Autophagic events during Plasmodium infection of hepatocytes

Malaria is a widespread vector-borne infectious disease that has grieved people for thousands of years and currently continues to be a major public health concern. The finding of parasites inside preserved mosquitoes from the Paleocene period is evidence of the long relationship between haemosporidia and animals (Poinar, 2005). One of the first documented descriptions of malaria comes from the second century BC (Cox, 2010). Chinese medical writings mention symptoms corresponding to the disease which later on got the name of malaria. Malaria is derived from the Medieval Italian words ‘mala’ and ‘aria’, which means bad and air, respectively. The idea that the disease came from the spoiled gasses released from the ground persisted throughout the nineteenth century. It was not until 1889, that Charles Louis Alphonse Laveran noticed a black pigment in the blood of people suffering from fever (Cox, 2010). He attributed this pigment to malaria and went on to describe the morphological changes of the malaria parasites during their blood cycle. He proposed the involvement of a mosquito in the transmission of the parasite. Such hypothesis was later proven by Ronald Ross who demonstrated with his studies pertaining to avian malaria that these parasites were indeed transmitted via the bite of infected mosquitoes (Cox, 2010). Shortly after, Batista Grassi and colleagues demonstrated that Ross’ findings about avian malaria transmission also applied to human malaria and introduced the genus Plasmodium and the species Plasmodium vivax and Plasmodium malariae. Grassi’s group also discovered that Anopheles mosquitoes were the species responsible for malaria transmission. Later on, William H. Welch named the parasite responsible for the most severe form of malaria, Plasmodium falciparum. In 1922, Watson Stephens described the fourth human malaria parasite, Plasmodium ovale. It was until 1947 that Henry Shortt and Cyril Garnham noted the hepatic phase of the infection in monkeys, confirming the findings afterwards with liver biopsies of infected volunteers with P. vivax. Subsequently, Krotoski established the persistence of liver stages in P. vivax and P. ovale. A fifth species named P. knowlesi, responsible to cause a zoonotic infection, is now recognized as an additional causal agent of human malaria since the first case of a natural infection described in 1965 (Jongwutiwes, 2004).