Systems Biology Approaches towards Immunity against *Plasmodium*

*Himangshu Patgiri, Ankita Khataniar, Pitimoni Boro, Sushmita Baishnab and Sanchaita Rajkhowa*

#### **Abstract**

Malaria is one of the most devastating infectious diseases known to humans. It is caused by unicellular protozoan parasites belonging to the genus *Plasmodium*. Till date, over 200 species of *Plasmodium* have been formally described, and each species infects a certain range of hosts. However, the human infection is limited to only five of the species, of which *P. falciparum* is the most responsible. Due to the emergence of parasite resistance to frontline chemotherapies and mosquito resistance to current insecticides which threaten the control programmes, new antimalarial therapeutics or approaches capable of predicting useful models of how different cells of the innate immune system function, is the need of the hour. Systems Immunology is a relatively recent discipline under Systems Biology to understand the structure and function of the immune system and how the components of the immune system work together as a whole. Thus, this chapter aims to give insight into the approaches of Systems Biology for investigating the immune factors that are formed during *Plasmodium falciparum* infection in the human body. Here, the numerous experimental and computational works with the ongoing methodologies using Systems Biology approaches along with the interactions of host and pathogen will be discussed.

**Keywords:** omics, *Plasmodium falciparum*, systems immunology, Systems Biology

### **1. Introduction**

*Plasmodium falciparum* is a protozoan parasite that causes malaria in humans and is transmitted through an insect vector, the female *Anopheles* mosquito. The species' malaria (also called malignant malaria or *falciparum* malaria) is the most deadly type of malaria with the highest incidence of complication and mortality rates. Malaria is a world-wide infectious illness that continues to be a leading source of morbidity and mortality in developing countries. Malaria is an ancient disease, with references to what was nearly actually a protozoan ailment believed to be malaria, appearing in a Chinese document from around 2700 BC, clay tablets from Mesopotamia from 2000 BC, Egyptian papyri from 1570 BC, and Hindu scriptures from the sixth century BC. For over 2500 years the thought that malaria fevers were caused by miasmas

rising from marshes for many years and it is usually believed that held that the word malaria comes from the Italian *mal'aria,* which spoiled air; however, this is controversial. The origins of the *Plasmodium* parasites infecting humans have long been a source of fascination. Ancient scriptures from China, India, the Middle East, Africa, and the European continent, contain descriptions of malaria-like illnesses indicating that humans have been fighting *Plasmodium* infections throughout our recorded history [1, 2]. Scientific studies were only possible after the discovery of the parasites themselves by Charles Louis Alphonse Laveran in 1880 and the incrimination of mosquitoes as vectors, first for avian malaria by Ronald Ross in 1897 and then for human malaria by Amico Bignami, Angelo Celli, Camillo Golgi, Ettore Marchiafava, Giovanni Battista Grassi and Giuseppe Bastianelli between 1898 and 1900.

Malaria is a world-wide infectious disease that continues to be a major cause of morbidity and mortality in developing countries. Malaria is found in more than 90 countries and affects over 40% of the world's population. Out of four species of malaria, *Plasmodium falciparum* is the lethal one. *P. falciparum* is responsible for more than 90% of the global malaria death and hence continues to be a major public health concern on a global scale. According to WHO, World Malaria report 2020, there are 241 million cases of malaria world-wide, resulting in 627,000 fatalities world-wide. In non-malarial nations such as North America and Europe, there are a considerable number of instances of imported malaria and local transmission following importation [2].

Variants in the human genome linked with resistance to *Plasmodium* infection and malaria-related illness are thought to be thousands of years old [3]. One long-held theory proposed that humans and chimpanzees both acquired *P. falciparum*-like infections from their common ancestor and that these parasites co-evolved for millions of years with their respective host species. *P. vivax,* on the other hand, is thought to have emerged hundreds of thousands of years ago, when the cross-species transmission of a parasite from a macaque occurred in South-eastern Asia [4, 5]. However, both of these notions have recently been debunked following the characterisation of a large number of new *Plasmodium* parasites from African apes. *P. falciparum* infection is now known to be relatively new for humans, having emerged after the acquisition of a parasite from a gorilla, most likely within the last 10,000 years [6, 7]. Characterisation of the numerous ape *Laverania* spp. discovered a parasite lineage in western gorillas with parasites that were nearly identical to *P. falciparum* [5, 7]. This was first misinterpreted that gorillas can be infected by human parasites [5]. However, after analysing the mtDNA sequences from significant numbers of additional wildliving gorillas, it was discovered that all extant *P. falciparum* strains from humans fall within the radius of these gorilla parasites [7]. *P. praefalciparum* is the name given to this gorilla parasite lineage to indicate its role in the origin of *P. falciparum*.

When compared to viruses and bacteria, eukaryotic protozoans present a larger genome and have a complex biology, which hinders the development of vaccines. Even though malaria is a curable disease, there are currently no established vaccines. Quinine and artemisinin, both extracted from the bark of the Peruvian Cinchona Succirubra tree and the Chinese herb *Artemisia annua*, are now the most potent antimalarials available. Artemisinin-based Combination Therapies (ACTs), which have just recently been accepted as a last option in the fight against malaria, are already being tested by ACT-resistant strains in Southeast Asia. With parasite resistance to all current antimalarial medications spreading, successful control and eradication will need the development of new tools and cost-effective antimalarial tactics [8]. The complex biology of *Plasmodium* poses a hindrance in the detailed understanding of

*Systems Biology Approaches towards Immunity against* Plasmodium *DOI: http://dx.doi.org/10.5772/intechopen.104614*

the mechanisms that control malarial infection, thus giving rise to technical challenges in the eradication of malaria. New approaches to elucidate key host–parasite interactions, and predict how the parasites will respond in various biological settings, could dramatically enhance the efficacy of intervention strategies [9]. Advances in the field of Systems Biology are well poised to meet these challenges.
