Many cancers are associated with infections (for example cervical cancer is linked to the human papilloma virus) but there is no stronger link between a human malignancy and a parasitic infection than that between cancer of the bile ducts and a liver fluke called Opisthorchis viverrini.
Scientists at The Queensland Institute of Medical Research (QIMR), with colleagues in Thailand and the USA, have now commenced a major international study to identify the mechanisms by which the liver fluke causes cancer of the bile ducts (also known as cholangiocarcinoma – CCA).
“Throughout East Asia there is a strikingly high prevalence of CCA in regions where the human liver fluke is endemic. CCA is extremely prevalent in Northeast Thailand, areas where uncooked cyprinoid fish are a staple of the diet. In Northeast Thailand and Laos, an estimated 6 million people are infected with Opisthorchis viverrini, and despite widespread drug treatment that has been implemented in the past, the prevalence of O. viverrini in some endemic areas approaches 70%”, said Dr Alex Loukas of the Helminth Biology Laboratory at QIMR.
“Moreover, in Thailand, liver cancer is the most prevalent of the fatal cancers, and rates of CCA in regions where the parasite is endemic are unprecedented.”
By way of comparison, CCA is responsible for about 24% of liver cancers in the U.S. compared with 87% in Khon Kaen, Thailand. The QIMR study will explore the genes of the parasite and characterise proteins secreted into the bile ducts to understand how chronic infection can lead to tumour formation. The group will also identify potential markers of the risk of developing heavy infection with the parasite and subsequent progression to CCA, information that will advance our understanding of the molecular pathogenesis of this disease and, moreover, to guide public health policies for control of liver fluke-associated CCA.
QIMR is also part of an international research consortium (funded by the Bill and Melinda Gates Foundation) the Human Hookworm Vaccine Initiative which will develop a vaccine against human hookworm infection. The group is developing recombinant vaccines against this blood-feeding nematode, a roundworm that infects 740 million people throughout the developing world.
“Hookworms have a voracious appetite for blood, and heavy infections result in anaemia. Such heavy blood loss is disastrous in infants and children and can cause physical and mental retardation,” said Dr Loukas. “Our recombinant vaccines will kill the larval stage of the worm, interfering with its ability to penetrate skin and establish an infection.”
The QIMR researchers are primarily responsible for developing the second component of what is envisaged to be a bivalent vaccine containing two proteins. The second protein is a haemoglobinase, an enzyme used by the parasite to digest host blood. Preliminary studies indicate that a vaccine based on the haemoglobinase enzyme interrupts the blood-feeding process of the hookworm, causing them to starve to death.