Reviewer's report
Title:The incidence and risk factors of herpes simplex virus type 2 after delivery
amongst Zimbabwean women.
Version: 1Date:16 June 2009
Reviewer: Kenneth Fife
Reviewer's report:
This manuscript examines HSV 2 infection in Zimbabwean women following
delivery. As the authors point out, few studies have evaluated women for HSV 2
acquisition in the postpartum period and there are theoretical reasons to think
that the risk might be higher. The authors appear to have taken advantage of
specimens collected for an HIV study to test stored specimens for HSV 2
antibody. The results are interesting and potentially important. I have one major
reservation about the manuscript as well as a number of more minor areas where
the authors might wish to make revisions to improve the manuscript.
The major compulsory revision requested relates to the assay used to identify
HSV 2 antibody positive research participants and how it was interpreted. The
authors used the HerpeSelect 2 ELISA and used the manufacturer’s
interpretation guidelines, i.e. that an EIA value >1.1 is interpreted as positive.
Most laboratories have found that this assay has specificity problems using this
cutoff value and these problems are generally more severe when testing sera
collected from Africans. The authors have cited a 2002 Journal of Clinical
Microbiology paper as justification for this approach. However, this paper was
written by the manufacturer of the test and the assays were run in the company’s
laboratory. Few other laboratories have been able to achieve this level of
specificity on sera from any location. Most investigators (including Dr. Rhoda
Ashley-Morrow, a co-author on the cited 2002 paper) are reluctant to use the
assay with that cutoff without doing some type of independent confirmation (see:
BMC Infect Dis 2005; 5:84-90 and Sex Transm Inf 2009; 85:92-96 as two of
many examples). The authors state that specimens from seroconverters “were
tested again using the same kit” as confirmation. It is not clear from the
manuscript if the authors mean that the same serum specimen was tested a
second time in an independent run of the assay or that a second serum
specimen from the same individual was tested. Neither is a validated approach to
confirming these test results. The authors should provide a more accepted way
of confirming these results, for example, using the Biokit test (see the BMC Infect
Dis reference cited above). If it is not possible to perform such confirmatory
testing, the authors should repeat their analysis using a more reliable EIA cutoff
value (most authors have used 3.5).
Minor discretionary revisions are as follows:
1. Methods, first paragraph – the authors should specify that the HSV 2 testing
component was specifically approved by the appropriate ethical committees. As it
is written, it is not clear if it was the parent (HIV) study or the HSV 2 study that
was approved.
2. Results, second paragraph – the authors should specify the number of male
partners who were tested. It is stated that the women were encouraged to bring
in their partners, but there is no information about how many actually came and
how many consented to HSV 2 testing. One reason for asking this question is
because the seroprevalence of HSV 2 is so similar in men and women. In most
population-based studies in most countries, the seroprevalence in women is
about twice that in men.
3. Results, next to last paragraph – in the last 2 sentences, it is not clear what
age differences are being presented. This does not appear to be the age
difference between converters and non-converters because 2 values are given. I
can find no data in Table 3 that match the rate ratio or p-value stated in these
sentences. This information needs to be clarified.
4. Discussion, page 11 – the statement is made “based on our findings we would
recommend HSV 2 suppressive therapy in pregnant women based on the
synergistic relationship between the two viruses” after acknowledging that HSV 2
suppression does not change the risk of HIV acquisition. It is not clear which of
the authors’ findings support this statement. This needs clarification.
5. Discussion, page 12 – the paragraph on intravaginal herbs seems to present
data not contained in any of the tables. Neither Table 1 nor 3 shows any
significant association with use of vaginal herbs and prevalent or incident HSV 2
infection but this paragraph presents a significant odds ratio. The source of this
information needs to be clarified.
6. References – the formatting of the references is inconsistent and should be
standardized.
7. Tables 1 and 3 – it is unclear what value the category “ever used a condom”
has and it is certainly unclear how to interpret a significant association (this is
mentioned by the authors in the discussion). The authors should consider
removing this category from the analysis and the tables.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests