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Together with HIV/AIDS and TB, malaria is one of the major public health challenges of the developing world. Prompt diagnosis is a priority. Rapid diagnostic tests are readily available, quick to yield results and can be effectively used in resource-limited settings.
by A. Yorston

  
Malaria is a life-threatening parasitic disease caused, in humans, by four species of the genus Plasmodium, namely Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae. P. vivax and P. falciparum are the most common types of malaria, with P. falciparum causing the most fatalities.
Approximately 40% of the world’s population, mostly those living in the world’s poorest countries, are at risk of malaria [1]. Malaria is found throughout the tropical and subtropical regions of the world and causes more than 300 million acute illnesses and at least one million deaths a year [1].

Clinical picture

Typically, malaria produces flu-like symptoms around nine to 14 days after an infective Anopheles mosquito bite; however this can vary with different malaria species. If appropriate drugs are unavailable or the parasite has gained resistance to them, the infection can rapidly progress and become life threatening. If left untreated, malaria can kill by infecting and destroying red blood cells, causing anaemia and by blocking capillaries that carry blood to the brain and other vital organs.

The World Health Organisation (WHO), UNICEF, UNDP and the World Bank launched the Roll Back Malaria Global Partnership (RBM) in 1998, to promote effective low-cost strategies for malaria treatment, prevention and control in Africa and other endemic regions of the world. With a goal to “halve the burden of malaria by 2010” [2], prompt diagnosis and access to targeted malaria treatment are priorities of the RBM partnership. Together with HIV/AIDS and TB, malaria is one of the major public health challenges of the developing world [3].

Disease management and the problem of drug resistance

Key to fighting malaria is combining both prevention and treatment strategies. At risk populations must have access to effective preventive measures, with those suffering from malaria having access to prompt and effective treatment. Among the factors contributing to the increasing malaria mortality and morbidity is the widespread resistance of P. falciparum to conventional antimalarial drugs, such as chloroquine, sulphadoxine–pyrimethamine (SP) and amodiaquine. Multidrugresistant

P. falciparum malaria is most widely prevalent in South-East Asia and South America, however Africa is now alsoaffected. Resistance to inexpensive monotherapies such as chloroquine and SP is developing rapidly, with increased mortality as a result [1]. 

It is evident that malaria parasites are developing unacceptable levels of drug resistance, with many insecticides also no longer effective against the mosquitoes carrying the disease [1].

Inappropriate use of antimalarial drugs during the past century has contributed to the increasing resistance. Traditional monotherapy antimalarial drugs were deployed on a large scale, and were often continued or poorly managed despite rising levels of resistance. In addition, there has been over-reliance on both quinoline compounds (quinine, chloroquine, amodiaquine, and mefloquine) and antifolate drugs (sulphonamides, pyrimethamine, and chlorproguanil), resulting in cross-resistance among these compounds [4].

In the last decade, a new group of antimalarials, the artemisinin compounds, have been effectively deployed on an increasingly large scale. These compounds produce a very rapid therapeutic response, are active against multidrug-resistant P. falciparum malaria, and are well tolerated by patients [4]. To date, no parasitic resistance to artemisinin compounds has been detected. If used alone, the artemisinins will cure P. falciparum malaria in seven days, but studies in South-East Asia have shown that combinations of artemisinin compounds with certain synthetic drugs produce high cure rates with just three days of treatment [5].

The WHO recommends that countries experiencing resistance to conventional monotherapies, should use combination therapies, preferably containing artemisinin derivatives [5], to tackle P. falciparum malaria.

Diagnosis

Early detection is vital in order to ensure prompt and effective treatment. People suffering from malaria should to be diagnosed and given effective, affordable drug treatment within 24 hours of the onset of symptoms [2]. Malaria diagnosis, particularly in remote areas lacking laboratory facilities, frequently relies on recognising patient symptoms. Initial flu-like symptoms of infection (fever, chills, sweats, headaches, muscle pains, nausea and vomiting) are not specific to malaria and, whilst effective clinical diagnosis is inexpensive, clinicians can often misdiagnose malarial infection.

Rapid, accurate and accessible detection of malaria has an important role in addressing the significant morbidity and mortality resulting from malaria misdiagnosis and in promoting the appropriate use of costly drugs. Rapid diagnostic tests offer the potential to provide accurate diagnosis to all at-risk populations including those unable to access good quality laboratory microscopy services [6].

Available in well-equipped clinics, microscopy can confirm clinical diagnosis and provide important information by identifying which parasite species are present and therefore which targeted drug treatment to initiate. However, the sensitivity of microscopic diagnosis is dependent not only on the experience of the technician but also on how well the equipment is maintained.

Microscopy is a standard technique used for diagnosing other diseases such as tuberculosis, however in remote areas reagents are limited, equipment and electricity are unreliable, and a delay in obtaining results may lead to incorrect initial treatment.

Rapid diagnostic tests

Rapid diagnostic tests are readily available, quick to yield results, and can be effectively used in resource-limited settings. Patients who have a malaria-like fever and test negative can be given a quinoline based drug, whilst the more expensive P. falciparumspecific treatment can be reserved for patients who test positive [6]. Growing P. falciparum resistance to anti-malarial drugs requires the use of more expensive combination therapies in Asia, Africa and South America, increasing the need for accurate diagnosis [5].

Rapid diagnostic tests have been developed on the immunochromatographic strip, or lateral flow format. Using finger-stick or venous blood samples and taking only 10-15 minutes to yield results, these rapid format tests do not require laboratory analysis. Providing visual results, clinic staff can easily learn to interpret the results. Two types of rapid test are available, those that are specific to P. falciparum, and those that are based on detection of P. falciparum and either P. vivax malaria or all four malarial species in the same test. An example

of the latter is BinaxNOW® Malaria. This rapid immunochromatographic test (available from Inverness Medical) allows differentiated detection of circulating P. falciparum antigen, and also detection of the pan-malarial antigen common to all four species (P. falciparum, P. vivax, P. ovale and P. malariae) in whole blood. The test uses two antibodies immobilised across the test strip. One antibody is specific for the histidine-rich protein II antigen of P. falciparum (P.f. HRPII). The other antibody is specific for an antigen that is common to all species.   The simple, three-step test does not rely on the availability of water, electricity or laboratory equipment, making it suitable for use in remote clinics with limited facilities.

Providing results in 15 minutes, BinaxNOW contributes to accurate early treatment and improved patient outcomes.

A global problem

It is important to note that malaria does not only affect the developing world – isolated, locally transmitted cases still occur in North America, and a growing number of international travellers are developing malaria. It is estimated that 30,000 international travellers fall ill with the disease every year [7].

With malaria prevalent in many of the world’s “holiday hotspots” and malaria-carrying mosquitoes able to stow away on international passenger flights and cargo shipments, travellers from malaria-free countries are highly susceptible to infection since they have little or no immunity and can be wrongly diagnosed on their return home. With limited experience in diagnosing tropical diseases not prevalent in their own countries, clinicians are able to use rapid diagnostic tests such as BinaxNOW Malaria, in combination with other standard laboratory tests, as an additional tool to help them diagnose malaria infections [8].

References

1. WHO, UNICEF. World Malaria Report 2005.

2. Roll Back Malaria Partnership. Looking Forward. 2004.

3. Roll Back Malaria Parnership What is Malaria? Info sheet www.

rbm.who.int/cmc_upload/0/000/015/372/RBMInfosheet_1.htm

4. WHO. Drug resistance in malaria. 2001.

5. WHO. Susceptibility of Plasmodium falciparum to antimalarial

drugs. Report on global monitoring 1999-2004. 2005.

6. Roll Back Malaria Partnership, WHO 2005.

7. WHO International travel and health report 2008.

8. Monbrison et al. European Journal of Clinical Microbiology &

Infectious Diseases 2004; 23:784-786.

The author

Amy Yorston, BSc, BMm, MMM

Vector Borne Diseases Snr

Product Manager

Inverness Medical, Bedford, UK