Cholera surveillance: from theory to deployment of rapid diagnostic tests
What are the issues surrounding cholera surveillance?
Wendelin Moser: Every year, we still have worldwide 1.3 to 4 million cholera cases and 21, 000 to 143, 000 cholera deaths. In addition to actions to improve sanitation and the supply of clean drinking water, the WHO's Global Task Force on Cholera Control (GTFCC) is recommending preventive vaccination campaigns in the regions concerned to reduce the risk further epidemic.
However, the limited worldwide vaccine supply and the short duration of immunity it confers, make it necessary to prioritize the regions where vaccination must take place based on higher incidence of cholera, which requires solid surveillance data. The current cholera surveillance suffers from several limitations, making it difficult to assess the real burden of cholera.
What are the current obstacles to surveillance?
WM. First of all, we need to correctly identify cases of cholera. In an epidemic situation, not all of the suspect people having cholera turn out to be positive; the rest have other diarrheal diseases. The reference method (gold standard) for diagnosis is laboratory confirmation by culture or polymerase chain reaction (PCR) from stool samples. However, the crucial lack of laboratory facilities in countries where cholera is endemic means that confirmation takes a long time and that most cases remain untested. In recent years, rapid diagnostic tests (RDTs) have been developed to facilitate testing at the point of care, without the need for a laboratory. Simpler than PCR or culture, which requires equipment and trained people, the RDTs require no special skills and can be performed fast and easy. They, however, come with limitations in accuracy of the result.
Thus, the main questions are: can they replace the gold standard to identify a cholera outbreak and are their results sufficient to estimate the real cholera incidence in different areas with different cholera burdens?
What are the main objectives of your study?
WM.: The aim of our study is to determine how to integrate the use of RDTs into routine cholera surveillance in the Democratic Republic of Congo and Niger. Our results will support the development of recommendation for all cholera affected countries. The study will take place in 4 health areas in Goma, the capital of North-Kivu province, where the incidence of cholera is high, and 4 health areas in the ex-Katanga region in the south of the country and in Niger (Maradi region), where the cholera incidence is low to medium. The study will evaluate the two most commonly used RDTs. Although they have already been studied, their sensitivity* and specificity** compared with the reference diagnostic method, PCR or culture, will be further assessed under real world conditions in different endemic settings. We will also compare their performance with and without enrichment of samples before analysis, as enrichment improves the specificity of these RDTs, which is often a barrier to their use in low-prevalence areas, at the cost of more complex sample preparation.
The other point that our study will tackle is the sampling strategy, or which patients should be tested by RDT among suspected cases to be able to determine the true incidence of cholera. Exhaustive screening of all suspected cholera cases using RDTs might not be necessary to get a representative incidence estimation and would represent a high financial burden. In addition, the limited shelf-life of RDTs (around 18 months) increases the logistical difficulties and an appropriate level of storage (centralized at the health zone or decentralized at the health facilities) has to be investigated find a compromise between rapid availability and a decreased wastage.
In the study, we will first test all suspected cases, which will enable us to estimate the real incidence of cholera in these health areas. Then, using statistical stimulation, we will determine what would be the best strategy if we only tested a part of all suspected patients. An additional aspect of the study investigates the potential of RDTs to replace culture or PCR for identifying cholera outbreaks much faster than through often far away laboratories. Given the limited accuracy of RDTs, the GTFCC proposed a method within which a certain number of suspect cases with a positive RDT results among all tested (e.g. 3 positives among 3-7 tested cholera suspects) are sufficient to identify a cholera outbreak with a high level of confidence.
What is your studies impact for cholera affected countries?
WM.: The main aim of the study is to investigate the current surveillance system on the ground and find creative solutions on how the Ministry of Health can integrate the RDTs without much effort into the existing cholera surveillance.
For studying the real-world situation and evaluating the weaknesses and points to improve the surveillance one of the sites in the south of the country is managed entirely by the Ministry of Health. The aim is to test the use of RDTs for real-life surveillance with minimal interference of the study team. In two health zones, people from the central health office were trained in the use and deployment of RDTs. They then trained nurses in all existing cholera treatment centers (CTCs) on the use of RDTs and on reporting of the results.
This pilot site will enable us to analyze how things work in practice: who uses the test? how are stocks managed? and then how does the information (number of cases, positive results) get communicated to provincial and national authorities? Since every surveillance system is different this part of the study will be replicated in the Maradi region, Niger, to see how it works in another context.
Additionally, the qualitative part of the study in all the sites will gather testimonies from health care workers on all levels on the feasibility and implementation of the use of RDTs.
At the end of the study, we should be able to issue recommendations on the use of RDTs and the choice of sampling strategies depending on the context, which will help to improve surveillance of this disease in all affected countries and ensure that preventive measures such as vaccination are implemented more quickly based on actual evidence.
To find out more: how is the performance of a diagnostic test measured?
By comparing the results from RDTs with the gold standard we can estimate the sensitivity and specificity of the RDTs, the two measures of the RDT performance. *Sensitivity is defined as patients correctly identified as cholera positives among all patients with a positive result. Likewise, **sensitivity is the ability of correctly identifying a patient as negative.
