Review of Two Decades of Cholera Diagnostics – How Far Have We Really Come?

Background: Cholera, an ancient scourge, continues to inflict high rates of mortality today. The rising incidence of epidemics in areas of poor sanitation and crowding highlight the need for better epidemic prevention and early response. Such interventions require the availability of rapid and accurate diagnostic techniques to trigger timely response and mitigate the scale of the outbreak. The current gold standard of bacterial culture is inadequate for rapid diagnosis, highlighting the overarching neglect of field diagnostic needs. This paper was written to support the World Health Organisation's Global Task Force on Cholera Control mandated Cholera and diarrhoeal disease laboratory Network (CholdiNet) in devising a protocol for the validation of Rapid Diagnostic Tests (RDTs) for Vibrio cholerae. The status of diagnostic tools for Vibrio cholerae is assessed, describing products that have been commercialised over the last two decades and discussing their peer-reviewed evaluation. Method: Review of post-1990 peer-reviewed and grey literature on rapid diagnostic tests for Vibrio cholerae. Results: Since 1990, twenty four diagnostic tests have been developed for the detection of Vibrio cholerae in human faecal samples. Fourteen of these have also been described in the literature, with rapid chromatographic-immuno assays (CIA) featuring strongly. Polymerase chain reaction (PCR) assays maintain the ability to detect the lowest amount of bacteria; however CIAs achieve both low detection thresholds and high sensitivity and specificity, making them possible candidates for use in field conditions. Field and laboratory studies were performed in a wide range of settings demonstrating variability in performance, however only a few of these studies were sufficiently stringent, highlighting five RDTs that showed promise in field conditions; COAT, IP cholera dipstick, SMART, IP dipstick and Medicos. In light of non-independent reporting, the authors would like to see these five products undergoing additional studies, with further technical improvements if needed and commercial production. The authors hope that public health use of such a RDT in limited-resource field conditions on stool samples may contribute to effective reduction in cholera epidemic spread. Author Summary: Rising prevalence of cholera outbreaks highlights the need for accurate detection tools. Diagnosing cholera early at the onset of an epidemic, at field level, should allow for a more timely response and a quick containment of the spread and thus a diminished case load. Currently the gold standard to identify the bacteria, Vibrio cholerae, from patient samples remains reliant on lengthy bacterial cultures and an array of biochemical tests. Furthermore, the need for highly-skilled operators and numerous laboratory resources underline the inadequacy of sophisticated tests for use in remote locations. Research to develop more appropriate tools has largely focused on rapid diagnostic tests and attempts to simplify existing technologies. This is yet to deliver evidence-based appropriate tools to address the burden-of-disease cholera inflicts. In light of this neglect we have taken the first step, assessing developments in commercialised diagnostic tools, reviewing previous evaluations undertaken in the literature since 1990. In doing so, we highlight evaluation study parameters that could benefit from stringent standardisation, and identify five tests that show promise for use in field conditions. The authors recommend an indipendent assessment of these products, including technical improvements as required and production to trigger early detection of cholera epidemics.