Editing African trypanosomiasis (section)

===Second Stage===
Fexinidazole may be used for the second stage of TbG, if the disease is not severe.<ref name=DRC2019>{{cite web |title=Fexinidazole, the first all-oral treatment for sleeping sickness, approved in the Democratic Republic of Congo – DNDi |url=https://www.dndi.org/2019/media-centre/press-releases/fexinidazole-sleeping-sickness-approved-democratic-republic-congo/ |website=dndi.org |date=29 January 2019 |access-date=4 November 2019}}</ref><ref name=WHO2020/> Otherwise a regimen involving the combination of [[nifurtimox]] and [[eflornithine]], [[nifurtimox-eflornithine combination treatment]] (NECT), or eflornithine alone appear to be more effective and result in fewer side effects.<ref name=Lut2013>{{cite journal | vauthors = Lutje V, Seixas J, Kennedy A | title = Chemotherapy for second-stage human African trypanosomiasis | journal = The Cochrane Database of Systematic Reviews | volume = 2013 | issue = 6 | pages = CD006201 | date = June 2013 | pmid = 23807762 | pmc = 6532745 | doi = 10.1002/14651858.CD006201.pub3 }}</ref> These treatments may replace [[melarsoprol]] when available.<ref name=Lut2013/><ref name=Lancet2013/> NECT has the benefit of requiring fewer injections of eflornithine.<ref name=Lut2013/>

Intravenous melarsoprol was previously the standard treatment for second-stage (neurological phase) disease and is effective for both types.<ref name=Lancet2013/> [[Melarsoprol]] is the only treatment for second stage ''T. b. rhodesiense''; however, it causes death in 5% of people who take it.<ref name=Lancet2013/> Resistance to melarsoprol can occur.<ref name=Lancet2013/>

'''Drug Development Projects'''.
A major challenge has been to find drugs that readily pass the blood–brain barrier. The latest drug that has come into clinical use is fexinidazol, but promising results have also been obtained with the benzoxaborole drug [[acoziborole]] (SCYX-7158). This drug is currently under evaluation as a single-dose oral treatment, which is a great advantage compared to currently used drugs. Another research field that has been extensively studied in ''Trypanosoma brucei'' is to target its nucleotide metabolism.<ref name="Hofer2023">{{cite journal | vauthors = Hofer A | title = Targeting the nucleotide metabolism of Trypanosoma brucei and other trypanosomatids. | journal = FEMS Microbiology Reviews | volume = 47 | issue = 3 | pages = fuad020 | date = 2022 | pmid = 37156497 | doi = 10.1093/femsre/fuad020 | doi-access = free | pmc = 10208901 }}</ref> The nucleotide metabolism studies have both led to the development of adenosine analogues looking promising in animal studies, and to the finding that downregulation of the P2 adenosine transporter is a common way to acquire partial drug resistance against the melaminophenyl arsenical and [[diamidine]] drug families (containing melarsoprol and pentamidine, respectively).<ref name="Hofer2023"/> Drug uptake and degradation are two major issues to consider to avoid drug resistance development.  In the case of nucleoside analogues, they need to be taken up by the P1 nucleoside transporter (instead of P2), and they also need to be resistant to cleavage in the parasite.<ref name="pmid27036940">{{cite journal | vauthors = Vodnala M, Ranjbarian F, Pavlova A, de Koning HP, Hofer A | title = Methylthioadenosine Phosphorylase Protects the Parasite from the Antitrypanosomal Effect of Deoxyadenosine: implications for the pharmacology of adenosine antimetabolites | journal = Journal of Biological Chemistry | volume = 291 | issue = 22 | pages = 11717–26 | date = 2016 | pmid = 27036940 | doi = 10.1074/jbc.M116.715615 | doi-access = free | pmc = 4882440 }}</ref><ref name="pmid28373184">{{cite journal | vauthors = Ranjbarian F, Vodnala M, Alzahrani KJ, Ebiloma GU, de Koning HP, Hofer A | title = 9-(2'-Deoxy-2'-Fluoro-β-d-Arabinofuranosyl) Adenine Is a Potent Antitrypanosomal Adenosine Analogue That Circumvents Transport-Related Drug Resistance | journal = Antimicrobial Agents and Chemotherapy | volume = 61 | issue = 6 | pages = e02719-16 | date = 2016 | pmid = 28373184 | doi = 10.1128/AAC.02719-16 | doi-access = free | pmc = 5444181 }}</ref>