Biology • Year 12 • Module 7 • Lesson 18
Malaria and Dengue: Global Case Study
Apply malaria and dengue content to real disease-burden data, a cause-and-effect chain on drug resistance, and a Dengvaxia case study scenario.
1. Interpret malaria burden data — sub-Saharan Africa 2000–2022
The graph below shows estimated malaria cases and deaths per 100,000 population in sub-Saharan Africa from 2000 to 2022. Key events are annotated. 8 marks
Data adapted from WHO World Malaria Report 2023. Sub-Saharan Africa regional estimates.
1.1 Describe the overall trend in malaria cases and deaths per 100,000 from 2000 to 2015. Include specific values. 2 marks
1.2 Using lesson content, identify two specific interventions that best explain the decline in malaria deaths between 2000 and 2015. For each, briefly explain its mechanism. 4 marks
1.3 The data show a notable spike in both cases and deaths in 2020. Identify a cause and explain the biological mechanism by which this caused malaria burden to increase. 2 marks
2. Cause-and-effect chain — artemisinin resistance in Plasmodium
Natural selection drives drug resistance in malaria. Complete the cause-and-effect chain below. Each filled box should follow logically from the cause on the left. 5 marks (1 per step + 1 overall outcome)
3. Compare malaria and dengue across five criteria
Complete the comparison table. Use specific terms, species names, and values from the lesson where available. 10 marks — 2 per row
| Feature | Malaria | Dengue |
|---|---|---|
| Causative pathogen (type and name) | ||
| Mosquito vector (genus/species + biting time) | ||
| Nature of immunity after infection | ||
| Best available vaccine and efficacy | ||
| Primary geographical burden |
4. Apply — The Dengvaxia program, Philippines 2016–2017
In 2016, the Philippine government launched a school-based dengue vaccination program using Dengvaxia (CYD-TDV), vaccinating over 800,000 children aged 9–10. Subsequent analysis revealed that children who had never previously been infected with dengue (seronegative) had a higher risk of severe dengue after vaccination. The program was halted and criminal investigations were launched. Dengvaxia is now recommended only for individuals with a confirmed prior dengue infection. 5 marks
4.1 Define antibody-dependent enhancement and explain why seronegative vaccinees were at higher risk of severe dengue after receiving Dengvaxia. 3 marks
4.2 Explain why the Dengvaxia case makes developing a safe dengue vaccine harder than developing a malaria vaccine. Refer to the number of serotypes and the role of ADE. 2 marks
Q1.1 — Trend description (2 marks)
Both cases and deaths fell substantially from 2000 to 2015 [1]. Cases declined from approximately 370 to 218 per 100,000 (a ~41% reduction) and deaths declined from approximately 121 to 51 per 100,000 (a ~58% reduction) [1 — both specific values required for full marks]. After 2015, both plateaued and failed to continue declining, suggesting progress stalled.
Q1.2 — Two interventions with mechanisms (4 marks)
Intervention 1 — Insecticide-treated bed nets (ITNs): Coverage rose from approximately 2% to 65% of sub-Saharan African households between 2000 and 2015. Pyrethroids on the nets kill Anopheles mosquitoes that land on them, and the net physically prevents bites during sleeping hours when Anopheles is active — reducing the chance that sporozoites are delivered to a human. [2 marks: 1 for naming the intervention; 1 for mechanism]
Intervention 2 — Artemisinin combination therapy (ACT): Became widely available in the 2000s as the standard treatment for clinical malaria. ACT rapidly kills blood-stage Plasmodium parasites in red blood cells, both curing illness and reducing gametocyte production — lowering the reservoir of infectious parasites that can be picked up by mosquitoes. [2 marks: 1 for naming the intervention; 1 for mechanism]
Q1.3 — 2020 spike cause and mechanism (2 marks)
The 2020 spike was caused by COVID-19 pandemic disruptions to malaria control services [1]. Lockdowns, healthcare system overload, and redirection of resources disrupted ITN distribution, IRS spraying programs, and access to ACT treatment — meaning fewer people were protected from bites and fewer clinical cases were treated, allowing more transmission and more deaths [1].
Q2 — Cause-and-effect chain (5 marks)
Effect 1 (natural selection): Among the large, genetically diverse Plasmodium population, rare parasites carrying mutations that reduce artemisinin binding survive treatment and reproduce while susceptible parasites are killed — selection pressure acts on variation in the parasite population. [1]
Effect 2 (parasite genotype): The resistant genotype (e.g. Kelch13 propeller mutations in P. falciparum) increases in frequency across the population as resistant parasites preferentially survive and reproduce. [1]
Effect 3 (clinical outcome): Standard ACT courses no longer clear the parasite rapidly in infected patients — treatment fails, patients remain ill longer, and gametocyte production continues. [1]
Effect 4 (spread): Resistant parasites are transmitted to new hosts via feeding Anopheles mosquitoes; the resistance allele spreads geographically from Southeast Asia into Africa. [1]
Overall outcome: The gold-standard treatment for malaria becomes less effective across a growing proportion of malaria-endemic regions, threatening progress in malaria control and requiring new drug combinations or pipeline alternatives. [1]
Q3 — Compare malaria and dengue (10 marks)
| Feature | Malaria | Dengue |
|---|---|---|
| Causative pathogen | Plasmodium spp. (eukaryotic protozoan parasite); P. falciparum most lethal | Dengue virus (DENV) — RNA flavivirus; four antigenically distinct serotypes (DENV 1–4) |
| Vector + biting time | Female Anopheles (nocturnal biter; rests indoors) | Aedes aegypti (daytime biter; urban, breeds in small water containers) |
| Nature of immunity | Partial, acquired — not sterilising; repeated infections build partial immunity but not full protection | Lifelong to one serotype; ADE risk on second serotype — prior exposure is both protective and a risk factor |
| Best vaccine + efficacy | R21/Matrix-M (~75–80% efficacy; WHO-approved 2023); RTS,S (~36%) | TAK-003 / Qdenga (~80–90% vs DENV-1/2; ~50% vs DENV-3/4); Dengvaxia only for seropositive individuals |
| Primary burden | Sub-Saharan Africa (95% of cases; 608,000 deaths/year; 76% children under 5) | Tropical Asia, Americas; global distribution expanding; ~390 million infections/year, ~20,000 deaths |
Award 2 marks per row (1 for each column having at least one correct specific detail).
Q4.1 — ADE and seronegative risk (3 marks)
Antibody-dependent enhancement (ADE) is the process by which antibodies from a previous dengue serotype infection bind to — but fail to neutralise — a second dengue serotype [1]. Instead of blocking infection, these antibodies facilitate entry of the second serotype into Fc receptor-bearing immune cells (monocytes/macrophages), dramatically amplifying viral replication and causing more severe disease [1]. Seronegative Dengvaxia recipients had no prior dengue infection, so their immune systems had never been primed. The vaccine effectively created a "virtual first dengue infection." If such a person was later exposed to a natural dengue serotype, their vaccine-induced antibodies behaved like a first-infection immune response — and via ADE made the real infection more severe than if they had been unvaccinated [1].
Q4.2 — Why dengue vaccine development is harder than malaria (2 marks)
Dengue exists as four antigenically distinct serotypes (DENV-1, 2, 3, 4), so a vaccine must provide strong, balanced, lasting immunity against all four simultaneously [1]. If the vaccine produces uneven protection (as with Dengvaxia), vaccinated individuals who encounter an unprotected serotype experience ADE — a risk that is absent in malaria vaccination because Plasmodium does not have the same multi-serotype immune paradox [1].