Does Hydroxychloroquine Work Against Malaria?

Hydroxychloroquine(Hcqs 200) is a well-known medication with a variety of uses, including autoimmune conditions like rheumatoid arthritis and lupus. However, its original purposeand one that continues to be relevant in specific regionsis the treatment and prevention of malaria. But does hydroxychloroquine still work against malaria today?

This article takes an in-depth look at hydroxychloroquines effectiveness against malaria, its current status in treatment guidelines, where it can still be used, and why resistance is a growing concern.

What Is Hydroxychloroquine?

Hydroxychloroquine is a synthetic derivative of chloroquine, developed to be a less toxic alternative with similar antimalarial properties. It was initially introduced in the 1950s and has since become a multifunctional drug used for:

• Treating autoimmune diseases like lupus and rheumatoid arthritis

• Preventing and treating malaria, especially caused by Plasmodium vivax, P. malariae, and P. ovale

Hydroxychloroquine belongs to a group of medications known as 4-aminoquinolines. These drugs work by entering infected red blood cells and interfering with the parasite's ability to digest hemoglobina critical process for its survival.

How Does Hydroxychloroquine Work Against Malaria?

Malaria is caused by Plasmodium parasites, which are transmitted to humans through the bite of infected female Anopheles mosquitoes. Once inside the body, the parasite multiplies in the liver and then infects red blood cells, leading to fever, chills, and other symptoms.

Hydroxychloroquine works by:

• Disrupting the parasite's digestion of hemoglobin

• Accumulating in the parasites acidic food vacuole, causing a toxic buildup of heme

• Damaging the parasites internal structure, leading to its death

This mechanism makes hydroxychloroquine effective against blood-stage Plasmodium parasites, especially in non-resistant areas.

Is Hydroxychloroquine Still Effective Against Malaria?

The answer is: It depends on the region and the species of Plasmodium.

? Where It Still Works:

• Central America (west of the Panama Canal)

• Haiti

• Parts of the Middle East and the Caribbean

• Areas with chloroquine-sensitive Plasmodium falciparum or Plasmodium vivax

In these regions, hydroxychloroquine may still be used for both prophylaxis (prevention) and treatment.

? Where It No Longer Works Well:

• Most of sub-Saharan Africa

• South and Southeast Asia

• South America

In these areas, Plasmodium falciparum has developed widespread resistance to chloroquine and hydroxychloroquine, making them ineffective and no longer recommended.

Which Malaria Types Can Hydroxychloroquine Treat?

Hydroxychloroquine is generally effective against:

• Plasmodium vivax

• Plasmodium ovale

• Plasmodium malariae

• Plasmodium knowlesi

It can also work against Plasmodium falciparum, but only in areas where resistance is not presentwhich are increasingly rare.

How Is Hydroxychloroquine Used for Malaria Prevention and Treatment?

?? For Prevention (Prophylaxis):

• Start 12 weeks before entering a malaria-endemic area

• Continue weekly during the stay

• Take for 4 weeks after leaving the area

• Typical adult dose: 400 mg once weekly

?? For Treatment (Acute Malaria):

• Initial dose: 800 mg (4 tablets of 200 mg)

• Followed by 400 mg after 68 hours, and then 400 mg daily for the next 2 days

• Total dose over 3 days: 2 grams (2000 mg)

Treatment protocols may vary depending on local resistance patterns and guidelines, so its essential to follow the advice of a healthcare provider.

What About Hydroxychloroquine Resistance?

Resistance is the primary reason hydroxychloroquine is no longer a frontline treatment in many parts of the world.

? What causes resistance?

• Mutations in the PfCRT gene of Plasmodium falciparum allow the parasite to pump the drug out of its digestive vacuole, rendering it ineffective.

? Where is resistance common?

• It is widespread in Africa, Asia, and South America

• In these areas, other medications like artemisinin-based combination therapies (ACTs) are preferred

Because of this, hydroxychloroquines role in global malaria control has diminished significantly over the last few decades.

Side Effects and Safety of Hydroxychloroquine

Hydroxychloroquine is generally well-tolerated when used correctly. Common side effects include:

• Nausea or stomach upset

• Headache

• Dizziness

• Mild skin rashes

More serious but rare side effects include:

• Retinal toxicity (with long-term use)

• Heart rhythm abnormalities (especially when used with other drugs)

• Muscle weakness

These risks are low during short-term use for malaria prevention or treatment, but monitoring is still advised.

Alternatives to Hydroxychloroquine for Malaria

Due to widespread resistance, other medications have largely replaced hydroxychloroquine in many countries:

? For Prevention:

• Atovaquone-proguanil (Malarone)

• Doxycycline

• Mefloquine

? For Treatment:

• Artemisinin-based combination therapies (ACTs) such as:

  • Artemether-lumefantrine

  • Artesunate-mefloquine

  • Dihydroartemisinin-piperaquine

These treatments are more effective in chloroquine-resistant areas and are the WHO-recommended standard for treating falciparum malaria.

Hydroxychloroquine and Drug Repurposing: Beyond Malaria

Hydroxychloroquine gained media attention during the COVID-19 pandemic as a potential antiviral treatment. However, rigorous studies have shown it is not effective for COVID-19 prevention or treatment, and major health organizations advise against its use for this purpose outside of clinical trials.

Still, hydroxychloroquine remains a valuable medication for:

• Lupus

• Rheumatoid arthritis

• Certain skin and autoimmune conditions

Yesbut with limitations. Hydroxychloroquine is still an effective treatment and preventive medication in areas where the malaria parasite has not developed resistance, such as parts of Central America and the Caribbean. However, in most parts of the worldespecially Africa and Southeast Asiaresistance has rendered it ineffective, and other modern therapies are preferred.

If you're planning to travel to a malaria-endemic region or considering malaria treatment, it's crucial to consult a healthcare provider for up-to-date recommendations based on current resistance patterns in your destination.

In summary:

• ? Hydroxychloroquine still works in select regions

• ? It is not effective in chloroquine-resistant areas

• ?? Should always be used under medical guidance

• ? There are more effective alternatives available today

Hydroxychloroquine may not be the universal solution it once was for malaria, but in the right settings, it still plays a valuable role.