The quiet breakthrough that helped turn the tide against a deadly disease
Imagine a fever so persistent it defies standard medication, in a place where warm, rainy climates create the perfect breeding ground for malaria.
This was the reality for residents of Hainan Island in the 1980s. For decades, the parasite Plasmodium falciparum had rendered chloroquine—the once-miraculous antimalarial—virtually useless on the island. Patients suffered, and health officials scrambled for a solution 1 3 .
The answer, it turned out, was not in a single new wonder drug, but in a strategic pairing of two existing ones: amodiaquine and sulfadoxine-pyrimethamine. A landmark study conducted in 1985-86 would demonstrate that while these drugs were moderately effective alone, their combination was a game-changer, offering a cure rate of up to 100% and dramatically speeding up recovery 1 .
This story is not just about a scientific experiment; it's about the clever strategy that became a cornerstone in the eventual elimination of malaria from Hainan.
Hainan Island, with its tropical climate and substantial rainfall, was an ideal environment for malaria-carrying Anopheles mosquitoes. For years, it was one of the Chinese provinces most severely affected by the disease 3 .
This resistance meant that the standard of care was failing. Doctors needed new weapons, and fast. Researchers turned their attention to two other antimalarial drugs:
The Plasmodium falciparum parasite has a complex lifecycle involving both humans and mosquitoes, making it particularly challenging to combat.
Sporozoites enter human bloodstream through mosquito bite
Parasites multiply in liver cells
Parasites infect red blood cells, causing symptoms
The critical question was whether these drugs could hold their own against Hainan's resilient malaria strain, or if an even more powerful approach was needed.
In 1985-86, a decisive study was launched on Hainan Island to find the most effective treatment for chloroquine-resistant malaria. The design was straightforward but powerful: enroll patients with confirmed P. falciparum malaria and assign them to different treatment groups to compare outcomes directly 1 .
The researchers divided the patients into four groups to ensure a clear comparison:
50 cases: Received 1800 mg of amodiaquine over three days.
21 cases: Received a single dose of 1500 mg sulfadoxine and 75 mg pyrimethamine.
50 cases: Received a combination of the two drugs.
49 cases: Received the three-drug combination of amodiaquine, sulfadoxine, and pyrimethamine.
The team then meticulously tracked three key outcomes for each group 1 :
The percentage of patients completely cleared of the parasite with no recurrence.
The average number of hours it took for a patient's fever to subside.
The average number of hours it took for the parasites to become undetectable in the blood.
The results, published in 1988, were striking. They revealed a powerful synergistic effect—where the combined action of the drugs was greater than the sum of their individual parts.
The amodiaquine-plus-SP combination achieved a perfect 100% cure rate, with no recrudescence. Furthermore, the combinations worked much faster to bring down fevers, a critical relief for suffering patients 1 .
| Treatment Group | Number of Cases | Cure Rate | Recrudescence Rate (RI/RII) | Mean Fever Clearance Time (hours) | Mean Parasite Clearance Time (hours) |
|---|---|---|---|---|---|
| Amodiaquine (AQ) alone | 50 | 65.3% | 34.7% | 30.7 | 60.3 |
| Sulfadoxine-Pyrimethamine (SP) alone | 21 | 90.5%* | 9.5%* | 56.1 | Not Specified |
| AQ + Sulfadoxine | 49 | 97.9% | ~2% | 25.0 | 57.1 |
| AQ + SP | 50 | 100% | 0% | 25.7 | 52.8 |
*Note: Of the 21 cases treated with SP alone, 19 were cured, one showed an RI recrudescence, and another had an S or RI response 1 .
The data spoke for itself. While amodiaquine alone was struggling and SP alone was better, the combinations were spectacularly successful.
The Hainan experiment was part of a much broader, decades-long war on malaria. The island's ultimate success, achieved in 2011, relied on a versatile toolkit of strategies and tools that evolved as the battle was won.
| Tool | Mechanism of Action | Role in Hainan's Elimination | Key Details |
|---|---|---|---|
| Drug Combinations (e.g., AQ+SP) | Attacks parasite with multiple mechanisms to overcome resistance and improve efficacy. | Treatment & Cure: Used to directly treat infections and achieve clinical cure. | Proven to be far more effective than monotherapies for resistant strains 1 . |
| Insecticide-Treated Bed Nets (ITNs) | Creates a physical and chemical barrier, killing mosquitoes that contact the net. | Core Prevention: A cornerstone of vector control, significantly reducing mosquito bites. | Widespread use led to a 77.5% decrease in cases within five years in the 1990s 3 . |
| Indoor Residual Spraying (IRS) | Kills adult mosquitoes that rest on indoor walls after feeding. | Supplemental Control: Used to suppress mosquito populations, especially in high-risk areas. | Sprayed with insecticides like DDT and later deltamethrin 3 5 . |
| Mass/Targeted Drug Administration | Uses antimalarial drugs in populations to clear parasites, reducing the reservoir of infection. | Transmission Reduction: Piperaquine-primaquine used in mass campaigns and for high-risk groups. | Administered before and during peak transmission seasons 3 . |
| "1-3-7" Surveillance Approach | A strict timeline for case response: report within 1 day, investigate within 3, respond within 7. | Sustaining Elimination: Crucial for preventing resurgence after local transmission was stopped. | Implemented in the final stages to rapidly contain every imported case 3 . |
The strategic combination of amodiaquine and SP proved to be the breakthrough needed to treat resistant malaria strains.
Insecticide-treated bed nets and indoor residual spraying reduced mosquito populations and transmission rates.
The "1-3-7" approach ensured rapid response to cases, preventing outbreaks and maintaining elimination.
The success of the amodiaquine and SP combination in Hainan was more than a local victory; it was a proof-of-concept for a strategy that remains relevant today. The study provided clear, actionable evidence that drug combinations could salvage the efficacy of existing medicines even in the face of strong resistance.
This approach of pairing drugs is the same principle behind today's global standard of care for malaria: Artemisinin-based Combination Therapies (ACTs) . The Hainan story underscores a timeless lesson in infectious disease management: to outsmart evolving pathogens, we must stay ahead by using our weapons wisely, often in smart, synergistic combinations.
Chloroquine resistance emerges in Hainan
AQ+SP combination study shows 100% efficacy
Implementation of comprehensive control measures
Hainan achieves malaria elimination
Hainan's ultimate triumph over malaria was achieved in 2011, a feat that required integrating these drug strategies with robust mosquito control and relentless surveillance 3 5 . The island's journey from a malaria hotspot to a malaria-free zone offers a powerful blueprint for other regions still fighting this ancient scourge, demonstrating that even the most resilient foes can be defeated with perseverance and intelligent strategy.