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Malaria treatments and prevention

Category: Medicines

Type

Involuntary

Introduction and description

 

 

Malaria is a mosquito-borne disease of both humans and other animals.  It is  caused by eukaryotic protists of the genus Plasmodium.

 There were an estimated 225 million cases of malaria worldwide in 2009 and an estimated 655,000 deaths from malaria in 2010.  According to the World Health Organization’s 2011 World Malaria Report, malaria accounts for 2.23% of all deaths worldwide. However, a 2012 meta-study from the University of Washington and University of Queensland, published in the Lancet,  estimated that 1,238,000 people died from malaria in 2010.

 For more details see the section on malaria.

Development of a mature Plasmodium falciparum gametocyte occurs over 10–12 days

Background

There are a number of drugs that are used to prevent malaria while travelling in areas where it exists. Most of these drugs are also sometimes used in treatment.

Because most Plasmodium are these days resistant to medications, one of three medications—mefloquine (Lariam), doxycycline, or the combination of atovaquone and proguanil hydrochloride (Malarone)—is frequently needed. Doxycycline and the atovaquone and proguanil combination are “the best tolerated”; mefloquine is associated with death, suicide, and neurological and psychiatric symptoms. 

In blue are Plasmodium falciparum malaria parasites in the
sexual, gametocyte stage of development

The use of preventative drugs is impractical for those who reside in areas where malaria exists, and their use is usually only in short-term visitors and travellers. This is due to the cost of the drugs, side effects from long-term use, and the difficulty in obtaining anti-malarial drugs outside of wealthy nations. The use of preventative drugs where malaria-bearing mosquitoes are present has even resulted in the development of partial resistance making treatment more difficult. It has not helped the local population either.

The signs and symptoms of malaria typically begin 8–25 days following infection; however, symptoms may occur later in those who have taken antimalarial medications as prevention, but where the prevention is ineffective.

Side effects

If we now take a look at the side effects of the pharmaceuticals, we find the following.

Using the eHealthme web site to obtain the actual side effects experienced by people, as recorded on Adverse Drug Reports and submitted by doctors to the FDA and SEDA in the USA, just some of the effects of Primaquine for example include:

Nausea Headache
Liver Function Tests Nos Abnormal Pyrexia
Myalgia Dehydration
Jaundice Nos Weight Decreased
Thrombocytopenia Insomnia
Urine Discolouration Depression
Pneumocystis Carinii Pneumonia Tremor
Rhabdomyolysis Drug Toxicity
Palpitations Aggression
Methaemoglobinaemia Hypertension

Mefloquine seems to be a major contributor to depression and suicidal thoughts, for example these are examples of just some of the side effects:

Female Male
Anxiety Anxiety
Insomnia Depression
Dizziness Insomnia
Paranoia Headache
Depression Confusional State
Fatigue Suicidal Ideation
Nausea Tinnitus
Nightmare Paranoia
Headache Hallucination
Dyspnoea Fatigue

 Death

Again, using the eHealthme web site to obtain the actual side effects experienced by people, as recorded on Adverse Drug Reports and submitted by doctors to the FDA and SEDA in the USA, the figures for death [USA only] are as follows:

  • Aralen - On Apr, 28, 2016: 96 people reported to have side effects when taking Aralen. Among them, 1 people (1.04%) has Death
  • Chloroquine phosphate - On Apr, 11, 2016: 777 people reported to have side effects when taking Chloroquine phosphate. Among them, 14 people (1.80%) have Death
  • Daraprim - On Apr, 28, 2016: 291 people reported to have side effects when taking Daraprim. Among them, 9 people (3.09%) have Death
  • Hydroxychloroquine sulfate - On Apr, 22, 2016: 7,674 people reported to have side effects when taking Hydroxychloroquine sulfate. Among them, 83 people (1.08%) have Death
  • Lariam - On Apr, 28, 2016: 2,906 people reported to have side effects when taking Lariam. Among them, 17 people (0.58%) have Death
  • Malarone - On Apr, 28, 2016: 1,983 people reported to have side effects when taking Malarone. Among them, 7 people (0.35%) have Death
  • Mefloquine - On Apr, 28, 2016: 471 people reported to have side effects when taking Mefloquine. Among them, 1 people (0.21%) has Death
  • Mepron - On Apr, 28, 2016: 788 people reported to have side effects when taking Mepron. Among them, 27 people (3.43%) have Death
  • Plaquenil - On Apr, 28, 2016: 14,798 people reported to have side effects when taking Plaquenil. Among them, 151 people (1.02%) have Death
  • Primaquine - On Mar, 29, 2016: 168 people reported to have side effects when taking Primaquine. Among them, 1 people (0.60%) has Death
  • Qualaquin - On Apr, 27, 2016: 149 people reported to have side effects when taking Qualaquin. Among them, 4 people (2.68%) have Death

How it works

 The mechanisms by which each drug can produce an hallucination, vision near death or actual death experience are different, however, they each result in the cause/effect chain of events in hypoxia – which is probably the main cause of the effects.

  •  Chloroquine, for example, can cause hypotension which can lead to hypoxia
  • Primaquine causes methemoglobinemia in all patients who take it.  Methemoglobin is an oxidized form of hemoglobin that can result in oxygen starvation to the brain - hypoxia.
 

The reason why Mefloquine causes hallucinations cannot be deduced with certainty because its mechanism of action is unknown.  Its side effects, however, may contribute.  Mefloquine can cause abnormalities with heart rhythms that are visible on an electrocardiogram. Combining mefloquine with other drugs that cause similar effects, such as quinine or quinidine, can increase these effects.  In this case, the cause of the hallucinations could be heart related hypoxia.

The drug is sold as two enantiomers.  According to some research, the (+)-enantiomer is more effective in treating malaria, and the (–)-enantiomer specifically binds to adenosine receptors in the central nervous system, and this too may account for some of its effects [see neurotransmitters – adenosine].

Ultimately the cause is Poisoning.

Observations

In the following descriptions, the number of hallucinations is shown in brackets by each drug.  The figures were obtained from the eHealthme web site and compiled from SEDA and FDA statistics .  I have provided a link to the drugs so that you can see all the side efects

Observation identifiers

Observation name

No of hallucinations

001549

Larium and Jane Austin

1

001550

Chloroquine

2

001551

Primaquine

23

001552

Mefloquine [Lariam]

217

018006

Aralen

2

018846

Daraprim

1

019118

Hydroxychloroquine

10

-

Lariam

214

019491

Malarone

92

019512

Mepron

18

015657

Plaquenil

35

019988

Qualaquin

2

 

TOTAL

607

 There are no figures on eHealthme for the following

  • Pamaquine - is an 8-aminoquinoline drug used for the treatment of malaria. It is closely related to primaquine.
  • Tafenoquine - (also called WR 238605 or SB-252263) is an 8-aminoquinoline drug that is currently being investigated as a potential treatment for malaria, as well as for malaria prevention. The main advantage of tafenoquine is that it has a long half-life and therefore does not need to be taken as frequently as primaquine.

In order to provide a contrast, we have also included some plant based healing treatments.  All these are to be found under the malaria heading as well, but we thought it might be useful as a contrast, to show that there are many many local plants that have been used effectively for millenia by each population, that if we are going on holiday to a region might be used effectively.  Needless to say, the local population have no need for expensive pharmaceuticals, as they already have the local plant treatments, as long as they use them!

Related observations