Within-host bayesian joint modeling of longitudinal and time-to-event data of Leishmania infection.
The host immune system plays a significant role in managing and clearing pathogen material during an infection, but this complex process presents numerous challenges from a modeling perspective. There are many mathematical and statistical models for these kinds of processes that take into account a...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2024-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0297175&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841555393942126592 |
|---|---|
| author | Felix M Pabon-Rodriguez Grant D Brown Breanna M Scorza Christine A Petersen |
| author_facet | Felix M Pabon-Rodriguez Grant D Brown Breanna M Scorza Christine A Petersen |
| author_sort | Felix M Pabon-Rodriguez |
| collection | DOAJ |
| description | The host immune system plays a significant role in managing and clearing pathogen material during an infection, but this complex process presents numerous challenges from a modeling perspective. There are many mathematical and statistical models for these kinds of processes that take into account a wide range of events that happen within the host. In this work, we present a Bayesian joint model of longitudinal and time-to-event data of Leishmania infection that considers the interplay between key drivers of the disease process: pathogen load, antibody level, and disease. The longitudinal model also considers approximate inflammatory and regulatory immune factors. In addition to measuring antibody levels produced by the immune system, we adapt data from CD4+ and CD8+ T cell proliferation, and expression of interleukin 10, interferon-gamma, and programmed cell death 1 as inflammatory or regulatory factors mediating the disease process. The model is developed using data collected from a cohort of dogs naturally exposed to Leishmania infantum. The cohort was chosen to start with healthy infected animals, and this is the majority of the data. The model also characterizes the relationship features of the longitudinal outcomes and time-to-death due to progressive Leishmania infection. In addition to describing the mechanisms causing disease progression and impacting the risk of death, we also present the model's ability to predict individual trajectories of Canine Leishmaniosis (CanL) progression. The within-host model structure we present here provides a way forward to address vital research questions regarding the understanding of the progression of complex chronic diseases such as Visceral Leishmaniasis, a parasitic disease causing significant morbidity worldwide. |
| format | Article |
| id | doaj-art-7b14b543697146098db79a72e6a34dd8 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-7b14b543697146098db79a72e6a34dd82025-01-08T05:33:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01192e029717510.1371/journal.pone.0297175Within-host bayesian joint modeling of longitudinal and time-to-event data of Leishmania infection.Felix M Pabon-RodriguezGrant D BrownBreanna M ScorzaChristine A PetersenThe host immune system plays a significant role in managing and clearing pathogen material during an infection, but this complex process presents numerous challenges from a modeling perspective. There are many mathematical and statistical models for these kinds of processes that take into account a wide range of events that happen within the host. In this work, we present a Bayesian joint model of longitudinal and time-to-event data of Leishmania infection that considers the interplay between key drivers of the disease process: pathogen load, antibody level, and disease. The longitudinal model also considers approximate inflammatory and regulatory immune factors. In addition to measuring antibody levels produced by the immune system, we adapt data from CD4+ and CD8+ T cell proliferation, and expression of interleukin 10, interferon-gamma, and programmed cell death 1 as inflammatory or regulatory factors mediating the disease process. The model is developed using data collected from a cohort of dogs naturally exposed to Leishmania infantum. The cohort was chosen to start with healthy infected animals, and this is the majority of the data. The model also characterizes the relationship features of the longitudinal outcomes and time-to-death due to progressive Leishmania infection. In addition to describing the mechanisms causing disease progression and impacting the risk of death, we also present the model's ability to predict individual trajectories of Canine Leishmaniosis (CanL) progression. The within-host model structure we present here provides a way forward to address vital research questions regarding the understanding of the progression of complex chronic diseases such as Visceral Leishmaniasis, a parasitic disease causing significant morbidity worldwide.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0297175&type=printable |
| spellingShingle | Felix M Pabon-Rodriguez Grant D Brown Breanna M Scorza Christine A Petersen Within-host bayesian joint modeling of longitudinal and time-to-event data of Leishmania infection. PLoS ONE |
| title | Within-host bayesian joint modeling of longitudinal and time-to-event data of Leishmania infection. |
| title_full | Within-host bayesian joint modeling of longitudinal and time-to-event data of Leishmania infection. |
| title_fullStr | Within-host bayesian joint modeling of longitudinal and time-to-event data of Leishmania infection. |
| title_full_unstemmed | Within-host bayesian joint modeling of longitudinal and time-to-event data of Leishmania infection. |
| title_short | Within-host bayesian joint modeling of longitudinal and time-to-event data of Leishmania infection. |
| title_sort | within host bayesian joint modeling of longitudinal and time to event data of leishmania infection |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0297175&type=printable |
| work_keys_str_mv | AT felixmpabonrodriguez withinhostbayesianjointmodelingoflongitudinalandtimetoeventdataofleishmaniainfection AT grantdbrown withinhostbayesianjointmodelingoflongitudinalandtimetoeventdataofleishmaniainfection AT breannamscorza withinhostbayesianjointmodelingoflongitudinalandtimetoeventdataofleishmaniainfection AT christineapetersen withinhostbayesianjointmodelingoflongitudinalandtimetoeventdataofleishmaniainfection |