Malaria

mechanism in the F-C or total phenolics assay is an antioxidant/reduction reaction. It has been used to measure total phenols, but it measures other reducing agents as well, and can be considered as another AOA method. The method is simple, sensitive and precise (Prior et al.

2005). Gallic acid is used as a reference standard, and the results are given as gallic acid equivivalents.

1.4. Malaria

Malaria is a life threatening disease caused by a Plasmodium parasite, transmitted to humans through the bite of a female Anopheles mosquito (Fig. 2). There are around 300 million cases of malaria worldwide each year, and nearly 1 million die from the disease (WHO, 2009). Ninety percent of these deaths occur in Africa south of Sahara (ASS), and most of them are children under the age of five. In Africa today malaria is understood as both a disease of poverty and a cause of poverty (Sachs & Malaney 2002).

Malaria is preventable and curable, but in most of the seriously infected areas (ASS) there has been little success in fighting the disease (WHO, 2009) due to the parasite developing resistance to affordable medicines, poverty and ineffective health systems. However during the last years some areas and countries like Zanzibar, Eritrea, Rwanda and Zambia have managed to reduce recorded cases and deaths by 50%, suggesting that the Millennium Development Goals targets can be achieved if there is adequate coverage of key interventions. In these countries insecticide-treated nets (ITN) have been distributed to around 60-75% of households, compared to 16% in Uganda (WHO, 2009) and the treatment of cases have been intensified. The international

disbursement to malaria-endemic countries (UD$ 0.65 billion in 2007) is still far from the US$ 5 billion required annually to ensure high coverage and maximal impact worldwide according to WHO (2009).

There are four types of parasites infecting people: Plasmodium falciparum, P. vivax, P. malariae and P. ovale. Plasmodium falciparum is the most deadly, and in Africa by far the most common parasite, causing 98% of cases (WHO, 2009). In humans the parasites first grow and multiply in the liver cells and then in the red blood cells (erythrocytes). In the blood successive broods of

11

parasites grow inside the erythrocytes and destroy them, releasing daughter parasites that continue the cycle by invading new red blood cells. The blood stage parasites are those that cause the symptoms of malaria, and it is also in this stage the infection can be demonstrated by a microscopy smear test (Center for Disease Control and Prevention, 2010). When sexual forms of blood stage parasites are picked up by a female Anopheles mosquito during a blood meal, a new cycle of parasite development and multiplication is started within the mosquito. After 10-18 days the parasite can be found in the mosquito’s salivary gland and are ready to be injected into a new human, thus carrying the disease on. In Plasmodium vivax and P. ovale a dormant stage can persist in the liver and cause relapses by invading the bloodstream weeks, or even years later.

When the parasite develops in the erythrocyte, numerous waste substances, also toxic ones accumulate in the infected red blood cells. When the blood cells lyse and release new parasites, the waste products are dumped into the blood stream which acts to produce fever and probably influence other severe conditions. Plasmodium falciparum infected red blood cells, particularly those with mature parasites, adhere to the vascular endothelium of venular blood vessel walls

Fig. 2. Malaria Transmission Cycle

12

and do not freely circulate in the blood. When this happens in the blood vessels of the brain it is believed to be a factor in causing cerebral malaria, which is associated with high mortality (Centers for Disease Control and Prevention, 2010).

Chloroquine (CQ) and the combination drug of sulphadoxine–pyrimethamine (SP) were, until recently, the main malaria treatment in Africa. Resistance to both drugs is now widespread (Pears et al. 2009). CQ was first used in the 1950s, and chloroquine resistance (CQR) appeared in Asia and South America in the early1960s. CQR did not appear in Africa until 1978, when the initial focus was in East Africa. It subsequently reached West Africa at the end of the 1980ies.

Artemisinin-based combination therapy (ACTs) is now the recommended and in many cases the only effective treatment of Plasmodium falciparum malaria. By 2009, 77 of 81 P. falciparum malaria-endemic countries had adopted ATCs for use in their drug policy. However in 11 of 13 African countries surveyed in 2007-2008, fewer than 15% of children below 5 years of age with fever had received an ACT, far below the WHO target of 80% (WHO, 2009). WHO is

monitoring the global supply and demand of the artemether-lumefatrine fixed-dose combination, as part of a memorandum of understanding with the manufacturer Novartis in 2001 to make Coartem® available at cost price in the public sector. In public sale the medicine is far more expensive than the traditional chloroquine, and in most rural areas in Uganda it was not even available in 2009.

Artemisinin is extracted from Artemisia annua L., a Chinese medicinal plant used against fever from old times, but ‘rediscovered’ in the 1970ies, when Mao intensified the fight against malaria.

It is now grown in many African countries, including Tanzania and Uganda, and factories to produce medicine are established in both countries. However the expansion of agricultural production of Artemisia annua and extraction of artemisinin were not matched by artemisinin demand by the ATC producers in 2006-2007, resulting in a surplus and very low prises on Artemisia raw product, even below production costs. The subsequent withdrawal of producers and extractors from the marked is likely to create shortage of artemisinin-based active

ingredients in 2010, when demand for ATC is expected to increase, partly because of increased mobilization of funds from international donors (WHO, 2009). There have already been some

13

reports on resistance towards artemisinin, and WHO is requesting pharmaceutical companies to stop producing oral monotherapy artemisinin products, which are still sold in some countries.