Malaria

 

by Erin  McKenzie-Carter

 

Etiologic Agent: There are four different eukaryotic parasites that cause malaria in humans under natural conditions.1 They are, Plasmodium falciparum, P. vivax, P. ovale, and P. malariae.4 P. falciparum and P. vivax cause the most infections throughout the world, with P. falciparum causing the more deadly form of malaria.1 The other two types of the Plasmodium genus (species P. ovale and P. malariae) have a dormant phase of their life-cycle and can be present in the host for months to years with no symptoms.1 The life cycle of these parasites will be discussed in more detail later.

 

Transmission: The etiologic agent that causes malaria, one of the four types of the Plasmodium parasite, is transmitted to humans via the female Anopheles mosquito.1 There are 430 different species of Anopheles mosquitoes, yet only 30-40 of them actually transmit the malaria parasite to humans.1

 

Reservoirs: The types of Plasmodium that infects humans does not infect animals, so therefore cannot be spread from animals to humans and vice versa.2 A recent study, which extracted Plasmodium parasites from humans and chimpanzees and compared the nucleotide sequence of surface proteins found that P. falciparum, the most deadly of the species to infect humans, might have evolved from P. reichenowi (a parasite that infects chimpanzees).2 Since malaria cannot be spread from animal-host to human-host, humans are the only reservoir that is really of interest to us.

 

General Characteristics of MO:

As previously stated, the MOs that cause malaria in humans are four different species of Plasmodium and they will be the species discussed here. These belong to the Eukaryotic domain and are protozoan parasites.4 Being a eukaryotic parasite, they have a complex life cycle which is described below.

 

Sporozites of Plasmodium from the salivary gland of mosquitoes enter the human blood stream when the mosquito bites.3 These sporozites invade liver cells and divide asexually to become merozoites.3 These merozoites then burst out of the liver cells to invade red blood cells (RBCs), where they mature to trophozoites.3 Some of the merozoites also become gametocytes instead of trophozoites, and are then taken up by mosquitoes.3 The gametocytes mature in the mosquitoes intestine into male and female gametes, when then form oocytes and mature into sporozites which then migrate to the salivary gland and are inserted back into human blood when the mosquito bites.3

 

Key Tests for Identification:

 The most widely used test, and the “gold standard” of tests for diagnosing malaria is a blood smear.1 This is stained, usually with Giemsa stain, and observed under 100X oil immersion.1 The early trophozite form of the Plasmodium can be seen in RBC, and has a characteristic “ring shape”.1 Also, to specifically distinguish P. falciparum, there are often more than one visible in the RBC, while with the other three species there is only one.1 Gametocytes can also be observed in the blood and appear crescent or sausage shaped.1

 

Many areas that are affected by malaria might not have access to high-tech microscopes, or have clinicians who are sufficiently trained to identify the MO. There is also another test that the CDC has introduced using antigen detection, which comes as a sort of kit.1 This test however, while quick and effective, it is also very costly.1

 

Yet another test that can be used is a PCR confirmation test. This test detects parasitic nucleic acids and is very reliable, but very expensive and requires a very specialized lab.1

 

Virulence Factors:

The Plasmodium species have two main virulence factors which are the ability to change surface antigens readily and toxins that are released.2 It is the toxins that are released that cause the symptoms associated with malaria; fever, chills, sweats, etc.2

 

 

Signs and Symptoms of disease:

Malaria is divided up into uncomplicated malaria (rarely seen) and severe malaria based on the type of Plasmodium that infects.1 The symptoms of uncomplicated malaria are fever, chills, sweats, headaches, muscle pain, nausea, vomiting, and general malaise.1 With the more severe malaria (caused by P. falciparum), more symptoms are present including mild jaundice, enlargement of the liver, increased respiratory rate, severe anemia, hemoglobinuria (hemoglobin in the urine), pulmonary edema, abnormal behavior, impairment of consciousness, seizures and possibly coma.1

 

Historical Information:

Malaria has been present in the human population for many, many centuries. Around 2700 BC the symptoms of malaria were described in the Nei Ching (Canon of Medicine).1 Also around the first century AD in India, Susruta is believed to have said that these symptoms were due to the bites of insects.1 In 1880 Charles Louis Alphose Laveran discovered the Plasmodium parasite in the blood of patients with malaria.1 In 1897 Ronald Ross confirmed that the parasites that cause malaria in fact are transmitted to humans via mosquitoes.1

 

The name “malaria” comes from the Italian, “mala aria”, meaning “bad air”.5 The bad air refers to the smelly air that swampy areas can have, and unknowingly at the time the word was coined, where the mosquitoes who transmit the malaria breed and live.5

 

Control/Treatment:

While total eradication of malaria would be ideal, it is not a realistic goal at this point. Instead, the CDC, since its beginnings has been working to control it.1 When a person is infected with malaria, it is ideal that they receive treatment within 24 hours.6 This of course is not always possible, but necessary, especially if they are infected with P. falciparum.6

 

The following is a list of drugs that is effective in attacking the parasite when it is present in the blood: chloroquine, sulfadoxine-pyrimethamine (Fansidar®), mefloquine (Lariam®), atovaquone-proguanil (Malarone®), quinine, doxycycline, and artemisin derivatives (not used in the U.S.).1

 

Prevention/vaccine info new trials?:

Since malaria is transmitted via mosquitoes, one of the most important things in preventing malaria is controlling mosquitoes (i.e. keeping them away from humans). This can include using insecticides to destroy larval breeding sites, wearing insecticide to keep mosquitoes from biting, or using an insecticide-treated bed net (ITNs).1

 

There is not currently a vaccine in use for malaria.7 There has been ongoing research for decades to create one and right now the Malaria Vaccine Advisory Committee to the World Health Organization has a goal of developing a vaccine by 2015 that would be 50% effective and last longer than one year and by 2025 developing one that would be more than 80% effective and last for longer than four years.7

 

Local and Global cases or outbreaks (w/ incidence figures):

Malaria used to be a lot more prevalent in the United States, but it was eradicated virtually completely by 1949.1 In 2000 there were 1,402 cases reported in the U.S., with most of them being from people who had recently traveled to countries where malaria is still endemic.6 Conversely, world-wide in 2003 the WHO estimates that there were 350-500 million new cases of malaria.6

 

References:

1. Centers for Disease Control and Prevention. Malaria. 6/30/09. http://www.cdc.gov/malaria/ (12/6/09).

 

2. Rich SM, Leendertz FH, Xu G, et al. “The Origin of Malignant Malaria” Proc Natl Acad Sci USA. 2009 Sep 1:106(35:14902. Pub Med. http://www.ncbi.nlm.nih.gov/pubmed/ (12/6/09).

 

3. McGraw Hill. Life Cycle of Plasmodium. http://highered.mcgraw-hill.com/olc/dl/120090/bio44.swf (12/6/09) *note, to open video, past link into search engine and follow link from there.

 

4. Tortora, G; Funke, B; Case, C. Microbiology: An Introduction. 10th ed. Benjamin Cummings. San Francisco: 2010

.

5. Reiter, Paul. “From Shakespeare to Defoe: Malaria in England in the Little Ice Age.” CDC: Emerging Infections Diseases. 2000. Jan-Feb Vol 6 No 1.  http://www.cdc.gov/ncidod/EID/vol6no1/reiter.htm (12/6/09).

 

6. World Health Organization. Malaria. 2009. http://apps.who.int/malaria/faq.html (12/6/09).

 

7. Malaria Vaccine Initiative. Accelerating Malaria Vaccine Development. 2009. http://www.malariavaccine.org (12/6/09).