Reviewer ’s report  
 
Title: Differential sexual network connectivity offers a parsimonious explanation for population -
level variations in the prevalence of bacterial vaginosis: a data -driven, model -supported 
hypothesis  
 
Version: 1 Date: 04 Sep 2018  
 
Reviewer: Ashley Hazel  
 
Reviewer's report:  
 
I think the general goal of this paper and its insights are intriguing and important.  Understanding 
more about the transmitted nature of BV and BV -associated microbiota is critical for a 
comprehensive understanding of STI risk and burden, especially among undertreated 
populations. I think this paper is on its way to being published, but I recommend a few important 
changes first.  
 
Major issues:  
--A big issue as I read this paper is that I do not understand the fundamental structure of it. Is this 
a review or an original study? The authors present a single new model of the relationship 
betwee n concurrency and BV transmission, but the rest of the paper reads like a synthesis of 
previously reported studies and data, i.e., a review paper. In isolation, both approaches are 
worthwhile but are rather thin. I suggest reworking the manuscript to have a standard original 
research paper structure (Introduction, Methods, Results, Discussion, etc.) that focuses on the 
model and the hypothesis it is testing. The review material can be reframed in Introduction and 
Discussion sections to motivate the model an d expand upon its utility to public health.  
--I have a few concerns about how the model is parameterized. As is, I think it is overly 
simplistic and not reliable to use to understand the likely complex process of BV -VMB 
transmission. However, the changes I suggest are very doable and would yield much more 
meaningful results.  
 
First, the high -connectivity model basically allows individuals to choose any new eligible partner 
at each time step, and any eligible partner is someone of the opposite sex. While it  is perfectly 
sensible when modeling some populations to assume total heterosexuality in sexual partner 
selection, that choice should be explicitly stated and an argument should be made for this. If the 
model is kept very simple in order to be more general izable, than the decision to restrict it to 
opposite sex partnerships needs to be justified. On the other hand, the total lack of any other kind 
of sorting beyond heterosexuality constructs a very unrealistic partner -selection landscape and 
biases the mode l in favor of stark transmission differences in comparison with the low -
connectivity population. If people choose their partners with the same probability across the 
population, then you essentially have random -mating conditions, which is both unrealistic and 
well established to lead to much higher transmission rates of STIs. Some type of sorting behavior 
should be included. I know you mentioned the potential to add such complexities at the end of 
the manuscript, but I think this is too fundamental to the n ature of sex -partner choice to leave it 
as a hypothetically nice addition down the road.  
Also, I think it is unrealistic to assume 100% transmission of BV -VMB after having sex with a 
partner with a BV -associated microbiota. Surely, there are many factors,  including a person's 
native CST, that would lead to variation in transmission. I realize that you probably do not have 
enough evidence to confidently estimate the transmission probability, but I would either choose a 
more conservative value (even somewhat  arbitrarily), or run the model over a distribution of 
probabilities. Using 100% transmission biases your model to producing positive results for the 
comparison between high - and low -connectivity populations.  
 
Minor issues:  
--In the abstract (p3, l5), the authors state that vaginal microbiome types "vary dramatically 
between different populations around the world." Given that the field is generally in agreement 
that there are five community state types among women across many populations, I don't 
understand  the characterization "varies dramatically."  
--Early in the background section (p4, l31 -37), the authors state that "Several longitudinal VMB 
studies have concluded that the VMB can be relatively stable over time, as well as be quite 
dynamic in a minority  of women." What do you mean? These sound like opposite 
characterizations of the VMB, so can you explain how they can both be true? Are you saying that 
in most women, the VMB is stable, but in some it is very dynamic? Or are you saying that it can 
occasion ally become very dynamics for short periods of time in some women? Is there any 
understanding about why or under what conditions stability varies?  
--p12, l31 -42, "These considerations leave us to conclude that the most parsimonious explanation 
for why the  prevalence of BV and various STIs is higher in certain populations than other is that 
these populations have more densely connected sexual networks." I would say "predict" rather 
than "conclude" because you do not have the ethnographic evidence from a ran ge of high -risk 
populations to make this conclusion. Rather you are hypothesizing that this is what you would 
find, if the data were available.  
--p13, l12: What does "genetically promiscuous" mean?  
--p14, l46: Is enough known about penile microbiota to s ay that they too should be classified into 
5 CSTs?  
--p14, l54: "...and other non -infectious causal factors...." Like what? Please explain.  
--Figure 2: I cannot tell what is happening in the low -connectivity graph over time. Has 
individual B taken on a new partner? In which case, who is now attached to A? Or, rather, is B 
representing both nodes now? Please make this graph and its labeling of nodes more clear.  
 
Typos and corrections:  
p6, l12: "Consistent condom use has been shown in a meta -analysis to BE[insert] associated..."  
p8, l7: Sentence needs comma immediately after references and before the word "studies."  
p12, l18 -22: Sentence needs a comma or colon after phrase "This explanation begs the 
question...." I also recommend moving "however" to the beginning of the sentence (with a 
comma following it).  
p12, l27: Remove word "explanation" from sentence. It is unnecessary and sounds redundan t 
with later use of "explain."  
p13, l12: "...P. maniculatus had a greater vaginal microbiome diversity...." Delete "a."  
p14, l29: "...rapid spread of BVAB and the various other STIs...." Delete "the."  
p15, l41: "...could translate inTO[insert] large dec lines...."  
p18, l5: "...study of Zozaya et al...." Should be "by" Zozaya, not "of."  
 
--Also, I found several typos in the supplemental material file, "Network Model Description." 
Please look that over and fix.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please sp ecify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
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3. Do you hold or are you currently applying for any patents relating to the content of the  
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