Malaria: Artemisinin and P. falciparum Dormancy

Relapse, recurrence, recrudescence, resistance, dormancy: these terms are all relevant when explaining why malaria sometimes makes a reappearance after it has been treated. Plasmodium sp. parasites have a whole arsenal of ways to foil our best attempts to get rid of them.

The terms above all mean something quite specific. Garcia and Bruckner explain that relapse and recurrence refer to a return of the infection that arises from merozoites remaining in the liver (Diagnostic Medical Parasitology, 1997). This is well documented with P. vivax and P. ovale, and is also responsible for the long period of time that can pass between infection and onset of symptoms.

[caption id="attachment_255" align="alignleft" width="300" caption="Plasmodium falciparum parasites in blood: CDC, Dr. Mae Melvin"][/caption]

Recrudescence, according to Garcia and Bruckner, results from parasites remaining in the red blood cells after treatment. Drug therapy has failed to kill them. This is not necessarily due to drug resistance – it may be because too little drug was administered or because the drug did not remain in the blood long enough - but resistance can play a part. When some individual parasites have a genetic ability to escape the effects of a drug, and are able to multiply and re-establish the infection after all the rest have been killed, drug resistance is the basis of recrudescence. Recrudescence is often seen with P. falciparum.

Now, Andrea Codd and others report on research that provides scientific evidence for dormancy (“Artemisinin-induced Parasite Dormancy: A Plausible Mechanism for Treatment Failure," Malaria Journal 10:56). It seems that treatment with artemisinin induces a dormant state in P. falciparum parasites in the blood, from which they can return and begin to multiply once again. The researchers describe it as “a drug-induced temporary pause in the development of some parasites.” This is a distinctly different situation from parasite survival due to the drug failing to kill all the parasites, or actual drug resistance, and it is yet another way that malaria can appear to be gone, and then return.

While the effect has only been observed in the laboratory so far, Codd et al propose that dormancy may account for many instances of recrudescence, and speculate that dormancy may occur with other antimalarial drugs as well.

The more we learn about Plasmodium spp., the better we see how versatile they are, how well equipped to survive, no matter what we throw at them.

Guinea Worm Eradication

The guinea worm, Dracunculus medinensis (dragon worm, serpent worm, medina worm) is the parasite of nightmares, the horrifying thin white worm that comes out through the skin causing terrible and enduring misery. It is real, but it may not be real for much longer.

Savelugu, Ghana; Feb. 8, 2007; Credit: The Carter Center
At Savelugu Hospital in Northern Region, Ghana,
former U.S. President Jimmy Carter and his wife,
Rosalynn, watch as a Guinea worm health worker dresses a
child's extremely painful Guinea worm wound.

Guinea Worm History

 The guinea worm probably evolved in Africa – that continent is its stronghold – but in its heyday, it occurred in many parts of the Middle East and India, and as far north as parts of the USSR. As recently as the 1980s three and a half million people endured the nightmarish infection every year.  A Feb 28 New York Times article by Donald G. McNeil Jr. provides the number of cases recorded in 2010: less than 1800, all in Sudan, Mali, or Ethiopia (“Parasitic Disease: Guinea Worm Takes a Step Closer to Eradication, Jimmy Carter Says”).

McNeil writes that guinea worm “has proved notoriously hard to eradicate around the world.” When one considers, however, that of all the diseases afflicting humans, only smallpox has been eradicated to date, the fact that guinea worm is likely to be second is very impressive.

Guinea Worm's Weakness

What’s this dragon’s weak spot? Simply put, it’s the worm’s absolute reliance on people using the same pool of water as both drinking water and a place to sooth the unbearable lesion where the worm protrudes from the skin. Keep the parasite out of the water, or give people a means to avoid swallowing it (like drinking through a straw filter), and you prevent infection.

This is what’s been done. A multi-year 300 million dollar effort (relatively inexpensive as such efforts go) pushed forward by Jimmy Carter and the Carter Center, guinea worm has been beaten steadily back. I chronicle this dramatic effort in the book, Parasites: Tales of Humanity's Most Unwelcome Guests.  Odds are, this parasite will disappear forever in my lifetime.