STUDENT PROJECT

GENITAL HERPES TYPE 2

SGD B10
Putu Emilia Dewi 1902511028
Shannen Callista 1902511051
George David 1902511074
Madeline Juliand Sitranata 1902511093
I Nyoman Wigraha Yoga 1902511109
Aurelius Filibertus Nong Vito 1902511128
Giovanca Verentzia Purnama 1902511148
Chrysanta Paramitha Karuniamaya 1902511170
Putu Rahayu Natalia Anggraini 1902511217
Komang Andjani Putri 1902511031
Marco 1902511057
Anesh Sharma 1902511251

PROGRAM STUDI SARJANA KEDOKTERAN

DAN PROFESI DOKTER
FAKULTAS KEDOKTERAN
UNIVERSITAS UDAYANA
DENPASAR
2020
 PREFACE

Praise to the Almighty God for His blessings, so the author can fulfill the student
project assignment in the Infection & Infectious Diseases Block entitled "Genital
Herpes Type 2" on time. This student project might not have been completed properly
without the help of various parties, for that the authors would like to thank:
1. Head of the Behavioral Changes and Disorders Block, dr. Made Susila Utama,
SpPD-KPTI, for arranging and guidance throughout the block.
2. Our Facilitator, Dr. dr. I A Ika Wahyuniari, M.Kes, for all of the direction, input,
and motivation in making this student project.
3. Our colleagues in the Undergraduate Medicine and Medical Profession Study
Program, Faculty of Medicine, Udayana University, for all of the support.
4. All parties that the author cannot mention one by one who participated in helping
in the completion of this student project.
The author hopes that this student project will be useful, inspire future research,
and increase the treasury of science in Indonesia.

Denpasar, 11 October 2020

Author

ii
 TABLE OF CONTENTS

COVER
PREFACE.......................................................................................................... ii
TABLE OF CONTENTS................................................................................. iii
TABLE OF iv
FIGURES......................................................................................
CHAPTER I INTRODUCTION…………………………………… 1
1.1 Background……………………………………… 1
1.2 Research Questions……………………………… 2
1.3 The Purposes of Writing………………………… 2
1.4 The Benefits of Writing………………………… 2
CHAPTER II CONTENTS…………………………………………… 3
2.1 Definition of Genital Herpes Type 2......………… 3
2.2 Epidemiology of Genital Herpes Type 2………… 3
2.3 Etiology and Risk Factors of Genital Herpes Type 3
2
2.4 Pathogenesis of Genital Herpes Type 4
2.....................
2.5 Diagnosis of Genital Herpes Type 4
2.........................
2.6 Differential Diagnosis of Genital Herpes Type 6
2......
2.7 Management of Genital Herpes Type 2..... 7
…………
2.8 Complications of Genital Herpes Type 2.....……… 8
2.9 Preventions of Genital Herpes Type 2.....………… 9
2.10 Prognosis of Genital Herpes Type 2.....………… 9
CHAPTER III SUMMARY.......……………………………………….. 10
REFERENCES................................................................................................ 11

iii
 TABLE OF FIGURES

Figure 2.1 Recommended Viral Diagnostic Algorithm for Genital Herpes Type 2. 5
Figure 2.2 Methods to Detect HSV and HSV-Spesific Antibody.............................6
Figure 2.3 HSV Laboratory Findings and Correlating Genital Herpes Symptoms. .6

iv
 1

CHAPTER 1
INTRODUCTION
1.1 Background
Indonesia is a very diverse country with many different attitudes towards
sexual relationship. The morale education of Indonesians typically includes sex
education in its core. Sex education in Indonesia is pretty much still a taboo subject to
cover. Indonesians view sex as something that cannot be expressed openly, in some
parts due to the education from religious activities, which is the building blocks of
Indonesia. This attitude towards sex is a two-edged sword. It can prevent free sex from
happening, but it also can reduce sex-related knowledge, which can result in more
cases of sexually transmitted infections or STIs.
Indonesia has many cases of free sex occurring in teenagers. One example of
that is the 2019 case in which 3 high school students with same-sex interests infected
with HIV virus. That is the result of free, unsafe sex. Students in Indonesia must be
educated to use safe sex procedures to avoid STIs. This is, again, prevented by the
taboo nature of sex education in Indonesia.
Herpes simplex virus type 2 (HSV-2) is a kind of sexually transmitted
infection, unlike herpes simplex virus type 1 (HSV-1) which is transmitted by non-
sexual contact1. HSV-2 is the most common cause of genital ulcers in many countries,
and it also has a great amount of prevalence around the world with an estimate of 417
million people in 2012.1 Higher seroprevalences are found internationally among
people who change sexual partners regularly and among homosexual men, which is a
sign that free, unsafe sex is actually the real problem in the spread of HSV-2 virus.2
There is one aspect of HSV-2 virus infection that must be focused on: the
asymptomatic infection. Evidence suggested that women have a significantly higher
seroprevalence than men. This is caused by men having asymptomatic HSV-2
infection more than women, resulting in higher virus transmission rates from men to
women.2 More people should be informed of asymptomatic infection so they can make
use of safer sex, avoiding more HSV-2 infections.
 2

The intended result of this paper is increased knowledge about HSV-2 infection
in more people and more clinician. This paper is also intended to provide a complete
insight to HSV-2 infection, so more people can avoid it.
1.2 Research Questions
The research questions of this writing include:
1. What is genital herpes type 2 infection?
2. How are the epidemiology, etiology and risk factors, pathogenesis, diagnosis,
differential diagnoses, and complications of genital herpes type 2?
3. How to manage and prevent the infection of genital herpes type 2?
4. How is the prognosis for patients with genital herpes type 2 infection?
1.3 Purposes of the Writing
Hence, the purposes of this writing are:
1. To understand what genital herpes type 2 infection is;
2. To enhance the knowledge about epidemiology, etiology and risk factors,
pathogenesis, diagnosis, differential diagnoses, and complications of genital
herpes type 2;
3. To understand the management and prevention methods of genital herpes type
2 infection;
4. To understand the prognosis for patients with genital herpes type 2 infection.
1.4 The Benefits of Writing
The benefits to be achieved from this writing are:
1. Public can acknowledge the importance of treating and preventing genital
herpes type 2 infection;
2. Medical community can further understand about the epidemiology, etiology
and risk factors, pathogenesis, diagnosis, differential diagnoses, complications,
management methods, prevention, and prognosis of genital herpes type 2
infection; and
3. Authors can enhance their knowledge about genital herpes type 2 infection.
 3

CHAPTER II
CONTENTS
2.1 Definition of Genital Herpes Type 2
Genital herpes type 2 caused by the HSV-2. HSV-2 is a family of Herpesviridae.
The virus occurs as either a primary or recurrent infection. 3 Reservoirs of this virus are
from human mucosa and ganglia, mostly transmit from sexual contact. HSV infect in
the mucosal epithelial cells and make a formation of vesicles, the virus travel to
ganglion and become long life latent infection. HSV-2 generally occur below the
waist. In genital infection the virus settles in sacral nerve ganglia. The systemic effect
of genital infections are painful genital vesicles, systemic effects like fever, malaise,
and myalgia.4 Genital herpes is one of the most common Sexually Transmitted
Infections (STI). HSV-2 infection commonly affecting adults ages 12 and older. This
infection often underestimated by people, make the symptoms become disguised.3
2.2 Epidemiology of Genital Herpes Type 2
There is an estimate of around 23.9 million people who are infected from HSV-2,
with people around the age of between 15 to 49 years and an incidence of 0.6%. Out of
this, around 14.7 million were women while 9.2 million were men. As prevalence
increased, there was an overall trend of decreasing incidence with age.5 The prevalence
of HSV-2 is 11.9% in America. It is highest amongst the Hispanic Black People and
lowest amongst the non-Hispanic Asian people. More so, prevalence can be affected
due to age, sex and race.6 Seroprevalence of HSV-2 is in range of few percentage
points without major differences in seroprevalence by nationality. The nationality-
specific seroprevalence was 6.0% in Qataris, 5.3% in Iranians, 3.1% in Sudanese and
0.5% in Pakistanis. Hence, these findings help to contribute towards our understanding
about the epidemiology of the HSV 2.7
2.3 Etiology and Risk Factors of Genital Herpes Type 2
HSV-2 can be transmitted during sexual activity. It directly spread through body
fluids from seropositive individuals. HSV can only remain for few days outside of
human body.3 Most of individual with HSV-2 are asymptomatic in primary infection.
vesicles can appear in 4-7 days after sexual contact. In first infection, virus can stay in
 4

sacral ganglion and recurrent in the present of low immune system. Other factors such
as fever, UV light, menstruation, stress or trauma can trigger the recurrent of genital
herpes type 2.8
There are several risk factors of HSV-2. Some of them are early sexual relations,
previous history of STDs, and multiple sexual partners. Pregnant woman have a high
risk to get HSV-2 infection if they previously had HIV. Patients with HIV tend to have
HSV-2. HIV can be a gateway to HSV-2 and reversely. Woman in tertiary health
center also have a higher risk to genital herpes infection.9
2.4 Pathogenesis of Genital Herpes Type 2
The transmission of HSV-2 usually by genital contact, with someone’s skin, sores,
genital surface, or fluid that contain with the virus. 10 After getting contact with
mucosal surfaces or abraded skin, virus will replicate in the site of the primary
infection (come from at the site of contact). In this replication phase, the viral envelope
will fuse with the membrane cell of the mucous membrane with the protection of HSV
glycoprotein C, while the DNA of HSV will incorporated into the nucleus. The capsid
will be transported to the dorsal root ganglia via retrograde. Latency phase can occur
after the viral replication in the ganglia, and it can lead to recurrent clinical outbreaks.
Specifically, the HSV-2 reactivation more efficient in the lumbosacral ganglia. The
more severe the primary infection, the more likely someone gets recurrent infection.11
2.5 Diagnosis of Genital Herpes Type 2
The diagnosis of genital herpes type 2 can be confirmed clinically through history
and physical examination because the lesions caused by this disease are generally
typical so that no further laboratory examination is necessary before the administration
of therapy. However, we need to do some laboratory examinations to confirm the
diagnosis in atypical lesions cases and differentiate between infections caused by
HSV-1 and HSV-2. The World Health Organization Guidelines for The Treatment of
Herpes Simplex Virus states that the diagnosis of HSV-2 can be made through the
detection of viral culture antigens, and nucleic acid amplification tests (NAATs) for
examining viral DNA.1 Serologic tests also can be performed to detect specific HSV-2
antibodies in patients, namely anti-HSV-2 IgG or IgM. Other supporting tests that can
 5

be done are antigen detection through enzyme immunoassay or fluorescent antibody

and polymerase chain reaction (PCR)12,13. The diagnosis can be seen in Figure 2.1.8

Figure 2.1 Recommended Viral Diagnostic Algorithm for Genital Herpes Type 2
In Figure 2.1, the laboratory tests are only performed for atypical lesions. The
resulting swabs of these lesions can be transported at room temperature or cooled at 4 °
C. Then, the lesion will undergo PCR and HSV-1/2 genotypic resistance testing using
thymidine kinase analysis (TK analysis). The detection of HSV and HSV-specific
antibody can be seen in Figure 2.2, while the HSV laboratory findings and correlating
genital herpes symptoms can be seen in Figure 2.3.8

Fig
ure 2.2 Methods to Detect HSV and HSV-Spesific Antibody
Of these tests, the NAATs test is more often used in clinical situations because it
provides high sensitivity, fast results, and ease of specimen collection and
 6

transportation.1 Meanwhile, according to the "Panduan Praktik Klinis bagi Dokter

Spesialis Kulit dan Kelamin di Indonesia", the sensitivity of examination with vesicles'
viral culture can reach 70%. Meanwhile, the sensitivity of cultures taken from pustules
and crusts is only less than 40%.12

Figure 2.3 HSV Laboratory Findings and Correlating Genital Herpes Symptoms
2.6 Differential Diagnosis of Genital Herpes Type 2
The symptoms of genital herpes Type 2 usually appear around the genital area,
like penis, vagina, buttocks, or anus. The symptoms of genital herpes type 2 are
tingling, itching, or burning around genital areas, sores, genital lesion, or blisters that
may break open then ooze fluid and form a crust. The other signs are feeling pain
when urinating, or swollen lymph nodes on the groin.14
The prevalence of STI is related to how many times the patient changes partner
and how many times they have sex without condom. It’s possible that the person has
multiple STI at the same time, considering it has similar method of infection. To make
sure the diagnosis is correct, the physician needs to compare the clinical symptoms
with other disease.15 There are few differential diagnosis of genital herpes type 2, one
of them is syphilis. Syphilis is STI that has similar symptoms like swollen lymph
nodes and fever, it may be associated with herpes disease. 16 Other differential
diagnosis include candidiasis which cause irritation on the vagina, burning sensation
while urinating, swelling on the vulva area. 17 Granuloma Inguinale also can be the
 7

differential diagnosis of herpes because there will be sores around the anal area if the
body get infected.18
2.7 Management of Genital Herpes Type 2
Antiviral therapy in genital herpes type 2 is divided into three depending on the
condition of the patient.19
1. First Clinical Episode of Genital HSV Infection
Patients experiencing the first episode of genital herpes should receive antiviral
therapy.19 Several antiviral drugs are recommended for people with HIV, people
with weakened immune systems, sufferers with severe episodes and pregnant
women are Acyclovir 400 mg orally three times a day (standard dose), Acyclovir
200 mg orally five times a day, Valaciclovir 500 mg orally twice daily, and
Famciclovir 250 mg orally three times a day. All therapy was given in ten days.1
2. Recurrent Clinical Episode of Genital HSV Infection (Episodic Therapy)
Therapy given in this phase should be started within one day after the onset of
the lesion or during the previous prodrome. 19 Several antiviral drugs are
recommended for people with HIV pregnant women, and people with weakened
immune systems are Acyclovir 400 mg orally three times a day for 5 days,
Acyclovir 800 mg twice daily for 5 days, or 800 mg three times daily for 2 days,
Valaciclovir 500 mg orally twice daily for 3 days, and Famciclovir 250 mg twice
daily for 5 days. Dosage for people living with HIV and immunocompromised
people are Acyclovir 400 mg orally three times a day for 5 days, Valaciclovir 500
mg orally twice daily for 5 days, and Famciclovir 500 mg orally twice a day for 5
days.1
3. Recurrent Clinical Episodes of Genital HSV Infection That are Frequent, Severe
or Cause Distress (Suppressive Therapy)
This therapy can reduce the recurrence frequency of genital herpes by 70% -
80%. Suppressive therapy can also reduce transmission which is frequently used
by people who have multiple partners (including MSM) and by those who are
HSV-2 seropositive without a history of genital herpes. 19 Several antiviral drugs are
recommended for people with HIV pregnant women, and people with weakened
 8

immune systems are Acyclovir 400 mg orally twice daily, Valaciclovir 500 mg
orally once a day, Famciclovir 250 mg orally twice a day. Dosage for people living
with HIV and immunocompromised people are Acyclovir 400 mg orally twice
daily, Valaciclovir 500 mg orally twice a day, and Famciclovir 500 mg orally twice
a day.1
2.8 Complications of Genital Herpes Type 2
1. Neurological complications

a. Aseptic Meningitis:

Aseptic meningitis occurs in 36% of women and 13% of men with primary HSV-2
infection (p < 0.001) with symptoms such as stiff neck, headache, and photophobia,
with or without fever. These patients with primary HSV-2 infections were ill enough
to require hospitalization; all had fever, severe headache, malaise, photophobia, nuchal
rigidity, positive Kernig's or Brudzinski's signs, and all had a lymphocytic pleocytosis
in cerebrospinal fluid.20

b. Extragenital Lesions:

Extragenital mucocutaneous lesions developed in 26% of women and 10% of men

with primary HSV-2 infection (p < 0.05). These lesions were most frequently located
on the but-tocks, groin, or thighs, but 8% of patients developed lesions on their fingers,
and HSV conjunctivitis sometimes occurred. The increased risk of extragenital lesions
in women compared to men probably results from exposure of the buttocks, thighs,
and fingers to infected cervical secretions.20
2. HSV-2 and HIV
The STIs are associated with an increased risk of HIV transmission. However,
among viral STIs, only HSV-2 has been studied extensively for its role in HIV
transmission, acquisition, and pathogenesis. It was then stated that people infected with
HSV-2 who also live with HIV (and other immunocompromised individuals) can have
a more severe presentation and more frequent recurrences. In addition, people with
 9

both HIV and HSV-2 infection are more likely to spread HIV to others and accelerates
the progression of HIV infection to AIDS.20,21
3. Neonatal herpes
Neonatal herpes is rare, occurring in an estimated 10 out of every 100,000 births
globally, but can lead to lasting neurologic disability or death. The major source of
neonatal HSV infection is via contact with the infected genital tract at the time of
delivery. Women who have genital herpes before they become pregnant are at very
low risk of transmitting HSV to their infants. However, the risk for neonatal herpes is
greatest when a mother acquires HSV infection for the first time in late pregnancy.20
4. Psychosocial impact
The recurrent symptoms of genital herpes may be painful and the infection can
lead to social stigma and psychological distress. These factors play an important
impact on quality of life and sexual relationships. However, over time, most people
with herpes adjust to living with the infection.20
2.9 Prevention of Genital Herpes Type 2
Abdool22 found that tenofovir gel is effective for prevent woman form HSV-2. In
other hand, complete partnership counselling is an crucial component of the medical
treatment of genital herpes patients. For this, HSV type-specific serology is an
significant instruments as it allows identification of the HSV-2 carrier. If no HSV-2-
specific antibodies can be discovered in the partner of an HSV-2 seropositive person
the couple should be advised to use condoms. If genital herpes symptoms are present
sexual intercourse should be discouraged. Since these measures are especially
important for the prevention of viral transmission during pregnancy both partners
should be told about their HSV serostatus and the feasible consequences of viral
transmission, both with symptomatic genital herpes and asymptomatic viral shedding.
Psychotherapy can help reduce the number of genital herpes recurrences in female
with excessive levels of emotional stress.2
2.10 Prognosis of Genital Herpes Type 2
There is no healing for HSV-2, early identification of symptoms, and prompt
institution of pharmacotherapy can take to suppression of viral replication. Abstinence
 10

during known viral shedding can reduce the risk of transmission to a seronegative
spouse. The Herpes viruses as a family are responsible for remarkable neurological
morbidity, and unluckily, HSV-2 persists in the seropositive individual for a lifetime.3
 11

CHAPTER III
SUMMARY
Genital herpes type 2 is caused by the Herpes Simplex Virus Type 2 (HSV-2)
which belongs to the family of Herpesviridae. HSV could infect the mucosal epithelial
cells and make a formation of vesicles. There is an estimate of around 23.9 million
people who are infected from HSV 2, with people around the age of between 15 to 49
years and an incidence of 0.6%. Out of this, around 14.7 million were women while
9.2 million were men. As prevalence increased, there was an overall trend of
decreasing incidence with age. Herpes simplex type 2 can be transmitted during sexual
activity. It directly spread through body fluids from seropositive individuals. HSV can
only remain for few days outside of human body. Most of individual with HSV genital
type 2 are asymptomatic in primary infection. The transmission of HSV-2 usually by
genital contact, with someone’s skin, sores, genital surface, or fluid that contain with
the virus and will replicate in the site of the primary infection. The diagnosis of genital
herpes type 2 can be confirmed clinically through history and physical examination
because the lesions caused by this disease are generally typical so that no further
laboratory examination is necessary before the administration of therapy. There are
few differential diagnosis of Genital Herpes type 2, such as syphilis, candidiasis, and
granuloma inguinale. Antiviral therapy in genital herpes type 2 is divided into three
depending on the condition of the patient, which are based on first clinical episode of
genital HSV infection and recurrent clinical episode of genital HSV infection (episodic
and suppressive therapy). The complications of genital herpes type 2 could be
neurological complications, HSV-2 and HIV, neonatal herpes, and psychosocial effect.
There is no healing for HSV-2, early identification of symptoms, and prompt
institution of pharmacotherapy can take to suppression of viral replication.
 12

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 13

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