The worm and the parasite: some tropical scourges call for a defense against an entire micro-ecosystem

Natural History, Feb, 2003 by T.V. Rajan

In the late 1960s, when I was a student at the All India Institute of Medical Sciences in New Delhi, my classmates and I had a microbiology professor who enjoyed taunting us as we struggled to identify badly preserved, poorly stained slides of parasite larvae and eggs. "You don't know what this is, do you?" he would say, cackling gleefully. "The eye does not see what the mind does not know." In truth, we scientists often don't understand what is staring us in the face. Like everyone else, we see what we see through the lens of a conceptual framework. The history of the treatment of filariasis, and of the research that has been done on the disease, is a perfect example of how a framework can guide, but also limit, our thinking.

The disabling and often disfiguring tropical disease known as lymphatic' filariasis is one of the multitude of diseases for which mosquitoes are the vector. Elephantiasis--the grotesque enlargement of a limb, breast, or scrotum, caused by blockage of the lymph vessels--is one of its most conspicuous manifestations. According to the World Health Organization, filariasis afflicts some 120 million people worldwide, and more than a billion may be at risk of contracting it. Surpassed only by malaria as a cause of human suffering from disease, filariasis imposes an enormous burden of illness, lost productivity, and economic hardship on already-poor countries of the global South.

The nematodes that cause this non-lethal but devastating illness are threadlike parasitic worms, primarily of the species Wuchereria bancroft and Brugia malayi. As with nearly every infection caused by a parasite, the precise mechanism that gives rise to the clinical disease is unknown. One can say with some confidence that none of the most obvious mechanisms are to blame: not the increasing population of larvae inside the human host; not the substances produced by the larvae, either living or dead; not the constant motion of the adult nematodes.

Transmission begins when a female mosquito siphons off a few microliters of blood from an infected individual. Two weeks later, when the ingested nematode larvae have developed into a stage that is infectious to humans, the larvae enter the insect's head. When she bites again, she transfers the nematode larvae to a second person. But the illness may remain asymptomatic for months or even years, leaving many of its carriers hard to identify.

On the basis of their own experiences in treating lymphatic filariasis, many of my medical mentors in India asserted that certain antibiotics were effective against the acute symptoms of the disease. Yet a quarter century ago (and, to a large extent, today as well) Western physicians pooh-poohed the Indian approach and held firmly to the admittedly logical, though in the end incomplete, position that infections caused by nematodes could not be treated with antibiotics. And here the story begins to take some twists.

Antibiotics are small molecules made primarily by soil-dwelling microorganisms of the genus Actinomyces, which compete with bacteria in the same ecosphere. These molecules can kill the bacteria that Actinomyces encounter, but they cannot kill eukaryotic cells--that is, any cell with a true nucleus enclosed by a membrane. Hence most living things made up of eukaryotic cells--and that includes nematodes, people, trees, and virtually anything else nonmicroscopic--are unharmed by antibiotics. So if antibiotics cannot destroy nematodes, how could the Indian physicians have treated a nematode-caused illness by administering them?

Filarial infections, it should be said, have some unusual features. Most people picture a patient with an infectious disease looking feverish, exhausted, and generally sick. Those and other "constitutional symptoms" of infectious illnesses are manifestations of the body's reaction to the invading microorganism; they are not caused by the infectious agent itself. When they detect the presence of alien organisms, the body's white blood cells synthesize proteins that cause a rise in temperature. The response is protective, enhancing the efficacy of the body's defense mechanisms. But one of the cardinal features of many parasitic diseases, particularly infections caused by nematodes, is the near-absence of constitutional symptoms. Nematodes can live in the body without eliciting such responses; even in the face of an active infection, many people do not experience acute symptoms.

Investigators have suggested that the longer two species live together symbiotically, the less chance that either one will disrupt the other's physiology. After all, the parasite needs a living home, not a dead one. Because many nematode infections seem to have coevolved with people over the aeons, most nematodes cause few if any disruptions of human physiology, hence few symptoms of infection. Yet many patients who contract filariasis suffer episodes of high fever, chills, trembling, and rigor. Acute filarial fever, in fact, can often look like an attack of an other disease that is rampant in many of the same countries where filariasis is common: malaria.