Singapore scientists develop novel immunisation method for malaria

Channel NewsAsia 30 Jul 09;

SINGAPORE: Scientists in Singapore, the Netherlands and France have developed a novel immunisation method that could lead to the development of a vaccine for malaria.

The findings of Associate Professor Laurent Renia from A*Star and his counterparts were published in the prestigious New England Journal of Medicine.

Their approach involved exposing two groups of healthy human subjects to mosquitoes once a month over a three-month period.

They exposed one group to mosquitoes infected with the malaria parasite and the other group to uninfected mosquitoes.

During the period of exposure, the human subjects were administered with chloroquine - an anti-malaria drug that prevented the malaria parasite - P. Falciparum - from multiplying in the blood.

After eight weeks of immunisation and four weeks after the discontinuation of chloroquine administration, both groups were re-exposed to infected mosquitoes.

The scientists found that those in the vaccine group had acquired complete protection against the malaria parasite.

This unique method of immunisation allowed the human immune system to direct its response to destroy the malaria parasite at an earlier stage.

Currently, methods include the use of genetically inactivated parasites or parasites that have been weakened by radiation to induce anti-malaria immunity. This has only succeeded in inducing up to 50 per cent protection in humans.

The disease infects about 350 million to 500 million people worldwide and kills over 1 million people a year. - CNA/vm

Malaria breakthrough
Today Online 31 Jul 09;

THE search for an anti-malaria vaccine has been given a boost after a group of scientists succeeded in developing a novel immunisation method that will induce fast and effective protection against the mosquito-borne disease.

The breakthrough in malaria research was made by Associate Professor Laurent Renia from A*Star's Singapore Immunology Network (Sign) and his counterparts in the Netherlands and France.

In the study, scientists exposed two groups of healthy humans to mosquitoes once a month over a three-month period. The "vaccine group" was exposed to mosquitoes infected with the malaria parasite, plasmodium falciparum, while the "control group" was exposed to uninfected mosquitoes. Participants were also given chloroquine, an anti-malaria drug.

Eight weeks after the last round of immunisation and four weeks after the discontinuation of chloroquine administration, the subjects from both groups were re-exposed to infected mosquitoes and tested for protection against plasmodium falciparum. The scientists found that those in the vaccine group had acquired complete protection against the parasite while those in the control group developed parasitemia, a condition where parasites are found in the blood.

The study indicated that this method of immunisation allowed the human system to direct its response to eliminating the plasmodium falciparum parasite at the earlier stage of its life cycle, as chloroquine would kill it at the later stage.

Assoc Prof Renia, principal investigator at Sign, said it is not practical to apply the experimental method used in the study as a means of vaccination. "But, this method of immunisation could be applied successfully to similar investigations to find biological markers which would indicate the extent of protection against malaria," he said.

Meanwhile, a third malaria cluster, involving four cases of suspected local transmission of vivax malaria near a row of shophouses located at the junction of Sembawang Road and Admiralty Road East, has been identified this week. But the latest cluster is not related to the two earlier clusters, according to the Ministry of Health.

Mosquito bites may be key to better vaccines
Grace Chua, Straits Times 31 Jul 09;

IN AN unorthodox experiment, scientists from the Netherlands, France and Singapore deliberately infected people with the parasite that causes malaria - by subjecting them to about 40 bites from infected mosquitoes.

As hoped, the scientists were able to inoculate the volunteers against the disease. Though this approach is not a practical solution, it paves the way for developing more effective malaria vaccines.

Most people infected with the plasmodium falciparum malaria parasite suffer debilitating fever and anaemia, and may even die from the illness. But some who contract the disease several times over many years can develop natural immunity to it.

To mimic the infection-and-immunity cycle, the researchers allowed infected mosquitoes to bite 10 healthy medical students in three rounds over three months. Five others in a control group were bitten by uninfected mosquitoes.

All were protected with the drug chloroquine, which kills malaria parasites in the bloodstream.

When the volunteers ceased taking the drug, all 15 were subjected to infected-mosquito bites. None of the 10 in the vaccination group developed malaria, while all five in the control group did.

Those who got sick were given outpatient care and recovered.

While vaccination by mosquito bite is nearly impossible to carry out, Dr Laurent Renia - an immunologist with the Agency for Science, Technology and Research's Singapore Immunology Network and one of the scientists on the project - said the project 'will help us understand how immunity develops, and use that mechanism to make a vaccine'.

Their work was published in the prestigious New England Journal of Medicine yesterday.

Other groups are currently studying vaccines based on weakened forms of the malaria parasite, or on parts or molecules from the parasite.

'Malaria vaccines are moving from the laboratory into the real world,' wrote Dr Carlos Campbell in an editorial in the same journal.

Dr Campbell - who directs a malaria programme at the Programme for Appropriate Technology in Health, a health foundation in the United States - also noted that vaccines would be part of a multi-pronged malaria-control approach that includes insecticide-treated bed nets and mosquito-control measures.

Malaria kills almost a million people each year, mostly children and in Africa. Commercially, no vaccines exist, and the parasite is also showing signs of resistance to more drugs.

Dr Renia also noted that the study was done on the more severe plasmodium falciparum strain of malaria, which kills more people and is predominantly in Africa.

In malaria cases here, the milder plasmodium vivax strain is predominant.

'The same strategy could work on vivax, but it would have to be tested,' he said.

Malaria resisting S-E Asia's best drugs
Study uncovers a delay in clearing parasites, which could be disastrous
Straits Times 31 Jul 09;

BANGKOK: Malaria is becoming resistant to the most powerful drugs available in South-east Asia, as the World Health Organisation (WHO) races to stop the spread of the strain that could be disastrous for global malaria control.

Treatments derived from artemisinin, the basis of the most effective anti-malaria drugs, took almost twice as long to clear the parasites that cause the disease in patients in western Cambodia, as in patients in north-western Thailand, according to a study published in the New England Journal of Medicine yesterday.

The delay in parasite clearance times shows that the drugs are losing their effectiveness against the disease in Cambodia, the study said.

The failure of artemisinin-based treatments would be disastrous for global efforts aimed at curbing the death and disease wrought by the malady, said Dr Arjen Dondorp, who led the study at the Mahidol Oxford Research Unit in Bangkok.

'There is no question that this is resistant to artemisinin,' Dr Carlos Campbell, a malaria expert with the Seattle-based Programme for Appropriate Technology in Health, or Path, wrote in an editorial accompanying the study.

'History warns us that it will intensify and spread unless containment steps are taken,' he added.

Scientists have known for decades that Pailin, a city near Cambodia's border with Thailand, is a breeding ground for drug-resistant malaria.

Malaria medications chloroquine and fansidar started to fail there in the 1950s and 1960s, before becoming ineffective elsewhere, according to the study.

Since the study was completed, delayed parasite clearance times have been observed in southern Cambodia, a sign that the resistant strain has already spread within the country, Dr Dondorp said.

He and his colleagues treated 40 people in Pailin and another 40 in Wang Pha in Thailand, with artesunate, a form of artemisinin, which is derived from a herb.

After three days, artesunate failed to clear the parasite in 55per cent of patients in Pailin, compared with 8per cent in Wang Pha.

Widespread artemisinin resistance 'would cause millions of deaths, without exaggeration', Dr Dondorp said in an interview in January.

Malaria strikes about 250million people each year and kills more than 880,000, mostly children under five, according to the WHO.

It is among the world's most destructive infectious diseases after Aids, which kills about two million people each year.

Symptoms include fever, chills, nausea and diarrhoea. Without treatment, sufferers can die of organ failure.

In Singapore, researchers said that the predominant strain of malaria - plasmodium vivax - was still treatable with different drugs such as chloroquine.

However, cases of the more serious Plasmodium falciparum strain - which have yet to surface in Asia - show signs of multi-drug resistance.

Dr Laurent Renia, a researcher at the Singapore Immunology Network, under the Agency for Science, Technology and Research, said: 'What is being seen (in Thailand and Cambodia) is not clear resistance, where drugs cannot eliminate the parasite, but signs - meaning that where it took two days to eliminate the parasite, it's now taking three, four days.

'Why is this worrying? Artemisinin is the last drug we have. Thailand and Cambodia are in the region. People travelling there could get infected and bring back a resistant strain.'

BLOOMBERG

Additional reporting by Grace Chua in Singapore

28 infected in Singapore since May
Straits Times 31 Jul 09;

SINGAPORE is seeing its worst malaria outbreak in years, with 28 people infected locally since early May.

The victims were living at, or had recently visited, one of three areas: Mandai/Sungei Kadut, Jurong Island or Sembawang.

The majority of those infected were foreign workers living in dormitories.

The National Environment Agency has been actively fogging and trapping mosquitoes at these sites in an attempt to contain the spread of the disease.

Singapore has been declared malaria-free since 1982, although it still sees between 100 and 300 cases a year. This is because the vast majority are people who contracted the disease overseas.

The last big outbreak was in 2006, when 13 people were infected locally.

SALMA KHALIK