Diarrhoeal diseases and other digestive disorders are leading causes of morbidity and mortality worldwide, with the highest burden concentrated in tropical and subtropical areas that often lack access to clean water and adequate sanitation, and where hygienic conditions are generally poor
. According to the World Health Organization (WHO), diarrhoea is classified into three different categories, namely (i) acute watery diarrhoea (lasting several hours or days); (ii) acute bloody diarrhoea (synonymous: dysentery); and (iii) persistent diarrhoea (lasting 14 days or longer)
. ‘Chronic diarrhoea’ is often referred to as an individual term applicable to diarrhoea lasting more than 4–6 weeks, but it still lacks an unambiguous definition.
With an estimated burden of 89.5 million disability-adjusted life years (DALYs) caused in 2010, diarrhoeal diseases rank fourth in the recently published Global Burden of Disease Study
. Acute diarrhoeal episodes are mainly due to bacterial and viral pathogens that may cause a variety of clinical syndromes ranging from self-limiting events to life-threatening diseases. Children are most vulnerable and diarrhoeal diseases were responsible for more than 1.4 million deaths in 2010, ranking this disorder at position seven on the main causes of death
. In the last decades, concerted efforts have considerably improved our understanding of the epidemiology, diagnosis, treatment and control of many diarrhoeagenic pathogens globally, for instance due to the introduction of rotavirus vaccination programmes in many countries since 2006
. As a result, mortality due to diarrhoeal diseases has been reduced from an estimated 2.5 million in 1990 to just under 1.5 million in 2010, a decrease of 42%
. However, few research activities have focused on the investigation of persistent diarrhoea and non-acute abdominal pain due to digestive disorders in the tropics. Hence, little is known regarding its aetiology, epidemiology and disease burden. It is widely acknowledged that intestinal parasites, particularly helminths and intestinal protozoa play a major role as causative agents of persistent digestive symptomatologies
Infections with helminths and intestinal protozoa belong to the neglected tropical diseases, along with other diseases caused by bacterial (e.g. Buruli ulcer), viral (e.g. dengue) and fungal infections (e.g. mycetoma)
. More than 5 billion people are at risk of neglected tropical diseases, with the common soil-transmitted helminths (i.e. Ascaris lumbricoides, hookworm and Trichuris trichiura), exhibiting the widest geographical distribution
. Due to their intimate connection with poverty, the highest prevalences of neglected tropical diseases are observed in remote rural and deprived urban settings in the developing world
[7, 9, 10]. Neglected tropical diseases drain the social and economic development in endemic countries and they negatively impact on people’s quality of life and well-being at all levels
A major challenge in the clinical management of persistent digestive disorders is the weakness of health systems in many low-income countries
[16–18]. Hence, affected people might only seek care at a late stage in their therapeutic itinerary, usually at primary health care centres
[19, 20]. However, these primary health care centres are often under-staffed and ill-equipped, resulting in a low quality of care. The causes of persistent diarrhoea and other digestive disorders are frequently misdiagnosed due to the often unspecific clinical presentations and the absence of evidence-based algorithms for in-depth investigation
[7, 21]. The notorious underfinancing of health systems in many tropical and subtropical countries explains the severe neglect of laboratory networks and the only limited availability of basic tests for diagnostic services (e.g. direct faecal smears for helminth diagnosis or blood films for malaria diagnosis)
. Hence, in many developing countries, current diagnostic and treatment algorithms are often empirical, whereas local prevalence data and differential diagnoses are rarely taken into account at the primary care level.
Against this background, NIDIAG, an international collaboration on integrated diagnosis-treatment platforms, funded by the European Commission, sets out to develop an improved system for delivering primary health care in resource-constrained settings and proposes an integrated approach to this challenge. Emphasis is placed on a patient-centred approach starting from the presentation at the primary health care level of a clinical syndrome that might be due to ‘common’ pathogens. Three clinical syndromes will be investigated in the NIDIAG framework, namely (1) neurological disorders
; (2) persistent fever
; and (3) digestive disorders. Here, we focus on digestive disorders, which we define as (i) persistent (≥2 weeks) abdominal pain; (ii) persistent (≥2 weeks) diarrhoea (dysenteric or non-dysenteric); and/or (iii) blood in the stool. These digestive disorders will be investigated at different study sites in tropical areas of Africa (Côte d’Ivoire and Mali) and Asia (Indonesia and Nepal). Before clinically applicable diagnosis-treatment algorithms can be developed, the following major challenges/open issues have to be addressed. Firstly, few studies analysed the spectrum of intestinal pathogens causing persistent digestive disorders in the tropics. Therefore, epidemiological investigations targeting all potential pathogens are desirable to define the most common bacteria, parasites and viruses in the different study settings. Secondly, most diagnostic tests have only been validated in Western settings, and hence their diagnostic accuracy in the tropics remains to be determined.
In this manuscript, pursuing an extensive literature review complemented with expert opinion, we provide an overview of potential pathogens (bacterial, parasitic and viral) that might give rise to digestive disorders as defined above. Available diagnostic tests for the identified pathogens are summarised and reviewed, and we propose pathogen-specific reference tests to be utilised for an in-depth diagnostic work-up of symptomatic patients in the different study sites.