Killer coma: the evolving story of sleeping sickness treatment

Citations of this article
Mendeley users who have this article in their library.


Imagine a disease that starts with a fly's bite and ends in death. The first stage of this disease causes non-specific symptoms such as itching and joint pains. If left untreated, it progresses to the second stage weeks, months, or even years later in which the affected person displays dramatic neurological and psychiatric symptoms before slipping into a fatal coma. This killer disease is endemic to several countries, putting millions of people at risk with around 12 000 people infected every year. Yet there is no field-friendly diagnostic test and, until recently, the most effective treatment for the second stage was almost as dangerous as the disease.<br />In a Seminar in The Lancet today, Reto Brun and colleagues discuss this very real disease—human African trypanosomiasis, more commonly referred to as sleeping sickness—caused by the protozoan parasite Trypanosoma brucei transmitted through the bite of the tsetse fly. The evolving story of the research, development, and implementation of new treatments for this disease, and the many obstacles that have had to be surmounted along the way, has some important lessons for similar action in other neglected tropical diseases. Such diseases, which only affect people in poor countries so are not profitable for commercial pharmaceutical companies, need special attention as discussed in a Viewpoint by Amitava Banerjee and colleagues in today's issue.<br />Although there are two effective drugs to treat stage-one disease, pentamidine and suramin, most people only realise that they are infected when stage-two symptoms appear and so do not seek treatment until then. The most common treatment at this stage is a derivative of arsenic, melarsoprol, which can melt plastic syringes, causes caustic burns, is extremely painful when injected, and kills about 5% of patients. More recently, eflornithine, a safer alternative, has been used in the treatment of second-stage disease. Originally developed to treat cancer, this “resurrection drug” (so dubbed because of its dramatic success in rousing people from coma) has had a bumpy ride. Eflornithine was never profitable for the original manufacturer, Hoechst Marion Roussel, who stopped production in 1995. In 2000, WHO began to search for a company that would continue to produce eflornithine. After Bristol-Myers Squibb ran a high-profile advertising campaign for its eflornithine-based women's facial hair remover, media attention to this cosmetic product helped to rouse drug companies' interest in eflornithine. In 2001, and again in 2006, Aventis (now Sanofi-Aventis) made a deal with WHO to continue to produce eflornithine for its use in sleeping sickness. However, despite its “miraculous” qualities, eflornithine also has some downsides—for example, it only works against T brucei gambiense and may lead to resistance if used alone.<br />Jump to 2009, and after The Lancet published a trial (organised by the medical humanitarian organisation Médecins Sans Frontières—MSF—and the not-for-profit Drugs for Neglected Diseases initiative—DNDi) of the safest and most effective treatment to date, nifurtimox-eflornithine combination treatment (called NECT), it was hoped that this treatment could be widely implemented. However, as recently reported in The Lancet Infectious Diseases, nifurtimox (currently used in the management of Chagas disease) is not registered for use in sleeping sickness. WHO is currently asking countries wanting to use the combination treatment to sign disclaimer letters in which ministries of health will take responsibility for use of this drug, manufactured by Bayer Schering Pharma. DNDi told The Lancet that so far four countries—the Democratic Republic of the Congo, Central African Republic, Chad, and Uganda—have signed the required agreement.<br />The continuing story of implementing effective and practical treatment for sleeping sickness is encouraging. The account of this uphill struggle is a tribute to the determination of all those involved to overcome every problem hampering progress. But does the process really need to be made this complex? Research into new diagnostic methods to help identify those with treatable stage-one disease is urgently needed as is further research into safe, practical, and effective treatments and the implementation of a sustainable and efficient NECT delivery system. Would it make any difference if sleeping sickness was nicknamed “killer coma”, or would the tsetse fly need to populate hot, humid savannahs other than those in sub-Saharan Africa for the lives of those infected with T brucei to become more important to the international community?<br />




The Lancet. (2010). Killer coma: the evolving story of sleeping sickness treatment. The Lancet, 375(9709), 93.

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free