Identification

Herpes simplex infection (HSV) is a viral infection characterized by local and systemic symptoms, latent and recurring localized at the entrance gate. There are two Herpes simplex, HSV1 and HSV2 viruses; which produce distinct clinical syndromes according to the input gate, respectively, oral or genital mucosa.

 Primary infection with HSV1 generally occurs in childhood at oral level, can be easy and inapparent. The signs disappear but the virus remains dormant. Due to a stimulus that varies from person to person, the infection may recur (relapse). ^[1]Cernescu C., Virusologie medicala, Ed Medicala 2008 ^[2]CDC, Heymann D.L., Manual de management al bolilor transmisibile. 2012.

Manifestations cliniceîn infection with HSV1:

• Gingivostomatită herpes,
• Herpes labial,
• Genital herpes. ^[3]Cernescu C., Virusologie medicala, Ed Medicala 2008|\ ^[4]CDC, Heymann D.L., Manual de management al bolilor transmisibile. 2012′. Clinically there are several syndromes of genital herpes:

1. Primary genital Herpes: with local lesions that last 3-6 weeks
2. Non-primary genital Herpes: In a patient presenting antibodies for HSV2, the manifestations are similar to recurring episodes
3. Recurring genital Herpes: The manifestations are lighter, the lesions persist 3-10 days
4. Asymptomatic genital Herpes: Patient presenting anti HSV1 antibodies without symptoms of herpes in history; 2/3 of the seropositive women acquired the asymptomatic infection. ^[5] Greene MF … and Resnik`s Maternal-Fetal Medicine: Principles and Practice. Elsevier, 2008, In: Herpes Simplex Infection. ^[6] *** Medscape. 2017 Genital Herpes in Pregnancy...

The primary infection with HSV2 has several clinical forms:

• Vulvovaginită,
• Cervicitis
• Endometritis
• Urethritis
• Herpes perianal,
• Panariţiu herpes,
• Pharyngitis herpes,
• Herpes meningitis.

Pregnant:

All pregnant women should be asked if they have a history of genital herpes. At the beginning of labor, all women should be asked carefully about the symptoms of genital herpes, including symptoms of prodromal (starting), all women should be carefully examined for herpes lesions.

Attention! The woman infected with HSV can develop infectious lesions for the newborn during childbirth.

Women without symptoms or signs of genital herpes may be born vaginally. Although the C-section does not completely eliminate the risk of HSV transmission in the newborn, women with recurrent genital herpes lesions at the onset of labour should be given a caesarean to reduce the risk of neonatal infection with HSV. ^[7]*** CDC, 2015 Sexually Transmitted Diseases Treatment Guidelines.\..

The transmission of the infection to the fetus depends on the type of maternal infection; This distinguishes several situations encountered in medical practice with different frequencies.

The risk of neonatal herpes according to Mother’s Status: ^[8]Vlădăreanu R., Afecțiunile medicale asociate sarcinii. Infomedica, Bucuresti, 1999, p.279.

1. Primoinfecțiala pregnant in Prepartum (or 1 month before birth) is at risk of neonatal herpes 50-75%.
2. Recurrence of pregnant in prepartum (or a month before birth) is at risk of neonatal herpes 2-5%.
3. History of genital herpes in pregnant or partner, without genital lesions in prepartum give a risk of neonatal herpes 1 to 1,000 births.
4. The absence of a history of genital herpes and genital lesions in pregnant prepartum give a risk of neonatal herpes 1 to 10,000 births.

If the prepartum (or a month before birth) occurs Primoinfecţia or a recurrence, the protocol is to perform the Caesarean.

The risk of transmission to the fetus is significantly higher in the case of women who acquire infection with HSV1 or HSV2 during pregnancy compared to those who have a chronic infection that reactivates at birth, 25-50% vs. < 1%. ^[9]Cernescu C., Virusologie medicala, Ed Medicala 2008`' <sup>[10]</sup>CDC, Heymann D.L., Manual de management al bolilor transmisibile. 2012`' ^[11]*** CDC, 2015 Sexually Transmitted Diseases Treatment Guidelines~’.. Therefore, 50-80% of cases of neonatal herpes are derived from mothers who are infected during pregnancy towards the end of it.

 

Congenital herpes defined prenatal cainfecţie of the fetus with HSV is extremely rare and frequently balances with the death of the fetus in the uterus. Those who survive have the following manifestations:

• Vesicular eruption,
• Ocular disorders (corioretinită, microphthalmia, cataract),
• Neurological disorders (Calcificăriintracerebrale, microcephaly, convulsions, multicystic),
• Growth retardation,
• Disorders in psychomotor development.

In the newborn mother infected with HSV:

• Neonatal herpes is a major problem.
• 50% of newborns in which the infection was confirmed by the production of cell cultures for viral isolation does not exhibit typical lesions on the skin or mucous membranes.
• Estimation of the frequency of herpes infection is subject to errors.
• Most neonatal herpes infections occur by contact of the fetus with maternal secretions during the crossing of the birth canal.
• It is estimated that 70-85% of neonatal HSV is caused by HSV2, but the newborn can be infected with HSV1, which accounts for approximately 1/3 of the etiology of genital herpes infections.
• HSV2 infection has a worse prognosis than HSV1.
• Primoinfecţia Herpes of the newborn is always symptomatic and manifests itself in the first 4 weeks postpartum under 3 different forms: ^[12]CDC, Heymann D.L., Manual de management al bolilor transmisibile. 2012~ ^[13]Kimberlin DW si colab. Committee on Infectious Diseases, et al. Guidance on management … herpes lesions. Pediatrics 2013;131:383–6.

1. Skin, eye, mouth (SEM)

• Damage to the skin, eyes and mouth.
• SEM is the most common, most characteristic and most readily diagnosed form of neonatal HSV.
• It comes from birth or zilele2-7.
• At the cutaneous level, blisters appear in the bouquet at the level of breech.
• The eye appears conjunctivitis or keratoconjunctivitis herpes.
• Herpes gingivostomatită and pharyngitis occur in the oral cavity.
• Without treatment, this form can be transformed into the next two forms.

2. Central nervous system damage

• Debuts after the 11th day of life with a painting of Pascal-severe encephalitis:
• Fever
• Irritability
• Encephalitis syndrome (lethargy, convulsions, Fontanelle, Opistotonus)
• It can evolve to a coma after 2-3 days.
• In CSF there are changes that may suggest diagnosis: pleocytosis, Albuminorahie, interferon
• Despite initiation of treatment, more than 50% of children with this form present neurological sequelae:
  • Developmental Disorders,
  • Epilepsy
  • Blindness
  • Cognitive disabilities.

3. Disseminated neonatal herpes is manifested as bacterial sepsis, with plurivisceraleal impairments, which is nediferențiabil clinically.

• The mortality rate is very high, 30%-50%, even with antiviral therapy.
• Onset is uncharacteristic, with fever, breast refusal, apnea, petechiae, jaundice, hypoglycaemia, acidosis, which evolves towards multiorganic damage:
  • CNS damage,
  • Hepatitis Fasciitis,
  • Interstitial pneumonia,
  • Myocarditis
  • Enterocolitis
  • Disseminated intravascular coagulation (CID),
  • Shock.
• 50% of cases are diagnosed by the presence of Erupţiieritemato-vesicular considered patognomonice. ^[14]Cernescu C., Virusologie medicala, Ed Medicala 2008~| ^[15]CDC, Heymann D.L., Manual de management al bolilor transmisibile. 2012′: ^[16]*** CDC, 2015 Sexually Transmitted Diseases Treatment Guidelines.`’..

 

Diagnosis of HSV infection in pregnant:

• In the case of symptomatic infection in pregnant, diagnosis is clinical, based on the appearance of lesions.
• Most of the time, however, non-specific presentations or light manifestations require a diagnosis of certainty, with importance in pregnancy management and the risk of transmitting the infection to the fetus.

 

The diagnostic methods of the HSV infection are:

1.  Virological Diagnosis

• Isolate HSV in cell cultures – gold standard (gold standard), but the method cannot be used in asymptomatic infections.
• The highlighting of viral antigens with the mark fluorescent or enzymatic antibodies (IFD, ELISA) – Cannot diagnose asymptomatic infections.
• Evidence of HSV DNA through PCR – can diagnose asymptomatic infections. The most useful method of diagnosis is the detection of HSV DNA through PCR. ^[17]Cernescu C., Virusologie medicala, Ed Medicala 2008″‘ ^[18]CDC, Heymann D.L., Manual de management al bolilor transmisibile. 2012″‘.

2. Serological diagnosis

• It is used to detect anti-HSV antibodies when other techniques are ineffective or inaccessible.
• In an infection with HSV, serological diagnosis is useful only in the following cases:
  • Diagnosis of Primoinfecţiei by highlighting the seroconversion or detection of specific IgM anti-HSV antibodies,
  • Diagnosis of asymptomatic excretion,
  • Diagnosis of herpes encephalitis,
  • Pregnant women are partners of people with active injuries, so they are at risk of getting infected from partners,
  • Retrospective diagnosis by detecting specific IgG anti-HSV antibodies.
• There are serological tests that do not differentiate between the two types of viruses but also specific tests of type (ELISA or Western Blot – Reference test). However, the specific type-diagnosis is not essential because the treatment regimen does not differ. ^[19]Cernescu C., Virusologie medicala, Ed Medicala 2008:` <sup>[20]</sup>CDC, Heymann D.L., Manual de management al bolilor transmisibile. 2012:`.

 Histopathological Diagnosis:

• Cytodiagnosis Tzanck or Pap test (quick and inexpensive but not specific and subjective test according to the evaluator).

 

Diagnosis of infection in the newborn:

• If the fetus has been exposed to the perinatal HSV, the secretions from the conjunctiva, oropharynx and rectum will be harvested in the first 24-48 postpartum hours.
• The newborn will be investigated cerebral imaging and ophthalmologically tested.
• Any rash vesicular to a newborn should be investigated for herpes infection.
• In 50% of cases, rash vesicular is absent, therefore all children under 4 weeks of CNS infection or septic syndrome should be evaluated for HSV, preferably by
• In the case of newborns with fever and pleocitosis, it is recommended PCR from the CSF for the detection of HSV DNA. ^[21]Cernescu C., Virusologie medicala, Ed Medicala 2008:| ^[22]CDC, Heymann D.L., Manual de management al bolilor transmisibile. 2012:| ^[23] *** CDC, 2015 Sexually Transmitted Diseases Treatment Guidelines.`..

 

Note Bene. In this document, the laboratory diagnosis was not treated in HSV infection, but there were several elements related to pregnancy and newborn. For the complete diagnosis of this infection, those interested will be addressed to infectionists physicians.

 

The infectious agent

HSV1 and HSV2 belong to the from Herpesviridae family family, subfamily Alfaherpesvirinae. The characteristic of this family is latency. Once the virus enters through skin lesions in the epithelial cells of the mucous membranes or epithelium, it persists in a dormant condition in the nerve tissues where it migrates:

• HSV1 usually persists in the trigeminal ganglion and causes orofaciale lesions,
• HSV2 has as its headquarters the lumbosacral ganglion and affects the genitourinary-annals area.

Both types can cause injuries in any of the 2 areas and cannot be clinically differentiated. ^[24]Cernescu C., Virusologie medicala, Ed Medicala 2008`|`.

 

Incidence and prevalence

• The real number of people infected with HSV is much higher than those diagnosed precisely due to the existence in a large proportion of asymptomatic infected patients.
• Studies conducted by PROF. Univ. Dr. Costin Callaway estimates that around 20% of the population of Bucharest is seropositive for HSV2, the percentage being higher in women and growing by the age of 15 years. Very important is that only a quarter of those seropositive for HSV2 have a symptomatic genital herpes, and in the case of women, the percentage is higher. ^[25]Cernescu C., Virusologie medicala, Ed Medicala 2008.'.
• In recent years, genital herpes has become one of the most common sexually transmitted diseases, recording alarming increases in the incidence thus, in the US, 1 in 5 adults is infected.
• In the US, 2% of women make genital herpes during pregnancy, and 25-65% of pregnant women have genital infection with HSV1 or HSV2. Several studies have reported an incidence of neonatal herpes of 8, 12, 31, 60 cases to 100,000 by naşterişi about 1500-2000 new cases annually. ^[26] *** CDC, 2015 Sexually Transmitted Diseases Treatment Guidelines.^. ^[27]*** Medscape. 2017 Genital Herpes in Pregnancy...
• Worldwide, 50-90% of adults present circulating antibodies against HSV; Infection with HSV 1 occurs before 5 years. HSV2 infection can usually occur with the start of sexual life.

Source

The infected man is the only source. ^[28]CDC, Heymann D.L., Manual de management al bolilor transmisibile. 2012.,..

Method of transmission

• The most common way of transmitting is contact with the saliva of a HSV1.
• Other routes of transmission:
  • Direct mucocutaneous-Snot contact with an ulcered herpes lesion,
  • Contact with secretions from asymptomatic excretorii HSV (saliva, genital secretion),
  • The child’s passing through the birth canal,
  • Autoinoculation: Transported through fingers from oral lesions to the genitourinary-annals or eye area (more frequently in children),
  • Transmission by means of contaminated objects (possible but very rare due to the sensitivity of viruses to the external environment),
  • Transplacental (less frequently),
  • Postpartum (5% by contact with the mother or medical staff carrying herpes or asymptomatic excretory lesions). ^[29] Cernescu C., Virusologie medicala, Ed Medicala 2008* ^[30]CDC, Heymann D.L., Manual de management al bolilor transmisibile. 2012* ^[31] *** CDC, 2015 Sexually Transmitted Diseases Treatment Guidelines.*. ^[32] *** Medscape. 2017 Genital Herpes in Pregnancy.*..

Risk groups

• Newborns from genitally infected mothers with HSV during pregnancy towards the end of it.
• Health personnel who come into contact with asymptomatic excretorii of herpes virus.
• The risk of transmission from an infected mother to newborns is:
  • High (30%-50%) among women who acquire genital herpes near birth,
  • Decreased (< 1%) in women with prenatal histories of recurrent herpes or who acquire genital HSV in the first half of pregnancy ^[33]Pinninti SG, Kimberlin DW. Maternal and neonatal herpes simplex virus infections. Am J Perinatol 2013; 30:113–9 ^[34]Brown ZA si colab. Effect of serologic status … from mother to infant. JAMA 2003; 289:203–9.
• Children in general. ^[35] CDC, Heymann D.L., Manual de management al bolilor transmisibile. 2012.\.

 

Incubation period

2 to 12 days. ^[36]Cernescu C., Virusologie medicala, Ed Medicala 2008`.' <sup>[37]</sup>CDC, Heymann D.L., Manual de management al bolilor transmisibile. 2012`.'.

Infectiousness Period

2-7 weeks after primary infection. The virus may intermittently remove the mucous membranes (asymptomatic excretion). In the case of recurrences, the virus can be removed up to 7 days after the lesions have disappeared. ^[38] CDC, Heymann D.L., Manual de management al bolilor transmisibile. 2012.|.

 

Prophylaxis

Pregnant:

• Most mothers of newborns who acquire neonatal herpes do not have the histories of obvious clinical genital herpes. ^[39]Brown ZA, et al. The acquisition of herpes simplex virus during pregnancy. N Engl J Med 1997; 337:509–15. ^[40]Pinninti SG, Kimberlin DW. Maternal and neonatal herpes simplex virus infections. Am J Perinatol 2013; 30:113–9.'.
• The high rate of asymptomatic infections with HSV and undiagnosed poses difficulty in preventing.
• To decrease the number of cases with neonatal HSV infection, the target is the identification of mothers “at risk” and the first step is to determine as early as possible the serological status of pregnant women.
• The history of HSV infection from both partners should be obtained from the first prenatal visit.
• Women with a history of negative HSV and especially those with a positive history partner should be advised not to have sexual relations during recurrences and to use the condom for the whole period of pregnancy, even if the partner has no lesions Active.
• Women who do not know that they have genital herpes should be advised to avoid vaginal contact during the third trimester with known or suspected genital herpes partners.
• Pregnant women without herpes known should be advised to refrain from responsive oral sex during the third trimester of pregnancy with known partners or suspected to have oro-labial herpes. ^[41] Brown ZA et al. The acquisition of herpes simplex virus during pregnancy. N Engl J Med 1997; 337:509–15.. ^[42]Pinninti SG, Kimberlin DW. Maternal and neonatal herpes simplex virus infections. Am J Perinatol 2013; 30:113–9.. ^[43]Brown ZA et al. Effect of serologic status and cesarean delivery…to infant. JAMA 2003; 289:203–9. ^[44]Brown ZA et al. Neonatal herpes simplex virus infection … at the time of labor. N Engl J Med 1991; 324:1247–52.. Abstinence throughout pregnancy is the best choice.
• Pregnant seronegative HSV2 should be retested prepartum, especially in the following situations:
  • Labor is triggered prematurely,
  • The membranes break premature,
  • A delay occurs in the intrauterine development of the fetus.
• It is recommended that women with frequent recurring episodes or active lesions near childbirth receive prophylactic treatment with Acyclovir.
• For any woman showing signs of HSV infection, a careful examination of the vulva, vagina and cervix is recommended at the onset of labor.
• Specific serological tests can be useful for identifying women who are at risk of infection with HSV, and guidance advice on the risk of getting infected with genital herpes during pregnancy should be ensured.  ^[45] Brown ZA et al. The acquisition of herpes simplex virus during pregnancy. N Engl J Med 1997; 337:509–15.*’. ^[46]Pinninti SG, Kimberlin DW. Maternal and neonatal herpes simplex virus infections. Am J Perinatol 2013; 30:113–9.”. ^[47]Brown ZA et al. Effect of serologic status and cesarean delivery…to infant. JAMA 2003; 289:203–9.' ^[48]Brown ZA et al. Neonatal herpes simplex virus infection … at the time of labor. N Engl J Med 1991; 324:1247–52.'.

In newborn

• The most effective method of prevention of neonatal HSV infection is the avoidance of fetal exposure to primary herpes lesions, the risk of transmission is lower in the case of recurring lesions.
• Cesarean birth is recommended.
• It will avoid the application of fetal electrodes on the scalp for monitoring during labor or forceps application, as they increase the risk of transmitting HSV.
• Newborns from mothers with active herpes genital lesions should be insulated and treated with Aciclovir.
• As neonatal herpes can be acquired postnatally, it is recommended that mothers, family members, medical staff with active herpes lesions (oral or anywhere on the skin) avoid direct contact with the newborn.
• The prevention of neonatal herpes depends both on preventing the acquisition of genital infection in pregnant women during pregnancy and avoiding the newborn exposure to herpes lesions. Since the risk for herpes is the largest in newborns of women who acquire genital herpes in the last trimester of pregnancy, these women should be consulted both by the gynecologist and the specialist in infectious diseases. ^[49] Brown ZA et al. The acquisition of herpes simplex virus during pregnancy. N Engl J Med 1997; 337:509–15.’. ^[50]Pinninti SG, Kimberlin DW. Maternal and neonatal herpes simplex virus infections. Am J Perinatol 2013; 30:113–9.’. ^[51]Brown ZA et al. Effect of serologic status and cesarean delivery…to infant. JAMA 2003; 289:203–9.\ ^[52]Brown ZA et al. Neonatal herpes simplex virus infection … at the time of labor. N Engl J Med 1991; 324:1247–52”.

Vaccination

There is currently no vaccine. ^[53]Cernescu C., Virusologie medicala, Ed Medicala 2008.~' ^[54]CDC, Heymann D.L., Manual de management al bolilor transmisibile. 2012.~' ^[55] *** CDC, 2015 Sexually Transmitted Diseases Treatment Guidelines.’|..

Birth to the infected woman with HSV 

All pregnant women with suspicion of genital herpes infection or prodromal symptoms should be subjected to caesarean, even if the membranes are intact. ^[56] *** Medscape. 2017 Genital Herpes in Pregnancy.’...

Breastfeeding

If the mother has perimamelonare lesions there is a danger of transmitting the virus to the newborn. ^[57]CDC, Heymann D.L., Manual de management al bolilor transmisibile. 2012.`'.

Treatment

Acyclovir and Acyclovir derivatives. ^[58]Cernescu C., Virusologie medicala, Ed Medicala 2008.,`.

 

Bibliography

1. Cernescu C., Virusologie Medicală, Ed Medicala 2008
2. CDC, Heymann D.L., Management Manual of communicable diseases. 2012
3. Greene MF, Creasy RK, Resnik R, Iams JD, Lockwood CJ, Moore T. Creasy and Resnik’s maternal-Fetal Medicine: Principles and Practice. Elsevier, 2008, In: Herpes Simplex infection.
4. Vlădăreanu R., Medical conditions associated with pregnancy. Infomedica, Bucharest, 1999, p. 279.
5. *** CDC, 2015 Sexually transmitted diseases Treatment Guidelines. Retrieved: https://www.cdc.gov/std/tg2015/herpes.htm
6. Kimberlin DW, Baley J, Committee on Infectious diseases, et al. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. Paediatrics 2013; 131:383 – 6.
7. Brown ZA, Hedersleben S, Zeh J, et al. The acquisition of herpes simplex virus during pregnancy. N Engl J Med 1997; 337:509 – 15.
8. Pinninti SG, Kimberlin DW. Maternal and neonatal herpes simplex virus infections. Am J Perinatol 2013; 30:113 – 9.
9. Brown ZA, Wald A, Morrow RA, et al. Effect of serological status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. JAMA 2003; 289:203 – 9.
10. Brown ZA, Benedetti J, Ashley R, et al. Neonatal herpes simplex virus infection in relation to asymptomatic maternal infection at the time of labor. N Engl J Med 1991; 324:1247 – 52.
11. *** Medscape. 2017 Genital Herpes in Pregnancy. Retrieved: Http://emedicine.medscape.com/article/274874-overview