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Accurate and reliable diagnostic tools are an essential requirement for neglected tropical diseases (NTDs) programmes. However, the NTD community has historically underinvested in the development and improvement of diagnostic tools, potentially undermining the successes achieved over the last 2 decades. Recognizing this, the WHO, in its newly released draft roadmap for NTD 2021–2030, has identified diagnostics as one of four priority areas requiring concerted action to reach the 2030 targets. As a result, WHO established a Diagnostics Technical Advisory Group (DTAG) to serve as the collaborative mechanism to drive progress in this area. Here, the purpose and role of the DTAG are described in the context of the challenges facing NTD programmes. [ABSTRACT FROM AUTHOR]

Background. Clinical management of human African trypanosomiasis requires patient follow-up of 2 years' duration. At each follow-up visit, cerebrospinal fluid (CSF) is examined for trypanosomes and white blood cells (WBCs). Shortening follow-up would improve patient comfort and facilitate control of human African trypanosomiasis. Methods. A prospective study of 360 patients was performed in the Democratic Republic of the Congo. The primary outcomes of the study were cure, relapse, and death. The WBC count, immunoglobulin M level, and specific antibody levels in CSF samples were evaluated to detect treatment failure. The sensitivity and specificity of shortened follow-up algorithms were calculated. Results. The treatment failure rate was 37%. Trypanosomes, a WBC count of ⩾100 cells/μL, and a LATEX/ immunoglobulin M titer of ⩾1:16 in CSF before treatment were risk factors for treatment failure, whereas human immunodeficiency virus infection status was not a risk factor. The following algorithm, which had 97.8% specificity and 94.4% sensitivity, is proposed for shortening the duration of follow-up: at 6 months, patients with trypanosomes or a WBC count of ⩾50 cells/μL in CSF are considered to have treatment failure, whereas patients with a CSF WBC count of ⩽5 cells/μL are considered to be cured and can discontinue follow-up. At 12 months, the remaining patients (those with a WBC count of 6-49 cells/μL) need a test of cure, based on trypanosome presence and WBC count, applying a cutoff value of 20 cells/μL. Conclusion. Combining criteria for failure and cure allows follow-up of patients with second-stage human African trypanosomiasis to be shortened to a maximum duration of 12 months. [ABSTRACT FROM AUTHOR]

Background. To date, no biological marker for treatment outcome in human African trypanosomiasis (HAT) has been described. The accuracy of biological markers for prediction of treatment outcome of HAT caused by Trypanosoma brucei gambiense was assessed. Methods. Cerebrospinal fluid (CSF) white blood cell (WBC) count and immunoglobulin M (IgM), trypanosome- specific antibody, total protein, and interleukin-10 levels were determined before and up to 24 months after treatment of late-stage HAT. Results. Treatment failure was experienced by 48 of 260 patients. Pretreatment CSF WBC counts ⩾102 cells/ μL, IL-10 concentrations ⩾37 pg/mL, LATEX/IgM end titers ⩾1:32, LATEX/T. b. gambiense end titers ⩾1:2, and protein concentrations ⩾674 mg/L were associated with treatment failure. Six months after treatment, patients with CSF WBC counts ⩽5 cells/μL were at low risk of HAT recurrence (negative predictive value, 10.93). After 12 months, the combination of CSF WBC count ⩾8 cells/μL and LATEX/IgM end titer ⩾1:4 predicted treatment failure with 97% specificity and 79% sensitivity. Eighteen months after treatment, each marker accurately predicted treatment outcome. The combination of CSF WBC count ⩾8 cells/μL and LATEX/IgM end titer ⩾1:4 was 100% specific for treatment failure after 18 and 24 months. Conclusions. HAT-affected patients with elevated pretreatment CSF levels of WBC, interleukin-10, IgM, trypanosome- specific antibody, and total protein are at risk of treatment failure. Six months after treatment, patients with CSF WBC counts ⩽5 cells/μL can be considered to be cured. The assessment of a combination of CSF WBC count and LATEX/IgM level allowed accurate prediction of outcome beginning at 12 months after treatment, as did each individual marker at 18 months after treatment. [ABSTRACT FROM AUTHOR]

Background. Treatment of second-stage sleeping sickness relies mainly on melarsoprol. Nifurtimox has been successfully used to cure melarsoprol-refractory sleeping sickness caused by Trypanosoma brucei ganthiense infection. Methods. An open, randomized trial was conducted to test for equivalence between the standard melarsoprol regimen and 3 other regimens, as follows: standard melarsoprol therapy (3 series of 3.6 mg/kg/day intravenously [iv] for 3 days, with 7-day breaks between the series); 10-day incremental-dose melarsoprol therapy (0.6 mg/kg iv on day 1, 1.2 mg/kg iv on day 2, and 1.8 mg/kg iv on days 3-10); nifurtimox monotherapy for 14 days (5 mg/ kg orally 3 times per day); and consecutive 10-day melarsoprol-nifurtimox combination therapy (0.6 mg/kg iv melarsoprol on day 1, 1.2 mg/kg iv melarsoprol on day 2, and 1.2 mg/kg/day iv melarsoprol combined with oral 7.5 mg/kg nifurtimox twice a day on days 3-10). Primary outcomes were relapse, severe adverse events, and death attributed to treatment. Results. A total of 278 patients were randomized. The frequency of adverse events was similar between the standard melarsoprol regimen and the other regimens. Encephalopathic syndromes occurred in all groups and caused all deaths that were likely due to treatment. Relapses (n = 48) were observed only with the 3 monotherapy regimens. Conclusion. A consecutive 10-day low-dose melarsoprol-nifurtimox combination is more effective than the standard melarsoprol regimen. [ABSTRACT FROM AUTHOR]

Studies the intrathecal immune response pattern for improved diagnosis of central nervous system involvement in human African trypnosomiasis. Concentrations of cerebrospinal fluid and serum immunoglobulin; Pattern of intrathecal immunoglobulin synthesis; Synthesis of trypanosome-specific antibodies.

To assess the efficacy of treatment for human African trypanosomiasis, accurate tests that can discriminate relapse from cure are needed. We report the first data that the spliced leader (SL) RNA is a more specific marker for cure of human African trypanosomiasis than parasite DNA. In blood samples obtained from 61 patients in whom human African trypanosomiasis was cured, SL RNA detection had specificities of 98.4%-100%, while DNA detection had a specificity of only 77%. Data from our proof-of-concept study show that SL RNA detection has high potential as a test of cure. [ABSTRACT FROM AUTHOR]