**1. Introduction**

Malaria is a prevalent infectious disease, affecting about 150 million people globally and responsible for around 4, 45,000 deaths annually [1]. Geographically, it is prevalent in 106 countries of the tropical and semitropical world. Africa accounts for 80% of total malaria cases and 90% global death. Malaria is caused by the apicomplexan protozoa *Plasmodium* genus which is transmitted from one to another through bitting by female *Anopheles mosquito* [2]. Five species are known to cause malaria fever in human *i.e. P. vivax*, *P. falciparum*, *P.ovale, P. malariae* and *P. knowelsi* [3, 4].

Among all plasmodium species, *P. vivax* is prevalent in central and South America, Asia [5]. *P. ovale* infections are rare and occur only in Africa i.e. <0.5% [6] *P. malariae* is present at the globe irregularly. *P. falciparum* is most fatal, because it produces large progeny in a short time and has the ability to cause cerebral malaria which is a severe complication and leads to death of the patient. Malaria has been a long-term health issue in world. In earlier 1960s to 1980s incidence of malaria prevalence have been highest, but now, there are several effort and projects handle by the international government to reverse malaria burden. Chemotherapy against the malaria parasite had been a vital component. However, resistance to existing

medicines is always a risk. Consequently, all treatments must be combinations of two or more active ingredients such that no compound is exposed as a monotherapy to high levels of parasites for a significant period of time wherever possible [7]. Artemisinin-based and nonartemisinin based combination with partner drug has been approved. This chapter will provides an overview of malaria, focusing on progress in drug discovery efforts, clinical development and the future highlight of malaria eradication agenda.

#### **1.1 Malaria pathogenesis**

Symptoms of malaria arose from hemozoin that released after rupture of infected RBCs. Hemozoin cause inflammation and take part in the immunogenic action in the blood which activates pro-inflammatory and anti-inflammatory cytokines [8]. Some studies have shown that IL-1B, IL-6, IL-8, and TNF-alpha increased in late-onset severe disease [9, 10]. Pathogenic phase of malaria is outcome of secreted cytokines tumor necrosis factor (TNF-α), interferon-γ (INF-γ), IL-6, IL-8, from macrophage and endothelial, and elevated level of as superoxide and nitric oxide (NO) [11]. These increased factor play role in dys-erythropoietic anemia, TNF-α may contribute to cerebral malaria through up-regulation of intracellular adhesion molecule-1 (ICAM-1) in cerebral blood vessel endothelium [12]. Pro-inflammatory cytokine induce cytokinemia and fever through interacting intracellularly with Toll-like receptor-9 (**Figure 1**), which lead to release of proinflammatory cytokines that can induce COX-2 up regulating prostaglandins [13, 14].

### **2. Diagnosis**

Diagnosis of malaria infection in a patient is of critical importance since symptoms of complicated malaria may develop suddenly, causing the death of the patient. Clinical diagnosis based on the patient's symptoms and on physical findings at examination

*Recent Advances in Antimalarial Drug Discovery: Challenges and Opportunities DOI: http://dx.doi.org/10.5772/intechopen.97401*

