we reviewed the records of all patients who received hat treatment in the period january 1 , 2001december 31 , 2003 , in the 23 treatment centers operating in north equator province . we included only those case - patients who had received complete treatment with melarsoprol , obtained from sanofi aventis ( paris , france ) under the world health organization donation program with 1 of the following regimens : 3 series of 3 injections ( 3.4 mg / kg ) at 7-day intervals for patients with a cerebrospinal fluid ( csf ) leukocyte count > 20 leukocytes / mm , or 2 series of 3 injections ( 3.4 mg / kg ) at 7-day intervals for patients with csf leukocyte counts of 520 leukocytes / mm . patients were asked to return for a routine follow - up visit to the hat treatment center at 6 , 12 , 18 , and 24 months after treatment or any time they felt unwell between visits . age , sex , disease stage , and results of parasitologic tests of the patients who experienced a relapse were recorded during the chart review . hat relapse was defined as follows : trypanosomes found in body fluids at any follow - up assessment or a csf leukocyte count > 20/mm and twice as high as the count at the previous follow - up visit . this case definition for relapse is used by the national program and in clinical trials ( 6 ) . patients who did not show up for suggested follow - up visits were not visited at home . the relapse rate was calculated as the number of patients with hat who experienced a relapse , divided by all patients who received full melarsoprol treatment during the study period . the study included 4,925 patients with second - stage parasitologically confirmed hat ; all were treatment - nave for hat , and none had been referred by another center . table 1 shows the relapse rate by geographic area for the years 2001 , 2002 , and 2003 . the patients from the central part of the province showed the highest relapse rates , and the trend increased over the 3 years (  for trend 22.3 , p<0.001 ) . table 2 shows characteristics of the patients with a relapse of hat after melarsoprol treatment . this proportion dropped to 73% after 2 years , according to the annual reports for 20012005 . only 4.8% of patients with first - stage illness experienced a relapse ; direct evidence of the parasite was found in 27% of these case - patients . these data show that high failure rates with melarsoprol are no longer limited to kasai province in drc . the hat focus of the equateur nord province does not border that in the kasai province , and given the limited contact between both provinces , resistant strains likely did not spread from kasai to equateur nord province . the reported failure rate is certainly underestimated because some of the patients who did not return for follow - up visits probably died at home or sought treatment elsewhere . we can not exclude the possibility that some retreated patients had been reinfected . however , the trend in observed incidence rates in equateur nord province had been declining since 2004 , and , regardless , the incidence was too low to contribute substantially to the observed 19.5% failure rate . the program used only basic parasitologic confirmation tests and none of the more sensitive concentration techniques , such as capillary tube centrifugation , quantitative buffy coat test , or the miniature anion - exchange column for trypanosomiasis during the study period , which explains the low proportion of relapses that were parasitologically confirmed . melarsoprol was used on a massive and unprecedented scale in equateur nord province from 1996 through 2005 , when 38,945 new patients received treatment with melarsoprol ( annual reports of national program 2000 and 2005 ) , so drug pressure ( i.e. , the use of a certain antimicrobioal agent potentially selecting out resistant strains ) was certainly present in the region . similarly high failure rates with melarsoprol in the kasai province led the national control program to introduce eflornithine as a first - line treatment there in 2006 . the cause of these high relapse rates remains unclear because until now melarsoprol resistance could not be demonstrated in parasites in vitro or in animal models ( 5 ) . the program used a shorter melarsoprol treatment regimen than that used by other countries , where 3 series of 4 injections are used . this difference is unlikely to be an explanation for the high relapse rates found , however , as in other provinces of drc , relapse rates with the same regimen remained considerably lower ( e.g. , a 1.4% reported relapse rate for bandundu province , according to the 2006 annual report of the national control program ) . given this high failure rate , a switch to the safer eflornithine regimen is the most obvious solution . however , this drug is more complex to administer : patients receiving it require intravenous fluids and a high standard of nursing care . eflornithine offers the additional advantage of lesser toxicity , which might enhance the acceptability of hat treatment . a cost - effectiveness analysis showed that eflornithine is the more cost - effective option whenever relapse rates with melarsoprol treatment exceed 15% ( 7 ) . legitimate concerns have been raised regarding the use of this drug in monotherapy as first - line treatment because there are no alternatives if resistance to it emerges . a clinical trial on the use of the combination dfmo ( alpha - difluoromethylornithine)nifurtimox is in progress ( 8) . public - private partnerships such as the drugs for neglected diseases initiative and others are currently investing in development of such drugs , but a new drug will not likely be available within the next decade .
a retrospective chart review of 4,925 human african trypanosomiasis patients treated with melarsoprol in 20012003 in equateur nord province of the democratic republic of congo showed a treatment failure rate of 19.5% . 
 this rate increased over the 3 years . 
 relapse rates were highest in the central part of the province .