Articles

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 Chloroquine had then been replaced by sulfadoxine-pyrimethamine treatment and the exact same sequence of events happened.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 is under constant development, particularly regarding Plasmodium species. Please feel free to contact us with specific requests or comments.

Hopes for a malaria vaccine are still up

New weapons are arriving to aid the fight against malaria, among them a vaccine that could eventually protect millions from infection.

After 30 years of development by GlaxoSmithKline, the Mosquirix vaccine, also known as RTS,S, was endorsed last year by the European drugs regulator and the World Health Organization (WHO). The data from the clinical trial show that malaria cases were reduced by between a third and a half in children aged 5 to 17 months which is lower than other vaccines.

Even if the first generation vaccine did not reach its full potential, WHO stays positive. The organization insures that the vaccine could prevent up to 700 deaths per 100,000 vaccinations amounting to a “significant health impact”. In order to test RTS,S in real life conditions, WHO has ordered 5 pilot programs to take place in Sub-saharan Africa.

xRapid, the mHealth App, has followed with interest the development of this vaccine. Jean Viry-Babel, xRapid’s CEO is “thrilled by the progress of RTS,S. Our fast, accurate and inexpensive diagnostic app is the perfect companion for the deployment of this first parasitic vaccine as we can provide blanket diagnostic at very low cost and very high accuracy virtually everywhere ».

More so because the xRapid malaria diagnostic has geolocation capability, and « we have always seen it as an enabler for targeted vaccination campaigns.Current vaccines have a peak efficiency of 6 months. Combining RTS,S with first hand knowledge of the seasonality and type of malaria could really optimize its effects » – Professor David Mendels, xRapid’s CTO.

Malaria & Military Medicine

How the oldest enemy is still fought today.

« it’s going to be a very long war if for every division I have facing the enemy, I have one sick in hospital and another recovering from this dreadful disease. »

– General Douglas MacArthur, Commander of the United States Army Forces in the Far East, 1941.

Between the 17th and 22nd of May this year xRapid attended and presented at the ICMM World Congress on Military Medicine in Bali. Our CTO David Mendels spoke about the digital diagnostic tool he has developed and how it can be deployed in the field in order to offer fast and accurate malaria diagnosis without needing to access laboratory services.

When thinking about malaria, the relationship it has with the world’s military forces may not be your first thought. However, the conditions that military personnel often find themselves in when fighting in tropical climates are often hotbeds for tropical disease, and for the effectiveness of military operations this can be devastating.

« More person-days were lost among U.S. military personnel due to malaria than to bullets during every military campaign fought in malaria-endemic regions during the 20th century. » 

U.S Navy Naval Medical Research Center.

The vast majority of people suffering from malaria suffer as a direct result of their immediate surroundings and situation. Communities that struggle with the disease often live and work in economically deprived, rural and tropical areas. Military operations fought in these areas risk the disease as the locals do, and in some cases are more at risk due to spending prolonged periods in temporary camps and not having built a relative immunity to the disease over years of indigenous living. This was particularly the case for the U.S Army during World War II campaigns in the Pacific and during the Vietnam War.

 

During WWII, the U.S military recorded over 500,000 cases of malaria whilst fighting against Japanese forces in the Pacific. During this period the Japanese controlled the global supply of quinine; the preferred anti-malarial at the time. This meant that the Americans were confined to using the sub-standard drug Atabrine, a treatment with severe side-affects. This development led scientists at WRAIR (Walter Reed Army Institute of Research) to launch the largest campaign to find new drugs for a disease the world had ever seen, and this led to the development of chloroquine.

 

Unfortunately the program was discontinued after the war ended, but history repeated itself two decades later during the Vietnam war. The Vietnam War saw an influx of hundreds of thousands of U.S soldiers into an area endemic with malaria that was resistant to the chloroquine developed by WRAIR. This spurred another round of research. However, it was Chinese scientists at the behest of the struggling Vietnamese army that developed artemisinin; the most common and effective anti-malarial still in use today.

Both of these wars were instrumental in the development of current malaria treatments and research into new treatments, diagnostic techniques and vaccines continues at WRAIR and other military research institutes throughout the world. However, despite considerable advances from inside and outside of military communities malaria does remain a serious issue for operations. Malaria is still a big risk for military personnel in the field due to the fact the parasite is so complex and adaptable. Developing new treatments and chemoprophylaxis requires extensive research and malaria parasites are constantly developing resistance to treatments.

The use of some chemoprophylaxis by militaries in order to prevent infection is a complicated business. Providing large amounts of chemoprophylactics for operations is expensive and fraught with logistical difficulty. Finding the optimum amount of a prophylactic drug to introduce into the bloodstream in order to provide protection from malaria balanced with minimal side effects  is difficult, but extremely important. As with Atabrine, many modern prophylactic drugs for malaria can have serious side effects.  The most notable of these, after being in the news in recent years, is mefloquine.  The most documented adverse effect of mefloquine is a striking neuropsychiatric problem. A small amount of soldiers in Afghanistan and Iraq taking mefloquine were implicated in a cluster of grisly murder-suicides between 2002 and 2004 and studies from the Irish military showed that soldiers taking mefloquine were 3-5 times more at risk of being a danger to themselves.

Added to the growing threat of drug resistance, these problems have meant that there is a growing call for an effective malaria vaccine from both military and civilian circles. The final goal of such a vaccine is of course malaria eradication, and military contributions towards this goal have been highly significant.

Two of the most important criteria for elimination as specified by the Military Malaria Research Program at WRAIR are highly effective vaccines and improved diagnostic methods. There has been breakthroughs in  these areas; a recent study for an effective child malaria vaccine has yielded positive results, although scientists are wary that the implications for global public health are currently intangible due to an increased susceptibility to malaria if the vaccine is not topped up with a booster shot in a timely fashion.

Problems with malaria diagnosis in elimination strategies, and for military operations and civilian populations more generally, are often to do with accessibility and accuracy. Malaria is a disease that can be treated effectively if it is caught early, and for military operations this means in the field. Sufficient laboratory equipment and expertise is hard to access, and RDTs (rapid diagnostic tests) alone are often not accurate enough.

This brings us back to the World Congress of Military Medicine in Bali, and why xRapid decided to exhibit there. xRapid is very portable and can be deployed to field hospitals during military operations or humanitarian efforts. It also requires less expertise to generate an accurate set of results than traditional optical microscopy. An accurate diagnosis with a parasite count figure included can inform treatment to the extent where medical professionals can prescribe exactly the right amount of anti-malarials, stopping over-treatment and slowing the rise of drug resistance. This makes xRapid a valuable weapon for militaries around the world.

The contribution that military communities have made towards malaria research over the past century has been hugely significant. Institutes such as WRAIR have been instrumental in developing some of the most widely used anti-malaria strategies in the world, many of which are still in use today. It is sometimes the case that war has makes these advances a necessity; the Vietnam War was arguably won and lost because of malaria. However, the culture of combating tropical disease in military organisations around the world has given way to some astonishing breakthroughs. Whilst there are always issues with new drugs or vaccines, these breakthroughs have saved hundreds of thousands lives.