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What’s the deal with Chloroquine?

Since its discovery and development in the 1940s, chloroquine has been disseminated across the world to treat all species of Plasmodium – the parasite causing malaria. It was highly valued for its potency against malaria parasites, but also for being safe, cheap to produce, and stable in tropical conditions. It was so safe and stable that it was added to table salt, in regions where malaria was endemic, to enhance malaria elimination efforts at that time. This and other indiscriminate uses had their consequences. In the late 1950s and early 1960s, resistance to chloroquine began to emerge in South East Asia and South America to Plasmodium falciparum, the malaria species causing most infections…

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 Chloroquine and Hydroxychloroquine

Commonly used on holidays in malaria prone destinations, chloroquine and hydroxychloroquine will not be over familiar to the emergency physician. However, it is one of the leading causes of drug overdose in malaria prone countries and also the occasional toddler has managed to consume the grandparents lupus or rheumatoid arthritis medication leading to lethal consequences.

 Chloroquine, Past and Present

Chloroquine's fame is as an antimalarial drug, and the history of antimalarials starts of course with quinine. That's the active compound in cinchona bark, whose medicinal properties had long been known among the natives of South America in the tropical parts of the Andes - the Incas and the people(s) that the Incas absorbed into their empire. It doesn't seem to have been used by them as a malaria treatment per se, but rather was known as a treatment for shivering, brought on by either low temperatures or by malaria itself.

Articles of Interest

Assessment of Long-Term Health Effects of Antimalarial Drugs When Used for Prophylaxis.

Chloroquine (and hydroxychloroquine) is used to treat diseases other than malaria, specifically rheumatoid arthritis and systemic lupus erythematosus. Serious adverse events (e.g., retinopathy, macular degeneration) have been reported in people using chloroquine for the treatment of rheumatoid arthritis and systemic lupus erythematosus; however, the chloroquine regimen for treating these diseases is 250 mg per day, a much higher dose than the once-weekly 500 mg dosing regimen used for malaria prophylaxis

Chloroquine against malaria, cancers and viral diseases

Quinoline (QN) derivatives are often used for the prophylaxis and treatment of malaria. Chloroquine (CQ), a protonated, weakly basic drug, exerts its antimalarial effect mainly by increasing pH and accumulating in the food vacuole of the parasites. Repurposing CQ is an emerging strategy for new indications. Given the inhibition of autophagy and its immunomodulatory action, CQ shows positive efficacy against cancer and viral diseases, including Coronavirus 2019 (COVID-19).

Chloroquine and Quinine

Chloroquine is used to prevent and treat malaria in limited geographical areas (e.g., Central America and the Far East) and to manage immunological disorders such as systemic lupus erythematosus and rheumatoid arthritis. It represents the most severe and frequent cause of poisoning by any antimalarial drug. Chloroquine is a frequent method of suicide in Africa

Chloroquine makes comeback to combat malaria

Scientists and healthcare personnel the world over fear that the malaria parasite will develop resistance to the current frontline treatment against malaria, Artemisinin-based Combination Therapies (ACTs). Therefore, it is especially good news that resistance monitoring at the University of Copenhagen shows that in several African countries, malaria parasites are succumbing to the formerly used drug chloroquine. The results have just been published in the American Journal of Tropical Medicine and Hygiene.

Chloroquine makes comeback to combat malaria

“In the near future, chloroquine and other malaria drugs not currently on the market will presumably be able to be used again, if we use them correctly. This means that the drug must be given in combination with other medicine and only to patients who have already developed a certain immunity to malaria and are therefore not at high risk. At the same time, we must reserve ACTs for the most exposed non-immune groups such as children. Chloroquine is one of the few drugs that can be given to pregnant women at the beginning of their pregnancy,” points out Ib Bygbjerg, adding that the patient can be treated with a high dose for a short period, another benefit.

Chloroquine Phosphate Injection: A Powerful Ally in the Fight Against Malaria

Chloroquine Phosphate Injection remains a vital component in the arsenal against malaria and other parasitic infections. Its efficacy in both treatment and prevention, coupled with its versatile administration, makes it an indispensable tool in modern medicine. As global efforts to combat malaria continue, Chloroquine Phosphate Injection plays a crucial role in improving patient outcomes and enhancing public health.

Drug-resistant malaria is emerging in Africa. Doctors are worried — yet hopeful

Malaria drugs have failed before. In the early 20th century, chloroquine helped beat back the pathogen worldwide. Then, about a decade after World War II, resistance to chloroquine surfaced along the Thailand-Cambodia border. By the 1970s, chloroquine-resistant malaria had spread across India and into Africa, where it killed millions, many of them children. "In retrospect, we know that chloroquine was used for many years after there was a huge resistance problem," says Rosenthal. "This probably led to millions of excess deaths that could have been avoided if we were using other drugs."

End of the road for Lariam? The malaria drug soldiers claim increases psychosis

The main challenge with preventing malaria is that some species of mosquito in certain countries have become resistant to the commonly used drugs such as chloroqine and proguanil. Lariam was developed to overcome such resistance and so was deemed to be useful if travelling to countries where there is a type of malaria that is particularly difficult to treat. But no single medicine is effective against all malaria parasites. The choice of a particular medicine depends on the sensitivity of the malaria parasites found in particular areas. But Lariam became increasingly controversial.

Insights in Chloroquine Action: Perspectives and Implications in Malaria and COVID‐19

The antimalarials chloroquine (CQ) and its analog, hydroxychloroquine (HCQ), have been tested for COVID‐19 treatment, and several conflicting evidence has been obtained. Therefore, the aim of this review was to summarize the evidence regarding action mechanisms of these compounds against Plasmodium and SARS‐CoV‐2 infection, together with cytometry applications. CQ and HCQ act on the renin angiotensin system, with possible implications on the cardiorespiratory system.

New Role for Chloroquine in Fight Against Malaria Envisaged by Researchers

The forgotten malaria drug chloroquine may yet prove effective against the disease provided it is administered in a different way.

The host targeting effect of chloroquine in malaria

Due to the rapid onset and spread of the COVID-19 pandemic, the treatment of COVID-19 patients by hydroxychloroquine alone or in combination with other drugs has captured a great deal of attention and triggered considerable debate. Historically, the worldwide use of quinoline based-drugs has led to a spectacular reduction in death from malaria. Unfortunately, scientists have been forced to seek alternative drugs to treat malaria due to the emergence of chloroquine-resistant parasites in the 1960s. The repurposing of hydroxychloroquine against viral infections, various types of cancer and autoimmune diseases has been ongoing for more than 70 years, with no clear understanding of its mechanism of action

Toxicity of chloroquine and hydroxychloroquine following therapeutic use or overdose

While chloroquine, a derivative of quinine, has been used as an antimalarial for 70 years, hydroxychloroquine is now used to treat conditions such as rheumatoid arthritis and systemic lupus erythematosus.

What is the role of chloroquine (hydroxychloroquine) in treating malaria?

Chloroquine can be used for malaria prophylaxis in geographic areas where resistance is not present

Resources

StatPearls

Chloroquine is FDA-approved for the treatment and prophylaxis of uncomplicated malaria in countries where chloroquine-sensitive malaria (certain strains of P. falciparum, P. ovale, P. vivax, and P. malariae) is present.