Question
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.
(a) Name the type of pathogen that causes malaria.
…… [1]
(b) 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.
(i) 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]
(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]
(c) 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.
trophozoite
Fig. 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 F446I 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
change in DNA change in protein PfK13 name of nucleotide nucleotide mutation amino acid before amino acid after present in present after mutation mutation kelch13 mutation
F446I thymine (T) adenine (A) phenylalanine (phe) isoleucine (ile)
C580Y guanine (G) adenine (A) cysteine (cys) tyrosine (tyr)
(i) Using gene kelch13 and mutation F446I as examples, explain the difference between a gene and a gene mutation.
…… [3]
(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 F446I 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 culture details DHA concentration DHA concentration number
20 nmol dm–3 700 nmol dm–3
1 strain A no mutation 3.15 0.00
2 strain A, F446I 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, F446I 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]
[Total: 11]
Mark scheme
3(a) protoctist ; 1
3(b)(i) any two from: 2
1 drugs have different, targets / mechanisms of action,
or
drugs, act on different, structures / processes / stages of life cycle ;
2 unlikely / less likely, for mutations against all drugs to occur ;
3 unlikely for resistance to occur against all the drugs ;
I immune / immunity
A described example
4 if there is resistance to one, the other drug(s) will, kill / AW, all pathogens ; AW
I ref. to effective
5 (so) prevents, gene / allele, from being passed on ;
6 AVP ;
e.g. low numbers left, so less probability of mutations arising
idea that if all pathogens are killed, no replication / no mutations, for resistance to develop
3(b)(ii) allow, pathogens / parasites, for Plasmodium 2
I increased time when person is infectious
any two from:
increased time when person, has Plasmodium in, blood / circulation ;
allow mark if reference to, blood / circulation, not made but reference is made to blood in statements about Anopheles
A person acts as a reservoir for Plasmodium
(so) quantity / concentration / number, of Plasmodium, remains high / increases ; AW
A ref. to allows Plasmodium, to reproduce / replicate
I ref. to genes passing to offspring
increased, time / risk / chance / AW, of, being exposed to, vectors / mosquitoes / Anopheles (for blood meal) ; AW
idea of more infected, Anopheles / mosquitoes available to feed on uninfected people ;
3(c)(i) 1 correct use of examples ; 3
two of gene, gene mutation, protein, altered protein
gene = kelch13
gene mutation = kelch13 mutation
or F446I
or (mutation has) adenine / A, not, thymine / T
protein/polypeptide = PfK13
altered protein isoleucine / ile, instead of, phenylalanine / phe
2 (mutation has), changed / altered / AW, sequence / arrangement / order, of nucleotides / bases, (in DNA) ;
ref. A replacing T still needs stated idea of a changed sequence
R if gene explanation also given and stated as sequence of amino acids
3 (gene) codes for the production of a, polypeptide / protein AW
or
(gene mutation) produces / results in, altered / changed / non-functioning / reduced function, polypeptide / protein ; AW
A produces changed sequence of amino acids
R if gene and gene mutation explanations given and one is incorrect
3(c)(ii) allow correct use of extracted data to help confirm points 3
allow ideas such as higher survival = greater (partial artemisinin) resistance
Key
20 / lower concentration = 20 nmol dm3 DHA
700 / higher concentration = 700 nmol dm3 DHA
survival / survival rate = mean percentage survival rate of trophozoite
any three from conclusions 1 to 5:
1 zero survival of no cultures 1 and 4 / no mutations, no survival / 0% survival rate / all killed, at, higher
mutation concentration / 700 ;
2 lower concentration / 20, higher survival rate than, higher concentration / 700
concentrations ora
compared higher concentration / 700, lower survival rate than, lower concentration / 20 ;
general statement or can take one culture to compare
3 (A and B strains with) mutations higher survival rate than no mutation
mutation (C580Y ora
and F446I) v (A and B strains with) no mutation lower survival rate than mutations ;
no mutation (control general statement for both strains, or A, or B
/ cultures 1&4) (if concentrations mentioned, need to refer to both concentrations)
4 strain A higher survival rate than strain B
compare strain A ora
with strain B strain B lower survival than strain A ;
general statement or comparing groups e.g. 1 and 4 or 2 and 5 or 3 and 6 (for both or one
concentration)
5 C580Y, higher survival than F446I / highest survival rate
C580Y v F4461 or
F446I lower survival rate than C580Y ;
general statement or compare 2 and 3, or 5 and 6, for both or one concentration