C13 Fig 1

Malaria: a global threat

Malaria threatens the existence of large numbers of children in tropical and subtropical areas of the world. Increasing malaria parasite drug-unresponsiveness and insecticides-unresponsive mosquitoes lead to emergence of new malaria foci. Insecticide-impregnated bed nets and case detection/prompt treatment with artesunate-based drug combinations offer the most effective control measures. Counterfeit antimalarial drugs pose a serious threat to malaria control. No effective vaccine has been introduced into clinical practice to date.

by Prof. E.A.G Khalil and Dr M.E.E. Elfaki

Malaria is a febrile parasitic disease that is transmitted by female mosquitoes with no known intermediate host except in the case of Plasmodium knowlesi. Malaria is prevalent over most areas of Asia, Africa, eastern Europe, south America and South Pacific. Hot climate and low socio economic conditions make malaria prevalent in these areas. Malaria affects 300 to 700 million people annually with 1-2 million deaths, mostly of children [1]. The malaria parasite can infect all age groups, but children and pregnant women are at an increased risk for developing the severe form of the disease. The red blood cells are the principal cells affected, the parasite usually affects red blood cells of all ages. There are five species of malaria parasite that cause human disease: Plasmodium falciparum, Plasmdium vivax, Plasmodium ovale, Plasmodium malariae and Plasmodium knowlesi.

Malaria can present in a mild uncomplicated form that is characterised by fever, headache, arthralgia, vomiting, malaise, sweating and splenomegaly. On the other hand a severe and complicated form exists that presents as severe anaemia, pulmonary oedema, seizures, coma and renal/respiratory effects. Brain effects can result in the death of 20% of even optimally treated individuals with residuals brain damage in some surviving children. Large numbers of individuals in endemic areas may harbour the parasite without obvious symptoms (subclinical infection); these individuals represent a reservoir during the dry season [2,3].

Under-nutrition is an underlying cause of malaria morbidity in children under the age of five [4]. Nutritional supplementation with vitamin A, zinc, selenium, iron and folate are reported to reduce malaria morbidity in children, probably through their effects on the immune system [5].

Immunity against malaria
The ability of humans to fight malaria relies on the presence of specialised immune cells that produce antibodies against malaria parasite proteins expressed on the surface of infected red blood cells (humoral immunity). Human immunity also relies on the production of cytokines, specialised proteins that arm immune cells and make them more capable of killing malaria parasites. In addition, specialised T-lymphocytes, namely CD8+ cells help the body to eliminate the parasite through destruction of infected cells (cellular immunity) [6,7].

Treatment of simple and complicated malaria
Chloroquine was the drug of choice for malaria treatment for some time, but this has dramatically changed due to the emergence of resistance in different parts of the globe. The same problem has occurred with other antimalarial drugs such as mefloquine, quinine and sulphadoxine [7,8]. Artesunate-based combinations are now used as first line treatment of simple malaria by many control programmes [10]. In addition, fixed-combination anti-malarials such as Dihydroartemsinin-piperaquine (DP) can effectively treat uncomplicated, multidrug-resistant falciparum malaria [11].

Intermittent preventive malaria treatment (IPT) using sulphadoxine/pyrimethamine has been shown to reduce the burden of malaria effectively in children in areas of seasonal transmission [12]. Supportive treatment is an important adjunct to antimalarial treatment (antipyretic, anticonvulsant and exchange blood transfusion) in severe P. falciparum malaria [13,14].

Control of malaria
Malaria morbidity and mortality can be markedly reduced with a sum of money not exceeding $ 3.0/adult. At the present time case detection and prompt treatment with artesunate-based combination drugs and the use of insecticide-treated bed nets (ITN) are the most effective control measures. ITN have proven to reduce malaria morbidity and mortality [10,15,16].

Counterfeit drugs
Counterfeit drugs present a major obstacle to malaria control programmes by prolonging morbidity and increasing mortality. About a third to one half of drugs sold in Africa and Asia are counterfeit drugs. There is some evidence that the problem of counterfeit drugs is increasing, especially in countries where regulatory authorities do not have the will to investigate and take action or do not have the necessary resources. However there is a lot of pressure not to publicise the issue of counterfeit anti-malaria drugs [17,18,19,20].

Vaccines against malaria
The ability of the malaria parasite evade the immune system is the main reason that no really effective vaccine has been produced to date. A number of the parasite molecules have been targeted as vaccine candidates in vain. Recently, the RTS,S/AS01 vaccine has been shown to provide protection against clinical and severe malaria in African children [21,22].

Better use of ITN, rapid and accurate diagnostic tests and the use of artesunate-based drug combinations can effectively control malaria. Counterfeit anti-malarials are a serious and under-estimated problem that could definitely cripple malaria control programmes in Africa and Asia.

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The authors
Prof. E.A.G. Khalil and Dr M.E.E. Elfaki
Department of Clinical Pathology
& Immunology

Institute of Endemic Diseases
University of Khartoum