Imagine a city the size of Vancouver, teeming with life, where 90-plus percent of the inhabitants are very young children. Now try to envision the horror of this place if everyone in it were dead.
This mental exercise dramatises, in the first case, the striking success of global efforts over the last 12 years to rein in killer malaria, and in the second, the daunting scope of the challenge that lies ahead. The benign image is of the 600,000 or so annual survivors who wouldn’t be here but for the inroads made since 2002 to prevent and cure the parasitic infection that’s spread by mosquitoes throughout much of the developing world. The latter gut-wrenching image depicts the 600,000 who still die each year.
The success to date is thanks to many factors — billions of dollars from governments and private donors, better and better-targeted insecticides, effective environmental measures, easy and cheap diagnosis, new medicines, education on how to prevent malaria and when to seek treatment, community empowerment to ensure people get the prophylactics and care they need. And it will take at least as large an arsenal — with luck, bolstered by a promising vaccine — if the fight is to end.
The catalyst and guiding hand for much of the progress, and no doubt a vital player for the future, is the Global Fund to Fight AIDS, Tuberculosis and Malaria. It has not only funded billions of dollars worth of work on several fronts since its first grants in April 2002, it has also marshalled political will around the world, focused prevention and treatment initiatives, and co-ordinated research to a degree never seen before.
The Global Fund’s role was one of my interests last fall when I set out on a round-the-world research trip, supported by my employer, The Vancouver Sun, and funded by a grant from the Canadian Institutes of Health Research. At every stop — the funding and research hubs of Washington and Geneva, and the fieldwork centres in Northern Liberia, Northern Namibia, Western Kenya, the Indian border region of Bangladesh and the remote hills of an off-the-beaten-path Philippine island — the depth and breadth of its influence became ever-more apparent. So did the complexity of the challenge — how to stay a step ahead of the parasites’ and mosquitoes’ ability to evolve, the dicey politics of cross-border approaches and the cost of not getting this right, the need for adaptable approaches in different cultural and geographical contexts or as infection rates rise or fall.
Wildly varying results in different countries — close to extirpation in some, but stalled or worsening in others — demonstrate that today’s tools and techniques can work, but only if they’re well implemented.
“Theoretically, we could eliminate malaria,” says Carl Lowenberger, a Simon Fraser University professor who has for 30 years worked to understand malaria vectors. And yet… new breeding sites can be created by something as simple as cows leaving footprints in the mud during a rainstorm, he said. Proven medicines and insecticides can lose their punch at least as rapidly as new ones can be developed. Funders tend to lose interest over the long haul. Successful anti-malaria programs require regional co-ordination and co-operation — rare commodities in places rife with national or tribal tensions. And anti-malarials even become a weapon of war, withheld by some governments at times to make it more difficult for rebels to get the upper hand.
“So you’ve got economics, you’ve got politics, you’ve got technology,” Dr. Lowenberger says. “I don’t think we’ll eradicate this disease in my lifetime.”
Mosquitoes usually get the blame for spreading malaria, but humans are also complicit, and our forebears helped turn the disease into the scourge it is today. Although the malaria parasite, a protozoan called plasmodium, has existed for at least 50 millennia, it didn’t become common until about 10,000 years ago. That was the dawn of agriculture, when people started living in larger, more settled groups. Such big pools of human hosts, with our nourishing blood and livers, are vital to the species’ life cycle — the one-celled parasites reproduce only in human bodies and mosquitoes can’t infect new victims unless they bite someone whose blood already carries plasmodia.
Today, malaria is a tropical disease, but until less than a century ago, it was also found in much of Europe and North America. Variants of the anopheles mosquito — the kind that carries the parasite — remain common across Canada and in most temperate countries, but good public health measures have extirpated the parasite. So malaria is no longer endemic in developed countries, though imported cases pop up occasionally.
Most variants of mosquitoes that carry the parasite are night-time or early-morning biters that can be foiled — or killed — by insecticide-treated bed nets.
There are parasite variants, too, the most lethal being plasmodium falciparum. All variants are tiny, too small to be seen with the naked eye, but when their manic reproductive cycle takes hold inside a human body, the results are catastrophic. Infected people get sick — chills, fever, sweats, fatigue. Without treatment, especially if victims are small children with yet-to-develop immune systems, many die.
In addition to the horrific death toll, the economic cost is huge. Hundreds of millions of working days are lost in scores of countries when workers fall ill or stay away from their fields or off the job to care for sick children.
And health is inextricably connected to education and economic progress.
“In a village where malaria is endemic, life expectancy goes down,” says Sir Fazle Abed, the founder and head of BRAC, a multi-faceted, Bangladesh-based NGO that has grown into one of the largest development agencies on Earth. “If half the time I’m sick, my productivity will go down, and I’ll always be a poor person. All kinds of other deprivations will happen because of my poverty, and each deprivation will mean I can never get out.”
Rosemin Kassam, an associate professor at UBC’s School of Population and Public Health, who has worked on malaria-related issues in Uganda and elsewhere, says the early impact of malaria on children can drag them down for life.
“Even if they don’t die, they’re likely to be left with some kind of morbidity. It can be significant — paralysis, brain damage and retardation, a lot of negative consequences. Even just carrying the parasite can create anemia, which can make it difficult to sit in school and concentrate.”
Malaria doesn’t only strike the poor — most malaria workers interviewed for this series, even professionals well paid by their countries’ standards, had bouts of it themselves and had seen it in their families. Yet the rich places — southern Europe, Washington D.C., the U.S. South, even Ottawa — eliminated it years ago.
The Global Fund aims to turn the tide in places where malaria remains endemic by not only co-ordinating prevention and cures, but also by covering much of the cost.
These costs are big when you add them up. Fifty-four donor governments have given or pledged more than $30 billion since the fund’s inception, and private sector partners, most notably the Bill and Melinda Gates Foundation, have added hundreds of millions more.
But individual interventions are cheap. The international benchmark for cost-effectiveness of health programs is $150 per year of healthy life, and a British study estimates that with malaria this cost is between $8 and $110 — depending on the location and distribution complexities — for insecticide-treated bed nets, or $89 for drugs to treat diagnosed cases.
The best tactics vary around the world, but every malaria-control program shares three key elements: Cheapest and best is prevention. This may include low-tech environmental measures — things such as clearing brush around water sources where mosquitoes breed or homes where victims sleep. But the most effective component is insecticide-treated bed nets, often accompanied by spraying walls. Various insecticides are used, even highly effective DDT in a handful of countries that haven’t banned it yet. Treated nets and sprayed walls provide double-barrelled protection. The obvious benefit is preventing sleeping people from being bitten. The not-so-obvious plus is that, even if a mosquito doesn’t die until after it has bitten, at least it won’t live long enough to bite again. This is significant because mosquitoes don’t carry the parasite unless they bite somebody who has it. So a mosquito that dies after biting once is not a danger.
The second essential element is diagnosis, which has become much easier and more reliable than in the past. The Global Fund’s promotion and widespread distribution of new rapid diagnostic tests — strips that react to a drop of a patient’s blood — mean even minimally trained volunteers can get accurate results. This is a major advance. Previously, every fever was assumed to be malaria, which meant expensive treatments were often wasted on people who needed different interventions.
The final step is treatment. This is also simpler, thanks to new combination drugs. Precise combinations vary from region to region and are changed as necessary to combat any resistance that develops in the parasite.
But insecticides and drugs face moving targets. Mosquitoes develop resistance to sprays and parasites become drug-resistant in alarmingly short order.
The parasite, in particular, is genetically primed to adapt, says Dr. Chris Ockenhouse, senior scientist with the PATH Malaria Vaccine Initiative in Washington, D.C.
He notes that while viruses typically comprise a couple of dozen proteins, the complex malaria parasite has 5,000. Its life-cycle includes six unique environments — three inside mosquito carriers and three in a human host — so it’s inherently adaptable.
Thus, widely used medicines rapidly lose their punch as new generations of parasites become immune.
For researchers pursuing the holy grail of an effective vaccine, the question is whether this adaptability will shorten the useful life of what they come up with. It may not, Dr. Ockenhouse said, because drugs and vaccines work differently. Drugs attack the infecting agents, so any parasite not killed will propagate its drug resistance. Vaccines, however, stimulate the body’s immune system to protect itself and don’t interact with the invader. So if parasites survive, it’s because of the person’s weak immune response, not the parasite’s genetic resistance.
Several potential vaccines are under development, but only one — a GlaxoSmithKline product targeting early stages of a malarial infection — has undergone somewhat successful trials and regulatory approval is being sought.
The most recent trials ran at 11 sites in seven African countries and focused on young children — six to 12 weeks in some cases, and five to 17 months in others. The best results were for the older children, who enjoyed roughly 50-percent protection for at least 18 months. This doesn’t mean half the vaccinated children never get malaria. Rather, they experience only half as many bouts of malaria as the unvaccinated — perhaps an average of two a year instead of four.
These results fall well below the performance of vaccines for most diseases, but for Dr. Walter Otieno of the Kombewa Clinical Research Centre near Kisumu, Kenya, they’re heartening.
For one thing, vaccination halves the risk of a protected child’s death or disability. For another, like every preventive measure, it shrinks the reservoir of human carriers who can infect mosquitoes that will, in turn, infect other humans.
So, Dr. Otieno thinks the vaccine should be rolled out for general use, and soon.
Yet 50-percent efficacy doesn’t look so good to many drug researchers working to refine artemisinin-based combination therapy (ACTs), which cures virtually all cases if victims are treated in time. (Artemisinin is isolated from the sweet wormwood plant Artemisia annu, a Chinese medicinal herb used for 2,000 years as an anti-malarial, among other applications.)
Viollaine Dallenback, the Geneva-based communications co-ordinator for the international Drugs for Neglected Diseases Initiative (DNDI), is more concerned with the push to find drug combinations that stay a step ahead of the parasite’s ability to adapt. Another key goal is a one-pill therapy to replace the current three- to 24-pill treatments, both of which tempt patients to take fewer than they need so they can hoard the rest for a possible subsequent bout.
Of course, the question of cost complicates any decision, whether dealing with the vaccine or a new drug, about when to start using a new product and on what scale. Massive rollouts are cheaper per dose, but, as DNDI executive director Bernard Pecoul points out, they may also trigger the development of resistance in the parasite.
And cost, ironically, becomes a bigger issue as countries or regions get closer to eliminating the disease.
In highly endemic places such as the jungle villages of Liberia, the biggest challenge isn’t figuring out who’s ill or what to do about it. It’s laying hands on drugs to treat the disease in a place where the fragile supply chain is often disrupted by dishonesty or incompetence. So the lucky get three pills to take — usually all they need — and the unlucky are left to suffer, or die.
By contrast, on the dusty plains of northern Namibia, where after a decade-plus of progress authorities dare to hope they’re on the cusp of eliminating the disease, a now-rare episode of malaria triggers a substantial response. First, the victim gets prompt and supervised treatment. Then a team moves in to trace the source of the infection, and to test and, if necessary, treat family members and close neighbours who may also have been exposed.
In northern Liberia, where the parasite used to infect as many as two of every three children at any given time and may still infect as many as one in four, there are still frequent stock-outs caused by logistical difficulties in getting medicines to remote jungle villages and/or outright theft so supposedly free medicines can be sold in the market. In northern Namibia, where the disease has been reduced to a handful of cases a year, free and effective health care is provided even for visiting Angolans, who cross the border in considerable numbers to get better quality care than they can get at home.
“So getting close to elimination is expensive,” said Chris Lourenco, who heads the Clinton Health Access Initiative’s malaria program in Namibia. “When you find a problem, you have to carpet-bomb it.”
This brings up what former British Columbia NDP MP Svend Robinson, who now works from Geneva to co-ordinate Global Fund relations with governments around the world, sees as the big challenge. It’s to keep focused on — and financially committed to — finishing the job rather than using early successes as an excuse to ease off.
Another former Liberal British Columbia MP Dr. Keith Martin, who now heads the Washington-based Consortium of Universities for Global Health, agrees that maintaining the will is key.
“We know how to prevent malaria deaths and disability,” he said. “Yet we still have 650,000 people a year dying from malaria. If we know what to do, why are they dying?”
Don Cayo is a columnist at The Vancouver Sun. Research for this article was supported by The Sun and financed by a grant from the Canadian Institutes of Health Research.