West Nile Virus, an Underdiagnosed Cause of Acute Fever of Unknown Origin and Neurological Disease among Hospitalized Patients in South Africa

Round 1

Reviewer 1 Report

In this manuscript entitled West Nile Virus, a missed cause of acute fever of unknown cause and neurological disease among hospitalized patients in South Africa, the authors show that West-Nile virus is an actual cause of neurological and febrile diseases in hospitalized patients in South Africa. This work highlights concerns about WNV circulation and public health importance for diagnosis of this pathogen especially in the context of unsolved acute fever and neurological disease of unknown origin.

The main points concerned for revision are more precision on results and demographic data.

Have the 2 positive specimens for RT-qPCR (from neurological cohort) also been tested for serological and VNT? If not, why? Should be interesting to have correlation between PCR results (and quantification), IgM level and VNT.

Results shown in tables are clear and understandable but, authors should include data to show sex ratio under each age group, but also severity and symptoms (table 2, 5 and 6). E.g. Are encephalopathies more current in children?

Table 4. Concerning the second cohort, why weren’t tests done when both blood and CSF samples were available? As you also mentioned that CSF is not crucial for diagnosis (lines 342-343), it could be interesting to have results for these patients in a separate table (e.g. patient X found positive for IgM in blood AND CSF…).

Concerning VNT, did you realize and test serum dilution? Why do not include VNT antibodies titer?

Minor

Title: could be improved, it contains two times the term cause; e.g. “unknow origin…”

Methods: a brief summary of WNV VNT method could be added

Line 236 : mistake in antibodies spelling

Author Response

Please see the attachment

Author Response File: Author Response.pdf

Reviewer 2 Report

No modifications necessary

Author Response

Thank you for your critical review of the manuscript.

Reviewer 3 Report

Dear Authors,

I have thoroughly read the manuscript named „West Nile Virus, a missed cause of acute fever of unknown 2 origin and neurological disease among hospitalized patients in South Africa”. I find the thematics important and results interesting.

Please find the point by point comments in the text below:

TITLE:

I suggest changing the title to WNV, an underdiagnosed cause of acute fever and neurological disease

Line 18. Please add confirmation of serological resuts and used molecular testing…

Line 22. Please write also the numbers.

Line 22.25. and throughout the text. Please include confidence intervals

Line 25. Please shortly state which neurological signs

Line 44. Please change the sentence in more

Line 166. Typo TCID

Line 161-173. This paragraph can be avoided.

Line 174. Comment: Usually cross-reactivity needs to be done simultaneously since the decission on cross reactivity depends on which titre was higher. This approach leaves possibility that a part of positive results declared for WNV is still cross reaction.

Table S1. Please add GenBank to accesion No title

Minor English language editing is necessary. 

Author Response

Please see the attachment. 

Author Response File: Author Response.pdf