Survival story led to malaria vaccine quest

Malaria is not just an abstraction for Kenyan researcher Lucy Ochola. As an infant, she contracted malaria, and survived. She was lucky -- in the western highlands of her homeland, infant mortality from malaria approaches 30 per cent.

Ochola suffered several bouts of malaria as a child, but progressively developed immunity, and has been malaria-free since about age 10.

Today she is studying the epidemiology of malaria as a PhD student at the Kenyan Medical Research Institute (KMRI) in the coastal city of Kilifi, where falciparum malaria is endemic, severe and frequently lethal.

Ochola and fellow PhD student Francis Ndungu, in Australia with KMRI director Dr Kevin Marsh, are among 366 scientists, many of them from malaria-affected countries, at the world's most important malaria conference, Molecular Approaches to Malaria, which winds up today in Lorne, Victoria.

Conference organiser Dr Brendan Crabb, of the Walter and Eliza Hall Institute of Medical Research in Melbourne, said the conference had attracted 266 delegates from overseas, including US Army and Navy researchers.

Local experiences

Crabb said it was crucial that delegates from countries where malaria is endemic attend major research conferences on the disease. "There is so much to learn from the intense local experiences that together form the larger malaria scenario and research effort," he said.

"Malaria is a permanently unravelling human disaster. It kills at least 5000 people a day, every week, every month, year after year. The big number is at least two million a year, but what it really means is a promising human life cut off every 15 seconds.

"And that's only accounting for deaths. Every year, an additional 500 million people are infected and debilitated. That's about 10 per cent of humanity, so the scale of the problem is almost beyond imagination -- but we are making progress."

Ochola said there were two malaria seasons a year in Kilifi. "The worst is between January and August, but many children become severely ill during the short rainy season from the end of November to December," she said.

Malaria remains an enormous and intractable problem throughout sub-Saharan Africa. Most Kenyan children are infected in infancy by the most virulent form of the malaria parasite, Plasmodium falciparum. While very few children develop cerebral malaria, which is almost invariably fatal, many children die of severe anaemia because the fast-replicating parasite ruptures infected blood cells during severe bouts of parasitaemia.

Ochola's PhD research project aims to develop better diagnostic methods for malaria. She has spent long hours in intensive-care wards, using ELISA tests to track the evolution of parasitaemia in severely infected children, as the parasite transforms between its trophozoite and schizont forms.

She also commutes occasionally to the Swiss Tropical Institute in Basel, to compare her findings against with computer-based models of parasitaemia cycles.

Early-stage trophozoites are visible in blood smears, but late-stage trophozoites and schizonts are invisible -- Ochola is trying to develop techniques to visualize them under a microscope.

'Complex undertaking'

KMRI director Kevin Marsh said that, despite promising progress towards a vaccine, and new anti-malarial drugs, he does not share the optimism of those who suggest a vaccine may be near. "For years, people have been saying a vaccine is about five years away, but I would be staggered and delighted if that were the case," he said.

"I always say [it will be in] about 20 years' time. It's not because research is slow, or because of a lack of funds -- it's just an enormously complex undertaking, far more complicated than, say, developing a vaccine for breast cancer. "It's probably more difficult than developing a vaccine for HIV-AIDS, and people have been working on that for about two decades.

"Even if an effective vaccine was developed now, the normal timeline for trialling it, building a facility to produce it, and distributing it commercially to malaria-affected countries is be around 10 years.

"Most people in the field accept that the eventual vaccine will involve multiple antigens. The AMA-1 antigen identified by the Hall Institute is a real front-runner, but we're not yet at the stage of identifying all the right antigens."

Natural immunity

Marsh said KMRI malaria researchers were investigating how people develop natural immunity to the disease, identifying novel genetic polymorphisms that confer resistance, and studying the parasite's physiology, trying to identify new drug targets, or develop improved therapies around existing drugs.

In the Kenyan highlands, where malaria has been historically endemic, about 30 per cent of people carry the recessive polymorphism in the haemoglobin gene that causes sickle-cell anaemia. Heterozygotes are protected against malaria, but in the homozygous state, the condition is usually lethal. Down on the Kenyan coast, the frequency of the allele is around 15 per cent.

Many Kenyans carry other protective genes, like the thalassaemia and G6PD genes. One of the genetic puzzles associated with malaria is that most Kenyans have a blood type called Duffy negative, which confers resistance to Plasmodium vivax, a less virulent cousin of P. falciparum.

"It's difficult to see how this could have come about, because P. vivax is not a killing parasite," Marsh said. "Perhaps it was more virulent in the past, before P. falciparum became the dominant species."

Marsh said genetic studies had discovered a number of new, common polymorphisms in sub-Saharan populations that, given the extreme selection pressure applied by the parasite, are likely to be associated with natural resistance to malaria.