CHAPTER ONE 1.0 INTRODUCTION 1.1 Background of study Malaria is a mosquito-borne infectious disease affecting humans and other animals caused by parasitic protozoans (a group of single-celled microorganisms) belonging to the Plasmodium type (WHO, 2014). According to the World Health Organization (WHO), malaria is a significant public health problem in more than 100 countries and causes an estimated 200 million infections each year, with more than 500 thousand deaths annually. Over 90% of these deaths occur in sub-Saharan Africa, where the disease is estimated to kill one child every 30 seconds (WHO, 2011). In other areas of the world, malaria causes substantial morbidity, especially in the rural areas of some countries in Asia and South America. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases it can cause yellow skin, seizures, coma, or death (Caraballo, 2014). Symptoms usually begin ten to fifteen days after being bitten, If not properly treated, people may have recurrences of the disease months later. The disease is most commonly transmitted by an infected female Anopheles mosquito. The mosquito bite introduces the parasites from the mosquito’s saliva into a person’s blood (WHO, 2014). The parasites travel to the liver where they mature and reproduce. Five species of Plasmodium can infect and be spread by humans. (Caraballo, 2014). Most deaths are caused by Plasmodium falciparum. The role of oxidative stress during malaria infection is still unclear. Some authors suggest a protective role, whereas others claim a relation to the physiopathology of the disease (Sohail et al., 2007). However, recent studies suggest that the generation of reactive oxygen and nitrogen species (ROS and RNS) associated with oxidative stress, plays a crucial role in the development of systemic complications caused by malaria. Malaria infection induces the generation of hydroxyl radicals (OH•) in the liver, which most probably is the main reason for the induction of oxidative stress and apoptosis (Guha et al., 2006). Additionally, Atamna et al. (1993) observed that erythrocytes infected with P. falciparum produced OH• radicals and H2O2 about twice as much compared to normal erythrocytes. Higher level of this free radicals can lead to oxidative stress. Oxidative stress, termed as an imbalance between production and elimination of reactive oxygen species (ROS) leading to plural oxidative modifications of basic and regulatory processes, can be caused in different ways. Increased steady-state ROS levels can be promoted by drug metabolism, over-expression of ROS-producing enzymes, or ionizing radiation, as well as due to deficiency of antioxidant enzymes. The consequence of oxidative stress once it is high, it can cause damage to the brain, metabolic disorders affecting electron transport chain. Reactive oxygen species (ROS), generated by endogenous and exogenous sources, cause significant damage to macromolecules, including DNA (Salmon et al., 2004). Furthermore, Spermatozoa are highly vulnerable to oxidative attack because they lack significant antioxidant protection due to the limited volume and restricted distribution of cytoplasmic space in which to house an appropriate armoury of defensive enzymes. In particular, sperm membrane lipids are susceptible to oxidative stress because they abound in significant amounts of polyunsaturated fatty acids. Susceptibility to oxidative attack is further exacerbated by the fact that these cells actively generate reactive oxygen species (ROS) in order to drive the increase in tyrosine phosphorylation associated with sperm capacitation. However, this positive role for ROS is reversed when spermatozoa are stressed. Under these conditions, they default to an intrinsic apoptotic pathway characterised by mitochondrial ROS generation, loss of mitochondrial membrane potential, caspase activation, phosphatidylserine exposure and oxidative DNA damage. In responding to oxidative stress, spermatozoa only possess the first enzyme in the base excision repair pathway, 8-oxoguanine DNA glycosylase. This enzyme catalyses the formation of abasic sites, thereby destabilising the DNA backbone and generating strand breaks. Because oxidative damage to sperm DNA is associated with both miscarriage and developmental abnormalities in the offspring, strategies for the amelioration of such stress, including the development of effective antioxidant formulations, are becoming increasingly urgent (Aitken et at., 2016).