The letter by Sarmati et al. [1] presents data indicating that they were unable to find a significant correlation between human herpesvirus (HHV)–8 seropositivity and a history of spontaneous abortion in a group of 245 human immunodeficiency virus (HIV) type 1–seronegative women but that they did observe a correlation between high HHV-8 antibody titers (≥1:1280) and spontaneous abortion. Although it is possible that an increased risk of spontaneous abortion may be associated with active infection with HHV-8, at this point there is not enough evidence to support such an association. Given that several human herpes viruses are well-known agents of fetal and/or perinatal infection and that primary maternal herpesvirus infection prior to 20 weeks of gestation in some women has been associated with spontaneous abortion [2], and given the dearth of information about the clinical manifestations of HHV-8 infection, Sarmati et al. are correct in suggesting that this question should be investigated further

Brayfield, Brad P.

Mitchell, Charles D.

West, John T.

Wood, Charles

English

UNL | Libraries

University of Nebraska - Lincoln 
DigitalCommons@University of Nebraska - Lincoln 
Virology Papers Virology, Nebraska Center for 
7-1-2003 
To the Editor: Reply to Sarmati 
Brad P. Brayfield 
University of Nebraska-Lincoln 
John T. West 
University of Nebraska-Lincoln, jwest2@unl.edu 
Charles D. Mitchell 
University of Miami, School of Medicine 
Charles Wood 
University of Nebraska-Lincoln, cwood1@unl.edu 
Follow this and additional works at: https://digitalcommons.unl.edu/virologypub 
 Part of the Virology Commons 
Brayfield, Brad P.; West, John T.; Mitchell, Charles D.; and Wood, Charles, "To the Editor: Reply to Sarmati" 
(2003). Virology Papers. 81. 
https://digitalcommons.unl.edu/virologypub/81 
This Article is brought to you for free and open access by the Virology, Nebraska Center for at 
DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Virology Papers by an 
authorized administrator of DigitalCommons@University of Nebraska - Lincoln. 
174 • JID 2003:188 (1 July) • CORRESPONDENCE
1 J U L Y
Correspondence
Reply
To the Editor—The letter by Sarmati et
al. [1] presents data indicating that they
were unable to find a significant correla-
tion between human herpesvirus
(HHV)–8 seropositivity and a history of
spontaneous abortion in a group of 245
human immunodeficiency virus (HIV)
type 1–seronegative women but that they
did observe a correlation between high
HHV-8 antibody titers (1:1280) and
spontaneous abortion. Although it is pos-
sible that an increased risk of spontaneous
abortion may be associated with active in-
fection with HHV-8, at this point there is
not enough evidence to support such an
association. Given that several human her-
pesviruses are well-known agents of fetal
and/or perinatal infection and that pri-
mary maternal herpesvirus infection prior
to 20 weeks of gestation in some women
has been associated with spontaneous
abortion [2], and given the dearth of in-
formation about the clinical manifesta-
tions of HHV-8 infection, Sarmati et al.
are correct in suggesting that this question
should be investigated further.
However, it is premature to assume on
the basis of the evidence presented by Sar-
mati et al. [1] that an association between
high HHV-8 antibody titers and sponta-
neous abortion exists. There are still a
number of questions that need to be ad-
dressed in relation to spontaneous abor-
tion and maternal HHV-8 infection. In the
study by Sarmati et al., it is not clear
whether the women who had higher an-
tibody titers were undergoing primary in-
fection with HHV-8, as might be suggested
by reactive HHV-8 IgM titers. Were any
of the products of conception necropsied
and examined for possible viral cytopa-
thology? It is also likely that other factors,
such as other opportunistic infections,
may have increased the risk for both spon-
taneous abortion and elevated HHV-8 IgG
titers. Furthermore, no mention of a time
frame between abortion and HHV-8 test-
ing was presented, nor was there any in-
formation on the number of abortions ex-
perienced, only a history of abortion.
Antibody titers likely fluctuate with time,
so it would be difficult to correlate the
HHV-8 antibody titer from a current preg-
nancy with a previous spontaneous abor-
tion event. Nevertheless, Sarmati et al.
have presented an interesting observation
of HHV-8 infection in relation to preg-
nancy in a population of HIV-1–seroneg-
ative women. Further analysis will need to
be performed on a larger population of
HHV-8–seropositive mothers with high
HHV-8 antibody titers (1:1280), to sub-
stantiate the increased risk of spontaneous
abortion among women with high HHV-
8 antibody titers.
We agree with Sarmati et al. [1] that
the role of maternal HHV-8 infection dur-
ing pregnancy and the outcome of in-
fants born to HHV-8–seropositive moth-
ers have not been fully investigated. With
regard to the outcome of infants born to
HHV-8–seropositive women in our study
[3], Sarmati et al. are correct to note that
we did not see a significant difference in
infant mortality between infants born to
HHV-8–seropositive and –seronegative
mothers by 12 months after delivery.
However, we did observe a modest in-
crease in mortality among infants born to
HHV-8–seropositive mothers, compared
with those born to HHV-8–seronegative
mothers (1.8 times more likely), by 36
months after delivery (authors’ unpub-
lished data). The mortality was exacer-
bated in the presence of HIV-1 coinfec-
tion. Our ongoing cohort study of
mother-infant pairs in Zambia focuses
primarily on in utero infection, vertical
transmission of HHV-8, and risk factors
associated with transmission. For this rea-
son, the outcome of previous pregnancies,
with regard to maternal HHV-8 serostatus
or maternal HHV-8 antibody titer, was not
a focus of our study; nevertheless, we did
analyze the number of reported miscar-
riages experienced in prior pregnancies,
using the same population described in
our previous study [3]. SAS software (ver-
sion 8; SAS Institute) was used to generate
odds ratios (ORs) and 95% confidence in-
tervals (CIs), and significance was mea-
sured using the x2 test. A total of 316
mothers who gave birth at the University
Teaching Hospital in Lusaka, Zambia, re-
ported a previous pregnancy; 155 were
HHV-8 seropositive, and 161 were HHV-
8 seronegative, as determined by lytic im-
munofluorescence assay, using BC-3 cells.
Forty (12.7%) of those women report-
ed a miscarriage in a prior pregnancy; of
these, 23 were HHV-8 seropositive, and 17
were HHV-8 seronegative. Similar to what
was reported by Sarmati et al. with regard
to spontaneous abortion, no significant
association was observed between HHV-
8 seropositivity in the mother at delivery
and a history of miscarriage in a prior
pregnancy (OR, 1.48; 95% CI, 0.75–2.88;
). As indicated above, HHV-8 an-Pp .25
tibody titers in the mothers at delivery
were not examined, so any relationship to
miscarriages cannot be assessed at this
time, nor would they be relevant to any
previous spontaneous abortion event.
Brad P. Brayfield,1 John T. West,1
Charles D. Mitchell,2 and Charles Wood1
1Nebraska Center for Virology, School of Biological
Sciences, University of Nebraska, Lincoln;
2Department of Pediatrics, University of Miami
School of Medicine, Miami, Florida
References
1. Sarmati L, Ticconi C, Santangelo R, Montano
M, Rezza G, Andreoni M. Does the risk of abor-
CORRESPONDENCE • JID 2003:188 (1 July) • 175
tion increase in women with high human her-
pesvirus-8 antibody titers [letter]? J Infect Dis
2003; 188:173–4 (in this issue).
2. Nahmias AJ, Josey WE, Naib ZM, Freeman
MG, Fernandez RJ, Wheeler JH. Perinatal risk
association with maternal genital herpes sim-
plex virus infection. Am J Obstet Gynecol 1971;
110:825–37.
3. Brayfield BP, Phiri S, Kankasa C, et al. Postnatal
human herpesvirus 8 and human immuno-
deficiency virus type 1 infection in mothers and
infants from Zambia. J Infect Dis 2003; 187:
559–68.
Reprints or correspondence: Dr. Charles Wood, Nebraska Center
for Virology, School of Biological Sciences, University of Ne-
braska, Lincoln, E318 Beadle Center, Lincoln, NE 68588-0666
(cwood1@unl.edu).
The Journal of Infectious Diseases 2003;188:174–5
 2003 by the Infectious Diseases Society of America. All
rights reserved. 0022-1899/2003/18801-0025$15.00


To the Editor: Reply to Sarmati

DigitalCommons@University of Nebraska

University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Virology Papers Virology, Nebraska Center for 7-1-2003 To the Editor: Reply to Sarmati Brad P. Brayfield University of Nebraska-Lincoln John T. West University of Nebraska-Lincoln, jwest2@unl.edu Charles D. Mitchell University of Miami, School of Medicine Charles Wood University of Nebraska-Lincoln, cwood1@unl.edu Follow this and additional works at: https://digitalcommons.unl.edu/virologypub  Part of the Virology Commons Brayfield, Brad P.; West, John T.; Mitchell, Charles D.; and Wood, Charles, "To the Editor: Reply to Sarmati" (2003). Virology Papers. 81. https://digitalcommons.unl.edu/virologypub/81 This Article is brought to you for free and open access by the Virology, Nebraska Center for at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Virology Papers by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. 174 • JID 2003:188 (1 July) • CORRESPONDENCE1 J U L YCorrespondenceReplyTo the Editor—The letter by Sarmati etal. [1] presents data indicating that theywere unable to find a significant correla-tion between human herpesvirus(HHV)–8 seropositivity and a history ofspontaneous abortion in a group of 245human immunodeficiency virus (HIV)type 1–seronegative women but that theydid observe a correlation between highHHV-8 antibody titers (1:1280) andspontaneous abortion. Although it is pos-sible that an increased risk of spontaneousabortion may be associated with active in-fection with HHV-8, at this point there isnot enough evidence to support such anassociation. Given that several human her-pesviruses are well-known agents of fetaland/or perinatal infection and that pri-mary maternal herpesvirus infection priorto 20 weeks of gestation in some womenhas been associated with spontaneousabortion [2], and given the dearth of in-formation about the clinical manifesta-tions of HHV-8 infection, Sarmati et al.are correct in suggesting that this questionshould be investigated further.However, it is premature to assume onthe basis of the evidence presented by Sar-mati et al. [1] that an association betweenhigh HHV-8 antibody titers and sponta-neous abortion exists. There are still anumber of questions that need to be ad-dressed in relation to spontaneous abor-tion and maternal HHV-8 infection. In thestudy by Sarmati et al., it is not clearwhether the women who had higher an-tibody titers were undergoing primary in-fection with HHV-8, as might be suggestedby reactive HHV-8 IgM titers. Were anyof the products of conception necropsiedand examined for possible viral cytopa-thology? It is also likely that other factors,such as other opportunistic infections,may have increased the risk for both spon-taneous abortion and elevated HHV-8 IgGtiters. Furthermore, no mention of a timeframe between abortion and HHV-8 test-ing was presented, nor was there any in-formation on the number of abortions ex-perienced, only a history of abortion.Antibody titers likely fluctuate with time,so it would be difficult to correlate theHHV-8 antibody titer from a current preg-nancy with a previous spontaneous abor-tion event. Nevertheless, Sarmati et al.have presented an interesting observationof HHV-8 infection in relation to preg-nancy in a population of HIV-1–seroneg-ative women. Further analysis will need tobe performed on a larger population ofHHV-8–seropositive mothers with highHHV-8 antibody titers (1:1280), to sub-stantiate the increased risk of spontaneousabortion among women with high HHV-8 antibody titers.We agree with Sarmati et al. [1] thatthe role of maternal HHV-8 infection dur-ing pregnancy and the outcome of in-fants born to HHV-8–seropositive moth-ers have not been fully investigated. Withregard to the outcome of infants born toHHV-8–seropositive women in our study[3], Sarmati et al. are correct to note thatwe did not see a significant difference ininfant mortality between infants born toHHV-8–seropositive and –seronegativemothers by 12 months after delivery.However, we did observe a modest in-crease in mortality among infants born toHHV-8–seropositive mothers, comparedwith those born to HHV-8–seronegativemothers (1.8 times more likely), by 36months after delivery (authors’ unpub-lished data). The mortality was exacer-bated in the presence of HIV-1 coinfec-tion. Our ongoing cohort study ofmother-infant pairs in Zambia focusesprimarily on in utero infection, verticaltransmission of HHV-8, and risk factorsassociated with transmission. For this rea-son, the outcome of previous pregnancies,with regard to maternal HHV-8 serostatusor maternal HHV-8 antibody titer, was nota focus of our study; nevertheless, we didanalyze the number of reported miscar-riages experienced in prior pregnancies,using the same population described inour previous study [3]. SAS software (ver-sion 8; SAS Institute) was used to generateodds ratios (ORs) and 95% confidence in-tervals (CIs), and significance was mea-sured using the x2 test. A total of 316mothers who gave birth at the UniversityTeaching Hospital in Lusaka, Zambia, re-ported a previous pregnancy; 155 wereHHV-8 seropositive, and 161 were HHV-8 seronegative, as determined by lytic im-munofluorescence assay, using BC-3 cells.Forty (12.7%) of those women report-ed a miscarriage in a prior pregnancy; ofthese, 23 were HHV-8 seropositive, and 17were HHV-8 seronegative. Similar to whatwas reported by Sarmati et al. with regardto spontaneous abortion, no significantassociation was observed between HHV-8 seropositivity in the mother at deliveryand a history of miscarriage in a priorpregnancy (OR, 1.48; 95% CI, 0.75–2.88;). As indicated above, HHV-8 an-Pp .25tibody titers in the mothers at deliverywere not examined, so any relationship tomiscarriages cannot be assessed at thistime, nor would they be relevant to anyprevious spontaneous abortion event.Brad P. Brayfield,1 John T. West,1Charles D. Mitchell,2 and Charles Wood11Nebraska Center for Virology, School of BiologicalSciences, University of Nebraska, Lincoln;2Department of Pediatrics, University of MiamiSchool of Medicine, Miami, FloridaReferences1. Sarmati L, Ticconi C, Santangelo R, MontanoM, Rezza G, Andreoni M. Does the risk of abor-CORRESPONDENCE • JID 2003:188 (1 July) • 175tion increase in women with high human her-pesvirus-8 antibody titers [letter]? J Infect Dis2003; 188:173–4 (in this issue).2. Nahmias AJ, Josey WE, Naib ZM, FreemanMG, Fernandez RJ, Wheeler JH. Perinatal riskassociation with maternal genital herpes sim-plex virus infection. Am J Obstet Gynecol 1971;110:825–37.3. Brayfield BP, Phiri S, Kankasa C, et al. Postnatalhuman herpesvirus 8 and human immuno-deficiency virus type 1 infection in mothers andinfants from Zambia. J Infect Dis 2003; 187:559–68.Reprints or correspondence: Dr. Charles Wood, Nebraska Centerfor Virology, School of Biological Sciences, University of Ne-braska, Lincoln, E318 Beadle Center, Lincoln, NE 68588-0666(cwood1@unl.edu).The Journal of Infectious Diseases 2003;188:174–5 2003 by the Infectious Diseases Society of America. Allrights reserved. 0022-1899/2003/18801-0025$15.00

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