Plasmodium Falciparum Control Strategies

Plasmodium Falcuparum Control Strategies

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Introduction

Malaria is a deadly disease and is estimated to be endemic in over 100 different countries [1]. It is caused by a protozoan parasite of the genus Plasmodium that lives in blood. There are over 200 different Plasmodium species, but only 11 known types actually infect humans. Of the different species, Plasmodium falciparum is the most dangerous to humans, because it has very high mortality rates [2].

The main vector for the spread of the Plasmodium falciparum parasite is mosquitoes. There are many types of mosquitoes , but only some of them suck blood, and only some species are malaria transmitters. The species Anopheles gambiae is one of the most efficient malaria vectors known. More information on the spread of malaria is available at http://microbewiki.kenyon.edu/index.php/Malaria_(Plasmodium_falciparum)_in_sub-Saharan_Africa

Because of the danger that malaria spread poses to so much of the world's population, there have been many approaches to controlling the spread of the disease. Unfortunately, there are no effective vaccines for malaria, although there are drugs which have been used to effectively treat the illness. Since it is not possible to simply immunize at-risk individuals, the focus of malaria prevention is on the vector which spreads it, Anopheles gambiae.[citation]

"As a protist, the plasmodium is a eukaryote of the phylum Apicomplexa. Unusual characteristics of this organism in comparison to general eukaryotes include the rhoptry, micronemes, and polar rings near the apical end. The plasmodium is known best for the infection it causes, malaria."

File:AnophelesGambiaemosquito.jpg.png

"This image of an Anopheles gambiae mosquitois a work of the Centers for Disease Control and Prevention, part of the United States Department of Health and Human Services, taken or made during the course of an employee's official duties."

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Plasmodium Falciparum Infection and Life Cycle

Plasmodium falciparum first enters the bloodstream of a human when it is released from the salivary glands of an Anopheles gambiae mosquito as a sporozoite. They make their way to the liver, where they infect liver cells and multiply. They are then released into the bloodstream as merozoites, where they can infect red blood cells and reproduce asexually.

File:AnophelesGambiaemosquito.jpg.png

"This image of an Anopheles gambiae mosquitois a work of the Centers for Disease Control and Prevention, part of the United States Department of Health and Human Services, taken or made during the course of an employee's official duties."

The reason for the difficulty in immunizing people against malaria is found in the sequencing of Plasmodium Falciparum genome. Gardner et al. analyzed the sequences in 2002, and compared the Plasmodium Falciparum genome to those of other free-living eukaryotic microbes. They found that the genome encodes fewer enzymes and transporters, but that it encodes a high proportion of genes dedicated to evading immune responses and host-parasite interactions [3].

File:File:Plasmodium falciparum 02.jpg

"Bloodsmear of a P.falciparum culture (K1 strain). Ring stages, Schizont in the lower center, Trophozoite on the left."

Anopheles Gambiae Immune Response

One approach to malaria control that has been studied has been that of using the mosquito immune response as a defense mechanism against malaria.

Tahar et al. found that when Plasmodium falciparum enters a mosquito, there is a systematic immune response [4]. The genes, NOS, defensin and GNBP, are regulated by the presence of gametocytes, the infectious stage of the parasite.

Meister et al. study the structure and function of transmembrane PGN Recognition Protein LC, which is a receptor of a signaling pathway which affects the proliferation of microbes in mosquito guts [5]. Their goal is to show how the PGRP-LC can regulate immune responses of mosquitoes against both Plasmodium falciparum, which infects humans, and Plasmodium berghei, which can infect rodents. They demonstrate that the connection between the defense mechanism regulated by PGRP-LC and the bacterial communities in mosquitoes can be used to control malaria transmission.

Bacterial Regulation of Plasmodium Falciparum

Boisierre et al. study the effect of environmental factors, in tangent with natural mosquito immune response, against Plasmodium falciparum infections [6]. Their goal is to determine what impacts the success or lack thereof of parasite transmission by Anopheles gambiae. Through analysis of bacterial flora in the guts of Anopheles gambiae they show that the types of microbial life present are a result of the mosquito breeding sites. In addition, the presence of Enterobacteriaceae is highly correlated with the success of Plasmodium falciparum.

Dong et al. analyze infection rates of Plasmodium falciparum in the Anopheles gambiae, a type of mosquito well known for transmitting malaria [7]. Their goal is to better understand how microbial flora can regulate the development and transmission of malaria. They find that there are large differences between septic and aseptic mosquitos, because of the varying amounts of microbial flora that grows in their guts. The microbes help to create immunce cells including anti-Plasmodium factors which may inhibit the development of Plasmodium falciparum.

Jin et al. seek a viable approach to malaria control, and do so by focusing on the Wolbachia pipientis bacteria, which can affect the development of malaria, as well as affect the mosquito population itself [8]. The Wolbachia pipientis bacteria do not infect Anopheles gambiae, which are the main transmitters of malaria, in nature. The authors introduce the bacteria experimentally to the Anopheles gambiae mosquitoes. They find that virulent strains of the bacteria can survive and replicate when injected into a mosquito, demonstrating that viable infections are possible.

Conclusion

Malaria is a persistent and dangerous infectious disease. By studying the most influential strain, Plasmodium falciparum, researchers have been able to better understand the mechanism of spread through Anopheles gambiae, and discover new possible approaches for malaria control.

References

[1] http://www.kff.org/globalhealth/upload/7882-04.pdf [2] Perlmann, P., and M. Troye-Blomberg. "Malaria blood-stage infection and its control by the immune system." Folia biologica 46.6 (2000): 210. [3] Gardner, Malcolm J., et al. "Genome sequence of the human malaria parasite Plasmodium falciparum." Nature 419.6906 (2002): 498-511. [4] Tahar, Rachida, et al. "Immune response of Anopheles gambiae to the early sporogonic stages of the human malaria parasite Plasmodium falciparum." The EMBO journal 21.24 (2002): 6673-6680. [5] Meister, Stephan, et al. "Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites." PLoS pathogens 5.8 (2009): e1000542. [6] Boissière, Anne, et al. "Midgut microbiota of the malaria mosquito vector Anopheles gambiae and interactions with Plasmodium falciparum infection." PLoS Pathogens 8.5 (2012): e1002742. [7] Dong, Yuemei, Fabio Manfredini, and George Dimopoulos. "Implication of the mosquito midgut microbiota in the defense against malaria parasites." PLoS pathogens 5.5 (2009): e1000423. [8] Jin, Chaoyang, Xiaoxia Ren, and Jason L. Rasgon. "The virulent Wolbachia strain wMelPop efficiently establishes somatic infections in the malaria vector Anopheles gambiae." Applied and environmental microbiology 75.10 (2009): 3373-3376.

Edited by Lydia de Pillis-Lindheim, a student of Nora Sullivan in BIOL187S (Microbial Life) in The Keck Science Department of the Claremont Colleges Spring 2013.