adult and children samples, 3 to 6 aliquots will be kept at -80°C for 
long term storage and will be used for future evaluation of diagnostic tests. 
Investigational products 
Reference standard tests to identify Salmonella Typhi: 
All blood samples collected from study participants will undergo blood culture. 
• Blood culture: Blood culture is considered as gold standard for the diagnosis of 
typhoid fever. Blood culture is a routine process for diagnosis of typhoid fever. 
Index tests: 
Index tests are RDTs that will be performed according to manufacturer’s instructions by 
trained laboratory personnel. The readers of the index tests and reference standard test will be 
blinded to the results of the other tests.  
Typhoid RDTs for inclusion in the study were selected by the study team based on a 
combination of the following criteria: 
• RDT is CE-marked 
• Published independent evaluation data  
• International availability 
• Volume of samples 
• Price of the test 
• Turnaround time 
RDTs will be procured by FIND and shipped to the study sites in Kenya. There are no 
financial ties of any nature with the manufacutrers. All selected RDTs which will be included 
in the study are shown in Table 2.  
Table: 2 Lists of RDTs 

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1 
SD Bioline Salmonella Typhi IgG/IgM Fast 
2 
Typhidot Rapid IgG/IgM combo test 
3 
TUBEX TF 
4 
Typhoid IgG/IgM Combo Rapid Test CE 
5 
Enterocheck WB 
6 
Test-itTM Typhoid IgM  
7 
Typhoid IgG/IgM Rapid Test Cassette  
8 
S.typhi-S.paratyphi "A" Direct Antigen Detection  
9 
DiaquickS.typhi IgG/IgM Ab 
10 
Diaquick S. typhi/paratyphi Ag cassette 
11 
Widal* 
*Widal test is included as index test because it is widely used for decision making of typhoid 
diagnosis and treatment. 
Specificity and sensitivity of only few RDTs are currently available in studies but varies from 
one study to another and from one geographical region to another. Overall TUBEX test from 
IDL Biotech has sensitivity of 78% and specificity of 87%, TestTM It from LifeAssay has 
sensitivity of 69% and specificity of 90%, Typhidot from Reszon Diagnostic has sensitivity 
of 78% and specificity of 77%.(9) Similarly reported sensitivity and specificity of SD Bioline 
Salmonella Typhi IgG/IgM from Abbott and Typhoid IgG/IgM Combo rapid test from CTK 
Biotech are 69%/76% and 40-79%/68-79% respectively. Detail information on each RDTs 
with package inserts are available. 
DATA MANAGEMENT 
Data handling and record keeping 
All participant data relating to the trial will be recorded in source documents and transcribed 
on to a paper Case Report Form (CRF) and/or an electronic CRF by trial site staff.  Data will 
then be entered from the paper CRF into FIND’s online clinical trials platform (OpenClinica 
Enterprise Edition version 4.0). Data will be verifiedto ensure they are accurate, correct and 
consistent with the source documents. CRF will be electronically signed by the study team on 
site. Data will be cleaned of errors by the study team throughout the trial as it is captured 
electronically. 
 
Records and documents, including signed ICFs, IAFs (when required) pertaining to the 
conduct of this trial will be retained by the study team for 5 years after trial completion. 

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Source Data and Source Documents 
Source documents will provide evidence for the existence of the participant and substantiate 
the integrity of the data collected. The study team will maintain adequate and accurate source 
documents and trial records that include all pertinent observations on each of the site’s trial 
participants. The study team will request previous medical records or reports (if available). 
Source documents or certified copies will be filed at the study site.  
Participant data will consist of medical history, clinical examination, laboratory testing. 
Observations from the clinical examination will be recorded directly in the paper CRF and/or 
the eCRF.  A paper CRF, which mirrors the design of the electronic CRF, may be used for 
ease of data entry by non-clinical and non-laboratory staff. The CRF will consist of some data 
that has been entered directly (e.g. source data) and some data that has been transcribed from 
other sources as detailed in the table 3. Any source data directly entered into the CRF will be 
clear and accurate, and will be signed and dated by the person who generated the data. 
Changes to source data will be traceable i.e. dated, initialed and explained (if necessary) and 
will not obscure the original entry.  
 
Table 3: Source data definition and record 
Type of source data 
Original place of entry 
Demographics 
Paper CRFs 
Medical history 
Medical records or Paper CRFs 
Specimen collecting time and date  
Clinical officers record 
Specimen time and date of receipt at the 
lab 
Paper CRFs or eCRFs 
Lab results 
Lab notebook or LIMS 
 
Other unidentified source data will be described in the Site Initiation Visit Report. Lab staff 
authorized by the PI will be trained and given a unique password to enter lab data originally 
recorded in laboratory notebooks or Laboratory Information Management System directly 
into the electronic CRF, thereby avoiding time consuming transcription on to a paper CRF 
first. 
The investigator will maintain a delegation log with roles and responsibilities related to the 
management of records. Additionally, the investigator will ensure adequate training of 
research team involved on data collection. The investigator will also be responsible for 
internal validation of data.  
 

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The study team will permit trial-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to participant medical records and source 
documents used for this trial. 
  
 
Data Management 
Details of the data collection and management will be described in the data management plan 
and in accordance with ICH GCP principles safeguarding the confidentiality of participants’ 
information. 
Each enrolled participant will be assigned a unique study participant ID number used to 
identify samples and information. The use of an anonymous participant ID will ensure 
participant’s confidentiality. To ensure that each clinical sample can be linked to clinical and 
laboratory results and tracked effectively from the collection site to the end-user, all lab 
request forms, sample collection pots, tubes and aliquots will be labelled using the 
participant’s ID using a set of barcode labels provided by FIND. 
Each set will be composed by the label types, according to the number and type of specimens 
collected at each site as described in Table 4. Labels will contain readable text and a barcode: 
Table 4: Composition of Barcode labels 
Label Type 
Content  
Text  
Barcode  
Use  
Core label 
• 
Study ID 
• 
Site ID 
• 
Participant ID 
Yes 
Yes 
Place on Information sheet, 
CRF, enrolment form and lab 
results form 
Specimen label 
• 
Study ID  
• 
Site ID  
• 
Participant ID  
• 
Event ID 
• 
Specimen type  
Yes 
Yes 
Place on blood culture bottle 
and serum tubes 
Aliquot label 
• 
Study ID  
• 
Site ID  
• 
Participant ID  
• 
Event ID 
• 
Specimen type  
• 
Aliquot ID  
Yes 
Yes 
Place on tubes containing 
serum for testing of 
investigational RDTs and for 
long-term storage of serum  
 
 
Data Management procedures, including the setup of the database, programming edit and 
range checks and querying, are described in the Data Management Plan.  
Whenever possible clinical data and laboratory results will be captured directly onto 
electronic CRFdesigned by FIND/KEMRI in the OpenClinica EDC system. Site staff will be 
responsible for entering their data from a paper CRF into OpenClinica where direct capture 
into EDC is not possible. Test results will be exported from the devices when possible and 

Version 2.0, 12thDec 2020 
 
 
 
 
Page 18 of 53 
electronic files will be transferred to FIND for further analysis. FIND will setup a secure data 
transfer system such as a File Transfer Protocol (FTP) server. Details will be provided in the 
Trial Manual. 
The site will be provided with individual password-protected accounts to access OpenClinica, 
following a training session given by FIND, either on site or remotely sharing screen through 
Skype or any other similar system.  
 
No information concerning the trial or the data generated from the trial will be released to any 
unauthorized third party without prior written approval of the study team.  
Statistical Analysis Plan 
The statistical analysis plan (SAP) will be developed and finalized before the start of 
enrolment and will describe in detail the methodology used to evaluate each of the endpoints. 
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints. 
- 
Efficacy Analyses 
 
Endpoint 
Statistical Analysis Methods 
1.1 
Point estimates of sensitivity and specificity for each test with 95% 
confidence interval, using Blood culture as reference standard. 
1.2 
Establish a biorepository of well characterized specimen collection that 
can be used to evaluate emerging tests.  
2.2 
Evaluation of operational characteristics of different RDTs including 
invalid and indeterminate rates. 
 
Analysis datasets  
The following datasets will be defined: 
 
• 
ITT (Intention-To-Test) all subjects successfully enrolled in the study 
• 
MITT (Modified-Intention-To-Test) all subjects in ITT for whom at least one 
test result is available 
• 
PP (Per-Protocol) all subjects in ITT for whom results for all tests are 
available (complying with the protocol)  
 
Description of statistical methods   
General approach  

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Estimates of accuracy 
Table 5 summarizes the way results of diagnostic tests are reported when two tests are 
compared. Based on the definitions in the table, the following values are defined: 
Sensitivity = TP / (TP + FN) 
Specificity = TN / (FP + TN) 
For each point estimate, a 95% confidence interval will be derived based on the Wilson’s 
score method. Missing and invalid results (e.g. the results for one specific test for a given 
participant) will not be imputed and will be removed from the analysis. 
Table 5 Definition of test results 
 
Reference Standard Outcome 
Test result 
 
Reference 
positive 
Reference 
negative 
Total 
Test result 
Positive  
TP 
FP 
PP = TP + FP 
Test result 
negative 
FN 
TN 
PN = FN + TN 
Total 
P = TP + FN 
N = FP + TN 
P + N 
TP = true positives, TN = true negatives, FP = false positives, FN = false negatives, P = 
positive, N = negative 
Analysis of the primary outcome(s) 
Outcome 1.1 
This outcome will be evaluated with the methodology described in section 4.1.1, using using 
blood culture as reference standard, on the PP population, for each test included in the trial. 
Outcome 1.2  
This outcome does not require any statistical analysis. 
 
 
 
 
 
Analysis of the secondary outcome(s)  
Outcome 2.1 
The number of indeterminate and invalid test results will be reported for each RDT, together 
with the relative percentage over the total number of tests performed. 
 
Baseline descriptive statistics  
Descriptive statistics tables will be generated to summarize the characteristics of the 
participants in the PP and ITT populations, per.  
The number of participants included and excluded will be reported, overall and for each 
clinical site and test. Among the included samples, the information will be broken down by 
the following variables: 
Socio-demographics: 

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•Age (<11, 12:17, >17) 
•Gender (female, male) 
•Clinical site 
Sample characterization: 
•Reference test positive or negative 
Results will be reported either in absolute numbers (e.g. number of subjects in a group) or 
summarized by mean, median, standard deviation, minimum, maximum and quartiles. 
 
 
 
Details on the methodology will be provided in the SAP. 
 
 
QUALITY MANAGEMENT  
 
Quality Management for this trial consists of Quality Control activities, training and capacity 
building, as well as the use of Standard Operating Procedures, Work Instructions, Tools and 
Templates.   
Training on the protocol, GCP and the use of the IVDs and laboratory tests will be provided 
by the study team.  A Laboratory Manual, which describes all of the sample testing 
procedures, will be provided by the study team prior to the commencement of the Trial.  
Training on the EDC system will be provided by FIND Data Management prior to first 
participant enrolment.  
 
 
Quality control (study monitoring)  
 
Quality control will be applied to each stage of data handling to ensure that all data are 
reliable and have been processed correctly. The study team will perform risk based 
monitoring of this trial, and associated Quality Control checks, as described in the 
Monitoring Plan. Independent trial monitors will perform source data review and source data 
verification to confirm that data entered into the CRF by authorized site personnel are 
accurate, complete, and verifiable from source documents; that the safety and rights of 
participants are being protected; and that the trial is being conducted in accordance with the 
currently approved protocol and any other trial agreements, ICH GCP, and all applicable 
regulatory requirements. 
Quality Assurance (auditing)  
As part of routine Quality Assurance, the study team will conduct an audit of the study sites.  
 

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Page 21 of 53 
  
 
 
Trial site closure 
 
The study team reserves the right to close the trial site or terminate the trial at any time for 
any reason at its sole discretion, provided there is reasonable cause and sufficient notice is 
given in advance to stakeholders of the intended termination. Investigational sites will be 
closed upon trial completion. A trial site is considered closed when all required documents 
and trial supplies have been collected and participant samples aliquoted and stored on site.   
 
PROJECT TIME FRAME 
 
Approximately six months from the time the site receives IEC Approval and is authorized to 
start enrolment. The table 7summarizes the estimated time frame for the main activities. 
Table 7: Time frame for main activities 
Months 
1-3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
Proposal 
Development 
x 
 
 
 
 
 
 
 
 
 
 
Ethical Approval 
 
x 
x 
 
 
 
 
 
 
 
 
Purchase and 
Delivery of 
Supplies 
 
 
x 
x 
 
 
 
 
 
 
 
Sample collection 
and processing 
 
 
 
 
x 
x 
x 
x 
x 
X 
 
Sample testing 
 
 
 
 
x 
x 
x 
x 
x 
X 
 
Data entry and data 
analysis 
 
 
 
 
 
 
 
 
 
X 
x 
Report entry 
 
 
 
 
 
 
 
 
 
 
x 
 
In addition, a subset of serum samples will be stored at KEMRI at -80°C for future evaluation 
of diagnostic tests. 
ETHICAL CONSIDERATIONS 
Regulatory and Ethics Approvals 
This trial will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki  
• Applicable Good Clinical Practice Guidelines: ICH GCP E6 (R2) 

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Page 22 of 53 
• Applicable laws and regulations 
The protocol, protocol amendments, ICF, IAF and other relevant documents (e.g. 
advertisements) must be submitted to an IRB/IEC by the investigator and reviewed and 
approved by the IRB/IEC before the trial is initiated. A copy of the IRB/IEC approval letter 
will be filed in the investigator site file. Any substantial amendments to the protocol will 
require IRB/IEC approval before implementation of changes made to the trial design, except 
for changes necessary to eliminate an immediate hazard to trial participants. Protocol 
amendments restricted to clerical edits only will be provided to the trial sites and submitted to 
the IRB/IEC for informational purposes.    
The investigator will be responsible for the following: 
• Providing written summaries of the status of the trial to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established 
by the IRB/IEC 
• Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
• Providing oversight of the conduct of the Trial at the site and adherence to 
requirements of ICH guidelines, the IRB/IEC, the WHO Good Clinical Laboratory 
Practice (GCLP), and with applicable national regulations. 
Informed Consent Process 
The investigator or his/her representative will explain the nature of the trial to the participant 
or his/her legally authorized representative in a language understandable to him/her and 
answer all questions about the trial.  
The investigator or his/her representative will inform the participants that their participation 
is voluntary. Participants or their legally authorized representative will be required to sign 
and date a statement of informed consent that meets the requirements of ICH GCP E6 R2 
guidelines where applicable, and of the IRB/IEC or study center.  
For children less than 18 years old, parental consent will be obtained, with assent from 
children (13 – 17 years) before enrollment. If the child agrees to participate, he/she will be 
asked to sign an Informed Assent Form. In all children, any opposition, resistance or protest 
to study procedures will be discussed with the parents/legally authorized representative to 
assess whether the behaviour is merely an expression of the anticipated but acceptable 

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Page 23 of 53 
burden, or is reason for concern on study continuation. When the analysis concludes that 
these are expressions of dissent, it will be respected. 
Before enrolling the participant in the trial a written informed consent will be obtained and 
ample time will be given to the participant to decide to participate in the trial. The date the 
written consent was obtained (as well as the time, ideally) will be recorded. The authorized 
person obtaining the informed consent will also sign and date the Informed Consent Form 
(ICF). 
It will be mandatory for illiterate participants to provide a thumbprint on the ICF or IAF and 
the ICF or IAF signed and dated by an impartial witness. 
A copy of the ICF(s) and IAF will be given to the participant or the participant’s legally 
authorized representative.  
Participants who are rescreened are required to sign a new ICF and IAF (when required). 
The ICF and IAF will contain a separate section that addresses the use of remaining samples 
for future evaluation studies of typhoid or other febrile illnesses tests. The investigator or 
authorized designee will explain to each participant the objectives of keeping those samples 
for future use. Participants will be told that they are free to refuse to participate and may 
withdraw their consent at any time and for any reason during the storage period.  
 
 
 
Benefit/Risk Assessment and Safety Monitoring 
 The in-vitro diagnostic tests (IVD) under investigation are considered low risk to Trial 
participants since only venepuncture will be performed. Foreseeable adverse events 
associated with venepuncture are mild, temporary discomfort at the venepuncture site, 
bruising, and phlebitis. Very rarely, patients may experience vaso-vagal syndrome during 
phlebotomy. Vaso-vagal reactions may include diaphoresis, nausea, syncope and rarely 
fainting.  
To minimize adverse events, all phlebotomy will be performed either by study clinical 
officers trained in phlebotomy, or by trained phlebotomists. In case of adverse event and SAE 
during phlebotomy, standard medical care will be provided to participants and the treating 
team as well as investigators will be informed and the event reported to the hospital 
management, PI and documented in the study record.  
Handling and manipulation of pathogenic samples will be performed according to the local 
biosafety requirements to further minimize risk of contamination for the technical personnel 
and the environment. Given the nature of the study, termination due to safety or other reasons 
is not anticipated. 

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Blood culture is recommended diagnostic test for typhoid fever in Kenya, so the report of 
blood culture, one of the reference test will be provided to clinician for further clinical 
management of participants, all other  index tests will not be used for the purposes of clinical 
management, and participants will be treated in accordance with national guidelines. The 
blood culture results from CMR-KEMRI labs will be available after an average of 5 days and 
will be sent to the clinician caring the participating patient All participants enrolled in the 
trial will receive standard-of-care health services from the health facility. All trial activities 
will be conducted by trained trial personnel.  
Knowledge gained from this trial may benefit society by providing information on the 
diagnostic accuracy of current typhoid tests. Data obtained in this trial will be made available 
to the WHO Essential Diagnostic list working group.  
Given the minimal risks associated with this trial and the potential benefits to society, the 
benefits outweigh the risks. As for any clinical trial, there is a possibility of unknown and 
unforeseen risk; yet this possibility is slim for this trial. If unforeseen risks are identified 
during the trial, FIND, trial partners, Institutional Review Boards (IRB)/ Independent Ethics 
Committees (IEC), and trial participants will be provided with relevant information.  
 
Data Protection 
Participants will be assigned a unique identifier generated by the study team. Any participant 
records or datasets will contain the identifier only; participant names or any information 
which would make the participant identifiable will not be used in any way.  
The participant will be informed that his/her personal trial-related data will be shared by the 
study sponsor, FIND in accordance with local data protection law. The level of disclosure 
will also be explained to the participant.  
The participant will be informed that his/her medical records may be examined by quality 
assurance auditors or other authorized personnel appointed by the study team, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 
 
An example of the Participant ID is shown below.  
 
 
 
 
 
 

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Page 25 of 53 
 
EXPECTED APPLICATION OF THE RESULTS 
 
As mentioned earlier, blood and bone marrow cultures are the gold standard for diagnosis of 
typhoid. Alternatives diagnostic tests that are easier to use, faster and cheaper are required. 
Numerous alternative tests have been developed such as RDTs or PCR and are currently 
available in the market. However data on their performance are limited mainly because 
evaluation studies are commonly focusing on three tests (Tubex, Typhidot and Test-It).When 
an alternative test is evaluated, comparison of its performance to other tests may not be 
possible since the reference tests used may differ between studies: while blood and bone 
marrow cultures are the gold standards, the poorly performant Widal test is sometimes used 
as the reference standard. This lack of harmonization in the study protocols negatively impact 
the identification of promising typhoid diagnostic tests and the generalization of performance 
data in different geographical areas of the world. In addition, access to samples from typhoid 
patients clearly hampers the evaluation of new typhoid tests. 
 
This collaborative study between KEMRI and FIND will systematically compare different 
point of care typhoid tests currently available in the market against the same set of reference 
standard in two geographically distant typhoid endemic areas in different continents (Asia 
and Africa).  The knowledge gained from this trial may benefit health providers’ by 
providing information on diagnostic accuracy of current typhoid test and to decide on utility 
of these commercial tests. The result obtained from this trial will also be made available to 
help inform the WHO Essential Diagnostic list (EDL) and stakeholder decision making more 
broadly. 
As a part of the study a biorepository will be established at site with well characterized 
samples which can be used in future evaluations of emerging technologies and/or to support 
innovative test development. 
 
 
 
 
 
 
 
 

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Page 26 of 53 
WASTE MANAGEMENT AND BIOSAFETY OF THE STUDY 
The blood samples that are to be used in this study have the potential to cause human 
infections. Measures will be put in place to ensure the safe handling of the blood samples so 
as to prevent infection to the study personnel and the community as well. The measure will 
include strict adherence of lab SoPs on waste management and biosafety, ensuring that only 
qualified personnel will be allowed to handle the blood samples, provision and use of suitable 
personal protective equipment (PPE) which is properly stored, cleaned as required, replaced 
when defective and separated from normal clothing, the study team will excersise safe 
collection, storage and disposal of biological waste from the study, including the use of 
secure and identifiable containers, after suitable treatment where appropriate as per the lab 
SOPs and safe handling and transport of a biological agents for disposal. 
 
STUDY LIMITATIONS 
Due to limited funding, the study will cover only three hospitals in 1 County of the 47 
Counties in Kenya, thus leaving out 46 other Counties.  
 
ROLES OF INVESTIGATORS: 
 
Dr. Robert Onsare: Overal implementation of the project including samples collection, lab 
processing and data analysis. 
 
Elizabeth Ndegwa: Elizabeth is a registrerd clinical officer and will provide clinical 
guidance in interaction with patients.  
 
Prof. Sam Kariuki: Will play an advsisory role in all aspects of the project. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Version 2.0, 12thDec 2020 
 
 
 
 
Page 27 of 53 
REFERENCES: 
 
1. Crump JA:Progress in Typhoid Fever Epidemiology.Clinical Infectious Disease. 
2019;68:4-9. 
2. Amicizia D, Micale RT, Pennati BM,Zangrilo F, Iovine M, Lecini E, Marchini F, Lai P.L, 
and Panatto D. Burden of typhoid fever and cholera: similarities and differences. 
Prevention strategies for European travellers to endemic/epidemic areas. Journal of 
Preventive Medicine and Hygiene.2019;60:271–285 
3. Ayukekbong J.A, Ntemgwa M and Atabe A.N. The threat of antimicrobial resistance in 
developing countries:cause and control strategies. Antimicrobial Resistance & Infection 
Control.2017;6:47. 
4. Hamaguchi S, Chong NC, Tra DT, Doan YH, Shimizu K,Tuan NQ, Yoshida LM, Mai 
LQ, Anh DD, Ando S,  Arikawa J, Parry CM, Ariyoshi K, and Thuy PT. Clinical and 
Epidemiological Characteristics of Scrub Typhus and Murine Typhus among 
Hospitalized Patients with Acute Undifferentiated Fever in Northern Vietnam. American 
Journal of Tropical Medicineand Hygiene. 2015;92:972‐978.  
5. Moore CE, Pan-Ngum W, Wijedoru LPM, Sona S, Nga TVT, Duy PT, Vinh PV, Chheng 
K, Kumar V, Emary K, Carter M, White L, Baker S, Day NPJ and Parry CM. Evaluation 
of the diagnostic accuracy of a typhoid IgM flow assay for the diagnosis of typhoid fever 
in Cambodian children using a Bayesian latent class model assuming an imperfect gold 
standard. American Journalof Tropical Medicineand Hygiene. 2014;90:114–120.  
6.  Khanam F, Sheikh A, Sayeed MA, et al. Evaluation of a Typhoid/Paratyphoid 
diagnostic assay (TPTest) detecting anti-Salmonella IgA in secretions of peripheral 
blood 
lymphocytes 
in 
patients 
in 
Dhaka, 
Bangladesh. PLoS 
Negl 
Trop 
Dis2013;7:e2316 
7. Baker, S., Favorov, M. & Dougan, G. Searching for the elusive typhoid diagnostic. BMC 
Infect Dis 10, 45 (2010) 
8. Bhaskaran D, Chadha SS, Sarin S, Sen R, Arafah S and Dittrich S. Diagnostic tools used 
in the evaluation of acute febrile illness in South India: a scoping review. BMC Infectious 
Disease. 2019;19:970. 
9. Wijedoru L, Mallett S andParry CM. Rapid diagnostic tests for typhoid and paratyphoid 
(enteric) fever. Cochrane Database Systematic Review. 2017;5:e008892.  
10. Mather RG, Hopkins H, Parry CM and Dittrich S. Redefining typhoid diagnosis: what 
would an improved test need to look like? BMJ Global Health 2019;4:e001831.  
11. Lim C, Wannapinij P, White L, Day NPJ, Cooper BS, Peacock SJ and Limmathurotsakul 
D. Using a Web-Based Application to Define the Accuracy of Diagnostic Tests When the 
Gold Standard Is Imperfect. PLOS ONE. 2013; 8: e79489.  
12. Lalremruata R, Chadha S, Bhalla P. Retrospective audit of the widal test for diagnosis of 
typhoid Fever in pediatric patients in an endemic region. Journal of Clinical and 
Diagnostic Research. 2014;8:22‐25.  
13. Zhou XH, Obuchowski NA and McClish DK. Statistical Methods in Diagnostic 
Medicine. 2011;2:193-228 
14. Njuguna HN, Cosmas L, Williamson J, Nyachieo D, Olack B, Ochieng JB, Wamola N, 
Oundo JO, Feikin DR, Mintz ED and Breiman RF. Use of population-based surveillance 
to define the high incidence of shigellosis in an urban slum in Nairobi, Kenya. PLoS One 
2013; 8(3): e58437. 
15. Maude RR, de Jong HK, Wijedoru L, Fukushima M, Ghose A, Samad R, Hossain MA, 
Karim MR, Faiz MA, Parry CM; CMCH Typhoid Study Group. The diagnostic accuracy 
of three rapid diagnostic tests for typhoid fever at Chittagong Medical College Hospital, 
Chittagong, Bangladesh. Trop Med Int Health. 2015 Oct;20(10):1376-84. 

Version 2.0, 12thDec 2020 
 
 
 
 
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BUDGET SUMMARY 
 
Unit  
Unit Cost 
Cost (EUR) 
Personal Cost 
 
 
Project supervisor (Manager), PhD-KEMRI Staff 
monthly salary: 2900 euros; gratuity:0, period: 9 months 
 
 
8,700 
3 Clinical Officers, Diploma (From Hospitals) - To give 55% 
monthly salary: 440 euros; gratuity: 0 
 
 
7,920 
2 Laboratory Technologists, BSc (From KEMRI) - To give 65% 
effort monthly salary: 440 euros; gratuity:0 
 
 
7,800 
Field Driver - KEMRI (70% effort) 
 
 
5,208 
Sub-Total 
 
 
29,628 
Blood Culture/Enrichment media/ reagents for blood samples (2,400 samples) 
 Columbia blood agar – 500g pack 
5 
136.7 
683.5 
MacCONKEY agar -500g pack 
5 
136.7 
683.5 
 Sulphur, Indole Motility media – 500g pack  
1 
122.1 
122.1 
 Urea agar and supplement - 500g pack @ 172.1x1pc =172.1 
1 
172.1 
172.1 
 TSI 
1 
172.1 
172.1 
 Simon citrate – 500g pack 
1 
122.5 
122.5 
 Glass test tubes  
3000 
0.3 
900 
Glass slides and cover slips (100 per unit) 
30 
25 
750 
 Petri dishes –3500 pcs  
 
 
1000 
 Disposable sterile wire loops  
20,000 
0.21 
2310 
 Cotton wool- 500g pack 
10 
4.4 
44.2 
 Syringes and needles (10ml) 100pc per unit 
60 
4 
240 
 Serology antiseras: - Polyvalent                                         
2 
215.1 
430.2 
                                 -Monovalent  
10 
215.1 
2151 
 Biohazard bags (Red, Yellow, Black) – 50 pcs  
48 
187 
8976 
 Sharps disposal containers  
12 
821.45 
9857.4 
Emersion oil  
1 
500 
500 
Aerobic Blood Culture bottles, 3000 pieces,50 pcs per unit 
=19,200 
60 
320 
19200 
Sub-Total 
 
 
48,315 
Consumables for archiving isolates, 600 samples   
  Sarstedtet Freezing vials  
750 
0.25 
187.5 
  10 by 10 freezer boxes  
7 
21 
147 
Sub-Total 
 
 
335 
Sample transport and Field trips 
Fuel for the field vehicle 
 
 
1,608 
Vehicle service and Maintenance 
 
 
3,192 
Sub-Total 
 
 
4,800 
Miscellaneous  
Office and lab Supplies & materials  
 
 
6,000 
Physical protective Equipment (PPE) for the laboratory 
personnel (Gloves, dust coats, face masks and Eye goggles) 
 
 
1428 
Sub-Total 
 
 
7,428 
                       Total Cost 
 
 
90,505 

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Page 29 of 53 
Indirect Cost (15%) 
 
 
13,575.765 
Grand Total 
 
 
104,081 
 
 
 
 
 
 
 
 
Budget Justification 
 
Personal Costs: 
 
The Project supervisor (Manager) is the Principal Investigator of the trial, he will supervise 
and coordinate field and laboratory staff in sampling activities for 9 months. 
 
Three Clinical officersfrom the sampling sites will be involved in the trial. They are currently 
working in those sites and part of their time will be dedicated to participant screening, 
consenting and blood drawing. 
 
Two full timeLaboratory technologist will be involved in the trial. They are currently 
working in KEMRI. They will process samples for blood culture, PCR and aliquot the serum 
for storage. Once the culture report comes they will also perform RDTs in stored samples in 
batches  
 
A designated KEMRI driver will be responsible for transportation of the staff to study sites 
and samples from study sites to laboratory at KEMRI. 
 
Blood Culture, Enrichment media and Reagents for Blood sample 
 
Blood culture is one of the reference tests of this study. This includes cost for aerobic blood 
culture bottles with enrichment media for blood culture. Once the blood culture is positive, 
cost of biochemical media and reagents to identify Salmonella Typhi is included in this 
section. 
 
Consumables for archiving isolates: 
 
The consumables for archiving serum samples of 100 blood culture positive and equal 
number of negative cases, each sample will be stored in 4 freezing vials which will be stored 
at KEMRI for 5 years. These samples will be used for future evaluation of new typhoid 
diagnostics. 
 
Sample transport and field trips: 
 
Fund to support daily transport of sample after collection from sites to KEMRI laboratory 
 
Miscellaneous costs: 
 

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Page 30 of 53 
This includes cost of office and laboratory supplies and personal protective equipment for 
laboratory staffs. 
 
 
 
 
 
 
 
 
 
APPENDIX 1: CASE REPORT FORMS 
 
CASE REPORT FORM-CLINIC V1.0 
Commercial typhoid test validation 
 
 
 
GENERAL INFORMATION 
1. Date of enrolment 
(DD/MM/YYYY) 
__ __ / __ __ / __ __ __ __ 
2. Site 
Mbagathi County Hospital 
Mukuru Kwa Reuben Missionary Clinic 
City Council Clinic 
3. Place of enrolment:          OPD 
Inpatient           Emergency ward 
 
INCLUSION CRITERIA (Answers to questions 1-5must be YES for the participant to be eligible.) 
YES 
NO 
 
 
 
1. Aged 8 years to 65 years? 
 
❑ 
❑ 
2. History of fever or axillary temperature of >37.50C for at least 3 consecutive days 
within the last 7 days prior to enrolment? 
 
❑ 
❑ 
3. Clinical suspicion of enteric fever? 
 
❑ 
❑ 
4. A signed informed consent and/or assent by participant and/or parent/legal 
guardian? 
 
 
 
5.  One of the following conditions: 
❑ 
❑ 
a. Presents to outpatient department or Emergency department? 
❑ 
❑ 
b. Admitted to hospital within 12 hours? 
 
 
EXCLUSION CRITERIA 
YES 
NO 
 
 
❑ 
❑ 
1. Unwillingness to participate in the study 
❑ 
❑ 
2. Known non-infectious / non typhoid Infectious causes of fever or other alternate 

Version 2.0, 12thDec 2020 
 
 
 
 
Page 31 of 53 
diagnosis of fever  
❑ 
❑ 
3. Inability to provide the required volume of blood 
❑ 
❑ 
4. Unwillingness to provide blood 
 
PARTICIPANT DEMOGRAPHICS 
 
 Date of birth (DD/MM/YYYY): 
__ __ / __ __ / __ __ __ __ 
 
Gender: 
❑Female 
❑Male 
 
CURRENT MEDICAL STATUS 
VITAL SIGNS 
 
Temperature (°C) 
❑ Axillary  ❑ Oral  ❑ Ear ❑ Skin 
 
 
.  
 
 
 
Any clinical symptoms at the time of screening? 
❑ Yes 
❑No 
If YES, check which ones (can be more than one): 
❑Abdominal pain 
 
❑Nausea 
 
❑Fatigue 
 
❑ Cough 
 
❑ Headache 
 
❑Diarrhea 
 
❑ Constipation 
 
❑ Vomiting 
 
❑ Rash 
 
❑ Conjunctival Redness 
 
 Other (specify) 
________________ 
________________ 
 
 
 
PAST MEDICAL STATUS 
Do you have history of any of the following in last 6 
months? 
❑ Yes 
❑No 
If YES, check which ones (can be more than one): 
❑Tuberculosis 
 
❑Typhoid 
 
❑Dengue 
 
❑ Malaria 
 
❑ Scrub Typhus 
 
 Other (specify) 
________________ 
________________ 
 
 
 
TREATMENT HISTORY 
1. Has the subject taken antibiotics since the 
symptoms started? 
❑ Yes 
❑No 

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If YES, check which ones (can be more than one): 
❑Ciprofloxacin 
Treatment start date: __ __/__ __/__ __ __ __  
        (DD/MM/YY) 
❑Ofloxacin 
Treatment end date:  __ __/__ __/__ __ __ __   
      (DD/MM/YY) 
❑Levofloxacin 
 
❑ Cefixime 
 
❑ Amoxycillin 
 
❑ Amoxycillin/clavulanate 
 
❑ Azithromycin 
 
❑ Other (specify) 
________________ 
________________ 
 
2. Has the subject taken any other treatment?  
❑ Yes 
❑No 
If YES, check which ones (can be more than one): 
❑ Antimalarial 
 
 
❑ Antipyretic 
 
 
❑ Other(specify) 
_______________ 
_______________ 
 
 
 
 
 
VACCINATION HISTORY 
 
Has the subject received a 
typhoid vaccine? (Single dose 
TVC vaccine) 
❑ Yes ❑No   ❑Don’t know 
If yes, when (DD/MM/YYYY): __ __/__ __/__ __ __ __ 
 
 
 
 
 
 
 
 
 
PRESUMED DIAGNOSIS 
 
Presumed diagnosis by 
the clinician: 
❑Enteric fever 
❑ Dengue 
❑Other:  
__________________ 
 
 
 
BLOOD COLLECTION 
 
1. Blood sample drawn           ❑YES         ❑NO 
2. Blood sample draw date (DD/MM/YYYY):__ __/ __ __/__ __ __ __     
at (24h00) __ __: __ __  
 
3. If not blood drawn, why?  ❑Patient Refused  ❑Supply shortage ❑Unable/difficult to          
                                                                                                            draw   
 

Version 2.0, 12thDec 2020 
 
 
 
 
Page 33 of 53 
 
 
 
 
 
 
 
 
Comments 
Date (DD/MM/YY) 
Initials 
Signature 
 
 
 
__ __ / __ __ / __ __ 
 
 
__ __ __ 
 
 
 
 
__ __ / __ __ / __ __ 
 
 
__ __ __ 
 
 
 
 
__ __ / __ __ / __ __ 
 
 
__ __ __ 
 
 
 
Data entry agent initials: _ _ _ 
 
Date of completion of data entry (DD/MM/YYYY): __ __/__ __/__ __ __ __ 
 
Investigator’s Signature: ___________________________    
 
Date of signature (DD/MM/YYYY): __ __/__ __/__ __ __ __  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Version 2.0, 12thDec 2020 
 
 
 
 
Page 34 of 53 
 
 
 
 
 
 
 
 
 
 
CASE REPORT FORM-Blood culture V1.0 
Commercial typhoid test validation 
REFERENCE TESTING BY BLOOD CULTURE 
 
 
Comments 
Date (DD/MM/YY) 
Initials 
Signature 
 
 
 
__ __ / __ __ / __ __ 
 
 
__ __ __ 
 
 
 
 
__ __ / __ __ / __ __ 
 
 
__ __ __ 
 
 
 
 
__ __ / __ __ / __ __ 
 
 
__ __ __ 
 
 
 
1. Technical operator initials: _ _ _ 
2. Aerobic blood culture performed (If no, put an explanation in comments) ❑Yes ❑ No 
3. Aerobic 
blood 
culture 
Incubation date 
(DD/MM/YYYY): 
__ __/__ __/__ __ __ __ 
Time (24h00): __ __: __ __ 
❑Positive  
❑ Negative         ❑Contamination 
 
If Positive: 
 Date (DD/MM/YYYY):__ __/__ __/__ __ __ __ 
Time (24h00): __ __: __ __ 
 
4. Salmonella Typhi  
❑Positive  
❑ Negative          
5. Other clinically relevant growth  
______________ 
6. Contaminants growth 
______________ 
7. Data reported to patients 
❑ Yes, Date (DD/MM/YYYY): 
__ __/__ __/__ __ __ __ 
 
 
❑ No, why: ___________ 
 

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Page 35 of 53 
Data entry agent initials: _ _ _ 
 
  Date of completion of data entry (DD/MM/YYYY): __ __/__ __/__ __ __ __ 
 
Investigator’s Signature: ___________________________    
 
Date of signature (DD/MM/YYYY): __ __/__ __/__ __ __ __  
 
CASE REPORT FORM-Serum preparation V1.0 
Commercial typhoid test validation 
 
 
SERUM PREPARATION  
1. Serum prepared  
 
❑Yes, if yes, Date (DD/MM/YYYY): __ __ /__ __/__ __ __ __ 
❑ No, if no Why:  
 
      If yes at 1. Serum stored? 
❑Yes   
If yes,  ____ aliquots stored 
Storage Location:  
 
❑ No, if No Why: 
________________________ 
 
Comments 
Date (DD/MM/YY) 
Initials 
Signature 
 
 
 
__ __ / __ __ / __ __ 
 
 
__ __ __ 
 
 
 
 
__ __ / __ __ / __ __ 
 
 
__ __ __ 
 
 
 
 
__ __ / __ __ / __ __ 
 
 
__ __ __ 
 
 

Version 2.0, 12thDec 2020 
 
 
 
 
Page 36 of 53 
 
Data entry agent initials: _ _ _ 
Date of completion of data entry: __ __/__ __/__ __ __  
Investigator’s Signature: ___________________________    
 
Date of signature (DD/MM/YYYY): __ __/__ __/__ __ __ __  
 
CASE REPORT FORM-RDTsV1.0 
Commercial typhoid test validation 
 
A. TYPHOID RDTs EVALUATION 
Test name 
Test Results 
 
Date (DD/MM/YYYY) 
Results 
Comments 
Widal Test 
Initial Test Result 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Repeat testing if invalid 
results 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Typhidot Rapid 
IgG/IgM combo 
test 
 
Initial Test Result (IgG) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Repeat testing if invalid 
results (IgG) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 

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Page 37 of 53 
Initial Test Result (IgM) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Repeat testing if invalid 
results (IgM) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
TUBEX TF 
 
Initial Test Result 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Repeat testing if invalid 
results 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
SD Bioline  
SALMONELLA 
TYPHI IgG/IgM 
Fast 
 
Initial Test Result (IgG) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Repeat testing if invalid 
results (IgG) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Initial Test Result (IgM) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Repeat testing if invalid 
results (IgM) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
 

Version 2.0, 12thDec 2020 
 
 
 
 
Page 38 of 53 
❑Inv 
Typhoid IgG/IgM 
Combo Rapid 
test CE 
 
Initial Test Result (IgG) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Repeat testing if invalid 
results) IgG 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Initial Test Result (IgM) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Repeat testing if invalid 
results (IgM) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Enterocheck WB 
 
Initial Test Result 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Repeat testing if invalid 
results 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Test itTM Typhoid 
IgM 
 
Initial Test Result 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 

Version 2.0, 12thDec 2020 
 
 
 
 
Page 39 of 53 
Repeat testing if invalid 
results 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Typhoid IgG/IgM 
Rapid Test 
Casette 
 
Initial Test Result (IgG) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Repeat testing if invalid 
results ) IgG 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Initial Test Result (IgM) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Repeat testing if invalid 
results (IgM) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
S.Typhi-
S.Paratyphi “A” 
Direct Antigen 
Detection 
Initial Test Result 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Repeat testing if invalid 
results 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
DiaquickS.Typhi 
IgG/IgM Ab 
Initial Test Result (IgG) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
 

Version 2.0, 12thDec 2020 
 
 
 
 
Page 40 of 53 
 
❑Inv 
Repeat testing if invalid 
results (IgG) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Initial Test Result (IgM) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Repeat testing if invalid 
results (IgM) 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
DiaquickS.typhi/
paratyphi 
Ag 
cassette 
 
Initial Test Result 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
Repeat testing if invalid 
results 
__ __/__ __/__ __ __ __ 
❑Pos 
❑ Neg   
❑Inv 
 
If any of the RDTs not done, put an explanation in comments below. 
 
Comments 
Date (DD/MM/YY) 
Initials 
Signature 
 
 
 
__ __ / __ __ / __ __ 
 
 
__ __ __ 
 
 
 
 
__ __ / __ __ / __ __ 
 
 
__ __ __ 
 

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Page 41 of 53 
 
 
 
__ __ / __ __ / __ __ 
 
 
__ __ __ 
 
 
Data entry agent initials: _ _ _ 
Date of completion of data entry (DD/MM/YYYY): __ __/__ __/__ __ __ __ 
Investigator’s Signature: ___________________________    
Date of signature (DD/MM/YYYY): __ __/__ __/__ __ __ __  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Page 42 of 53 
APPENDIX 2: Consent and assent forms 
 
(a)(i) Adult Informed Consent Form: English Version 
Version 2.0 of 11 August 2020 
 
Study Title: Comparative study of commercially available typhoid point of care tests to 
benchmark current and emerging tools 
Study Centre:   KEMRI                                                       Study Site: 
Principal Investigator: Dr. Robert Onsare 
Sponsor: FIND 
Language: English 
 
This Informed Consent Formhastwoparts: 
• Information Sheet (to share information about the study with you) 
• Certificate of Consent (for signatures if you agree to take part) 
 
You will be given a copy of the full Informed Consent Form 
 
Part 1: Information sheet: 
Introduction 
Dear Sir/madam, 
Good day, we are a group of researchers from the Kenya Medical Research Institute 
(KEMRI), Nairobi. The study is supported by the Foundation for Innovative New Diagnostics 
(FIND), a charity working to develop new ways of diagnosing sick people having fever to 
understand the cause of their illness. FIND works together with researchers, scientists, 
governments and companies to develop affordable and easy to use tests for diagnosing 
typhoid and other febrile illnesses. We are doing a study on typhoid, a disease that is common 
in this area and is caused by germs transmitted by eating contaminated food and taking 
contaminated drinks and can lead to complications if it is not treated. The symptoms of 
typhoid are however similar to those from other diseases caused by other bacteria, parasites 
or viruses, and which must be treated with different treatments than typhoid. It is therefore 
important to correctly diagnose and understand the cause of the fever symptoms, to give the 
correct treatment and help you to recover from your disease. Such a diagnosis is not easy, and 
we are conducting the study to try to improve it. You have fever or you had fever within the 
last 7days, and we suspect that you might suffer from typhoid. This is why we are asking you 
if you would like to participate in the study. Participation is voluntary, and you have the right 
to refuse. Before you decide you may take a moment to talk to your family or friends about 
the study. I will now give you some more information about the study. If my words are not 
clear, please ask me to stop and I will take time to explain. If you have questions later, you 
can ask me or the other study staff, at any time. 
 

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Page 43 of 53 
 
Purpose of the study 
It is very common that patients have fever symptoms like you. Unfortunately, it is difficult to 
quickly and easily identify the cause of these symptoms. In some cases, the fever can be due 
to typhoid which can be treated with antibiotics. Such antibiotics should however not be used 
if your fever is caused by a viral or parasitic infection. Currently typhoid is diagnosed by 
blood culture which takes 5 to 7 days to get result. Doctor has to wait for 5-7 days to know if 
the fever is due to typhoid and to decide of the best treatment. 
Rapid Diagnostic Tests are other tests that may be used to diagnose quickly and easily 
typhoid. However, there are several ones and nobody knows for sure which test is the best to 
diagnosetyphoid. So, the reason why we are doing this study is to find out which of these 
Rapid Diagnostic Tests works better. 
The study will last for about 12 months, however, for you as an individual, your time in the 
study will be from when you accept to be part of the study and sign this form until you have 
given a sample of your blood. This should take more than 1 or 2 hours for you. We will need 
to collect samples from a maximum of 4,900 patients (adults and children) in 2 different 
countries in Pakistan and Kenya. 
 
Study Procedures  
If you agree to participate in the study, we will ask you some questions about your healthand 
any treatments that you might have taken recently. Then, we will take 14ml (3 table 
spoon)/7ml of blood from your vein. 
It is important that you understand that blood will be collected from your vein for routine 
diagnosis whether you decide to be in the study or not. You will get the same treatment, 
whether you decide to be in the study or not. For all patients, we will collect blood. The only 
difference, if you are in the study, is the volume of blood to be collected from your vein. The 
following table gives you an idea of the differences. 
 
Type of Sample 
In the study 
Not in the study 
Blood from your 
vein 
14 mL of blood (3 tea spoon) (> 
14 years) 
7 mL of blood (1 and ½ tea 
spoon) (8-14 years) 
10 mL of blood for blood culture 
(2 tea spoon) 
3.5 mL of blood for blood culture 
(1/2 tea spoon) 
 
If you decide to be part of the study, some of your blood will be used to perform blood 
culture. Another part of your blood will be used with the rapid diagnostic tests. The leftover 
venous blood will be kept for 5 years at the KEMRI in Nairobi, Kenya, for future research on 
infectious diseases. If you would like these leftovers to be destroyed at the end of the study, 
please inform the study doctor. We will seek permission from the Ethics committee from 
KEMRI to use your sample for future studies (the Ethics committee is a group of people who 
review studies to ensure that your rights are protected). 
 

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Page 44 of 53 
What are the risks and benefits? 
This study may or may not lead to a direct benefit to you.  The tests and the blood culture will 
be free of charge for you. The study will be beneficial for your community as a whole. In 
fact, we hope it will help doctors worldwide to better diagnose typhoid and give the right 
treatment to sick people.  
Your participation in this study has little risks for you; the only difference with usual care is 
that we will take more blood from your vein. You may feel the pain from the needle stick. It 
may cause discomfort or a small bruise as with any other blood test that requires a venous 
blood sample. A new needle will be used for each participant, so there is no risk of 
transmitting infection.  
 
Follow-up and treatment 
This study is only about diagnostic tests and we will not test any new drug or other therapy. If 
you are diagnosed with typhoid from blood culture you will be treated following the current 
standard treatment in Kenya. If your blood culture for typhoid is negative, you will be treated 
following the national guidelines for management of non-typhoid febrile illness. We will not 
use other test results to diagnose you. If considered necessary by the doctor, you will be 
referred to the appropriate health facility and treated according to standard of care available 
in Kenya. 
 
What are the costs? 
You will not receive money from KEMRI or FIND or any other person as a result of the use 
of your blood in medical research or testing.  
You will not be paid to take part in the study; however, we will make sure that you don’t 
have to pay additional costs from your participation. All diagnostic tests for this study will be 
free of charge.  
 
Payment for injury 
It is unlikely that you will suffer any physical harm caused by one of our sample collection 
procedures. Should this ever occur, you will be treated and fairly compensated for it 
according to local laws and any insurance policy in effect. You agree to give away to KEMRI 
and FIND, for free, any property rights you might have in your bodily fluids and any medical, 
scientific or commercial products such as drugs or diagnostics or other inventions created 
through the study or use of those fluids. Your participation in this study is a free gift in the 
spirit of human kindness to help future generations fight illness and remain healthy.   
 
How will confidentiality be respected? 
We will not share any of your personal information outside of the KEMRI study team. Your 
name will not be mentioned on any sample, or on the data collected during the study. You 
will be given a unique number, which will be used to identify the samples and data collected. 
If the results of this study get published in a scientific journal, your name will not appear on 
the publication. All members of the research team commit to protect the confidentiality of the 
information you provide. The members of the Ethics Committee, auditors, and Sponsor’s 
representatives (FIND study monitors and auditors) may access your personal information, 

Version 2.0, 12thDec 2020 
 
 
 
 
Page 45 of 53 
however, all these people have to respect the confidentiality, and your personal information 
will not be revealed publicly. 
 
Your participation is entirely voluntary 
It is your choice to decide whether you want to be in the study or not. Whatever your decision 
is, all the diagnostic tests will be provided free of cost to you. Also, the treatment you will 
receive will not be affected by your decision to be in the study or not. Finally, you can decide 
to be in the study, and later on change your mind. This decision will not affect the quality of 
your care. Just tell me, you don’t need to provide any reason for this. During this study, if 
new information becomes available that may affect your willingness to continue the study, 
we will tell you. If you decide to continue in the study, we will ask you to sign a new consent 
form with the new information.   
The use of samples for any future studies will require the approval of an ethics committee (a 
group of people who review studies to ensure that your rights are protected). 
 
Whom to contact in case of problem or question? 
Deciding whether or not to participate in this study is completely voluntary. Refusal to 
participate will not adversely affect you in any way, and if you choose to discontinue your 
participation at any time there will be no penalty.  
 
You can contact Dr. Robert Onsare, Tel.+254 20 2723006, Email: RSOnsare@kemri.org,  at 
the Centre for Microbiology Research (CMR), KEMRI Nairobi in case you: (i) have any 
more questions or (ii) feel that you might have been harmed by being in the study.  
 
Should you have any questions about your rights as a research participant, please contact the 
Secretary, Scientific and Ethics Review Unit (S.E.R.U) of the Kenya Medical Research 
Institute (KEMRI) Tel. 2722541 ext. 3307/ 0717719477; P.O Box 54840-00200, Nairobi-
Kenya, E-mail: SERU@kemri.org. 

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Page 46 of 53 
 
Part 2: Consent Form 
• 
For ADULT, literate patients 
I have read the Participant Information Sheet concerning this study or have understood the verbal 
explanation and I understand what will be required of me if I take part in this study. 
I understand that the blood I will provide will be tested for typhoid and that they will be stored in 
freezers in a safe and secure facility for up to 5 years in KEMRI, Nairobi, Kenya. After that time 
they will be destroyed.   
I understand that the stored fluids will belong to KEMRI &FIND. I understand that KEMRI 
&FIND will use these fluids to develop or evaluate new tests to diagnose typhoid and possibly 
other illnesses. I understand that other researchers and other companies may want to use these 
fluids for other medical research, testing, and product development and I agree to such use. I 
understand that I will not receive money from FIND or any other company as a result of the use 
of my fluids in medical research or testing and I give away for free any property rights I might 
have in my bodily fluids and any medical, scientific or commercial products or inventions 
created through the study or use of those fluids. My participation in this study is a free gift in the 
spirit of human kindness to help future generations fight illness and remain healthy. 
I understand that study staff, representatives from KEMRI, FIND, members of the ethics 
committee overseeing this study and the regulatory authority (ies) will be given access to my 
medical records so they can verify what was done and look at the data. In signing this, I 
authorize access to my medical records.  
I understand that I may drop out of this study at any time, for any reason, without penalty and 
without any loss of medical care. I have read the patient information sheet, or it has been read to 
me, and I have understood the purpose of the study, the procedure to be conducted, and the risks 
and benefits related to my participation. I have had the opportunity to ask questions and all have 
been answered to my satisfaction.  I consent voluntarily to participate as a participant in this 
study and: 
 I agree that part of my samples get stored for future research on infectious diseases  
 I don’t agree that part of my samples get stored  
 
 
Print Name of Participant (Last 
name/Firstname):______________________________________________________ 
 
 
Signature of Participant ________________________________________ 
Date ___________________________ 
 
Day/month/year 
 
 
 
 
 
 
 
 

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Page 47 of 53 
 
Part 3: For witnesses of ADULT, illiterate participants: 
I have witnessed the accurate reading of the consent form to the potential participant, and the 
individual has had the opportunity to ask questions. I confirm that the individual has given 
consent freely.  
 The participant agrees that part of his/her samples get stored for future research on infectious 
diseases diagnosis 
 The participant does not agree that part of his/her samples get stored  
 
Print name of witness (Last name/First name)_______________________________            AND         
Thumb print of participant 
 
 
Signature of witness _____________________________________ 
Date ________________________ 
         Day/month/year 
 
Sehemuya 3: Kwa Mashaidi wa Watu Wazima Wasiojua Kusoma au Kuandika 
Nimeshuhudia usomaji sahihi wa fomu ya idhini kwa mshiriki, na mtu huyu amepata nafasi ya 
kuuliza maswali. Ninadhibitisha kuwa mtu huyu, ametoa idhini kwa hiari. 
 Mshiriki anakubali kwamba, sehemu ya sampuli zake, zitahifadhiwa kwa utafiti wa siku 
zijazo kwenye utambuzi wa magonjwa ya kuambukiza. 
 Mshiriki hakubali kuwa sehemu ya sampuli zake zitahifadhiwa.  
Chapisho 
la 
Jina 
la 
Shahidi 
(Jina 
la 
Mwisho/Jina 
la 
Kwanza) 
______________________________ 
Saini kwa kutumia kidole cha Gumba 
 
 
 
Saini ya Shahidi _____________________________________ 
Tarehe ____________________________________________ 
 
 

Version 2.0, 12thDec 2020 
 
 
 
 
Page 48 of 53 
Siku/Mwezi/Mwaka _________________________________ 
Part 4: Statement by the researcher/person taking consent 
I, the undersigned, have defined and explained to the participant in a language he/she 
understands, the procedures of this study, its aims and the risks and benefits associated with 
his/her participation. I have informed the participant that confidentiality will be preserved, that 
he/she is free to withdraw from the trial without affecting the care he/she will receive at the 
hospital. I confirm that the participant was given an opportunity to ask questions about the 
study, and all the questions asked by the participant have been answered correctly and to the best 
of my ability. I confirm that the individual has not been coerced into giving consent, and the 
consent has been given freely and voluntarily.  
 A copy of this Informed Consent Form has been provided to the participant. 
Print Name of Researcher/person taking the consent (Last name/First name)  
____________________________________ 
 
 
 
 
 
 
Signature of Researcher /person taking the consent__________________________ 
Date ___________________________ 
 
 
 
           Day/month/year 
 
Sehemu ya 4: Taarifa ya Mtafiti/ Mtu anaye chukua idhini 
Nimeelezea mshiriki kwa kutumia lugha anayeelewa, taratibu za utafiti, malengo, faida na hatari 
zinazohusiana na ushiriki wake. Nimemwelezea mshiriki kuwa, usiri utahifadhiwa na kwamba 
yuko huru kujiondoa kwenye utafiti huu wakati wowote bila kuathiri matibabu na utunzaji 
atakaoupokea hospitalini. Ninathibitisha kuwa, mshiriki alipewa nafasi ya kuuliza maswali juu 
ya utafiti na maswali yote yaliyoulizwa na mshiriki yamejibiwa kwa usahihi na kwa uwezo 
wangu wote. Ninathibitisha kuwa mtu huyu, hajalazimishwa kutoa idhini na idhini imetolewa 
kwa hiari. 
Nakala ya fomu hii ya kufahamisha imetolewa kwa mshiriki. 
Chapisho la Jina la Mtafiti/Mtu anayepokea fomu ya idhini hii (Jina la Mwisho/Jina la Kwanza) 
___________________________________________________________________ 
Saini ya Mtafiti ________________________________________ 

Version 2.0, 12thDec 2020 
 
 
 
 
Page 49 of 53 
Tarehe _______________________________________________ 
Siku/Mwezi/Mwaka ____________________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 (b) (i) Children 13-17 years Informed Assent Form: English Version 
Version 2.0 of 11 August 2020 
 
Study Title: Comparative study of commercially available typhoid point of care tests to 
benchmark current and emerging tools 
Study Centre:      KEMRI Kenya                                                   Study Site: 
Principal Investigator:  
Sponsor: FIND 

Version 2.0, 12thDec 2020 
 
 
 
 
Page 50 of 53 
Language: English 
 
This Informed Consent Formhastwoparts: 
• 
Information Sheet (to share information about the study with you) 
• 
Certificate of Consent (for signatures if you agree to take part) 
 
You will be given a copy of the full Informed Consent Form 
 
Part 1: Information sheet: 
Introduction 
Hi, my name is____________________________________ and I work for Kenya Medical 
Research Institute (KEMRI). My job is to study a disease called typhoid in Kenya. We are doing 
a new study in typhoid. We want to find better methods to identify the cause of the disease in 
people who, like you, have fever or had fever within the last 7 days. I am going to give you 
information and invite you to be part of a research study. You can choose whether or not you 
want to participate. We have discussed this research with your parent(s)/guardian and they know 
that we are also asking you for your agreement. If you decide to be in the study, your 
parent(s)/guardian also have to agree. But if you do not wish to take part in the study, you do not 
have to, even if your parents have agreed.  
You may take a moment to think before you decide, and you may discuss anything in this form 
with your parents or anyone else you feel comfortable talking to. You can decide whether to 
participate or not after you have talked it over. There may be some words you don't understand 
or things that you want me to explain more about because you are interested or worried. Please 
ask me to stop at any time and I will take time to explain. 
 
Why are we doing this research?  
We want to find better and faster ways to understand which type of germ makes adults and 
children sick with Typhoid. There are several Rapid Diagnostic Tests available in market which 
could be used to identify typhoid, to help the doctor decide which treatment he or she should 
give you. We don’t know however if these rapid tests works well. We therefore need to evaluate 
it before we can recommend its use throughout Kenya. 
 
Why am I asking you to be involved? 
We are conducting the research in both adults and children. In Kenya, children of your age often 
have fever with typhoid, and today we have little and time-consuming means to figure out 
whether fever is due to typhoid or not. If we want to use already available Rapid Diagnostics 
Tests to get better and quick result then we need to make sure that it works for children as well as 
for adults.  
 
Do you have to be involved in the research? 

Version 2.0, 12thDec 2020 
 
 
 
 
Page 51 of 53 
You don't have to be in this research if you don't want to be. It’s up to you. If you decide not to 
be in the research, it’s okay and nothing changes. This is still your hospital or health center, 
everything stays the same as before.  Even if you say "yes" now, you can change your mind later 
and it’s still okay. 
What is going to happen to you? 
If you agree to participate in the study, after you visit the doctor and suspected to have typhoid 
we will ask you some questions about your health. Then, we will take 7ml (in age group 8-
14years) (3 table spoon) and 14 mL (in >14 years of age) of blood from your vein, out of which 
3.5ml (in 8-14 years of age) and 10m ( in >14 years of age) will be used to perform blood 
culture, which is a routine procedure to diagnose typhoid fever. Addition to this 3.5ml (in 8-14 
years of age) and 4ml (in >14 years of age) of blood (app 1 table spoon) will be taken to do other 
tests to diagnose typhoid.  
It is important that you understand that blood will be collected from your vein for routine 
diagnosis whether you decide to be in the study or not. You will get the same treatment, whether 
you decide to be in the study or not. For all patients, we will collect blood. The only difference, 
if you are in the study, is the volume of blood to be collected from your vein. The following table 
gives you an overview of the differences. 
 
Type of Sample 
In the study 
Not in the study 
Blood 
from 
your 
vein 
14 mL of blood (3 table spoon)  
(> 14 years) 
7 mL of blood (1 and ½ table 
spoon) (8-14 years) 
10 mL of blood for blood culture (2 
table spoon) 
3.5 mL of blood for blood culture 
(1/2 table spoon) 
 
If you decide to be part of the study, the samples will be used to perform the routine diagnostic 
tests and the other tests that are necessary for the study. The leftover venous blood will be kept 
for 5 years at the KEMRI in Nairobi, Kenya, for future research on infectious diseases. If you 
would like these leftovers to be destroyed at the end of the study, please inform the study doctor. 
We will seek permission from the Ethics committee from KEMRI to use your sample for future 
studies (the Ethics committee is a group of people who review studies to ensure that your rights 
are protected). 
Is this research bad or dangerous? 
There is little difference between the study and what usually happens to children with fever when 
they get to the hospital or the health center. You may feel the pain from the needle stick. It may 
cause discomfort or a small bruise as with any other blood test that requires blood to be taken 
from the arm. A new needle will be used for each patient, so there is no risk of transmitting a 
disease. 
 
Is there anything good that will happen to you? 

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This study may or may not lead to a direct benefit to you.  The tests and the blood culture will be 
free of charge for you. The study will be beneficial for your community as a whole. In fact, we 
hope it will help doctors in worldwide to better diagnose typhoid and give the right treatment to 
sick people.  
Your participation in this study has little risks for you; the only difference with usual care is that 
we will take more blood from your vein. You may feel the pain from the needle stick. It may 
cause discomfort or a small bruise as with any other blood test that requires a venous blood 
sample. A new needle will be used for each participant, so there is no risk of transmitting 
infection 
There will be no reward for taking part in the study. 
Will everybody know about it? 
We will not tell other people that you are in this research and we won't share information about 
you to anyone who does not work in the research study. 
Can you choose not to be in the research? 
There is no obligation for you to be in this research. No one will be mad or disappointed with 
you if you say no. It’s your choice. You can think about it and tell us later if you want. You can 
say "yes" now and change your mind later and it will still be okay. This decision will not affect 
the quality of your care.  Just tell me or the study doctor, you don’t need to give any justification 
for this. 
Whatever your decision is, all the diagnostic tests will be provided free of cost to you. Also, the 
treatment the doctor will give you will be the same if you are in the study and if you are not.  
Who can you talk to or ask question to? 
You can ask me questions now or later. I have written a number and address where you can 
reach us and discuss any study related issues or, if you are nearby, you can come and see us. If 
you want to talk to someone else like your teacher or Doctor or your auntie, that's okay too. You 
can also talk to the Doctor regarding issues about the study. 
 
 
 
Whom to contact in case of problem or question? 
You may contactDr. Robert Onsare, Tel.+254 20 2723006, Email: RSOnsare@kemri.org,  at the 
Centre for Microbiology Research, KEMRI Nairobi in case you: (i) If you have any problem or 
question related to the study or (ii) feel that you might have been harmed by being in the study.  
 
Should you have any questions about your rights as a research participant, please contact the 
Secretary, Scientific and Ethics Review Unit (S.E.R.U) of the Kenya Medical Research 
Institute (KEMRI) Tel. 2722541 ext. 3307/ 0717719477; P.O Box 54840-00200, Nairobi-
Kenya, E-mail: SERU@kemri.org. 

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