From the front line

We hear from Professor Daouda Ndiaye – a Senegalese researcher taking on malaria – about a new test promising to save lives by being faster, more accurate and easier to use.

A new method of testing for malaria that will put less strain on lab technicians and provide more accurate results at the same time could be a watershed moment in the battle against a disease that is one of the top three killers of children worldwide. Malaria can progress from mild symptoms to being life threatening in a matter of hours and therefore, quick and accurate diagnostics are vital to reduce the significant morbidity and mortality caused by malaria. Testing and scaling up new methods to access the hardest-to-reach and highest-risk populations is a vital piece in the malaria control jigsaw.

My own commitment to the fight against malaria began when, as a child growing up in Senegal, I survived severe malaria, which also infected many in my suburban community, Pikine, because of case management issues at that time. Fortunately these issues have been addressed today by current strategic programs against malaria implemented through the National Malaria Control Programme of Senegal (NMCP) and its partners. Later, my brother contracted the disease. I was still at an early stage of my medical studies but, thankfully, I was able to recognise the symptoms and identify it so he could be treated. At that point I vowed to build my medical knowledge to help others.

Malaria can progress from mild symptoms to being life threatening in a matter of hours

I took a Masters in Sciences and Biology, a Doctorate at Cheikh Anta Diop University (UCAD), Senegal, a Parasites and Mycology diseases specialisation degree between Dakar and Paris. I then went on to study for my PhD at the Department of Immunology of Infectious Diseases, Harvard University, through the Fogarty training program, under the mentorship of Professor Dyann Wirth. I then returned to Senegal where I am now leading the Centers of Excellence on Malaria and the Genomics of infectious diseases, working to control malaria and eliminate the disease. Better methods of vector control and prevention, such as mosquito nets and sprays, have succeeded in controlling malaria however, for malaria elimination, world organisations need to adapt the way they support the fight against the disease. This includes more accurate and faster testing, which has always been a step behind control and treatment, and finding new ways to access the hardest to reach and highest risk populations. This is especially true for those in sub-Saharan African medical centres, which are typically overcrowded.

In collaboration with partners such as the NMCP, the Center for Disease Control and Prevention (CDC) and Cheikh Anta Diop University of Dakar, field evaluations of the illumigene Malaria LAMP test in Senegal, have shown this test to be up to 400 times more sensitive than microscopy and much more if compared to RDT. This greatly enables the possibility to detect sub-microscopic/sub-RDT parasitemia which are known to contribute to malaria transmission, and their detection (and appropriate treatment) is necessary to advance malaria elimination.

[caption id="attachment_53508" align="alignnone" width="450"] There were more than 200 million malaria cases last year[/caption]

The test has several advantages over current diagnostic methods – microscopy and rapid diagnostic testing (RDT) – especially in the context of malaria elimination. It has demonstrated 100% sensitivity in detecting the five human-infecting malaria species P. falciparum, P. ovale, P. vivax, P, malariae and P. knowlesi – and seems to be able to do so without the need for controlled laboratory conditions. It can also be used by technicians with no specialist training on extensive laboratory technology or molecular methods. The test is not designed to replace the current diagnostic tools – which still have great value for case management in health facilities – but will complement these tests especially in the detection of very low parasite density infections. It employs Loop-Mediated Isothermal Amplification (LAMP) technology to amplify parasite DNA using the power of the most sensitive molecular testing. The current format is a Plasmodium-specific test but it can be easily adapted to specifically detect each of the Plasmodium species of interest. It has the potential to improve malaria parasite detection – delivering very real benefits for laboratories across Europe, significantly reducing the burden on specialised technicians, end of the day samples and weekend hours.

RDT is faster and easier to use but it is significantly less accurate when parasitemia carriage becomes low to very low

Microscopy is a highly accurate test that is appropriate for case management at point of care. However it relies on the skill of the microscopists – who preferably have several years’ of training and regular refresher courses, which means substantial regular financial support. Without it, the rate of incorrect diagnosis by inexperienced healthcare practitioners using microscopy can be high, which then means incorrect information for case management. PCR is highly sensitive and diagnosis is comparably consistent with the new LAMP test. However, it requires complicated and expensive equipment, as well as heating and cooling of the reagents, making PCR unsuitable for many basic settings.

RDT is faster and easier to use but it is significantly less accurate when parasitemia carriage becomes low to very low. This is particularly true in pre-elimination settings, which can result in the often fatal misdiagnosis of infected patients, as well as the potential of increased transmission. Another common outcome of inaccuracy is a lack of trust among doctors particularly in pre-elimination endemic regions, who still prescribe anti-malarials even when the RDT comes back with a negative result. In our field evaluation, the use of illumigene technology detected patients who were missed by microscopy and RDT.

Globally malaria remains one of the most common infections spread by blood transfusion, despite improved blood screening protocols.

The Senegal NMCP, supported by local and international partners, has done a wonderful job during the past 15 years in controlling malaria at nationwide level, especially in the Northern part of the country. This pre-elimination region will greatly benefit from the addition of a super-sensitive test that can detect low to very low parasite density infections and or carriage that can be performed more quickly and more easily, and that allows for greater flexibility in lab conditions to produce accurate results. It will be literally life-changing for communities at these particular pre-elimination regions. There are also new malaria challenges for the West: Increasing travel and immigration in Europe and the Middle East has seen the number of cases growing significantly, particularly among settled immigrants who travel to visiting friends and relatives in their country of origin. Blood banks have become another vehicle for transmitting the disease. Globally malaria remains one of the most common infections spread by blood transfusion, despite improved blood screening protocols. All these scenarios can be addressed by the availability of an easy yet sensitive test.

In summary, high-quality diagnosis is crucial to patient outcomes as well as helping to better manage malaria by reducing the risk of furtherincidence, especially in pre-elimination settings, through untreated carriers. illumigene Malaria is a step forward in this quest.

Author: Professor Daouda Ndiaye  is Professor of Parasitology and Mycology and Chief of the Laboratory of Parasitology and Mycology at the University Cheikh Anta Diop in Dakar Senegal