Follow-up of an Asymptomatic Chagas Disease Population of Children after Treatment with Nifurtimox (Lampit) in a Sylvatic Endemic Transmission Area of Colombia

Fiorella Bianchi, Zulma Cucunubá, Felipe Guhl, Nadia Lorena González, Hector Freilij, Rubén Santiago Nicholls, Juan David Ramírez, Marleny Montilla, Astrid Carolina Flórez, Fernando Rosas, Victor Saavedra, Nubia Silva

Resultado de la investigación: Contribución a RevistaArtículo

24 Citas (Scopus)

Resumen

Antecedentes La enfermedad de Chagas es una antropozoonosis causada por Trypanosoma cruzi. Actualmente se utilizan dos fármacos para el tratamiento etiológico de la enfermedad: Nifurtimox (Lampit) y Benznidazol. Este estudio presenta un ensayo cuasi-experimental (grupo no control) de sesenta y dos pacientes que fueron tratados por la enfermedad de Chagas con Nifurtimox (Lampit), y luego se les dio seguimiento durante 30 meses después del tratamiento. También se evaluó la seguridad del Nifurtimox (Lampit) para la enfermedad de Chagas en este grupo de niños principalmente entre los 4 y 19 años de edad. Materiales y métodos Los 62 pacientes incluidos en el estudio fueron seleccionados cuando resultaron seropositivos para dos de cada tres pruebas serológicas fundamentalmente diferentes. Todos los niños fueron tratados durante dos meses de acuerdo con los protocolos establecidos por la OMS. Se realizó un seguimiento cada veinte días para evaluar la seguridad del tratamiento. En 43 pacientes, dos pruebas serológicas diferentes: ELISA e IFAT; y se realizaron dos pruebas parasitológicas: hemocultivo y PCR en tiempo real (qPCR) para evaluar la respuesta terapéutica, definida como negativización serológica postratamiento. Principales conclusiones Todos los pacientes completaron el tratamiento con éxito, y seis pacientes abandonaron el seguimiento posterior al tratamiento. Los efectos adversos ocurrieron en el 74% de los pacientes, pero sólo el 4,8% de los casos requirieron suspensión temporal para lograr una adherencia del 100% al tratamiento de 60 días, y todos los síntomas se revierten después de la finalización del tratamiento. Tanto la carga parasitaria (medida mediante qPCR) como la de anticuerpos (absorbancia ELISA) evidenciaron una reducción significativa de la mediana 6 meses después del tratamiento de 6,2 a 0,2 equivalentes de parásitos/mL, y de 0,6 a 0,2 unidades de absorbancia respectivamente (p<0,001). La negativización serológica por ELISA fue evidente desde 6 meses después del tratamiento, mientras que por IFAT sólo después de 18 meses. La negatividad serológica por las dos pruebas (ELISA e IFAT) fue del 41,9% (IC del 95%: 26,5-57,3) después de 30 meses después del tratamiento. qPCR fue positiva en el 88,3% de los pacientes antes del tratamiento y sólo en el 12,1% de los pacientes después de 30 meses. El análisis de supervivencia indicó que sólo el 26,3% (IC del 95%: 15,5-44,8) persistió con una qPCR negativa durante todo el período de seguimiento. 4. Conclusiones Nifurtimox fue muy bien tolerado y redujo con éxito la carga parasitaria y los títulos de anticuerpos. La reinfección, los parásitos lisiados o la falta de actividad antiparasitaria podrían explicar estos casos de qPCR persistentemente positivos.
Idioma originalEnglish (US)
PublicaciónPLoS Neglected Tropical Diseases
DOI
EstadoPublished - feb 27 2015

Huella dactilar

Nifurtimox
Asymptomatic Diseases
Colombia
Chagas Disease
Population
Therapeutics
Serologic Tests
Enzyme-Linked Immunosorbent Assay
Parasite Load
Safety
Trypanosoma cruzi
Real-Time Polymerase Chain Reaction
Suspensions
Parasites

Citar esto

Bianchi, Fiorella ; Cucunubá, Zulma ; Guhl, Felipe ; González, Nadia Lorena ; Freilij, Hector ; Nicholls, Rubén Santiago ; Ramírez, Juan David ; Montilla, Marleny ; Flórez, Astrid Carolina ; Rosas, Fernando ; Saavedra, Victor ; Silva, Nubia. / Follow-up of an Asymptomatic Chagas Disease Population of Children after Treatment with Nifurtimox (Lampit) in a Sylvatic Endemic Transmission Area of Colombia. En: PLoS Neglected Tropical Diseases. 2015.
@article{7508180a0388429a9dd6c5423c1806a6,
title = "Follow-up of an Asymptomatic Chagas Disease Population of Children after Treatment with Nifurtimox (Lampit) in a Sylvatic Endemic Transmission Area of Colombia",
abstract = "Background Chagas disease is an anthropozoonosis caused by Trypanosoma cruzi. Two drugs are currently used for the etiological treatment of the disease: Nifurtimox (Lampit) and Benznidazole. This study presents a quasi-experimental trial (non-control group) of sixty-two patients who were treated for Chagas disease with Nifurtimox (Lampit), and were then followed for 30 months post-treatment. The safety of Nifurtimox (Lampit) for Chagas disease in this group of children primarily between 4 and 19 years old was also evaluated. Materials and methods The 62 patients included in the study were selected when resulted seropositive for two out of three fundamentally different serological tests. All children were treated during two months according to protocols established by WHO. Monitoring was performed every twenty days to evaluate treatment safety. In 43 patients, two different serological tests: ELISA and IFAT; and two parasitological tests: blood culture, and real time PCR, (qPCR) were performed to assess therapeutic response, defined as post-treatment serological negativization. Principal findings All patients completed the treatment successfully, and six patients abandoned the post-treatment follow-up. Adverse effects occurred in 74{\%} of patients, but only 4.8{\%} of cases required temporary suspension to achieve 100{\%} adherence to the 60-day treatment, and all symptoms reverted after treatment completion. Both parasite load (measured through qPCR) and antibodies (ELISA absorbance) evidenced a significant median reduction 6 months after treatment from 6.2 to 0.2 parasite equivalents/mL, and from 0.6 to 0.2 absorbance units respectively (p<0.001). Serological negativization by ELISA was evident since 6 months post-treatment, whereas by IFAT only after 18 months. Serological negativization by the two tests (ELISA and IFAT) was 41.9{\%} (95{\%}CI: 26.5–57.3) after 30 months post-treatment. qPCR was positive in 88.3{\%} of patients pre-treatment and only in 12.1{\%} of patients after 30 months. Survival analysis indicated that only 26.3{\%} (95{\%}CI: 15.5–44.8) persisted with negative qPCR during the whole follow-up period. Conclusions Nifurtimox was very well tolerated and successfully reduced parasite load and antibody titers. Re-infection, lysed parasites or a lack of anti-parasitic activity could explain these persistently positive qPCR cases.",
author = "Fiorella Bianchi and Zulma Cucunub{\'a} and Felipe Guhl and Gonz{\'a}lez, {Nadia Lorena} and Hector Freilij and Nicholls, {Rub{\'e}n Santiago} and Ram{\'i}rez, {Juan David} and Marleny Montilla and Fl{\'o}rez, {Astrid Carolina} and Fernando Rosas and Victor Saavedra and Nubia Silva",
year = "2015",
month = "2",
day = "27",
doi = "10.1371/journal.pntd.0003465",
language = "English (US)",
journal = "PLoS Neglected Tropical Diseases",
issn = "1935-2727",
publisher = "Public Library of Science",

}

Follow-up of an Asymptomatic Chagas Disease Population of Children after Treatment with Nifurtimox (Lampit) in a Sylvatic Endemic Transmission Area of Colombia. / Bianchi, Fiorella; Cucunubá, Zulma; Guhl, Felipe; González, Nadia Lorena; Freilij, Hector; Nicholls, Rubén Santiago; Ramírez, Juan David; Montilla, Marleny; Flórez, Astrid Carolina; Rosas, Fernando; Saavedra, Victor; Silva, Nubia.

En: PLoS Neglected Tropical Diseases, 27.02.2015.

Resultado de la investigación: Contribución a RevistaArtículo

TY - JOUR

T1 - Follow-up of an Asymptomatic Chagas Disease Population of Children after Treatment with Nifurtimox (Lampit) in a Sylvatic Endemic Transmission Area of Colombia

AU - Bianchi, Fiorella

AU - Cucunubá, Zulma

AU - Guhl, Felipe

AU - González, Nadia Lorena

AU - Freilij, Hector

AU - Nicholls, Rubén Santiago

AU - Ramírez, Juan David

AU - Montilla, Marleny

AU - Flórez, Astrid Carolina

AU - Rosas, Fernando

AU - Saavedra, Victor

AU - Silva, Nubia

PY - 2015/2/27

Y1 - 2015/2/27

N2 - Background Chagas disease is an anthropozoonosis caused by Trypanosoma cruzi. Two drugs are currently used for the etiological treatment of the disease: Nifurtimox (Lampit) and Benznidazole. This study presents a quasi-experimental trial (non-control group) of sixty-two patients who were treated for Chagas disease with Nifurtimox (Lampit), and were then followed for 30 months post-treatment. The safety of Nifurtimox (Lampit) for Chagas disease in this group of children primarily between 4 and 19 years old was also evaluated. Materials and methods The 62 patients included in the study were selected when resulted seropositive for two out of three fundamentally different serological tests. All children were treated during two months according to protocols established by WHO. Monitoring was performed every twenty days to evaluate treatment safety. In 43 patients, two different serological tests: ELISA and IFAT; and two parasitological tests: blood culture, and real time PCR, (qPCR) were performed to assess therapeutic response, defined as post-treatment serological negativization. Principal findings All patients completed the treatment successfully, and six patients abandoned the post-treatment follow-up. Adverse effects occurred in 74% of patients, but only 4.8% of cases required temporary suspension to achieve 100% adherence to the 60-day treatment, and all symptoms reverted after treatment completion. Both parasite load (measured through qPCR) and antibodies (ELISA absorbance) evidenced a significant median reduction 6 months after treatment from 6.2 to 0.2 parasite equivalents/mL, and from 0.6 to 0.2 absorbance units respectively (p<0.001). Serological negativization by ELISA was evident since 6 months post-treatment, whereas by IFAT only after 18 months. Serological negativization by the two tests (ELISA and IFAT) was 41.9% (95%CI: 26.5–57.3) after 30 months post-treatment. qPCR was positive in 88.3% of patients pre-treatment and only in 12.1% of patients after 30 months. Survival analysis indicated that only 26.3% (95%CI: 15.5–44.8) persisted with negative qPCR during the whole follow-up period. Conclusions Nifurtimox was very well tolerated and successfully reduced parasite load and antibody titers. Re-infection, lysed parasites or a lack of anti-parasitic activity could explain these persistently positive qPCR cases.

AB - Background Chagas disease is an anthropozoonosis caused by Trypanosoma cruzi. Two drugs are currently used for the etiological treatment of the disease: Nifurtimox (Lampit) and Benznidazole. This study presents a quasi-experimental trial (non-control group) of sixty-two patients who were treated for Chagas disease with Nifurtimox (Lampit), and were then followed for 30 months post-treatment. The safety of Nifurtimox (Lampit) for Chagas disease in this group of children primarily between 4 and 19 years old was also evaluated. Materials and methods The 62 patients included in the study were selected when resulted seropositive for two out of three fundamentally different serological tests. All children were treated during two months according to protocols established by WHO. Monitoring was performed every twenty days to evaluate treatment safety. In 43 patients, two different serological tests: ELISA and IFAT; and two parasitological tests: blood culture, and real time PCR, (qPCR) were performed to assess therapeutic response, defined as post-treatment serological negativization. Principal findings All patients completed the treatment successfully, and six patients abandoned the post-treatment follow-up. Adverse effects occurred in 74% of patients, but only 4.8% of cases required temporary suspension to achieve 100% adherence to the 60-day treatment, and all symptoms reverted after treatment completion. Both parasite load (measured through qPCR) and antibodies (ELISA absorbance) evidenced a significant median reduction 6 months after treatment from 6.2 to 0.2 parasite equivalents/mL, and from 0.6 to 0.2 absorbance units respectively (p<0.001). Serological negativization by ELISA was evident since 6 months post-treatment, whereas by IFAT only after 18 months. Serological negativization by the two tests (ELISA and IFAT) was 41.9% (95%CI: 26.5–57.3) after 30 months post-treatment. qPCR was positive in 88.3% of patients pre-treatment and only in 12.1% of patients after 30 months. Survival analysis indicated that only 26.3% (95%CI: 15.5–44.8) persisted with negative qPCR during the whole follow-up period. Conclusions Nifurtimox was very well tolerated and successfully reduced parasite load and antibody titers. Re-infection, lysed parasites or a lack of anti-parasitic activity could explain these persistently positive qPCR cases.

U2 - 10.1371/journal.pntd.0003465

DO - 10.1371/journal.pntd.0003465

M3 - Article

C2 - 25723465

JO - PLoS Neglected Tropical Diseases

JF - PLoS Neglected Tropical Diseases

SN - 1935-2727

ER -