November 17, 2020

Is there a Plant-based Treatment for Malaria?

Introduction

Approximately 210 million people get infected with malaria, and close to 440,000 people die from the disease. These numbers affect mostly young children in Africa, and currently, no vaccine has been approved for human use for malaria. The gravity of the situation is clear, for it only takes an infected mosquito to bite and transmit the parasite to numerous people. Preventative measures are key and organizations such as the World Health Organization, chooses to remind individuals in the tropical and subtropical countries to wear protective clothing, set up bed nets at night and use insect repellents. But there are medicines that are currently used as part of the treatment for the disease, which are effective (when diagnosed correctly), even though there is no official vaccine (“Malaria”).  

Malaria, AKA the “King of Diseases”, is caused by protozoan parasites of the genus Plasmodium and the most serious type of it known as Plasmodium falciparum. There are other human species as well, such as P. vivax, P. ovale, and P. malariae. The need for effective and practical diagnosis is increasing, especially since it is a global issue. To do this, diagnosis needs to be more streamlined and for that, it is important that early symptoms are caught at the right moment, especially since they are very nonspecific and variable (Tangpukdee). 

______________________________________________________________________________

Symptoms

Earliest symptoms - make it hard to diagnose and can be overlapping with other viral or bacterial infections (Tangpukdee). These are considered as the more common combination of symptoms: 

  1. Fever
  2. Headache
  3. Myalgia
  4. Chills and weakness
  5. Abdominal pain
  6. Diarrhea
  7. Nausea
  8. Vomiting 

 

Malaria “attacks”: some individuals can experience these “attacks” that begin with shivering and chills, followed by high fever, then sweating, then back to normal temperature (“Malaria”). These are considered the stages for the classical malaria attack, as written by the CDC, and lasts for about 6-10 hours. 

Serious, severe malaria occurs when organ complications come into play and failures or abnormalities in the blood or metabolism are observed. According to the CDC, here are the following manifestations:

  1. Cerebral malaria
    1. Abnormal behavior
    2. Impairment of consciousness
    3. Seizures
    4. Coma
    5. Other neurological abnormalities
  1. Severe anemia due to destruction of red blood cells (hemolysis)
    1. Can lead to hemoglobin in the urine (hemoglobinuria) as a result. 
  1. ARDS (Acute Respiratory Distress Syndrome)
    1. It is an inflammatory reaction in the lungs that basically inhibits oxygen exchange, which is what our lungs are responsible for. 
    2. This could occur even after parasite counts have decreased after treatment
  1. Low blood pressure due to cardiovascular system collapse
  2. Acute kidney journey
  3. Excessive acidity in the blood and tissue fluids - Metabolic acidosis
  4. Low blood glucose - Hypoglycemia (can also occur in pregnant women with uncomplicated malaria)
  5. Hyperparasitemia
    1. When more than 5% of the RBCs are infected by malaria parasites

**There are many strains of the parasite and these symptoms are from the common strains observed.**

Malaria Relapses: within P. vivax and P. ovale infections, patients who may have recovered the first time around can suffer from additional attacks - “relapses” - after months or even years without symptoms. These relapses occur due to P.vivax and P. ovale have parasites (“hypnozoites”) that can remain dormant in your liver and can reactivate later. There are treatments to reduce these relapses and should follow the treatment of the first attack (“CDC - Malaria - About Malaria - Disease”). 

______________________________________________________________________________

Treatment

Maximum drug effects, as observed, were between 18-24 hrs of parasite development; once again, showing the importance of early diagnosis. Increase in parasitic metabolic activity correlated with decreased drug sensitivity. 

  1. Chloroquine (CQ)
  2. Quinine (QN)
  3. Artemisinin (AR)
  4. Sodium artelinate (SA)

AR and its related compounds produced the most rapid parasitic clearance, followed by CQ and then QN. Basically, the artemisinin compounds, which behaved similarly, “had an overall broader time window of antimalarial effect than either CQ or QN ''(Terkuile, 91). In severe malaria cases, artemisinin derivatives also showed greater likelihood of inhibiting parasite cycle than other drugs.

CQ shows the most rapid onset of action out of the four drugs by inhibiting the parasite’s protein and nucleic acid synthesis. In contrast, there is a lag time of 1-4 hours before AR compounds begin to show any of the measurable effects, but after this, the reaction is very rapid as compared to CQ and QN. 

Based on this information, the delayed activity of AR and SA would be in favor for those with blood concentrations that were constant or above the concentration that inhibited parasite activity (or the inhibitory concentration) for several hours. Basically, these drugs are stage dependent and thus, the stage of infection will dictate which drug is best fit (Terkuile, 92). 

______________________________________________________________________________

Plant Based Treatment

Based on an assessment conducted by Alshawsh et al., the following information provides an overview of some Yemeni Medicinal plants that have antimalarial properties (specifically against Plasmodium falciparum). 

The following medicinal extracts are commonly used in Yemen by traditional healers and the study conducted evaluated their behavior against isolates of Plasmodium falciparum, in vitro (not in a biological setting, isolated). 

The IC50 of a medicine is the concentration of the medication in the blood that can inhibit the replication of the malarial parasite. It is the concentration at which 50% of the parasitic replication will be inhibited (“Concentration”). A low concentration indicates that less of the medication is needed to have an effect, thus implying the efficiency of the product.

Out of the 6 plants, there were three that were found to have significant positive effects with their IC50 value being less than 4 microgram/ml. 

 

 This table shows all the medicines lined up and compared with the SMI or inhibition rate of the parasite of Chloroquine, which is a widely used drug for malaria. Among all of the medicines, only Acalypha fruticosa, Azadirachta indica, and Dendrosicyos socotrana showed any inhibition against parasite growth. 

  1. Acalypha fruticose
    1. Traditional Uses: Antiinflammatory, antimalarial, antibacterial.
    2. Active components: Tannins, terpenoids, flavonoids, proteins, polysaccharides
    3. IC50 = 1.6 microgram/ml
  1. Azadirachta indica
    1. Traditional Uses: Antimalarial, fever, digestive disturbances, skin problems, general fatigue, intestinal parasites, diabetes, fungal infections, inflammatory diseases.
    2. Active components: Flavonoids, terpenoids Polysaccharides, proteins, tannins
    3. IC50 = 2.0 microgram/ml
  1. Dendrosicyos socotrana
    1. Traditional uses: Urinary retention, cystitis, symptoms of diabetes, problems with the liver and burns, constipation 
    2. Active components: Terpenoids, proteins, polysaccharides
    3. IC50 = 2.3 microgram/ml

Based on the commonalities within the active components, the presence of tannins, polysaccharides and proteins in the aqueous extracts (Table 2), might have been responsible for the antiplasmodial (against malaria, stemming from the genus Plasmodium) activity of those products(Alshawsh).

Another plant based on West African Plants, conducted by Zirihi et al., researched 33 plant extracts and found certain plants that have been described with having antiplasmodial activity – which is what we are looking for in medications (Zirihi, G.N.).

  1. The root extract of Rauvolfia vomitoria (IC50 = 2.5 micrograms/ml, SI = 9-10)
    1. Important medicinal plant used for many illnesses such as neuropsychiatry disorders, jaundice, gastro-intestinal, measles, and more.
  2. The stem bark extract of Funtumia elastica (IC50 = 3.3 micrograms/ml, SI >15)
    1. Traditionally used for the treatment of haemorrhoids
  3. The stem bark extract of Fagara macrophylla (IC50 = 2.3 micrograms/ml, SI = 9-12)
    1. Has a potent “antifeedant activity” (naturally occurring substance in the plant that causes an unfavorable reaction in the organism that consumes it) against the larvae of both Spodoptera frugiperdaand Spodoptera littoralis (species of moth)
    2. Hypothesized that these substances also make the plant have antiplasmoidial activity.

Work Cited

 

Alshawsh, Mohammed A et al. “Assessment of antimalarial activity against Plasmodium falciparum and phytochemical screening of some Yemeni medicinal plants.” Evidence-based complementary and alternative medicine : eCAM vol. 6,4 (2009): 453-6. doi:10.1093/ecam/nem148

“CDC - Malaria - About Malaria - Disease.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 4 Jan. 2019, www.cdc.gov/malaria/about/disease.html.

“Concentration.” The Free Dictionary, Farlex,

medical-dictionary.thefreedictionary.com/concentration. 

“Malaria.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 13 Dec. 2018, www.mayoclinic.org/diseases-conditions/malaria/symptoms-causes/syc-20351184. 

Tangpukdee, Noppadon et al. “Malaria diagnosis: a brief review.” The Korean journal of parasitology vol. 47,2 (2009): 93-102. doi:10.3347/kjp.2009.47.2.93

Terkuile, F., et al. “Plasmodium Falciparum: In Vitro Studies of the Pharmacodynamic Properties of Drugs Used for the Treatment of Severe Malaria.” Experimental Parasitology, vol. 76, no. 1, 1993, pp. 85–95., doi:10.1006/expr.1993.1010.

Zirihi, G. N., Mambu, L., Guédé-Guina, F., Bodo, B., & Grellier, P. (2005). In vitro antiplasmodial activity and cytotoxicity of 33 West African plants used for treatment of malaria. Journal of Ethnopharmacology, 98(3), 281-285. doi:10.1016/j.jep.2005.01.004

Written by Disha Srivastava