NECT is next: implementing the new drug combination therapy for Trypanosoma brucei gambiense sleeping sickness

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Term Occurence Count Dictionary
trypanosomiasis 2 infectiousdiseases
Chagas disease 2 infectiousdiseases
eflornithine 30 infectiousdiseasesdrugs
pentamidine 1 infectiousdiseasesdrugs
sleeping sickness 1 infectiousdiseases

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Select Drug Character Offset Drug Term Instance
eflornithine 2013 for T. b. gambiense HAT have been limited: pentamidine for first-stage disease, and melarsoprol or eflornithine for second-stage disease. Eflornithine is safer and often more effective than melarsoprol, which is
eflornithine 2328 numerous HAT-endemic foci. However, despite an increasing proportion of second-stage HAT treated with eflornithine during recent years [5], melarsoprol remains in use in many treatment centers due to eflornithine's
eflornithine 2426 with eflornithine during recent years [5], melarsoprol remains in use in many treatment centers due to eflornithine 's long, burdensome treatment administration requirements, which are difficult to implement in resource-constrained
eflornithine 2613 difficult to implement in resource-constrained settings.In April 2009, a new treatment option, nifurtimox- eflornithine combination therapy (NECT), was added to the WHO Essential Medicines List (EML) for the treatment of
eflornithine 3055 of existing treatments. Surveillance of adverse events was strongly recommended [7]. Compared with eflornithine monotherapy, NECT is easier to administer and requires fewer human and material resources. In the current
eflornithine 3789 efficacy, and preventing resistance, this avenue was explored by evaluating drug combinations including eflornithine and melarsoprol, along with nifurtimox, a drug used to treat another trypanosomal illness, Chagas disease
eflornithine 4273 drug-combination studies at HAT treatment sites in northern Uganda, which revealed the potential of the nifurtimox- eflornithine combination as a highly effective and well-tolerated therapy [11], [12]. Based on these initial studies,
eflornithine 4549 a demonstration trial comparing this therapy to the best available therapy at the time, intravenous eflornithine for 14 days [13].This study was completed through a multicentric extension in the Democratic Republic
eflornithine 5003 TPH]). The whole multicentric study extended from 2003 through 2008. The combination of nifurtimox and eflornithine was found to be a marked improvement for second-stage HAT therapy, with key advantages over the previous
eflornithine 5321 centers in DRC and RoC, NECT was shown to be easier to administer than, and noninferior in efficacy to, eflornithine monotherapy for the treatment of second-stage T. b. gambiense HAT [14]. The drug combination was fairly
eflornithine 5554 patients treated with NECT had half as many major drug-related adverse events as those treated with eflornithine alone (14% versus 29%; P = 0.002). The noninferiority in efficacy of NECT versus eflornithine monotherapy
eflornithine 5652 with eflornithine alone (14% versus 29%; P = 0.002). The noninferiority in efficacy of NECT versus eflornithine monotherapy (as measured by 10% difference in cure rates) was demonstrated by 96.5% cure rate for NECT
eflornithine 5791 by 10% difference in cure rates) was demonstrated by 96.5% cure rate for NECT group versus 91.6% for eflornithine group in the intention-to-treat patient population, and 97.7% versus 91.7% in the per-protocol population,
eflornithine 5945 population, and 97.7% versus 91.7% in the per-protocol population, both at 18 months follow-up.While eflornithine monotherapy requires 56 intravenous (IV) infusions over 14 days, NECT requires only 14 infusions over
eflornithine 6449 the cost of the drugs, which are donated) is €39 per patient, compared with €107 per patient for eflornithine monotherapy kits (unpublished data, MSF-Logistique, February 2010). This large cost difference is due
eflornithine 6731 materials, resulting in less volume and weight to transport (four NECT treatments per kit, compared with two eflornithine monotherapy treatments per kit). Cost differences may be even larger when taking into account indirect
eflornithine 7312 cost-effectiveness study showed that the cost per life saved was similar between melarsoprol and standard eflornithine monotherapy [16]. It is therefore reasonable to assume that NECT's cost per life saved will be lower
eflornithine 10255 400,000 tablets of nifurtimox per year to WHO through 2014. Aventis and later sanofi-aventis have donated eflornithine to WHO through two consecutive 5-year agreements since 2001. Kits are being made available free of charge
eflornithine 10641 four full treatments of NECT. The volume per NECT treatment is reduced by more than half compared to eflornithine monotherapy.10.1371/journal.pntd.0000720.g001Figure 1Preparation of a nifurtimox-eflornithine combination
eflornithine 10735 compared to eflornithine monotherapy.10.1371/journal.pntd.0000720.g001Figure 1Preparation of a nifurtimox- eflornithine combination therapy (NECT) kit at MSF-Logistique, Mérignac, France.Photo credit: V. Carlier/MSF-Logistique.The
eflornithine 11907 case-fatality rates. Nevertheless, melarsoprol remains widely used for second-stage T. b. gambiense HAT where eflornithine is not available or practical [20]. According to a 2008 assessment of eight provinces in DRC, 50% of
eflornithine 12128 patients with second-stage HAT were still being treated with melarsoprol (with the other half treated with eflornithine monotherapy) (unpublished data, PNLTHA). Alarmingly, in one district, Bandundu, which had the heaviest
eflornithine 13506 restricted to treat relapses of T. b. gambiense HAT after initial first-line treatment with NECT or eflornithine , and to treat second-stage HAT due to T. b. rhodesiense.Transport and supplyLogistical difficulties
eflornithine 13925 supply and access are perpetual issues for NTD treatment programs. The donations of nifurtimox and eflornithine from the drug manufacturers are most welcome and must be sustained for NECT to be widely implemented.TrainingAlthough
eflornithine 14220 protocols, the training needs for NECT are still considerable in treatment centers that have not yet used eflornithine . Care providers must be trained in the correct nursing care of IV catheters, precise and time-dependent
eflornithine 14358 trained in the correct nursing care of IV catheters, precise and time-dependent IV administration of eflornithine , daily oral administration of nifurtimox under surveillance (directly observed treatment [DOT]), monitoring
eflornithine 14785 level context, and/or at risk of vomiting the tablets. Less-intense training is needed in places where eflornithine monotherapy has already been introduced, since the NECT protocol is similar but simpler.Vertical approaches
eflornithine 17770 60% (947/1,570) were in the first stage of HAT [34]. Second-stage patients were treated with standard eflornithine monotherapy, which in this remote region required substantial logistical support and a significant effort
eflornithine 19474 requirement of two IV infusions per day for one week. Although this protocol is shorter and simpler than eflornithine monotherapy, and safer than melarsoprol, it is still resource- and training-intensive. Thus, a simpler
eflornithine 20522 reaches all patients in need.Continuous wide-scale utilization of the toxic drug melarsoprol and of eflornithine in monotherapy, which may trigger parasitic resistance to this life-saving drug, highlight the urgency
pentamidine 1957 diagnosis, treatment, and vector control.Drug treatments for T. b. gambiense HAT have been limited: pentamidine for first-stage disease, and melarsoprol or eflornithine for second-stage disease. Eflornithine is safer
Select Disease Character Offset Disease Term Instance
Chagas disease 1063 Health Organization (WHO) as requiring Innovative and Intensified Disease Management (IDM), along with Chagas disease , leishmaniasis, and Buruli ulcer [3]. These particular NTDs have poorly understood burdens, lack optimal
Chagas disease 3893 eflornithine and melarsoprol, along with nifurtimox, a drug used to treat another trypanosomal illness, Chagas disease (American trypanosomiasis), and shown to have varying efficacy against HAT [8]–[10].From 2001 through
sleeping sickness 702 5/2010Publication date (epub): 5/2010IntroductionFatal if untreated, human African trypanosomiasis (HAT; sleeping sickness ) afflicts an estimated 50,000–70,000 people each year [1], all in sub-Saharan Africa, with only a
trypanosomiasis 680 date (collection): 5/2010Publication date (epub): 5/2010IntroductionFatal if untreated, human African trypanosomiasis (HAT; sleeping sickness) afflicts an estimated 50,000–70,000 people each year [1], all in sub-Saharan
trypanosomiasis 3918 along with nifurtimox, a drug used to treat another trypanosomal illness, Chagas disease (American trypanosomiasis ), and shown to have varying efficacy against HAT [8]–[10].From 2001 through 2004, Epicentre, the research

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