Using reverse genetics to elucidate the role of sporozoite specific proteins S14 and SCOT1 in Plasmodium

Abstract

The earliest account found in the literature for malaria was made by Hippocrates in ancient Greece. He made an observation that places around marshes or stagnant water had a higher prevalence of the disease. The Romans also made similar observations, and the word malaria derives from the Latin words mal aria which translates to bad air (Oaks S.C Jr 1991). These early observations drove several futile efforts to isolate the causative agent from the soil and water samples from malaria-endemic areas. In 1897 a British military doctor, Ronald Ross who was working in India, was able to decipher that the parasite was transmitted to the invertebrate host by the mosquito vector. Ross made his groundbreaking discovery using the avian malaria model. He was closely followed by Italians, Giovani Battista Grassi, Amico Bignami and Guiseppe Bastianelli. Malaria has been the scourge of the tropics for millennia and was most likely present in the earliest human populations (Brier, 2004). Studies of ancient Egyptian mummified human remains led to the identification of specimens with porotic hyperostosis (cranial thickening which is indicative of severe anemia) and splenomegaly (enlarged spleen), common symptoms of malaria (Brier, 2004). The advancement in the feild of molecular biology, investigators were able to establish that Tutankhamun (c. 1333-1324 BC) suffered from malaria but were unsure that it was the cause of his death (Hawass et al., 2010, Timmann & Meyer, 2010). It is believed that malaria was spread along the shipping routes from Africa to South East Asia, India, China, and to Europe. Written accounts of malaria are found from ancient Greece and Rome by Hypocrates (460 – 370 BC) and Celsus (25 BC – 54 AD) respectively. Romans were the first to name the disease ‘mal aria’ meaning ‘bad air’, they believed the disease spread due to the noxious air of Roman marshlands. Active measures such as draining marshlands correlated to reduction of malaria episodes adding validation to their hypothesis. It took over 2 millennia in uncovering the real cause responsible for the disease. Although several theories were put forward since the fall of the Roman Empire, few major scientific breakthroughs were made regarding malaria until 1880, when a French clinician named Alfonse Laveran working in Algeria noted the presence of Review of Literature & Introduction 2 black pigment in the spleen and brain of his patients that died of malaria. He consequently studied the blood of malaria patients until finally witnessing the exflagellation of a gametocyte leading to the confirmation for parasitic origin of the disease (Garnham, 1966). This particular observation was called ‘filariae of the blood’ until its classification as genus Plasmodium. The identification of the parasite sparked interest in the mechanism of transmission and vector involved. Despite suspicion throughout history by physicians throughout the world direct evidence linking malaria to mosquitos was not available. In the year 1897 Surgeon-Major Ronald Ross and Dr. Patrick Manson were able to identify malarial parasite in midguts of Anopheles mosquitos in after feeding on a malaria patients. Other mosquito types fed on patients lacked the parasite. They observed ‘germinal rods’ (sporozoites) in infected mosquito salivary glands which led them to the conclusion that parasite transfer occurs via mosquito bite (Ross & Smyth, 1897). Ross successfully demonstrated transmission from insect to host in birds but evidence of mosquito to man transmission came in 1899 by Bignami and Grassi. They were able to follow the parasite’s lifecycle to completion and their experiments were repeated and confirmed by Dr. Patrick Manson in London a year later (Grassi & Noe, 1900, Manson, 1900). Since then, malaria control has focused on insecticides for destroying vector breeding grounds, mosquito nets and repellents. Using these measures has resulted in a reduction of malaria incidents in the developing world and eliminated malaria from much of the developed world where countries boast the infrastructure and capital to effectively control the spread of disease. Several advancements in research methodology such as in vitro culture of Plasmodium falciparum (Jensen & Trager, 1978), and the sequencing of the P. falciparum genome (Gardner et al., 2002) and development of various animal models have aided drug and vaccine research immensely. Despite all this, malaria persists and devastates the tropics to this day.