This repository contains all code for the Bayesian survival analysis of the efficacy profile of the Sanofi-Pasteur CYD-TDV dengue vaccine (Dengvaxia), developed primarily by Daniel J. Laydon and Neil M. Ferguson of the MRC Centre for Global Infectious Disease Analysis at Imperial College, London. Full model details are available in
The model is written in C++, using OpenMP to improve performance on multi-core processors. C++ source and header files are located in the subdirectory DengVaxSurvival, ready for loading and building from Visual Studio. R output processing code can be found in the subdirectory R.
The directory ParamFiles/Data contains simulated sample data
for our default model (SimData.txt), and for models that separate cases by disease severity
(SimData_Hosp.txt and SimData_Severe.txt), as well as models
without serotype effects (SimData_NoSerotype.txt).
The target executable of the C++ source code is named DengVaxSurvival.exe, which takes a single
command line argument specifying a parameter file. So the syntax for running the executable is
DengVaxSurvival.exe Params_ParticularModelSettings.txt.
The code is heavily parallelized and (broadly) will run faster with more cores, ideally on a
high-performance cluster. However the model can also be run locally if the source code is
recompiled having turned off/commented out two lines in the header file Macros.h, namely
#define USE_CLUSTER and #define USE_COMMAND_LINE.
If run locally, we have set number of cores at 6 (in main.cpp), which again can be changed if desired.
Note that OpenMP compiled executables on Windows will typically rely on a .dll file, provided with
the compiler, or with a runtime environment. For convenience, compiled executables, and the
accompanying .dll file are included in the bin folder. If you rebuild the code, you will need to
look for the .dll matching your compiler. The location for Visual Studio may be similar to
VC\Redist\MSVC\14.28.29325\x64\Microsoft.VC142.OpenMP within the folder
C:\Program Files (x86)\Microsoft Visual Studio\2019\Enterprise\.
We have provided example batch (.bat) files to reproduce our main model (Example_MainModel.bat)
which includes serotype and age effects, and other model variants that use the
parameter files detailed below.
The executable reads in a parameter file, named Params_ParticularModelSettings.txt,
that govern which features are turned on or off,
(initial) model parameter values, and the outputs that are required,
(e.g. MCMC chains, augmented data, survival curves, attack rates, hazard ratios, seroprevalence etc.).
Example parameter files are provided in the directory ParamFiles.
By default, the features specified in the parameter files produce an output string that identifies the features present in that model run. This output string is then included within all output file names. The output strings are long, unweildly and difficult to interpret. We apologise for the inconvenience and are working to make this less painful.
Our main model (with both age and serotype effects) has output string
VAC_SILENT_PASSIVE_nENWX_SS_VEs_FSKs3_AGSVEheteroAdd_AS_Hazmult_fAdjHaz_prs1_2_SFU (called with
Example_MainModel.bat).
Model with age effects only has output string
VAC_SILENT_PASSIVE_nENWX_FSKs3_AGSVEhetero_AS_Hazmult_fAdjHaz_prs1_2_SFU (called with
Example_AgeEffectsOnly.bat).
Model with serotype effects only has output string
VAC_SILENT_PASSIVE_nENWX_SS_VEs_FSKs3_fAdjHaz_prs1_2_SFU (called with
Example_SerotypeEffectsOnly.bat).
Model with neither age nor serotype effects has output string
VAC_SILENT_PASSIVE_nENWX_FSKs3_fAdjHaz_prs1_2_SFU (called with
Example_NoAgeOrSerotypeEffects.bat).
The above models all assume the "vaccine-as-silent-infection" mechanism, and do not separate cases by disease severity.
The parameter file,
Params_K_SEROPOS_PASSIVE_nENWX_SS_VEs_FSKs3_AGSVEheteroAdd_AS_Hazmult_fAdjHaz_prs1_2_SFU.txt
(called with Example_NoImmunePriming.bat), models a variant without such immune priming.
Finally, parameters that model hospitalised and non-hospitalised disease separately are given in
file Params_VAC_SILENT_PASSIVE_nENW_MILDSEVERE_hospX_SS_VEs_FSKs3_AGSVEheteroAdd_AS_Hazmult_fAdjHaz_prs1_2_SFU.txt.
(called with Example_Hosp.bat).
Modelling severe and non-severe disease separately can be accomplished using
Params_VAC_SILENT_PASSIVE_nENW_MILDSEVEREX_SS_VEs_FSKs3_AGSVEheteroAdd_AS_Hazmult_fAdjHaz_prs1_2_SFU.txt
(called with Example_Severe.bat).
Please note that these parameter files use different simulated data files SimData_Hosp.txt and SimData_Severe.txt
Default output strings are created in the C++ function
StructureDefs.h::Housekeeping_Struct::CreateOutputString,
and in the R function DirectoriesEtc.R::ChooseOutputString.
No_Iterations and BurnIn.
All model outputs are .txt files. If run locally, model output (e.g. parameter chains, survival tables, attack rates, estimated
age-specific seroprevalence) is by default stored in
ParamFiles/Output, although all outputs are untracked by git as
they can be quite large.
The folder R contains scripts to process and plot model output. By default, these scripts expect model output to be located in ParamFiles/Output.
The following papers are relevant to the model and trial data. Please note that some of them may require a subscription.
- https://elifesciences.org/articles/65131
- https://science.sciencemag.org/content/353/6303/1033.abstract
- https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002181
- https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61428-7/fulltext
- https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61060-6/fulltext
- https://www.nejm.org/doi/10.1056/NEJMoa1411037?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0www.ncbi.nlm.nih.gov
- https://www.nejm.org/doi/full/10.1056/nejmoa1506223
Source code is licensed under the GPLv3.
It is Copyright Imperial College of Science, Technology and Medicine. The lead developers are Daniel J. Laydon and Neil M. Ferguson.
This repository includes code modified from RANLIB which is licensed under the LGPLv3.