The Egyptian Journal of Hospital Medicine (October 2017) Vol.

69 (4), Page 2209-2214

Infection with Genital Herpes Virus and Its Treatment in Relation

to Preterm Delivery
Ahmad Ayed Derham1, Hanadi Hezam AL-Thobiati2, Mohannad ali alghamdi1,
Nasir Ahmad Alsubai2, Lamees Hatim Aldoobie1, Razan Hussain Alhasawi3, Sara Falah Alsahafi3
1 King Abdulaziz University, 2 Umm AL-Qura University,
3 Batterjee Medical College for Science and Technology
Corresponding Author: Ahmad Ayed Derham, email: [email protected]

ABSTRACT
Infection with herpes simplex is a standout amongst the most well-sexually transmitted infections. As
the infection is common in women of reproductive age it may be contracted and transmitted to the fetus
amid pregnancy and the new-born. Herpes simplex virus is a significant cause of neonatal infection,
which could lead to death or long-term disabilities. Infrequently in the uterus, as it happens frequently
during the transmission delivery.
The most serious danger of transmission to the fetus and the new-born happens in case of an early
maternal infection contracted in the second half of pregnancy. The danger of transmission of maternal-
fetal-neonatal herpes simplex could be diminished by applying a treatment with antiviral medicines or
depending on a caesarean section in some particular cases. The aim of this paper is to provide
recommendations on the management of herpes simplex infections in pregnancy and approaches to
decrease perinatal transmission of herpes simplex virus.
Keywords: Genital Herpes, Herpes Simplex Virus, Caesarean, Perinatal Transmission.

INTRODUCTION
Genital herpes is a main public- health repeat rate is four to six scenes for each year
concern as a result of its recurrent nature, its [7]
. Pregnant ladies with untreated genital herpes
ability to be transmitted asymptomatically, and amid the first or second trimester seem to have a
its potential for complications [1]. This sexually more noteworthy than two-overlap danger of
transmitted disease is initiated by herpes preterm conveyance contrasted with ladies not
simplex virus types 1 and 2 (HSV-1 and HSV- exposed with herpes, especially in connection to
2), in most cases by HSV-2 [2]. HSV-2 is the premature rupture of membrane and early
reason of most genital herpes and is nearly preterm conveyance (less than or equal 35 week
always sexually transmitted. HSV-1 is generally of gestation) [8]. Pregnant women who get
transmitted in childhood through non-sexual antiherpes treatment have a lower danger of
contacts. Nevertheless, HSV-1 has emerged as a preterm conveyance than untreated ladies, and
principle causative agent of genital herpes in their preterm conveyance chance is like that
several developed countries [3, 4]. The highest seen in unexposed women.
occurrence of HSV infections occurs in women The study was approved by the Ethics Board
of reproductive age, the danger of maternal of King Abdulaziz University.
transmission of the virus to the foetus or
neonate has become a main health concern [5]. MATERIALS AND METHODS
Women recently diagnosed with genital herpes • Data sources and search terms We
will habitually experience psychological distress conducted this review using a comprehensive
and concern about future sexual relationships search of MEDLINE, PubMed, EMBASE,
and pregnancy. Cochrane Database of Systematic Reviews, and
Demographically, HSV-2 infection is more Cochrane Central Register of Controlled Trials
typical in women than in men, and in the non- from January 1, 1980, through February 28,
Hispanic black populace, there is an expanded 2017. The following search terms were used:
predominance in both genders. Even between Genital Herpes, Herpes Simplex Virus,
people with comparative quantities of lifetime Caesarean, Perinatal Transmission, HSV-1,
sexual accomplices, this difference between the HSV- 2, and Disseminated Herpes Infection.
ethnicities remains [3]. Most individuals with • Data extraction
symptomatic genital herpes will encounter Two reviewers independently reviewed studies,
repetitive contaminations inside the principal abstracted data, and resolved disagreements by
year of the essential disease, and the middle
2209
Received:30 / 7/2017 DOI : 10.12816/0041518
Accepted: 9/ 8 /2017
 Infection with Genital Herpes Virus…

consensus. Studies were evaluated for quality. A those infected with the HIV virus, are at
review protocol was followed throughout. increased danger of more severe and frequent
Transmission of HSV symptomatic recurrent episodes of genital
Components related with transmission herpes amid pregnancy and of asymptomatic
incorporate the sort of maternal contamination detaching of HSV at term. Since co-infection
(primary or recurrent), the nearness of with HSV and HIV outcomes in an increased
transplacental maternal killing antibodies, the replication of both viruses, there are worries that
length of break of layers before conveyance, the genital reactivation of HSV might increase the
utilization of fetal scalp electrodes and the danger of perinatal transmission of both HIV
method of delivery. The dangers are most and HSV [16, 17].
noteworthy when a lady procures another
disease (essential genital herpes) in the third Neonatal herpes simplex virus infections
trimester, especially inside a month and a half The importance of neonatal herpes simplex
of conveyance, as viral shedding may endure virus infection differs and depends on the extent
and the infant is probably going to be conceived of the infection (Table 1). Local infections are
before the advancement of defensive maternal the most frequent and benign type. Nonetheless,
antibodies [9, 10]. Rarely, intrinsic herpes may serious infections may happen and can lead to
happen because of the transplacental death or long-term CNS morbidity. Neonatal
intrauterine disease. Case reports propose that HSV infections may be categorised as
the skin, eyes and CNS might be influenced and disseminated disease (25%); central nervous
there might be fetal development limitation or system disease (30%); and disease restricted to
fetal death [11, 12]. the eyes, skin or mouth (45%). Mortality has
Disseminated herpes is more mutual in reduced to 30% for disseminated disease and
preterm infants and happens almost entirely as a 4% for central nervous system disease over the
result of primary infection in the mother. Even previous two decades. Nearly 20% of
though recurrent genital herpes is linked with a pretentious neonates will have long term
very low risk of neonatal herpes, recurrent neurologic sequelae. Kimberlin et al
herpes at the time of delivery, which is normally recommends that neonatal suppression treatment
asymptomatic or unrecognised, might cause the with acyclovir in infants with HSV might
localised forms of neonatal herpes: both local improve neurodevelopmental results [18].
CNS disease and skin, eye and mouth infection.
Transplacentally attained HSV antibodies do Table 1: Types and Sequelae of Neonatal HSV
not avert herpes virus spreading to the brain of the Infection
neonate [13]. Data from the USA propose that Disease Type Incidence Mortality Long-
about 2% of women obtain genital HSV % % term
infection in pregnancy and most of these Morbidity
maternal infections are asymptomatic or %*
unrecognised [9, 10]. Nonetheless, acquisition in CNS 35 15 65
the KSA in pregnancy can vary particularly Disseminated 20 60-80 40
given differing rates of neonatal herpes between Localized 45 0 5
KSA and USA. It may be difficult to disease
differentiate clinically between recurrent and
of skin, eye,
primary genital HSV infections, as several first
mouth
episodes HSV infections are not true primary
*Morbidity includes mental retardation,
infections [14].
chorioretinitis, seizures, and other CNS effects.
Disseminated herpes infection in the
mother
Antiviral treatment
Disseminated herpes, which might exist with
Acyclovir
hepatitis, disseminated skin lesions or a
combination of these conditions, is infrequent in Acyclovir, a nucleoside analogue, was the
adults. However, it has been more frequently first antiviral treatment accepted for the
reported in pregnancy, particularly in the treatment and prevention of HSV infection.
immunocompromised. The maternal mortality Acyclovir selectively inhibits viral DNA
replication of HSV, whereas having little
related with this condition is high [15]. All
influence on normal cells. Acyclovir is selective
immunocompromised women, for example,

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 Ahmad Derham et al.

for HSV-infected cells for the reason that it load or to insusceptible concealment is obscure.
needs phosphorylation by a viral enzyme Acyclovir has been named a classification B
(thymidine kinase) to acyclovir monophosphate. drug (no teratogenic impacts were found in
Phosphorylation does not ensue in uninfected examined animal, however no or restricted
cells, where it residues virtually undetectable. human investigations are accessible).
After its conversion to acyclovir
monophosphate in infected cells, other cellular Valacyclovir and famciclovir
enzymes convert it to acyclovir triphosphate, Since the presentation of acyclovir, more up
which acts to inhibit HSV-specific DNA to date second-age antivirals have been
polymerase, consequential in termination of the presented (eg, valacyclovir, famciclovir).
DNA transcript. With primary HSV infection in Valacyclovir is indistinguishable to acyclovir
non-pregnant women, acyclovir decreases the with the exception of the expansion of an ester
length of local pain, dysuria, and viral shedding, side chain that expands bioavailability. Once
and it reduces the time to crusting and healing retained, it is changed over to acyclovir in vivo.
of lesions [19]. With day-to-day usage, acyclovir This takes into consideration higher serum
likewise decreases symptomatic recurrences and levels with a less-visit dosing plan. Famciclovir
subclinical viral shedding. is a nucleotide simple that has a more extended
Amid pregnancy, acyclovir crosses the intracellular half-life. Likewise with acyclovir,
placenta and gathers in the amniotic liquid. these second-generation agents have been used
Postpartum, acyclovir contemplates in breast for treatment of symptomatic primary and
milk. Fetal serum focuses are proportionate to recurrent lesions in addition to daily
maternal serum fixations. A potential suppression. Both valacyclovir and famciclovir
disadvantage of acyclovir treatment is deferred have been labelled category B drugs [20].
and diminished counter acting agent reaction to The recommended prescriptions of the 3
an essential HSV disease. Regardless of antiviral agents are as follows:
whether this is because of a diminished viral

Table 2: Recommended Dosages of the Antiviral Agents for Genital Herpes Infection
Indication Acyclovir Valacyclovir Famciclovir
First episode 400 mg tid OR 200 mg 5 1000 mg bid (for 7- 250 mg tid (for 7-10 d)
times/d (for 7-10 d) 10 d)
Recurrent 400 mg tid (for 3-5 d) OR 800 500 mg bid (for 3 1000 mg bid (for 1 d)
mg PO tid (for 2 d) d)
Daily suppression 400 mg bid 500 mg qd or 1000 250 mg bid
mg qd (if more
than 9
recurrences/year)

Table 3: Recommended Dosages of the Antiviral Agents for Genital Herpes Infection for the pregnant
women
Indication Acyclovir Valacyclovir
Primary or first-episode 400mg TID for 7-10 days 1g orally BID for 7-10 days
infection
Symptomatic recurrent 400mg TID for 5 days OR 800mg 500g orally, BID, for 3 days or 1g
episodes orally BID for 5 days orally, daily, for 5 days
Daily suppression 400mg orally, TID from 36 weeks 500mg orally, BID, from 36 weeks
estimated gestational age until estimated gestational age until delivery
delivery
Severe or disseminated 5-10mg/kg, intravenously, every 8
disease hours for 2-7 days, then orally
therapy for primary infection to
complete 10 days

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 Infection with Genital Herpes Virus…

Prevention of postnatal transmission acyclovir gathering. No new-born child in either

 In 25% of cases a likely source of assembles created neonatal HSV, and no gravida
postnatal infection is responsible, experienced poisonous quality from acyclovir.
typically a close relative of the mother The creators reasoned that the example measure
[21]. was too little to exhibit a critical advantage from
 Efforts to prevent postnatal transmission acyclovir and suggested that acyclovir be
of HSV are consequently essential and utilized just in clinical trials. Since that time,
advice should be given to the mother. extra randomized clinical investigations have
 The mother and all those with herpetic been played out, each exhibiting non-significant
lesions who may be in contact with the diminishments in caesarean conveyances for
neonate, including staff, should practice intermittent HSV flare-ups and no distinctions
careful hand hygiene. in neonatal results. A meta-analysis in 2003

 People with oral herpetic lesions (cold combined the results of five randomized clinical
sores) must not kiss the neonate. trials assessing the use
Strategies to prevent HSV transmission of antenatal suppressive acyclovir in 799 gravidas
  [24]
Antiviral suppression for gravidas with
. The results of the meta-analysis are
first-episode infections during pregnancy shown in Table 3.
Distinguishing that recurrent infections occur Table 3: Antiviral Trial Results
more regularly within the first year after a Outcome Acyclovir Placebo OR
primary infection, Scott et al randomized 46 % % (95% CI)
gravidas with first genital outbreak amid Recurrent 3.5 15.5 0.25
pregnancy to either acyclovir (400 mg tid) or HSV infection (0.15-0.40)
placebo beginning at 36 weeks' gestation [22]. at delivery
Women receiving acyclovir experienced a Asymptomatic 0 3.1 0.09
major decrease in the percentage of HSV HSV shedding (0.02-0.39)
recurrences at delivery and caesarean deliveries at delivery
for HSV (36% versus 0%). On the other hand, Total 16.7 25.9 0.61
the decrease in the total number of caesarean cesarean (0.43-0.86)
deliveries in enrolled women was not deliveries
statistically noteworthy (40% versus 19%). No Cesarean 4 14.7 0.30
patients in this examination had asymptomatic deliveries for (0.13-0.67)
shedding at the season of conveyance, and no HSV
new-born child created neonatal HSV
contamination or had complexities from
acyclovir. No endeavour was made to recognize All of the observed results were significantly
primary infections, non-primary first-episode reduced with suppressive use of acyclovir (no
infections, or first perceived recurrent
95% confidence interval comprised the value of
infections. This examination was, be that as it
1). No cases of neonatal herpes were stated in
may, the first to show the utility of antiviral
any of the 799 infants in all 5 studies, whether in
concealment in diminishing the quantity of
the acyclovir or placebo group. Because of the
repeats at time of delivery.
fewness of neonatal HSV infections, far larger
 numbers of subjects are necessary to determine
Routine antiviral suppression for
a significant difference in this important result.
gravidas with a history of genital HSV
In 1998, Brocklehurst and partners played out a
Recommended regimen for suppressive therapy
twofold visually impaired fake treatment
for pregnant women with recurrent genital
controlled trial that included 63 ladies with a
herpes
background marked by intermittent HSV disease
[23]  Acyclovir 400mg orally three times per
. These ladies were randomized to either
acyclovir (200 mg qid) or placebo, both starts at  day
 Valacyclovir 500mg orally twice a day
36 weeks' development. Non-significant
diminishments were found in repetitive HSV
flare-ups at conveyance, caesarean conveyances Identification of seronegative gravidas at risk
for HSV, and aggregate caesareans in the for primary and non-primary first-episode
genital HSV infections

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 Ahmad Derham et al.

This method is the most aspiring of all mostly a sexually-transmitted disease.

strategies to avoid vertical transmission. Its Currently, the American College of
reasoning is based on the observation that most Obstetricians and Gynecologists has not
neonatal HSV transmission happens not in recognized routine maternal HSV serology
gravidas with a history of genital HSV, but screening [27].
somewhat in women who have primary or non-
primary first-episode genital infections at the CONCLUSION
time of labor. If routine serologic screening Because of the high prevalence of genital
shows that a woman was at hazard for primary HSV infections and the potentially devastating
HSV (no antibodies) or non-primary first- consequences of neonatal HSV disease, it is
episode infection either only HSV-1 or HSV-2, significant that clinicians understand how to
she might be counselled to prevent genital- distinguish and treat neonatal HSV infections in
genital or oral-genital contact in order to avoid a timely manner, and how best to decrease
new genital infections throughout the third mother-to-child transmission. Results for
trimester of pregnancy and, therefore, decrease neonatal HSV infections have improved in the
neonatal HSV infections. past 30 years, but there is continued need for
An alternate strategy would be to check the further studies to help maximize the prevention
serologic status of the sexual partner too and to and treatment of this disease.
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