>PUBLICATION The Toronto Star > *> > DATE Friday October 4, 2002 > > > SECTION/CATEGORY LIFE > > > PAGE F05 > > > BYLINE Peter Calamai > > > > > > HEADLINE: Scientists close in on a mass murderer; Genome map a big advance but, for now, malaria is still best fought with bednets > > > > > > Peter Calamai > > > > > > Malaria is part of daily life for most of Tanzania's 35 million > > > residents. Every year roughly half the population suffers from > the > > > chills and fevers of the disease and about 100,000 die from > > > it. > > > > > > Most of the deaths are children under five, so it is rare for > the > > > extended families of the East African country not to say > > > goodbye > to > > > at least one young brother, sister or cousin in a typical > > > year. > > > > > > "It's a normal part of their lives to lose a child to malaria. > It > has > > > a real impact but it's always been like that so it's > > > accepted," > says > > >** Graham Reid, a British tropical medicine expert who manages a > > > Canadian-financed health project in two rural districts of > Tanzania. > > > > > > In some parts of the country- such as along the picture postcard > > > Tanzania coast of azure water, swaying palms and white sand > beaches- > > > people may be bitten as many as 1,000 times a year by infected > > > mosquitoes. Myths and poverty have kept many victims from > seeking > > > treatment at rural health clinics, which often struggle with > staffing > > > and supplies. > > > > > > Malaria scythes a similarly deadly path across much of Africa, > > > sparing only higher elevation areas that aren't hot enough or > > > countries like South Africa and Zimbabwe, where it has been > brought > > > under control. > > > > > > The continent's annual malaria death toll is well over a > > > million > and > > > could be as high as two million, with children five and under > making > > > up 90 per cent. > > > > > > So you might expect people like Graham Reid to be very excited > about > > > the multi-million-dollar deciphering of the genetic codes for > the > > > most prevalent malaria mosquito and the deadliest malaria > parasite, > > > dual breakthroughs announced this week by huge teams involving > 160 > > > researchers in 10 countries. Experts generally agree that > > > these > gene > > > catalogues should accelerate development of affordable malaria > > > vaccines, improved drugs to treat the disease, more effective > > > chemicals to repel the biting mosquitoes and a range of > techniques > to > > > neutralize mosquitoes that carry the parasite, including > designer > > > insecticides. > > > > > > Instead Graham is thinking about $3 bednets and how many lives > these > > > could save while the malaria genome breakthroughs struggle > through > an > > > expected decade-long development process before producing the > > > promised new anti-malaria weapons. > > > > > > Hung from the ceiling (or a tree branch) these mesh nets > > > spread > wide > > > at the base to cover an entire bed, perhaps one holding several > > > family members. The bednets are impregnated with a pyrethroid > > > insecticide that repels the night-biting Anopheles gambiae, the > > > primary mosquito species transmitting the malaria parasite in > humans. > > > > > > Marketed under brand names like "Sweet Dreams," the bednets are > > > produced in three Tanzanian factories and sold along with a > packet > of > > > the insecticide for renewing the coating. The mosquito-repelling > > > effect extends up to 500 metres in all directions, so even > neighbours > > > without bednets can benefit. > > > > > > "To a large extent the malaria problem can be dealt with by the > > > interventions we have now, like bednets. The challenge is to > help > the > > > health care system deliver even these measures. Then it might be > > > ready when the new drugs and vaccines come along," said Reid > > > in > a > > > telephone interview from Dar es Salaam, Tanzania's chief city. > > > > > > The experimental project managed by Reid since 1996 has > demonstrated > > > that health care services can be delivered far more > > > efficiently > in > > > rural areas of Tanzania at only marginally greater cost. The > > > key > to > > > success is aligning the spending with the burden that each > disease > > > imposes on the population. > > > > > > Before the establishment of the Tanzania Essential Health > > > Interventions Project (TEHIP), for example, malaria received 5 > per > > > cent of the health budget in the Morogoro district. Health > planners > > > simply didn't have an accurate picture of the disease's impact, > > > largely because the child malaria victims mostly die at home and > > > aren't picked up by the country's rudimentary vital > > > statistics. > > > > > > TEHIP's researchers began going door-to-door in Morogoro three > times > > > a year asking about sickness and deaths. They found that malaria > > > actually accounted for 30 per cent of the lives lost in the > district. > > > On the other hand, tuberculosis which was getting 22 per cent > > > of > the > > > budget, accounted for only 4 per cent of the total health > burden. > > > > > > Spending a dollar more per person annually was enough to > > > realign > the > > > district's health resources. > > > > > > Strengthening national health delivery systems in Africa is > obviously > > > essential to bringing malaria under control. A bigger issue is > the > > > low priority that research into malaria prevention and > > > treatment > has > > > been getting until very recently in the developed world, even > though > > > the disease ranks with AIDS and tuberculosis as the Big Three > killers > > > of the world's poor. > > > > > > Jeffrey Sachs, a development economist at New York's Columbia > > > University, points out that Western nations stopped supporting > > > malaria prevention programs in the 1980s after deciding that a > global > > > eradication attempt over the previous three decades had failed > in > > > sub-Saharan Africa. In fact, the eradication campaign largely > skirted > > > Africa to successfully concentrate on the subtropics where the > > > intensity of transmission is much lower (a score of bites a year > > > rather than hundreds). > > > > > > Throughout the 1990s, the World Bank did not make a single > > > loan > for > a > > > malaria control program in sub-Saharan Africa, despite numerous > > > requests. And the death rates soared, says Dr. Kevin Kain, a > > > University of Toronto expert in infectious diseases. > > > > > > "We're looking at the equivalent of 10 jumbo jets full of > children > > > crashing every day with all lives lost. But it hasn't caused the > > > death of children in our backyard. It's happening in someone > else's > > > backyard. It's happening in Africa," says Kain. > > > > > > So low a priority is malaria compared to AIDS and other > > > diseases > with > > > better publicity machines that there is no accurate worldwide > data > on > > > current donor spending for prevention and treatment programs. > The > > > best estimate is somewhere between $100 million and $200 > > > million > a > > > year, for a disease causing between two and three million deaths > > > annually. > > > > > > Contrast that to the nearly $1 billion earmarked in the > > > current > U.S. > > > budget alone for bioterrorism research at the National > Institutes > of > > > Health (money diverted from other NIH programs). Five > > > Americans > died > > > from the only recent instances of bioterrorism, in the form of > > > anthrax-laced letters that may well have been sent by a fellow > > > American. > > > > > > Another indication of the world's benign neglect of those > threatened > > > by malaria is the inaction of pharmaceutical companies, > > > usually > eager > > > to showcase their contributions to bettering the human > condition. > > > Only three of the more than 1,200 new drugs registered in North > > > America between 1975 and 1996 were antimalarials, according to > > > a > news > > > article in this week's issue of Nature, the British science > journal > > > which also published the research findings about the malaria > parasite > > > genome. > > > > > > A few new drugs have reached the stage of clinical trials but > they > > > largely come from the same families of chemical compounds- > quinolines > > > and antifolates- that are already being rendered ineffective by > > > resistance in the most deadly parasite, Plasmodium falciparum. > > > > > > More than half the malaria parasites in Africa and southeast > Asia > are > > > now resistant to chloroquine, the low-cost drug long used as the > > > primary treatment. And mosquitoes are increasingly resistant > > > to > DDT, > > > the insecticide of choice in poor countries. > > > > > > As well, scientists fear that global warming could allow > resistant > > > mosquitoes and parasites to move into areas where malaria has > been > > > unknown for more than half a century, such as southern Europe > and > the > > > American South. > > > > > > Only last week malarial mosquitoes were discovered along the > Potomac > > > River outside Washington D.C. Two teenagers from nearby > > > Maryland > are > > > recovering from a relatively milder form of malaria this > > > summer > after > > > bites from local mosquitoes. > > > > > > In 1997, a Toronto woman contracted the same mild strain of > malaria > > > from a local mosquito, the first such case for about a > > > century. > In > > > the 1800s, however, malaria was widespread in southern Ontario > and > > > Hamilton harbour was renowned for malaria mosquitoes, says > > > Kain, > who > > > runs the Centre for Travel and Tropical Medicine at Toronto > General > > > Hospital. > > > > > > Four strains of malaria parasites infect humans, In each case > the > > > parasite is transmitted only by the female mosquito which > requires > a > > > blood meal to mature its eggs. A mosquito injects the infectious > > > stage of the parasite into a human when it bites to suck up > blood. > > > > > > The parasite moves through the blood stream to the liver where > it > > > changes form and multiplies inside liver cells. Eventually the > cells > > > burst, inundating the blood stream with another form of the > parasite > > > which enters red blood cells. > > > > > > When another female mosquito bites, the parasite passes to the > > > mosquito along with the human blood, and the cycle starts over > again. > > > > > > Malaria attacks can last as long as two hours, with > > > temperatures > of > > > 42 C or higher interspersed with chills, and recur as > > > frequently > as > > > every few days. Victims are weakened from vomiting and anemia > caused > > > by the loss of red blood cells. Young children and pregnant > women > are > > > especially at risk of developing severe and fatal malaria and > need > > > urgent medical care. > > > > > > Even in non-severe malaria cases, adults are often > > > incapacitated > for > > > weeks at a time. > > > > > > "Plasmodium falciparum is the parasite that causes most of the > deaths > > > and it's a really challenging foe," says Kain. "It keeps > changing > its > > > face to the immune system as it moves through the human body. No > > > single control strategy is going to be the answer." This is > where > the > > > new genetic catalogues for the malaria parasite and mosquito > should > > > come into their own. They permit researchers to pursue such new > > > interventions as: > > > > > > Undermining the ability of mosquitoes to find blood through > > > genetically engineered repellents. > > > > > > Improving the genetic modification of parasite-resistant > mosquitoes, > > > which would then be released to breed. > > > > > > Disabling the gene that lets the parasite fight off anti-malaria > > > drugs. > > > > > > Identifying the genes involved in insecticide resistance. > > > > > > "Once we identify these genes we can screen proposed new > insecticides > > > to see if they act on the same genes. We can also monitor where > > > resistance is occurring in the natural population and how the > > >** resistant genotype is spreading," said Rob Holt, the 34-year-old > > > Canadian who led the team which deciphered the mosquito's > genetic > > > code. > > > > > > Although news reports made the genome breakthroughs seem almost > > > technologically routine, both were especially challenging. > Holt's > > > research team had to examine the DNA of hundreds of individual > > > Anopheles gambiae because the mosquitoes vary a lot > > > genetically > from > > > one to the next. > > > > > > The scientists then pooled the DNA results to come up with the > genome > > > of a "typical" example of this malaria mosquito. > > > > > > The mosquito work was done under a U.S. government grant by a > > > Maryland private company, Celera Genomics Inc. which pioneered > and > > > perfected the "shotgun" approach of decoding random sections > > > of > DNA > > > from all over the genome and then sticking the segments > > > together > by > > > matching the overlaps. With its high throughput process, > > > Celera > was > > > able to crack the mosquito's genetic code starting 14 months > ago- > > > "the fastest genome project, start to finish," says Holt. > > > > > > Over at The Institute for Genomic Research (TIGR), also in > Rockville, > > > Md., it took researchers six years to unravel the genetic code > for > > > the malaria parasite. Part of the reason is that TIGR scientists > > > first had to convince funding agencies that the job was possible > > > since the parasite's DNA was notoriously unstable. > > > > > > Successful decoding of two of the parasite's 14 chromosomes > secured > > > the necessary funding. Improved sequencing technology over the > last > > > few years means that the money initially allotted for Plasmodium > > > falciparum alone is now enough to also cover two of the three > other > > > malaria parasites that infect humans. > > > > > > Such accelerated research progress combined with the promise > > > of > a > > > strengthened health delivery system mean that for the first > > > time > in > a > > > half-century, prospects are bright that Africa's mass child > killer > > > will be brought under control. > > > > > > For more on the battle against malaria, visit these Web sites: > > > > > > Malaria genetic breakthroughs: www.sciencemag.org and > www.nature.com > > > > > > Tanzanian Essential Health Interventions Project: www.idrc.ca > and > > > type TEHIP in "Search" box > > > > > > Insecticide-impregnated bednets: www.idrc.ca and type bednets in > > > "Search" box > > > > > > Mapping of Malaria Risk in Africa: www.mara.org.za > > > > > > ILLUSTATION HIGH RISK: Children play in a river of sewage > in > a > > > Nairobi slum, the perfect breeding ground for > > > mosquitoes, many of which are likely to carry > > > malaria, usually spread by the Anopheles > gambiae > > >** mosquito, right. Peter Bennett, International > > > Development Research Centre ON THE > > >FRONTLINE: > Don > > > de Savigny, left, and Graham Reid operate the > > > Tanzania Essential Health Interventions > Project, > a > > >** Canadian-financed program that serves two rural > > > districts. > > > > > > SEARCH TERMS INTERNATIONAL; DEVELOPMENT; CANADIAN > > > > > >*** END OF STORY*** > > >