Probably you have heard that malaria is a life-threatening disease responsible for thousands of deaths globally each year, right?

Also,

If you are from sub-Saharan Africa or other tropical regions where malaria is prevalent like Cambodia, news reports on malaria epidemics, outbreaks, and resurgence aren’t new to you.

Malaria is a deadly yet preventable infectious disease caused by Apicomplexan protozoans known as Plasmodium. Infected female Anopheles mosquitoes are responsible for spreading malaria parasites from one person to another.

It is an ancient disease that has been in existence as early as 413 B.C. and 1500 B.C. in ancient Greek and Egypt respectively. The malaria parasites were discovered by the French doctor, Dr. Alphonse Laveran in 1880.

Despite the numerous efforts tailored toward malaria treatments, control, and preventive measures that are in place, this parasitic infection remains to be a thorn in the flesh in endemic regions.

In 2021, malaria was responsible for over 600,000 mortalities worldwide. Young African children below 5 years who succumbed to malaria infection accounted for 80% of all malaria deaths.

Apart from malaria-related deaths, parasitic infection causes health complications like:
• Iron-deficiency anemia
• Cerebral malaria
• Organ failure- liver, kidney
• Acute respiratory distress syndrome (Breathing difficulties)
• Hypoglycemia (low blood sugar)
• Jaundice
But do you know that malaria is treatable, preventable, and curable?

When you visit a hospital when presenting symptoms similar to malaria, your doctor will carry out prerequisite malaria screening procedures: medical history, temperature, and malaria diagnosis using microscopy or rapid diagnostic test (RDTs).

These procedures are vital in eliminating misdiagnosis and the administration of wrong treatment plans to patients with suspected malaria cases.  This is because malaria symptoms such as fever, vomiting, and shivering chills are non-specific. They do mimic other illnesses such as the common cold and typhoid.

Your doctor will prescribe a malaria treatment regimen based on the following factors:

  • Your age
  • Disease severity-this is determined by the initial level of malaria parasite levels (parasitemia) in your body
  • Plasmodium species present in malaria blood smear
  • Whether you are pregnant or not
  • Hypersensitivity to certain classes of malaria medications
  • If you recently traveled to malarious regions (imported malaria)
  • Medical history of glucose-6-phosphate dehydrogenase deficiency in vivax malaria-endemic regions

Below are antimalarial therapies useful in the treatment of uncomplicated and severe forms of malaria in endemic and non-endemic regions.

Uncomplicated or acute malaria therapies

Artemisinin-based combination therapies (ACTs)

ACTs are a class of 3-day course oral malaria medicines that consist of a combination of two drugs with different modes of action against the malaria parasite. Often, they are made of artemisinin derivatives that are fast–acting, and a partner drug with a slower terminal half-life elimination period.

These artemisinins and their semisynthetic derivatives are extracted from the Chinese sweet wormwood plant popularly known as Artemisia annua. Examples are:

  • Artemether,
  • Artesunate
  • Arteether
  • Dihydroartemisinin

The partner drugs can be:

  • Lumefantrine
  • Piperaquine
  • Amodiaquine
  • Pyronaridine
  • Mefloquine

All the active metabolites of artemisinin have shorter terminal elimination half-lives: it only takes 1-2 hours for our body systems to eliminate artemether and dihydroartemisinin after administration.

On the contrary, partner drugs like lumefantrine and piperaquine have longer half-lives of 4-6 and 20-30 days respectively.

The purpose of the artemisinin derivatives in ACTs is to clear the Plasmodium rapidly in our bloodstream.

By contrast, the partner drugs such as lumefantrine serve to eliminate the remaining malaria parasites. This, in turn, decreases the likelihood development of drug resistance or recrudescence.

ACTs that meet WHO’S prequalification criteria as first-line therapies for uncomplicated falciparum malaria are:

  ACT Drug

 Brand Name
Artemether-lumefantrine (AL)  Coartem®,Lumewell®,Lonart-RS, Artelcare®, Purefantrine Forte®,   Asminal®
Artesunate-sulphadoxine-pyrimethamine (AS-SP) Arsugin SP, Co-Arinate Adult®, Co-Arinate Adulte ®,

Co-Arinate Adult FDC®
Artesunate-mefloquine( AS-MQ) Mefliam Plus®
Artesunate-amodiaquine (AS-AQ) Camoquin®, Flavoquine®,ASAQ Winthrop®
Dihydroartemisinin piperaquine (DHAP)

Duocotexin®, Artekin®,Eurartesim® dysure®, Arquincare®,Malcidin®, Mosmal®, Upxin®
Artesunate-pyronaridine (PA)- Newest

Pyramax®, Artecom®

 

How many countries recommend the use of ACTs?

In response to counter the widespread chloroquine drug resistance, 67 countries globally, 41 of them being African nations, have adopted ACTs as their first-line treatment for acute malaria.

Different countries have adopted the use of particular ACTs: the Ministry of Health in Kenya, Uganda, and Tanzania recommend the use of artemether-lumefantrine as the first-line drug.

In case of treatment failure, dihydroartemisinin-piperaquine serves as the second-best alternative.

In South Sudan, artesunate–amodiaquine is the treatment of choice for uncomplicated malaria while artemether–lumefantrine is the second-line drug.

Countries in the  Greater Mekong Region-Cambodia, Myanmar, Laos, Thailand, and Viet Nam- have opted for the newest ACT, pyronaridine-artesunate.

This is because of the skyrocketing artemisinin-resistant and multidrug-resistant uncomplicated falciparum malaria cases.

Read also: The Emerging Threat of Artemisinin Resistance on Malaria Control

Plasmodium vivax infections

Chloroquine is the first line treatment for chloroquine-sensitive malaria infections except in:

  • Oceania
  • Indonesia
  • Horn of Africa
  • Madagascar
  • Sabah
  • New Papua Guinea
  • Parts of Central and South America
  • Asia-Pacific region

Pyronaridine-artesunate is also the recommended ACT for the treatment of chloroquine-resistant vivax malaria.

A 14-day course of primaquine or a single dose of tafenoquine is used as a radical cure for malaria relapses. Relapses are a result of the reactivation of the latent liver malaria stages, the hypnozoites in Plasmodium vivax.

Primaquine, however, is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency as it causes acute hemolytic anemia.

What are the advantages of ACTs?

According to malaria research reports on several antimalarial efficacy studies on different classes of ACTs worldwide, the findings indicate that these medications have many benefits:

  • Safe and well-tolerated by children and adults
  • High efficacy of >90% cure rates resulting in fast resolution of malaria symptom
  • Prevent the likelihood of the selection of malaria parasites to drug resistance and its eventual spread
  • Prevent cases of recrudescent malaria infections. Recrudescent infections are usually observed in patients with Plasmodium malariae on the 28th treatment follow-up day. The scenario arises when the antimalarial drug prescribed fails to eliminate the red blood stages of the parasite –the ring-form trophozoites/ ring stages-completely due to inadequate treatment. It may also happen when one is non-compliant to finish the prescribed drugs or the existence of drug-resistant malaria parasites.
  • Kill early sexual stages of malaria parasites(gametocytes) thereby preventing infection of female Anopheles mosquitoes and subsequent disease transmission to humans

ACTs limitations may include:

  • ACTs like Coartem ® require fatty food intake for optimum drug absorption
  • Incomplete completion of the prescribed full dose of ACT regimen due to non-compliance
  • Incidents of adverse drug effects such as vomiting, nausea, or diarrhea

Treatments for complicated/severe malaria

Severe malaria is a type of illness that involves complications like cerebral malaria or organ failure. Out of the five human malaria parasites, Plasmodium falciparum has been implicated as the major cause of complicated malaria.

WHO recommends parenteral artesunate either intramuscularly or intravenous injection for a minimum of 24 hours in children and adults.

Once you are out of severe malaria dangers, your doctor will then administer the full dose of ACT when you can tolerate or swallow the medicines.

Other alternatives that doctors may consider at the malaria pre-referral care stage are:

  • Intramuscular artemether- when parenteral artesunate is lacking
  • Intramuscular quinine- if both parenteral artesunate and intramuscular artemether are lacking
  • Rectal artesunate in children under 6 years old- when parenteral artesunate, intramuscular artemether, and intramuscular quinine are unavailable

Which malaria medications are safe for expectant mothers?

Effective malaria management in expectant mothers is crucial in preventing maternal and neonatal mortalities and other pregnancy complications.

These are spontaneous abortions, low birth weight babies, premature babies’ stillbirths, and maternal anemia.

To avert these grave dangers, expectant mothers in endemic regions are advised to attend frequent antenatal clinics for intermittent preventive treatment of sulphadoxine-pyrimethamine (IPT-SP).

The use of ACTs is NOT SAFE  in the first trimester: embryotoxicity findings from animal models indicate that artemisinin derivatives have teratogenic effects:

  • Pregnancy loss
  • Congenital malformations of the heart and skeletal system
  • Fetal resorption

They can, however, be used during the second and third trimesters of pregnancy.

WHO recommends quinine monotherapy or quinine-clindamycin combination therapy for malaria treatment in all trimesters of pregnancy.

Malaria prophylaxis for travelers

When you are planning to travel to high–risk malaria regions, you should take prophylactic malaria drugs 1 or 2 days before and during your stay in the area.

It is also mandatory for an individual to take the drugs 7 days after leaving malaria-endemic regions.

Malaria prophylaxis treatment guidelines vary from one country to another.  For instance, atovaquone-proguanil (Malarone®), mefloquine, or doxycycline are the most commonly used prophylactic drugs in Kenya.

Are there malaria vaccines?

Yes,

Thanks to the unrelenting devotion and teamwork of malaria researchers from PATH Malaria Vaccine Initiative (MVI) and GlaxoSmithKline (GSK) companies!

RTS, S/AS01 (RTS, S) is the first and the only approved human malaria vaccine available for the prevention of pediatric Plasmodium falciparum infections. It is available under the Mosquirix ® brand name in malarious sub-Saharan African regions with moderate and high disease transmission rates.

 

There has been a wide deployment of RTS, S malaria vaccination following the encouraging and promising findings from Phase 3 pilot clinical trial studies in Kenya, Ghana, and Malawi. The study involved two groups of children aged between 6-12 weeks and 5-17 months.

Bottom line

The effectiveness of malaria treatment options depends on many factors including malaria parasite of interest, severity, health status, and the region where the patient acquires the infection.

  • You must seek prompt medical attention when you are presenting symptoms similar to malaria.
  • You must also always keep in mind the 3Ts for malaria treatment and management (Test, Treatment, Track).
  • Avoid buying over-the-counter drugs to prevent misdiagnosis and prescription of lower ACT doses.