Diagnosis of neglected tropical diseases among patients with persistent digestive disorders (diarrhoea and/or abdominal pain ≥14 days): Pierrea multi-country, prospective, non-experimental case-control study.
BACKGROUND
Diarrhoea still accounts for considerable mortality and morbidity worldwide. The highest burden is concentrated in tropical areas where populations lack access to clean water, adequate sanitation and hygiene. In contrast to acute diarrhoea (<14 days), the spectrum of pathogens that may give rise to persistent diarrhoea (≥14 days) and persistent abdominal pain is poorly understood. It is conceivable that pathogens causing neglected tropical diseases play a major role, but few studies investigated this issue. Clinical management and diagnostic work-up of persistent digestive disorders in the tropics therefore remain inadequate. Hence, important aspects regarding the pathogenesis, epidemiology, clinical symptomatology and treatment options for patients presenting with persistent diarrhoea and persistent abdominal pain should be investigated in multi-centric clinical studies.


METHODS
This multi-country, prospective, non-experimental case-control study will assess persistent diarrhoea (≥14 days; in individuals aged ≥1 year) and persistent abdominal pain (≥14 days; in children/adolescents aged 1-18 years) in up to 2000 symptomatic patients and 2000 matched controls. Subjects from Côte d'Ivoire, Indonesia, Mali and Nepal will be clinically examined and interviewed using a detailed case report form. Additionally, each participant will provide a stool sample that will be examined using a suite of diagnostic methods (i.e., microscopic techniques, rapid diagnostic tests, stool culture and polymerase chain reaction) for the presence of bacterial and parasitic pathogens. Treatment will be offered to all infected participants and the clinical treatment response will be recorded. Data obtained will be utilised to develop patient-centred clinical algorithms that will be validated in primary health care centres in the four study countries in subsequent studies.


CONCLUSIONS
Our research will deepen the understanding of the importance of persistent diarrhoea and related digestive disorders in the tropics. A diversity of intestinal pathogens will be assessed for potential associations with persistent diarrhoea and persistent abdominal pain. Different diagnostic methods will be compared, clinical symptoms investigated and diagnosis-treatment algorithms developed for validation in selected primary health care centres. The findings from this study will improve differential diagnosis and evidence-based clinical management of digestive syndromes in the tropics.


BACKGROUND
ClinicalTrials.gov; identifier: NCT02105714 .
Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. kpolman@itg.be.
Katja
K
Polman
Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland. soeren.becker@becker-malente.de.|University of Basel, Basel, Switzerland. soeren.becker@becker-malente.de.|Institute of Medical Microbiology and Hygiene, Saarland University, Homburg/Saar, Germany. soeren.becker@becker-malente.de.
Sören L
SL
Becker
Division of Tropical and Humanitarian Medicine, Geneva University Hospitals, Geneva, Switzerland. emilie.alirol@hcuge.ch.
Emilie
E
Alirol
Department of Paediatrics and Adolescent Medicine, B P Koirala Institute of Health Sciences, Dharan, Nepal. nishakesharybhatta@yahoo.com.
Nisha K
NK
Bhatta
Department of Microbiology, B P Koirala Institute of Health Sciences, Dharan, Nepal. bhattarai03@yahoo.com.
Narayan R
NR
Bhattarai
Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. ebottieau@itg.be.
Emmanuel
E
Bottieau
Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland. martin.bratschi@unibas.ch.|University of Basel, Basel, Switzerland. martin.bratschi@unibas.ch.
Martin W
MW
Bratschi
London School of Hygiene and Tropical Medicine, London, United Kingdom. sakibburza@gmail.com.
Sakib
S
Burza
Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland. couljeanvae@yahoo.fr.|University of Basel, Basel, Switzerland. couljeanvae@yahoo.fr.|Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire. couljeanvae@yahoo.fr.|Département Environnement et Santé, Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, Abidjan, Côte d'Ivoire. couljeanvae@yahoo.fr.
Jean T
JT
Coulibaly
Institut National de Recherche en Santé Publique, Bamako, Mali. mamanieledk@yahoo.fr.
Mama N
MN
Doumbia
Division of Tropical and Humanitarian Medicine, Geneva University Hospitals, Geneva, Switzerland. ninonseiko.horie@hcuge.ch.
Ninon S
NS
Horié
Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. jjacobs@itg.be.
Jan
J
Jacobs
Department of Microbiology, B P Koirala Institute of Health Sciences, Dharan, Nepal. basudhak@gmail.com.
Basudha
B
Khanal
Institut National de Recherche en Santé Publique, Bamako, Mali. aland954@hotmail.fr.
Aly
A
Landouré
Centre for Tropical Medicine, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia. yodi_mahendradhata@yahoo.co.uk.
Yodi
Y
Mahendradhata
University of Cape Town, Cape Town, South Africa. fmeheus@gmail.com.
Filip
F
Meheus
Coris BioConcept, Gembloux, Belgium. pascal.mertens@corisbio.com.
Pascal
P
Mertens
Centre for Tropical Medicine, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia. fransiska.msitorus@gmail.com.
Fransiska
F
Meyanti
Centre for Tropical Medicine, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia. herdiana.elsa@gmail.com.
Elsa H
EH
Murhandarwati
Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire. eliezerngoran@yahoo.fr.|Département Environnement et Santé, Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, Abidjan, Côte d'Ivoire. eliezerngoran@yahoo.fr.
Eliézer K
EK
N'Goran
London School of Hygiene and Tropical Medicine, London, United Kingdom. rosanna.peeling@lshtm.ac.uk.
Rosanna W
RW
Peeling
Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. rravinetto@itg.be.|Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium. rravinetto@itg.be.
Raffaella
R
Ravinetto
Department of Internal Medicine, B P Koirala Institute of Health Sciences, Dharan, Nepal. sumanrijal2@yahoo.com.
Suman
S
Rijal
Institut National de Recherche en Santé Publique, Bamako, Mali. msacko@afribonemali.net.
Moussa
M
Sacko
Institut National de Recherche en Santé Publique, Bamako, Mali. srenion@yahoo.fr.
Rénion
R
Saye
Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland. pierre.schneeberger@unibas.ch.|University of Basel, Basel, Switzerland. pierre.schneeberger@unibas.ch.|Department of Epidemiology and Molecular Diagnostics, Agroscope Changins-Wädenswil ACW, Wädenswil, Switzerland. pierre.schneeberger@unibas.ch.|Department of Virology, Spiez Laboratory, Federal Office for Civil Protection, Spiez, Switzerland. pierre.schneeberger@unibas.ch.
Pierre H H
PH
Schneeberger
Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. cschurmans@itg.be.
Céline
C
Schurmans
Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire. kigbafori.silue@gmail.com.|Département Environnement et Santé, Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, Abidjan, Côte d'Ivoire. kigbafori.silue@gmail.com.
Kigbafori D
KD
Silué
Centre for Tropical Medicine, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia. j.atthobari@gmail.com.
Jarir A
JA
Thobari
Institut National de Recherche en Santé Publique, Bamako, Mali. traorem@afribonemali.net.
Mamadou S
MS
Traoré
Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands. E.A.van_Lieshout@lumc.nl.
Lisette
L
van Lieshout
Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. hvanloen@itg.be.
Harry
H
van Loen
Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium. tverdonck@itg.be.
Kristien
K
Verdonck
Institute of Medical Microbiology and Hygiene, Saarland University, Homburg/Saar, Germany. lutz.mueller@uniklinikum-saarland.de.
Lutz
L
von Müller
Divisions of Infectious Diseases and Medical Microbiology, J.D. MacLean Centre for Tropical Diseases, McGill University Health Centre, Montreal, Canada. cedric.yansouni@mail.mcgill.ca.
Cédric P
CP
Yansouni
Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire. yaojoel@yahoo.fr.|Département Environnement et Santé, Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, Abidjan, Côte d'Ivoire. yaojoel@yahoo.fr.
Joel A
JA
Yao
Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire. ykpatrick@yahoo.fr.
Patrick K
PK
Yao
Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland. p.yap@unibas.ch.|University of Basel, Basel, Switzerland. p.yap@unibas.ch.
Peiling
P
Yap
Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium. mboelaert@itg.be.
Marleen
M
Boelaert
Division of Tropical and Humanitarian Medicine, Geneva University Hospitals, Geneva, Switzerland. francois.chappuis@unige.ch.
François
F
Chappuis
Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland. juerg.utzinger@unibas.ch.|University of Basel, Basel, Switzerland. juerg.utzinger@unibas.ch.
Jürg
J
Utzinger
D015746:Abdominal Pain / Q000209:etiology; D000293:Adolescent; D000818:Animals; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D019411:Clinical Laboratory Techniques / Q000191:economics / Q000592:standards; D003362:Cost-Benefit Analysis; D007560:Cote d'Ivoire / Q000453:epidemiology; D003967:Diarrhea / Q000150:complications / Q000175:diagnosis / Q000191:economics / Q000453:epidemiology* / Q000382:microbiology / Q000469:parasitology; D005243:Feces / Q000469:parasitology; D005260:Female; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D007223:Infant; D007231:Infant, Newborn; D008302:Mali / Q000453:epidemiology; D009390:Nepal / Q000453:epidemiology; D011446:Prospective Studies; D012307:Risk Factors