Improving the diagnostic work-up of neurological disorders in rural Central Africa

Neurological disorders are diseases of the central and peripheral nervous systems, in other words, the brain, spinal cord, nerve roots, cranial and peripheral nerves including autonomic nervous system, neuromuscular junction, and muscles (WHO 2016). Prevalence, morbidity and mortality are considerable worldwide and are on the rise (Bergen DC & Silberberg D. 2002) The frequency of neurological disorders and the pattern of causative conditions are little documented in low-resource primary care settings, and particularly in sub-Saharan Africa. In the few observational studies conducted in African hospitals for the past 20 years, neurological disorders accounted for 7 to 24% of all admissions. Central nervous system (CNS) infections were suspected in one third of all patients admitted with neurological symptoms (Kwasa TO et al. 1992; Birbeck GL et al. 2001; Bower JH et al. 2007; Winkler AS et al. 2009). In contrast with other aetiologies of neurological disorders, most CNS infections may be considered as “severe and treatable diseases” (Bruzzone R et al. 2009). This is the case for conditions such as human African trypanosomiasis (HAT), cerebral malaria, bacterial meningitis, CNS tuberculosis, neurosyphilis, cryptococcal meningitis or toxoplasma encephalitis, to name a few. If left untreated, death or serious sequels usually occur; mortality rates of neurological admissions were as high as 30% in the abovementioned studies. However, outcome may be favourable with timely and appropriate management. In resource-constrained settings more than elsewhere, such “severe and treatable” conditions should be targeted in priority in the clinical decision-making process (Pauker SG & Kassirer JP. 1980). As a whole, the aetiological spectrum of neuro-infections in the tropics differs dramatically from that in temperate climates. Most CNS infections with worldwide distribution affect disproportionally the (sub)-tropical regions, like for example HIV infection, bacterial meningitis, tuberculosis or (neuro)cysticercosis. Other conditions such as malaria or HAT are restricted to the tropics and may have a very focal distribution, in areas suitable to effective transmission. Also, many infections with potential neuropathogenicity belong to the group of 17 Neglected Tropical Diseases (NTDs) on which attention has been recently brought (WHO. 2010). As underlined, most of these infectious conditions may be considered as “severe and treatable” since they cause considerable human suffering but are often vulnerable to preventive or therapeutic measures (Hotez PJ et al. 2007). However, in most tropical settings, epidemiology of NTDs and other infectious diseases (IDs) is largely unknown (Hotez PJ et al. 2009), seriously impairing the case finding and clinical decisionmaking. On top of this, most neuro-infections present with non-specific symptoms in their early stages leading to important diagnostic delays (Hasker E et al. 2011, Lorent N et al. 2008). To make matters worse, neurological diagnoses frequently require relatively advanced technology to reach an accurate diagnosis, such as electroencephalography, electromyography, computed tomography (CT) or magnetic resonance imaging (MRI) of the CNS, as well as culture or molecular workup of the cerebrospinal fluid (CSF). Since this is far beyond reach of tropical rural settings, the current diagnostic approach and empirical therapies relies almost exclusively on clinical judgment and firstline laboratory results (blood analysis and CSF examination), with the major limitation that the confirming or excluding powers of most clinical and laboratory features have never been adequately quantified, in settings lacking reference diagnostic methods. Several rapid diagnostic tests (RDTs) have been developed in the last decade and have considerably improved the management of conditions like malaria or HIV infection (Bisoffi Z et al. 2009; Lubelchek R et al. 2005). However, their diagnostic contribution has never been evaluated to date within a multi-disease (syndromic) approach. This PhD study aims to describe the current clinical spectrum of neurological disorders in the rural province of Bandundu (DRC), to identify the clinical, laboratory and RDT diagnostic predictors of the main infectious aetiologies and to quantify their respective predictive contributions. The main objective is to generate evidence-based guidelines contributing to the field diagnosis of various neurological conditions, such as neuro-infections or late-onset epilepsy. This PhD proposal has been elaborated within the framework of the European-funded NIDIAG (Neglected Infections Diagnosis) project that is aimed at improving the diagnosis of Neglected Tropical Diseases causing challenging syndromes (neurological disorders, prolonged fever, chronic diarrhoea/abdominal pain) in low-resource tropical areas (www.nidiag.org).

Trefwoorden:B780-tropische-geneeskunde