Interview conducted by April Cashin-Garbutt, BA Hons (Cantab) on 25th July 2012
Please could you tell us a little bit about malaria and who it affects?
Malaria is caused by a multi-staged parasite which is transmitted by the bite of infected female anopheles mosquitoes. It affects millions of people and kills more than 500,000 people throughout the world every year. It is one of the leading preventable causes of illness and death amongst children and pregnant women in Africa and parts of Asia. The two main species that effect man are Plasmodium falciparum and P. vivax. Both P. vivax and P. falciparum are prevalent throughout large areas of Asia and South America, while Africa is mainly affected by P. falciparum alone.
What are the symptoms of malaria?
Malaria has a range of severities. Some people in areas of intense transmission develop immunity and can carry the parasite without symptoms. In uncomplicated cases the main symptoms are fever, chills and muscle ache but these symptoms are often indistinguishable from other causes of fever.
Cases which are not promptly identified and effectively treated can progress, within a few days, to more severe symptoms including high fever, impaired or loss of consciousness, convulsions, breathing difficulties and other severe conditions. At this stage, the parasite makes infected red-blood cells “sticky” and these block the microscopic blood vessels in organs including the lungs and brain (cerebral malaria) causing severe damage. Death or permanent disablement may follow.
Your recent research suggests that malaria is being substantially overdiagnosed in south and central Asia. Please could you explain how you have showed this?
Our study was conducted in primary care clinics in Afghanistan which are fairly typical of most of south and central Asia. Because of Afghanistan’s difficult past, much investment has been made in healthcare in the last 10 years. For this reason we think that the clinics in Afghanistan are either as good as or better than most primary care public-sector clinics in the region.
In conducting the study, we observed the diagnosis and treatment of 2357 patients with fever and compared this to a reference diagnosis for malaria. We identified that when diagnosis of malaria is based only on signs and symptoms – normal in many low-resource settings – more than 99% of cases were treated with a malaria drug when they did not actually have malaria.
The use of microscopic examination of the patients’ blood (which is the standard method of parasite based diagnosis) did improve this, but around 40-50% of patients still did not receive appropriate malaria treatment. Most of these were patients who did not have malaria but were prescribed with a malaria drug when they did not need one.
What do you think are the reasons for this substantial overdiagnosis of malaria?
Firstly, diagnosis of malaria was inaccurate whether it was based on signs and symptoms alone, or the microscopic examination of patients’ blood. Many of the cases identified in the clinic did not, in fact, have malaria (there were around 20-30% false positives by microscopy and over 90% by signs and symptoms) and many with malaria were missed (around 10% false negatives by microscopy).
Secondly, the treating clinician (doctors, nurses and midwives) continued to prescribe malaria drugs even when the microscope based test result was negative. The reason for this is that the symptoms of malaria are not specific to one disease and clinicians may have a lack of confidence in the accuracy of the diagnosis. Clinicians fear missing a case of malaria and may also believe that malaria is a bigger problem than it is in reality. This leads to an emphasis on malaria above other diseases.
Why is misdiagnosis of malaria such a bad thing?
Misdiagnosis results in the wrong treatment being given for a disease that the patient doesn’t have. This means that the disease that they do have does not get treated appropriately. The newer Artemisinin Combination Therapy (ACT) drugs that are now recommended for treating malaria are more costly than the older drugs, so this also introduces significant wastage into the resource poor health systems.
How can misdiagnosis of malaria be prevented?
By improving the coverage and quality of malaria diagnosis and changing practice amongst clinicians. Our research group, the ACT Consortium, is investigating ways in which practice can be changed in order to improve delivery of quality malaria drugs. This includes using enhanced training programmes, improved quality assurance and other supporting interventions. The aim is to contribute to improving access to treatment in malaria positive patients and reducing the overuse of malaria drugs when patients do not have malaria.
Are there plans in place to achieve this reduction in misdiagnosis?
This issue has attracted a lot of attention recently. It is now realised to be a big clinical problem and an important source of inefficiency in providing the more expensive ACTs to a larger number of people. Malaria microscopy needs improved quality assurance and it is hoped that malaria rapid diagnostic tests will increase access to accurate diagnosis. These efforts will be incomplete unless those who provide treatment have sufficient training and confidence to provide treatment accurately.
A big change in practice is required. There are two issues that need to be addressed – better diagnosis and prescription practice is needed to improve targeting of drugs; and better coverage of accurate diagnosis and effective drugs are required to improve access to these life-saving items.
How do the malaria misdiagnosis levels in parts of Asia compare to the rest of the world?
Misdiagnosis and treatment of malaria has been found in almost all areas where researchers have looked for it. Our data is comparable to other studies in Africa and Asia and this shows that it is an urgent, worldwide problem. We must focus on improving existing services and, as services expand to new areas, they must do so with optimised quality. This is needed in almost all malaria endemic areas and is why the WHO Global Malaria Programme has recently launched the T3 campaign – Test, Treat and Track. This is to ensure that all patients receive a malaria test, all those who need treatment receive it, and all cases are registered at the point of care to improve disease surveillance.
How do you think the misdiagnosis of malaria compares to the misdiagnosis of other conditions?
Our paper indicates that the use of antibiotics increases in patients diagnosed as malaria negative. This may mean that patients are simply over treated with antibiotics instead of antimalarial drugs. At the moment we don’t have a good picture of the diseases that cause uncomplicated fever that resembles malaria. Most of this is likely to be non-severe and self limiting disease, but some may be more severe diseases.
It is important to improve not only diagnosis of malaria, but also the other causes of fever. Over treatment with antibiotics also has significant drawbacks including the development of antibiotic resistance, so it is important to distinguish bacterial, viral and malarial causes of fever and improve treatment of all causes of fever, rather than just malaria.
How do you see the future of malaria diagnosis progressing?
There certainly needs to be a big increase in the use of parasite based malaria tests and improvements in the way these are delivered. This includes the newer generation of malaria rapid diagnostic tests. The effort required is akin to the recent and very dramatic rise in the coverage and use of insecticide treated nets in Africa for prevention of malaria led by the UN Secretary General’s Special Envoy for Malaria, Ray Chambers. The expansion of quality diagnostics needs a similar effort in terms of political and resource support because if we are to meet the targets for malaria control and elimination laid out by the UN Millennium Development Goals, then accurate diagnosis and treatment is going to be necessary at all levels of the health system from the most rudimentary clinics in rural developing countries to urban hospitals.
What are your future plans for research into this field?
We are currently conducting studies on the use of rapid diagnostic tests in clinics and by community health workers in village health posts. The results will be available later this year. This is intended as multi-disciplinary operational research that examines clinical, economic and behavioural aspects of diagnosis and treatment of fever. It is important to conduct high quality research in order to ensure that results are credible and that actions which may cost millions of dollars are based on sound evidence of best practice.
Beyond that, we need a better understanding of how diagnosis can be made routinely available in the private sector in malaria endemic countries. Drug sellers, pharmacies and private practitioners are an important source of antimalarial drugs and early research indicates that rates of over diagnosis are also high in this sector. This will require a different approach to interventions for the public sector, where most research has focussed.
Another line of enquiry will involve better treatment for fever that is not caused by malaria. As malaria decreases, more patients have non-malarial causes of fever. We need to know what causes these fever episodes and how we can treat cases better.
What inspired you to work in infectious disease epidemiology?
I was always interested in infectious diseases through school and as an undergraduate in physiology at UCL. I did my post-graduate studies at LSHTM. Travelling in low-income countries, where the disparities between industrialised and developing countries are so obvious, was an important influence. The range of sciences in infectious disease control also appeals to me – from the molecular level looking at genes and biochemistry, to ecology, to epidemiology all the way to economics, politics and international relations. How this knowledge plays out on the ground is the important thing – we have to remember that the goal is effective disease control which contributes to development and improving lives and livelihoods.
Where can readers find more information?
ACT Consortium at LSHTM: http://www.actconsortium.org/
LSHTM: http://www.lshtm.ac.uk/
WHO Global Malaria Programme: http://www.who.int/malaria/en/
WHO Malaria Factsheet: http://www.who.int/mediacentre/factsheets/fs094/en/
WHO T3 initiative: https://www.who.int/
And T3 youtube video: https://www.youtube.com/watch?v=vnsoTPE_PUc
About Dr Toby Leslie
Dr Leslie is a lecturer in infectious disease control at LSHTM. He received his MSc in Control of Infectious Disease in 2002 and went to Pakistan to work as a research assistant. He received his PhD in 2009 on malaria treatment and control in Pakistan and Afghanistan and was awarded the Woodruff Medal.
He has worked for a number of NGOs and agencies in Afghanistan and published papers on infectious disease epidemiology and malaria control. He is a founding director of a locally registered Afghan NGO, the Health Protection and Research Organisation (www.hpro.org.af), which aims to conduct research, evaluation, and technical training to support the Government of Afghanistan in improving health and social welfare.
Since 2008, Dr Leslie has been the manager of the ACT Consortium projects in Afghanistan conducting operational research on delivery of malaria diagnosis and treatment. In 2012 he took a position as Policy and Programmes Liaison Coordinator for the ACT Consortium at LSHTM.
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