Early prediction of treatment efficacy in second-stage gambiense human African trypanosomiasis.
BACKGROUND: Human African trypanosomiasis is fatal without treatment. The long post-treatment follow-up (24 months) required to assess cure complicates patient management and is a major obstacle in the development of new therapies. We analyzed individual patient data from 12 programs conducted by Mé...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | http://europepmc.org/articles/PMC3367996?pdf=render |
| _version_ | 1818147869767499776 |
|---|---|
| author | Gerardo Priotto François Chappuis Mathieu Bastard Laurence Flevaud Jean-François Etard |
| author_facet | Gerardo Priotto François Chappuis Mathieu Bastard Laurence Flevaud Jean-François Etard |
| author_sort | Gerardo Priotto |
| collection | DOAJ |
| description | BACKGROUND: Human African trypanosomiasis is fatal without treatment. The long post-treatment follow-up (24 months) required to assess cure complicates patient management and is a major obstacle in the development of new therapies. We analyzed individual patient data from 12 programs conducted by Médecins Sans Frontières in Uganda, Sudan, Angola, Central African Republic, Republic of Congo and Democratic Republic of Congo searching for early efficacy indicators. METHODOLOGY/PRINCIPAL FINDINGS: Patients analyzed had confirmed second-stage disease with complete follow-up and confirmed outcome (cure or relapse), and had CSF leucocytes counts (CSFLC) performed at 6 months post-treatment. We excluded patients with uncertain efficacy outcome: incomplete follow-up, death, relapse diagnosed with CSFLC below 50/µL and no trypanosomes. We analyzed the 6-month CSFLC via receiver-operator-characteristic curves. For each cut-off value we calculated sensitivity, specificity and likelihood ratios (LR+ and LR-). We assessed the association of the optimal cut-off with the probability of relapsing via random-intercept logistic regression. We also explored two-step (6 and 12 months) composite algorithms using the CSFLC. The most accurate cut-off to predict outcome was 10 leucocytes/µL (n=1822, 76.2% sensitivity, 80.4% specificity, 3.89 LR+, 0.29 LR-). Multivariate analysis confirmed its association with outcome (odds ratio=17.2). The best algorithm established cure at 6 months with < =5 leucocytes/µL and relapse with > =50 leucocytes/µL; patients between these values were discriminated at 12 months by a 20 leucocytes/µL cut-off (n=2190, 87.4% sensitivity, 97.7% specificity, 37.84 LR+, 0.13 LR-). CONCLUSIONS/SIGNIFICANCE: The 6-month CSFLC can predict outcome with some limitations. Two-step algorithms enhance the accuracy but impose 12-month follow-up for some patients. For early estimation of efficacy in clinical trials and for individual patients in the field, several options exist that can be used according to priorities. |
| first_indexed | 2024-12-11T12:42:06Z |
| format | Article |
| id | doaj.art-ffcb4d6ea9fd463f8afea71f6d53d767 |
| institution | Directory Open Access Journal |
| issn | 1935-2735 |
| language | English |
| last_indexed | 2024-12-11T12:42:06Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-ffcb4d6ea9fd463f8afea71f6d53d7672022-12-22T01:06:57ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27352012-01-0166e166210.1371/journal.pntd.0001662Early prediction of treatment efficacy in second-stage gambiense human African trypanosomiasis.Gerardo PriottoFrançois ChappuisMathieu BastardLaurence FlevaudJean-François EtardBACKGROUND: Human African trypanosomiasis is fatal without treatment. The long post-treatment follow-up (24 months) required to assess cure complicates patient management and is a major obstacle in the development of new therapies. We analyzed individual patient data from 12 programs conducted by Médecins Sans Frontières in Uganda, Sudan, Angola, Central African Republic, Republic of Congo and Democratic Republic of Congo searching for early efficacy indicators. METHODOLOGY/PRINCIPAL FINDINGS: Patients analyzed had confirmed second-stage disease with complete follow-up and confirmed outcome (cure or relapse), and had CSF leucocytes counts (CSFLC) performed at 6 months post-treatment. We excluded patients with uncertain efficacy outcome: incomplete follow-up, death, relapse diagnosed with CSFLC below 50/µL and no trypanosomes. We analyzed the 6-month CSFLC via receiver-operator-characteristic curves. For each cut-off value we calculated sensitivity, specificity and likelihood ratios (LR+ and LR-). We assessed the association of the optimal cut-off with the probability of relapsing via random-intercept logistic regression. We also explored two-step (6 and 12 months) composite algorithms using the CSFLC. The most accurate cut-off to predict outcome was 10 leucocytes/µL (n=1822, 76.2% sensitivity, 80.4% specificity, 3.89 LR+, 0.29 LR-). Multivariate analysis confirmed its association with outcome (odds ratio=17.2). The best algorithm established cure at 6 months with < =5 leucocytes/µL and relapse with > =50 leucocytes/µL; patients between these values were discriminated at 12 months by a 20 leucocytes/µL cut-off (n=2190, 87.4% sensitivity, 97.7% specificity, 37.84 LR+, 0.13 LR-). CONCLUSIONS/SIGNIFICANCE: The 6-month CSFLC can predict outcome with some limitations. Two-step algorithms enhance the accuracy but impose 12-month follow-up for some patients. For early estimation of efficacy in clinical trials and for individual patients in the field, several options exist that can be used according to priorities.http://europepmc.org/articles/PMC3367996?pdf=render |
| spellingShingle | Gerardo Priotto François Chappuis Mathieu Bastard Laurence Flevaud Jean-François Etard Early prediction of treatment efficacy in second-stage gambiense human African trypanosomiasis. PLoS Neglected Tropical Diseases |
| title | Early prediction of treatment efficacy in second-stage gambiense human African trypanosomiasis. |
| title_full | Early prediction of treatment efficacy in second-stage gambiense human African trypanosomiasis. |
| title_fullStr | Early prediction of treatment efficacy in second-stage gambiense human African trypanosomiasis. |
| title_full_unstemmed | Early prediction of treatment efficacy in second-stage gambiense human African trypanosomiasis. |
| title_short | Early prediction of treatment efficacy in second-stage gambiense human African trypanosomiasis. |
| title_sort | early prediction of treatment efficacy in second stage gambiense human african trypanosomiasis |
| url | http://europepmc.org/articles/PMC3367996?pdf=render |
| work_keys_str_mv | AT gerardopriotto earlypredictionoftreatmentefficacyinsecondstagegambiensehumanafricantrypanosomiasis AT francoischappuis earlypredictionoftreatmentefficacyinsecondstagegambiensehumanafricantrypanosomiasis AT mathieubastard earlypredictionoftreatmentefficacyinsecondstagegambiensehumanafricantrypanosomiasis AT laurenceflevaud earlypredictionoftreatmentefficacyinsecondstagegambiensehumanafricantrypanosomiasis AT jeanfrancoisetard earlypredictionoftreatmentefficacyinsecondstagegambiensehumanafricantrypanosomiasis |