Limbe, Haiti, July 1972: Another morning at Hôpital le Bon Samaritain—the only medical outpost in a tropical valley with no paved roads, telephone, or electricity. From daybreak, patients filled the crude wooden benches of the waiting room. By midmorning, they also covered the floor. The scene was overpowering: Grandparents with rusty sputum and the rattle of tuberculosis; children with tattered clothes and broken bones; infants with swollen bellies, flaking skin, and mustardy diarrhea.
But one of these children was not just undernourished; she was unresponsive. I noticed her skin tone. Amid the rich brown faces of West African ancestry, she looked pale. Belle, a missionary nurse whose ancestry was pure Iowa cornfield, hurried over. She brushed a hand across the youngster’s forehead, gently rocked her neck to check for meningitis, then pulled down her eyelids. They were bloodless.
“Paper white! Hemoglobin’s way down. Add fever and coma. What’s your diagnosis?”
You’re asking me? I thought, terrified. I was just a summer volunteer. I wouldn’t start medical school for two months. In fact, after a few weeks in Haiti, I was wondering if I wanted to start at all.
“Quick!” Belle said. “Find Madame Toni and ask her for chloroquine while I track down Dr. Hodges. This is one wicked case of malaria.”
Suddenly I “konprannéd,” to borrow a verb from my meager Creole vocabulary. A lightbulb shone. The child’s pallor was due to malaria parasites destroying her hemoglobin-rich red blood cells. Her fever and coma indicated the infection had invaded her brain. Didn’t she need oxygen, a transfusion, a desperate ride over rutted roads to a better-equipped hospital an hour away? No. All she needed was for Dr. Hodges to snake a bitter dose of chloroquine down her throat. The girl was awake within hours. The medicine was magic.
I recently recalled that little girl and countless other children saved from certain death by chloroquine because I was reading about 80 U.S. Marines struck with falciparum malaria a few weeks after deploying to Liberia in August 2003. By day, the soldiers were clearing abandoned buildings on the steamy African coast. At night, according to Navy doctors who later investigated the cases, they slept in shorts and T-shirts on the roof. Their nighttime encampment without mosquito nets was a recipe for malaria. Worse, most of them forgot to take their weekly preventive medication, a modern-day relative of chloroquine called mefloquine.
Fortunately, prompt treatment aboard a hospital ship and in military intensive care units averted deaths among the 80 Marines, although a few experienced seizures, coma, and respiratory failure requiring ventilators. Today the average African child with severe malaria is not as fortunate. Although parents can buy chloroquine for pennies at almost any roadside stand (between 100 and 200 metric tons of chloroquine are consumed in Africa every year), the drug stopped working miracles decades ago. Effective alternatives are alien, unavailable, or unaffordable. Of the world’s 1 million to 2 million malaria-related deaths each year, the majority occur among rural residents of the tropics living on less than a dollar a day. Unless better drugs arrive soon in their villages and towns, deaths from malaria will most likely double in coming years.
To understand why malaria is a world health crisis today, it’s best to start with the pathogen: a single-celled Plasmodium falciparum parasite that has been stowing away in humans for millennia. The microbe usually enters its host via the parasite-laden saliva of a female Anopheles mosquito. Minutes after she inserts her proboscis, threadlike organisms surf the human bloodstream, gain their beachhead, the blood-rich liver, and silently multiply. Seven to 10 days later, 10,000 to 30,000 descendants restorm the bloodstream, each ready to raid a red blood cell and siphon hemoglobin to fuel the birth of another 10 to 20 babies per cell. The end result? Every 48 hours, another round of breaking, entering, and breeding, accompanied by malaria’s infamous fevers and chills. The cycle of transmission is sustained when a new mosquito bites an infected person and picks up more parasites.
Despite the parasite’s prodigious growth in the human body, the ferocious onslaught doesn’t always kill the infected person. Some people can better fend off malaria because they bear genetic mutations that hinder the ability of the parasite to grow within red blood cells (see “Good Genes Can Help,” page 51). For most people who lack access to antimalarial drugs, the main line of defense is immunologic. In malaria-rich places like equatorial Africa and Haiti, the immune system is constantly pressured to make antibodies and fighter cells that reduce the amount of parasites in the bloodstream. As a result, many older children and adults keep their infections in check with an occasional “booster shot” from a malarial mosquito. Not that they escape. Repeated bouts of illness take their toll in anemia and debilitation. The economic losses attributable to malaria in Africa alone, including lost investment revenues, have been estimated at 1 to 4 percent of Africa’s gross domestic product, up to $12 billion a year.
In a worst-case scenario, malaria-clogged blood vessels in the brain and other organs bring death within days, especially in youngsters, who have immature immune systems, and adults (like the Marines in Liberia) with no immunity to malaria. This explains how malaria still kills as many as a million children under 5 every year.
What the numbers don’t tell is chloroquine’s heroic 50-year record in preventing an even greater bloodbath.
In medicine, great discoveries often have an inauspicious origin. Chloroquine is an example. Chemists at IG Farben in Germany originally synthesized the compound in 1934 and shared the formula with Winthrop Stearns, an American sister company. Then Farben chemists made a wrong turn: Mistakenly thinking the parent compound was toxic, they abandoned it for a weaker relative called Sontochin. As World War II loomed, communication between the pharmaceutical firms broke down, and almost a decade passed before French soldiers unearthed a stash of German-made Sontochin following the fall of Tunis. Knowing of America’s desperate search for new antimalarial drugs (by then, the U.S. government and Winthrop scientists had screened roughly 14,000 candidate compounds), French military doctors shipped samples back to the States for further testing.
With just a few chemical modifications, Sontochin gained much greater potency, and chloroquine was born. But the exultation at Winthrop was short lived when researchers realized that the new cure was, in fact, identical to Sontochin’s long-forgotten predecessor, already sitting on their shelf. The sad upshot for the Allies? Chloroquine production geared up too late for the drug to save lives during campaigns in the notoriously malarial Pacific and the Mediterranean. Within 20 years, mass chloroquine treatment, along with DDT spraying and other antimosquito measures, removed the threat of disease from more than 500 million people living in formerly malaria-ridden areas.
Despite choloroquine’s smashing success, figuring out how it worked on a subcellular level took a lot longer to unravel. The first real clue was the drug’s ability to concentrate in the food vacuole—or so-called acid stomach—of the malaria parasite. This specialized compartment is where the organism digests hemoglobin, releasing an iron metabolite called heme that is normally toxic to microorganisms. To avoid heme’s damaging effects, malaria parasites convert it to an insoluble product, hemozoin, that stains their victims’ internal organs a dark, rusty brown. Chloroquine controls the parasites by interrupting this heme detoxification step, exposing them to their own poisonous by-products. Because of the way it accumulates inside the parasite, the drug works even when it is present in extremely low concentrations.