The Fever Trail: In Search of the Cure for Malaria

Reviewed by: John S. Marr, MD

July 29, 2002

Introduction

By Mark Honigsbaum
Farrar, Straus and Giroux
Copyright 2001
307 pages
ISBN: 0-374-15469-4
$25.00 hardcover

Quinine ranks with licorice, ipecac, cannabis, and opium as one of the oldest botanics in medical history, but unlike the others, quinine not only alleviated a symptom --fever, it was the first medication ever that cured a disease. As the author notes, its success led to early homeopathic contention that nature's wonders really worked.

Many books have been written about digitalis, opium, and cannabis, but few works have been devoted to quinine. The Fever Trail: In Search of the Cure for Malaria is a modern first. Mark Honigsbaum, an Englishman who contributes to The Observer and other periodicals, has produced a delightful book about this long-neglected bark from the cinchona tree and its effect on the world.

The Fever Trail is largely devoted to the early botanic English adventurers, philanthropists and capitalists who searched for and exploited the unique medication. Antepenultimate chapters discuss quinine replacements -- from Atabrine through Malarone and the future promise of qing-hao (artemisinin). The last chapter is devoted to the recent frustrating and elusive search for an effective malaria vaccine.

According to most experts, malaria did not exist in the Americas prior to Spanish contact, yet crude bark preparations containing quinine were presumably used for thousands of years by indigenous peoples as a febrifuge. The Spaniards soon "discovered" that the bark also offered symptomatic relief of malaria. Its early exportation to and use in Italy and Spain was soon expanded to other European countries as the preparation's effectiveness against the dreaded ague was recognized there.

The cinchona bark developed into a very lucrative product for Spain and, later, newly independent South American countries. The trees were largely inaccessible to inquisitive English, French, and maritime entrepreneurs. European explorers and botanists, however, were close to discovering alternative riverine/jungle/mountain trails that led to the ultimate source of "Jesuit powder" hidden on the slopes of the Northeastern Andes.

Better still, these tradesmen wished to get cuttings and seeds for Asian tree farms. By the early nineteenth century, it was well known that the bark -- it allegedly cured the Spanish Condesa de Chinchón (the author debunks that myth) -- was critical for the health of any country that was intent on colonial expansion.

There is more, however, to The Fever Trail than the historical intrigues that comprise 9 of 12 chapters. By themselves, the early diary/document-derived narratives are fascinating, but their stories eventually morph into the history and elucidation of the cause of malaria and the most recent challenges of 21st century malariologists. The author rounds out the historical quotient by reviewing known documents behind the search, discovery, exportation, refinement, and purification of the bark's alkaloids and malaria history.

The underlying rationale for quinine use -- malaria treatment -- holds the chapters together. Occasionally Honigsbaum wanders into other insect-borne diseases (eg, yellow fever, West Nile, and leishmaniasis), but his keel is for the most part steady, addressing various preventive and curative scenarios. It is therefore surprising that the one error I detected alerted me to a larger lacunar neglect -- the ban on DDT.

The author states that the United States banned its use in 1982 and offers a footnote (p. 225). This ban was 10 years earlier, and footnote (which I thought might address the me-too ban of DDT by malarious-hyperendemic countries) was not about DDT's maligned past, but a brief paragraph on its possible selective reintroduction. If anything, a whole chapter should have been devoted to this insecticide.

In this case, it is as if DDT has joined thalidomide and asbestos as a too-hot topic, a nonnegotiable evil substance, that the author decided to avoid. This is too bad. DDT is never mentioned again, nor is the World Health Organization's (WHO's) malaria eradication proposal that collapsed largely due to the lack of an effective, inexpensive long-term insecticide residual (DDT). This selective omission of a fair discussion of the early WHO eradication program and the DDT controversies are significant flaws in an otherwise meticulously researched book.

The only other irksome criticism regards Honigsbaum's otherwise elegant 5 maps at the beginning of the book. They are attractively drawn, but the trails of the 3 major English adventurers are difficult to follow. Thumbing back to these maps in order to follow their routes, the reader would like to trace their travels and travails as they passed through Aguirre-like jungles and treacherous rivers, towering mountains and primitive towns, but the maps' dotted trails are confusing -- no arrows point a forward direction, and, in one map, an insert's black and white inking of rivers and estuaries are reversed.

Nevertheless this book is an excellent informative read, far transcending older tracts on malaria's history.[1] But one should anticipate the abrupt change from Boswellian accounts to a crisp, accurate exploration of the malaria parasite's discovery and epidemiology, and then to an even smaller summary of future challenges.

It is impressive and noteworthy to mention that Honigsbaum visited all the places of quinine's history -- Old and New World -- and interviewed dozens of historical and scientific experts. He immersed himself in the exegesis of a tree and its life-saving bark to critically assess the likelihood of a brighter future for the prevention/treatment of this most ancient scourge. Given his narrative style and assiduous research, one hopes that he will give us an update in the years to come.

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