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 Chloroquine had then been replaced by sulfadoxine-pyrimethamine treatment and the exact same sequence of events happened.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.

 

A look back at 9 months of xRapid in Papua Indonesia

For the past nine months, xRapid has been assisting two health workers in their daily work life in Papua, the easternmost province of Indonesia. Due to the hot humid climate, the island is endemic to malaria. The whole population has been affected by the Plasmodiumparasite, mainly vivax and few falciparum.

In order to fight this deadly disease, these health workers have reached us through our Indiegogo campaign “End Malaria on Bangka Island, Indonesia” back in 2015. Shortly after, in November, they received a protocol training in Jakarta with xRapid’s CTO Professor David Mendels and started diagnosing patients two months later.

Early diagnosis is the gateway for effective malaria treatment, and thanks to xRapid the nurse was able to save a three days old baby. The newborn wasn’t feeling well, could not eat and had a fever. Even though it is unlikely that babies are born with malaria, the nurse still decided to test her with the automated diagnostic app and the result was positive. Without xRapid, the little girl wouldn’t be alive today.

Being able to use xRapid to know if malaria is involved helps relieve some of my stress when trying to treat patients with limited diagnostic resources, plus appropriate treatment can be given.” – Nurse

As early adopters these health workers helped us adapt our protocol to harsh conditions. “The nurse doesn’t have access to many medical consumables, thanks to her we discovered that we can make the hemolysis with just water instead of the Saponin solution. The slides are less clear of course, but the app can still run and identify the parasites.” – Pr David Mendels, xRapid’s CTO.

We hope that these health workers keep saving many other lives.

Tu Youyou wins the 2015 Nobel Prize for Medicine

As head of the research group that developed artemisinin, Tu Youyou took a nontraditional and innovative approach to the fight against malaria.

Here at xRapid we are delighted by the news that Tu Youyou has been awarded this years Nobel Prize for Medicine.

The Chinese researcher spearheaded the discovery of our most effective anti-malarial, and the science behind the discovery is truly amazing and well worthy of such high esteemed recognition.

Malaria is caused by a parasite, the most virulent being Plasmodium falciparum. At about 1-2 micrometers in size,  the parasite penetrates red blood cells where it consumes hemoglobin and starts its reproduction cycle. When it consumes hemoglobin the parasite rejects heme, which is poisonous to its trophozite stage. As a result the parasite stacks the heme into nano-crystals, and encapsulates it within a protein, called HRP2. This is a protective screen which stops heme from killing the parasite. Artemisinin does one simple thing, and does it really well: it stops the production of HRP2. This stops the growth and development of the parasite, which effectively kills itself with the product of its digestion. A fundamentally excellent breakthrough from the Chinese research team.

What makes Tu Youyou’s discovery so astonishing isn’t just the genius of her science. Her approach explored every avenue of possibility before the « eureka » moment. She thought both through and around the problem and discovered a reference to the use of sweet wormwood to treat malaria during the Jin dynasty at around 400AD.  Sweet wormwood contains the active compound that would go on to save millions of lives worldwide; artemisinin. The initial tests for an effective drug did not go well, but Tu Youyou’s passion and drive eventually generated excellent results after piecing together fragments of ancient text and even testing the drug on herself.

Today, artemisinin combination therapy is the preferred form of anti-malarial as stated by the WHO. Despite burgeoning resistance to the drug growing in Asia, it is still the most effective treatment for one of the worlds biggest killers. In line with the Millenium Development Goals, having a Nobel Prize awarded for a malaria fighting breakthrough is an encouraging recognition from the worlds best and brightest. There is a growing agenda to eradicate the disease, and an acknowledgement that the innovative problem solving shown by Tu Youyou is of the utmost importance feels deserved.

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xRapid is still holding units specifically designated for trial purposes. If you or any of your connections are interested in testing our technology with us please email info@xRapid.com or call us on +44 (0) 203 4881213. 

 

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.