Reviewer ’s report  
Title: Vulvovaginal candidiasis: Species distribution of Candida and their antifungal 
susceptibility pattern  
 
Version: 0 Date: 05 Sep 2017  
 
Reviewer: Brian M Peters  
 
Reviewer's report:  
Summary  
 
This manuscript by Bitew and Abebaw seeks to determine the socio -demographic factors and 
prevalence of Candida species associated with vulvovaginal candidiasis. There are some 
strengths of the study, including the relatively large patient cohort, controlle d clinical study 
design, and novel identification method for vaginal yeasts. I have some concerns regarding 
overall conclusion and data interpretation. Please find more detailed comments below.  
 
Major comments:  
1. My major concern lies in the definition o f vulvovaginal candidiasis used by the authors. In 
line 101, the authors state that clinicians looked for signs of "vaginal abnormalities" and then 
vaginal specimens were taken and sent for microbiological identification. However, there is 
no explanation o f what clinical signs were actually assessed. Vaginal candidiasis is a disease 
driven by the host immune response (i.e. immunopathology) with well -defined clinical 
symptoms, such as itching, burning, pain of the vaginal mucosa, often accompanied by a 
white  discharge. Neutrophilic influx can be readily observed by routine Papanicolaou 
staining. However, none of these criteria were used to clinically define vaginitis, nor were 
patients questioned for vaginal symptoms. Therefore, it seems that this is a study of vaginal 
carriage or vaginal colonization rates, and not incidence of vaginitis. Therefore, this needs to 
be reflected throughout the manuscript and the title needs to change accordingly.  
2. Line 110: As a second point to that above, a vulvovaginal candi diasis case is defined as 
positive culture for Candida. Because Candida is carried at the vaginal mucosa (and other 
mucosal sites) asymptomatically, strictly positive culture cannot define the disease and must 
be accompanied by other clinical signs. Otherw ise, the authors have only assessed vaginal 
carriage, which is still important to better understand disease etiology.  
3. Line 308, 322. The authors state that echinocandins may be used to treat C. krusei vaginitis, 
despite the fact that C. krusei is 100% s usceptible to other azoles (e.g. voriconazole). I 
personally think it would be a bad idea to treat with echinocandins for fear that C. albicans or 
other pathogenic yeast at other mucosal sites may develop resistance to this last line of 
antifungal therapy.  The authors should reconsider their recommendation and reflect this in 
the discussion.  
4. Line 168: Vaginitis was not correlated with age in your study in the age ranges assessed. 
However, age is certainly a correlate of susceptibility (prepubescent girls  and post -
menopausal women rarely develop VVC). This should be more explicitly stated.  
5. Line 317: "Change in species distribution…" The data generated in this study does not 
support this conclusion as there has been no assessment of colonization over tim e. Therefore, 
changes cannot be measured.  
 
Minor comments:  
1. While the Vitek 2 system has provided good results and has been shown to correlate well 
with routine clinical testing, it would have been nice to see at least a handful of each species 
compared  to the M38 -A2 CLSI susceptibility testing, as these are the clinical breakpoints 
used for therapeutic decisions.  
2. Line 130 -138: While this is a nice description of the Vitek 2 system, much of the information 
is not needed.  
3. Line 203: If microscopy or microbial culture is not used to diagnose VVC, then describe how 
it is diagnosed (e.g. clinical signs). Most commonly a KOH test and standard light 
microscopy is used to exclude BV and identify vaginal yeasts.  
4. Line 224: Dis cuss why you think level of education correlates with enhanced carriage of 
Candida? Is this a reflection of socio -economic status?  
5. Line 270: The authors hypothesize that relatively high incidence of C. krusei could be 
explained by fluconazole resistanc e and outcompetition of other susceptible species. If true, 
why does C. glabrata also not outcompete other Candida species, given that many isolates of 
C. glabrata are inherently resistant to fluconazole? Some discussion could be added here.  
6. Line 290: Y es, resistance to fluconazole does not seem to be a major problem for VVC, but it 
is for other forms of candidiasis. Be specific here.  
 
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 specify  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.  
No 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
I recommend additional statistical review  
Quality of written English  
Please indicate the quality of language in the manuscri pt: 
Needs some language corrections before being published  
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, fundi ng, or salary from an 
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from t he publication of this manuscript, either now or in the future?  
3. Do you hold or are you currently applying for any patents  relating to the content of the 
manuscript?  
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
5. Do you have any other financial competing interests?  
6. Do you have any non -financial com peting interests in relation to this paper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests.  
 
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