SummerSim 2017: Using Sensitivity analysis to examine the effects of an Ebola vaccine - Reviewer Zvi Roth
Jacob Barhak
SummerSim Paper Review / Dr. Zvi Roth (FAU)
Paper 22:
Stephanie Wiafe, Emma Veilleux-Gravel and Robert Smith, “Using Sensitivity Analysis to Examine the Effects of an Ebola Vaccine”
(4/19/17)
I enjoy going through the paper. It addresses an important subject – assessment of one of the more potent vaccines developed for the Ebola outbreak. The model developed by the authors is ambitious in its scope, both in terms of its number of compartments as well as in terms of the realistic way that the vaccine effects are integrated into the model. At this point in time I would recommend to deem the paper as “Borderline” until some of the issues that need to be clarified get resolved. Let me list my concerns in the order of appearance in the paper:
1) The Introduction section summarizes well the key features of the Ebola disease and the societal and economic misery caused by the last Ebola outbreak. It makes a strong case for the urgent need to develop vaccines. To that effect the Introduction points out to multiple important references. What the Introduction has not done so far, but it should, is to discuss issues that are relevant for the mathematical modeling done later in the paper: What are other references that model the last or earlier Ebola outbreaks? In what way is the new model attempts to improve on existing models? What is known about simpler models of Ebola – for instance, were the pairwise infection, recovery and death coefficients estimated for some of the models based on given infection and mortality figures? It seems from the Bibliography that the only reference to other modeling efforts is that by Salem and Smith (reference 14), and explanation is provided regarding the differences in the models.
2) On page 2 of the paper the following curious statement is made “…during the Ebola virus outbreak in West Africa, there was an observed increase in children dying from other vaccine-preventable diseases, such as measles,..”. I was a little disappointed discovering later on that the above effect was not captured by the authors’ model.
3) On page 3 of the paper there is a statement “Once infected, with an incubation period averaging 11 days, individuals begin to experience the onset of symptoms…”. It is indeed well known, even in the simplest SIR model, that proper time delay effects must be added to any spread of infectious diseases model. The model proposed by the authors has no delay effects.
4) Numbers should be added to each of the formulas.
5) For the model on page 5 all the variables and coefficients seem to be explained, with the exception of ?, associated with the amount of vaccines.
6) On page 7 the authors mention that “Using previous Ebola outbreaks and their corresponding populations at the time, an average contact rate was calculated.” Let me suggest that the authors explain it a little more. Obviously, earlier outbreak mathematical models involve less compartment due to the lack of any vaccines at the time. Contact rate coefficients are always estimated by multiple simulation runs, while least squares fitting simulation outputs (like simulated mortality figures) to the respective actual data (say actual mortality figures). In such parameter fitting the correct delay effects must be added. The authors further mention that several other contact rate parameters were simply taken from the paper by Salem and Smith. Again, it is important to understand how these were obtained.
7) For the formulas on page 8, involving non-obvious extensions to the “Basic Reproduction Ratio Numbers” some more detailed derivations must be provided, and references as well (possibly such as the paper by Dickermann et al, J. Math. Biology, 1990 and others).
8) The p variable in the dV/dt equation is a typo error.
9) Figures 4-6 are not visible. All I can see is a faint line at zero, which obviously does not explain at all the far reaching observation made on page 11 relating the eradication of the Ebola virus to the waning effect of the vaccine.
I am looking forward to the continuation of the dialog.
Jacob Barhak
Second Review by Zvi Roth:
and for their good answer regarding the omission of time delay effects. For the
latter, the comment explaining the role of "exposed" compartments in
eliminating the need for explicit delay figures, should be included in the
paper.
additional concerns:
involve "infectious dead body". Need to fix the figure.
parameters were chosen. I think that all "assumed" parameters must be briefly
explained. In addition, the parameters that were taken from some references
should be checked to see whether these relate to real data (in these papers) or
to "assumed" parameters in these other papers.
are needed. Sorry.
Professor
Department of Computer & Electrical Engineering & Computer Science
Florida Atlantic University
Engineering East Building, Room 519
777 Glades Road
Boca Raton, FL 33431
561-297-3471
Jacob Barhak
Everything is satisfactory now. I deem the paper Acceptable.
Regards,
Zvi