tag:theconversation.com,2011:/uk/topics/malaria-parasite-22247/articlesMalaria parasite – The Conversation2023-11-23T19:02:31Ztag:theconversation.com,2011:article/2134602023-11-23T19:02:31Z2023-11-23T19:02:31ZDrug resistance may make common infections like thrush untreatable<p><em>Antimicrobial resistance is <a href="https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance">one of the biggest global threats</a> to health, food security and development. This month, The Conversation’s experts <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">explore how we got here and the potential solutions</a>.</em></p>
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<p>We’ve all heard about antibiotic resistance. This happens when bacteria develop strategies to avoid being destroyed by an antibiotic. </p>
<p>The consequences of antibiotic resistance mean an antibiotic previously used to cure bacterial infections no longer works effectively because the bacteria have become resistant to the drug. This means it’s getting harder to cure the infections some bacteria cause.</p>
<p>But unfortunately, it’s only one part of the problem. The same phenomenon is also happening with other causes of infections in humans: fungi, viruses and parasites.</p>
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Read more:
<a href="https://theconversation.com/the-rise-and-fall-of-antibiotics-what-would-a-post-antibiotic-world-look-like-213450">The rise and fall of antibiotics. What would a post-antibiotic world look like?</a>
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<p>“Antimicrobial resistance” means the drugs used to treat diseases caused by microbes (bugs that cause infection) no longer work. This occurs with antibacterial agents used against bacteria, antifungal agents used against fungi, anti-parasitic agents used against parasites and antiviral agents used against viruses.</p>
<p>This means a wide range of previously controllable infections are becoming difficult to treat – and may become untreatable. </p>
<h2>Fighting fungi</h2>
<p>Fungi are responsible for a range of infections in humans. Tinea, ringworm and vulvovaginal candidiasis (thrush) are some of the more familiar and common superficial fungal infections. </p>
<p>There are also life-threatening fungal infections such as aspergillosis, cryptococcosis and invasive fungal bloodstream infections including those caused by <em>Candida albicans</em> and <em>Candida auris</em>. </p>
<p>Fungal resistance to antifungal agents is a problem for several reasons. </p>
<p>First, the range of antifungal agents available to treat fungal infections is limited, especially compared to the range of antibiotics available to treat bacterial infections. There are only four broad families of antifungal agents, with a small number of drugs in each category. Antifungal resistance further restricts already limited options.</p>
<p>Life-threatening fungal infections happen less frequently than life-threatening bacterial infections. But they’re rising in frequency, especially among people whose immune systems are compromised, including by <a href="https://7news.com.au/news/qld/first-heart-transplant-patient-to-die-from-fungal-infection-at-brisbanes-prince-charles-hospital-identified-as-mango-hill-gp-muhammad-hussain-c-12551559">organ transplants</a> and chemotherapy or immunotherapy for cancer. The threat of getting a drug-resistant fungal infection makes all of these health interventions riskier.</p>
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Read more:
<a href="https://theconversation.com/how-do-candida-auris-and-other-fungi-develop-drug-resistance-a-microbiologist-explains-203495">How do _Candida auris_ and other fungi develop drug resistance? A microbiologist explains</a>
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<p>The greatest <a href="https://www.frontiersin.org/articles/10.3389/fimmu.2017.00735/full">burden of serious fungal disease</a> occurs in places with limited health-care resources available for diagnosing and treating the infections. Even if infections are diagnosed and antifungal treatment is available, antifungal resistance reduces the treatment options that will work.</p>
<p>But even in Australia, common fungal infections are impacted by resistance to antifungal agents. Vulvovaginal candidiasis, known as thrush and caused by <em>Candida</em> species and some closely related fungi, is usually reliably treated by a topical antifungal cream, sometimes supplemented with an oral tablet. However, instances of <a href="https://www.theage.com.au/national/victoria/they-can-t-sit-properly-doctors-treat-growing-number-of-women-with-chronic-thrush-20230913-p5e499.html">drug-resistant thrush</a> are increasing, and new treatments are needed.</p>
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<h2>Targeting viruses</h2>
<p>Even <a href="https://theconversation.com/why-are-there-so-many-drugs-to-kill-bacteria-but-so-few-to-tackle-viruses-137480">fewer antivirals</a> are available than antibacterial and antifungal agents. </p>
<p>Most antimicrobial treatments work by exploiting differences between the microbe causing the infection and the host (us) experiencing the infection. Since viruses use our cells to replicate and cause their infection, it’s difficult to find antiviral treatments that selectively target the virus without damaging us. </p>
<p>With so few antiviral drugs available, any resistance that develops to one of them significantly reduces the treatment options available. </p>
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Read more:
<a href="https://theconversation.com/why-are-there-so-many-drugs-to-kill-bacteria-but-so-few-to-tackle-viruses-137480">Why are there so many drugs to kill bacteria, but so few to tackle viruses?</a>
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<p>Take COVID, for example. Two antiviral medicines are in widespread use to treat this viral infection: Paxlovid (containing nirmatrelvir and ritonavir) and Lagevrio (molnupiravir). So far, SARS-CoV-2, the virus that causes COVID, has not developed significant resistance to either of these <a href="https://www.cidrap.umn.edu/covid-19/low-levels-resistance-paxlovid-seen-sars-cov-2-isolates">treatments</a>. </p>
<p>But if SARS-CoV-2 develops resistance to either one of them, it halves the treatment options. Subsequently relying on one would likely lead to its increased use, which may heighten the risk that resistance to the second agent will develop, leaving us with no antiviral agents to treat COVID. </p>
<p>The threat of antimicrobial resistance makes our ability to treat serious COVID infections rather precarious.</p>
<h2>Stopping parasites</h2>
<p>Another group of microbes that cause infections in humans are single-celled microbes such as <em>Plasmodium</em>, <em>Giardia</em>, <em>Leishmania</em>, and <em>Trypanosoma</em>. These microbes are sometimes referred to as parasites, and they are becoming increasingly resistant to the very limited range of anti-parasitic agents used to treat the infections they cause. </p>
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Read more:
<a href="https://theconversation.com/antibiotic-resistance-microbiologists-turn-to-new-technologies-in-the-hunt-for-solutions-podcast-217615">Antibiotic resistance: microbiologists turn to new technologies in the hunt for solutions – podcast</a>
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<p>Several <em>Plasmodium</em> species cause malaria and anti-parasitic drugs have been the cornerstone of malaria treatment for decades. But their usefulness has been significantly reduced by the <a href="https://www.mmv.org/our-work/mmvs-pipeline-antimalarial-drugs/antimalarial-drug-resistance">development of resistance</a>. </p>
<p><em>Giardia</em> parasites cause an infection called giardiasis. This can resolve on its own, but it can also cause severe gastrointestinal symptoms such as diarrhea, nausea, and bloating. These microbes have <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207226/">developed resistance</a> to the main treatments and patients infected with drug-resistant parasites can have protracted, unpleasant infections. </p>
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<img alt="3D illustration of Giardia lamblia protozoan" src="https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/559783/original/file-20231115-19-5oxysw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption"><em>Giardia</em> parasites (illustrated here) cause giardiasis.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/giardia-lamblia-protozoan-causative-agent-giardiasis-1038065005">Shutterstock</a></span>
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<h2>Resistance is a natural consequence</h2>
<p>Treating infections influences microbes’ evolutionary processes. Exposure to drugs that stop or kill them pushes microbes to either evolve or die. The exposure to antimicrobial agents provokes the evolutionary process, selecting for microbes that are resistant and can survive the exposure. </p>
<p>The pressure to evolve, provoked by the antimicrobial treatment, is called “selection pressure”. While most microbes will die, a few will evolve in time to overcome the antimicrobial drugs used against them. </p>
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Read more:
<a href="https://theconversation.com/how-do-bacteria-actually-become-resistant-to-antibiotics-213451">How do bacteria actually become resistant to antibiotics?</a>
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<p>The evolutionary process that leads to the emergence of resistance is inevitable. But some things can be done to minimise this and the problems it brings. </p>
<p>Limiting the use of antimicrobial agents is one approach. This means reserving antimicrobial agents for when their use is known to be necessary, rather than using them “just in case”.</p>
<p>Antimicrobial agents are precious resources, holding at bay many infectious diseases that would otherwise sicken and kill millions. It is imperative we do all we can to preserve the effectiveness of those that remain, and give ourselves more options by working to discover and develop new ones.</p>
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<p><em>Read the other articles in The Conversation’s series on the dangers of antibiotic resistance <a href="https://theconversation.com/au/topics/the-dangers-of-antibiotic-resistance-146983">here</a>.</em></p><img src="https://counter.theconversation.com/content/213460/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christine Carson receives funding from state and federal funding agencies, and the CUREator program, a national biotechnology incubator delivered by Brandon BioCatalyst. She has a commercial interest in companies developing diagnostic tests and preventing viral infections.</span></em></p>We’ve all heard of antibiotic resistance. The same thing is happening with other causes of infections in humans: fungi, viruses and parasites. This is making thrush and other infections hard to treat.Christine Carson, Senior Research Fellow, School of Medicine, The University of Western AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1727002021-12-10T05:46:41Z2021-12-10T05:46:41ZThe warning lights are on for malaria medicines in Africa<figure><img src="https://images.theconversation.com/files/436076/original/file-20211207-136652-kzthjf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Medicines, insecticides and nets may deliver short-term anti-malaria goals.
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p><em>Reports of sporadic resistance to modern malaria drugs have begun appearing in recent years, and are now confirmed in <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00142-0/fulltext">Rwanda</a> and <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2101746">Uganda</a>. The Conversation Africa’s Ina Skosana asked infectious diseases experts Deus Ishengoma and Fredros Okumu to explain this development and what the implications are.</em></p>
<h2>What is drug resistant malaria and how did it come about?</h2>
<p>Resistance occurs when the effectiveness of a drug is reduced and it no longer provides a full cure against the targeted infection. It usually starts with only a few mutated parasites that survive treatments in an area. But it can spread rapidly because these resistant parasites continue to reproduce, while the susceptible ones are killed by the treatments. </p>
<p>For example, <a href="https://www.ncbi.nlm.nih.gov/books/NBK2616/">chloroquine</a> was once considered to be the magic bullet against malaria. But malaria parasites evolved to survive it. The resistance spread in the 1980s and 1990s. It took more than 20 years of gradual failure before African governments and the World Health Organisation (WHO) agreed to change the guidelines and stop using chloroquine.</p>
<p>One reason for this was that the alternative medicines, notably artemisinin combination therapy (ACTs), were way <a href="https://pubmed.ncbi.nlm.nih.gov/16098946/">too expensive and out of reach</a> for most patients in the low-income countries</p>
<p>The other alternative drug at the time, sulfadoxine-pyrimethamine, was also showing <a href="https://academic.oup.com/trstmh/article-abstract/103/Supplement_1/S11/1908160">signs of failure</a>. </p>
<p>The methods for diagnosing malaria were less accurate and not always available back then. So children with fever were commonly treated as if they had malaria. This situation <a href="https://academic.oup.com/trstmh/article-abstract/103/4/333/1917327">required a low-cost</a> and widely available medicine, even if imperfect. </p>
<p>An even bigger problem was the lack of real-time data on the extent, impact and magnitude of drug resistance. The delayed appreciation of drug resistance caused an unnecessarily <a href="https://www.ncbi.nlm.nih.gov/books/NBK2616/">large number</a> of severe malaria cases and preventable deaths across Africa in the late 1990s and early 2000s.</p>
<p>The WHO then recommended the use of artemisinin combination therapy (ACTs). These are cocktails, in which the most important ingredients are derivatives of artemisinin, a plant extract first synthesized in 1972 by the Chinese chemist, Tu Youyou, who later won the <a href="https://www.nobelprize.org/prizes/medicine/2015/tu/facts/">Nobel Prize in Physiology and Medicine in 2015</a>. Because the ACTs are mixtures, it is difficult for malaria parasites to resist them.</p>
<p>Soon after the introduction of ACTs, reports of resistance to artemisinins started to emerge. These were initially in <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa0808859">south-east Asia</a>.</p>
<p>Since 2006, the WHO has been advising countries not to use single drugs (<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1463909/">especially any artemisinin drug on its own</a>). Instead, countries should use mostly combination therapies.</p>
<p>Unfortunately, for management of severe malaria, there are still no alternatives, so the recommended options still consist of only one active ingredient instead of mixtures. Examples are <a href="https://www.mmv.org/access/products-projects/injectable-artesunate-treatment-severe-malaria">artesunate injections</a> or the <a href="https://www.mmv.org/access/products-projects/artesunate-rectal-capsules-pre-referral-intervention-children-severe">rectal artesunate</a> capsules recommended for low income remote settings to buy families time and save lives of babies before reaching appropriate care.</p>
<p>These single drug options are the ones most threatened by the emerging resistance to front-line treatments for severe malaria in Africa. Moreover, <a href="https://www.medrxiv.org/content/10.1101/2021.09.24.21263966v1">new evidence</a> now suggests that rectal artesunate capsules may actually not reduce malaria deaths unless the underlying health systems are sufficiently strong. Therefore, new options are even more urgently required here. </p>
<h2>What do recent developments signal?</h2>
<p>In Africa, most malaria-infected people who receive treatment in good time are fully cured and suffer no long-term effects. However, a minority can be unresponsive to standard treatments. Scientists and health practitioners are increasingly concerned that the situation may worsen in the years to come.</p>
<p><a href="https://www.sanger.ac.uk/external_person/djimde-abdoulaye/">Professor Abdoulaye Djimde</a> is the director of the Malaria Research and Training Centre at the University of Bamako in Mali. He was among the experts who first demonstrated (in 2001) how certain genetic changes in malaria parasites were linked to resistance against chloroquine. We <a href="https://www.youtube.com/watch?v=YJQee6MSPTQ">recently asked him</a> about the evidence for resistance to artemisinins in Africa. He thought deeply for moments before stating sadly that “the lights are yellow”. By this he meant that front-line drugs remain largely effective, but the likelihood of widespread failure is growing fast. </p>
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<figcaption><span class="caption">Malaria Meds: a MasterClass with Profs. Timothy Wells, Pierre Hugo, George Jagoe & Abdoulaye Djimde.</span></figcaption>
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<p>Efforts to develop new medicines have gained momentum, but no new drugs are expected in the market for at least several years. </p>
<p>The good news is that resistance to artemisinins has not spread widely in Africa. A recent <a href="https://www.sciencedirect.com/science/article/pii/S2211320721000282">review</a> by a consortium of African scientists concluded that African malaria parasites already have the genetic changes potentially associated with resistance to artemisinins. But the frequency of these changes is still very low. Surveillance of these genetic elements must be ramped up and performance of drug treatments closely monitored. </p>
<p>It matters because of the scale of the potential problem. There are <a href="https://www.who.int/news-room/fact-sheets/detail/malaria">241 million malaria cases</a> resulting in <a href="https://www.who.int/news-room/fact-sheets/detail/malaria">627,000 deaths</a> annually – even without widespread drug resistance in Africa, where nearly all these deaths occur. </p>
<h2>What needs to happen?</h2>
<p>First, we must recognise the urgency of this situation and develop a plan. In a recent conversation, <a href="https://www.who.int/about/people/biography/pedro-alonso">Prof. Pedro Alonso</a>, the director of the WHO Global Malaria Programme, reminded us that the drug resistance in Africa is emerging independently of the situation in south-east Asia, and we should not wait until complete <a href="https://www.who.int/initiatives/mekong-malaria-elimination-programme">failure</a> emerges in Africa. </p>
<p>Prof. Alonso also recommended the following four measures. </p>
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<li><p>Accelerate research and development for alternative medicines and other tools to control malaria. </p></li>
<li><p>Maintain healthy markets to attract more manufacturers to produce malaria medicines. </p></li>
<li><p>Continuously improve the quality of care for malaria patients and reduce the use of single medicines also known as monotherapies. </p></li>
<li><p>Enhance surveillance to track drug resistance within and across borders. </p></li>
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<p>There are <a href="https://www.cdc.gov/malaria/malaria_worldwide/reduction/dx_rdt.html">now low-cost rapid diagnostics</a> for detecting malaria even in rural settings. There are also far better scientific methods for monitoring performance and <a href="https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwip2PDT0af0AhUFp3IEHdh8B6sQFnoECAsQAQ&url=https%3A%2F%2Fapps.who.int%2Firis%2Fhandle%2F10665%2F43914&usg=AOvVaw0Ktmohkc3iTigQk0q2-Hb7">safety of malaria medicines</a>.</p>
<p>More importantly, <a href="https://www.who.int/malaria/mpac/mpac-october2019-session7-report-consultation-on-genomics.pdf">molecular surveillance</a> allows us to detect the resistance signals in circulating malaria parasites long before the medicines begin failing. This way, public health authorities and drug developers can stay ahead of the game, by adjusting treatment guidelines.</p>
<p>One example is a <a href="https://mesamalaria.org/mesa-track/molecular-surveillance-malaria-parasite-populations-and-antimalarial-drug-resistance">programme</a> we recently established in Tanzania to track genetic changes in the circulating malaria parasites and how these parasites respond to current treatments.</p>
<p>Countries must endeavour to prevent as many cases as possible and <a href="https://www.who.int/news/item/06-10-2021-who-recommends-groundbreaking-malaria-vaccine-for-children-at-risk">limit</a> the likelihood of severe malaria. </p>
<p>The <a href="https://www.who.int/groups/malaria-policy-advisory-group/about">WHO Malaria Policy Advisory Group</a> has emphasised the need to intensify investigations into artemisinin resistance in Africa and urged the <a href="https://www.who.int/teams/global-malaria-programme">Global Malaria Programme</a> to consider what to do if partner drugs become less effective.</p>
<p>Beyond this, we must learn from history and from recent trends. Most importantly, we all need a honest reflection of what it will really take to eliminate malaria. The overriding lesson is that problems such as resistance are merely <a href="https://dash.harvard.edu/bitstream/handle/1/37369526/WG3-1.%20Rethinking%20Malaria%20Control%20and%20Elimination%20in%20Africa_Okumu%20et%20al.pdf?sequence=10&isAllowed=y">symptoms of greater challenges</a>. Medicines, insecticides and nets may deliver short-term anti-malaria goals. But sustainable progress towards elimination requires more <a href="https://www.project-syndicate.org/commentary/malaria-prevention-mosquito-nets-not-enough-by-fredros-okumu-2019-04">holistic approaches</a>.</p><img src="https://counter.theconversation.com/content/172700/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Fredros Okumu is mosquito biologist and public health expert. He is director of science at Ifakara Health Institute in Tanzania, a Senior Fellow of Aspen Institute New Voices Fellow and a World Economic Forum Young Global Leader. <a href="https://twitter.com/Fredros_Inc">https://twitter.com/Fredros_Inc</a>. He is a member of the WHO Malaria Policy Advisory Group and reports having received research funding from the Bill and Melinda Gates Foundation and the Wellcome Trust, among others
</span></em></p><p class="fine-print"><em><span>Dr. Deus S. Ishengoma is Principal Research Scientist at the National Institute for Medical Research (NIMR), Tanzania. He is a public health expert working on genomic surveillance of malaria and on new ways to improve case management.
Dr. Ishengoma receives funding from Bill & Melinda Gates Foundation, the World Health Organization, US President’s Malaria Initiative and the US National Institute of Health.
</span></em></p>Treatments for uncomplicated malaria remain mostly robust. But the arsenal against severe malaria and deaths is rapidly weakening. New options are urgently required.Fredros Okumu, Director of Science, Ifakara Health InstituteDeus Ishengoma, Principal Research Scientist, National Institute for Medical Research (NIMR)Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1594602021-04-23T13:14:01Z2021-04-23T13:14:01ZWhat Nigeria must do to eliminate malaria: three researchers offer insights<figure><img src="https://images.theconversation.com/files/396622/original/file-20210422-23-q4yulg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Reliable and affordable tests are crucial in eliminating malaria </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/health-official-takes-blood-sample-of-a-woman-for-malaria-news-photo/522828816?adppopup=true">Pius Utomi Ekpei/AFP via Getty Images </a></span></figcaption></figure><p>Nigeria accounts for nearly a <a href="https://www.who.int/news-room/feature-stories/detail/world-malaria-report-2019">quarter</a> of deaths from malaria in the world – in 2018 the numbers stood at 95,000. Three of the country’s top malaria researchers reflect on why the numbers remain so high.</p>
<p>What does Nigeria need to do to eliminate malaria?</p>
<h2>Olukemi K. Amodu: research and innovate</h2>
<p>Malaria remains an important public health hazard globally. It is <a href="https://www.malariaconsortium.org/news-centre/pregnant-women-and-children-under-five-are-still-at-grave-risk-from-malaria-says-whoandrsquo-s-annual-report.htm#:%7E:text=According%20to%20the%20report%2C%20there,Africa%20were%20infected%20with%20malaria.">responsible</a> for high disease and death rates especially among children under five and pregnant women.</p>
<p>The malaria burden in Nigeria is high – <a href="https://www.who.int/news-room/feature-stories/detail/world-malaria-report-2019">25%</a> of cases globally. The causes include the climate, high transmission potential, socioeconomic development, an overstretched health care system and displaced populations.</p>
<p>Eliminating the disease will take sustained local funding and a strong political commitment at the federal and state levels. This requires a strong recognition of the risk to children and pregnant women.
The elimination plan must include focused research and strengthening health systems. It must also be population specific.</p>
<p>It must incorporate <a href="https://www.who.int/heli/risks/vectors/malariacontrol/en/">World Health Organisation-recommended</a> core interventions. One of these is vector control: protective measures such as insecticide treated materials, spraying to kill mosquito larvae and indoor spraying. The other is diagnostic testing and prompt treatment with effective medicines.</p>
<p>Nigeria needs sustained, interdisciplinary and multi-faceted research. This should be an interplay of basic sciences, clinical epidemiology, field epidemiology, social and behavioural studies. This will ultimately help in studying the differences and diversities in the population. Our federal government must invest more in this type of research.</p>
<p>Malaria prevalence data, clinical epidemiology, parasite diagnostics and rates are important tools for evaluating control efforts. Studies of population biology, genetics and density of the malaria parasite and vector will help find effective diagnostics, new indigenous drugs and new vector control methods. </p>
<p>There must be equal access to health management tools for malaria at all levels. This must embrace educating patent medicine sellers and incorporating knowledge of traditional or herbal medicine practices.</p>
<p>We need to develop new interventions for malaria control suitable for our population. </p>
<p>For example, people say insecticide treated nets are inconvenient, so we also need to develop new ways to use the available protective measures.</p>
<h2>Olusegun George Ademowo: beat the mosquitoes</h2>
<p>Efforts should be geared towards drastic reduction of contact between humans and mosquitoes. Surveillance is a very important component of malaria elimination.</p>
<p>Environmental management aims to control mosquitoes by removing their breeding sites and larvae. This can be done through clearing bushes around the house and other buildings. It’s important to dispose of broken pots and bottles, fix potholes on our roads and keep gutters clean.</p>
<p>We must also have reliable and affordable diagnostic means for detection of malaria parasites. The most user friendly is the rapid diagnostic test. It detects specific malaria antigens in a person’s blood if they are infected. The most sensitive tests should be identified and made available in health care facilities. They are needed in primary health care and recommended for home use. Expert microscopy should be used to validate the kits periodically.</p>
<p><a href="https://www.malariaconsortium.org/pages/112.htm">Artemisinin-based combination drugs</a> are the most acceptable for treatment. They should be made accessible and affordable. Special attention should be given to vulnerable groups: children, pregnant women and non-immune individuals visiting Nigeria from non-malarious countries.</p>
<p>The government must also be willing to eliminate malaria in Nigeria. <a href="https://health.gov.ng/doc/Final-NMEP-M_E-Plan-2014-2020-May-3rd-updated-09_05_16.pdf">The Malaria Elimination Programme</a> should be strengthened to evolve relevant home grown means to achieve its goals. The staff must be accountable and dedicated and a monitoring and evaluation system should be put in place.</p>
<h2>Segun Isaac Oyedeji: from nets to vaccines</h2>
<p><a href="https://www.reuters.com/article/us-africa-malaria-events-timeline-idUSKCN0YU0ER">In 1955</a>, the WHO launched the Global Malaria Eradication Programme to eradicate malaria globally. </p>
<p>But not all countries were involved in the programme. After some achieved elimination, its financiers stopped financial support and it stalled. Consequently, the responsibility to eliminate malaria now falls on individual countries. </p>
<p>To eliminate malaria in Nigeria, there must be sincere and sustained commitment by the government, policy makers and citizens. We must be ready to scale up existing malaria control measures and targeted interventions. </p>
<p>Available tools and strategies are currently targeted towards vector control, prompt and accurate diagnosis and effective treatment. These have enormous impact on malaria elimination programmes, succeeding in countries that have <a href="https://www.who.int/malaria/areas/elimination/malaria-free-countries/en/">eliminated malaria</a> and others at the pre-elimination phase. </p>
<p>The following control measures must be enforced and implemented:</p>
<p>We must ensure that at least 75% of the population use long-lasting insecticidal nets to kill or repel the mosquito that transmits the infection. This would give us “herd-protection” because mosquitoes would find less infected hosts and transmission of the parasite will reduce drastically. Those who have the nets must use them effectively. </p>
<p>We must make sure all pregnant women get treatment.</p>
<p>Government and policy makers may also consider the need for mass drug administration for the entire population at the same time.</p>
<p>Our health systems must be restructured, strengthened and made ready to face the challenges of malaria elimination.</p>
<p>Governments must commit to scale up funding for malaria control, the same way they aggressively pursued COVID-19 <a href="https://ncdc.gov.ng/diseases/guidelines">prevention and control</a>.</p>
<p>Development of an antimalarial vaccine will also be important for regional malaria elimination and future eradication effort. Getting a vaccine is a global effort and we are at <a href="https://www.gavi.org/gavi-statement-on-latest-trial-data-on-malaria-vaccine-candidate-rts-s?gclid=Cj0KCQjwvYSEBhDjARIsAJMn0liPzKALNoWuhGDC3jPl9d-7pOVC8AcZe2ttwKvndJJXNWP6J3D-fSAaAugEEALw_wcB">phase III trial</a> currently. Ghana, Kenya, Malawi, Tanzania and Mozambique are involved as study centres or trial sites.</p><img src="https://counter.theconversation.com/content/159460/count.gif" alt="The Conversation" width="1" height="1" />
Nigeria must invest more in research and incorporate World Health Organisation-recommended interventions to eliminate malaria.Wale Fatade, Commissioning Editor: NigeriaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1474312020-10-19T15:07:57Z2020-10-19T15:07:57ZMalaria parasites in Nigeria are genetically diverse: a danger but also a useful tool<figure><img src="https://images.theconversation.com/files/362148/original/file-20201007-20-ozffrs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/protozoan-plasmodium-falciparum-in-the-stage-royalty-free-illustration/1193685708?adppopup=true">Kateryna Kon/Getty Images </a></span></figcaption></figure><p>Malaria is one of the world’s most dangerous <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254980/">parasitic disease</a> and a major public health challenge, especially in Africa. </p>
<p>Each year, over <a href="https://www.who.int/publications/i/item/world-malaria-report-2019">200 million</a> new cases of malaria occur globally. This leads to the death of over 400,000 individuals, most of whom are children below the age of five. <a href="https://www.who.int/publications/i/item/world-malaria-report-2019">Nigeria accounts</a> for about a quarter of all malaria cases and deaths worldwide. </p>
<p>Malaria is caused by parasites of the genus <em>Plasmodium</em>. Humans acquire malaria when an infected female <em>Anopheles</em> mosquito bites an individual and injects <em>Plasmodium</em> parasites into the bloodstream. Five species of <em>Plasmodium</em> parasites are able to cause malaria in humans but the most dangerous and deadly is <em>Plasmodium falciparum</em>. It accounts for over <a href="http://apps.who.int/iris/bitstream/10665/200018/1/9789241565158_eng.pdf?ua=1">96%</a> of all <em>Plasmodium</em> species in Nigeria.</p>
<p>It has the ability to vary or mutate its genetic make-up, especially when under pressure, to generate diverse strains or <a href="https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000336">variants</a>. The result is enormous genetic diversity in natural populations. And this has consequences for malaria control and treatment. The high genetic diversity in the parasite population could lead to gradual selection of more virulent or powerful strains. That could lead in turn to the emergence and proliferation of <a href="https://www.nature.com/articles/s41598-019-50152-w">drug-resistant parasites</a>. </p>
<p>But the genetic diversity of malaria parasites is also a strong tool for monitoring the emergence, increase and spread of drug-resistant parasites. Scientists can use the information from the genetic differences to distinguish between parasites carrying drug-sensitive genotypes and those carrying drug-resistant genotypes.</p>
<p>Our research has already <a href="https://www.sciencedirect.com/science/article/pii/S1995764513601029?via%3Dihub">confirmed</a> that in malaria-endemic countries such as Nigeria, infected individuals carry <em>P. falciparum</em> parasites that are <a href="https://www.tandfonline.com/doi/abs/10.1179/136485908X252340">genetically complex or diverse</a>. What we didn’t know was how diverse the parasites are in the micro environment, such as within households and among children of the same family. </p>
<p>We thought that knowing the population structure within households could help us understand more about the pattern and development of the disease. It could also inform development of appropriate guidelines and control measures. </p>
<p><a href="https://malariajournal.biomedcentral.com/articles/10.1186/s12936-020-03415-1">We found that</a> even in the micro environment, <em>P. falciparum</em> parasites exhibit high genetic diversity. This finding was similar to results from larger communities in malaria endemic regions and has the same important implications. The implication is that a one-size fits all intervention or approach against the parasites may not be effective. </p>
<h2>Different types in one home</h2>
<p>We <a href="https://malariajournal.biomedcentral.com/articles/10.1186/s12936-020-03415-1">investigated </a> the genotypes of malaria parasite populations in children from 43 unrelated households or families in Lafia, North-central Nigeria. </p>
<p>We used a very sensitive molecular technique to determine parasite genotypes in each blood sample. We focused on a gene called MSP-2. This gene has two types, called FC27 and 3D7. Only one of these types (either FC27 or 3D7) is present in a single parasite at the stage when it enters a person’s blood.</p>
<p>Our findings showed that parasites in the study population carry genotypes containing both FC27 and 3D7. But the types were not uniformly distributed among the children in the study households. There were children living under the same roof and infected by parasites that were genetically different. This diversity could help explain why siblings of the same household experience different disease patterns or outcomes. The genetic differences in the parasites could also make the children respond differently to treatment as some children may carry drug-sensitive parasites while others carry drug-resistant parasites.</p>
<p>In some households, all the infected children may have parasites carrying mixed genotypes of both FC27 and 3D7 alleles – two parasite genotypes in one child. In other households, one of the children could be infected with parasites carrying FC27, while another child would have parasites carrying another genotype. In a few households, all the children had infection with parasites carrying genotype of only one MSP-2 type (either FC27 or 3D7), which may suggest inoculation by a single or related mosquito.</p>
<h2>Implications of our findings</h2>
<p>High genetic diversity of <em>P. falciparum</em> populations in an area is an indication that malaria transmission in the area is high. This can lead to competition for survival in the parasite population. That may in turn lead to the emergence of mutant parasites, gradual selection and spread of more virulent strains. These strains would have acquired mutation in genes associated with resistance, especially when under drug or immune selection pressure. </p>
<p>Genetic diversity of the parasite population may also be a tool for surveillance and monitoring of the status or emergence of drug-resistant parasites in a community. </p>
<p>Parasites that become drug-resistant through mutation may <a href="https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002450">increase the risk of treatment failure</a>. The relationship is not direct, though, and remains to be established. </p>
<p>Similarly, genetic diversity could be a challenge for developing a malaria vaccine. A vaccine is designed to target a particular antigen, the substance that causes the human body to recognise and fight an infection. If the parasite has several other antigens, the vaccine won’t work for them all.</p>
<p>Genetic diversity also matters when it comes to diagnosing malaria. The blood test kit is looking for a particular feature in the parasite’s genes. If the feature is slightly different from the standard, it <a href="https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(18)30631-1/fulltext">won’t be</a> picked up.</p>
<h2>Conclusion</h2>
<p>Our studies have shown that <em>P. falciparum</em> parasites exhibit high genetic diversity in natural populations, including the micro environment, in areas where malaria transmission is high. </p>
<p>Genetic diversity is a survival strategy the parasites use to escape from host immune defences and fight against malaria control interventions. But it is also a way to keep a watch for mutants that may be resistant to drugs. And it’s a tool for evaluating intervention programmes.</p><img src="https://counter.theconversation.com/content/147431/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Segun Isaac Oyedeji receives funding from:
Deutscher Akademischer Austausch Dienst (DAAD), Germany.
International Centre for Theoretical Physics (ICTP) Trieste, Italy.
International Centre for Theoretical Science (ICTS) Bengaluru, India.
</span></em></p>Genetic diversity of a parasite population might help us watch for drug-resistant parasites.Segun Isaac Oyedeji, Lecturer, Federal University, Oye EkitiLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1088332019-01-14T13:15:47Z2019-01-14T13:15:47ZWhy does malaria recur? How pieces of the puzzle are slowly being filled in<figure><img src="https://images.theconversation.com/files/253242/original/file-20190110-32154-tqk3cy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Some people suffer from repeated attacks of malaria. These can occur weeks to months or longer after contracting the disease. The phenomenon is only too familiar to those who were bitten by mosquitoes carrying the type of malaria-causing organism known as <a href="http://dx.doi.org/10.1016/j.pt.2015.02.003"><em>Plasmodium vivax</em></a>. Whereas the malaria agent in Africa is primarily <em>Plasmodium falciparum</em>, <em>P. vivax</em> is the most widespread of the more than half a dozen malaria parasite species that infect humans globally.</p>
<p>An unresolved issue is why people experience recurrences of <em>P. vivax</em> malaria despite having received treatment for the disease. There’s also still not absolute clarity about where – in which organs and tissues – the parasites that are responsible for persisting infections hide. Because we don’t know this, we can’t determine how to kill them. Without filling in these blanks, we won’t be able to achieve the goal of eradicating malaria parasites everywhere in the world. </p>
<p>For the past four decades, I have intermittently been giving consideration to what makes malaria recur long after people have become infected by <em>P. vivax</em>, and have made some significant conceptual breakthroughs. These, combined with subsequent research by other scientists, have greatly enhanced our understanding of why malaria recurs. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/253245/original/file-20190110-43538-2nzaiu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/253245/original/file-20190110-43538-2nzaiu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/253245/original/file-20190110-43538-2nzaiu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/253245/original/file-20190110-43538-2nzaiu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/253245/original/file-20190110-43538-2nzaiu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/253245/original/file-20190110-43538-2nzaiu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/253245/original/file-20190110-43538-2nzaiu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">An Anopheles mosquito.</span>
<span class="attribution"><span class="source">Ashley Burke</span></span>
</figcaption>
</figure>
<p>The most recent advance has been the ultimate acceptance of the theory I first propounded seven years ago. Namely, that the parasite multiplies – undetected – in more organs and <a href="http://dx.doi.org/10.1038/nrmicro3111">tissues</a> in the body than only the liver and bloodstream (which is conventional dogma). </p>
<p>One of the outcomes of this new conclusion is the increasing realisation that drugs might not eliminate malaria parasites with equal <a href="https://doi.org/10.1016/j.pt.2018.08.010">efficacy</a> in all of the parts of the body that they inhabit. This is a possible explanation (there are others too) for why malaria can recur despite treatment. </p>
<p>We still don’t have all the answers. But significant new insights are emerging which have important implications for the treatment of malaria, and eventually its eradication. </p>
<h2>The journey of discovery</h2>
<p>For some time now, it has been assumed that there’s only one source of malarial <a href="https://doi.org/10.1007/978-3-662-43978-4_3495">relapse</a>, namely, a <a href="http://dx.doi.org/10.1016/j.pt.2011.10.005">dormant</a> liver stage of the <em>P. vivax</em> parasite called the <a href="http://dx.doi.org/10.1007/s00436-010-2072-y">“hypnozoite”</a>. This term, which I <a href="http://dx.doi.org/10.1007/s10739-010-9239-3">coined</a> 41 years ago, is derived from the Greek words hypnos (sleep) and zoon (animal). Thus, a “sleeping animal”.</p>
<p>When a hypnozoite wakes up, it multiplies in the liver cell in which it’s living, resulting in the formation of a large number of progeny, called merozoites. After emerging from the liver cell, they invade red blood cells and reproduce inside them. When these cells burst, they release merozoites which then enter other red blood cells, in which the cycle is repeated.</p>
<p>It’s the ongoing proliferation of merozoite stage parasites in the bloodstream that leads to a recurrent bout of symptomatic illness. </p>
<p>Until now, liver cells – and especially blood vessels – have generally been considered to be the only habitats in humans where malaria parasites live and multiply.</p>
<p>But biomedical knowledge has changed. It’s now becoming <a href="https://www.researchgate.net/publication/328702818_Over-attribution_of_Plasmodium_vivax_malarial_recurrences_to_hypnozoite_activation">clearer</a> that recurrences are caused by not only merozoites inside blood vessels, but in fact by merozoites outside blood vessels too. </p>
<p>Seven years ago, I pointed out for the <a href="http://www.samj.org.za/index.php/samj/article/view/5220/3455">first time</a> (on the basis of some complicated initial <a href="http://dx.doi.org/10.1093/infdis/jis393">evidence</a>) that <em>P. vivax</em> recurrences can also be explained if there is a reservoir of merozoites outside the bloodstream.</p>
<p>The concept is simply that the non-bloodstream origin of <em>P. vivax</em> malarial recurrences can be both merozoites that occur outside blood vessels and hypnozoites in the liver (not hypnozoites only). </p>
<p>More recently, I figured out at the University of the Witwatersrand that <a href="https://doi.org/10.1017/S003118201800032X">bone marrow</a> probably serves as a merozoite reservoir for the <em>P. vivax</em> parasite. Other researchers had already suggested the <a href="https://doi.org/10.1017/S003118201800032X">possibility</a>. </p>
<p>Additionally, I have repeatedly rationalised that the same thing might apply to the <a href="https://doi.org/10.1016/j.pt.2018.08.010">spleen</a>, and perhaps other sites too. This was concluded by joining the dots (in other words, theoretically), partly through analysis of published literature, some of it relatively obscure.</p>
<h2>A paradigm shift</h2>
<p>This improved understanding is an important development and has implications for both the treatment of malaria and <a href="http://dx.doi.org/10.1016/j.pt.2017.03.002">elimination</a> of malaria parasites in human populations. This is because there are indications that a drug that kills merozoites in one site in the body will not necessarily kill all merozoites that occur elsewhere.</p>
<p>So not only might the patient not be cured, but parasites may periodically enter the circulating bloodstream and be sucked up by mosquitoes when they feed. This can result in further transmission of malaria when the infected mosquitoes bite other people. </p>
<p>But scientific dogma is often firmly entrenched. It took until last year for the idea that there is a dual origin of non-bloodstream parasites in <em>P. vivax</em> recurrences (both merozoites outside the bloodstream and hypnozoites) to gain <a href="https://doi.org/10.1016/j.pt.2018.08.010">acceptance</a>.</p>
<p>Disbelief – as well as some demonisation in knee-jerk reactions to my unconventional views – is progressively metamorphosing into agreement. This is happening mainly because of new research at Harvard University, the University of Glasgow, and elsewhere. Studies have yielded <a href="https://doi.org/10.1016/j.pt.2018.08.010">results</a> which can be adduced as additional support for my seven-year-old concept.</p>
<p>Consequently, a dramatic – and welcome – shift in attitude is taking place. Malariologists are <a href="https://doi.org/10.1016/j.pt.2018.08.010">beginning</a> to reiterate my concept and repeat supporting evidence for it that I had unearthed and included in bits and pieces in my publications in recent years, as well as presented at international <a href="https://www.researchgate.net/profile/Miles_Markus">conferences</a>.</p>
<h2>What’s next</h2>
<p>More research is being carried out to gain an even deeper understanding of the process of malarial recurrence. It involves studying parasites in cell culture, laboratory <a href="http://dx.doi.org/10.1016/j.pt.2016.02.006">mice</a>, and non-human primates, using sophisticated imaging and other cutting edge techniques. In association with this work, drug-related investigations are being undertaken in order to find out how best to treat patients who have <em>P. vivax</em> malaria.</p><img src="https://counter.theconversation.com/content/108833/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Miles B. Markus received relevant funding from the Bill & Melinda Gates Foundation; the British Council; the Royal Society (U.K.); the Wellcome Trust; and the South African Medical Research Council. A relevant conference travel grant was awarded by the National Research Foundation of South Africa.</span></em></p>Significant new insights are emerging for the treatment of malaria, and eventually its eradication.Miles B. Markus, Honorary Professorial Research Fellow, University of the WitwatersrandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/900942018-03-06T12:17:42Z2018-03-06T12:17:42ZMalaria control strategies reduce the caseload - but bring new challenges<figure><img src="https://images.theconversation.com/files/201913/original/file-20180115-101495-z6ksid.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Treated bed nets are effective in preventing malaria where mosquitoes bite indoors and late at night.</span> <span class="attribution"><span class="source">Katrina Manson /Reuters</span></span></figcaption></figure><p>Kenya’s <a href="https://theconversation.com/kenyan-study-shows-why-reusing-old-mosquito-nets-should-be-encouraged-76358">two major malaria prevention strategies</a> – indoor residual spraying of homes in high transmission areas and the issuing of insecticide treated nets – have led to a significant <a href="https://malariajournal.biomedcentral.com/articles/10.1186/s12936-017-2119-y">reduction in malaria transmission</a>.</p>
<p>The two methods were introduced in the country’s western highlands, traditionally considered a high transmission area, about a decade ago and have resulted in the disease’s caseload <a href="https://malariajournal.biomedcentral.com/articles/10.1186/s12936-017-2119-y">decreasing by about 80%</a>. </p>
<p>But the drop in cases has brought a new challenge: people have begun <a href="https://www.ncbi.nlm.nih.gov/pubmed/9186382">losing their immunity to the disease</a>. The consequence is that they are prone to contracting more complicated forms of the malaria that could result in death.</p>
<p>There are two types of immunity that people are able to develop naturally: clinical immunity and parasitological immunity. </p>
<p>People living in high transmission areas develop clinical immunity naturally after being exposed to the parasite and receiving successful treatment. Their bodies are able to resist infection. </p>
<p>They are also able to develop parasitological immunity. After being bitten by many infected mosquitoes over a long period, their bodies are able to withstand higher numbers of parasites in their blood. </p>
<p>When people don’t have parasitological immunity, they face the risk of becoming severely ill when the number of parasites in the blood increases. This can take the form of severe anaemia, cerebral malaria and eventually death. Children are particularly susceptible. </p>
<p>In our <a href="https://malariajournal.biomedcentral.com/articles/10.1186/s12936-017-2119-y">study</a> we focused on parasitological immunity in children. We wanted to understand how malaria prevention interventions such as bed nets and indoor spraying were preventing people from developing parasitological immunity. </p>
<p>We found that children who were less exposed to malaria as they grew up had lower levels of parasitological immunity. This exposed them to developing more severe strains of malaria.</p>
<p>Our findings should be taken on board as part of Kenya’s broader malaria prevention strategies. The government needs to maintain strong monitoring and surveillance networks to ensure that existing interventions are still sufficient. And it needs to work out new interventions to deal with the consequences of its interventions. </p>
<h2>Our study</h2>
<p>There is no functional test to measure the level of immune protection a person has developed. Some people have higher levels of immunity with fewer parasites in their blood. </p>
<p>Even though it’s not possible to pin down how individuals will react to malaria it is nevertheless possible to work out a person’s parasitological immunity. </p>
<p>Parasitological immunity is established by measuring the proportion of red blood cells that are infected in the body. Most people who get malaria have less than 1% of their red blood cells infected with the parasite, which rapidly multiplies. A person with 5% of their red blood cells infected is considered severely toxic. </p>
<p>We compared two sets of children, looking at the relationship between age and parasite density. We did two sets of surveys nine years apart. The first was done between June 2002 and December 2003 and the second between January 2012 and February 2015. School children between the ages of six and 13 were tested for malarial parasites in both periods. </p>
<p>When we did the first set of tests, malaria prevention tools had not yet been introduced in the highlands. The second set of children were exposed to the prevention tools. </p>
<p>We recorded the blood parasite densities – and thus infections trends – in each of the age groups. By doing this we were able to compare how the parasite density had changed between those who had grown up with bednets and indoor spraying or taken anti-malarial drugs, and those who hadn’t. </p>
<p>We found that people who had not experienced early interventions had high levels of immunity. </p>
<h2>A new gap</h2>
<p>But there’s a knock-on effect that complicates the scenario even further. People who hadn’t taken anti-malarial medicines or used treated bed nets were more likely to <a href="http://www.who.int/ith/diseases/malaria/en/">infect mosquitoes</a> because they continued to carry parasites in their blood. </p>
<p>This makes the rest of the population more susceptible to infections, with implications for the country’s broader malaria prevention strategy. </p>
<p>The risk of increased infection brings added complexity to government’s efforts. The only way to meet the challenge is to ensure that there are sufficient monitoring and surveillance strategies. </p>
<p>Another reason monitoring and evaluation matters is because mosquitoes are able to evolve and <a href="https://www.ncbi.nlm.nih.gov/pubmed/22861380">develop resistance to insecticides</a>. In addition malaria parasites can <a href="https://www.ncbi.nlm.nih.gov/pubmed/11517439">become resistant</a> to anti-malarial drugs.</p>
<p>Mosquitoes have also been shown to <a href="https://www.ncbi.nlm.nih.gov/pubmed/26209103">change their behaviour</a>, such as avoiding contact with insecticide treated surfaces. Where bed nets are used they have been shown to change from night time feeding to <a href="https://malariajournal.biomedcentral.com/articles/10.1186/s12936-015-0763-7">daytime or evenings before people go to sleep</a>. </p>
<p>If the government does not pick up these new trends early, as well as new and more severe infections, it will lose the gains it’s made against fighting malaria.</p><img src="https://counter.theconversation.com/content/90094/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrew Githeko receives funding from NIH.</span></em></p><p class="fine-print"><em><span>Ednah Ototo does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Kenya has managed to reduce the number of malaria cases in parts of the country. But this, in turn, has led to immunity levels dropping.Andrew Githeko, Chief Research Officer, Kenya Medical Research InstituteEdnah Ototo, PhD Candidate , Medical Parasitologist, Kenya Medical Research InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/861202017-10-25T12:18:34Z2017-10-25T12:18:34ZPrompt response to malaria outbreak is critical as risk of disease spreads<figure><img src="https://images.theconversation.com/files/191347/original/file-20171023-1728-1tvijhi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Changes in climatic conditions have led to an increase in malaria in East Africa.</span> <span class="attribution"><span class="source">Adriane Ohanesia/Reuters</span></span></figcaption></figure><p>A malaria outbreak has <a href="http://www.nation.co.ke/news/Malaria-cases-go-up-as-over-1-000-test-positive/1056-4145796-8hy8fx/index.html">killed 26 people</a> in <a href="https://www.google.com/url?url=http://www.kenya-information-guide.com/marsabit-county.html&rct=j&frm=1&q=&esrc=s&sa=U&ved=0ahUKEwj6n9yL4oTXAhVDbhQKHa05DN4QFggnMAI&usg=AOvVaw3UqudjtUM3PCF49kdFuZUK">Marsabit</a> in northern Kenya over the past one month. Over 1,000 people have been treated for the disease. </p>
<p>The outbreak, which is worse than previously recorded in the area for this time of year, can be attributed to a number of factors. These include a dysfunctional health service: there aren’t any qualified health workers to test for malaria and there is a shortage of drugs to treat the disease. The situation has been made worse by a four-month <a href="https://www.standardmedia.co.ke/health/article/2001257465/why-nurses-union-stalemate-could-be-resolved">long strike by nurses</a> in public hospitals.</p>
<p>But the main reason for the spike in cases seems to be that health services were caught off guard by off-season rains. Unlike in the highlands of Western Kenya, there are no malaria epidemic early warning systems for arid and semi-arid regions in the country. </p>
<h2>Malaria in low risk areas</h2>
<p>Malaria control in low risk areas like Marsabit is mainly based on prompt diagnosis and effective treatment rather than preventative measures such as the use of treated bed nets and indoor residual spraying. </p>
<p>Unfortunately during the rainy season, there is a surge of malaria cases and deaths due to people’s <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117811/">low immunity</a> and delays in seeking treatment. Other factors that affect people being treated successfully is poor <a href="https://malariajournal.biomedcentral.com/articles/10.1186/PREACCEPT-23175627763684">access to health facilities</a>. It’s not uncommon for health centres to be 10 kilometres or more apart. </p>
<p>The availability of drugs at the primary health care facilities also influences whether patients seek medical help.</p>
<p>Malaria should be treated within 24 hours of the onset of symptoms. But some health workers in low risk malaria areas are not familiar with the symptoms. Improving malaria diagnosis should be a top priority in all rural health centres.</p>
<p>On top of this is the fact that facilities are poorly staffed. Managing malaria relies heavily on functional health facilities. These health facilities rely on skilled workers such as doctors, clinical officers, nurses and laboratory staff. The <a href="https://www.capitalfm.co.ke/news/2017/08/beds-empty-public-hospitals-nurses-strike-enters-second-month/">ongoing four month nurses’</a> strike has affected health services. Patients have been forced to go to <a href="https://www.standardmedia.co.ke/article/2001242591/helpless-patients-jam-private-health-facilities-in-kakamega">private facilities</a> and those that cannot afford to pay return home unattended.</p>
<p>Additional challenges that communities in Marsabit face is the fact that there’s poor drainage which increases malaria mosquito breeding areas. Drains should be <a href="http://www.who.int/water_sanitation_health/hygiene/settings/hvchap5.pdf?ua=1">properly designed and maintained</a> to ensure that water flows away quickly, smoothly and is properly disposed.</p>
<h2>Climate change and increasing malaria cases</h2>
<p><a href="https://www.standardmedia.co.ke/health/article/2000196872/climate-change-linked-to-recent-cholera-hepatitis-a-outbreaks">Climate change</a> is predicted to increase the severity of droughts and floods. This <a href="https://link.springer.com/chapter/10.1007/978-1-4020-6174-5_4">increases the risk of epidemics and outbreaks</a>. Arid lands are prone to flooding and their aquatic systems have become reservoirs of diseases like malaria and cholera.</p>
<p>Changes in climatic conditions have also led to an increase of malaria cases in the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429085/">Kenya’s east African highlands</a>. Highland areas were considered <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429085/">free of malaria cases</a> during the 19th century. But in the last two decade malaria has spread to the central Kenya highlands including Nyeri county which is 1,800 metres above sea level. The annual temperature has increased from <a href="https://en.climate-data.org/location/4370/">17.1°C</a> to above 18°C which is suitable for local malaria transmission.</p>
<h2>Moving forward</h2>
<p>There should be functional health facilities countrywide to effectively control malaria. This can be done by ensuring that an effective vector control programme and active field based <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674909/">malaria surveillance programme</a> are in place. This complements the existing passive health facility surveillance system.</p>
<p>The surveillance system should be designed to identify malaria transmission <a href="http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001993">hot spots</a> for the roll out of preventive measures like insecticide treated bed nets or <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372949/">indoor residual spraying</a>. The use of long lasting chemicals that <a href="https://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-8-234">kill mosquito larvae</a> to discourage breeding in homesteads should also be explored more keenly.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pubmed/10065206">Community based health facilities</a> should be improved to avoid long distance travels to seek health services. Enhanced <a href="https://www.standardmedia.co.ke/health/article/2000197998/understanding-diseases-caused-by-mosquitoes">public health education</a> may also contribute to more people recognising the malaria symptoms and seeking treatment immediately. It could also reduce reliance on ineffective herbal medicines. </p>
<p>The use of radios and other forms of communication should be used to educate people about impending malaria outbreaks. Residents could learn to associate unusually heavy rains and flooding to an expected malaria outbreaks so they can take precautionary measures.</p>
<p>And the feasibility of increasing mobile health clinics in remote arid areas should be explored.</p>
<p>A combination of these actions would help minimise malaria outbreaks.</p><img src="https://counter.theconversation.com/content/86120/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrew Githeko receives funding from IDRC/DFID, NIH, WHO</span></em></p><p class="fine-print"><em><span>Ednah Ototo works for Kenya Medical Research Institute</span></em></p>Malaria is a major public health problem that affects 106 countries globally. A rigorous and systematic approach to predict and control malaria transmission is needed.Andrew Githeko, Chief Research Officer, Kenya Medical Research InstituteEdnah Ototo, PhD Candidate , Medical Parasitologist, Kenya Medical Research InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/765332017-04-24T15:59:47Z2017-04-24T15:59:47ZMosquito discovery sheds light on how malaria is spread in South Africa<figure><img src="https://images.theconversation.com/files/166494/original/file-20170424-12650-e50q0e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A second Malaria causing mosquito has been discovered in South Africa .</span> <span class="attribution"><span class="source">Flickr</span></span></figcaption></figure><p>Across the world there are limited tools available for controlling mosquitoes. The two <a href="https://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-12-62">most successful</a> and widely used initiatives are indoor house spraying and the use of insecticide treated bed nets. These target mosquitoes that feed on humans inside their homes and then rest indoors. Hundreds of millions of bed nets have been distributed across Africa in the <a href="http://apps.who.int/iris/bitstream/10665/200018/1/9789241565158_eng.pdf">last 15 years</a>. </p>
<p>But there are no methods that control mosquitoes that operate outdoors. This is a major challenge across the continent. It poses a particular problem for South Africa which has set itself the goal of <a href="https://theconversation.com/parts-of-southern-africa-are-within-tantalising-reach-of-eliminating-malaria-49848">eliminating malaria by 2018</a>.</p>
<p>The reason is the variable behaviour of the main malaria carrying mosquito in the country, <em>Anopheles arabiensis</em>. Although it prefers to feed on people inside their houses – and rest there while its eggs develop – it’s not averse to doing so outside. This makes it less amenable to house spraying which means that it’s never completely eradicated from an area.</p>
<p><a href="https://www.nature.com/articles/srep43779">Our research</a> has uncovered that another mosquito vector, <em>Anopheles vaneedeni</em>, also carries the parasite and is also amenable to biting and breeding outside. <em>Anopheles vaneedeni</em> has been known about since 1977, it has never – before now – been identified as a malaria carrying vector in nature. </p>
<p>Our discovery is a step in the right direction. It gives weight to the view that until effective methods are developed for controlling outdoor mosquitoes, eliminating local malaria transmission in southern Africa will be extremely difficult. The fact that we now know about <em>Anopheles vaneedeni</em> means that we can target our research towards knowing more about this vector’s behaviour. This, in turn, can open the door to finding solutions.</p>
<h2>South Africa’s history with malaria</h2>
<p>Historically there were cases of malaria throughout the north-eastern areas of the country which have subtropical climates: Limpopo, Gauteng, Mpumalanga and KwaZulu-Natal. There have been epidemics around Pretoria and as far south as Port St Johns on the south east coast. In 1932, for example, there were over 22,000 deaths from malaria in northern Kwazulu-Natal. </p>
<p>South Africa adopted malaria intervention strategies as early as the 1950s. As a result, the burden was reduced and areas affected by the disease shrank. Now only the far north-eastern part of Limpopo Province, eastern Mpumalanga and far northern Kwazulu-Natal, bordering Mozambique, continue to be affected. </p>
<p>South Africa has a long history of intense malaria control activities. Entomologists in the country have been studying malaria mosquitoes for close to 100 years. </p>
<p>South Africa was a pioneer in one of the early methods adopted by the World Health Organisation (WHO) to fight malaria. Extensive surveys conducted in parts of the country showed how effective it was to spray insecticides indoors to protect people from mosquito bites. This method was adopted by the WHO in the 1950s for their <a href="http://www.who.int/malaria/about_us/en/">global malaria eradication programme</a>. </p>
<p>As part of our research we assist the provincial malaria control programmes by collecting mosquitoes and doing the necessary laboratory analysis to identify the species and detect malaria parasites in these mosquitoes. </p>
<h2>What we found, and the significance</h2>
<p>We carried out an extensive collection of mosquitoes in outdoor resting places such as clay pots and modified plastic buckets. Using these methods, we found that <em>Anopheles vaneedeni</em> was indeed carrying the parasite. </p>
<p>This species was shown to be capable of transmitting malaria parasites in laboratory experiments in 1977, but has not, until now, been implicated in transmission in the field. It will happily feed on humans outdoors, and definitely liked our outdoor clay pots as resting sites.</p>
<p>We also found specimens of both <em>Anopheles arabiensis</em> in the clay pots. Until now it was thought that only this species was responsible for ongoing malaria transmission in South Africa. We now know that this situation is more complex because other Anopheles species is also responsible for the ongoing transmission.</p>
<h2>The trouble with outdoor vectors</h2>
<p>It’s now clear that the drivers of malaria in South Africa are more complicated than previously believed. Methods that target the immature stages of the mosquito’s life cycle – such as when the larvae breed in rain pools, ponds, swamps, streams, rice paddies – are generally only applicable in very specific situations. It would be impossible to treat every rain puddle on the continent. </p>
<p>Another intervention being explored is the use of sterile male mosquitoes – female mosquitoes mate only once in their lifetime and if the male is sterile, she will not produce viable eggs. </p>
<p>We are also testing novel compounds that might disrupt the parasite development inside the mosquito or kill mosquitoes that feed on cattle. </p>
<p>A lot of research, internationally, is going on into novel traps and control methods and we are collaborating with groups in the UK, US and Tanzania who want to test these methods. </p>
<p>The first step towards a successful malaria control or elimination programme, is “knowing the vector”. That means understanding the behaviour of the mosquitoes – their feeding and resting patterns, the mating behaviour of the males and females, the preferred aquatic habitat of the immature stages, their geographic distribution, and what their response is to insecticides. The Anopheles vaneedeni can now also be studied in this light.</p><img src="https://counter.theconversation.com/content/76533/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Maureen Coetzee receives funding from the National Research Foundation, the Medical Research Council, UK-MRC/DFID, Wellcome Trust and US-NIH. </span></em></p><p class="fine-print"><em><span>Basil Brooke receives funding from the National Research Foundation, the Medical Research Council of South Africa and the Centres for Disease Control & Prevention (GDD). </span></em></p><p class="fine-print"><em><span>Lizette Koekemoer receives funding from NTeMBI. Department of Science and Technology and the International Atomic Energy Agency. </span></em></p>Malaria in South Africa is close to being eliminated but to complicate matters scientists have identified a second mosquito transmitting the disease.Maureen Coetzee, Director of Wits Research Institute for Malaria in the Faculty of Health Sciences, University of the WitwatersrandBasil Brooke, Associate Professor at the Wits Research Institute for Malaria in the Faculty of Health Sciences, University of the WitwatersrandLizette Koekemoer, Associate Professor at the Wits Research Institute for Malaria in the Faculty of Health Sciences, University of the WitwatersrandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/635272016-08-04T19:39:26Z2016-08-04T19:39:26ZHow Africa is helping expand the global antimalarial drug pipeline<figure><img src="https://images.theconversation.com/files/133125/original/image-20160804-478-1wq3xuz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A scientist at the University of Cape Town's H3D drug discovery centre. </span> <span class="attribution"><span class="source">Supplied</span></span></figcaption></figure><p><em>Globally more than <a href="http://apps.who.int/iris/bitstream/10665/200018/1/9789241565158_eng.pdf?ua=1">three billion people</a> are at risk of contracting malaria. In 2015 alone, an estimated 214 million new cases were recorded. Of these 88% occurred in Africa, which shoulders the heaviest malaria burden. And of the 438,000 malaria deaths worldwide in the same year, 90% were in Africa.
One of the most difficult challenges in malaria control is antimalarial drug resistance. It also has substantial implications for global public health.
To tackle drug resistance, the only solution is for new drugs to be developed that are able to resist and/or circumvent antimalarial drug resistance. Scientists at the University of Cape Town’s drug discovery and development centre, <a href="http://h3d.co.za/">H3D</a>, have taken a critical step here, discovering a second new compound that could eventually be developed into an antimalarial medicine.
The centre’s founder and director, Professor Kelly Chibale, explains the significance of their discovery.</em></p>
<p><strong>What effect have large drug breakthroughs had on trends in malaria infection and death rates?</strong></p>
<p>Drug breakthroughs provide hope for the future and contribute to the global malaria drug pipeline, given the constant threat of antimalarial drug resistance. When a drug breakthrough successfully makes it all the way to the market for patients to take, a reduction in both malaria infections and death rates can be expected.</p>
<p>But the challenge is that only some drug breakthroughs lead to the successful development and launch of a medicine onto the market for patients to take. </p>
<p>Drugs kill a disease-causing organism like the malaria parasite by, for example, inhibiting a biological target such as a certain key enzyme or biochemical process that is important for the parasite to survive. The drug works because of specific interactions with the biological target. Among other factors, drug resistance emerges when changes or mutations occur in the biological target in such a way that the drug molecule cannot interact in a specific way with the target.</p>
<p>In some cases resistance has emerged within one year; with other drugs it can take longer. How soon resistance emerges depends on various factors, including the type of biological target, patient compliance and improper use.</p>
<p>Resistance means that we cannot use the drug at the same safe dose as was determined during clinical trials. When a drug target has undergone a mutation, the drug is no longer effective at killing the parasite at the safe dose. To increase the dose might lead to toxicity and side-effects.</p>
<p><strong>What impact has drug resistance had on malaria infection and deaths?</strong></p>
<p>Even when resistance is confined in a certain area, if that drug-resistant strain gets transmitted to another area, it will spread drug resistance. Drug resistance has rendered some drugs useless and malaria impossible to treat (using such drugs) in certain parts of the world. There are different drug-resistant strains in different parts of the world. </p>
<p>Resistance to antimalarial medicines has significantly increased the global cost of controlling malaria over time. This is due to the fact that new drugs must continually be developed to replace medicines that have become ineffective. Patients for whom the treatment is not working require repeated consultations at health facilities. This often results in lost work days, absences from school and increased costs to the health system. </p>
<p>Malaria infections and deaths will easily increase if transmission of the infectious parasite strains go unabated. Untreated malaria leads to death.</p>
<p><strong>A new candidate for a drug (MMV048) was found in 2012. What has happened since?</strong></p>
<p>MMV048 is still in clinical development undergoing human trials. Human clinical trials are extremely expensive and take a long time. They involve at least three phases. </p>
<p>Assuming funding is readily available it can take at least a minimum of six to eight years and even longer if a drug has to be tested in combination with other drugs during human clinical trials. This would require a phase four study. If funding is not available for each phase, the process can be significantly delayed.</p>
<p>Then there is an average of two years to seek regulatory approval and five to 10 years for post marketing-surveillance. </p>
<p>The are other factors, such as delays in recruiting patients for the trials or not having enough human subjects for the trials.</p>
<p>MMV048 has finished its first phase of human trials. One of the major obstacles to taking MMV048 forward to the next phase, phase two human trials, is a lack of funding. Until and unless we are successful with fundraising, the phase two trials will be delayed. </p>
<p><strong>You have found a new candidate – UCT943. What is the significance of this?</strong> </p>
<p>This candidate is significant on several levels. First, we have a promising molecule that has been added to the global antimalarial drug pipeline with the potential to contribute to malaria prevention, control and eradication. </p>
<p>Second, our data so far shows that UCT943 has promise to be more potent against the parasite. It also promises to be easier to formulate. This means that the active pharmaceutical ingredient has good chemical properties to formulate it into a capsule or tablet.</p>
<p>Third, UCT943 strengthens the inhibitor programme of the biological target parasite enzyme phosphoinositide 4-kinase. This enzyme is important for the parasite to survive. What this means is when UCT943 gets into the parasite, it blocks this enzyme’s natural function, resulting in parasite death.</p>
<p>And finally, the candidate was discovered by an international team led by <a href="http://h3d.co.za/">H3D</a>, the first integrated drug discovery and development centre in Africa. Being the first of its kind on the continent, this centre and this discovery have put South Africa on the drug discovery map internationally. It is a unique opportunity for South Africa and Africa to provide a portal of collaboration to major global companies. Internationally, pharmaceutical companies are lining up to partner with top-level universities in science and medicine. Through H3D this is already happening at the University of Cape Town.</p>
<p><strong>What happens next?</strong></p>
<p>Pre-clinical development before phase one human trials may commence. Pre-clinical development will include extensive long-term safety and/or toxicology testing, and large-scale manufacture of UCT943 to manufacture enough material for clinical trials. The pre-clinical development is expected to take 18 months.</p><img src="https://counter.theconversation.com/content/63527/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Kelly Chibale receives funding from Medicines for Malaria Venture (Switzerland), South African Technology Innovation Agency (TIA), Department of Science and Technology (DST) and Strategic Innovation Partnerships unit of the South African Medical Research Council.</span></em></p>Scientists have discovered a second new compound that could eventually be developed into a medicine to help eradicate malaria.Kelly Chibale, Professor of Organic Chemistry, University of Cape TownLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/607992016-06-16T13:08:07Z2016-06-16T13:08:07ZWhy new-fangled mosquito controls should not replace tried and tested methods<figure><img src="https://images.theconversation.com/files/126741/original/image-20160615-14027-1wmpx9s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Controlling mosquitoes has a large effect on controlling the diseases they carry.</span> <span class="attribution"><span class="source">Alvin Baez/Reuters</span></span></figcaption></figure><p>In the last 40 years of mosquito-borne viruses such as malaria, yellow fever and dengue, scientists have introduced myriad interventions to control the population of mosquitoes. This is because controlling mosquitoes has a large effect on controlling the diseases since the mosquito is the vector that carries them. </p>
<p>Novel mosquito-control approaches have included everything from deploying sterile male mosquitoes to soaps that could prevent people in high-risk malaria areas from contracting mosquito-borne diseases. </p>
<p>Zika, the latest mosquito-borne virus to be declared a <a href="http://www.portal.pmnch.org/emergencies/zika-virus/articles/one-year-outbreak/en/">global health emergency</a>, has once again propelled innovations to tackle the control of mosquitoes. </p>
<p>There is talk of trying to stop Zika by giving mosquitoes a <a href="http://www.recode.net/2016/5/31/11825676/gates-foundation-chief-code-conference-">sexually transmitted disease</a> and even injecting plants with a bacterium that would alter the <a href="http://www.smithsonianmag.com/science-nature/malaria-zika-and-dengue-could-meet-their-match-mosquito-borne-bacteria-180959271/?no-ist">mosquito’s genome</a> and eliminate its thirst for blood.</p>
<p>Many of these innovations are good ideas but collectively they are only one of the tools in the armament of fighting mosquito-borne diseases. And they should not draw focus away from the tried and tested public health measures to control mosquito-borne diseases. These include environmental sanitation and access to clean water. </p>
<h2>Different innovations</h2>
<p>Making male mosquitoes sterile was one of the first innovations introduced in the 1970s when malaria was considered a problematic disease. This was becase the malaria parasite had become resistant to front line drugs.</p>
<p>Several other quick fixes have also been offered. <a href="http://www.cdc.gov/malaria/malaria_worldwide/reduction/vector_control.html">These</a> include fungi, worms and fish that parasitise and kill larval mosquitoes before they transform into adult mosquitoes. But these innovations were all found to be ineffective.</p>
<p>Changing the genetic makeup of the mosquito has also been explored. It results in mosquitoes that are not susceptible to the parasite. But this approach is still many years from application in field settings. </p>
<p>Having grown up on the banks of a heavily polluted canal in Nigeria and with limited access to potable water, the innovation that most fascinated me is a <a href="http://www.foxnews.com/health/2016/05/12/mosquito-repellent-soap-invention-seeks-to-wash-away-africa-malaria-threat.html">mosquito-repellent soap</a>.</p>
<p>Two African scientists created the soap from natural oils and plants. The hope was that it could successfully prevent mosquito-borne diseases because it is cheap to produce and relies on existing habits such as bathing, cleaning and doing laundry.</p>
<p>But there is a catch. People need access to clean water to use the soap. Given that globally more than 700 million people still lack <a href="http://www.who.int/water_sanitation_health/hygiene/en/">access to safe water</a>, an innovation like a mosquito-repellent soap could become just another quick fix that only serves some but distracts from the complex task of providing more workable solutions.</p>
<p>The use of <a href="http://www.malariaprotection.com/es/wp-content/downloads/research/lindsay.pdf">mosquito-repellent soaps</a> is in fact not a new idea. Natural insect repellents have been in use for millennia and soaps containing such ingredients have been available for at least 30 years.</p>
<p>But natural mosquito-repellent soaps have been shown to have lower efficacy when compared to soaps containing the synthetic repellent DEET. More so, most of those natural ingredients could be <a href="https://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-10-S1-S11">harmful to health</a>. Many of them cause cancer.</p>
<p>Some of these innovations have worked on a small scale but are not as effective on a larger scale. And although the innovations focus on mosquito control, this is only one of many factors that result in the spread of mosquito-borne diseases. </p>
<h2>A complex set of diseases</h2>
<p>The reality is that there are many <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2640300/pdf/9716967.pdf">factors responsible</a> for the persistence and global spread of mosquito-borne diseases. These are complex.</p>
<p>They include: </p>
<ul>
<li><p>insecticide and drug resistance;</p></li>
<li><p>changes in public health policies;</p></li>
<li><p>emphasis on emergency response;</p></li>
<li><p>demographic and societal changes; and </p></li>
<li><p>genetic changes in pathogens. </p></li>
</ul>
<p><a href="http://www.wpro.who.int/mvp/climate_change/about/en/">Climate change</a> is also implicated. Since insects have no internal control over their body temperature, as ambient temperatures rise their distribution may expand through increased reproductive rate, biting behaviour, and survival. </p>
<p>Humidity and the availability of water for breeding in areas that are usually dry also promotes vector distribution and longevity. The incubation period of pathogens in vectors is temperature-dependent and becomes shorter in warmer conditions. </p>
<p>Unprecedented population growth, mostly in developing countries, has resulted in major movements of people, primarily to urban centres. This unplanned and uncontrolled urbanisation has led to inadequate housing and deteriorating water, sewage, and waste-management systems. These produce ideal conditions for mosquito-borne diseases to be transmitted. </p>
<p>My personal experiences and those of the hundreds of patients I treated for recurrent malaria in the slums of southern Nigeria are proof of this.</p>
<h2>The best approach</h2>
<p>So, what is the best way to prevent mosquito-borne diseases? </p>
<p>The variation in malaria’s epidemiology in and between countries shows that a multi-pronged approach is needed. This includes:</p>
<ul>
<li><p>providing and improving public health infrastructure;</p></li>
<li><p>research to develop effective drugs and vaccines; and </p></li>
<li><p>improved vector control using proven techniques while taking up new innovations.</p></li>
</ul>
<p><a href="http://www.sciencedirect.com/science/article/pii/S1473309905702681">Research</a> has shown that mosquito control measures built around environmental management are non- toxic, cost-effective, sustainable and highly effective in reducing morbidity and mortality. Those environmental measures including standing water, vegetation and drainage management all rely on access to clean water and sanitation.</p>
<p>The <a href="http://www.unicef.org/wash/3942_statistics.html">impact</a> of adequate access to clean water, sanitation and hygiene go beyond mosquito control. They are essential for human survival. Access to these basic needs has a positive impact on the overall health, wealth and economic development of people and communities around the world.</p>
<p>Improving access to water also goes a long way in preventing – and even eliminating – other water and sanitation-related diseases such as cholera, <a href="http://www.mayoclinic.org/diseases-conditions/trachoma/basics/definition/con-20025935">trachoma</a>, <a href="http://www.who.int/mediacentre/factsheets/fs115/en/">schistosomiasis</a>, worm infestations and <a href="http://www.who.int/dracunculiasis/disease/en/">guinea worm disease</a>. </p>
<p>UNICEF <a href="http://www.unicef.org/wash/3942_statistics.html">estimates</a> that if countries in need were able to get basic, low-cost water and sanitation facilities, the world would save around US$263 billion a year. Those savings would come from obviated health and labour expenses. </p>
<p>The threats that mosquito-borne diseases pose to global health are as real as the are complex. The response must be broad and calculated. It must apply proven interventions while trying out new ideas. </p>
<p>Public health innovations should be considered as just one tool in our armament. They should not distract us, as they sometimes have, from the complex task of protecting and promoting global health through interventions like improving access to clean water, sanitation and hygiene.</p><img src="https://counter.theconversation.com/content/60799/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Utibe Effiong does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Innovations targeted at mosquito control are good but should not draw focus away from the tried and tested public health measures to control mosquito-borne diseases.Utibe Effiong, Resident Physician at St Mary Mercy Hospital and Research Scientist for the Exposure Research Laboratory, University of MichiganLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/573592016-04-15T00:27:41Z2016-04-15T00:27:41ZMutant malaria parasites resistant to antimalarial Atovaquone cannot spread: new research<figure><img src="https://images.theconversation.com/files/117662/original/image-20160406-29002-xwldve.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Scientists found that malaria parasites resistant to antimalarial Atovaquone cannot survive inside their mosquito host. </span> <span class="attribution"><span class="source">Anest/www.shutterstock.com</span></span></figcaption></figure><p>Resistance to a commonly used antimalarial medication, Atovaquone, can’t spread to the general human population, new research suggests. </p>
<p>This is significant as scientists have been racing against malaria parasites’ rapid resistance to various antimalarial medications. </p>
<p>Resistance to antimalarial drugs hinders effective treatment of malaria, a life-threatening mosquito-borne infectious disease of which almost half of the world’s population (3.2 billion) are at risk of contracting. </p>
<p>An international team of researchers led by scientists from Eijkman Institute and University of Melbourne published the research today in <a href="http://science.sciencemag.org/content/352/6283/349">Science</a>. </p>
<p>The research shows that Atovaquone, a component of an effective antimalarial drug Malarone, interrupts the life cycle of resistant parasites in the mosquito phase.</p>
<p>“Drug resistance will not spread [to other patients] because mosquitoes will not be able to spread [the resistant strain]. This shows that Atovaquone is a safe drug,” co-principal investigator of the research, Professor Sangkot Marzuki, molecular biologist at the Eijkman Institute for molecular biology in Jakarta said. </p>
<p>Senior research officer from the Burnett Institute Paul Gilson, who was not involved in the research, said the findings show an “important breakthough” in malaria treatment. </p>
<p>“The big picture is that Atovaquone, once thought of as a second rate drug because parasites can easily become resistant to it, might be extremely effective at stopping malaria transmission and could therefore be important for disease eradication,” he said. </p>
<p>Like other antimalarials, Atovaquone is prone to resistance. The research findings debunked the assumption that resistance to Atovaquone will spread as it has with other antimalarials such as Artemisinin.</p>
<p>Commenting on the research, James McCarthy, professor of infectious diseases at Queensland Institute of Medical Research, who was not involved in the study said: “this suggests that the drug may be very useful in helping stop the spread of Artemisinin resistant parasites”. </p>
<p>“This [the research] would allow us to think about using Atovaquone to try to stop Artemisinin-resistant parasites from spreading because they would still be sensitive to Atovaquone,” Co-principal investigator Professor Geoffrey McFadden from University of Melbourne said. </p>
<p>Currently, Artemisinin-resistant malaria parasites have been discovered in the greater Mekong Delta and Indonesia. “If it gets away from there it then could become global,” Professor McFadden said.</p>
<p>Professor Marzuki said the findings are “important for future research on drug development” to treat not only malaria but also other parasitic diseases. </p>
<p>Malaria parasites have two life cycles: first, in their mammalian hosts, such as mice or humans; second, in their mosquito hosts. </p>
<p>The research shows that some malaria parasites developed a genetic mutation that protected them against Atovaquone in early life inside their mammalian hosts. But the mutation eventually killed the parasites in the mosquito life phase by stopping production of an essential type of energy as they grew. </p>
<p>Professor McFadden called it a “genetic trap”. </p>
<p>The research shows that Atovaquone can stop the life cycle of the resistant parasites, stopping them from spreading in the field, because it targets a protein called cytochrome b. </p>
<p>This protein, located inside the parasite’s cell – specifically in the mitochondria – is essential for the cells of the parasite to breath and release energy. </p>
<p>“The research shows that the target molecule of the drug is very important for the survival of the parasite in mosquitoes,” Professors Marzuki said. “Therefore, it’s a good target for future drug development for malaria and other parasitic diseases,” he added.</p>
<p>Professor Marzuki said using mice models, the team of researchers looked into how the parasites mutate inside their mammalian hosts and become resistant to the drug. The researchers isolated resistant mutants by periodically exposing parasites that are infecting mice with dosages of Atovaquone that would not kill the parasites entirely.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/118521/original/image-20160413-23623-5ri33o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/118521/original/image-20160413-23623-5ri33o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/118521/original/image-20160413-23623-5ri33o.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/118521/original/image-20160413-23623-5ri33o.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/118521/original/image-20160413-23623-5ri33o.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/118521/original/image-20160413-23623-5ri33o.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/118521/original/image-20160413-23623-5ri33o.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Malaria parasite.</span>
<span class="attribution"><span class="source">Courtesy of University of Melbourne</span></span>
</figcaption>
</figure>
<p>Professor Marzuki said the resistant parasites show mutations in their mitochondrial-DNA that expresses the gene for cytochrome b. </p>
<p>Professor Marzuki said this mutant strain survives in the mammalian host perhaps because even though cytochrome b could not function well in this strain, malaria parasites only need low respiratory activity when living in the red blood cells. </p>
<p>The researchers then tested the transmissibility of the resistant strain. They observed whether mice that had been bitten by mosquitoes that had bitten mice infected by the resistant strain will be infected too. The tests show the mosquitoes could not transmit the resistant strain to other mice.</p><img src="https://counter.theconversation.com/content/57359/count.gif" alt="The Conversation" width="1" height="1" />
Resistance to a commonly used antimalarial medication, Atovaquone, can’t spread to the general human population, a new research found.Prodita Sabarini, CEO/Publisher, The Conversation IndonesiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/511712015-11-26T14:01:09Z2015-11-26T14:01:09ZExplainer: what is a gene drive and how could it wipe out malaria?<figure><img src="https://images.theconversation.com/files/103345/original/image-20151126-28268-14pvpdi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Our understanding of the natural world is now so great we can manipulate the DNA blueprints for any living thing on Earth. We can replace genes for traits we don’t like with others we prefer and even add genes that don’t occur naturally in an organism. Over the last few years, scientists have developed several methods for editing genes in this way and excitement over one in particular, the CRISPR-Cas9 system, has reached fever pitch. </p>
<p>We have also developed a way to introduce these gene changes to an entire population of a species. This “gene drive” process has most recently <a href="http://www.bbc.co.uk/news/health-34898931">been used</a> to alter the DNA of small groups of mosquitoes so that they no longer carry the malaria parasite, raising the possibility of eliminating the disease altogether. But meddling with nature in this way carries huge implications that need careful consideration.</p>
<h2>Gene editing</h2>
<p>Gene-editing techniques involving cutting genes at specific sites in the DNA of an embryo in order to disrupt those genes’ function or insert other genes. For instance, <a href="https://theconversation.com/explainer-crispr-technology-brings-precise-genetic-editing-and-raises-ethical-questions-39219">the CRISPR-Cas9 system</a> uses enzymes that can cut specific gene sequences from DNA, guided by a similar molecule known as RNA. Natural gene repair mechanisms then kick in and can be used to disrupt the function of the original gene or replace it with a completely different one.</p>
<p>CRISPR systems actually aren’t new – they have existed in nature for millions of years. Bacteria use them to fend off viral infections by adding part of the virus’s DNA to their own. So why all the fuss? CRISPR-Cas9 makes artifical gene-editing much easier and cheaper, enabling scientist to target specific bits of DNA. By comparison, another method known as TALENS requires the construction of complex proteins. As a result, CRISPR gene-editing is heralding advances in biomedicine such as <a href="http://www.statnews.com/2015/11/05/doctors-report-first-use-gene-editing-technology-patient/">cancer treatments</a> and protecting individuals <a href="http://www.independent.co.uk/news/science/crispr-breakthrough-announced-in-technique-of-editing-dna-to-fight-off-deadly-illnesses-10420050.html">from infections</a></p>
<p>But there are other ways gene-editing has the potential to help in the fight against infectious diseases. <a href="http://www.nature.com/news/gene-drive-mosquitoes-engineered-to-fight-malaria-1.18858">Very recently</a>, CRISPR methods have been used to make mosquitoes resistant to malaria infections and coupled with a “chain reaction” to drive this gene modification (the resistance to malaria parasite) through the population.</p>
<h2>Gene drive</h2>
<p>This process is referred to as a “gene drive”, and again is not new: nature spreads evolutionary changes through a population all the time. It doesn’t mean changing the DNA of all living individuals in a population. Instead it’s about ensuring a specific genotype (a certain version of a gene) is passed on to the descendants of modified individuals.</p>
<p>A sexually reproducing organism usually has a 50% chance of inheriting a specific genotype from one of its parents. Using a gene drive can bias the inheritance pattern to increase that chance to nearly 100%, ensuring almost all descendants possess the genotype. As those descendants mate and produce their own offspring, the proportion of organisms with the genotype increases until it can be found in the entire population.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/103346/original/image-20151126-28284-7ks03l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/103346/original/image-20151126-28284-7ks03l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/103346/original/image-20151126-28284-7ks03l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/103346/original/image-20151126-28284-7ks03l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/103346/original/image-20151126-28284-7ks03l.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/103346/original/image-20151126-28284-7ks03l.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/103346/original/image-20151126-28284-7ks03l.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Gene warfare on malaria.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
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</figure>
<p>The idea that you can “replace” a population’s genotype is particularly appealing when that population is responsible for spreading disease, as mosquitoes are with malaria. Malaria is preventable and curable but still kills over <a href="http://www.who.int/mediacentre/factsheets/fs094/en/">400,000 people each year</a>.</p>
<p>The potential for using a gene drive to engineer insects (particularly mosquitoes) was discovered <a href="http://www.nature.com/nature/journal/v218/n5139/abs/218368a0.html">in the 1960s</a>. But the advent of CRISPR’s cheap and easy gene-editing puts this research onto a whole new footing. Researchers at the University of California, Irvine, <a href="http://www.pnas.org/content/early/2015/11/18/1521077112.abstract">recently published</a> a proof-of-princple study demonstrating the techniques can alter a population of the main type of mosquito that carries malaria in urban India, <em>Anopheles stephensi</em>.</p>
<h2>Putting into practice</h2>
<p>The longer term aim, in this instance, might be to release a persistent, modified mosquito into the environment to assist in the control a public health problem. This would be an area-wide release programme to compliment existing control interventions that would require case-by-case assessment of all the cost and benefits. For example, mathematical modelling would be needed to work out how many modified mosquitoes to release, how long it would take for the mosquito population to be clearly affected and how long it would take to impact public health.</p>
<p>One obstacle to the practical use of gene-drives is the need for relevant regulations, or at least the application of existing laws on genetic modifications. Gene-drive technologies are still some way off from the necessary environmental risk assessments for field trials and releases that would sufficiently scrutinise the risks to the environment and/or human health. These sorts of CRISPR-based modifications might even need a whole new set of regulatory structures that require a fuller debate about novel biotechnological advances.</p>
<p>Rapidly targeting genome modifications has the power to advance many aspects of basic and translational biomedical sciences. The potential benefits to reducing the impact of infectious disease and genetic disorders, including cancers, and improving the way the immune system works are huge. But the technology isn’t without pitfalls.</p>
<p>CRISPR systems rely on a guide molecule to make sure the DNA sequence is cut in exactly the right place. Getting this wrong will probably cause damage to non-target genes that could harm the organism. And just because we can edit the DNA within a species doesn’t mean we should. We need strong leadership at all levels – ethical, scientific, political – and appropriate regulations to ensure these new technologies can prosper without unintended consequences.</p><img src="https://counter.theconversation.com/content/51171/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael Bonsall receives funding from BBSRC. </span></em></p>New genetic technology could change the DNA of entire species to prevent them from spreading diseases.Michael Bonsall, Professor of Mathematical Biology, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/499862015-11-03T04:06:11Z2015-11-03T04:06:11ZThe quest to find a drug that nails the tricky malaria parasite<figure><img src="https://images.theconversation.com/files/100525/original/image-20151102-16554-rjrqi5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A doctor observes mosquitoes to better understand the malaria parasite which has been developing a resistance to the anti-malarial drugs.</span> <span class="attribution"><span class="source">Reuters/RIcardo Rojas</span></span></figcaption></figure><p><em><em>This article is part of a series The Conversation Africa is running during malaria week in the Southern African Development Community. You can read the rest of the series <a href="https://theconversation.com/africa/topics/sadc-malaria-week">here</a>.</em></em></p>
<p>Malaria is a killer that has spent thousands of years adapting to the habits of its victim. Although the first confirmed case of human malaria dates to 450 AD, a millennia and a half later, the world is still battling the parasite that causes this disease. Today at least <a href="http://www.who.int/malaria/media/world_malaria_report_2014/en/">3.3 billion</a> people, or almost half of the world’s population, are at risk of contracting malaria. The heaviest burden is in Africa where an estimated 90% of malaria deaths occur.</p>
<p>To eliminate malaria and alleviate the disease scientists have to develop drugs that kill the parasite in the blood. But to prevent the spread of the disease in a community, these drugs also have to kill transmissible versions of the parasite that develop. </p>
<p>The challenge is that the world is running out of usable antimalarial <a href="http://www.who.int/malaria/media/world_malaria_report_2014/en/">drugs</a>. Antimalarial drugs that are widely used have a limited usable lifespan. This is because parasites develop resistance. The current drugs are becoming less effective as the parasite develops resistance against them. </p>
<p>To tackle this problem, researchers are investigating potential antimalarial drugs with multiple <a href="http://www.biomedcentral.com/content/pdf/s12936-015-0572-z.pdf">targets</a> to overwhelm the parasite and reduce resistance development. Multi-target drugs may also speed up the drug discovery and development process.</p>
<p>The multi-target inhibitors that we are <a href="http://www.biomedcentral.com/content/pdf/s12936-015-0572-z.pdf">studying</a> have been shown to target both the disease causing and transmissible forms.</p>
<h2>Understanding the malaria parasite</h2>
<p>The malaria parasite is an amazing shape shifter. It is able to change its shape in different environments to cause and spread the disease. In infected humans, the parasite lives within red blood cells leading to the symptoms and complications of the disease. The main symptoms include fever, headaches and vomiting which usually appear between 10 and 15 days after the mosquito <a href="http://www.who.int/topics/malaria/en/">bite</a>.</p>
<p>But when a female mosquito bites a human infected with malaria, a special form of the parasite, called a gametocyte, is drawn up from the person along with their blood. This special parasite then develops further in the newly infected mosquito and matures into another form of parasite that can be transferred to another human when the mosquito bites someone else. This leads to the spread of malaria. </p>
<p>With repeated exposure to a drug, the parasite cleverly adapts to the presence of the drug by changing its DNA. This means that the drug target in the parasite is no longer affected by the drug or that the parasite gets rid of the drug before it can reach its target. </p>
<p>To slow down the ability of the parasite to develop drug resistance, malaria medicine has been formulated into a combination therapy. It combines two antimalarial drugs that target different biological processes in a single tablet. It is considerably more difficult for the parasite to simultaneously change both targets in order to become resistant against both drugs. With combination therapies, the parasite has a significantly reduced chance of developing resistance compared to a single therapy. </p>
<p>Even though combination therapies have assisted in slowing down parasite drug resistance, the parasite is developing drug resistance to an antimalarial drug faster than new drugs are being developed and approved. </p>
<h2>A multi-pronged approach</h2>
<p>To increase and sustain the antimalarial armoury, drug developers need to deliver drugs faster and increase the lifespan of the drugs that are in circulation. </p>
<p>The answer to this conundrum may lie in the field of antibiotic drug discovery. </p>
<p>The antibiotic field is currently developing resistance-resistant <a href="http://www.cell.com/trends/pharmacological-sciences/abstract/S0165-6147(14)00172-2">antibiotics</a> that have multiple targets instead of single targets. Instead of a combination therapy that targets two single targets, a multi-target drug has numerous targets which the parasites need to develop resistance against. This makes it exponentially more effective than a combination therapy in resisting resistance. </p>
<p>One example of the outstanding success of this strategy is the TB drug, <a href="http://openres.ersjournals.com/content/1/1/00010-2015.full">SQ109</a>, which is currently in phase II clinical trials. It inhibits multiple targets with potent inhibition of TB cell growth and very low rates of spontaneous drug resistance. </p>
<p>A multi-target drug approach may provide the desired drug discovery breakthrough required to treat malaria. It would speed up the delivery of candidates into clinical practice and decrease drug resistance. </p>
<p>Ultimately, it would stop the spread of malaria by targeting the transmissible forms. In this way, we hope to stay one step ahead of the malaria parasite and make a dramatic difference to curb and eliminate the disease.</p><img src="https://counter.theconversation.com/content/49986/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Bianca Verlinden receives funding from the SA National Research Foundation and SA Medical Research Council. </span></em></p><p class="fine-print"><em><span>Lyn-Marie Birkholtz receives research funding from the SA National Research Foundation and the SA Medical Research Council. </span></em></p>Across the world scientists are trying to find a new drug that the malaria carrying parasite will struggle to develop a resistance to.Bianca Verlinden, Postdoctoral Research Fellow, Molecular Parasitology, Department of Biochemistry, University of PretoriaLyn-Marie Birkholtz, Associate Professor (Biochemistry) DST/NRF South African Research Chair (SARChI) in Sustainable Malaria Control, University of PretoriaLicensed as Creative Commons – attribution, no derivatives.