Plasmodium falciparum is one species of Plasmodium that causes the life-threatening disease malaria. With early diagnosis and the correct drug treatment, the pathogen can be eliminated from the body, particularly if the disease is not severe.

1. (a)Name the type of pathogen that causes malaria.[1]
2. (b)(i)To help prevent the development and spread of drug resistance in Plasmodium, the World Health Organization (WHO) recommends using a treatment known as artemisinin-based combination therapy (ACT). ACT involves two different types of drug: • a fast-acting drug derived from a compound known as artemisinin, which causes a rapid decrease in the number of P. falciparum • one or more longer-acting, non-artemisinin, drugs that eliminate any remaining pathogens. Suggest why using ACT with the two different types of drug is more effective in preventing the development of drug resistance in Plasmodium than a treatment using only one type of drug.[2]
3. (b)(ii)In some areas, partial artemisinin resistance has developed. This means ACT takes a longer time for the pathogen to be eliminated from the body. Explain why there is an increased risk of transmission of the pathogen to other people if a person is receiving ACT and the pathogen has partial artemisinin resistance.[2]
4. (c)(i)ACT can act on the stage of the life cycle of P. falciparum that occurs within red blood cells. The cells of P. falciparum in this stage are known as trophozoites. Fig. 3.1 is a photomicrograph of a blood smear (thin layer of cells). Some of the red blood cells contain trophozoites. [Figure 3.1] PfK13 is a protein that has an important role in the development of the trophozoite stage of P. falciparum. The gene kelch13 codes for PfK13. Two different mutations of kelch13, known as F4461 and C580Y, were investigated to see if they were associated with partial artemisinin resistance. Details of these mutations are summarised in Table 3.1. [Table 3.1] name of mutation | change in DNA | change in protein PfK13 | nucleotide present in kelch13 | nucleotide present after mutation | amino acid before mutation | amino acid after mutation F4461 | thymine (T) | adenine (A) | phenylalanine (phe) | isoleucine (ile) C580Y | guanine (G) | adenine (A) | cysteine (cys) | tyrosine (tyr) Using gene kelch13 and mutation F446l as examples, explain the difference between a gene and a gene mutation.[3]
5. (c)(ii)In the investigation, the survival rate of trophozoites within red blood cells was determined for two different concentrations of an artemisinin-based drug known as DHA. Two different strains, A and B, of P. falciparum were tested. Three different cultures of each strain were involved: • no mutation in kelch13 (control) • kelch13 F4461 mutation • kelch13 C580Y mutation. Table 3.2 shows the six different cultures tested and the trophozoite survival rate for each culture. [Table 3.2] mean percentage survival rate of trophozoite culture number | culture details | DHA concentration 20 nmol dm-3 | DHA concentration 700 nmol dm-3 1 | strain A no mutation | 3.15 | 0.00 2 | strain A, F4461 mutation | 26.00 | 0.73 3 | strain A, C580Y mutation | 33.08 | 0.91 4 | strain B no mutation | 2.86 | 0.00 5 | strain B, F4461 mutation | 13.50 | 0.53 6 | strain B, C580Y mutation | 17.50 | 0.63 State the main conclusions that can be drawn from the results shown in Table 3.2.[3]

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