Superbug: an emerging and quickly spreading threat to the race against malaria

While the malaria death count in Cambodia dropped to just one case in 2016, a new threat to the race against the disease arises in south-eastern Asia: superbugs. A superbug is a drug-resistant, human-killing parasite that modern medicine struggles to combat.

In the case of malaria, the superbug that is currently spreading in south-eastern Asia is multi-drug resistant. This means that the DHA-piperaquine therapy (that combines both artemisinin and piperaquine drugs) used nowadays to treat falciparum malaria, is becoming useless. This superbug is spreading rapidly in western Cambodia, north-eastern Thailand and southern Laos and only concerns the deadliest form of malaria: Plasmodium falciparum.

How did this superbug appear? Humans have unintentionally helped the parasite to develop itself. The DHA-piperaquine therapy, when taken correctly, is very efficient against malaria. But in many cases, people only take artemisinin on its own, take incomplete courses or take substandard-quality drugs. In other cases, they don’t even make it to clinics for diagnosis and treatment. All these cases, which are very common in the world’s poorest areas, drive drug resistance. That is what happened recently in south-eastern Asia.

Scientifically speaking, the emergence of the superbug is due to a single mutant parasite lineage, that replaces parasites containing less artemisinin-resistant mutations. This lineage appears to be fitter, more transmissible and able to spread more widely.

The phenomenon had already been observed twice in history. The first time (from the late 1950s to the 1970s) chloroquine-resistant malaria parasites appeared in Asia and then spread into Africa leading to a resurgence of malaria and causing millions of deaths. Chloroquine had then been replaced by sulfadoxine-pyrimethamine treatment and the exact same sequence of events happened.

If this scenario repeats itself, it could lead to a global public health disaster. Specialists say superbugs are the most dangerous threat to the progress achieved so far. Efforts to control malaria in Asia must be stepped up urgently before it spreads into Africa and becomes close to untreatable.

What are the solutions to overcome the threat? The Global Fund has created the Regional Artemisinin-Resistance Initiative (RAI) to fight this superbug. “We are currently working to close gaps in supply chains, so the right drugs are in the right places at the right time” reported the RAI Head of Program. Another solution lies in the efficient gathering of surveillance data (via efficient diagnosis reporting) so that when an outbreak flairs up, an appropriate response can be deployed immediately.

 

xRapid-Lab: the malaria parasite counter is now live on the App Store!

Following a successful trial period in many European tropical medicine institutes, xRapid-Lab, the automated counter for malaria cultures, is now live on the App Store.

This new tool supports all researchers working on lab culture of Plasmodium falciparum, by counting parasites and red blood cells faster.

xRapid-Lab is an automated system that counts parasites and red blood cells in Plasmodium cultures, saving time and money. Using an iPhone attached to the microscope, the app captures and analyses images from thin smear blood slides. It gives, in less than 2 minutes, the parasitemia, the parasite development stages and the red blood cells count. xRapid-Lab provides as well a detailed report for each of the samples tested and is, as a result, a simple way to track synchronous or asynchronous cultures

xRapid-Lab

xRapid-Lab is under constant development, particularly regarding Plasmodium species. Please feel free to contact us with specific requests or comments.

Fancy trying our new automated Plasmodium identifier?

After developing the first version of xRapid-Lab in partnership with few Tropical Medicine Institutes, xRapid would be delighted to provide you with the Plasmodium identifier for free and as long as you need. Comments and suggestions will be welcomed in order to develop a new version that will match every researcher’s identification and counting needs.

If you want to take part in the development of a disruptive identifier, contact us at info@xrapid.com

In the meantime, you can watch all the features that have been added so far:

A disruptive tool to assist researchers in labs

Thanks to a combined effort of governments, researchers, industries and non-governmental organisations progress have been made in malaria research. The world continues however to face many challenges: from anti-malarial drug and vaccine to insecticide resistance. In laboratories, research is making use of cultures of parasites: this involves long and tedious workflows that are somewhat different from the usual diagnostic of a Plasmodium from a thin smear. When we realised that researchers were measuring the parasite count many times a day, we thought we should try to help.

xRapid-Lab test for labs reserachers

 

As a result, xRapid is developing xRapid-Lab, a tool that can count all the red blood cells and parasites of all stages faster than a human eye. It has been a particularly interesting development, certainly benefiting from the interactions with non-clinical researchers: “we realized very quickly that not only xRapid-Lab would be better if we worked alongside specialists of culture, but that this would also be of real benefit to the main Malaria diagnostic app”, says David Mendels, CTO of xRapid. “In fact, we got our hands on highly synchronised samples, which have helped redefine our classification process and speed-up the analysis by an order of magnitude. We are excited to ship these improvements as soon as we are done with testing and validation”.

xRapid-Lab is currently undergoing beta-testing with a few partners, contact us at info@xrapid.com if you would be interested in joining this testing.

xRapid is strengthening its partnership with VSO Malawi

For several months xRapid, the automated diagnostic app has been collaborating with VSO (Voluntary Service Overseas), a major charity in the fields of education, healthcare and poverty alleviation. This NGO (Non-Governmental Organisation) works in 25 developing countries and with 542 local partners. The VSO Malawi branch was referred to us by our Apple partner through their Worldwide Education Strategic Initiatives Group.

The Rainy season results in an increase in malaria cases. According to the World Health Organisation, 3 million out of the 16 million inhabitants contracted malaria in 2013. During malaria season, the need for a reliable, accurate and fast diagnostic tool is key.

On the 3rd of June, we started testing with VSO Malawi at CHAM (Christian Health Association of Malawi) Hospital, Lilongwe. Thanks to xRapid-Malaria they will be able to double their testing capacity and save even more lives.

We are delighted to work with such a dedicated NGO and especially with  Dario Gentili, Country Director, Temwa Kasakula, Senior Program Manager, Symon Nayupe, lab technician, and all the team. Their devotion to fighting malaria is a great source of hope!

You can watch the training video here:

xRapid-Lab: A revolution in automated slides counting

Imagine counting 1.000 RBCs, all the young rings, the trophozoites and the schizonts in less than a minute.

Several researchers have requested a system similar to xRapid to characterise their cultures of Plasmodium – a tedious, cumbersome and repetitive task. We are happy to bring them xRapid-Lab, a natural extension of our app xRapid-Malaria, tuned to their needs.

Using a system of pattern recognition, xRapid-Lab can count all the red blood cells and parasites of all stages faster than a human eye. The xRapid automated counter captures and analyses images from thin blood slides giving, in less than 2 minutes, a detail report for each of the samples tested. xRapid-Lab offers an easy way to track a synchronous or an asynchronous cultures.

“Specifically, we had to go back to our AI engine and improve it for the detection of stages of development of the Plasmodium parasite rarely seen in patients blood (schizonts of p. Falciparum come to mind). I find it very exciting, as we are learning a lot from those special cases, and will be able to feedback that expertise at counting to better our diagnostic tool in the near future.” – Pr Mendels, xRapid’s CTO.

 

Contact the sales team for your free trial of xRapid-Lab: sales@xrapid.com

xRapid-Lab

xRapid#TB – Calling testing partners for automated tuberculosis diagnostic

The xRapid diagnostic platform is entering a new phase in its development. After successfully deploying xRapid#Malaria, we are looking for scientific and commercial partners for xRapid#TB.

The digital image processing and artificial image of xRapid, used in our malaria detection kit, offer a large number of other disease diagnosis opportunities. Recently, we have tuned our algorithms to detect yet another killer: mycobacterium tuberculosis.

At the moment, the xRapid platform is able to diagnose active tuberculosis cases, where blood containing sputum is stained with the traditional Ziehl-Neelsen method. We successfully tested xRapid#TB on a limited set of slides ranging from negative to more than 100 000 bacilli.

In order to further develop our e-health app and protocols, we are currently seeking partners who would like to use the kit (still a simple iPhone and adapter on your microscope) in its alpha and beta versions.

 

This is the chance to be at the beginning of our next adventure!

xRapid#TB

New resources on iTunes U

There is never a wrong time to learn more about Malaria, particularly when you are working for xRapid. At the same time, iTunes U is an ideal vector for training our users and updating the resources made available to them. So, we are happy to announce that we have opened, together with Surya University, the xRapid & Malaria course, in both English and French.

You can subscribe to these courses in iTunes U at the following links:

French: https://itunesu.itunes.apple.com/enroll/FNS-EWT-NXF
English: https://itunesu.itunes.apple.com/enroll/FZA-DFN-ZLL
At the moment, you will find the protocols to make a thin or thick blood smears, all illustrated, together with the manual and app guides. We have also uploaded a presentation that was given at the 41st International Congress of Military Medicine (Bali, Indonesia, May 2015) by Prof. David Mendels, our CTO. iTunes U also features a forum, per course, which can be used to discuss some of the aspects of our technology.

We are currently organizing some of the important material we have gathered during the course of research and training on xRapid, so these iTunes U channels should be updated monthly. You will also find author-prepared preprints of scientific publications as soon as we can make them available to the general public.

“How accurate is xRapid?”

Our CTO and Co-founder David Mendels answers our most commonly asked question.

One of the questions we often get asked is “how accurate is xRapid”. It’s a good question, but can be surprisingly difficult to answer. The simple answer is that we have created an automatic, optical test that performs within a 0.1% discrepancy of perfect accuracy. However, the more complicated answer takes us down a harder path. This is because there are no solid and universal standards for these sorts of measurements; one could argue that there aren’t for most diagnostics, as they tend to be very distinct from traditional methods of engineering.

Looking at material stiffness, for instance, you can determine its value from the displacement response it gives to a known applied force. Both displacement and force are calibrated from a known standard, and the measurement, or “diagnostic”, is fully codified; how many repetitions of the measurements should we take, how do we extract the data from the response curve and so on. Unfortunately this is not such a simple process with biological diagnostics. We do have guidelines from the WHO, but they are not enough to ensure the robustness of our product. This means that we have to build our own internal standards with the help of our scientific partners that not only adhere to WHO guidelines, but also enable consistent results between machines, operators, preparation methods and the other variables effecting the accuracy of our test.

So how can we ensure our test is so accurate?

The past 18 months have been a learning experience for all of us at the company, and in so many different ways. One thing that we have increased our efficiency on to a very high standard is experimental testing. These tests are vital for building acceptable internal standards and legitimising the accuracy of our tool.

Let’s take one of our recent tests as an example. We were looking at the combined influence of staining time, operators and equipment on the parasite count from a thick smear experiment. These are labour intensive experiments which we run in a fully randomized statistical design. It ensures that the results are representative of the widest range of experimental conditions. We perform the diagnostics on a set of slides from the same blood, prepared by our partner; the Pitié-Salpétrière Hospital in Paris, France’s reference center for Tropical diseases. All external factors are tested simultaneously, and we use statistical analysis to make sense of the relative importance of each one, and the combined influence they exhibit. These tests, spanning a large number of experimental conditions, are also interesting because they give us a value of the absolute and relative error of the diagnostic within a known range of uncertainty.

Comparing ourselves to the Gold Standard.

One of the difficulties of quality control  is that we need to have a traceable route to compare our diagnostic results to. xRapid is more than software; it is also a piece of equipment, the mobile microscope, the iPhone, and a set of procedures. Eventually, after building an extensive data bank of images for analysis, the software testing can be fully automated. However this is not the case for everything else, nor is it the case for the reference material. We use the parasitemia determined by trained microscopists as a reference. This means that any parasitemia has been checked by at least two expert microscopists.

One difference between our process and the traditional measurement, is that the statistical analysis delivers a confidence interval. For example, we determined on our set of slides that the parasitemia was 0.41% with a confidence interval of +/- 0.07%, which compares well to the value quoted by our expert partners (0.45%). Stemming from that set of experiments, we do not need to adjust the method further, but must ensure that the results are consistent whichever counting method is selected and for the widest range of sample preparation conditions.

The near future:

In our immediate future we need to keep working on both staining methods and the software. The goal is to eventually split those two quality assurance processes so that they can be run separately, once we have determined that their testing is robust on its own.

Our most recent tests are very positive; as mentioned earlier we are working with a highly respected institution in the field in La Pitié-Salpétrière, and our recent results have performed beyond expectations when compared to the diagnosis made by their experts on the same samples. As we move forward we expect new challenges and variables to spring up, but the quality of testing being done both internally and externally gives us confidence that these obstacles can be quickly and efficiently overcome.